Quantitative nucleotide sequence relationships of mammalian RNA tumor viruses. A molecular hybridization technique has been used to quantitatively measure the nucleotide sequence relationships of selected mammalian RNA tumor viruses. Reciprocal cross-hybridization tests were done in which a given radioactively labeled, viral genomic RNA species was annealed with an excess of unlabeled, complementary DNA product synthesized in endogenously instructed reverse transcriptase reactions. Hybrid formation was measured with pancreatic RNase A. Three representative mammalian RNA tumor virus groups were examined: murine viruses, simian viruses, and feline viruses. The results of reciprocal cross-hybridization testing have revealed that the murine viruses consist of four distinctly related subgroups: (i) the Friend leukemia virus/Rauscher leukemia virus subgroup, (ii) the Gross leukemia virus subgroup, (iii) the Moloney sarcoma virus subgroup, and (iv) the Kirsten sarcoma virus subgroup. Simian sarcoma virus, the only simian virus examined, appeared to share limited interspecies sequence relationships with members of the other virus groups and in particular with Kirsten sarcoma virus. Of the two members of the feline virus group tested, Rickard feline sarcoma virus and RD-114, each was placed in a separate, unrelated subgroup. Rickard feline sarcoma virus exhibited limited sequence relatedness with members of the other virus groups, whereas RD-114 exhibited none.


Interspecies antigenic determinants of the reverse transcriptases and p30 proteins of mammalian type C viruses. The major internal structural proteins (p30) of type C viruses isolated from several mammalian species were studied by radioimmunoprecipitation and competitive radioimmunoassays. Three antigenically distinguishable sets of interspecies determinants could be demonstrated by both methods. One set of determinants shared by viruses of rodent origin (mouse and rat) can be detected readily in feline leukemia viruses but not in other type C viral groups. The p30 proteins of murine viruses also contain a second discrete set of antigenic determinants related to those in infectious primate viruses and endogenous porcine viruses, but not detected in the feline leukemia virus group. The p30 proteins of endogenous viruses of baboons and domestic cats share yet a third set of cross-reactive determinants not detected in type C viruses isolated from other species of animals. Enzyme inhibition studies performed with antisera raised toward the reverse transcriptases of these same groups of type C viruses showed the same patterns of immunological cross-reactions as observed with p30 proteins. The antigenic cross-reactions between the homologous proteins of type C virus isolated from genetically distant animals may reflect transmission of type C viruses across species barriers.


Transurethral prostatectomy in patients with severe hip deformity. The use of a modified lithotomy position and perineal urethrotomy has permitted transurethral prostatectomy in patients with severe hip disease. The procedure is described.


[Monocyte function in chronic uremia (author's transl)]. Monocyte function studies in vitro have been performed in 21 patients with terminal, dialysis-treated uremia and, in parallel, in 21 healthy normal subjects. In uremia the attachment, spreading activity, and reduction of nitroblue tetrazolium were shown to be significantly enhanced, indicating a metabolic activation of the monocytes. The phagocytosis of IgG-coated red cells, however, was significantly impaired. A modification of the monocyte IgG-receptor in uremic conditions is supposed; its relevance for the immunosuppression in uremic states is discussed.


[Autoantibodies against heartmuscle sarcolemma in sera of patients with an idiopathic cardiomyopathy (author's transl)]. 68 patients with clinical and hemodynamical diagnosis of idiopathic cardiomyopathy (CM) were analysed for antibody in their sera using an immunofluorescence sandwich technique after titration of the sera in tissue sections. 60 of these patients had antibodies against heart muscle sarcolemma with titers up to 1:64. Out of these, the antibodies in 9 sera could be absorbed with group A streptococci. The antibodies reacted in no case with striated or smooth muscle sarcolemma. The 25 patients with an obstructive type of CM showed the highest titers and 12 of them, in addition, had antinuclear factors in their sera. These findings suggested an auto-allergic etiology for most cases of idiopathic CM.


The effects of captivity stress on the blood chemical values of the chacma baboon (Papio ursinus). Baboons were trapped and transported to the colony within 3 days of being captured. Blood was collected on Tuesdays and Fridays for blood chemical determinations. The changes in albumin and globulin resulted in marked changes in the albumin: globulin ratio. Cholesterol values showed a sudden and marked drop and the values were still below normal at the end of 9 weeks. Blood sugar values increased to significantly elevated levels and marked changes occurred in the enzyme activity and plasma corticosteroid activity. Male and female animals differed in their response with regard to the values found in some parameters. A period of adaptation or conditioning of 8 weeks was found to be required for an animal to reach stability in its blood chemical values.


A simple staining method for vaginal smears using red ink. In adult rhesus monkeys each phase of 37 menstrual cycles was accurately classified by cellular identification of vaginal smears stained with red ink. This technic was simple, quick, and inexpensive, and produced well-stained slides in a few seconds.


Mast cell increase in the duodenum and kidney of magnesium-deficient rats. Rats were maintained on a magnesium-deficient diet for 1 to 5 weeks to study the mast cell (MC) populations in their duodenum and kidney. A marked increase of intestinal subepithelial mast cells was observed in these animals as compared with normal controls. The cells in both groups showed an identical reaction for mucopolysaccharides but the 5-hydroxytryptamine content tended to be higher in the cells of magnesium-deficient animals. Proliferation of MC was also observed in the renal cortex of the magnesium-deficient rats. This finding is significant because MC are known to be virtually absent from normal kidneys. Magnesium deprivation resulted in numerous MC not only in the intertubular spaces but also within the glomeruli. Possible correlations between these and other pertinent observations are discussed with regard to certain renal diseases. The discussion is extended to the possible mechanism through which magnesium could influence secretory processes in MC.


Casein-induced experimental amyloidosis. V. The response of lymphoid organs to T and B mitogens. Functional and morphologic studies were performed on the lymphoid organs of inbred CBA/J mice receiving chronic casein administration. In the spleen, this regimen produces marked reticuloendothelial proliferation between 8 and 16 injections (preamyloid phase) and amyloid deposition between 16 and 24 injections. No amyloid was found in the thymus, lymph nodes, and bone marrow of these animals. Phytohemagglutinin and concanavalin A lymphocyte responses as measured by 3-H-thymidine incorporation were reduced in the spleen and lymph node of preamyloid animals but demonstrated partial recovery during the amyloid phase. Phytohemagglutinin and concanavalin A stimulation of thymic cells was significantly increased during both stages of amyloid induction, although the histologic studies revealed a marked involution of the thymic cortex. Lipopolysaccharide stimulation of spleen cells was normal in preamyloid and amyloid animals whereas in lymph node and bone marrow lipopolysaccharide responses were significantly decreased. The findings suggest a selective removal of subsets of T cell populations in the spleen and thymus and migration of B cells from bone marrow to the spleen during experimental amyloidosis.


A mandatory treatment program for skid row alcoholics; its implication for the Uniform Alcoholism and Intoxication Treatment Act. Mandatory and voluntary treatment programs for Skid Row alcoholics are described, and the implications of the Uniform Alcoholism and Intoxication Treatment Act are discussed.


Personality differences in patients at three alcoholism treatment agencies. Results of personality inventories completed by patients in three alcoholism treatment and two control groups revealed differences between the personality profiles of these groups, suggesting that different types of programs attract different types of clients.


The clinical significance of hepatitis B virus antigens and antibodies. There are two well-characterized antigen-antibody systems which relate specificially to viral hepatitis B. Tests for HBsAg and anti-HBs are readily available and of great benefit to the diagnosis, prevention and understanding of hepatitis B. Tests for HBcAg and anti-HBc are still research techniques which requires further development before they can be used at the level of everyday medical practice. HBsAg in an individual indicates that he harbors the virus of hepatitis B; it may be present in the absence of liver disease or be found in association with both acute and chronic type B hepatitis. The presence of HBsAg also suggests that HBV may be causally related to some cases of periarteritis nodosa, chronic glomerulonephritis, and hepatoma. Although HBV is readily transmitted in blood, the major portion of post-transfusion hepatitis now appears to be serologically unrelated to either the hepatitis B virus ("serum") or the hepatitis A virus ("infectious"); the etiology of these cases is currently undetermined. There is increasing evidence that HBV may be transmitted by modes other than blood, but the exact mechanisms of such transmission is not established. The combined transmission of HBV by blood and other routes has resulted in a large number of persistent carriers of HBsAg in the world. There is no current method to alter this carrier state. The hepatitis risk of such persistent carriers to their personal and professional contacts is under investigation.


Epidemiology of Escherichia coli K1 in healthy and diseased newborns. Although at least 100 different Escherichia coli capsular antigens have been recognised, strains possessing the K1 antigen are responsible for 77% of neonatal E. coli meningitis cases.  K1 strains were found in 20-40% of rectal swab cultures from healthy infants, children, and adult women.  Vertical transmission from mother to infant was the most common means of aquiring K1 organisms in term infants.  Premature babies in a nursery with little maternal contact aquired K1 strains later then did term infants, and this aquisition may have been related to carriage by nursery staff.  Capsular content and fermentation reactions of cerebrospinal-fluid K1 organisms were comparable to those found in rectal strains from healthy individuals.  E. coli K1 with identical O and H antigens were found in maternal and infantile cultures of babies with E. coli meningitis.  It seems very likely that host immune mechanisms play a significant role in the pathogenesis of neonatal E. coli K1 meningitis.


Plasma-lipids and glucose/insulin relationship in non-insulin-requiring diabetics with and without retinopathy. Serum-lipid concentrations and their relationship to blood-glucose and serum-insulin were examined in non-insulin-requiring diabetics, 62 with and 45 without retinopathy.  The age, sex-body-weight, and duration of known diabetes was comparable in the two groups.  All were treated by diet only or diet and oral hypoglycaemic agents.  Patients with retinopathy had higher fasting serumtriglyceride and serum--cholesterol levels than those without.  Compared with a non-diabetic population, significantly more diabetics with retinopathy had raised derum-lipids.  The lipid concentrations did not correlate with body-weight, serum-thyroid-stimulating-hormone levels, renal involvement, or fasting blood-sugar.  While the blood-sugar concentrations were similiar in the two groups the absolute insulin increment and the relative insulin response to a 50 g. oral glucose load were significantly lower in those with retinopathy than in those without.  The impairment of insulin response correlated significantly with the frequency of hyperlipidaemia.  It is suggested that insulin deficiency with secondary hyperlipidaemia is characteristic of diabetic patients with retinopathy.


