Release of renal prostaglandins during endotoxin-induced hypotension

The appearance of prostaglandins in dog's blood during endotoxin-induced hypotension was studied by use of the dialysis modification of the blood bathed organ technique. An increase in prostaglandins, mainly E2 and F2alpha was found in renal venous blood, whereas no such increase was seen in blood from the abdominal aorta, the inferior vena cava or the femoral vein. Three possible trigger mechanisms for this increase i.e. hypotension, reduced flow and reflexogenic sympathetic stimulation, have been investigated. It is suggested that, in addition to these three factors, circulating hormones such as noradrenaline, angiotensin or bradykinin, play a role in this release mechanism. Administration of indomethacin produced a restoration of the systemic blood pressure to its pre-endotoxin value; concomitantly a disappearance of the prostaglandins from the circulation was observed. It is concluded that prostaglandins contribute to the hypotension induced by endotoxin. Whether they are beneficial or detrimental remains to be resolved.     

A comparative study of passive haemagglutination methods for the detection of hepatitis B surface antigen in routine hospital practice

Two passive haemagglutination methods for detecting HBsAg were compared. In general, the method using turkey erythrocytes was found preferable to the method employing sheep cells since it is more rapid and more sensitive, and less frequently gave rise to false positive reactions with sera from staff, blood donors, and patients not receiving haemodialysis. The turkey cell test gives rise to more false positive screen tests than the sheep cell test when monitoring renal dialysis patients since approximately 10% of the sera of these patients were found to contain turkey cell agglutinins, but this presents no particular difficulty if the recommended absorption procedures are used.     

The response of cells in culture to fractionated radiation: a theoretical approach

A mathematical model has been constructed to simulate the response of cells in vitro to fractionated doses of radiation. The model is capable of describing most of the radiobiological functions that are commonly studied. Input data are measurable cell properties. The details of the model and methods of acquiring the input data are outlined and a comparison with experimental observations on two radiobiological functions, survival curves and recovery curves are discussed in some detail.     

Study on the relationship between plasma prolactin levels and androgen metabolism in man

The purpose of the study was to investigate the effect of hyperprolactinemia on the metabolism of androgens in man. A group of 6 normal men was treated for 4 consecutive days, on separate periods, with Sulpiride which is known to raise plasma prolactin (PRL) concentration. The effect of the treatment on plasma steroids was verified in basal conditions and under stimulation by HCG. In the controls, a parallel rise in testosterone (T) and dihydrotestosterone (DHT) was observed in response to HCG stimulation. In experimental hyperprolactinemia, the rise in T in response to HCG, similar to that of the controls, was accompanied by a markedly diminished rise in DHT. Similar results were observed in a patient with hyperprolactinemia following apparent accidental section of the pituitary stalk. These data demonstrate the interference of increased levels of PRL in the metabolism of testosterone into the active DHT form by 5alpha-reductase. They suggest that this mechanism could possibly impair the gonadal function in man.     

Evidence for the presence of components of the alternative (properdin) pathway of complement activation in respiratory secretions

Activation of the alternative complement pathway by respiratory secretory IgA was demonstrated by incubating purified, aggregated preparations of serum and secretory IgA with neat human serum. No depletion of the early components (C1-4) was observed, but 63 and 70% of C3-9, respectively, were consumed. The C3-9-consuming capacity of heat-aggregated nasal secretions from an IgA-deficient volunteer was compared with heat-aggregated nasal secretions from a normal volunteer known to have secretory IgA. The deficient secretions consumed C3-9, whereas the IgA deficient secretions did not. Reconstitution of the nasal secretions from the IgA-deficient volunteer with purified secretory IgA produced alternative pathway activation. Factor B of the alternative complement pathway was found to be present in 16 of 18 bronchoalveolar lavage samples (BALF) from normal volunteers. Simultaneous measurement of lavage and serum albumin and Factor B concentrations rendered it unlikely that Factor B was merely a transudative product from serum in half the samples but rather suggested that it may be a component of lower respiratory tract secretions. The presence of an intact alternative complement pathway in BALF was indicated by showing that cobra venom factor and endotoxin cleaved functionally pure human C3 when mixed with BALF, but had no effect on C3 in the absence of BALF.     

