[Paraneoplastic syndromes in cancer of the kidney (author's transl)]. Starting with the description of their own observations of paraneoplastic syndromes in adult patients with cancer of the kidneys, the authors discuss the possible pathogenetic mechanisms and the more characteristic clinical features of said syndrome. They conclude by advocating a systematic search for such paraneoplastic syndromes as an aid to early diagnosis of renal malignancy and also as a working parameter for assessing the evolution of the tumor and the effectiveness of treatment.


[Osteosarcoma: current views on pathology and new therapeutic perspectives. II: Criteria of prognosis and treatment (author's transl)]. The authors review recent studies and trials concerning the treatment of osteosarcoma, with special attention to current trends in immunology, radiology, surgery, and chemotherapy. Progress in immunobiological research seems to promise interesting practical developments; even today, however, modern chemotherapy combined with suitable ablative surgery affords a remarkably better prognosis for this malignancy.


Lipid metabolism in endotoxic shock.

Lipid metabolism in endotoxic shock. A brief overview of the alterations in the control of free fatty acid (FFA) and triglyceride (TG) turnover following the administration of Escherichia coli endotoxin is presented. Hormone-sensitive lipase activity was increased following either in vivo or in vitro administration of endotoxin. In conscious dogs, the rate of appearance of glycerol was also increased while that of FFA was not changed, indicating that in addition to increased lipolysis, increased reesterification in the adipose tissue may also be present. Myocardial utilization of FFA was decreased and that of lactate increased following endotoxin both in vivo and in vitro using isolated myocytes. Both myocardial and adipose tissue lipoprotein lipase activity were decreased following endotoxin, indicating a possible decrease in TG removal by these tissues. Additional studies are warranted to further elucidate the interrelation between the changes of lipid and carbohydrate metabolism and those of hemodynamics in shock.


Ketotifen in childhood asthma: a double-blind placebo controlled trial. In a three week double-blind cross-over controlled trial in twenty asthmatic children, ketotifen (HC 20-511, 'Zaditen', Sandoz) showed no significant difference from placebo, although there was a consistent trend in favour of the active drug.


Multi-channel, probe colorimeter for use with the micr-ELISA test, which makes use of disposable flat-bottom microhemagglutination plates. We describe a multiprobe colorimeter that permits the reading of enzyme-linked immunosorbent assays (ELISA) in situ, by use of microhemagglutination plates. The use of dipping probes eliminates interference from meniscus effects and air-bubble entrapment. Detailed validation tests have been done and potential sources of inaccuracy identified.


Enzyme immunoassay for serum lidocaine in antiarrhythmic therapy. We have adapted the commercially available EMIT kit [Clin. Chem. 23, 1161 (1977)] to the Gilford System 3500 Analyzer. Sample volume is 10 microliter. We compare reagent blank-corrected absorbance changes at 340 nm between 15 and 55 s for samples and a series of calibrators, and calculate results with use of a logarithmic transformation. Within-run precision (CV) for a serum pool with 4.0 mg of added lidocaine per liter was 2.7% (n = 45); day-to-day precision was 3.3% (n = 15). Analytical recoveries of 2 to 6 mg of lidocaine per liter were 90-102% (average, 97.3%). Results correlated significantly with those by a gas-chromatographic technique. No clinically significant interferences by concomitantly administered medications were observed. The procedure is rapid (42 samples per hour) and is well suited to the fast response required in monitoring lidocaine therapy. Usefulness of the assay data in the management of arrhythmias in the coronary care unit is discussed.


Importance of blood-collection tubes in plasma lidocaine determinations. In 25 clinical samples serum lidocaine concentrations fell from a mean of 6.5 +/- 2.1 mg/L (mean +/- SD) to 4.9 +/- 1.8 mg/L (p less than 0.001) when the blood sample was allowed to make contact with the stopper of the Vacutainer collection tube. In vitro experiments showed that this effect of the stopper occurred only with whole blood and was dependent on sample concentration. The plasma binding of lidocaine decreased from a normal value of 56% +/- 2.2 (mean +/- SD) to 28% +/- 2.2 (p less than 0.001) when exposed to the Vacutainer stopper. We conclude that a chemical leached from such stoppers displaces lidocaine from its plasma-binding sites and that the drug is then redistributed into the erythrocytes, producing spuriously low lidocaine concentrations in plasma or serum. Such artifacts are important in therapeutic drug monitoring and can lead to erroneous clinical decisions.


Analytical luminescence: its potential in the clinical laboratory. The various types of chemiluminescent and bioluminescent reactions are described. Applications of luminescence in the analysis of substancs of clinical interest are surveyed. The advantages, disadvantages, and prospects for luminescent assays are discussed.


Fluorescence protection immunoassay: a new homogeneous assay technique. We describe a "fluorescence protection immunoassay," in which formation of an immune complex of a fluorescer-labeled antigen sterically protects the fluorescer from binding by antibodies to it. Competitive binding of unlabeled antigen by its antibody prevents formation of the fluorescer-labeled antigen immune complex, and allows anti-fluorescein to quench the fluorescence by binding to the fluorescer. This phenomenon is the basis of a new homogeneous assay technique that requires no separation step. The steric exclusion of anti-fluorescein from fluorescein-labeled human IgG immune complexes was altered by changing the molecular dimensions ob both antifluorescein and the immune complex. The assay did not require highly purified fluorescein-labeled human IgG. An assay is demonstrated in which was used a fluorescein-labeled human IgG conjugate containing IgG that was only 10% pure. Measurement of IgG in human serum samples correlated well with results by radial immunodiffusion. The method is applicable to the assay of both proteins and analytes of low molecular mass.


A systems approach to fluorescent immunoassay: general principles and representative applications. We have developed an automated system for the immunoassay of subnanogram quantities of clinically interesting compounds by molecular fluorescence. The system includes all the necessary reagents and an automated fluorometer. The microprocessor-based instrument consists of a measurement and data-processing module and an automated sampling unit. With use of 10 pmol/L amounts of fluorescent dyes such as fluorescein, measurements with precision and accuracy of 1--3% are attained. In a competitive-binding fluorescence immunoassay, antigen labeled with a fluorescent dye competes with antigen in the sample or standard for a limited amount of antibody immobilized on a polyacrylamide bead 2--5 micrometers in diameter. After separating antibody-bound from free tracer, we measure the amount of fluorescence bound to the beads. In representative example assays, correlation of fluorescence immunoassay (y) with a reference radioimmunoassay (x) of thyroxine was y = 1.01x + 13 nmol/L, r = 0.98. Correlation of fluorescence immunoassay (y) with a reference radioimmunoassay (x) of triiodothyronine was y = 0.99x + 0.004 nmol/L, r = 0.96.


Implementing a computer-based electro-oculographic analysis system. Electro-oculographic recordings of caloric-induced nystagmus were conducted in a number of normal and disordered subjects. On the basis of the results, implementation of a clinical measuring system is considered; this is based on the interbeat interval, selected in view of its favourable sensitivity and stability. Two stages of processing are involved; first, the determination of the interbeat intervals, second the analysis. The first stage has been implemented off-line on a general purpose computer and also, in on-line mode, by special purpose electronics. The second stage requires computer analysis. We have used the rank magnitude sequences of interbeat intervals as the basis of the analysis.


Impact of genetic counseling: a review of published follow-up studies. Retrospective follow-up studies on the impact of genetic conseling, published since 1970, are reviewed in the present paper. Particular attention has been paid to evaluation of understanding of genetic information, planning of later pregnancies and real changes in family composition. A rather wide divergence was found with regard to these three parameters, probably more related to the design of the studies than to a divergence in counselees' understanding and decisions, emphasizing that more, and especially more methodologically sound studies are necessary to evaluate the impact of genetic counseling.


Research in leprosy. A report of a committee set up by the medical research council to study future prospects. Recommendations for future research in leprosy include (i) cultivation of M. leprae in vitro; (ii) genetic control of susceptibility, including twin studies and HLA typing; (iii) precise antigenic analysis of M. leprae; (iv) mechanisms involved in the macrophage response to mycobacterial infections; (v) more use of experimental models such as normal mice infected with M. lepraemurium; (vi) reassessment of the protection afforded by BCG; (vii) assessment of protection afforded by killed (armadillo) M. leprae vaccine; (viii) pathogenesis of erythema nodosum leprosum including a study of the effect of thalidomide; and (ix) development of in vitro systems for drug sensitivity testing.


Antibodies to histones in systemic lupus erythematosus. Antibodies to histones were investigated in the serum of forty-five patients with spontaneously occurring systemic lupus erythematosus (SLE) who were not receiving any form of treatment. Twenty-three had active and twenty-two had inactive disease. Thos with active disease were also studied after the initiation of corticosteroid treatment to determine the effect of treatment on anti-histone antibodies. Both a complement fixation method and indirect immunofluorescence of acid-eluted histone-reconstituted tissue sections were used, with excellent correlation between these two methods. Eleven of the forty-five SLE patients, but none of forty-five normal controls had antibodies to histone. Untreated patients with active and inactive disease had a similar incidence of antibodies to histone. They disappeared, however, soon after the initiation of treatment in the patients with active disease. Patients with antibodies to histones had a higher prevalence of cutaneous vasculitis, anaemia, lupus nephropathy and Raynaud's phenomenon, but a lower prevalence of lupus brain involvement than those without such antibodies. Only the latter, however, reached statistical significance.


The kinetics and quality of acquired resistance in self-healing and metastatic leishmaniasis. Quantitative methods for enumerating viable L. enriettii in tissues have been used to determine the course of cutaneous leishmaniasis in guinea-pigs. The development and kinetics of acquired resistance have been evaluated in self-healing and chronic metastatic forms of the disease. It is revealed that 3 weeks after a primary local infection, a standard challenge infection is totally eliminated within 7 days. This resistance is as strong in animals with a current infection as it is in those that have fully recovered from such an infection. Animals developing metastatic disease also develop resistance to the standard challenge. This is initially as strong as in animals with only localized disease, but wanes with the progression of the infection. Although the quality of resistance becomes poorer in animals with metastatic infection, it is not lost completely. The relationship between acquired resistance and the resolution of the primary infection is discussed.


