Candida pyarthrosis of the hip and renal homotransplant. Report of a case treated by femoral head and neck resection and 5-fluorocytosine. A 54-year-old female with chronic renal failure who had undergone renal homotransplantation and who was being maintained for 3 months on immunosuppressive therapy, developed Candida pyarthrosis of the hip. The patient posed a management problem because of the nephrotoxicity of the antibiotics required to control Candida. The literature was of little help in resolving the treatment dilemma because only 4 other cases of Candida pyarthrosis in adults, and only one other on immunosuppressive therapy, have been reported. Surgical excision of the head and neck of the femur was elected because the combined use of Amphotericin B and 5-fluorocytosine posed an unacceptable risk of renal damage while the use of 5-fluorocytosine alone might allow development of step-wise resistance to the drug. Femoral head and neck resection and a 7-month course of 5-fluorocytosine brought the infection under control and allowed normal would healing. With increasing number of compromised susceptible patients, the frequency of serious infections caused by ordinarily saphrophytic organisms is likely to increase. There is a need for more case reports on management, including the consequences of surgical excision of Candida infected tissues.


The management of kyphosis in patients with myelomeningocele. Kyphosis in myelomeningocele is a progressive condition, which can lead to severe deterioration of function and skin ulceration over the apex of the kyphus. Since bracing is impractical, surgical correction and stabilization is the recommended method of management. Three different techniques are in current use. An anterior procedure using a plate and u-bolt shackles, an anterior approach using a bone strut, and a posterior approach excising a wedge, and the spinal cord if it is functionless. We recommend the wedge excision combined with posterior Harrington compression instrumentation and spinal fusion extending well above and below the resection. Regardless of the approach used, it is the long spinal fusion both anterior and posterior, which will maintain correction.


The classic: kyphosis dorsalis juvenilis. Kyphosis dorsalis juvenilis, the so-called apprentice or muscular kyphosis, is caused by disturbances in the vertebral epiphyses and not as originally suggested by muscular spinal insufficiency. The pathology resembles Calvé-Perthes osteochondritis deformans juvenilis coxae and can therefore be labelled as Osteochondritis deformans juvenilis dorsi.


Traumatic kyphosis of the thoracolumbar spine. The rationale of acute and chronic orthopedic management of traumatic throacolumbar kyphosis is determined by the type and location of the injury. The performance of laminectomy is condemned due to its historical failure in both the acute and chronic phase and its violation of simple mechanical principles.


Thromboembolism.

Thromboembolism. Fatal thromboembolism in pregnancy and the puerperium is becoming less frequent but remains the second commonest cause of maternal death. The mechanism responsible for the pathogenesis is complex and the predisposition to thrombus formation in pregnancy is probably the interaction of several different factors. Because of the risks of anticoagulant therapy, it is important to establish the diagnosis of thromboembolism before commencing treatment using venography and pulmonary angiography when necessary. When anticoagulants are used in pregnancy, coumarin derivatives can be used until 36 weeks and then substituted by heparin; alternatively heparin alone can be given throughout pregnancy. Subcutaneous heparin has no fetal effects and can be used successfully on an outpatient basis. Prevention is always better than cure, and it is essential that well-established preventive measures should be carried out diligently so that the incidence of this rare, but dreaded, complication can be reduced to an absolute minimum.


Psychiatric disorders including drug therapy and addiction. The follow-up of 238 women with antenatal and puerperal psychiatric illness indicated that drugs used for these conditions may affect the outcome of pregnancy. This may be due to the fact that psychotropic drugs have an effect on hormonal balances and neurotransmitters. Although antenatal and puerperal psychoses have symptoms which relate them to the main psychiatric categories, they are definite clinical entities (Bucknill and Luke, 1874; Hamilton, 1962); this no doubt reflects the major social and hormonal changes which occur during pregnancy and the puerperium.


Drug trial in rheumatoid arthritis: a new design. The comparative efficacy and safety of naproxen and ibuprofen were studied in 64 patients with rheumatoid arthritis. A new trial design with three aspirin periods interspersed during the study was used. By passing a smooth curve through the values obtained for the various measures of disease activity during the aspirin periods, one could calculate the difference between what would have been expected on aspirin therapy and what was found during therapy with the two trial drugs. These differences, or "incremental values," allowed each patient's variations to be analyzed individually, thus eliminating the necessity of assuming that a patient's disease was constant. Napoxen and ibuprofen were comparable in efficacy to each other and to aspirin, but both drugs caused significantly less severe side effects than aspirin. Although analysis of the incremental values showed essentially the same results as a standard analysis of the raw data with only a modest increase in sensitivity in this particular study, the novel trial design may prove useful in future drug studies in patients with rheumatoid arthritis and other chronic but fluctuating diseases.


An interpretation of the intravenous glucose tolerance test in the light of recent findings on the kinetics of glucose and insulin in man. 1. A theoretical investigation of the intravenous glucose tolerance test has been carried out based on recent findings on the kinetics in man of insulin production, distribution, disposal and action, and of glucose turnover and distribution. 2. A good fit to published data on four groups of subjects required a scheme that includes two extravascular glucose spaces and separate venous, arterial and capillary volumes. The fit to the data was little affected by variations within the physiological range of venous and arterial volumes, cardiac output, glycosuria and the properties of the less-accessible glucose pool. 3. The only variables needed to account for the differences between the groups were kinsulin (a measure of the mean sensitivity of insulin-dependent tissues to insulin action) and the readily accessible glucose space. 4. Three published schemes for insulin kinetics were used. They were all consistent with the data and gave very similar relative values for kinsulin in the four groups. 5. It is shown that a rigorous interpretation of the test requires a knowledge of the hepatic response to the glucose load during the test. These effects are not well characterized in pathological states, e.g. diabetes and injury. Consequently conclusions about insulin resistance in these states drawn only from the test are doubtful.


Effect of cyclo-alkyl lactamimides upon human pepsins and pepsinogens. 1. Eight cyclo-alkyl lactamimides have been investigated for potential inhibitory action upon the pepsins and pepsinogens. 2. Human pepsins 1, 3 and 5 and swine pepsin were inhibited only slightly. 2. Human and swine pepsinogens were inactivated progressively by lactamimides as the number of methylene groups in the nitrogen-containing ring increased. The most potent inactivator studied was N-(cis-2-phenylcyclopentyl)-azacyclotridecan-2-imine hydrochloride. 4. Substitution of benzyl and tertiary butyl groups in the N-containing ring increased the pepsinogen-inactivating property of the cyclo-alkyl lactamimides. 5. N-(cis-2-Phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride may be of potential importance as a therapeutic agent in peptic ulcer, and modifications to the molecule which might increase its pepsinogen-inactivating ability are suggested.


Comparative effects of oestrogen and a progestogen on bone loss in postmenopausal women. 1. The value of progestogen therapy in the prevention of postmenopausal bone loss was assessed in 30 women, by a preliminary randomized controlled trial of gestronol or mestranol, in comparison with a placebo. 2. When the skeletal response was measured by photon absorptiometry, bone mineral loss was prevented by both the oestrogen and the progestogen. 3. We confirm that mestranol significantly reduced the urinary output of hydroxyproline-containing peptide, but this did not occur during gestronol therapy, suggesting that progestogen has a different action on bone, perhaps stimulating bone formation.


Computer-assisted method for multi-exponential curve fitting for determining cerebral blood flow. A computer program has been developed for use in determining cerebral blood flow using an inert radioactive gas. The basic algorithm involves the determination of multiple exponential coefficients from the complex concentration-time function. The exponential coefficients are determined by 'peeling' away slower exponentials complex function one at a time. The procedure involves the use of a small laboratory computer in the interactive graphics mode. The method is currently in use analyzing data in a cerebral vascular research laboratory.


An interactive program on the PDP-11 for computing organ blood flow from data obtained using the radioactive microsphere technique. An interactive, BASIC-PLUS language program is described for computation of various parameters of blood flow in research animals from data obtained using the radioactive microsphere technique. This program used in conjunction with the PDP-11 computer gives the following output for a variable number of organs studied simultaneously: (1) descriptive statistics on counts per minute; (2) total blood flow to an organ; (3) blood flow to an organ per unit weight; (4) resistance to flow in that organ; (5) total systemic arterial resistance; (6) cardiac output; and (7) percent of cardiac output distributed to each organ. Further, separate outputs can be generated when a series of different isotopes are used in the same animal to study different experimental conditions.


Stationarity and normality test for biomedical data. Biomedical data, such as EEG, EMG and neural impulse sequences, are regarded as the stochastic phenomena of biological systems, and the statistical properties of such time series are often examined. Most of the statistical analysis processed in the frequency and the time domain are based on the assumption that the time series is weakly stationary and normally distributed. Therefore, as the basis of the statistical analysis of the biomedical data, it is necessary to know whether they satisfy the conditions of weak stationarity and normality. However, impulse response and evoked potential biomedical data, are not regarded as the stationary time series. Therefore, other analysis is required. In this paper, the authors present four programs, TEST1, TEST2, TEST3 and TEST4, to examine above conditions. Furthermore, in order to clarify the characteristic of each program, the time series were generated by the computer and examined by the test programs.


A computer system automatic analysis of vectorcardiograms. This computer system performs the analysis of orthogonal electrocardiograms for vectorcardiographic (VCG) display and classification. The data acquisition can be performed 'on-line' with the complete analysis in 'real-time', or off-line by processing a magnetic tape. The original computational methods for beat averaging and wave recognition are described. Some features, such as the quality of the visual display of the VCG traces, the availability of a measurement matrix allowing the quantitative analysis of the VCG and the use of a data bank for storage, retrieval and statistical studies make this system very efficient for clinical purposes, introducing the concept of 'Computer Assisted Vectorcardiography'.


Comparison of intra-articular methotrexate with intra-articular triamcinolone hexacetonide by thermography. A comparison of intra-articular methotrexate and intra-articular triamcinolone hexacetonide was made in 42 arthritic patients with persistent bilateral knee effusions. One knee was injected with either 5 mg methotrexate (two injections of 2.5 mg a week apart) or a single injection of 20 mg triamcinolone. An objective assessment of both knees was made by quantitative thermography at 0,3,7,14 and 21 days. Joints injected with triamcinolone showed a greater fall in thermographic index (T.I) than the joints injected with methotrexate, which showed similar change to the non-injected knee joints in both groups. Four patients received larger doses of methotrexate, up to 20 mg, though the fall in T.I. was still less than the mean fall for triamcinolone injected joints. Peak venous blood levels of methotrexate were reached 1 hour after intra-articular injection, and a sphygmomanometer cuff inflated around the leg above the injected knee for periods of up to 1 hour did not appreciably delay this. Methotrexate had no immediate anti-inflammatory effect, even in psoriatic arthropathy, and did not give the relief of intra-articular steroid.


