[Metabolic and neurochemical effects of nicergoline on the central nervous system. A review of the experimental studies (author's transl)].

The effects of 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol(5-bromonicotinate) (nicergoline, Sermion) on the energy metabolism in the animal CNS during and after cerebral hypoxia and ischemia have been studied by various authors by different methodological approaches. For this purpose both electrophysiological (EEG and cortically evoked potentials) and neurochemical parameters (adenylates, creatinphosphate and some intermediates of glycolysis and Krebs cycle) were analysed in dogs and cats. These studies concordantly show that nicergoline exerts a favourable activity during the post-hypoxic and post-ischemic period. In fact the recovery of the electrophysiological and neurochemical parameters is always more rapid in nicergoline-treated animals than in controls. The effects of nicergoline on the EEG pattern, on the energy potential and citrate concentration are particularly interesting.


[Interaction between anti-aggregating and anticoagulant agents. A double blind study on the concomitant administration of nicergoline and acenocoumarols].

A double blind study was carried out comparing 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) and placebo in 60 thromboembolic patients on long-term controlled acenocoumarol treatment. Aim of the trial was to assess the hypothesis of an interaction on both the coagulatory parameters and the clinical findings. No significant variations of the acenocoumarol daily dose were required in nicergoline treated group and no interaction was demonstrated in coagulatory parameters. Prothrombin activity and thrombo-test evaluated fortnightly were not statistically different in nicergoline and placebo groups while the platelet antiaggregating activity of nicergoline was confirmed after a three months' treatment. Bleeding time was unaffected. Minor differences in clinical findings were observed in the two groups.


[Psychopathometric double blind study with nicergoline versus placebo in geriatric patients with slight transit syndromes].

A double-blind study was carried out on 56 geronto-psychiatric in-patients who suffered from cerebral metabolic and nutritional disturbances to prove the effectiveness of 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate (nicergoline, Sermion). After a washout-phase of eight days the patients in the verum group received 3 x 1 dragée at 10 mg for a period of 12 weeks. For methodical reasons only patients with slight transit syndromes and, of these, only the first four weeks of examination were included in the present analysis. Thus 8 verum and 9 placebo patients remain whose findings during the trial are recorded in three procedures of capacity and two procedures of self-assessment (syndrome short test, repeating figures and letters, reading letters; scale for general somatic discomfort, scale for vegetative functional disturbances). In the measuring procedures there is a tendency towards improvement under the treatment with nicergline compared with placebo during the first three weeks. But the present results are not sufficient to come to a clear decision on the effectiveness of nicergoline in patients with cerebrovascular insufficiency.


Pharmacological and toxicological properties of creatinol O-phosphate. A review.

N-Methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP) has proved to possess anti-ischemic and anti-arrhythmic activities associated with improved ionic balance and heart performance. These activities, which have also been shown in clinical studies, are more evident in pharmacological and clinical conditions involving a hypoxic damage of the heart muscle. Pharmacokinetic studies have shown that absorption of COP administered i.m. is complete. COP is distributed in all organs, and in particular, in the kidney, liver and myocardium. After being dephosphorylated, this drug is eliminated with urine. Dephosphorylation of COP occurs in the kidney and liver. COP crosses the membrane of the myocardial cell, concentrating in the cytosoluble fraction. The results of the toxicological studies confirm that COP has no side effects, is excellently tolerated and has a favourable therapeutic index.


Creatinol O-phosphate therapy in patients with inadequate coronary circulation. Double-blind clinical trial.

N-Methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was checked on patients suffering from inadequate coronary circulation (12 patients had a recent myocardial infarction and 13 were suffering from angina pectoris) versus a reference substance (solvent of COP) in a double blind study. COP improved rhythm disturbances, chest pains and symptoms of contractility failure to a statistically significant degree.


[The role of nicergoline in the symptomatic treatment of arterial hypertension and chronic cerebrovascular insufficiency. A study on 359 observations (author's transl)].

An examination was carried out on the efficacy of 10-methoxy-1,6-diemethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) on the symptoms of functional side effects of arterial hypertension and chronic circulatory insufficiency as regards the psychomotoric activity and the relational activity; 359 patients suffering from crebrovascular insufficiency were included in the study. The compound was applied in a daily dose of 10 mg i. m. for 5 days and then in a daily dose of 15 mg orally for 1 month. In the entire symptom complex of cerebro-vascular insufficiency a positive effect of nicergoline could be observed; the results of all clinical criteria and their therapeutic relevance are discussed.


Activity of creatinol O-phosphate on persistent ventricular premature beats in ischemic heart disease. Double blind clinical trial.

In a double-blind investigation N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was checked versus a reference substance (solvent of COP) on volunteers affected by ischemic heart disease with persistent ventricular premature beats (VPB). COP was able to reduce VPB by 50--100% in 85% of the volunteers treated with this drug. This fact and the virtual absence of side-effects of COP lead the authors to the conclusion that COP merits more extensive investigations in this field in view of its clinical employment alone or in association with specific antiarrhythmic agents.


[Mutagenic and carcinogenic actions of some polycyclic aromatic hydrocarbons].

The carcinogenic and mutagenic actions of benz(a)pyrene (BP) and its derivatives 6-methyl-, 6-formyl-, 6-chloro-, 6-hydroxy-, 6-acetoxy-, 6-methoxy- and 4(5)-methoxy-BP were studied in mice and bacteria Salmonella typhimurium TA-98 and TA-100, respectively. The potent carcinogenic agents BP, 6-methyl-, 6-formyl-BP proved also mutagenic in bacteria of both strains. Weak carcinogenic compounds (6-chloro-, 6-methoxy-, 4(5)-methoxy-BP) and noncarcinogenic ones (6-acetoxy-, 6-hydroxy-BP) either turned out nonmutagenic or mutagenic in one of two bacterial strains tested. The differences in carcinogenic and mutagenic actions of the substances under study are not relative to the rate of their oxidation in the enzymatic system.


[Functional relationship between submaxillary gland and basal parts of intestinal cryptae and endocrine function of the pancreas].

The effect of fasting, glucose load and administration of the diabetogenic agent dithison on the cells of pancreatic islets, submaxillary glands and basal parts of intestinal cryptae was studied in rabbits by means of the histochemical dithison test. A potential relationship between these cells in realization of endocrine regulation of carbohydrate metabolism is suggested.


[Morphometric studies of pancreas islets of rats after subphrenic vagotomy].

Analysis of the morphometric data showed that 7 days after vagotomy significant changes ocurred in the pancreatic islets, mainly as a result of variation in B cells. At later periods (45 and 90 days after surgery) normalization of some morphofunctional parameters is noted, however, absolute restoration is not achieved.


Liver surgery.

Surgery on the liver is a major undertaking and probably should only be attempted by surgeons suitably trained and with adequate experience. Lack of such experience perhaps accounts in part for the high mortality rate still associated with major liver surgery following trauma since the operation must be carried out by the surgeon on the spot under difficult conditions. Modern sophisticated diagnosis techniques now allow accurate localization and assessment of liver lesions and the short-term technical results of elective surgery are improving. Despite this, the long-term effects of liver surgery for malignancy are poor but it is often justified to relieve symptoms. Transplantation is still in its infancy and although the results look disappointing the occasional reports of long-term survivors should encourage further work in this field.


Characterization of an inducible porter required for L-proline catabolism by Escherichia coli K12.

L-Proline can serve as sole source of carbon and nitrogen for the growth of Escherichia coli K12 and other Enterobacteria. L-Proline uptake and L-proline oxidase are subject both to catabolite repression and to specific induction by L-proline or glycyl-L-proline, although their regulation is not strictly coordinate. A strain defective for L-proline uptake due to a lesion at the locus putP does not show elevated uptake activity either on relief of catabolite repression or when grown on glycyl-L-proline as nitrogen source. The apparent Km for L-proline uptake decreases up to 14-fold as uptake Vm increases when cells are induced for both L-proline uptake and L-proline oxidase; cells with increased uptake activity, alone, do not show an altered Km. Although L-proline is metabolized during the uptake measurements, uptake is always active. The observed variations in uptake Km are unlikely to result from the escape of radioactive L-proline metabolites or from reversal of the transport reaction during the uptake measurements. We conclude that the L-proline porter encoded in putP is responsible for 80 to 90% of the constitutive and for the inducible L-proline uptake activity of wild-type bacteria. Although this porter is amplified in cells induced for L-proline catabolism, the observed values for uptake Vm may not be taken as a direct indicator of porter concentration.


Hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase response to litter size in suckling rats.

Rats were raised in litters of 3 or 14 from the 3rd postnatal day. Already, 2 days later on day 5, those raised in groups of three had elevated blood cholesterol and insulin levels and a very much lower hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG) CoA) reductase activity, than the other group. When aged 40 days, hepatic HMG CoA reductase activity was higher in the group raised three rats per litter than in the large litter group.


Phosphorescence evidence for the role of solvent--protein interactions in the energetics of conformational flexibility of liver alcohol dehydrogenase.

When tryptophyl side chains are hidden within relatively inflexible domains of globular proteins, the lifetime of the phosphorescence from these residues provides a measure of the local conformational flexibility. The phosphorescence decay from the tryptophan buried at the base of the nucleotide-binding domain in liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) was monitored between 1 and 40 degrees C to determine the energetics associated with the rate of local unfolding. The slow rate at which this process takes place is found to result from a high entropic barrier rather than from the disruption of strong intramolecular interactions. This observation along with the response of the system to solvent perturbations points to the significance of solvent-protein interactions in determining conformational flexibility.


Hybrid plasmids complement a putP mutation in Escherichia coli K12.

Clarke and Carbon have prepared a colony bank of 2000 Escherichia coli strains each containing a random segment of the Escherichia coli chromosome inserted into the EcoR1 restriction site of the plasmid ColE1. We have screened the colony bank by conjugation and have identified three strains bearing hybrid plasmids that complement a defective putP gene. Each of these strains shows increased L-proline uptake activity in comparison with the unmodified host or with the host bearing noncomplementing hybrid plasmids. However, CS520, the DNA source strain employed in constructing the hybrid plasmids, is a putP mutant. Since Escherichia coli possesses two L-proline porters, a variety of possible complementation mechanisms are discussed.


