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Calcitonin gene-related peptide levels are elevated in patients with sepsis.
Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator.
Plasma levels of CGRP have been elevated in animal models with sepsis.
This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis.
Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis.
Volunteers were afebrile and had normal pulse and blood pressure.
Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities.
CGRP was extracted and assayed by radioimmunoassay for iodine 125-labeled human CGRP.
In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000).
Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005).
These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state.
| 0Bacterial Infections and Mycoses
|
Thoracic empyema: causes, diagnosis, and treatment.
Thoracic empyema is a disease that has been recognized for centuries.
The principles of management as stated by Hippocrates remain more or less unchanged.
Diagnosis can be masked by the underlying cause, preemptive antibiotic treatment, or the now frequently associated debilitating diseases.
With no other specific investigation, the main diagnostic test remains diagnostic thoracentesis.
When an empyema is encountered, the objectives are to save life; eliminate the empyema, its complications, and chronicity; return pulmonary mechanics to normal; and reduce the duration of the hospital stay.
The introduction of antibiotics has dramatically influenced the spectrum of the disease now encountered.
If the original infection is adequately treated, empyema rarely occurs.
Penicillin has removed the major cause of empyema, and further developments in antibiotics now mean that the majority of empyemas occur when patients are disabled by other disease processes or malnutrition, or where there remains a delay in medical attention.
These patients are often less able to withstand the prolongation of the infective processes that is sometimes encountered with the staged approach to treatment.
Developments in operative and postoperative care have meant that these patients can best be treated by more aggressive and definitive surgical management.
| 0Bacterial Infections and Mycoses
|
Chancroid: results from an outbreak in Houston, Texas.
A recent (and continuing) epidemic of chancroid in Houston has included morphologic variation in the disease, including so-called dwarf, classic, giant, transient, follicular, phagedenic, and pseudogranuloma inguinale types.
Most cases were clearly acquired by unprotected sexual encounters with local prostitutes.
The strain of Haemophilus ducreyi responsible for this outbreak was relatively easily cultured on routine media; unexpected sensitivity of this strain to vancomycin rendered the recommended "selective" growth medium much less optimal for isolation.
Therapeutic success uniformly followed the use of intramuscular ceftriaxone sodium; one case responded to oral ciprofloxacin hydrochloride.
| 0Bacterial Infections and Mycoses
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A resurgence of acute rheumatic fever in a mid-South children's hospital.
A resurgence of acute rheumatic fever (ARF) has been reported in many areas of the United States in recent years.
We retrospectively reviewed the medical records of inpatients with a new diagnosis of ARF from 1982 through 1988 at a children's hospital that serves a six-state referral area in the mid-South.
Thirty patients were identified, 21 of whom were seen in 1987 (13) and 1988 (8).
The rate of new cases of ARF per 1000 hospital discharges (0.7) was significantly greater for 1987 and 1988 than it was (0.15) from 1982 through 1986.
Patients with recently diagnosed ARF were predominantly from nonurban areas, and polyarthritis was the most common recent major manifestation.
Reasons for the resurgence of ARF in the US, including the mid-South, are unclear, but our experience serves to support recently published guidelines for the diagnosis and management of streptococcal pharyngitis in light of this resurgence of ARF.
| 0Bacterial Infections and Mycoses
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Drug therapy for Helicobacter pylori infection: problems and pitfalls.
Antibacterial chemotherapy against Helicobacter pylori is currently being assessed by open or randomized controlled clinical studies for its efficacy in eradicating this bacterium from the stomach of patients with gastritis or gastroduodenal ulcer.
Whereas there is presently no "optimal" agent and treatment scheme, the combination of some antibiotics (metronidazole, tinidazole, amoxicillin) with bismuth salts proves definitely superior in vivo to either of these agents administered alone.
Several reasons have been proposed, to explain the clinical failure after treatment: insufficient concentration of active drugs in gastric mucus, instability of some agents at an acidic pH, inappropriate formulation of drug, insufficient duration of treatment, and variable compliance of patients.
Recently, it has appeared from several clinical trials that H.
pylori may rapidly acquire resistance to some antibiotics, and that this event might also account for clinical failure.
A critical review of the literature on H.
pylori treatment indicates that association of bismuth and antibiotics or of antibiotics alone both may efficiently reduce the risk of emergence of resistance and improve the therapeutic outcome.
Guidelines of treatment are suggested in order to avoid the future misuse of antibiotics that would increase selection of antibiotic-resistant H.
pylori and negatively affect the ecology of the gastric microflora.
Likewise, an accurate definition of a subset of patients with H.
pylori who really will require treatment needs to be rapidly established.
| 0Bacterial Infections and Mycoses
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Risk factors for Staphylococcus aureus nosocomial pneumonia in critically ill patients.
Staphylococcus aureus nosocomial pneumonia has become an important infection not only because of an apparently increasing incidence but also because of its high mortality rate.
A total of 50 episodes of nosocomial pneumonia in critically ill patients in which etiologic diagnosis was well established were prospectively followed in a medical-surgical intensive care unit (ICU).
S.
aureus was isolated in a total of 13 episodes.
In the univariate analysis the variables significantly associated with S.
aureus nosocomial pneumonia were below 25 yr of age, coma, nonuse of corticosteroids, and antecedent trauma.
A step-forward logistic regression analysis defined only coma as significantly influencing the risk of developing S.
aureus nosocomial pneumonia.
We suggest that antimicrobial drugs active against S.
aureus must be included in the initial empirical antimicrobial regimen for treating nosocomial pneumonia in patients with coma.
The identification of factors influencing the etiology and the possibility of earlier effective antimicrobial treatment may represent a further step in the control of nosocomial pneumonia in critically ill patients by improving its prognosis.
| 0Bacterial Infections and Mycoses
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Tuberculous meningitis. Short course of chemotherapy.
In March 1986, we began a 6-month short course trial of therapy for tuberculous meningitis, in which 28 patients were analyzed.
The diagnosis was based on the following cerebrospinal fluid test results: in 53.5% of the cases, Mycobacterium tuberculosis was identified by direct smear; in 57%, culture in Lowenstein-Jensen medium was positive; in 83.3%, the detection of anti-bacille Calmette-Guerin (BCG) antibodies by enzyme-linked immunosorbent assay was positive; and in 74%, the dosification of adenosine deaminase activity was positive.
In addition, in 21.4% of the cases, the diagnosis was established by means of autopsy findings.
Moreover, the diagnosis was supported by bacteriological analyses from another tissue or body fluids.
Despite the administration of an antituberculous therapy, 32.4% of the patients died: all of the decreased had reached the last stage of the disease by the beginning of treatment.
Sixteen percent of the patients who survived after more than 18 months of follow-up after therapy had ended suffered neurological sequelae.
With the 6-month therapeutic regimen, the morbidity/mortality is similar to that found in the longer-course therapies.
The latter regimen is therefore thought to be a good and acceptable therapeutic option for the treatment of tuberculous meningitis.
| 0Bacterial Infections and Mycoses
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Patterns of bacterial infection in calves implanted with artificial hearts.
Device-related infection is one of the most serious potential consequences of total artificial heart (TAH) implantation.
This complication must be addressed before the full potential benefit of these devices, especially fully implantable devices, can be realized.
A review of research reports and clinical data was conducted to ascertain if similarities existed between the patterns of infection reported in human TAH recipients and those seen in the experimental animal models.
Infection was reported in approximately 57% of the human TAH recipients and approximately 47% of the implanted animals.
Implant periods ranged from 1-620 days for the humans, and 32-287 days for the animals.
The spectrum of organisms isolated from both groups were similar, with a high proportion of infections caused by Pseudomonas aeruginosa and Staphylococcus epidermidis.
In addition, numerous isolates of Enterobacter and Enterococci were obtained from the animals.
Positive blood cultures have often been observed in animals within 2-4 weeks following implantation of the devices.
The similarities noted in this review suggest that the calf may be an appropriate animal model in which to study the pathogenesis of TAH-related infection.
| 0Bacterial Infections and Mycoses
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Prevention of infection in a porous tracheal prosthesis by omental wrapping.
The ideal tracheal prosthesis has to permit complete incorporation by epithelialization of the luminal surface.
This is not possible with the currently available impermeable solid silicone tube.
The authors developed a reinforced, porous polyurethane tubular prosthesis which has the potential for complete incorporation.
However, because these prostheses are implanted in a contamined area such as the airway, they all become infected.
In order to prevent infection, the authors evaluated the effect of omental wrapping in guinea pigs.
The authors' tubular prosthesis was implanted subcutaneously in the abdominal area with the ends open to the air.
Ten prostheses were wrapped with omentum and 10 prostheses were not.
In 4 weeks, all control prostheses were infected and marsupialized.
All the wrapped prostheses remained in place and were macroscopically not infected.
Microscopically, all wrapped prostheses were well vascularized and were incorporated by granulation tissue, which did not occur in the prostheses of the control group.
From these results the authors conclude that omental wrapping would be an effective way to prevent infection of porous tracheal prostheses in an open-to-the-air situation, and allow rapid tissue ingrowth and incorporation in the host.
| 0Bacterial Infections and Mycoses
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Parents' vs physicians' utilities (values) for clinical outcomes in potentially bacteremic children.
Our previous analyses of decision strategies in children 3-24 months with acute-onset fever greater than or equal to 39 degrees C and no evident bacterial focus of infection indicated that the risks of routine blood cultures (the unnecessary hospitalization and treatment of children who clear their bacteremia spontaneously) outweigh its benefits (the prevention of a few cases with major infectious sequelae).
Because those analyses were based on parents' values for beneficial and adverse clinical outcomes, we wished to examine whether those values differed in physicians and, if so, whether the differences were sufficient to change the results of the decision analysis.
Using a pre-tested linear analog utility (value) scale, we evaluated eight potential clinical outcomes in potentially bacteremic children by surveying 121 parents of healthy 3-24-month-old children attending a private pediatric group practice and 57 attending physicians of a tertiary-care children's hospital emergency room.
Utilities were based on a 0-1 normalization, where 0 is the utility of the worst outcome (meningitis or other major bacterial infection, plus venipuncture), and 1 the utility of the best outcome (complete recovery without venipuncture or hospitalization), and were analyzed using a recently developed statistical model of utility.
The majority of parents and physicians combined the imputed components of the outcomes (disease, pain of venipuncture, and stress of hospitalization) in a nonlinear fashion.
Parents assigned substantially lower utility (i.e.
greater disutility) to venipuncture, minor infection, and hospitalization than did physicians, and these utilities were even lower in parents with other children at home.
| 0Bacterial Infections and Mycoses
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Low gastric acid as a risk factor for cholera transmission: application of a new non-invasive gastric acid field test.
Although gastric acid is thought to be an important host defense against certain enteric infections, field studies of the role of gastric acid in preventing enteric infections have been hampered by the lack of a suitable non-invasive test.
Because low gastric acid output (GAO) is an established risk factor for cholera, we assessed after validation, whether a new non-invasive test which estimates GAO by measuring breath hydrogen excess after ingestion of magnesium and a stimulant of gastric acid secretion, could discriminate between persons at high and at low risk of developing cholera.
Fifteen age-matched pairs, participants in the field trial of two oral cholera vaccines in rural Bangladesh, were tested.
In each pair the "case" was a person who had recovered from severe cholera at least 6 months before testing and the "control" was a person who resided in the home of a cholera patient but remained uninfected.
The stimulated breath hydrogen was higher in controls (median hydrogen excess = 369 mumol/80 min) than in cases (median hydrogen excess = 150 mumol/80 min) (p less than 0.05) and was higher in controls in 12 out of 15 pairs.