Specificity of the macrophage spreading test with reference to Leishmania antigens and correlation with delayed hypersensitivity. The inhibition of the macrophage spreading test, claimed to be an in vitro correlate of delayed hypersensitivity, was examined in guinea-pigs immunized with L. enriettii and L. tropica soluble antigens. Cells from peritoneal washings of the guinea-pigs were tested in presence of the homologous and heterologous antigens and also without antigen. Inhibition of macrophage spreading compared to control preparations was noted only in the presence of the homologous antigen when the skin test response of the donor animal was relatively small. The degree of inhibition decreased as the skin test volume increased and when skin test volumes were large there was actual stimulation of macrophage spreading, rather than inhibition. The addition of heterologous antigen to the peritoneal cell preparation always resulted in the augmentation of macrophage spreading above control levels. The possible mechanisms of this in vitro technique and its use as a taxonomic or diagnostic tool are discussed.


Circulating immune complexes in serum from patients with dengue haemorrhagic fever. Circulating immune complexes were detectable in 80% of serum from patients with dengue haemorrhagic fever. The immune complexes were detected for the first time on day two after the onset of the fever. The amount of complexes reached the maximum value on day 4 or 5 after onset, or when the patients developed shock or subsidence of fever, after which the complexes decreased in number. The number of complexes also correlated well with the clinical grading (severity) of the disease, i.e. the maximum amount was shown in grade III. These complexes may play a part in the pathogenesis of this disease.


Epidemics of infectious diseases in newborn nurseries. The newborn nursery is a frequent site of epidemics of infectious disease. The unique susceptibility of neonates to colonization, their intimate exposure to hospital personnel, and their frquent contact with possibly contaminated inanimate objects are major factors contributing to the risk of nursery epidemics. Most  of the epidemics described have been caused by bacteria; the role of viruses in nosocomial infections is not well defined but is undoubtedly greater than presently appreciated. All bacteria implicated in nursery epidemics have the capacity to survive or even multiply in the environment or on human skin or to cause gastrointestinal disease. Analysis of the etiologic bacteria, the epidemiology of outbreaks studied, and extensive clinical research indicate that bacterial transmission in this setting occurs primarily by manual contact and very infrequently by the respiratory route. The cornerstone of a program to prevent infectious diseases in the nursery consists of active, disease-oriented surveillance by specially trained personnel; microbiologic surveillance is important only when specifically indicated. Practical technical considerations for prevention of infectious diseases in nurseries are available. Programs to eradicate an ongoing epidemic must be individualized.


Renal uptake of 99mTc-sulfur colloid in liver transplant patients. There was renal uptake of 99mTc-sulfur colloid in liver-spleen studies performed on three liver transplant patients. Unlike all previously reported patients, none was in congestive heart failure. The mechanism of this uptake is unknown, but in our three patients it did not correlate with hepatic or renal function.


Serum potassium and uric acid changes during treatment with timolol alone and in combination with a diuretic. Timolol, 10 to 40 mg daily, given to 103 patients with uncomplicated arterial hypertension induced significant increments of serum potassium at all dose levels (p less than 0.05). The magnitude of the increments was dependent on daily timolol dosage. When hydrochlorothiazide and amiloride were added, serum potassium decreased (p less than 0.001), but a major determinant of the magnitude of the decrease was the dosage change of the timolol. Serum uric acid was influenced in a paradoxical way during timolol monotherapy; there was a rise in all 3 dosage groups (p less than 0.02) but the lowest group showed the largest increase and vice versa. On addition of hydrochlorothiazide and amiloride, there was a further increase in serum uric acid, the magnitude of which depended on the concomitant reduction in the dose of timolol, with reductions in dose causing a larger rise in serum uric acid and increments, a smaller rise. The increments of serum uric acid were greater in females than in males during both treatment periods. The results indicate that beta blockers induce dose-dependent rises in serum potassium and may counteract undesirable effects of diuretics on serum potassium. Beta blockers seem to have a paradoxical effect on serum uric acid and may aggravate the hyperuricemia induced by diuretics.


Effect of diclofenac and naproxen on gastroduodenal mucosa. The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclofenac, 100 mg/day, for 1 wk was investigated in 14 subjects in a double-blind randomized crossover study. Endoscopic examination of the gastroduodenal mucosa was carried out before and after each drug with regard to gastritis and hemorrhagic and erosive lesions. A 20-cm visual analogue scale was used for grading severity of mucosal changes. Naproxen caused statistically significant increases inmedian scores for all 3 variables, and 10 subjects showed a score increase in at least 1 variable; reaction to diclofenac occurred in only 4 subjects and the changes in median scores were not significant.


Effectiveness of topical steroids in the control of radiation dermatitis: a randomised trial using 1% hydrocortisone cream and 0.05% clobetasone butyrate (Eumovate). Radiation dermatitis often presents as a problem for patients and radiotherapists during treatment. Topical corticosteroids have been shown to have an anti-inflammatory effect in the treatment of many skin diseases and are commonly prescribed during a course of radiation treatment. A comparison of two different steroid creams, 1% hydrocortisone cream and 0.05% clobetasone butyrate (Eumovate), in a double blind trial was carried out in 54 patients undergoing radiation therapy for breast cancer. 'The cream' was administered when patients reached a given dose of 2000 rad (or earlier if required) whether a skin reaction was present or not. The aim of the trial was to evaluate the general effectiveness of steroids in controlling radiation dermatitis and whether one type of cream was superior to the other. The majority of patients using either cream derived benefit in its soothing effect. There was, however, a significant difference in the intensity of reactions seen, patients using clobetasone butyrate developed more severe radiation reactions despite both groups having similar radiation doses. The possibility of two differing populations having different responses to radiation is discussed as is the 'breakthrough phenomenon' described in the literature. It is concluded that neither cream should be used as first choice in the control of radiation dermatitis.


Venous aortography--a forgotten technique. A simple technique of venous aortography is described. Eleven patients were examined, 10 with suspected aortic aneurysms. The diagnosis was confirmed in six cases and the relationship of the aneurysm to the renal arteries shown in five of them. Three patients were shown to have a normal aorta. One patient with a suspected saddle embolus was shown to have a normal aorta and iliac arteries. There was one failure but there were no serious complications. The technique is a reliable and simple method of visualising arotic aneurysms, especially if subtraction prints are made.


Minimising side effects in lumbar radiculography. An attempt was made to reduce the side effects associated with the use of Metrizamide in lumbar radiculography by the removal of the contrast medium on completion of the examination. Almost complete removal was achieved in 103 patients and of these 73% had no symptoms after examination, while 8% had severe symptoms. Eleven of 14 patients in whom removal was not attempted or was not successful had significant symptoms after examination. It is concluded that aspiration of Metrizamide will reduce the incidence and severity of the side effects associated with the use of this contrast medium.


Immunologically mediated tubulo-interstitial nephritis in children. 14 children with proven or presumably immunologically mediated tubulo-interstitial nephritis are presented. In 2 patients anti-tubular basement membrane antibodies were detected. In 6 immunofluorescence microscopy showed granular deposits of immunoglobulin and/or complement likely representing interstitial location of immune complexes. The findings by immunofluorescence were not significant in the remaining 6 patients. However, the association of renal disease to extra-renal disorders, namely chronic active hepatitis and ulcerative colitis, or uveitis or the presence of an epithelioid granuloma with multinucleated giant cells suggests that in such patients an immunologic disorder might be responsible for the tubulo-interstitial nephritis.


Immunological aspects of pyelonephritis. Several virulence factors, such as O and K antigens and capacity to attach to uroepithelial cells, seem to be required for Escheria coli to cause acute pyelonephritis. These factors induce an immune response, however, which can modify the course and clinical expression of the infection. During acute pyelonephritis, autoantibodies to the Tamm-Horsfall protein increase. These antibodies, which probably are evoked by a cross-reaction noted between structures of E. coli LPS and the Tamm-Horsfall protein, may add to the renal tissue engagement in interstitial nephritis caused by bacterial pyelonephritis.


Renal damage due to urinary tract infection. Chronic pyelonephritis is a disease of childhood which is carried on into adult life. Children under the age of 4 in whom UTI, vesico-ureteric reflux and pyelotubular back-flow coexist appear to be particularly at risk of developing kidney damage. Attempts to prevent kidney damage in adults by detection and treatment of covert UTI are doomed to failure because persistent bacteriuria in the adult is a consequence of underlying abnormality of the urinary tract rather than its cause. Our main hope for the prevention of kidney damage associated with bacteriuria and reflux is to detect and treat these conditions at the earliest possible age.


Prophylaxis and therapy of venous thromboembolism. Heparin is an anticoagulant drug which is used for the prophylaxis and treatment of venous thromboembolism and for the treatment of some cases of arterial thromboembolism. Venous thromboembolism is the commonest preventable cause of death in hospitalized patients, and the best approach to reduce its morbidity and mortality is the use of safe, effective, prophylaxis in patients at high risk. The use of low doses of heparin given s.c. (5000 units, 8 hourly)) has been shown in prospective clinical trials to be effective prophylaxis against venous thrombosis and nonfatal and fatal pulmonary embolism in patients undergoing general abdominothoracic surgery, without producing dangerous bleeding. Low-dose heparin, however, is not totally effective in patients undergoing hip surgery and suprapubic prostatectomy. The lack of benefit in these patients may be related to the intensity of the provocation to thrombosis. The use of heparin in large doses to treat thrombosis is associated with hemorrhagic complications in up to 30% of patients. There is evidence that continuous i.v. heparin is associated with fewer hemorrhagic complications than intermittent i.v. heparin, but the frequency is not related to the dose or to the use of laboratory monitoring. Hemorrhagic complications occur more frequently in elderly patients and in females and is more common following surgical operations. The frequency of recurrent venous thromboembolism is low in patients on therapeutic doses of heparin, and there is no difference in the frequency of recurrence in patients receiving heparin by continuous i.v. or intermittent i.v. administration.


Continuous in vivo oxygen saturation in newborn infants with pulmonary disease: a new fiberoptic catheter oximeter. We measured the in vivo oxygen saturation of hemoglobin in the arterial blood of 34 sick newborn infants with a new, rapidly responding, continuously recording, catheter oximeter. The oxygen saturation, SaO2, was found to fluctuate between 85 and 95% in infants with pulmonary disease who are in a stable condition and breathing spontaneously. Severe disaturation occurred during apnea and after procedures such as chest percussion and suctioning of the endotrachael tube. The effects of changes in respiratory therapy were quickly manifested by changes in SaO2. This was particularly useful in guiding resuscitation of newborn infants who were asphyxiated at birth. Blood sampling for measurement of PaO2 can be done less frequently, reducing the need for blood transfusions in small infants.


