One of two growth hormone genes in coho salmon is sex-linked.

Salmonid fishes have two growth hormone genesresulting from their polyploid ancestry. We used the polymerase chain reactionto examine genetic variation in the third intron (C) of both of these genes incoho salmon (Oncorhynchus kisutch). A polymorphism in the length of intron C inGH-1 is due to a variable number of copies of a 31-nt repeat that is absent fromGH-1 of the closely related chinook salmon (Oncorhynchus tshawytscha) andrainbow trout (Oncorhynchus mykiss). Thus, this tandem repeat sequence hasbecome established in the genome of coho salmon since the separation of thisspecies from its closest relatives. All male coho salmon examined have an alleleat the second growth hormone gene, GH-2, that is not found in females. GH-2 isthus on the sex chromosome and there is no recombination between GH-2 and thesex-determining locus (SEX). Sequences of intron C indicate much greaterdivergence between the X chromosome-specific allele and the Ychromosome-specific allele within coho salmon than between the Xchromosome-specific alleles of coho and the closely related chinook salmon.Thus, absence of recombination between GH-2 and SEX apparently predatesseparation of these two species.     

Haemodynamic effects of rectal methohexitone for induction of anaesthesia in children

Pulsed Doppler and two-dimensional echocardiography were used to determine the haemodynamic effects of rectal methohexitone in 12 children 32.4 +/- 3.8 months old and weighing 13.3 +/- 1.1 kg (mean +/- SEM). Heart rate, blood pressure and echocardiographic measurements of cardiac output, stroke volume and left ventricular end-diastolic and end-systolic volumes were obtained prior to the induction of anaesthesia. Anaesthesia was induced with 25 mg.kg-1 two per cent rectal methohexitone. Immediately following the onset of sleep all cardiovascular measurements were repeated. Following the induction of anaesthesia with rectal methohexitone there was a significant increase in heart rate. Blood pressure, cardiac index, stroke volume and ejection fraction were unchanged. It is concluded that rectal administration of two per cent methohexitone for the induction of anaesthesia in healthy paediatric patients has minimal haemodynamic effect.     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.     

Antibacterials. synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 4. Multiply-substituted aryl derivatives.

The synthesis and structure-activity relationship (SAR) studies of the effect of different polysubstitution patterns in the aromatic ring of 5-(acetamidomethyl)oxazolidinone antibacterials (I) on antibacterial activity are presented. Compounds I were prepared by the six-step synthesis described previously (Gregory, W. A.; et al. J. Med. Chem. [formula: see text] 1989, 32, 1673), electrophilic aromatic substitution reactions of 3-substituted compounds, and functional-group interchange reactions of 3,4-disubstituted compounds. Antibacterial evaluation of compounds I against Staphylococcus aureus and Enterococcus faecalis gave the following results. The 2,4- and 2,5-disubstituted derivatives have weak or no antibacterial activity. Antibacterial activities of 3,4-disubstituted compounds are comparable to those of the 4-monosubstituted analogues for small 3-substituents (smaller than Br), but decline rapidly for larger 3-substituents. 3,4-Annulated derivatives are comparable in activity to their open-chain analogues. 3,5-Disubstituted and 3,4,5- and 2,4,6-trisubstituted derivatives are devoid of antibacterial activity.     

Abdominal chemo- and mechanosensitivity in ruminants and its role in the control of food intake.

Ruminant animals have evolved a large and complex set of stomachs which allow fermentation of fibrous food by symbiotic micro-organisms. These stomachs are well innervated and generate signals which are thought to be important in the control of voluntary food intake. Tension receptors in the muscular wall of the rumen and reticulum are slowly adapting and provide a measure of distension while epithelial receptors are rapidly adapting and provide information on the fibrousness of the digesta; they are involved in the control of stomach motility and voluntary food intake in order to prevent excessive distension. The epithelial receptors are also sensitive to the chemical nature of the digesta, particularly acidity. There are mechano- and chemoreceptors in the abomasum (true stomach) and duodenum and chemoreceptors in the liver, all of which have been implicated in the control of intake. It is relatively easy to prepare and maintain ruminants with a rumen fistula and many studies have shown the effects of such manipulations as distension of balloons in the rumen on voluntary intake. With fibrous, slowly digested feeds intake is primarily limited by rumen distension. With more rapidly digested feeds, however, the products of digestion play an important role in controlling intake. Short-chain fatty acids are the main products of fermentation and infusion of their salts into the rumen depresses food intake to a much greater extent than infusion into the general circulation. Acetate or propionate given into the rumen are more effective, mole for mole, than butyrate but must be given at rates exceeding the natural rate of production in order to have a significant effect. It has been suggested that much of the effect of sodium acetate is via the increase in the osmolality of rumen fluid but there is considerable uncertainty as to the physiological significance of osmotic effects, especially when animals have free access to water and can prevent excessive increases in tonicity by increasing their water intake. Other constituents of rumen fluid have been implicated in the control of food intake, particularly lactic acid and nitrogenous compounds, especially as these can be found in fermented feeds such as silage. The omasum controls the flow of digesta to the abomasum; it is therefore well placed to control rumen fill and thus intake but there has been little study in this area and this is also true for the abomasum.(ABSTRACT TRUNCATED AT 400 WORDS)     

Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery: A Randomized Controlled Trial

Background: Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear.

Methods: Patients having major surgery expected to last at least 2 h were randomly assigned to nitrous oxide-free (80% oxygen, 20% nitrogen) or nitrous oxide-based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery.

Results: Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide-free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56-0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31-0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide-free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02).     

A high fidelity tissue-based cardiac surgical simulator.

OBJECTIVE: Issues concerning the training and certification of surgical specialists have taken on great significance in the last decade. A realistic computer-assisted, tissue-based simulator developed for use in the training of cardiac surgical residents in the conduct of a variety of cardiac surgical procedures in a low-volume cardiothoracic surgery unit of a typical developing country is described. The simulator can also be used to demonstrate the function of technology specific to cardiac surgical procedures in a way that previously has only been possible via the conduct of a procedure on a live animal or human being. METHODS: A porcine heart in a novel simulated operating theatre environment with real-time simulated haemodynamic monitoring and coronary blood flow, in arrested and beating-heart modes, is used as a training tool for surgical residents. RESULTS: Standard and beating-heart coronary arterial bypass, aortic valve replacement, aortic homograft replacement and pulmonary autograft procedures can be simulated with high degrees of realism and with the superimposition of adverse clinical scenarios requiring valid decision making and clinical judgments to be made by the trainees. CONCLUSIONS: The cardiac surgical simulation preparation described here would appear to be able to contribute positively to the training of residents in low-volume centres, as well as having the potential for application in other settings as a training tool or clinical skills assessment or accreditation device. Collaboration with larger centres is recommended in order to accurately assess the utility of this preparation as an adjunctive cardiothoracic surgical training aid.     

Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine treatment

Objective: Interindividual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable during smoking and transdermal nicotine treatment, even among individuals taking in nominally similar doses of nicotine. This report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict concentrations during transdermal nicotine treatment. Methods: Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to individual characteristics such as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters. Results: Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance (baseline plasma concentration divided by cigarettes per day) together with other factors could account for 18 to 33% of the variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study. Conclusion: Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable individual pharmacokinetic parameters and absorbed dose of nicotine. Considering the interindividual variability of plasma nicotine and cotinine concentrations together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility of a therapeutic drug monitoring approach for transdermal nicotine treatment – particularly for high dose regimens (> 22 mg per 24 hours). Received: 7 May 1996 / Accepted in revised form: 21 August 1996