The Membrane Lipid Cholesterol Modulates Anesthetic Actions on a Human Brain Ion Channel

Background: Molecular theories of general anesthesia often are divided into two categories: (l) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.

Methods: Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.

Results: Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half.     

Behaviors and attitudes associated with eating disorders: perceptions of college athletes about food and weight

This study surveyed male and female athletes from 22 midwesterncolleges and universities regarding behaviors and attitudesassociated with anorexia nervosa and bulimia nervosa. The responserate was 66% (N= 695) and the findings indicated that the bodyimage of some athletes may be distorted; one-seventh perceivedthemselves as fat even though they were not. Many athletes seemedpreoccupied with food and weight; almost one-third reportedroutinely thinking about food and weight and more than one-thirdreported dramatic annual weight fluctuations (9 lb or greater)related to bingeing and fasting. Athletes also did not feelin control when they ate and their habits related to food consumptionappeared to be extreme; one-tenth reported a lack of controlwhen they ate, more than one-third binged, one-twentieth ateuntil they were physically ill, and a similar proportion preferrednot to eat in the presence of others. In addition, it was foundthat as many men as women athletes reported these perceptionsbut significant sex differences were noted for specific items.It was suggested that behaviors and attitudes be viewed on acontinuum with normals at one end, eating disordered individuals at the other end,and college athletes in between. Health education that focuseson behaviors and attitudes as symptoms of eating disorders wasrecommended for athletes and those working closely with athletes.Future research was suggested to determine reasons for the undesirablebehaviors and attitudes and to study the onset, development,long-term effects and whether these behaviors and attitudeslead to an eating disorder.     

Development of a protein phosphatase-based assay for the detection of phosphatase inhibitors in crude whole cell and animal extracts

Diarrhetic shellfish poisoning (DSP) is a serious and globally widespread phytoplankton-related seafood illness. Although DSP is rarely life-threatening, it causes incapacitating diarrhea and vomiting with no known medical treatments. In addition, phytoplankton producing DSP toxins have been identified in temperate coastal waters worldwide, and their numbers may be increasing as a result of coastal eutrophication. The toxic effects of the major DSP toxins, okadaic acid and dinophysistoxin-1 (35-methylokadaic acid), appear to originate from their inhibitory activity against a family of structurally related serine/threonine protein phosphatases (PSPases). In particular, the inhibition of essential PSPases (e.g. PP1 and PP2A) has catastrophic consequences in most eukaryotic cells. Exploiting the potent inhibitory property of the DSP toxins, we have developed an enzyme-based assay (PP2A assay) capable of detecting both okadaic acid and dinophysis- toxin-1 in nanogram amounts. The assay employs purified PP2A, which has an extremely high affinity for both DSP toxins. This provides the PP2A assay with a level of sensitivity comparable to, or surpassing, that of most monoclonal antibody probes. To evaluate the PP2A assay as a means of detecting contaminated shellfish, a series of spike recovery experiments was conducted. The findings from these studies suggest that the PP2A assay has the potential for development into a rapid and relatively simple method for detecting PSPase inhibitors in crude extracts produced from shellfish.     

The breath of life: medical technology and the careers of people with post-respiratory poliomyelitis

Abstract This paper examines the impact of medical technology on the careers of people with post-polio respiratory disability. The data have been taken from multiple in-depth interviews with ten people who contracted polio during the epidemics of the early 1950s, all of whom used or had used a variety of methods of mechanical respiratory support. It focuses on ideologies of disability and the adoption of technology, the management of respiratory insufficiency and strategies of'trading off whereby the benefits of technology are maximized and the costs minimized. While technology made an enormous contribution to the quality of life of these people, the problems it created transformed both their experience of the illness and the character of their everyday existence.     

Measurements of Blood Pressure, Oedema and Proteinuria in a Pregnant Population of New Zealand

Summary: This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that Mood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Ffg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of >33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women. Ankle oedema was significantly associated with the development of both gestational hypertension and preeclampsia but the incidence of oedema was noted in only 11.9% of the subjects.     

Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck

Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m² intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.