The clinical course of mesangial proliferative glomerulonephritis. Patients with a pure mesangial proliferative glomerulonephritis may present with either hematuria, asymptomatic proteinuria, or nephrotic syndrome. For patients with hematuria, the clinical course is self-limited, and spontaneous resolution of recurrent episodes of macroscopic hematuria occurred in many of these patients. For patients with asymptomatic proteinuria, a spontaneous decrease in proteinuria occurred and none of these patients developed a progressive course. The clinical course of patients with nephrotic syndrome was similar to that usually observed in children and adults with pure minimal change lesions. A complete remission of the nephrotic syndrome occurred in most of these patients during treatment with prednisone and cyclophosphamide. Overall, the prognosis for the patients reported in this series was quite good.


Acquired C1 esterase inhibitor deficiency and angioedema: a review. A case of acquired C1INH deficiency with angioedema is described. Fifteen cases are thus far recorded. The clinical syndrome of angioedema in these patients closely resembles hereditary angioedema (HAE). Most cases are associated with a paraprotein, cryoglobulin, or autoantibody, which presumably initiates C1 activation and C1 Inhibitor consumption. C1INH, C4 and C2 levels are low in acquired C1INH deficiency, as in HAE. A distinguishing feature is that C1 titers are very low in the acquired disease and only minimally depressed, if at all, in HAE. Most cases have appeared in patients with an underlying lymphoproliferative or autoimmune disease. Therapy is directed at the underlying disorder, but androgen therapy may be helpful in preventing attacks. Future potential therapeutic approaches are discussed.


[Effect of metal dust on the respiratory system. I. Experimental studies]. The Wistar rats were intratracheally administered 50 mg of PbO dust, the same amounts of metalliferous dust from one of lead--and zinc works and of ferrotungsten dust, and 10--15 mg of cadmium dust (greater doses of cadmium dust resulted in animals' death). After 6 months, and in the case of cadmium dust after 9--12 months, the animals were dissected and their lungs were morphologically examined and hydroxyproline level was determined. In all groups hydroxyproline was found to be increased but fibrosis was different, especially in the group exposed to cadmium dust.


[Effect of metal dust on the respiratory system. II. Clinical examinations]. Studies were carried out in 4 groups of workers occupationally exposed to cadmium, tungsten, manganese and lead. All those groups were homogeneous, composed exclusively of men aged 35--45, of similar height, body weight, and duration of employment above 10 years. Following the same criteria, a group of forestry workers, unexposed to dust, was randomly selected. The smoking habit was similar in all groups. Several--days--clinical observation included a detailed interview (MRC questionnaire), physical and radiological examination and a wide range of functional tests of lungs. The results reveal clinical and physiopathological symptoms which might be indicative of emphysema. The results of some studies also indicate the possibility of intraparenchymatous fibrosis of lungs in the tungsten--exposed--workers. No clear effects upon the respiratory system were found.


[Blood coagulation system in workers exposed to noise and vibration]. The authors examined the blood coagulation system in the following 3 groups of workers occupationally exposed to noise and vibration: A--those in whom the examination was conducted 7--16 hrs after finishing the work, B--those in whom the examination was conducted at the 3rd or 4th hour of work, and C--those suffering from angioneurosis of the vibration syndrome of II or III period who have not been exposed to vibration for some recent years. These investigations indicated the lack of blood equilibrium tending to hypercoagulability, shortened duration of plasma recalcination, increased elasticity coefficient of mE thromboelastogram coagulation, increased fibrinogen concentration; these changes were most evident in the group with advanced vibration disease and in those in whom the examination was conducted at their working time. Fibrinolysis duration was significantly prolonged during work, and shortened in those with advanced angioneurosis. In the opinion of the authors, those disturbances in the blood equilibrium system may be accounted for by the conformation changes of proteins.


[Effect of vibration and noise on the fat balance in exposed workers]. In 265 workers exposed to local vibration of low and medium frequencies and to industrial noise, the level of total lipids, phospholipids, beta lipoproteins and total cholesterol in the blood serum was examined. The level of all those substances, except cholesterol, was found to be increased. Based on the discussion, the possibility is assumed of the influence of the neurohormonal system upon the disturbances in lipometabolism.


[Effect of vibration and noise on glycosaminoglycan (mucopolysaccharide) and hydroxyproline excretion]. In 126 humans occupationally exposed to local vibration and in 50 humans exposed to general vibration, glycosaminoglycanuria (GAG) and hydroxyprolinuria (HP) were examined. In addition, all subjects were exposed to industrial noise. An increased GAG excretion in those exposed to the vibration of low and medium frequencies was found, which is indicative of a damage to the basic substance of the connective tissue. The exposure to the lowest frequencies increases the HP excretion, thus indicating a damage to the collagen fibers.


[5-Hydroxyindoleacetic acid and creatinine excretion in thermal stress]. The determination of 5-HIIA and creatinine excretion in thermal stress was performed in two series, in the first (I) on 102 healthy men aged 20--45 yrs (58 smokers and 55 non-smokers) and in the second one (II) on 20 men after drinking of 1 1 water immediately before thermal stress. The subjects remained at rest in the climatic chamber for 90 min in the temperature of 45 +/- 1 degrees C and relative humidity of 70 +/- 5 per cent. Thermal stress resulted in a significant increment of body temperature after 45 min and after consecutive 45 min of exposure, and lack of steady state. Creatinine and 5-HIIA were determined in two urine portions after 45 and after consecutive 45 min of exposure. Total amounts of excreted 5-HIIA and creatinine in the first urine portion in (I) and (II) were significantly higher in comparison with normal values; they did not depend on the amount of urine voided. The 5-HIIA excretion was significantly higher in smokers after the first 45 min of exposure only. Total amounts of excreted 5-HIIA and creatinine after another 45 min of exposure in (I) and (II) were significantly lower. The high correlation has been found between excretion of 5-HIIA and creatinine, indicating a similar process of excretion of both substances. Hydratation before the thermal stress exerted advantageous effect on the thermoregulation in men. The results of this study have been discussed in conjunction with the data in literature.


[Criteria used in the evaluation of the usefulness of surface-active agents in the fight against dustiness in coal mines]. The paper specifies the technical and biological criteria for evaluating the surface-active compounds used in preventing the dustiness, mainly in mines. In addition, effects of these compounds on the organism were discussed.


[Radiological picture of pneumoconiosis in welders]. In the group of 35 welders with pneumoconiosis, the evolution of radiological changes was observed, after cessation of work in exposure. In 9 cases radiological changes retreated completely; in 16 cases they were clearly reduced, whereas in the remaining 10 persons no changes in radiological picture were found. The findings indicate that the radiological changes in welders' lungs may be reversible and as such they are most probably induced by dust retention.


[Effects of detergents on lead absorption]. The effects of orally administeredated detergents (rokafenol and siarczanol) on the absorption of lead from rabbits alimentary duct were reviewed. The absorption of lead was evaluated by the activity of delta--aminolevulinic acid dehydratase of erythrocytes, delta--aminolevulinic acid level in urine and the level of lead in the blood and liver. The detergents were found to increase the absorption of lead.


Hyperglucagonemia in liver cirrhosis with portal-systemic venous anastomoses: responses of plasma glucagon and gastric inhibitory polypeptide to oral or intravenous glucose in cirrhotics with normal or elevated fasting plasma glucose levels. Plasma immunoreactive glucagon (IRG) was examined in volunteers with biopsy-proven cirrhosis of the liver after recovery from surgical portal--caval anastomosis. A wide range of increased total plasma IRG concentrations was found after overnight fast in groups of cirrhotic subjects with and without fasting hyperglycemia. Gel filtration chromatography of plasma showed a major component in the 3500-mol wt fraction in all cases so studied. Administration  of glucose i.v. caused rapid suppression of total plasma IRG in normoglycemic and non-insulin-dependent hyperglycemic cirrhotic subjects. After administration of oral glucose, total plasma IRG was suppressed rapidly in normoglycemic cirrhotic subjects, while non-insulin-dependent hyperglycemic cirrhotic subjects exhibited delayed but prolonged suppression. Chromatography of selected plasma with glucose-suppressed total IRG showed a major decrease in the 3500-mol wt component in every case. Exaggerated increments of plasma gastric inhibitory polypeptide were demonstrable in both groups of cirrhotic individuals after administration of oral glucose, and it is speculated that this peptide may contribute to stimulation of glucagon secretion in liver disease associated with insulin deficiency.


A continuous analyzer for monitoring respiratory gases and expired radioactivity in clinical studies. A system for the continuous monitoring of gas exchange as well as 14CO2 from metabolic studies is described. The analyzer incorporates modifications over previously published systems. These modifications include accurate control of analyzer pressure for stable baselines during the long periods of measurement, accurate control of temperature, the measurement of oxygen consumption during high oxygen patient therapy, the measurement of oxygen consumption of patients on a mechanical respirator, and describes a unique flux system to calibrate the analyzer detectors. The closed system provides expired breath data for O2, CO2, and 14CO2 on critically ill patients for long periods of time without stressing the patient and without using a face mask or mouthpiece. These data allow for the calculation of daily energy expenditures of hypermetabolic patients and for the assessment of various metabolic responses with 14C substrates.


Release of human pancreatic polypeptide and gastrin in response to intraduodenal stimuli: a case report. A recent clinical case afforded an opportunity to study the effects of duodenal stimulation on plasma human pancreatic polypeptide and gastrin concentrations, independent of gastric stimulation. A distension stimulus was provided by rapid injection of 100 ml of water and saline via a T-tube into an isolated duodenal afferent limb. In a third experiment, the saline contained 200 pg/ml of heptadecapeptide human gastrin. Within 2 min after each injection, a rapid rise in circulating human pancreatic polypeptide levels appeared that fell promptly towards basal thereafter. Injections of 100 ml of Flexical, a supplemental tube feeding, resulted in a biphasic human pancreatic polypeptide response, the initial peak comparable to that seen following distension with water, saline, or saline containing gastrin, and a second peak of much greater magnitude and duration followed the initial peak. Plasma gastrin concentrations were not influenced following any of the stimuli. Duodenal distension alone may induce an early transient increase in plasma human pancreatic polypeptide concentrations, while intraduodenal nutrients per se may induce a later increment of greater magnitude and duration.


