Some hygienic and clinical observations on styrene exposure. Styrene exposure levels in the range of 100--300 ppm as an 8-h time-weighted average have been measured in small shops manufacturing glass fiber reinforced plastic products such as boats, steeping baths, etc. Exposure control through determinations of mandelic acid in the urine at the end of the workday has been found suitable and convenient. Over the years during the 1970s, there seems to have been amendments in the exposure situation in Sweden if judged from mandelic acid monitoring. More or less severe central nervous disturbances have been observed among the workers. Elevated levels of amino-transferases have been recorded but are of unclear long-term importance to liver function.


Thermal degradation products of homopolymer polystyrene in air. Polystyrene without additional compounds was treated in a laboratory oven at elevated temperatures (200 degrees, 350 degrees, 500 degrees C) under slight air flow (0.7 l/min). The thermal degradation products appearing in different phases (gases, vapors, aerosols) were collected and analyzed by methods of chromatography. Thermogravimetric analysis showed the thermal degradation of the polymer to begin at 270 degrees C in air and stop at 425 degrees C. The main groups of vaporized compounds generated were monoalkyl-substituted aromatic hydrocarbons and their oxidized products, of which styrene monomer and benzaldehyde were the most abundant. Only trace amounts of carbon monoxide and aliphatic compounds (hydrocarbons, aldehydes, and acids) were produced. The aerosol produced, the amount of which increased as the temperature rose, contained mainly fragments of the polymer chain (e.g., dimers and trimers of styrene). The traces of styrene, cumene, and ethylbenzene that appeared at 200 degrees could represent residual compounds in the initial polymer and indicate the beginning of the thermal degradation. If proportional concentrations are kept as a criterion, the important products, from the point of view of industrial hygiene, were styrene, benzaldehyde, styrene oxide, acetophenone, and l-phenylethanol. The large amount of aerosol that appeared may also be of practical importance.


Health status of styrene-polystyrene polymerization workers. Styrene monomer is a greatly used chemical, chiefly in the production of polystyrene. A cross-sectional health survey of 493 production workers was undertaken at the oldest and largest monomer production, polymerization, and extrusion facility in the United States. Relative exposure durations and levels were obtained from occupational histories and corroborated by spot air sampling, blood and fat styrene concentrations and levels of urinary mandelic and phenylglyoxylic acids. Statistically significant differences between the prevalence of abnormalities in high and low exposure groups were found for the following: history of acute prenarcotic symptoms, history of acute lower respiratory symptoms, peroneal nerve conduction velocities, relative lymphocytosis, and elevated gamma glutamyl transpetsidase. The following showed no distinct pattern in prevalence when analyzed by exposure group: chest radiographic changes; indices or restrictive, obstructive and small airway dysfunction; other hepatic and hematological parameters; carcinoembryonic antigen level; sputum cytopathology; radial nerve conduction velocities; and ophthalmological findings. Clinically significant abnormalities were rare.


Survey of mortality among employees engaged in the manufacture of styrene and polystyrene at the BASF Ludwigshafen works. A mortality survey of 1,960 employees currently or previously exposed to styrene at work has shown that the observed number of deaths from cancer or other causes is no higher than the number expected in the German population or in a group of BASF employees. Analyses of deaths occurring after a minimum period of five years in groups exposed for different durations (5 years, 10 years, 15 years, more than 15 years) indicated no increase in mortality with exposure time. This latter observation also applied to malignant tumors; therefore it may be inferred that prolonged exposure to styrene is not a cancer hazard.


Mortality experience of styrene-polystyrene polymerization workers. Initial findings. A group of 560 individuals has been identified as employed on 1 May 1960 with at least five years seniority in a plant manufacturing styrene and polystyrene. In this plant workplace exposures included styrene, benzene and ethylbenzene, among other materials. All of the 560 individuals have been traced through 1975 and their vital status determined. Expected and observed deaths, by cause, were determined from 1 May 1960 or the tenth anniversary of employment in the plant through 31 December 1975. Over this relatively short period of time a deficit of deaths compared to that of the general population was observed (106.41 expected versus 83 observed). Among the 83 deaths, one was of leukemia, one of lymphoma and an additional death was accompanied by leukemia. A review of 361 additional death certificates revealed five additional cases of leukemia and four of lymphoma. The available information from the limited follow-up in time of the time of the cohort and from the randomly collected death certificates, while suggestive of a possible risk, is not definitive.


Mutagenicity study of workers employed in the styrene and polystyrene processing and manufacturing industry. Mutagenicity studies were undertaken on lymphocytes from the following groups of persons exposed to styrene or polystyrene: one group from a styrene manufacturing plant, one from a polystyrene plant, and three from plants processing unsaturated polyester resins with different manufacturing methods. For all the groups the concentration of styrene in the atmosphere of the workplace was measured at various points and the amount of urinary mandelic acid was determined. In each case 100 metaphases were analyzed for chromosomal aberrations. The results were compared with reference groups.


Chromosome aberrations in lymphocytes of workers exposed to styrene. Workers exposed to styrene in the reinforced plastics industry show a significant increase of chromosome aberrations, mainly chromosome breaks, in peripheral blood lymphocytes. The high incidence of aberrant lymphocytes (mean 15.1 +/- 4.8%; referents 2.0 +/- 1.3 %) was retained when the same men were reexamined one year later (mean 16.2 +/- 2.9 %). However, the frequency of sister chromatid exchanges (SCE), a newly developed sensitive parameter for the detection of recombinational exchanges linked with DNA repair, was not significantly increased (mean 5.3 +/- 1.0 SCE/cell) in comparison to the referents (mean 4.4 +/- 0.6 SCE/cell). This finding suggests a specific role of styrene or its metabolites in inducing genetic lesions mainly manifesting themselves as chromosomal breaks.


Possible metabolic interaction of styrene with organic solvents. Excretion of metabolites of styrene (dose: 2.2 mmol/kg i.p.) in 24-h urine was suppressed when rats were coinjected intraperitoneally with either toluene or trichloroethylene (dose: 2.2--11.0 mmol/kg) in addition to styrene, while a coinjection of n-hexane, ethyl acetate, methylchloroform, or acetone at an equimolar dose was ineffective in all cases. Suppressive effects of toluene and trichloroethylene were further confirmed by 6-h vapor exposure to (a) 0 to 1,300 ppm of toluene in addition to 150--170 ppm of styrene and (b) 0 to 4,000 ppm of trichloroethylene together with 100 or 150 ppm of styrene. The relationship between the amounts of three metabolites (i.e., phenylglyoxylic, mandelic and hippuric acids) in urine and styrene concentration in air was also determined.


Interaction of styrene and acetone with drug biotransformation enzymes in rat liver. In the presence of hepatic microsomes, styrene produced a type I difference spectrum, which demonstrates that styrene binds to the catalytic site of ferricytochrome P-450. A comparison of the binding parameters for the interaction of styrene with noninduced, phenobarbital-induced, and 3-methylcholanthrene-induced microsomes indicated that styrene is predominantly bound by cytochrome P-450 and not by cytochrome P-448. Inhalation exposure to a mixture of acetone (1,000 ppm, 6 h/d) and styrene (300 ppm, 6 h/d) for 5 d caused a distinct decrease in hepatic free nonprotein sulfhydryl groups. This decrease could be observed both with and without phenobarbital treatment. Acetone inhalation alone also enhanced ethoxycoumarin O-deethylase activity in rats without pretreatments. Acetone inhalation also increased the cytochrome P-450 content of liver microsomes, but it had no effect on NADPH cytochrome c reductase or epoxide hydratase activity. Combined exposure to styrene and acetone enhanced NADPH cytochrome c reductase activity in nonphenobarbital-treated rats, but no effect was seen in the phenobarbital-treated animals. Phenobarbital treatment of animals can greatly modify the biotransformation and toxicity of styrene, phenobarbital inducible P-450 hemoprotein playing a predominant role in its metabolism. Simultaneous inhalation exposure to acetone also interacts with the metabolism of styrene.


The role of glutathione in the toxicity of styrene. The role of glutathione in the toxicity of styrene has been proposed based on the observations that glutathione inhibits the covalent binding of styrene and styrene oxide in vitro and that the administration of these compounds to animals decreases the glutathione content in the liver in vivo. In this study methionine (a precursor of reduced glutathione) or diethylmaleate (a depletor or reduced glutathione) was administered to hamsters concomitantly with styrene. Methionine protected the liver against the hepatotoxicity of styrene as indicated by the serum alanine aminotransferase activity. Diethylmaleate potentiated the hepatotoxic effect of styrene. A threshold value for hepatic glutathione of about 1 mmol/l was found for styrene toxicity. Cell damage occurred when the concentration of reduced glutathione in the liver has a central role in the development of cell damage caused by styrene.


Effects of thermal degradation products of polystyrene on drug biotransformation and tissue glutathione in rat and mouse. Rats and mice were exposed to the fumes of oxidative thermal degradation of polystyrene (350 degrees C). A decrease in the reduced glutathione (GSH) in both liver and lung was detected immediately after both the acute (mice, 3 h) and subacute (rats, 3 weeks) exposures were stopped. Later on an elevation in the amount of GSH due to the increased synthesis (rebound effect) could be seen. Cytochrome P-450 content in mouse liver was initially decreased after acute exposure, but the prolonged treatment doubled the amount of the P-450 hemoprotein in liver microsomes. After acute exposure 7-ethoxycoumarin 9-deethylase activity in mouse liver was doubled in 24 h. When the exposures were continued, this enhancement in ethoxycoumarin O-deethylase activity gradually disappeared. O-deethylase activity was also enhanced in rat liver and lung after subacute exposure. The exposures given had no effect on diphenyloxazole hydroxylase, and the effects on the conjugating enzymes (epoxide hydratase, UDPglucuronosyltransferase, glutathione S-transferase)) were insignificant in rat liver.


Arene oxides in styrene metabolism, a new perspective in styrene toxicity? The metabolism of styrene was studied in the rat after intraperitoneal administration of the cold and the 14C-labeled compound. In addition to phenylethylene glycol, mandelic acid, benzoic acid and hippuric acid, phenolic metabolites, namely, 4-vinylphenol, p-hydroxymandelic acid, p-hydroxybenzoic acid, and p-hydroxyhippuric acid, were identified in the urine of the treated animals. These biotransformation products were characterized by mass spectrometry and by comparative thin layer chromatography with standard compounds. Results of covalent binding studies of 14C-phenylethylene glycol to rat liver microsomal proteins suggest that these phenolic compounds may be formed as a result of chemical rearrangements of unstable arene oxides, reactive intermediates possibly implicated in styrene toxicity.


