Drug-induced parkinsonism in the rat- a model for biochemical investigation of the parkinson-syndrome. III. The incorporation of D-glucose-14C(U) in amino acids of brain and liver from rats pretreated with reserpine or with phenothiazines. Following treatment with reserpine or alternatively with a combination of phenothiazines (Randolektil, Majeptil) a drug-induced parkinsonoid reaction was provoked in rats. Twenty min before decapitation, 18 muCi d-glucose-14C(U) was administered intravenously. Concentration and radioactivities of glutamic acid (glu), glutamine (gln), serine (ser), and glycine (gly) were assayed in some regions of brain and in liver. Separation was performed by a combination of paper electrophoresis and chromatography or by an automatic amino acid analyzer. 1 After reserpine, the concentrations of serine and glycine were increased ten-fold while their specific activities decreased by the same factor. The interconversion serine-glycine was not affected. The concentration of glutamic acid was reduced while its specific activity remained constant. 2. After phenothiazines, the concentrations of serine and glycine in brain were also increased but their specific activities were decreased to a different degree. This indicates an additional effect on the serine-synthesis from glucose. The interconversion serine-glycine was also altered. The concentration of glutamic acid was decreased but specific activity was constant except in the thalamus region tested. 3. The influence of both treatments on amino acid turnover in liver differed from the observed impairment of brain metabolism. 4. Possible correlations between the changes in amino acid metabolism, catecholamines, and the neurologic parkinsonian symptoms are discussed.


Generalization of morphine and lysergic acid diethylamide (LSD) stimulus properties to narcotic analgesics. The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever in an operant chamber resulted in reinforcement following the administration of morphine or LSD and the opposite lever was reinforced after saline. After discriminated responding was stable, stimulus generalization tests with narcotic analgesics and antagonists showed that the stimulus properties of morphine generalized to methadone and meperidine, and partially to pentazocine, all of which produce morphine-like subjective effects in humans. Morphine stimulus properties did not generalize to nalorphine or cyclazocine, which produce dissimilar subjective effects. The stimulus properties of LSD generalized partially to cyclazocine, but not to nalorphine. In humans cyclazocine and nalorphine produce a high incidence of psychotomimetic effects, but the subjective effects of cyclazocine are differentiable from those of LSD.


A comparison of the effects of flurazepam 30 mg and triazolam 0.5 mg on the sleep of insomniacs. The effects of oral, bedtime triazolam 0.5 mg and flurazepam 30 mg, on the laboratory sleep of 12 insomniacs were compared in a double blind, crossover study. A 22 consecutive night schedule was used: Nts. 1--2 placebo; 3--6 first drug; 7--8 placebo; 9--14 no drugs; 15--16 placebo; 17--20 second drug; 21--22 placebo. In 6 Ss first drug was triazolam and second drug was flurazepam. In the other 6 Ss the drug order was reversed. Effects on sleep were assessed objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by physical exams, clinical lab tests, and twice daily questionnaires. During their administration the two drugs were practically indistinguishable in their effects. Both significantly reduced objective and subjective measures of insomnia, such as total wake time and sleep latency. On discontinuation the drugs differentially affected sleep, e.g., on the first post flurazepam night total sleep time was significantly more than baseline whereas on first post triazolam night, total sleep time was significantly less than baseline. There were no remarkable side or toxic effects with either drug.


Clinical significance of plasma chlorpromazine levels. II. Plasma levels of the drug, some of its metabolites and prolactin in patients receiving long-term phenothiazine treatment. Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolactin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4-6 weeks on placebo and during 6-12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug.


Characteristics of pentobarbital discrimination in the gerbil: transfer and antagonism. Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED50 of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED50: 8.5-9.6 mg/kg) and metrazol (ED50:24.9-27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100-1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb, solely. Gerbils trained without a drug s-imulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2.


Structure-activity relationships among desmethyl derivatives of neuroleptics and antidepressants for substrate specificty to indolethylamine N-methyltransferase from rabbit lung. Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation.


Effects of flurazepam (Dalmane) on anterior pituitary secretion. Sleep stages and release patterns for growth hormone (GH), luteinizing hormone (LH) and prolactin were evaluated in two subjects during a three week period in which flurazepam 30 mg was administered nightly. Sleep stages were monitored throughout the placebo-baseline, drug and placebo-withdrawal conditions. Blood samples were obtained on nights three and four of baseline, after two and three weeks of drug administration and following extended drug withdrawal. In both subjects, flurazepam produced a marked suppression in stages 3 and 4 (slow wave) sleep which was maintained throughout the drug administration period. Following withdrawal, there was a slight increase in slow wave sleep above baseline levels. With all three hormones, no clear cut changes were observed in mean nightly output, pulse amplitude and pulse frequency from baseline to the drug and the withdrawal conditions. Thus, the decrease in slow wave sleep produced by administering flurazepam 30 mg was not accompanied by any clear cut changes in GH, LH or prolactin.


Biochemical localization of gamma-glutamyl transpeptidase within cellular elements of the rat cerebral cortex. The presence of the enzyme gamma-glutamyl transpeptidase was established in cellular elements of the rat cerebral cortex. Lowest enzyme activity was found in the total cerebral homogenate while approximately four-fold increased enzymatic activities were evident in capillary-enriched, glial-enriched and purified neuronal fractions.


The acid--base status: a mathematical approach to its definition. The respiratory and non-respiratory factors of acid--base status have been evaluated mathematically. New units of measurement for derangements of the acid--base balance are proposed.


pH, temperature, humidity and the dynamic force-area curve of dipalmitoyl lecithin. Both high pH at 25 degrees C and humidity at 37 degrees C prevent DPL films from attaining zero surface tension, whereas humidity at 25 degrees C and high pH at 37 degrees C do not. At 37 degrees C DPL lowered surface tension to zero when spread from organic solvent or when absorbed from aqueous 0.15 M NaCl in the surface balance in which the surface film was exposed to the room air (dry film). Upon saturation of the atmosphere with water vapor in equilibrium with the aqueous phase at 37 degrees C in a closed chamber, DPL lost the ability to produce zero surface tension, and the gamma min of the DPL film increased from zero to 22 dyne/cm. Addition of DPL in chloroform to distilled water before dispersion by sonication did not prevent the effect of the humidity. However, when the chloroform solution of DPL was added to 0.15 M NaCl before sonication, the adsorbed film produced immediately a stable gamma min of zero in a saturated atmosphere, 37 degrees C. In the absence of chloroform, with DPL adsorbed from either distilled water or 0.15 M NaCl, the effect of humidity was reversed either by removing the chamber and returning the wet film to room air or by introducing small quantities of dispersing agents such as cholesteryl palmitate. However, whereas the effect of humidifying the air was reversible indefinitely, the effect of cholesteryl palmitate (zero surface tension, wet or dry film) was irreversible. This means that there are substances or conditions that can assist DPL films in maintaining zero surface tension when such films are exposed to humidity-saturated air at 37 degrees C.


A micro-method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation and lipolysis in vitro in needle biopsies of human adipose tissue. A method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation into adipose tissue in vitro in needle biopsy specimens of human fat has been developed. 20-150 mg of subcutaneous fat is incubated in an albumin buffer containing a physiological spectrum and concentration of fatty acids and glucose. Release of glycerol and fatty acids to the incubation medium and incorporation of labelled palmitic acid and labelled glucose into extracted adipose tissue lipids are determined simultaneously. The labelled fatty acids are found in the fatty acid part and the labelled glucose only in the glycerol part of extracted diglycerides and triglycerides. These glycerides are completely recovered and indicated FIAT and GLIAT values. Methodological errors for all vaiables are about 10%. All processes increase linearly with tissue weight and incubation time. FIAT and GLIAT increase linearly with increasing concentration of a physiological spectrum of fatty acids (=constant fractional incorporation). The method is simple, and several analyses from one subject can be performed on one day with a minimum of discomfort to the patient.


Crohn's disease of the distal large bowel. This study describes the clinical features and management of 80 patients with Crohn's disease affecting initially only the rectum with or without involvement of the sigmoid colon. Most patients were treated medically, and the various measures used are considered; the cumulative probability of completing five years under conservative management was 60% among survivors. The related mortality was very low and confined to patients treated surgically; with 655.24 patient-years of follow-up the number of observed deaths was lower than the number expected from all causes. Since this distribution of the disease is usually seen in older patients and carries a favourable prognosis, it it suggested that it should be considered as a well-defined variant of the condition.


Immunogenetic analysis of H-2 mutations. IV. Mapping of and immune reactions to the H-2fa mutation. H-2fa is a spontaneous mutation that occurred in an (A.CA X A)F1 female mouse and was later transferred on an A-strain background [congenic line A.CA (M506) or M506]. Skin grafts exchanged between M506 and A.CA strains are rejected within 4 weeks after grafting. Significant reaction is observed when these two strains are used as responders and stimulators in mixed lymphocyte culture or in a splenomegaly graft-versus-host assay. The mutant antigen induces strong cell-mediated lymphocytotoxicity. The mutation maps in the K end of the H-2 complex. The capacity of mutant antigens to induce relatively strong lymphocyte proliferation is explained by hypothesizing that the T-cell receptors reacting with K- or D-region products can more easily recognize subtle than drastic alloantigenic differences.


Maternal immunocompetence. I. The graft-versus-host reactivity of lymphocytes from pregnant rats and the distribution pattern of 51Cr-labeled lymphocytes in pregnant mice. Lymphocytes from the peripheral blood, spleen, or para-aortic lymph nodes of prrimigravida L rats carrying (L X BN) F1 (LBN) fetuses are fully capable of mounting graft-versus-host (GVH) reactions in LBN F1 recipients. The reactivity of lymphocytes from interstrain pregnant (L X BN) or intrastrain pregnant (L X L) rats, or from rats postpartum from these pregnancies, is equivalent to that of normal virgin females over a full dose-response curve, ruling out both specific and nonspecific effects of pregnancy on the intrinsic GVH competence of the maternal thymus-derived (T) lymphocyte. Attempts to block GVH reactivity with serum from pregnant rats were unsuccessful. In addition, when the distribution pattern of 51Cr-labeled syngeneic and semiallogeneic lymphocytes was studied in intact primigravida mice, there was no difference between interstrain and intrastrain pregnant mice, and there was no evidence of immunologically specific 'trapping' in the para-aortic lymph nodes draining the interstrain pregnant uterus.