Human adipose tissue in culture. VIII. Studies on the insulin-antagonistic effect of glucocorticoids. Biopsies of human adipose tissue were maintained for 1 wk in vitro with physiologic (1.5-30 X 10(-8) M) or pharmacologic (300 X 10(-8) M) concentrations of hydrocortisone or 1000 muU/ml insulin, or both. After this period, the explants were washed and incubated for 2 hr according to techniques generally used to study fat cell metabolism. Physiologic concentrations of hydrocortisone mainly exert an insulin antagonistic effect. Thus, the long-term effects of insulin in increasing lipolysis, as well as glucose metabolism to triglycerides, were reduced, as were the acute effects of insulin on these parameters. At these concentrations, the glucocorticoid itself did not influence the basal metabolic rates when due consideration was given to simultaneous changes in mean fat cell size. At higher concentrations, which may easily be reached during nonspecific glucocorticoid therapy, the glucose metabolism was reduced. Hydrocortisone decreased the number of insulin receptors. However, this cannot solely explain the insulin-antagonistic effect, since it was not overcome by a supramaximal concentration of insulin. Insulin and hydrocortisone together increased the lipoprotein lipase (lpl) activity several times. The resultant changes in LPL appear to depend upon the insulincorticosteroid ratio.


Adipose cell morphology and control of lipolysis in a patient with partial lipodystrophy. A previously unreported patient with partial (cephalothoracic) lipodystrophy is described. Glucose tolerance and plasma lipids were normal, but plasma insulin increased to 340 muU/ml during an oral glucose tolerance test. Plasma free fatty acids were appropriately suppressed by oral glucose, insulin, and nicotinic acid, and were increased by infusion of norepinephrine. The lipolytic responses was also normal in response to two stimuli for endogenous catecholamine release: upright posture and 2-deoxyglucose infusion. There was a gradual development of postural hypotension in response to upright posture despite appropriate reflex tachycardia. Anhidrosis was present over the lower half of the body during this test, in a distribution corresponding to the area of adipose tissue hypertrophy. Anhidrosis was also seen in this region in response to warm ambient temperature. Adipose cells from the atrophic area were smaller than those from the hypertropic area, but the atrophic cells were only 65% of the volume of the hypertrophic cells by two different methods. Thus, loss of cells occurred. Glucose-1(-14)C utilization and in vitro lipolysis were similar in the two cell preparations; the difference were explicable by cell size and did not suggest a metabolic abnormality. Counts of unmyelinated nerves were similar in the two areas. These findings indicate that in this patient the lipodystrophy was associated with normal fat cells and an autonomic dysfunction. However, the findings cannot completely explain the pathogenesis of her disorder. Loss of fat cells, rather than symmetrical shrinkage, occurred in the upper half of the body.


Atropine suppression of basal and metoclopramide-induced human pancreatic polypeptide secretion in man. The administration of metoclopramide (MET) increased human pancreatic polypeptide (hPP) levels in 17 of 18 male and female control subjects. In all the control subjects, the increase was from a mean (+/- SD) basal level of 96 +/- 60 pg/ml, to a peak of 221 +/- 170 pg/ml. The peak occurred at 30 min, and levels had decreased by 60 min in all subjects. Atropine pretreatment in five male control subjects significantly decreased basal hPP levels and completely abolished the response to MET. It thus likely that the hPP increase consequent to MET administration is related to the latter's cholinergic properties.


Primary oxalosis: clinical and biochemical response to high-dose pyridoxine therapy. Although pyridoxine hydrochloride (vitamin B6) is known to reduce the endogenous production of oxalate in some individuals with primary oxalosis, the dose for a satisfactory trial of treatment is not established. We report two cases of primary oxalosis on a daily regimen of 1 g pyridoxine hydrochloride, in which 24-hr urinary oxalate excretion decreased by 60% and 70%, respectively, with corresponding clinical benefit. The responses have been sustained up to 2.5 yr in one case, and 20 mo in the other. In the patient with renal failure, serum creatinine decreased from 243 to 146 mumole/liter after 15 mo of treatment. The decrease in glycollic acid excretion in both patients was consistent with an increase of glyoxalate transaminase activity by the vitamin. Supranormal levels of erythrocyte glutamic oxaloacetate transaminase (egot) activity were observed during therapy, and these may be useful as a measure of the effective dose of pyridoxine.


Evaluation of the control of glucagon secretion by the parasympathetic nervous system in man. To evaluate the influence of the parasympathetic nervous system on human glucagon secretion, we have measured the plasma immunoreactive glucagon (IRG) levels after the administration of edrophonium, bethanechol chloride, and 2-deoxyglucose, and have compared the IRG responses to hypoglycemia in normal, atropinized, and vagotomized man. Edrophonium administered i.v. and bethanechol chloride administered s.c. did not affect IRG levels. Two-deoxy-glucose resulted in symptomatic neuroglucopenia with resultant vagal discharge, as evidenced by increased gastric acid secretion; but no changes in IRG concentrations were observed. The IRG response to insulin-induced hypoglycemia in normal subjects was not influenced by the administration of atropine. In seven subjects with a truncal vagotomy and no increased gastric acid secretion during insulin-induced hypoglycemia, the IRG increases were indistinguishable from those of control subjects in terms of timing, peak level obtained, or total glucagon response. We conclude that the cholinergic system is unlikely to play an important role in modulating glucagon secretion in man.


Caval occlusion technique for hepatic venous sampling: a new approach to estimating splanchnic substrate balance in conscious dogs. We have proposed a new technique for sampling hepatic venous blood in conscious dogs. Sub-hepatic vena caval blood flow was temporarily occluded by a previously implanted inflatable snare so that all blood entering the inferior vena cava was hepatic venous effluent. Hepatic venous blood samples were collected from the inferior vena cava 8 seconds after beginning caval occlusion, with the total interval of flow occlusion lasting 12 to 15 seconds. No behavioral or metabolic alterations were observed when or metabolic alterations were observed when hepatic venous effluent was repetitively sampled using the caval occlusion technique. Net splanchnic glucose balance (NSGB) was measured in conscious dogs receiving saline, glucose or glucagon infusions. NSGB measurements made with the caval occlusion technique were in accord with previous results obtained via tracer methodology or arterio-venous difference techniques utilizing hepatic vein catheterization. The caval occlusion technique thus provides a method for collecting hepatic venous blood samples from conscious animals without the difficulties associated with hepatic vein catheterization.


Effects of insulin on the response of immunoreactive glucagon to an intravenous glucose load in human diabetes. The effects of exogenous insulin upon the response of immunoreactive glucagon (IRG) to i.v. glucose were studied in diabetic and nondiabetic subjects. In nondiabetics, a rapid injection of 25 g of glucose lowered plasma IRG levels. In adult-onset diabetics, the glucose-induced decline in IRG was normal despite a subnormal glucose-induced insulin rise, in contrast to impaired IRG suppressibility previously reported when such patients received an oral glucose load. The magnitude of their glucose-induced IRG decline was not augmented by exogenous insulin, even when insulin levels were acutely raised above 300 micro units/ml. In juvenile-type diabetics, basal IRG levels were normal following overnight insulin infusion, but the glucose-induced IRG decline was only half that of the nondiabetics. However, it became normal when hyperinsulinemia was acutely produced by supplementary insulin. Thus, whenever insulin levels rise in response to an increase in hyperglycemia, as they do spontaneously in nondiabetics and in adult-type diabetics and as they do when juvenile diabetics are given supplementary insulin together with the glucose bolus, the decline in IRG in response to an i.v. glucose load is as great as in nondiabetics. The findings are compatible with the view that glucose-induced suppression of IRG may require a concomitant rise in insulin.


Serum levels of neurophysin in pregnancy and in the postpartum period: relation to 17beta-estradiol levels. Changes in serum neurophysin levels were studied in women during normal pregnancy and after delivery. Neurophysin was elevated as early as the sixth week of gestation and gradually increased until, at the latest, the twentieth week. A significant positive correlation was obtained between serum concentrations of neurophysin and those of 17beta-estradiol. In serum samples with 17beta-estradiol levels exceeding 5 ng/ml, neurophysin was consistently elevated above the normal control range. After delivery, serum neurophysin concentrations declined quite rapidly. The levels returned to those of nonpregnant women by 6 days postpartum. These results support the view that a high rate of secretion of 17beta-estradiol may be one of the factors responsible for the elevated levels of serum neurophysin in pregnancy and that this effect disappears rapidly after the disposal of estrogen, independent of the duration of the elevated estrogen levels.


Effects of long-term physical training on body fat, metabolism, and blood pressure in obesity. Twenty-seven women with varying degrees of obesity were physically trained for 6 mo on an ad lib. diet. Body fat changes were positively correlated with the number of fat cells in adipose tissue. Obese women with fewer fat cells decreased in weight during training whereas women with severe obesity and an increased number of fat cells even gained weight. Blood pressure decreased consistently after training. Blood pressure elevation was not associated with body fat mass, nor was a decrease in blood pressure associated with a decrease in body fat or with pretraining blood pressure level. There were, instead, correlations between decreases in blood pressure on the one hand and initial concentrations and decreases in plasma insulin and triglycerides and blood glucose on the other. These results suggest an association between elevated blood pressure and metabolic variables. The possibility of treating and preventing early essential hypertension with methods that also correct the metabolic derangement, such as diet and exercise, should be given high priority in further research.


Uptake of glycine by human kidney cortex. The transport of glycine was investigated in histologically normal adult human kidney cortical slices. Uptake occurs against a gradient and shows concentration dependence. Kinetic analysis reveals two systems for transport of glycine with apparent transport Km values of 0.511 and 34.2 mM. Glycine transport on the high-Km system is competitively inhibited by 50 mML-proline. Transport inhibition on the low-Km system could not be directly evaluated, but on theoretic grounds appears not to be inhibited by L-proline or hydroxyproline. Alpha-aminoisobutyric acid, valine, and thioproline are also shown to inhibit glycine uptake. Low medium sodium or anaerobic incubation depress the uptake of glycine. These observations are consistent with previous reports of glycine transport in rat kidney and support the proposals for the mechanism of familial iminoglycinuria based on in vivo investigations.