Cardiorespiratory monitoring in postoperative patients: I. Prediction of outcome and severity of illness. An index for prediction of outcome for use as a measure of the severity of illness was developed by a nonparametric multivariate analysis of cardiorespiratory data from 113 critically ill postoperative general surgical patients. This severity (predictive) index was based on a computerized algorithm that compares a given observed value with the frequency distributions of survivors and nonsurvivors. The difference in the mean values of this index for survivors and nonsurvivors was statistically significant (p less than 0.001) during each stage of shock. Sensitivity of the index in prediction of survival ranged from 70-93% depending upon stage, the specificity of the index ranged from 76-92%, and the predictive accuracy ranged from 87-96%. The severity index is used as a process measure to track the course of critically ill patients and to evaluate the efficacy of alternative therapies.


Cardiorespiratory monitoring in postoperative patients: II. Quantitative therapeutic indices as guides to therapy. Immediate (proximate) and late (optimal) therapeutic goals for critically ill postoperative general surgical patients were based on the frequency distributions of cardiorespiratory data of the survivors immediately after resuscitation and in the late stage of shock, respectively. An algorithm was developed which expresses in quantitative terms the distance from observed values for each variable to both of these therapeutic goals. Further, composite indices were also made of related cardiorespiratory variables that reflect the important aspects of acute circulatory failure and its therapy; i.e., volume, flow, tissue perfusion, oxygen transport, and bodily response to stress. The therapeutic indices of nonsurvivors were found to have greater mean deficits that survivors (p less than 0.05) during all but the middle stage of shock. The therapeutic indices greatly aid in the organization and display of monitored cardiorespiratory variables by expressing the circulatory defects in easily understood indices that can be related to therapeutic interventions. Moreover, the interactions of the various aspects of cardiorespiratory function before and after therapy may be easily observed.


A double-blind controlled trial of amineptine versus trimipramine in depression. A double-blind controlled trial was carried out in 50 depressed out-patients to compare the effectiveness and tolerability of amineptine (200 mg per day) with that of trimipramine (75 mg per day). Patients were allocated at random to receive one or other of the trial drugs over a period of 45 days. Assessments were made before, during and after treatment of a number of target symptom clusters. Whilst overall response to treatment was the same with both drugs, trimipramine was superior in those patients presenting with anxiety and insomnia. Amineptine, however, was more effective not only against depressive mood and psychomotor retardation, but also against loss of libido, hypochondriacal features and social withdrawal. Both drugs were relatively well tolerated, but trimipramine had a sedative effect which proved troublesome in some patients.


Cross-over trial comparing the antidepressant effects of amineptine and maprotiline. A double-blind controlled, cross-over trial was carried out in 70 depressed patients to compare the effectiveness and tolerability of amineptine with that of maprotiline. Patients were allocated at random to receive treatment with either 150 mg amineptine or 75 mg maprotiline daily for 6 weeks before being treated for a further 6 weeks with the alternative drug. Comparison of the response to treatment at the end of each period showed that amineptine was significantly better than maprotiline, and this was particularly marked in the 46 patients with exogenous depression where an effect was usually evident within 3 to 5 days. Only 6 patients in this group failed to show a response to amineptine compared with 19 to maprotiline. Both drugs appeared to be equally effective overall in patients with endogenous depression, although when amineptine was given as the second treatment there was an improvement in retardation. Few side-effects were reported during either treatment period.


Levamisole (R 12564) in the prevention of recurrent upper respiratory tract infections in children: a double-blind, placebo-controlled study. A double-blind, placebo-controlled trial was carried out in 33 children suffering from chronic or recurrent upper respiratory tract infections to assess the effectiveness of levamisole in reducing the number, duration, and severity of infective episodes. A weight-related dosage of levamisole was used (2.0 to 2.5 mg per kg body weight), patients taking a single dose on 1 day per week over an autumn-winter period of 4 months. The results showed that patients in the levamisole-treated group had statistically significantly fewer periods of upper respiratory tract infection and when they occurred the episodes were milder and shorter in the levamisole group and required less antibiotics. No side-effects were noted.


A crossover clinical trial of piroxicam, indomethacin and ibuprofen in rheumatoid arthritis. A single-blind, crossover trial was carried out in 24 patients with definite or classical rheumatoid arthritis to compare the effectiveness and tolerability of piroxicam (20 mg once daily) with that of indomethacin (25 mg 3-times daily), ibuprofen (400 mg 3-times daily) and placebo. Each drug was given in random order for a period of 1 week. Pain, joint tenderness and morning stiffness decreased and grip strength increased with piroxicam compared to placebo; no statistically significant difference could be found between piroxicam and the two other active agents. A reduction in joint circumference could not be demonstrated with piroxicam or ibuprofen but most patients did not have reducible swelling in their finger joints. Piroxicam was just as effective as the other two drugs overall, but fewer side-effects were noted with piroxicam.


Double-blind clinical trial of the antidepressant action of amineptine. A double-blind controlled study was carried out in 51 patients with moderate to severe depression to compare the effectiveness and tolerability of amineptine (200 mg per day) with that of amitriptyline (75 mg per day) given over a period of 6 weeks. Assessments of overall response to treatment, judged clinically, taking into account the patients' views, and also comparing total scores on the Hamilton Rating Scale, showed that amineptine was equally as effective as amitryptyline in producing a marked improvement in most patients. The results suggest, however, that amineptine was more rapid in action as well as being better tolerated. Analysis of the scores for individual items on the rating scale showed up differences between the two drugs in their influence on a number of the items and in the time of onset of improvement.


Childhood enuresis.

Childhood enuresis. Enuresis is not a disease, but rather a benign clinical disorder that is very common in young children. In considering the many facets of enuresis, physicians caring for children with this disorder should always remember the dictum "Primum non nocere". Most children with enuresis will be found to have primary enuresis, that is, no organic disease or psychopathology will be found. Physicians should proceed cautiously and should avoid costly, harmful and unnecessary workups. Treatment of few disorders is more dependent on the art and skill of clinical medicine than that of childhood enuresis. All of the physician's talents and compassionate nature enter into the proper evaluation of and therapy for this disorder. Physicians must keep in mind the high spontaneous cure rate. This factor alone should encourage them to be extremely optimistic about the outcome of enuresis in their pateints.


Malignant melanoma and its therapy: a review. Malignant melanoma (MM) is an important cutaneous neoplasm. In classic cases, histologic levels of tumor invasion have been used as indicators of prognosis. Recent research suggests that vertical tumor thickness may be an equally valuable guide to prognosis and also to therapy. The standard surgical approach of wide excision and regional lymph node dissection may not be mandatory for all patients with MM. Regional perfusion of accessible primary tumors as an adjunct to surgery has yielded encouraging results. Immunotherapy of MM alone and in combination with chemotherapy may improve the poor outlook for disseminated MM.


Uremic pruritus: a review.

Uremic pruritus: a review. The subject of itching associated with renal failure is discussed. Possible pathogenetic mechanisms and available therapeutic modalities are presented.


The noneffectiveness of neomycin ointment when used prophylactically following skin electrodesiccation and curettage. Neomycin ointment is shown to be no more effective than placebo ointment in preventing site infection after biopsy according to a double-blind, placebo controlled study, analyzed according to an armitage restricted design, two-sided test, sequential analysis.


Protoplast formation and the visualization of nuclei in the eukaryotic microbe, Achlya. Protoplasts have been released form 21 h germlings of the aquatic fungus, Achlya. The commercial enzyme preparation Driselase was utilized to digest the hyphal walls. Protoplast release began 20 min after incubation at 25 degrees C, and was completed by 2 hr after enzyme addition. The fluorescent dye mithramycin was utilized to observe nuclei both in tract hyphae and in isolated protoplasts.


Human cells in suspension. 1 Human lymphoid and granulopoietic cells in primary and secondary cultures: effects of in vitro induction and prolonged methanol acetic acid fixation on metaphase chromosome structure. Modifications of Hungerford's method (1965) for production of chromosomal slides from human lymphoid cells in culture have been developed. Modified in vitro induction of banding and uncoiling has been used to produce chromosomal slides from human neoplastic cells of granulopoietic origin. The chromosomes are well spread and appear either long, thin and segmented or uncoiled. It is suggested that it is the combined action of the prolonged fixation used, and the in vitro induction, which leads to the observed structural alteration of the chromosomes. A method for increasing the yield of metaphase cells when working with bone marrow has been developed on the basis of culturing the granulopoietic cells in medium containing colony stimulating factor (CSF). Comparative analysis of metaphases from primary and secondary cultures of bone marrow cells showed that the culturing conditions for the secondary cultures do not induce chromosome abnormalities in the cells during the growth period.


Mechanical work on the lungs and work of breathing with positive end-expiratory pressure and continuous positive airway pressure. The mechanical work on the lung required during spontaneous breathing with positive end-expiratory pressure (PEEP) was compared with different methods of continuous positive airway pressure (CPAP) in nine young healthy athletes (surfers) at levels of 5, 10, 15, and 20 cm H2O. At the level of 20 cm H2O, PEEP increased the mean total work per minute by 116 percent and the total work per liter by 121 percent. The percent increase rose linearly with the level of PEEP. In contrast, with methods of CPAP that maintained the airway pressure (Paw) constant, the total work per minute decreased by 45 per cent at a PEEP of 10 cm H2O and remained at this level with PEEP of 15 and 20 cm H2O. Use of PEEP did not increase the functional residual capacity (FRC) in these spontaneously breathing subjects. In contrast, CPAP resulted in a rise in FRC proportional to the level of CPAP. This suggests that CPAP must be applied in a manner that maintains Paw constant to provide optimal assistance to ventilation.