Styrene use and occupational exposure in the plastics industry. The commercial production of styrene was started in the 1930s. Currently 7 million tons of styrene a year is made worldwide by the catalytic dehydrogenation of ethylbenzene or by a process in which styrene is produced as a coproduct with propylene oxide. An estimated 62% of the styrene monomer is consumed in the manufacture of polystyrene, 12% in acrylonitrile-butadiene-styrene resins, 17% in styrene-butadiene rubber and latex, 7% in unsaturated polyester resins, and 2% in other applications. Occupational exposure to styrene occurs in monomer production and polymerization plants, during the fabrication of plastic products from monomeric or partly prepolymerized styrene, and during the transportation and handling of liquid styrene. Due to unreacted residual monomer or thermal degradation of the polymer, low concentrations of styrene can be detected during the use of plastic products. The most extensive and intensive exposure occurs in the reinforced plastics industry, in which over 200,000 workers are exposed to a styrene concentration typically ranging from 20 to 300 ppm.


Accumulation of styrene monomer and neurochemical effects of long-term inhalation exposure in rats. A simplified compartment model indicated that fat styrene content might be used as an index of the whole body styrene burden. Intermittent exposure of adult male rats to 300 ppm 5 d a week, 6 h daily for 1 to 11 weeks showed an initial steady increase in the fat styrene content up to the 4th week and an exponential decrease thereafter. This phenomenon might have resulted from the enhancement of styrene oxidation due to the prolonged exposure. The effect of the increased oxidation on the body styrene burden is theoretically doubled after 9.1 weeks of exposure. Neurochemical effects after that time might have resulted from an increased binding of styrene oxide in the cellular macromolecules, e.g., to their sulfhydryl groups. The activity of the metabolite towards the cellular constituents could very well explain the increased proteolysis possibly caused by lysosomal labilization. The present data also lend support to the theory of the importance of metabolic activation to styrene and other solvent toxicity.


Pharmacokinetics of inhaled styrene in rats and humans. The pharmacokinetic profile of inhaled styrene was examined in rats exposed to levels of 80, 200, 600 or 1,200 ppm for periods of up to 24 h. At levels up to 200 ppm for 6 h, styrene was cleared from the blood according to a two-compartment linear pharmacokinetic model, but at levels of 600 ppm and above the clearance was saturated. In going from 80 to 1,200 ppm (a 15-fold increase), the area under the blood concentration/time curves (AUC) increased by a factor or 112. Fat tissue was shown to comprise the second compartment of the two-compartment pharmacokinetic model. It is suggested that saturation of styrene clearance is due mostly to saturation of the metabolic capacity for styrene. In humans exposed to 80 ppm of styrene for 6 h, styrene was cleared from the blood according to a two-compartment linear pharmacokinetic model similar to that for rats. A maximum blood concentration of 0.9 microgram/ml was reached at the end of the exposure. Most of the inhaled styrene was excreted in the urine as phenylglyoxylic and mandelic acids, and only a small amount as styrene in the expired air. Simulation of the pharmacokinetic model showed that no continued accumulation of styrene would occur during repeated, daily 8-h exposures to 80 ppm. These data reveal that the rat is a reasonable pharmacokinetic model for styrene in humans. At levels of exposure up to 200 ppm, styrene is cleared from the body very efficiently and will not continue to accumulate upon repeated exposure. But at levels of styrene sufficiently high to saturate the metabolic clearance capacity, the integrated dose (measured by the AUC) will be much greater than expected based on exposure levels alone. Therefore, the extrapolation of toxicity observed at high levels of styrene exposure to that expected at low levels may not be justified.


Styrene, its metabolism and the evaluation of hazards in industry. The main products of styrene biotransformation excreted in human urine are mandelic and phenylglyoxylic acids. Phenylethylene oxide seems to be the first metabolite; this compound has been reported to be mutagenic and carcinogenic. The polarographic determination of mandelic acid has been used for about 20 years in Czechoslovakia as an exposure test for persons occupationally exposed to styrene. Only single cases of health damage have been reported to be due to styrene exposure during this time. Recently, however, elevated frequencies of chromosomal aberrations in peripheral lymphocytes have been observed in persons exposed to styrene in Czechoslovakia. The amount of phenylethylene oxide that can be formed in the human body during exposure to 50 ppm of styrene in air during a workshift is about 0.7 g. It would be hardly justifiable now to believe that styrene is not carcinogenic and mutagenic in man. The present Czechoslovakian maximum allowable concentration of styrene (200 mg/m3) should be reduced, and the concentration of 50 mg/m3 may be recommended as reasonable at this time. The corresponding biological limit value of mandelic acid might be 300 mg/l of urine from the last 2 h of the workshift.


[Neuropsychiatric manifestations in patients with systemic lupus erythematosus]. Psychological and neurological assessment of patients with systemic lupus erythematosus has identified 15 with definite evidence of non-focal cerebral involvement. During the period of neuropsychiatric disease, cerebral blood flow was measured using 15O2 brain scans and sera were tested for the presence of 2 brain-reactive antibodies: antineuronal and lymphocytotoxic antibodies. 12 patients had psychiatric symptoms, while 13 had various neurological abnormalities. Striking abnormalities in cerebral blood flow were observed in 12 patients. All sera contained at least one brain-reactive antibody; 13 contained antineuronal antibody, although there was an inconsistent association between clinical features and antibody titre, while 12 contained lymphocytotoxic antibodies. According to these investigations the nature of the neuropsychiatric abnormalities would depend on both vascular and immunopathogenic mechanisms.


[Influence of hormonal contraception on serum lipoproteins]. Cholesterol and triglyceride measurements in lipoproteins (VLDL, LDL, HDL) separated by preparative ultracentrifugation showed that women aged 20 to 29 using oral hormonal contraceptives had increased LDL triglycerides without significant changes in serum lipids. Among older women (aged 30 to 39), changes induced by hormonal contraception were more pronounced. Triglycerides were increased in VLDL and LDL, with a significant rise in serum triglycerides. The LDL cholesterol was elevated without significant changes in serum cholesterol. None of the women had overt hyperlipoproteinemia. Routine serum cholesterol and triglyceride measurements may not reveal the changes in cholesterol and triglyceride lipoprotein content which may play a role in the increased incidence of cardiovascular disease among women using the "pill".


[Successful embolectomy of the superior mesenteric artery]. Successful embolectomy of the superior mesenteric artery in a 75-year-old man is reported. The decisive points in early diagnosis are discussed and the specific diagnostic methods for the correct decision are presented. The fulminant evolution of the disease leaves little time in which to decide. Early embolectomy brings about complete cure. It is a life-saving operation and there are no contraindications.


[Blood pressure determination in children: normal values for a given age group]. Blood pressure was measured under standardized conditions in 151 first-grade schoolchildren. The values of this small sample were normally distributed and statistical analysis was therefore performed. The systolic blood pressure of boys and girls was 102.0 +/- 9 mm Hg and the diastolic blood pressure 69.5 +/- 7.3 mm Hg. Boys and girls were also analyzed separately. The data fit in very well those from the literature, and it is concluded that the values from the literature, especially those of the "Task force of blood pressure control", can be used with high probability for Berne and Switzerland as well. Additional findings: The skin thickness of all children and of girls correlates with blood pressure in the normal range. The family history with regard to risk factors is probably only of importance if precise questions are asked, since general inquiries about obesity, myocardial infarction, and hypertension did not yield useful results.


[Treatment of chronic renal insufficiency by hemofiltration. Clinical experiences during the first year of utilization in Geneva]. Seven ESRD patients were treated by hemofiltration (HF) for 3--4 months using an experimental HF machine and RP6 filters (Hospal). Ultrafiltration flow was 56--85 ml/min. Data of this treatment period were compared with a similar period of customary hemodialysis (HD). With HF, blood creatinine was identical but BUN was higher than with HD. Hematocrit, plasma sodium, potassium, bicarbonate, calcium, phosphorus, alkaline phosphatases, uric acid, and cholesterol did not differ during the two periods. HF did not produce a significant lowering of blood pressure. Clinical tolerance was markedly better with HF.


[Biology of breast cancer: current approaches to new treatment modalities]. After years of progress, there appear to be few new developments in the treatment of breast cancer at the present time. Aspects of breast cancer are discussed which might offer new therapeutic possibilities. The rather schematic management of the patient with breast cancer is less than well matched with the variable biology and the multitude of factors influencing risk and prognosis. Epidemiological, hereditary, and environmental, as well as endocrinological, immunological, and psychoneurological variables are believed to determine the spontaneous course of the disease and the therapeutic results. One way of improving treatment results is better evaluation of such biological factors in a given patient and variation of treatment plans according to individual needs.


[Incidence of lactose intolerance in postmenopausal osteoporosis]. The incidence of lactose intolerance was determined in 31 women with idiopathic postmenopausal osteoporosis. Nine subjects exhibited a pathological rise in blood glucose (less than 20 mg/100 ml) after receiving 50 g lactose. The absorption of glucose and galactose, xylose, and fat was normal in the 31 patients. Daily intake of calcium was below the normal range in 3 subjects with and in 6 subjects without lactose intolerance. The association between lactase deficiency and osteoporosis is stressed.


[Course and prognosis of reflux disease under conservative and surgical treatment]. Radiology, endoscopy and function tests were performed in 30 patients with primary reflux disease. Follow-up examinations were performed 3.2 +/- 1.5 years later. Esophagitis was more frequent in men. Severity of esophagitis correlated neither with the duration of symptoms before diagnosis nor with the results of function tests. Neither esophagitis nor function tests allowed a prediction on the long-term severity of symptoms. Episodic symptoms were more frequent in patients with esophagitis and constant symptoms more frequent in those without esophagitis. The indication for conservative and surgical treatment mainly depended on chance. Good therapeutic results were obtained in only 11 of 17 patients undergoing conservative treatment and in 9 of 13 patients undergoing surgical treatment. 6 patients of the surgical group had postfundoplication symptoms. Thus, the results of conservative and surgical treatment were quantitatively similar and rather disappointing.