New variant of phenylketonuria with progressive neurological illness unresponsive to phenylalanine restriction. Three children, two of them siblings, with an unusual type of phenylketonuria are described.  The three patients, two of them observed from the neonatal period, had a progressive neurological illness which was unlike that of classical phenylketonuria, and which did not respond to a low phenylalanine diet.  The biochemical features suggested that the block in the conversion of phenylalanine to tyrosine was less severe than in the classical disease, and phenylalanine rho-hydroxylase activity, measured in one patient was normal.  It is suggested that the patients have a disorder of biopterin metabolism possibly due to a defect of the enzyme dihydropteridine reductase.


Factor VIII and glomerulonephritis.

Factor VIII and glomerulonephritis. To find out if determination of factor VIII,which most probably is synthetised in the intima of blood-vessesls, is of value for predicting the severity of vessel damge in glomerulonephritis, factor-VIII activity, factor-VIII-related  antigen, and glomerular filtration-ratewere esto,ated om 85 patients with early glomerulonephritis on admission, and in 70 of these at follow-up for up to 4 years. The levels of factor-VIII activity and factor-VIII-related antigen on admission were normal in those patients who recovered. Where renal function was impaired on admission or becaome so during follow-up, factor VIII  was high. Determination of factor VIII might thus be of prognostic value in early glomerulonephritis.


Weight carrying after myocardial infarction. The blood-pressure responses to carrying a 15 kg. weight in a shoppong basket, and in a rucksack on the back, were compared in 13 ambulant male patients who were convalescing from an uncomplicated myocardial infarction.  In 8 of the patients a sustained-handgrip test was also performed.  Carrying the weight in the hand produced a distinct increase in blood-pressure, which did not occur when the weight was carried on the back. There was also a significant increase in blood-pressure during sustained handgrip.  In view of the lack of symptoms with these circulatory changes, it is concluded that more specific advice about the possible dangers of sustained static exercise should be given to patients recovering from myocardial infarction.


Intra-amniotic urea and low-dose prostaglandin E2 for midtrimester termination. The efficacy and morbidity of injecting a standard dose of urea (80 g.) and a lower dose of prostaglandin E2 (P.G.E2) (2-5 MG) than that used previously have been assesed in 110 patients. All aborted--in a mean time of 10 hours 41 minutes. The average inpatient stay was 3-3 days. 5 patients (4-5%) had a cervical laceration.


Effect of pectin, guar gum, and wheat fibre on serum-cholesterol. 36 G of wheat fibre, pectin, or guar gum was given over 2-week periods to healthy volunteers taking normal diet. Mean serum-cholesterol levels fell significantly while the volunteers were taking guar and pectin by 36-3 and 29-2 mg, per 100. respectively, but rose slightly after wheat fibre by 6-7, mg per 100., Attention should be focused on fruit and vegetable gels rather than wheat fibre in the search of natural hypocholesterolaemic agents.


Gut bacteria and their metabolic activities in familiar polyposis. Earlier work had suggested that patients with large-bowel cancer can be characterized by carriage of clostridia capable of dehydrogenating the nucleus of steroids and by high faecal bile-acid concentrations.  Familial polyposis is an inherited disease which untreated, will progress to cancer of the large bowel, and those affected might be expected to have these metabolic characteristics.  However, enviromental factors seem to play no part in polyposis.  Investigation of as yet unaffected children of known polyposis patients revealed that the gut flora of half of them did not degrade cholesterol in vivo andnor did flora from patients in whom polyposis had already been diagnosed.  The reason for this is unknown, but if the same patients develop polyposis (i.e., they carry the abnormal gene) we would have a simple diagnostic test which could replace the continuing follow-up now required for the siblings and children of patients with polyposis.


Relation of renal growth to diabetic glomerulosclerosis. In diabetes mellitus abnormal quantiites of glycoprotein may be formed in the basement membrane of the glomerulus and both renal function and size may increase. It is suggested that these changes, of quite different potential significance, have a common origin an increased rate of uridine-triphosphate synthesis resulting from hyperglycemia.


Medical care of childhood leukaemia.

Medical care of childhood leukaemia. The medical care given to a population-based sample of children with leukaemia was reviewed between two to three years after diagnosis.  Just over half the children had been treated at local hospitals, and the others referred to centres specialising in treatment of leukaemia.  Local hospitals could be divided according to the therapeutic regimen used; the survival of children given optimal regimens at local hospitals was equivalent to that of two of the three special centres.  Assessment of social, psychological, satisfaction or cost outcomes showed no difference between the groups.  It is concluded that a regional policy for childhood leukaemia should be concerned to improve treatment regimens at local hospitals rather than attempt to concentrate care at a few centres.


Effect of a vaccination programme on the distribution of rubella antibodies in women of  childbearing age. Results of routine rubella hemagglutination-inhibiting antibody tests on 39,005 serum samples showed that 9-5% of women of childbearing age in the Leeds region were seronegative, and a further 9-2% had low antibody titres of 1/8 or 1/16.  Since routine rubella vaccination of schoolgirls began in 1970 the frequency of seronegative women in the fifteen to nineteen year age group has fallen by 5-7%.  Clinical rubella was confirmed serologically in 140 women, 58 of whom were pregnant.  30 of these pregnancies were terminated, 2 resulted in spontaneous abortions, and 26 proceeded to term.  One infant had congenital rubella.


Role of glucagon and other hormones in development of diabetic ketoacidosis. Blood concentrations of pancreatic glucagon, cortisol, noradrenaline, adrenaline, and growth hormone have been measured during the first 41 hours of insulin deprivation in six insulin-dependent diabetics to assess the importance of these hormones in the pathogenesis of diabetic ketoacidosis. Plasma-glucagon showed an early small significant rise and thereafter a slow increase to a plateau during the remaining experimental period. Plasma-cortisol increased only at the end of the insulin-deprivation period, while plasma-catecholamines and serum-growth-hormone concentrations did not change. In the three of the six patients who developed significant ketosis, plasma-glucagon showed a close correlation with blood-ketones and plasma-free-fatty-acids while for the whole group the change in glucagon concentration correlated significantly with the rise in ketone-body concentration. It is suggested that the excess of glucagon in addition to the insulin lack may be an important factor in determining the degree of hyperglycaemia had hyperketonaemia in the early stages of insulin deprivation.


Use of factor-VII-rich prothrombin complex concentrate in liver disease. A prothrombin complex concentrate rich in factor VII has been used in the management of the clotting defect in thirteen patients with liver disease. Adequate correction of coagulation was achieved immediately after infusion in all cases. Within 4 hours there was some deterioration and by 24 hours the results approximated to pre-fusion values. Liver biopsies were performed without haemorrhagic complication in the immediate post-infusion period. There was no evidence of induced intravascular coagulation. Since other prothrombin complex concentrates have proved disappointing, both in their failure to correct the clotting defect and in their production of disseminated intravascular coagulation, this factor-VII-rich concentrate may be the treatment of choice in patients with liver disease who require temporary correction of their coagulation defect.


Lack of causal association between Coxsackie B4 virus infection and diabetes. An epidemic of Coxsackie B4 virus infection in an isolated group of islands in the Bering Sea in 1967 provided an opportunity to test the suggestion that infection with this virus might be associated with an increased incidence of diabetes. In 1973 islanders were tested by glucose-tolerance tests and their two-hour plasma glucose levels were analysed in the light of serological evidence of CB4 infection five years earlier. There was no evidence of any increased prevalence of diabetes in those who had been infected in 1967.


Intravenous tyramine pressor response in depression. Tyramine-dose/pressor-response curves have been determined in 27 control subjects and 19 patients with primary depressive illness. In the depressive group, significantly lower doses of tyramine were required to elevate the systolic blood-pressure by 30 mm. Hg.


Subcutaneous intraperitoneal prosthesis for maintenance peritoneal dialysis. A subcutaneous intraperitoneal proslysis has been successfully implanted in three chronic uraemic patients. Fifty peritoneal dialyses have been done during 6-3 patient-months, without complications. During this short experience, peritonitis was not seen at all. The patients' acceptance of the prosthesis was good. Lack of abdominal tubes or bags is a remarkable technical improvement of this device.


Role of prostaglandins in the pathogenesis of acute renal failure. It is suggested that impaired glomerular infiltration in acute renal failure may be due, if only in part, to the derangement of a normal local feedback mechanism involving prostaglandins. According to this hypothesis, prostaglandins made in the medulla normally enter the loop of Henle and thus are present in distal tubule fluid reaching the macula densa. In the absence of direct vascular channels connecting the renal medulla with the outer cortex, this may be the only route by which medullary prostaglandins can reach the cortex without being destroyed by dehydrogenases. Under most circumstances in which renal perfusion and glomerular filtration fall, flow through Henle's loop continues, albeit at a reduced rate. This slowed flow through the loop and augmented prostaglandin release combine to produce a high concentration of prostaglandin in fluid leaving the medulla which, acting on the macula densa, counteracts the vasoconstrictor stimulus. If, however, filtration stops completely because of overwhelming vasoconstriction, flow along the loop also stops ans prostaglandins no longer reach the macula densa. Thus, the prostaglandin feedback loop would be opened, constrictor mechanism remain unchecked, and filtration failure perpetuated. It is proposed that such a self-perpetuating mechanism might operate in acute renal failure.


The quality of life on maintenance haemodialysis. Eighteen haemodialysis patients were interviewed in order to rate their quality of life. The data revealed a striking change in the life of most patients compared with the period before illness. Most patients had severe loss in income and for many family life deteriorated. Emotional adaptation tended to be successful in those patients before their illness. Ratings of quality of life of "good" were given to only six patients, "fair" to five, and "poor" to seven. Women seem to enjoy a better adaptation to life maintained by haemodialysis than men.


The infant's self-regulation of food intake and weight gain. Difference in metabolic balance after growth constraint or acceleration in utero. Methods of infant feeding, volume of milk intake, the introduction of solid supplements, and weight gain since birth have been studied in 191 babies at the age of 2 months. There were four groups: a hospital sample infants born to women who had been hypertensive during pregnancy, and infants who had been small-for-dates (S.F.D.) or large-for-dates (L.F.D.) at birth. Among bottle-feeders, S.F.D. infants took significantly more milk per kilogramme body-weight than infants in the hospital sample and hypertensive series; L.F.D. infants took significantly less. Within each group there was a negative correlation between actual weight at 2 months and milk intake per kilogramme body-weight. These findings are at variance with previous studies made on normal babies. Mean weight gain per kilogramme birth-weight per day was significantly increased in the S.F.D. series and reduced in the L.F.D. series compared with the hospital sample. Although mean milk intake per day at the age of 2 months was less for S.F.D. babies than for L.F.D. babies, mean weight gain per day was greater for S.F.D babies. In both extreme groups there was a tendency for breast-fed babies to revert towards the median faster than bottle-fed babies. These feeding and growth patterns of S.F.D. and L.F.D. babies suggest that there are powerful self-regulatory controls within the infant, and that the metabolic balance of S.F.D. infants is different from that of L.F.D. infants in the early postnatal months.