The effect of protein modification reagents on the chemotactic response in Salmonella typhimurium.

Several classes of reagents that covalently modify proteins have been shown to inhibit the ability of Salmonella typhimurium to reverse the direction of its flagellar rotation. Such reversal normally allows the bacterium to tumble and reorient its movement in a more favorable direction. These reagents include those that react with amino, guanidino, sulfhydryl, and disulfide groups on proteins. At high concentrations, most of these compounds also cause the paralysis of flagellar rotation. Tumbling in bacterial chemotaxis has been shown to be dependent on the methylation of a class of membrane proteins. The effects of these reagents in an in vitro methylation system have been studied. The results obtained suggest that most of these compounds are probably not acting on intact cells by inhibiting the activities of the cheR methyltransferase or the methyl-accepting proteins.


The interaction of polymeric viologens with hydrogenases from Desulfovibrio desulfuricans and Clostridium pasteurianum.

The interaction between hydrogenases from either Desulfovibrio desulfuricans or Clostridium pasteurianum and electron donors methyl viologen or polymeric viologens was examined. Extracts from each organism contained a single gel electophoretic band of active hydrogenase. The hydrogenase of D. desulfuricans was much more stable than that of Cl. pasteurianum. With methyl viologen apparent Km and Vm values were 0.5 mM and 0.62 mumole H2/min per milligram protein for the Cl. pasteurianum and 0.7 and 6.2 mumole H2/min per milligram protein, respectively, for the D. desulfuricans enzyme. The hydrogenases bound the polymeric viologens more tightly than methyl viologen, more so for the enzyme of D. desulfuricans than for Cl. pasteurianum. Maximal rate of hydrogen production was less with the polymeric than with methyl viologen. The results suggest that the D. desulfuricans enzyme in conjunction wiion than that from Cl. pasteurianum.


[Development of bacterial populations of telluric, enteric, and marine origin in planktonic systems exposed to urban pollution; mathematical data analysis].

A study of the comparative distribution of different types of bacterial populations in the sea area where the city of Marseille rejects its waste water shows that, when in contact with the marine environment, a great part of the allochthonic bacterial population undergoes physiological stress expressed by an abrupt reduction of the effectives and by weak values of the energetic charge. The presence of coliforms and streptococci in waste water lens, at important distances from discharging conduits, shows the possibility of a large diffusion for a fraction of the bacterial populations that withstand the initial stress. From mathematical analyses, an inverse correlation is revealed between detergents and the bacterial population as a whole, and between phenols and various allochthonic bacterial populations. The above results were evidenced through a sampling strategy based upon a 24-h-cycle study and a search for mathematical correlations between several biological, chemical, and physical parameters.


A simple device for uniform inoculation of nutrient surfaces.

A simple and inexpensive device for uniform surface inoculation is described. Efficiency and uniformity of inoculation were estimated with agar plates exposed to a bacterial suspension, containing 10 different strains, atomized with a spray gun. The fine mist settled, after a fall of 106 cm, upon the agar surfaces at the bottom of a cylindrical chamber. No significant differences were observed with regard to uniformity of inoculation between nine plates.


Further simplification of the Guizotia abyssinica seed medium for identification of Cryptococcus neoformans and Cryptococcus bacillispora.

A simplified Guizotia abyssinica seed-based medium for presumptive diagnosis of Cryptococcus neoformans and C. bacillispora (Paliwal and Randhawa 1978) was further simplified by replacing seed extract with pulverized seeds. This medium gives unambiguous results, avoids false-positive reactions with 13 other yeastlike organisms, and is simple and relatively inexpensive to prepare.


Chemotactic responses of Vibrio alginolyticus to algal extracellular products.

A capillary assay was used to evaluate the chemotactic responses of Vibrio alginolyticus to three common algal extracellular products. Acrylate and glycolate attracted the motile marine bacterium. The peak response occurred with 10(-2) M of each chemical. Acrylic and glycolic acid also attracted V. alginolyticus, with the peak response occurring at 5 x 10(-4) M of each chemical. Higher concentrations of the organic acids resulted in a decreased response. The bacteria also displayed positive chemotaxis to dimethyl sulfide.


A modified tube method for the cultivation and enumeration of anaerobic bacteria.

A new type of tube (the Lee tube) has been developed for use in the cultivation and enumeration of obligate anaerobes. The Lee tube is a double-walled, screw-capped tube which allows the formation of a thin cylinder of agar medium between the two walls. Anaerobiosis is achieved through deoxygenation of the deep cylinder of agar during sterilization, a minimum of head space, and use of a reducing agent to absorb oxygen introduced during the inoculation procedure. For several species of Clostridium, Bacteroides fragilis, Fusobacterium necrophorum, Veillonella alcalescens, and Pectinatus cerevisiiphilus, colony counts of cultures in the Lee tubes were comparable with those obtained in pour plates incubated in a BBL GasPak system and in anaerobic roll tubes.


[Immunofluorescence investigation of formol-paraffin material].

Immunohistochemical methods were employed for the investigation of bioptic and necroptic material fixed in formol and embedded in paraffin after it had produced very little or no fluorescence at all in the use of routine immunofluorescence techniques. Partial digestion with pepsin or trypsin or both enzymes in succession mostly facilitated positive immunohistological reaction. This particular procedure gives more scope to the methodological possibilities of histological material examination in that it offers an opportunity for the immunohistological investigation of even old material not specially preserved for immunohistological purposes but routinely fixed in ordinary formol. The simplification adds general availability to the method.


[Nuclear insulin assay after a starch and maltose load in chronic diseases of the pancreas: a preliminary note (author's transl)].

In a group of 48 patients with chronic pancreatitis the authors investigated the variations of blood insulin content after stimulation with starch and maltose, and compared these changes with the correspondind glycemia values. The two curves, practically matching in normal subjects, tend to diverge considerably in patients with chronic pancreatitis. According to the authors, since the assessment of exocrine pancreas function by common laboratory methods is none too satisfactory, this method may yield better appreciation of extant damage to the pancreas.


[Graduated and constant compression of the lower extremities in the prevention of postoperative deep venous thrombosis and of pulmonary thromboembolism. Clinical trial].

The authors report their experience with graded-pressure elastic hose (TED Stockings) for the prevention of deep venous thrombosis of the lower limbs and pulmonary embolism in high-risk, bedridden postoperative patients. The trial was designed according to a closed sequential program and gave positive, statistically significant results in terms of preventing pathology with this type of hose.


Inflammatory reactions in onchocerciasis: a report on current knowledge and recommendations for further study.

This report concerns the host's reactions to the presence of the parasite both in the course of the natural disease and during drug treatment. The various stages of Onchocerca volvulus are discussed in terms of the type of tissue reaction seen. The discussion then turns to basic hypotheses concerning the etiology of these reactions, emphasis being placed on the fact that while pathological changes are considerable in some locations there is a remarkable lack of reaction in others. Some of the mechanisms possibly involved in this apparent absence of host response are discussed, including anti-complement factors, poor antigenicity, acquisition of host antigen, immune tolerance, and blocking antibodies. In any study of the inflammatory response it is recommended that critical evaluations be made of histological material, haematological studies, the definition of the antigenic nature of O. volvulus, characterization of immunological reactivity of patients, and the definition of the migratory pathways of the parasite.The marked host reactions seen following chemotherapy, especially those related to the interaction of the drug diethylcarbamazine with microfilariae, are discussed at some length. The etiology of these reactions is considered and recommendations are made for the experimental elucidation of the mechanisms involved. Emphasis is placed on the necessity for detailed sequential histopathological and immunopathological studies in the definition of the tissue lesions found in onchocerciasis. Characterization of these lesions will assist greatly the approach to control of the adverse reactions seen during treatment.The use of anti-inflammatory agents in clinical trials is discussed and comments are made concerning the most suitable clinical situations for testing drugs and the types of drug that should be tested.


Intestinal immunity and vaccine development: a WHO memorandum.

As part of the research component of the WHO Diarrhoeal Diseases Control Programme, a Scientific Working Group met in August 1978 to review recent advances in knowledge of intestinal immunity, the application of genetic techniques in enteric vaccine development, the status of currently available immunizing agents against cholera, typhoid fever, and Shigella dysentery, and the prospects for the development of new or improved vaccines against the well known and newly recognized agents such as rotavirus and enterotoxigenic Escherichia coli. In each of these areas, the Group made specific recommendations for further research that should be considered for support under the WHO research programme in the field of diarrhoeal diseases.


Tanzania Filariasis Project: a provocative day test with diethylcarbamazine for the detection of microfilariae of nocturnally periodic Wuchereria bancrofti in the blood.

In coastal Tanzania, an area where the microfilariae (mf) of Wuchereria bancrofti exhibit nocturnal periodicity, the administration of 2 mg diethylcarbamazine (DEC) per kg body weight in the daytime provoked mf to enter the peripheral blood. In persons on normal daily activities the daytime DEC provocative method proved to be as sensitive in detecting microfilaraemia as was the examination of night blood. Its use in routine surveys is therefore justified. Although mf densities by day and night were highly correlated (r = 0.83) they tended to be lower after provocative daytime DEC than in the corresponding night blood, except in very light infections. This method was also useful in assessing the parasitological response to mass chemotherapy with DEC, but, in comparison with the results of the night blood examinations, the sensitivity and magnitude of the counts in persons remaining positive progressively decreased as the period of DEC administration increased. A correction factor has to be calculated to take account of this, and/or additional night blood samples must be taken.The dose of 2 mg of DEC per kg body weight used was readily acceptable to the people in coastal East Africa, whose cooperation is difficult to obtain for night blood surveys. Apart from W. bancrofti, the only human filarial infection occasionally encountered in this area was Dipetalonema perstans. Because of the risk of a severe Mazzotti reaction the test is contraindicated in onchocerciasis endemic regions. Severe reactions may also occur in subjects with loaiasis.


Initial experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium.