The results, which are consistent with past invasive assessments of the association between hypochlorhydria and cholera, suggest that this non-invasive test may be useful in evaluating GAO in epidemiological field studies.
| 0Bacterial Infections and Mycoses
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Tampon absorbency, composition and oxygen content and risk of toxic shock syndrome.
Tampon use has been identified as a major risk factor for toxic shock syndrome, although the etiologic role of tampons is not clearly understood.
Two epidemiologic studies conducted to date have reported an association between tampon absorbency and risk of toxic shock syndrome.
This finding is not corroborated by laboratory studies, however, which have suggested that absorbency may be a marker for other characteristics that create an environment conductive to the elaboration of toxic shock syndrome toxin 1.
We used data from the previously reported Tri-state study to estimate simultaneously the effects of tampon oxygen content, absorbency and chemical composition.
Although the data are sparse, oxygen content was more strongly associated with risk of toxic shock syndrome than either absorbency or chemical composition.
The results suggest that it may be possible to develop a highly absorbent tampon that is not associated with a high risk of toxic shock syndrome.
| 0Bacterial Infections and Mycoses
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Development and potential use of antibody directed against lipopolysaccharide for the treatment of gram-negative bacterial sepsis.
Gram-negative bacterial sepsis remains a major cause of lethality in hospitalized patients, despite routine therapy consisting of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support.
Because a large body of evidence supports the concept that Gram-negative bacterial lipopolysaccharide (endotoxin, LPS) is responsible for many of the direct and host mediator-induced deleterious effects, recent work has been centered on the development and use of anti-LPS antibody preparations in order to ameliorate lethality.
Both polyclonal and monoclonal antibody preparations directed against the common deep core/lipid A region of LPS are cross-reactive in vitro and cross-protective in vivo against a wide range of challenge organisms and LPS, and preliminary clinical trials indicate that a reduction in lethality may be possible.
The precise endotoxin epitope against which antibody should be directed in order to maximize protection, however, has not been established.
This modality most probably will become a standard form of adjunctive therapy within the next several years for the treatment of Gram-negative bacterial sepsis.
| 0Bacterial Infections and Mycoses
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Altered Ca2+ homeostasis and functional correlates in hepatocytes and adipocytes in endotoxemia and sepsis.
Decreased cytosolic [Ca2+] and impaired Ca2+ release in response to an IP3 challenge are among perturbations in hepatocyte Ca2+ homeostasis associated with endotoxemia and sepsis.
These changes are consistent with the accompanying alterations in appropriate physiologic functions, e.g., activation of glycogen phosphorylase and gluconeogenesis, mediated by [Ca2+]c and defective phosphorylation of relevant enzymes.
Attenuation of IP3 binding to the subcellular fractions that are imputed to be targets of IP3 and a decrease in the size of the IP3-sensitive pool of releasable Ca2+ are underlying components of the mechanism of the reduced Ca2+ release upon IP3 stimulation and its metabolic sequelae.
ET treatment leads to a significant increase in Ca2+ associated with the cell surface compartment of adipocytes, a reduction in 45Ca2+ uptake by endoplasmic reticulum and higher cytosolic [Ca2+] under basal conditions and upon ACTH stimulation than that observed in cells of control rats.
The reduced 45Ca2+ uptake is also manifest in adipocytes of septic rats.
Alterations in adipocyte metabolism induced by ET include increased oxidation of glucose to CO2 (an insulin-like effect) and increased lipolysis upon NE and ACTH stimulation.
| 0Bacterial Infections and Mycoses
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Suppression of herpes simplex virus type 1 reactivation from latency by (+-)-9-([(Z)-2-(hydroxymethyl)cyclohexyl]methyl) guanine (L-653,180) in vitro.
Latent herpes simplex virus type 1 (HSV-1) infection was induced in human embryonic lung cells in vitro by using a combination of viral replication inhibitors and elevated temperature.
Under reactivating conditions (superinfection by human cytomegalovirus or temperature manipulation), a nonantiviral thymidine kinase inhibitor (L-653,180) was found to suppress or delay reactivation of HSV-1 from latently infected human embryonic lung cells.
L-653,180 alone or in combination with interferon was ineffective as a primary or acute viral replication inhibitor and was unable to induce latent HSV-1 infection in cell culture.
These data suggest that initial or acute virus replication and replication resulting from reactivation from latency are separate events.
| 1Virus Diseases
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Treatment of adult chickenpox with oral acyclovir.
Thirty-one late adolescents and adults with varicella were studied.
Patients identified within 72 hours of varicella exanthem were offered open treatment with acyclovir (4 g/d), and those patients identified after 72 hours of exanthem were followed up but not treated.
Twenty-two patients were treated with acyclovir.
Nine patients were not treated.
No severe complications occurred in any of the 31 patients.
Minor complications, including prolonged fever, localized secondary infections, persistent cough, and prolonged fatigue were more frequent in the untreated group.
If the acyclovir therapy was begun within the first 24 hours of varicella exanthem, then the rash and clinical illness were dramatically lessened.
Treatment with oral acyclovir should be considered for varicella in adults who are identified within the first 24 hours of exanthem.
| 1Virus Diseases
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Infection of mice with lactate dehydrogenase-elevating virus destroys the subpopulation of Kupffer cells involved in receptor-mediated endocytosis of lactate dehydrogenase and other enzymes.
In previous experiments in rats, we have shown that the rapid plasma clearance of a number of clinically important enzymes is due to receptor-mediated endocytosis by Kupffer cells and other resident macrophages.
Others have shown that infection of mice with lactate dehydrogenase-elevating virus, a virus that proliferates in macrophages, leads to reduced plasma elimination of these enzymes.
This paper integrates these two sets of experiments.
Plasma elimination of intravenously injected, radioactively labeled lactate dehydrogenase M4 and mitochondrial malate dehydrogenase in mice was shown to be caused in part by uptake in liver, spleen and bone.
Uptake of lactate dehydrogenase M4 by these tissues was, to a large extent, saturable and the two dehydrogenases competitively inhibited each other's clearance.
These results suggest that, also in mice, these enzymes are partly cleared from plasma by endocytosis by way of a common receptor on cells (probably macrophages) from liver, spleen and bone marrow.
Morphometrical data showed that normal mouse liver contains 23 x 10(6) Kupffer cells/cm3.
This number was reduced to about 30% of that of controls 24 hr after infection of mice with lactate dehydrogenase-elevating virus but returned to normal within the next 9 days.
The saturable component of uptake of lactate dehydrogenase M4 by liver, spleen and bone had disappeared 24 hr after infection with the virus, and did not return after the Kupffer cell population had recovered.
Our findings suggest that lactate dehydrogenase M4 is, to a large extent, removed from the circulation by way of a receptor on a subpopulation of macrophages that is permissive for replication of lactate dehydrogenase-elevating virus.
| 1Virus Diseases
|
Chronic encephalitis caused by leukoencephalopathy.
As mentioned previously, both MS and PML are demyelinating conditions of the CNS and pose diagnostic difficulties in their differentiation because of similarities in their clinical findings.
However, certain features unique to each of these diseases are helpful in clinical diagnosis.
MS, unlike PML, is a disease of unknown cause.
Polygenetic influences in combination with exposure to an environmental agent and immune-mediated factors may be operative in the pathogenesis of MS.
Age of onset peaks in the third to fourth decades with a predominance in women, as contrasted with PML, which peaks in the fifth to sixth decades in most non-AIDS-associated cases with a slight predominance in men.
MS is more prevalent in areas farther from the equator: North America, Europe, Australia, and New Zealand.
Common initial symptoms seen in MS include bilateral limb weakness (with the legs being affected twice as often as the arms), hyperreflexia, spasticity, optic neuritis, diplopia, incoordination, and paresthesias.
(Paresthesias are typically found in the lower limbs in a symmetric pattern, but may follow no obvious anatomic distribution and often do not correspond to the distribution of sensory symptoms.
Vibration and position sense are more frequently disturbed than pain and temperature.) Intellectual impairment and mental deterioration are uncommon early in MS, whereas they are a more frequent initial presentation in PML.
In addition, the presence of speech impairment and monoparesis or hemiparesis with homonymous hemianopsia is more suggestive of PML.
Brain stem involvement is infrequent.
| 1Virus Diseases
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In situ hybridisation with digoxigenin-labelled DNA probes for detection of viral genomes.
The applicability of a recently developed non-radioactive DNA labelling and detection method, which uses the digoxigenin (DIG) enzyme linked immunosorbent assay (ELISA) system, for the detection of viral infections in pathology specimens by in situ hybridisation, was examined.
Its efficacy was compared with that of biotin and radioisotope labelling methods.
Three cases of progressive multifocal leucoencephalopathy, two of verruca vulgaris, and seven cases of laryngeal papilloma were studied.
The sensitivity of the DIG labelled probe was almost the same as that of a 35S-labelled probe in the dot-blot hybridisation test.
Using in situ hybridisation with 35S-labelled and DIG labelled probes, the levels of the hybridised signals detected were similar.
The biotin labelled probe was less sensitive, particularly in the cases of laryngeal papilloma.
The DIG labelling and detection method was highly sensitive and applicable to the detection of viral infection by ISH, and is preferable to a radiolabelled probe, especially when in situ hybridisation is done in the pathology laboratory.
| 1Virus Diseases
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Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection.
Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration.
Cytological analysis included immunocytochemical investigation with the alkaline phosphatase-antialkaline phosphatase (APAAP) method.
All patients had confirmation of cytological diagnosis by lymph node biopsy.
Fifteen aspirates with follicular hyperplasia were evaluated.
Eleven patients showed B cell predominance.
The B cell population did not show light chain restriction.
Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated.
Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction.
The cytological diagnosis included two mycobacterial infections and four cystic lesions.
Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma.
These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients.
| 1Virus Diseases
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Measles antibody: reevaluation of protective titers.
A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA.
Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001).
Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02).
Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002).
By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10).
The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level.
| 1Virus Diseases
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Measles incidence, vaccine efficacy, and mortality in two urban African areas with high vaccination coverage.
Measles incidence, vaccine efficacy, and mortality were examined prospectively in two districts in Bissau where vaccine coverage for children aged 12-23 months was 81% (Bandim 1) and 61% (Bandim 2).
There was little difference in cumulative measles incidence before 9 months of age (6.1% and 7.6%, respectively).
Between 9 months and 2 years of age, however, 6.1% contracted measles in Bandim 1 and 13.7% in Bandim 2.
Even adjusting for vaccination status, incidence was significantly higher in Bandim 2 (relative risk 1.6, P = .04).
Even though 95% of the children had measles antibodies after vaccination, vaccine efficacy was not more than 68% (95% confidence interval [CI] 39%-84%) and was unrelated to age at vaccination.
Unvaccinated children had a mortality hazard ratio of 3.0 compared with vaccinated children (P = .002), indicating a protective efficacy against death of 66% (CI 32%-83%) of measles vaccination.
These data suggest that it will be necessary to vaccinate before age 9 months to control measles in hyperendemic urban African areas.
| 1Virus Diseases
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Occurrence of groups A and B of respiratory syncytial virus over 15 years: associated epidemiologic and clinical characteristics in hospitalized and ambulatory children.
Over 15 years respiratory syncytial virus (RSV) isolates from 1209 hospitalized and ambulatory children were examined for strain group and in a subset for subgroup to determine the associated epidemiologic and clinical characteristics.
Three patterns of yearly outbreaks existed: (1) strong predominance of group A strains (9 years with 83%-100% A strains), (2) relatively equal proportions of group A and B strains (4 years), and (3) strong predominance of group B strains (78%-85%) in 2 years, separated by a decade.
The first pattern of highly dominant A strains occurred in cycles of 1 or 2 consecutive years with a single intervening year in which B strains were greater than or equal to 40% of the isolates.
Subgroups A1 and A2 predominated, while B2, 3, and 4 occurred almost equally.