A double-blind trial of patient-controlled nitrous-oxide/oxygen analgesia in myocardial infarction. The analgesic effect of self-administered nitrous oxide 50%/oxygen 50% ('Entonox" analgesic apparatus) was compared with air given by the same method in a double-blind trial in 81 patients with myocardial infarction. Self-administered nitrous oxide/oxygen, which was associated with a low frequency of side-effects, proved significantly more effective than air in the early relief of severe cardiac pain, but not in the relief of moderate or slight pain or when administration was continued after ten minutes.


Sucrose in oral therapy for cholera and related diarrhoeas. Sucrose was tested as a possible alternative to glucose in oral diarrhoea therapy. Eighteen patients were given oral sucrose plus electrolytes as a maintenance solution. Fifteen of these patients could be maintained using this solution, but three developed massive increases in net fluid losses with increases in plasma specific gravity, necessitating termination of oral therapy. Twelve patients tested all had significant concentrations of stool reducing sugar. The data contrast with the rarity of treatment failures of oral glucose-electrolyte solutions. Glucose, therefore, is preferable to sucrose for oral therapy of diarrhoeal diseases.


Alcohol intoxication and serum osmolality. The relation between serum osmolality and blood-alcohol was studied prospectively in 565 acute trauma patients. The two measurements were closely correlated. It is therefore possible to estimate the blood-alcohol from serum osmolality to assist in the clinical management of acutely injured patients.


Vitamin-D status in long-stay geriatric patients. Very low concentrations of plasma-25-hydroxycholecalciferol, 25(OH) D3, were found in patinets in a long-stay geriatric hospital.


A biological role for the major histocompatibility antigens. A central function of the major histo-compatibility (H) antigens may be to signal changes in self to the immune system.  Virus-induced modification of strong transplantation antigens apparently results in recognition by thymus-derived lymphocytes (T cells), with subsequent clonal expansion and immune elimination of cells bearing non-self determinants. The extreme genetic polymorphism found in the major H antigen systems of higher vertebrates may reflect evolutionary pressure exerted by this immunological surveillance mechanism.


The hazards of bulk oxygen delivery systems. Many hospitals throughout the world obtain oxygen from a supply of bulk liquid oxygen which is delivered throughout the hospital via pipelines. An incident in which, through a series of malfunctions, dangerously high pressure developed in the hospital oxygen pipeline is described. The oxygen delivery systen described lacked a relief valve to vent excessive pressures. In North America such a relief valve is required on all oxygen delivery systems. An alarm system is also required which detects rises in pipeline pressures. Regulations in the U.K. do not provide for pressure-relief valves on liquid oxygen pipeline systems. In the U.K. there is also no regulation on alarms to warn of high pipeline pressures. High-pressure accidents are a real threat to patients and hospital staff unless proper safeguards are built into oxygen delivery systems.


Frequency of ischaemic exercise E.C.G. Changes in symptom-free men with various forms of primary hyperlipaemia. Serum cholesterol and triglycerides were measured in approximately 12,000 men attending a screening centre. 130 symptom-free men (aged thirty-five to sixty-five) were selected from the top 2% with the highest lipid values. They, and 59 normolipaemic controls, were studied by recording electrocardiograms (E.C.G.) before and during exercise. The frequency of so-called ischaemic E.C.G. changes (ST-segment depressions Minnesota code 4.1-4.4) increased with age both in controls and in the hyperlipaemic group. Ischaemic E.C.G. changes were significantly more common in all types of hyperlipaemia (types IIA, IIB, III, and IV) than in controls. The high frequency of the exercise E.C.G. changes in symptom-free hyperlipaemic men reinforces the argument for early treatment of hyperlipaemia to prevent ischaemic heart-disease.


A day-surgery programme for children incorporating anaesthetic outpatient clinic. A day-surgery programme for children incorporating an outpatient anaesthetic assessment clinic was welcomed by parents and general practitioners and resulted in better deployment of hospital resources.  It is suggested that the difficulties usually associated with day-case surgery can be reduced by holding an outpatient assessment clinic a few days before operation.


Immunological abnormalities in splenic atrophy. Multiple immunological abnormalities have been demonstrated in fourteen patients with evidence in the blood-film of hyposplenism due to splenic atrophy.  Reduction in spleen size was confirmed radiologically, and impairment of phagocytosis by the spleen was demonstrated by studying the survival and fate of chemically damaged autologous red blood-cells. Eight of the patients had intestinal malabsorption, and there was a high frequency of autoimmune disease in the remainder.  Although patients with splenic atrophy showed little evidence of impairment of normal immune responses, there was a high frequency of autoantibody formation.  There is thus an association between widespread immunological disturbances, notably autoimmunity, and splenic atrophy.


Photon absorptiometric analysis of bone density in primary hyperparathyroidism. The density of bone in the distal third of the radius was measured in 13 men and 17 women with primary hyperparathyroidism. The bone density was significantly reduced (as compared to age-matched controls) in 7 of 11 postmenopausal women. However, it was reduced in only 2 of 13 men and in 1 of 6 premenopausal women. Thus, most of the postmenopausal women with primary hyperparathyroidism had low bone density, whereas most men and premenopausal women with this condition had normal bone density. The results support the conclusion that oestrogen deficiency may contribute to the development of bone disease by sensitising bone to the action of parathyroid hormone.


Antibody to hepatitis-B core antigen in patients with primary hepatic carcinoma. Antibody to hepatitis-B core antigen (anti-HBc) was assayed in the serum of patients with primary hepatic carcinoma (P.H.C.) and controls from Hong Kong, West Africa, and the United States.  In each region the prevalence of anti-HBc was higher in P.H.C. patients than in controls, ranging from 70 to 95% in the patients and from 20 to 68% in the controls from Asia and Africa; 24% of P.H.C. patients and 4% of controls from the U.S. had anti-HBc.  These data support the hypothesis that chronic infection with hepatitis-B virus is aetiologically related to P.H.C., especially in Asia and Africa, although other factors must also be involved.


Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. The efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism has been investigated in a multicentre prospective randomised trial. 4121 patients over the age of forty years undergoing a variety of elective major surgical procedures were included in the trial; 2076 of these were in the control group and 2045 patients received heparin. The two groups were well matched for age, sex, weight, blood-group, and other factors which could predispose to the development of venous thromboembolism. 180 (4-4 %) patients died during the postoperative period, 100 in the control and 80 in the heparin group: 72% of deaths in the control and 66% in the heparin group had necropsy examination. 16 patients in the control group and 2 in the heparin group were found at necropsy to have died due to acute massive pulmonary embolism (P smaller than 0-005). In addition, emboli found at necropsy in 6 patients in the control group and 3 in the heparin group were considered either contributory to death or an incidental finding since death in these patients was attributed to other causes. Taking all pulmonary emboli together, the findings were again significant (P smaller than 0-005). Of 1292 patients in whom the 125-I-fibrinogen test was performed to detect deep-vein thrombosis (D.V.T.) 667 were in the control group and 625 in the heparin group. The frequency of isotopic D.V.T. was reduced from 24-6% in the control group 7-7% in the heparin group (P smaller 0-005). In 30 patients D.V.T. was detected at necropsy; 24 in the control and 6 in the heparin group (P smaller 0-005). 32 patients in the control group and 11 in the heparin group developed clinically diagnosed D.V.T. which was confirmed by venography (P smaller than 0-005). In addition, 24 patients in the control and 8 in the heparin group were treated for clinically suspected pulmonary emoblism. The difference in the number of patients requiring treatment for D.V.T. and/or pulmonary embolism in the two groups was again significant (P smaller than 0-005). 9 patients were found at necropsy to have died from haemorrhage; 5 were in the control and 4 in the heparin group. A careful objective analysis of operative and postoperative bleeding in 1475 patients showed no statistically significant difference in the blood-transfusion requirements or in the fall in the postoperative haemoglobin level either in the individual operative groups or in the group as a whole. However, the difference in the number of patients who developed wound haematoma in the heparin and control groups was significant (P smaller 0-01). The results of the trial indicate that this form of prophylaxis can now be recommended for use on a large scale in "high-risk" patients undergoing major surgery.


Serum fibrin(ogen) degradation products in diagnosis of deep-vein thrombosis and pulmonary embolism after hip surgery. Levels of fibrin(ogen) degradation products (F.D.P.) have been measured by radioimmunoassay for degradation product E (FgE) and by tanned-red-cell haemagglutination-inhibition immunoassay (T.R.C.H.I.I.) in the serum of thirty-three patients undergoing total hip replacement. Levels of F.D.P. did not correlate with thermographic evidence of deep-venous thrombosis. However, in 34 patients with pulmonary embolism, levels of F.D.P. measured by the T.R.C.H.I.I. were transiently raised at the time of embolus, and FgE concentrations were increased for up to 5 days preceding the embolus. Since the measurments of FgE is simple, convenient, and cheap, this estimation might constitute a valuable screening test for major thromboembolic episodes in the postoperative period.


Serial determinations of human placental lactogen in the management of diabetic pregnancy. Serial human placental lactogen (H.P.L.) determinations were carried out in 98 diabetic women during the third trimester of pregnancy. H.P.L. levels were consistently higher than those in normal pregnant women. When patients were classified according to the severity of their diabetes (White classification), no significant differences in H.P.L. were detected between groups. Changes in blood-sugar during the day did not affect H.P.L. readings, and insulin requirements during pregnancy could not be related to H.P.L. levels. 10 pregnancies ended in fetal death, and in 4 of them H.P.L. levels were persistently below 4 mug. per ml. Of these 4 infants only 1, whose intrauterine death remains unexplained, could have been saved, 2 having fatal malformations and another infant having died during an episode of maternal ketoacidosis. Among the 6 unsuccessful pregnancies in which H.P.L. levels were greater than 4 mug. per ml., congenital malformations accounted for 5 losses and hyaline-membrane disease for a single neonatal death. These results indicate that H.P.L. determinations probably have a very limited role in the successful management of diabetic pregnancy.


