Direct measurement of the thermal responses of nude resting men in dry environments

Summary Two nude resting men were exposed for two-hour periods to each of 25 dry environments, with air temperatures ranging between 12.8° C and 49.1° C and wind speeds between 0.67 m/sec and 4.94 m/sec. The mean radiant temperature of the surroundings was kept equal to the air temperature. Rates of radiant and convective heat exchange were measured directly, separately and continuously. The men had reached a thermal steady state after 105 min in the warm environments, but not in the cold environments. Graphs are presented to show the effect of ambient temperature and wind speed on the radiation and convection rates attained after 105 min, as well as on metabolic rate, sweat evaporation rate, rectal temperature and mean skin temperature. These graphs revealed some important aspects of the behaviour of man's thermal control system. In particular the physiological conductance increased with increasing ambient temperature and then saturated at an ambient temperature near 35° C. This saturation resulted in a constant difference between rectal temperature and mean skin temperature irrespective of the environmental conditions.Published with the permission of the Chamber of Mines of South Africa.     

Immunohistochemistry of neurone specific enolase with gamma subunit specific anti-peptide monoclonal antibodies.

AIMS--To investigate the application in immunohistochemistry of gamma-subunit specific anti-peptide monoclonal antibodies to human neurone specific enolase (NSE); and to determine their reactivity with formalin fixed, wax embedded sections of normal tissue and neuroendocrine tumours. METHODS--Immunohistochemical staining was performed on sections of formalin fixed, wax embedded tissue with two monoclonal antibodies (NSE-P1 and NSE-P2) raised against different synthetic peptides specific for the gamma subunit of human enolase (neurone specific enolase). RESULTS--Both antibodies gave strong immunostaining in normal tissues and cells known to contain NSE. There was no immunoreactivity in tissues containing either the alpha alpha or beta beta isozymes of enolase. The reactivity of the antibodies with a range of neuroendocrine tumours was also studied and both antibodies gave strong immunostaining of tumour cells in the different tumours. CONCLUSIONS--The use of synthetic peptides from defined regions of a molecule as immunogenes provides antibodies of high specificity. These monoclonal antibodies to NSE are ideally suited for immunohistochemical studies and they should be particularly useful in histopathology as they react with epitopes which are resistant to formalin fixation and wax embedding.     

Identification and isolation of a common tumor-associated molecule using monoclonal antibody

A monoclonal antibody, 16B-13, derived from the immunization of BALB/c mice with a lung tumor line, immunoprecipitates a common tumor-associated molecule with an apparent mol. wt of 37,000 from lactoperoxidase-ionated lung carcinoma, colon carcinoma, gastric carcinoma, brest carcinoma, melanoma and lymphona cells, but not from normal fibroblasts. Analysis by two-dimensional gel electrophoresis of the cell surface-labeled 16B-13 antigen from a colorectal and a melanoma cell line reveals four components with similar mol. wts but with different isoelectric points. The antigen purified froma a colorectal carcinoma cell line by immunoaffinity chromatography was shown to be a 37,000 mol. wt polypeptide similar to that obtained by the lactoperoxidase-labeling procedure. However, the purified antigen from the melanoma cell line shows the presence of a 65,000 mol. wt polypeptide and the loss of the 37,000 mol. wt component as detected by Comassie blue staining and immunoprecipitation.     

Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

The clinical pharmacokinetics of the novel antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717)

Summary The pharmacokinetics of the new antifolate CB 3717 were studied in 20 patients during its phase-I clinical evaluation. The drug was administered at doses of 100–550 mg/m² in 1-h and 12-h infusions, resulting in peak plasma concentrations of CB 3717 of 40–200 M. There was a linear relationship between the dose and both CB 3717 AUC and peak plasma levels. Following a 1-h infusion, drug levels in the plasma decayed biphasically (t_1/2=49±9 min, t_1/2=739±209 min). 27%±2% of the dose was excreted in urine in the 24-h period after treatment, suggesting that the major route of elimination was via the bile. Furthermore, the parent compound CB 3717 and its desglutamyl metabolite, CB 3751, were found in a faecal collection although the metabolite was not detected in plasma or urine samples. Plasma protein binding of CB 3717 was extensive (97.6%±0.1%). Significant quantities of CB 3717 penetrated into ascitic fluid but not into cerebrospinal fluid.Residual drug was detected in postmortem kidney tissue from a patient who died of progressive disease 8 days after treatment with 330 mg/m² CB 3717. Thus, dose-limiting renal toxicity (maximum tolerated dose 600 mg/m²) may be due to drug precipitation in the renal tubules. Elevation of liver enzymes, in particular transaminases, occurred frequently as a toxic manifestation of CB 3717 therapy. In 11 patients studied after their first treatment there was a positive correlation between the rise in serum alanine transaminase and peak drug levels (r=0.69, P=0.02)These pharmacokinetic studies have shown that, by analogy with experimental systems, cytotoxic plasma levels of CB 3717 are archieved in man. In addition, they have been valuable in interpreting toxicities observed during phase-I clinical studies.This work was supported by grants from the Medical Research Council and Cancer Research Campaign, U. K.     

