Oropharyngeal swallowing in normal adults of different ages. In an effort to evaluate the effect of normal aging on oropharyngeal events of swallowing, 80 normal volunteers, stratified by gender into four age groups, were studied. Liquid and semisolid swallows were performed and recorded simultaneously using videofluoroscopy and manometry. Several parameters, including total duration of oropharyngeal swallowing, were significantly longer in the oldest age group than in any other age group. A delay in initiation of maximal hyolaryngeal excursion primarily accounted for the longer durations with increased age. Significant durational changes also were found as a function of bolus consistency and presence or absence of the manometry tube. Females had a longer duration of upper esophageal sphincter (UES) opening. The amplitude of pharyngeal pressures, duration of peak pharyngeal pressures, and rate of propagation of the contractions were not significantly different for age, gender, or consistency of bolus. No significant differences were found between age groups or between genders in UES pressure. Normal aging affects some parameters of swallowing, while others are preserved.


Selection of the chimpanzee over the baboon as a model for Helicobacter pylori infection. Baboons (Papio sp.) and chimpanzees (Pan troglodytes) were screened for the presence of Helicobacter pylori. The gastric mucosae of the baboons were colonized by large spiral bacteria. However, a group of adult chimpanzees were identified that were free of spiral gastric bacteria, with five animals being recruited into an H. pylori challenge study. These animals were inoculated orogastrically with one of four strains of H. pylori and followed for up to 26 weeks. H. pylori was established in one of these animals during a primary challenge and in two other animals on secondary challenge. It was shown that the chimpanzee can be infected with H. pylori and that the inflammatory response in these animals mimics that seen in humans. Infection was marked by an antibody response to H. pylori-specific antigens in two animals. It was observed that H. pylori antibody-negative chimpanzees had no apparent infection by H. pylori or related bacteria. Thus serological screening of chimpanzees can be used to identify candidate animals for further evaluation.


Gastric acidity and gastroesophageal reflux patterns in patients with esophagitis. Esophageal pH-metry is the test of choice for diagnosing gastroesophageal reflux. However, although it allows acid refluxes to be distinguished, it is of limited value for identifying alkaline or mixed (acid mixed with alkaline material) refluxes. To evaluate the ability of dual pH-metry to identify alkaline or mixed refluxes, the gastric acidity and gastroesophageal reflux pattern were evaluated simultaneously in 64 patients with mild-moderate esophagitis, in 28 patients with severe or complicated esophagitis, and in 20 healthy subjects. A dual esophageal gastric pH-probe allowed three different types of esophageal reflux to be distinguished: (a) acid refluxes, defined as a drop in esophageal pH to values less than 4 together with a gastric pH less than 4; (b) mixed refluxes, defined as a drop in esophageal pH from baseline to values greater than 4 associated with rises in gastric pH to greater than 4 values; (c) alkaline refluxes, defined as a rise in esophageal pH to greater than 7 associated with a simultaneous increase in gastric pH to greater than 4. Gastric acidity was more significantly reduced in patients with severe or complicated esophagitis than it was in healthy subjects (P less than 0.01). The reflux pattern in both mild-moderate and severe esophagitis was characterized by mainly acid refluxes and a marked increase in the time the esophagus mucosa was exposed to acid (P less than 0.001). Pure alkaline refluxes were rare (less than 1%) in both healthy subjects and esophagitis patients. The number of mixed refluxes was considerably higher in severe esophagitis patients than it was in either mild-moderate esophagitis patients or controls (P less than 0.05). The finding of mixed refluxes in severe or complicated esophagitis suggests that biliary acids and/or pancreatic enzymes are involved in the pathogenesis of severe forms of esophagitis.


Objective evidence of aspirin use in both ulcer and nonulcer upper and lower gastrointestinal bleeding. To obtain the best evidence for nonsteroidal anti-inflammatory drug (NSAID) use in gastrointestinal (GI) bleeding, a detailed patient history was supplemented with objective tests of aspirin use, i.e., high-performance liquid chromatography of plasma and platelet cyclo-oxygenase inhibition, which detect aspirin intake within 24 and 120 hours, respectively. Seventy-one patients consecutively admitted for upper or lower GI bleeding and 138 age- and sex-matched controls were studied. Five bleeders were excluded for confounding factors, e.g., warfarin. Of the other 66 bleeders, 45 had upper GI bleeding (28 from peptic ulcer, 14 from duodenal ulcer, and 14 from gastric ulcer) and 21 lower GI bleeding. Evidence of current NSAID use (of which 89% was aspirin) was found in 80% of bleeders vs. 24.3% of controls (P less than 0.0001), for an odds ratio of 13.7 (95% confidence interval, 6.39-27.27). The cyclo-oxygenase test uncovered 21.5% more aspirin users than history alone. Severity of bleeding was not different in acetylsalicylic acid users. The surprisingly high association of current intake of NSAIDs, especially aspirin, with nonulcer GI bleeding including colonic bleeding, changes the conventional view of the following hierarchy of the risk: NSAID----peptic ulcer----bleeding to: NSAIDs----GI bleeding. This view has important implications for current ulcer cotherapy prophylactic strategies, which could fail to prevent greater than 50% of GI bleeding episodes.


The muscarinic receptor gene expressed in rabbit parietal cells is the m3 subtype. To investigate the nature of the muscarinic receptors present on parietal cell membranes, binding studies and polymerase chain reaction (PCR) amplification of parietal cell messenger (m) RNA were undertaken. Displacement of N-[3H]methylscopolamine by various muscarinic antagonists showed displacement with a single affinity. The apparent dissociation constant values were as follows: atropine (nonselective), 1.95 +/- 0.28 nmol/L; pirenzepine (M1), 169 +/- 24 nmol/L; AF-DX 116 (M2), 1542 +/- 33 nmol/L; and hexahydrosiladifenidol (M3), 29 +/- 3.4 nmol/L. These data confirmed the existence of only an M3 receptor linked to acid secretion as defined pharmacologically. PCR amplification of parietal cell mRNA with primers designed for detection of all known muscarinic receptor subtypes showed that only m3 fragments were produced from parietal cell mRNA, whereas m1 and m2 products could be detected in brain or cardiac mRNA. The m3 nature of the PCR product was confirmed by Southern blotting with 32P-labeled human m3 complementary DNA. Hence the two carbachol affinities and the separable cellular responses following muscarinic activation are caused by separate coupling pathways of the M3 receptor.


A wave of inhibition precedes primary peristaltic contractions in the human esophagus. Animal studies have shown that primary esophageal peristalsis is preceded by a wave of inhibition spreading rapidly down the esophagus and lasting longer in more distal segments. In humans, its presence in the esophageal body cannot be demonstrated manometrically because of the absence of tone. To study deglutitive inhibition in humans, an artificial high-pressure zone was created by inflating an intraesophageal balloon to a critical level. The pressure changes at the interface between the balloon and the esophageal wall at various levels along the esophagus were measured. In this artificial high-pressure zone, deglutition induced a relaxation beginning simultaneously at various levels of the esophagus but lasting progressively longer in progressively more distal segments. Latency from onset of deglutition to onset of relaxation at 13 cm and 8 cm above the lower esophageal sphincter and at the lower esophageal sphincter was 0.06 +/- 0.19 seconds, 0.10 +/- 0.31 seconds, and 0.89 +/- 0.53 seconds, respectively; latency to contraction was 4.45 +/- 0.54 seconds, 6.04 +/- 0.79 seconds, and 9.14 +/- 1.04 seconds, respectively. This is the first direct evidence that deglutition produces in the human esophagus a wave of inhibition that precedes the primary peristaltic contraction.


p53 gene mutations in gastric and esophageal cancers. The presence of point mutation of the p53 gene in exons 5, 6, 7, and 8 was examined in 10 cases of gastric adenocarcinoma and 5 cases of esophageal squamous cell carcinoma by polymerase chain reaction and direct nucleotide sequencing. Mutations of the p53 gene were found in 5 cases of gastric cancer and 4 cases of esophageal cancer. The mutations in the stomach cancers consisted of four missence mutations (exons 5 and 8) and one frame shift (exon 7). In the esophageal cancers, three missence mutations (exons 6, 7, and 8) and one point mutation within the splice donor site of intron 5 were found. Of the seven missence mutations in the two cancers, five showed the transition from G to A and two from G to T. All these changes occurred in the highly conserved region of the p53 protein. These results suggest that mutations of the p53 gene are genetic events in the pathogenesis of gastric adenocarcinoma and esophageal squamous cell carcinoma.


Hyperplasia of histamine-depleted enterochromaffinlike cells in rat stomach using omeprazole and alpha-fluoromethylhistidine. In the rat, gastric histamine is stored mainly in the enterochromaffinlike cells. Gastrin releases histamine from these cells, and long-term hypergastrinemia results in hyperplasia. The effect of sustained hypergastrinemia on histamine-depleted enterochromaffinlike cells was studied by measuring histidine decarboxylase activity and histamine concentrations and by using quantitative histology. Hypergastrinemia maintained for 6 weeks was induced by inhibition of gastric acid secretion with omeprazole (400 mumol.kg-1.day-1) given orally, and histamine synthesis was inhibited for the same length of time with alpha-fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps. In rats given omeprazole alone, the effects of the resulting hypergastrinemia on the enterochromaffinlike cells was reflected in increased histidine decarboxylase activity, increased histamine concentration, and increased number of enterochromaffinlike cells. The general trophic effects on the stomach were seen as increased stomach and oxyntic mucosal weight and increased mucosal thickness. Treatment with alpha-fluoromethylhistidine plus omeprazole markedly reduced the histidine decarboxylase activity and histamine concentration, but the weight of the stomach and oxyntic mucosa, the enterochromaffinlike cell density, and intensity of histidine decarboxylase immunostaining were increased to at least the same extent as after omeprazole alone. These observations indicate that enterochromaffinlike cell histamine is not important for a full expression of gastrin-evoked trophic effects in the stomach.


Acute-phase induction of manganese superoxide dismutase in intestinal epithelial cell lines. Cellular protection from immune-generated oxygen free radicals is initiated by the reduction of oxygen radicals by manganese superoxide dismutase (MnSOD) and copper/zinc superoxide dismutase (Cu/ZnSOD). Using rat adult (IEC-6) and fetal (IRD-98) intestinal epithelial cell lines, factors involved in the regulation of the SODs at the messenger RNA (mRNA) level were examined. Exposure of IEC-6 and IRD-98 to Escherichia coli lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-alpha) results in a marked increase in MnSOD mRNA as early as at 1 hour. Cotreatment of cells exposed to LPS or TNF-alpha with actinomycin D or cycloheximide showed that de novo transcription but not protein synthesis is required for the LPS- and TNF-alpha-dependent induction in MnSOD mRNA. Treatment with interleukin 1 beta results in a 12-fold increase in MnSOD mRNA, but no change was observed with interleukin 6 or interferon alpha. No change was observed in the level of Cu/ZnSOD mRNA under any condition tested. The results indicate that MnSOD functions as a cytokine-regulated acute phase protein involved in cellular protection from free radical-mediated damage.