Rapid onset of action of oral labetalol in severe hypertension. Nine patients with persistently elevated diastolic blood pressure, exceeding 130 mmHg, received an oral dose of labetalol ranging from 200 mg to 400 mg. In all patients, this produced a significant and gradual decline in recumbent systolic and diastolic blood pressure, unaccompanied by symptoms or complications, with only minor changes in heart rate. Individual variation in the rate of blood pressure fall suggested differences in absorption and first-pass metabolism. It is suggested that the efficacy of oral labetalol merits further investigation in the rapid control of severe hypertension.


Tinidazole and metronidazole in the treatment of intestinal amoebiasis. Sixty adult patients with symptomatic intestinal amoebiasis and with Entamoeba histolytica present in stools were allocated at random to treatment with tinidazole or metronidazole, both administered in a dose of 2 g once daily for 3 consecutive days. The treatment period was extended in patients with stools positive for Entamoeba histolytica on the day following the last treatment day. Fifty-six patients, 29 on tinidazole and 27 on metronidazole, completed the trial as per the protocol. Twenty-eight patients (96.5%) on tinidazole and 15 (55.5%) on metronidazole were cured. Parasitological cure with partial relief of symptoms was obtained in 1 (3.5%) and 5 (18.5%) patients on tinidazole and metronidazole, respectively. Seven patients (26%) on metronidazole were treatment failures. Treatment had to be extended beyond 3 day in 53% of patients (8/15) on metronidazole as opposed to 11% (3/28) on tinidazole (p less than 0.01). The total number of side-effects, their severity, and the types were more in the metronidazole group. No toxic effects due to either drug were recorded. Tinidazole provided significantly higher cure rates than metronidazole in the treatment of symptomatic intestinal amoebiasis (p less than 0.01), and was better tolerated than metronidazole.


Short course of single daily dosage treatment with tinidazole and metronidazole in intestinal amoebiasis: a comparative study. Tinidazole or metronidazole was administered at random to 56 patients with symptomatic intestinal amoebiasis. The dose of each drug given was 2 g once daily for 3 consecutive days. Tinidazole cured 92.6% patients (25/27) and metronidazole 58.6% patients (17/29). The difference was statistically significant (p less than 0.01). Tinidazole was better tolerated compared with metronidazole.


Comparative study of tinidazole and metronidazole in amoebic liver abscess. Twenty proven cases of amoebic liver abscess were treated at random with either tinidazole or metronidazole. The dose of both was 2 g once daily for 2 days. Clinical, radiological, and biochemical follow-up was done for 30 days. Of the 19 patients who completed the trial, complete recovery was observed in all 10 patients given tinidazole and in 5 of 9 patients given metronidazole (p=0.05). Moreover, patients on tinidazole required repeat aspirations less frequently than those on metronidazole. Mild gastrointestinal side-effects occurred in 1 patient on metronidazole. The results suggest that tinidazole is a more efficacious drug than metronidazole, with rapid therapeutic effect.


Single-dose treatment of giardiasis in children: a comparison of tinidazole and metronidazole. One hundred children suffering from symptomatic giardiasis were treated with either tinidazole or metronidazole in random order. Both the drugs were given as a single oral dose calculated on the basis of 50 mg/kg body weight. Parasitological and clinical cure was obtained in 40 (80%) of 50 patients given tinidazole and in 18(36%) of 50 patients given metronidazole. This difference in cure rates was significant (p less than 0.01). Furthermore, control of diarrhoea and negative stool conversion for G. lamblia were achieved earlier with tinidazole than with metronidazole, the differences being significant (p less than 0.01) from the 8th post-treatment day. Gastro-intestinal side-effects of mild degree occurred in 6 patients on tinidazole and in 2 patients on metronidazole; they comprised nausea, vomiting, and bitter taste. Neither drug caused any abnormal deviation in blood counts or in biochemical tests of liver and kidney function.


Basic experiments with clotrimazole administered orally. A series of experiments was carried out with the antimycotic agent clotrimazole to establish MICs against a number of different yeasts and to estimate its blood levels following oral administration. Marked differences were noted between the MIC against A and B serotypes of Candida albicans in its yeast-like cell form, that against Type B being nearly 10-times higher than against Type A. Against the mycelial form, however, the MIC was much lower and there was little difference between the levels for the two serotypes. Clotrimazole administered in oral tablet form appeared to be poorly absorbed, little being transferred to the blood. Urinary levels were low and large amounts of the drug were detected in the faeces. Serum levels were below MIC levels in all cases examined. Blood levels 3-times as great as those after the same dosage in tablet form were produced when clotrimazole was given in oil solution and even with 250 mg, effective blood levels were achieved and maintained.


A dose-response study of atenolol in mild to moderate hypertension in general practice. A double-blind, crossover, multicentre study of 98 previously untreated patients with mild to moderate essential hypertension was carried out in general practice to assess the effect of 50 mg, 100 mg, and 200 mg atenolol, given once daily, compared with that of placebo over a period of 4 weeks each. At the end of the double-blind phase, all patients took 100 mg atenolol daily for a further 8 weeks. All three doses of atenolol produced statistically significant falls in systolic and diastolic pressure and pulse rate (p less than 0.001). The lowest pressures were achieved with 100 mg daily; a difference of 22/15 mmHg at the end of the double-bling phase, and a difference of 25/16 mmHg at the final observation. Body weight, blood urea, blood uric acid, and serum electrolytes remained within normal limits throughout the study. The incidence of side-effects with 50 mg and 100 mg atenolol was not significantly different from that caused by placebo, but the incidence of tiredness at the 200 mg dose level was greater than that caused by placebo and by the lower doses. The incidence of possible side-effects elicited by a questionnaire was low, the greatest number being volunteered by patients taking placebo. It is concluded that the optimal dose of atenolol for treating patients with mild to moderate hypertension in general practice is 100 mg daily.


A short-term comparative trial of salsalate and indomethacin in rheumatoid arthritis. A short-term, double-blind, placebo-controlled crossover study was completed in 15 patients with classical or definite rheumatoid arthritis to compare the antirheumatic activity of salsalate (3 g/day) with placebo and indomethacin (75 mg/day). Subjective and objective assessments showed that both salsalate and indomethacin were significantly superior to placebo. Grip strength was not improved by either of the drugs. Patient preference was in favour of indomethacin, but the difference between it and salsalate was insignificant.


Mefenamic acid and dextropropoxyphene with paracetamol as analgesics in the accident department. A double-blind study was carried out in 48 patients with soft-tissue injuries to compare the effectiveness of mefenamic acid and dextropropoxyphene plus paracetamol in relieving acute post-injury pain. Patients received capsules containing either 250 mg mefenamic acid or 32.5 mg dextropropoxyphene hydochloride plus 325 mg paracetamol and were instructed to take up to 6 capsules daily as necessary. By the third post-injury day both preparations had controlled pain adequately and lessened local tenderness in most cases. There was no significant difference in response between the two patient groups. Two patients in each group stopped treatment because of gastro-intestinal intolerance, and a further 4 patients in each group reported troublesome side-effects.


Use of pizotifen in severe migraine: a long-term study. Severe migraine attacks in 47 patients who were unresponsive to clonidine hydrochloride were treated with 1.5 mg pizotifen for a mean period of 6 month. The attack incidence, duration and severity were more than halved in 64% (30 patients), 25% becoming headache-free. Side-effects were not serious but weight gain was a problem in some subjects. Pizotifen administration allowed withdrawal of methysergide and ergotamine compounds without rebound headache. It appeared specially remedial in those whose migraine could be triggered by dietary factors. Follow-up 22 patients at 15 months confirmed these findings, 48.6% remaining 'improved' by the criteria of the trial (28% headache-free), and underlined the marked reduction in symptomatic drugs required and the absence of toxicity in long-term treatment.


A comparison of an antacid plus antispasmodic combination and aluminium hydroxide in dyspepsia. A single-blind, between-patient comparative study was carried out in general practice to assess the effectiveness of antacid plus antispasmodic combination tablets (240 mg dried aluminium hydroxide B.P., 144 mg magnesium hydroxide B.P.C., and 5 mg dicyclomine hydrochloride B.P.) and aluminium hydroxide B.P. tablets (500 mg) in the management of chronic dyspepsia. Twenty patients received the combination tablets and 17 the single antacid tablets. They were instructed to chew 2 tablets 3 or 4-times daily and an additional 2 tablets at night if necessary. Patients were assessed initially, and then at 2 and 4 weeks. Both preparations were effective in controlling dyspeptic symptoms. Heartburn and nausea showed an early, significantly greater (p less than 0.05) response to the combined tablet, as did night pain after 4 weeks. Tablet intake of both preparations averaged out at just under 7 tablets per day.


Analgesia following oral surgery for day patients: a clincial comparison of two analgesics. A single-blind, between-patient study was carried out in 167 patients following oral surgery to compare the effectiveness and tolerance of two combination analgesic preparations; pentazocine (15 mg) plus paracetamol (500 mg) and dextropropoxyphene hydrochloride (32.5 mg) plus paracetamol (325 mg). Assessments of pain and pain relief were made over two periods, initially over the 90 minute period following administration of either preparation and secondly, over the subsequent 3 days following discharge. At the hospital, those patients receiving pentazocine plus paracetamol achieved a greater relief of pain than those receiving dextropropoxyphene plus paracetamol, though the differences did not reach statistical significance. At home, pain relief was very similar for both groups of patients, both preparations being effective and well tolerated.


Tricyclic antidepressants: a review of their toxicology. The tricyclic antidepressants have a complex interaction with several tissues both in experimental animals and in man. Side effects exerted by these drugs may be so severe as to justify a careful management of each individual depressed patient. The clinician must be aware of these effects above all in treating overdose poisoning and suicide attempts. This paper reviews the tricyclic-induced organic and psychologic disturbances, attention being paid to the antidepressant pharmacodynamics and the importance of biogenic amines-reuptake inhibition. Further studies on the pharmacokinetics of tricyclic antidepressants are needed however to clarify the mechanisms of their side effects. In this situation, increased drug levels should be tried only after lower dosages have proved ineffective in relieving the depressive symptomatology. In any case, the greatest caution should be used in the treatment of patients with cardiovascular diseases, severe hypertension, glaucoma, or a tendency to retain urine. Nevertheless, at present no new antidepressant has been found which may offer more selective therapeutic advantages than the classical tricyclic thymoleptics (imipramine-like drugs).