Intravenous urography in investigation of hypertension. Eighty intravenous pyelograms, carried out as part of the routine investigation of hypertension, revealed only one unsuspected renal lesion of possible relevance to the long-term management. Such a low therapeutic return, in the light of its cost and not entirely negligible risk, raises doubts about the place of excretion urography amongst the screening tests aimed at discovering tractable underlying causes of hypertension.


A model for gastric cancer epidemiology. It is postulated that one major subtype of gastric carcinoma ("intestinal type") is the end- result of a series of mutations and cell transformation begun in the first decade of life. The mutagen could be a nitroso compound synthesised in the upper gastrointestinal tract by the action of nitrite (i.e., from food or saliva) on naturally occurring nitrogen compounds. Under normal conditions these nitroso compounds do not reach the gastric epithelial cell, presumably because their synthesis is inhibited by antioxidants present in food or because of their inability to pass the mucous barrier. The barrier may be overcome by abrasives or irritants such as hard grains, food with high sodium-chloride concentration, or surfactants. Once the first mutation occurs, the glandular gastric epithelium is gradually changed to intestinal-type epithelium, the mucous barrier altered, and the pH elevated. Under these conditions, bacteria proliferate in the gastric cavity and facilitate the conversion of nitrates to nitrites, thereby increasing the nitrite pool and the probability of formation of mutagenic-carcinogenic nitroso compounds. This process of gastric atrophy and intestinal metaplasia goes on for 30 to 50 years until some of the individuals affected have the final mutation or cell transformation which allows the cell to become autonomous and invade other tissues.


Immunological basis for latency, recurrences and putative oncogenicity of herpes simplex virus. The development of latency and recurrent infection after primary herpes simplex virus (H.S.V.) infection can be interpreted in terms of cell-mediated and antibody responses to virus-specific antigens and Fc receptors on the surface of the infected cells. Primary infection will induce immune responses to the virus, and antibody and cell-dependent cytotoxic mechanisms will kill most of the virus and virus-infected cells which are accessible to killer cells. H.S.V. will be sequestrated to the nerves and will migrate centripetally along the axons to the trigeminal or sensory ganglia. Latency in the trigeminal ganglion may be mediated by IgG antibodies binding to both H.S.V. antigens and Fc receptors. Derepression of the viral genome may be induced by factors which weaken the binding of antibodies to the antigen and Fc receptor; the virus will replicate and migrate centrifugally along the axon, to be shed at the nerve endings. In the presence of some defect in T lymphocytes, acting at the neuroepithelial junction, a recurrent herpetic lesion will be precipitated. There is some evidence that H.S.V. may be associated with squamous-cell carcinoma, and it is postulated that the enhanced cell-mediated and antibody responses to H.S.V. may destroy cells containing the viral genome but allow the emergence of an oncogenic genome. Double binding of the Fc receptor and H.S.V. antigen by IgG antibodies or immune complexes on the surface of carcinoma cells may prevent killing and allow these cells to proliferate into invasive tumours.


Sulphone resistance in leprosy. A review of one hundred proven clinical cases. An account is given of the first hundred consecutive proven cases of sulphone resistance in leprosy, detected in Malaysia between 1963 and 1974. Proof of resistance was clinical in eighty patients and was obtained by drug-sensitivity testing in mice in ninety-six patients; 76 cases were proved both clinically and experimentally, and there was no discrepancy between the two methods. Sulphone resistance was confined to patients with lepromatous-type leprosy--i.e., patients with a large bacterial population. Clinical evidence of relapse due to drug resistance appeared 5-24 years after the start of sulphone treatment. Low dosage favoured the appearance of resistance; therefore regular treatment of lepromatous leprosy with dapsone in full dosage is recommended. The attainment of "skin smears negative for leprosy bacilli" is no test of cure of lepromatous leprosy.


Hypersecretion and length of history in duodenal ulceration. Maximal gastric secretion, measured by the histamine-infusion test, was, as expected, significantly greater in a group of 81 patients with duodenal ulcer than in a group of 72 controls. After standardising for the effect of stature on maximal secretion, only 24 of the patients were found to be true hypersecretors. However, maximal secretion in the ulcer group increased with length of history of symptoms, and extrapolation back to zero length of history suggested that there was no significant hypersecretion at that time. These facts support the hypothesis that it is the presence of the ulcer that leads to hypersecretion rather than the converse. Possible mechanisms involved are chronic ingestion of antacids to counter dyspepsia, or gastric distension due to pylorospasm.


Pituitary function after treatment of intracranial tumours in children. Pituitary-function tests have been done in twenty-seven patients at various times after treatment in childhood for intracranial tumours not directly involving the hypothalamic-pituitary region. Impaired growth hormone (G.H.) responses to hypoglycaemia and 'Bovril' were found in ten children. There seeems to be progressive impairment in G.H. production with time after treatment. During the first 3 months after neurosurgery no child was found to be G.H. deficient, but the peak G.H. response of this group seemed to be blunted when compared with a control group of children who had been treated for abdominal tumours. The rest of anterior-pituitary function in G.H.-deficient children seems quite normal except for a significantly greater basal thyroid-stimulating hormone (T.S.H.) level and T;S.H. response after thyrotrophin-releasing hormone. Two girls have developed secondary amenorrhoea, and one is G.H. deficient.


Fetal blood drawing.

Fetal blood drawing. A small sample of fetal blood suitable for studies of haemoglobin synthesis was obtained from a placental vessel under endoscopic visualisation in 23 of 26 patients in whom the procedure was attempted prior to second-trimester abortion. Fetal blood loss, calculated in 23 cases, was between 0-2 ml. and 2-5 ml., and fetal blood-volume depletion varied from 0-5% to 15%. No short-term ill-effects were demonstrated in mother or fetus in any of 16 patients in whom the injection of aborti-facient was postponed for between 16 and 24 hours after the procedure.


Hepatitis-B virus and Indian childhood cirrhosis. The surface and core componenets of hepatitis-B virus have not been detected in livers of patients suffering from Indian childhood cirrhosis using procedures such as immunoperoxidase, immunofluorescence, and orcein staining as well as electronmicroscopy. This finding, together with the other features of the disease, suggests that infection by this virus plays no significant role in the aetiology of Indian childhood cirrhosis.


Meningococcal infections in Bolton, 1971-74. Between December 1970, and the end of June, 1974, there were 82 cases of meningococcal infection, including 14 deaths, in the metropolitan borough of Bolton. This outbreak, caused by a sulphonamide-sensitive group-B strain, was characterised by a high attack-rate in young children, reaching a peak of 184 per 100,000 per year in the 6-11-month age-group. All the deaths were in children under 3 years of age. Nasopharyngeal carriage of the epidemic strain was found in 34% of close family contacts investigated before receiving sulphonamide prophylaxis.


Fulminant meningococcal septicaemia. A hospital experience. In the first 5 months of 1975, 12 cases of meningococcal septicaemia were seen at a children's hospital where in previous years the condition was seen only sporadically. 3 of these children were dead on admission, 5 died shortly after admission, and 4 responded to treatment. Neisseria meningitidis was recovered from cerebrospinal fluid or blood or both in all cases, and the clinical illness was characterised by fever, prostration, and cutaneous purpura of abrupt onset. There were no significant previous illnesses, no recognisable prodromata, and, bacteriology apart, no pattern of laboratory results. There was a suggestion of centre-city clustering in the home background, although 2 of the patients came from rural areas. At necropsy gross adrenal haemorrhage was found in 6 of the 8 fatal cases, and upper gastrointestinal bleeds in the 5 deaths which were not sudden.


Cardiac and pulmonary effects of acebutolol. In a double-blind randomised study, single intravenous doses of propranolol (0-1 mg. per kg.), practolol (1 mg. per kg.), acebutolol (1 mg. per kg.), or placebo were each administered at weekly intervals to six healthy volunteers. Forced expiratory volume in 1 second (F.E.V.1), resting and exercise heart-rate, and resting and exercise peak flow-rate (P.F.R.) were determined before and at 2, 3, 4, and 6 hours after each treatment. Venous blood-samples were also obtained at these times. Compared with placebo, resting heart-rate was reduced after all three drugs, but the corresponding differences in exercise heart-rate were much greater, more consistent, and of greater statistical significance. At 2, 3, and 4 hours when acebutolol and propranolol produced equivalent cardiac beta-blocking activity (judged by reductions in exercise heart-rate), their mean plasma concentratios were in the ratio of about 8/1; and at 2 hours when practolol and acebutolol gave rise to almost equivalent cardiac beta blockade, their mean plasma concentratio ration was 3/1. At times, reductions in F.E.V.1 and resting P.F.R. after propranolol (but not after practolol or acebutolol) were significantly greater than the corresponding changes after placebo. The reductions in exercies P.F.R. after propranolol (6 hours) and acebutolol (4 hours) (but not after practolol) were significantly greater than the changes after placebo.  Changes in F.E.V.1, resting and exercise P.F.R. after propranolol, and the corresponding changes after practolol, were significantly different, all of which confirmed that practolol was more cardioselective than propranolo. In general, the reductions in F.E.V.1 and resting P.F.R. after acebutolol were slightly smaller than after propranolol, excepting at 6 hours when the difference between them was significant. The reductions in exercise P;F.R. after acebutolol and propranolol were of the same order, there being no significant differences between the two, whereas the reductions after acebutolol were clearly greater than the corresponding changes after practolol, the differences being significant at 2, 3, and 4 hours.


Randomised controlled trial of yoga and bio-feedback in management of hypertension. 34 hypertensive patients were assigned at random either to six weeks' treatment by yoga relaxation methods with bio-feedback or to placebo therapy (general relaxation). Both groups showed a reduction in blood-pressure (from 168/100 to 141/84 mm. Hg in the treated group and from 169/101 to 160/96 mm Hg in the control group). The difference was highly significant. The control group was then trained in yoga relaxation, and their blood-pressure fell to that of the other group (now used as controls).


The curability of breast cancer.

The curability of breast cancer. Results are presented of a long-term follow-up of patients with breast cancer seen in the Cambridge area from 1947 to 1950. After 21 years the survival curve of the breast-cancer patients runs parallel to the expected survival curve of a similar normal population. This suggests that 18% of all the breast-cancer patients may be regarded as cured of their disease in the sense defined by Easson and Russell. An analysis of the causes of death in the study group after 20 years' follow-up shows an excess of deaths from breast cancer. The number is 16 times more than would be expected in the normal population, although the overall death-rates in the two groups are the same. This questions the concept of cure.