Distribution of benorylate in plasma, synovial fluid and tissue in rheumatoid arthritis. Six patients, not previously treated, with classical seropositive rheumatoid arthritis and highly active synovitis of one or both knee joints were treated with 4 g of 40% benorylate suspension twice daily for a period of 9--14 days prior to synovectomy. Blood samples were taken at scheduled times during administration of the drug. At operation, synovial fluid and tissue samples were taken and their salicylate, paracetamol and benorylate content measured. Plasma levels of salicylate and paracetamol were, in general, significantly higher than the concentration of these metabolites in the synovial fluid. Benorylate was found in the synovial tissues concentrated especially in the highly inflamed synovial villi. It is probable that benorylate and its metabolites penetrate the synovia but further studies are needed to determine if the metabolites are concentrated in the different synovial cell layers in the same way as benorylate itself. It is possible that part of the clinical effect of benorylate is due to its presence in the synovial tissue and that it has a direct effect in vivo on the synovial membrane. It is also possible that the pharmacokinetic properties of benorylate permit it to enter cell layers inaccessible to its metabolites.


The passage of benorylate into the synovial fluid and tissue of rheumatoid patients. After a preliminary wash-out period of 3-7 days during which no anti-inflammatory drugs were given, 11 female patients with classical or definite rheumatoid arthritis were given 8 g of benorylate as the 40% suspension 3-7 days prior to synovectomy of the knee. Samples of synovial tissue and fluid from the affected knee were assayed for their content of benorylate, salicylate and paracetamol in an attempt to relat these concentrations to the length of medication and the severity of the disease process as measured clinically, by X-ray, by open inspection at operation and by histology of the synovial tissue. The esterase activity of the blood and synovial fluid was also measured by the capacity to hydrolyse benorylate used as substrate.


A long-term study of benorylate in patients with rheumatoid arthritis. The analgesic and anti-inflammatory efficacy and adverse effects of benorylate were studied over a period of 6 months in 33 patients suffering from definite or classical rheumatoid arthritis. The average dose used was 6 g daily and examinations were made before treatment and at regular intervals during treatment to assess the clinical status of the patient, tolerance to the drug and any effect on blood, liver or renal function. Benorylate had a satisfactory effect in 28 patients. Additional treatment was requried in 3 cases and treatment discontinued in 2 cases. Distinct improvement of grip strength, morning stiffness and E.S.R. in 25 cases indicates the anti-inflammatory efficacy of benorylate. There were no signs of toxicity to bone marrow, liver or kidney. Severe side effects such as stomch ulcers, gastrointestinal bleeding and severe allergic complications were not observed. Side effects such as constipation and tinnitus that occurred at the beginning of treatment were mainly of a a passing nature and disappeared without a need to change therapy. Benorylate is suitable for the treatment of recent rheumatoid arthritis of a low to moderate activity as well as for long-term treatment.


A double-blind study of the analgesic action of benorylate suspension in osteoarthritis of the hip and knee. This study compared benorylate suspension and placebo in a double-blind randomised cross-over design to investigate their analgesic effect in osteoarthritis of the hip and the knee. Benorylate and placebo were each given for 7 days. Assessment of efficacy and tolerance was carried out on the 7th day of each period. The results were subjected to sequential analysis and the analgesic effect of benorylate suspension was significantly demonstrated after 8 case reports. Mild digestive side effects appeared in 30% of patients. In addition, benorylate suspension was well tolerated in an open trial carried on for 30 to 90 days in 7 patients.


Benorylate: a report on 2 years' experience of its use in rheumatoid arthritis and other chronic rheumatic diseases. 52 outpatients with rheumatoid arthritis or osteoarthritis were given benorylate (as the 40% suspension) in doses of up to 8 g daily. Peroids of medication were varied but some patients were given the drug for nearly 2 years. Assessments of clinical progress were made at regular intervals by recording both subjective and objective measurements including duration of morning stiffness, grip strength, joint size. Laboratory investigations include renal function tests, liver function tests, blood picture and occult blood. No serious side effect, attributable to benorylate was reported and it was concluded that the drug is satisfactory for the long term treatment of rheumatic diseases.


Clinical study of a new anti-inflammatory and analgesic compound, benorylate, in rheumatic disorders. Benorylate is obtained by esterification of acetylsalicylic acid and N-acetyl p-aminophenol (4-acetamidophenyl 2-acetoxybenzoate). Experimentally, this new product has been shown to be a good analgesic and anti-inflammatory agent. A clinical trial was carried out in order to study the efficacy, side effects and tolerance of this new product. In a group of 49 hospitalised patients aged from 20 to 70 years who were treated with this new product, 15 had ankylosing spondylitis, 11 had chronic progressive rheumatoid arthritis, 4 had Reiter's syndrome, 4 had psoriatic arthropathy, 8 had osteoarthrosis of the hip and 7 had various forms of rheumatism. The drug was administered orally in suspension form, initially three times per day, then twice, the total daily doses being 15 ml (6 g) or 20 ml (8 g). Treatment was regarded as effective in 62% of the cases, and of these 62%, 46% good and very good results were obtained. In 88% of the patients, tolerance was satisfactory and of these, it was excellent in 80%. Only in 2 cases did treatment have to be discontinued on account of side effects. From the biological point of view, uricaemia was significantly reduced in 7 patients, and in 6 patients uricuria increased. With regard to the level of salicylate in the blood assays showed that it is the same for 6 g benorylate and for 4 g aspirin. Benorylate has been shown to be an effective treatment for both inflammatory and degenerative rheumatic disorders. The results of its use can be compared with those obtained by acetylsalicylic acid, but is better tolerated. In addition, in chronic disorders it is better to have to take the product only twice per day.


A review of benorylate - a new antirheumatic drug. Benorylate (Benoral, Benortan) is the esterification product of paracetamol and acetylsalicylic acid. It has anti-inflammatory, analgesic and antipyretic properties. Benorylate is probably absorbed as the intact molecule which accounts for its good gastric tolerance. After absorption, benorylate is hydrolysed into its components, salicylate and paracetamol, which then follows the usual routes of metabolism. Benorylate per se is also found in inflamed tissue and several studies, both in vivo and in vitro, have shown that it probably has an anti-inflammatory action of its own. Pharmacokinetic studies have shown that a twice daily administration of benorylate should be sufficient for a therapeutic effect and this has been confirmed by its use in patients. Clinical studies have compared benorylate with aspirin, indomethacin, ibuprofen and phenylbutazone and have shown its value in rheumatoid arthritis, osteoarthrosis and other musculoskeletal conditions. The overall tolerance is excellent. Some minor gastric disturbances are reported from time to time, but these are less than with comparable doses of aspirin. Studies measuring occult blood loss in the stools have shown that this is not a significant problem with benorylate and that the majority of patients lose no more blood than the controls.


Simultaneous pharmacokinetics of benorylate in plasma and synovial fluid of patients with rheumatoid arthritis. Twenty patients with definite or classical rheumatoid arthritis and chronic knee effusions were each given an oral dose of 4 g benorylate as the 40% suspension. Synovial fluid and plasma samples were obtained up to 9 hours after drug administration and assayed for their salicylate and benorylate content. A mean peak benorylate plasma level of 2.18 +/- 0.19 mug/ml occurred 30 min after drug administration but declined rapidly and benorylate was virtually undetectable in the plasma 90 min later. The mean peak benorylate synovial fluid level of 0.74 +/- 0.21 mug/ml occurred 3 hours after drug administration but the concentration remained steady for at least a further 9 hours. A mean peak plasma salicylate level of 119 +/- 14.2 mug/ml and mean peak synovial fluid salicylate level of 78 +/- 13.6 mug/ml occurred 3 hours after benorylate administration. Both levels declined slowly over some hours. This study shows that benorylate per se readily enters the synovial fluid in patients with rheumatoid arthritis and continues to accumulate there even when undetectable in the plasma. It is possible that the lipophilic nature of the benorylate molecule facilitates its uptake by the inflamed synovial tissue.


Muscle crossbridges: absence of direct effect of calcium on movement away from the thick filaments. Fluorescence depolarization experiments show that the rotary mobility of myosin heads is hindered by the assembly of the thick filament. Calcium, with or without magnesium adenosine triphosphate, dose not alter this hindrance in synthetic filaments. This implies that calcium does not directly move the crossbridges toward thin filaments on activation of muscle.


[Identification of organic substances by means of spectral methods in forensic toxicology. I. Infrared spectroscopy]. In the introduction the author gives an outline of the principles of infrared spectroscopy and possibilities of its use for the identification of organic substances. On examples from practice he demonstrates the use of infrared spectroscopy in forensic toxicology. He desribes methods for the isolation of substances from biological material and methods of their purification. The applied methods are used for common toxicological analyses. Attention is drawn to the possibility of comprehensive identification of the structure or a comound based on an analysis of the infrared spetrum and analysis of a mixture of two substances is is described. Infrared spectroscopy is a very suitable method for the unequivocal identification even of very small amounts of substances obtained from material (biological and corpora delicti) in intoxications with organic substances, such a as drugs, pesticides, etc.