Legionnaires' disease. A sporadic case.

Legionnaires' disease. A sporadic case. A patient with Legionnaires' disease developed consolidated pneumonia with severe hypoxemia and mental confusion; his condition improved with therapy with positive end-expiratory pressure, steroids, and chloramphenicol. The retrospective diagnosis was made by a fourfold rise in indirect fluorescent antibody titers. The chest x-ray films showed bilateral alveolar infiltrates and air bronchograms.


Prophylaxis with isoniazid in inactive tuberculosis. A Veterans Administration Cooperative Study XII. Based on a study indicating a significant rate of reactivation of tuberculosis in Veterans Administration patients with inactive disease, a cooperative study was initiated to determine the prophylactic effect of isoniazid on the rate of reactivation. A randomized double-blind study was designed, utilizing three regimens, two with isoniazid and one with placebo only. Two consecutive years of taking pills in one of the three regimens was followed by five years of observation. A total of 7,036 patients with inactive disease, some of whom had received prior chemotherapy, were entered into the study. Only 63 reactivations of tuberculosis were found, for a total rate of reactivation of 9/1,000 (less than 1%) over the seven-year period. Although no significant differences in the rate of reactivation were found among any of the regimens, there was a significant reduction in the rate of reactivation among those who had not received any prior chemotherapy and received isoniazid (INH) in this study, compared with those who received placebo only.


Cardiac arrhythmias during routine tests of pulmonary function in patients with chronic obstruction of airways. We studied the frequency of cardiac arrhythmias during routine tests of pulmonary function by using continuous electrocardiographic recording and a computerized method to quantitate arrhythmias. A total of 150 patients with chronic obstruction of airways were studied before, during, and after routine tests of pulmonary function performed before and after intermittent positive-pressure breathing (IPPB) with a bronchodilator aerosol. The only significant (P less than 0.01) change was an increased frequency of atrial premature beats during tests of pulmonary function. Spirometric studies, maximal voluntary ventilation, and IPPB with a bronchodilator aerosol were equally likely to induce atrial premature beats. Routine tests of pulmonary function represent an additional causal factor in producing arrhythmias in patients with obstruction of airways, although no clinical consequences were evident in the course of the study.


Effect of tidal volume and positive end-expiratory pressure on compliance during mechanical ventilation. In 12 patients requiring therapy with mechanical ventilation for acute respiratory failure, total static compliance (Cst) increased from 29 +/- 4 ml/cm H2O at a tidal volume (TV) of 5 ml/kg to 42 +/- 7 ml/cm H2O at a TV of 15 ml/kg. Similarly, Cst increased from 42 +/- 7 ml/cm H2O to 52 +/- 8 ml/cm H2O between 0 and 6 cm H2O of positive end-expiratory pressure (PEEP). At high levels of pulmonary inflation (ie, high PEEP and large TV) compliance decreased. The changes of total respiratory compliance with TV were mainly due to changes in pulmonary compliance. With PEEP, the functional residual capacity increased, and specific compliance did not change. Two mechanisms may be responsible for the changes in compliance. First, varying TV or PEEP will alter the position of tidal ventilation on the pressure-volume curve, resulting in an increase in compliance with increasing TV and PEEP up to a point, where overdistention occurs and compliance decreases. Secondly, the function of the surface-lowering substance may be altered in acute pulmonary parenchymal disease, thus disturbing the regulation of surface tension over the range of pulmonary inflation studied.


Measurements of cardiac output in seriously ill patients using a CO2 rebreathing method. A CO2 rebreathing method for the measurement of cardiac output was evaluated by comparison with the direct Fick O2 method in 26 studies performed in 18 patients who were critically ill. The method requires measurement of CO2 output by collection of expired gas, of arterial PCO2, and of mixed venous PCO2 by rebreathing. Twenty-five comparisons were within +/- 20% of the direct Fick measurements, at cardiac outputs varying between 1.4 and 6.4 L/min. Knowledge of the cardiac output increased the quality of the interpretation of arterial blood PO2 measurements in the assessment of pulmonary gas exchange disturbances.


The management of acute quinidine intoxication. A 16-year-old patient survived severe intoxication with quinidine. Hypotension, rapidly progressing to oliguria and shock, was resistant to the usual therapeutic interventions but responded favorably to the use of an intra-aortic balloon pump. Some hemodynamic implications are discussed. Pulmonary edema occurred and was treated with positive end-expiratory pressure. Electrocardiographic disturbances in conduction, transient bradycardia and recurrent ventricular arrhythmias characterized the initial 36-hour critical period. Unexplained electrolyte abnormalities occurred and further complicated management.


Reconstruction of the superior vena cava in a patient with a thymoma. Surgical treatment was attempted in a 71-year-old man who had superior vena caval syndrome caused by incomplete obstruction of the superior vena cava with a thymoma. Using a temporary internal shunt, the superior vena cava was almost entirely resected together with the tumor and reconstructed by autogenous venous grafts. Patency of the reconstructed vein was proved by angiography one year after the operation. He has been asymptomatic for 15 months after surgery.


Mode of action of 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone ethanolamine salt (Hoe 296). Mode of action studies were made with Hoe 296, a new synthetic antimycotic, mainly in Candida albicans. The specific parameters examined included possible effects on (i) osmotic fragility, (ii) respiration, (iii) uptake and incorporation of radioactive leucine and adenine, and (iv) leakage or efflux of intracellular K+ and other materials. As a result, fungitoxic activity of Hoe 296 appears to be attributed to inhibition of uptake of precursors of macromolecular syntheses from the medium. Uptake and accumulation of leucine in the internal pool of starved cells was more susceptible to the drug than subsequent incorporation into proteins. Hoe 296 was also effective in altering the cell permeability, but greater drug concentrations were required to induce appreciable leakage of cellular constituents, such as 260 nm-absorbing materials, folin-positive substances and potassium ions, from the cells. Osmotic fragility or endogenous respiration was virtually insensitive to the drug. Partial inhibition by relatively high concentrations of Hoe 296 of the respiratory activity of yeast cells or mitochondria therefrom with exogenous substrates can be explained by decreased uptake of the substrates from the medium.


Silver sulfadiazine: lack of mutagenic activity. Silver sulfadiazine was found to be devoid of mutagenic potential in a sensitive mutagenicity assay using Salmonella typhimurium. In view of the close relationship between mutagenicity in this system and carcinogenicity in animals, these findings suggest that silver sulfadiazine is apparently also devoid of carcinogenic properties.


Qualitative study of paradoxical zone phenomenon of penicillins against 17 bacterial species of clinical importance. Using a triple agar layer technique and enzymatic inactivation of penicillin, the occurrence of a paradoxical zone phenomenon (illustrated by a typical 'target' image around the reservoir of antibiotic) was determined for several bacterial species specially chosen with regards to their taxonomic position, clinical importance and penicillin susceptibility. Among gram-positive bacteria, a paradoxical zone was obtained for approximately 43% of the strains studied here (all 10 strains of Staphylococcus aureus, all 10 strains of Streptococcus faecalis, 7 of 10 strains of group B beta-hemolytic streptococci, 1 of 10 group A strains, 3 of 10 strains of alpha-hemolytic streptococci, 3 of 10 strains of Clostridium perfringens but for none of 10 strains each of Streptococcus pneumoniae, and Listeria monocytogenes). Among gram-negative bacteria, a target image was regularly obtained with Haemophilus influenzae (all 10 strains tested) and Proteus species (9 of 10 strains) but with none of the following species: Escherichia coli, Salmonella, Shigella, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Neisseria meningitidis and Bacteroides fragilis. Therapeutic implications of these observations are difficult to assess, and need further investigation.


[Postpyloric resection of a complicated ulcer on the posterior wall of the duodenum within the scope of form-and function-preserving gastric surgery. Technic and 1st results]. By combining different methods available in modern gastric surgery, we have developed a new procedure in surgical treatment of the complicated ulcer of the posterior duodenal wall. Our new technique allows the radical resectioning of the ulcer and includes all the advantages of nonresectioning operations in form- and function-preserving surgery. The technique of open anastomosis with an one-row, one-layer suture only slightly injures the gut that is to be anastomosed and thus eliminates complications in the healing process. The pylorus is completely preserved. The great advantages of avoiding gall reflux into the stomach, of preserving its total capacity, and of preserving the possibility of a portioned evacuating of the stomach can not yet be fully estimated.


Membrane and intracellular hydrolysis of peptides: differentiation, role and interrelations with transport. The possible relative importance of the membrane and intracellular peptidases of the enterocytes in splitting dietary peptides to amino acids has been analysed. On the anoxic criterion, membrane hydrolysis was found to be predominant. Model experiments revealed cooperative interactions between the membrane enzyme and the coupled transport system. This cooperativity allows the main characteristics of oligomer transport to be described in terms of membrane digestion. Comparison of the behaviour of membrane and intracellular peptidase under different conditions has shown that the former are largely involved in digestion and the latter in intracellular metabolism. It is suggested that the efficiency of the membrane system is high enough to account for the hydrolysis of protein, especially taking into account the stimulation of enzyme processes in the brush border that occurs after ingestion of protein and carbohydrate. A sequential model based on the concept of three interacting enzyme layers (glycocalyx, lipoprotein membrane and cytosol) is presented.


Transport and hydrolysis of peptides by microorganisms. The structural specificities of the dipeptide and oligopeptide permeases of E. coli are briefly reviewed and related to the requirements found for other microorganisms. New, quick, sensitive methods for studying peptide transport are described, based on the following: (i) peptide-dependent incorporation of free radioactive amino acid into newly synthesized protein by a double amino acid auxotroph, (ii) colorimetric assay of peptide-dependent enzyme synthesis by an amino acid auxotroph, (iii) dansyl fingerprint technique. These approaches provide information on peptide binding affinity to a permease and rates of peptide uptake and amino acid efflux. Among current and future research areas considered are: the influence of the pKb of the N-terminal amino group on transport, generality of peptide transport in microorganisms, energy coupling and regulation, involvement of binding proteins, and the 'smugglin' concept. Peptide hydrolysis, and nutritional ultilization of peptides, by microorganisms are briefly discussed.