Initial studies of the tolerance and efficacy of praziquantel in the treatment of human infections due to Schistosoma haematobium were conducted at the WHO Tropical Diseases Research Centre, Ndola, Zambia. The first stage of the trial was a double-blind assessment against placebo of the tolerance and efficacy of oral doses of 1x20, 2x20, or 3x20 mg/kg in patients with a minimum schistosome egg excretion of 50 per random 10-ml sample of urine. Later a single-blind trial was carried out of the efficacy of three oral doses, each of 20 mg/kg, given at 4-hour intervals, or of a single oral dose of 50 mg/kg.In 79 young Zambians with S. haematobium infections (and often other parasitic infections), patient tolerance to the drug was very good, only minor post-treatment symptoms of intermittent epigastric pain, anorexia, and headache being noted, all of short duration.No changes of clinical relevance were detected in the results of a battery of haematological and biochemical tests. Post-treatment eosinophilia occurred in 42% of drug-treated patients but also in 30% of those given placebo. Serial electrocardiograms revealed no changes of significance.At six months after treatment, of 73 patients followed up, only 1 case of parasitological failure was detected. At one year, 66 (83.5%) of 79 patients with S. haematobium infection were followed up and 2 (2.5%) parasitological failures were detected.Two years after treatment, 45 (57%) of 79 patients with S. haematobium showed negative urines, 7 (9%) had positive hatching tests, and 27 (34%) were absent.


Preliminary trials with praziquantel in human infections due to Schistosoma mansoni.

As part of a programme of multicentre trials of the tolerance and therapeutic effect of praziquantel, clinical trials were carried out in Brazil in patients with active Schistosoma mansoni infections, each of whom had a minimum geometric mean egg output of 100 eggs per gram of faeces calculated from multiple pretreatment stool examinations.The first stage was a double-blind assessment of tolerance and efficacy of oral doses of 1 x 20, 2 x 20, or 3 x 20 mg of praziquantel per kg of body weight. Subsequently, single-blind trials explored the effects of 3 x 20 mg/kg at 4-hourly intervals, and a single dose of 50 mg/kg.Side effects increased in frequency as dosage increased. Nausea, epigastric pain, headache, dizziness, and drowsiness were all noted but their severity was mild or moderate and they disappeared in 48 hours. In general, monitoring laboratory tests showed little change.Following a stringent parasitological follow-up, 96% of 28 patients followed at 1 year after treatment with either 3 x 20 mg/kg or 1 x 50 mg/kg were cured. Praziquantel seems to be a very promising drug against S. mansoni and further clinical trials should be strongly encouraged.


Double-blind studies of tolerance to praziquantel in Japanese patients with Schistosoma japonicum infections.

The first clinical trials of praziquantel against Schistosoma japonicum infections in Japan were planned to assess tolerance only. Three double-blind studies against placebo involving a total of 51 patients were conducted with dosages of praziquantel of 1 x 20 mg/kg body weight, 2 x 20 mg/kg, 3 x 20 mg/kg given on one day.The frequency of unwanted side effects was higher in the group of patients given praziquantel at a dose of 3 x 20 mg/kg than in all other drug- or placebo-treated patients. In general, the side effects, which included drowsiness, headache, lumbago, abdominal fullness, or epigastric discomfort, lasted for several hours but disappeared spontaneously. The results of laboratory tests showed no significant changes caused by treatment.The overall assessment showed excellent or good tolerance in all patients treated with praziquantel at the lower dose levels. In those given 3 x 20 mg/kg, tolerance was excellent in 1 of 12 patients, good in 9, and fair in 2, whereas the respective placebo-treated group showed excellent tolerance in 3 of 12, good in 7, and fair in 2.


Preliminary clinical trials with praziquantel in Schistosoma japonicum infections in the Philippines.

Praziquantel, a new antischistosomal compound, was tested for tolerance and efficacy against placebo in two double-blind clinical trials in Philippine patients infected with Schistosoma japonicum.The compound was given orally at a dose of 3 x 20 mg/kg at intervals of 4 hours to a total of 82 patients-some without advanced disease and some with hepatosplenic involvement. A total of 43 patients received placebo. In a single-blind trial, 42 patients were given a single oral dose of 50 mg/kg. Monitoring of vital organ functions included comprehensive laboratory tests and serial electrocardiograms. In 38 patients with hepatosplenic involvement due to advanced stages of infection, serial electroencephalograms were additionally recorded. No toxic effects were observed in any of these examinations.Undesirable side effects occurred in 53% of the patients given 3 x 20 mg/kg and in 70% after a dose of 1 x 50 mg/kg. They consisted mainly of abdominal discomfort, fever, sweating, and occasionally giddiness, but in general were transient and mild. At 6 months post-treatment, 60 of 75 patients treated with 3 x 20 mg/kg and 29 of 41 treated with 1 x 50 mg/kg were completely negative for eggs. At 12 months post-treatment, 25 of 33 and 14 of 26 patients in the two treatment groups were cured. Thus the divided dosage gave a superior therapeutic result. Praziquantel proved to be free of major toxicity, and was well tolerated, highly effective, and easy to administer. Confirmation of results in extended trials may soon permit large-scale treatment.


Trial of BCG vaccines in south India for tuberculosis prevention: first report--Tuberculosis Prevention Trial.

The protective effect of BCG vaccination is being evaluated in a controlled community trial near Madras in south India. After tuberculin and sensitin testing and radiographic and bacteriological examinations, BCG vaccines and placebo were allocated randomly to about 260 000 individuals, of whom 115 000 were definitely tuberculin negative at the time of vaccination. Intensive efforts are being made, by means of regular follow-up surveys, to identify all new cases of tuberculosis occurring in the community. This report presents the findings of the first 7(1/2) years of follow-up. Incidence of infection was high in the study population. However, incidence of bacillary disease was more frequent among initial tuberculin reactors, especially among the older persons, than among non-reactors of whom the majority were in the younger age groups. The distribution of new cases of bacillary tuberculosis among those not infected at intake did not show any evidence of a protective effect of the BCG vaccines.


Release of active and inactive renin by the human kidney.

1. Active and inactive renin were assayed in plasma of the renal veins and the inferior vena cava below the kidney in eight patients with hypertension and unilateral renal abnormalities, 20 min after the patients had resumed the upright position. 2. The concentration of active renin on the affected side was significantly higher than that on the non-affected side. The concentration of inactive renin on the affected side was significantly lower than that on the non-affected side and in the inferior vena cava. 3. These findings suggest either that the affected kidney mainly secretes active renin, which is then converted into inactive renin in the extrarenal circulation, or that the affected kidney activates inactive renin.


The immunology of human and animal cysticercosis: a review.

In this review of the literature concerning the immunology of animal and human cysticercosis, emphasis is placed on whether previous exposure to the antigen confers protection to the host. Statistical analysis of the published data indicates that immunized animals have a lower risk than non-immunized animals of contracting cysticercosis, there being large variations within and between different host-cysticercus relationships. There is no indication as to which antigen is best for immunization but, although live parasites in all stages of development, or extracts, appear to give protection, embryos, eggs, and excretions are most frequently used. Antibodies appear to be the principal mediators of resistance, but the action seems to be only upon very young larvae, while fully grown cysticerci are unharmed. Several immunological methods are valuable in the diagnosis of cysticercosis, the choice depending more on the purpose of the study than on differences in their ability to discriminate between healthy and sick. The presence of anticysticercus antibodies in the serum of up to 50% of human patients indicates that human vaccination may be possible in high-risk areas; the remaining patients pose an interesting problem open to speculation and research on immunological evasion, immunodepression, and the existence of serotypes.


Direct radioimmunoassay and immunocytochemical localization of renin in human kidneys.

1. Highly specific antibodies to human renin were prepared in rabbits and used for the preparation of a renin-free substrate, the direct radioimmunoassay of renin in plasma and kidneys, and the localization of renin with fluoresceinated antibodies. 2. In a patient with a partially infarcted kidney, plasma renin activity was increased, and could be activated by acid. The direct measurement of plasma renin by radioimmunoassay gave identical values before and after acidification. 3. In the ischaemic part of the kidney, renin content was high, both by the enzymatic and the direct method of measurement. It was low in the non-ischaemic part of the kidney. 4. All afferent and some interlobular arteries of the obsolescent glomeruli were stained with fluoresceinated anti-renin antibodies. In the non-ischaemic area, the juxtaglomerular appratus did not stain. 5. Renin can now be measured in human plasma and kidney as an entity, by a specific radioimmunoassay. A direct investigation of this intrarenal hormone is now possible at the renal tissue level.


Renin precursor synthesis and renin-binding proteins in the mouse.

1. The precursor synthesis of renin, the storage form in the kidney and the submaxillary gland, and the molecular nature of the forms in plasma were studied in the mouse. 2. Renin is synthesized as a precursor (pre-prorenin) with a molecular weight of 50,000. 3. Renin is stored in the submaxillary gland and the kidneys as fully active renin with a molecular weight of 40,000. 4. The predominant form of renin in plasma is the active mol. wt. 40,000 form. High-molecular-weight forms of renin (800,000 and 70,000) are also present in plasma. 5. Pure 125I-labelled mol. wt. 40,000 renin binds after a change in the tertiary structure, to the plasma protease inhibitors alpha 2-macroglobulin, inter-alpha-trypsin inhibitor and alpha2-antithrombin. It binds also to lipoprotein and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins. 6. The high-molecular-weight forms of renin in plasma may be complexes of renin with plasma protease inhibitors and lipoprotein.


Acute and chronic effects of nifedipine on plasma renin activity and plasma adrenaline and noradrenaline in controls and hypertensive patients.

1. Nifedipine, a calcium antagonist drug, was given sublingually (10 mg) to seven normal subjects and 19 patients with essential hypertension. In addition, 12 of the hypertensive subjects then received nifedipine (10 mg thrice daily) for 3 weeks. 2. Sublingual administration of nifedipine in hypertensive patients induced a prompt and sustained reduction of blood pressure, without a significant increase of heart rate; in normotensive subjects blood pressure did not change, and heart rate was significantly increased. After chronic treatment, blood pressure remained reduced and heart rate did not rise. 3. Plasma catecholamines and plasma renin activity increased significantly in normotensive subjects after acute administration. 4. After both acute and chronic administration, only plasma noradrenaline was significantly increased in hypertensive patients; in long-term treatment, it was increased in both the lying and standing positions. 5. Nifedipine is an active antihypertensive drug, which may induce some degree of sympathetic activation.