A greater clinical severity for Group A strains was suggested by children with group A infections requiring intensive care significantly more often (15.4 vs.
8.3%, P = .008).
Further, strongly dominant A strain years were associated with higher proportions of RSV admissions requiring intensive care (16.6% vs.
5.5%, P less than .01).
Strains of subgroups A2 and B4 were more frequently found in hospitalized patients and A1 in outpatients, and the 2 years with the highest rates of intensive care admissions were those in which subgroup A2 dominated.
| 1Virus Diseases
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Effect of vaccination on serotype-specific antibody responses in infants administered WC3 bovine rotavirus before or after a natural rotavirus infection.
In an evaluation of WC3 bovine rotavirus (serotype 6) vaccine in infants, some subjects experienced a natural serotype 1 rotavirus infection before vaccination and others after.
Therefore, the effects of both WC3 and natural rotavirus strains as either primary or boosting immunogens on serotype-specific neutralizing antibody responses could be determined.
After primary natural infection (symptomatic or asymptomatic), neutralizing antibody titers were highest to serotype 1 but were consistently high to serotype 3, and low titers (greater than or equal to 20) to serotypes 2 and 4 were often detected.
Previous vaccination with WC3 had little effect on the magnitude of these responses.
In contrast, subjects infected with serotype 1 strains before vaccination experienced large (average, 12-fold) rises in neutralizing antibody to human serotypes 1-4 when vaccinated with WC3.
Thus, although WC3 and the natural strains are distinct serotypes, their epitopes were sufficiently similar that reinfection with WC3 could boost neutralizing antibody titers to human serotypes in subjects primed by a previous natural infection.
| 1Virus Diseases
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Cytomegalovirus and Rasmussen's encephalitis
In-situ hybridisation with a biotinylated cytomegalovirus (CMV) DNA probe was done on brain biopsy specimens from 10 patients with Rasmussen's encephalitis (RE) and 46 age-matched control patients with other neurological diseases.
All 10 patients with RE had intractable epilepsy and focal neurological deficits, and there was perivascular cuffing, microglial nodules, astrogliosis, and neuronal loss.
CMV genomic material was demonstrated in 7 of the 10 patients with RE (in neurons, astrocytes, oligodendrocytes, and endothelial cells) and in 2 of the 46 control patients.
Probes for herpes simplex virus and hepatitis B virus were negative in all patients and in fibroblast controls.
The results suggest that CMV is a likely cause of Rasmussen's encephalitis.
| 1Virus Diseases
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Use of single fiber EMG and macro EMG in study of reinnervation.
The use of single fiber EMG and macro EMG in studies of reinnervation is discussed.
SFEMG gives information about changes in the topography of the motor unit and in function of transmission in terminal nerve, motor endplate and muscle fiber.
Dynamics of reinnervation may be studied with this technique.
The amount of reinnervation is obtained from macro EMG studies.
The capacity for reinnervation is discussed for a few conditions as well as factors that limit the reinnervation process.
| 1Virus Diseases
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Measles in Israel, the West Bank, and Gaza: continuing incidence and the case for a new eradication strategy.
Measles continues to occur in epidemic waves in Israel, Gaza, and the West Bank, causing morbidity and mortality.
In Israel, immunization of infants against measles began in 1967, and 90% had been immunized by the mid-1980s.
In Gaza and the West Bank, where immunization of infants against measles began in 1973 and 1976, respectively, the immunization rate reached 75% in the late 1970s and increased to greater than 90% in the 1980s.
Measles epidemics, which previously had occurred in 5- to 7-year cycles, occurred every 2-4 years in the 1980s and affected individuals who were older than those affected in previous years.
Israel's commitment to eradicating measles by 1992 will require a substantially expanded immunization program in comparison with the traditional program that requires immunization of infants alone.
The benefits of several alternative immunization strategies considerably exceed their costs.
A new, two-dose immunization will be needed as a minimal strategy, and a campaign for administering booster doses to school-aged children may be required as well to achieve control and eradication of measles.
Measles is a serious but preventable public health problem; appropriate strategies must be devised by national and international public health officials to control the disease in developing and developed countries.
| 1Virus Diseases
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Impact of cytomegalovirus infection on organ transplant recipients.
Cytomegalovirus (CMV) is the single most important infectious agent affecting recipients of organ transplants, with at least two-thirds of these patients having CMV infection 1-4 months after transplantation.
Latently infected allografts are the major exogenous source of CMV infection in transplant recipients, although leukocyte-containing blood products can also transmit the virus.
Three patterns of CMV infection are recognized: primary infection, reactivation infection, and superinfection.
Primary infection has the greatest clinical impact.
The clinical effects of CMV infection include infectious disease syndromes such as pneumonia and chorioretinitis; an immunosuppressed state that predisposes to potentially lethal opportunistic infection; and the initiation of a process that can result in allograft injury.
Progress has been made in controlling CMV infection; hyperimmune anti-CMV globulin and certain antiviral drugs appear promising for prophylaxis, and the combination of hyperimmunoglobulin and ganciclovir appears promising for therapy.
| 1Virus Diseases
|
American blood donors seropositive for human T-lymphotropic virus types I/II exhibit normal lymphocyte subsets.
Recent reports have demonstrated that some lymphocyte subsets are abnormal in Japanese blood donors who are seropositive for human T-lymphotropic virus type I (HTLV-I).
To determine if similar changes characterize American blood donors who are seropositive for HTLV-I/II, lymphocyte subsets were measured in 42 HTLV-seropositive and 42 HTLV-seronegative blood donors.
The seronegative individuals were matched by age, race, and gender to the seropositive individuals.
Peripheral blood mononuclear cells were treated with a panel of 12 monoclonal antibody pairs and then analyzed by two-color flow cytometry.
No significant differences were observed between the seropositive and seronegative groups with respect to the absolute number of circulating lymphocytes or the percentages of lymphocytes belonging to the subsets assessed.
These subsets included B, T, CD4, and CD8 cells and subpopulations of CD4 and CD8 cells defined by the coexpression of markers that appear (CD25, HLA-DR, CD38) or disappear (Leu 8, CD45RA) after activation.
These findings indicate that HTLV-seropositive persons in the American blood donor pool do not exhibit the lymphocyte subset alterations reported for HTLV-I-seropositive blood donors in Japan.
| 1Virus Diseases
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Measles update.
The incidence of measles in the United States dramatically increased in the 1980s, from a low of 1,497 cases in 1983 to over 17,000 cases in 1989.
Family physicians can help reverse this trend by following the revised immunization schedule, which includes a measles-mumps-rubella (MMR) booster for preschool-age children.
New guidelines also recommend that either the two-dose MMR schedule or serologic evidence of immunity be required for all persons entering college or employed in the medical field.
Immunization policies for physician's offices should ensure that all office staff have acquired measles immunity and that a triage policy separating patients with rash from those with other illnesses is utilized.
Mild upper respiratory illness, a history of seizures, nonanaphylactic egg allergy and asymptomatic human immunodeficiency virus infection are not contraindications to measles vaccine.
All cases of measles should be reported to the local health department.
| 1Virus Diseases
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HIV seroconversion in two homosexual men after receptive oral intercourse with ejaculation: implications for counseling concerning safe sexual practices.
Seroconversion for HIV antibody occurred in two homosexual men who reported no anal intercourse for greater than or equal to 5 years and multiple episodes of receptive oral intercourse with ejaculation.
Neither man reported intravenous drug use or receipt of blood products.
The last antibody-negative specimen was also negative by the polymerase chain reaction and p24 antigen assays.
All sexually active persons should be clearly counselled that receptive oral intercourse with ejaculation carries a potential risk of HIV transmission.
| 1Virus Diseases
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Are stressful life events risk factors for herpes zoster?
To determine if psychologically stressful life events are risk factors for herpes zoster, we conducted a case-control study of zoster and self-reported recent negative life events and major changes in spousal relationships.
The subjects were 101 healthy community-dwelling cases of zoster and 101 healthy controls matched for age, sex, and race and generated by random digit dialing.
The Geriatric Scale of Recent Life Events was administered to case and control subjects, and additional questions were asked regarding the perception of the life event.
The results showed that case subjects experienced negative life events significantly more often than subjects in the control groups in the 2 months before zoster onset by analysis of discordant pairs (26 versus 10, odds ratio 2.60, 95% confidence interval [CI] 1.13, 6.27, P = .012), 3 months before (29 versus 11, odds ratio 2.64, 95% CI 1.20, 6.04, P = .007), or 6 months before (35 versus 16, odds ratio 2.00, 95% CI 1.04, 3.93, P = .012).
The mean number of total life events was significantly higher in cases at 6 months before zoster (case means = 2.64, control means = 1.82, P = .008), but there were no significant differences at 2, 3, or 12 months before.
There were no significant differences between case subjects and control subjects for spousal events, or any given single life event.
In conclusion, we found that whereas patients with herpes zoster experienced the same kinds of life events in the year preceding the illness as did control subjects, recent events perceived as stressful were significantly more common among patients with zoster.
| 1Virus Diseases
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Human immunodeficiency virus and the primary care physician.
As the scope and size of the human immunodeficiency virus (HIV) epidemic grows, the primary care physician will need to assume a greater role.
A knowledge of HIV risk factors and the ability to perform pretest and posttest counseling for HIV testing is essential.
Counseling patients on HIV risk reduction should be part of the HIV risk interview.
An understanding of the benefits and contraindications of testing, as well as a respect for the impact of testing, is important.
All HIV-seropositive individuals should undergo a complete history and review of symptoms as soon as test results are known.
Judicious use of laboratory testing, including monitoring of CD4 cell counts, is recommended.
Pneumocystis carinii prophylaxis and zidovudine therapy should be offered to patients with appropriately low CD4 counts.
| 1Virus Diseases
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Isolation of human T-cell lymphotropic virus type 2 from Guaymi Indians in Panama.
Human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and with a chronic degenerative myelopathy.
However, another major type of HTLV, HTLV-II, has been isolated only sporadically, and little is known of disease associations, transmission routes, and risk factors for HTLV-II infection.
Recent studies indicate that a high percentage of certain groups of i.v.
drug users and blood donors are infected with HTLV-II.
Seroepidemiologic studies have found an elevated rate of seroreactivity to HTLV among Guaymi Indians from Bocas del Toro Province, Panama.
To identify the cause of seroreactivity among this unique population we used HTLV-II-specific polymerase chain reaction techniques to detect HTLV genetic sequences from blood leukocytes of three seropositive Guaymi Indians.
The HTLV-II primer-amplified polymerase chain reaction products from two of these subjects were partially sequenced and matched published HTLV-II nucleotide sequences in both p24 gag (94% of 107 bases) and pol (98% of 112 bases) regions.
A CD4+ T-lymphocyte line established from one of these same subjects produced HTLV-II-specific proteins when tested in antigen-capture and immunoblot assays, as well as mature HTLV particles.
The demonstration of HTLV-II infection in this geographically and culturally isolated Central American Indian population without typical risk factors for HTLV infection suggests that HTLV-II infection is endemic in this population and provides an important clue to potential natural reservoir for this virus.
| 1Virus Diseases
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Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys.
Potential reasons for the lack of pathogenicity of the simian immunodeficiency virus SIVagm in its natural host, the African green monkey (AGM, Cercopithecus aethiops), were investigated with respect to immunological mechanisms.
The functional immune response of monkeys to infection was similar (though not identical) to that of humans to infection with human immunodeficiency virus type 1 (HIV-1).
In the sera of infected animals, neutralizing antibodies were found to be low or absent, and in particular there was no neutralization of the various isolates by homologous sera.
There was no detectable antibody/complement cytotoxicity, though AGM sera were able to initiate antibody-dependent cellular cytolysis of infected cells in the presence of healthy effector peripheral blood lymphocytes.