Treatment of the adult respiratory distress syndrome with continuous positive airway pressure. Fifteen patients in the early stages of the adult respiratory distress syndrome with severe hypoxemia who were capable of maintaining adequate spontaneous ventilation were treated with continuous positive airway pressure (CPAP). The optimal level of CPAP was adjusted for each patient to achieve the highest oxygenation with the least adverse hemodynamic effects. The optimal intravascular volume, judged by pulmonary arterial occlusion pressure, was maintained by infusion of lactated Ringer's solution. Application of an optimal CPAP ranging between 10 and 25 cm H2O significantly reduced the intrapulmonary shunt, increased the forced vital capacity, and decreased the respiration rate. The improvement in pulmonary status was achieved with no significant changes in cardiac output or the arterial-mixed venous oxygen content difference. Early application of an adjusted level of positive end-expiratory pressure using CPAP in patients with adequate levels of fluid is an effective and safe method of treating selected groups of patients in the early stages of the adult respiratory distress syndrome.


Effects of glucocorticosteroids in patients undergoing coronary artery bypass surgery. Glucocorticosteroid, methylprednisolone sodium succinate (MPSS), 30 mg/kg of body weight, or dexamethasone sodium phosphate (DSP), 6 mg/kg of body weight, were given intravenously to 60 patients, divided into two groups of 30 45 minutes prior to cardiopulmonary bypass for coronary artery bypass. These two groups were compared with 30 patients in a control group receiving a placebo and undergoing the same surgery. The study was carried out in a double-lind fashion. Patients receiving MPSS had a significantly higher cardiac index in both the preoperative and postoperative periods. This was accompanied by a decreased peripheral resistance. Patients receiving either MPSS or DSP also showed some evidence for the "washout" phenomenon indicating the possibility of better microcirculatory flow. Gluconeogenesis may have been enhanced in both groups receiving MPSS or DSP, but the evidence was greater in thos patients receiving MPSS. There were no hospital deaths in any of the three groups totaling 90 patients.


The effects of oestrogen on hypothalamic tissue. Oestrogens exert potent influences on hypothalamic differentiation and on sexual function throughout life. During the period in which the hypothalamus differentiates, the availability of oestrogens (or aromatizable androgens) to the hypothalamus results in a male pattern of gonadotropin secretion and in male sexual behaviour in the adult. Lack of oestrogens during this period results in a cyclic schedule of gonadotropin secretion and in female sexual behaviour. Oestrogens or their metabolites determine future sex-specific activity by facilitating synapse formation in developing target circuits. The onset of puberty may also in part reflect oestrogen-stimulated synapse formation in the hypothalamus. In contrast, oestrogen given to an adult female rat causes specific multifocal lesions in the lateral arcuate nucleus. Such animals exhibit persistent oestrus and small multicystic ovaries. Since the same anovulatory syndrome can be produced by mechanical disruption of neuronal pathways from more anterior regions to the arcuate nucleus, it would appear that oestrogen could effect a 'disconnection' of the circuit responsible for cyclic drive of gonadotropin secretion. Furthermore, old female rats spontaneously exhibit the same type of reproductive derangement as well as the arcuate lesion. Thus direct effects of oestrogens on neuronal circuitry within the hypothalamus may be responsible for (1) sexual differentiation, (2) the onset of puberty and sexual activity, and (3) cessation of reproductive function in the female rat.


[Oral candidiasis in leukoplakia and carcinoma of the oral cavity (author's transl)]. The incidence of Candida albicans and other candida species were examined by mycological culture and histologically in 193 patients with various forms of oral leukoplakia and 14 patients with carcinoma of the oral mucosa, the results being compared with a control group of 137 subjects with a normal mucosa. Comparing the leukoplakia groups one with the other and with the control group revealed definite, usually statistically significant, differences in the incidence of fungi: 46.4% of patients, 29.2% among controls. The incidence of oral fungi was 35.4% among those with noxigenic leukoplakia, 50% in precancerous leukoplakia, 71.5% in mucosal carcinoma, and 49% in nosogenic leukoplakia (mainly lichen planus mucosae). The fungal elements could be demonstrated histologically much less frequently than by culture, but the difference of demonstration was statistically more significant between the different forms of leukoplakia. It is probable that chronic candidiasis in leukoplakia is not carcinogenic as such but is the microbiological and indicator of a local or systemic disorder of the cellular immune system.


[Bronchospasmolytic effect of reproterol as aerosol (author's transl)]. In an intraindividual double-blind study the effect of 1% (2.5 mg) and 2% (5 mg) reproterol aerosol was investigated in 30 patients with chronic obstructive bronchitis and asthma. Both solutions had a statistically highly significant bronchospasmolytic effect when airways resistance and specific conductance were measured. The effect was demonstrable immediately after termination of inhalation. Cardiac frequency and blood pressure remained unchanged. No subjective side effects were reported.


[Serum antibodies in cystic and alveolar hydatid disease (author's transl)]. Serum samples of 107 patients with cystic and 30 with alveolar hydatid disease were tested for antibodies with hydatid fluid and extract from cyst material of E. alveolaris as antigens. Complement-fixation, indirect haemagglutination and an indirect enzyme immune (ELISA) technique were employed. The results indicate an antibody picture which confirms the value of serum-antibodies in the diagnosis of hydatid disease. Diagnostically insufficient antibody formation was present in seven patients with cystic and two with alveolar hydatid disease. The indirect haemagglutination test with alveolaris antigen proved to be the most sensitive reaction for antibody demonstration of both echinococci, while the same antigen in the ELISA technique gave species-specific results in patients with E. alveolaris.


Management of the perineal wound after rectal excision for neoplastic disease: a controlled clinical trial. Two methods of management of the perineal wound after rectal excision for neoplastic disease were compared in a prospective randomized clinical trial in 65 patients. Twenty-eight patients (Group A) were treated by partial closure of the perineal wound and cigarette drainage of the pelvic space, according to the method proposed by Gabriel. Thirty-seven patients (Group B) were treated by complete suture of the perineal wound and suction drainage of the pelvic space according to the method proposed by Altemeier. Immediate and late results were better in patients in Group B. They achieved healing per primam in 62.82 per cent of cases and had significantly shorter hospital stays than patients in Group A. Three months postoperatively, 91.42 per cent of patients in Group B and 59.25 per cent of those in Group A had complete healing of the perineal wounds, with a statistically significant difference (chi2 with Yates correction = 7.27, P less than 0.01). The development in 10 patients of Group B of perineal abscesses or hematomas necessitated reopening of the perineal wounds: however, the postoperative courses were similar to those of patients in Group A. It is concluded that healing by primary intention with use of the method described herein is the treatment of choice for managing the perineal wounds in patients undergoing rectal excision for neoplastic disease.


[Results of 200 renal transplantations (author's transl)]. Two hundred renal transplantations were performed on 187 patients between July, 1972 and June, 1978. On a follow-up of 6--78 months the survival rate after allogenic transplantation was 80% at one year and 64% at five years. Satisfactory renal function was present in 62% at one year and 31% at six years. Gastrointestinal complications were common and caused about 40% of all deaths. Severe infections were the second most common cause of death. Local complications required explantation in 4%, and caused death in 0.5% of cases. Change in the treatment regimen, using less massive immunosuppressive measures during acute rejection, lowered the death-rate without a higher loss of transplants. The death-rate was 16% at three months and 26% at one year in the first of the 200 transplantations, but 6% and 12%, respectively, in the last 50 consecutive transplantations. The survival rate of patients with transplants is thus comparable to that of patients receiving chronic haemodialysis.


Control of the blood glucose in diabetes mellitus is it valuable? Is it feasible. The controversy over the whether strict blood glucose control prevents or attenuates the complications of diabetes is still unresolved, but the available data support the value of good blood glucose control. The resolution of the controversy is not feasible at present because of the complexity and financial cost of a definitive prospective study and because we may not presently possess pharmacological agents which can accomplish the goal of long term strict control of the blood glucose. Finally, whereas we regard retinopathy, nephropathy and neuropathy as valid pathological endpoints, we are not secure in assuming that blood glucose represents the critical measurement for longitudinal assessment of metabolic control. Studies evaluating control based on blood and urine glucose assessments are complicated by the failure of the data to reflect changes in minute to minute regulation. Thus, the relative insensitivity of some of these parameters of control could account for failures to demonstrate a correlation between adequacy of therapy and diabetic complications.


[A new electrophoretic method for coating metalceramic elements with opaque]. A new, electrophoretical method of coating dental alloys (Au or Ni-Cr) with opaque is described for the first time. The comparison of this method with the known wet brush technique shows that bubbles or voids might occur at the interface between metal and opaque when applying the first ceramic layer manually whereas the electrophoretical one generates a thin and dense layer of porcelain being free of voids within the adherence zone. Those bubbles are considered to be inherent with the brush technique. The author suggests to galvanize dental alloys particularly noble metals in order to suppress any anodic reactions. General advantage for the bond due to galvanization are expected no matter how the opaque was applied.


[Casting of dental alloys with special reference to the bonding capacity of Ni-Cr alloys]. A short review on castability of dental alloys -- for which a definition is proposed -- reflects the different factors influencing the results of a casting. In this case solid sieves and plates are cast by use of one gold-base alloy (Type III) and two base metal alloys used for porcelain veneering. All three alloys filled the sieve pattern to a 100%, whereas they performed differently when cast as thin, solid squares. The most continuous results were achieved with a Ni-Cr-alloy whose melting temperature can be recognized since the ingots flow together when this point is reached. Since the plate pattern is most difficult to cast due to surface to bulk ratio it is assumed that a complete casting can only be achieved when the performance of the alloy is good and all required conditions match. Thus, this type of test seems to be suitable to determine the castability of a dental alloy. The sieve test should be used to investigate and to improve the influence of the different factors as for example burnout time and temperature of the mold and sprue size.


[Double-blind study on the anti-inflammatory effect of indomethacin after surgical removal of lower wisdom teeth]. The use of indomethacin (Amuno, Indocid) to prevent postoperative complications following oral surgery was checked in double blind tests. Impacted and half-impacted lower third molars from 100 patients were surgically removed; 50 were given indomethacin orally and 50 were given a placebo. Postoperative body temperature and pain were recorded on the first and second days after surgery. Trismus and cheek swelling were also measured.


[A splitcast made of plastic].

[A splitcast made of plastic]. A new two-piece plastic split cast consisting of an assembly plate and a disposable part was described; its use as a diagnostic an control device was discussed. The split is available for all standard articulators.