Fasting as a provocative test in neuromuscular diseases. A 38-hr fast was used as a provocative test in patients suspected of having defects in muscle substrate utilization. In five controls and nine patients, exercise capacity and respiratory exchange ratio were determined before and at the end of the fast. Blood was collected at intervals during the fast from ten controls and nine patients for creatine kinase (CK), free fatty acids, (FFA) beta-hydroxybutyrate, acetoacetate, free and total carnitine, glucose, and alanine. Two patients with myophosphorylase deficiency had increased exercise capacity, and a marked fall in CK, and one had a lesser fall in blood glucose than normal at the end of the fast. Two patients with known lipid myopathies (carnitine deficiency and carnitine palmityl transferase deficiency) had decreased exercise capacity and apparent increased dependence on carbohydrate metabolism during the fast. Carnitine concentrations became even more abnormal in the patient with carnitine deficiency during fasting. Several patients with less well-defined defects were also significantly different from the controls in several respects, indicating that the fast might be useful for finding new defects.


Diabetes, blood lipids, lipoproteins, and change of environment: restudy of the "new immigrant Yemenites" in Israel. Restudy of 306 "new immigrant Yemenite" Jews, an ethnic group in which, upon their arrival in Israel, no diabetes was detected, revealed, 25 yr after their immigration, an increased incidence of diabetes and higher plasma and lipoprotein-lipid levels. The prevalence of diabetes (defined as "glucose intolerance") rose to 11.8% (13.2% males and 9.7% females). Obesity in females resulted in increased prevalence of diabetes in all age groups, while in males it affected the older age group only. The male/female diabetic ratio was affected by weight status--in the underweight, diabetes was more prevalent in males, in the overweight, the rate of diabetes in females equaled that of males. In nondiabetics (those with normal glucose tolerance), neither the glucose tolerance nor the insulin response deteriorated with aging. Most diabetics had a delayed insulin response. However, about 50% of nondiabetics and diabetics had insulin response peak at 60 min and similar insulin levels. It appears that in newly discovered adult-onset diabetics in this population there is no shortage of insulin, but rather shortage of insulin action. In nondiabetics, the levels of plasma cholesterol and triglycerides (TG) were higher than levels upon their arrival. In diabetics, the plasma TG, cholesterol, and LDL-cholesterol levels were higher when compared to those of nondiabetics, especially in the group of overweight males. Hyperlipoproteinemia was diagnosed in 27.7% of diabetics and 11.0% of nondiabetics. In diabetics, the HDL/LDL cholesterol ratio was found to be reduced, significantly so in overweight diabetics.


The response of bone apposition rate to some nonphysiologic conditions. The response of bone apposition to some nonphysiologic conditions was investigated. In rabbits, the normal osteogenic rhythm was totally abolished shortly following treatment of hydrocortisone at a dose of 2 mg/kg body weight daily. A new rhythm developed after the treatment was continued for 20 1/2--34 days. The rate of bone apposition was significantly depressed compared to normal data reported previously. In rats receiving one U.S.P. unit of parathyroid extract daily for 14 days, the rate of bone apposition was significantly higher than that in control rats. In both sepcies, the response to an exogenous hormone was identified for all skeletal locations. It was concluded that new bone apposition was a function of activated osteoblasts, and that this function responded only to general body control mechanisms.


Further development and automation of a high pressure liquid chromatography method for the determination of glycosylated hemoglobins. A previously described high pressure liquid chromatography system for the determination of glycosylated hemoglobin concentrations has been automated and simplified. With this methodology it is possible to perform up to 60 analyses per day for hemoglobin A1a+b% and hemoglobin A1c%. Where an estimate of the total fast hemoglobin alone is required, then a considerably greater number of analyses can be performed. The individual values are calculated directly with an electronic integrator. The mean coefficient of variation of the duplicate determinations of 48 samples was 0.63 +/- 0.83% (mean +/- SD). Aliquots of pooled hemolysates have been maintained in liquid nitrogen at -90 degrees C and run at the beginning and end of each daily analytical run over an 18-mo period. Both the inter- and intra-run coefficients of variation of these values have remained consistently less than 3%. Therefore, the methodology offers a reliable and accurate method of containing glycosylated hemoglobin values for clinical use.


Cultural factors affecting the use of family planning services in an Aboriginal community. The attitudes of the women of an Aboriginal community towards family size, spacing, and planning are briefly reviewed. It is shown that the felt need of the women for a means of control of reproduction and their approval of contraception is not matched by the use of the available family planning services. It is suggested that this gap between attitudes and use is due to the lack of practical recognition by the providers of these services of the indigenous conventions which surround the discussion and management of menstruation, pregnancy, childbirth, and contraception. Several ways in which family planning services could be made more acceptable culturally to both women and men of Aboriginal communities are proposed.


Respiratory function in aboriginal school children. Two hundred and three school-age Aboriginal children living on Cherbourg Aboriginal Settlement have had lung function tested with a dry spirometer. As with other non-Caucasian children, the forced vital capacity (FVC) was about 25% below values for Caucasian children, but the ratio between forced expiratory volume in one second and forced vital capacity (FEV1/FVC ratio), the mean mid-expiratory flow rate (MMEFR) and testing before and after a bronchodilator showed no evidence of widespread airways disease. Analysis of a subgroup of 126 children showed that birthweight, weight at one year of age, and current nutrition did not affect the level of the FVC.


Attitudes towards family planning among the women of a Northern Australian Aboriginal community. The results of a survey of the attitudes of 92 women from an Aboriginal community towards childbearing and family planning are presented. The majority of the women stated a preference for well-spaced families of a size which enabled a mother to care adequately for her children. The respondents were almost unanimously in favour of the use, when desired, of Western contraceptive methods. One of the authors (JR) suggests that these attitudes reflect traditional norms of family structure, and that they are also based on a critical appraisal by the women of the community of the demands of caring for young children. These demands are exacerbated by a depressed socioeconomic environment.


Infant mortality in 12 Aboriginal settlements: Queensland, 1972--1976. The infant mortality rate amongst Aborigines from 12 Queensland Aboriginal settlements and missions over the years 1972 to 1976 was 72 per 1000 live births. This rate is comparable with that for Queensland of 60 years ago. The Aboriginal infants had twice the present-day Queensland risk of neonatal death and eight times the risk of postneonatal death. Prematurity was the major cause of neonatal deaths; gastroenteritis and pneumonia were the major causes of infant deaths. These rates emphasise the need for community and preventive health care for the Aboriginal children, particularly during the postneonatal period.


Schistosome dermatitis in the Swan Estuary, Western Australia. The avian blood fluke, Austrobilharzia terrigalensis (Trematoda: Schistosomatidae), is recorded in Western Australia for the first time, and is implicated as the cause of dermatitis among users of the Swan estuary in Perth. Quantitative data provided by a questionnaire sent to affected people showed that infection occurred from November to March in the shallows throughout the "middle" estuary and that children from five to 14 years old were most frequently affected. Most cases of dermatitis were contracted between 11 a.m. and 12 noon--the time of day when the emergence of A. terrigalensis cercariae from the intermediate host, Velacumantus australis, reaches a peak. Exposure times varied considerably, but were generally between 30 and 90 minutes, with dermatitis appearing 12 to 24 hours later. The lesions, which were sometimes widespread over the body and itched severely, persisted for one to two weeks and longer if they were secondarily infected. Approximately 38% of affected people consulted doctors about their condition. These results are discussed in relation to findings on the ecology of the parasite's intermediate and definitive hosts.


The radioisotope spleen scan in the assessment of patients with suspected spleen trauma. The radioisotope spleen scan was reviewed in 29 patients with suspected trauma of the spleen who had been admitted for observation to a surgical ward. At the time of the study, all patients had stable pulse rates and blood pressures. The scans of six patients showed space defects and, of these, splenic injury was subsequently proven operatively in five patients. As a detector of splenic trauma, the radionuclide scan proved to be reliable. Although the findings of radioisotope scanning are not specific for trauma, the interpretation of the scan in conjunction with other observations increases the accuracy of diagnosis.


Granuloma inguinale in Northern Queensland. Thirteen cases of granuloma inguinale were diagnosed in just over a twelve-month period at the Australian Government Health Laboratory and the General Hospital, Townsville. Seven patients were males, four of whom were immates of Her Majesty's Prison, Townsville. Two of the patients were married, and two were sisters. All the female patients were pregnant at the time of diagnosis. The provisional diagnosis was confirmed by the presence of intracytoplasmic Donovan bodies in crushed tissue smears stained with Wright's stain and pinacyanole. The diagnosis of granuloma inguinale could not be reliably made from sections of formalin-fixed tissue alone. The clinical findings, methods of laboratory diagnosis, management and treatment of this disease are also described with an added emphasis on treatment during pregnancy.


Solitary liver abscess: a continuing medicosurgical problem. The management problems of 22 patients with solitary liver abscess are reviewed. To achieve earlier diagnosis, and reduce the high mortality rate of this condition (32% in this series), clinicians need to change their data base of the clinical presentation and also to incorporate liver imaging as part of the routine investigation of a patient with pyrexia of uncertain origin. The problems associated with operative diagnosis, and with methods of surgical drainage are discussed. The need for careful bacteriological cultures is emphasized, and the use of the most appropriate antibiotics is described. While in many cases the cause of the liver abscess remains unknown, in Australia the possibility of the abscess being amoebic or an infected hydatid cyst should be kept in mind.