As in the human/HIV system, macrophages from AGMs are readily infected by SIVagm.
Two possibly important differences between the AGM/SIVagm system and the human/HIV system are (i) the low immune response of the AGMs to the core protein of SIVagm and (ii) the significantly lower inhibitory effect of SIVagm proteins on the proliferation of AGM lymphocytes.
| 1Virus Diseases
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Increasing incidence of varicella hospitalizations in United States Army and Navy personnel: are today's teenagers more susceptible? Should recruits be vaccinated?
Hospital records for 10,687 United States Army and Navy adult varicella (chickenpox) admissions were reviewed.
Annual hospital admission rates for varicella increased more than fourfold in the active-duty army during 1980 to 1988 and more than 18-fold among active-duty navy enlisted personnel during 1975 to 1988.
Fifty-seven percent of varicella admissions occurred in the most junior military members, aged 17 to 20.
More than half of the total varicella admissions occurred in personnel with less than a year of military service.
Multivariate analysis of the navy data confirmed increasing time-related trends of risk, suggesting a national temporal trend of increased varicella susceptibility in US teenagers and young adults.
Administering a safe and effective varicella vaccine to army and navy recruits could prevent more than 7260 hospital-bed days during the first year of use.
| 1Virus Diseases
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A routine tool for detection and assessment of epidemics of influenza-like syndromes in France.
A regression model for the nonepidemic level of influenza-like syndrome has been estimated from the 55,200 cases collected between October 1984 and August 1988 using the French Communicable Diseases Computer Network.
The start of a major epidemic in 1988-89 was detected early.
The size of the epidemic, for the entire country, was estimated at approximately 4.3 million cases.
The excess cost of sick-leave, among those of working age, was estimated at $86 million.
| 1Virus Diseases
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An HIV-1 and HIV-2 cross-reactive cytotoxic T-cell epitope.
The HLA-B27-restricted HIV gag cytotoxic T-lymphocyte (CTL) epitope, 265-279, is highly conserved amongst HIV-1 isolates, only one, HIV-1ELI, having a single amino acid substitution.
Over the same region HIV-2 differs by five amino acids.
As a broadly cross-protective AIDS vaccine should protect against infection from all isolates of HIV-1 and HIV-2, we tested CTL specific for the HIV-1 265-279 epitope with peptide analogues from HIV-1ELI, HIV-2 and two simian immunodeficiency virus (SIV) isolates, and with recombinant vaccinia viruses expressing the respective gag genes, to determine whether there was any cross-reactivity for this CTL epitope.
CTL from the HIV-1-infected donor could recognize the HIV-1ELI peptide, the HIV-2 peptide and recombinant vaccinia virus-infected target and one of the two SIV peptide-treated targets.
Epitopes that exhibit such cross-reactivity may be valuable in vaccine design.
| 1Virus Diseases
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CD4+ monocyte counts in persons with HIV-1 infection: an early increase is followed by a progressive decline.
In this study, we asked whether there is a difference in the number of CD4+ and CD4- peripheral blood monocytes as CD4+ T cells decrease during HIV-mediated immunodeficiency.
Monocytes and T cells from 90 HIV-positive and 43 HIV-negative persons were analyzed by flow cytometry.
The 90 HIV-positive patients represented the entire spectrum of CD4+ T-cell counts.
We report that as CD4+ T cells decrease, the number of CD4+ monocytes decrease in parallel.
Moreover, significantly higher CD4+ monocyte counts were observed in persons with early stage HIV disease, i.e., greater than 800 CD4+ T cells/mm3, than in HIV-negative persons with greater than 800 CD4+ T cells/mm3.
Potential implications of these findings are discussed.
| 1Virus Diseases
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Impact of mass treatment of onchocerciasis with ivermectin on the transmission of infection.
Onchocerciasis is a major blinding disease that, until recently, has been essentially untreatable.
Ivermectin is a safe and effective drug for the mass treatment of onchocerciasis and when used on an individual basis, it reduces the ability of the treated person to transmit Onchocerca volvulus infection.
In the present study, the effect of community-based ivermectin treatment on the degree of transmission within the community was assessed by determining the incidence of new infection in children.
Ivermectin was distributed annually on three occasions to the eligible members of a population of approximately 14,000 people living on a rubber plantation in a forest area endemic for onchocerciasis.
After 2 years, the prevalence of infection in 5-year-old children decreased by 21%.
The annual incidence in an uninfected cohort of children decreased by 35% and, after age-specific adjustment, the reduction in incidence in 7- to 12-year-old children was 45%.
Thus, community-based distribution of ivermectin led to a significant reduction in incidence of new infection.
These findings suggest that ivermectin can be important in reducing the transmission of onchocerciasis.
| 2Parasitic Diseases
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Ascariasis.
Ascaris lumbricoides is the most common helminth to infect humans.
Infection occurs when contaminated soil containing mature eggs is swallowed.
Clinically, infection ranges from the asymptomatic carrier state to life-threatening pulmonary disease or intestinal obstruction.
Diagnosis is most frequently established by identification of the eggs in stool specimens.
Treatment with antiparasitic drugs is effective in preventing serious complications and eradicating the parasite from all members of the household.
| 2Parasitic Diseases
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Humoral and cell-mediated immune responses to the Plasmodium falciparum antigens PF155/RESA and CS protein: seasonal variations in a population recently reexposed to endemic malaria.
Resurgence of falciparum malaria occurred in the Central Highlands of Madagascar in the 1980s and the disease is currently hyperendemic.
We determined the humoral and cellular responses to synthetic peptides reproducing the repeat sequences of 2 major Plasmodium falciparum antigens: the Pf155/RESA and the circumsporozoite (CS) protein.
Blood samples from 83 subjects living in a rural community near Antananarivo were obtained at the beginning and the end of the transmission season.
At enrollment, 40 subjects presenting with and 43 without blood parasites had similar T cell proliferative response and antibody level to all antigens tested.
However, P.
falciparum-infected individuals exhibited a decrease in the absolute number of T lymphocytes, due to a diminished number of CD8+ and natural killer lymphocytes.
The number of CD4+ cells was similar in both groups.
In the overall population, 45% of subjects had a T cell response to at least 1 RESA peptide (29-35% responding to a given peptide) and 35% to the CS protein peptide.
Thirty-two percent of the donors presented with RESA antibodies and 23% had CS protein antibodies.
After 20 weeks, at the end of the transmission season, cellular proliferative responses to all antigens markedly decreased as evidenced by a decrease of both the number of responders and mean stimulation indexes.
Humoral response to RESA, as detected by erythrocyte membrane immunofluorescence (number of responders and mean antibody titers) markedly increased.
Humoral responses to the CS protein and RESA peptides were similar.
| 2Parasitic Diseases
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In vitro growth inhibition of Plasmodium falciparum by sera from different regions of the Philippines.
Sera from different malaria endemic regions of the Republic of the Philippines were compared for their ability to inhibit growth of Plasmodium falciparum in vitro.
Dialyzed serum was added to synchronous cultures containing schizonts for either the total 48 hr test period or only the last 24 hr in order to analyze the effects on erythrocytic invasion and intraerythrocytic growth, respectively.
Reduction in 3H-hypoxanthine uptake was used to determine the percent of inhibition compared to nonimmune serum.
One hundred seventy sera from Mindanao and Palawan in the South, the centrally located island of Mindoro, and Luzon in the North, were tested against 4 P.
falciparum strains from the Philippines and 1 from Africa.
Indirect fluorescent antibody titers were not predictive of inhibition.
Inhibition of merozoite invasion rather than intraerythrocytic parasite growth is suggested by this study.
Generally, sera were more inhibitory to parasite strains from the same geographical area than to those from more remote areas.
| 2Parasitic Diseases
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Comparison of active and passive case detection of cutaneous leishmaniasis in Guatemala.
To estimate the degree to which passive case detection underestimates the true incidence of cutaneous leishmaniasis in Guatemala, we compared data from the passive surveillance system of the Guatemalan Ministry of Health with a cross-sectional population-based survey of cutaneous leishmaniasis in Guatemala.
Of the 2,938 persons interviewed, 143 (5%) reported having had cutaneous leishmaniasis at some time in the past, 37 (1.3%) reported the onset of infection in the 12 months before the survey, 31 (1.1%) had active infections, and 16 (0.5%) had parasitologically confirmed infections.
Calculated on the basis of these reports and the estimated population of the endemic area, the total number of new cases in the leishmaniasis-endemic area in the 12 months before the survey was approximately 2,574; during the same 12 month period, Ministry of Health data based on passive surveillance listed 64 cases of cutaneous leishmaniasis.
In Guatemala, incidence estimates based on passive surveillance may underestimate the occurrence of cutaneous leishmaniasis by as much as a factor of 40.
| 2Parasitic Diseases
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Diffuse cutaneous leishmaniasis acquired in Peru.
A case of diffuse cutaneous leishmaniasis (DCL) acquired in Peru is described.
The causative agent was Leishmania mexicana amazonensis as determined by isoenzyme analysis and species-specific monoclonal antibody binding characteristics.
Histological examination of biopsy material showed a large number of intracellular and extracellular amastigotes and few lymphocytes.
Treatment with meglumine antimoniate (Glucantime) administered iv at a dosage of 20 mg antimony/kg body weight/day for 60 days resulted in visible improvement of the lesions, but not in clinical or parasitological cure.
| 2Parasitic Diseases
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Transmission indices of Loa loa in the Chaillu Mountains, Congo.
A longitudinal entomological survey of the vectors of loiasis was conducted in the Missama area (Lekoumou region) in the Congo from September 1987 to August 1989.
The principal catching site was a palm grove surrounded by forest 3 km from the village.
Landing/biting densities of Chrysops were measured by standardized fly catches lasting 11 hr carried out twice a month.
Vector landing densities were also assessed in the Bantu and Pygmy villages and in the fields.
Populations of Chrysops from the palm grove were examined 6 times a month for infection with the infective stage of Loa loa.
Chrysops silacea was the predominate vector except at the beginning of the rainy season, when C.
dimidiata was the prevailing species.
Chrysops were caught throughout rainy season, from October to June.
The host-seeking activity of C.
silacea was greatest in the middle of this season (February), but occurred sooner (October) for C.
dimidiata.
The following variables associated with transmission were calculated from our observations in the palm grove (the first figure corresponds to the first year of the study and the figure in parentheses corresponds to the second year).
It was calculated that 2.658 (2.185) C.
silacea and 1.412 (1.182) C.
dimidiata could bite a person in the palm grove per year, including an average of 14.4 (12.7) infective C.
silacea and 9.8 (7.2) infective C.
dimidiata.
The percentage of all dissected flies with third stage larvae in the head and the mean number of larvae in the head/infective fly were 0.57% and 10.1 +/- 6.8 for C.
silacea and 0.66% and 11.2 +/- 6.5 for C.
dimidiata, respectively.
The estimated annual transmission potentials were 171.1 (102.9) for C.
silacea and 116.1 (73.8) for C.
dimidiata.
In the palm grove, transmission was ensured by 2 effective vectors during the rainy season (October to May).
Although the annual biting rate for both species was twice as low in the village as in the forest, our data suggest that effective transmission occurs there also.
| 2Parasitic Diseases
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In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice.
The in vivo effects of antimicrobial agents against Toxoplasma gondii were evaluated in mice that were infected intraperitoneally with 10(4) tachyzoites of the RH strain by determination of survival rates and study of the kinetics of growth of T.
gondii in infected mice.
At various intervals after infection, subcultures of serial dilutions of blood, lung, and brain homogenates were performed in fibroblast tissue cultures for determination of parasitic loads.
Pyrimethamine (18.5 mg/kg per day), sulfadiazine (375 mg/kg per day), and clindamycin (300 mg/kg per day) were administered for 10 days from day 1 or day 4 after infection.