Chlorinated aromatic hydrocarbons in fish from an area polluted by industrial effluents. The content of chlorinated fat-soluble aromatic hydrocarbons was determined in fish from an area polluted by industrial effluents. The fish species investigated were selected among those used for human consumption. For some samples, both the fillet and liver were investigated. For others the whole fish was used. The following compounds were analysed and quantified: Trichlorobenzene, tetrachlorobenzene, pentachlorobenzene, hexachlorobenzene, heptachlorostyrene, octachlorostyrene and polychlorinated biphenyls. The results idicate an appreciable accumulation in fish of the higher chlorinated compounds as pentachlorobenzene, hexachlorobenzene, heptachlorostyrene and octachlorostyrene. Other chlorinated hydrocarbons as decachlorobiphenyl, pentachloronaphthalene, hexachloronaphthalene and hexachlorostyrene were identified, but not quantified. The total content of fat-soluble chlorine was determined in some samples before and after sulphuric acid treatment. The content of chlorine in the identified and quantified compounds accounted for between 40 and 100 per cent of the total amount of chlorine present in the samples as persistent (sulphuric acid resistant) compounds.


Studies on the synthesis of polynucleotides--synthesis of a dodecaribonucleoside undecaphosphate and a hexadecaribonucleoside pentadecaphosphate. This paper describes the synthesis of oligoribonucleotides by T4 RNA ligase and their identification. The products are a dodecaribonucleotide CpGpGpA32pCpUpCpGpUpCpCpA and a hexadecaribonucleotide ApUpUpC32pCpUpCpGpUpCpCpA, representing the 3'-end nucleotide sequences of the yeast alanine transfer RNA. Particular emphasis was placed on the conditions for the joining reaction, using oligoribonucleotides of defined sequence as the substrates. CpGpGpA32pCpUpCpGpUpCpCpA was synthesized with 32pCpUpCpGpUpCpCpA as the donor, and CpGpGpA as the acceptor in rather low ratio of acceptor to donor. Both the yield and purity of the joining product were above 90%. 32pCpGpGpA32pCpUpCpGpUpCpCpA was used in turn as the donor, and ApUpUpC as the acceptor for further synthesis of the hexadecaribonucleotide ApUpUpC32pCpGpGpA32pCpUpCpGpUpCpCpA with a yield of 60%.


Campylobacter infections. First reports from Red Cross War Memorial Children's Hospital, Cape Town. We report 10 cases of Campylobacter fetus infection, isolated during a 7-month period, which were all sensitive to erythromycin. The aetiology and epidemiology are discussed.


Dermal micro-angiopathy in patients with analgesic nephropathy. Skin biopsy specimens of 10 patients suffering from analgesic nephropathy revealed a micro-angiopathy similar to that seen in the kidney and urinary tract of patients with this disease. It is considered to be part of a disseminated micro-angiopathy. Similar changes were not observed in normal controls or in patients suffering from chronic renal disease due to other causes.


Tear-deficient keratoconjunctivitis. Clinical diagnosis of a common eye problem. A chronic keratoconjunctivitis that is common under dry climatic conditions is described. A characteristic biomicroscopical appearance of the eye was found in 29 healthy patients with red, uncomfortable eyes and abnormal tear function. A diagnosis of tear-deficient keratoconjunctivitis can be made on the basis of these findings and treated effectively.


Some clinical aspects of geriatric surgery. The relative frequency of surgical problems in the aged is discussed and some statistics based on experience are given. General rules in the management of the aged are suggested and the situation is analysed with stress on biological age and past influences. The increased importance in surgery of fluid loss as well as shock is discussed. A regimen for fluid replacement therapy is suggested. Problems in history-taking and the investigation of the elderly surgical patient are debated, and the value of ice as an anaesthetic agent for geriatric patients is discussed. Points about postoperative care are made. The problem of emergency surgery in the elderly, with emphasis on conservatism, is set out. The importance of avoiding complications, of reassurance and of optimism is stressed.


Precise biopsy investigation of the kidney using computed axial tomography. Computed axial tomography (CAT) allows pinpoint renal localization for percutaneous renal biopsy. A method for using CAT is described. This method may also be used for accurate localization of masses in the retroperitoneal space, lung, kidney, liver, bone or pancreas.


Fatal jaundice in pregnancy.

Fatal jaundice in pregnancy. An epidemic of jaundice in pregnancy is described. The mortality during the first 2 years was 45%, but decreased as the epidemic waned. Biochemical, social and epidemiological investigations revealed that the cause was probably the hepatitis group A virus. No previous epidemics appear to have occurred in South Africa.


Hypnotherapy for the child with chronic eczema. A case report. Chronic eczema in a child usually produces much discomfort and distress. Associated behaviour problems further complicate the issue. A comprehensive approach to treatment is therefore essential. Hypnotherapy may be a useful adjunct in the overall management. An illustrative case history is presented. Combining hypnotherapy with child guidance and medical treatment led to the relief of symptoms and improved behavioural pattern in a boy aged 10 years.


Acute renal failure among Blacks and Indians in South Africa. This study of 150 patients suffering from acute renal failure (ARF) showed that the cause was medical in 98 patients, gynaecological in 26, surgical in 15 and obstetric in 11. In contrast to the findings of similar studies in Europe and the USA, the commonest medical causes of acute renal failure were nephrotoxins (mainly from herbal medicine) and infections. The commonest gynaecological cause of ARF was self-induced abortion. The relevant clinical and biochemical features are described. The overall mortality was 35%. Adverse factors affecting prognosis were septicaemia, jaundice, the cause of the ARF, and delay in beginning dialysis. While financial costs may prohibit the establishment of renal units for the treatment of chronic renal failure in many parts of Africa, ARF may easily be treated.


Forward progression of spermatozoa. Standardization of results. The principal aim of this study was to determine whether subjective estimations of sperm velocity in our laboratory could readily be translated into objective figures. The technique for measuring the progression of human spermatozoa in seminal plasma in objective fashion was the one used by Janick and MacLeod in 1970. We therefore compared our objective figures with those of these authors and found a remarkable correlation between their values and ours. However, we went a step further and standardized the different objective values found in the study. Three simple equations were determined, by means of which each laboratory will be able to standardize their subject scale for forward progression of the spermatozoa.


Exocrine pancreatic function in patients with idiopathic necrosis of the femoral head. Exocrine pancreatic function after secretin and cholecystokinin stimulation was examined in a group of patients with idiopathic necrosis of the femoral head and in a normal control group. The volume output, bicarbonate and amylase concentrations in the patient group were not significantly lower than in the control group. Taken individually, however, 3 out of 8 patients with idiopathic necrosis of the femoral head had abnormal pancreatic function tests. In 4 patients there was a significant alcohol intake, with a history suggestive of acute pancreatitis in 2. This suggests that in some patients chronic pancreatitis may be a factor in the pathogenesis of idiopathic necrosis of the femoral head.


The five-year survival rate in urban patients with ovarian carcinoma. The 5-year survival of 253 patients with ovarian malignancy of epithelial origin is reviewed. Although this is closely related to the clinical stage at presentation, the overall survival is poor, because the majority present with disease which has spread beyond the pelvis. There are more deaths in the first 2 years after diagnosis; thereafter the survival curve gradually flattens off and becomes almost horizontal during the 4th and 5th years.


Postpartum insertion of the combined multiload copper intra-uterine device (M L Cu 250). The results obtained from postpartum insertion of the combined multiload copper intra-uterine device (M L Cu 250) are presented. The study was prompted by a pilot study in the Netherlands which showed that few expulsions occurred with "postplacental" insertion of the multiload intra-uterine device. Seventy-five patients had devices inserted between 6 and 72 hours postpartum, and the patients were followed up for 6 months after insertion, with an overall continuation rate of 77,6%. This study showed that the postpartum insertion of this device is a safe and acceptable form of contraception, particularly in patients who are unlikely to continue with other forms of contraception.


Clinical and haematological problems associated with severe abruptio placentae. A clinical study was done of 80 patients in whom abruptio placentae was severe enough to cause intra-uterine death of the fetus. Central venous pressure pressure was measured when ever possible to ensure adequate fluid replacement. Although the minority of the patients were shocked when admitted, blood replacement averaged 5 units per patient. The caesarean section incidence was 21%. Only 1 patient developed renal failure for which peritoneal dialysis was done. No maternal deaths occurred. Serial coagulation studies were done in 58 patients. Diffuse intravascular coagulation was present in the majority. After delivery of the fetus, however, tests became normal.


Fetal heart rate changes associated with standard, segmental and modified segmental epidural block. Three different techniques for epidural block were used and compared in an attempt to lower the incidence of fetal heart deterioration patterns occurring after the block. Segmental epidural block allowed of lower dosages of bupivacaine, but only when the patient knelt on all four was it possible to eliminate post-block fetal heart deterioration completely.


An evaluation of routine midtrimester ultrasonic scanning. In a 2-year period 1,987 patients had a combined ultrasonic A and B scan between 16 and 30 weeks' gestation. The ultrasonic assessment of gestational age was shown to be more accurate than a definite menstrual history in 19,5% of patients using parameters of birth weight for gestation and the time of onset of spontaneous labour. All 31 sets of twins in the series were diagnosed at the first scan. There were 2 perinatal deaths among the twins, a perinatal mortality of 3,2%. Four unsuspected anencephalic fetuses were diagnosed and these pregnancies were terminated before 28 weeks. Two unsuspected molar pregnancies were diagnosed and evacuated. There were 58 false-positive diagnoses of placenta praevia, and 2 cases were missed. The situation of the placenta as revealed by ultrasound bore no relationship to abruptio placentae, but there was a significant relationship between a low-lying placenta and a history of threatened aboriton.


A survey of obstetric anaesthesia in the Republic of South Africa and South West Africa. In this report we analyse the results of a questionaire sent to 341 hospitals throughout the Republic and South West Africa, asking for details of their caesarean section rate and obstetric anesthetic techniques used. Non-specialist practitioners provided 90% of anaesthetic services in the 131 (38,4%) hospitals from which replies were received. General anaesthesia was used in preference to regional anaesthesia in 90% of these hospitals. Of the institutions surveyed, 24% used neither stomach emptying nor antacid therapy pre-operatively. These and other results pertaining to their choice of anaesthetic agents and techniques are presented and discussed.


Advantages of left over right lateral tilt for caesarean section. The relative merits of right and left lateral tilt were assessed in 75 parturients at elective caesarean section. Significant maternal hypotension (aortocaval occlusion) occurred more frequently with rightward tilt (left hip supported). The clinical and biochemical status of the fetus was generally more favourable with left lateral tilt, as were the maternal-to-fetal blood gas gradients and relationships. The routine use of left lateral tilt is advocated.