[Diflunisal, a new analgesic, and oxyphenbutazone in the treatment of sprains and dislocations (author's transl)]. In a randomized double-blind study efficacy and tolerance of diflunisal, 375 mg twice daily, and oxyphenbutazone, 200 mg twice daily, were compared in 40 patients (aged 21 to 70 years, average 38 years), with moderate or severe complaints after spraining or dislocating ankle or wrist. The drugs were given for five days. Both proved to be highly efficacious, diflunisal slightly more so. Among the 20 patients in the diflunisal group one developed diarrhoea, another gastritis; in the oxyphenbutazone group one developed gastritis, another herpetiform pustules. There were no clinically significant abnormalities in routine biochemical tests.


A mouse geneticist's impatient waiting for the arrival of embryo-freezing techniques. Four cases from the author's own experience are discussed where the freezing and freeze-storage of mouse embryos would have saved much research time, preserved valuable genetic material, and enabled important genetic studies to have been made. These cases illustrate the problems encountered when transporting a large collection of inbred mouse strains; the necessity to discontinue--because of lack of space--strains that nobody wants at the moment but that might become invaluable in the future; the unavoidable loss of parental stocks used for the development of a new congenic line; and the difficulties one faces when studying a genetic system that is extremely polymorphic. The need for a centralized and possibly international embryo freezing and storing facility is advocated.


[Geometric-mathematical study on the occlusal interference in calotte articulation]. Calculations of occlusal interferences in calotte articulation are reported. It is shown that magnitudes of error due to the different radii of the given calotte and mounting template utp to +/- 20 mm amount to 0.1 mm at most. On the other hand the occlusal errors due to different angles of incidence of the mounting template may attain a magnitude which prevents incorporation of total prostheses.


[Errors in corrective impressions and their prevention]. In order to keep the degree of polymerisation of moulding materials as low as possible until they are applied, a lower working temperature for the first and second material is necessary. In addition, the preliminary impression is cooled in ice water so that the flow capacity of the correcting compound in the capillary cleft is improved and unreliable model reduction can thus be avoided.


[The effect of active removable orthodontic appliances on the dental enamel]. It could be demonstrated that enamel defects which are caused by maxillo-facial fixing elements of actively removable implements were reproducible in laboratory experiments. With minimal pressure of the wire bow of 50 grams and 250,000 lift, or individual vertical movements on the enamel surface resulted in a micrometer area of scouring.


[Results of follow-up studies on support methods for partial dentures]. Prosthetic provision with removable part-replacement was divided into 7 groups according to the type of support and the prognosis was established on the basis of caries activity and several criteria of the periodontal condition, separated according to anchoring or supporting teeth as well as the remaining teeth. Generally regressive changes must be expected which become more marked with reduction in the number of teeth and support possibilities.


[Experimental studies on the stress endurance of traumatized periodontium]. The reaction of intra-osseous fixed front teeth against defined forces was electronically registered as a distance-force function. The record was submitted to computer-assisted analysis. Comparison of the functions was made via the paramaters of algebraic definition. Analysis led to the submission that the resistance of tooth and tissues is primarily limited by the quality of the surrounding osseous tissue, which itself reacts in a rubber-elastic fashion.


[Clinical, bacteriological and histological mucosal findings in the regions of bridge pontics]. Clinical, bacteriological and histological findings based on 30 bridges with ceramic and metal members showed that covering large mucosal surfaces need not lead to severe inflammatory changes of the mucosa or papilla. If the intermediate members have to rest on a punctiform or small surface of the alveolar crest on hygienic and tissue-sparing grounds, the use of glazed porcelain or--with certain reservations-- of highly polished metal can be justified when required for phonetic, functional or aesthetic reasons.


[Effect of the base design on the dynamic behavior of the one piece cast prosthesis for the upper jaw]. Examinations on models were undertaken under similar experimental conditions to determine the elastic behavior of supported maxillary combination prostheses, which differ according to the shape of the transverse palatal elements. On the basis of the determination of the deformation indices the typical functional behaviour is demonstrated and recommendations are made regarding the construction of the base and connector elements.


[Comparative studies on the accuracy of fit of upper complete dentures with plastic or cast metal bases]. The conclusion was reached on the basis of statistically significant results that the tendency to cleft formation is significantly less in cast plates than in plastic plates, particularly in the region of the critical dorsal border zone.


[Ceramic bonding with alloys of non-noble metals]. The composition of the three non-precious metal alloys used in Germany was qualitatively analysed. The surface border between ceramics and metal was examined by scan electron microscope. Results showed that a gapless apposition can be established between metal and ceramic by proper preparation of the metal alloy and the ceramic mass.


[Exfoliative cytology during topical treatment of oral leukoplakia with vitamin A acid]. Vitamin A acid (VAS) has proved itself an effective local therapeutic agent for intra-oral leucoplakia. Clinical remission characterized by a decrease in horny lumps and the eosinophilic index and an increase in intermediary cells was achieved in 32 out of 50 cases. In the course of maintenance therapy development towards an exfoliocytologically healthy mucosa proceeds via increasing parakeratosis. VAS therapy is essentially thought of as symptomatic therapy.


[Determination of the surface topography of etched dental surfaces]. Klinger and Gabriel recently described a method for the determination of surface topography in which the surface is probed by a mechano-electrical movable handle attached to defined line-scanner pattern. The evaluation of the "surface topogram" thus obtained is elucidated with the aid of a surface topogram of a straight fissure. A contour map is drawn with the help of this surface topogram for an area of about 300 micron X 500 micron of a cauterized surface in the enamel of a transverse cut. This shows that broad cauterization structures occur not only in the enamel near the dentine but also in the area of outer enamel which is caused by differential dehiscence or splitting of enamel prisms with different orientation towards the cut surface.


Affinity labelling of alcohol dehydrogenases. Chemical modification of the horse liver and the yeast enzymes with alpha-bromo-beta(5-imidazolyl)-propionic acid and 1,3-dibromoacetone. 1. DL-alpha-Bromo-beta(5-imidazolyl)-propionic acid is a potential affinity labelling reagent for metallo-enzymes. It has been used with the alcohol dehydrogenases from liver and yeast. The liver enzyme is chemically modified and inactivated in a Michaelis-Menten-type reaction, where one molecule of the reagent is bound per subunit. The enzyme is protected from the inhibitor in a competitive manner by imidazole, 2,2'-dipyridyl, 1,10-phenanthroline and cyclohexanone, which all combine with the active-site zinc. The protection by chloride, acetate and NADH, which are considered to bind at the general anion binding site, is not strictly competitive. Inactivation has an optimum at pH 8.5. For the liver enzyme, the reagent was found to decrease the initial rate of ethanol oxidation. Prior to the irreversible alkylation of Cys-46, reversible binding is shown to occur at the active-site zinc atom. The yeast enzyme was extremely resistant to the reagent and no specific modification was found. 2. The potential affinity labelling and crosslinking reagent, symmetrical 1,3-dibromoacetone although unstable, has also been used for chemical modification. With the liver enzyme, concentrations below 5 mM gave a reaction of the Michaelis-Menten-type at pH 7.0. Several ligands known to complex with the active-site region protect the enzyme against the reagent. Dibromoacetone gave rapid inactivation of the yeast enzyme. Despite the fact that a pseudo-first-order reaction was observed with respect to enzyme as well as inhibitor, no saturating effect was found. In this work, dibromoacetone reacted like a monofunctional reagent.


Inhibition of chloramphenicol binding to Escherichia coli 70S ribosomes by 2'(3')-O-aminoacyl-dinucleoside phosphates derived from the aminoacyl-tRNA acceptor terminus. The effect of 2' and 3'-O-aminoacyl-dinucleoside phosphates cytidylyl(3'-5')-2'(3')-O-L-phenyl-alanyladenosine (I), cytidylyl(3'-5')-3'-deoxy-2'-O-L-phenylalanyladenosine (IIa), cytidylyl(3'-5')-2'-deoxy-3'-O-L-phenylalanyladenosine (IIIa), cytidylyl(3'-5')-3'-deoxy-2'-O-glycyladenosine (IIb), cytidylyl(3'-5')-2'-deoxy-3'-O-glycyladenosine (IIIb), cytidylyl(3'-5')-3'-deoxy-2'-O-L-leucyladenosine (IIc), cytidylyl(3'-5')-2'-deoxy-3'-O-L-leucyladenosine (IIIc), cytidylyl(3'-5')-3'-O-L-phenylalanyladenosine (IIId) as analogs of the 2'(3')-aminoacyl-tRNA termini, on chloramphenicol binding to 70S Excherichia coli ribosomes was investigated. The association constants (Kb) of the investigated compounds were determined by the equilibrium dialysis method. Based on the constancy of Kb over the range of inhibitor concentration, it was determined that the binding site of the 2' isomers IIa-IIc overlaps with the chloramphenicol site, whereas the variability of Kb for the 3' isomers IIIb, IIIc and especially IIIa seems to indicate that they do not achieve a complete fit. The consistently higher values of the Kb values for the 3' isomers IIIa-IIIc relative to that of the 2' isomers IIa-IIc also indicate a stabilization of the binding of the former due to a specific interaction between its amino acid portion and a ribosomal site.


Structural studies on yeast 3-phosphoglycerate kinase. Isolation by affinity chromatography and characterization of the peptides produced by cyanogen bromide cleavage. Location of the single cysteinyl residue in the primary structure. Cyanogen bromide cleavage of yeast 3-phosphoglycerate kinase yielded four fragments which account for the amino acid composition of the entire molecule. These results are consistent with a single polypeptide chain of molecular weight 42 000. Affinity chromatography on Sepharose-mercurial followed by gel filtration on Sephadex was used with success for separation of peptides. The carboxyl and N-terminal fragments were characterized. The N-terminal fragment contained the single cysteinyl residue of the protein. After cyanylation and subsequent cleavage, this cysteinyl residue was located near position 100.


Purification and properties of phage P22 c2 repressor. The c2 repressor of phage P22 has been purified to homogeneity. It specifically binds to lambdaimm21 and P22 DNA. Its affinity for the presumed operator mutant P22 virB is reduced. The initial dissociation rates of the complex between c2 repressor and lambdaimm21 DNA are 0.02 min-1 at 0 degrees C, 0.08 min-1 at 20 degrees C and 0.17 min-1 at 32 degrees C. The dissociation rates of complexes formed between the c2 repressor and the lambdaimm21 operators OR, OL and OR vira were measured and compared to the corresponding rates obtained with 21 cI repressor.