Untreated control mice died within 9 days and showed early and predominant lung involvement.
All mice treated with sulfadiazine administered from day 1 survived and were apparently healthy; parasitic loads decreased early after treatment, but a relapse was observed 5 days after the cessation of therapy.
When pyrimethamine was administered from day 1, 7 of 11 mice died within 25 days; by determination of parasitic loads, the effect of pyrimethamine was only demonstrable from day 6, and a relapse was constantly observed after the cessation of therapy.
When pyrimethamine and sulfadiazine were administered in combination, 100% of mice survived; when therapy was started at day 1, parasites remained undetectable; in mice treated from day 4, parasites were eradicated by day 8 but infection relapsed 8 days after the cessation of therapy.
All mice treated with clindamycin from day 1 or day 4 died within 10 days, but parasitemia was always undetectable.
| 2Parasitic Diseases
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Diagnosis of intestinal amebiasis using salivary IgA antibody detection.
This investigation sought to determine whether detection of salivary IgA antibodies to Entamoeba histolytica could identify intestinal amebic infections among 223 school children.
Four groups of children were identified through coproparasitoscopic examination: E.
histolytica as other parasites only (20%); and parasite-free (25%).
The diagnostic accuracy of salivary IgA antibodies to an E.
histolytica membrane extract was 91.5% (sensitivity, 85%; specificity, 98%), maintaining high predictive value at different prevalences.
Also, a positive correlation (r = .753, P less than .001) was observed between fecal E.
histolytica membrane antigen levels and salivary IgA antibody activity.
Measurement of IgA antibodies in saliva may be useful in diagnosing intestinal infections with E.
histolytica within a wide range of prevalences.
Moreover, sampling of saliva may be a useful non invasive test for immunoepidemiologic surveys.
| 2Parasitic Diseases
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Effects of albendazole on Echinococcus multilocularis infection in the Mongolian jird.
Albendazole chemotherapy of larval Echinococcus multilocularis was studied in the Mongolian jird by administration of medicated feed at various concentrations and durations.
The effects were evaluated by comparison of treated and control groups in terms of host mortality, larval metastases to the lungs, and final weight and histologic appearance of larval tissue.
Viability of larval tissue at necropsy of each animal was tested by inoculation into two noninfected jirds.
Albendazole-medicated feed (0.05%-0.10%) significantly inhibited larval growth.
Other effects of the drug included larval degeneration and necrosis, inhibition of protoscolex formation, decreased pulmonary metastases, and reduced mortality of hosts.
Adverse effects on the parasite correlated significantly with serum albendazole metabolite levels and duration of therapy.
However, serum albendazole levels in jirds equal to or exceeding concentrations achieved in humans receiving daily doses of 10 mg/kg of body weight did not kill the parasite.
| 2Parasitic Diseases
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Variations in malaria transmission rates are not related to anopheline survivorship per feeding cycle.
Anopheline survivorship, vectorial capacity, and mosquito infection probability estimates from mosquito infection rates were determined 4 times in 1 year in a Papua New Guinea village.
Estimates of survivorship over the length of the extrinsic incubation period differed significantly during the year.
However, survivorship per feeding cycle, individual mosquito vectorial capacity, and mosquito infection probability did not vary significantly.
Estimates of these parameters were then compared to estimates of survivorship, individual vectorial capacity, and mosquito infection probability in mosquito populations in other villages in the study area.
Since survivorship per feeding cycle did not vary significantly among the mosquito populations in these villages, changes in malaria transmission potential can be better gauged from estimates of survivorship over the length of the extrinsic incubation period.
However, as measurements of relative inoculation rates are easier to perform and have been related to parasite prevalences in children in this area, estimates of inoculation rates are a preferred option for estimating malaria transmission in the Madang area of Papua New Guinea.
| 2Parasitic Diseases
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Geographical distribution of Plasmodium falciparum erythrocyte rosetting and frequency of rosetting antibodies in human sera.
Uninfected erythrocytes bind spontaneously to those infected with certain strains of Plasmodium falciparum.
This is known as spontaneous erythrocyte rosetting.
We have studied the occurrence and frequency of rosetting in 75 fresh patient isolates and have identified rosetting strains from Africa, South America, and Asia.
Rosetting was present in 49% of the isolates tested; the frequency of rosetting red blood cells (RBC) in individual isolates was 0-75% when scored during the first cycle of in vitro growth.
Rosetting antibodies were found in 15 out of 73 (21%) Liberian sera as measured by disruption of rosettes in vitro.
However, antibodies able to inhibit CD36 dependent cytoadherence of P.
falciparum-infected RBC were not detected in these sera.
Erythrocyte rosetting is a geographically widespread phenomenon.
Rosetting antibodies seem to be induced by natural infection and the molecular mechanism of rosette formation seems distinct from that of endothelial cytoadherence.
| 2Parasitic Diseases
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Studies in owl monkeys leading to the development of a synthetic vaccine against the asexual blood stages of Plasmodium falciparum.
During the development of a synthetic vaccine for human use against the asexual blood stages of Plasmodium falciparum, monkey trials were performed to assess safety, immunogenicity, and protectivity.
We determined the minimal infective dose of the P.
falciparum FVO strain, the kinetics of the immune response induced by vaccination with the synthetic peptide mixture (S7 + S12 + S17) or the synthetic hybrid polymeric protein SPf66, and the induction of protective immunity against the experimental challenge with 2 P.
falciparum strains.
A clear boosting effect was observed, determined by the increased antibody titers against synthetic peptides S7, S12, S17, and SPf66, and by improvement in the protective immune response against the challenge.
These studies suggest that either the peptide mixture or the synthetic hybrid polymeric protein are excellent choices for the development of a vaccine against P.
falciparum.
| 2Parasitic Diseases
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Immunization of owl monkeys with a combination of Plasmodium falciparum asexual blood-stage synthetic peptide antigens.
A mixture of 3 synthetic peptides (35.1, 55.1, and 83.1) corresponding to portions of the 35 kDa, 55 kDa, and 83 kDa proteins from the asexual blood stages of Plasmodium falciparum and a polymer of a syntheic peptide incorporating the 3 individual peptides (SPf66) were tested as candidate malaria vaccine antigens in Aotus nancymai.
Monkeys were immunized with combinations of the 3 peptides from 2 separate sources (Centers for Disease Control [CDC], Atlanta, GA or Colombia) or with the synthetic polymer.
Animals immunized with a combination of the 3 peptides from CDC had higher antibody titers to the 35.1 and 55.1 peptides than to the 83.1 peptide.
Monkeys immunized with a combination of the 3 peptides produced in Colombia developed higher levels of antibody to the 55.1 than to the 83.1 and 35.1 peptides.
Animals immunized with the polymer produced detectable antibodies to the 55.1 peptide alone.
Following challenge with P.
falciparum, no differences were observed between the 3 vaccine groups and 2 control groups with respect to the number of animals with parasitemias greater than or equal to 10%.
The inconsistency of serologic response to all 3 peptides in these animals contrasted with previous trials performed in Colombia where the monkeys developed high antibody titers against the 3 peptides and were protected against the experimental infection.
| 2Parasitic Diseases
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Ultrasonographical investigations of onchocerciasis in Liberia.
The efficiency of ultrasonography (US) for the diagnosis and clinical characterization of onchocerciasis was evaluated.
US was performed on 120 probands in Liberia.
Ninety-two patients had generalized onchocerciasis, 21 patients suffered from the chronic hyperreactive form of onchocerciasis (sowda), and 7 probands served as controls.
Patients were examined by US with linear (7.5 MHz and 5 MHz) and sector (3.5 MHz) scanners.
US results were evaluated by examination of extirpated nodules.
The US structure of nodules revealed a typical pattern consisting of a homogeneous echogenicity with small echodense particles and a lateral acoustic shadow, and differentiation from lymph nodes, lipoma, or fibroma was achieved.
Within the onchocercomata, calcifications or fluid were identified.
Regarding the estimation of the worm burden, it is important to note that in 24 patients, additional nodules not previously palpated were found by US.
Also, the number of worm centers in palpable conglomerate nodules were determined more exactly by US than by palpation.
In 4 of 16 sowda patients, impalpable nodules were found by US.
In 13 patients with positive microfilaria counts, no nodules could be detected.
The highly characteristic ultrasonographical pattern of onchocercomata may serve as a basis for further US investigations in onchocerciasis.
| 2Parasitic Diseases
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Quantitative in vitro drug potency and drug susceptibility evaluation of Leishmania ssp. from patients unresponsive to pentavalent antimony therapy.
Quantitative in vitro drug sensitivity of 32 Leishmania isolates (16 from patients failing pentavalent antimony [SbV] therapy) was determined using a radiorespirometric microtechnique (RAM).
Of 30 isolates with histories, 22 (73%) RAM tests agreed with patient history; the remaining 8 (27%) did not.
There was no difference in RAM drug sensitivity: clinical correlation between 15 isolates tested blindly and 15 with known clinical history (4 did not agree with clinical history in both).
Test sensitivity appeared to be limited only by the sensitivity of the Leishmania to SbV and could be detected at 2 micrograms/ml Sb (about 10% of serum drug level).
An isolate from a patient with untreated self-healing cutaneous disease was drug resistant.
Using RAM, parasite drug sensitivity can be quantified apart from patient physiologic and immunologic variables intrinsic to clinical data.
Potency differed a maximum of 100% (weight% Sb:weight% Sb) among drug lots and also between Glucantime and Pentostam.
Potency changes between drug lots were not explainable based on Sb content or test-to-test variability.
This microtest offers a rapid method for evaluating the drug sensitivity of patient isolates and for determining of the activity of pentavalent antimonials and other candidate anti-leishmanials prior to the initiation of therapy.
| 2Parasitic Diseases
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Parasite antigenemia in untreated and treated lymphatic filarial infections.
To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis.
Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis.
Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals.
Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11.
All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment.
Antigenemia levels slowly declined over a period of several months in all but one treated individual.
Forty-two months after treatment, progressively rising antigen levels are present in 10 patients.
Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia.
Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment.
| 2Parasitic Diseases
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Echinococcus infestation of the biceps brachii. A case report.
Echinococcus is a genus of tapeworm endemic in certain parts of the world but found only rarely in the United States.
An extremely unusual case of an intramuscular infestation involving an extremity occurred in a 41-year-old man.
Since the infestation closely resembled a soft-tissue tumor on clinical and roentgenographic examination, the patient was treated with an incisional biopsy of the mass, which consisted of a cystic cavity filled with clear fluid.
The diagnosis of an Echinococcus cyst was made only after permanent section analysis revealed numerous scoleces within the cyst lining.
The patient was asymptomatic six months after cyst excision but still remains at risk for recurrence of the infestation.
The present report serves to alert the reader to this rare but potentially fatal condition.
Preoperative diagnosis is imperative to avoid inadvertant rupture of a hydatid cyst, which releases viable scoleces into the systemic circulation and may precipitate an anaphylactic reaction.
| 2Parasitic Diseases
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B cell responses to paramyosin. Isotypic analysis and epitope mapping of filarial paramyosin in patients with onchocerciasis.
To examine the fine specificity of the human immune response to filarial paramyosin, the antigenicity of an expressed rcDNA (2.55 kb) of Dirofilaria immitis paramyosin was detailed by ELISA.
Using sera from patients infected with Onchocerca volvulus, we analyzed both the entire paramyosin molecule and six subcloned fragments for their IgG, IgG subclasses, and IgE responses.
Patients from both Guatemala (64% positive) and Ghana (100% positive) reacted to paramyosin with specific IgG levels above normal controls.
Although there was no anti-paramyosin subclass restriction common to all patients, the IgG3 response in the Ghananians was significantly greater than that of Guatemalans (p less than 0.001).