Effect of intravenous and oral omeprazole on 24-hour intragastric acidity in duodenal ulcer patients. Nine patients with duodenal ulcer were on separate occasions given omeprazole, 20 mg orally, 10 mg intravenously (IV), and 40 mg IV once daily for 5 days. On day 1, the median reduction of 24-hour intragastric acidity was 42.2% for the 20-mg oral dose and 54.8% and 88.4% for the two IV doses, respectively, but the between-patient variability was considerable for all three doses. On day 5, the degree of reduction had increased for all three doses to a median value of 99.9% for the 20-mg oral dose and 95.7% and 99.9% for the two IV doses, respectively. Plasma omeprazole concentrations increased significantly from day 1 to day 5 only for the 20-mg oral and 40-mg IV doses. Thus, the increased pharmacological effect of omeprazole during repeated once daily administration can only partly be explained by increased plasma concentrations, suggesting that some additional factor(s) must influence the degree of reduction of 24-hour intragastric acidity. Thus, when determining the optimal dose of omeprazole for acid inhibition, the route and duration of administration must be taken into consideration; after 5 days of once-daily administration of doses as low as 10 mg IV and 20 mg orally are effective and dependable in reducing 24-hour intragastric acidity in patients with duodenal ulcer. However, a daily dose of 40 mg IV omeprazole is not sufficient to keep intragastric pH above 4 in all patients during the first day of treatment.


Rectal mucosal pathology varies with human immunodeficiency virus antigen content and disease stage. Rectal mucosal biopsy specimens from 75 human immunodeficiency virus (HIV)-seropositive and 16 HIV-seronegative subjects were examined. The histopathologic changes were correlated with immunoperoxidase staining for UCHL-1 and HIV core protein p24, quantitative p24 enzyme-linked immunosorbent assay (ELISA) assay in homogenized rectal tissue and serum, and a modified Walter Reed clinical stage. Four phases were seen in the HIV-infected subjects: (1) early phase, in Walter Reed stage 1-2 subjects, with nearly normal histology and low p24; (2) inflammatory phase, typically in Walter Reed stage 3-4 subjects, with a superficial lamina propria infiltrate of lymphocytes, plasma cells, and eosinophils with degranulation, abundant UCHL-1 staining, and maximal p24 by both immunoperoxidase staining and ELISA; (3) transitional phase, in many Walter Reed 5 and some Walter Reed 6 subjects, with normal lymphocyte population density but with subtle inflammatory changes; and (4) lymphoid depletion phase, mainly in Walter Reed stage 6 subjects, with decreased lymphocytes but often with endothelial cell activation and apoptosis. These phases presumably result from effective HIV suppression by a relatively intact immune system, followed by maximal HIV infection and lymphocyte activation, then progressive lymphocyte depletion. The inflammation correlated with the presence and amount of HIV in rectal tissue determined by immunohistochemistry and ELISA and was maximal before overt immunodeficiency developed. Intestinal mucosa could be a preferred site of HIV proliferation and T-cell destruction.


Identification of an abnormal esophageal clearance response to intraluminal distention in patients with esophagitis. Esophageal clearance responses were studied by a new technique comprising a miniature electronic strain gauge attached to an inflatable balloon in 30 normal volunteers and 48 patients with gastroesophageal reflux disease. The pressure changes around the balloon and traction forces acting on the balloon were measured during graded balloon distention (0-12 mL of air for 30 seconds each inflation) in the lower and midesophagus. All normal volunteers responded to distention with development of swallow independent contractions above the balloon [65 mm Hg/30 s (range, 45-100 mm Hg/30 s)] together with generation of an aboral traction force [15 g (range, 9-20 g)]. Patients with reflux esophagitis showed a higher distention threshold for initiation of these responses, induced fewer proximal contractions [24 mm Hg/30 s (range, 0-38 mm Hg/30 s); P less than 0.01 vs. normal], and generated weaker traction forces [4 g (range, 0-6 g) at 10 mL P less than 0.01 vs. normal]. Patients with the most severe esophagitis showed greatest impairment of the clearance response (correlation = 0.7, P less than 0.01) and the greatest esophageal residence of refluxed acid (correlation = 0.5, P less than 0.01). These abnormalities appear to be of relevance to the pathophysiology of esophageal reflux disease although it remains to be determined whether they are the cause, or the result, of the esophagitis.


Survival and causes of death in patients with inflammatory bowel disease: a population-based study. Relative survival up to December 31, 1986 was analyzed for all patients diagnosed with ulcerative colitis (UC) (n = 2,509) and Crohn's disease (CD) (n = 1,469) within the Uppsala Region, Sweden 1965-1983. After 10 years survival was 96% of that expected for UC and CD. Patients with ulcerative proctitis, left-sided colitis, and pancolitis at diagnosis had relative survival rates of 98%, 96%, and 93% respectively. Survival did not differ by extent at diagnosis for patients with CD. After including prevalent cases, 684 deaths occurred compared with 481.1 expected deaths [standardized mortality ratio (SMR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Inflammatory bowel disease was the main reason for this excess mortality. Colorectal cancer increased mortality (50 deaths observed vs. 15.2 expected). Death from other cancers were not greater than expected. Obstructive respiratory diseases, especially bronchitis, emphysema, and asthma increased mortality SMR = 1.5 (95% CI = 1.1-2.2) in UC. Cerebrovascular disease mortality occurred less often than expected (SMR = 0.7; 95% CI = 0.5-1.0). Mortality for other diseases and groups of diseases was close to that expected.


Inhibition of pancreatic adenocarcinoma cell growth by lovastatin. RAS protein (p21 ras) requires farnesyl (an intermediate of cholesterol synthesis) for activation. Activating mutations of K-ras gene have been detected in most human pancreatic adenocarcinomas. In the present study, the effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, the rate-limiting enzyme of cholesterol synthesis, on the growth of five pancreatic cancer cell lines (human-CAV, MIA Paca2, CAPAN2 and PANC1, and hamster-H2T) in vitro and of two cell lines (CAV and H2T) in vivo was examined. Inhibition of cell growth was observed with lovastatin doses at or above 2.5 micrograms/mL for H2T, CAV, MIA Paca2, and CAPAN2 or 10 micrograms/mL in PANC1. The H2T cell line was studied further to determine the reversibility of growth inhibition. Mevalonic acid (1 mmol/L) reversed lovastatin-induced inhibition of cell growth if it was added with lovastatin (2.5 micrograms/mL). Similarly, removal of lovastatin from the medium within 24 hours after treatment allowed recovery of cell growth. The effect of lovastatin on cell growth was irreversible after 48 hours of exposure. The survival fraction of H2T cells was markedly decreased by 1- or 24-hour exposure to 75 micrograms/mL but not to doses ranging from 0.5 to 60 micrograms/mL of lovastatin. Growth of pancreatic carcinoma xenografts (CAV and H2T) in nude mice was inhibited by a subcutaneous infusion of lovastatin (50 micrograms/h). These results indicate that mevalonic acid or a metabolite in the cholesterol synthesis pathway is necessary for growth of pancreatic cancer cells and suggest that lovastatin should be further examined as a potential therapeutic agent for pancreatic cancer.


Adrenergic modulation of interdigestive pancreatic secretion in humans. Whether the adrenergic pathways participate in the control of interdigestive pancreatic function in humans is uncertain. To determine if changes in alpha- or beta-adrenergic tone modulate interdigestive pancreatic enzyme output, 16 healthy subjects were intubated with an orojejunal tube to collect and quantify pancreatic trypsin secretion and record motility. After observation of a complete interdigestive cycle (control period), eight groups of two subjects each received 2-hour intravenous infusions of the alpha- and beta-agonist epinephrine (50 ng.kg-1.min-1), the alpha-antagonist phentolamine (5 mg/2 min followed by 500 micrograms/min), the beta-antagonist propranolol (5 mg/2 min followed by 80 micrograms/min), or saline as control, alone or in combination. Drugs were assigned in a random mode according to a 2(3) factorial design. Analysis of variance showed that epinephrine decreased trypsin output by 43% (P less than 0.05). By contrast, trypsin output was increased fourfold in the presence of phentolamine (P less than 0.01), whereas propranolol had no effect. These data suggest that an inhibitory alpha-adrenergic tone modulates human interdigestive pancreatic enzyme secretion whereas beta inputs are less important.


Early midzonal oxidative stress preceding cell death in hypoperfused rat liver. Intralobular heterogeneity of oxidative stress and its topographic relationship with cell death during low-flow hypoxia were shown in perfused rat liver by digital microfluorography using dichlorofluorescin diacetate, a fluorochrome sensitive to intracellular hydroperoxide formation, and propidium iodide, which labels the nuclei of nonviable cells. The surface of the liver loaded with two precursors was microscopically visualized, and the fluorescence of dichlorofluorescein, a highly fluorescent molecule generated by hydroperoxide-mediated dichlorofluorescin oxidation, was digitally processed. Dichlorofluorescein fluorescence significantly increased in midzonal regions as early as 20 minutes after starting the 25% low-flow hypoxia. At 40 minutes the fluorograph showed multiple dotted patterns, and the intensity peaked at 60 minutes. The onset of cell death studied by propidium iodide was observed at 40 minutes, and its topographic distribution corresponded to the dichlorofluorescein-enhanced midzonal regions. Allopurinol diminished the early midzonal oxidative stress and retarded the onset of cell death. The current findings show that xanthine oxidase-dependent oxidative stress and the resultant cell death during low-flow hypoxia are spatially restricted in the intermediate zone between the periportal and pericentral regions.


[Environmental pollutants and fertility disorders. Heavy metals and minerals]. So far, the influence of lead, cadmium and mercury on human fertility has hardly been considered. First experiences by the authors with the chelating agent 2,3 dimercaptopropane-1-sulfonate (DMPS), which mobilizes heavy metals deposited in the body, seem to favour an association between the body load of heavy metals and complications during the menstrual cycle and during pregnancy. By means of an extensive survey of references, the importance of heavy metals for reproduction is demonstrated. In addition, the deficiency of particular minerals and their interaction with heavy metals are considered. Indications are given for diagnosis and therapy of the exposure to heavy metals. The practical procedure is demonstrated by means of three case studies.