Optical spectroscopic study of the ADP-myosin interaction. The binding of ADP to heavy meromyosin, and the separated subfragment 1 components S-1(A1) and S-1 (A2), has been observed by ultraviolet spectrophotometry. The results are compatible with the presence of spectroscopically equivalent and independent sites, one per head, at both 10 degrees C and 25 degrees C. We do not observe the heterogeneity of binding and of the spectroscopic response that has been reported. The binding has also been followed by other methods sensitive to the effect of ligand on the aromatic residues of the protein, viz. intrinsic fluorescence of heavy meromyosin and changes in the near-ultraviolet Cotton effects of myosin, and its active fragments. Within the limits of our experimental precision, the binding profiles, based on concentration of myosin heads, are the same for myosin as for subfragment 1. A perturbation in the circular dichroism is also generated by pyrophosphate, which competes with ADP. The spectra suggest that subsites for the purine ring and the diphosphate can be recognized. The sensitivity of binding profiles obtained by methods of the kind used here to cooperative or antagonistic interactions between the binding sites has been analysed. It is clear that sizeable effects of this nature could be concealed by the binding curves, even for high experimental precision.


Metabolic stability of the two forms of initiation factor IF-3 in Escherichia coli during the growth cycle. Possible alteration in the ratio of the long and short forms of initiation factor IF-3 (FEBS Lett. 79, 264-275, 1977) during the growth cycle of Escherichia coli was examined. The ratio was found to remain unchanged between the exponential and stationary growth phases. Contrary to an earlier report (Eur. J. Biochem. 29, 319-325, 1972), the total amount of IF-3 relative to the ribosome content in stationary phase cells was essentially the same as in midlogarithmic phase cells. The activity of IF-3, assayed after its separation from other initiation factors by chromatography, was also the same in extracts from midlogarithmic and stationary phase cells. The data show that in Escherichia coli the ratio of IF-3/ribosome is maintained constant. The ribosomes themselves have been shown to retain virtually full activity in vitro during this transition indicating that growth-cycle-dependent biochemical modifications of the ribosome do not affect its protein synthetic capacity per se.


Effect of libexin combinatum (libexine and emetine) on phagocytosis by polymorphonuclear granulocytes and alveolar macrophages. The ability of human polymorphonuclear granulocytes and alveolar macrophages from rats to ingest Saccharomyces cerevisiae was tested in vitro in the presence of various concentrations of emetine and libexine. Emetine 4.0 and 40.0 microgram/ml caused an increase in the phagocytic index of polymorphonuclear granulocytes and alveolar macrophages. After oral administration of emetine the phagocytosis-enhancing effect was still apparent. Intracellular killing was not influenced by emetine or libexine.


The rotating rodent: a two component system? The hypothesis that the rotating rat requires both nigro-striatal and mesolimbic dopaminergic components for activity has been tested. 6-Hydroxydopamine lesions were induced unilaterally in either or both the ascending nigrostriatal and mesolimbic dopamine pathway. In one group of rats the nucleus accumbens was destroyed bilaterally with electrolesions. Circling behaviour was only recorded when there was both an imbalance in striatal dopamine concentrations concomitant with stimulation of the limbic dopamine regions. Lesions of the mesolimbic dopamine pathway resulted in changes in drug-induced motor activity but postural asymmetry or circling behaviour was not observed. The results support the hypothesis that the rotating rodent requires two functional dopamine components: striatal dopamine imbalance causing a postural asymmetry and stimulation of mesolimbic dopamine systems providing a locomotor component. The relevance of these components in this animal model is discussed with reference to dopaminergic agonist and antagonist drugs.


Quantitative alterations of immune serum globulin concentrations in pigs transplanted with a renal allograft. The variation of immune serum globulin concentrations in 14 pigs was determined after unilateral allogenic renal transplantation. Measures by which it is possible to exert certain immunological influences were not taken. Subsequent to transplantation there was observed a significant decrease in both IgM and IgG which was not correlated with the behaviour of plasma proteins and albumin. Because of the relatively small loss of IgG in the urine of animals on which transplantations were performed, this cannot be considered to be the cause of the decrease in immunoglobulin. It was already on the 3rd day after transplantation that an increase in IgM was observed which after reaching a peak of about + 30% was again followed by a distinct decrease of which the minimum was noted between the 6th and 15th days after transplantation. 10 animals died within the first phase, and in 4 of them death occurred on account of rejection for which histological evidence could be obtained. Although 3 of the 4 animals surviving for a longer period of time were also observed to suffer from distinct rejective crises between the 8th and 15th day after transplantation, they were able to overcome those crises without any therapeutical intervention. After some time, however, they were experiencing another IgM peak (this time greater than + 80%) which was followed, after 3 to 11 days, but the final crisis of rejection and death of the animal. In a few cases, glomerular IgM deposits were found in transplanted kidneys.


Distribution of contractile proteins and adrenergic nerves in the adrenal gland of guinea-pig, rat and ox as revealed by immunofluorescence and the glyoxylic acid technique. Myosin and actin were localized in the adrenal gland, using antibodies against these proteins which were isolated from chicken gizzard. Myosin and actin were preferentially located in vascular walls including endothelial cells and in the capsule. In rat and guinea-pig adrenal cortex, the amount of contractile elements in vascular walls corresponded well to the density of adrenergic nerves as revealed with the glyoxylic acid method.


Increased susceptibility of Trypanosoma lewisi infected, or decomplemented rats to Salmonella typhimurium. Rats infected with Trypanosoma lewisi or decomplemented by injection of cobra venom factor or complement activating factor of trypanosomes were found to be more susceptible to infection with Salmonella typhimurium. Decomplemented rats subsequently infected with T. lewisi developed higher blood parasitemia than did normal T. lewisi infected rats.


[Comparative histological-morphometric study of the marginal zone and the germinal center of the rat spleen after endotoxin injection (author's transl]. Basing on the knowledge of structure and function of the marginal zone of the lymph follicle of the spleen in correlation with migration of lymphocytes to the red pulp and from there back to the lymph follicle (filtration of lymphocytes, so-called marginal zone bridging channel, role of the marginal sinus) a comparative study on the size of the marginal zone and germinal center following endotoxin-injection is presented.


Effects of pregnancy on the glucose-induced insulin release from cultivated pancreatic islets of the rat. 7-day-cultured islets from pregnant Wistar rats released at 5.6 mM glucose significantly more insulin than islets from nonpregnant rats, whereas in vivo this heigthened glucose sensitivity is lost 48 h post partum.


Comparison of the localization of several muscle proteins in relaxed and contracted myofibrils. The localization of several muscle proteins in relaxed and contracted myofibrils is compared. The morphology of the myofibrils and the behavior of these proteins was also investigated under extraction conditions.


The influence of the rostropontine-ventrolateral region on the sleep-wakefulness cycle. Lesions affecting the ventrolateral area of the nucleus reticularis pontis oralis produced, in chronic implanted cats, a significant decrease of paradoxical sleep.


Mepartricin, a polyene active on both Trichomonas and Candida. Lack of mutagenic activity. Mepartricin, the methyl ester of partricin, is a new polyene antibiotic with antifungal and antiprotozoal activity. The antitrichomonas activity in vitro is comparable to that of metronidazole, the widely used drug recently demonstrated to possess mutagenic activity and thus to be used with caution in therapy. Clinical investigations have shown that mepartricin can be successfully used in the topic treatment of vaginal trichomoniasis and candidiasis. The mutagenic activity of mepartricin has been evaluated using the Ames' test and compared to that of metronidazole. No mutagenic activity was detected for mepartricin. The drug can thus be proposed as a safer and efficient alternative to metronidazole.


The effect of acutely elevated blood glucose levels on luteinizing hormone and follicle-stimulating hormone release following an intravenous gonadotropin-releasing hormone injection. The effects of an acute blood glucose increase on the capacity of the pituitary gland to release gonadotropins (luteinzing hormone [LH] and follicle-stimulating hormone [FSH]) were studied in 21 women. Each woman received two intravenous challenges of 100 microgram of gonadotropin-releasing hormone (GNRH). Between these injections the blood glucose level was increased in 10 of the women by orally adminstering 100 gm of glucose. Although there were significantly higher blood glucose and plasma insulin levels in the latter group, the LH and FSH response to the second GNRH injection was not different. There was also no significant relationship between the basal blood glucose level and the gonadotropin (LH and FSH) response to GNRH. Acute elevations of blood glucose do not appear to alter the ability of the anterior pituitary cells to release gonadotropins.


[Aging and endocrine pancreas (author's transl)]. To test the hypothesis that diabetes is a form of accelerated aging, the following observations were made. 1) The incidence rate of diabetes mellitus had its peak at around 50 years of age with a gradually decreasing rate thereafter. This was clearly different from the manner of incidence of such disease as arteriosclerosis which increased with advancing age. 2) 100g of the oral glucose tolerance test performed on elderly subjects aged 60 to 89 years revealed high incidence of abnormal tolerance, 21% diabetic and 53% borderline types. 3) The insulin secretory capacity to glucose load of subjects was not different from that of young and middle-aged subjects from 20 to 49 years old. Therefore, decreased tolerance to glucose load could not ba ascribed to deficient insulin secretion. 4) No abnormality of glucagon response to glucose load was found in the old. 5) Serum beta-N-acetylhexosaminidase activity was not increased in elderly subjects, again contrasting with the increased activity found in diabetics. 6) Both glycolytic and gluconeogenic enzyme activities were decreased in the liver of aged rats. 7) No specific abnromality in insulin secretory response was observed in Werner's syndrome which might be considered to be a model for aging. All the above observations do not support the aforementioned hypothesis. Abnormality of glucose tolerance frequently observed in elderly subjects appears to be caused by other pathogenesis than diabetes mellitus.


Determination of thymidine in serum used for cell culture media. Thymidine concentrations in serum used for cell culture media were determined with an assay based on isotope dilution. In this assay, incorporation of (3H)-thymidine into  DNA of cultured cells was measured in the presence of 5 and 20% serum as a function of the concentration of unlabeled thymidine added to the medium. In three batches of horse serum, thymidine concentrations were 0--0.17 micron, while in fetal calf serum values of 0.75--2.1 micron were obtained. Dialysis of serum resulted in a reduction of thymidine levels by factors of at least 10.