Recent advances in experimental leprosy. Within the last 15 years we have learned to identify Mycobacterium leprae, determine its viability, screen the efficacy of antileprosy drugs, and monitor the bacilli for drug sensitivity. We have evidence that subclinical infections occur frequently among contacts of patients with leprosy and that the different manifestations of leprosy reflect differences in resistance to M leprae. We are developing hypotheses about the mechanism of these differences. We have experimentally transmitted lepromatous leprosy to normal armadillos, and from these we can obtain amounts of leprosy bacilli which fully substitute for harvests from in vitro cultures. Furthermore, if susceptibility of armadillos can be determined without infecting them and if we can breed them under controlled conditions, we would have an animal model for investigating fundamental and applied areas of leprosy which otherwise are intractable. How much our knowledge has advanced is illustrated by a project of the World Health Organization which calls for the preparation of pure, specific antigens from the now available abundance of leprosy bacilli, which might become valuable as diagnostic and epidemiologic tools and as immunoprophylactic and even immunotherapeutic weapons.


The survival of carp (Cyprinus carpio) outside water. The possible use of the swimbladder of carp as auxiliary respiratory organ when the animals are exposed to air has been studied. After exposure to air, blood pH and pO2 and mean swimbladder O2 concentration decrease and blood pCO2 increases in normal animals. Exposure to air after ligation of the pneumatic ducts results in increases in blood pH and pCO2 and decreases in blood pO2 and swimbladder carbon dioxide concentration. Possible reasons for these observations are discussed.


The effects of mechanical preparation and acidification of the colon on the healing of colonic anastomoses. The results of clinical studies have suggested that inadequate preoperative mechanical preparation of the colon is a significant factor in the pathogenesis of disruption of colonic and colorectal anastomoses. A possible explanation for the adverse effect of poor mechanical preparation is that ammonia released from feces has a cytotoxic effect on the healing anastomosis. It has been suggested that acidification of the colonic lumen prevents the release of fecal ammonia and protects the anastomoses. The effects of mechanical preparation of the colon and colonic acidification were studied in anastomoses in the left colon of rats. Colonic acidification was produced by the oral administration of a synthetic disaccharide lactulose solution. Mechanical preparation resulted in a significant increase in the bursting wall tension in anastomoses on the seventh postoperative day. The oral administration of lactulose resulted in a reduction in the colonic mucosal pH, but this was not accompanied by improved healing of anastomoses, as judged by measurements of colonic bursting pressure, bursting wall tension and total challagen content. Mechanical preparation of the colon is an important factor in the safety of colonic anastomosis. However, the results do not suggest that acidification of the colonic lumen significantly improves the quality of colonic healing.


Higher activity of oxidative drug demethylation in the liver microsomes from dystrophic mouse. The activities of NADPH-dependent oxidative demethylation of aminopyrine and other methyl compounds in the liver microsomes from dystrophic mice were found to be about 30% higher than those of the normal mice. Consumption of reduced pyridine nucleotides during the demethylation reactions was also significantly larger in the dystrophic mouse system than in the normal mouse system. The synergistic effect of further addition of NADH on the oxidative demethylation in the reaction system with NADPH, however, was not significant in either the normal or the dystrophic mouse system. The activities of NADPH-cytochrome c reductase and lipid peroxidation were also higher by about 30% in the dystrophic mouse than in the normal mouse, but the contents of cytochrome P-450 and phospholipids in the liver microsomes from normal and dystrophic mice were not appreciably different. The results suggest the possibility that the progressive muscular dystrophy may involve abnormal features in not only muscle but also liver and other tissues.


Non-adrenergic inhibition of the electrical activity of the antrum muscle fibers of the guinea-pig stomach. The changes in the electrical activity of the antrum muscle fibers of the guinea pig stomach caused by ATP and its related compounds were compared with those caused by catecholamines. The antrum preparation exhibited spontaneous electrical activity and this was suppressed or inhibited by treatment with catecholamines (adrenaline, noradrenaline and isoprenaline). The inhibitory actions of catecholamines were observed in the presence of tetrodotoxin or alpha-blockers (phentolamine or phenoxybenzamine) while the effects were antagonized by beta-blockers (propranolol or DCI). At higher concentrations than that of catecholamines, ATP or related nucleotides also produced the inhibitory effect on the spike activity and the generation of slow waves. The inhibitory actions of ATP and related substances were still observed in the presence of alpha- or beta-adrenergic blockers. Furthermore, the inhibition was present after treatment with tetrodotoxin. From these results, it is concluded that the inhibitory action of ATP and related compounds is due to a direct action on the antrum muscle and is not mediated via alpha- or beta-adrenoceptors.


pH of amoebic liver pus.

pH of amoebic liver pus. Amoebic liver pus has an acidic pH. Hence the pleural aspirate from an amoebic empyema due to rupture of an amoebic liver abscess has an acidic pH. In contrast, the pH of pleural aspirates from effusions and empyema of non-amoebic aetiology were noted to have an alkaline pH. The clinical significance of these observations is discussed.


The differential diagnosis of bronchial asthma in children. Bronchial asthma in children is not uncommon in the tropics. Conditions simulating this disease in the tropics have been discussed with a view to arriving at a diagnosis without sophisticated investigations.


[Intermediate metabolism and respiratory function in peritonitis]. During observations of 26 patients and in acute and chronic experiments on 31 dogs under conditions of peritonitis the author studied neurohumoral relations and the effect of hydrocortisone on the respiratory function. A conclusion is made on the vital importance of the consistent associated corrective neurohumoral therapy with cholinomimetics and corticosteroids in peritonitis.


[Study of acid phosphatase II from Pichia guilliermondii yeasts]. Acid phosphatase II (AP II) was isolated from the cell-free extract of Pichia guilliermondii Wickerham ATCC 9058 and partially purified. The enzyme is a non-specific phosphomonoesterase. It hydrolyzes p-nitrohenyl-phophate (NPP), beta-glycerophosphate, glucose-6-phosphate, guanosine-5'-monophosphate, adenosine-5'-monophosphate, cytidine-5'-monophosphate, uridine-5'-monophosphate, alpha-naphtylphosphate, FMN. The order of the substrates corresponds to the degree of their hydrolysis decrease. The Michaelis constant of the enzyme was 1.4-10-3 M for NPP as a substrate, pH optimum was 5.5 and temperature optimum-40C. AP II was strongly inhibited by MoO4-2, F-, inorganic phosphate, Cu2+ and Be2+. The activity of the enzyme in the yeast cells does not change noticeably during growth on media with low and high iron content.


[Effect of physical and chemical factors on Pasteurella multocida bacteriophages]. Studied was the effect of some physical factors (temperature, pH of various values) and some chemical ones (urea, sodium citrate, sarcolysin, methylene blue, acridine orange, pyronin, crystal violet, potassium permanganate, fuchsin, tetracycline and tetraolean) on phages specifically lysing Pasteurella multocida strains, having the following signature: 3, 4, 6, 22, 32, 115, 967, 1075, and C-2. All investigated phages showed signs of inactivation at 48 degrees C with a further linear dependence, and at 65 degrees C up to 99.99 per cent of them were inactivated. With phages of group III inactivation discontinued between 50 and 60 degrees C, at 65 degrees C it being equal to that observed with I and II group phages. It was found that a broth medium of pH 7.5 was the optimum one for P. multocida phages. With altered pH values lowest percentage of survived phage particles showed I group phages, while those of II and III group proved more stable. So far as the chemical factors were concerned it was established that with the exception of pyronin and potassium permanganate which inactivated the P. multocida phages from 90 to 100 per cent, all other agents produced full inactivation (100 per cent). However urea did not inactivate I group phages, both it and sodium citrate inactivated partially II and III group phages. The variations established with the phages in terms of their physical and chemical behaviour may serve as subsidiary signs bearing upon their classification.


Studies on new process procedures in plasma fractionation on an industrial scale. I. Determination of the pH value of ethanol containing protein solutions at low temperatures. A suitable combined pH electode is evaluated which provides reproducible readings under the extreme conditions of the cold ethanol plasma fractionation procedure. Adequately reproducible correlations are found between the pH measurements in protein solutions with an ethanol content of up to 40% at temperatures as low as -8 degrees C and the determination in diluted samples at room temperature using the standard procedure.


Studies on new process procedures in plasma fractionation on an industrial scale. II. Experiments in concentrating dilute albumin solutions using hollow fiber ultrafiltration. Ultrafiltration with a hollow fiber device was studied as an alternative method to the lyophilization or thin-layer distillation techniques in the production of salt-poor, concentrated human albumin preparations for clinical use. A number of process parameters are discussed. Combination of gel filtration and ultrafiltration provides an interesting alternative to the currently used systems.


[The influence of vitamin a, gentamicin and anoxaemia on urinary enzyme excretion (author's transl)]. The excretion patterns of several urinary enzymes were investigated in the following four experimental groups of Wistar rats and compared with the normal range of each urinary enzyme studied. One group received vitamin A in high dosage; a second group was given vitamin A before and after bilateral clamping of the renal artery for 30 minutes; in the third group the renal arteries were clamped for 30 or 60 minutes; the last group of experimental animals received first low (2mg/kg, 4mg/kg) and subsequently high doses (100 mg/kg) of gentamicin. Vitamin A administration produced no increase in urinary enzyme activity, even in the group of rats with ischaemically-damaged kidneys, where ischaemia (clampin of the arteries) was responsible per se for an increase in enzyme excretion. With low doses of gentamicin the urinary enzymes remained within normal limits, but increased immediately to significantly pathological values after the first dose 100 mg/kg gentamicin.


[Urinary enzyme levels in healthy human subjects and in rats (author's transl)]. Urinary MDH, LDH, gamma-GT, LAP and muramidase levels were studied in 11 healthy persons with a wide age range and in 51 male Winstar rats weighing 300 to 400 g. Normal ranges of these urinary enzymes were determined and compared with the results of other authors.


