[Surgery for laryngeal stenosis in infants in liable in case of failure to produce a worse condition resulting on a definitive disability (author's transl)]. The proper treatment for these stenosis is the "evolutive calibrage" which takes advantage of the normal growth of the larynx with no risk of aggravation.


[Management of sialorrhea in mentally retarded children by salivary denervation (6 cases) (author's transl)]. Sialorrhea in mentally handicapped children makes rehabilitation difficult and may provoke dyspneic spells. We have interrupted in 6 cases the parasympathetic innervation to the major salivary glands by a bilateral intratympanic neurectomy of Jacobson's nerve and chorda tympani. Results were satisfactory in 2/3 of cases.


[Cochlear mechanics: new experimental data (author's transl)]. The goal of this research is to confirm or disprove the presently accepted theories concerning the cochlear mechanism using: -- enlarged mechanical models of the cochlea, reproducing the known anatomy as accurately as possible, -- true sinusoidal stimuli or transient, -- objective documents (photographs and films).


[The origin of acoustic neurionoma. An ultrastructural study of operated neurinoma incipiens (author's transl)]. The origin of eighth nerve neurinoma has been studied by several authors with the light microscope, particularly on serial sections of decalcified temporal bone. The microsurgical approach of small neurinomas has led the present authors to an ultrastructural study of this problem. In the cases in which the origin could be seen, the tumor appeared to arise from the ganglion vestibulare (Scarpae). This fact is correlated with the neural crest origin of the ganglion, and with its ultrastructural characteristics in the normal human.


[The treatment of sub-glottic stenosis by continuous dilatation. Long term results (author's transl)]. From 1973 to 1977, 15 patients with laryngeal stenosis were treated by a method of continuous dilatation in the ENT department of the "Enfants Malades" Hospital. The results were viewed with regard to the importance of the complications, the chance of decanulation, the carrying time of the canula, adaptation to effort, functional respiratory tests, the value of language, intellectual and psychic repercussions, and repercussions on the social life. In this series the method of dilatation seems remarkably reliable.


[Effects of neurectomy of the tympanic plexus on secretion of the parotid gland in man. Histopathological, histochemical and clinical study (author's transl)]. This study involved five patients suffering from bilateral chronic parotiditis and then with a persistent unilateral fistula of the parotid gland. Two types of parotid biopsy were examined: the first taken during surgery and the second six months later. All of the specimens underwent histopathological and histochemical investigations. Definitive degeneration and atrophic type changes were seen in all the parotid fragments removed six months after selective neurectomy of the tympanic plexus. Six months after surgery, all of the patients were cured.


[Immediate improvement in facial paralysis after surgical decompression (author's transl)]. 17 cases of severe facial paralysis were studied before and after microsurgical decompression, by quantitative electromyography (electromyogram integrated in volts) at the site of the zyogmatic arch. -- In 76% of cases, no significant improvement was measured. -- An immediate, frank improvement occurred infrequently (12%), was short-lived and did not have any influence on the final result.


[Auricular tuberculosis with regressive facial palsy after surgical intervention (author's transl)]. The authors have observed the complete regression of a facial palsy in a tuberculous otitis by precocious decompression of the nerve and anti-tuberculous medical treatment.


[Medullary carcinoma of the thyroid (author's transl)]. Medullary carcinoma of the thyroid develops in the parafollicular C cells, the origin of which is in the neural crest. It is characterized clinically by the presence of motor diarrhea, vasomotor attacks, and immunologically by the presence of an amyloid stroma and the appearance of an anaplastic carcinoma. It is frequently associated with a pheochromocytoma (Sipple's syndrome), parathyroid adenomas and cytaneo mucosal manifestations (phacomatosis, multiple mucosal neuromas). The C cells may secrete thyrocalcitonin and the estimation of the substance may be sometimes used in pre-operative diagnosis and, above all, subsequent observation and examination for the presence of metastases. Treatment is based upon surgery (total thyroidectomy) with lymphnode dissection. Complementary treatment (radiotherapy, chemotherapy, opotherapy) is given only when surgery is inedequate or recurrences occur.


[Surgery of the facial nerve (author's transl)]. The indication of facial nerve surgery are wider than currently believed. The incision of the fibrous sheath, the suture termino-terminal, the nervous graft even very long, the hypoglosso anastomosis give all better results than all other surgical technics. The potentiality of nervous regeneration exist in old people and after very long delay.


Cellular immunity in patients with laryngeal cancer developing additional primary malignant tumors. Eleven patients with laryngeal cancer associated with additional primary tumors underwent cutaneous delayed hypersensitivity tests and lymphocyte stimulation studies with phytohemagglutinin for evaluation of their cellular immunity. Five of the 11 patients were anergic or hypoergic as shown by skin tests to recall antigens and seven of nine patients had impaired lymphocyte transformation. Depressed immunity was more often observed in patients with an active malignancy. The level of serum immunoglobulins was elevated in two of eight studied patients, and in the remaining patients was within the normal range. All patients had a history of excessive smoking. Most frequently, second tumors were found in the lung, urinary tract and skin. The prognosis seemed to be determined by the additional tumor rather than by the laryngeal cancer.


Juvenile fibromatosis.

Juvenile fibromatosis. Juvenile fibromatosis is a benign lesion with locally aggressive characteristics. Wide surgical excision is the treatment of choice. Radiation therapy can be used for inoperable cases or as adjunctive therapy. Steroid therapy has not been used extensively and deserves further evaluation. In the head and neck area, juvenile fibromatosis must be very carefully diagnosed and treated due to the serious consequences that result from inadequate control.


Width of the internal auditory canal. A histological study. Vertical and horizontal measurements were made of the widths of the internal auditory canals of 435 histologically prepared temporal bones. The mean vertical width, measured at the porus acusticus, was 3.68 mm (range 2.10 to 5.26 mm), and the mean horizontal width, measured in the middle region of the canal, was 3.72 mm (range 2 to 5.8 mm). The 144 ears selected for study because they exhibited slowly progressive sensorineural hearing loss showed a distribution of canal widths similar to that of the group as a whole. Histological examination of the internal auditory canals failed to show any type of soft tissue lesion which might have contributed to narrowing of the canals. The study provides no anatomical or histological evidence for the existence of a small internal auditory canal syndrome.


Nasal hemangioma of pregnancy.

Nasal hemangioma of pregnancy. The nasal hemangioma of pregnancy is an uncommon but impressive cause of epistaxis. One patient with this condition recently treated at the Keller Army Hospital, West Point, exemplifies the problems encountered in the diagnosis and treatment of this puzzling disorder.


Necrotizing sialometaplasia of the nasopharynx. Necrotizing sialometaplasia is an uncommon salivary gland disease originally described by Abrams et al in 1973. The disease may occur wherever salivary gland tissue is found. Theories on the etiology of this disorder have been advanced, but never definitely determined. Treatment consists of adequate biopsy and observation until healing occurs at six to eight weeks. While the disease is considered benign, its similarity to more aggressive neoplasms can be both disturbing and misleading to the patient and the clinician. Such a case of necrotizing sialometaplasia of the nasopharynx is presented to demonstrate the clinical and histological similarity of this disease to carcinoma. In this case, the patient first presented with a neck mass which could easily have been mistaken for a regional metastasis. The current literature is reviewed.


Cochlear and brain stem responses in hearing loss following neonatal hyperbilirubinemia. The site of lesion in hearing loss following neonatal hyperbilirubinemia is unclear. Histopathological studies have implicated the brain stem auditory nuclei while other investigations have hinted at a lesion in the cochlea. In order to clarify this issue, attempts were made to record responses from the auditory pathway in 13 patients with hearing loss following neonatal hyperbilirubinemia. The neural response from the auditory nerve was absent in 11 of the 13 patients and present only in response to high intensity stimuli in 2 patients. However, the response of the cochlear hair cells (cochlear microphonic potential) was present in 9 of the 13 patients. In most other cases of sensorineural hearing loss, with no history of hyperbilirubinemia, the hair cell response was absent. This is functional evidence for auditory nerve damage in cases of hearing loss following neonatal hyperbilirubinemia while the hair cells are spared.


Congenital cerebrospinal otorrhea.

Congenital cerebrospinal otorrhea. Four locations for congenital cerebrospinal fluid fistula in the region of a normal labyrinth are reviewed. A congenital leak may occur through the petromastoid canal, a wide cochlear aqueduct, Hyrtl's fissure, or the facial canal. A fistula through the initial segment of the fallopian canal was successfully repaired in a two-year-old boy who had three episodes of meningitis following otitis media. Knowledge of these four sites of congenital defects provides a guideline for the surgeon in the identification and repair of cerebrospinal fluid leaks in the region of the labyrinth.


Fibrinolytic activity in patients with acute tonsillitis. Three parameters in blood fibrinolysis, viz, the levels of fibrinogen, plasminogen, and fibrinogen and/or fibrin degradation products (FDP), were measured in patients with acute tonsillitis and the results were compared with those for healthy adults. The fibrinogen content in acute tonsillitis increased significantly (P less than .001), that of plasminogen decreased significantly (P less than .005), while FDP showed a higher value (P less than .01). The significance of the fibrinolytic system in acute tonsillitis is discussed.


Anatomical effects of sudden middle ear pressure changes. Acute middle ear (ME) and inner ear changes following brief unilateral phasic ME pressure changes (up to +/- 6000/mm H2O) were studied in the guinea pig. Middle ear findings included perforation of the tympanic membrane, serous and serosanguinous exudate and hemorrhage of tympanic membrane and periosteal vessels. Changes were related to magnitude of applied pressure. Perforation and hemorrhage were more commonly seen with negative rather than positive pressure. Air bubbles behind the round window were seen with positive pressures. Occasional distortion, but never perforation of the round window, was noted. Hemorrhage of the scala tympani was observed with both positive and negative pressures; scala vestibuli hemorrhage was found with negative ME pressure. In some instances pressure direction and magnitude related changes were seen in the contralateral ear.


Median palatal cyst. A reminder of palate fusion. The existence of a median palatal cyst has been questioned. Such a lesion would represent an unusual anomaly of a unique embryological process. The radiologic and pathologic criteria necessary to establish such a diagnosis are inconclusive in the ten case reports that have appeared in the English language literature. A median palatal cyst that is distinct from other palatal defects would have specific characteristics that included: 1) a true epithelial-lined cyst; 2) no salivary gland, vascular, or neural elements in the cyst wall; and 3) location in the palate at a distance sufficiently posterior to avoid confusion with structures of the nasal palatine region. We report the findings of a palate lesion excised from a 27-year-old male which by location and histology were consistent only with a median palatal cyst. These data appear to authenticate, for the first time, the median palatal cyst as a distinct pathological entity.