Haemodynamic profile of angiotensin II antagonism in essential hypertensive patients.

1. The haemodynamic response to antagonistic (10 microgram min-1 kg-1) and agonistic (40 microgram min-1 kg-1) doses of saralasin was studied in young essential hypertensive patients. Blood pressure behaviour alone was thought to be inadequate to describe the response pattern. 2. Pre-saralasin setting of the renin-angiotensin axis was varied with salt intake (15 and 290 mmol of Na+/day) each for 10 days. This failed to influence blood pressure or plasma volume. 3. Antagonist blockade after low salt lowered blood pressure in three patients with the highest plasma renin values. Cardiac output rose in two of these, but it dropped in all others. 4. Decreases in cardiac output occurred with both doses of saralasin and even with suppression of the renin-angiotensin axis. This response is therefore unlikely to be due to removal of myocardial or venous angiotensin effects. 5. The renin-angiotensin system played a part in maintenance of blood pressure only with severe salt restriction and in a small proportion of cases. 6. No heart rate effect was seen with sarcalasin. 7. Blood pressure and total peripheral resistance responses were dependent on pre-(antagonist/agonist) setting, but heart rate and cardiac output were not influenced by this factor.


Angiotensin II blockade during combined thiazide-beta-adrenoreceptor-blocker treatment.

1. Sixteen patients (11 male, five female), median age 41 years, with essential hypertension insufficiently controlled by hydrochlorothiazide (75 mg/day; diastolic blood pressure greater than or equal to 100 mmHg), were studied. 2. Plasma renin concentration [renin], plasma angiotensin II concentration ([ANG II]), plasma volume and exchangeable sodium (NaE) were determined, and a saralasin infusion (5.4 nmol min-1 kg-1) was carried out while the patients were on thiazide alone and, in 14 cases, 3 months after addition of a beta-adrenoreceptor blocker (propranolol, six, metoprolol, six, and atenolol, two patients). 3. On thiazide alone, saralasin caused a significant decrease in mean arterial blood pressure in 12 out of 16 patients. The saralasin response was closely related to pre-saralasin plasma [ANG II] (r = 0.73, P less than 0.01). Plasma [renin] and [ANG II] were higher than normal in the group as a whole. 4. After addition of a beta-adrenoreceptor blocker systolic and diastolic blood pressure decreased from 164/109 mmHg to 136/94 mmHg. Plasma [renin] and [ANG II] decreased by 40 and 58% respectively. At this point, saralasin caused no significant change in mean arterial pressure. No close correlation was found between plasma [renin] or [ANG II] or saralasin response on thiazide treatment and changes in blood pressure during subsequent thiazide/beta-adrenoreceptor-blocker treatment. Plasma volume and NaE did not change significantly. 5. In patients with thiazide-induced stimulation of the renin-angiotensin system, addition of a beta-adrenoreceptor blocker leads to suppression of the system and, at the same time, ANG II-dependence of blood pressure disappears. This contributes to the antihypertensive effect of beta-adrenoreceptor blockers in this particular situation.


Contribution of the kidneys but not adrenal glands to the acute antihypertensive effects of captopril in spontaneously hypertensive rats.

1. Captopril (100 mg/kg, orally) decreased blood pressure in spontaneously hypertensive (SH) rats. 2. Bilateral adrenalectomy either before or after captopril administration did not alter the antihypertensive effect of captopril. 3. Bilateral nephrectomy reversed the established antihypertensive effect of captopril and prevented any change in blood pressure to a subsequent dose of captopril. 4. It is concluded that kidneys but not adrenal glands are essential to the antihypertensive actions of captopril in SH rats.


Haemodynamic effects of captopril in hypertensive patients: comparison with saralasin.

1. Captopril (25 mg) reduced plasma angiotensin II (ANG II) by 53% (P less than 0.001) and mean brachial artery pressure (MBAP) by 18.7 mmHg (P less than 0.001) within 75 min in 26 hypertensive patients. After 2 months (on 150-600 mg/day) MBAP had decreased by 27.1 mmHg (n = 18) with no further change of plasma ANG II. delta MBAP was significantly related to control log plasm renin (PRA)  and log ANG II in both conditions. 2. The acute depressor response to captopril was 11.2 mmHg greater (P less than 0.001) than delta MBAP during saralasin infusion (n = 12). 3. Heart rate slightly increased after acute administration of captopril (+3.3 beats/min; P less than 0.005), but cardiac output was not significantly affected; systemic vascular resistance decreased by 10% (P less than 0.01) with unchanged pulmonary vascular resistance. 4. During chronic administration, oxygen consumption, cardiac output and stroke volume increased by 15% (P less than 0.01), with unchanged heart rate; systemic vascular resistance had dropped by 30% (P less than 0.001). 5. Plasma ANG II and plasma aldosterone decreased, and PRA and ANG I increased acutely, with no further changes during chronic treatment.


Alpha-adrenergic suppression of renin secretion in the rat independent of renal vasoconstriction.

1. The effect of alpha-adrenergic stimulation, with phenylephrine, on isoprenaline-provoked renin secretion was studied in the isolated perfused rat kidney. 2. Infusion of phenylephrine increased renal perfusion pressure and prevented renin secretion in response to isoprenaline. 3. Renal vasoconstriction was abolished and the response in renin secretion to isoprenaline was restored by alpha-adrenoreceptor blockade with phenoxybenzamine. 4. In contrast, when renal vasoconstriction was prevented by dihydrallazine, suppression of renin release by phenylephrine still occurred. 5. These observations support an inhibitory effect of a non-vascular alpha-adrenergic mechanism on renin release. It is suggested that the alpha-receptor mediating this effect is directly related to the renin-producing juxtaglomerular cell.


Plasma noradrenaline concentration in hypertensive and normotensive 40-year-old individuals: relationship to plasma renin concentration.

1. Forty-year-old individuals with mild essential hypertension, identified during a survey of a population born in 1936, were investigated. Forty-year-old normotensive subjects, drawn from the same population, served as a control group. 2. Plasma noradrenaline concentration and plasma renin concentration at rest supine and after acute stimulation, as induced by frusemide intravenously and ambulation, did not differ from reference values in the 40-year-old normotensive controls. In the hypertensive group a close correlation (r = 0.77, P less than 0.001) was found between plasma noradrenaline and plasma renin concentration after acute stimulation. 3. Sympathetic nerve activity, as defined by measurements of plasma noradrenaline, is normal in mild essential hypertension. Discrepancies described in the literature are probably related to a lack of comparability between hypertensive and normotensive study populations.


The effect of mental stress on catecholamines, their metabolites and plasma renin activity in patients with essential hypertension and in healthy subjects.

1. Ten patients with essential hypertension and ten healthy men were submitted to mental stress consisting of Kraepelin's arithmetic test combined with noise. Concentrations of plasma and urine catecholamines and of their metabolites as well as plasma renin activity before and after the test were studied. 2. In both groups a significant increase of noradrenaline and adrenaline in blood and noradrenaline in urine was observed. The urinary excretion of dopamine fell significantly in both groups after stress. 3. After mental stress a significant increase in urinary excretion of 3-methoxy-4-hydroxyphenylglycol was observed in both groups. The excretion of vanillylmandelic acid decreased significantly only in healthy subjects. 4. The plasma renin activity rose significantly in both groups but the increase was more pronounced in healthy subjects.


Origin of kallikrein in rat and human exocrine glands and kidney.

1. The cellular localization of kallikrein was investigated in rat and human exocrine glands and kidney by a direct immunofluorescence technique. 2. Kallikrein was found in the duct system of the rat and human major salivary glands. 3. Kallikrein was found in the distal tubular cells of the rat kidney. Attempts to localize kallikrein in the human kidney were unsuccessful. 4. In the rat and human pancreas, kallikrein was found as a pro-enzyme in the acinar cells.


Inhibition of urinary kallikrein excretion by semi-purified renin in the rat.

1. Rat kidney extracts obtained at successive stages of a purification procedure, which allows the separation of renin and kallikrein, were used in order to investigate their effect upon urinary excretion of kallikrein, sodium, potassium and water in hyperhydrated rats. 2. Only the purified fraction containing renin reduced kallikrein excretion. The decrease of kallikrein coincided with a considerable increase in sodium, potassium and water excretion. 3. The natriuretic effect of renin extract did not depend on the presence of kallikrein. The injection of a mixture of renin and kallikrein attenuated the effect of renin alone, indicating that both enzymes exert antagonistic actions on the excretion of electrolytes and water by the kidneys. 4. A purified fraction of kidney extract containing no kallikrein and only traces of renin activity, had a stimulatory effect on kallikrein, water and electrolyte excretion.


Urinary kallikrein in normotensive subjects and in patients with essential hypertension.

1. Excretion of urinary kallikrein was normal in 13 out of 15 patients with uncomplicated essential hypertension. 2. Frusemide increased urinary kallikrein excretion in normotensive subjects and in patients with essential hypertension. The stimulating effect of frusemide on urinary kallikrein was significantly diminished in patients with essential hypertension. 3. No correlations of urinary kallikrein with sodium, potassium, and aldosterone excretion were found. 4. The results do not support the idea that urinary kallikrein plays a primary role in the pathogenesis of essential hypertension.


Urinary prostaglandins and kallikrein in essential hypertension.

1. Urinary prostaglandins (PG), kallikrein and plasma renin activity (PRA) were measured in 35 patients with essential hypertension and 22 normotensive controls before and 15 min after frusemide (40 mg intravenously). 2. PGE2 and kallikrein excretion rates were lower in hypertensive subjects, and failed to rise to the same extent after frusemide. PGF2 alpha excretion was not significantly different in the two groups of patients either before or after frusemide. PRA rose less in the hypertensive subjects after frusemide. 3. These findings support the view that there is an abnormality of renal vasodilator systems (PGE2 and kallikrein) in essential hypertension.