[Ultrasound diagnosis of blood flow in benign and malignant breast tumors]. Malignant tumours can be differentiated from the benign ones by their vascular blood supply. We employed three methods to analyse the blood flow: the angiodynograph, the duplex system, and the continuous-wave Doppler method, and measured the blood flow in 151 patients on the preoperative day. Histology revealed a malignoma in 92 cases and a benign tumour in 59 cases. It was found, that in more than 90% of the malignomas, a high blood flow was identified in or around the tumour by means of the colour method (angiodynography), which could be quantified by the pulsed-wave Doppler. A significantly lower blood flow was evident in the benign tumours with a markedly increased resistance index (by 80%) established by means of the pulsed-wave Doppler. Continuous-wave (CW) Doppler showed a significantly higher blood flow with almost all malignomas in the entire breast, than was the case with benign changes. Our studies showed, that the enhanced blood flow in and around malignant tumours can be visualised by means of update technology, angiodynography being particularly suitable for demonstrating the flow by the B-mode. Quantification, however, is, at present, only possible by employing the duplex method with pulsed-wave Doppler. CW Doppler is suitable only for blood flow diagnosis of the entire organ, but it requires great precision of working method and is time consuming; tumour blood flow cannot be visualised on-target by this method.


[The diagnostic value of rectal ultrasound in the assessment of parametrial infiltration of cervix cancer]. In addition to rectal palpation, rectosonography seems to be a promising method in pretherapeutic examination of the parametrium in patients with cervical carcinoma. To evaluate the usefulness of this examination we determined the sensitivity and specificity of rectal palpation performed by one examinator, rectal palpation performed by changing examiners, and rectal sonography. The results of the clinical examination of 128 parametria (64 women) were compared to histological findings following Wertheim-Meigs operation. Sensitivity and specificity were as follows one examiner 48% and 96%, changing examiners 44% and 94%, rectosonography 55% and 99%. In conclusion, we suggest that rectal sonography is a careful and moderate method that can be an important supplement to rectal palpation in pretherapeutic staging of cervical cancer.


[On the value of "informational evening classes for mothers and fathers" within the scope of prenatal care]. In 1989, the Department of Gynaecology and Obstetrics, University of Cologne, questioned the 288 participants of the "informative evenings for mothers and fathers", a primarily preventive measure offered as a preparation for childbirth. The survey aimed at reviewing these evenings, i.e. to make a critical and exact evaluation of their usefulness and quality as one of the numerous events offered to expectant mothers. The following results were obtained: The women who visited the informative evenings were mostly pregnant for the first time, educated above average, for the most part working women and of German nationality. Their attitude towards preventive measures, i.e. regular check-ups during pregnancy as well as smoking behaviour, the wish to breast-feed and the attendance of other birth preparation courses, is well founded. Consequently, this group of women can be described as a highly selected. Their motivation to come to the evenings resulted mostly from the wish to obtain specific clinical information, to become familiar with the maternity ward, to meet midwives and doctors, in order to lose some of their fears and to increase confidence. Contents and structure of these evenings were mostly able to meet the expectations of the visitors. Unsatisfactory, however, was the low number of foreign woman, those with difficult pregnancies and women of a low social status i.e. patients, who above all, need intensive assistance and attention.


[Differential diagnosis of seizures in the peripartal period]. Seizures remain an important cause of maternal morbidity and mortality during pregnancy and the puerperium. Encouraged by some cases treated in our clinic (9 cases have been observed between 29. 12. 1989 and 22.5. 1991), the management of differential diagnosis in seizures are discussed in this article. Despite all possibilities of using technical apparatus for investigations, case history and clinical examination remain the basics of diagnosis with regard to paroxysm. EEG is an important, noninvasive method for judgement of cerebral function. It can be carried out continuously as a bedside-test and is extremely helpful in the differential diagnosis of eclampsia versus epilepsia. With a view to substantial defects as a possible convulsant factor, visualised examination procedures, e.g. cranial computed tomography (CCT) and magnetic resonance imaging (MRI) are available. Especially MRI has advantages in the diagnostic procedure. It could help to find the cause of cerebral structure defects and to clear the question of aetiology. Thus, a specific therapeutic procedure might become possible.


[Drug dependence, smoking and fetal growth retardation]. Illicit drug abuse, as well as smoking, are known risk factors in the development of intrauterine growth retardation. In an attempt to clarify the influence of these two aetiological factors, a retrospective analysis was carried out. 35 drug- and nicotine-addicted pregnant women were compared to 104 smokers and 101 non-smoking controls with regard to foetal outcome. Relative risk estimates for intrauterine growth retardation of the drug and nicotine group were 3.14 (95% confidence limits 1.88-5.25; p = 0.0001) whereas the smoking group had 1.39 (95% confidence limits 0.96-2.02; p = 0.0482) compared to non-smoking controls. The foetal outcome was best in the latter group: children of drug-addicted mothers had a considerably higher morbidity and mortality rate. This study shows an almost threefold risk for intrauterine growth retardation in drug-addicts who smoke, compared to nicotine abuse alone.


[Fibromatosis of the breast].

[Fibromatosis of the breast]. Fibromatosis of the breast is a rare benign mesenchymal transformation of the connective tissue, the origin of which is probably situated in the fascia of the pectoral muscle and the Cooper's ligaments. In the clinical and radiological examination, it is difficult to differentiate between a mammary carcinoma or other malignant tumours of the breast. Only histological examination can lead to the final diagnosis. Large-scale excision of these tumours, which have a tendency to relapse, is the therapy of choice. The diagnostic problems are shown in a case of a 26-year old patient.


[Ovarian cancer in ovarian remnant syndrome?]. We report on a malignant pelvic tumour in a 69-year old woman, whose uterus and adnexa had been removed 22 years ago because of endometriosis. Clinical and pathological findings pointed to an ovarian cancer in an ovarian remnant syndrome. In a case of a carcinoma, it is difficult to furnish proof of an ovarian remnant syndrome. Differential diagnoses, especially the ureteral adenocarcinoma, are discussed.


[Obstetrical management of dysfibrinogenemia with increased thrombophilia]. Dysfibrinogenaemias are characterised by qualitatively abnormal fibrinogen, causing functional defects. In pregnant women, the incidence of recurrent abortions and placental abruption as well as haemostatic complications is high. In this case report, we report on a 22 year old woman with dysfibrinogenaemia complicated by thrombotic episodes. After two stillbirths under dramatic circumstances (placental abruption, eclampsia) and after an early abortion (7th gestational week), the patient was treated by subcutaneously administered heparin. Pregnancy ended successfully by delivery in the 39th gestational week.


Considerations for selecting effective analgesic regimens in dental practice. A variety of analgesic regimens can be developed, based on sound pharmacological principles, in response to the empirical estimate of pain intensity. Including optimal doses of nonopioids to reduce the amount of opioid required is recommended. Furthermore, when pain is anticipated, the nonopioid regimen can be administered on a regular schedule rather than as needed. Preventing pain is better than attempting to reduce it after full intensity has been reached. Careful selection of an effective regimen can prevent breakthrough pain, along with stress and anxiety, which are factors that often require desperate attempts for relief. Options for the dentist to consider are summarized in Table 5 and may be simulated through substitution of other NSAID or opioid equivalents.


Skin tumors may imitate infectious processes. A small nodule on the middle finger of the right hand of a right-handed dentist was removed and found to be benign. The lesion recurred and showed increased collagen deposition and vascularity; it was diagnosed as a dermatofibroma. In the absence of a specific incidence of trauma, the cause of such a lesion is a matter of speculation. Such lesions can develop as local tissue reactions to wounds that are the result of routine operatory procedures. This points to the need for careful handling of sharp instruments. Because of the serious consequences of a malignancy or infection from HIV, nodules and other lesions of unknown etiology that appear suddenly should not be ignored.


Adverse reaction to dental corticosteroids. The case of an 18-year-old woman who experienced prominent, episodic cognitive dysfunction and affective symptoms, which coincided with a brief administration of dexamethasone, has been presented. Because her symptoms were subtle and intermittent, and because she was no longer taking corticosteroids when she sought medical attention, the diagnosis of a corticosteroid-induced mental disorder was delayed. This case demonstrates the need for heightened awareness, among all practitioners, of the effects of corticosteroids on mental functions. Because it is not possible to predict who will experience mental disturbances with even small doses of corticosteroids, all patients (and their families, if possible) should be informed about the possibility of adverse reactions. Dentists and physicians need to weigh the risks and benefits of corticosteroid therapy carefully. Clinicians also should be suspicious of psychiatric disturbances in proximity to corticosteroid use (i.e., even in a patient who is not taking corticosteroids, but who has a history of corticosteroid treatment).


A three-rooted mandibular second premolar. If an endodontic problem is diagnosed in a mandibular premolar, and root canal therapy is provided, it must be considered that second and third canals might exist. Although the existence of a third canal would be rare, a thorough evaluation may help to prevent future complications. In the case presented here, failure to recognize a third canal might have resulted in incomplete instrumentation and canal obturation, and endodontic failure. Variations in root canal morphology and the number of canals might not have been detected even during close inspection of the pulp chamber floor. Therefore, the dentist must have a thorough knowledge of root canal morphology and its variations.