Surgical anatomy of the orbit.

Surgical anatomy of the orbit. When operating in and around the orbit, the key to a successful operative result is precise, anatomic localization. This study was constructed to give pertinent anatomic measurements to which the maxillofacial surgeon may refer. The safe distances noted from this study are: 1) medially 30 mm from the anterior lacrimal crest; 2) inferiorly 25 mm from the infraorbital foramen; 3) superiorly 30 mm from the supraorbital notch; and 4) laterally 25 mm from the frontozygomatic suture.


A simple micromethod for 25-hydroxyvitamin D estimation. A quick and simple method for estimating 25-hydroxyvitamin D is described, It involves dichloromethane extraction followed by competitive protein-binding assay without chromatography. This assay can be performed on 100 microliter of serum and enables 50 samples to be estimated in one working day. The simplicity, speed, and sample size of this method make it very suitable for use in a routine clinical biochemistry laboratory. It is particularly useful when calcium disorders secondary to abnormalities in vitamin D intake and metabolism are suspected.


Screening for Cushing's syndrome using early morning urine samples. Urinary free 11-hydroxycorticosteroid/creatinine ratios (UFC/Cr)were determined in early morning urine samples from 138 obese subjects attending endocrine clinics in the Glasgow area. The majority of patients (128) had UFC/Cr ratios within the normal range for non-obese subjects (5-55 mumol/mol). Of those with elevated UFC/Cr ratios, further investigations of the hypothalamic-pituitary-adrenal axis confirmed a diagnosis of Cushing's syndrome due to bilateral adrenal hyperplasia in six of the cases and adrenal tumours in a further two patients. In the remaining two patients there was evidence of intermittent adrenal hyperactivity with inconsistent responses to insulin-induced hypoglycaemia tests.


Re-examination of effect of paracetamol on serum uric acid measured by phosphotungstic acid reduction. The drug paracetamol (N-acetyl-p-aminophenol; acetaminophen) caused a spurious increase in serum uric acid measured by phosphotungstic acid reduction methods. However, the increase was less than 0.12 mmol/1 at plasma levels of paracetamol found in overdosage (40 mg/100 ml) and was small at therapeutic concentrations (less than 4 mg/100 ml). It is concluded that few patients with joint pain who have taken paracetamol paracetamol as an analgesic will have clinically misleading values for serum uric acid.


Extracranial meningioma.

Extracranial meningioma. A patient is presented with findings of separate intracranial and extracranial meningiomas, each of a different histologic type. A calcified fibrous meningioma, with secondary psammomatous features, presented as a left neck mass associated with hoarseness, dysphagia, a unilateral facial weakness and hearing loss. A noncalcified asymptomatic intracranial syncytial meningioma was discovered in the left frontal lobe after computerized tomographic and angiographic study of the cranial contents. The origin of the extracranial meningioma producing multiple unilateralcranial nerve disturbances and serous otitis media is discussed. The noncontiguous tumors in this patients are felt to have separate origins, with the extracranial lesion most likely arising in the temporal bone.


Inhibition of labyrinthine nystagmus by visual fixation: effects of ablation of visual cortex and superior colliculi. A study was conducted to destroy two specific areas of the cat's visual system in order to determine if these lesions would affect the visual inhibition of calorically-induced vestibular nystagmus. The occipital visual cortex was removed in eight cats and the superior colliculi were removed bilaterally in nine cats. Postoperative vestibular testing revealed no significant change in the electronystagmography tracings and response to visual fixation. These findings suggest that, in cats, the visual inhibition of labyrinthine nystagmus is not dependent upon the integrity of the visual cortex or superior colliculi. The hypothesis is brought forward that the visual inhibition of the vestibular nystagmus is merely a reflex of the brain stem to light stimulus, mediated via the cerebellum.


Classification of tumors of the ovary: developmental and ultrastructural considerations. The classification of ovarian tumors presents a difficult problem because of the great variety of tumor types that can occur. The complex structure of the normal ovary and the diversity of cell types present at different stages of development contribute to this difficulty. Developmental and ultrastructural studies have helped to clarify the problem by indicating specific cell types that correspond directly with the major tumor categories. Tumors may thus be grouped as being of epithelial, germ cell or sex cord stromal origin. The ultrastructural features of tumors in the different categories indicate common characteristics shared with corresponding cell types in the developing ovary. The findings clearly support a histogenetic approach in the classification of ovarian tumors.


Measurement of thyroglobulin in the circulation: clinical and technical considerations. The concentration of thyroglobulin (TG) in the circulation can be measured by a sensitive, specific, convenient radioimmunoassay. TG is found in the circulation of virtually all normal subjects. It is present in elevated concentrations in patients with a wide variety of thyroid diseases including benign and malignant tumors, multinodular goiter, subacute thyroiditis, Graves' disease and others. At the present time, the most important clinical role of TG measurements is in the evaluation of patients who have been treated for thyroid cancer. As greater clinical correlation is obtained, the usefulness of TG determinations will increase. Anti-TG autoantibodies cause false results in the assay and present the major technical problem which needs to be resolved.


Voluntary motor commands in human ballistic movements. The integrated electromyogram of the first dorsal interosseous muscle in normal humans presents a brief early burst in voluntary ballistic abduction of the index finger. Unexpected decrease in torque load does not change the burst. By contrast, in fast ramp abduction with a time-to-peak of 0.5 second, the electromyographic activity is fairly continuous up to the peak displacement, and it is silenced with a delay of 50 msec by unexpected unloading. Thus fast ramp, but not ballistic, voluntary contractions are under current long loop control from proprioceptive input. In a second set of experiments, the analysis of single motor unit potentials with highly selective electrodes in interosseous muscle indicated that ballistic thresholds are smaller than ramp thresholds under either isotonic or isometric conditions. However, the recruitment rank of the motor units was identical in finger abductions carried out in either ramp or ballistic modes.


Carcinogen activation by human uterine enzymes. Three topics are briefly reviewed relating to carcinogenesis of estrogen responsive tissues: (a) enzymology of benzo(a)pyrene activation by human tissues, (b) microsomal activation of estrogens to estrogen arene oxides and (c) estrogen and progesterone receptor studies in endometrial carcinoma. The following working hypothesis is stated on the etiology of gynecologic tumors: "Environmental chemicals, such as cigarette smoke, polycyclic and polyhalogenated hydrocarbons, etc., induce special forms of cytochrome P-450 monooxygenase and related enzyme systems which can activate endogenous or prescribed estrogens and non-steroid antiestrogens to act as initiators and/or promoters of neoplasia in estrogen-dependent organs." The role of estrogen receptors is perceived as a homing device or cellular "Trojan Horse" for these activated estrogens.


Single-dose pharmacokinetics and anticonvulsant efficacy of primidone in mice. The pharmacokinetics and efficacy of the anticonvulsant primidone (PRM) and its active metabolites, phenobarbital (PB) and phenylethylmalonamide (PEMA), were studied after single-dose administration in mice. The half-life of PB is twice that of PRM and PEMA. The plasma/brain ratios provide evidence of poor penetration of PRM into brain. The results support our findings of negligible or absent PRM concentrations in the brains of patients on primidone therapy who were undergoing surgery for intractable epilepsy. The anticonvulsant properties of PRM, PB, and PEMA against maximal electroshock in mice were also studied with the use of the metabolic inhibitor SKF 525A. The half-life, potency, peak anticonvulsant effect, and effective dose curves of these compounds indicate that the anticonvulsant effect of short-term oral PRM administration in mice is from derived PB.


Performance evaluation of a blood gas system in a central and satellite laboratory. In many hospitals blood gases are performed in several laboratories. It is important to establish that values obtained in all laboratories are identical and that the same quality control program is used. Evaluation of the performance of blood gas apparatus has been made in two of our laboratories. Result reproducibility was assessed by means of gas analyzer system control. Measurements were made in duplicate of patients' specimens in the same instrument and duplicate measurements of patient samples with both instruments. A13 day evaluation using this system was carried out in both laboratories during all shifts and showed excellent agreement with the manufacturer's reported values. The combined standard deviation for pH at all levels was 0.009,pCO2 -0.83 mmHg and pO2 - 3.9 mmHg. Patients' samples analyzed in the same instrument showed an absolute average difference between duplicates for pH of 0.003, pCO2 - 0.62 mmHg and pO2 -0.87 mmHg. The comparison of duplicate samples in the two instruments in the different laboratories showed an absolute average difference for pH of 0.009,pCO2-1.7mmHg and pO2 - 1.6 mmHg.


New kinetic procedure for the measurement of conjugated bilirubin with a centrifugal analyzer. A procedure has been developed for the automated measurement of conjugated bilirubin in serum with a centrifugal analyzer. The conjugated bilirubin is measured by a fixed time kinetic method which monitors the reaction between conjugated bilirubin and diazotized sulfanilic acid at 550 nm. Results are calculated based on a comparison of the reagent blank-corrected absorbance changes between 15 seconds and 75 seconds for sample vs changes in an empirical standard. The standard used is N-(1-naphthyl) ethylene diamine dihydrochloride (NEDC) which reacts with diazotized sulfanilic acid at a rate comparable to conjugated bilirubin. The standard is calibrated by comparison with a modified Jendrassik and Grof procedure using a serum blank-corrected centrifugal analyzer reference method. The method is linear to 150 mg per 1 with a sensitivity of 3.0 milliabsorbance units per 1.0 mg per 1 of conjugated bilirubin using a 35 mul sample volume. Within-run precision is 1 percent for elevated concentrations of bilirubin. Hemolysis introduces a negative interference, the nature of which is discussed.


Estrogen receptors and tumor associated antigens in breast cancer. The  methods of performing estrogen and progesterone receptors and the role of receptors in the management of the patient with breast cancer are reviewed. Quality control of the assays and concentrations of receptor protein in normal tissues is emphasized as is the possible relationship of estrogen receptor protein to carcinoembryonic antigen.