The safety of amniocentesis in relation to site and method. A method of low suprapubic amniocentesis after elevation of the fetal head during vaginal examination has been found to be a safe and valuable obstetric procedure. The incidence of the only complication in 1 362 consecutive amniocenteses, viz. rupture of the membranes, was similar to the spontaneous rate and could well be unrelated to the procedure. Failure to obtain amniotic fluid occurred in 13 patients and in a further 18 patients the amniotic fluid was blood-stained. High, peri-umbilical amniocentesis without ultrasonic control is not justified in obstetric practice because of the possible complications.


The association between measured and clinically assessed amniotic fluid volume and fetal growth and nutrition. A close correlation was found between amniotic fluid volume measured by using para-aminohippuric acid and the clinical assessment of volume. No correlation was found between measured amniotic fluid volume and fetal weight, length, or weight for gestational age.


Reversal of active labour. A case report. The clinical course of primiparous patient who presented in premature labour at 31 weeks' gestation is described. Cervical dilatation was reversed from 9 cm and pregnancy continued for 6 days. The possible causes and mechanism are discussed and the implications are considered.


Combined congenital diastasis of the inferior tibiofibular joint with contralateral distal femoral bifurcation and hemimelia of the medial structures. A case report. A case of congenital bilateral lower limb deformities is presented. Diastasis of the distal tibia and fibula has the appearance of a severe clubfoot. Recognition of this condition and early surgical treatment are important. Tibial aplasia is best treated by disarticulation and early mobilization.


Low back pain as the presenting symptom of renal artery aneurysm. A case report. Hypertension of recent onset in a 29-year-old woman was associated with low pain radiating to the right groin. Angiography showed the presence of a large aneurysm of the right renal artery. Resection of the aneurysm and nephrectomy cured the hypertension.


Some clinical and cultural correlates of violent death. Forty-one patients admitted to hospital over a 5-year period because of charges arising from their having caused a violent death were studied. Data pertaining to the victim, the weapon used and the locality are analysed. The diagnostic categories for the patients are set out and the course and outcome are followed. Implications for future management are discussed, with particular reference to relevant social and cultural factors.


Buccal smears and numerical sex chromosome anomalies. The results of buccal smear examinations of patients in five institutes for mental retardates, a psychiatric hospital, a home for physically handicapped children, two schools for the deaf, a normal primary school and a newborn nursery are reported. Extra X chromosomes were found in 4/1 000 mentally retarded males, in 1,8/1 000 mentally ill patients and in 1,3/1 000 newborn females. Extra Y chromosomes were found in 1,5/1 000 males, and 3,6/1 000 males were noted to have non-fluorescing Y chromosomes, a normal variant.


[The role of chromosomes in the aetiology of human abortion]. Of 27 specimens of abortus tissue from first-trimester spontaneous abortions investigated, 26% had chromosome abnormalities. In contrast, the investigation showed that the incidence of chromosome abnormalities in 36 midtrimester cases was only 2,8%. Two of 19 ectopic pregnancies had abnormal chromosome complements.


Pellet gun injuries of the eye.

Pellet gun injuries of the eye. A nationwide survey of pellet gun injuries to the eye, sustained over a 5-year period, was carried out. Eighty-seven cases were reported. Seventy-seven per cent were found to have a final visual acuity of 6/60 or worse on the Snellen chart. The pathological findings and possible steps to reduce the incidence of these injuries are discussed.


Impact of inflation on private pensions of retirees, 1970-74: findings from the retirement history study. Many private pension plans have provided benefit increases or other forms of protection against inflation to their retired workers in recent years. This article, based on panel data from the Retirement History Study, examines the extent to which completely retired persons in their sixties benefited from these increases from 1970 to 1974. The private pension benefits of retirees rose slightly during the period, but their purchasing power declined sharply on account of the considerable growth in the inflation rate. Social security benefits, on the other hand, rose substantially more than the consumer price index. As a result, total retirement benefits largely maintained or nearly maintained their purchasing power.


Response to recipiency under public assistance and SSI. This research focuses on the attitudes, perceptions, and program preferences of aged and disabled persons who received public assistance in 1973 and supplemental security income payments in 1974. The Social Security Administration gathered the data in a nationwide survey of the low-income aged and disabled. Most respondents did not feel embarrassed or bothered about receiving public assistance in 1973 and were generally satisfied with their treatment by the welfare agency. Response to SSI in 1974 was even more favorable. Satisfaction with agency performance remained at a high level and feelings of embarrassment generally declined. SSI was preferred over public assistance by most respondents. Administrative efficiency and the size of cash benefits apparently were more important considerations than the degree of stigma perceived.


Burn rehabilitation-a team approach.

Burn rehabilitation-a team approach. The team concept in the treatment of burned patients is an effective approach in caring for the physical, psychological, and social needs of the patient. Through the initiation of early rehabilitation services, long-term problems can be prevented and a quicker return to a meaningful life style is possible.


Problems and complications of burn shock resuscitation. The problems and complications of the fluid resuscitation phase of the treatment of major thermal burns are many and varied. Emphasis has been placed on the most important organ system responses commonly observed in the first week after injury. The efficacy of treatment and the lack of available treatment are outlined. The mechanical complications occurring from poorly selected and monitored fluid administration sites, complications of monitoring, problems of constrictive edema (usually in the extremities), airway problems, respiratory care, and innumerable other technical aspects were purposely omitted. While these problems and complications are extremely important and occur commonly in our experience, they are in the realm of technical performance of good emergency and intensive care medicine and their optimal management does not affect the problems and complications of the residual organ systems.


Carbonic anhydrase inhibition in glaucoma: hazard or benefit for the chronic lunger? Carbonic anhydrase inhibitors, of proven value in the longterm management of glaucoma, have a number of troublesome side effects, most of which are well-known. However, their potential hazards to patients with chronic obstructive lung disease have received little attention. The author reviews the physiological effects of carbonic anhydrase inhibition on carbon dioxide metabolism and the implications for the chronic lung patient. The untoward pulmonary complications associated with the use of carbonic anhydrase inhibitors are of particular importance to ophthalmologists, since chronic lung disease and glaucoma, both common disorders in the elderly, frequently coexist in the same patient.


A simplified stimulus value notation using preferred stimulus combinations for Goldmann quantitative perimetry. In an effort to return to the simplicity intended by Goldmann, the authors propose adoption of a two-digit stimulus value (SV) nomenclature for defining targen area luminance and contrast on a properly standardized Goldmann-type perimeter. The system is designed to aid the examiner in target selection, mental interpolation and isopter construction, and to facilitate computer manipulation.


Neuro-ophthalmologic dilemma: chronic optic neuritis? A patient with an 8-month history of chronic progressive visual loss was referred to the Neuro-ophthalmology Consult Office of Washington University with a diagnosis of chronic optic neuritis. Previous diagnostic studies, including CAT scan, had been negative. Because chronic progressive visual loss is considered a hallmark of mass lesion, more vigorous investigation, including repeat CAT scans, was undertaken, leading to the diagnosis and removal of a 2 cm meningioma.


Improved lensometry with a programmed calculator-lensometer combination. The arithmetic associated with prescription calculation seems to be the major source of error and inefficiency in the performance of traditional lensometry. We have found that a programmed calculator used in combination with a lensometer achieves greater accuracy in less time than does the lensometer alone. This approach may be a useful alternative to the physician who does not wish to make a substantial investment in a fully automatic device.


Thromboplastin calibration. Experience of the Dutch reference laboratory for anticoagulant control. Standardization of the thromboplastin most commonly used for anticoagulant control in The Netherlands has been achieved by the Dutch Reference Laboratory for Anticoagulant Control. The system established for control indicates the performance characteristics of each batch of thromboplastin in patients relative to a national calibration batch. Calibration constants were assessed according to an ICTH/ICSH proposal and with a reproducibility of approximately 2% (CV). With the use of a given calibration constant of the International Reference Preparation of Thromboplastin (1.0) and after assessment of the calibration constant of the National Reference Preparation in international terms (0.93), the accuracy of calibration with the various modifications of the calibration procedure is of the order of magnitude of 3% (CV). On the basis of the calibration protocol, physicians will be provided with correlation tables containing, for their convenience, prothrombin (thromboplastin) times in terms of the reference thromboplastin (uniform, i.e., batch-independent, prothrombin times), conventional prothrombin activity (percentages), and in due course with International Calibrated Ratios. With this approach current practice in the prescription of oral anticoagulants will be maintained. Opportunity is given, however, to aim at internationally proposed therapeutically optimal target values.


The abnormal factor IX of hemophilia B+ variants. A rather large proportion of the hemophilia B patients can be characterized as hemophilia B+ because of the presence in their plasma of a protein which is immunologically identical with human factor IX. In a group of 33 hemophilia B patients we found 14 cases of hemophilia B+ belonging to 11 independent pedigrees. The variant factor IX molecules of these families have been compared with respect to the following properties: 1) factor IX activity and its dependence on phospholipid concentration; 2) factor IX antigen; 3) prolongation of prothrombin time with an ox brain thromboplastin; 4) electrophoretic mobility; 5) Ca(+) binding capacity; 6) affinity for binding to heparin and 7) susceptibility of the factor IX antigen to contact-induced activation. In the study of these parameters the use of a precipitating antibody against highly purified human factor IX showed to be of great value. According to our criteria at least 7 different factor IX variants were present in the 11 families with hemophilia B+ studied. Because of this rather high heterogeneity a suitable nomenclature for subclassification of hemophilia B+ variants is proposed.


The binding of calcium ions to bovine factor X by rate dialysis. The binding of Ca+2 to bovine factor X (molecular weight of 74,000) (Yue und Gertler 1977) was studied by the technique of rate dialysis and with the use of 45Ca+2. The binding data are consistent with a model of sequential mechanism. One mole of Ca+2 binds to the glycoprotein with a dissociation constant of 5.2 X 10(-5) M and additional 39 +/- 4 moles of Ca+2 bind to this zymogen with a dissociation constant of 3.7 X 10(-3) M. The binding of the high affinity Ca+2 causes a functionally significant change in the zymogen, and (calcium) (factor X) complex is the real substrate in the activation process by the protease in Russell's viper venom.