Clomipramine (Anafranil) and behaviour therapy in obsessive-compulsive and phobic disorders. In a comparative study of three treatment regimens in patients with obsessive-compulsive or phobic manifestations, the most favourable therapeutic findings were seen in the clomipramine (Anafranil, Geigy Pharmaceuticals) plus behaviour therapy group and the least favourable therapeutic findings in the clomipramine plus simulated behaviour therapy group. The findings that a combination of behaviour therapy and clomipramine results in more favourable therapeutic changes than either of the two treatments alone is in line with reported studies in the literature.


Double-blind controlled study in phobias and obsessions. A double-blind between-patient study is described which was aimed at assessing the efficacy and tolerability of clomipramine (Anafranil, Geigy Pharmacetuicals) in clinically depressed patients with obsessive-compulsive and phobic psychopathological traits. Twenty patients of either sex aged between 18 and 65 years were randomly allocated to treatment with clomipramine (50 mg twice daily) or to treatment with an identical placebo. Patients were assessed at the commencement of the study and at two-weekly intervals over the six-week duration of the trial. By the methods of assessment used, clomipramine proved to be highly statistically significantly superior to placebo.


Alteration of islet cell populations in spontaneously diabetic mice. Endocrine-cell populations in the islets of Langerhans of mutant mice with a severe hypoinsulinemic diabetes (ob/ob or db/db on the C57BL/KsJ background) or with a mild hyperinsulinemic diabetes (ob/ob or db/db on the C57BL/6J background) were studied quantitatively by immunofluorescence and morphometry. In severely diabetic mice, islets presented a reduced proportion of insulin containing cells but increased glucagon-, somatostatin-, and pancreatic polypeptide (PP)-containing cells, as compared with islets of control (+/+) mice. An inverse change was observed in islets of mildly diabetic mice: islets were hypertrophic and composed mostly of insulin-containing cells, with decreased proportions of glucagon-, somatostatin-, and PP-containing cells. In both types of diabetic syndromes, the changes in cell populations induced a qualitative alteration of cellular interrelationships in the affected islets.


Diabetic glomerulopathy following unilateral nephrectomy in the rat. One month following induction of diabetes with streptozotocin, one half of diabetic and control rats underwent unilateral nephrectomy. Subsequently, all animals were studied with respect to renal function and glomerular alterations of diabetes. Blood pressure levels were similar in all animals. Diabetic and control animals with unilateral nephrectomy had similar but elevated serum creatinine levels and lower creatinine clearance values as compared with the intact rats. However, on a per kidney basis the creatinine clearance levels were higher in the animals with unilateral nephrectomy. At both three and six months following nephrectomy, markedly increased mesangial matrix thickening and mesangial deposition of IgG and C3 were observed in diabetic rats with unilateral nephrectomy as compared with intact diabetic animals. Nephrectomy had no detectable effects on glomerular morphology or immunohistochemistry of nondiabetic rats. Thus, unilateral nephrectomy in the rat increases, at as early as three months, the severity of diabetic glomerular lesions.


Transplantation of nuclei from lymphocytes of adult frogs into enucleated eggs: special focus on technical parameters. The technique of transplantation of nuclei from adult lymphocytes into enucleated eggs from Xenopus laevis (South African clawed toad) is described. The splenic lymphocytes from the one-nucleolus mutant were bound via their immunoglobulin receptors to nylon fibers, derivatized with the antigen used for immunization. A technique for coupling other cell types with Woodward reagent is also described. The cells were broken by aspiration into a micropipette and injected into enucleated eggs. The egg pronucleus was eliminated by UV treatment followed by surgical removal. The origin of the genome of developing embryos was determined on karyotype preparations by looking for the nucleolar organizer on the chromosome pair No. 12. Participation of egg pronucleus in development was frequent as judged by the incidence of gynogenetic diploid individuals and of tetraploid animals exhibiting characteristics of both recipient egg and somatic cell donor karyotypes. Apparently normal, lymphocyte-dervived tadpoles were obtained, but they died at 12 days. This shows that differentiated cells from adults, such as lymphocytes, can re-express the genes necessary for ontogeny.


Treatment of alcoholic hepatitis with encephalopathy. Comparison of prednisolone with caloric supplements. A previous report from this institution demonstrated significant improvement of caloric intake and survival in patients with alcoholic hepatitis and hepatic encephalopathy given prednisolone when compared with placebo. The purpose of this study was to compare the effects of prednisolone with a regimen of 1600 calories per day without prednisolone. Fourteen patients with alcoholic hepatitis and encephalopathy were studied. All 7 on caloric supplementation and 2 of 7 given prednisolone died (p less than 0.01). These results suggest that prednisolone therapy reduces the mortality of those patients with alcoholic hepatitis and hepatic encephalopathy. This effect does not appear to be related to total caloric intake.


Parallel between circadian rhythms of intestinal disaccharidases and foot intake of rats under constant lighting conditions. The relationship between the circadian rhythmic changes in the disaccharidase activities of the small intestine and the circadian feeding pattern was investigated in rats kept in the dark or in the light continuously for 4 weeks. Rats kept continuously in the light and fed ad libitum showed no rhythmic change in food intake or disaccharidase activities, but when they were only fed during a restricted time of day, their disaccharidase activities showed rhythmic changes with higher activities around the feeding time. In contrast, rats kept continuously in the dark and fed ad libitum showed circadian variations in food intake and disaccharidase activities essentially similar to rats kept under the normal light-dark lighting schedule. These findings show that the rhythm of disaccharidase activities is synchronized with the feeding rhythm, not with the lighting rhythm.


Neurohormonal control of pancreatic secretion. A review. This is a review of current information concerning the role of hormones and the autonomic nervous system in the control of exocrine secretions of the pancreas. A greater emphasis has been placed on the role of hormones because of information accumulated during the last several years. With the development of radioimmunoassay techniques, it is now possible to correlate circulating hormone concentrations with biological function. The role of hormones has been discussed with the framework of the secretin-glucagon family, the cholecystokinin-gastrin family, and other proposed gastrointestinal hormones and related peptides. Gastrin, secretin and cholecystokinin-pancreozymin are three prime gut hormones that regulate pancreatic secretion. Other hormones that may have a role in pancreatic secretion include glucagon, vasoactive intestinal polypeptide, chymodenin, somatostatin, pancreatic polypeptide, motilin, and bombesin. Neural mechanisms play an important although not so succinct a role in the over-all control of exocrine secretion. A complex relationship exists between the parasympathetic nervous system and the release of the hormones and their effect on pancreatic acinar and duct cells.


Effect of cimetidine on intrinsic factor and pepsin secretion in man. The effect of cimetidine on gastric acid, pepsin, and intrinsic factor secretion was assessed in normal male subjects. Cimetidine (300 mg) completely inhibited acid, pepsin, and intrinsic factor concentration and output stimulated by betazole. In contrast, basal output of pepsin and intrinsic factor was not inhibited. We conclude that H2-receptor antagonists inhibit betazole stimulation of intrinsic factor output in addition to their well-known inhibition of acid secretion.


Cimetidine treatment of duodenal ulceration: short term clinical trial and maintenance study. Eighty-five patients with endospcopically confirmed duodenal or pyloric canal ulcers entered a double blind trial with 1200 mg of cimetidine per day or placebo for 6 weeks. Eighty-four per cent of patients treated with cimetidine and 38 percent of those receiving placebo healed their ulcers (P less than 0.001). Measurement of basal acid output and maximal acid output before and after treatment showed no significant change but patients who failed to heal their ulcers had a higher basal acid output and maximal acid output than those who healed. Patients who smoked or drank alcohol had the same healing rate as abstainers. Sity-seven patients with duodenal ulceration healed by a 6-week course of cimetidine were randomly allocated to 400 mg of cimetidine twice daily or placebo in the maintenance trial. Actuarial analysis of the number of relapses in each group demonstrates that cimetidine is highly effective in preventing relapse.


Cimetidine versus intensive antacid therapy for duodenal ulcer: a multicenter trial. In a randomized double blind multicenter trial, patients treated with cimetidine (800 or 1200 mg daily) or an intensive regimen of Al-Mg antacid (210 ml daily) had similar rates of duodenal ulcer healing and pain relief. After 4 weeks of treatment, the proportion of patients with ulcer healing by endoscopy were: cimetidine (1200 mg), 21 of 33 (64 percent); cimetidine (800 mg), 19 of 32 (59 percent); and antacids, 15 of 29 (52 percent). These proportions did not differ significantly. Eighty per cent of cimetidine-treated patients became asymptomatic by week 4, as did 63 percent of antacid-treated patients (P greater than 0.1). No untoward effects were observed during cimetidine treatment. Twenty-seven per cent of antacid-treated patients reported diarrhea.


Long term cimetidine in the management of severe duodenal ulcer dyspepsia. Sixty patients who had been referred for elective ulcer surgery, and in whom a remission had been induced, entered a prospective double blind controlled trial of a single daily dose of 400 mg of cimetidine given at bedtime, or placebo. Eighty per cent of patients receiving placebo suffered symptomatic relapse and recurrence of duodenal ulceration at endoscopy within 6 months. The mean interval to relapse was 10 weeks. On the other hand, only 27 percent of patients had a recurrence during the 6-month period on low dose cimetidine therapy. No significant toxic or other side effects which could be attributed to the drug were observed.


Cimetidine in the treatment of duodenal ulcer: review and commentary. The published world literature on the efficacy of cimetidine, a histamine H2-receptor antagonist, in the treatment of duodenal ulcer is reviewed. In eight prospective randomized double blind placebo-controlled studies, cimetidine was administered to 348 duodenal ulcer patients with an incidence of endoscopically verified healing incidence of 37 percent in 300 placebo-treated patients. Healing rates were similar in patients receiving cimetidine in doses ranging from 0.8 to 2.0 g per day. It appears that at least 3 to 4 weeks of cimetidine therapy are needed to achieve healing rates of about 70 percent. In most trials, cimetidine was superior to placebo in achieving symptom relief in patients with duodenal ulcer. The drug has not been shown to result in acid rebound after cessation of therapy. There are no published prospective studies on the question of whether treatment with cimetidine results in increased ulcer for the short term treatment of duodenal ulcer. More data are required for an assessment of long term therapy with cimetidine.