Progressive myelopathy due to extramedullary hematopoiesis: case report and review of the literature. Extramedullary hematopoiesis (EMH) in the spinal epidural space is a rare but treatable cause of progressive paraparesis in patients with a variety of hematological and systemic disorders. We report a case of extensive thoracic epidural EMH causing progressive spastic paraparesis in a patient with agnogenic myeloid metaplasia. The literature describes 11 additional cases of myelopathy due to epidural EMH. All patients had EMH in the midthoracic region with elevated cerebrospinal fluid protein and abnormal spine roentgenograms or myelograms. Treatment with decompressive laminectomy, radiation therapy, or both, resulted in marked or complete recovery in 7 of 10 patients. Patients who develop paraparesis and who have a disorder associated with EMH should be evaluated rapidly for this treatable condition.


[Pathways of enzymatic inactivation of levomycetin in El Tor vibrios with plasmid and chromosome resistance to the antibiotic]. Two possible mechanisms of enzymatic inactivation of levomycetin, i.e. acetylation of OH-groups and reduction of the n-nitrophenylic component by the cells and cell-free extracts of V. eltor 2044 with the plasmid or chromosome types of antibiotic resistance were studied in vitro. The vibrio containing the extrachromosome determinants were resistant to a number of antibiotics. The rate of levomycetin acetylation by them under conditions of intensive aeration and reduction of the antibiotic aromatic nitrogroup in the absence of oxygen was high. The cells with the chromosome resistance had a trace activity of levomycetin acetyltransferase. Still, they rather rapidly reduced levomycetin into its aminoderivative (during 2-hour incubation in the atmosphere of nitrogen 70-80% of the substrate are transformed into its summary arylamine). The antibiotic sensitive vibrio practically had no capacity for acetylation of levomycetin but could transform it into the reduced aminoderivative though to a less extent than the antibiotic resistant cells.


Comparison of anaerobic susceptibility results obtained by different methods. Susceptibility tests using 7 antimicrobial agents (carbenicillin, chloramphenicol, clindamycin, penicillin, cephalothin, metronidazole, and tetracycline) were run against 35 anaerobes including Bacteroides fragilis (17), other gram-negative bacilli (7), clostridia (5), peptococci (4), and eubacteria (2). Results in triplicate obtained by the microbroth dilution method and the aerobic modification of the broth disk method were compared with those obtained with an agar dilution method using Wilkins-Chalgren agar. Media used in the microbroth dilution method included Wilkins-Chalgren broth, brain heart infusion broth, brucella broth, tryptic soy broth, thioglycolate broth, and Schaedler's broth. A result differing by more than one dilution from the Wilkins-Chalgren agar result was considered a discrepancy, and when there was a change in susceptibility status this was termed a significant discrepancy. The microbroth dilution method using Wilkins-Chalgren broth and thioglycolate broth produced the fewest total discrepancies (22 and 24, respectively), and Wilkins-Chalgren broth, thioglycolate, and Schaedler's broth had the fewest significant discrepancies (6, 5, and 5, respectively). With the broth disk method, there were 15 significant discrepancies, although half of these were with tetracycline, which was the antimicrobial agent associated with the highest number of significant discrepancies (33), considering all of the test methods and media.


Avermectins, new family of potent anthelmintic agents: producing organism and fermentation. The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named Streptomyces avermitilis. The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode Nematospiroides dubius when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 mug/ml.


Avermectins, new family of potent anthelmintic agents: isolation and chromatographic properties. The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of Streptomyces avermitilis. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components. A reverse-phase high-pressure liquid chromatography assay for the quantitative determination of all components was used extensively to monitor the purification methods.


Avermectins, new family of potent anthelmintic agents: efficacy of the B1a component. When given to sheep as a single oral dose at 0.1 mg/kg, the B(1a) component of the avermectins caused a reduction of >95% in the numbers of Haemonchus contortus, Ostertagia circumcincta (including inhibited L(4) larvae), Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora, and Oesophagostomum columbianum. When given to cattle as a single oral dose at 0.1 mg/kg, avermectin B(1a) was >95% effective in reducing the numbers of Haemonchus placei, Ostertagia ostertagi (including inhibited L(4) larvae), T. axei, T. colubriformis, C. oncophora, Cooperia punctata, Oesophagostomum radiatum, and Dictyocaulus viviparus. Avermectin B(1a) was similarly effective, with the exception of a detectable loss in activity against adult C. oncophora, when administered to cattle as a parenteral injection. Some of these ruminant parasites were fully susceptible to dosages of avermectin B(1a) at 0.025 mg/kg, e.g., D. viviparus, O. radiatum, O. ostertagi, and H. contortus. Avermectin B(1a) removed 83 to 100% of Ancylostoma caninum from dogs given a single oral dose of 0.003 to 0.005 mg/kg. The poultry nematodes Capillaria obsignata and immature Ascaridia galli were effectively removed by avermectin B(1a) at 0.05 and 0.1 mg/kg, respectively, but 0.1 mg/kg was not effective for Heterakis gallinarum. Thus, the avermectins would appear to have unprecedented potency and spectrum of biological activity.


Quantitative nasal cultures from carriers of Staphylococcus aureus: effects of oral therapy with erythromycin, rosamicin, and placebo. Serial quantitative nasal cultures were performed on 87 healthy nasal carriers of Staphylococcus aureus, who were randomly assigned to 7 days of oral therapy with erythromycin, rosamicin (an investigational macrolide antibiotic), or placebo. Staphylococcal carrier rates decreased during therapy with both antibiotics; however, erythromycin was significantly more effective in lowering carrier rates than was rosamicin. The anti-staphylococcal effects of both antibiotics were similar when the mean numbers of S. aureus isolated from positive cultures during therapy were compared. Side effects to each regimen were minimal.


Antibiotic action of N-methylthioformohydroxamate metal complexes. The antibiotic activity of metal complexes of N-methylthioformohydroxamic acid against gram-negative Escherichia coli NIHJ and gram-positive Staphylococcus aureus 209P was investigated. The kinetically labile, square-planar, divalent (Cu, Ni, and Pd) and octahedral, trivalent (Fe, Co, and Cr) complexes displayed activity, whereas the more inert platinum(II) or rhodium(III) complex displayed no activity, or activity only at elevated concentrations. The free ligand did not suppress the growth of the above organisms, and the sulfur atom of the ligand in its metal complexes appears crucial for activity. Uptake studies of radioactively labeled N-methylthioformohydroxamic acid, its nickel(II), platinum(II), iron(III), and rhodium(III) complexes were conducted in the Escherichia coli K-12 RW193 mutant, which is defective in the production of its native iron(III) transport agent, enterobactin. Uptake of (55)Fe or (63)Ni label from their metal complexes appeared to occur as free inorganic metal ions. The antibiotic activity of the iron(III) and nickel(II) complexes was not due merely to an enhanced accumulation of metal ions by the cell. Metal complexes of [(35)S]N-methylthioformohydroxamic acid enhanced the accumulation of (35)S label compared to that of the free ligand. The antibiotic activity and uptake data are discussed in terms of possible modes of action.


In vitro activity of 39 antimicrobial agents against Treponema hyodysenteriae. The in vitro activities of 39 antimicrobial agents against 23 isolates of Treponema hyodysenteriae, the majority of which were field isolates, were determined by the agar dilution technique. Quinoxalines, pleuromutilin, nitroimidazoles, and nitrofuran were the most active. Their activities ranged from </=0.10 to 1.56 mug/ml. Lincomycin, penicillins, chloramphenicol, tetracyclines, cephalosporins, three peptides (virginiamycin, thiopeptin, and bacitracin), and one aminoglycoside (gentamicin) exhibited intermediate levels of activity ranging from 0.39 to 50 mug/ml. Four peptides (enduracidin, viomycin, bicyclomycin, and colistin), three aminoglycosides (kanamycin, streptomycin, and neomycin), polyene, and other agents, including novobiocin, vancomycin, rifampin, nalidixic acid, and p-arsanilic acid, displayed limited activities ranging from 12.5 to >/=100 mug/ml. Macrolides showed varying degrees of activity depending upon isolates.


Interpretation of the disk diffusion susceptibility test for amikacin: report of a collaborative study. Because excessively high rates of false resistance have been encountered with the 10-mug amikacin disk in diffusion susceptibility tests, a study was performed to examine existing zone diameter interpretative criteria and to compare the accuracy of 10- and 30-mug amikacin disks by the error rate-bounded classification scheme. Although current zone diameter interpretative criteria eliminate false susceptibles, there is an unacceptably high rate of false resistants. This problem can be resolved in most instances by revising the zone diameter interpretative criteria for the 10-mug disk (resistant, </=9 mm; indeterminate, 10 to 11 mm; susceptible, >/=12 mm) or, preferably, by replacing the 10-mug disk with a 30-mug disk and adopting new interpretative criteria (resistant, </=14 mm; indeterminate, 15 to 16 mm; susceptible, >/=17 mm). Because of significant differences in performance among media, it is necessary to include Pseudomonas aeruginosa ATCC 27853 among controls routinely tested and to exclude from use lots of Mueller-Hinton agar yielding results outside the 75% tolerance (90% confidence) limits for amikacin.


In vitro evaluation of seven cationic detergents as antiplaque agents. The bactericidal efficacy of seven cationic detergents was studied in vitro against intact performed plaques of representative strains of four oral dental plaque-forming microorganisms: Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus, and Actinomyces naeslundii. Both absolute (plaque bactericidal index) and relative (chlorhexidine coefficient) indexes of antiplaque activity were established. Only cetyltrimethylammonium bromide was more efficacious than the reference agent, the bisbiguanide chlorhexidine, for the apparently more potent tooth-adherent cariogenic and periodontopathic elements, respectively, of the in vivo plaque microflora, S. mutans and A. viscosus.


Large-scale production and concentration of human lymphoid interferon. A stable and predictable production system is described for pilot plant quantities (milligram) of human lymphoid interferon, using suspension culture of an African Burkitt's lymphoma derived cell line Namalva with induction by Newcastle disease virus, B-1 strain. Cell cultures were grown in impeller-driven 50-liter fermentors with dilution of the postinduction culture using serum-free medium. High levels of dissolved oxygen were necessary for optimum cell growth. A total of 4,207 liters of interferon culture was produced in a series of 116 fermentor runs. An average yield of 3.5 log(10) international units of interferon per ml was realized before processing. Trichloroacetic acid was used to precipitate the interferon. An average of 3.35 log(10) international units of interferon per ml was recovered in the final nonpurified product.