Sodium balance, urinary prostaglandin E2 and renin in normal man.

1. Urinary prostaglandin (PG) E2 excretion and plasma renin were measured in five healthy volunteer subjects for 2 h after intravenous injection of frusemid (protocol A) and during salt restriction for 7 days with frusemide added on the 2 last days (protocol B). 2 In protocol A, peak values in PGE2 and urine flow were reached in 10-20 min, after which the values rapidly subsided. Plasma renin increased twofold in 60 min. 3. In protocol B, even during severe antinatriuresis (day 5) and during maximal negative sodium balance (day 7), no change in urinary PGE2 excretion was observed. Plasma renin increased twofold on day 5 and increased tenfold on day 7. 4. The result of protocol B does not suggest any essential role of renal PGE2 for sodium excretion or sodium homeostasis in man. The result of protocol A may point to a role of renal prostaglandins for the diuretic action of frusemide.


Factors determining the variability of arterial pressure in hypertension.

1. Intra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Pressure was analysed beat by beat by computer and variability measured as the standard deviation of the normally distributed frequency histogram. 2. Variability was strongly influenced by physical activity, being least during sleep and increasing progressively with bed rest and ambulation. Variability during daytime was not related to time. 3. Systolic variability correlated directly with systolic pressure. An independent inverse relationship with baroreflex sensitivity was observed. Systolic variability tended to increase with obesity. 4. None of the following were related independently with variability: age; race; sex; plasma renin activity; plasma angiotensin II; plasma noradrenaline; plasma adrenaline.


Studies on the mechanism of mineralocorticoid-induced blood pressure increase in man.

1. To gain insight into the mechanism of mineralocorticoid-induced blood pressure rise in man we performed haemodynamic studies in six normotensive volunteer subjects before and during administration of the synthetic steroid 9 alpha-fluorocortisol (0.8 mg daily) for a period of 6 weeks. In a further study, performed in seven subjects, plasma noradrenaline concentration and reactivity to exogenous noradrenaline were determined before and during administration of the mineralocorticoid. 2. Within the first week of steroid administration an increase in mean arterial blood pressure could be demonstrated, which was due to an increase in cardiac output. After the sixth week the elevated blood pressure was the consequence of an increased total peripheral resistance. 3. Plasma noradrenaline concentration decreased and reactivity to exogenous noradrenaline increased during steroid administration. 4. The mechanism underlying the increase in total peripheral resistance during long-term mineralocorticoid administration remains unclear. Increased sympathetic tone does not seem to be a factor since plasma noradrenaline decreased considerably. Pressor response to noradrenaline increased probably due to decreased sympathetic tone.


Haemodynamics during long-term thiazide treatment in essential hypertension: differences between responders and non-responders.

1. Blood pressure, systemic haemodynamics, plasma volume, renin and aldosterone were measured during placebo treatment and after 1, 4 and 12 weeks of hydrochlorothiazide in 13 patients with uncomplicated essential hypertension. Nine of these patients were also studied after 24 and 36 weeks of treatment. 2. Mean arterial pressure was lowered significantly during hydrochlorothiazide treatment. In seven patients the fall in mean arterial pressure was lowered significantly during hydrochlorothiazide treatment. In seven patients the fall in mean arterial pressure was greater than 10% (responders); four of these were studied for 36 weeks. The remainder were considered non-responders. 3. Hydrochlorothiazide lowered cardiac output. The maximal decrease was observed after 12 weeks of treatment (P less than 0.01). In responders this was followed by a return to pretreatment values and a significant decrease in total peripheral resistance, whereas in non-responders cardiac output remained reduced and total peripheral resistance was permanently elevated. 4. Changes in plasma volume, renin and aldosterone were not significantly different in responders and non-responders although non-responders tended to show a greater degree of plasma volume depletion and a more pronounced increase in plasma aldosterone. 5. Thus it is unlikely that the initial decrease in cardiac output is an important determinant of the long-term haemodynamic effect of thiazide diuretics.


An evaluation of tienilic acid, a new diuretic uricosuric agent, in the therapy of arterial hypertension.

1. Tienilic acid and hydrochlorothiazide were evaluated in a double-blind trial in order to investigate their antihypertensive and metabolic effects. 2. After 5 weeks, the decreases in blood pressure and the changes in plasma or serum electrolytes, urea, creatinine, glucose, cholesterol and triglycerides, and in creatinine clearance, did not differ in the two groups of patients. 3. In patients taking tienilic acid a significant decrease in serum uric acid and an increase in urate clearance was observed, whereas in patients receiving hydrochlorothiazide a slight increase in serum uric acid, with no modification of urate clearance, occurred. 4. The diuretic and antihypertensive actions of tienilic acid and hydrochlorothiazide are very similar. The uricosuric/hypouricaemic effect of tienilic acid could assume clinical relevance in long-term therapy of hypertensive patients.


Response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to long-term administration of captopril in patients with severe, treatment-resistant malignant hypertension.

1. The response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to inhibition of angiotensin I converting enzyme (kininase II) with captopril has been studied in patients with severe, treatment-resistant, malignant hypertension. 2. Nine patients with a past history of severe hypertension, supine diastolic blood pressure greater than 120 mmHg before conventional antihypertensive therapy and resistant to conventional antihypertensive therapy were studied. 3. Captopril administration resulted in a marked decrease in arterial blood pressure and plasma aldosterone concentration and an increase in plasma renin activity. 4. Although arterial blood pressure remained significantly below the values observed during the control period, pressure did tend to increase again after 3 days. Addition of hydrochlorothiazide kept arterial pressure significantly below pretreatment control values.


Effect of increasing doses of labetalol on blood pressure, plasma renin activity and aldosterone in hypertensive patients.

1. Four different doses of labetalol (150, 300, 600 and 900 mg/day) were given for 1 week to each of four groups of patients with essential hypertension (six patients for each group). 2. Labetalol decreased mean blood pressure and heart rate to the same extent on the first and the seventh days of treatment. Only standing blood pressure showed a dose-dependent inhibition both in the supine and upright position. 3. Labetalol exerted a net inhibitory effect on plasma renin activity, which was related to basal renin values and was already maximal at the lowest doses. This effect was well maintained in the supine position. This effect was well maintained in the supine position, although during standing it tended to be less evident with increasing doses. 4. Urinary aldosterone was decreased in a dose-dependent fashion and its changes were largely independent fashion and its changes were largely independent of plasma renin activity. 5. Neither basal values nor changes of renin and aldosterone were related to the hypotensive effect of labetalol. 6. During labetalol treatment urinary sodium excretion fell for 2-3 days and then returned to basal values. The retentive effect of labetalol on sodium was directly related to the decrease of blood pressure, and the successive sodium escape might be explained either by the observed increase of plasma volume (indirectly measured by packed cell volume) or by aldosterone inhibition.


Systemic haemodynamic effects of biofeedback in borderline hypertension.

1. Six patients with borderline hypertension underwent training in exteroceptive biofeedback (BFB) in order to increase or decrease arterial pressure. 2. Systemic haemodynamics, intravascular volume and peripheral renin activity were determined before, during and after training sessions. 3. BFB training resulted in a significant reduction in mean arterial pressure (from 116 +/- 4.6 to 101 +/- 2.5 mmHg) mediated through a fall in total peripheral resistance; cardiac output, heart rate, intravascular volume and plasma renin activity remained unchanged. 4. In contrast, the increase or decrease of arterial pressure that occurred during BFB training was produced predominantly through changes in cardiac output and heart rate respectively, whereas total peripheral resistance under these circumstances remained unaffected. 5. The haemodynamic effects of BFB seem remarkably similar to the immediate or chronic effects of beta-adrenoreceptor blockade, initially producing a fall in cardiac output followed by a reduced arterial pressure associated with a decreased total peripheral resistance.


The evidence that salt is an important aetiological agent, if not the cause, of hypertension.

1. Salt intake and the incidence of hypertension correlate between populations. 2. Salt intake within a population may correlate with the incidence of hypertension. 3. Disorders that lead to retention of salt cause hypertension. 4. Modest salt restriction reduces blood pressure in many patients. 5. Reducing salt balance and preventing the compensatory rise in angiotensin II controls blood pressure in most patients. 6. Salt is the probable cause of the epidemic of hypertension in the Western world; this could be prevented by salt restriction.


Pressor responsiveness to angiotensin in renovascular and steroid hypertension.

1. The pressor response to angiotensin II was reduced in rats with early (less than 6 weeks) and chronic (greater than 4 months) Goldblatt two-kidney, one-clip hypertension and enhanced in DOCA-salt hypertension. 2. Converting enzyme inhibition with captopril brought the angiotensin pressor response curves into closer proximity although the DOCA hypertensive rats were minimally hyper-responsive and rats with early and chronic renovascular hypertension showed slightly reduced responsiveness. 3. After bilateral nephrectomy the pressor responses to angiotensin were similar. 4. The pressor response to angiotensin II in these animals was inversely related to plasma renin concentration and therefore largely dependent upon receptor occupancy by endogenous angiotensin II. There is no evidence for enhanced pressor responsiveness to angiotensin in either renovascular or DOCA hypertension.


Relationship between exchangeable sodium and blood pressure in different forms of hypertension in man.

1. Arterial pressure and exchangeable sodium (NaE) were measured in patients with Conn's syndrome, essential hypertension, renal artery stenosis and chronic renal failure. Comparison was made with a control group. Urine sodium excretion was measured separately from the two kidneys in patients with renal artery stenosis. 2. Compared with control, mean NaE was significantly increased in Conn's syndrome, and was normal in essential hypertension, renal artery stenosis and chronic renal failure. 3. The correlation of arterial pressure with NaE was positive and significant in Conn's syndrome, essential hypertension and chronic renal failure. 4. In contrast the correlation was significantly negative in unilateral renal artery stenosis. Patients with lowest NaE had hyponatraemia, hypokalaemia and secondary hyperaldosteronism. 5. Urinary sodium excretion from the unaffected kidney in unilateral renal artery stenosis correlated positively with arterial pressure, possibly reflecting the phenomenon of pressure-natriuresis. Patients subsequently responding least well to surgery excreted least sodium from the untouched kidney for a given arterial pressure. 6. The findings suggest important roles for arterial pressure in the regulation of sodium balance (predominant in renal artery stenosis), and for sodium balance in the regulation of arterial pressure (predominant in Conn's syndrome). The observations in essential hypertension are compatible either with an exact balance between these mechanisms or with the existence of some other mechanism raising blood pressure.