Heparin from intestine and lung source administered in large dose to dogs with acute myocardial ischemia. Similar and dissimilar effects on electrocardiograms and adenosine triphosphate. Intestinal mucosa heparin (IMH) and beef lung heparin (BLH) were infused into dogs subjected to myocardial ischemia by intermittent coronary artery occlusions. The IMH was from a mixture of beef, sheep, and pig intestinal mucosa. Initial control occlusion and recovery was followed by a second occlusion with 60,000 units of IMH or BLH added. Electrocardiographic S-T segment elevations (ST) were measured acutely. There were no significant differences in ST in non-ischemic myocardium before occlusions or with occlusions. In ischemic myocardium, IMH significantly lowered control ST 84% in amount (t = 6.1 p less than 0.00005), and 76% in number (t = 11.6 p less than 0.00001). BLH lowered control ST a significant, lesser, 36% in amount (t = 3.6 p less than 0.008), and 35% in number (t = 3.2 p less than 0.01). The difference between IMH and BLH in ischemic myocardium was a significant adenosine triphosphate (ATP) levels were assayed after 90 min. ATP levels were 31% higher in both ischemic and non-ischemic myocardium in IMH-treated dogs than in BLH-treated. It was concluded that IMH and BLH are functionally different, and IMH was significantly more effective.


Heparin-neutralizing activity, total progressive antithrombin and ethanol gel test in acute chest pain. 92 patients admitted to a cardiac monitoring unit with chest pain were investigated. The mean heparin-neutralizing activity of the 34 patients with severe myocardial infarction was found to be significantly different from the mean of 70 normal controls. However, there was considerable overlap between individual observations and the normal range. Only 5 of the 34 patients with severe myocardial infarction had antithrombin levels outside the normal range. In patients with a severe myocardial infarct tested on the 2nd and 3rd day after infarction there was s significant increase in the number of positive ethanol gel tests compared with the other patients studied.


The effects of a combined alpha- and beta-blocking drug, labetalol, on some aspects of platelet function. The effects of the combined alpha- and beta-adrenoreceptor blocking agent labetalol on human blood platelets as estimated by platelet aggregation, platelet count, bleeding time and platelet factor 3 activity were studied in 5 patients. The drug reduced adrenaline-induced platelet aggregation in vitro. However, it did not influence the above platelet function test in therapeutic plasma concentrations in vivo.


In vitro and in vivo effects of adrenaline and phentolamine on platelet function. In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions. The threshold concentration (TC) of ADR inducing the typical two-phase response in aggregation tests when added to platelet-rich plasma (PRP) varied in different pools of plasma, but always induced an evident PF4 release and increased PF3 availability. A further increase in both parameters was obtained with higher concentrations but without any significant dose/response correlation. Adding PHEN alone to PRP did not induce platelet aggregation or modify PF4 release induced by stirring, but it reduced PF3 availability. On the other hand, PHEN prevented the effects of ADR in different platelet tests, at appropriate concentrations. Intravenous infusion of ADR lowered the TC, and increased PF3 availability and PF4 release. In vivo administration of PHEN, in contrast, increased TC and reduced PF3 availability, while PF4 remained unchanged.


[Difference in susceptibility to mastitis between the Dutch-Friesian and Meuse-Rhine-Yssel breeds of cattle (author's transl)]. A randomized study in the Netherlands showed that symptoms of mastitis were more common in animals of the Meuse-Rhine-Yssel breed than they were in those of the Dutch-Friesian breed. The samples were taken at random from large groups of animals (approximately 10,000) of the dairy cattle population in the Netherlands, quarter samples being examined for the presence of the causative organisms of mastitis and cell counts being made. Differences between the two breeds were also observed in herds on the experimental farm "'t Gen" on which the animals were reared and kept in the same environment. Therefore, there is some justification in defining these differences as genetic. The results of the studies suggest that a group of animals showing lower cell counts during the first lactation will be less susceptible to mastitis. Studies in a cow-house of the Central Veterinary Institute revealed a significant difference in increase of the cell count between animals of the Dutch-Friesian breed and those of the Meuse-Rhine-Yssel breed following intramammary injection of a staphylococcal beta toxin. Further analysis of the results of the randomized study showed that differences in susceptibility to mastitis do not become plainly apparent until later in life. In view of the results of these studies, it would seem advisable to pay more attention to differences in susceptibility to mastitis in stock-breeding.


Secular trends in height and weight of Japanese pupils. In the city of Sendai, the height and weight of pupils at the ages of 11.5 to 12.0 years and 14.5 to 15.0 years have been measured in every spring and autumn since 1936. The analyses of the data summarized for 40 years revealed reduction in physique of the pupils in early 1940's and a marked growth acceleration in late 1940's till 1960's, followed by reduction in secular growth rates in late 1970's. The reduction is more prominent in the core part of the city. The results are compared with those from two extremes in Japan, i.e., megalopolitan areas and remote areas, and also those from European and North American countries.


Urinary excretion of acid glycosaminoglycans and hydroxyproline in a patient with oculo-cerebro-renal syndrome. The metabolism of ground substance in connective tissue of an 18-year-old boy with oculo-cerebro-renal syndrome was studied. He had characteristic clinical and laboratory findings described by Lowe et al. such as growth retardation, mental deficiency, glaucoma, cataracta, decreased muscle tone, metabolic acidosis, aminoaciduria and osteomalacia. The urinary excretion of acid glycosaminoglycans and of total hydroxyproline were 27 mg/day (as glucuronic acid) and 280 mg/day respectively on admission. Both values decreased to the upper limits of normal level transiently during treatment with alkali and vitamin D2. At that time, an improvement in bone abnormalities, a decrease of serum alkaline phosphatase, and an elevation of serum inorganic phosphate were observed. The therapy prevented him from progressive osteomalacia and cured him of it, but mucopolysacchariduria and hydroxyprolinuria did not disappear. Analytical electrophoresis on cellulose acetate sheets showed that urinary acid glycosaminoglycans were composed of undersulfated chondroitin 4-/6-sulfate and heparan sulfate with a ratio of 6:4, on admission. After oral administration of alkali, the excretion of heparan sulfate decreased and undersulfated chondroitin 4-/6-sulfate was determined as a main component of urinary acid glycosaminoglycans. The clinical and laboratory data in this case suggested that the increased excretion of acid glycosaminoglycans and total hydroxyproline was caused by abnormal metabolism in connective tissues, especially by the bone abnormalities, in this syndrome.


Urinary acid glycosaminoglycans in a patient with oculo-cerebro-renal syndrome. An 18-year-old boy with oculo-cerebro-renal syndrome excreted a large amount of acid glycosaminoglycans in urine. The identification and characterization of the acid glycosaminoglycans were carried out by the methods of preparative column electrophoresis, ion exchange chromatography, gelfiltration, paper chromatography of the chondroitinase digests and chemical analysis. On admission to hospital, the main components of the urinary acid glycosaminoglycans were undersulfated chondroitin 4-sulfate of large molecular weight and heparan sulfate. Three months after oral administration of the supplement of alkali, the excretion of heparan sulfate and the molecular size of chondroitin 4-sulfate decreased significantly, although the amount of urinary acid glycosaminoglycans remained at a high level (about 25 mg/day). The decrease of heparan sulfate and the shift to a smaller molecule of chondroitin 4-sulfate were coincident with the improvement in clinical and laboratory findings. These results suggest that the abnormal metabolism of acid glycosaminoglycans is a characteristic manifestation in this case and the studies on ground substance metabolism might be an important approach to the pathogenesis of this syndrome.


The effect of various hormones on the humoral immune response of murine lymphocytes in vitro. Human chorionic gonadotropin (HCG) and steroid hormones were tested for their direct effects on murine lymphocyte humoral response to sheep RBCs using an in vitro culture system. A significant increase in plaque forming cells (PFC) was induced by the addition of HCG at a dose of either 50 i.u. or 500 i.u. However, no increase was observed by the addition of steroid hormones. HCG may contribute to the success of fetal allografts by increasing the number of blocking antibodies in the early stages of pregnancy.


Early endoscopic features of stomach cancer and its mode of growth. To establish the earliest sign of stomach cancer in endoscopy and to reveal the subsequent morphologic changes of the lesion, we studied retrospectively 41 cases of stomach cancer. The eariest sign  consisted of redness, small polypoid lesions, flat mucosa with slight unevenness and small depressed lesions. There was no clear correlation between the observation period and the size of cancer lesion in cases of early stomach cancer. In cases of advanced cancer, however, the observation period correlated with the size of cancer lesion to a certain extent, and the correlation between the area of cancer (Y cm2) and the observation period (X months) gave a linear equation of Y = 0.68X-3.13.


A new myelin-like laminated body found in two cases of pulmonary alveolar proteinosis. Electron microscopic observations were made on lung tissue, broncho-pulmonary lavage fluid and sputum in 2 cases of pulmonary alveolar proteinosis. Diagnosis was established by open lung biopsy in both cases. In Case 1 the electron microscopic samples were obtained from the surgical specimen. In Case 2 an electron microscopic observation was made only on the lavage fluid and sputum. The alveolar air spaces were full of amorphous or fine granular-appearing material intermingled with two kinds of laminated bodies (abbreviated to "Lamella A" and "Lamella B"). Lamella A, about 0.2 approximately 4 micrometer in diameter, presented a concentric laminated structure with approximately 300 A periodicity and was found in the alveolar air spaces, lung washings and sputum. It corresponded to what has hitherto been reported in the same disease and was always located outside the cells. Lamella B showed a laminated structure of high electron density, approximately 50 A in periodicity, usually looking like a concentric circle with a diameter of 0.5 micrometer or less. It was intensely stained with methenamine silver. It was mainly observed in mesenchymal cells of the alveolar septa and free macrophages in the alveolar air spaces, although it also occurred in the type I and type II alveolar epithelial cells. Furthermore, the Lamella B could be found in the alveolar air spaces outside the cells and in the bronchopulmonary lavage fluid. This body has not been demonstrated previously and, although its significance in this disease is still uncertain, the structural similarity of the Lamella B to the intra-alveolar material suggests a possible role of it in the production of intra-alveolar material.


Effect of estrogen upon the juxtaglomerular apparatus and the renin-angiotensin system in rats. Administration of 1.5 mg/kg of estriol intramuscularly and 15 mg/kg of stilbestrol disulfate intraperitoneally daily for 15 days caused an increase in plasma renin substrate (PRS), accompanied by an increase in plasma renin activity (PRA) and a slight decrease in plasma renin concentration (PRC). Contrary to the slight suppression of PRC, juxtaglomerular granulation index (JGI) was significantly increased in rats treated by estrogen. In the rats which developed hypertension by estrogen PRA, PRC and JGI were a little higher than those in the rats which remained normotensive after the same estrogon treatment, but these differences were not statistically significant. Therefore, it seems rather difficult to attribute the development of estrogen hypertension only to the quantitative changes in the renin-angiotensin system.