Purification of a streptococcal bacteriocin (viridin B) and its separation from alpha-hemolysin. Viridin B, a bacteriocin produced by Streptococcus mitis, copurified with the alpha-hemolysin after ammonium sulfate precipitation and gel filtration on Sephadex G-200. The bacteriocin and hemolysin were separated in some instances by ion-exchange chromatography on diethylaminoethyl-Sephadex A-50, but the two substances were shown to be distinct after polyacrylamide gel electrophoresis. Attempts at recovery of nonhemolytic or nonbacteriocinogenic mutants were unsuccessful after exposure to mutagenic agents. The molecular weight of viridin B was determined to be approximately 87,000.


Antibiotic susceptibility of Streptococcus mutans: comparison of serotype profiles. A total of 82 strains of Streptococcus mutans representing serotypes a through g were tested for susceptibility to erythromycin, penicillin, methicillin, lincomycin, tetracycline, vancomycin, gentamicin, streptomycin, neomycin, kanamycin, bacitracin, and polymyxin B. Strains included stock cultures and isolates from human and animal dental plaque. Minimal inhibitory concentrations were determined by a broth-microdilution procedure. The major differences in antibiotic susceptibility observed among the serotypes resulted with antibiotics which act on the cell surface. Bacitracin was most active against serotype a strains and polymyxin B against serotype b strains. Serotypes a, d, and g were less susceptible than the other serotypes to methicillin.


Clinical pharmacology of intravenously administered trimethoprim-sulfamethoxazole. Pharmacokinetic studies of intravenously administered trimethoprim-sulfamethoxazole (TMP-SMX) were conducted in 11 patients with cancer while they received therapy with this drug combination for infection. Each patient received 160 mg of TMP and 800 mg of SMX every 8 h. The highest plasma concentrations of both agents were attained at the end of a 1-h infusion period, and the levels were maintained above 38 mug of free SMX and 2 mug of TMP per ml for 2 to 4 h on day 1. On day 4, these concentrations were exceeded at all time intervals of blood sampling. High concentrations of TMP and free SMX were recovered in the urine during the 8-h period. The plasma half-lives of TMP and free SMX, as determined during the first 8-h period, were 7.6 and 8.6 h, respectively. Compared with SMX, TMP had an approximately 2.5 times higher volume of distribution. This drug combination was well tolerated by the patients and unaccompanied by drug-related toxicity.


Role of vancomycin as a component of oral nonabsorbable antibiotics for microbial suppression in leukemic patients. A total of 38 adult patients with acute leukemia who were undergoing remission induction chemotherapy in regular patient rooms were randomly allocated to one of two oral nonabsorbable antibiotic regimens for infection prophylaxis (gentamicin, vancomycin, and nystatin [GVN] or gentamicin and nystatin [GN]) to evaluate whether vancomycin was a necessary component. The patient population in both groups were comparable. Tolerance to GVN was less than GN but compliance was approximately equal (>85% in both groups). Patients receiving vancomycin demonstrated greater overall alimentary tract microbial suppression; however, acquisition of potential pathogens was approximately equal in both groups. The incidence of bacteremia, as well as the overall incidence of infection as related to the number of days at various granulocyte levels, was also approximately equal in both groups. Group D Streptococcus species were poorly suppressed by GN compared with GVN, although no patient developed an infection with these organisms. Colonization by newly acquired gram-negative bacilli was significantly less in the GN group (GN, 3 colonizations; GVN, 13 colonizations; P < 0.01). It is concluded that vancomycin may be safely eliminated from the GVN regimen provided microbiological data is monitored to detect resistant organisms.


Photochemical inactivation of deoxyribonucleic and ribonucleic acid viruses by chlorpromazine. Chlorpromazine, a widely used tranquilizing drug of the phenothiazine group, was found to be a very potent photochemical inactivator of both deoxyribonucleic acid and ribonucleic acid viruses in the presence of long-wave ultraviolet light (320 to 380 nm). Neither the light alone nor chlorpromazine alone caused any appreciable inactivation. The known chlorpromazine photoreactions with nucleic acids are somewhat similar to those of psoralen (furocoumarin) derivatives. As in the case of the psoralens, chlorpromazine is capable of photoinactivating viruses totally within a few minutes under near-physiological or other gentle conditions. The antiviral effects of the chlorpromazine photoreaction could make it valuable for the development of inactivated viral vaccines as well as for use in the photochemotherapy of viral dermatoses.


Influence of probenecid on serum levels and urinary excretion of cinoxacin. Serum levels and urinary excretion of cinoxacin were examined in healthy individuals after a two-step intravenous infusion in the presence and absence of probenecid. After dosing cinoxacin alone, steady-state serum levels were approached in 1 h and were maintained for an additional 2 h with a reduced infusion rate. After probenecid pretreatment, serum levels of cinoxacin continued to increase during 3 h of infusion, reaching levels approximately double those obtained with cinoxacin alone. The mean elimination half-life of cinoxacin from serum was increased from 1.3 to 3.5 h in the presence of probenecid, and renal clearance was significantly reduced, with 46% of dosed drug appearing in 7-h urines of probenecid-treated subjects compared with 68% in subjects receiving cinoxacin alone. Probenecid had no apparent influence on cinoxacin distribution in the body but caused a significant decrease in the rate of cinoxacin extrarenal elimination, possibly due to competition for a common metabolic pathway.


Comparison of microdilution and broth dilution techniques for the susceptibility testing of yeasts to 5-fluorocytosine and amphotericin B. Microdilution and broth dilution techniques were compared for the susceptibility testing of 50 clinical yeast isolates to 5-fluorocytosine and amphotericin B. Good correlation between methods was obtained with all isolates except Cryptococcus neoformans.


Pitfalls in collecting blood specimens for antibiotic assay. Obtaining blood samples for antibiotic analysis from intravenous lines through which the antibiotic had been administered was critically evaluated. Flushing volumes required to remove contaminating antibiotic varied with the type of antibiotic and with different plastics. Obtaining blood specimens from the intravenous lines is not practical in infants and not advised in adults.


In vitro activity of mezlocillin and its related compounds against aerobic and anaerobic bacteria. A total of 900 clinical isolates of aerobic (462 isolates) and anaerobic (438 isolates) bacteria were tested against mezlocillin in comparison with other penicillins, and the aerobes were also tested against cephalothin, cefoxitin, and cefamandole. Among penicillins, mezlocillin was the most effective against Escherichia coli, Klebsiella pneumoniae, Salmonella species, Pseudomonas aeruginosa, and Bacteroides fragilis. Mezlocillin was more effective than cephalothin against Klebsiella pneumoniae.


High-pressure liquid chromatographic assay of chloramphenicol in biological fluids. Chloramphenicol can be assayed by a sensitive and selective high-pressure liquid chromatographic assay technique. The method described is easily adapted to analysis of many other drugs.


Antimicrobial susceptibilities of rough, smooth, and mucoid colony types of Pseudomonas isolated from cystic fibrosis patients. Minimal inhibitory concentrations of carbenicillin, chloramphenicol, tetracycline, gentamicin, tobramycin, and trimethoprim-sulfamethoxazole were determined for rough, smooth, and mucoid Pseudomonas sp. isolates from sputa collected from 40 cystic fibrosis patients. Ninety-four percent of the minimal inhibitory concentrations obtained by using mixed inocula of colonies of different morphological types fell within one serial dilution of the most resistant minimal inhibitory concentration obtained when each colony type was tested separately.


Dissociated resistance among cephalosporins. When disks containing cefuroxime (CXM) or HR 756 (756) were placed next to cefoxitin (FOX) on plates inoculated with Enterobacter resistant to FOX, there was marked flattening of the zones of inhibition produced by CXM or 756, but colonies growing near the CXM or 756 disks were found to be fully susceptible to these drugs on retesting. In contrast, when a checkerboard titration with CXM or 756 and FOX was done in broth, organisms growing in the presence of high concentrations of either of the former plus FOX were found to be resistant on retesting. Broth cultures of Enterobacter were found to contain small numbers of mutants which were resistant to and inactivated CXM and 756. Evidence is presented suggesting that the addition of FOX induces similar properties in the whole culture, which then becomes resistant to all of the nine cephalosporins tested and to four of six penicillins tested. Such cultures rapidly reverted to susceptible when FOX was removed or inactivated, and an explanation is offered as to why this did not happen in fluid media.


Purification, properties, and cytotoxic effect of a bacteriocin from Mycobacterium smegmatis. The bacteriocin produced by Mycobacterium smegmatis ATCC 14468 was isolated, and a study was made of its chemical, physical, and biological properties. No appreciable bacteriocin activity was found in the culture supernatant fluids, but it was released in appreciable quantities after disruption of the cells. The material was purified 49-fold by means of chromatography on diethylaminoethyl-cellulose, ammonium sulfate fractionation, gel filtration on Sephadex G-200, and chromatography on diethylaminoethyl-Sephadex A-50. Its molecular weight was determined to be approximately 75,000 from the elution profile on Sephadex G-200 chromatography. The bacteriocin was resistant to deoxyribonuclease, ribonuclease, lipase, ultraviolet irradiation, and freeze-thawing, whereas it was relatively less thermostable and was sensitive to proteolytic enzymes. The lethal effect of the bacteriocin was demonstrated by the decrease in viable counts of the bacteriocin-sensitive indicator strain, M. diernhoferi ATCC 19340. The bacteriocin preparation inhibited the growth of HeLa-S3 cells.


Bacampicillin, Ampicillin, Cephalothin, and Cephapirin levels in human blood and interstitial fluid. The diffusibility of bacampicillin, ampicillin, cephalothin, and cephapirin into human interstitial fluid was investigated by using crossover studies. We compared bacampicillin with ampicillin and found that bacampicillin was better absorbed after oral administration. Blood, interstitial fluid, and urine levels were consistently higher in volunteers who received bacampicillin. We compared cephalothin with cephapirin and found that blood and interstitial fluid levels were comparable throughout the study.


Sporulation and the production of serine protease and cephamycin C by Streptomyces lactamdurans. Streptomyces lactamdurans, producer of the antibiotic cephamycin C, excretes at least two proteases. Physiological studies indicate that antibiotic synthesis and serine protease formation are coordinately regulated. Both are produced only after culture growth ends, and they appear with essentially identical kinetics. In addition, strains which produce superior levels of cephamycin C form equally superior levels of the serine protease. Genetic evidence reveals that the syntheses of the antibiotic and serine proteases are associated with sporulation. Mutants which fail to produce aerial hyphae (bald mutants) also fail to synthesize the antibiotic and serine proteases.