[Cellular immunity against bacteria (intracellular and extracellular parasites) in experimentally aged rats (author's transl)]. The authors study the activity of RES in rats with Progeria-like syndrome of Selye, at the occasion of a repeated infection with bacteria--intracellular parasites (Brucella abortus 19) and bacteria--extracellular parasites (Diplococcus pneumoniae). They establish that immunization improves the activity of RES of the experimentally aged rats; still, its phagocytic and digestive functions remain by far feebler than those of the rats unsubjected to experimental ageing. By the aged animals the RES insufficiency is more pronounced towards the intracellular bacterium Brucella abortus 19, than towards the extracellular Diplococcus pneumoniae.


[Resistance against intra- and extracellular bacteria in experimentally aged rats (author's transl)]. The authors study the cellular activity of RES against the microbes intracellular and extracellular parasites in rats with pronounced Progeria-like syndrome of Selye. RES of the experimentally aged animals copes, through with a certain delay, with the invading extracellular bacterium Diplococcus pneumoniae, but is utterly helpless against the intracellular microbe Br. abortus 19. These relations are completly inverted in the rats that have not been experimentally aged.


[Aminopeptidases in the serum and urine of patients with hyperthyroidism]. In patients with hyperthyroidism the serum activities of the leucine aminopeptidase (LAP) and the alanine aminopeptidase (AAP) as well as the alanine aminopeptidase excretion in the urine were determined. A significantly increased activity of the leucine aminopeptidase in the serum and an increased excretion of alanine aminopeptidase in the urine were found. The AAP in the serum did not show a significant increase of activity. On account of the changes in the serum and in the urine before and during therapy a low-grade participation of the hepatobiliary and renal systems which are clinically not uppermost is to be assumed. Increased excretion of AAP and hyperthyroidism coincide nearly without exception in out patients. Correlation-statistical investigations make it probable to regard the increased excretion of AAP in the urine as an indirect parameter of the peripheral metabolism in hyperthyroidism.


[Vetorial presentation of left-ventricular pressure parameters for the assessment of ventricular function]. The ventricle function can be established by the vectorial description of left-ventricular pressure parameters or flow sizes, respectively. The vector diagrammes result from the momentaneous pressure within the ventricle on the X-axis and the differentiated pressure curve or the aortic flow, respectively, on the Y-axis. Well surveyable from the vector loop received (LVP/dp/dt) are established dp/dtmax, dp/dtmin, LVPmax, LVEDP as well as the tg of the pressure increase speed or the pressure decrease speed, respectively, pro developed pressure. By way of example medicamentous changes of the vector diagrammes were induced and the parameters mentioned established. The vectorial demonstration of the left-ventricular haemodynamics seems to give additional informations concerning the phase of centraction and relaxation


[Round table discussion. Ulcer - vagus - gastrin]. 1. Both gastrin and the vagus nerve play a part in the pathogenesis of the duodenal ulcer. Which of these two factors is of greater significance--this problem is still subject to discussion as is the question whether other factors such as duodenal neutralization are more important than hitherto assumed. 2. At this time no reliable and harmless drugs that speed up the healing of duodenal ulcers and prevent relapses are yet available. Candidates for this are H2 receptor blockers, prostaglandines and possibly substances resembling secretin. 3. Only some of the participants considered it necessary to do endoscopic and radiological follow-ups in duodenal ulcers. 4. Proximal gastric vagotomy for the treatment of duodenal ulcers is still undergoing clinical trials. At present this method should only be used by surgeons with a special interest in gastric surgery who also dispose of the technology and the staff for careful postoperative checks on these patients. The advantages of proximal gastric vagotomy consist in sparing truncation, low mortality and good functional results. 5. In gastric ulcers--contrary to duodenal ones--malignancy should always be suspected. If medical treatment does not lead to complete remission within a few months, surgery must be performed. 6. Many surgeons still prefer resection to vagotomy and excision in the management of gastric ulcers.


[Stress ulcer: clinical aspects, pathogenesis, diagnosis and therapy]. The frequency, the treatment and the mortality of stress induced ulcers and erosions of the upper alimentary tract are surveyed. The experimental data concerning such ulcers and erosions are reported. Most important is the local mucosal ischaemia with a concomitant reabsorption of H-ions. Intravasal coagulation processes and a local diminution of the Vitamin A content may be additional factors. 37 stress induced bleedings observed in 460 patients of a surgical intensive care unit are analysed. The mortality of the conservatively treated group was 60% and higher than the mortality after operative treatment (42%). The high mortality was due to the associated states of shock, hypoxaemia and sepsis. A prospective study comporting 50 patients of a medical intensive care unit shows the little importance of intravasal coagulation for gastrointestinal bleedings during septicaemia. The possible influence of psychological factors for the induction of stress induced bleedings was analysed on 112 tetraplegics and paraplegics, all under the same conservative treatment comporting high doses of Dexamethason. The frequency of gastrointestinal bleedings was very high in complete traumatic tetraplegia (41%), smaller in complete traumatic paraplegia (16%), much lower in incomplete traumatic and complete non-traumatic lesions.


[Interaction between gastrointestinal hormones and endocrine regulation]. The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a "long distance" impact; their role within pathophysiology is also of interest. GIP ("gastric inhibitory peptide"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application.


[Uterine activity under tocolysis through a beta-sympathomimetic (author's transl)]. The actual mechanism of tocolytic effect of beta-mimetics is not yet known. While they are able to stop labour, the effect in vitro on myometral filaments is very different. In contrast to this, the socalled Ca++ -antagonists have an excellent relaxing effect on myometrium in vitro, but they are clinically ineffective. To clear up the mechanism of tocolysis, the uterine activity under tocolytic therapy was observed by external tocography. Whereas in normal pregnancy the portion of Braxton-Hicks-contractions and phases of inactivity--equivalent to the intervals of labour -- increases and the portion of Alvarez waves decreases, under tocolysis these changes are not to be found for a long time. The portion of Braxton-Hicks-contractions and phases of inactivity together is smaller than in normal pregnancy. The proportion of Braxton-Hicks-contractions to phases of inactivity corresponds well to normal pregnancy. The changes of uterine activity in normal pregnancy are explained as a process of increasing coordination. The tocolytic effect is regarded as a disturbance of this process.


[Effect of arterial hypoxia and acidosis on fibrillation threshold in the cat heart in vivo]. The influence of severe arterial hypoxia and acidosis on the fibrillation threshold was checked in 22 cats. Two groups were formed: in 10 cats (group I) acidosis was produced by 2-N lactic acid infusion; in the second group of 12 animals the respirator was turned off for 60 seconds, thus producing a low arterial PO2. If hypoxia and acidosis were severe enough, the fibrillation threshold was significantly lowered in either group. The pathophysiological mechanisms of these findings are discussed.


Reversible transformation of precipitated and nonprecipitated lipoproteins recombined from proteins and lipids of erythrocyte membranes. The sedimentation at low speed centrifugation of a lipoprotein recombined from the lipids and the strongly bound proteins of the human erythrocyte membrane depends on pH: between 4.5 and 6.0, most of the liproprotein sediments, whereas at pH 7.0-8.5, up to 90% remains in the supernatant. Precipitation of the lipoprotein can be reversed by increasing the pH, followed by a brief sonication. The mobility of spin-labelled protein groups in the lipoprotein increases with increasing pH. This mobility increase is also reversible and is of equal magnitude in precipitated and nonprecipitated recombinates. It is concluded that, because of these reversibilities, determination of the yield of liproprotein formation in recombination experiments must include analysis of both precipitated and nonprecipitated lipoproteins.


Galactans and anti-galactans from invertebrates. Antibody-like substances with anti-carbohydrate specificities directed against different structures of galactans have been detected in several invertebrates.


["Synthetical" aiptasia mutabilis RAPP (coelenterata) (author's transl)]. After being cultivated in the dark for some months and after being fed with food free of carotenoids during the time Aiptasia mutabilis (Coelenterata) loses its symbiontic algae (rich in brown fucoxanthin) and becomes transparent white. This disarranged symbiosis may be regenerated under light cultivation by adding different species of Chlorophyceae (Chlorella, Dunaliella) and chrysophyceae (Ochromonas, Cyclotella), but not of Cyanophyceae (Anabaena, Nostoc, Oscillatoria, Anacystis). - This changeable life system between coelenterata and algae may be a good example for further studies of the endosymbiosis problem.


Studies on the undecapeptide of ferricytochrome c using ESR, Mössbauer and visible spectroscopies. The ESR, Mössbauer, and visible spectra of the undecapeptide of ferricytochrome c (HPp) were measured for both the solid peptide and solutions of the peptide at pH 1.5, 7, and 10. At the low pH, the iron exists in the HPp in the high-spin species. At neutral and alkaline pHs, the low-spin ferric species predominate. The results of these measurements support the previous suggestions concerning the ligands in the fifth and sixth position of HPp at the neutral and alkaline pHs. The spectra of lyophilized preparations of HPp show the presence of both high and low-spin ferric species. The study of the Mössbauer spectra of the lyohilized preparations as function of temperature shows that there exists a spin-spin equilibrium between the two spin states. The relative amounts of the two components vary with the preparation. In these preparations there exist two components, one of which exists in the equilibrium mixture and the second in the high-spin form.


Studies on Hymenolepis microstoma in vitro. II. Effect of yeast extract on development and maturation. Four day old in vivo Hymenolepis microstoma were cultured in vitro for 6 days in media containing 2, 1, 0.5 and 0.1% yeast extract. Worms from all groups including control group increased in length and produced nearly equivalent numbers of proglottids. However, worms grown in yeast extract added media produced significantly more mature proglottids and were heavier than those in the control medium. The possibility of pyridoxin involvement has been contemplated. Effects of osmotic pressure and pH on the development of worms are discussed.