Recruitment within the groups of gamma 1, alpha 2 and alpha 3-motoneurons in dogs and humans following bladder and anal catheter pulling. Conduction velocity frequency distribution histograms were constructed from lower sacral root recordings of single intrafusal (gamma) and extrafusal (alpha) motoneurons. The velocity distributions of occasional and stimulated activity before and following bladder and anal catheter pulling were almost identical for dogs and humans. The limits of the velocity ranges of alpha 1(FF), alpha 2(FS) and alpha 3(S) and gamma beta(?)-motoneurons were determined from the broadness of the single peaks. The borders of the partly fused peaks of gamma 1 and gamma 21-motoneurons were estimated from their different functional properties. Activity levels of the alpha 1, alpha 2, alpha 3, gamma beta, gamma 1 and gamma 21-motoneurons were too complex to allow safe conclusions from the dog measurements, probably because of the representation of leg and tail in addition to sphincter functions in the lower sacral root. In the human dorsal S4 root, in which mainly efferent functions of sphincters only were contained, the gamma 21, gamma 1, alpha 2 and alpha 3-motoneurons showed simple behaviour. Distribution changes of conduction velocities in each group of alpha and gamma-motoneurons were used for recruitment analysis. Following stimulation in dogs and humans, within the groups of gamma 1, alpha 3 and alpha 2-motoneurons, slowly conducting fibres were activated before the faster conducting ones. The alpha 3-motoneurons were recruited later than the alpha 2-motoneurons. In the dog, low gamma 1 and alpha 2-motoneuron velocities occurred preferentially 0 to 0.2 s following strong bladder catheter pulling, probably in the mono- and oligosynaptic pathways. Low conduction velocities of alpha 3-motoneurons occurred more often 1 to 1.2 s following stimulation. At 2 to 2.2 s following stimulation, the high gamma 1 and alpha 2-motoneuron velocities were more activated. At 4 to 4.2 s following stimulation, low gamma 1 and alpha 2-motoneuron velocities were recruited again. Following strong bladder catheter pulling, co-recruitment of the gamma 1 and alpha 2-motoneurons seemed to occur. Following anal catheter pulling in the dog there was no co-recruitment of gamma 1 and alpha 2-motoneurons. In the case of gamma 1-alpha 2 co-recruitment, the gamma 1-motoneurons were recruited additionally once in between the co-recruitment. The higher frequency of recruitment of the gamma 1-motoneurons, and the separate recruitment of the gamma 1 and alpha 2-systems, indicate that the activation of gamma 1 and alpha 2-motoneurons are not strongly linked.(ABSTRACT TRUNCATED AT 400 WORDS)


Ventral root afferent and dorsal root efferent fibres in dog and human lower sacral nerve roots. Two pairs of wire electrodes were used to record single afferent action potentials from ventral roots and single efferent action potentials from dorsal roots of dogs and humans. A human lower sacral ventral root contained about 20 to 30% afferents among fibres with a diameter larger than 5 microns; a comparable ventral root of a dog contained about 1% afferents. Human S3, S4 and S5 dorsal roots contained 3, 18, and 20 to 30% efferent fibres respectively; a comparable dorsal root of the dog contained less than 1% efferent fibres. Primary and secondary muscle spindle afferents, Golgi tendon organ afferents, and afferents from the mechanoreceptors of the urinary bladder and anal canal mucosa were activated in a dog ventral root by pulling bladder and anal catheters. Their peak group conduction velocities were 82, 57, 71 and 18 m/s at 34 degrees C respectively. The dog afferents conducted more than 30% faster than did comparable human nerve fibres. By strongly pulling the bladder catheter, the static human dorsal root gamma 21-motoneurons increased their activity for about 7 s which in turn strongly increased the dorsal root spindle afferent activity for more than 10 min; the human static intrafusal gamma-motoneurons seemed to show cumulative properties.


Alamethicin-induced pore formation in biological membranes. The effects of alamethicin on the membrane barrier function of rabbit erythrocytes, human platelets and sarcoplasmic reticulum vesicles, as well as on that of brain microsomes and liver mitochondria of the rat were compared. An upset of the barrier function was observed for plasma membranes of brain microsomes as well as for erythrocyte and platelet membranes at alamethicin concentrations ranging between 25-80 micrograms/ml. The membrane barrier functions of sarcoplasmic reticulum vesicles, of endoplasmic reticulum vesicles of rat brain microsomes, and of liver mitochondria were disturbed at 3-7 micrograms/ml alamethicin. The different sensitivities of plasma and intracellular membranes to alamethicin were supposed to be due to the presence of considerable quantities of cholesterol in plasma membranes as well as to peculiarities of their protein compositions.


Threshold stimulation and accommodation of the Hodgkin-Huxley axon. The charge-duration and strength-duration relations for just threshold rectangular stimuli were numerically investigated for the Hodgkin-Huxley axons of different lengths and different membrane capacitances under normal conditions and blockage of the development of accommodative processes. Two linear portions could be distinguished on the charge-duration curve. One of them followed the Weiss law. The other one represented a portion of a straight line passing through the zero point of the coordinates. The slope of the second portion was determined by the charge for very short stimuli (Q0), the slope of the first portion, and the maximum time to excitation (tau max). The rheobase reflected the slope of the second portion. Upon varying the fibre length the slope of the first and the second linear portions and the rheobase changed. The membrane capacitance substantially affected both the value of Q0 (as in the case of myelinated fibres) and the rheobase. The accommodative processes affected the Q0, the slope of the first line, tau max, and, consequently, the rheobase. The effect of potassium activation was stronger than that of sodium inactivation. The slope of the first line, tau max, and the rheobase might be considered more comprehensive indicators of the accommodative processes than the usually used indicators.


Effect of stimulus (postsynaptic current) shape on fibre excitation. Effects of variation of the stimulus pulse shape on the excitation of a nonmyelinated nerve fibre were studied using a mathematical model based on the Hodgkin-Huxley equations. Efficiency of smoothly changing pulses was compared with that of rectangular pulses. For pulses shorter than the time to excitation, the rate of the stimulus rise did not determine the ability of a smoothly changing pulse to excite the fibre. For a given stimulus duration, the main factor was the pulse area or the charge delivered by the pulse. The strength-duration curve for smoothly changing pulses was a nonmonotonic function, in contrast to the curve for rectangular pulses. The dependence of latency on changes in the pulse area was non-linear. It would be nonmonotonic when the pulse area variation were due to the stimulus duration or the stimulus rise duration. More that one propagating intracellular action potential (IAP) could arise upon fibre activation by a long smoothly changing threshold stimulus. Upon activation of relatively short fibres the IAP could arise not at the site of the smoothly changing stimulus injection. The rectangular pulses of long duration were more efficient than the corresponding smoothly changing ones. Irrespective of the shape, the pulses whose duration at the foot is 1-2 ms, are more suitable for a prolonged threshold fibre activation.


Group conduction velocities and nerve fibre diameters of alpha and gamma-motoneurons from lower sacral nerve roots of the dog and humans. Single action potentials and their conduction times were recorded extracellularly from dog and human lower sacral nerve roots. Conduction velocity frequency distribution histograms were constructed and peaks of single extrafusal and intrafusal motoneuron distributions were identified. The electrophysiologically measured roots were removed and morphometrically analysed. Nerve fibre diameter frequency distribution histograms were constructed with respect to 3 myelin sheath thickness ranges, and peaks of single motoneuron group distributions were identified. The identified motoneuron classes, characterized by their group peak values of conduction velocity at about 36 degrees C and fibre diameter were: dog: intrafusal: gamma 22(23ms-1/4.8 microns),gamma 21(33/5.7), gamma 1 (43/6.7),gamma beta?(54/10.1) extrafusal: alpha 3(61ms-1/11.7 microns),alpha 2(72/13.6), alpha 11 (81/15.2), alpha 12(86/16.8),alpha 13(95/19) human: intrafusal: gamma 21(15ms-1/5.8 microns), gamma 1(20/6.8), gamma beta?(27/7.2) extrafusal: alpha 3(37ms-1/8.3 microns),alpha 2(50/10.2), alpha 1(60/13.1) The 60 (alpha 3) to 30% (alpha 1-motoneurons) higher conduction velocities in dogs as compared to humans seem to originate in the 40 (alpha 3) to 30% (alpha 1-motoneurons) larger nerve fibre diameters. However, the myelin sheath seemed to be 0.1 to 0.2 microns thinner in dogs than in humans. The pair-values "conduction velocity-fibre diameter" of the alpha and gamma-motoneuron groups were lying on different correlation curves in the velocity-diameter plane indicating structural and/or geometrical differences between alpha and gamma-motoneurons.


Plasmid maintenance in Bacillus stearothermophilus is strain-dependent. We studied the segregational stability of plasmids based on pTB913, a 4.5-kb rolling-circle plasmid derived from the thermophilic Bacillus plasmid pTB19. In Bacillus stearothermophilus the stability of pTB913 derivatives appeared to be strain-dependent. In strain CU21 large amounts of single-stranded pTB913 DNA were found and the plasmid was highly unstable at 57 degrees C. In strain NUB3621, however, very low amounts of single-stranded plasmid DNA were formed and pTB913-based replicons were only slightly unstable at 57 degrees C. The NUB3621/pTB913 host-vector system seems appropriate for molecular cloning. A RepA-based replicon, also derived from pTB19 but replicating by a theta mechanism, was highly unstable in B. stearothermophilus NUB3621.


Electrochemical sterilization of bacteria absorbed on granular activated carbon. The electrochemical sterilization of bacteria adsorbed on granular activated carbon (GAC) was demonstrated. The survival ratio of bacteria on GAC was dependent upon the applied potential. The survival ratio of Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Saccharomyces cerevisiae vs. saturated calomel electrode (SCE) was below 1% at 0.75, 0.8, 1.0 and 0.65 V, respectively. The electrochemical sterilization of tap water containing E. coli was carried out when 3.5 ml of the cell suspension (4.0 x 10(2) cells/ml) was incubated with 2.0 g of GAC for 5 h at 0.7 V vs. SCE. The number of E. coli adsorbed on GAC and the cell concentration in the water decreased rapidly. E. coli on GAC were electrochemically killed and the cell numbers did not increase.


Transconjugants of Agrobacterium radiobacter harbouring sym genes of Rhizobium galegae can form an effective symbiosis with Medicago sativa. It is known that the Rhizobium galegae genomes contain megaplasmids. The suicide vector pSUP2111 with nifH gene of R. meliloti was introduced into the strains CIAM 0703 and CIAM 0711 of R. galegae inducing effective nodules on Galega orientalis plants. The formation of self-transmissible megaplasmids was observed. The megaplasmid transfer into non-nodulating R. meliloti mutants resulted in partial complementation of the nodulation defect in recipient strains though only one transconjugant showed the nitrogen-fixing activity in symbiosis with alfalfa and another one in symbiosis with G. orientalis plants. Among the Agrobacterium strains harbouring R. galegae megaplasmids there were four classes of transconjugants: (1) Nod+ Fix- in symbiosis with goat's rue plants (three strains); (2) Nod+ Fix- on Medicago sativa (two strains); (3) Nod+ Fix+ on M. sativa (five strains); (4) Nod- with both plant hosts (11 strains).


Description of conidia from submerged cultivation of Thermomyces lanuginosus for use as a uniform inoculum. Conidia produced by submerged cultivation of the thermophilic fungus Thermomyces lanuginosus were superior to conidia from agar plates when used as inoculum, due to a faster and more synchronous germination. With conidia derived from submerged liquid culture at 40-45 degrees C more than 90% germination was achieved at 50 degrees C within 3 h whereas the same percentage germination was only achieved after 5 h incubation of conidia produced on agar plates. The temperature during conidial formation, and conidial age at the time of harvesting, were factors influencing germination of the conidia.