Modification of the colorimetric assay for chloramphenicol in the presence of bilirubin. We recently found that bilirubin interferes with the colorimetric chloramphenicol assay of Kakemi et al. (K. T. Kakemi, T. Arita, and S. Ohashi, Yakugaku Zasshi 82:342-345, 1962). Levels of serum bilirubin alone (4 to 6 mg/dl) resulted in apparent concentrations of chloramphenicol which appear to be in the therapeutic range. Concentrations of serum bilirubin greater than 8 mg/dl resulted in levels of apparent chloramphenicol associated with toxicity (>50 mug/ml). Small amounts of activated charcoal added to the isoamyl acetate extraction step of the assay eliminated this interference by bilirubin.


Effect of pyran on latency after herpes simplex virus infections. The immunomodulator pyran protected mice against both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections. In infections of the lip with HSV-1, prophylactic administration of pyran reduced the severity of the herpetic lesions and enhanced their resolution, but did not decrease the high incidence of development of latent HSV-1 infection of the trigeminal ganglia. In vaginal infections with HSV-2, prophylactic administration of pyran either systemically or locally reduced mortality, reduced the incidence of mice with vaginal HSV-2 infection, and did not alter the low incidence of latent infection of the spinal dorsal root ganglia. Pyran treatment before systemic herpetic infection after intravenous inoculation of HSV-2 also reduced mortality and virus replication, as evidenced by a decreased antibody response in the survivors, and it either reduced latent infection in the spinal dorsal root ganglia or did not predispose mice to latent infection. Treatment with the immunomodulator appeared to inhibit or reduce HSV infection early in viral pathogenesis in all three model systems, producing protection from clinical disease and resulting in less virus to induce a systemic antibody response, with either a reduction in latent virus infection or no enhancement of development of latency. In all of the HSV models, the development of latent herpetic infection was closely correlated with sufficient virus replication early in the infection to induce a systemic neutralizing-antibody response.


Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice. Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form.


Comparison between agar and broth minimum inhibitory concentrations of cefamandole, Cefoxitin, and cefuroxime. The in vitro susceptibility to cefamandole, cefoxitin, and cefuroxime of clinical isolates of Streptococcus faecalis, Klebsiella, and indole-positive Proteus was assayed using minimum inhibitory concentration (MIC) determinations in broth and on solid media. It could be demonstrated that the agar dilution MICs obtained when S. faecalis was tested against cefuroxime and when indole-positive Proteus strains were tested against cefamandole tended to be considerably lower than those obtained with the broth dilution technique. The Klebsiella strains tested did not show any major differences with regard to MICs in broth or on solid media. Using an animal experimental infection model it could be demonstrated that with indole-positive Proteus the higher broth MIC correlated better to the observed data than the lower agar MIC when a beta-lactamase-producing strain was tested. The data obtained indicated that the beta-lactamase of the indole-positive Proteus strain was inducible. The results of the study gave evidence for a risk of false susceptibility of some bacterial species against cefamandole when agar techniques, e.g. paper disk diffusion, are used. For cefuroxime, the same phenomenon can be expected with S. faecalis and to some extent with indole-positive Proteus. In this study, cefoxitin seemed considerably less affected by the technique used for susceptibility testing.


Bactericidal effect of combinations of antimicrobial drugs and antineoplastic antibiotics against Staphylococcus aureus. Six antineoplastic antibiotics were tested against ten strains of Staphylococcus aureus. Four showed bacteriostatic and/or bactericidal activity against each of the ten strains, and two were only bacteriostatic for seven and nine strains, respectively. Using the cellophane transfer technique, combinations of these antineoplastic antibiotics with 16 antibacterial drugs were screened for combined bactericidal activity. Synergism or antagonism was demonstrated in about one-third of the combinations. Checkerboard titrations and killing curves confirmed these findings and indicated that the effective concentrations of the antibacterial agents were similar to those attainable in the serum after therapeutic doses of these drugs. Although the pharmacokinetics of the six antineoplastic antibiotics in humans are not fully known, at least one of them has a peak serum level corresponding to those values at which a bactericidal effect was produced in vitro.


Pharmacokinetic determinants of penicillin cure of gonococcal urethritis. In a 1964 study of the pharmacokinetic determinants of penicillin cure of gonococcal urethritis, 45 male prisoner volunteers were experimentally infected with strains of Neisseria gonorrhoeae having known in vitro penicillin susceptibility. After developing urethritis, subjects received intramuscular penicillin G and had serum samples obtained serially to determine penicillin concentration. Using a multiple regression technique, we studied patient-associated parameters and parameters of the serum penicillin curves to determine the best predictors of treatment results. Cure was best predicted by the time the serum penicillin concentration remained above three to four times the penicillin minimum inhibitory concentration of the infecting strain (probability of correct classification, >0.80). Those cured had serum penicillin concentrations which remained in this range for means of 7 to 10 h. Our findings confirm principles of antimicrobial therapy derived from animal models and may have application in studying therapy of gonorrhea and other infectious diseases.


Effect of time and concentration upon interaction between gentamicin, tobramycin, Netilmicin, or amikacin and carbenicillin or ticarcillin. An aminoglycoside antibiotic and carbenicillin or ticarcillin are widely used in the treatment of patients with gram-negative bacillus infections. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycosides at two concentrations with carbenicillin or ticarcillin at four concentrations. By linear regression analysis, the inactivation of each aminoglycoside was shown to be directly proportional to the concentration of carbenicillin (P < 0.001). Inactivation was significantly (P < 0.01) greater for gentamicin and tobramycin than for amikacin or netilmicin at all carbenicillin concentrations. At carbenicillin concentrations of 300 and 600 mug/ml, significantly (P < 0.005) less inactivation of amikacin occurred when compared to netilmicin. Ticarcillin produced a significant (P < 0.025) inactivation of gentamicin and tobramycin, with inactivation being directly proportional to ticarcillin concentration. No inactivation of amikacin or netilmicin activity occurred unless the ticarcillin concentration was 600 mug/ml. No significant change in aminoglycoside activity occurred when stored with ticarcillin or carbenicillin at concentrations ranging from 100 to 600 mug/ml at -70 degrees C for 56 days. When an aminoglycoside and carbenicillin or ticarcillin are indicated in patients with renal failure, this study supports the use of ticarcillin with either amikacin or netilmicin.


Antifungal activity of tioconazole (UK-20,349), a new imidazole derivative. Tioconazole (UK-20,349), a new antifungal imidazole derivative, was compared with miconazole for activity in vitro against Candida spp., Torulopsis glabrata, Cryptococcus neoformans, Aspergillus spp., and dermatophyte fungi (Trichophyton spp. and Microsporum spp.). Tioconazole was more active than miconazole against all the fungal species examined except Aspergillus, against which both agents showed similar activity. Both tioconazole and miconazole inhibited the growth of all fungi examined at concentrations well below their quoted minimum inhibitory concentrations. Their activity against fungi in vivo was investigated in mice infected systemically with Candida albicans. Both agents significantly reduced the numbers of viable Candida cells recoverable from the kidneys of infected animals, with tioconazole producing a generally more marked reduction. After administration of a single oral dose (25 mg/kg) to beagle dogs or white mice, higher and more sustained circulating levels of bioactive drug were detectable of tioconazole than of miconazole. These observations suggest that tioconazole may have potential in the treatment of both superficial and systemic mycoses in humans.


Effects of miconazole and dodecylimidazole on sterol biosynthesis in Ustilago maydis. Miconazole at minimal fungitoxic concentrations inhibits ergosterol biosynthesis in sporidia of Ustilago maydis by interference with sterol C14 demethylation. The action is analogous to that of the fungicides triarimol and fenarimol. The fungicide 1-dodecylimidazole at low concentrations (0.1 to 0.25 mug/ml) inhibits sterol C14 demethylation; however, at higher concentrations (1.0 mug/ml or greater) it also inhibits 2,3-oxidosqualene cyclization and subsequent transmethylation. It is postulated that this diversity of effects of 1-dodecylimidazole results from binding of the inhibitor to sterol carrier protein(s).


Pharmacokinetics of intravenous amoxicillin in pediatric patients. Pharmacokinetic parameters were obtained from 14 infants and children receiving intravenous amoxicillin. Peak serum values increased proportionally to the increase in dose; the serum half-life was similar in the three dose groups studied.


Skin potential and EMG changes induced by cutaneous electrical stimulation. I. Normal man in arousing and non-arousing environment. Skin potential and EMG responses induced in normal man by electrical stimuli applied to the skin were recorded in the four limbs in order to study somato-sympathetic and somato-motor reflexes. Different patterns of responses were observed in different conditions: alarm, habituation, sensitization and arousal. During alarm, sensitization and arousal, the responses were present in the four limbs; during habituation, the responses were only present in the stimulated and in the contralateral limb. Three sensory thresholds to cutaneous electrical stimulation were identified in habituated subjects: tactile, tingling and pain. Cutaneous and EMG responses appeared at tingling threshold. A relationship between skin potential level and skin potential response was observed.


Skin potential and EMG changes induced by cutaneous electrical stimulation. II. Subjects with reflex sympathetic dystrophies. In a group of patients suffering from reflex sympathetic dystrophies, the skin potential and EMG responses induced by electrical stimuli applied to the skin were recorded in the four limbs in order to study somato-sympathetic and somato-motor reflexes. In most patients, the amplitude, delay and shape of the cutaneous responses as well as the pattern of the EMG responses were different from those observed in normal subjects. In particular, it was possible to correlate the pattern of the cutaneous and muscular responses with the severity of the disease. The cutaneous sensory thresholds to electrical stimuli (tactile, tingling and pain threshold) showed different values in the dystrophic and in the contralateral limb. In all patients, a block of the sympathetic chain ipsilateral to the dystrophic limb was performed with local anesthetics. 1 h after the block, the cutaneous responses disappeared not only in the blocked limb but also in the contralateral limb. 48 h after the block, muscular and cutaneous responses as well as sensory thresholds showed a pattern similar to that observed in normal subjects. These findings show that the sympathetic block provides a resetting of the sensory thresholds and reflexes.