Enflurane-induced hypotension modifies transmural blood flow distribution in the canine left ventricle. Coronary and systemic circulations, and contractility and oxygen consumption of the left ventricular myocardium were depressed as arterial enflurane concentration increased in acute experiments with 22 adult mongrel dogs. Uneven transmural blood flow in the left ventricular free wall did not appear and the inner/outer ratio remained near 1.0 until a very deep stage of the anesthesia was attained and as far as diastolic aortic pressure was maintained above 40 mmHg, according to the microsphere injection study. Once diastolic pressure fell below 35--40 mmHg, the ratios started to be reduced significantly. When arterial enflurane content reached 53.0 +/- 2.1 mg/100 ml (mean +/- s.e.), the ratio became 0.84 +/- 0.08 (p less than 0.001), and simultaneously calculated DPTI/TTI ratio also showed a significant redution from the control (0.79 +/- 0.03, p less than 0.001). The I/O and DPTI/TTI ratios, however, did not correlate significantly with each other until very deep enflurane anesthesia was attained. The lower limit of autoregulation of coronary vascular bed was suggested to be near 35--40 mmHg of diastolic aortic pressure during deep enflurane anesthesia in the dog. Among systolic time intervals measured directly during the study, PEP and ICT showed significant negative correlations with Vmax and LV dp/dt max, while LVET neither changed nor correlated significantly with stroke volume or other parameters representing myocardial contractility during the course of enflurane anesthesia.


Morbid changes of the mandible in familial polyposis of the colon. The study was made to ascertain whether the radiographs of the mandible of patients with familial polyposis of the colon show osteomas. Orthopantomography of the mandible was taken in 10 cases of familial polyposis of the colon and 6 cases of the unaffected family members. And radiographic and histological studies were performed in another autopsied case. As a result, radiographic studies revealed sclerotic masses of the mandible in 10 of the 11 cases. In some cases, the changes were also found in the maxilla. The number of sclerotic masses ranged from 2 to 11, and they were associated with odontomas in 2 cases and impacted teeth in one case. Two of the 6 unaffected family members were found to have one or two sclerotic masses. At autopsy of a case died of cancer of the sigmoid colon, a radiographic study of the excised mandible revealed 11 sclerotic masses measuring 5 mm in diameter each, as well as one impacted tooth. A bucco-lingual cross action through the mandible in the canine area revealed central osteomas. Histological examination showed the osteomas were composed primarily of mature, lamellar bony tissue.


Cytologic changes of cervical cancer according to the degree of invasion. Cellular samples (cervical scrapings) obtained with wooden spatulas from patients with carcinoma in situ, early invasive cancer, and advanced cancer of the uterine cervix were examined. The number of malignant cells in the preparation increased with extent of the lesion. The granular chromatin structures of the nuclei of abnormal cells were observed in almost all cases, and the occurrence of irregularly distributed coarsely granular chromatin increased gradually with the extent of the cancer. Hyperchromasia of malignant cell nuclei and irregular thickening of the nuclear envelope were seen in almost all cases of the lesions. The occurrence of malignant and dysplastic cells of the deep layer types decreased with progression of the lesion from carcinoma in situ to early invasive cancer, and to advanced cancer. There was also a relative increase in the ratio of malignant cells to dysplastic cells.


Inhalation toxicity studies on cigarette smoke (VIII). 6-week comparative experiments using modified flue-cured cigarettes: general toxicology. Details are given of studies carried out to compare the inhalation toxicity to rats of smoke from cigarettes modified to give a range of deliveries of particulate matter. Dosimetry work showed that under conditions similar to those used for subsequent toxicity experiments, smoke particulates deposited in the lower respiratory system within the approximate dose range of 500--700 microgram TPM/g lung tissue. Respiratory monitoring showed that the response of animals to a range of smoke exposure conditions was similar and did not change during the course of the experiments. This observation was confirmed by monitoring of blood carboxyhaemoglobin levels after exposure to smoke. During exposure to smoke the rate of respiration decreased to approximately 40% of the pre-exposure rate. Tidal volume, after an initial slight decrease, showed a progressive increase throughout the smoke exposure period. Bodyweight gain was reduced in those animals subjected to smoke exposures. True sham-smoked animals showed a body weight gain intermediate between that of smoke and cage control rats. The clear indications of such between-group differences in response to treatment, coupled with the indicators of consistent dosing of animals under the defined exposure conditions, form a sound basis for the interpretation of terminal pathology.


Teratogenic and dominant lethal studies of patulin in mice. Teratogenicity of daily intraperitoneal (i.p.) injections of 1.5 or 2.0 mg/kg of patulin on days 6 through 17 of pregnancy and mutagenic effects of acute i.p. exposure of 3.0 mg/kg of patulin on male germ cells were evaluated. Resorption of all implanted embryos occurred at 2.0 mg/kg/day of patulin, while a significant reduction in the average body weight of 19-day-old fetuses from patulin-treated mothers, compared to control fetuses, was noticed at 1.5 mg/kg/day without any lethal effects on the implanted embryos. Patulin was embryocidal, possibly fetotoxic but was neither teratogenic nor mutagenic to mice.


The oral toxicity of 1-amino-3-chloro-propanol hydrochloride (CL 88236) in rats. 1-amino-3-chloro-2-propanol (CL 88236) was administered by oral gavage for 12 consecutive weeks to rats at dose levels of 50, 250 and 500 mg/kg/day. All levels gave rise to toxicological effects. Epididymal necrosis and/or atrophy of the seminiferous epithelium was found for some males with each dose of CL 88236. The kidney and liver weights of male and female rats given CL 88236 were higher than control values but no histological changes were found in these organs.


A circadian susceptibility/resistance rhythm for potassium cyanide in male BALB/cCr mice. Circadian rhythms in mortality and/or survival time following a single intraperitoneal injection of a LD50 of potassium cyanide were studied. In two investigations, different but comparable subgroups of inbred male BALB/cCr mice were treated at 4-h intervals (under conditions standardized for chronobiologic study) during 24-h spans. Mice were observed for exact time-to-death during the first hour after treatment as well as overall mortality during the entire 24-h post-injection span following each KCN treatment timepoint. In both studies, mortality from KCN exhibited a 24-h rhythm. Highest mortality occurred in mice injected at 1600 (80% mortality) in Experiment 1 and 2000 (100% mortality) in Experiment II. Lowest mortality occurred at 0400 (40% mortality) in Experiment I and 0800 (30% mortality) in Experiment II. The need to consider the circadian organization of physiologic function when bioassaying toxicity is discussed.


Effect of Di-(2-ethylhexyl) phthalate (DEHP) on chemical constituents and enzymatic activity of rat liver. Effect of Di(2-ethylhexyl) phthalate (DEHP), was investigated on chemical constituents and activity of certain enzymes of rat liver. A significant increase in liver weight; total and relative to body weight; decrease in total, free and esterified cholesterol; and no change in dry weight, moisture; RNA, DNA, total lipids, phospholipids, pyruvic acid and lactic acid contents was observed in liver of DEHP-treated rats as compared to controls. Activity of 3 mitochondrial enzymes, malic dehydrogenase, cytochrome-c-oxidase and diaphorase were significantly decreased while that of NADH-cytochrome c reductase, RNAase and DNAase remained unaltered upon treatment. The results suggest that DEHP exerts its hepatotoxic effects by interfering with bioenergetics of the cell.


Carbon tetrachloride induced ultrastructural alterations in pancreatic acinar cells and in the hepatocytes. Similarities and differences. We found that 14C from 14CCl4 gets covalently bound to rat pancreas and liver microsomal lipids. The intensity of this process in 320 times smaller in the former than in the latter organ. We did not detect any cytochrome P-450 (P-450) or ethylmorphine N-demethylase activity in pancreatic microsomes in contrast to the high content of those components occurring in liver. Similarly, CCl4 induced lipid peroxidation is observed in liver preparations but not in pancreas. There was no evidence for any histological alterations in pancreas 24 h after administration of a toxic dose causing marked cnetrolobular necrosis in liver. CCl4  causes profound ultrastructural alterations in the hepatocytes involving early the endoplasmic reticulum, the Golgi complex and the nuclear envelope and later the entire cell. In selected clones of pancreatic acinar cells we observed an intense dilatation in the rough endoplasmic reticulum and polysome detachment from their membranes, the appearance of myelin figures and occasionally of large autophagic vacuoles. No alterations in other organelles were detected but a slight increase in the number of lipid droplets was observed. CH2Cl2 did not behave similarly.


Effect of oral ethanol administration on choline and ethanolamine phosphorylating activities in liver and brain of mice. The effect of intake of ethanol on choline- and ethanolamine kinase activities in liver and brain tissues of mice was studied over a period of 31 days. With a single dose of ethanol there was an initial slight increase in hepatic kinase activity, while brain kinase activity decreased. The activities returned to the normal level after 21 h. Intragastric intubation of 1 ml of 30% aqueous ethanol daily for 1 month to mice led to a decrease in activity of both enzymes in both tissues.


Long-term toxicity studies on Chocolate Brown HT in rats. Groups of 48 males and 48 female rats were given diets containing 0 (control), 500, 2000 or 10,000 ppm Chocolate Brown HT for 2 years. These treatments had no adverse effect on mortality, body-weight gain, food or water consumption, haematology, renal function, serum constituents, organ weight or histopathology. From the incidence of tumours observed in the control and test animals it is concluded that Chocolate Brown HT did not exert any carcinogenic effect and that the no-untoward-effect level was 10,000 ppm.


A comparison of iron histochemical methods for use on glycol methacrylate embedded tissues. Four histochemical tests for iron and four procedures for its removal were investigated in regard to their suitability for glycol methacrylate embedded tissues. The HCl-ferrocyanide and chlorate hematoxylin methods were easily modified for plastic sections. The latter does not use iron-containing reagents. Desiderization was complete both after a fifteen minute exposure in 1% Na2S2O4 in 0.1 M acetate-HCl buffer (pH 4.5) and, if an acid method is preferred, after twelve hours in 5% oxalic acid. A six hour treatment in 3.7 N H2SO4 also removed all histochemical iron but was accompanied by a relatively greater loss of tissue basophilia.