Autoantibodies to prolactin-secreting cells of human pituitary. A new autoantibody which reacted with anterior-pituitary tissue was deteected by immunofluorescent staining. Of 287 patients having one or more autoimmune endocrine diseases, sera from 19 reacted with pituitary glands obtained at hypophysectomy for breast cancer. Using specific rabbit antibodies to each of the six pituitary hormones and rhodamine-labelled goat-anti-rabbit-immunoglobulin (Ig) followed on the same unfixed cryostat section by a patients's serum counterstained with fluorescein-conjugated sheep-anti-human-Ig, it was posssible to show that the autoantibodies reacted specifically with the hypertrophied prolactin cells in these glands. The antibodies, belonging to the 3 main Ig classes, were complement fixing, with titres varying from 1 to 80. Double staining of prolactin cells and analogy with other autoimmune systems suggested that the antigen is in cytoplasmic organelles involved in the synthesis or delivery of the hormone. No pituitary antibodies were found in panhypopituitary cases, but there are indications that antibodies to other pituitary cells exist in some sera and that an autoimmune process may account for some cases of isolated pituitary hormone defects occurring in adult life.


Integrated programme of dialysis and renal transplantation. Results in 155 patients. 155 patients were referred for treatment of irreversible renal failure between Jan. 1, 1970, and Oct. 31, 1974. 8 (5%) patients were not accepted for treatment. An integrated programme of dialysis and transplantation (based on finding a cadaver transplant for every patient) has achieved an actuarial survival-rate of 88% at 1 year and 79% at 4 years. Of those surviving at 4 years, 85% are maintained by a functioning transplant. Only 4/122 transplants have been from living related donors. It is suggested that these results demonstrate that cadaveric transplantation, closely integrated with dialysis, offers an acceptable chance of life and full rehabilitation while not demanding from the community an unacceptable percentage of health resources.


Is "T4 toxicosis" a normal biochemical finding in elderly women? The lack of equivalence in the distrubtion of normal ranges for free thyroxine index (FT4I) and free triiodothyronine index (FT3I) in the over sixty-five age-group, as compared with the fifteen-sixty-five age-group, supports the idea that "T4 toxicosis" is a common biochemical finding in elderly women. The disparity between FT4I and FT3I ranges was also reflected in the true free T4 and free T3 levels which were measured in some cases. These results suggest that when an increased FT4I is found in an elderly woman with cardiac disease, caution should be exercised in interpreting the result as indicating that thyrotoxicosis is the cause of the cardiac disorder. Estimation of total T3, FT3I, or free T3 seems useful in confirming euthyroidism in such cases.


Arsenical air pollution and lung cancer. Average mortality-rates from lung cancer for White males and females in the U.S.A. 1950-69 WERE SIGNIFICANTLY INCREASED IN COUNTIES WITH COPPER, LEAD, OR ZINC SMELTING AND REFINING INDUSTRIES, BUT NOT IN COUNTIES WHERE OTHER NON-FERROUS ORES ARE PROCESSED. The excess mortality was not attributed to differences in geographic region, population density, urbanisation, socioeconomic status, or other manufacturing processes. The findings suggest the influence of community air pollution from industrial emissions containing inorganic arsenic.


Drug-induced pseudolupus.

Drug-induced pseudolupus. Of fifteen patients with pseudolupus (a syndrome characterised by recurrent fever, myalgia, arthralgia, pleuritis, pulmonary infiltrates, pericarditis, myocarditis, and by mitochondrial antibodies in the absence of nuclear antibodies), all had been treated with "Venocuran", one of a great number of drugs used for venous diseases. This drug, available in twenty countries under various names, contains phenopyrazone, horse-chestnut extract, and cardiac glycosides extracted from various plants. Further studies revealed that up to 90% of long-term users of venocuran acquired mitochondrial antibodies. This was not true for patients with venous diseases being treated with other drugs. About 30% of long-term users of venocuran might experience prodronal symptoms, such as myalgia and arthralgia, while more than 10% could develop the full disease.


Local production of specific IgE antibodies in allergic-rhinitis patients with negative skin tests. A group of patients with allergic rhinitis had a clinical history strongly suggestive of house-dust-mite (Dermatophagoides pteronyssinus) allergy but negative skin reactions when prick tested with D. pteronyssinus extracts. These patients were proved to be clinically allergic by nasal provocation with this allergen. Although radioallergosorbent tests showed that these patients lacked specific IgE antibodies in their serum, they did have specific antibodies in their nasal secretions. These findings indicate that these patients had allergic rhinitis mediated by the local production of IgE antibodies.


Infusion thrombophlebitis and infection with various cannulas. A prospective study was carried out of the frequency of thrombophlebitis and bacterial contamination of cannulas associated with four commonly used intravenous cannulas of differing length and chemical composition. For all cannulas the frequency of thrombophlebitis increased significantly with time. Long 'Teflon' cannulas were significantly more likely to be contaminated with bacteria and associated with thrombophlebitis than all other cannulas, while the low frequency of thrombophlebitis with butterfly stainless steel cannulas was shown to be due to their short duration of use. It is suggested that long teflon cannulas should be avoided and that infusion thrombophlebitis could be eliminated as a clinical problem by the use of intermittent short duration intravenous infusions.


Gloved hand as applicator of antiseptic to operation sites. A 95% ethanol solution containing 0-5% chlorhexidine digluconate caused a significantly greater mean reduction in skin bacteria (99-9% plus or minus 0-024) when rubbed by a gloved hand on to the skin of one hand for two minutes than when applied to the same area for the same time with the traditional gauze applicator for operation sites (90-7% plus or minus 2-12). The latter reduction, however, was greater than that reported in five previous experiments in which application of the same solution for the same time to two hands gave mean reductions varying from 79% to 84%. An aqueous solution and a 70% alcoholic solution of chlorhexidine also gave significantly greater reduction (and alcoholic povidone iodine almost significantly greater reduction) when applied by a gloved hand than on gauze. It is inferred that the effectiveness of skin disinfection depends both on the antiseptic used and on the manner of application, and varies with the amount of friction used in applying the antiseptic. Further studies on disinfection of the surgeon's hands with 0-5% chlorhexidine in 95% alcohol rubbed on and allowed to dry have supported its value and acceptability; the mean bacterial counts of washings from gloves of surgeons after operations were lower after the use of this method than after other preoperative preparations of the hands.


Return of spermatogenesis after stopping cyclophosphamide therapy. A follow-up of twenty-six male patients with azoospermia after stopping cyclophosphamide treatment showed a return of spermatogenesis in twelve patients within 15-49 months (mean 31 months). In one patient spermatogenesis returned despite 34 months of treatment with 100 mg. of cyclophosphamide daily. The period of follow-up after stopping cyclophosphamide therapy varied from 5 months to 4 years. After 6 months on cyclophosphamide all patients remained azoospermic while taking the drug. Return of spermatogenesis was not significantly associated with age, duration of cyclophosphamide therapy, total dose, or time of follow-up after stopping treatment; however, the number of patients in the study was small.


Reduction in severity of acute renal failure in rats by beta-adrenergic blockade. The effectiveness of beta-adrenergic blockade in preventing acute renal failure (A.R.F.) in rats was studied in the hypoxia model produced by unilateral nephrectomy and clamping of the contralateral renal artery for 70 minutes. Beta-adrenergic blockade effectively reduced the severity of A.R.F. in this experimental model. Treatment with a combination of propranolol and a synthetic angiotensin-II competitive inhibitor (P113) produced no further improvement. These results are consistent with the view that intrarenal release of renin is to some extent involved in the pathogenesis of A.R.F.


Possible stimulation of thermogenesis in brown adipose tissue by thyroid-stimulating hormone. It is suggested that in addition to stimulating the thyroid gland (i.e., the main regulator of metabolic-rate in adults) thyroid-stimulating hormone (T.S.H.) stimulates the second thermoregulatory organ (i.e., the brown adipose tissue). Brown fat functions as a thermogenic organ in hibernating animals, in newborn infants, and during cold acclimatisation. However, B.F. may persist in childhood and in some adults. Its hypertrophy in response to T.S.H. could account for certain unexplained features of myxoedema in which serum-T.S.H. is raised, such as swelling of the supraclavicular fat pad and the less commonly encountered symptoms of ascites or pericardial and pleural serous effusions which can persist for years in undiagnosed cases and respond rapidly to thyroxine when serum-T.S.H. returns to normal. Lack of thyroxine is not the cause of these features since they are not found in pituitary myxoedema, where thyroid hormone levels are as low but T.S.H. is absent.


Induced abortion and subsequent outcome of pregnancy. A matched cohort study. The effect on subsequent pregnancy outcome related to abortion was studied in a sample of 26,000 births in Taiwan. When no adjustment was made for confounding maternal variables, significant relationships were found between previous abortion and various problems of outcome of subsequent pregnancies. However, in a matched-pair cohort study controlling for relevant maternal characteristics, all such relationships disappeared. It is concluded that the deleterious effects of abortion on subsequent pregnancy outcome reported by others may be a consequence of the failure to adjust for maternal factors which are related both to abortion status and pregnancy outcome, and not to abortion itself.


Early detection of false-positive acid-fast smears. An epidemiological approach. An unusual series of positive acid-fast smears, including positive stains of a commercial saline solution, has been studied. Short of waiting 2--6 weeks for culture results, a laboratory investigation of these findings appeared hopeless: repeat staining failed to confirm the origin smear results, and a review of laboratory techniques and supplies failed to pinpoint any source of specimen or smear contamination. An alternative epidemiological approach was adopted. A review of the laboratory records indicated that, during the time the unusual series occurred, there had been a distinct change in the distribution of positive smears by type of specimen submitted and by ward of origin. The change in distribution indicated that the unusual series was probably part of a larger episode of false-positive acid-fast smears caused by random specimen or smear contamination in the hospital laboratory. Culture results eventually confirmed this and showed that the period of random laboratory contamination had ended just before the present investigation (thus explaining the failure of the initial approach). This experience suggests that ongoing analysis of specimen and ward distribution of positive acid-fast smear results will enable hospitals to detect episodes of false-positive smears earlier, thus reducing erroneous diagnoses and permitting prompt evaluation of sources of specimen and smear contamination.