[Effect of various methods of the preservation and preparation for study of human peripheral blood on erythrocyte morphology (scanning electron microscopy)]. In the paper the authors describe the influence of various ways of preservation and preparation of peripheral human blood on the morphology of erythrocytes. The investigation was performed by a scanning electrone microscope JSM-35 JEOL--Japan). The basic types of erythrocytes were shown, which were encountered in the samples. It was established that dehydratation and various methods for fixation of erythrocytes did not affect their morphology. The authors found changes, which occurred in erythrocyte morphology after blood preservation in anticoagulant,FBFR and as a whole blood at various intervals. The action of centrifugal forces in the process of centrifugation of blood on various types of erythocytes was indicated as well. The results of the studies were illustrated with 21 pictures, made at magnification of 3000 X up to 15 000 X.


[Measurement of the Na2 35S04 in donor cornea with a view to assessing its biological properties]. The authors carried out studies on 425 pig cornea, conserved in a modified solution for tissue cultures at 4 degrees C. The intensitivity for incorporation of Na235SO4 in this nutritive medium gave higher percentage than the preservation of cornea in moist chamber.


[Theoretical aspects of the quantitative study of the chemical structure-biological action relationship]. The study of the interrelationship between the chemical structure of the drug molecule and their biologic activity is one of the most modern aspects of current pharmacology and pharmacochemistry. The information, obtained by these studies, contributes for more precise and detailed understanding of the mechanisms of drug molecule interaction with some biologic structures, and this helps to clarify a series of biologic and physiological phenomena. The authors describe in this paper some methods, which are used, when the dependences between structure and action are search for as well as the basic physiocochemical and quantum -- chemical values, which determine the pharmacological effect of drugs.


[Changes in the motor activity of an isolated intestinal loop from the jejunum of dogs exposed to an endotoxin]. The author examined the motor activity of an isolated Loop in vivo of founonnarcotised dogs under the conditions of chronic experiments before and after administration of E. coli in dose of 0.1, 0.5, 1.0, and 2.0 mg/body weight. There was inhibition of the movements of the intestinal loop, which was manifested by a reduction of the frequency and amplitude of the intestinal contractions. The inhibition of the motor activity was explained by the disturbances in the circulation and neuro-bunoral control of the intestinal smooth muscle.


[Concepts of inhibition in psychiatry].

[Concepts of inhibition in psychiatry]. Following a historical approach, the authors first describe the original development of the concept of inhibition in neurophysiology and then analyze the subsequent adaptations made in psychiatry around such concept including those of: -- Pavlov, Hull, Watson and the behaviorists, -- Freud and the Freudian School, -- clinicians and psychopharmacologists. The concept of inhibition has thus various meanings in psychiatry. Although some unity is achieved on the semiological level, this aspect cannot explain the extent of the process.


[Carpipramine in psychoses].

[Carpipramine in psychoses]. A survey of 131 psychotic subjects treated with carpipramine and a synthesis of the Japanese, German and French publications about this drug were done. The most valuable results were obtained in hebephrenics and in depressed schizophrenics. Carpipramine has a definite desinhibitory action against motor retardation, lack of energy, ideo-motor slowliness and blunting of the affect. At low doses, paranoid schizophrenics become worse. The emerged delusional and anxious phenomena, can be avoided by using higher doses. This drug possesses two kinds of effects: antidelusional and desinhibitory actions. If it does not seem to be a true antidepressant, Carpipramine proves useful in deficits of the psychomotor tone, which were resistant to antidepressant drugs.


[Carpipramine in neuroses].

[Carpipramine in neuroses]. Having outlined the limits of drug-therapy in neuroses, where it may support psychotherapy, a treatment the use of which is still questioned by some, the authors review the rare publications involving the indications of Carpipramine in neurotic syndroms. Active upon symptom patterns consisting essentially of asthenia, inhibition and psychomotor impairment, raising the level of activity, stimulating enthusiasm and relational activity, Carpipramine would appear to represent a new advance in the treatment of some neurotic syndroms, partially encompassing the border-line indications of anti-depressants and those of certain disinhibitory neuroleptic agents.


[Carpipramine in child psychiatry].

[Carpipramine in child psychiatry]. The use of Carpipramine in 35 children and teenagers, most of them suffering from psychosis, has confirmed its beneficient action in the majority of those cases (5 negative scores for 20 good and very good scores). The early-observed improvement concerned inhibition, lack of energy, moroseness, favouring the patients' integration in the institutional context.


[Carpipramine and drug addiction].

[Carpipramine and drug addiction]. This study is related to the therapeutic effects of Carpipramine in conditions of pharmacodependance to opiates. The withdrawal in 47 subjects by decreased doses of methadone, clinically presenting 42 amotivational syndroms and 5 depressions. On the other hand, 3 withdrawal trials using chimiotherapy, including Carpipramine, failed. Carpipramine seems to have an important disinhibitory effect in amotivational syndrom and tolerance is excellent. Lack of desire for this psychotropic drug makes its use safe by drug addicts.


Localization of angiotensinogen in rat liver by immunocytochemistry. Plasm angiotensinogen, the protein precursor of angiotensin, is produced by the liver. The present study investigated the location of angiotensinogen in sections of rat liver using the unlabeled peroxidase-antiperoxidase bridge technique of Sternberger. Specific reaction products of the antibody localization method were most pronounced in the cytoplasm of hepatocytes in the pericentral zone of the liver lobule. Controls, in which antibody was preabsorbed with angiotensinogen, did not form reaction product. The gradient of angiotensinogen observed within liver lobules resembled that demonstrated by metabolic zonation. The distribution of angiotensinogen differed from the scattered distributions found for other plasma proteins.


Synthesis and accumulation of proinsulin and insulin during development of the embryonic rat pancreas. Endocrine B cells differentiate normally in embryonic rat pancreatic rudiments cultured in vitro. The specific concentration of immunoreactive insulin based on total protein increases by about 1000-fold during the developmental period, corresponding to days 13--20 of gestation. The rate of (pro)insulin synthesis, measured from the level of radioactive leucine incorporated into insulin, quantitatively accounts for the insulin accumulated during this period. In addition, the relative incorporation of leucine into proinsulin compared to insulin is constant during development and is similar to that found in the B cells of adult islets. Thus, there appears to be no significant change in the rate of conversion of proinsulin to insulin during B cell differentiation.


Thyrotrophs in old age. An immunocytologic study of human pituitary glands. In order to reveal whether thyrotroph cells of the human pituitary are affected by aging, a histologic and immunocytologic study was undertaken on the pituitaries of patients over 80 years of age (10 men, 10 women), dying of various acute illnesses and the findings compared with those of a younger age group (10 men, 10 women), dying of various acute illnesses between the age of 20-56 years. The incidence, distribution, granulation, cytoplasmic vacuolization, as well as immunoreactivity of TSH cells, showed no major differences related to age and sex. Lack of involution of thyrotroph cells in old subjects indicates that the pituitary is capable of producing TSH with advancing age.


Contrasting effects of maternal fertility and birth rank on the occurrence of neural tube defects. The relationships between the occurrence of anencephalus and spina bifida, sibship size and birth rank were examined, using linked records for births in British Columbia. Comparison of 414 sibships in which at least one infant had a neural tube defect with 1362 randomly chosen unaffected sibships showed that the affected sibships were larger. There were both more births than expected after the affected birth, and shorter intervals between births before the affected birth. Within sibships, the risk of anencephalus or spina bifida decreased strongly with increasing birth rank. No associations were seen with maternal age at first birth.


Purification and molecular properties of a new colicin. The process of isolation and purification of a new colicin isolated from a Citrobacter strain is described. Escherichia coli sensitive cells are protected by vitamin B12 from the action of this bacteriocin; this suggests that it belongs to the E group of colicins. Therefore, we have called it colicin E4. It has a molecular weight of 56 000 and two molecular forms of isoelectric points 9.4 and 8.2 are separated in electrofocusing on polyacrylamide gels. It has a sedimentation coefficient of 3.4 S and the absorption coefficient A1(280%) nm is 6.23 cm(-1). Using an antibody raised against pure colicin E4, no cross-reaction was detected against colicins A, E1 or K. The physiological effect of colicin E4 on sensitive cells is very similar to that of colicins E1, K or I which disrupt the energized membrane state.


The influence of ribonucleoside triphosphates, and other factors, on the formation of very-salt-stable RNA-polymerase . su+III-tRNA(tRNATyr)-promoter complexes. The formation of a stable RNA-polymerase . su+III-tRNA-promoter complex was found to require sigma factor and the incorporation of ribonucleoside triphosphates which match the 5' sequence of the su+III tRNA transcript. This complex, stable to at least 2 M KCl, can be retained on a Millipore filter. Its formation closely parallels the extent of transcription obtained from the su+III tRNA promoter in response both to increasing ionic strength and to temperature during incubation of RNA polymerase with the DNA. The RNA-polymerase . DNA complex retained during this assay therefore appears to relate directly to that formed during promoter-directed transcription. The formation of RNA-polymerase . su+III-tRNA-promoter complexes is sensitive to the presence of ppGpp.


Low-molecular-weight substrate for the lysozyme of T4 bacteriophage. It has been shown that muropeptide CB, the chemically defined product of Escherichia coli B murein digestion by phage lambda endolysin, is the substrate for T4 lysozyme. This is the tetrasaccharide GlcNAc-MurNAc-GlcNAc-anMurNAc in which the carboxyl groups of MurNAc and anMurNAc residues are substituted by tetrapeptide LAla-DGlu-msA2pm-DAla (MurNAc = N-acetylmuramic acid, GlcNAc = N-acetyl-D-glucosamine, anMurNAc = 1,6-anhydro-N-acetylmuramic acid, LAla  = L-alanine, DGlu = D-glutamic acid, msA2pm = meso-diaminopimelic acid). The substrate contains one bond hydrolysable by T4 lysozyme. The products of hydrolysis are the easily identifiable disaccharide muropeptides C6 (GlcNAc-MurNAc-LAla-DGlu-msA2pm-DAla) and CA (GlcNAc-anMurNac-LAla-DGlu-msA2pm-DAla). Thus the substrate may be used for the specific identification of murein N-acetylmuramoylhydrolases of the T4 lysozyme type, as well as for any quantitative measurement of the enzymatic reaction.