Fifty opiate addicts treated with methadone blockade. Eight-year follow up. An extended follow up of the first 50 opiate addicts in Australasia to be treated with methadone blockade is described. At follow up, 43 patients were traced and assessed. Results show that 65% of the 43 patients completed the recommended three years of blockade therapy, with an identical proportion of patients recording no new criminal convictions; and 53.5% were reported as being drug-free, with the exception of prescribed methadone. The therapy in 28% of patients was judged as being completely successful, while 70% of patients complied with criteria of leading reasonably happy and productive lives. Methadone blockade (over 100 mg a day) offers the opiate addict an excellent opportunity for recovery and rehabilitation, provided that the treatment is properly understood, administered, and followed up.


Acalculous cholecystitis: results of cholecystectomy. The results in a small series of patients with clinical cholecystitis, but who had no stones, on whom operation was performed are compared with results in a larger series of patients who had stones. The results suggest that, if a clinical diagnosis is made and other causes of symptoms have been excluded, the results of operation are almost as successful as in those having stones. Patients should not be denied operative relief if the symptoms strongly suggest gall bladder disease even if no stones are shown on X-ray examination.


The interaction between ethanol and antihistamines: 2. Clemastine. Eighty paid student volunteers (35 male, 45 female) were used in an experiment to investigate the effects of a therapeutic dose of clemastine (1 mg) alone and in combination with a social dose of ethanol (0.54 g/kg) on perceptual, cognitive and motor functions. Both drugs were given orally. Clemastine did not significantly modify performance when given alone, and the performance decrements induced by ethanol were not enhanced by clemastine premedication.


Metastatic medullary carcinoma of the thyroid complicated by Cushing's syndrome. A patient with metastatic medullary carcinoma of the thyroid, Cushing's syndrome, and severe diarrhoea is presented. The manifestations of Cushing's syndrome were controlled with a combination of aminogluthethimide and metyrapone. The cause of the diarrhoea has not been found, and it remains resistant to treatment.


Medullary carcinoma of the thyroid presenting as fatal asphyxia. Medullary carcinoma of the thyroid is a rare entity. Most cases present with a lump in the neck. An unusual presentation as fatal asphyxia is reported.


Glass laceration injuries and prevention. Accidents involving glass in doors, sidelights, specially vulnerable windows, and shower screens are an important cause of injury, and occasionally death. Most of the injuries are superficial cuts and abrasions, but many involve deep lacerations of tendons, nerves and muscles. The accidents occur mainly in children and young adults with the highest rate being among males aged from 15 to 19 years. The number and severity of these injuries could be reduced through the wider use of appropriate forms of safety glazing: laminated glass or toughened glass in new installlations, and the application of a plastic safety film to existing glass.


Physicians and death: some Australian data. Despite a significant interest in bereavement in this country there are little hard data on attitudes to, beliefs about, and experiences with, death and dying in the Australian context. This paper reports the results of a survey in the area with special reference to the responses of medical practitioners and medical students.


Testing hearing with the brain-stem evoked response. The brain-stem electroencephalograph (EEG)-evoked response (BSER) constitutes a reliable and objective method of testing hearing in infants, and in uncooperative, or retarded patients. The procedure is harmless and painless, and involves recording the EEG brain-stem responses to clicks presented by headphones. The patient may be sedated, or even anaesthetized, if necessary. Because of the equipment and time involved, the procedure is not recommended as a routine screening procedure, but constitutes a valuable adjunct to conventional audiological testing, especially in doubtful cases.


The effects on intellectual functioning of open prefrontal leucotomy. The Wechsler Adult Intelligence Scale and the Wechsler Memory Scale were administered to 32 patients both before and six months after they received open prefrontal leucotomies. The preoperative and postoperative test results are compared, consideration being given to individual patients as well as to the group. The mean results for the group provide no evidence of any post-operative intellectual deterioration. However, it seems probable that in individual cases such deterioration occurred. In most of these cases brain damage would appear to be responsible, and the ability "to comprehend and size up a total situation" is seen as the area of functioning primarily affected.


Improved survival of patients with cystic fibrosis. The survival of 320 patients, who were born in and after 1958 with cystic fibrosis and managed by the Departments of Thoracic Medicine and Gastroenterology, Royal Children's Hospital, Melbourne, is reviewed. Eighty per cent of patients survived to 11 years of age, and 64% to 18 years. Of patients managed between 1973 and 1977, 91% survived to 12 years of age, and 80% to 17 years of age. In the same period, 79% of patients survived for 16 years after diagnosis. Forty-four per cent of the 240 patients currently being managed have no significant permanent lung disease, and only 9% have advanced disease.


Relationship between the time of birth and the development of immediate hypersensitivity to grass-pollen antigens. Eighty-six children aged three to 14 years were skin-tested for immediate hypersensitivity to antigens which are seasonal (grass pollens) or non-seasonal (car, dog, house-dust mite) in occurrence. Children who reached the age of three months during a time of environmental exposure to grass pollen demonstrated a significantly increased incidence of immediate hypersensitivity reactions to three grass pollens, as compared with children born at other times of the year. No significant difference was found in their reactions to the non-seasonal antigens. These findings indicate a relationship between the time of birth and the subsequent development of immediate hypersensitivity in childhood. It is suggested that infants are particularly susceptible to sensitization when presented with antigen around three months of age.


Ureteric stricture associated with analgesic nephropathy. A case of localized ureteric stricture in a woman with analgesic nephropathy is reported. The problems of diagnosis and management are briefly discussed.


Chlorbutol toxicity and dependence.

Chlorbutol toxicity and dependence. A case of chlorbutol toxicity and dependence is presented. A very long elimination half-life (13.2 days) was found in the patient. The data suggest that chlorbutol is an unsuitable sedative to be available freely to the public.


The health of the preschool child.

The health of the preschool child. A standardized medical examination of four to five year old children was introduced into Victorian preschools in 1977. This combined a neurodevelopmental screening with a physical examination. In a study to verify the effectiveness of this examination, a random sample of 512 children from inner urban and disadvantaged outer urban preschools was examined and compared with a group of 500 children from preschools in more advantaged areas. Of these 1012 children, 264 (26%) required referral for one or more previously unrecognized disabilities. The number of children referred for intervention or therapy from the disadvantaged group was 176 (34%) compared with 88 children (17.6%) from the more advantaged group. A standardized examination of the preschool child is desirable, so that consistently comparable results can be obtained and epidemiological trends can be more readily identified.


Lung function in an Australian population: 1. Spirometric standards for non-smoking adults. Relationships between age, height, weight and spirometry with FEV0.5, FEV1, FVC and FEV1/FVC are described for a sample of 6275 female and 6511 male non-smoking adults living in New South Wales. Prediction equations for ventilatory function tests are derived from non-smokers and compared with other standards that are available in a population sample of 31172 subjects. It is concluded that the standards described in this paper are more appropriate for use in Australian populations. Nomograms for predicting FEV1 and FVC in females and males are provided.


Method of delivery and developmental outcome at five years of age. A controlled follow-up study examined the impact of delivery method on developmental outcome of the child. The modes of delivery investigated were low forceps delivery (188 infants), midcavity forceps delivery (51 infants), forceps rotation with forceps delivery (57 infants), manual rotation with forceps delivery (67 infants), elective caesarean section (101 infants) and spontaneous delivery (control, 207 infants). Breech presentation (100 infants) was separately compared with the vertex presentation groups. Sample selection controlled for complications during pregnancy and low birthweight and was restricted to married English-speaking mothers. The children were assessed at the age of five years on verbal and non-verbal subtests of a standardized intelligence scale, tests of gross motor coordination, and auditory and visual tests. A full paediatric examination was also performed. Breech presentation children performed less well on tests of balance and fine motor coordination and on visual acuity and stereopsis testing than children who presented in the vertex position. No deleterious effect of delivery method was found. In the absence of other complicating events (like a poor antenatal history, prematurity, and a disorganized home environment) delivery complication constitutes an early risk factor which the growing child is able to overcome.


Urinary ferritin protein in subjects with prosthetic heart valves and other disorders. Twenty-four-hour urine ferritin protein excretion (UFPE) was elevated in the great majority of patients with prosthetic cardiac valves. In this group, there was a positive correlation with the presence of haemosiderin in the urine and with another indirect measure of reduced red-cell survival, namely, serum lactic dehydrogenase. In a number of hospital patients with various disorders, UFPE was also increased. In this latter group, however, there was no constant accompanying haemosiderinuria or elevation of lactic dehydrogenase. The measurement of UFPE can be added to the list of screening tests for intravascular haemolysis, but analysis of the different isoferritins in urine is necessary to fully understand the mechanism of excretion in the different groups.


The effects on personality of open prefrontal leucotomy. The Sixteen Personality Factor Test was administered to 28 patients both before and six months after they received open prefrontal leucotomies. The preoperative and postoperative test results are compared. Preoperatively the group was excessively apprehensive, tense, affected by feelings, sober, shy, and humble. After leucotomy these aspects of personality all showed significant change in the direction of normality. With the exception of the humble versus assertive aspect, however, the mean scores in each case remained outside the normal range.


Management of the neurogenic bowel using durolax solution. A simple and effective bowel care regime is described which has been in use in the Spinal Injuries Unit at Prince Henry Hospital, Sydney, for more than 10 years. Three times a week, Durolax solution (bisacodyl 10 mg in 5 ml of propylene glycol), usually 5 mL undiluted or diluted with 5 mL of tap water, is introduced into the rectum using a catheter and syringe. A faecal softener is given 24 hours before the Durolax solution. Evacuation usually results within 30 minutes, tending to occur sooner with continued use of the regime. The procedure is well tolerated and there have been no serious problems.


Maternal deaths in South Australia 1970 to 1975. During the period from 1970 to 1975 there were 128 087 confinements in South Australia and 30 maternal deaths were reported, representing a maternal mortality rate of 23 per 100 000 confinements which is lower than in previous reports. Twenty-one deaths were directly due to complications of pregnancy and childbirth, and  nine were due to associated conditions. The fall in the maternal mortality rate was largely due to a reduction in the number of deaths from abortion and in the number of confinements to women in the higher-risk older age groups. Infection appeared for the first time as a major cause of maternal death. Avoidable factors may have contributed to 47% of the deaths.


Diazinon and porphyria cutanea tarda.