Comparison of midazolam and thiopental for rapid sequence anesthetic induction for elective cesarean section

Sixty healthy mothers undergoing elective cesarean section received at random either midazolam 0.2 mg/kg or thiopental 3.5 mg/kg with succinylcholine 1 mg/kg for rapid sequence intravenous anesthetic induction. Maintenance of anesthesia was identical in all patients: 50:50 N2O in oxygen, halothane 0.5% and pancuronium 0.05 mg/kg. Hemodynamic responses were similar, as were the biochemical status of mothers and infants, and maternal to fetal blood gas/acid base gradients. Correlation between maternal arterial and fetal (umbilical venous/arterial) pH, PCO2 and base excess values were statistically better with midazolam. However, 1-min Apgar minus color (A-C) scores less than 5/8 (representing "severe" neonatal depression) were recorded in five infants after midazolam, three of whom required tracheal intubation, and one whose mother was given thiopental. This difference reached statistical significance (P less than 0.05). It is concluded that midazolam is less suitable than thiopental for anesthetic induction in patients undergoing cesarean section.     

Retrograde air embolization in coronary operations

Observations during coronary operations are presented that prove that if the ascending aorta is cross-clamped and suction applied to the left side of the heart or to the aortic root for venting purposes, the pressure rapidly drops in the coronary arterial system and a situation is created in which air may enter through the coronary arteriotomy and pass into the aortic root and the left ventricle. Another mechanism to explain the occurrence of some cases of "iatrogenic" air embolism has also been presented: introduction of air into the ascending aorta while cardioplegic solution is being injected through peripherally attached bypass grafts. Air trapped in these grafts or in the coronary artery itself may propagate proximally as well as distally in the coronary arteries and may reach the aortic root even if the left side of the heart is left unvented. These mechanisms may be responsible for heretofore unexplained cases of "iatrogenic" air embolization. We recommend careful purging of air, which may be present, from the left ventricle and aortic root every time before the aortic cross-clamp is removed during coronary operations.     

Petit mal epilepsy: a review and integration of recent information

Petit mal (absence) epilepsy remains one of the most enigmatic of neurological disorders, and there is no widely accepted theory of its etiology. This review covers some of the current issues concerned with the disorder, including treatment and prognosis, neurochemical research, behavioral and psychophysiological effects of wave-spiked discharges, and EEG studies of seizure control. With respect to treatment, although effective drug therapy (valproic acid, ethosuximide) exists for the "pure" form of absence epilepsy, other forms, in which there is an admixture of grand mal seizures, are less amenable to pharmacotherapy. Moreover, the frequency of fatal hepatic toxicity following valproic acid therapy has been estimated at 1 in 20,000. With respect to prognosis, follow-up studies indicate that many patients do not outgrow the disorder but continue to suffer absence seizures well into adulthood. In recent years, there has been considerable research on the neurochemical basis of absence epilepsy. Current theories, including those that implicate gamma-aminobutyric acid, catecholamines, and "endogenous" epileptogens, are summarized; and requirements for an experimentally induced animal model of absence epilepsy are discussed. The majority of behavioral studies of the disorder have concerned the effects of petit mal-type discharges on sensory and cognitive processes. Some of these studies are reviewed; and recent work bearing on these issues, involving event-related brain potentials, is presented. Our review concludes with a discussion of research aimed at the development of electrophysiologically based approaches to the reduction of seizure frequency in patients with absence epilepsy.     

Risk of Gastrointestinal Bleeding With Extended Use of Nonsteroidal Anti-Inflammatory Drug Analgesia After Joint Arthroplasty

BackgroundChronic nonsteroidal anti-inflammatory drug (NSAID) use is associated with gastrointestinal bleeding via inhibition of endogenous mucosal protection and platelet aggregation. This study aimed to determine whether extended NSAIDs after joint arthroplasty is associated with increased risk of gastrointestinal bleeding.MethodsThis was a retrospective study examining 28,794 adults who underwent joint arthroplasty by one of 50 surgeons from 2016 to 2018. Episodes of gastrointestinal bleeding within 90 days postoperatively were identified prospectively. Postoperative medications were reported directly by patients with electronic questionnaires. The primary analysis was performed using binary logistic regression.ResultsA total of 74 (0.26%) episodes of gastrointestinal bleeding occurred within 90 days (median 8 days) postoperatively. Of 5086 patients with complete data included in the primary analysis, 59.6% had used NSAIDs with median duration of 2 weeks (interquartile range, 0-6 weeks). Patients with gastrointestinal bleeding were significantly older (71.3 vs 67.0 years), required longer hospitalizations (2.1 vs 1.5 days), and more commonly had a history of peptic ulcers (10.8% vs 0.9%). However, there was no positive association between NSAID use and gastrointestinal bleeding. In fact, the odds of gastrointestinal bleeding were lower in patients taking NSAIDs. Gastrointestinal bleeding was associated with anticoagulants, antiplatelet agents, and, to a lesser extent, aspirin.ConclusionNSAIDs were not associated with gastrointestinal bleeding and may be prescribed safely for a majority of patients after joint arthroplasty. The greatest odds of gastrointestinal bleeding occurred in patients with peptic ulcer disease and those who received antiplatelet and anticoagulation agents. Increasing age and bilateral surgery were also associated with gastrointestinal bleeding.Level of EvidenceLevel III.