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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 109 records · Page 6Linked to original sources
PubMed1995

Role and benefits of carbohydrate in the diet: key issues for future dietary guidelines.

There is now widespread advocacy for a reduction in fat intake. Furthermore, there is little evidence that an increase in protein intake would be advisable. Therefore, a greater proportion of carbohydrate energy in the diet has become a central tenet of current dietary advice. A careful examination of the benefits of a "high"-carbohydrate diet must therefore occupy our attention. Three aspects of the role of carbohydrate in the diet will be considered: 1) the role of carbohydrate in the control of food intake in humans, 2) the effect of carbohydrate on energy metabolism as measured by long-term feeding experiments in small numbers of human subjects, and 3) whether a large carbohydrate intake leads to increased lipogenesis in humans.

Dietary Carbohydrates↗
PubMed1995

Autonomic nervous system activity in weight gain and weight loss.

Studies in both animals and humans indicate that the autonomic nervous system (ANS) responds to changes in systemic energy balance. In the present study, ANS response to weight change was examined by sequential blockade of cardiac autonomic innervation with parasympathetic (atropine) and sympathetic (esmolol) blockers. Change in heart period (interbeat interval) from baseline after atropine defined the amount of parasympathetic control (PC), and the subsequent change after esmolol defined the amount of sympathetic control (SC). In nonobese subjects, weight gain to 10% above initial body weight resulted in a decrease in PC and an increase in SC, and conversely, weight loss to 10% below initial weight resulted in an increase in PC and a decrease in SC. In obese subjects, weight loss resulted in the same pattern of changes in PC and SC. The major changes were in the parasympathetic arm of the ANS. These findings support the hypothesis that the ANS acts to oppose weight change.

Adrenergic beta-Antagonists↗
PubMed1995

Family support and other social factors precipitating suicidal ideation.

To examine the effects of family support and demographics on suicidal behavior, 385 subjects completed a demographic questionnaire and a Suicidal Ideation Questionnaire (SIQ). Sixteen percent described themselves as "serious" ideators, while 59% were seen as ideators, numbers consistent with past suicide research. Multiple regression analyses revealed that the type of caregiver a person reported having while growing up accounted for a significant amount of the variance on ideator status. Serious ideators were more common among single parent households. Although many demographic variables were assessed, only the primary caregiver a person had as a child impacted their status as a suicidal ideator. This suggests that suicidal behaviors may occur due to a complex interaction between social factors and childhood care. The influence of living in a single-parent home may contribute to whether or not a person considers suicide.

Adolescent↗
PubMed1995

Weighing the options: criteria for evaluating weight-management programs. The Committee to Develop Criteria for Evaluating the Outcomes of Approaches to Prevent and Treat Obesity.