The use of 1-anilino-8-naphthalene sulfonate as fluorescent probe for conformational studies on ribulose-1,5-bisphosphate carboxylase. The influence of Mg2+ ions and temperature on the structure of the enzyme ribulose-1,5-bisphosphate carboxylase was investigated using the fluorescent probe 1-anilino-8-naphthalene sulfonate (ANS). The binding of ANS to the enzyme molecule caused a significant increase of fluorescence emission which was further enhanced by the addition of Mg2+. The temperature dependence of the fluorescence emission indicated a conformational change of the enzyme between 12 and 24 degrees C. The Mg2+ and the temperature effects were additive. ANS itself did not change the conformation of the enzyme. The influence of the substrates carbon dioxide and ribulose-1,5-bisphosphate, and the effect of the pH of the medium and of a sulfhydryl reducing reagent on fluorescence emission were analysed.


Physiological effects of sucrose substitutes and artificial sweeteners on growth pattern and acid production of glucose-grown Streptococcus mutans strains in vitro. The synergistic effects of four sucrose substitutes, polysorbate and five artificial sweeteners were studied in vitro on growth pattern and acid production of seven glucose-grown Streptococcus mutans strains, representing the five serological groups after Bratthall. Four distinct growth patterns during glucose fermentation were observed: high rate of growth with low acid production, moderate growth rate with moderate acid production, moderate growth rate with high acid production, and slow rate of growth with moderate acid production. Depending on the strain used, the final OD at 546 nm ranged from 0.55 to 0.99 and the final pH of the medium varied between 4.65 and 4.15. While added sucrose substitutes, with exceptions, usually enhanced growth rate, most artificial sweeteners suppressed or, at higher concentrations, even inhibited growth of S. mutans; addition of polysorbate to the medium always increased growth rate of S. mutans significantly. The presence of sucrose substitutes during glucose fermentation had no effect on final pH of the medium, but addition of artificial sweeteners, especially sodium saccharin, elevated final pH up to 1.8 units. The observed physiological patterns and differences within the several strains of S. mutans during glucose fermentation in vitro do not necessarily relate to the five serological groups of the species.


Tautomerism of isoguanosine and solvent-induced keto-enol equilibrium. Ultraviolet and infrared absorption spectroscopy, in aqueous and non-aqueous media, have been employed to study the tautomerism of 9-substituted isoguanines, including the nucleoside isoguanosine. With the aid of a series of model compounds, it was shown that 9-substituted isoguanines, and isoguanosine, in aqueous medium are predominantly in the form N (1) H, 2-keto-6-amino. In dioxane solution the tautomeric equilibrium is shifted in the direction of the enol form. The shift towards this form is accentuated for those analogues in which the exocyclic amino group is methylated. With the aid of N6,N6, 9-trimethylisoguanine, and 9-octyl analogue, the tautomeric constant was studied as a function of concentration, temperature, and solvent polarity, and the results applied to evaluate the tautomeric equilibria of 9-methylisoguanine and isoguanosine as a function of these variables. In general the enol form is favoured by a decrease in solvent polarity, by a decrease in concentration in dioxane, or an increase in temperature in chloroform solution. Syntheses are described for several N6 amino and methylamino derivatives of 2-methoxy-9-methylpurine, and 3-methyl-5-oxo-7,8-dihydroimidazo (2,1-i) purine, which served as an analogue of the unavailable 1,9-dimethylisoguanine.


Isolation and properties of yeast mutants with highly efficient thymidylate utilization. A screening procedure is presented which allows the isolation of yeast mutants (typ tir) with highly efficient utilization of exogenous deoxythymidine-5'-monophosphate (5'-dTMP) (greater than 50%). Data are given concerning the phenomenon of 5'-dTMP utilization in general: (i) The ability of S. cerevisiae to incorporate exogenous 5'-dTMP was found to already to be a wild type feature of this yeast, i.e. apparently not to be due to any mutation such as typ, tup, tmp, per or tum. Consequently these mutations are interpreted as amplifiers of a pre-given wild type potency. So far eight stages of 5'-dTMP utilization were detected as classified by the optimal 5'-dTMP requirement, with 5'-dTMP biosynthesis blocked, of the corresponding mutant strains isolated. All of them fit well into a mathematical series of the type "2n x 1.5" (n = 0, 1, 2, ..., 11), where the product term for n = 11 represents the 5'-dTMP requirement (mug/ml) of the best 5'-dTMP utilizing wild type strain found. (ii) Amplification of the 5'-dTMP utilizing potency obviously is due to any genetically determined alteration of the yeast 5'-dTMP uptaking principle itself or of physiological processes accompanying the monophosphate's uptake. (iii) The functioning of 5'-dTMP uptake requires acidic (less than or equal to pH 6) conditions in the yeast cell's outer environment. (iv) Some yeast typ and typ tlr mutants were found to exhibit a more or less pronounced sensitivity towards exogenously offered 5'-dTMP. The response of a sensitive strain towards inhibitory concentrations of the nucleotide apparently is co-conditioned by the presence or absence of thymidylate biosynthesis. With 5'-dTMP biosynthesis blocked the 5'-dTMP mediated inhibition is a permanent one and finally leads to the death of a cell. With a functioning thymidylate biosynthesis, in contrast, the inhibition is only temporary. (v) Yeast typ or typ tlr strains were observed to dephosphorylate exogenous 5'-dTMP to thymidine due to a phosphatase activity which cannot be eliminated at pH 7 + 70 mM inorganic phosphate conditions in the growth medium. This 5'-dTMP cleavage obviously occurs outside the cell and does not seem to be correlated both to the monophosphate's uptake and to the phenomenon of 5'-dTMP sensitivity. The destruction of 5'-dTMP does not disturb (5'-dTMP) DNA-specific labelling.


[Electron microscopic findings in a polyneuropathy complicating panarteritis nodosa]. Electromicroscopial changes were observed in arterioles, nerves, and striated skeleton muscle cells in a case of clinically and histologically definite polyarteritis nodosa with polyneuropathy. Inflammatory infiltrates were found in and around arteriolar walls; motor nerves were partly demarkated and presynaptic motor endplates were degenerated. The myofibrills of skeleton muscle cells showed a disorganization that is regarded as the morphological substrate for the clinically observed muscular weakness in this case.


[Treatment of threatened early abortion (6th-16th week of pregnancy) of Th 1165a (Partusisten)]. The report is presented about the treatment of the abortus imminens in the early pregnancy between the 6th and 16th weeks with a new tocolytical substance Th 1165a (Partusisten) on the basis of 61 patients. 40 of the patients reached full term delivery (41 new borns). All new borns except one with multiple chromosomal abnormalities were without any pathological evidence. Two pregnancies terminated into abortion. We could achieve tocolysis in each and every case consistantly by a special worked out scheme. Side effects, which are described due to other beta-adrenergic substances were minimal. Eventual cardiovascular side effects were prevented by additional administration of Isoptin. The results are good. Therefore the administration of Partusisten in the treatment of the imminent abortions in the early pregnancy between the 6th and 16th weeks is sensefull.


[Effect of the vernix caseosa content in the amniotic fluid on the actual pH-value of the amniotic fluid]. To determine the eventual influence of the vernix caseosa on the actual pH-value of the amniotic fluid we compared the pH-value of 50 samples of non-filtered amniotic  fluid and the pH-values of filtered portions of the same samples. The samples were taken after delivery of the fetus. We found a distinct shift of the pH-values of the filtered portions to alkaline values. It is recommended that these results should be taken into consideration in laboratory analysis of amniotic fluid.


[Serologic properties of strains of Cl. perfringens isolated from the intestinal contents of healthy subjects]. A study was made of the quantitative content in the intestine of C1. perfringens strains in 6 healthy persons who stayed in a hermetically sealed space for 1 month and for 1 year. C1. perfingens strains were isolated from the fecal samples of each of the volunteers at various periods of the trial. A total of 570 strains of C1. perfringens of type A with anticellular sera obtained to the strains of various serological groups were studied. Serological properties of C1. perfringens strains of type A present in the intestinal contents of man were nonhomogeneous. This pointed to the simultaneous presence in the intestine of strains belonging to several serological types. A partial or complete replacement of one strain by another (differing by serological properties) occurred in the course of not over one month. C1. perfringens strains of type A present in the intestine of each volunteer were subdivided into serological types individual for each of the persons under observation. This pointed to the fact than no interexchange of strains of the mentioned bacteria occurred between different persons in the hermetically sealed space.


[Resistance to levomycetin and activity of several enzymes in Escherichia coli and the agent of plague]. The authors compared the activity of acetyl-CoA-synthetase and of the enzymes belonging to the group of asparaginic acid in levomycetin sensitive and resistant strains of Y. pestis and E. coli. There were revealed marked differences in the activity of aspartase, fumarase, synthetase and desamidase of L-asparagin, and also of the enzyme activated by acetate in the E. coli strains with plasmide resistance. Transmission of R-factor to the pestis was accompanied by decomposition of L-asparadein, formation of AC-CoA. At the same time transformation of L-asparaginic acid catalyzed by aspartase remained on the same low level in the sensitive pestis cultures and their variants with the R-factor. When the resistance was controlled by chromosomal resistance markers, the activity of the enzymes providing formation of L-asparagic acid, its amide and L-malic acid showed no significant change. In chromosomal type of resistance in the mutants of pestis and E. coli the acetyl-CoA-synthetase reaction was as a rule somewhat increased.


Hypophyso-gonadal function in the cryptorchid child: differences between unilateral and bilateral cryptorchids. In 22 normal boys, 33 unilateral and 14 bilateral cryptorchids, a gonadal function test (2000 IU of HCG im each day for three days and assays of plasma testosterone and plasma oestradiol-17beta before and after the HCG administration) as well as an LH-RH test were carried out. In 60% of the cases, both normal and cryptorchid boys, plasma oestradiol-17beta (both in basal conditions and after stimulus) were found to be less than the sensitivity (5 pg/ml) of the method, While the plasma testosterone was similar under basal conditions in the three groups of children, after HCG it was significantly lower than the mean value of the control group only in the bilateral cryptorchids. The testosterone levels, both under basal conditions and after stimulus, are correlated to bone age only in the normal boys and in the unilateral cryptorchids. There were no significant differences among the various groups for either LH and FSH both under basal conditions and after LH-RH. The LH curve area during the LH-RH test is in correlation with bone age only in the normal children.