Isolation of a renal thiol protease that activates inactive plasma renin.

1. A thiol protease with properties similar to those of cathepsin B (EC 3.4.22.1) has been isolated and purified from human renal cortex. 2. This enzyme can generate renin activity from renin-suppressed and anephric human plasma at pH 5.5. 3. The renin activity thus generated is inhibited completely by antibody to purified human renal renin. This activation therefore represents the release of inactive renin.


Kinin system in clinical and experimental rheumatoid inflammation: a short review.

The kallikrein, kininogen, kinin and kininase system along with other inflammatory chemical mediators are important components for the initiation and maintenance of clinical and experimental rheumatoid-like inflammatory conditions. Numerous studies carried out in the last few years, however, strongly suggest that the kinin-forming system intervenes in a far wider range of physio-pathological processes than has been considered previously. The authors summarize present knowledge concerning the system and review some of the latest experimental findings and opinions.


Plasma levels of glucose and lactate after intravenous glipizide administration in some insulin-dependent diabetics. Therapeutic effects of an associated glipizide-insulin treatment.

A study was carried out to evaluate the effectiveness of glipizide in insulin-dependent diabetic patients. An intravenous glipizide (2 mg) test was carried out in 7 patients before and after a period of associated insulin-glipizide treatment (mean daily dose of 80.7 i.v. lente insulin and 14.3 mg glipizide for 9.1 months) to assess the capacity of the sulphonylurea to reduce acutely the plasma glucose and lactate levels. Glipizide did not produce glucose variations in either test but did result in a significant decrease, in the first test only, in mean plasma baseline levels of lactate, which were higher than normal in these patients. There was no reduction in daily insulin requirements after the period of associated glipizide-insulin treatment. It is concluded that, in the dosage used, intravenous glipizide probably has no hypoglycaemic effects in insulin-dependent diabetics. Moreover, it did not prove useful in combination with insulin. However, the reduction in plasma lactate may be related to an acute enhancement of the exogenously administered insulin. This improvement in the insulin effect may be an acute one among the so called "extra-pancreatic" actions which have been demonstrated for glipizide and other sulphonylureas.


A multi-centre general practice trial of a pindolol/clopamide combination ('Viskaldix') in essential hypertension.

A large, open, multi-centre study was carried out in general practice to evaluate the effectiveness and tolerance of a combination of 10 mg pindolol plus 5 mg clopamide, in single tablet form, in the treatment of patients with essential hypertension. Computer analysis of the records of 8989 patients who completed the 8-weeks' study period showed that treatment with the combination product, in a dosage of 1 tablet daily in 83% of the patients, resulted in excellent blood pressure control in the majority (75%) of cases, irrespective of age or previous antihypertensive treatment, and was particularly effective in those with mild to moderate hypertension who had previously not received any therapy. Side-effects were generally not troublesome and only 8.3% of patients stopped treatment for this reason. The most commonly reported side-effects were dizziness, nausea, tiredness and headache.


Placebo-controlled, double-blind clinical trial of alprenolol in African hypertensive patients.

A placebo-controlled, double-blind clinical trial of alprenolol was carried out in 20 hypertensive Africans. The active drug and placebo were each administered for 8 weeks using a crossover design. Alprenolol was given in the form of a slow-release tablet preparation at a dosage of 200 mg twice daily. Four patients were withdrawn from the study either because of side-effects (2 patients) or non-compliance (2 patients). The mean reduction in blood pressure obtained in the 16 patients who completed the trial was less than that usually reported in Caucasians.


Mobility of epidermal growth factor surface receptors and modulation by cytoplasmic actin.

Epidermal growth factor (EGF) receptors were demonstrated in cultured bovine odontogenic epithelial and ectomesenchymal cells and in rat embryonic and foetal lung fibroblasts by immunofluorescent reactivity with EGF and anti-EGF traced with a fluorescein-isothiocyanate-labelled goat anti-rabbit globulin. Mobility of EGF receptors, either alone or cross linked by anti-EGF, was manifest as sequential changes in staining patterns progressing from a random pattern to clusters, supranuclear caps and large perinuclear globules. Double fluorochrome studies showed that supranuclear caps of EGF receptors occurred in sites closely related to those occupied by cytoplasmic actin; the latter was demonstrated by anti-actin antibody traced with a rhodamine-labelled goat anti-human globulin. Prior treatment of cells with 2 x 10-5 M cytochalasin B for 10-120 min promoted capping of EGF receptors, while its presence throughout the staining procedure inhibited capping. The dual opposing effects of cytochalasin B on capping suggest that actin may have roles in the opposing functions of EGF receptor anchorage and mobility.


[Foodstuff additive-induced intolerance reactions].

Additional materials in food and consumers' goods can produce different allergic reactions. The more important additional materials and reactions produced by them are discussed. They introduce to us the phenomenon of the intolerance and the different cross reactions during treatment of the pathomechanism. The causal clearing up of the intolerance reactions is made by provocation tests, with the help of which pathological reactions may be prevented.


Sucrase and cellular development.

The cellular changes that take place as the intestinal cell migrates from crypt to villus are morphologically and biochemically remarkable. It is fortunate that many of these phenomena can be delineated by following enzymic activities. Sucrase-isomaltase is a particularly fascinating enzyme complex because it is a marker of the differentiated cell. Sucrase is inducible with steroids and protected by the substrate sucrose. Purified enzyme can be used to stimulate production of specific antibodies in goats; these antibodies have been used as probes to locate enzymically active and inactive antigen in the cells of the crypt and villus respectively. Further examination of the enzyme has indicated a molecular weight of 200 000--350 000. These higher molecular weight components are located in the brush border of the enterocytes. Lower molecular weight subunits are antigenically active and are in the cytosol. It is assumed that these smaller components are enzymically inactive pre-combination subunits of the sucrase-isomaltase complex and that the sucrase-isomaltase of the brush border is an aggregate of these subunits. The California sea lion, which is deficient in intestinal sucrase activity, does have isomaltase activity. This finding supports the concept that there are different gene complexes for sucrase and for isomaltase.


The differentiation and redifferentiation of the intestinal epithelium and its brush border membrane.

This paper briefly reviews the progress of investigations during the past 30 years into the development of the intestinal epithelium, and surveys the directions in which research in this field is now advancing. Early studies showed that the differentiation of the epithelium is a discontinuous process, and also focused attention on the enzyme specialization of the brush border. The phases of differentiation were found to be under the control of the pituitary--adrenal system, with the outflow of glucocorticoids influencing both structural and biochemical aspects of enterocyte development in fetal and postnatal stages. More recent evidence has shown that thyroid hormones can also regulate epithelial differentiation, even in the absence of adrenocortical function. Organ culture is now becoming an important means of probing into the processes underlying overt differentiation, and methods for culturing pure populations of enterocytes are being perfected. Studies of developmental alterations in the constituents of the brush border membrane, and of synthesis and glycosylation of membrane constituents, are contributing to the development of an integrated account of the differentiation of this membrane, through which all nutrients must pass.


The role of enteropeptidase in the digestion of protein and its development in human fetal small intestine.

Enteropeptidase converts trypsinogen into active trypsin, which not only hydrolyses some peptide bonds of food proteins but also activates a number of pancreatic zymogens. For this reason enteropeptidase is a key enzyme in the digestion of dietary proteins and its absence may result in gross protein malabsorption.


The role of lingual lipase in neonatal fat digestion.

Lingual serous glands (von Ebner) contain a potent lipase that hydrolyses triglycerides to a mixture of partial glycerides (di- and monoglycerides), glycerol and free fatty acids. Studies in man and in rat have shown that similar lipolytic activity is present in oesophageal and gastric aspirates and suggest that the intragastric digestion of dietary fat is initiated by lingual lipase. In the rat the lingual serous glands are initiated in 19- to 20-day fetuses; lipase activity is first detected in 20-day-old fetuses and increases 14-fold by birth. The data suggest that in the fetus lipase activity originates predominantly in the serous demilune cells of mucous glands whereas after birth the enzyme is synthesized and stored in the rapidly differentiating serous glands. In man lipolytic activity is present in gastric aspirates as early as 26 weeks of gestational age. Our studies suggest that the lipolytic activity has characteristics similar to those of adult human and rat lingual lipase; the enzyme is present in the oesophageal pouch of infants with oesophageal atresia indicating that in infants, as in adults, it probably originates in the lingual serous glands. Since the enzyme is active in the absence of bile salts and has a low pH optimum it is ideally suited to act in the stomach and probably compensates in the premature for low pancreatic lipase activity. The lipolytic activity could be important, not only in the digestion of dietary fat, but in helping to overcome the temporary bile salt deficiency and to solubilize dietary fat through the formation of amphiphilic reaction products.


Membrane digestion and nutrient assimilation in early development.

Advances in the study of membrane digestion are described which relate to techniques for the separation of the apical glycocalyx and the study of the distribution of enzymes between the latter and the cell membrane. The regulatory properties of brush border enzymes have been demonstrated. Membrane digestion by pancreatic enzymes adsorbed on the mucosal surface and by enteric enzymes predominates in early development, whereas intraluminal digestion develops during the transition to definitive (adult) nutrition. Substrate and other, non-substrate factors are involved in the regulation of intraluminal and membrane digestion in ontogeny. The importance of lipid components of the diet for the maintenance of proximal-distal gradients of enzyme activity in the small intestine during the transition from milk to adult nutrition is discussed. At this period of development hydrocortisone affects both the synthesis of enzymes and their incorporation into the enterocyte membrane. The inducibility of different enzymes is not identical. The hypothesis has been proposed that stress is one of the factors inducing or repressing the synthesis of brush border enzymes. These effects are mediated through the hypothalamus, adrenals, hypophysis and thyroid. The experimental findings demonstrate that various stressors are responsible for the induction of sucrase, maltases, gamma-amylase, peptidases and alkaline phosphatase, and for the repression of lactase in suckling rats.