Platelet density and size: the interpretation of heterogeneity

Platelets have been separated according to buoyant density using a colloidal silica-polyvinylpyrrolidone system and subjected to electronic sizing. All density populations were found to be heterogeneous in size, the most dense platelets ranging from less than 3 fl to greater than 21 fl in both man and rat. Light platelet fractions contained no platelets greater than 13 fl in either species. Cohort labeling with [75Se]selenomethionine showed no indication of significant change in platelet buoyant density with ageing; greater specific activity found in young, dense platelets appears to be related to increased protein synthetic activity shown in vitro and likely to occur also in their precursor megakaryocytes. It is postulated that dense, intermediate and light platelets are released synchronously by the three different ploidy classes of megakaryocyte, that varying density indicates differing structural characteristics and presumably differences in function. The present findings do not deny the possibility that platelets decrease in size with ageing but if such occurs, it is not associated with a significant change in platelet buoyant density.     

Nondisjunction in aging female mice

Oocytes from CBA mice varying in age from 2 to 11 months were cultured to the metaphase II stage of meiosis and the chromosomes analyzed. The oocytes from three maternal age groups were compared with respect to the mean number of oocytes obtained per mouse, the frequency of maturation to metaphase II, and the frequency of numerical chromosomes abnormalities. Both the mean number of oocytes obtained per mouse and the frequency of maturation decreased markedly with maternal age. The frequency of chromosome abnormalities in the oocytes increased with maternal age from the young to the middle-aged mice but dropped off in the oldest maternal age group. No hyperploid (n + 1) oocytes were observed in the young or old group of mice, but 5.2% hyperploidy occurred in the middle-aged group. It is suggested that the lack of hyperploid oocytes in the old CBA females might be due to a threshold effect in which oocytes that are damaged by the number of univalents present at metaphase I become atretic and do not progress to metaphase II. The frequency of diploid (2n) oocytes was 1.7% and was not maternal-age dependent.     

Recovery of ventilatory response to carbon dioxide after thiopentone, morphine and fentanyl in man

Ventilatory responses to CO2 (delta VI/delta PCO2) were measured half, one, two and four hours after infusions of thiopentone, morphine, fentanyl and saline in healthy men in order to test the idea that variation in clinical recovery and control of breathing after anaesthetic drugs are associated with interindividual differences in control measurements of delta VI/delta PCO2. Ventilatory response to CO2 was profoundly reduced one half hour after each drug, in contrast to the observation during air breathing that ventilation and end tidal PCO2 had returned to within 10 per cent of control. Mean delta VI/delta PCO2 increased progressively at one, two, and four hours, returning to near control after thiopentone, but remaining less than 80 per cent of control four hours after morphine and fentanyl. From the regression equations of each ventilatory response, ventilation at PCO2 of 58 and 70 mmHg (VI58 and VI70) were computed to estimate displacement of the response curves by the drugs. Following thiopentone there was no significant change of V158. In contrast ther was a highly siginificant fall of VI58 one half hour after fentanyl (p less than 0.01), with progressive return towards control at one, two, and four hours; similar changes were observed after morphine. For each drug, changes of VI70 were substantially greater than corresponding changes of V158. At all times during these recovery measurements, subjects were conscious and co-operative and, by traditional clinical criteria, were judged to have recovered from the effects of the drugs. Differences between high and low responding subjects were assessed by plotting control measurements against values obtained half and one hour after drugs. No systematic differences were found. These findings suggest that delta VI/delta PCO2 is a sensitive indicator of central nervous activity, but do not support the concepts that individuals with low delta VI/delta PCO2 might be more susceptible to the ventilatory depressant effects of anaesthetic drugs, or that low delta VI/delta PCO2 might be associated with delayed return of spontaneous breathing after general anaesthesia. Plasma thiopentone levels at half, one, and four hours were highly reproducible, in contrast to the wide variation of delta VI/delta PCO2 among subjects in this study. These findings together support the notion that wide variation in clinical recovery from anaesthesia may have a primary physiological basis in addition to variation caused by interindividual differences in drug dosage, biotransformation and excretion.