Influence of temporal lobe lesions on photic-evoked responses in occipital visual areas. In 20 patients with temporal lobe lesions and 10 controls, the averaged photic-evoked responses (APERs) and their dispersion pattern (DP) were investigated in inion-vertex-lead and bilaterally in inion-parietal leads (I-P3 and I-P4). The patients with temporal lobe lesions, regardless of lesion location in temporal areas, displayed either absence of APER (the whole APER or only the initial components) or a latency increase without amplitude changes. The DP was generally abnormal. The role of the temporal lobe in the organization of APER in visual areas is discussed.


Relapsing neuropathy, cerebral atrophy and folate deficiency. A close association. The case of a 48-year-old woman with a relapsing radial palsy which followed diarrheic episodes is reported. She had low folate concentrations in serum and cerebrospinal fluid, as well as low and borderline values of cerebrospinal fluid and erythrocyte folates. She had chronic gastrointestinal disease with edema of jejunal mucosa. The patient had some degree of cerebral atrophy. The effect of folate therapy on the neuropathy was spectacular. A beneficial effect of the therapy has been observed on both EEG tracings and neuropsychological performances after 6 months of treatment.


Lowered cutaneous and urinary levels of polyamines with clinical improvement in treated psoriasis. Polyamine metabolism is important in cell proliferation and may play a role in the epidermal cell hyperproliferation of psoriasis. We have determined changes in polyamine levels in skin and urine accompanying clinical improvement in psoriasis following topical therapy. Nine hospitalized patients were examined at the beginning and end of their courses of treatment. Skin biopsy specimens and portions of 24-hour urine collections were analyzed for polyamines with a modified automatic amino acid analyzer. Treatment resulted in lower cutaneous levels of putrescine (by 50%, P less than .05), spermidine (by 24%, P less than .05), and spermine (by 35%, P less than .005), and lower urinary levels of spermidine (by 20%, P less than .025) and spermine (by 35%, P less than .025). These results suggest that in psoriasis, the skin significantly contributes to the levels of spermidine and spermine in systemic fluids. Topical therapy may reduce epidermal cell proliferation in psoriasis by lowering polyamine levels.


Cancer and scleroderma.

Cancer and scleroderma. Of 2,141 patients with scleroderma who were seen at the Mayo Clinic, Rochester, Minn, between 1959 and 1975, 78 had 87 internal malignancies. The relative frequency of the types of cancers was similar to that for the general population. The increased numbers of patients with breast and uterine carcinomas were consistent with the female preponderance in scleroderma. Contrary to previous reports, carcinoma of the lung was not the most frequent malignancy associated with scleroderma. The lymphoma-leukemia malignancies were second only to breast carcinoma in frequency, comprising about 17% of the malignancies. Both conditions developed within a three-year period in 68% (45/66) of our patients affected with systemic scleroderma, and this subgroup comprised a high mortality group. This study is not an epidemiologic one in the strictest sense, but it is a review of the experience of the Mayo Clinic with patients who have had both scleroderma and an internal malignancy.


Lymphangiosarcoma arising from lymphangioma circumscriptum. A lymphangiosarcoma arose at the site of a preexisting lymphangioma circumscriptum on the skin of the anterior part of the abdominal wall. To our knowledge, this is only the second such case to be reported, and in both patients, the preexisting lymphangioma circumscriptum had been exposed to substantial x-ray therapy. Since it is possible that x-irradiation may play a role in the development of this unusual malignant neoplasm, it seems advisable that lymphangioma circumscriptum not be exposed to substantial amounts of such radiation, if feasible.


Cutaneous and venous complications of pentazocine abuse. A 55-year-old man with a two-year history of intramuscular pentazocine abuse had classical cutaneous findings as well as secondary venous thrombosis, which, to our knowledge, is previously undescribed. Histologic evaluation, including direct immunofluorescent microscopy, did not establish the mechanism of tissue destruction.


Folded skin associated with underlying nevus lipomatosus. A mentally retarded female infant had abnormalities of the feet, hemiplegia, and an underlying nevus lipomatosus. To our knowledge, this represents the second reported case of marked folding of the skin; with an underlying nevus lipomatosus; this case demonstrated an association of this cutaneous disorder with multiple defects, including chromosomal abnormalities, which have not been previously reported.


Relapsing polychondritis associated with cutaneous vasculitis. A patient with relapsing polychondritis associated with cutaneous vasculitis is described in detail. Clinically, a systemic chondritis complicated by conjunctivitis, iritis, otitis media, tracheal stenosis, sinusitis, and cutaneous vasculitis were observed in this case. Corticosteroids have been effective in controlling the clinical symptoms as well as the vasculitis.


Localized pruritus-notalgia paresthetica. Notalgia paresthetica, possibly an isolated sensory neuropathy involving the posterior primary rami of thoracic nerves T2 through T6, and appearing as pruritus of the back, is apt to be encountered by both dermatologists and neurologists. Two cases illustrate this disorder.


Primary cutaneous cryptococcosis.

Primary cutaneous cryptococcosis. Cryptococcal infections in immuno-compromised patients are of major importance. Current opinion holds that cutaneous cryptococcal infections in these patients indicate disseminated disease. In our renal transplant patient with primary cutaneous cryptococcosis, intravenously administered antifungal chemotherapy resulted in resolution of the disease and appears to have prevented disseminated infection.


Photosensitivity reaction to dibucaine. Case report and experimental induction. In a 13-year-old girl, photoallergic dermatitis was caused by dibucaine hydrochloride, which was used as a local anesthetic in the treatment of her dental caries. The action spectrum for the photosensitivity reaction was in the long-wave ultraviolet (UVA) range. Spectrophotometrically, dibucaine absorbed UVA up to 380 nm, and in the vitro irradiated chemical showed an altered absorption spectrum. The agent is fluorescent under UVA light. The allergic photocontact sensitization could be experimentally induced in guinea pigs. The chemical properties and high sensitization rate of experimental induction suggested that dibucaine may be a potent photosensitizing chemical. Dibucaine should be included in routine photopatch test materials.


Cutaneous phycomycosis. Report of three cases with identification of Rhizopus. Three cases of pustular and ulcerative cutaneous phycomycosis developed postoperatively in orthopedic patients following exposure to a contaiminated surgical adhesive (Elastoplast). A review of the pertinent literature revealed no other similar series of reported cases. The epidemiologic investigation of these cases is discussed. This experience demonstrates that with appropriate exposure, normal saprophytes can invade the skin in immunocompetent patients, producing active and invasive lesions.


[Semen analysis under photochemotherapy (PUVA-therapy) (author's transl)]. In 9 male patients with psoriasis vulgaris a semen analysis before and during photochemotherapy with 8-methoxypsoralen and UVA (PUVA) was performed to rule out drug-induced toxic damage of spermatogenesis or impairment of fertility due to scrotal hyperthermia. Two hours after oral application of 40--60 mg 8-methoxypsoralen the patients had been irradiated in UVA high intensity treatment units. PUVA-treatments were performed four times weekly until total body clearing was achieved. For complete remission 13--26 (mean 20.5) PUVA-treatments were necessary. Corresponding total UVA-doses were 35.3--191.0 (mean 83.2) Joule/cm2. The investigated parameters total motility, progressive motility, spermatozoa density, total spermatozoa count, spermatozoa morphology, and seminal plasma fructose remained unchanged. Only the volume of the ejaculate showed a small decrease during 3 months of therapy. From this pilot study there is no evidence that PUVA-therapy leads to an impairment of fertility in male patients within their reproductive age.


[Histology of the pigmented granular rankenneuroma (author's transl)]. We report on a case of a 40 years old female patient with a lentil-sized tumor of the left pinna present since early childhood. Histologic examination revealed pigmented granular "rankenneuroma". The lesion is unencapsulated but fairly well marginated in the dermis. It is composed of varying numbers of spindle-shaped or polyhedral cells arranged in intertwining and parallel bands separated by strands of collagen. The fascicles follow the preexisting nerve truncs. All layers of the dermis may be involved, but only rarely is the superficial subcutaneous tissue invaded. The fascicles of the tumor are generally constructed in a similar fashion. In the center one see argyrophile granular alterated unpigmented cells- Those elements are surrounded by mostly bipolar cells containing varying amounts of melanin. Silverstaining shows transition from spindle-shaped cells to granular degenerated elements. It is thought that the tumor most likely originates from the proliferation of the granular degenerated Schwann cells. The characteristic feature of tumor parenchyme is the association of the granular Schwann cells with cutaneous melanoblasts.


[Beneficial effect of oral retinoid in psoriatic hyperproliferation. Autoradiographic studies on involved and non involved skin (author's transl)]. In 16 patients with generalized psoriasis treated with oral retinoid (Ro 10-9359; 1 mg/kg body weight/(day) autoradiographic studies were performed before, and 24 h, 48 h, 1 week and 3 weeks after beginning of treatment on involved and non involved epidermis. During the first week no significant changes of all cellular parameters were found. However, after 3 weeks of continuing medication the increased 3H-thymidine labelling index was markedly lowered and the prolonged DNA synthesis time was shortened; whereas, the cell cycle time remained unaffected. The findings revealed that oral retinoid has a distinct influence on epidermal cell proliferation towards normalization in both involved and non involved epidermis in psoriasis. The time needed for this effect indicates that the drug does not directly interfere with the cell cycle. It seems reasonable, therefore, to combine oral retinoids as a basic adjuvant drug with other antipsoriatic techniques, such as retinoid + anthralin, retinoid + PUVA, retinoid + UVB.


[Spindle-shaped cell blue naevus with lymph nodes "metastases" (author's transl)]. "Metastases" in lymph nodes are not only found from cellular blue naevi but also from their spindle-shaped cell fascicular type. These "metastases" are mostly situated in the fibrous capsule, very rarely in the parenchyma of the lymph nodes. Individually the cells resembled those of the cutaneous tumour. Their occurence in the peripheral sinuses should be verified. Epitheloid vessel-wall cells (glomus-type cells), sometimes pigmented and occasionally found in large cell aggregates, can be noted in the capsule of the lymph nodes. By several authors, these cells are considered to be benign naevus cells. The histopathogenesis and the clinical importance of the "metastases" from blue naevus are discussed.