Diarrhoea associated with heat-stable enterotoxin-producing strains of Escherichia coli. Five patients who developed acute watery diarrhoea while travelling in Mexico in October, 1974, were found to have enterotoxigenic Escherichia coli in their stool which produced heat-stable enterotoxin (S.T.) without producing heat-labile enterotoxin (L.T.). These S.T.-only E. coli, which have previously been described as causing diseases in animals, must now be regarded as pathogenic for humans as well.


Rotavirus enteritis in the West Midlands during 1974. During 1974 in the West Midlands of England, 38% of children less than 6 years old with enteritis were excreting rotaviruses. Children aged from 6 months to 3 years were those most commonly infected. Rotavirus infections were most common during winter with only a few sporadic cases during summer. A possible pathogen was detected in 59% of patients examined.


Staphylococcus aureus transmitted in transplanted kidneys. Staphylococcus aureus septicaemia developed shortly after transplantation in both recipients of transplanted kidneys from a donor who had received electrical burns. In each case the organism appeared initially in the urine. All staphylococci isolated were phage type 6/47/54/75. Transplant nephrectomy was necessary in both recipients because of complications of infection, and one recipient died. These results draw attention to the possible significance of Staph. aureus in the urine of recipients after transplantation and to the potential risk of transplanting kidneys from a burned donor.


Electrolyte disturbances in beer drinkers. A specific "hypo-osmolality syndrome". A syndrome is described which affects subjects whose consumption of beer is considerable but who take no or little ordinary food. The symptoms include fatigue, dizziness, and muscular weakness; the biochemical changes are hyponatraemia and hypokalaemia. The disorder is rapidly resolved by stay in hospital. Beer is poor in Na (1-2 meq. per litre). Consequently these patients' intake of Na was low, and the production of urea was very low.


Serum-phenytoin levels in management of epilepsy. Steady-state serum-phenytoin levels were measured in five patients whose phenytoin dosage was changed three or more times for therapeutic purposes. Data from four of these patients and from fifteen others have been used to construct a nomogram which permits the clinician, given a single, accurate, steady-state phenytoin level, to adjust the dosage to achieve the desirable therapeutic concentration of 60 or 80 mumol per litre (15 or 20 mug. per ml.).


C1-bypass complement-activation pathway in patients with chronic urticaria and angio-oedema. During the routine screening of 152 patients with urticaria or angio-oedema for hypocomplementaemia, 4 patients were found to have low serum levels of the third component of complement (C). These patients were noteworthy and differed from previous reports of patients with urticaria-like skin lesions and hypocomplementaemia because of the absence of immune-complex disease. In addition to the low C3, 2 of these patients were unique on the basis of low serum levels of haemolytic C1, C1q, C1s, and properdin factor B, but normal concentrations of C4 and C2. These C abnormalities may reflect a new clinical entity, and these cases form the first description in man of the C1-bypass complement-activation pathway.


Splenectomy for haematological cytopenias in patients with malignant lymphomas. Haematological cytopenias caused by increased splenic activity occurred in 86 patients with malignant lymphomas (50 patients with stage III or IV Hodgkin disease [H.D.] and 36 with non-Hodgkin lymphomas). Splenectomy was performed in 84 of these 86 patients. There was complete or partial correction of the haematological defect in 90% of the H.D. patients and 89% of the non-Hodgkin patients. Chemotherapy or radiotherapy was started after the haematological defect had been corrected by splenectomy, and as a result 79% of the H.D. patients and 75% of the non-Hodgkin patients had a complete or partial remission of their disease. Increased splenic activity should be considered as a cause of a haematological cytopenia in patients with malignant lymphomas even in those with bone-marrow involvement, since splenectomy is accompanied by excellent results in terms of disease remission with subsequent therapy. 2 patients with H.D. (4%) and 5 with non-Hodgkin lymphomas (14%) died in hospital after splenectomy. Thus the operation was associated with acceptable mortality and morbidity despite the advanced stage of disease in most cases.


Dichotomy between immunoglobulin synthesis by cells in gut and blood of patients with hypogammaglobulinaemia. Eleven of fifteen patients with late-onset hypogammaglobulinaemia were found to have significant numbers of immunoglobulin-containing cells in the lamina propria of the gut. In six of them typical plasma cells were detected. In contrast the blood lymphocytes of only two of these patients could be induced to synthesise immunoglobulin by stimulation with pokeweed mitogen in vitro. Moreover, one patient in whom immunoglobulin-containing cells and plasma cells were detected in the rectum and jejunum failed to show similar cells in a peripheral lymph-node even after immunisation with pneumococcal polysaccharide type-III antigen in the drainage area of the node. It is possible, therefore, that the gut is a privileged site for the differentiation of B cells in these patients.


Thymopoietin and myasthenia gravis: neostigmine-responsive neuromuscular block produced in mice by a synthetic peptide fragment of thymopoietin. Thymopoietin is the thymic hormone responsible for inducing the differentiation of thymocytes. A synthetic peptide corresponding to positions 29-41 of bovine thymopoietin II, which can reproduce this function of the parent molecule in vitro, also caused neostigmine-responsive neuromuscular block in mice similar to that which thymopoietin itself produces, and which resembles the neuromuscular block of myasthenia gravis. This 13 aminoacid sequence must therefore contain the key residues in the thymopoietin molecule responsible for both T-cell differentiation and neuromuscular effects. These data provide further support for the view that myasthenia gravis is a consequence of thymic disease associated with systemic release of thymopoietin, with ensuing neuromuscular block. This evidence supports the empirically proven treatment of myasthenia gravis by early total thymectomy.


New rapid method for diagnosis of deep venous thrombosis. The plasma concentration of the platelet-specific protein beta-thromboglobulin was measured in fourteen patients who had been investigated for deep venous thrombosis by venography or 125I-fibrinogen scanning. All six patients with a proven thrombus had a raised plasma concentration of beta-thromboglobulin. Eight patients in whom no thrombus could be demonstrated had plasma concentrations of beta-thromboglobulin similar to a control group of thirty-five normal individuals. These results indicate that the measurement of plasma beta-thromboglobulin concentrations may be of use in the diagnosis of deep venous thrombosis.


Hospital doctors' career structure and misuse of medical womanpower. Biological and culturel differences between men and women lead to severe discrimination against women doctors who bear the burdens of pregnancy, child-rearing, and housework. These lead, from equality within medical school and at qualification, to increasing failure to obtain posts commensurate with their innate abilities. Women doctors who temporarily and partially drop out of full-time practice have been studied frequently, but men (who are equally expensive to train) have not, despite their disappearing from National Health Service practice through emigration, death, alcoholism, suicide, or removal from the Medical Register. In a working lifetime of forty years, a woman doctor with an average family is likely to do seven-eighths of the work of a doctor who has not had to carry the primary responsibility of bearing and rearing children. Doctors with dependants are handicapped, and a separate career structure might be set up for them. Supernumerary consultant posts are proposed.


A search for common tumor specific antigen and serum blocking factor in head and neck epidermoid carcinomas. In vitro, colony inhibition tests using lymphocytes and serum from 42 patients with other carcinomas, and 12 control patients with no carcinoma, were performed using cultured target cells (CALI). Target cell colony counts were significantly diminished by lymphocytes of 2 of 12 (16.7 percent) patients with no cancer, compared with those 26 of 42 (61.9 percent) patients with epidermoid carcinoma. An unexpected finding was significant colony inhibition of lymphocytes of 23 of 27 (85.2 percent) patients tested within 24 months of diagnosis of carcinoma compared with significant inhibition in only 3 of 15 (20 percent) patients tested after 24 months of diagnosis of carcinoma. Serum blocking factor was found in 9 of 42 (21.4 percent) patients with epidermoid carcinoma.  It was found on follow-up that four of these nine (44.4 percent) had later recurrent or new tumors compared to recurrence or new tumor incidence of only 6 of 33 (18.2 percent) patients with no serum blocking factor present in the serum.


[Hepatic reaction in ulcerative colitis and Crohn's disease (author's transl)]. Within the framework of a prospective study on the course and prognosis of ulcerative colitis and Crohn's disease begun in 1968, serial blind needle biopsies of the liver were carried out for the early establishment of liver involvement. In 201 needle biopsies taken in 114 patients with ulcerative colitis, normal findings were observed in 51, fatty infiltration in 24, and accompanying inflammation in 23, fatty infiltration together with a mesenchymal reaction in 8, fatty liver in 6 and sclerosing cholangitis and granulomatous hepatitis in 1 patient each. Of 69 needle biopsies taken in 45 patients with Crohn's disease we established normal findings in 13, an insignificant accompanying inflammation in 19, fatty infiltration in 5, granulomatous hepatitis in 3, fatty liver in 2, fatty liver together with a mesenchymal reaction in 2 and serum hepatitis in 1. Laboratory tests (alkaline phosphatase, SGOT, SGPT, BSP excretion) are not particularly suitable as screening tests. The diagnostic yield of serial blind needle biopsies of the liver is low and, despite the low-risk nature of the method, often dispensable. Laparoscopy, or at least blind needle biopsy of the liver, should be retained for the further clarification of serious deviations of laboratory values from the normal range, or of suspicious palpation findings.


[Treatment of thyroid storm with plasmapheresis (author's transl)]. The conventional treatment of thyrotoxicosis is based on central and periphery therapeutic measures which respectively block the thyroid hormone production and subdue the hormone effect in the tissue. On account of long biological hal-life of thyroxine conventional methods of treatment fail to achieve a rapid reduction of the excessively high serumhormone level. As the overwhelming proportion of thyroid hormone is boud to serum proteins, plasmapheresis presents itself as a possibility of achieving this therapeutic aim. In the following a report is given on the successful practice of plasmapheresis in two cases of thyrotoxiicosis. In each of these, 1.4 and 1.2 litres of plasma respectively were re moved in all. Immediate combined use of plasmapheresis and conventional therapy appears to constitute a definite improvement in the treatment of thyrotoxicosis.


Cytogenetic effect of bleomycin on human leukocytes in vitro. Human leukocytes treated with bleomycin (BLM) for clinical use, at concentrations of 0.1, 0.5, 1.0, 10 and 50 mug/ml were studied. Both chromosome- and chromatid-type aberrations were observed. The groups of larger chromosomes were more affected at every concentration. At dosages from 0.1 to 10 mug/ml no significant difference of effects on chromosomes was observed. However, a dose-difference of about 500 times showed significant differences in effect both on the degree of chromosomal aberration and on mitotic indices.