Update on the toxicity of inhaled methyl methacrylate vapor.

The current threshold limit value (TLV) of 100 ppm for methyl methacrylate vapor was originally set because it was considered to be a value sufficiently low to preclude either systemic toxicological effects or discomfort from irritation in workers chronically exposed to the vapor. Shortly after this limit was proposed we became interested in evaluating the toxicological properties of methyl methacrylate vapor and, subsequently, of providing experimental data which would be useful in evaluating the adequacy of this TLV. The purpose of this article is to review some of the more relevant literature prior to 1976 which pertains to inhalation exposure and to summarize our more recent data which resulted from statistically designed studies employing acute and subchronic exposures to known concentrations of the vapor including the near-TLV value of 116 ppm.


DNA binding and mutagenicity of 7-substituted derivatives of benz[A]anthracene.

The binding of carcinogenic 7-hydroxymethylbenz[a]anthracene (7-HOCH2-B[a]A) and 7-acetoxymethylbenz[a]anthracene (7-AcOCH2-B[a]A) to calf thymus DNA was studied in the presence or absence of microsomal enzymes or nucleoside phosphates. In the absence of microsomes or ATP little or no binding was detected for either hydrocarbon (HC). Microsomal enzymes significantly enhanced the binding of both HC's to DNA when compared to control as measured by radioactivity bound to DNA. When 7-HOCH2-B[a]A was incubated at 37 degrees with ATP there was a linear increase in binding over a six hr period. Of the nucleoside phosphates tested, ATP, and to a lesser extent ADP and CTP, mediated binding of 7-HOCH2-B[a]A suggesting formation of a reactive phosphate ester. Mutagenicity studies with 7-acetoxymethyl, 7-hydroxymethyl, 7-formyl-, 7-methyl-, and 7-methoxymethyl-B[a]A were conducted using the Salmonella reverse mutation assay. All compounds exhibited mutagenic activity in the presence of S-9; only 7-AcOCH2-B[a]A was active without S-9 indicating this compound to be an ultimate mutagen.


An enzyme-immunoassay for estriol.

A practical method was developed for enzyme-immunoassay of serum estriol, with alkaline-phosphatase as a marker enzyme. Alkaline-phosphatase was conjugated with estriol-6-(O-carboxymethyl) oxime using water soluble carbodiimide. The estriol-alkaline-phosphatase complex, which has both enzyme activity and capacity to bind anti-estriol serum, was obtained by Sephadex G-200 gel filtration. This complex, which was stable for at least 3 months at 4 degrees C, was used as enzyme-labelled estriol. Anti-estriol serum raised against estriol-6-(O-carboxymethyl) oxime bovine serum albumin was employed. "Bound and free" estriol were separated by the double antibody method. A linear relation was obtained between estriol concentration and antibody-bound alkaline-phosphatase activity in the range of 0.2-100 ng estriol/ml. In this assay system, cross-reactivity with other steroids was negligible under physiological conditions, and endogenous alkaline-phosphatase, which increases during the late pregnancy, caused no interference. The coefficients of variation were 3.3-14.2% (within assays), and less than 22% (between assays), and the mean recovery rate was 77.5%. Serum estriol values determined by the present method correlated well with those determined by radioimmunoassay (r=0.90 for total estriol; r=0.98 for free estriol). The present method of enzyme-immunoassay is suitable for measurement of serum estriol during pregnancy.


Features of ginseng saponin-induced corticosterone secretion.

Ginseng saponin administered intraperitoneally to rats induced a significant rise in plasma corticosterone, while it tended to increase plasma glucose and to decrease plasma immunoreactive insulin. Oral or intraperitoneal administration of ginseng saponin increased plasma corticosterone in unanesthetized, pentobarbital-anesthetized or alloxan-diabetes rats. The histamine-induced rise in plasma corticosterone was suppressed by pretreatment with diphenhydramine, whereas the ginseng-induced rise was not. Ginseng saponin decreased rectal temperature while it increased plasma corticosterone. Ginseng-induced corticosterone secretion was superimposed on the basal levels of plasma corticosterone due to fasting and circadian rhythm. Thus ginseng saponin would be a kind of stressful agent and have different features associated with the stimulation of the pituitary-adrenocortical system from several other chemical agents.


Statistical methods for censored survival data.

Methods of statistical analysis of censored survival times are briefly reviewed and illustrated by application to clinical trials data. These include estimation of the survival curce, nonparametric tests to compare several survival curves, tests for trend, and regression analysis. Extensions of the methodology are made for application to epidemiologic case-control studies. These are used to estimate relative risks for leukemia associated with radiation exposures. A final section provides some annotated references to the recent literature.


Statistical computing in the United States.

Recent history and developments related to the increase in statistical computing activities in the United States and by U.S. participants in international efforts are reviewed, with emphasis on important events, organizations, references, and products which contribute to informed selection and use of statistical programs. Three features matrices for major statistical packages are included as potential aids to Japanese statisticians in assessing the utility of these packages in biostatistical applications.


Statistics in Japanese universities.

The teaching of statistics in the U.S. and Japanese universities is briefly reviewed. It is found that H. Hotelling's articles and subsequent relevant publications on the teaching of statistics have contributed to a considerable extent to the establishment of excellent departments of statistics in U.S. universities and colleges. Today the U.S. may be proud of many well-staffed and well-organized departments of theoretical and applied statistics with excellent undergraduate and graduate programs. On the contrary, no Japanese universities have an independent department of statistics at present, and the teaching of statistics has been spread among a heterogeneous group of departments of application. This was mainly due to the Japanese government regulation concerning the establishment of a university. However, it has recently been revised so that an independent department of statistics may be started in a Japanese university with undergraduate and graduate programs. It is hoped that discussions will be started among those concerned on the question of organization of the teaching of statistics in Japanese universities as soon as possible.


Some concepts in toxicology.

Toxicology seeks to understand and quantify injurious chemico-biological interactions. The application of this understanding is prediction of the likelihood of occurrence of injury to human health or to undesirable alteration of ecological balance. The key to understanding chemical induced biological injury is development of improved methods of measuring changes in cellular function and structure and the application of these methods to elucidate the mechanisms and factors that modulate chemical injuries. The key to application of this understanding is appropriately designed dose-response and time-response studies which will, with appropriate consideration of biological mechanisms, allow prediction of conditions of exposure (and their confidence limits) that represent finite levels of risk of injury. The underlying data base required is extensive and will be drawn from traditional studies as well as new methods of testing and risk assessment.


Wisdom, technology, and the good life.

Wisdom lies in extraction of good from new and old. Wisdom alone produces a society of wise men unable to leave their caves. Technology alone produces a society ruled by cold, despotic facts. A proper combination of wisdom and technology can produce the good life. That requires recognition of our ambivalence toward technology, a move away from our superspecialization of technologists and nontechnologists and toward a clearer understanding of technology as a most important servant of man.


Assessment of myocardial function in the horse. 1. Theoretical and technical considerations.

The paper discusses the various parameters which are currently used in attempts to assess the contractile efficiency of the myocardium in various species. These procedures depend upon accurate recording of intracavity pressure. The response of a catheter-mounted microtransducer compared with a fluid-filled catheter manometer system is illustrated to show the advantage of the former in providing a true representation of pressure changes.


Intestinal barriers to water-soluble macromolecules.

Neonates of some species of mammals absorb water-soluble macromolecules from the lumen of the gut to the circulation. This is a means for providing the neonate with passive immunological protection. The accepted model for absorption of macromolecules, particularly immunoglobulin G (IgG), has at least three phases: adherence of the macromolecule to the brush border on enterocytes; internalization of the macromolecule within the enterocytes; and egress of the macromolecule into the lamina propria. With regard to the absorption of IgG, adherence is thought to be a specific reaction of ligand (IgG) with a plasmalemma binding site. Pinocytosis is activated and internalization follows. Egress into the lamina propria occurs at the basal-lateral membrane by a process of reverse pinocytosis. Unbound (unprotected) macromolecules that are internalized in the pinocytosic fluid are shunted off to lysosomes and either digested or stored therein. Neonatal rodents fit this model for macromolecular absorption. However, in another group of neonates (e.g., pig, cow, horse), nonselected absorption takes place, in that IgG and other macromolecules are transported from the gut lumen to the blood. In a third group of neonates, (e.g., human, guinea pig) absorption of IgG is either of low order or nonexistent. Since neonatal mammals possess a mechanism for absorbing macromolecules, there is the potential for internalizing toxic macromolecules if the toxin is presented to the neonate's enterocytes in competitive amounts. Adults retain remnants of the neonatal absorptive mechanism.


[The postnatal growth of the skull in the house mouse Mus musculus Linné, 1758, and in 2 different large subspecies of the field mouse Microtus arvalis Pallas, 1779. I. Introduction, materials and methods].

In order to describe postnatal skull growth in Mus musculus, Microtus arvalis arvalis and M. a. asturianus, a total of 408 animals were raised and measured. The growth rate of single bones was followed by means of a maximum-likelihood estimator for the parameters A, B and C of the growth function Y(t) = A-B exp(-Ct). Supplementary techniques used to estimate the morphological divergence of the different taxa included methods of allometry research and multivariate statistical methods such as discriminate analysis and MANOVA. Drawings of selected stages of skull-bone ossification are provided to assist researchers in determining the age of undated specimens.


Investigation on the transfer of fleas among small mammals using radioactive phosphorus.