Cimetidine and placebo in the treatment of benign gastric ulcer: a multicenter double blind study. A randomized, prospective, multicenter trial of the effects of cimetidine on benign gastric ulcer was conducted in 60 outpatients. Endoscopic assessment was used as the criterion for healing. Although none of the differences was statistically significant, mean healing rates were higher and mean decreases in ulcer size were greater with cimetidine than they were with placebo. Twenty-four per cent of the ulcers healed completely in 2 weeks when cimetidine was administered, compared with a placebo healing rate of 14 percent. At 6 weeks in the incidence of healing increased to 60 percent in the cimetidine group and 41 percent in the placebo group. The mean percentage of decrease in ulcer size was greater at both 2 and 6 weeks in the cimetidine group than it was in the placebo group. In both, the cimetidine and placebo groups, relatively liberal intake of a potent antacids in treatment of gastric ulcers has not been defined definitively. Thus, a possible beneficial effect of cimetidine may have been obscured. For more clear discimination between the effects of cimetidine and placebo in healing of gastric ulcer, studies utilizing either no antacid or antacids of low neutralizing capacity will be needed.


Cimetidine, antacid, and hospitalization in the treatment of benign gastric ulcer: a multicenter double blind study. Two hundred forty patients with benign gastric ulcer were treated in a controlled clinical trial to assess the effect on healing of cimetidine, antacids, and hospitalization. Inpatients and and outpatients were randomly assigned to one of three treatments: cimetidine plus antacid, cimetidine plus dummy antacid, or placebo tablet plus antacid. In 206 patients who met criteria for analysis, ulcer healing as shown by endoscopy occurred by 12 days in 11 to 26 percent and by 42 days in 58 to 76 percent. There were no significant differences in healing between hospitalized and nonhospitalized patients or between treatment subgroups. Symptomatic response was equivalent in all groups. The median antacid consumption was 328 mEq of in vitro buffering capacity per day. Patients taking antacids experienced significant diarrhea compared with those taking no antacid. This investigation suggests that the effect of cimetidine is equivalent to that of large amounts of antacid, but because a true placebo group was not studied it is not possible to conclude from this study alone whether either agent influenced healing. In contrast to widespread belief, initiation of treatment in the hospital did not enhance healing, but because patients were not randomly assigned to inpatient and outpatient status no final conclusion about the effect of hospitalization on healing can be drawn.


Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double blind controlled trial. The effectiveness of cimetidine for symptomatic relief in patients with chronic gastroesophageal reflux was studied in a multicenter, double blind clinical trial. Patients were entered into the study for a total of 8 weeks, receiving either cimetidine, 300 mg four times daily, or identical placebo tablets. Throughout the trial, frequent assessments were made of symptom severity and frequency, combined with careful measurement of antacid use. Esophagoscopy, esophageal acid sensitivity, and lower esophageal pressures were performed before and at the completion of the treatment period. Significant (P less than 0.05) decreases in symptom frequency and severity were noted throughout the study in the cimetidine-treated patients, as compared with the placebo group. This subjective improvement was corroborated by a concomitant decrease in antacid use, which was significantly (P less than 0.05) reduced in the cimetidine-treated group. In addition, significant improvement in esophageal acid sensitivity resulted from cimetidine therapy. No objective improvement in esophageal endoscopic appearance or sphincter pressures was noted. The results of this double blind trial indicate that cimetidine is more effective than the placebo for the relief of symptoms of gastroesophageal reflux.


Reduction of aspirin-induced gastrointestinal bleeding with cimetidine. Aspirin induces gastric mucosal damage and bleeding in the presence of acid. Cimetidine, the histamine H2-receptor antagonist, reduces basal and stimulated acid secretion. Arthritic patients taking fixed doses of aspirin who were found to have aspirin-induced occult gastrointestinal bleeding were given cimetidine in a randomized double blind, crossover study. Autologous 51Cr-labeled blood was measured in 4-day stool collections at the end of each 4-week period of placebo and cimetidine therapy in 22 acid-producing patients. Mean daily fecal blood loss was reduced during cimetidine therapy to 2.2 +/- 0.3 ml per day, compared with 4.1 +/- 0.7 ml per day during placebo therapy (P= 0.002).


[Mutagenic effect of new chemical compounds. IV. Mutagenic effect of dialkylaminoethyl esters of 5,6-dihydro-7H-benz(c)carbazol-carboxylic acids]. The mutagenic effect of dialkylaminoet hyl esters of 5,6-dihydro-7H-benz(c)carbazole-carboxylic acids on biochemical mutants (Escherichia coli P-678, Actinomyces rimosus 222) is found. Hydrochloride of diethylaminoethyl ester of 5,6-dihydro-7H-benz(c)carbazole-9-carboxylic acid, which induced reversible and direct mutations, proved to be the most active compound, its mutagenic activity exceeding considerably the activity of ethylene imine.


[Genetic structure of an isolated group of the indigenous population of northern Siberia--Nganasans (Tavgiitsi) of Taymyr. I. History, erythrocyte and serum blood systems, isoenzymes]. Nganasans is a small samodyen-speaking ethnic group originated from several clans of reindeer hunters. Pedigree studies revealed no consanguineous matings of uncle-niece, aunt-nephew, first cousins type among 120 families studied. Rather rarely mating between second cousins could be observed. The reviewed traditional kindship system based on bilateral exogamy is an explanation. Data on 12 blood systems and 6 red cell enzymes distribution in two main localities almost totally studied have been presented. No A2, r, K, MS alleles were observed. Hgh frequencies of Ns, R2, Fya, Jka, Gm1 have been found. Diegoa was seen in only one family. Polymorphism on PGM1, 6-PGD, AK and AP, monomorphism on LDH and MDH has been observed.


Identification of the gal3 insertion in Escherichia coli AS IS2. The gal3 mutation in Escherichia coli, located in the operator-promoter region of the gal operon, is identified as an IS2 insertion in the polar orientation I relative to the direction of transcription. This mutation, which may be considered the earliest example of a polar mutation caused by an IS insertion, is shown by heteroduplex analysis of phage lambdagal3 to be located about 170 base pairs from the promoter-proximal end of the chlD-pgl deletion in lambdagal8. It appears indistinguishable in position, sequence and orientation from the IS2 insertion carried by lambdagal8-490. The endpoints of the bacterial DNA segments in lambdagal3 and lambdagal8 are physically mapped in relation to attL.


Enzymic markers of thyroid C cells in some rodents. The paper provides comparative data of the localization of histochemical reactions demonstrating the activities of alpha-glycerophosphate and succinate dehydrogenases, acid phosphatase, non-specific esterases and non-specific acetylcholinesterase in the C cells of thyroids of 26 animals belonging to 5 rodent species. The family Muridae is represented by the Wistar albino rat and albino mouse, the family Microtidae by the bank vole Clethrionomys glareolus (Schreber 1780), the field vole Microtus agrestis L. 1761, and the pine vole Pitymys subterraneus De Selys-Longchamps 1825. The observed enzyme activity differences were most conspicuous on comparing the rat and mouse thyroids and in a much less degree the Microtidae thyroids. Among the histochemical reactions tested that for succinate dehydrogenase proved to be least effective as a C cell marker, alpha-glycerophosphate dehydrogenase being better, and acid phosphatase and non-specific esterases the best (not in the rat thyroid). The reaction for non-specific cholinesterase (with some limitations) gave satisfactory results in the C cells of all animal's thyroids. The present paper continues earlier studies [19] on the morphology of the C cells in thyroid glands of the rodents of the families Muridae and Microtidae and aims at supplementing them with histochemical data of enzymic activities. It deals with enzyme reactions that are employed as C cell markers in Mammals other than Rodents.


[Reduction mammaplasty].

[Reduction mammaplasty]. The Strömbeck reduction mammaplasty is a widely standardized technique with great safety leading to predictably good results if the principles are regarded. The most important point is the position of the nipple. An individual shape of the future breast can be achieved by different positions of the standard Strömbeck pattern or by variation of the pattern itself. The procedures are described and illustrated by the results, showing that the standardized method leaves enough room for individual variations.


[Prolene and vicryl as synthetic sutures for intradermal suture technics]. It could be shown that beside the non-absorbable synthetic suture material (Polypropylene) for the subcuticular continuous skin suture absorbable synthetic suture material (Polyglactin 910) is suitable for the buried subcuticular skin suture to obtain good esthetic scars in plastic surgery. Experiences with Polyglactin 910 in over 300 patients are presented. In no case wound healing was disturbed as a result of the suture material. Further application will give more information about the usefulness of the absorbable synthetic suture material Polyglactin 910 for the buried subcuticular skin suture.


Enzymatic defects of hereditary porphyrias: an explanation of dominance at the molecular level. In four of the five autosomal dominant porphyrias four different partial enzymatic defects of the porphyrin biosynthetic pathway have been discovered in the last few years. With the exception of protoporphyria, the residual enzymatic activity in carriers of these defects is approximately equal to 50% of that found in controls. In each case the pattern of excretion of porphyrin and/or porphyrin precursors reflects the stie of the partial metabolic block. There are indications, at least in intermittent acute porphyria, that the degree of penetrance of the disorder varies according to the level of phenotypic expression, being highest for the enzyme deficiency, lower for the excretion of precursors and lowest for the clinical symptoms. It is proposed that environmental factors, and probably also gene interaction, are the cause of the different degrees of penetrance.


Daily single-dose gentamicin therapy in experimental pyelonephritis. The therapeutic efficacy of gentamicin given once or three times a day was compared in a model of experimental renal infection in rats. The same amount of gentamicin given either in a single injection or three injections a day produced no statistically significant difference in the treatment of incipient infection. The effect of this mode of administration on advanced infection depended on the length of the therapy. After five days, administration of the same dose given in a single injection or three injections did not result in significant differences. After ten days the therapy proved more effective when gentamicin was injected three times a day. In comparison a single daily dose, amounting to two thirds of the total dose when given three times a day every eight hours, revealed after five days of therapy a statistically significantly lower bacterial count in the kidney than three daily injections of gentamicin.