Diazinon and porphyria cutanea tarda. Cutaneous application of diazinon to rats over a period of 12 weeks gives rise to a condition biochemically indistinguishable from porphyria cutanea tarda. Faecal porphyrin levels are elevated with the appearance of isocoproporphyrin in the faeces. Oral administration of diazinon does not appear to cause any disturbance of porphyrin metabolism.


Medications for the elderly.

Medications for the elderly. Medications were checked by a trained nurse during the course of her duties in a controlled study of 150 elderly people with cerebrovascular disease. The cost of medications was marginally reduced in a group of people receiving the additional supervision, while it rose by 12.0% in a control group. In the group visited by the nurse, containers were labelled correctly for significantly more people than was the case with the control group.


How can I improve my teaching?

How can I improve my teaching? There is nothing mysterious about improving teaching. To learn to teach better teachers should: (a) be prepared and motivated to learn; (b) consider their needs and interests in order to specify whay they want to learn; (c) secure feedback and information in relation to the performance or skill they want to learn; and (d) try new teaching methods suggested by the feedback.


A survey of adults with flame burns at a Melbourne hospital. A prospective survey has been made of 81 patients with flame burns who were admitted to the Alfred Hospital, Melbourne, in the years 1973 and 1974. Young males who got burnt in and around their homes were most frequently encountered. Indications of the importance of predisposing conditions, flammable liquids and apparel in the burn incidents are discussed together with the need for extension of the survey.


Health of overseas students attending an Australian university. The Asian students at Monash University, 80% of whom are seen at the University Health Service in any one year (and nearly all of them are seen over a three-year period) appear to be healthy and well-adjusted. They have no more and no less emotional problems than local students. The occasional severe breakdowns because of the difficulties that arise, impress themselves on memory, and can give rise to a false impression of the number of overseas students having severe emotional problems. The Asian students frequently have disorders of the upper part of the respiratory tract, especially hay fever. Their quieter behaviour makes them less accident prone. The Asian females show a much lower incidence of sexually transmitted diseases.


Oxolinic acid in the treatment of urinary tract infections. Oxolinic acid was successfully used in eradicating bacteriuria in 86% of a highly selected group of 42 patients with chronic and recurrent urinary infections. Thirty-eight (92%) of patients had underlying renal abnormalities, 19 (45%) had impaired renal function. Emergence of resistant organisms in 3 patients (7%), and a high incidence of side effects necessitating withdrawal of treatment in 12 patients (29%), limit the usefulness of this agent to special situations. In patients with moderate and severe renal impairment, oxolinic acid achieves adequate urinary concentration, does not accumulate in the serum and is not nephrotoxic. The drug is safe and effective to use in patients with renal impairment.


Value of latex test in cryptococcal meningitis. The history of a man suffering from chronic cryptococcal meningitis is presented. A series of cerebrospinal fluid and serum specimens from this patient were investigated retrospectively by latex agglutination for the presence of cryptococcal antigens. The results were related to other laboratory findings, and to the patient's clinical progress. The cryptococcal latex agglutination test was shown to be potentially useful in the diagnosis, management, and prognosis of such patients.


Herpetic whitlow.

Herpetic whitlow. Three cases of herpetic whitlow are reported. This occupational hazard of medical and paramedical personnel caused by finger infection by ther herpes simplex virus is often confused with bacterial (pyogenic) infection of the pulp of the finger or thumb. Unnecessary surgical drainage may then be carried out, with prolongation of morbidity. Wider recognition of this entity should enable a correct clinical diagnosis to be made in every case. The treatment is conservative as the condition is self-limiting. Topical application of idoxuridine appears to be beneficial.


Myocardial infarction in Queensland provincial cities, 1975. A survey was made of patients admitted to hospitals with a diagnosis of acute myocardial infarction in seven Queensland provincial cities between January 1, and December 31, 1975. Estimates of the incidence of, and mortality from, myocardial infarction are made, and details of the type of care offered, patient characteristics, and length of stay in hospital and intensive care units are presented.


Lung function in an Australian population: 2. Spirometric performance and cigarette-smoking habits. The FEV1, FVC and FEV1/FVC% in 12016 females and 18 359 males were related to cigarette-smoking habits. Over all, non-smokers had significantly better lung function than cigarette smokers. Ex-smokers of either sex had significantly higher FEV1 and FEV1/FVC% than cigarette smokers, but the FVC values were higher only in females. With consumption in excess of 10 cigarettes per day, deterioration in lung function was manifest in both sexes, but was greater in males than females. The mean chronological age of males who smoked from 30 to 50 cigarettes per day was 12.9 years and 9.6 years less than would have been predicted on the basis of their FEV1 and FVC values respectively. The corresponding values in women were 9.3 years and 7.9 years respectively. Additionally, the deterioration in lung function with increasing age was greater in cigarette smokers than in non-smokers.


Queensland tick typhus in Sydney: a new endemic focus. A new endemic focus of Queensland tick typhus was defined when two cases of Rickettsia australis infection were recognized in Sydney. Although the tick vector is distributed throughout coastal, eastern Australia these are the first cases diagnosed south of Lismore, New South Wales.


[Clinical expressions of plasmocytoma (author's transl)]. Multiple myeloma is the most frequent type of hemoblastic disorders including paraproteinemia. Most cases show a disseminated involvement; few patients have solitary lesions of the bones or connective tissues. Different localizations are the reason for the multiform clinical picture of the disease. The main symptoms result from neurological and dermatological involvement, less usual are gastrointestinal complaints. Fractures, neurological deficiencies, lack of antibodies and failure of the kidneys determine the course of plasmocytoma. Our case reports are demonstrating examples of the different clinical expressions.


[Operative treatment of mamma carcinoma and its aftermath from the view of radiotherapist (author's transl)]. It is reported about 234 patients suffering from postoperative complications after mamma surgery due to carcinoma. All patients were postoperatively treated with a combined telecobalt and x-ray radiation. The results show that serious complications as lymphoedema and periphery neurologic disturbances depend in a great extent on the technique of surgery, especially when the axilla is involved by the cut direction. Postoperative complications of breast cancer are increased only insignificantly by radiatio. Therefore it is suggested to reduce the frequence of radical surgery, and modified radical surgery of breast cancer, in favour of single mastectomy plus postoperative radiation.


[Leiomyoblastoma (epithelioid leiomyoma) of the stomach: a pathomorphological and retrospective study of 6 cases (author's transl)]. Gastric leiomyoblastoma is a well defined mesenchymal tumor originating from the smooth muscle tissue (tunica propria) of the body and pyloric antrum of the stomach. Although these tumors are usually benign, some of them may be malignant or potentially malignant. On gross inspection the mostly solitary lesions protrude hemispherically or polypoidly into the gastric lumen. The mucous membranes overlaying the tumor may be eroded or deeply ulcerated so that gastric hemorrhage is the most important clinical finding. Microscopically the tumor tissue is composed of large, rounded or polyhedral cells, which often contain empty vacuoles in their finely granulated acidophilic cytoplasm. The round or oval nuclei are located in the center or at the periphery of the cell, sometimes giving the impression of "signet ring" cells. The size and chromatin density of the nuclei may vary, mitotic figures are rare or missing. Often the tumor cells are disaggregated by accumulations of PAS-positive edema, which may also contain many large and confluent empty vacuoles. The reticulum stain reveals a dense network of fibers encircling individual or small groups of tumor cells, as it is characteristic for smooth muscle tissue. In 4 cases we observed small nodules, which were composed of concentrically arranged fibers and tumor cells resembling hemangiopericytoma without central blood vessel. During 6 years (1970 to 1975) we observed 6 cases of gastric leiomyoblastoma. None of these patients had evidence of recurrent disease or metastatic spread 2 to 6 1/2 years after operation and histological diagnosis of the tumor.


[Conditions for rational drug treatment in childhood (author's transl)]. In pediatrics it is difficult to define indications of drug therapy, appropriate dosage and therapeutic reliability of drugs because experimental pharmacology in this age group has many obstacles. To provide information on optimal drug selection 83 pediatric clinics were asked to define their choice of drug treatment for particular purposes. The results were compared with an investigation of 1969. Trends of pediatric drug treatment during the last decade can be recognized.


[Pharmacokinetics and dosage regimen in children (author's transl)]. Dosage recommandations are mostly established empirically. With many drugs more accurate dosage is necessary and possible: antibiotics, cytostatic drugs, but also heart glycosides and anticonvulsives. Some pharmacokinetic standard values vary according to age. The distribution volume in infants is normally substantially greater than in older children. For infants the first or single dose has to be higher in relation to body weight to get the same concentration as for older children. In general, the elimination rate is slower in younger children. Therefore in long-time therapy the interval between doses has to be longer. After the 6th to 12th week the differences in elimination rates are negligible. The absorption from the rectum is neither reliable nor predictable. Suppositories are only allowed if it is possible to calculate the effect of a drug on the patient. Enteral absorption in infants is slower than in older children. Therefore maximum concentration will be reached later and will be not as high as in older children. The local concentration correlates well with plasma concentration. Drugs in bib or feeder have no effect.


[Possible indications for recently developed antibiotics [author's transl)]. Properties and possible indications of recently developed antibiotics are described. For the treatment of pseudomonas aeruginosa infections of all penicillins azlocillin is the most favourable drug (instead of carbenicillin), for treatment of esch. coli infections it is mezlocillin (instead of ampicillin). Becampicillin and equally amoxycillin are more than ampicillin suitable for oral application (because of almost complete absorption). Cefaclor has a broader spectrum and stronger activity than cefalexin and will replace cefalexin in future. Sisomicin is similar to gentamicin and has no essential advantages. Netilmicin seems to be less oto-and nephrotoxic than gentamicin and may be used with less risk of side-effects in patients with renal insufficiency. Amikacin is reserved for infections by gentamicin-resistant bacteria.