DNA-dependent RNA polymerase from the archaebacterium Sulfolobus acidocaldarius. Purified DNA-dependent RNA polymerase from Sulfolobus acidocaldarius is composed of 10 different subunits, one of which is present as four copies. Their molecular weights are 122 000, 101 000, 44 000, 32 000, 24 000, 17 500, 13 800, 11 800 (four copies), 11 200, 10 800, summing up to a total Mr of 423 500. The sedimentation velocity is 13.5 S, indicating that at 0.5 M NH4Cl the enzyme exists in the monomeric form. At pH 9.2 in cellogel electrophoresis two of the subunits migrate towards the cathode. The composition is quite different from that of a typical eubacterial RNA polymerase. Its complexity reminds one of eucaryotic RNA polymerase. Maximal transcription of DNA from a Halobacterium halobium phage øH (øH DNA) proceeds at pH 8.5 AND 75 DEGREES C. The enzyme is stable up to 75 degrees C and strictly requires a DNA template. øH DNA and poly[d(A-T) . d(A-T)] are the most efficient. The temperature dependence of the transcription rate is characteristic for the template. Actinomycin D and heparin prevent transcription, while rifampicin, streptolydigin and alpha-amanitin have no effect. During storage, even at -- 70 degrees C, the enzyme loses its activity to transcribe øH DNA, whereas transcription of poly[d(A-T) . D(A-6)] remains unaffected.


Porcine pancreatic lipase. Sequence of the first 234 amino acids of the peptide chain. The single polypeptide chain of about 460 amino acids of porcine pancreatic lipase (EC 3.1.1.3) has been fragmented into five peptides by cyanogen bromide cleavage [Rovery, M., Bianchetta, J. & Guidoni, A. (1973) Biochim. Biophys. Acta, 328, 391--395]. The sequence of the first three cyanogen bromide peptides (CNI, CNII, CNIII), including a total of 234 amino acids, was fully elucidated. Automatic or manual Edman degradation was performed on the different peptides. Fragmentations of the CN peptides were accomplished by digestions with trypsin (after citraconylation or 1,2-cyclohexanedione treatment), chymotrypsin and Staphylococcus aureus external protease. Hydrolysis of unreduced material by pepsin and thermolysin, performed in order to determine the S-S bridge positions, provided useful overlapping peptides. The glycan moiety of lipase is bound to Asn-166. The non-essential tyrosine specifically blocked by diisopropylphosphorofluoridate is Tyr-49 in a cluster of asparagine and glutamine residues. The existence of a highly hydrophobic sequence (206--217) at the C terminus of the CNII fragment is noteworthy.


The structure of a transcriptional unit on colicin E1 plasmid. In an RNA-synthesizing system in vitro, a low-molecular-weight RNA consisting of about 110 residues (RNA-I) was efficiently synthesized on DNA of colicin E 1 plasmid (ColE1) and its deletion derivatives. The promoter site for RNA-I was analysed by testing the RNA polymerase-binding ability and template activity of restriction fragments; it was mapped in the region between the replication initiation site and the colicin immunity gene of ColE1. The direction of transcription was determined by hybridization tests to the separated strands of the template. The DNA region directing RNA-I was sequenced, and RNA-I was assigned on the sequence based on the nearest-neighbour data of RNA. The sequences of its promoter and terminator regions were also deduced. Although the function of this small RNA species is unknown, a unique secondary structure could be constructed from its sequence and sensitivity to RNase.


The ternary 5-S RNA complex of proteins L 18 and L 25. A small-angle X-ray scattering titration study. The 5-S RNA (A) and the proteins L 18 (B) and L25 (C) from Escherichia coli ribosomes form a ternary complex of the type ABC with a stepwise stability constant, log K111 approximately equal to 6.5. This is indicated from X-ray scattering titrations recorded at 21 degrees C in ribosomal reconstitutional buffer. When the ternary ABC complex forms there is only a limited change in the scattering curve compared to that of 5-S RNA, indicating that 5-S RNA does not undergo a major conformational change during the complex formation. The increase in the radius of gyration from 3.61 nm (5-S RNA) to 3.95 nm (ABC complex) as well as the experimental scattering curve can be explained by models where it is assumed that the elongated L 18 and L25 models are quite far from the electron density centre and where the protein molecules interact mainly with the minor arms of the supposed Y-shaped 5-S RNA molecule.


The association of actin with a thyroid lysosomal fraction. A lysosome-enriched fraction was prepared from bovine thyroid tissue using sucrose gradient centrifugation. An inhibitor of DNAase I was found to co-sediment and co-purify with the lysosomal fraction. This inhibitory activity is blocked by heavy meromyosin in the absence of ATP, and a component of 42000 molecular weight can be isolated by affinity chromatography on DNAase I linked to Sepharose. These results are consistent with the presence of an actin-like protein in a lysosome-enriched preparation from bovine thyroid tissue. Also, an increase in the level of membrane-associated actin is observed in response to thyrotropin stimulation of the thyroid tissue


Yeast phenylalanyl-tRNA synthetase. Affinity and photoaffinity labelling of the stereospecific binding sites. The localization of the binding sites of the different ligands on the constitutive subunits of yeast phenylalanyl-tRNA synthetase was undertaken using a large variety of affinity and photoaffinity labelling techniques. The RNAPhe was cross-linked to the enzyme by non-specific ultraviolet irradiation at 248 nm, specific irradiation in the wye base absorption band (315 nm), irradiation at 335 nm, in the absorption band of 4-thiouridine (S4U) residues introduced in the tRNA molecule, or by Schiff's base formation between periodate-oxidized tRNAPhe (tRNAPheox) and the protein. ATP was specifically incorporated in its binding site upon photosensitized irradiation. The amino acid could be linked to the enzyme upon ultraviolet irradiation, either in the free state, engaged in the adenylate or bound to the tRNA. The tRNA, the ATP molecule and the amino acid linked to the tRNA were found to interact exclusively with the beta subunit (Mr 63000). The phenylalanine residue, either free or joined to the adenylate, could be cross-linked with equal efficiency to eigher type of subunit, suggesting that the amino acid binding site is located in a contact area between the two subunits. The Schiff's base formation between tRNAPheox and the enzyme shows the existence of a lysyl group close to the binding site for the 3'-terminal adenosine of tRNA. This result was confirmed by the study of the inhibition of yeast phenylalanyl-tRNA synthetase with pyridoxal phosphate and the 2',3'-dialdehyde derivative of ATP, oATP.


RNA polymerase from the fungus, Aspergillus nidulans. Large-scale purification of DNA-dependent RNA polymerase I (or A). The DNA-dependent RNA polymerase I (or A) from the lower eukaryote Aspergillus nidulans has been purified on a large scale to apparent homogeneity by homogenizing the fungal hyphae in liquid nitrogen, extraction of the enzyme at high salt concentration, precipitation of RNA polymerase activity with polymin P (a polyethylene imine), elution of the RNA polymerase from the polymin P precipitate, ammonium sulphate precipitation, molecular sieving on Bio-Gel A-1.5m, binding to ion-exchangers and DNA-cellulose affinity chromatography. By this procedure 1.6 mg of RNA polymerase I can be purified over 2000-fold from 500 g wet weight of starting material with a yield of 30--35%. The isolated RNA polymerase I is stable for several months at -20 degrees C. The subunit compostion has been resolved by polyacrylamide gel electrophoresis on two-dimensional gels, using either non-denaturing of 8 M urea (pH 8.7) cylindrical gels in the first dimension and sodium dodecyl sulphate slab gels in the second dimension. The putative subunits have molecular weights of 190,000, 135,000, 63,000, 62,000, 43,000, 29,000, (28,000), 16,000 and probably 13,000 and 12,000. Two distinct forms of RNA polymerase I (Ia and Ib) have been resolved by DEAE-Sephadex A-25 chromatography showing ample differences in enzymatic properties and subunit pattern. Additional information is given on RNA polymerase II (or B) which appears to be highly insensitive to alpha-amanitin at concentrations up to 400 micrograms/ml.


Recognition of tRNA Trp by initiation factors from Escherichia coli. Binding of acetyl or formyltryptophanyl-tRNA Trp from Escherichia coli or beef liver to E. coli ribosomes is strongly stimulated by E. coli initiation factors and requires GTP. The N-acylated tryptophan is puromycin reactive. Polypeptide chain initiation with acetyltryptophan dependent on poly(U,G) has been demonstrated and is highly dependent on added initiation factors. tRNA Trp appears, therefore, to share some structural features with tRNAfMet of significance to the process of polypeptide chain initiation.


Mitochondrial protein-synthesizing machinery in Saccharomyces cerevisiae grown in different metabolic conditions. Variability of seryl-tRNA and alanyl-tRNA isoacceptor patterns. 1. The isoacceptor patterns of mitochondrial seryl and alanyl-tRNAs from Saccharomyces cerevisiae grown under different conditions and committed to fermentative or respiratory metabolism have been studied by reversed-phase chromatography. 2. An extensive variability of the chromatographic patterns of the four isoacceptors for serine and of the three isoacceptors for alanine has been observed as a function of carbon source and stage of growth, but the main differences were observed in the different stages of growth on glucose. 3. In order to distinguish the effects due to stage of growth from those due to relief from glucose repression, the isoacceptor patterns of mitochondrial tRNA were compared in repressed and derepressed resting cells; results show that some of the mitochondrial species are almost undetectable in resting repressed cells, but are the major ones after recovery of respiration. 4. Two of the serine isoacceptors (species 1 and 2), one of which is absent or not acylable in repressed resting cells, are different gene products.


Somatic antigens of Shigella. The structure of the specific polysaccharide of Shigella newcastle (Sh. flexneri type 6) lipopolysaccharide. The specific polysaccharide was obtained from the lipopolysaccharide of Shigella newcastle by mild acid hydrolysis and further purified by permeation chromatography on Sephadex G-50. It was found to consist of L-rhamnose, 2-acetamido-2-deoxy-D-galactose, D-galacturonic acid residues and O-acetyl groups in the molar ratios of 2:1:1:1. On the basis of 1H and 13C nuclear magnetic resonance spectroscopy, methylation analysis, partial acid hydrolysis, Smith degradation, and chromium trioxide oxidation, the following structure can be assigned to the repeating oligosaccharide unit of the polysaccharide:-4)DGalA(beta 1-3)DGalNAc-(beta 1-2)LAc3Rha(alpha 1-2)LRha(alpha 1-, where GalA = galacturonic acid. GalNAc = N-acetylgalactosamine, Ac3Rha = 3-O-acetylrhamnose. The structural and immunochemical data presented prove that Sh. newcastle lipopolysaccharide belongs to a 'non-classical' type of somatic antigens with acidic O-specific polysaccharide chains.