Cloning of poly(3-hydroxybutyric acid) synthase genes of Rhodobacter sphaeroides and Rhodospirillum rubrum and heterologous expression in Alcaligenes eutrophus. From genomic libraries of the purple non-sulfur bacteria Rhodospirillum rubrum Ha and Rhodobacter sphaeroides ATCC 17023 in the broad-host range cosmid pVK100, we cloned a 15- and a 14-kbp HindIII restriction fragment, respectively. Each of these fragments restored the ability to accumulate poly(3-hydroxybutyrate) (PHB), in the PHB-negative mutant Alcaligenes eutrophus PHB-4. These hybrid cosmids also complemented PHB-negative mutants derived from wild-type R. rubrum or R. sphaeroides. Both fragments hybridized with the PHB synthase structural gene of A. eutrophus H16 and conferred the ability to express PHB synthase activity. Only the 15-kbp HindIII fragment from R. rubrum conferred on the mutant PHB-4 the ability to form large PHB granules (length up to 3.5 microns).


Cohort change in images of older adults, 1974-1981. This study examines images of older people held by adults of all ages at two points in time. The two surveys, 7 years apart (1974 and 1981), permit the examination of cohort changes in such perceptions over time. Multivariate analysis indicated that social class and health status evaluations of older adults declined between the two surveys, principally because of the assessments by more recent cohorts. With regard to media portrayals of older adults, more recent cohorts felt that the media portrayals of older adults were distorted by presenting a more positive picture than what older people actually experienced.


In search of a discourse on aging: the elderly on television. This article analyzes the images of aging presented in five of the prime-time television programs of 1989 most watched by the elderly: Murder, She Wrote, The Golden Girls, Matlock, Jake and the Fatman, and In the Heat of the Night, all of which have central elderly characters. An examination of the title sequences reveals that earlier television stereotypes of the elderly "as more comical, stubborn, eccentric, and foolish than other characters" have been replaced by more positive stereotypes of them as powerful, affluent, healthy, active, admired, and sexy.


Subjective age: a test of five hypotheses. This paper discusses the concept and measurement of subjective age. Five hypotheses are proposed based on earlier studies of subjective age and tested using data from 607 randomly selected adults from five states. The data supported only two of the hypotheses: (1) the agreement between chronological age and subjective age declines steadily throughout the adult decades and (2) people in their 30s are the most likely to see themselves as different, either younger or older, from their chronological age. We conclude that generalizations about subjective age may depend on the subjects providing the data.


The quo vadis of gerontology: on the scientific paradigm of gerontology. A critical examination of fundamental assumptions of gerontological research reveals problematic sources of concept and theory development. For example, the misery and resource perspectives on aging and the aged are viewed as "overflow" from ideals of Western society. When empirical findings conflict with researchers' theories, the latter must be reexamined and revised. We should look to the aged themselves for new hypotheses, and focus on such concepts as creativity, wisdom, and play.


Improving nursing home care through training and job redesign. Nursing assistants have the primary contact with older residents of nursing homes. The Penn State Nursing Home Intervention Project's short-term longitudinal study assessed the single and combined effects of two interventions designed to affect nursing assistants' performance by increasing their knowledge and motivation: skills training and job redesign. Statistically significant differences in nursing assistants' knowledge were evident in comparisons between intervention and control sites, but performance was not improved. Implications for policy, practice, and research are discussed.


Ineffective staff, ineffective supervision, or ineffective administration? Why some nursing homes fail to provide adequate care. This study involved 530 nursing staff working in 25 for-profit and nonprofit nursing homes, two of which failed to meet resident care standards required for state recertification. Staff members' job attitudes, opinions regarding elderly residents, and perceptions of the organization climate varied between the successful for-profit and non-profit homes. The organization climate in the failed homes was significantly different from the climate in either the successful for-profit or successful nonprofit homes.


Personal and environmental influences on nursing home satisfaction. Data were collected from the administrator, staff, and a sample of 289 residents in 51 nursing homes in order to assess the influence of organizational factors on residents' satisfaction with the nursing home. Longevity of personnel, level of benefits, wages for nursing assistants and their perception of the charge nurse's fairness and competence as well as the degree of personalization of residents' rooms were all related to residents' satisfaction with the nursing home.


The role of support in alleviating stress among nursing assistants. This paper provides a direct test of the buffering hypothesis that the negative effects of stressors (measured as burden, burnout, and perceived job pressure) on nursing assistants working in long-term care institutions are moderated by social support (at work and external to work). The buffering hypothesis was not confirmed, though some support for a main effects view was found. Social support at work, specifically training to work with residents with cognitive impairment, and support from family and friends can assist nursing assistants in dealing with burnout and perceived job pressure. However, major steps in alleviating burden, burnout, and perceived job pressure must be to decrease or change the workload and provide rewards on the job.


Nurse's aides in nursing homes: the relationship between organization and quality. This study examines the work of the nurse's aide through a combination of participant observation and in-depth interviews with 30 nurse's aides. Data were analyzed using the grounded theory method of constant comparative dimensional analysis. Findings suggest that strategies developed by individual nurse's aides to organize their work are important determinants of both the quality of care and worker turnover. Quality of care may be better explained by Litwak's theory about the difficult juxtaposition between primary and formal groups than by the nurse's aides' lack of knowledge.


Adaptation and age-related expectations of older gay and lesbian adults. Results from a study of lesbian women and gay men in the Midwest over the age of 50, who indicate high levels of involvement in the gay community, provide a picture of the aging process of these adults that builds on previous research efforts. Respondents reported acceptance of the aging process, and high levels of life satisfaction, despite predictable problems associated with aging and sexual orientation. Being active in the gay community was an asset to accepting one's own aging.


Black and white dementia caregivers: a comparison of their adaptation, adjustment, and service utilization. We compared black (n = 33) and white (n = 119) caregivers of dementia patients on indices of adaptation, adjustment, and utilization of supportive services. Black and white caregivers differed most notably on marital and financial/insurance status, but there were few differences between them in their adaptation to dementia responsibilities. Black caregivers, however, evidenced less burden and less desire to institutionalize their relatives and were more likely to report more unmet service needs than were whites.


An evaluation of a group program for spouses of frail elderly veterans. We examined the effectiveness of a multicomponent group program for spouses of frail aging veterans that included support, education, problem solving, and stress reduction. Compared with caregivers who received no intervention, those in the group program showed significant increases in use of active behavioral coping strategies, knowledge of community resources, perceived independence in the marital relationship, and personal changes in the caregiving relationship. They also experienced significant decreases in subjective burden and the stress and severity of caregiving problems.


A longitudinal analysis of factors related to survival in old age. Data from a longitudinal study of the elderly in rural North Wales are used in an exploratory study of the relationships between very broadly defined social circumstances and longevity. A statistical modeling approach is adopted and has some nonroutine features necessitated by missing data on dates of death. A variety of demographic, socioeconomic, social network, quality-of-life, dependence, and health variables are found, individually, to be related to survival. Multivariate analysis demonstrated that many of these relationships are spurious and, in particular, there is no prima facie evidence that survival is affected by social networks or quality-of-life factors. However, socioeconomic factors emerge as important for the old elderly.


Nursing home responsiveness to research requests: results of a field study. This study used data from a random sample of Wisconsin nursing homes to analyze nursing homes' response to requests to participate in a field study. Multiple organizational characteristics predicted responsiveness. Facilities with greater financial resources were more likely to grant access to researchers. Stable administration and local facility control predicted higher response rates to a survey of nurses. Stable ownership and stable administration predicted higher resident consent rates.


Senior-to-senior mediation service project. Conflicts experienced by elderly persons regarding housing, consumer problems, the quality and availability of health and social services, family problems, and other issues often require mediation. This program demonstrates the important potential of using seniors as volunteer mediators to assist other seniors. It also suggests that training in conflict management skills enhances competence of volunteers in solving their own conflicts.


Clinical neurophysiology studies in headache: a review of data and pathophysiological hints. In migraine between attacks EMG studies are normal. Recordings during attacks need to be performed. Temporalis exteroceptive silent period is useful in the differential diagnosis of headaches and sheds some light on the pathophysiology of tension-type headache.


Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease. The prognostic significance of peritoneal cytology among 269 women with clinical stage I and II carcinoma of the endometrium was studied. All patients were surgically staged and had undergone selective pelvic and para-aortic lymphadenectomies. Patients with clear cell and papillary serous carcinomas were excluded from the analysis. Thirty-four (12.6%) patients had malignant cells in the peritoneal washings (positive peritoneal cytology). The effect of positive peritoneal cytology on survival depended upon the extent of disease present. If the disease was confined to the uterus, positive peritoneal cytology did not influence survival; if the disease had spread to the adnexa, lymph nodes, or peritoneum, positive peritoneal cytology had a significant adverse effect on survival, decreasing it at 5 years from 73 to 13%, all recurrences being at distant sites. These findings suggest that treatment specifically directed at positive peritoneal cytology is not warranted unless extrauterine disease is present, and when it is, systemic rather than intra-abdominal treatment will be required to affect survival.


A matched comparison of single and triple incision techniques for the surgical treatment of carcinoma of the vulva. Thirty-two patients with invasive squamous cell carcinoma of the vulva (SCC) undergoing radical vulvectomy or radical local excision with bilateral superficial groin node dissection using a triple incision technique (TI) were matched for new FIGO stage, lymph node status, size of lesion, and site of lesion with patients with SCC undergoing traditional radical vulvectomy with en bloc bilateral groin (but not pelvic) node dissection using a single incision (SI) technique. Average operative time (134 min: 191 min), blood loss (424 ml: 733 ml), and hospital stay (9.7 days: 17.2 days) were significantly less in the TI group. After SI 6/32 (19%) patients and after TI 1/32 (3%) patients experienced complete breakdown of the groin wounds. There was no significant difference in overall survival (P = 0.56) or disease-free survival (P = 0.53) between the two groups. There was no significant difference in survival between the two groups by lesion size or by FIGO (1989) stage. Disease recurred in six patients after SI compared with seven after TI (P = 0.75). There were no skin bridge recurrences in the TI group. Two patients in each group had isolated vulvar recurrences and all four were successfully treated by local excision. These data indicate that outcome following TI surgery is essentially equal to that of SI in early-stage disease but major morbidity is much reduced.


Total and lipid-bound serum sialic acid as markers for carcinoma of the uterine cervix. Concentrations of total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined in serum samples from 88 patients with squamous cell carcinoma of the cervix, 26 normal subjects, and 44 patients with benign uterine or ovarian disease. TSA concentrations in patients with cervical cancer were found to correlate with advanced-stage disease. LSA concentrations were only increased in stage IV of the disease. Sensitivity of the test for stage IB was zero for TSA and 27% for LSA. The specificity of both markers was about 80% due to a low incidence of false-positive values in the pathologic control group. Measurements of TSA or LSA appear to be of no value for the early detection of cervical cancer or to complement the clinical staging of this tumor.