Effect of phenethyl alcohol and other organic substances on cellulas production. Cellulase can be produced from growth in noncellulosic substrate if the growth rate of the producing organism is restricted. Phenethyl alcohol (PEA) is a growth inhibitor and was used to control the growth of M. verrucaria in attempts to obtain increased cellulase production. Cellulase yield was found to be increased without a restriction in growth rate when PEA was present in low concentrations (0.03% v/v). The effect was observed for other organisms but notably L. trabea, which produced considerable enzyme from a small quantity of mycelium. Here increased cellulase synthesis was concomitant with restricted growth. Other chemicals with PEA-like structure (e.g. benzyl alcohol) resulted in similar or more extensive cellulase synthesis. Of the substances tried, propyl alcohol was most effective, followed by acetone. PEA causes a swelling of cell walls and inhibits spore formation. This and other data given suggest that PEA affects the cytoplasmic membrane or the cell wall or both. Cellulase synthesis is considered to take place in the membrane and wall region of the cell.


Histamine release, formation of prostaglandin-like activity (SRS-C) and mast cell degranulation by the direct lytic factor (DLF) and phospholipase A of cobra venom. Cobra venom, alone and in combination, on mast cell degranulation, histamine release and formation of prostaglandin-like activity (SRS-C) was studied in perfused guinea-pig lungs and in mast cell-containing rat peritoneal cell suspensions. For comparison, the effect of equivalent doses of whole cobra venom was investigated. 1. Cobra venom caused mast cell degranulation, histamine release and SRS-C formation in both systems. For comparable effects much higher doses had to be used in guine-pig lungs than in rat peritoneal cell suspensions. 2. Phase A showed little degranulation of mast cells in both systems, a limited histamine release in rat peritoneal cell suspensions and none in perfused guinea-pig lungs. It caused a considerable SRS-C formation in both, lung tissue and peritoneal cell suspensions. 3. DLF caused histamine release, SRS-C formation and mast cell degranulation in both systems; in rat peritoneal cell suspensions it acted almost as strong as equivalent doses of cobra venom, in guinea pig lungs it was much less active. 4. In rat peritoneal cell suspensions the effects of DLF and phase A in combination did not exceed the sum of their single effects. In guinea-pig lungs these two substances interacted in a potentiating synergism. It is concluded that DLF is the main cytotoxic principle of cobra venom, whereas ph-ase A alone is not cytotoxic. The difference in the synergism of DLF and ph-ase A between rat peritoneal cells and guinea-pig lungs may be due to two different actions of DLF and species differences as regards sensitivity against these actions.


Triiodothyronine radioimmunoassay in the assessment of thyroid function. This report describes the development of a sensitive, precise, radioimmunoassay for the measurement of triiodothyronine in unextracted serum, documents serum levels of triiodothyronine in various states of thyroid dysfunction, and assesses the role of the triiodothyronine radioimmunoassay as a routine test of thyroid function.


Comparison of apical sealing methods. A preliminary report. A comparison of the seal provided by gutta-percha root canal filling, heat-sealed gutta-percha, retrograde amalgam filling, and retrograde Durelon filling was made by observation of dye penetration around the above filling materials in extracted teeth. A small but not significant difference between gutta-percha, heat-sealed gutta-percha, and retrograde amalgam was noted. Retrograde Durelon filling gave a poor seal in comparison to gutta-percha and retrograde amalgam filling, but the difference between it and the heat seal was not significant.


[Detection and determination of alpha-feto-protein in human serum. Use in hepato-gastroenterology]. The presence of alpha-foeto-protein (A.F.P.) was sought in the serum of 520 patients, suffering from various digestive disorders, using two methods: double immuno-diffusion and counter immuno-electrophoresis on cellogel--a more sensitive technique. A.F.P. was detected on 90 of the 520 patients. A.F.P. was measured by radial immunodiffusion or by electro-immunodiffusion on cellogel. Study of the values obtained in various kinds of hepatic disorders indicates that high levels (more than 10 mg/1) are seen almost solely in association with primary carcinoma of the liver, whilst lower levels (less than 10 mg/1) are found in the majority of hepatic disorders, without having any precise significance. The interest of the clinician should therefore be directed not towards the presence or absence of A.F.P. but to its level, which alone is significant.


Maturation of a hypermodified nucleoside in transfer RNA. E. coli C6 rel- met- cys- was cultured in a fully supplemented medium and in media lacking cysteine or methionine. tRNA isolated from the three cultures containted, respectively, a normal complement of modified nucleosides; a deficiency in thiolated nucleosides and a deficiency in methylated nucleosides. Both sulfur-deficient tRNA and methyl-deficient tRNA contained large amounts of N-6- (delta-2-isopentenyl) adenosine and small amounts of the 2-methylthio derivative. Methyl-deficient tRNA contained, in addition a large amount of a cytokinin active, differently modified nucleoside that is believed to be a sulfur derivative of N6-(delta-2-isopentenyl) adenosine. The structure of this compound is unknown. When methly-deficient tRNA and the precusor the tRNA-Tyr su3-+ A25 were enzymatically methylated in vitro, methyl groups were incorporated into derivatives of isopentenyladenosine. These results indicate that the biosynthesis of the 2-methylthio derivative of isopentenyladenosine may occur in a sequential manner, i.e., thiolation of isopentenyladenosine followed by methylation.


Immunoaffinity chromatography of human beta-hexosaminidase A. A highly specific method for the purification of human beta-hexosaminidase A employing immunoaffinity chromatography is described. Using an antiserum against the unique antigenic determinant, alpha, of beta-hexosaminidase A, and elution with 8.0M urea, a 283-or 417-fold purification of the enzyme was obtained in a single step from crude human placental homogenate.


The development of experimental allergic encephalomyelitis with immunizing doses of myelin basic protein. Rabbits immunized with low (11.25 mg) and high (57.50 mg) doses of myelin basic protein from several species develop antibasic protein antibodies, delayed type hypersensitivity, and clinical and pathological signs of experimental allergic encephalomyelitis. More than 55% of rabbits immunized with relatively high doses of basic protein develop disease. The absence of circulating antibasic protein antibodies in immunorespondent animals is associated with the appearance of clinical or histological signs of experimental allergic encephalomyelitis; however, the presence of humoral antibodies did not prevent completely the development of disease. Delayed-type hypersensitivity, specific for the basic protein, appears as early as 5 days after immunization and is maintained in nondiseased and surviving animals. Neither excess encephalitogen nor encephalitogen-induced antibody is sufficient to suppress completely the eventual development of clinical or histological manifestations of disease.


Biological properties of a type C virus isolated from a human X mouse hybrid cell line. The biological properties of the HMV-1 virus, spontaneously released from a human X C57BL/6 mouse hybrid cell line, were similar to those of RadLV, the prototype B-tropic virus of C57BL/6 mice. Both viruses replicated on B-type mouse cells and in the wild mouse cell line SC-1. The plaque-forming abilities of the two viruses were relatively low, but gradually increased after passage in new host cells. Both viruses were neutralized by AKR antisera but not by FMR antisera. HMV-1 virus could rescue the defective sarcoma genome from S+H- mouse cells. The pseudotype sarcoma virus so produced was deficient in "helper virus" activity. Newborn mice inoculated with HMV-1 virus remained tumor-free over a 1-yr observation period.


[State of the renin-angiotensin system in thyrotoxicosis]. A study was made of the blood plasma renin activity in 63 patients suffering from thyrotoxicosis before the treatment and in 42 healthy individuals.  In comparison with the healthy, renin activity was increased in patients with thyrotoxicosis and displayed a positive correlation with the severity of the disease the level of protein-bound iodine, tachycardia and the degree of loss of weight.  Stimulation of the renin-angiotensin system by the salt-free diet, hydrochlorthiazide and by placing the body into orthostatic position caused a relatively weaker increase in the renin activity in comparison with such in healthy individuals.  Following successful treatment and the occurrence of an euthyroidal state renin activity proved to fall to the normal level.  An increased renin activity was combined with increased urinary aldosterone excretion with a normal serum electrolyte level.  Such combination pointed to the secondary character of aldosteronism.  Block of the alpha- and beta-adrenergic receptors led to reduction in the level of renin activity.  Despite the frequent affection of hepatic function there was revealed no correlation between the increase in the renin activity and the pathological results of hepatic tests.  Plasma renin activity was reduced in 8 patients with myxedema.  It is supposed that the principal factors causing activation of the renin-angiotensin system in thyrotoxicosis were the loss of water and electrolytes by the organism and the appearance of oversensitivity to adrenergic receptors.


[Activity of the hypophyseal-thyroid gland system in relation to the funcitonal state of the sex glands.  Report I]. Experiments were conducted on intact female rats; it was revealed that the content of protein-bound iodine (PBI) in the blood depended on the stage of the estral cycle.  It was decreased at the metestrus and diestrus stages.  Castration produced an even greater reduction in the blood PBI content.  The blood PBI content proved to elevate in administration of estradiol dipropionate (EDP) to castrated rats.  The TSH content in the hypophysis increased at the metestrus and diestrus stages and decreased at the proestrus and estrus stages.  The relationship was reverse in the case with the blood TTH content.  Castration was followed by a marked increase in the TSH content in the hypophysis accompanied by a reduction in the blood hormone level.  The TSH concentration in the hypophysis decreased and in the blood increased under the effect of EDP in castrated animals.  The data obtained indicated that the interrelationship between the thyroid gland and the sex glands was realized at the level of the hypophysis, and possibly, of the hypothalamus.


Combination chemotherapy of Rauscher leukemia and ascites tumors by narcissus alkaloid with standard drugs and effect on cellular immunity. The therapeutic activity of the narcissus residual alkaloid A-2 against Rauscher leukemia has been compared with 10 standard anticancer drugs, and synergistic or additive combination pairs have been selected using a viral leukemia and two transplantable tumor systems. An increased beneficial effect has been demonstrated by a combination of the alkylating and DNA-binding agents and the alkaloid against the three malignant tumors, while a beneficial effect by combining the alkaloid and the antimetabolites (either 6-MP or 5-azacytidine) was seen only against the viral leukemia. The alkaloid has no suppressive activity against cellular immunity as tested by PHA reactivity and allogeneic tumor rejection systems.


