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.     

Location of nucleolar organizing regions on the chromosomes of the Syrian hamster (Mesocricetus auratus) and the Djungarian hamster (Phodopus sungorus)

Terminal chromosome associations ("satellite associations") in ASG-banded preparations have been used to determine the number and location of staellites in the Syrian hamster (Mesocricetus auratus) and the Djungarian hamster (Phodopus sungorus). Five pairs of satellites are found in the former and four in the latter. Nucleolar organizing regions (NORs) were visualized with the Ag-AS silver precipitation technique, and their number and position corresponded exactly with the number and position of satellites in Phodopus, where positive chromosome identification can be made in the absence of banding. Numerical agreement is exact in Mesocricetus as well, and the morphology of the silver-tagged NOR-bearing chromosomes strongly suggests that corrrespondence also occurs in this species.     

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.     

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.     

Biological role of alcohol dehydrogenase in the tolerance of Drosophila melanogaster to aliphatic alochols: utilization of an ADH-null mutant

The toxicity of the first eight primary alcohols and of four secondary alcohols was compared in a wild-type strain (having active ADH) and an ADH-negative mutant. Differences between LC50 measured in the two strains allowed an evaluation of the biological activity of the enzyme. In vitro, ADH is mainly active on secondary alcohols, while in vivo its main role is the detoxification and metabolism of ethanol. These observations suggest that originally ADH was involved in unknown metabolic pathways and that its utilization in ethanol metabolism could be a recent event.     

Effects of exogenous hormones and glucose on plasma levels and hepatic metabolism of amino acids in the fetus and in the newborn rat

The present study examines the role of insulin, glucagon and cortisol in the regulation of gluconeogenesis from lactate and amino acids in fetal and newborn rats. Injection of glucagon in the full-term fetal rat caused a rise in glucose (and insulin) and a fall in blood levels of most individual amino acids, stimulated hepatic accumulation of 14C-amino isobutyric acid and 14C-cycloleucine and increased the conversion of 14C lactate, alanine and serine to glucose in vivo and in vitro (liver slices). Such changes were equivalent to the changes seen in 4 h old newborn rats. When glucagon was administered at birth, little difference was observed between control and treated animals in plasma amino acids and a smaller increment in conversion of 14C substrate to glucose occurred. By contrast, insulin injection at birth caused hypoglycemia, suppression of levels of certain amino acids and inhibition of conversion of 14C substrates into glucose. Glucose injection at birth caused elevated glycemia and plasma insulin and suppression of most amino acid levels and of conversion of 14C substrate into glucose. Cortisol injection at birth caused a marked, generalized by hyperaminoacidemia, a stimulation of glucagon secretion and of conversion of 14C substrates into glucose. These observations support the thesis that glucagon plays a major role in the induction of hepatic gluconeogenesis and that insulin acts as an antagonist hormone.     

Surgical significance of extrahepatic biliary tree anomalies

A patient with an anomalous insertion of the right hepatic duct into the cystic duct was noted during cholecystectomy and confirmed by operative cholangiography. This case and related anomalies of the bile ducts are of sufficient importance that, because of the technical difficulties and dangers incidental to their presence, no surgeon who operates on the gallbladder and bile ducts can afford to be unaware of their existence. Adequate exposure, careful dissection, and accurate knowledge of the regional anatomy plus a realization of the frequency and multiplicity of abnormalities of the extrahepatic biliary tree are requisites for safe biliary tract surgery. In addition, carefully performed operative cholangiography can be an indispensable aid in the clarification of anatomic variations. In case of recognized operative injury to the extrahepatic biliary tree, primary repair or biliary-intestinal anastomosis can usually be carried out with good results.     

Circadian rhythms of serum renin activity and serum corticosterone, prolactin, and aldosterone concentrations in the male rat on normal and low-sodium diets

To investigate the control of aldosterone secretion, non-stress levels of serum aldosterone, corticosterone, and prolactin, and renin activity were determined at 4-h intervals during 24-h light-dark cycles in adult male rats on regular and low-sodium diets. Circadian rhythms of plasma aldosterone, prolactin, and corticosterone concentrations and of serum renin activity were demonstrated during a regular sodium diet. When the rats were on a low-sodium diet, a circadian rhythm of serum corticosterone and aldosterone concentration was observed, but there was no circadian variation in serum renin activity or in serum prolactin concentration. Serum aldosterone concentration correlated with serum corticosterone concentration (r = 0.48) and serum renin activity (r = 0.36) during a low-sodium diet. Serum prolactin concentration did not correlate with serum aldosterone concentration or serum osmolality. These data are compatible with a role for renin and ACTH, but not for prolactin, in the modulation of aldosterone secretion in the rat.