Structure of the 50S ribosomal subunit from Escherichia coli. Investigation of the intact subunit and core particles by electron microscopy and analogue image processing. Structures of 50S ribosomal subunits, CsCl and ethidium bromide core particles from these subunits have been investigated by electron microscopy and image processing by FAIRS. This method revealed structural details which are obscured in individual images, and enabled to distinguish six crown forms, different in their side protuberances, and two kidney forms. Crown forms were imaged as symmetrical or asymmetrical forms. The latter type was far more frequent in untreated populations than the first. The depletion of proteins by both agents caused stepwise degradation of the side protuberances in the crown forms thereby transforming asymmetrical to symmetrical forms. It is concluded from these findings that asymmetrical and symmetrical forms in untreated populations represent also structurally different particles. From the higher complexity in terms of component composition and structure it is concluded that the asymmetrical crown forms are more likely to represent the native structure of isolated 50S subunits than the symmetrical forms. Existing models for this subunit are discussed in terms of this finding.


Jugular venous reflux in cerebral radionuclide angiography: an explanation. A case of isotopic jugular venous reflux, reaching the opposite jugular vein, is described. Phlebography and aortography were simultaneously performed in this patient and showed the innominate vein narrowed and pinched between the sternal notch and the aortic arch. This narrowing depends on the position of the left arm.


Extramicrosomal drug metabolism.

Extramicrosomal drug metabolism. Drug metabolizing enzymes which are not located in the microsomes such as oxidoreductases are reviewed. It has been reported that a cytoplasmic NAD+-dependent dehydrogenase could be involved in the dehydrogenation of secondary or primary alcohols, and that peroxidases, located in all extranuclear cell-fractions, are able to oxidize certain drugs. Among the conjugating enzymes, mainly the glucuronidases and 0-Methyltransferases have been reported to be localised in the microsomes. Sulfatation, mercapturic acid formation and acetylation seem to occur in the supernatant of animal liver cells. Binding to glycine has been found in the mitochondria. Examples of combined action of microsomes and other cell fractions are presented. Esterases are found in the microsomes and cytoplasmic fraction of animal cells and also in the extracellular fluid (blood-plasma). They are more stable than monooxygenases whose activity depends on the intact microsomal structure and are therefore readily accessible in human biological material. Metabolic problems involving human esterases can often easily be solved by in vitro experiments. Results concerning the biochemical degradation of propanidid, mefrusid, acetyl salicylic acid and an acetyl salicylic acid ester are reported.


Therapy of chronic consequences of brain ischemia. Comparison between two drugs acting on brain circulation and metabolism. With the purpose to define the specific activity of substances acting on the cerebral circulation and metabolism, (-)eburnamonine and cinnarizine were compared in a double-blind study carried out in a group of 106 elderly patients suffering from established chronic brain ischemia. The photoscintigraphic and rheoencephalographic studies carried out on some of the patients showed that only (-)eburnamonine had a clear-cut activity on brain circulation. (-)Eburnamonine also showed an activity on kidney circulation. With regard to the clinical picture, a statistical evaluation of the results obtained showed that both drugs improve psychic disturbances and the overall clinical picture. Cinnarizine appears to influence, to a slightly greater extent, some neurological symptoms, while (-)eburnamonine exerts a significantly better action on daily living activities and general psychic efficiency.


Clinical evaluation of (-)eburnamonine in comparison with nicergoline in patients suffering from chronic brain ischemia. The activity of (-)eburnamonine, a substance acting on the cerebral circulation and metabolism, was compared with that of nicergoline in a double-blind study carried out on a group of 28 patients (16 males and 12 females), suffering from established chronic brain ischemia. The treatment consisted of the administration for the first 5 days of 80 mg/day and for the following days of 60 mg/day of (-)eburnamonine, in 14 subjects. Nicergoline was administered to the other 14 subjects: 20 mg/day for the first 5 days and then 15 mg/day. The treatment was protracted for at least 20 days. (-)Eburnamonine appeared to influence some symptoms more rapidly and significantly than nicergoline. After 20 days of treatment the overall improvement obtained with (-)eburnamonine was 31 and 18% with nicergoline. No side effects or impairment of the biochemical tests appeared during either treatment.


Hemodynamic and metabolic factors in human cerebral ischemia. Hemodynamic and metabolic cerebral measurements (CBF, CMRO2, CMRG, CSF) were evaluated in stroke patients. To investigate the effects of chronic cerebral circulatory insufficiency, CBF and CMRO2 were also studied. Further nontraumatic investigations of CBF measurement will allow a better understanding of clinical cases.


Platelet aggregation: methodology and physiopathology. The physiopathological role of platelet aggregation in some thromboembolic and atherosclerotic complications is strongly suggested on the basis of many indirect findings. The qualitative methodological approach to this problem generally used until recently is rapidly giving way to a quantitative, biochemical approach. Platelet aggregation, however, even if expressed in terms of nanomoles of a product obtained in a sophisticated reaction system, will continue to deceive investigators and clinicians who fail to view it in the adequate (although still uncertain) context of rheological and vascular interactions.


Induction of thymocytotoxic autoantibodies after injection of bacterial lipopolysaccharides in mice. The injection of bacterial lipopolysaccharides (Salmonella typhimurium and Escherichia coli LPS) has been shown to induce thymocytotoxic autoantibodies in various strains of mice (C57BL/6, BALB/c, DBA/2, AKR, A/J and C3HeB/FeJ). Titers up to l:16 were observed. Such antibodies did not develop in C3H/HeJ mice which are low responders to LPS. The thymocytotoxic antibodies had the following characteristics: (a) 2-mercaptoethanol sensitivity, (b) optimal reactivity at 4 degrees C, (c) cytotoxicity for autologous and syngeneic thymocytes but not for spleen cells. The cytotoxicity decreased after absorption with thymocytes, spleen cells or brain tissue but not with kidney or liver homogenates. These LPS-induced thymocytotoxic antibodies were similar to the natural thymocytotoxic antibody occurring in NZB mice.


The central cervical nucleus in the cat. I. A Golgi study. The central cervical nucleus (CCN) in the upper cervical cord of the cat was studied with the Golgi rapid, Golgi Cox, and Golgi Kopsch methods. The majority of the neurones were large, multipolar, with dendrites radiating out from the nucleus dorsolaterally, laterally, and ventrally. Occasionally, small triangular or spindle shaped neurones were seen with dendrites following the rounded countour of the CCN. The axons from the large neurones were mostly directed towards the anterior commissure. Occasionally, the initial part of the axons from the smaller neurones were observed. They gave off collaterals within the CCN. The bulk of afferents came from the dorsal funiculus and spread out to form an afferent plexus around the CCN neurones. A small number of afferents was observed from the lateral funiculus. They were thinner than those from the dorsal funiculus and entered the CCN from its lateral aspect. The afferents from the dorsal funiculus had the same orientation as the dorsolaterally directed dendrites and the lateral funicular afferents the same as the laterally oriented dendrites.


Autolytic changes in the rat adenohypophysis. A histologic, immunocytologic and electron microscopic study. Thirty-nine adult female Long Evans rats were decapitated and the heads stored at room temperature. The pituitaries were removed at intervals from 30 minutes to seven days, fixed, embedded and studied by histology, immunocytology and electron microscopy. Histologically, changes were noticeable after two hours postmortem. Immunoperoxidase staining showed postivity for growth hormone, prolactin, FSH, LH and TSH up to seven days after sacrifice, appearing even stronger in the advanced stages of autolysis. Fine structural alterations were evident at 30 minutes and more conspicuous later. Changes included dilation, partial degranulation and whorl formation of RER, swelling of Golgi complexes and mitochondria, chromatin clumping, lysis, rhexis and pyknosis of nuclei, cytosegresome formation and disruption of cell membranes. Secretory granules remained well preserved throughout, although some exhibited fusion or reduced electron density. Dilation of capillaries with accumulation of erythrocytes, platelets and fibrin fibers were prominent findings. The severity of changes varied considerably from cell to cell indicating that the rate of autolysis is not the same among different cell types and is possibly affected by the actual functional state of the cell. It appears that increased membrane permeability and disruption of plasmalemma represent important steps in the autolytic process.


Localization of substance P-like immunoreactivity in Hydra. Substance P-like immunoreactivity was found in Hydra attenuata mainly but not exclusively in the nerve and interstitial cells, localized in the cytoplasm and on the cell surface membranes.


Synthesis and biological activities of some indolo[2,3-c]isoquinoline derivatives. Indolo[2,3-c]isoquinoline derivatives have been synthesized and tested for their antimicrobial activities. Some of them display good in vitro activity against fungi and gram-positive bacteria.


[A study on the immunoreactive luteinizing hormone-releasing hormone in villi by radioimmunoassay in the first trimester (author's transl)]. We extracted the immunoreactive luteinizing hormone-releasing hormone (IR-LHRH) from villous and plasma in the first trimester of pregnancy with 0.2N acetic acid and the florisil absorbtion method. Recovery rate was 40.0 +/- 4.08% in the former and 62.5 +/- 9.5% in the latter, respectively. These IR-LHRH were measured by radioimmunoassay, which showed sensitivity from 5 to 500 pg/ml. The villous IR-LHRH was compared with synthetic LH-RH by a dilution curve in different concentrations and the column gel filtration of sephadex-G25. The dilution curve of synthetic LH-RH and sample material showed a significant correlation, and the elution time of villous IR-LHRH on the column was something faster than that of synthetic LH-RH. The concentration of villous IR-LHRH showed 20--100 pg/0.1g dry weight in the first trimester of pregnancy, and the peak was at 9 weeks of normal pregnancy and at 8 weeks of inevitable abortion respectively, but these IR-LHRH levels were not changed between pre- and post-dilation and curettage. From this evidence, we considered that IR-LHRH show activity of the local hormone in villous tissue similar to somatostation.