Heterogeneous negative chemography with human erythrocytes. A negative chemographic effect, or fading of the latent image, has been found in autoradiographic studies of human red blood cells. The effect is heterogeneous, being restricted to a halo-shaped region over each cell.


The in vivo metabolites of [14C] progesterone in bovine muscle and adipose tissue. Muscle and adipose tissue were obtained from steers and dairy cows following subcutaneous administration of [14C] progesterone. Following extraction, purification and separation by column, thin layer and gas-liquid chromatography, various radioactive residues from these tissues were identified by their chromatographic mobility, crystallization to constant specific activity and mass spectra. Progesterone constituted 54% of free radioactivity extracted from muscle and 69 and 73% of radioactivity in the free and conjugated portions of extracts, respectively, from fat. Metabolites identified were: 5alpha-pregnane-3,20-dione, 9%, 0%, 0%, 20beta-hydroxy-4-pregnen-3-one, 8%, 11%, 3%; 3alpha-hydroxy-5beta-pregnan-20-one, 13%, 2%, 2%, 3alpha-hydroxy-5alpha-pregnan-20one, 3%, 3%, 6%; 20 alpha-hydroxy-5alpha-pregnan-3-one, 0%, 2%, 3%; of radioactivity in muscle (free) and fat (free and conjugated fractions), respectively. Tentatively identified in fat extracts by chromatographic mobility were: 20alpha-hydroxy-4-pregnen-3-one, 1%, 1% and 3beta-hydroxy-5beta-pregnan-20-one, 0%, 2% of radioactivity in free and conjugated fractions, respectively. The average concentration of steroid in these animals due solely to treatment, calculated from the specific activity of the [14C] progesterone administered, was 3.4 and 18.1 ng/g in muscle and subcutaneous fat, respectively.


Competitive inhibition of specific steroid-protein binding: practical use of relative competition ratios for the derivation of equilibrium inhibition constants. The relative competition ratio (RCR) is widely used to express the relative affinities of inhibitor(s) and agonist for a binding protein. The RCR is not a constant; it depends on the concentrations of binding sites and of radioactive hormone, and on the presence of nonsaturable binding component(s). According to the assay conditions used, equating the RCR value to the ratio Ka/Ki of the equilibrium association constants of agonist and inhibitor can lead to large errors. In the case of homogeneous non-interacting binding sites, simple correction factors permit one to calculate the ratio Ka/Ki from the measured RCR value. Calculations are given for the eventual contribution of nonsaturable binding components. Corrections can be unnecessary under well defined experimental conditions, where the bound fraction of hormone in absence of competitor is reduced by using a large dilution of binding protein and/or an increased concentration of radioactive hormone.


Intestinal calcium-binding protein (CaBP) and bone calcium mobilization in response to 25R,26 and 25S,26-dihydroxycholecalciferol in intact and nephrectomized rats. Since intestinal calcium-binding protein (CaBP) can be regarded as an expression of the hormone-like action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the duodenal enterocyte we have investigated the potential biological activity of 25R and 25S,26-(OH)2D3 (two recently synthesized epimers of vitamin D3 metabolite) to promote intestinal CaBP production as compared to bone calcium mobilization in vitamin D and calcium-deficient rats. In our assay steroids exhibited a 72 hour calcemic response. Our results show a linear relationship between CaBP synthesis and the logarithm of the dose (130-2080 pmol dose range) of either 25R or 25S epimer. The CaBP response was comparable for both epimers. Similarly bone calcium mobilization response was dose related as a linear function of the logarithm of the administered dose. Again, calcemic response was comparable for both epimers. In our model these two epimers were about as active on intestine to increase CaBP amount as on bone to elevate serum calcium level. Bilateral nephrectomy abolished CaBP response to a large dose (1040 pmol) of either 25R or 25S epimer but did not abolish it to a 130 pmol dose of 1alpha,25-(OH)2D3.


Testosterone and 17-methyltestosterone from hyodeoxycholic acid. The preparation of the title compounds from hyodeoxycholic acid is described. A modified Oppenauer oxidation using alumina in place of conventional alkoxide catalyst is outlined.


The fluorometric assay of rat plasma corticosterone: evaluation of nonspecific fluorescence. An analysis of 168 plasma samples from intact rats, one to 35 days of age, was performed using both brief and specific fluorometric procedures. The amount of fluorescence produced by the brief procedure which could be attributed to corticosterone ranged from a maximum of 72% to a minimum of 16% of the total fluorescence value. Corticosterone represented 50% or more of the brief assay value in only five out of 18 groups of animals assayed. Following statistical analysis of the nonspecific fluorescence, a significant variation was found due to the age of the animal. A highly significant increase in nonspecific fluorescence was found in 21-day old animals following histamine injection. It was concluded that the brief fluorometric assays for corticosterone were of little value if specificity was desired.


Intraocular fate of dexamethasone disodium phosphate topically applied to the eyes of rabbits. After instillation of 3H-dexamethasone into the eyes of a rabbit, 3H-9alpha-fluoro-11beta-hydroxy-16alpha-methyl-1,4-androstadiene-3,17-dione was found in the aqueous humor. The same metabolite was also formed by incubating 3H-dexamethasone with the anterior ocular tissues of rabbit. Identification of 3H-9alpha-fluoro-11beta-hydroxy-16alpha-methyl-1,4-androstadiene-3,17-dione was performed by its mobility on a thin layer plate and by proving its radiochemical homogeneity after recrystallization with the unlabeled sample which had been synthesized from dexamethasone by oxidation with sodium bismuthate. When dexamethasone disodium phosphate was instilled into rabbit's eyes, it was hydrolyzed to free dexamethasone and then metabolized to 9alpha-fluro-11beta-hydroxy-16alpha-methyl-1,4-androstadiene-3,17-dione.


Preparation of 3-epi-ecdysone and 3-epi-20-hydroxyecdysone. 3-Dehydro-ecdysone and 3-dehydro-20-hydroxyecdysone were prepared and characterized. Reduction of these compounds with NaBH4 gave 3-epi-ecdysone and 3-epi-20-hydroxyecdysone, which were characterized fully by mass and p.m.r. spectrometry as well as by derivative formation.


Glucocorticoid inhibition of FSH-induced estrogen production in cultured rat granulosa cells. The effects of glucocorticoids on the steroidogenesis of ovarian granulosa cells were investigated. Cortisol and dexamethasone inhibited the increase in aromatase activity induced by FSH in cultured rat granulosa cells. In the same cultures progesterone production was stimulated to a maximum of 167% of the control level. This differential effect of glucocorticoids on estrogen and progesterone production by the granulosa cells indicates that glucocorticoids exert specific inhibition of the induction of aromatase by FSH and do not cause a general suppression of granulosa cell activity. In contrast to their inhibition of the FSH induction of aromatase enzymes, glucocorticoids did not interfere with the activity of pre-existing aromatase enzymes. In granulosa cells containing full aromatase activity, treatment with cortisol and dexamethasone did not inhibit aromatization of androstenedione to estrogens whereas two known aromatase inhibitors (dihydrotestosterone and 4-androstene-3, 6, 17-trione) were effective. These results indicate that the glucocorticoids exert a selective inhibition of the FSH-induction of aromatase activity in rat granulosa cells by a mechanism other than directly interfering with the aromatization reaction.


5alpha-Cholesta-7,24-dien-3beta-ol as a major sterol of the male hamster reproductive tract. Marked variations in the 3beta-hydroxysterol content of hamster spermatozoa were observed as they progress through the epididymis. Cholesterol is the major sterol of caputal spermatozoa while the concentration of precursors of cholesterol was higher than that of cholesterol in caudal spermatozoa. One of these precursors has been identified as desmosterol. A second sterol has now been identified as 5alpha-cholestra-7,24-dien-3beta-ol by GLC-MS and by NMR. Its concentration is approximately 3-fold higher than that of cholesterol. This 3beta-hydroxysterol is also found in epididymal tissue.


Metabolism of (24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids and 27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid in guinea pigs. [7beta-3H]-(24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids and [7beta-3H]-27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid (C27 and C26 bile acids having the same nuclear configuration as cheno-deoxycholic acid and its precursor, 3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic-acid) were synthesized and administered intraperitoneally to bile fistula guinea pigs. The biliary bile acids formed were hydrolyzed and analyzed by thin layer chromatography, and the metabolites were identified by the inverse isotope dilution method. The results showed that both (24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids were not metabolized by the liver and were excreted unchanged as their taurine and glycine conjugates whereas 27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid was converted to chenodeoxycholic acid.


Steroid metabolism in human breast cancer cell lines. The metabolism of 1,2-3H-androstenedione was studied in 2 cell lines, MCF-7 (estrogen responsive) and BT-20 (estrogen nonresponsive) over 48 hrs. Water soluble and unconjugated metabolites were separated by solvent partition and the former was submitted to chromatography on Sephadex LH-20 and enzyme hydrolysis. The resulting unconjugated steroids were separated by paper chromatography and identities were established by reverse isotope dilution. The unconjugated steroids initially obtained were separated by chromatography and identified by reverse isotope dilution. About 70% of the androstenedione was metabolized by both cell lines. However, the respective conversions to conjugates by MCF-7 and BT-20 were 31% and 0.32%. In the former, glucosiduronates predominated (94%) and consisted of androsterone (55%), etiocholanolone (9.4%) and androstanediol (5alpha-androstane-3alpha,17beta-diol) (9.3%). Androsterone comprised most of the unconjugated metabolites in both cell lines. Androstanediol was found in both cell lines, 2% in MCF-7 and 12% in BT-20. Testosterone, 5alpha-androstane-3,17-dione and 3beta-hydroxy-5alpha-androstan-17-one were isolated only from MCF-7. The metabolism of 3H-estriol was studied in a similar way. Both cell lines produced about equal amounts of estriol-3-sulfate (9%) and a compound with properties of estriol-3-glucosiduronate (0.15--0.5%). The results worthy of emphasis are: 1. The far greater conjugation of androgens exhibited by the MCF-7 cell lines as compared to the BT-20 cell lines; 2. In MCF-7, the high conversion of androstenedione to etiocholanolone (glucosiduronate form), a metabolite reported to form only in liver and sebaceous cysts; 3. The possible formation in both cell lines of estriol-3-glucosiduronate, normally a metabolite of the intestine.