Epilepsy associated with hypocalcemia: description of a family. The unusual occurrence of epilepsy and hypocalcemia in the same family is described. Epilepsy was present in three siblings (convulsive generalized in two females and partial in one male). All six family members had calcium ion, plasmatic phosphorus, plasmatic and erythrocytic potassium, urine calcium and phosphate concentration below the normal levels. Altered values of calcium-induced potassium membrane permeability were found in three subjects (two of them also affected by epilepsy). The assumption that alterations of membrane structure or function play an essential role in determining familial epilepsy and that the normal "set point" for calcium is genetically determined in familial hypocalcemia could explain the concomitance of both pathologies to some extent.


Urodynamic evaluation of 12 ataxic subjects: neurophysiopathologic considerations. Twelve ataxic subjects (seven with Friedreich's heredo-ataxia and five with a cerebellar vascular or traumatic lesion) were examined by way of urodynamic evaluation. The results explain the role the cerebellum plays in the modulation of the micturition reflex and confirm the importance of bilateral encephalic damage in causing vesico-sphincteral malfunctioning and the important role of the lateral myelon cords in transporting bladder proprioceptive sensitivity.


Trafficking of syngeneic murine lymphokine activated killer T cells following intraperitoneal administration in normal and tumor bearing mice. Nongenetically restricted T cells may be important host effector cells in women with ovarian cancer receiving intraperitoneal (ip) IL-2 therapy. We developed an in vitro technique to produce murine lymphokine-activated killer T cells. Murine splenocytes were cultured in the presence of 1000 U/ml IL-2 for 10 to 15 days. Phenotypical analysis showed 95% of total cells to express the pan T phenotype Thy 1.2 and no NK cell phenotypes by Day 7 in culture. These cells were labeled with 51Cr and their trafficking pattern after ip administration into normal and M5067 tumor bearing mice was examined. Various organs and tissues were collected at different timepoints and monitored for radioactivity. Within 4 hr., about 60% of the counts were associated with the bowel, peritoneum, and omentum of both normal and tumor bearing mice. About 15% of counts were associated with the blood, lung, kidney, spleen, and liver of both normal and tumor bearing mice.


A clinicopathological study of 30 melanomas of the vulva. Thirty cases of malignant melanomas of the vulva were studied for prognostic factors. Ulceration, tumor thickness, and positive inguinal lymph nodes were the most important prognostic factors. Morphometry did not demonstrate any prognostic meaning. Traditionally a radical vulvectomy and bilateral inguinal lymph node dissection were the therapy of choice, but this treatment modality did not show a better survival than less radical treatment. A low-risk and a high-risk group of patients have been identified for recurrence. The low-risk patient has a nonulcerative tumor, less than 3 mm thick, without clinical evidence of inguinal lymph node metastases, and should be treated by local excision with a 2- to 3-cm margin. The high-risk patient has a tumor which is ulcerative and/or more than 3 mm thick and should also be treated by local excision without elective inguinal node dissection. If clinical suspicion of inguinal lymph node metastases exists, an inguinal node dissection is advocated for better local control of the disease.


Time information in Poggendorff visual illusion: visual evoked potentials. Using the component sets of the Poggendorff visual illusion as optical stimuli (comprising two horizontal and parallel segments intersected by two oblique segments), we recorded the respective visual evoked potentials (VEPs). Depending on the different delta t passing between the constitutive elements of the Poggendorff illusion, it was found that there was a greater latency of VEP components for the visual stimulus presentation sequence in which oblique segments are projected before horizontal segments.


A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage Ib-IIa cervical cancer patients with pelvic lymph node metastases. Seventy-one patients with Stage Ib-IIa cervical cancer treated by radical hysterectomy and found to have pelvic lymph node metastases were entered on a randomized trial comparing standard pelvic radiotherapy versus three cycles of combination chemotherapy with cisplatin, vinblastine, and bleomycin followed by pelvic radiotherapy. After a median follow-up of 2.5 years, 24 patients have relapsed. In 12 patients, the first evidence of relapse was in the pelvis, in 11 patients the first relapse was evident at a distant site, and in 1 patient the local recurrence and distant metastases were documented simultaneously. No difference in disease-free or overall survival has emerged between the two treatment groups. Relapse was more common in patients with non-squamous tumors (44%) and in those with metastases in several pelvic lymph nodes. We conclude that patients with pelvic lymph node metastases have a rather poor prognosis, but it remains to be determined how they should best be treated after radical surgery.


The significance of cone biopsy resection margins. This 12-year retrospective study examines the significance of margin involvement with dysplasia at cone biopsy in relation to follow-up. Of 300 cone biopsies, 123 (41%) had margin involvement. These cases of margin involvement were associated with more severe dysplasia (P less than 0.0001) and a higher chance of subsequent abnormal cytological follow-up (P less than 0.0001) and residual dysplasia at subsequent surgery (P less than 0.0001). Involvement of the endocervical margin at the initial cone biopsy was a sensitive predictor of future abnormality, with an incidence of subsequent abnormal cytology of 29% and residual disease of 82% in those undergoing further surgery. In those cases where the margins had been clear, the incidence of abnormal cytological follow-up was 8%, with 12% residual disease in those undergoing subsequent surgery. Margin involvement was a better predictor of residual disease at repeat surgery than abnormal follow-up cytology (positive predictive value, 79% vs 60%, respectively).


Endoluminal ultrasound staging of cervical cancer. Clinical staging of cervical cancer is incorrect in approximately one-third of patients who undergo surgical staging. Pretreatment laparotomy is the staging method of choice for patients with cervical cancer at Memorial Sloan-Kettering Cancer Center. We performed transabdominal, transvaginal, and transrectal ultrasound staging on 12 patients. In 5 of 6 patients undergoing radical hysterectomy, clinical ultrasound and surgical staging were consistent. One patient could not tolerate rectal probe sonography. Ultrasound staging was correct in 1 of 6 patients with advanced disease. A new technique of cervical imaging with transrectal ultrasound and vaginal douche is described. We believe it unlikely that ultrasound will improve the accuracy of clinical staging in patients with cervical cancer.


Long-term follow-up of ovarian cancer with monthly determinations of serum CA 125. Monthly serum CA 125 determinations were used for monitoring of 33 patients with advanced nonmucinous epithelial ovarian cancer during the follow-up after the primary treatment. The observation time ranged between 3 and 7 years. All patients had elevated CA 125 levels at the start of chemotherapy with subsequent normalization during treatment. Seventeen patients were classified as having no evidence of disease during the whole follow-up period. Out of 649 samples analyzed from these patients only 6 of the samples from 4 patients were greater than 35 U/ml (rate of false positives, 0.9%). These high values were all singular; the serum samples for the preceding and following months were normal. Out of 20 verified recurrences in 15 patients, 19 had elevated CA 125 levels (sensitivity, 95.0%). The CA 125 increase was the only sign that initiated clinical investigation in 16 recurrences (sensitivity for early diagnosis, 80.0%). With examination under anesthesia, fine needle aspiration for cytology, CT scan, and sometimes laparoscopy or laparotomy a relapse could be verified in 13 of these cases (sensitivity for the whole procedure, 65.0%). In 2 recurrences the increase in CA 125 was obvious at the same time as the clinical evidence of recurrence and in 1 case the elevation was delayed. One additional patient is presently under investigation because of an increase in CA 125. We conclude that monitoring with monthly determinations of serum CA 125 is a reliable method with very few false-positive values. We regard this as a step forward in the management of the follow-up of ovarian cancer patients.


Carcinoma of the cervical stump.

Carcinoma of the cervical stump. Treatment, prognosis, and complication rate were retrospectively studied in 46 patients with cervical stump cancer. There were no differences in clinical stage distribution and histopathological findings between these patients and patients with cervical cancer of the intact uterus. However, 43 patients were treated by radiation therapy and only 3 patients had a cervical amputation. The 5-year survival rate was 62%, which is comparable to that of cervical cancers. Late complications were found in 22 patients: 3 (7%) had symptoms of severe radiation reactions of the bladder (necrosis or vesicovaginal fistels), 14 (31%) had severe radiation reactions in the rectum and the sigmoid (severe proctitis, stenosis, or rectovaginal fistels) and 7 (18%) had large vault necrosis. It is concluded that the frequency of cervical stump cancer is low, but cancer in the cervical stump is difficult to treat and the rate of severe late complications is so high that it should be considered when one is deciding between supravaginal and total hysterectomy. Moreover, screening for cervical cancer should be performed regularly after supravaginal hysterectomy.


Descriptive epidemiology of ovarian cancer in Europe. Trends in ovarian cancer mortality over the period 1955-1989 were analyzed for 25 European countries (excluding the Soviet Union and a few small countries) on the basis of the official death certification data from the World Health Organization database. The overall variation in age-standardized ovarian cancer mortality at all ages declined appreciably, from over 17-fold during the period 1955-1959 (i.e., between 10.5/100,000 in Denmark and 0.6/100,000 in Spain, world standard) to 3.4-fold (i.e., between 9.9/100,000 in Denmark and 2.9/100,000 in Spain) in the late 1980s. When a comparison was made between the late 1950s and the 1980s, ovarian cancer mortality increased in most European countries, except Denmark, Sweden, and Switzerland, where certified mortality was already elevated in the late 1950s, although also in these countries the peak rate around or over 10/100,000 was reached during the 1960s. However, when the changes over the last decade were considered, ovarian cancer mortality trends were downward in all Nordic countries, Germany, Switzerland, Austria, and Czechoslovakia. Mortality was rising somewhat, though to a smaller extent, in Ireland, Britain, and Southern Europe. Trends were more favorable in middle-aged women (35 to 64 years), and, to an even greater extent, in young women (aged 20 to 44), among whom substantial declines, particularly over the last decade, were observed in most European countries, approaching 50% in Britain and Scandinavia. These trends are discussed in terms of changes in risk factor exposure (i.e., trends in average parity and oral contraceptive use), diagnostic and therapeutic improvements, ovariectomy, and changes in case ascertainment and certification.


Intraperitoneal cisplatin chemotherapy in ovarian carcinoma patients who are clinically in complete remission. Three courses of intraperitoneal cisplatin chemotherapy with systemic thiosulfate protection were administered to 31 stage II-IV ovarian carcinoma patients who were clinically in complete remission after completion of postoperative cisplatin-based combination chemotherapy. The 5-year survival rate was 60.4% and the median progression-free interval 35 months. Among 25 patients who underwent second-look laparotomy, the survival and the duration of the progression-free interval were significantly better in those with a pathologically confirmed complete response. Short-term intraperitoneal cisplatin chemotherapy should be considered for consolidation of treatment in ovarian carcinoma patients who are clinically in complete remission.