Halothane anaesthesia in caesarean section. The safety and efficacy of halothane anaesthesia were investigated in 97 caesarean sections using 0.4-0.6% halothane added to a mixture of 61 N2O/3-4 1 O2. The administration of halothane was initiated before intubation and terminated immediately prior to delivery. Only one patient reported memories from the operation. The mean Apgar score 1 min after delivery (8.5) was significantly better than that (8.2) in 100 caesarean sections in which a mixture of 71 N2O/3 1 O2 was used. In 17 caesarean sections, the halothane concentrations were examined after 0.9% halothane had been given for exactly 1 min after intubation. It was found that halothane reached and passed the placenta after only 1 min. The levels in the maternal artery and umbilical vein were comparable. The levels in the maternal artery, maternal vein and umbilical vein were markedly higher than in the umbilical artery, which indicated an accumulation of halothane in the foetal tissues. However, due to the vigour of the newborn, halothane concentrations 10 min after birth were very low. The half-life of halothane in the maternal circulation was approximately 1 min with the described method of administration. Blood gas determinations, which were made in seven newborns, proved satisfactory.


The haemodynamic effects of unsupplemented nitrous oxide-oxygen-relaxant anaesthesia in cardiac patients. The effect on the systemic and pulmonary circulation of unsupplemented nitrous oxide in about 30% oxygen, with and without IPPV, was investigated in five cardiac patients and compared with control periods at rest with air breathing. The results of this investigation show that nitrous oxide in conventional oxygen concentration does not cause any great haemodynamic changes. During tracheal intubation, however, significant increases in both systemic and pulmonary blood pressures were registered. However, these pressures reverted to the control values immediately after the tracheal intubation. The results of this study support many earlier clinicaly good experiences obtained when using this conventional nitrous oxide-oxygen mixture in cardiac patients.


Histochemical studies on the adrenal glands of the marmosets (Callithrix jacchus and Callithrix penicillata). The histrochemistry of the adrenal glands was studied in four adult male marmosets (two Callithrix jacchus and two Callithrix penicillata). It was impossible to demonstrate any reactivity to UDPG-GT, ADH, alanyl aminopeptidase, leucine aminopeptidase, xilitol (NAD-dependent) dehydrogenase, beta-glucuronidase and aryl-sulfatase in these glands. Total phosphorylase was found in scattered cells of the glomerulosa and adjacent outer fasciculata of one C. penicillata. The dehydrogenases (LDH, G-6-PDH,6-PGDH, NADPH2-TR,ICDH,SDH,NADH2-TR, alpha-GPDH, beta-OHBDH) as well as the hydrolases (except alkaline phosphatase, ATPase, and acetylcholinesterase) showed a stonger reactivity in the cortical part. Some hydrolases (naphthol acetate esterase, acid phosphatase) and cytochrome oxidase were less reactive in the zona glomerulosa, where the dehydrogenases were more abundant. The outer fasciculata and the reticularis also showed a strong dehydrogenase reactivity.


Alkaline phosphatase activity in the human tonsils and its relation to tonsillar diseases. Alkaline phosphatase activity was examined in the human tonsils in fetal life and after repeated attacks of acute tonsillitis and in quinsy. Gomori's metal precipitate technique was used to demonstrate the phosphatase activity using four different substrates: sodium beta-glycerophosphate and adenosine triphosphate at pH 9, riboflavin 5-phosphate at pH 9.2 and 5-monophosphoric acid at pH 8.3. (2) The phosphatase activity differs somewhat according to the phosphate ester used as a substrate illustrating an example of 'substrate specificity'. (3) Alkaline phosphatase activity was increased in the case of both acute and chronic inflammation. This increase has been discussed in relation to such phenomena as transformation of lymphocytes into macrophages and antibody formation.


Amperometric and polarographic study of the SH-activity of MEPRIN (alpha-mercapto-propionylglycine). The SH-groups of alpha-mercapto-propionylglycine (MEPRIN) are remarkably stable in diluted solution either at room temperature or at 50 degrees C, even if storing takes place under air-bubbling. The SH-activity was measured by polarographic method and amperometric titration. Neutralization of the carboxyl group decreases the stability of the sulfhydryl groupings. Evaporation of neutralized solution leads to a 30--50 per cent decrease of SH-activity. Lyophilization reduces this loss by 10--15 per cent. Neutralization is best carried out in the absence of oxygen; in this case, 94 per cent of the sulfhydryl activity will persists, irrespective of the pH. The dissociation constant of MEPRIN-SH is pK' = 8.47. The SH-stability of the product is satisfactory when neutralized in nitrogen atmosphere to pH 3--5; a loss of only 5 per cent can be expected after storing in an oxygen-free 10(-3) molar solution for 144 hours. Between pH 6 and 8 this value is 31 per cent on the average, while at pH 9 it is more favorable again.


Effects of phospholine iodide on the metabolites of the glycolytic, pentose phosphate and sorbitol pathways in the rabbit lens. Steady-state concentrations of the key intermediates from the glycolytic, pentose phosphate, and sorbitol pathways as well as the pyridine nucleotides were measured from the lens after 0.25% phospholine iodide had been instilled into rabbits' eyes twice a day for 18 weeks. In the lenses of those rabbits which had received treatment in both eyes fructose-1,6-diphosphate and pyruvate levels were increased, whereas 6-phosphogluconate, sorbitol and alpha-glycer0phosphate concentrations were decreased. alpha-Ketoglutarate and concentrations and ratios of NAD+ and NADH did not show any changes. In contrast, NADPH and total NADP concentrations as well as the NADPH/NADP+ ratio were decreased, and therefore total NAD/total NADP ratio increased after treatment. It appears that instillation of long-acting 0.25% phospholine iodide into rabbits' eyes results in increased glycolytic activity in the lens in response to the increased energy demand, wheras the activities of other metabolic pathways are suppressed.


Clinical and cytogenetic studies in undescended testes. 168 boys and 2.5-16.8 years with unilateral or bilateral undescended testes or anorchia were studied. Retention was severe (canalicular or intraabdominal) in 1/4 and moderate in 3/4 of the cases. In unilateral retention, the volume of the scrotal testis was usually normal throughout childhood whereas pubertal testicular growth was delayed. In unilateral anorchia, the scrotal testis showed compensatory hypertrophy. In all age groups examined, the mean volume of the undescended testes was abnormally small. Undescended testes were accompanied by abnormalities of the epididymis in 3.6% of cases, of the ductus deferens in 7.8% and of the spermatic vessels in 8.3%. In anorchia such abnormalities were found regularly. Inguinal hernia accompanied 62.8% of the undescended testes and was most frequent in severe cases. Patients aged 8.0-9.9 years with unilateral undescended testis had advanced bone age. Cytogenic investigations of 167 patients revealed one case of Klinefelter's syndrome (47, XXY). Gonadotrophin treatment was tried in 50 patients and was succesful in 12. Surgical results were satisfactory in 86.1% of the operated testes.


Endocrinological studies in undescended testes. A cross-sectional study was carried out on 168 boys aged 2.5-16.8 years with unilateral or bilateral testicular maldescent. Urinary excretion of testosterone, delta4-androstenedione, LH and FSH was investigated. The results were related to chronological age, bone age and sexual maturation stage. Urinary testosterone excretion was elevated in unilateral and bilateral cases of undescended testis under 9 years of age. The pubertal increase of testosterone excretion seemed to be moderately delayed in the patients. In pubertal stage V the testosterone excretion was normal. The mean testosterone/androstenedione relationship was normal in all age groups up to 14.9 years and increased in patients above this age. After HCG stimulation, the testosterone excretion increased at all ages studied whereas the androstenedione excretion increased only in bilateral cases under 11 years of age. Urinary LH excretion was diminished in bilateral cases aged 6.0-7.9 years and elevated in unilateral cases in pubertal stage V. Urinary FSH excretion was normal below 8 years of age, moderately elevated in bilateral cases aged 8.0-11.9 years and increased in unilateral cases in pubertal stage V. Patients with bilateral anorchia in pubertal stage I, had normal basal testosterone and androstenedione excretion while the LH and FSH levels were increased. The findings in this study indicated that disturbances in the pituitary-gonadal function of cryptorchids might be operative from early childhood and throughout pubertal years.


Allo-aggression in chickens. II. Cellular expression of the AA gene products. B1-anti-B2 and B2-anti-B1 allo-antisera were raised by i.v. immunization of homozygous B1/1 and B2/2 chickens, respectively, with B1/2 cells of the following sources: peripheral blood leucocytes (PBL), erythrocytes, thymus cells and bursa cells. Purified suspensions of these all produced anti-B allo-antibodies which could both haemagglutinate red blood cells and strongly inhibit the GVH reactivity of blood lymphocytes of the original donor type. Absorption studies of the sera using cells of the same four sources showed that they could all completely remove the GVH inhibitory antibodies. A fact of particular importance is that B-haplotype determined antigens which are common to erythrocytes and lymphocytes seem to include the gene products of the allo-aggression locus, as earlier defined (Simonsen 1975).


[Epileptic headaches (author's transl)]. The author describes three observations characterized by the following similar features: 1. Children, between 2 and 9 years, suffering from attacks of sterotyped headaches. 2. EEG with bursts of high- voltage paroxysmal discharges, mainly during hyperventilation. 3. Efficiency of antiepileptic drugs contrary to antimigrainous treatment. These headaches are considered by the author as "epileptic", and this diagnosis is discussed.