Proteinase binding and enhancing factor from human skin. Fresh human skin extract made in salt solution after a prior buffer extraction was shown to enhance the hydrolysis of N-alpha-benzoyl-DL-arginine beta-naphthylamide (BANA) by trypsin. This trypsin enhancing effect was further shown to be both stabilizing and activating. After chromatography on Sephadex G-100, the trypsin binding factor was found in fractions of void volume. Protease binding took place in physiological and hypotonic but not in hypertonic NaCl-solutions (0.5 mol/l). The proteinase binding factor was further purified by trypsin-Sepharose 4 B affinity chromatography. It was found to bind also chymotrypsin and elastase and to be thermostable (100 degrees C for 20 min), precipitable at acidic pH (3.5), and by acetone and ammonium sulphate (60% saturation). The bound proteinases were found to preserve their hydrolytic activity towards protein substrates. Bound trypsin and chymotrypsin could completely be inhibited by soybean trypsin inhibitor. The binding factor did not react with anti-human-alfa2-macroglobulin antiserum from rabbit.


Urinary histamine in severe atopic dermatitis. Urinary histamine was studied in 11 patients with severe atopic dermatitis and 17 controls, as well as in seven atopics prior to and 6 months following hyposensitization. No statistically significant differences were found between the groups. Urinary histamine seems to be of no value as an indicator of disease activity in atopic dermatitis.


[Skin impedance and phoreographic index in psoriasis. Relationship with action kinetics of three treatments]. In a previous study, impedance measurements and phoreographic response were shown to quantify significant differences between involved and non-involved skin in psoriasis. The same techniques were used to objectivate the evolution on skin condition on patients treated with dioxyanthranol, difluprednate, and photochemotherapy associated with 8-methoxypsoralen. Each of these treatments was applied to four subjects. On patients treated with dioxyanthranol or difluprednate, impedance and phoreographic response return to "normal" values within 5--10 days and 1--2 days, respectively. It takes a longer time with photochemotherapy, and it is noteworthy that the treatment also alters the phoreographic response of non-involved skin. The changes observed in electrophysiological parameters are discussed in relation with recent ideas on pharmacology of antipsoriatic treatments and on dynamic properties of biological membranes. The results are in good correlation with clinical data and exemplify the usefulness of these methods in following the treatment kinetics.


Influence of age and of desmotropic drugs on the step phenomenon observed in rat skin. Comprehensive analysis of the mechanical properties of rat skin revealed the "step phenomenon". This particular observation was made after constant strain rate (analysis of stress strain curves) as well as after constant load (creep experiments). Relative low extensions or low loads were necessary to provoke the steps. In most cases two, sometimes three steps were observed. The step phenomenon was found mainly in skin strips punched out perpendicularly to the body axis. Probably some bonds in the fibrous network are broken giving way to additional elongation whereafter stronger links take over the stress. Since earlier studies demonstrated a pronounced influence of age and of desmotropic drugs on mechanical properties at ultimate load, e.g., tensile strength, ultimate modulus of elasticity, and ultimate strain, also the step phenomenon was studied under these conditions. In stress-strain experiments most of the steps were found at the ages of 2 and 4 months. Total stress loss and total work loss due to the steps were the highest at the age of 4 months. If, however, these values were calculated as percentage of ultimate values, the highest figures were found in young animals. Elongation gain due to the steps also showed a maximum at time of maturation, e.g., 4 months. Similar findings were achieved in creep experiments at medium load (200 g). After treatment with prednisolone acetate more steps and after treatment with D-penicillamine fewer steps were observed. In stress-strain experiments total stress loss and total work loss due to steps were more than twice as high than controls after prednisolone treatment and only one half after D-penicillamine. If calculated as percentage of ultimate stress or percentage of work input, these changes disappeared because of similar changes at ultimate load. However, elongation gain due to steps, which was not significantly influenced by prednisolone acetate but significantly decreased by D-penicillamine, showed the same changes when calculated as percentage of ultimate strain. Under all conditions the step phenomenon mainly influenced the extension parameters. The data presented here confirm earlier observations that mechanical properties at low loads or low and medium extensions show at least to some extent a different pattern under the influence of maturation and age and after treatment with desmotropic drugs compared to the mechanical parameters at ultimate load.


Interaction of methotrexate and betamethasone with experimental phototoxic inflammation to PUVA (Psoralen and UVA) in mice. The influence of methotrexate and of betamethasone on a following phototoxic reaction to 8-methoxypsoralen and long-wave ultraviolet light (PUVA) was studied in the mouse. High PUVA doses were not influenced by the two drugs tested. Both methotrexate and betamethasone tended to diminish the PUVA response when psoralen was given in a medium dose.


The sensitizing capacity of naturally occurring quinones. Experimental studies in guinea pigs. II. Benzoquinones. Experimental studies on the sensitizing capacity of naturally occurring benzoquinones, isolated from plants and woods have been carried out in guinea pigs of the Pirbright white strain. Seven compounds were available: primin, three dalbergiones, mansonia quinone (mansonone A), 2,6-dimethoxybenzoquinone and rapanone. With five of these substances (primin, mansonone A, three dalbergiones) guinea pigs could be sensitized. Primin, the allergen of Primula obconica Hance (primrose) proved to be the most effective one of all quinones tested in this and the preceding studies. As a similar but weaker sensitizer R-3, 4-dimethoxydalbergione from Machaerium scleroxylon Tul. (Pao ferro, Caviuna vermelha) could be identified. The results obtained with mansonone A, a sesquiterpenoid quinone from Mansonia altissima A. Chev. demonstrate that even naturally occurring orthoquinones are capable of inducing contact allergy. Allergic cross reactions could be obtained between all chemically related mansonones A-F. The results are in good accordance with the view that the sensitizing capacity of naturally occurring quinones depends on the fundamental quinoid structure and the length, position and configuration of the aliphatic side-chain.


Increased elongated and stabilized microtubules in psoriatic keratinocytes. Microtubules (MT) occur in the keratinocytes as 20 nm broad tubular structures with an electron-lucent core surrounded by an electron-dense wall. The number and the length of the MT increased to the upper epidermal layers. In the normal keratinocytes the MT were relatively short (maximal length 2.2 microns) and slightly tortuous. Their outline was tenuous and irregular. Sometimes the MT were interrupted indicating a high fragility. In the upper layers of the psoriatic epidermis the MT reached a maximal length of 3.1 microns, showing a greater elongation than in the normal epidermis. The MT were stright and distinctly limited, most likely resulting from a higher grade of stabilization or polymerisation. By their interaction with the tonofilaments the MT may contribute to the stability of the cell shape, delaying the flattening of the psoriatic keratinocytes in the upper epidermal layers. Nowhere did the MT make direct contact with the cell membrane. At some places they did gain access to the cell membrane by short microfilaments.


Monocytopoiesis in malignant melanoma: untreated, during immunotherapy and chemoimmunotherapy. Monocytopoiesis and blood monocytes were investigated in patients with superficial spreading melanoma stages I and II. Monocyte production was moderately increased in 4 of 9 untreated patients. Postoperative prophylactic BCG-vaccination gave rise to increased proliferation activity in 3 of 4 patients with previously normal monocytopoiesis. However, monocyte production returned to normal between the 4th and 6th month of BCG immunotherapy. Monocytopoietic hyperproliferation did not occur if DTIC was administered simultaneously with BCG. These results indicate that BCG-vaccination increases monocytopoiesis during the first months of treatment only. This effect is abrogated by concomitant chemotherapy.


The effect of oral zinc loading on the absorption of 65zinc in the rat. Seven groups of 8 rats each were orally loaded with zinc, the daily dose varying from 1.8 to 58 mg, corresponding to about 3 to 100 times of their estimated daily intake of zinc. To record the absorption of zinc, the rats were given a single dose of 65Zn. The retention of the isotope was measured in a whole animal counter at regular intervals. The dose of 58 mg was obviously toxic, since half of the animals died within 5 days. The net absorption of zinc in the remaining experimental groups was found to vary from about 7% in the group receiving the smallest loading dose to 1.8% in the group receiving the highest dose. From the absorption values, as determined by extrapolation of semilog retention curves, the total amount of absorbed zinc was estimated. It was found to differ from about 170 micrograms to about 530 micrograms zinc daily, increasing three times as the loading dose was increased 16 times. This discrepancy suggests the existence of regulatory mechanisms of the absorption of zinc from the intestine.


Therapy of psoriasis with retinoid plus PUVA: clinical and histologic data. In a group of 40 patients suffering from wide-spread psoriasis oral administration of a retinoid (Ro 10-9359) was followed by PUVA therapy. The clearance rate was increased by 30% as compared to PUVA alone. Except for cheilitis no side effects were seen. Histological analysis in 20 patients before, during and after therapy revealed an intensification of psoriatic tissue changes after retinoid treatment. Loss of corneal layers, massive exoserosis, and neutrophil migration were prominent features. Mitotic counts were not increased by the pretreatment. The increased susceptibility of diseased skin to PUVA as produced by this drug appears to be based on several factors related to the tissue changes revealed by histology.


[Fatty acid composition of lipids from the hair in psoriasis vulgaris (author's transl)]. The composition of fatty acids of hair lipids and the sum of hair and scalp lipids from subjects with Psoriasis vulgaris and a control group was determined by gas liquid chromatography. The analyses indicates that the percentage compositions of lauric acid was distinctly higher by Psoriasis vulgaris.


HLA-antigens in systemic lupus erythematosus (SLE). Histocompatibility antigens were determined in 27 patients with SLE and 283 normal blood donors. HLA-B8 was significantly increased in patients with SLE (59.3%) as compared to the controls (20.5%, Pc less than 0.005). The relative risk for HLA-B8 was 5.64. No correlation could be demonstrated to specific organ involvement, immunopathological data, age of onset or prognosis.


Lymphocyte response to mitogens in patients with malignant melanoma. Lymphocyte blast transformation of 23 melanoma patients was compared to that of 22 healthy persons after stimulation with the mitogens PHA, ConA, and PWM. Transformation rate of lymphocytes in microcultures was measured following 3H-Thymidin uptake in a Liquid-Scintillation-Counter. Calculations were based on analyses of variance. There was no significant difference in blastogenetic response between the 2 groups (patients and controls), but there were differences between the used mitogens.