IgE anti-paramyosin responses showed positive correlations with IgG2 (p less than 0.001), IgG4 (p less than 0.002), and IgG1 (p less than 0.04) responses.
Epitope mapping using the IgG response to the six subclones demonstrated preferential recognition of the amino terminal end of the molecule (nucleotides 1 to 360).
IgG2 reactivity was clearly localized to the most amino-terminal 120 amino acids, and the IgG4 antibodies recognized amino acids immediately adjacent to this fragment.
These studies examining the fine specificity of anti-filarial immune reactions should provide a method for understanding how parasites either evade or induce host immune responses.
| 2Parasitic Diseases
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Visceral leishmaniasis in a Scottish child.
A Scottish girl acquired visceral leishmaniasis (kala-azar) while on holiday in Majorca.
She presented with the infection, six months later, in Scotland.
Because of inexperience with the disease and a degree of scepticism unnecessary investigations were carried out resulting in a delay in treatment.
| 2Parasitic Diseases
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Activated eosinophils increase vascular permeability and resistance in isolated perfused rat lungs
The effects of eosinophils activated with phorbol myristate acetate (PMA) on isolated perfused rat lungs were examined.
Eosinophils were obtained from lungs of rats infected with Toxocara canis by bronchoalveolar lavage, incubated with PMA, and administered to an isolated perfused rat lung preparation.
Vascular endothelial permeability was assessed by measuring the capillary filtration coefficient (Kf,c) in the perfused lungs.
In lungs receiving either no eosinophils (control) or nonactivated eosinophils, there were no changes in pulmonary hemodynamics or Kf,c.
However, in lungs receiving 2 x 10(6) eosinophils activated with PMA, there was a transient 4.8-fold increase in pulmonary vascular resistance that peaked at 30 min, primarily due to the constriction of small arteries and veins.
After the initial pressor response, Kf,c was increased to 7.5 times control at 130 min and resulted in marked lung edema, increased wet-dry weight ratios, and edema on histologic examination.
Pulmonary arterial pressure and Kf,c responses were dose related for eosinophil numbers between 1 x 10(6) and 4 x 10(6) cells.
Peak airway pressure (Paw) during constant tidal volume ventilation also increased in lungs receiving activated eosinophils compared to the control and nonactivated eosinophil groups.
These findings indicate that activated eosinophils are potent effector cells and can cause pulmonary vasoconstriction, bronchoconstriction, and vascular endothelial injury without widespread plugging of capillaries by aggregated eosinophils.
| 2Parasitic Diseases
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Cisplatin-fluorouracil interaction in a squamous cell carcinoma xenograft.
Patients with squamous cell carcinoma of the head and neck are treated with cisplatin and fluorouracil according to a schedule based on the findings of clinical studies.
A similar schedule showed a supra-additive effect in the treatment of xenografted human squamous cell carcinoma of the head and neck.
We sought to ascertain whether this schedule was optimal.
A single intraperitoneal injection of cisplatin (7.5 mg/kg) was combined with three injections of fluorouracil given during a 24-hour period (total dose, 150 or 80 mg/kg) before, during, or after cisplatin administration.
The combined effect of cisplatin and fluorouracil on tumor growth and toxic effects was schedule dependent.
Consideration of both toxic effects and tumor growth inhibition, as assessed by reduction of the area under the growth curve, the optimal administration interval was found to be fluorouracil given 3 days after cisplatin administration.
| 3Neoplasms
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HLA class I and class II antigen expression on squamous cell carcinoma of the head and neck.
We compared human major histocompatibility (HLA) class I and class II antigen expression on squamous cell carcinoma of the head and neck with that on normal mucosa.
Frozen sections of a consecutive series of 30 squamous cell carcinomas were stained with the monoclonal antibodies W6/32 (class I) and anti-DR (class II) using an immunoperoxidase technique.
Normal mucosa showed class I and class II expression in the basal layers only.
Class I expression on tumors was diffuse in 87%, patchy in 10%, and scattered in 3%.
Class II expression on tumors was diffuse in 20%, patchy in 53%, scattered in 20%, and absent in 7%.
Patterns of expression did not correlate significantly with clinical parameters, including survival, except that class II diffuse and patchy patterns were found to correlate with more poorly differentiated tumors.
| 3Neoplasms
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Computed tomography of metastatic cervical lymph nodes. A clinical, computed tomographic, pathologic correlative study.
A retrospective comparative study of 63 neck dissections was undertaken to evaluate further the accuracy of high-resolution computed tomography (CT) in the detection of nodal metastases, as previous studies have indicated a trend toward the superiority of CT scanning over palpation.
The respective values of neck examination, CT scanning, and histopathologic examination were assessed in 51 patients with head and neck cancer who underwent a total of 63 neck dissections.
The overall agreement between clinical examination findings and histopathologic findings was 92% vs 81% for CT scanning.
A retrospective analysis of the CT findings failed to reveal greater accuracy.
We found nodes measuring 10 mm or more with central low density always to be malignant.
Because CT scanning seems to offer little advantage over palpation in the nonirradiated neck, it should not be regarded as an essential tool in the staging of nodal disease.
After radiation therapy, as neck dissection is only performed because of clinical or radiologic suspicion, CT scanning is of utmost importance.
| 3Neoplasms
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Invasive migration of epidemic Kaposi's sarcoma cells in vitro.
Kaposi's sarcoma (KS) is a low grade malignant neoplasm which shows invasive growth and often occurs in immunosuppressed patients with the Acquired Immune Deficiency Syndrome (AIDS; epidemic KS).
It is also found in elderly men where it is usually limited to the skin (classic KS).
The present study investigated the chemotaxis and invasive migration of epidemic KS cells in vitro and compared them to cells grown from classic KS lesions and to fibroblasts.
Epidemic KS cells demonstrated invasive migration through reconstituted basement membrane (Matrigel) as well as through interstitial connective tissue (collagen I) in early passages, whereas fibroblasts did not invade either barrier.
Epidemic KS cells in late passages did not show any invasive migration.
Following pretreatment with tumour necrosis factor alpha (TNF-alpha) there was no enhanced migration through the Matrigel and collagen I for epidemic KS cells, whereas classic KS cells showed an increased migration through the type I collagen barrier.
| 3Neoplasms
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Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth.
We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells.
B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells.
When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells.
Growth in B-CLL serum did not reduce their lytic potential.
Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions.
We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL.
| 3Neoplasms
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Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus.
Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC).
These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas.
DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements.
All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin.
None of the specimens had detectable CB, bcl-2, or c-myc rearrangements.
However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus.
Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements.
This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases.
Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas.
| 3Neoplasms
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The pharmacokinetics of plasminogen activator inhibitor-1 in the rabbit.
The pharmacokinetics of the activated and latent forms of plasminogen activator inhibitor-1 (PAI-1) isolated from HT1080 fibrosarcoma cells (HT1080 PAI-1) and a nonglycosylated form of human PAI-1 isolated from a yeast expression system (rPAI-1) were followed in the rabbit.
As assessed by an immunologic assay specific for human PAI-1, guanidine HCI activated HT1080 PAI-1 and rPAI-1 entered the total plasma volume following intravenous bolus administration and exhibited a biphasic clearance pattern.
The t1/2s of HT1080 PAI-1 for the initial and beta phases equalled 6.0 and 24.8 minutes, respectively.
The t1/2s of rPAI-1 for the initial and beta phases equalled 8.8 and 34.0 minutes, respectively.
Similar results were obtained by measuring PAI-1 activity in plasma and with trace amounts of 125I-rPAI-1, suggesting that the above pharmacokinetic behavior could also apply to endogenous PAI-1.
The liver was the main site of rPAI-1 clearance.
Unactivated, latent PAI-1 exhibited a very different pharmacokinetic profile.
Over 80% of latent rPAI-1 cleared from the circulation within 10 minutes (t1/2 = 1.7 minutes).
The difference in clearance behavior between activated and latent PAI-1 may be related to the ability of activated PAI-1, but not latent PAI-1, to rapidly form high-molecular-weight complexes with plasma binding factors which were observed in vitro and in vivo.
Because PAI-1 could potentially tilt the fibrinolytic balance toward a prothrombotic state, its rapid clearance may represent an important control mechanism governing the circulating levels of this key component of the fibrinolytic pathway.
| 3Neoplasms
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Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole.
In the 1980 Census the median family income among blacks in Suffolk County, New York (i.e., $19,604) was much higher than that for American blacks as a whole (i.e., $12,618) and 94.1% of that for American whites (i.e., $20,840), but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites.
Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US.
Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks, these numbers were still significantly greater than expected on the basis of death rates among American whites.
Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women.
Specific cancer sites, which differ in the direction of the association between incidence and socioeconomic status, age, and gender must be considered in comparisons of cancer mortality by race and socioeconomic level.
Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates.
| 3Neoplasms
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Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival.
Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma.
Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status.
In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68, also correlated significantly with biochemical PgR measurements.
The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women.
Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative.
In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC).
In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease-free survival.
Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease.
These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR.
The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR.
| 3Neoplasms
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Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study.
Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C).
Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course.
The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages.
Twelve (48%) achieved complete remission (CR) of ALL.
There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patients with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14).
Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10).
The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days).
This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs.
44 days median.
Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension.
Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request.
In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months).
All nine patients relapsed in the marrow.
Among the entire group of 26 patients, only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant).
Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered.
| 3Neoplasms
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Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy.
The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) given postoperatively.
When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy.
The major criticism of such an analysis is its bias.
This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen.
Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy.
| 3Neoplasms
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Doxorubicin for unresectable hepatocellular carcinoma. A prospective study on the addition of verapamil.
A prospective study was conducted to assess the safety and efficacy of the addition of oral verapamil to intravenous Adriamycin (doxorubicin) for the management of patients with unresectable hepatocellular carcinoma (HCC).
All 28 patients studied had histologically verified disease, and cirrhosis was present in 20 of the 21 patients with adequate tissue sampling.
The overall median survival was 57 days.
Chemotherapy was terminated in seven patients after one course of treatment.
Partial response and complete response were noted in four patients (19%) and one patient (4.8%), respectively, among the 21 patients evaluated.
Side effects related to the chemotherapy were present in all patients studied.
Death from fulminating sepsis occurred in three of the 13 patients with leukopenia.
Symptomatic myocardial dysfunction developed in one patient.
The addition of verapamil apparently did not potentiate the tumoricidal effect of systemic Adriamycin on HCC but probably did increase its complications.
| 3Neoplasms
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A phase I trial of cisplatin in hypertonic saline and escalating doses of 5-fluorouracil by continuous intravenous infusion in patients with advanced malignancies.
Thirty-four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high-dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5-fluorouracil (5-FU).
Five treatment levels of 5-FU, ranging from 500 to 900 mg/m2/day for 5 days, were studied.
Leukopenia, thrombocytopenia, and oral mucositis were the dose-limiting toxicities encountered.
Nephrotoxicity was minimal.
Ototoxicity and peripheral neuropathies were rare and mild in this patient group, but most patients received only a small number of treatment cycles.
Diarrhea was not dose-limiting.
Two complete responses (one non-small cell lung cancer and one sweat gland carcinoma) were observed.
No other major responses were noted.
With the dose of CDDP set at 35 mg/m2/day for 5 consecutive days, the maximum tolerated dose (MTD) of a concurrent 5-day 5-FU infusion was found to be 900 mg/m2/day.
The recommended dosages for Phase II trials are 35 mg/m2/day CDDP and 800 mg/m2/day 5-FU for 5 consecutive days.
Cancers of the lung, breast, gastrointestinal tract, and genitourinary tract would be reasonable targets for Phase II studies.
| 3Neoplasms
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Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin.
The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection, and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion.
Objective responses were seen in 11 of the 13 evaluable patients (84%).