Influence of pH and pCO2 on alpha-receptor mediated contraction in brain vessels. The response of isolated brain vessels to various pH levels or carbon dioxide tensions was analyzed. Reduction of the pH induced a slight relaxation of the vessel, whereas an increase in the pH produced a slight contraction. These effects were markedly exaggerated when the alpha-adrenergic receptors in the vascular wall were activated by noradrenaline. During these conditions the contractile response to noradrenaline was reduced by about 40% at a pH of 7.01, while, on the other hand, the response was enhanced 3-fold at a pH of 7.80. Variations in carbon dioxide  tension of the buffer solution between 16 mmHg and 64 mmHg produced no consistent change, provided the pH remained constant. The results indicate that an interaction between the perivascular pH and the adrenergic alpha-receptor mediated contraction in brain vessels may occur.


[Logical analysis of the respective influence of 3 experimental variables using a diagram by L. Carroll. Application of this method to a clinical trial of 2 forms of Noveril]. The analysis of the results gathered in a double-blind randomized cross-over clinical trial of dibenzepine was systematized in order to evidence the relation existing between the experimental variables and the effects measured. The suggested method of analysis is based on logic and makes profit of a diagram by Carroll. This method seemingly permits rigourous and clear conclusions.


Effects of chlorthalidone on serum and total body potassium in hypertensive patients. Total body potassium has been estimated in 26 hypertensive patients who were hypokalaemic as a result of long-term chlorthalidone treatment (mean 20.5 months), while they were on chlorthalidone and 4 weeks after this had been discontinued. The mean difference amounted to only 95 mEq (not significant). In 6 additional patients not previously treated with chlorthalidone, serial total body potassium estimations revealed a mean potassium deficiency of 245 mEq after 33 days and of 106 mEq after 100 days. These results suggest that the mechanism causing the initial potassium loss is partly reversed or compensated later on. In patients with uncomplicated hypertension, no significant potassium deficiency was detected during long-term treatment. Eighteen of our patients received 39 mEq potassium chloride supplements daily for 4 weeks; this caused a mean rise in serum potassium from 3.23 mEq/l to 3.38 mEq/l (not significant). Total body potassium did not change at all. We conclude that potassium chloride supplements are not an effective treatment of hypokalaemia in this condition. Correction of the extracellular pH by ammonium chloride in 6 patients on chlorthalidone, who demonstrated a slight metabolic alkalosis, gave rise to a mean increase in plasma potassium from 2.78 mEq/l to 2.96 mEq/l (not significant). The hypokalaemia in hypertensive patients on long-term chlorthalidone treatment cannot be explained by either a potassium deficiency or the change in extracellular pH.


Liver enzymes in alcohol-discordant twins. Seventy moderately alcohol-discordant male twin pairs have been investigated with respect to some liver enzymes. No differences were found as regards S-ALAT, while significantly higher enzyme levels were demonstrated for S-ASAT, S-ALP and S-GT among the high alcohol consumers compared to their low consuming co-twins. Especially S-GT was found to be a valuable and sensitive test in the detection of even a moderate alcohol intake in working and socially well adapted subjects. These results were obtained in a subject group in which the influence of genetic factors was kept to a minimum.


[Ulcerative rectocolitis. Somatic aspects (author's transl)]. Regional enteritis (Crohn's disease) and ulcerative rectocolitis, both "non specific inflammatory diseases of the bowel", might be diseases with a common etiology but with clinical features corresponding to a different tissular response to a noxious factor. Both diseases are however characterized by distinct clinical, radiological, histological peculiarities; evolution also is different, as appears from the rarity of malignant degeneration in Crohn's disease and its frequence in ulcerative colitis; a psychological support seems to be classical in ulcerative colitis but is on the contrary unusual in regional ileitis. Besides the interference of psychological factors in the outbreak of an ulcerative colitis, besides the infectious and genetic theories, the immunological theory appears as one of the most interesting and promising. In a significant percentage of cases of ulcerative colitis, anticolon antibodies are evidenced, which exhibit a crossed reaction with bacterial antigens, especially with those of Escherichia coli 014. Besides this humoral immunity a cellular immunity exists also: lymphocytes of patients with ulcerative colitis behave as a toxic agent towards colic tissue cultures; this cytotoxicity parallels the course of the disease and provides an explanation for the sometimes dramatic therapeutic effects observed after administration of immunosuppressive drugs and antilymphocytic serum. Moreover, colic antigen can block this cytotoxicity; the immunologically active portion of this antigen may be isolated and its administration in patients with ulcerative colitis may perhaps induce a specific immunosuppression and influence the evolution of the disease.


On the nature of brain stem disorders in severe head injured patients. II. A study on caloric vestibular reactions and neurotransmitter treatment. The results of electro-oculographic recordings made after caloric vestibular stimulation (C.O.G.) in severe head injured patients are discussed. It was found that: 1. The C.O.G. correlates with the state of consciousness of the patients. 2. The rate of improvement of the C.O.G. correlates with the rate of the clinical improvement. 3. A prediction of the duration of unconsciousness can be made by repeated C.O.G. scores as well as by repeated scoring of the clinical state. 4. In all patients a paradoxical response is present except in those who have regained clear consciousness and in those persisting in a vegetative state, so the presence of a paradoxical response indicates the possibility of further improvement. It was supposed that in patients with a paradoxical response a functional brain dysfunction was present, which was at least partly caused by disturbed neurotransmitter metabolism. Therapeutic trials with L-DOPA and physostigmine were successful in patients with a paradoxical response, but without any result in those without this phenomenon. The responses to L-DOPA and to physostigmine are related respectively to motor pattern and to verbal or non-verbal communication.


Adrenergic blockade in subarachnoid haemorrhage. Over the last 15 years progressive interest has developed in the relationship between subarachnoid haemorrhage, sympathetic nervous system over-activity and the genesis of cerebral artery spasm. Following on from earlier work, vide infra, suggesting that adrenergic blockade might influence the course and prognosis of patients with subarachnoid haemorrhage, two double blind trials have recently been completed in Southampton. The first trial attempted to establish whether or not a single intracarotid injection of phenoxybenzamine improved the mortality and late morbidity of patients with subarachnoid haemorrhage. Results suggested that it did not. The second trial, comprising two groups of 50 patients each, attempted to assess the influence of prolonged treatment with propranolol on the course and prognosis of these subarachnoid haemorrhage patients. Early results suggest that, as with the alpha-blocker, the mortality and severe morbidity was not improved by beta-adrenergic blockade.


Comparison of function of the distal base between myoglobin and peroxidase. The heme-linked protonation of a ferrous horseradish peroxidase is assigned to a distal amino acid residue. The conclusion is drawn from analyses of reactions that involve the protonation. Unfortunately it is difficult to apply it to the myoglobin case because no reaction has been found which is coupled with the protonation of the distal histidine. It is therefore of special interest to note that the pK value of 5.7 has been assigned to the distal histidine of metmyoglobin from binding kinetics with ligands20). It is well known that the reaction with hydrogen peroxide is quite different for the two types of hemoproteins. The distal base may be associated with the stabilization of the primary compound with hydrogen peroxide and also another amino acid residue may serve as a nucleophile for the stabilization of the pi-cation radical of porphyrin in the case if peroxidases. Numerous papers have dealt with heme substitution, heme linked protonation and reactions of hemoproteins related to the present subject. In this short paper, however, the discussion has mostly centered around the data obtained recently in our laboratory.


Biological effects of cyclosporin A: a new antilymphocytic agent. The fungus metabolite cyclosporin A is a small peptide acting as a novel antilymphocytic agent. It strongly depressed appearance of both direct and indirect plaque-forming cells and produced a clear dose-dependent inhibition of haemagglutinin formation in mice upon oral administration. Skin graft rejection in mice and graft-versus-host disease in mice and rats were considerably delayed by cycloporin A which also prevented the occurrence of paralysis in rats with experimental allergic encephalomyelitis. This compound was not only highly effective in preventing development of Freund's adjuvant arthritis, but in addition improved the symptoms in rats with established arthritis, although it is inactive in acute inflammation. This new agent contrasts with other immunosuppressives and cytostatic drugs in its weak myelotoxicity. Experimental evidence suggests that cyclosporin A, rather than being cytostatic or lympholytic, affects an early stage of mitogenic triggering of the immunocompetent lymphoid cell.


Ultrastructural comparison of the midgut epithelia of fleas with different feeding behavior patterns (Xenopsylla cheopis, Echidnophaga gallinacea, Tunga penetrans, Siphonaptera, Pulicidae). This morphological study describes the ultrastructure of the midgut of three flea species, including temporary parasitic fleas (both sexes of Xenopsylla cheopis, males and immature females of Echidnophaga gallinacea and Tunga penetrans) and stationary parasitic fleas (mature females of E. gallinacea and T. penetrans). (1) Three cell types (a,b,c) constitute the midgut epithelium, each appearing in a characteristic and constant frequency along the whole midgut, a) The functional digestive cells form the main part of the epithelium as one layer of cylindric cells. Nuclear volume and nucleus/cytoplasm ratio have been estimated (with morphometric methods) to be the same in both sexes of E. gallinacea and T. penetrans. b) Some single regenerative cells or nests, containing 5-10 cells per section plane, lay at the base of the epithelium (2-3 cells or nests per cross section of a midgut). c) Secretory cells are characterized by their opaque cytoplasm which contains electron-dense vesicles. They have few microvilli and no basal labyrinth and are placed between digestive cells only as single cells (1-2 per cross section of a midgut). (2) After the first bloodmeal some ultrastructural changes occur in the midgut of all fleas. These changes are interpreted as a structural reflection of metabolic processes such as secretion of digestive enzymes, resorption, storage and transport of digested nutrients, and synthesis of digestive enzymes. (3) More conspicious changes occur in the midgut of the stationary parasitic and maturing females of E. gallinacea and T. penetrans. The nuclear volumes of the digestive cells reach the two-fold and eight-fold value, respectively. The nucleus/cytoplasm ratio decreases by half. The corresponding cytoplasmic growth of each cell is reflected in an enlargement of the whole midgut. The digestive cells form long apical cell extensions. The nucleus, basal labyrinth, rer, and golgi complex all change their morphology, and this can be interpreted as the result of a higher level of metabolic activity than during the first bloodmeal. (4) The midgut of the oviparous female of T. penetrans undergoes a process of compensatory hypertrophy which consists in the cellular hypertrophy of each digestive cell and in an extensive proliferation of the regenerative cells. A unique structure, called 'nuclear halo' appears within the process of cellular hypertrophy. This structure consists of a layer of 70-100 A thick filaments along the periphery of the nucleus. The nuclear halo contains few ribosomes and is screened from the cytoplasm by an rer cisterna. The filaments may contain RNA molecules which are on their way to the cytoplasm. It has been demonstrated that the structure of the midgut epithelium is influenced by the nutritive and parasitic behavior of the flea. The stationary and oviparous E. gallinacea and T. penetrans reveal an extensive and irreversible change of their midgut epithelium.