From one generation to the next: changes in fertility, family size preferences, and family planning in an Indian state between 1951 and 1975. Over the last 25 years modernization in Karnataka, India, resulted in a large reduction in infant and child mortality, substantial increases in literacy, and initiation of an intensive family planning program. The drop in the birth rate during this period, however, was much less than would be anticipated under such circumstances. Two surveys carried out in 1951--52 and 1975 provide data on current and cumulative fertility, family size preferences, and knowledge and use of family planning. A comparison of these data leads to the conclusion that the level of family planning activities was not high enough to counteract the increase in the fertility of married women that was a consequence of modernization.


Contraceptive prevalence in Paraguay.

Contraceptive prevalence in Paraguay. Contraceptive use, source of contraception, history of abortion, current pregnancy intention, and fertility rates are evaluated for a national sample of women using data from the Paraguay Contraceptive Prevalence Survey, conducted in 1977. The survey found that 15.5 percent of all women aged 15--44 and 23.6 percent of ever-married women were using effective contraceptive methods. The urban/rural difference in contraceptive use paralleled fertility differentials: over 40 percent of ever-married women were using contraception in Greater Asuncion and other urban areas compared with 15 percent in rural areas. Overall, the data indicate that high-parity rural women have the greatest need for family planning services in Paraguay.


The effects of husband and wife education on family planning in rural Turkey. The effect of two family planning educational approaches--husband-wife and wife-only--on contraceptive knowledge, attitudes, and practice in the Etimesgut Health District are evaluated. Data collected for education and control groups show that husband-wife education was more effective than wife-only education and that wife-only education was more effective than the education received by the control group. Data collected from husbands and wives show that education had a positive effect on changing attitudes toward family planning. Most clear cut are findings that participation of men in the educational programs increased recruitment to the family planning program and decreased contraceptive discontinuation.


Chemotherapy of schistosomal colonic polyposis with oxamniquine. Schistosomal polyposis of the colon is a common complication of schistosomiasis. In severe infections it may be associated with considerable morbidity. Surgery is associated with high morbidity and mortality. Niridazole therapy is of limited therapeutic value because of its hepatotoxicity but oxaminiquine has been found to be effective and safe. Several dosage regimens have been tried but a total dose of 40 mg/kg over two days in two equally divided doses has been found to have an effective therapeutic action on the polypi, with correction of the anaemia, hypoalbuminaemia and serum iron.


Mother-child relation in human schistosomiasis mansoni : skin test and cord blood reactivity to schistosomal antigens. Reaction to schistosomal antigen was studied in children born to mothers infected with Schistosoma mansoni. Values of immediate (15 min) skin reactions were more elevated and values of delayed (24 h) skin reactions were significantly higher in children born to infected mothers than in children born to uninfected mothers. The macrophage migration inhibition test, done on cord blood cells, was positive to schistosomal antigen in 40% of children born to infected mothers and negative in all children born to uninfected mothers. These results suggest prenatal sensitization to schistosomal antigen in children born to mothers infected with S. mansoni.


Studies with Brugia pahangi. 20. An investigation of 23 anthelmintics using different screening techniques. 23 anthelmintics were tested against Brugia pahangi microfilariae and infective larvae in vitro and in Aedes aegypti infected with B. pahagi and jirds (Meriones unguiculatus) infected with a B. pahangi/patei hybrid. There was little correlation between the results obtained in vitro and in infected insects and the results obtained in these tests gave no indication of the activity in jirds. Three of the compounds were macrofilaricidal in jirds and these were tested in cats infected with B. pahangi. One of these--5-benzamido-2(4-thiazolyl)-benzimidazole--was macrofilaricidal in cats and it is suggest that it should be tested in other filarial systems. It is concluded that the insect and in vitro tests are not good primary screens for filaricidal activity.


Echinococcus multilocoularis infection in India: First case report proved at autopsy. The occurrence of Echinococcus multilocularis is reported in India for the first time. The patient was a young man, various clinical diagnoses were made and he finally died after an attempted membranotomy for suspected membranous obstruction in the inferior vena cava. Autopsy revealed classical E. multilocularis infection of the liver with direct spread of the inferior vena cava, the right atrium and through the diaphragm into the base of the left lung. It also had caused an outflow tract obstruction to the hepatic venous flow by direct physical pressure distorting the proximal intrahepatic portion of the inferior vena cava. In addition the patient had multi-valvular lesions of rheumatic origin and a terminal infective endocarditis due to staphyloccal infection.


Efficacy of medical treatment of schistosomal obstructive uropathy as determined by 131I-Hippuran renography. Ten male patients with obstructive uropathy secondary to Schistosoma haematobium and with associated bacteriuria were evaluated with serial urograms, renograms and renal function tests (endogenous creatinine clearance, maximal urinary concentration and total hydrogen ion excretion) before and after medical treatment. The mean duration of follow-up was 4.2 months. Significant improvement was observed in the renograms and the renal function tests while the degree of obstructive uropathy as determined by urography remained essentially unchanged. Thus the renogram can be a more sensitive test for evaluating the efficacy of treatment in patients with schistosomal obstructive uropathy.


Serum and urinary ribonuclease in children with schistosomal hepatic fibrosis. Serum and urinary RNase activity was determined in 15 normal children and in 52 children in various clinical stages of schistosomal hepatic fibrosis. The activity of serum RNase was compared with that of serum GOT, GPT and AP. The activity of serum and urinary RNase in the different schistosomal groups was significantly higher than in healthy children. The elevated levels of serum and urinary RNase activity were possibly due to malnutrition with tissue catabolism, zinc-deficiency and liver cell injury. Treatment with Astiban and protein-rich diet resulted in a significant decrease in serum and urinary RNase activity and an in significant drop in serum GOT, GPT and AP. Serum and urinary RNase appear to be more sensitive indices for evaluating the early metabolic disturbances in schistosomal patients than GOT, GPT or AP. Our findings also showed that the severity of cases could be graded according to the level of urinary RNase.


Sporotrichosis in Sudan.

Sporotrichosis in Sudan. Two cases of lymphocutaneous sporotrichosis are reported from Sudan in a boy aged four and a half years and a girl aged 16 years respectively. Diagnosis was based mainly on the clinical findings and the dramatic response to treatment with oral potassium iodine, as well as the histological finding of yeasts compatible with the yeast phase Sporothrix schenkii.


Stable chimerism induced in noninbred rabbits by neonatal injection of spleen cells from alltoype-suppressed adult donors. II. Distribution of donor and recipient allotypes on blood lymphocytes, in serum immunoglobulins, and in specific antibodies. Long-lasting and stable lymphoid cell chimerism has been noted in three littermates of a group of five rabbits given injections at birth of spleen cells of an allotype-suppressed adult rabbit. The chimeric state manifested itself by the simultaneous display of light and heavy chain markers directed by donor and recipient genotypes in serum immunoglobulins (Ig), on blood lymphocytes, and on antibody molecules made in response to stimulation with three test antigens. Although the genotypes of two of the chimeras were found to be a1a1/b9b9 and the third to be a1a1/b6b9, phenotypically all three were a1a2/b5b6b9. By all of the criteria used to analyze to distribution of allotypes, Ig with the recipients' own allotypes predominated over that controlled by the donor's genotype. With only minor deviations the same proportions of recipient to donor types prevailed in total serum Ig and in the antibody fractions tested.


IGA nephropathy in HLA-identical siblings. This report describes a patient with end stage IgA nephropathy who received a renal transplant from his asymptomatic HLA-identical brother. A biopsy of the donor kidney performed at the time of transplantation showed evidence of widespread electron-dense mesangial deposits. On immunofluorescence these deposits stained with IgA, documenting clinically occult IgA nephropathy in this otherwise healthy donor. These findings are of particular interest in view of the association of IgA nephropathy with the HLA-Bw35 alloantigen, and raise the possibility that asymptomatic disease, already present in a donor kidney, may have accounted for what has previously been called "recurrence" of this disease in renal allograft recipients.


Burns and epileptic fits associated with cysticercosis in mountain people of Irian Jaya. The number of patients with burns, admitted to the hospital in Enarotali, Central highlands of Irian Jaya, New Guinea, Indonesia, markedly increased during the last years. Before 1973 only a few cases were hospitalized whereas from 1973 to 1976 157 cases were admitted. Most of the burns (74.5%) were classified as third and fourth degree burns. Clinical observation and stool examination revealed epileptic seizures, cysticercus-nodules and eggs or proglottids of Taenia in respectively 62.8%, 33.1% and 16.6% of the cases with burns. Among infants, burns were not associated with clinical manifestations of cerebral cysticercosis. In the age group of over 11 years 88 out of 121 cases had epileptic seizures before or during hospitalization. It is assumed that the increasing number of burns during the last years is caused by the high prevalence of cerebral cysticercosis.


Cysticercosis cerebri in Irian Jaya. A case report. A case is presented in which epilepsy was caused by diffuse involvement of cysticerci in the cortical layer of both cerebral hemispheres. The diagnosis was confirmed by histopathological examination. In the area of Irian Jaya cerebral cysticercosis should always be taken into consideration as the possible cause of epilepsy.


The significance of migrant Fulani and human trypanosomiasis in Kainji Lake area of Nigeria. The transhumance-route followed by the Fulani around Lake Kainji area of Nigeria is presented. Between January and February 1977 130 Fulanis were interviewed at different locations. Most respondents were between 20-60 years of age. In addition to cattle rearing, farming is practised among the Fulanis interviewed at Kaiama and Olli. Those interviewed at Faku practised pastoral transhumance. Less than 15% of the respondents had previous knowledge of human sleeping sickness. Although examination of blood films (thin and thick) did not reveal any blood trypanosome, the transhumance pastoral mobility will be an important factor in any outbreak of human trypanosomiasis around Kainji Lake area in future.


Toxoplasmosis among the Ticuna Indians in the state of Amazonas, Brazil. Results of a serologic survey for Toxoplasma gondii among 408 Ticuna Indians from five villages in western Brazil are presented and compared with the results of 61 non-Indian inhabitants of the town of Codajas, Amazonas. Indirect hemagglutination antibody titers greater than or equal to 64 were found in 39% of the Ticuna population as compared to 77% of the Codajas population. Prevalence rates of titers greater than or equal to 256 were 20.3% for Ticunas and 39.3% for Codajas. Prevalence rates of titers greater than or equal to 256 in Ticuna villages where dietary habits were most variable were higher and more similar to those of non-Indian populations than were the prevalence rates of this titer range in villages where the animal food source was predominantly fish.