The United States is experiencing an epidemic of obesity among both adults and children. Approximately 35 percent of women and 31 percent of men age 20 and older are considered obese, as are about one-quarter of children and adolescents. While government health goals for the year 2000 call for no more than 20 percent of adults and 15 percent of adolescents to be obese, the prevalence of this often disabling disease is increasing rather than decreasing. Obesity, of course, is not increasing because people are consciously trying to gain weight. In fact, tens of millions of people in this country are dieting at any one time; they and many others are struggling to manage their weight to improve their appearance, feel better, and be healthier. Many programs and services exist to help individuals achieve weight control. But the limited studies paint a grim picture: those who complete weight-loss programs lose approximately 10 percent of their body weight, only to regain two-thirds of it back within 1 year and almost all of it back within 5 years. These figures point to the fact that obesity is one of the most pervasive public health problems in this country, a complex, multifactorial disease of appetite regulation and energy metabolism involving genetics, physiology, biochemistry, and the neurosciences, as well as environmental, psychosocial, and cultural factors. Unfortunately, the lay public and health-care providers, as well as insurance companies, often view it simply as a problem of willful misconduct--eating too much and exercising too little. Obesity is a remarkable disease in terms of the effort required by an individual for its management and the extent of discrimination its victims suffer. While people often wish to lose weight for the sake of their appearance, public health concerns about obesity relate to this disease's link to numerous chronic diseases that can lead to premature illness and death. The scientific evidence summarized in Chapter 2 suggests strongly that obese individuals who lose even relatively small amounts of weight are likely to decrease their blood pressure (and thereby the risk of hypertension), reduce abnormally high levels of blood glucose (associated with diabetes), bring blood concentrations of cholesterol and triglycerides (associated with cardiovascular disease) down to more desirable levels, reduce sleep apnea, decrease their risk of osteoarthritis of the weight-bearing joints and depression, and increase self-esteem. In many cases, the obese person who loses weight finds that an accompanying comorbidity is improved, its progression is slowed, or the symptoms disappear. Healthy weights are generally associated with a body mass index (BMI; a measure of whether weight is appropriate for height, measured in kg/m2) of 19-25 in those 19-34 years of age and 21-27 in those 35 years of age and older. Beyond these ranges, health risks increase as BMI increases. Health risks also increase with excess abdominal/visceral fat (as estimated by a waist-hip ratio [WHR] > 1.0 for males and > 0.8 for females), high blood pressure (> 140/90), dyslipidemias (total cholesterol and triglyceride concentrations of > 200 and > 225 mg/dl, respectively), non-insulin-dependent diabetes mellitus, and a family history of premature death due to cardiovascular disease (e.g., parent, grandparent, sibling, uncle, or aunt dying before age 50). Weight loss usually improves the management of obesity-related comorbidities or decreases the risks of their development. The high prevalence of obesity in the United States together with its link to numerous chronic diseases leads to the conclusion that this disease is responsible for a substantial proportion of total health-care costs. We estimate that today's health-care costs of obesity exceed $70 billion per year.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Weight↗
PubMed1994

pH dependence of K+ conductances of rat cortical collecting duct principal cells.

The K+ channels of the principal cells of rat cortical collecting duct (CCD) are pH sensitive in excised membranes. K+ secretion is decreased with increased H+ secretion during acidosis. We examined whether the pH sensitivity of these K+ channels is present also in the intact cell and thus could explain the coupling between K+ and H+ secretion. Membrane voltages (Vm), whole-cell conductances (gc), and single-channel currents of K+ channels were recorded from freshly isolated CCD cells or isolated CCD segments with the patch-clamp method. Intracellular pH (pHi) was measured using the pH-sensitive fluorescent dye 2'-7'-bis(carboxyethyl)-5-6-carboxyfluorescein (BCECF). Acetate (20 mmol/l) had no effect on Vm, gc, or the activity of the K+ channels in these cells. Acetate, however, acidified pHi slightly by 0.17 +/- 0.04 pH units (n = 19). Vm depolarized by 12 +/- 3 mV (n = 26) and by 23 +/- 2 mV (n = 66) and gc decreased by 26 +/- 5% (n = 13) and by 55 +/- 5% (n = 12) with 3-5 or 8-10% CO2, respectively. The same CO2 concentrations decreased pHi by 0.49 +/- 0.07 (n = 15) and 0.73 +/- 0.11 pH units (n = 12), respectively. Open probability (Po) of all four K+ channels in the intact rat CCD cells was reversibly inhibited by 8-10% CO2. pHi increased with the addition of 20 mmol/l NH4+/NH3 by a maximum of 0.64 +/- 0.08 pH units (n = 33) and acidified transiently by 0.37 +/- 0.05 pH units (n = 33) upon NH4+/NH3 removal. In the presence of NH4+/NH3 Vm depolarized by 16 +/- 2 mV (n = 66) and gc decreased by 26 +/- 7% (n = 16). The activity of all four K+ channels was also strongly inhibited in the presence of NH4+/NH3. The effect of NH4+/NH3 on Vm and gc was markedly increased when the pH of the NH4+/NH3-containing solution was set to 8.5 or 9.2. From these data we conclude that cellular acidification in rat CCD principal cells down-regulates K+ conductances, thus reduces K+ secretion by direct inhibition of K+ channel activity. This pH dependence is present in all four K+ channels of the rat CCD. The inhibition of K+ channels by NH4+/NH3 is independent of changes in pHi and rather involves an effect of NH3.