Nutrition of Glossina morsitans: metabolism of U-14C threonine during pregnancy. Following injection of U-14C threonine into the haemolymph of adult female Glossina morsitans during late pregnancy, radioactivity was detected in the postparturient female and in its offspring, in threonine, lipids, and a range of non-essential amino acids. The level of radioactivity recovered from the larva was higher than that remaining in the injected adult, and the radioactivity recovered was considerably higher in the amino acid than in the lipid fraction. Administration of labelled threonine into maternal haemolymph on each of the first 8 days of the 9-10 day long pregnancy cycle was followed 24 h later by measurement of radioactivity in the developing oöcyte and in the intra-uterine progeny. The patterns of nutrient uptake are discussed in relation to vitellogenesis in the oöcyte and to growth of the larva. Analysis of the expired carbon dioxide and excreta was carried out 24 h after maternal injection of labelled threonine on the first or eighth day of pregnancy. Carbon dioxide and excreta from females in early pregnancy showed significantly higher radioactivity than those from females in late pregnancy. In both cases, radioactivity in the amino acid fraction from the excreta was extremely small and about 95% of the total activity was in uric acid. These results are discussed in terms of the utilization of threonine in relation to the metabolic demands for various nutriments by the pregnant female.


Development of Trypanosoma (Trypanozoon) brucei in Glossina morsitans inoculated into the tsetse haemocoel. Classically, infective development of Trypanosoma (Trypanozoon) brucei in tsetse flies is thought to take the route crop-midgut-hindgut proventriculus-hypopharynx-salivary gland, where the parasites reach their infective phase. It has been shown experimentally that T. (T.) brucei is capable of developing up to the infective stage in G. morsitans following inoculation of bloodstream form trypanosomes into the haemocoel. The rabbit on which flies were maintained became infected 18 days after exposure to the bite of experimentally inoculated flies. The possibility that T. (T.) brucei may be transmitted cyclically from tsetse flies to a mammalian host without necessarily following the classical, prescribed route is discussed. Apart from the normal longitudinal binary fission, various modes of multiplication were observed among trypanosomes in the haemocoel, modes which have not been observed previously in the tsetse fly.


Filaments of Trypanosoma brucei: some notes on differences in origin and structure in two strains of Trypanosoma (Trypanozoon) brucei rhodesiense. Filaments attached to trypanosomes of two strains of T. (T.) brucei were studied by electron microscopy and two distinct types identified: short-thick and long-thin. The former are associated with stumpy trypanosomes and are secretions, via the flagellar pocket, which originate in the area of the Golgi complex, during the infection of the host. They are referred to as 'secretory filaments'. Their diameter is 0.09 to 0.14 mum. The long-thin filaments are associated with slender forms of trypanosome in various artificial situations; those shown by negative staining are believed to be cytoplasmic extrusions from the anatomically weak extremities of the parasite and are referred to as 'plasmanemes'. Their diameter is 0.06 mum. Both types appear to maintain their structure without the aid of the normal type of unit membrane as myelin formations.


[New species of Microsporidia, parasite of Myriapoda-Diplopoda of South Dahomey]. A new microsporidian parasitic in Myriapoda-Diplopoda of Sud-Dahomey (Habrodesmus falx Cook & Oxydesmus granulosus Palisot de Beauvois) is described by photonic microscopy. It can be recognized by its thick-enveloped pansporoblasts yielding from 30 to 66 elongate and ovoid spores measuring 4,8 mum in length and 2,2 mum in diameter. The spore is uninucleate. This microsporidian forms cysts in the anterior part of the host affecting the musculature of the digestive tract, the adipose tissue and segmentary muscles. However, it appears necessary to study this parasite again by means of electron microscopy for a better understanding of its life-cycle and in order to place it in the Microsporidian taxonomy.


[General survey of the present distribution of helminths in Iran and comparison with those of past years]. In this paper the literature on helminthiasis in Iran is reviewed and the distribution, prevalence and intensity of infections caused by helminths are discussed. A comparison of prevalence and intensity of infections was accomplished in the recent 10 years by the author. Hookworm infections are found mostly in the north along the Caspian sea, but its prevalence is declining. Trichostrongylus are found in Iran with a high prevalence in central country. Schistosoma haematobium is found in one Province in the south, but its prevalence is declining because of large scale control activities. The Guinea worm rarely occurs in Iran. The prevalence of Fasciola hepatica is high among livestock and is occasionally found in man. Taenia saginata is found in most parts of Iran. Taenia solium is seldom found in animals with a prevalence of 0.03%. Trichinella spiralis is infrequently found in animals. Dioctophyma renale is found in straying dogs in the north or Iran, the percentage is 13-35%. Oxyuriasis is widespread among children.


Otitis media of infancy and early childhood. A double-blind study of four treatment regimens. A double-blind, randomized trial of four antimicrobial regimens was conducted in 383 infants and children with acute otitis media. The drugs used were penicillin V, amoxicillin trihydrate, erythromycin estolate, and erythromycin estolate with trisulfapyrimidines. Aspiration of middle ear fluid for culture was done before treatment and repeated during treatment if fluid persisted. Etiologic bacteria were most commonly pneumococci (31%) or Haemophilus sp (22%), and an additional 5% of patients had both organisms. Amoxicillin was the most effective in promoting initial response in pneumococcal infection. For Haemophilus infections, the cure rates with amoxicillin and the erythromycin-trisulfapyrimidines mixture were significantly better than with the other two regimens, and serous otitis did not occur during the follow-up period; however, new episodes of otitis were comparable in the four groups. Amoxicillin and the erythromycin estolate-trisulfapyrimidines combination appear to be somewhat more effective than penicillin V or erythromycin estolate.


Influences on role expansion.

Influences on role expansion. Several factors are influencing role expansion for registered nurses, among them the shortage of primary care physicians, the federal government, the physician's assistant movement, the growing complexity of acute hospital care, educational reform, and the women's liberation movement. As state licensure statutes are revised to allow for role expansion, the changing laws themselves become a factor supporting the movement.


Maternal and fetal effects of lumbar epidural analgesia for labor and delivery in patients with gestational hypertension. The effects of continuous lumbar epidural analgesia for labor and delivery were studied in 20 women with gestational hypertension. Maternal hemodynamics, renal function, acid-base, and blood gas findings were examined together with newborn APgar scores and umbilical vessel blood gas and acid-base values. Minimal change occurred in maternal renal function and hemodynamics. Maternal and bewborn aicd-base and blood gas findings were comparable to those  of normotensive control subjects also receiving epidural analgesia. Apgar scores in both groups of subjects wer good. Continuous epidural analgesia is recommended as a useful form of therapy in the management of labor and delivery in women with gestational hypertension.


Circulatory response to atropine in sheep fetus. Atropine was given to the semichronic sheep fetus intravenously. Fetal heart rate, fetal perfusion pressure, and carotid blood flow increased. Cerebral blood flow was measured with the radioactive microsphere technique. Atropine was capable of increasing the cerebral blood flow. Elevation of carbon dioxide also caused an increase in cerebral blood flow, adding to the effect of atropine.


Nutritional deficiency, immunologic function, and disease. Several experiments conducted by our group over a period of 6 years have shown that nutritional stress, especially protein and/or calorie deprivation, leads to many, often dramatic, changes in the immune responses of mice, rats, and guinea pigs. Chronic protein deprivation (CPD) has been shown to create an enhancing effect on the cell-mediated immune responses of these animals. Humoral responses under CPD conditions were most often found to be depressed, but sometimes were unaffected, depending on the nature of the antigen employed. Chronic protein deprivation, consistent with the pattern just mentioned, improved tumor immunity by depressing production of B-cell blocking factors, and, in at least one instance, resistance to development of mammary adenocarcinoma in C3H mice was associated with evidence of increased numbers of T suppressor cells. Profound nutritional deficits (less than 5% protein per total daily food intake) depressed both cellular and humoral immunity. Early, though temporary, protein deprivation caused a long-term depression of both cellular and humoral immunity also, with the humoral component being the first to recover. Manipulation of protein and calories was found to have a profound effect on certain autoimmune conditions. Diets high in fat and low in protein favored reproduction but shortened the life of NZB mice, whereas diets high in protein and low in fat inhibited development of autoimmunity and prolonged life. Chronic moderate protein restriction permitted NZB mice to maintain their normally waning immunologic functions much longer than mice fed a normal protein intake. Further, the low-protein diet was associated with a delay in development of manifestations of autoimmunity. Decreasing dietary calories by a reduction of fats, carbohydrates, and proteins more than doubled the average life span of (NZB X NZW)F1 mice, a strain prone to early death from autoimmune disease. Histopathologic studies using immunofluorescent microscopy revealed that the development of the renal lesions caused by the deposition of antigen-antibody complexes, which is so characteristic of these mice, was markedly delayed.