Four patients had a complete remission (30%) and seven patients, a partial remission (54%).
Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients.
Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients, transient skin changes, hematologic (Grade 3/4) abnormalities in four patients, and pulmonary fibrosis in one elderly patient.
These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin.
| 3Neoplasms
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Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86).
In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery.
Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986.
Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP).
A strict randomization of patients was not feasible.
A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally.
The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent.
A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage.
The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs.
41/59 [69%]).
Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response.
| 3Neoplasms
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Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988.
Potentially curative radical pancreaticoduodenectomy for ampullary adenocarcinoma was performed in 24 patients over a 35-year period.
The overall operative mortality was 12.5%.
Actuarial survival rate at 5 years was 61% +/- 13.4 standard error of the mean (SEM) and subsequently remained unchanged.
In the same time period, 21 patients underwent potentially curative radical pancreaticoduodenectomy for periampullary tumors of pancreatic origin.
Similar analysis showed an overall operative mortality of 23.8% and a survival rate at 5 years of 27% +/- 12.5 SEM.
The results of radical pancreaticoduodenectomy for ampullary carcinoma in the most recent years (1976 to 1988) were compared with those of former years (1953 to 1975).
There were no statistically significant differences in the 5-year survival rate; however, the operative mortality decreased from 25% in the former period to 6.3% in the recent period.
Survival was dependent on nodal status.
The 5-year survival rate was 78% +/- 11.5 SEM in the absence of nodal metastasis versus 50% +/- 25 SEM in the presence of regional nodal metastasis.
These findings support the concept that radical pancreaticoduodenectomy offers a realistic probability for cure in a selected group of patients with carcinomas of the ampulla of Vater.
| 3Neoplasms
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Expression of Ki-1 antigen (CD30) in mesenchymal tumors.
Expression of CD30(Ki-1) antigen has long been considered to be restricted to activated lymphocytes and related tumors.
However, expression of this antigen has also been detected in embryonal carcinomas, in nonembryonal carcinomas, in malignant melanomas, and even in some myeloid cell lines and macrophages at late stages of differentiation.
In this study, using monoclonal antibody Ki-1, expression of CD30 antigen was immunohistochemically examined in frozen sections of 28 benign and 63 malignant mesenchymal tumors.
The authors found CD30 expressed in two of four leiomyomas, seven of 11 leiomysarcomas, one of six rhabdomyosarcomas, two of two aggressive fibromatoses, one of three fibrosarcomas, two of four synovial sarcomas, one giant cell tumors of tendon sheaths, all five malignant fibrous histiocytomas, all three osteosarcomas, one of three Ewing's sarcomas, in a tumor cell subpopulation of two of ten malignant schwannomas, and in the Schwann cell compartment of one of two ganglioneuromas tested.
Furthermore, CD30 was consistently expressed in the myoepithelial compartment of 13 fibroadenomas.
However, all five lipomas, all seven liposarcomas, all three neuroblastomas, both ganglioneuroblastomas, both chondrosarcomas, and tumors of disputed origin tested were consistently CD30 negative.
These findings indicate that, outside the lymphatic system, CD30 antigen is not restricted to epithelial neoplasms but may also be present in tumors of mesenchymal origin.
The authors conclude that CD30 antigen, although having limited utility in the differential diagnosis of tumors of questionable histogenesis, may eventually define relevant subgroups within the main tumor categories.
| 3Neoplasms
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Immunophenotypes in "classical" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings.
This study evaluates the expression of a series of membrane antigens, normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone, in 90 selected cases of "classical" (mouse red blood cell-receptor+, CD20+, CD5+, surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics.
Clustered (CD23, 25, 39, 40, 27, 1c, w75) and unclustered (NuB1, 7F7, KiB3) monoclonal antibodies (MoAb) were tested.
Almost all cases showed high reactivity to CD23, 27, w75, 39, 40, and NuB1: expression of CD1c was very low and that of 7F7, KiB3, and CD25 was variable.
The reactivity of 7F7 and KiB3 was strictly correlated, and they correlated individually with CD25.
Results show that the most frequent B-CLL phenotype (CD19+, 5+, 23+, 27+, 39+, NuB1+, KiB3 +/-, 7F7 +/-, and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone.
No correlation was found between MoAb expression, surface immunoglobulin (SIg) class or type, clinical stage, disease activity, or age at diagnosis.
The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients).
This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease.
| 3Neoplasms
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Prognostic implication of ecto-5'-nucleotidase activity in acute lymphoblastic leukemia.
Ecto-5'-nucleotidase (5'-N) activity was determined in 191 patients (71 children and 120 adults) with acute leukemia.
Elevated values for 5'-N were registered in common acute lymphoblastic leukemia (ALL), but blast cells of T-cell ALL (T-ALL) and common ALL antigen-negative non-T-ALL had low enzyme activity comparable with the values of acute non-lymphocytic leukemia.
Dependence of remission duration on 5'-N activity was analyzed in 74 adults with ALL, treated similarly in a prospective multicenter trial.
The remission curves for ALL patients with 5'-N activity lower than 10 nmol/h x 10(6) cells were substantially and significantly better than those of patients with high activity (greater than 10 nmol/h x 10(6) cells).
This difference was also evident in the immunologic subclass common ALL.
Statistical evaluation showed that an interaction between immunologic subtype of the blast cells and their 5'-N activity had prognostic significance for remission duration.
In addition to the independent factor, initial age, this interaction was also prognostic for survival.
| 3Neoplasms
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Lewis system alterations in gastric carcinogenesis.
Alterations in the expression of type 1 blood group-related antigens (Lewis a and b) were examined immunohistochemically in 371 consecutives gastric biopsy and 80 surgical specimens from patients of gastric carcinoma.
The ABH and Lewis phenotype and secretor status of the patients were correlated with histologic findings.
An anomalous expression of Lewis a antigen was found in 88 of 249 gastric biopsy specimens of Lewis (a-b+) phenotype patients.
The prevalence of this anomaly increased with the evolution of the premalignant process, in agreement with the commonly accepted model of gastric carcinogenesis.
Thus, anomalous Lewis a antigen appeared in 66.6% of gastric dysplasia cases, in 64.6% of intestinal metaplasia, in 15.4% of atrophic gastritis, and in 7.4% of superficial gastritis.
No alterations were found in subjects with normal gastric mucosa.
Forty-seven of the 49 Lewis (a-b+) phenotype gastric carcinoma patients showed antigenic alterations in tumor cells (anomalous Lewis a antigen in 36 and loss of Lewis antigens in 11).
In 26 of these gastric specimens an anomalous Lewis a antigen was present in areas of intestinal metaplasia and/or dysplasia away from the area of neoplastic transformation.
The expression of Lewis a antigen in Lewis (a-b+) phenotype patients is a frequent phenomenon in gastric neoplastic cells and could result from the blocked synthesis of Lewis b antigen with accumulation of its precursors.
These findings suggest that, during gastric carcinogenesis, antigenic alterations may precede neoplastic transformation.
An anomalous Lewis a antigen could constitute a significant index of severity of the histologic lesion and contribute to identifying high-risk individuals.
| 3Neoplasms
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Comparison of DNA content in gastric cancer cells between primary lesions and lymph node metastases.
Cytophotomtric DNA contents of tumor cells in primary lesions and the corresponding metastatic lymph nodes were compared in 61 cases of gastric cancer to determine whether the DNA content remains stable during lymph node metastasis.
The DNA distribution patterns were grouped into three types, according to the proportion of aneuploid cell population.
Changes in DNA patterns between primary and metastatic lesions were evident in 36 of 61 patients (59.0%); in the remaining 25 (41.0%), the same DNA distribution patterns were noted for both lesions.
In 33 of these 36, DNA pattern in the primary carcinoma was transformed into a more narrowly scattered one in the metastatic lesion of the lymph node.
Mean and modal values and the frequency of cells over tetraploid (4c) or hexaploid (6c) were significantly higher in the primary lesion compared with findings in the metastatic lesions.
This reduction in DNA content in the metastatic lesions was a more frequent occurrence in differentiated (18 of 23) than in undifferentiated adenocarcinoma (15 of 35) (P less than 0.01).
Therefore, in primary lesions with a widely scattered DNA ploidy, the tumor cells with a smaller DNA ploidy frequently metastasized to lymph nodes, particularly in cases of a differentiated carcinoma.
Such observations may be pertinent in future designing of treatment protocols.
| 3Neoplasms
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Mucinous adenocarcinoma of the submandibular gland.
A rare tumor not easily classifiable among published histologic categories for salivary gland tumors is reported.
The neoplasm developed within the submandibular gland of a 78-year-old woman with invasion of the mandible and metastasis to regional lymph nodes.
Histopathologically, cuboidal cells possessing clear cytoplasm and displaced round nuclei proliferated and exhibited an adenomatous pattern.
Many cystic spaces surrounded by tumor cell strands were seen, mucus substance filled in the cystic spaces, and the tumor cells seemed mucus-secreting, but neither epidermoid cells nor papillary appearance could be observed.
Electromicroscopically, numerous mucous droplets of low electron density were prominent in the cytoplasm, and the tumor cells had sparse irregular microvilli on the luminal surface.
Mucin histochemistry, including paradoxical concanavalin A staining, revealed that the tumor cells contained neutral and acid mucins, and these were identified as class II and III mucosubstances.
No other neoplastic lesion, except recurrent metastatic neck nodes, has been detected 6 years after the first examination, and it seems that the tumor is a rare primary mucinous adenocarcinoma of the submandibular gland.
| 3Neoplasms
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The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients.
Characterization of breast cancer cells by histology, flow cytometry, and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy, plus tamoxifen for patients with positive hormone receptors.
Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin-embedded blocks obtained from the primary tumor.
Quality control studies on reproducibility, tissue heterogeneity, and analysis procedures have been included.
Of the 197 patients studied, aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%.
Our results demonstrated that number of positive nodes, receptor status, and grade were of prognostic value.
Cell cycle kinetic data were not of independent prognostic value in this series.
However, ploidy could differentiate in prognosis in the receptor-negative subgroup.
Patients with receptor-negative tumors had a significantly better overall survival if the tumor was diploid in nature.
Cell kinetics was not significantly prognostic for either receptor subgroup, although patients with higher %S tended to have better relapse-free and overall survival.
This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome.
| 3Neoplasms
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Comparison of the conventional method of lymph node staging with a comprehensive fat-clearing method for gastric adenocarcinoma.
Discrepant results in long-term survival between United States and Japanese patients with resectable gastric adenocarcinoma may result from more accurate staging in the Japanese series.
The authors compared a comprehensive fat-clearing method with the conventional pathology method of lymph node sampling in 11 patients undergoing curative gastrectomy and extended lymphadenectomy at their institution.
Comprehensive fat-clearing doubled total lymph node counts (P less than 0.01), identified smaller lymph nodes (P less than 0.001), and identified more histologically involved nodes of significantly smaller size (P less than 0.001).
Comprehensive fat-clearing pathologically upstaged 29% of the authors' eligible specimens.
Accurate pathologic staging is necessary when comparing Japanese and United States survival data for resectable gastric adenocarcinomas.
| 3Neoplasms
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Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas.
Neuron-specific enolase (NSE) is the isoform of enolase, a glycolytic enzyme found in the neuroendocrine system.
Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems.
Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma.
The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma.
The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13).
Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l, n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l, n = 24).
However, there was no difference in the percentage of patients with elevated NPY levels.
These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors.
| 3Neoplasms
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A newly established human osteosarcoma cell line with osteoblastic properties.
A human osteosarcoma cell line, HuO9, was established from a tumor that was heterotransplanted into athymic nude mice.
Antiserum against nude mouse spleen cells was added to the early passage cultures to eliminate the host fibroblastic cells.