Animals↗
PubMed1994

Analysing ion channels with hidden Markov models.

Ion channel current amplitudes (mu) and open probabilities (Po) have been analysed so far by defining a 50% threshold to distinguish between open and closed states of the channels. With this standard method (SM) it is very difficult or even impossible to analyse channels of different size in one membrane patch correctly. A stochastical model, named the hidden Markov model (HMM), separates between observation noise and the stochastic process of opening and closing of ion channels. The HMM allows the independent analysis of mu, Po, and mean dwell times (tau) of different channels in one membrane patch, without defining threshold levels. Using this method errors in the analysis are not summarized like in the SM because all different analysing procedures (e.g. filtering, setting of threshold, fitting processes) are done in one step. Two different K+ channels in excised basolateral membranes of the cortical collecting duct of rat (CCD) were analysed by the SM and the HMM. The mu value of the intermediate-conductance K+ channel (i-K+) was 3.9 +/- 0.1 pA (SM) and 3.8 +/- 0.2 pA (HMM) for 11 observations. The Po value of this channel was 10.2 +/- 4.2% (SM) and 10.1 +/- 4.0% (HMM). The mean tau values were 5.4 +/- 0.6 ms for the open state and 9.6 +/- 2.2 ms and 145 +/- 21 ms for the closed states (SM) and 7.8 +/- 1.1 ms, 7.7 +/- 0.9 ms and 148 +/- 24 ms (HMM), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1994

Impact of postoperative nausea and vomiting in the surgical setting.

Postoperative nausea and vomiting is one of the most common complications of inpatient and day case surgical procedures. In a climate where total cost of an illness is becoming increasingly important, postoperative nausea and vomiting is a major contributor to direct and indirect costs for both the hospital and patient. In patient terms, the impact of increased recovery room stays and extra nursing time required by PONV patients has been estimated to range from 96-576 more surgical procedures which may be performed in an 'average' day case surgery centre. Postoperative nausea and vomiting is perceived by patients to account for equal or more debilitation than surgery itself and may cause them to lose wages due to absence from work. Reducing the incidence of nausea and vomiting and its associated problems may therefore provide opportunities to improve patient care, decrease the size of waiting lists and improve utilisation of scarce healthcare resources.

Activities of Daily Living↗
PubMed1993

Determination of linkage positions in peracetylated (methyl) xylo-oligosaccharides with fast atom bombardment mass spectrometry.

Distinction between the linkage types 1-->2, 1-->3 and 1-->4 of xylobioses can be achieved on the basis of the unimolecular decomposition spectra of the oxonium ions of the per-O-acetylated methyl glycosides. The spectra of the oxonium ions of various unbranched xylotri-, tetra- and pentaoses allow determination of the linkage position between the xylose residues. This indicates that in unbranched peracetylated xylo-oligosaccharides the linkage between the xylose residues at the non-reducing end can be determined.

Carbohydrate Conformation↗
PubMed1993

K+ channels in the basolateral membrane of rat cortical collecting duct.

Impalement studies in isolated perfused cortical collecting ducts (CCD) of rats have shown that the basolateral membrane possesses a K+ conductive pathway. In the present study this pathway was investigated at the single-channel level using the patch-clamp technique. Patch-clamp recordings were obtained from enzymatically isolated CCD segments and freshly isolated CCD cells with the conventional cell-free, cell-attached and the cell-attached nystatin method. Two K+ channels were found which were highly active on the cell with a conductance of 67 +/- 5 pS (n = 18) and 148 +/- 4 pS (n = 21) with 145 mmol/l K+ in the pipette. In excised patches the first channel had a conductance of 28 +/- 2 pS (n = 15), whereas the second one had a conductance of 85 +/- 1 pS (n = 53) at 0 mV clamp voltage with 145 mmol/l K+ on one side and 3.6 mmol/l K+ on the other side of the membrane. So far it has not been possible to characterize the smaller channel further. Excised, and with symmetrical K+ concentrations of 145 mmol/l, the intermediate channel had a linear conductance of 198 +/- 19 pS (n = 5). After excision in the inside-out configuration the open probability (Po) of this channel was low (0.18 +/- 0.05, n = 13) whereas in the outside-out configuration this channel had a threefold higher Po (0.57 +/- 0.04, n = 12). Several inhibitors were tested in excised membranes. Ba2+ (1 mmol/l), tetraethylammonium (TEA+, 10 mmol/l) and verapamil (0.1 mmol/l) all blocked this channel reversibly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Cation specificity and pharmacological properties of the Ca(2+)-dependent K+ channel of rat cortical collecting ducts.