Preoperative serum CA-125 levels in borderline tumors of the ovary. Preoperative serum CA-125 levels were evaluated in 38 patients who underwent primary surgery for epithelial ovarian tumors of borderline malignancy at the Brigham and Women's Hospital and Massachusetts General Hospital between 1981 and 1990. Surgical staging was Stage I in 25 (66%) patients, Stage II in 2 (5%) patients, Stage III in 10 (26%) patients, and Stage IV in 1 (3%) patient. The mean sizes of mucinous and serous ovarian tumors were 21.9 and 10.3 cm, respectively (P = 0.0002). All 13 patients (100%) with mucinous tumors had Stage I disease, while 12 (50%) of 24 patients with serous tumors were Stage I. Combining all cell types, 10 (40%) of 25 patients with Stage I disease had an elevated preoperative CA-125 level, while 2 (100%) of 2, 9 (90%) of 10, and 1 (100%) of 1 patient with Stage II, III, and IV disease, respectively, had increased preoperative levels. Among patients with serous tumors, 3 (25%) of 12 Stage I patients had an elevated preoperative CA-125 level, while 11 (92%) of 12 Stage II-IV tumors had elevated levels (P less than 0.001). These data suggest that preoperative CA-125 level correlates with stage of disease in patients with serous borderline ovarian tumors.


Phase II trial of amonafide in previously treated patients with advanced ovarian cancer: a Southwest Oncology Group study. Twenty-three patients with metastatic or recurrent Stage III or IV epithelial ovarian cancer who were refractory to or relapsed following previous chemotherapy with cisplatin or a cisplatin analog were entered into a phase II study of amonafide. The starting dose of amonafide was 300 mg/m2 delivered daily over 1 hr by intravenous infusion. In the absence of myelosuppression, the dose of amonafide was escalated by increments of 75 mg/m2 to a maximum of 450 mg/m2. There were 19 eligible and 17 fully evaluable patients. Grade 3 or 4 leukopenia occurred in 14 (74%) patients and grade 3 or 4 thrombocytopenia in 6 (32%) patients. No objective complete or partial responses were observed. Four patients had stable disease for 3, 4, 4.5, and 6 months, respectively. Therefore, amonafide in the doses used in the present trial does not have significant activity in previously treated patients with ovarian cancer.


Successful treatment of persistent partial mole with oral methotrexate therapy. Two patients with persistent partial molar pregnancy were successfully treated with oral methotrexate therapy. The advantages of this form of therapy are discussed.


Bronchial metastases from ovarian carcinoma. Report of a case and review of the literature. A patient with ovarian cystadenocarcinoma developed respiratory insufficiency due to bilateral endobronchial metastases, 6.5 years after treatment of the primary tumor. Ovarian cancers frequently metastasize to the pleura and lung parenchyma. Clinically significant bronchial metastases are rare. Only three cases have been reported previously. As in our patient, bronchial metastases tend to occur after a relatively long interval from diagnosis of the primary tumor, and survival may be prolonged after their appearance.


Choriocarcinoma in a term placenta with maternal metastases. Choriocarcinoma of the nonmolar placenta is presumptively a rare entity and is usually associated with widespread maternal metastases at the time of diagnosis. Nonmetastatic disease goes unrecognized and undiagnosed because placental carcinoma can be limited to a few villi, and grossly evident disease is often misinterpreted as a placental infarct. The optimal treatment for patients with choriocarcinoma of the placenta is not known but aggressive combination chemotherapy is suggested for patients with metastatic disease. Historically, the prognosis for both mother and infant has been poor.


Inhibition by butylated hydroxytoluene and its oxidative metabolites of DMBA-induced mammary tumorigenesis and of mammary DMBA-DNA adduct formation in vivo in the female rat. The phenolic food antioxidant butylated hydroxytoluene (BHT) has been reported to inhibit the initiation stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in the female rat. However, the mechanism for this antitumorigenic effect of BHT is unknown. The present studies were conducted to evaluate the relative effect of the parent chemical BHT and two of its major oxidative metabolites, 2,6-di-tert-butyl-4-hydroxymethylphenol (BHT-BzOH) and 2,6-di-tert-butyl-1,4-benzoquinone (BHT-quinone), on DMBA-induced rat mammary tumorigenesis and on the formation of rat mammary DMBA-DNA adducts in vivo. The ip administration of either BHT or BHT-quinone at 200 mg/kg body weight for 2 wk before until 1 wk after DMBA administration inhibited the development of mammary tumours as compared with controls. The extent of tumour inhibition by BHT (39%) was greater than that exhibited by BHT-quinone (25%). The administration of BHT-BzOH at 200 mg/kg body weight did not inhibit mammary tumorigenesis. Thus, the inhibition of DMBA-induced mammary tumorigenesis by BHT does not appear to be mediated by the oxidative BHT metabolites BHT-BzOH or BHT-quinone. In addition, there was a good quantitative correlation between the inhibition of mammary tumorigenesis by BHT and BHT-quinone and their respective abilities to decrease total binding in vivo of DMBA to mammary DNA. The inhibition of specific mammary DMBA-DNA adducts by BHT was not identical to the inhibition of adducts by BHT-quinone. However, the decrease in formation of the major mammary adduct derived from the anti-dihydrodiolepoxide of DMBA bound to deoxy-guanosine most closely correlated to the relative abilities of BHT and BHT-quinone to inhibit mammary tumorigenesis. When mammary adduct formation was examined in response to BHT dose, the administration of BHT at doses of 100 mg/kg body weight and 200 mg/kg body weight resulted in the inhibition of anti-derived but not syn-derived mammary DMBA-DNA adducts. Together, these studies suggest that in addition to the inhibition of total mammary DMBA-DNA adduct formation, the inhibition of mammary DNA adducts formed from the anti-dihydrodiolepoxide of DMBA also may be specifically important in the inhibitory effect of BHT on DMBA-induced mammary tumorigenesis.


Influence of modulators of epoxide metabolism on the cytotoxicity of trans-anethole in freshly isolated rat hepatocytes. The effect of modulating epoxide metabolism by inhibiting microsomal and cytosolic epoxide hydrolases and depleting glutathione, on the cytotoxicity of trans-anethole has been examined in freshly isolated rat hepatocytes in suspension. Hepatocytes derived from female Sprague-Dawley CD rats by collagenase perfusion were incubated in suspension and sampled at intervals over a 6-hr period. Cytotoxicity was assessed by the leakage of lactate dehydrogenase into the culture medium and in the cells after lysis. Glutathione was determined by fluorimetry. Anethole showed a dose-dependent cytotoxicity at concentrations ranging from 5 x 10(-4) to 5 x 10(-3) M, with concentrations of 10(-3) M and above causing greater than 63% leakage of lactate dehydrogenase in 6 hr. Microsomal epoxide hydrolase was inhibited by trichloropropene oxide (10(-4) M) and cyclohexene oxide (10(-3) M), and cytosolic epoxide hydrolase by 4-fluorochalcone oxide (5 x 10(-4) M). Cellular glutathione was depleted by diethyl maleate (5 x 10(-4) M), and its synthesis inhibited by 2.5 x 10(-3) M-L-buthionine (S,R)-sulphoximine. Suspensions treated with a sub-cytotoxic concentration of anethole (5 x 10(-4) M) showed a rapid increase in cytotoxicity when 4-fluorochalcone oxide was present (complete loss of viability within 2 hr), while pretreatment of hepatocytes with diethyl maleate in combination with buthionine sulphoximine, to deplete glutathione, slowly increased the cytotoxic response at later times (after 4 hr of incubation). The association of the effects of 4-fluorochalcone oxide with the inhibition of cytosolic epoxide hydrolase is strengthened by the inability of chalcone oxide, a close structural analogue of 4-fluorochalcone oxide, which has no effect on epoxide hydrolase or glutathione conjugation, to influence the effects of anethole on hepatocytes. These data are discussed in terms of the role of anethole epoxide in the cytotoxicity of trans-anethole.


Optimization of the sensitivity of high-performance liquid chromatography in the detection of heterocyclic aromatic amine mutagens. Solid-phase extraction with the weak cation-exchange resin Fractogel TSK CM650(S) (TSK CM) was used to optimize the sensitivity and chromatographic resolution by HPLC of the mutagenic heterocyclic aromatic amines MeIQx, 4,8-DiMeIQx, IQ, MeIQ, PhIP, Trp-P-1, Trp-P-2, amino-alpha-carboline and the co-mutagens norharman and harman. The clean-up using cation exchange was applied after purification on Extrelut and propylsulphonic acid-silica gel cartridges (PRS tandem purification). Only the clean-up with TSK CM enabled low detection limits of the mutagenic compounds to be achieved (in the order of ng heterocyclic amines/g experimentally overheated process-flavour sample).


Vomitoxin-induced dysregulation of serum IgA, IgM and IgG reactive with gut bacterial and self antigens. The effect of dietary vomitoxin exposure on immunoglobulins that react with naturally occurring gut bacterial and self antigens was assessed in the B6C3F1 mouse. Ingestion of 25 ppm vomitoxin for 4 and 8 wk resulted in significantly elevated total IgA but depressed total IgG and IgM in serum when compared with control mice fed semi-purified diet only. IgA specific for phosphorylcholine (PC) and inulin (haptens associated with intestinal bacteria) increased significantly in mice fed vomitoxin whereas IgM with the identical specificity decreased. When sera were assessed for autoantibodies recognizing DNA and bromelated mouse red blood cells (MRBC), vomitoxin-exposed mice exhibited elevated specific IgA as compared with controls. This occurred together with decreases in DNA-specific IgG and IgM, and decreases in MRBC-specific IgM. Additionally, vomitoxin exposure did not enhance the specific serum IgA response to orally administered trinitrophenylated sheep red blood cells (TNP-SRBC), but significantly depressed TNP-specific serum IgG. The results suggest that hyperelevation of total and specific serum IgA for oral and self antigens occurs during vomitoxin feeding and that may be coupled with down-regulation of total and specific IgM or IgG. These effects could be contributory to the capacity of vomitoxin to induce IgA immune complex glomerulonephritis.


Genetic toxicology of acrylic acid.