[Present state of antimycotic therapy (author's transl)]. In the local treatment of various forms of dermatophytosis tolnaftate used to be the most convincing drug. More recent developments have led to a group of imidazol derivatives which have a broader spectrum and are also effective against yeasts. Polyene antibiotics are still very useful in the treatment of Candida mycoses. There are only few drugs available for systemic treatment of mycoses. Grisefulvin is only effective against dermatophytes. Amphotericin B, given intravenously, is a very useful drug against a series of systemic mycoses but it's value is decreased by serious side effects. Fluorocytosin shows less unwanted effects than Amphotericin B, but many fungi are resistent against this antimycotic or may become so during treatment. Of the imidazol group only miconazole is available for systemic intravenous therapy. Further developments of systemic antimycotics are of great importance.


[Surgical treatment of congenital heart malformations. Indications and surgical management (author's transl)]. Congenital malformations of the heart have to be expected in approximately 0,8% of all newborns. The majority of them needs surgical treatment and can be corrected anatomically with a low operative risk (atrial and ventricular septal defects, patent ductus arteriosus, coarctation, valvular aortic and pulmonary stenosis etc.). Surgical repair of complex anomalies includes either palliative or functionally corrective procedures and has a much higher operative and early postoperative mortality (transposition of the great arteries, tetralogy of Fallot, tricuspid atresia etc.). Surgery becomes urgent in babies suffering from congestive heart failure and/or progressive severe hypoxia during the first months of life. Early total surgical repair or primary palliation and two-stage correction depends on the kind of anomaly and has to be selected individually. Hemodynamical classification, general distribution and surgical considerations of the most common congenital malformations of the heart are described.


[Distribution of obstetrical and postnatal risk-factors in 400 randomly selected newborns. A study using Prechtl's concept of optimal conditions (author's transl)]. The distribution of obstetrical and postnatal risk-factors in a population of 400 newborns was investigated. For documentation, an extended list of Prechtl's list of optimal obstetric conditions was used. The newborns had been selected randomly from two populations, born 1972 in two different hospitals (County hospital, University hospital). The reduction of optimal conditions was calculated by percentiles. It was found that the number -3 (of 52 items, representing full optimal conditions) defined the 10th percentile of the population; number -5 the median, and number -10 the 90th percentile. In addition, percentiles were calculated regarding the history of the mother and the history of the infant respectively. Using the distribution of reduced obstetrical and postnatal optimal conditions allows to compare the history of a single newborn or the histories of a population of newborns with defined problems. Newborns with rather low negative numbers of reduced optimal conditions are at lower risk regarding their psychomotor development wheras newborns with high negative numbers carry a much higher irsk in this respect.


[Hydrothorax during the neonatal period (author's transl)]. The congenital hydrothorax is a rare cause of the RDS in the newborn. Our observations on three patients with bilateral pleural effusions and 44 cases from the literature will be discussed; we emphasize the importance of this serious disease in the newborn period. The pathogenesis is largely unknown, however, its possible etiology like birth trauma or dysplasia of the lymphatic system are discussed. It should be pointed out that this condition can be rapidly recognized by radiographic examination and successfully treated. The reported survival rate is 29 out of 44 (66%).


[Partial trisomy of the long arm of the chromosome no. 6 (author's transl)]. The clinical features of a new chromosomal syndrome are described. The patient, a 10(9)/12 years old girl, presents a marked psychomotor retardation with short stature, microcephaly, myopia, alterations in dermatoglyphics, and some other dysmorphic signs.


Design and analysis of experiments on mutagenicity. II. Assays involving microorganisms. The design and statistical analysis of mutagenicity experiments involving microorganisms and a single dose of mutagen are discussed. Test statistics are derived for use in determining the mutagenicity of a chemical when survival data are available and also when such data are not available. One's likelihood (power) of correctly concluding a chemical is mutagenic is examined, and minimum total sample sizes required for 95% power are presented. It is found that one generally has greater power when survival data are available. Required precision is estimating survival is discussed in reference to type-1 and type-2 errors. The proper use of the formulae and figures presented is illustrated by examples.


The impact of severely damaged cells in cytogenetic research. In a large multilaboratory cytogenetic study of interlaboratory variations using 4 dose levels of triethylenemelamine and a control, a severely damaged cell was operationally defined as a cell which contained at least 10 aberrations of any type. A review of this study suggested that the use of this definition introduced a bias in the measurement and interpretation of results for the other cytogenetic categories studied. As a result, the original severely damaged cells were carefully reanalyzed to investigate the characteristics of this bias and to seek procedures to minimize or eliminate it. Results characterize this bias and demonstrate that when a severely damaged cell is defined as one containing at least 20 aberrations and those aberrations in the remaining non-severely damaged cells are classified by specific type, the bias is significantly reduced and chromosome analysis can be improved as a test system.


Gender of infants conceived on different days of the menstrual cycle. The baby's sex was studied in 3658 births to Jewish women who observed the orthodox ritual of sexual separation each month and who resumed intercourse within two days of ovulation. The day of resuming intercourse relative to ovulation was estimated from the characteristics of each woman's menstrual cycle and the number of days of sexual abstinence observed after the last menstruation. The proportion of male babies was significantly higher (65.5 +/- 3.9 per cent, mean +/- S.D.) in the offspring of women who resumed intercourse two days after ovulation. This proportion tended to be lower on or near the day of ovulation than on the previous one or two days. These results, which were consistent in different demographic subgroups, demonstrate that insemination on different days of the menstrual cycle does lead to variations in sex ratio. Couples should be cautioned against attempting to conceive a boy by delaying intercourse until after ovulation, until further research has established whether delayed fertilization causes birth defects.


Recurrent abdominal pain of childhood due to lactose intolerance. The role of lactose malabsorption was studied prospectively in 80 schoolchildren with recurrent abdominal pain. Malabsorption was documented in 40 per cent (16 of 59 whites, 12 of 16 blacks and four of five Hispanic children) on the basis of elevated levels of hydrogen in their breath. Those with lactose malabsorption, however, were not clinically distinguishable on the basis of past milk ingestion (P greater than 0.05), weekly pain frequency (median, five vs. six times), presence of diarrhea (40 vs. 27 per cent) or symptom response to lactose load. In children with malabsorption who completed a six-week diet trial, 70 per cent reported increased frequency of pain (P less than 0.002) when placed on their usual lactose-containing diet. Lactose malabsorption has a substantial role in the symptoms of children with recurrent abdominal pain, and it should be considered before performing invasive procedures or assuming a psychogenic origin.


Can China's health care be transplanted without China's economic policies? China's economic policies of the past 25 years have shaped its present health-care system. China's leadership has decided to have neither a national health-insurance system nor a national health service. Instead, it decided that its health system would mirror the workings of its industrial and agricultural system. Decisions to minimize imports, ban private economic activity, assign university graduates on a compulsory basis, control wages, maintain a large domestic standing army and prevent professions or universities from acquiring independent status led directly to the present system of medical care. Consequently, transplantation of China's striking achievements in health-care delivery to the United States or other countries is unlikely to occur in the absence of transfer of the underlying economic policies.


Immune interferon in the circulation of patients with autoimmune disease. The observation that type II, or immune, interferon could be produced by peripheral-blood leukocytes in vitro on an immune-specific basis suggested that it also might be produced in vivo in various autoimmune disorders. We found immune interferon in the serums of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma and Sjögren's syndrome. Among 28 patients with systemic lupus erythematosus, 71 per cent of those with active and 21 per cent of those with inactive disease showed interferon in their serums. Serial serum samples showed a good correlation between interferon titers and disease activity. Moreover, interferon titers correlated positively with antibodies to DNA and negatively with serum levels of the third component of complement. It is possible that the production of interferon may contribute to immunologic aberrations in auto-immune diseases and also protect the already compromised host from viral infections.


Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. In percutaneous transluminal coronary angioplasty, a catheter system is introduced through a systemic artery under local anesthesia to dilate a stenotic artery by controlled inflation of a distensible balloon. Over the past 18 months, we have used this technic in 50 patients. The technic was successful in 32 patients, reducing the stenosis from a mean of 84 to 34 per cent (P less than 0.001) and the coronary-pressure gradient from a mean of 58 to 19 mm Hg (P less than 0.001). Twenty-nine patients showed improvement in cardiac function during follow-up examination. Because of acute deterioration in clinical status, emergency bypass was later necessary in five patients; three showed electrocardiographic evidence of infarcts. Patients with single-vessel disease appear to be most suitable for the procedure, and a short history of pain indicates the presence of a soft (distensible) atheroma likely to respond to dilatation. We estimate that only about 10 to 15 per cent of candidates for bypass surgery have lesions suitable for this procedure. A prospective randomized trial will be necessary to evaluate its usefulness in comparison with surgical and medical management.


Increasing minority recruitment to the health professions by enlarging the applicant pool. Over an eight-year period, 707 students from minority groups or with economically disadvantaged backgrounds were selected from junior and senior-high-school classes throughout the state of Arizona and admitted to a Med Start program emphasizing careers in the health professions. The program featured recruitment into clubs, training in leadership, counseling by other minority students, work experience and specialized courses in English, mathematics and basic biologic sciences. Attrition was remarkably low. At the time of follow-up study, 369 of these students had sought further education beyond high school, and 220 of this group had enrolled in or completed health-education programs. Although obviously not a controlled experiment, this experience suggests that the pool of minority and economically disadvantaged applicants for careers in the health professions can be enlarged.


Mineralocorticoid-induced hypertension in patients with orthostatic hypotension. The mechanism of recumbent hypertension induced by fludrocortisone was studied in seven patients with orthostatic hypotension. All showed increases in blood pressure in the recumbent and standing positions, and hypertensive levels were achieved on recumbency in four of them. Hypertensive retinopathy developed in two patients and cardiomegaly in one. Initial blood-pressure elevations were associated with sodium retention and plasma-volume expansion. However, with long-term treatment, plasma volume decreased to control levels despite further blood-pressure increases. Treatment did not affect plasma levels of catecholamines but did enhance pressor responsiveness to infused norepinephrine in some subjects. Hemodynamic studies indicated that hypertension in the recumbent position was related to increases in total peripheral-vascular resistance and not to changes in cardiac output. Clinically, hypertension in the recumbent position is an important risk of fludrocortisone treatment in patients with orthostatic hypotension. This unusual model of chronic mineralocorticoid-induced hypertension is not volume dependent but is related to increased peripheral-vascular resistance.