The transfer of fleas Megabothris turbidus, Ctenophthalmus agyrtes, Nosopsyllus fasciatus etc. was investigated by labelling the bank vole (Clethrionomys glareolus Schreb.) with radioactive phosphorus. On the one hand, the process of flea transfer was traced among different individuals of the same host species, and on the other, among different host species (C. glareolus, Apodemus flavicollis Melch.). The investigations revealed that the flea transfer in a rodent nest visited by another host depended partly on the number of fleas present in the nest, partly on the period spent by the new-comer in it. Conversely, the number of fleas transferred in the nest by the newly arrived host depended on the temperature of nest bedding and on the initial nest occupation by other host.


[Current aspects of rheumatoid arthritis].

According to recent investigations two factors might play an essential role in the pathogenesis of rheumatoid arthritis (R.A.). Besides genetic components, i.e. the HLA-system and familial aggregation, the immune processes, mediating tissue inflammation and injury, are acknowledged as having established roles in the pathogenesis of R.A. The present report reemphasizes recent data concerning the autoimmunity and the immunologic network with trends of therapy in R.A. In view of the effectiveness of new nonsteroidal antiinflammatory drugs, a double-blind study of suxibuzon vs. indomethacin in 30 patients with active R.A. is described in detail. Both drugs were active and similar in their efficacy at 4 weeks as judged by clinical and laboratory measurements. No serious toxic side-effects were observed in both treatment regimens.


[Anatomical structures, physiology and pathophysiology of cerebrospinal fluid metabolism; a review for an understanding of cerebrospinal fluid findings].

The very different macroscopic and microscopic details of the structures involved in production and reabsorption of cerebrospinal fluid in the different parts of the central nervous system are causing confusing laboratory findings in cerebrospinal fluids, the ingredients of which change even under normal condition in these different parts. Moreover the chemical ingredients of cerebrospinal fluid differ especially from the normal situation during some diseases of the central nervous system. Although we can be sure that there is much more diagnostic information in cerebrospinal fluid, we mainly prefer certain standard methods today, as there are cell counts and measuring of the protein concentration, as diagnostic parameters. Their unspecific changes during several pathologic states do not yet allow to point out the exact localization of the disease, nor can they contribute in every case in finding the cause of the disease. Therefore other and more specific diagnostic laboratory methods are to be developed, which will make possible more precise statements about the nature and the localization of central nervous system diseases.


[Effect on carbohydrate metabolism of a new saluretic, etozolin].

The influence of Etozolin (Elkapin) on the carbohydrate metabolism was studied in 10 healthy volunteers, 6 patients with chemical diabetes and 10 with overt diabetes by blood glucose measurements and oral glucose tolerance tests with determinations of serum insulin levels. The healthy volunteers received 800 mg Etozolin per day during the treatment period of 3 days, the two groups of patients 400 mg Etozolin for 8 days. The laboratory parameters of the treatment period were compared with the corresponding values of the pre- and posttreatment periods and evaluated statistically. There was no statistically significant difference in the carbohydrate metabolism between the 3 test periods in all groups studied. As a result of the induced diuresis body weight, serum electrolytes and urine volume changed significantly during the Etozolin treatment as compared with the pre- and posttreatment values. Other changes of laboratory parameters could not be seen. In diabetic hypertensive patients a significant reduction of blood pressure was observed.


Establishment of a human lymphoblastoid cell line with specific antibody production against group A streptococcal carbohydrate.

A human lymphoblastoid cell line, secreting specific antibody against Group A carbohydrate (A-CHO) was established by pre-selection of antigen binding normal human lymphocytes, followed by Epsetin Barr virus (EBV) induced immortalization. Culture supernatants were assayed for anti A-CHO antibodies by radioimmunoassay, N-acetyl-glucosamine-coupled T4-phage plaque inhibition tests and passive hemagglutination. As a rule, the supernatants contained about 10 micrograms/ml anti-A-CHO antibodies of the IgM-kappa type. The antibody was fractionated and partially purified on an N-acetyl glucosamine Sepharose 4B column with a recovery of about 3 micrograms/ml of supernatant.


Isolation of type-specific antibody to streptococcus pyogenes by affinity chromatography.

Rabbit type-specific opsonic antibodies to type 1 and type 12 streptococci were isolated by affinity chromatography on immobilized phage-enzyme extract. They were tested by precipitation in gel, bactericidal test and radioimmunoassay. Only type-specific activities were demonstrated. These activities were distributed homogeneously according to avidity. No suggestion of opsonizing and precipitating activities being separable from each other was found. These highly purified rabbit antibodies were marked by radioiodination and used to titrate human anti-M antibodies by competition. These marked antibodies were also used for the study of type-specific antigenic determinants on streptococcal antigens.


Interaction of wheat-germ agglutinin with streptococci and streptococcal cell wall polymers.

Wheat-germ agglutinin agglutinates all strains of group A and group C streptococci, a part of the strains tested of groups B and E and some strains of other streptococcal groups. It also agglutinates peptidoglycan of several streptococcal groups and precipitates some group-specific carbohydrates of streptococcal cell walls as well as some teichoic acid extracts. The basis for agglutination and precipitation of streptococci and streptococcal cell wall polymers appears to be the interaction of the combining sites of the agglutinin with N-acetyl-D-glucosamine residues present in the cell wall polymers, either in terminal or in internal positions respectively.


[Malaria hypothesis--the significance of the hereditary red cell traits Hb S and glucose-6-phosphate dehydrogenase deficiency in malaria (author's transl)].

The high frequencies of the Hb S and G6PD-deficiency genes in the tropics are explained by their relative resistance against malarial infection. They may confer advantage through lower infection rates or through lower parasitaemia. There is evidence that heterozygote carriers of these genes are partially protected. The mechanism of resistance is known for Hb S but not completely understood for the G6PD-deficiency gene. Other red cell factors are discussed with respect to innate resistance against malaria.


[Conditions influencing the activity of fosfomycin in vitro (author's transl)].

The determination of the antibacterial activity of fosfomycin in vitro is most suitably carried out in serial dilution tests on Mueller-Hinton agar. In this, the reproducibility of the minimal inhibitory concentrations (MIC) is the best and is the least dependent on the size of the inoculum. In addition, there is no "skip-tube" effect with this method of determination. The reproducibility of the MIC values increases for several bacterial species on addition of glucose-6-phosphate and at the same time the inhibitory values are lower. If human urine is used as the nutrient medium, the inhibitory values of fosfomycin increase for many species. The action of the antibiotic is not reduced on addition of human blood to the Mueller-Hinton agar.


[Bacteremia associated with subfebril urinary tract infections (author's transl)].

Blood samples of 115 patients of both sexes admitted to the hospital with urinary tract infections were examined for bacteremia. Out of 115 patients 12 (10%) had positive blood cultures associated with significant urinary counts (greater than or equal to 10(5) organisms/ml). Although 10% of the patients showed positive blood cultures indicating bacteremia none of them had shaking chills, fever or any other clinical signs of septicaemia. None of the patients from whom blood samples were taken had yet received antimicrobial therapy. Bacterial isolates from urine and blood were identical. Microorganisms most frequently isolated were found in the following order: E. coli, Proteus species, K. pneumoniae and coagulase negative staphylococci. Neoplasms, obstruction of the urinary tract and age were found to be high risk factors.


[Diagnosis of trichinellosis and special aspects of a modified immunofluorescence test (author's transl)].

Trichinella spiralis was detected in 1835 by Paget, an English student. Since the introduction of the meat investigation law for trichinosis in 1937 the infection with this parasites became a rare condition. The last endemies in Germany occurred in 1967 and 1977. They restimulated the discussion regarding the efficiency and sensitivity of the routinely used methods for the detection of Tr. spiralis. 69 patients, suffering from infection with Tr. spiralis were investigated using a modified IFT. This method was compared with other serological techniques for the determination of Tr. spiralis and was found very sensitive and specific. Further immunological investigations showed an increased lymphocyte stimulation with Trich. antigen in most patients suffering from trichinellosis. When added autologous serum however the proliferation of lymphocytes was inhibited. The reason for this phenomenon might be a factor with immunosuppressive property produced by the adult worms.


Serial renin-angiotensin studies in spontaneously hypertensive and Wistar-Kyoto normotensive rats. Transition from normal- to high-renin status during the established phase of spontaneous hypertension.

To characterize the renin-angiotensin system in the Aoki-Okamoto spontaneously hypertensive rat (SHR) more fully, serial measurements of plasma renin activity (PRA), plasma renin concentration (PRC), renin reactivity (as relative index of circulating modifiers of the renin reaction) and renin substrate concentration were made in 6- to 64-week-old SHR and in age-matched Wistar-Kyoto normotensive rats (WKY). In the evolving phase of SHR hypertension (6 and 13 weeks of age), PRA was comparable to WKY control values, whereas mature SHR with established hypertension developed, between 13 and 35 weeks of age, a high-PRA state persisting through 64 weeks of age. In 64-week-old SHR, increased plasma volume (3.54 +/- 0.91 in SHR vs. 3.18 +/- 0.90 ml/100 g body weight in WKY, p less than 0.025), together with increased PRA (24.9 +/- 3.8 in SHR vs. 13.1 2.2 ng AI/ml plasma/hr in WKY, p less than 0.025), suggest that volume decrease cannot explain increased PRA. In 42-week-old SHR, PRA was incompletely suppressed by deoxycorticosterone acetate plus 1% saline orally for 4 days: 4.9 +/- 1.2 in SHR vs. 0.6 +/- 0.8 ng angiotensin I/ml plasma/hr in WKY, p less than 0.001. Modestly increased renin reactivity of plasma was observed in SHR at all ages studied, supporting the ubiquity of increased circulating accelerators (or decreased inhibitors) of the renin reaction in hypertensive states. However, elevated renin reactivity did not account for the transition from normal to high PRA observed in mature SHR, nor did renin substrate concentration, which was consistently lower in SHR than in age-matched WKY. Temporal patterns of, and strain differences in PRA were closely paralleled by variations in PRC but not by other reaction components. Significant elevation of serum creatinine in old SHR support the presence of renal injury. We conclude that PRA and PRC are normal in evolving SHR hypertension and progress to abnormally elevated levels after hypertension is established. We postulate that "high-renin" hypertension may develop as a consequence of the hypertensive state per se, perhaps due to nephrosclerotic vascular disease.