Genetic toxicology of acrylic acid. Acrylic acid was tested for gene mutations in the in vitro CHO/HGPRT assay, for chromosome aberrations in CHO cells in culture, and for potential to induce unscheduled DNA synthesis in rat hepatocytes in culture. In vivo assays performed included the Drosophila sex-linked recessive lethal assay by both the feeding and injection routes, the in vivo cytogenetic assay in rat bone marrow cells after both a 1-day and 5-day oral dosing regimen, and a dominant lethal assay in mice by both an acute and 5-day dosing regimen. All results were negative (non-mutagenic) except for the in vitro chromosome aberration assay. This latter result is consistent with the previously reported possible clastogenic activity suggested by the results of the mouse lymphoma L5178Y TK locus assay in which a predominance of small-colony mutants was observed (Moore et al., Environmental and Molecular Mutagenesis 1988, 11, 49-63). The rapid clearance of acrylic acid in animals and the weight of evidence of genetic toxicity testing, including negative in vivo data in both somatic and germ cells, indicate a lack of genetic toxicity of acrylic acid in vivo.


Comparative study of the biodisposition of benzanthrone in different rodent species. The bio-elimination and organ retention of [14C]benzanthrone, an anthraquinone dye intermediate, were determined in rats, mice and guinea pigs. Urinary excretion of benzanthrone during 96 hr was higher in guinea pigs (28%) compared with rats and mice (19%). However, faecal elimination during 96 hr was higher in rats (39%) and mice (42%) than in guinea pigs (25%). Urinary elimination of benzanthrone in rats and mice was highest between 12 and 24 hr, while guinea pigs showed a peak value between 24 and 48 hr. The maximum amount of radiolabelled benzanthrone was eliminated through faeces at 24-48 hr in all the three animal species. The retention of [14C]benzanthrone in the liver was comparable in rats (11.2%) and mice (11.9%), while in guinea pigs it was substantially higher (21.9%). The testes of rats and mice were devoid of radioactivity, whereas those of guinea pigs showed a marginal retention (1.25%) of 14C. The present study suggests that guinea pigs are more prone to benzanthrone toxicity than are rats and mice since the bio-elimination of this compound is slower and its organ retention is higher in this species.


Inhibition by germanium oxide of the mutagenicity of cadmium chloride in various genotoxicity assays. The effects of germanium oxide on the genotoxicity of cadmium chloride were investigated. The incorporation of [3H]thymidine into testicular DNA was inhibited in mice injected ip with 1.35, 1.80 or 2.70 mg cadmium chloride/kg body weight. Germanium oxide (0.05 or 0.1 mg/kg body weight, sc) alone did not affect [3H]thymidine incorporation into testicular DNA but 0.05 mg germanium oxide/kg antagonized the inhibitory effect of 1.35 mg cadmium chloride/kg. However, combinations of the other doses of the two compounds did not show statistically significant antagonistic effects. Cadmium chloride significantly increased the frequencies of micronucleus formation in polychromatic erythrocytes, and of chromosome aberrations in the bone marrow of mice treated with 0.7, 1.4 or 2.7 mg/kg body weight, in a dose-related manner. These effects were inhibited by germanium oxide at doses of 0.1 or 0.5 mg/kg body weight, although germanium oxide alone did not affect micronucleus formation or the chromosome aberration rate. Cadmium chloride produced a dose-related increase in the frequency of sister chromatid exchanges in cultured human lymphocytes at concentrations of 5, 10 or 50 mumol. This effect was also inhibited by germanium oxide (0.05 or 0.1 mumol), although germanium oxide alone had no effect. There was a dose-related increase in the frequency of sperms with abnormal head morphologies from mice treated with 0.6, 1.1 or 2.2 mg cadmium chloride/kg body weight and this too was antagonized by the injection of germanium oxide (0.1 or 0.5 mg/kg body weight). Germanium oxide alone did not affect the frequency of sperm-head abnormalities.


An update on research with coffee/caffeine (1989-1990). The interest in research with coffee has been increasing in recent years, and this has resulted in a surge of publications dealing with a variety of pharmaco-physiological effects of coffee/caffeine. This review attempts to update the information on the research with coffee/caffeine, including epidemiological studies, laboratory investigations and tests with volunteers, published in 1989 and 1990. It groups published articles according to observed or investigated biological effects. The most significant findings and differences between studies are pointed out with brief commentaries on the results. The overall assessment for the safety of drinking coffee and the effect of coffee on human health, based on the literature published in 1989 and 1990, indicates that certain controversial issues are still unresolved.


[Auto- and hetero-aggression in Gilles de la Tourette syndrome]. A 29-year old patient with Gilles de la Tourette's syndrome exhibited severe compulsive self-mutilation and hostility leading to long-term hospitalisation. A history of refractory self-mutilation increases the risk for suicidal acts, which represent a rare complication in the course of the Tourette disorder.


[Musical pseudo-hallucination in acquired hearing loss]. Auditory hallucinations take various forms including the perception of tinnitus, voices, and, rarely, music. While formed hallucinations are usually ascribed to psychiatric illness, we describe a syndrome of musical hallucinations in mentally sane patients, who are hard of hearing or deaf. 26 cases from the literature are supplemented by 6 own observations, including the first description of two cases in a single family. The different modes of emergence, the spectrum of clinical features and their course are outlined. Differential diagnostic, pathogenetic and therapeutic aspects are discussed.


[Psychology and psychopathology of firesetting behavior 1955 to 1991--a review]. After a historical introduction and some short remarks on criminal arson, this review of the literature since 1955 mainly focuses on pathological firesetting. It deals with all important aspects of the psychiatry of firesetting: arson by persons referred to psychiatric examination, by the mentally ill, and by psychiatric inpatients, the relationship between arson and sexuality, psychoanalytical contributions, arson by children and juveniles, therapy and prevention of firesetting behaviour. Female arsonists, recidivism, and suicide by burning are considered separately.


Characterization and uses of monoclonal antibody derived against DNA binding domain of the ets family of genes. A monoclonal antibody recognizing ets proteins from a variety of species has been developed. This antibody recognizes ets1, ets2, erg, and other related proteins. It has a high affinity for the ets1 protein. The epitope for the pan ets mAb consists of about 13 amino acids. This antibody can be used to isolate and characterize new members of ets gene family derived from a c-DNA expression library, as well as to identify other "ets motif" binding proteins.


Identification of metallothionein in cultured cells by immunoblotting and immunofluorescence using a new monoclonal antibody. A hybridoma clone (MT45-5-3) producing an IgG-class monoclonal antibody specific for metallothioneins (MTs) was established. The monoclonal antibody (MT45) cross-reacted with mouse, rat and rabbit Cd(2+)-induced MTs 1 and 2 and Zn(2+)-induced MT 2 as assessed by enzyme-linked immunosorbent assay. When the antibody was used to detect the MTs transferred to nylon membranes after SDS-polyacrylamide gel electrophoresis, the antibody reacted with cultured human cell MTs as well as rat, mouse and rabbit MTs 1 and 2 even after carboxymethylation. The antibody could be used for the indirect immunofluorescence test for Cd(2+)-induced MTs in cultured human and mouse cells.


Kinetic and energetic parameters of imipramine binding to monoclonal antibodies as measured by fluorescence spectroscopy. Monoclonal antibodies which bind small drugs are useful for the study of the interactive forces involved in antibody-ligand complexation. Detailed understanding of these supramolecular forces requires a careful examination of structural and thermodynamic parameters of the interacting molecules. Fluorescence spectroscopy techniques are very useful in this regard. We report here, the kinetic and energetic parameters of four monoclonal antibodies made against the tricyclic antidepressant imipramine. These monoclonal antibodies were found to possess high to very high binding affinity constants, ranging from 10(7) to 10(10) M-1, and caused fluorescence quenching or enhancement of a fluorescein labelled imipramine. The dissociation rates of the fluorescent ligand from the complexes were measured at different temperatures in order to provide some insight regarding the kinetic and energetic (thermodynamic) parameters of the antibody-ligand binding interactions.


Role of metabolic waste products in the control of cell proliferation and antibody production by mouse hybridoma cells. In order to determine the factors limiting the proliferation and productivity of mouse hybridoma cells in batch/fed-batch cultures, we tested the influence of various environmental parameters on the growth of a model cell line VO 208. We observed that, among the major metabolic waste products, ammonium ions at concentrations superior to that present in the medium at the end of a batch culture do not exert a significant toxic effect on cell growth, whereas in contrast, lactic acid is cytotoxic at concentrations reached in cultures. Feeding of fructose instead of glucose during the stationary phase of the culture markedly prolongs the life span of the culture and enhances the antibody secretion accordingly. However, we failed to observe a satisfactory proliferation pattern in cultures grown in a glucose-free fructose-supplemented medium. We also noted that vitamin supply may be limiting in fed-batch cultures. It thus appears that thorough examination of the cell metabolic needs allows the designing of a culture regimen which significantly improves cell growth and secretion.


B-cell hybridoma as intraperitoneal tumor model: correlation between tumor growth and monoclonal antibody production. Murine B-cell hybridoma cells producing an immunoglobulin G1 (K13), specific for human immunoglobulin kappa chains were inoculated intraperitoneally in mice. After intraperitoneal injection of 10(6) K13 hybridoma cells, superficial intraperitoneal implants and ascites developed, resulting in death after 10 +/- 3 days (mean +/- SD). An immunoradiometric assay was developed to measure K13 in murine blood, ascites and culture supernatant. The assay utilized polymer beads coated with human immunoglobulin G. The amount K13 bound to the particles was measured with a 125I-labelled monoclonal rat antibody (LO-MG1-13) specific for mouse IgG1. The assay could be used over a wide working range (2-500 micrograms/l). Kinetic studies suggested that about 10(5) secreting cells were required for detection of K13 in blood. After injection of 10(6) cells, K13 was measurable in blood 1 day later in all animals. Nine of 33 mice injected with 10(5) or less cells survived, and initially showed rising K13 blood levels followed by decreasing blood levels. In conclusion, a close relationship was established between i.p. growth of the hybridoma K13 cell line and the MAb blood levels. The basic concepts of this assay can readily be adopted for other clones with the limitation that pure antigen is needed for solid phase extraction of the MAb from mouse blood.


Monoclonal antibodies specific to sailfish serum albumin: development of an assay for the identification of fish species in the field. Balb/c mice were immunized with albumin purified from sailfish (Istiophorus albicans) serum. Hybridomas were produced and screened by ELISA for reactivity with the purified albumins of sailfish, blue marlin (Makaira nigricans) and white marlin (Tetrapturus albidus). Monoclonal antibodies (MAbs) from 16 different clones exhibited activity against sailfish albumin. Thirteen of the MAbs showed cross-reactivity with the marlin species. Three MAbs exhibited distinct specificity for sailfish albumin. One of these species specific MAbs (M2D1) was conjugated to horseradish peroxidase (HRP) in order to construct an ELISA for identification of sailfish from serum. The ELISA for sailfish correctly identified eight sailfish from 26 billfish serum samples. The MAb-peroxidase conjugate was highly specific toward sailfish in that no reaction against heterologous species was detected.