Direct immunofluorescence studies in granuloma annulare, necrobiosis lipoidica and granulomatosis disciformis Miescher. Direct immunofluorescence studies in granuloma annulare, necrobiosis lipoidica and granulomatosis disciformis Miescher are reported. In all 29 cases fibrillar deposits of fibrin in the necrobiotic areas have been found. Complement, mainly C3, was present in the region of the dermo-epidermal junction in 83% of the cases. Although the walls of the vessels in the superficial layers of the dermis showed a positive staining with antifibrinogen and complement, those around the necrobiotic areas were negative in most of the cases. The possible significance of these findings for the pathogenesis has been discussed.


Particular RNA fragments as promoters of leukocyte and platelet formation in rabbits. Under well-defined conditions, ribosomal RNA from Escherichia coli is fragmented by pancreatic ribonuclease, leading to the appearance of particular RNA fragments. Some of these fragments act as primers for in vitro replication of DNA extracted from blood-cell and platelet-forming tissues. In experimental rabbits they restore in a rapid and harmless way normal circulating leukocyte and platelet levels when these have been drastically decreased by various chemotherapeutic agents mainly used in anticancer therapy. Imbalance between polynuclear and lymphocyte count provoked in rabbits by cyclophosphamide can be rapidly corrected by treating the animal with active RNA fragments.


Biological activity of synthetic subunits of streptococcus peptidoglycan. I. Pyrogenic and thrombocytolytic activity. The ability of some synthetically prepared analogues of Streptococcus peptidoglycan subunits (dipeptide, tetrapeptide, glycodipeptide and glycotetrapeptide) to cause fever in rabbits and lysis of rabbit blood platelets was studied. While di- and tetrapeptides did not exhibit these activities, glycodipeptides and glycotetrapeptides displayed pyrogenic and thrombocytolytic activities comparable with those of natural peptidoglycans.


Suppressive action of Candida albicans on the immune response in mice. This study was carried out to determine whether Candida albicans infection has a suppressive effect on the immune response in mice and, if so, whether the suppressive effect influences the response towards T-dependent or T-independent antigens. ICR mice were injected with SRBC with or without C. albicans, or with bacterial LPS with or without C. albicans. The immune response of the mice towards SRBC or towards the LPS was compared by the assay for PFC, hemagglutination and hemolysis tests. The results showed a decrease in the number of PFC in spleens of mice inoculated with SRBC and C. albicans as compared to mice inoculated with SRBC alone, but no decrease in animals injected with LPS and C. albicans as compared to those immunized with LPS alone. No significant differences in the titers of hemagglutinins and hemolysins in sera of mice inoculated with SRBC or with SRBC and C. albicans were observed. C. albicans infection had no effect at all on the hemagglutinins and hemolysins titers in sera of mice inoculated with LPS. These data indicate that C. albicans affects the early phase of the immune response primarily towards T dependent antigens.


Frequency, serodiagnosis and epidemiological features of subacute sclerosing panencephalitis (SSPE) and epidemiology and vaccination policy for measles in the Federal Republic of Germany (FRG). In the FRG, SSPE, a slow infection of the brain in children and young adults, known to be associated with a chronic measles virus infection, has an estimated incidence of 2.6 cases per million total population (61 million) and 9.7 cases per million population below the age of 19 years (16 million). In the 156 SSPE cases between 1968 and 1977 the characteristic clinical, epidemiological and serological features were found. Measles antibodies were present in the CSF and the serum titers as measured in conventional (CF--HI--IFA) and new (RIA and ELISA) tests were significantly higher than those in siblings, parents, age-matched controls as well as in patients with recent measles or after live measles vaccination. Only in children with recent wild virus infection after previous vaccination with inactivated Split measles vaccine were similar elevated serum antibody levels observed. In the SSPE cases as well as in the former group, antibodies of the IgM-class were seldom detectable and isolation of infectious measles virus from brain tissue and lymphnode derived cell cultures was rarely accomplished. The search for a co-factor or triggering agent of SSPE such as inactivated or live measles virus vaccination, concomitant childhood infection or vaccination with onset of measles or SSPE was inclusive. The seroepidemiological observation of higher frequency and titer levels of EBV- and toxoplasmosis antibody in SSPE patients as compared to siblings and parents and the suspicion that arbor virus infection may have some influence on triggering SSPE must be further substantiated. It appears that this relatively rare disease arises after an early, normal measles infection in an immunologically competent child without special genetic characteristics, mainly belonging to the lower socio-economic group, by a change of the measles virus and the immune response of the host.


Clinical trial with an anti-rabies human diploid cell vaccine (HDCV). A clinical trial with an anti-rabies human diploid cell vaccine (HDCV) Mérieux, has been carried out by the Government Central Laboratories and the District Health Office, Ministry of Health, Jerusalem, Israel, on 25 persons bitten by stray dogs and cats. These bitten persons were given 6 injections of the above-mentioned vaccine on days 0, 3, 7, 14, 30 and 90 post-exposure. A through medical examination was carried out by a qualified physician in order to establish the local and systemic side effects. These side effects were trivial and were mostly observed with the third and fourth injections. In addition a neutralization test on mice was carried out with all sera taken on the days of injection. There was a prompt and adequate development of neutralizing antibodies even on the seventh day after the beginning of treatment, and before the fourth injection. In several cases there was a very high level of neutralizing antibodies even reaching as much as 500 I.U./ml. In conclusion these results have shown that the diploid cell vaccine is a very safe immunogenic vaccine and the authors recommend its use for pre- and post-exposure.


[Antitetanus vaccination: preliminary results of a study in Africa]. Two commercialized anatoxins, titrating 30 Lf per dose and adsorbed on Ca phosphate and Al hydroxide respectively, were studied in comparison with an experimental anatoxin titrating 25 Lf per dose and adsorbed on Al phosphate, and with a placebo. 595 schoolchildren from Cameroun were randomly assigned to four groups and inoculated twice, with a year's interval between the two inoculations. Serological checks were carried out by double-blind trials using the passive hemagglutination (HA) method on days 7, 90, 365 and 395. HA titers rose substantially after three months and then fell during the 12th month. The HA method does not give a clear indication of the amount of protection obtained after only one inoculation, but this amount would seem to be small according to the results of neutralization tests carried out on samples. It is only after the second injection that protection is provided for most subjects. Results vary depending on the anatoxin and are not linked to the--benign--clinical reactions observed. This study confirms that if anatoxins with high antigenicity are to be used, two injections are necessary and sufficient to guarantee good immunity protection.


Some problems--and their solutions--in the production of DTP (diphtheria, tetanus, pertussis) vaccine. The desirability of choosing methods and equipment to meet local needs such as yield per cycle and ready availability of components of media and other reagents, and of simple equipment such as good quality glassware, of replacement parts for more complex equipment, and, most of all, of technical assistance is emphasised. Particular emphasis is given to ways of increasing yield from agar and static-liquid culture and to simple methods of separating bacteria from large volumes of culture using bacterial-precipitants. Designs are given for simple growth and mixing vessels, including magnetically-stirred units which require a minimum of servicing. It is strongly recommended that the basic production-unit should be a simple, multipurpose, high-quality stainless-steel vessel of appropriate size: such a unit has a working-life of at least 10 years. Regardless of the type of equipment used, simple or complex, the need, at all times, for well-trained technical staff is also stressed.


Potency and suppurative adenitis in BCG vaccination. Studies performed up to now in animal and man show that potent BCG strains guarantee a higher protection against tuberculosis than strains with weak virulence. Vaccine prepared from a strong BCG strain may be administered in lower doses, reducing the incidence of suppurative adenitis to a level acceptable by the individual patients and the health authorities.


Experience with testing for mycoplasma with five different methods. Five methods for mycoplasma-content detection in cell-cultures are established in this laboratory. Results with about 20 different cell lines continuously grown in this laboratory in some determinations indicate that four methods give good correspondence. A microbiological method gave contrary results in many cases. It is possible that new infections will grow on mycoplasma broth but the older infections are adapted to cell-culture and give negative results on artificial medium. New low-level infections cannot be detected by the other methods which do not include any efficient enrichment step. The most convenient method in our opinion is a DNA-staining method according to Chen because this is a very quick, inexpensive and easily performable process. In practice it seems necessary to check cell cultures in two ways, firstly with a quick method and additionally with the microbiological test to ensure the detection of new low-level infections.


Central nervous system defects in early human abortuses. Thirteen embryos with various central nervous system (cns) defects were examined macroscopically and by serial sectioning, and were compared with seven control embryos. All had been aborted spontaneously. Examples of anencephaly, anencephaly with spina bifida, spina bifida alone, encephalocele, iniencephaly and cyclops were found. Histological assessment was directed mainly to the cns, the skeletal axis, the neural-crest derivatives and remaining viscera. The cns was affected by postmortem change in some cases. Brain tissue was absent in most anencephalic embryos and spinal-cord tissue was absent at the level of the external lesion in all except one of the spina-bifida embryos. Defects such as diastematomyelia were found occasionally. Widespread abnormalities were found in the cartilaginous vertebral colun. The meninges were unusually vascular, but other neural crest derivatives appeared to be normal. The possible causes of absent brain or spinal cord are discussed and the findings are compared with the pathology of cns defects in childhood.


Methods of assessing diabetic control.

Methods of assessing diabetic control. Control of diabetes from complete normalisation to less adequate degrees of metabolic regulation needs to be assessed with regard to conditions of evaluation and to severity of the disease. Under optimal conditions the therapeutic events should occur with well-timed regularity. Different assessment criteria are appropriate depending on the severity of the deficiency of endogenous insulin. Plasma and urine glucose and ketone body measurements remain the practical standards for assessing diabetic control. Abnormalities of lipid and protein metabolites serve to augment the scope of the assessment. Triglycerides and haemoglobin AIc are also useful indicators of control. In mild (Type II) diabetes it may be possible to achieve normal plasma glucose measurements two hours after meals. Such aims carry a risk of hypoglycaemia in severe (Type I) diabetes. Normoglycaemia and aglycosuria in severe diabetes are feasible only preprandially in most cases. The use of urine glucose tests requires evaluation of blood-to-urine glucose relationships. Practical and convenient methods for identifying patients with high or low "renal thresholds" are described. Investigational methods for characterising diabetic patients assess the variability of glucose and other variables during therapy, as well as the degree to which normal values are attained. Such assessment methods may gain increasing practical importance as therapeutic approaches to diabetic control which are experimental at present come into practice.