Prealbumin as a hapten carrier protein in certain varieties of dermatitis. A significant decrease of serum prealbumin levels and an increased proportion of prealbumin bearing lymphocytes in peripheral blood have been found in patients of hapten-induced diseases. Prealbumin deposition in the vessel walls, and/or prealbumin positive cells (granulocytes, lymphocytes, macrophages) in the dermis have been observed in patients with proved drug allergy as well as allergic contact dermatitis using immunofluorescence technique. The eluates from membrane of lymphocytes of patients with drug allergy contained a mitogenic substance, probably antigen and sometimes prealbumin as well. These results also support the earlier suggested hypothesis that the prealbumin may act as a hapten carrier protein.


Ichthyosis nigricans: ultrastructural study of the melanin pigmentary disturbances. Hyperpigmented skin from a 10-year-old white boy with ichthyosis nigricans has been studied. Histological and ultrastructural studies reveal that the hyperpigmentation is related to both epidermal and dermal hypermelanosis. Melanocytes are hyperactive. The different stages of melanosome synthesis and melanisation appear to be normal. Increased dermal pigmentation probably results from a dischargement of the melanin granules into the dermis secondary to melanocyte alterations. Ichthyosis nigricans is a typical example of melanin pigmentary disturbances of the skin, resulting from disturbances in the normal interactions between melanocytes and keratinocytes.


Urinary polyamine levels in patients with psoriasis. Polyamine contents in 24 h urine of 16 psoriatic patients and seven healthy individuals are measured. The average values of putrescine and spermine showed slight increase in the psoriatic group, while those of spermidine were unchanged. When psoriatic patients are divided into three groups according to the extent of their skin lesion, the putrescine level is found to be higher in the group more severely affected.


Autoradiographic study on some proliferative properties of human buccal mucosa. This study was designed to investigate the proliferative activity of the buccal mucosa in healthy adult persons with regard to individual age. Punch biopsy specimens were taken from the buccal mucosa of 19 individuals (10 females, 9 males) ranging in age from 24 to 80 years, and were then examined autoradiographically, applying nuclear 3H-thymidine labelling in vitro under oxygen pressure of 2.2 atm. The mean total labelling index in the progenitor compartment amounted to 26.0 +/- 2.6% including 6.2 +/- 2.0% labelled basal nuclei and 19.8 +/- 2.6% labelled suprabasal nuclei. Related to 1,000 mu surface length, the mean number of basal cells runs up to 270.7 +/- 38.6 and the total nuclear labelling index to 70.9 +/- 10.4. This high rate of S phase nuclei, exceeding that of the epidermis several times, depends on the ample progenitor compartment as well as on the basal epithelium length which, as compared to the epithelium surface length, was shown to be extended by a mean proportion of 1.75. None of the autoradiographic results obtained in the present study revealed an age dependency of the buccal mucosa proliferative activity. The magnitude of the proliferative pool constitutes the matrix of the high renewal rate of the healthy buccal mucosa and provides a steady state of superficial cell loss and basal cell regeneration, that was proved, at least in the normal mucosa, to continue until senile age.


Microcalorimetric investigations of the metabolism of isolated human epidermis. Microcalorimetry was used for the evaluation of metabolic and enzyme activity in human epidermis. The endogenous metabolism with a heat production Q = -2 muW/mg wet weight could be stimulated to Q = -12 muW/mg by adding glucose to the buffer. To test the enzyme activity, hydrogenation of pyruvate to lactate by lactate dehydrogenase (LDH) was chosen as an essential step of anaerobic glycolysis. The LDH activity of epidermis slices amounted to 22 mU/mg epidermis. The microcalorimetric method is discussed as a test procedure for specimens of healthy and diseased skin and for cell cultures.


Pure melanocyte cultures: differential serum requirements of guinea pig keratinocytes and melanocytes in primary epidermal cell cultures. Contrary to melanocytes guinea pig keratinocytes do not attach and grow in primary epidermal cell cultures if plated in media containing guinea pig serum. This phenomenon is based on the low content or lack of guinea pig serum of a factor(s) promoting keratinocyte attachment. This factor, which is contained in fetal calf serum, binds to the keratinocyte cell surface and can be removed by trypsin. Guinea pig epidermal cell cultures plated in medium containing guinea pig serum therefore lead to pure or almost pure melanocyte cultures.


Lymphocyte proliferation during PUVA therapy. The lymphocyte proliferation of 15 psoriatic patients was sutdied after stimulation with tuberculin, trichophytin, varidase, concanavalin A (Con A), and pokeweek mitogen (PMW) during the first and the eighth PUVA treatment, 2 h after oral intake of 8-methoxypsoralen (8-MOP), immediately after UVA-irradiation, and 24 h later. There was a significant decrease of the lymphocyte proliferation, after stimulation with Con A (P less than 0.05), trichophytin (P less than 0.01) and varidase (P less than 0.05), not with PWM and tuberculin, during the first PUVA treatment by 8-MOP alone. This decrease was not significantly changed by the following UVA irradiation and could not be demonstrated after 24 h. No dark effect of 8-MOP on the lymphocyte proliferation could be seen during the eighth treatment. 8-MOP seems to influence lymphocyte proliferation in the dark by interfering with the cell surface, not with the nucleus. The disappearence of this effect during PUVA therapy could be explained by a modification on the surface structure of lymphocytes.


Effects of glucocorticosteroids on cultured human skin fibroblasts. III. Transient inhibition of cell proliferation in the early growth stages and reduced susceptibility in later growth stages. An immediate depression of the rate of cell proliferation occurred upon addition of glucocorticosteroids to cultures of human skin fibroblasts in the early growth stages. A reduced sensitivity or even insensitivity of the fibroblasts to growth inhibition inhibition was found upon the addition of the steroids at later stages of cell growth, when the cell density has increased. The inhibition in the early growth stages is transient and is most pronounced if the cultured medium is not renewed. This transient inhibition is not due to the development of steroid-resistant cell lines, and resembles the effect called tachyphylaxis, as is also observed in vasoconstriction tests.


[Blind ureters. Proposed classification and study of the national statistics with the contribution of 2 cases]. The authors put forward the bases for a classification of the different kinds of B.U., according to the direction which it takes, the situation of the blind end and the accompanying, renoureteral malformations in the system itself. They review the Spanish statistics in which 38 cases of 6 kinds are compiled, included among the 15 in the classification suggested, as well as presenting two of their own. They refer to the possible ischemic cause of this anomaly.


[Massive kidney infarct by occlusion of the main artery]. Massive kidney infarct, due to total occlusion of the main artery, is not a frequent process in clinical urology. The most frequent causes are endocarditis, arteritis, atheromatosis and traumatisms. The complete blockage of the renal artery means that the tissue irrigated by the same is bloodless and prone to necrosis and it must be taken into account that although the renal parenchyma cannot withstand for more than 1 to 2 hours the lack of a blood supply, the obstructions or ischemias of shorter duration cause tissue disorders of greater or lesser importance, affecting more quickly and more intensely the cells of the tubules, than those of the glomerules and later the connecting tissue. Clinically, kidney infarcts may sometimes go unobserved and on many other occasions their symptoms are by no means typical although the most characteristic feature is a more intense, sharp, acute pain with macroscopic hematuria, proteinuria and cylindruria and, in the radiological exploration, kidney "silence" but with the excretory duct intact shown by means of retrograde uretero-pyelography. The kidney angiography will reveal the existence of the arterial obstruction, with the resulting avascular image. Extrapremature surgical treatment would be ideal in the cases of massive infarct but this would also require an extrapremature diagnosis, which would enable the embolectomy (where necessary to be carried out, thereby saving the kidney. However, under normal working conditions, taking into account the period of time which inevitably elapses between the patient feeling pain in the kidney and his reaching the Emergency Department and the necessary examinations being carried out which enable the correct diagnosis to be made, the number of hours which have passed make attempts at conservative surgery completely useless. The authors present the case of a 37-year old patient who, 15 days after presenting a picture of right kidney colic, went to the Emergency Department in our Centre where the doctor on duty merely performed a symptomatic treatment and the patient was not admitted to our Department until several days later. In the different radiourographic examinations carried out, right kidney mutism was observed, as well as the permeability of the excretory duct. The aortography revealed the total occlusion of the right renal artery. As more than 20 days had elapsed since the patient first presented the colic pain and before we examined him, there was no other therapeutic solution but the performing of a nephrectomy. The examination of the organ  removed confirmed the diagnosis but the origin of the arterial obstruction could not be clarified for sure.


Preoperative assessment of resectability for carcinoma of the thoracic esophagus. Part I. Esophagogram and azygogram. The length and radiologic type of tumor, esophageal axis and azygogram were examined in 208 patients with carcinoma of the thoracic esophagus who underwent esophageal resection from 1965 to 1975. An histologic examination was performed on all resected specimens. These examinations were used as diagnostic aids to determine the resectability of esophageal carcinoma before surgery. Tumor length did not seem an adequate parameter on deciding resectability; nor did the radiologic type of tumor. Examination of the esophageal axis was in determining resectability. The azygogram gave the most accurate information about resectability of these 4 parameters. The probability of a correct diagnosis regarding differentiation of noncurative a3 lesions from other resectable lesions was 85.6%.


[Zinc in prostatic physiopathology. I. Role of zinc in the physiology and biochemistry of the prostatic gland]. To sum up the role of zinc in prostatic physiology and biochemistry: a) Zinc is found in normal prostate tissue in a greater concentration than in any other organ in the economy, ranging between 0.70 and 1 mgm/gm. of dry tissue. b) The concentration of prostate liquid and semen is greater than that in any other organic liquid. c) It appears that the prostate gland is a zinc storing organ (or deposit). d) The zinc concentration in prostatic tissue is directly proportional to the amount of alveolar tissue existing in the gland. e) It has been shown that the Zn concentration is greater in the nuclear sediment of the different subcellular fractions of the human prostate gland. f) The prostate gland seems to supply zinc to the human sperm and plays an important role in the metabolic activity of the spermatozoid. g) There seems to be a clear difference between the distribution and absorption of radioactive zinc in the different lobes of the prostate gland. h) Zinc also plays an important part in the enzymatic activity of the prostate gland and in the polymeric organization of the RNA and DNA and is vital for cell division. i) Prostatic Zn has a clear hormonal dependency.


[Air cystometry].

[Air cystometry]. A better study and more correct diagnosis of neurogenous bladder is to be achieved with cystomanometric studies. The authors analyse the use of air as a medium, explain the method and stress the simplicity, quickness and absence of complications with air. Finally, they mention the recent use of carbon dioxide, particularly in urethral profilometries.