A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis. We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.


Serum ferritin as a possible marker of the hemochromatosis allele. To determine whether a correlation exists between the biochemical expression of hemochromatosis and the HLA genotype, we studied 174 family members of 32 persons with the disease. Persons who shared both HLA haplotypes with the proband (and presumably having two hemochromatosis alleles) differed significantly from those who shared only one haplotype (and presumably having one hemochromatosis allele) in terms of serum iron (P less than 0.001 for both sexes), unsaturated iron-binding capacity (P less than 0.01 for female and P less than 0.0001 for male subjects) and serum ferritin (P less than 0.0001 for female and P less than 0.00001 for male subjects). The only significant difference between relatives having one hemochromatosis allele and age and sex-matched controls was related to serum ferritin values in male subjects (P less than 0.05, despite considerable overlap). In our hands, serum ferritin was the best indicator of disordered iron metabolism and was elevated among most homozygous but among few heterozygous family members.


Hereditary hemochromatosis. Phenotypic expression of the disease. Previous studies have shown that hemochromatosis is an inherited, autosomal-recessive disease and that the gene is closely linked to the HLA locus on chromosome 6. We obtained a lod score for linkage of +9.8 for a recombination fraction of 0.0 and a gene frequency of 0.056, the frequency estimated in this population. We studied the phenotypic expression of the disease in 261 members of 10 pedigrees. In heterozygotes over 20 years of age, there was an intermediate increase in transferrin saturation and a limited increase in hepatic iron but no clinical manifestations. In male heterozygotes, the average amount of iron in the liver increased from about 0.2 to 1.3 g. Abnormal homozygotes accumulated iron progressively with time, with men accumulating about 18 g in the liver. All measurements of iron status were increased in abnormal homozygotes. Hemochromatosis is inherited as an autosomal-recessive disease, with partial biochemical expression in heterozygotes.


Exercise stress testing. Correlations among history of angina, ST-segment response and prevalence of coronary-artery disease in the Coronary Artery Surgery Study (CASS). To determine to what extent the diagnostic accuracy of stress testing is influenced by the prevalence of coronary-artery disease, we correlated the description of chest pain, the result of stress testing and the results of coronary arteriography in 1465 men and 580 women from a multicentered clinical trial. The pre-test risk (prevalence of coronary-artery disease) varied from 7 to 87 per cent, depending on sex and classification of chest pain. A positive stress test increased the pre-test risk by only 6 to 20 per cent, whereas a negative test decreased the risk by only 2 to 28 per cent. Aothough the percentage of false-positive results differed between men and women (12 +/- 1 per cent versus 53 +/- 3 per cent P less than 0.001), this difference was not seen in a subgroup matched for prevalence of coronary-artery disease. We conclude that the ability of stress testing to predict coronary-artery disease is limited in a heterogeneous population in which the prevalence of disease can be estimated through classification of chest pain and the sex of the patient.


Human chorionic gonadotropin in the plasma of normal, nonpregnant subjects. To determine whether ectopic secretion of a protein hormone can occur normally, we studied plasma from normal, nonpregnant subjects for the presence of a placental hormone, human chorionic gonadotropin. We extracted and purified this hormone from other plasma proteins. We identified the hormone in the final residue on the basis of its dose-response curves in a specific radioimmunoassay and calculated the plasma concentration after correction for losses. Because this assay is sensitive to concentrations as low as 2 pg per milliliter, human chorionic gonadotropin could be detected in the plasma of 12 of 16 blood donors; the median concentration was 19 pg per milliliter (range, less than 2 to 361). This immunologic human chorionic gonadotropin was further characterized from a pool of normal plasma by gel filtration on Sephadex G-100 and was found to be identical to the standard form of the hormone. The concentration in this pool from 13 normal men was 18 pg per milliliter. The source of this ectopic hormone production is unknown, but may be normal, rapidly proliferating nonmalignant cells.


[Variation of the yeast flora in the buccal cavity between controls and subjects treated with psychotropic drugs]. The yeasts of buccal cavity were studied in a group of seventy-five subjects treated by psychotropic drugs in a psychiatric hospital, in a group of fifty-one subjects treated by psychotropic drugs at home, and in a basis group (100 + 50). It is found yeasts on 84% of treated subjects in a psychiatric hospital and only 40% in the other populations.


Biochemical and serological characteristics of soluble yeast phase antigens of Histoplasma capsulatum. Soluble antigens of whole yeast-phase cells were extracted with a 0.1 M phosphate buffer containing 0.1 M sodium chloride and 0.02% iodacetate. After being separated by differential filtration into fractions less than or greater than 50,000 daltons these antigens were purified by molecular sieve and chromatographic separations on ionic exchange resins. Two high molecular weight fractions obtained from diethylaminoethyl-cellulose (DEAE) at pH 8.0 and 7.0 with tris (hydroxymethyl) aminomethane (Tris) buffer were M antigens; those obtained at pH 4.0 and 4.0 with salt were H antigens. The four fractions had protein to carbohydrate ratios of 7.3, 14.0, 8.4, and 6.5 respectively, and all had essentially the same amino acid composition with no methionine and tyrosine and little histodine, arginine, phenylalanine and lysine. They had high concentrations of glucose, less mannose and traces of galactose. The low molecular weight fractions had the new complex "Y antigen", M antigen with protein to carbohydrate ratios of 1.4, 1.4 and 0.3 respectively. The amino acid and sugar composition of Y antigen strongly resembled the composition of the low molecular weight H and M antigens. Unlike the high molecular weight antigens, these low molecular weight antigens had methionine in relatively high concentrations; they had the same sugars as their respective high molecular weight counterparts. The yeast phase antigens differed from their respective mycelial counterparts in the following ways: glucose was the major sugar in the yeast phase with less amounts of mannose and traces of galactose, whereas in the mycelial antigens, mannose was the major sugar, with lesser amounts of galactose, and hexosamine. The H and M antigens of the yeast phase had high concentrations of glycine and alanine, whereas in the mycelial phase, these antigens had high concentrations of threonine and proline; the H and M antigens of the yeast phase had 5 to 16 times the protein to carbohydrate ratio observed for the same antigens of histoplasmin.


Crystal structure and molecular interactions of tropomyosin. The three-dimensional structure of tropomyosin filaments has been determined by X-ray crystallography. The ends of the molecules were located by reference to the single pair of cysteine residues. Departures from the alpha-helical-coiled coil conformation may occur in localised domains along the molecule as well as at the overlapping ends.


Organisation and sequences at the 5' end of a cloned complete ovalbumin gene. A clone which contains the complete chicken ovalbumin gene, including its leader coding sequences, has been isolated. From electron microscopic analysis of this DNA we conclude that the minimal size of the transcriptional unit for ovalbumin is 7.7 kilobases. The DNA sequence of the region surrounding the 5' end of the ovalbumin gene is presented. Comparison of this sequence with those of other eukaryotic genes reveals striking similarities, possibly related to a promoter region, approximately 30 base pairs upstream from the site coding for the 5' end of the mRNA.


Nerve fibre topography in the retinal projection to the tectum. The orderly layout of visual fibres in the optic nerves of cichlid fishes suggests that they are guided most of the way to the brain by contact with their neighbours. Before they reach the visual map in the tectum, however, their arrangement in the cross-section of the nerve is reorganised in a way which requires longer-range guidance.


Characterisation of deletions which affect the expression of fetal globin genes in man. Deletions in the DNA of individuals with hereditary persistence of fetal haemoglobin (HPFH) and 8 beta-thalassaemia have been mapped as a means of identifying regulatory sequences involved in the switch from fetal to adult globin gene expression. The end points of these deletions have been precisely located with respect to restriction endonuclease cleavage sites within and surrounding the gamma-, delta- and beta-globin genes in normal human DNA and the deletion maps were used to obtain definitive evidence for the physical linkage of the fetal and adult beta-like globin genes in the order 5'Ggamma-Agamma-delta-beta 3'. Correlation of haematological data and the location of deletions in two cases of HPFH and one case of deltabeta-thalassaemia suggest that a region of DNA located near the 5'-end of the delta-globin gene may be involved in the suppression in cis of gamma-globin gene expression in adults. The interpretation of a second case of deltabeta-thalassaemia is complicated by the fact that the deletion removes the Agamma-gene in addition to the region near the 5'-end of the delta-globin gene.


The three-dimensional structure of tubulin protofilaments. A three-dimensional image of tubulin protofilaments, reconstructed to 20 A resolution from electron micrographs of negatively stained zinc-induced sheets, has been used to generate an improved model for microtubule substructure. This model has been used to phase a reconstructed image from X-ray amplitudes, which is compatible with the electron microscope results.


Efficient translation of prokaryotic mRNAs in a eukaryotic cell-free system requires addition of a cap structure. In this and the accompanying paper we demonstrate that certain prokaryotic mRNAs, when modified at their 5'-termini with a cap structure, are translated in a eukaryotic cell-free protein synthesising system as efficiently as, or more efficiently than, eukaryotic mRNAs. Apparently, the prokaryotic mRNA contains all the information necessary for efficient recognition and initiation by eukaryotic translational components, except for the cap structure.


Sequence, structure and activity of phosphoglycerate kinase: a possible hinge-bending enzyme. The fitting of sequenced peptides to a high-resolution X-ray map of phosphoglycerate kinase has yielded the complete sequence and structure of the horse muscle enzyme. Metal ADP and ATP substrates are bound to one of the two widely separated domains in an environment that seems unsuitable for phosphoglycerate binding. The most plausible binding site for the phosphoglycerate substrate is on the other domain about 10 A from the ATP, which implies the possibility of a large scale hinge-bending of the domains to bring the two substrates together in a water-free environment for catalysis.


Embryonic development of identified neurones: differentiation from neuroblast to neurone. Individually identified neurones are sufficiently large and accessible in grasshopper embryos to permit visualisation and impalement with intracellular microelectrodes from the time of their birth to their maturation. In this article part of the temporal pattern of differentiation from an identified neuroblast (precursor cell) to a group of identified neurones is described.