Anomalous results of studies on drug interaction in man. I. Nortriptyline and antipyrine. Conflicting results were obtained in three drug interaction experiments designed to determine in man effects of chronic nortriptyline administration on plasma antipyrine half-lives. In an apparently similar design, each experiment utilized normal volunteers whose plasma antipyrine half-lives were measured before and after chronic nortriptyline administration. The same dose of liquid nortriptyline (0.2 mg/kg p.o. t.i.d. for 8 days) was used in each experiment. All subjects in the first study prolonged their plasma antipyrine half-lives, whereas seven of nine subjects in the second study significantly shortened their plasma antipyrine half-lives. In the third experiment seven of nine subjects showed no significant change in plasma antipyrine half-life. An explanation for these conflicting results obtained in the same laboratory under apparently similar experimental conditions was sought in the nature of the volunteers and in subtle changes in such variables as differences in the batches and length of storage of liquid nortriptyline.


Anomalous results of studies on drug interaction in man. II. Halofenate (mk-185) and antipyrine, bishydroxycoumarin, and warfarin. Three highly reproducible experiments on drug interaction in normal human volunteers provided anomalous results: chronic halofenate administration shortened plasma antipyrine and bishydroxycoumarin half-lives but prolonged plasma warfarin half-lives. This dissociation in the effect produced by a chronically administered drug on the metabolism of test drugs has not previously been reported in man. Chronic halofenate administration to rats, mice and dogs stimulated several hepatic microsomal drug-metabolizing systems, including those responsible for bishydroxycoumarin warfarin hydroxylation.


Blood histamine levels and arteriovenous concentration differences after the intravenous administration of the basic compounds l-3 and 48/80 in the anaesthetized dog. The effects of the i.v. administration of inulin trinicotinate-monomethochloride (L-3) on haemodynamics, airway pressure and blood histamine levels were studied in chloralose-anaesthetized dogs and compared with the effects of compound 48/80. The control arterial histamine level was 0.041 plus or minus 0.002 mug/ml (mean plus or minus SEM) as determined by a fluorometric assay. L-3 (0.15 mg/kg) released high amounts of histamine, as indicated by a peak level in arterial histamine of 0.212 plus or minus 0.027 mug/ml within 3 min, which was not futher enhanced on increasing the dosage of L-3 to 1 mg/kg. After the i.v. injection of 0.15 mg/kg of 48/80 the peak level in arterial histamine was 0.146 plus or minus 0.008 mug/ml, and the level was further markedly elevated to 0.918 plus or minus 0.068 mug/ml after the administration of 1 mg/kg of 48/80. The concomitant fall in systemic blood pressure and the rise in airway pressure can be satisfactorily explained on the basis of histamine liberation. Whereas these parameters as well as the blood histamine concentration gradually returned to control values, the heart rate remained elevated during the observation period of 2 h. The arteriovenous differences in blood histamine across various tissues and organs following L-3 and 48/80 administration indicated histamine release mainly from skin and muscle and histamine uptake by the kidney, the digestive tract and to a lesser extent the lungs. The portal-hepatic vein differences revealed no consistent changes in liver histamine balance. As regards the lungs and liver, the present results suggest a dynamic equilibrium between histamine release and uptake in these organs in the intact animal. Both, L-3 and 48/80 elicited a similar pattern of histamine release and uptake. The extreme histamine releasing capacity of 1 mg/kg of 48/80 may be explained by an additional non-selective mechanism of histamine liberation.


The denervated Meissner corpuscle. A sequential histological study after nerve division in the Rhesus monkey. The effects of denervation upon the Meissner corpuscle were evaluated by sequential fingertip biopsies in 3 rhesus monkeys, following transection of all the sensory innervation of the hand. Histological techniques were used to identify changes in the neural, connective, and enzymatic components of the Meissner corpuscles. Denervation of the Meissner corpuscle resulted in rapid and complete degeneration of the axon terminal and a slowly progressive degeneration of the connective tissue component of the corpuscle, characterized by loss of lobulation, lamellar collapse, and a steadily diminishing corpuscular size. The physiological basis and the clinical implications of these findings are discussed. The literature is reviewed.


[Thymoma and lupus disease (apropos of 2 cases]. Two new cases of association between a thymoma and a lupus illness are reported. The first was a women aged 42 years in whom were discovered simultaneously systemic lupus erythematosus (SLE) and a slowly invading thymoma, the histology of which was characterized by the predominance of epithelial cells; excision of this tumour did not appear to affect the evolution of the SLE. In the second case, a patient aged 60 years suffered from SLE ten months after the removal of a benign thymoma in which there was a predominance of lymphocytes. The SLE in this patient was easily controlled for more than a year by small doses of corticoids, but resulted in death after three years when anuria was associated with meningeal signs after the cessation of corticotherapy. The comparision of the data from these cases with those from eleven other cases in which there was association between a thymoma and SLE, brought to light several interesting facts. It is rare that SLE clearly precedes the discovery of the thymoma; it usually occurs afterwards or the two are discovered almost simultaneously. Collagenosis is of importance only when it coexists with a thymoma : starting later much more often than is usual in cases of SLE. The tumours were, in all but two cases, benign thymomas of different histological types, and their removal did not apparently influence the evolution of the SLE.


Cytochemical differences in leucocytes of normal adult males and females. Peripheral blood samples were drawn from 50 patients (25 males and 25 females) with no apparent haematologic disorders. Smears were stained for Periodic Acid-Schiff and beta-glucuronidase reactions. Diffuse to moderate activity was observed in leucocytes for both stains. There was a significant difference in males and females in positive reactions in monocytes stained for beta-glucuronidase and in lymphocytes and granulocytes stained for PAS.


Induction of histamine release and densensitization in human leukocytes. Protein A from Staphylococcus aureus has been found to react with all human leukocyte preparations tested. In 70 percent of the experiments the reaction leads to histamine release. Furthermore, protein A treatment of cells at 37 degrees C, both in complete and Ca-2+-free medium, results in the inhibition of anti-IgE-induced histamine release in all cell preparations, indicating that protein A and anti-IgE antibodies release histamine from the same cells. This inhibition seems to be due to the blocking or exhaustion of a step in the biochemical pathway, leading to histamine release activated by both protein A and anti-IgE. In some cell preparations desensitization but no histamine liberation is induced by protein A. No inhibition occurs if the protein A treatment is performed at 4 degrees C. It is concluded that protein A elicits histamine liberation and desensitization by acting on IgG present on the surface of the basophil granulocytes. Treatment of leukocytes at 37 degrees C with anti-IgE antibodies, or F(ab)2 fragments from such antibodies, also results in an inhibition of a subsequent anti-IgE-induced histamine release. Desensitization with low doses of anti-IgE results in an inhibition of the same type as that obtained with protein A. Supraoptimum amounts of anti-IgE or high amounts of monovalent Fab fragments from anti-IgE immunoglobulin G give an inhibition that could be due to a competition between the sensitizing and the challenging agents for combining with cell fixed IgE molecules. This inhibition is independent of temperature and calcium concentration.


Conditions for inducing T helper cells in vitro. Lymphoid cells of CBA mice were triggered to act as specific helper cells by incubation with protein antigen (usually keyhole limpet haemocyanin (KLH)) in Marbrook cultures in vitro. After optimum priming, these helper cells, at optimal numbers, stimulated B cells (from unprimed spleens) to respond to trinitrophenyl-KLH in vitro. The in vitro-induced helper cells were carrier-specific. B cell depletion before helper cell induction increased the efficiency of helper cell induction and thus provided further proof of the T-cell nature of in vitro helper cells. Heterogeneity within T helper cell precursors is suggested on the basis of differences in antigen dose requirements of precursor cells in cortisone-resistant thymocytes, spleen, or lymph nodes.


B-cell mitogenic effects on human lymphocytes of rabbit anti-human beta 2-microglobulin. Rabbit Ig against human beta2-microglobulin was found to be mitogenic for human peripheral lymphocytes, tonsil lymphocytes, and appendix and spleen cells. Anti-beta2-m gave increased DNA synthesis, with peak responses on day 3 or 4 and showed a dose-response effect when diluted. The effect was seen in both serum-free and serum-containing culture medium. Anti-beta2-m, as well as lipopolysaccharide, induced polyclonal antibody production and intracellular immunoglobulin synthesis in blast cells, which is taken as evidence that these substances are human B-cell mitogens. Anti-beta2-m, but not lipopolysaccharide, could, in these experiments, activate peripheral blood lymphocytes, in addition to lymphoid cells from other sources. Thus, anti-beta2-m can serve as a functional marker for peripheral human B lymphocytes.


Urethral pressure profile in prostatic surgery. The urethral pressure profile was registered in 30 patients with benign hypertrophy of the prostate. In 6 patients the pressure profile measurement was repeated following prostatectomy and in 5 patients following transurethral resection of the prostate. Four patients with incontinence following prostatic surgery were also examined. Characteristic and reproducible profile patterns are demonstrated.


[Indications for radiotherapy in gastrointestinal tumors]. As a pre- or postoperative measure, radiotherapy can contribute to the treatment of many gastrointestinal malignancies. Postoperative radiotherapy is recommended in malignant lymphoma of the stomach and the intestine, as well as for invasive and totally resected carcinoma of the recto-sigmoid in order to prevent local recurrences. Preoperative radiotherapy can be attempted for carcinoma of the lower third of the esophagus and extended carcinoma of the stomach and the rectum, as long as no better therapeutic association is available. Finally, curative radiotherapy can be administered for squamous cell carcinoma of the esophagus and the anus, with a reasonable chance of success, to avoid subjecting the patient to major surgery.


[Hemotherapy in malignant hematologic diseases]. For the majority of patients with malignant blood diseases the ideal transfusion products are blood components instead of whole blood. The therapeutic use of packed red cells, platelets, leukocytes and albumin is briefly discussed.


[Prevention of the post-transfusion hepatitis]. For prophylaxis of posttransfusion hepatitis three procedures can be considered: 1. recognition of "infectious" blood donors, 2. elimination of the infectious agent from the blood units (or blood derivatives), 3. protection of the recipient by immunophrophylaxis. Among all available methods screening of blood donors for hepatitis B antigen (HB-sAg) by a sensitive test (e.g. radioimmunoassay or reversed passive hemagglutination) is presently the most efficient. Despite this precaution it can be estimated that three to four cases of overt posttransfusion hepatitis will still occur in 1000 transfusions in this country. A number of these might be due to agents other than hepatitis B virus, but another proportion may also be attributed to non-transfusion-induced infection originating from the hospital environment. Efforts are required to reduce this source of infection.