The luminal membrane of principal cells of rat cortical collecting duct (CCD) is dominated by a K+ conductance. Two different K+ channels are described for this membrane. K+ secretion probably occurs via a small-conductance Ca(2+)-independent channel. The function of the second, large-conductance Ca(2+)-dependent channel is unclear. This study examines properties of this channel to allow a comparison of this K+ channel with the macroscopic K+ conductance of the CCD and with similar K+ channels from other preparations. The channel is poorly active on the cell. It has a conductance of 263 +/- 11 pS (n = 36, symmetrical K+ concentrations) and of 139 +/- 3 pS (n = 91) with 145 mmol/l K+ on one side and 3.6 mmol/l K+ on the other side of the membrane. Its open probability is high after excision (0.71 +/- 0.03, n = 85). The channel flickers rapidly between open and closed states. Its permeability in the cell-free configuration was 7.0 +/- 0.2 x 10(-13) cm3/s (n = 85). It is inhibited by several typical blockers of K+ channels such as Ba2+, tetraethylammonium, quinine, and quinidine and high concentrations of Mg2+. The Ca2+ antagonist verapamil and diltiazem also inhibit this K+ channel. As is typical for the maxi K+ channel, it is inhibited by charybdotoxin but not by apamin. The selectivity of this large-conductance K+ channel demonstrates significant differences between the permeability sequence (pK > pRb > pNH4 > pCs = pLi = pNa = pcholine = 0) and the conductance sequence (gK > gNH4 > gRb > gLi = gcholine > gCs = gNa = 0). The only other cations that are significantly conducted by this channel besides K+ (gK at Vc = infinity is 279 +/- 8 pS, n = 88) re NH+4 (gNH4 = 127 +/- 22 pS, n = 10) and Rb+ (gRb = 36 +/- 5 pS, n = 6). The K+ currents through this channel are reduced by high concentrations of choline+, Cs+, Rb+, and NH+4. These properties and the dependence of this channel on Ca2+ and voltage classify it as a "maxi" K+ channel. A possible physiological function of this channel is discussed in the accompanying paper.

Animals↗
PubMed1993

Regulation and possible physiological role of the Ca(2+)-dependent K+ channel of cortical collecting ducts of the rat.

In the luminal membrane of rat cortical collecting duct (CCD) a big Ca(2+)-dependent and a small Ca(2+)-independent K+ channel have been described. Whereas the latter most likely is responsible for the K+ secretion in this nephron segment, the function of the large-conductance K+ channel is unknown. The regulation of this channel and its possible physiological role were examined with the conventional cell-free and the cell-attached nystatin patch-clamp techniques. Patch-clamp recordings were obtained from the luminal membrane of isolated perfused CCD segments and from freshly isolated CCD cells. Intracellular calcium was measured using the calcium-sensitive dye fura-2. The large-conductance K+ channel was strongly voltage- and calcium-dependent. At 3 mumol/l cytosolic Ca2+ activity it was half-maximally activated. At 1 mmol/l it was neither regulated by cytosolic pH nor by ATP. At 1 mumol/l Ca2+ activity the open probability (Po) of this channel was pH-dependent. At pH 7.0 Po was decreased to 4 +/- 2% (n = 9) and at pH 8.5 it was increased to 425 +/- 52% (n = 9) of the control. At this low Ca2+ activity the Po of the channel was reduced by 1 mmol/l ATP to 8 +/- 4% (n = 6). Cell swelling activated the large-conductance K+ channel (n = 14) and hyperpolarized the membrane potential of the cells by 9 +/- 1 mV (n = 23). Intracellular Ca2+ activity increased after hypotonic stress. This increase depended on the extracellular Ca2+ activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