Uromucoid (Tamm-Horsfall's mucoprotein) in amniotic fluid and in urine in children. Uromucoid (Tamm-Horsfall's mucoprotein) was not detected in amniotic fluid from pregnancies with gestational are 12-18 weeks, but was detected in 5 of 9 samples of amniotic fluid from full-term pregnancies, and in urine from all full-term infants investigated 1st day of life. This suggests that uromucoid excretion under normal conditions established near term. Change from intrauterine to extrauterine life may rapidly induce uromucoid excretion, as this protein was found in premature infants (32-34 weeks of gestation) at the 2nd day of life. Healthy newborn infants had a lower uromucoid concentration in urine than children 7--13 years old. In newborns with uncomplicated prematurity, idiopathic respiratory distress syndrome and full-term asphyxiated newborns, the uromucoid concentration in urine during the 1st week of life was not different from healthy newborn infants. Though uromucoid is found to be the major constituent of hyaline casts, the excretion of casts did not correlate to the uromucoid concentration.


Development of glomerular fibrinolytic activity in the rat. Fibrinolytic activity of the glomeruli was studied in rats of different age using the fibrin-slide technic. In normal rats glomerular fibrinolytic activity (GFA) was relatively low. After a single injection of liquoid (sodium polyanethol sulfonate), a pronounced increase of GFA was evident. The superficial nephrons had a significantly higher GFA than the juxtamedullary nephrons. Compared with rats 2 months of age, rats 2 weeks of age showed a greater GFA in all the glomeruli.


Differential effects of diuretic agents on electrolyte excretion in the dog. Role of renal hemodynamics. The sulfonamide derivative diuretics acetazolamide, metolazone and furosemide produce differing degrees of natriuresis and varying patterns of phosphate excretion. At least part of the explanation for these diverse actions could be related to divergent effects of the drugs on total renal blood flow (TRBF) and its intracortical distribution (IBFD). To test this hypothesis, and to determine if a consistent thesis regarding alterations in interenal blood flow could be developed, clearance studies were performed in chronically thyroparathyroidectomized dogs in which radioactive microsphere methodology was utilized to evaluate the distribution of blood flow within the renal cortex. These data were then compared with those available in the literature. The variations which the drugs induced in TRBF and IBFD did not help to explain the differences in their diuretic actions. However, a consistent hypothesis relating natriuresis, perfusion pressure, renal vascular resistance, TRBF and IBFD could be developed based on the data from this study and those available in the literature.


Symptomatic hypomagnesemia associated with gentamicin therapy. A 57-year-old male developed hypomagnesemia, hypokalemia and hypocalcemia during the course of repeated gentamicin therapy. Renal wasting of magnesium and potassium was demonstrated. Associated endocrine abnormalities included decreased level of serum immunoreactive parathyroid hormone and increased levels of plasma renin and aldosterone. Our findings are compared to those previously reported by other investigators.


Origin of urinary fibrin-fibrinogen degradation products in renal glomerular disease. The origin and mechanism of renal clearance of urinary 'fibrin-fibrinogen degradation products' (FDP) were studied in patients with renal glomerular diseases associated with heavy, non-selective proteinuria and high levels of urinary FDP. The results indicated that the urinary FDP arose primarily by the filtration of unaltered plasma fibrinogen through a damaged and abnormally permeable glomerular basement membrane and that a variable degree of lysis of the filtered fibrinogen occurred in the urine. The lysis of cross-linked fibrin in intraglomerular deposits, as evidenced by the presence of dimeric fragment D in the urine, appeared to contribute only a small amount to the total urinary FDP excretion.


Effect of hypoxia and ischemia on the distribution of protein in brain cellular fractions. The effect of postdecapitative ischemia (5 min at 37 degrees) and hypoxia (5% O2, 95% N2, 30 min) on the distribution of protein radioactivity in the cellular fractions of guinea pig cerebral cortex was studied. Ischemic conditions resulted in the increase of total radioactivity level and protein content in the mitochondrial fraction. In the cytosol the opposite effect was observed; the radioactivity and protein content were decreased. The amino acid analysis of microsomal proteins and the distribution of glucose-6-phosphatase activity, differing from those in control animals, suggest structural disturbances in the microsomal fraction. The results indicate a different sedimentation of proteins in the given experimental conditions. After hypoxia such effects were not observed.


Simultaneous measurement of regional blood flow and glucose extraction in rat brain. A method has been described which allows the measurement of cerebral blood flow (CBF) and solute transport across cerebral capillary wall in the same regional sample of rat brain. An inert diffusible indicator (iodoantipyrine) was used to measure a blood flow, in mixed gray and white matter, or approx. 1.0 ml/min/g. Using 3H2O as a reference molecule, the flux of [14C]D-glucose into brain was determined at blood glucose concentration levels between 0.1 and 60 mM. In all discrete areas of brain sampled, a consistent Vmax of 1.92 micromol/min/g and a Km of 8.35 mM was found. Glucose extraction by brain was inversely related to CBF, while a direct relationship was noted for glucose clearance.


Macromolecular synthesis in mitochondria isolated from different regions of developing rat brain. DNA, RNA, and protein synthesis in mitochondria isolated from cerebral hemispheres, brain stem, and cerebellum of 10- and 30-day-old rats was measured. Synthesis of different macromolecules was affected by the respective mitochondrial specific inhibitors, showing a good level of purity of mitochondrial preparations. DNA and protein synthesis in 10-day-old rats was about 70% higher than in 30-day-old animals. In contrast, RNA synthesis did not decrease with age in all the regions examined.


Gangliosides and other lipid micelles. A study of amine binding by a dialysis/fluorescence method. The binding of serotonin to bovine adrenal medulla gangliosides (BAMG), bovine brain gangliosides (BBG), and BBG-synthetic lecithin mixed micelles has been demonstrated by a rapid technique using fluorescence monitoring of dialysis rates. BAMG micelles bound 0.10 mM serotonin at about half the efficiency of BBG micelles having the same sialic acid concentration (0.50 mM) in water. In water, the effect of BBG micelles was essentially identical to that of mixed micelles containing the same quantity of BBG. Ca2+ (1.20 mM), however, cancelled the effect of the mixed micelles on serotonin dialysis and reduced the effect of BBG micelles to about one quarter of that observed in water. These and other observations are related to earlier studies and to neurochemical processes which may involve gangliosides.


Mitochondrial DNA, RNA, and protein synthesis in different regions of developing rat brain. In vivo and in vitro (tissue slices) incorporation of labeled precursors into DNA, RNA, and proteins was measured in mitochondria obtained from cerebral hemispheres, cerebellum, and brain stem of rats at different days of postnatal development. To compare the synthesis of macromolecules in mitochondria with that in other subcellular fractions, the incorporation of labeled precursors into DNA, RNA, and proteins extracted from nuclei and into RNA and proteins extracted from microsomes and cytoplasmic soluble fractions was also measured. The results obtained showed that the incorporation of [3H]thymidine into DNA and of [14C]leucine into proteins of nuclei and mitochondria from the various brain regions examined decreased during postnatal development; however, at 30 days of age the specific radioactivity of mitochondrial DNA was higher than that of nuclear DNA. [3H]Uridine incorporation into RNA decreased from 10 to 30 days of age in nuclei while in mitochondria it was quite similar at both ages. This result may be due to a faster turnover of mitochondrial RNA compared to that of mitochondrial DNA and proteins. The results obtained suggest an active biosynthesis of macromolecules in brain mitochondria and might indicate an intense biogenesis of these organelles in rat brain during postnatal development.


Changes in fluid compartments and ionic composition in the isolated chick retina during SD. Total content of water, extracellular spaces (ES), na+, K+, and C1- in the isolated chick retina were measured in the presence (test) or absence (control) of spreading depression (SD). During SD in medium with 0.5 mM or 2 mM MgSO4, there is an increase in the intracellular concentration of Na+ and C1- and a decrease in the intracellular concentration of K+. A decrease in the ES was only found in the medium with 2 mM MgSO4 together with a diminished outmovement of K+. We suggest that a decrease in the ES is due to an increased absorption of K+ by the Muller cells, causing its swelling and consequently a decrease of the ES. The addition of sucrose (17 mM) to the incubation medium as the extracellular marker markedly decreased the intracellular concentration of C1- in control retinas, blocked the inward movement of this ion to the tissue during SD and also changed the K+ movement during the phenomenon in medium with 2 mM MgSO4. We suggest that C1- is an important ion in the ionic balance of the Muller cells and that sucrose must have its site of action at these cells.


[Assessment of regional cerebral blood flow (rCBF) and vascular changes in angiographic studies in cases of cerebral ischemia]. In 22 patients the regional cerebral blood flow (rCBF) was measured after intra-arterial injection of xenon 133Xe. In all patients cerebral angiography was performed after that and in 4 patients aortic arch angiography was done as well. In 2 cases of subclavian artery stenosis with normal state of the branches of the internal carotid artery the rCBF was not decreased. On the other hand, a significant decrease of rCBF was found in cases of transient cerebral ischaemic episodes with angiographically demonstrated bilateral stenosis of the afferent arteries and coexistence of stenosis of the afrerent arteries supplying the brain and intracranial arteries. On the basis of an analysis of rCBF angiograms the authors suggest the conclusion that a joint evaluation of the clinical manifestations, results of rCBF measurements and angiograms increases the accuracy of assessment of the condition of the cerebral circulation in patients qualified for patency-restoring operations.


[Rheoencephalographic evaluation of carotid artery compression test in patients with ischemic cerebral stroke]. The rheoencephalographic method was applied for evaluating the common carotid artery compression test in 87 cases, including 49 patients with ischaemic strokes and 38 healthy subjects. In all 174 tests were done. No complications were observed. The investigation confirmed the usefulness of the test for the diagnosis of carotid artery occlusion. The test should be used routinely in rheoencephalographic investigations in patients with ischaemic cerebral strokes.