The cell line retained a high activity of liver/bone/kidney-type alkaline phosphatase (ALP) and secreted osteocalcin, i.e., bone gamma-carboxyglutamic acid-containing protein (BGP), into the medium.
The addition of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the ALP activity as well as the level of BGP secreted into the medium.
The ALP of 1,25(OH)2D3-treated cells has the same inhibition characteristics to heat and amino acids as that of untreated cells.
Synthetic human parathyroid hormone stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) approximately 100-fold within five minutes.
However, the stimulation was not observed with a synthetic human thyrocalcitonin.
When HuO9 cells were transplanted into the back of a nude mouse, a tumor with an abundant osteoid formation and mineralization was produced.
The results indicate that the HuO9 cell line expresses well-differentiated osteoblastic phenotypes.
HuO9 is the first established human cell line to produce BGP, and it provides a useful model for the studies of osteoblasts and the regulatory mechanisms of BGP production.
| 3Neoplasms
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Oncocytic glomus tumor of the trachea.
An oncocytic variant of glomus tumor of the trachea occurred in a 47-year-old woman.
She experienced intermittent cough and hemoptysis for about three years.
Bronchoscopy and chest CT scan showed a small reddish polypoid tumor on the lower end of the trachea.
Bronchoscopic biopsy was carefully done and was diagnosed as oncocytoma.
A wedge resection of the tumor was done.
Tumor cells were characterized by strongly eosinophilic granular cytoplasm on light microscopy and by numerous closely packed round or ovoid mitochondria with prominent tubular cristae on electron microscopy.
They were arranged in a sheet around small vessels, as a result of which the biopsy diagnosis of oncocytoma was changed to oncocytic glomus tumor.
To our knowledge, this is the first report of an oncocytic glomus tumor arising from the trachea.
| 3Neoplasms
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Multicentric endobronchial granular cell myoblastoma.
Granular cell myoblastoma (GCM) is a rare benign neoplasm involving the tracheobronchial tree.
It is believed to arise from the Schwann cell.
Four cases of tracheobronchial GCM, all of which were multicentric, are presented and a conservative therapeutic approach is suggested.
| 3Neoplasms
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Endosonography of pararectal lymph nodes. In vitro and in vivo evaluation.
One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound.
With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes.
Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation.
Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent.
The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude).
The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz x cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz x cm)].
The results demonstrate that involved nodes can principally be differentiated from not involved nodes.
Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent.
| 3Neoplasms
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Characterization and significance of sulfonylurea receptors.
This study describes and characterizes a putative sulfonylurea receptor.
The radioligand used was [3H]glipizide (9 Ci/mmol).
The beta-cell plasma membranes were derived from a transplantable rat insulinoma generated by subcutaneous injection of RINm5F cells and purified by ultracentrifugation on a 15-55% sucrose gradient.
Specific binding of [3H]glipizide to purified beta-cell plasma membranes was determined to be maximal at temperatures of 4-23 degrees C, pH 7.3, and an incubation of 2 h.
Scatchard analysis indicated a single binding site with Kd = 7 nM and sulfonylurea binding of 0.93 pmol/mg membrane protein.
Displacement of [3H]glipizide from the purified beta-cell plasma membranes by various sulfonylureas and their analogues correlated well with their known hypoglycemic and insulin-releasing activities.
Various agents, including nutrients, agents affecting Ca2+ flux, gastrointestinal hormones, and pancreatic hormones, had no effect on [3H]glipizide binding to the beta-cell plasma membranes.
Putative sulfonylurea receptors on beta-cell and brain cell plasma membranes have been reported by several groups of investigators.
Sulfonylurea binding to the beta-cell is hypothesized to close an ATP-sensitive K+ channel, which leads to depolarization of the membrane and activation of a voltage-dependent Ca2+ channel.
| 3Neoplasms
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The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome.
Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle.
This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively.
Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours.
These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins.
| 3Neoplasms
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Aromatase activity of human granulosa cells in patients with polycystic ovaries treated with dexamethasone.
The effect of dexamethasone (DEX) (9 alpha-Fluro-16 alpha-methyl prednisolone) on secretion of steroids by human granulosa luteinized cells was studied by culturing cells from mature follicles of women with polycystic ovarian disease and treated for infertility in the in vitro fertilization program.
Patients were treated with DEX 0.5 mg/d until the day of human chorionic gonadotropin administration.
The cells were cultured for 24 hours in the presence of androstenedione (10(-7)M).
After incubating for 24 hours, the medium was replaced and the cells were incubated for an additional 24 hours.
The medium was then harvested and assayed for estradiol (E2) and progesterone (P).
Results were compared with those of a control group who was not treated with DEX.
Estradiol production by cells was significantly lower in the study group treated with DEX.
Progesterone production was not influenced by DEX.
Follicular fluid levels, E2, and androgens did not vary with DEX treatment, whereas cortisol levels markedly decreased and P levels increased with the treatment.
These findings suggest that glucocorticosteroids can directly influence granulosa luteinized cell function.
| 3Neoplasms
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Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience with 42 cases.
Before surgery, 12 patients with suspected leiomyoma and 12 patients with suspected leiomyosarcoma were studied by endoscopic ultrasonography (EUS), computed tomography (CT), endoscopy, and barium swallow.
The results were correlated with surgery and histology.
Ten leiomyomas, one benign gastric ulcer, one carcinoid metastasis, eight leiomyosarcomas, two leiomyoblastomas, one mucus secreting adenocarcinoma, and one bronchial carcinoma were diagnosed.
Eighteen additional patients suspected to have benign submucosal lesions by endoscopy and barium meal were treated non-surgically, and studied by EUS and CT.
EUS was superior to other imaging techniques in the detection, staging, and follow-up of submucosal smooth muscle tumors because of clear imaging of the intramural abnormality and adjacent lymph nodes.
| 3Neoplasms
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Growth of group A rotaviruses in a human liver cell line.
Recent observations in children with rotavirus gastroenteritis and in infant mice given rotavirus vaccine by oral administration suggest that this well-known gastrointestinal pathogen may infect the liver.
To examine this possibility, the susceptibility of Hep G2 cells to infection with a variety of rotavirus strains was tested.
These cells were used because they are considered to be well differentiated and exhibit many liver-specific functions.
The Hep G2 cells supported the growth of the simian strain rhesus rotavirus (MMU 18006), a strain currently being used in vaccine trails, but did not support the growth of any human strain (D, DS1, Price or ST3).
The rhesus rotavirus infection was cytopathic and resulted in release of lactate dehydrogenase.
Rhesus rotavirus growth in Hep G2 cells displayed trypsin-enhanced infectivity and was inhibited by pretreatment of cells with Arthrobacter ureafaciens neuraminidase but not with neuraminidase from Clostridium perfringens.
Hep G2 cells were also permissive for another simian strain (SA11), a bovine strain (UK) and single gene substitution reassortants containing VP7 (the major outer capsid neutralization protein) from a human rotavirus strain and the remaining 10 genes from either rhesus rotavirus or UK.
In general, UK and its reassortants produced lower levels of antigen than did rhesus rotavirus and its reassortants.
Hep G2 cells and other hepatic cell lines may prove to be useful tools to explore the hepatotropic potential of wild-type rotaviruses and candidate vaccine strains.
| 3Neoplasms
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HBV-DNA sequences in tumor and nontumor tissue in a patient with the fibrolamellar variant of hepatocellular carcinoma.
One patient with the fibrolamellar variant of hepatocellular carcinoma was found to be seropositive for HBsAg and anti-HBe.
DNA from tumor and nontumor areas of the liver was examined by molecular hybridization for hepatitis B virus DNA sequences.
Undigested DNA from the tumor gave a high-molecular-weight smear, and restriction-enzyme analysis indicated a single instance of integration.
Nontumor liver tissue was analyzed from three separate areas.
Hepatitis B virus DNA was detected in two of these; restriction-enzyme digestion suggested they contained different sites of viral integration.
As with the typical hepatitis B virus-related hepatocellular carcinoma, analysis of hepatitis B virus DNA from nontumorous liver yielded a different pattern of high-molecular-weight bands, indicating that the virus genome had integrated at different chromosomal locations than that seen in the tumor.
The finding of integrated hepatitis B virus DNA, especially in tumorous but also in nontumorous liver, would be consistent with an oncogenic role for hepatitis B virus in certain instances of fibrolamellar tumors and in the more typical hepatitis B virus-related hepatocellular carcinoma.
| 3Neoplasms
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Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients.
To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival.
All patients were diagnosed between 1983 and 1987.
A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss greater than 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), gamma-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival.
According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age x 0.03 + Ascites x 0.8281 + BUN x 0.0137 + Serum sodium x (-0.0538) + gamma-Glutamyltranspeptidase x 0.0019 + Bilirubin x 0.0734 + Tumor size x 0.33 + Toxic syndrome x 0.4965 + Metastases x 0.55).
These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials.
| 3Neoplasms
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Left ventricular fibroma: echocardiographic diagnosis and successful surgical excision in three cases.
The management of three patients with left ventricular fibromas is outlined.
All were asymptomatic children.
Routine chest radiography suggested cardiac masses.
M-mode and two-dimensional echocardiography were valuable adjuncts to conventional angiography in assessing these children.
Electrocardiographic changes, present in all cases, were shown to regress postoperatively.
We stress the importance of these noninvasive aids in the initial investigation and outline our operative methods of reconstruction.
| 3Neoplasms
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Upper gastrointestinal pathology in familial adenomatous polyposis: results from a prospective study of 102 patients.
Multiple gastric and duodenal biopsy specimens from 102 asymptomatic patients with familial adenomatous polyposis, taken during a prospective endoscopic screening programme were examined.
One hundred patients had microscopic gastroduodenal pathology, often in the absence of macroscopic lesions.
Adenomas were found in 94 patients in the duodenum, in the second and third parts.
Hyperplasia of villous and crypt epithelium was also seen, sometimes in the absence of adenomas: this may be a precursor of neoplastic change.
In the stomach fundic gland polyps were the commonest abnormality, seen microscopically in 44 patients.
Chronic antral gastritis was common in patients without fundic polyps.
Gastric adenomas were present in six patients, all of whom also had duodenal adenomas.
If duodenal adenomas in familial adenomatous polyposis have a similar malignant potential to those in the colorectum sequential endoscopy and biopsy are necessary to detect cancer in these patients.
| 3Neoplasms
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Activation and inducer subset phenotype of the lymphocytic infiltrate around epidermally derived tumors.
An in situ analysis of the mononuclear cell infiltrate found in association with a range of benign, premalignant, and malignant epidermal tumors is described.
The predominant cell phenotype was that of the recently described immunoregulatory helper/inducer T lymphocyte.
A large number of lymphocytes expressed antigens associated with cellular activation, suggesting an ongoing immunologic response by the host against the tumor, although evidence of in situ proliferation of these cells was lacking.
These findings suggest that the infiltrate found in association with cutaneous tumors does not represent passive accumulation of lymphocytes from the circulation but rather an active antitumor response.
| 3Neoplasms
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Benign lymphangioendothelioma.
We have studied eight cases of an acquired lymphatic endothelial lesion for which we propose the name "benign lymphangioendothelioma." The lesions developed as solitary, slowly extending, erythematous macules and plaques, usually occurring on the extremities or the shoulders in adolescents or adults.
The characteristic histopathologic feature is permeation of the dermal collagen by flattened, endothelium-lined channels and spaces.
Hemorrhage, iron deposition, and inflammation were not part of the lesion.
Ulex europaeus agglutinin I labeled the lesional endothelial cells consistently, but factor VIII-related antigen labeling was negative.
This histologic pattern and the special studies suggested a lymphatic lesion.
Surgical excision, performed in six patients, was not followed by recurrence.
| 3Neoplasms
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