[An investigation into the influence of human serum on the in-vitro activity of various cephalosporins (author's transl)]. Cephalosporins are being given more and more frequently empirically as initial therapy, until the bacteriological findings become available. The wide selection of cephalosporins available make the choice of the most suitable one difficult for the clinician. Cephazolin, cephradine and cephacetrile were tested against three standard bacteria strains (Escherichia coli, Staphylococcus aureus, Kelebsiella pneumoniae) in normal broth and with the addition of 30% inactivated human serum; the geometric mean of the minimum inhibitory concentration (MIC) was determined by serial dilution, and the minimum bactericidal concentration (MBC) by inoculation onto solid medium. On the addition of 30% serum, cephazolin showed a reduction in effectivity of up to 360% for the MIC and up to 74% for the MBC, cephacetril up to 250% for the MIC and 100% for the MBC, and cephradin a maximum loss of 16%. Successful treatment of a severe infection requires a high drug level or a corresponding tissue titer. Due to the high tissue concentration of cephradin and the unrivalled stable antibacterial effectivity in serum, this antibiotic can be recommended for clinical use.


Correlation of minimum inhibitory concentration and beta-lactamase activity. The beta-lactamase activity of 510 recently isolated Enterobacteriaceae was investigated with a quantitative photometric test. Beta-lactamase could be detected in 55 percent of the Enterobacteriaceae. At the same time minimal inhibition concentration (MIC) of beta-lactam antibiotics was determined. There was no correlation between MIC values and lactamase activity. For correct antibacterial therapy the clinician requires information on the lactamase activity of isolated bacteria in addition to the antibiogram. The qualitative test is useful for screening.


In vivo maturation of B cells in the spleen of nude mice following administration of bacterial lipopolysaccharide. Morphological changes of the splenic white pulp in athymic nude mice (nu/nu) and their normal littermates (nu/ + ) following intraperitoneal injection of bacterial lipopolysaccharide were studied by light and electron microscopy, immunofluorescence and autoradiography. Early blast formation and subsequent appearance of IgM-containing cells were observed by 72 h and at 120 h, respectively, in the periarteriolar sheath of nu/nu mice and in the follicular area of nu/ + mice. Ultrastructural details of blasts and the time course of their development were similar in both nu/nu and nu/ + mice. Lymphoblasts showed a large nucleus with a prominent nucleolus, many polysomes and poorly developed smooth endoplasmic reticulum. Plasmablasts had a nucleus with coarse heterochromatin and copious cytoplasm filled with dilated rough endoplasmic reticulum. Generally, lymphocytes proliferated and differentiated through lymphoblasts to plasmablasts by 72 h and finally to plasma cells at 120 h. However, this development was asynchronous since lymphoblasts, plasmablasts and plasma cells were observed simultaneously at 72 h. It was suggested that a B cell subset responsive to bacterial lipopolysaccharide matures to antibody-forming cells in the thymus-dependent area in nu/nu mice and in the thymus-independent area in nu/ + mice.


Host response to Treponema pallidum infection. III. Demonstration of autoantibodies to heart in sera from infected rabbits. Sera from rabbits infected intratesticularly with Treponema pallidum but not from animals injected intratesticularly with other bacteria or with extract of normal rabbit testes demonstrated autoantibody to heart tissue. The antibody was organ-specific with cross-reactivity to skeletal muscle but was not species-specific. It could not be absorbed by T. pallidum, T. reiteri, Veneral Disease Research Laboratory reagent or rabbit mitochondrial preparation. The antibody had a transitional pattern of appearance; it could be demonstrated between 30 and 60 days after infection but it decreased or disappeared thereafter. In many instances, it could be shown between 2 and 3 years after infection. The finding of the heart-reacting antibody strongly suggests an autoimmune phenomenon associated with T. pallidum infection.


Double blind trial involving: Teorema, a new antirheumatic, vs. indometacin in rheumatoid diseases. Teorema and indometacin were administered to patients with degenerative and inflammatory joint diseases and degenerative vertebral column diseases for a period of 21 days. 24 patients were included in the 3 groups distinguished by diagnostic criteria. The daily Teorema dose was 420 mg in 21 cases and 210 mg in 3 cases; that of indometacin was 150 mg in 22 cases and 75 mg in 2 cases. Both drugs were given orally as capsules (25 mg indometacin/capsule and 70 mg Teorema/capsule). Both compounds produced a highly significant improvement of symptoms. Laboratory tests at regular intervals failed to reveal any substantial deviations from normal in both treatment groups. In conclusion, the results of the double blind trial suggest that Teorema, a new anti-inflammatory substance, when administered at a dose of approximately 420 mg/day, produces a beneficial effect in many rheumatoid conditions, while causing remarkably few side effects.


[New drug combination for medical management of hyperlipemia: clinical study]. Sixteen patients with different kinds of hyperlipidemia were treated with Atroplex (Mg-Chlorphenoxyisobutyrate 350 mg, Mesoinositol-Hexanicotinate 250 mg), a new serum lipid decreasing drug. Within an interval of 60 days' standard treatment of 3 tablets of Atroplex, the serum level of cholesterol was reduced by 16-20% and that of triglycerides by 36-49%. This significant effect was obvious over the whole period of treatment. According to the compound of Clofibrate, Atroplex interfered with the anticoagulant treatment with phenprocoumon. In spite of this an AC-therapy is possible during the Atroplex medication, if the AC doses are reduced by 30-50%.


The Egyptian sycamore tree: its use in dermatology. An extract of the sycamore tree, known by the ancient Egyptians for its medicinal properties, was used to treat certain dermatoses in a group of Egyptian patients. Twenty-one patients having a variety of conditions including pityriasis alba, atopic dermatosis, psoriasis and tina infections were given a cream containing the active material. The response was excellent.


Role of S. wien in the epidemic epizootiology of salmonellosis, zoonosis of dramatic distribution. The appearing of S. wien and its diffusive and pathogenic distribution are reported within the general framework of Salmonelloses and the problems of epidemiological and epizootiological nature that arise this zoonosis. The measures to be adopted are also stressed in view of a more strict control and protection of human and animal health together with environmental hygiene from Salmonella infection and other Enterobacteria which are increasingly met inhuman and animal pathology. In future notes the components of this worldwide problem of hygiene and economy will be examined in detail.


Preoperative intermittent positive pressure respiration as preparation for emergency valvular surgery for pulmonary edema. Immediate emergency surgery is the accepted treatment of intractable pulmonary edema due to valvular heart disease. The presence of severe tissue hypoxia, acidosis, low cardiac output state and renal insufficiency results in a high operative risk. Delay of operation by several hours may prove advantageous in that it permits improvements of the patient's condition by means of intermittent positive pressure respiration with correction of acidosis and at the same time allows for treatment of the cardiac failure. Three illustrative cases are presented, all successfully managed by preoperative treatment in an intensive care unit. The pathophysiological basis of this therapeutic approach is discussed.


[Inducing factors in chronic urticaria]. Causes which have an exacerbating effect on chronic urticaria are described and their approximate incidence is reported. A challenge test battery is described.


[Erythema dyschromicum perstans].

[Erythema dyschromicum perstans]. The case of a 4 1/2 year old girl with the typical clinical picture of erythema dyschromicum perstans is presented. A survey of the literature on this dermatosis is described.


[Rhabdomyosarcoma of the skin].

[Rhabdomyosarcoma of the skin]. Rhabdomyosarcomas are malignant tumors, and especially occur in childhood. In adults they are extremely rare. A pleomorphe rhabdomyosarcoma of the skin, localized on the nose of an 85-year old female patient, is reported. After surgical removal the defect was reconstructed with a full skin graft. The four histologic types of rhabdomyosarcoma (pleomorphic, alveolair, embryonal, botryoid) are discussed.


[The fate of people with hypertrichosis throughout history]. Since the 16th century there are well documented examples for cases of hypertrichosis universalis. They are often confused with legends and stories of wild men. The patients were often shown at courtyards and later on at fairs. The observation of a new case of hypertrichosis universalis lanuginosa combines the description of hairiness and teeth with its psychical and physical development. Our patient was socially intergrated ones kept from outsider position.


[Double-lobed rotation pedicle flap].

[Double-lobed rotation pedicle flap]. This is a report on the bilobed rotation pedicle flap, a special type of pedicled flap transfer. The method is suitable for reconstruction of roundish skin defects, dermis and subcutaneous tissue with diameters from 8--15 cm, especially in dermato-tumorsurgery in trunk and thigh regions. The regional flap consists of two tongue-shaped donor lobes separated by the wound. The conventional form of the bilobed flap has an angle of 180 degrees between the bases of the lobes. By shifting the tissue at the surrounding of the defect, the procedure has the distinct advantage of camouflaging the donor sites. In addition it reduces the size of the wound. With the final transposition of the relatively small lobes large defects can be closed without the use of additional skin grafts. The method, here described in ten cases, is a simple way to resurface and reconstruct the wound with good functional and cosmetic result.


[Unusual picture of a localized argyrosis]. Blue to black patches appeared in the scar of a sectio caesarea performed 30 years ago. Histology and electron microscopy showed a localized argyrosis due to silver suture material used in the operation.


Diaminobenzidine cytochemistry in cryo-ultramicrotomy for the detection of peroxidases. Rat erythrocytes and lymphoid cells were fixed by glutaraldehyde and encapsulated in bovine serum albumin plus rabbit IgG globulins for cryo-ultramicrotomy. A technical procedure is described by which endogenous peroxidases of erythrocytes in ultrathin frozen sections were detected by hydrogen peroxide and diaminobenzidine as hydrogen donor. Modifications of this classical cytochemical procedure proved also useful in cryoultramicrotomy for immunoperoxidase labeling of antigenic determinants in rabbit IgG globulins which have been crosslinked within the supporting matrix of cells.


Prevalence and epizootiology of equine salmonellosis. Feces from 1,451 horses entering a veterinary hospital over a 13-month period were cultured for salmonella. A total of 46 horses (3.2%) yielded 1 or more salmonella-positive fecal cultures. Twenty horses were found to be excreting salmonella in the feces on admission, and 5 of these later had severe diarrhea associated with enteric salmonellosis. Abdominal surgery and other severe stresses were associated with all cases of severe enteric salmonellosis. Serotypes of salmonella isolated included Salmonella agona (15), S anatum (14), S typhimurium (7), S typhimurium var copenhagen (4), S infantis (2), S montevideo (1), S meleagridis (1), S drypool (1), and an unnamed Salmonella serotype (1). Seven deaths were attributed to 4 serotypes (S typhimurium, 3; S anatum, 2; S typhimurium var copenhagen, 1; and S montevideo, 1). A marked seasonal incidence is isolations was found with isolations highest in later summer to early fall and lowest in the spring. It was also found that horses can shed salmonella intermittently, and a minimal of 5 consecutive negative fecal cultures is recommended before considering a horse not to be infected with salmonella.