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Background: In patients with heart failure, the degree of intraventricular mechanical dyssynchrony (intra-VMD) at baseline may predict reversal of cardiac remodeling with cardiac resynchronization therapy (CRT)., Objective: The purpose of this study was to determine the prevalence and clinical significance of intra-VMD in patients admitted for advanced decompensated heart failure (ADHF)., Methods: We prospectively enrolled 50 patients with ADHF without previous CRT implantation who had been admitted to a specialized heart failure intensive care unit because of hemodynamic derangements. All patients underwent comprehensive echocardiographic evaluation within 12 hours of admission and after 48 hours from baseline evaluation after intensive medical therapy. Intra-VMD was assessed by the opposing wall time-to-peak myocardial velocity intervals in a four-segment model using color-tissue Doppler imaging., Results: In our study cohort (mean age 57 +/- 11 years, left ventricular ejection fraction 26 +/- 10%, QRS width 127 +/- 31 ms, cardiac index 2.0 +/- 0.6 L/min/m(2)), significant intra-VMD (>or=65 ms) was present in 44% of subjects at baseline, and 56% of patients presented with QRS >120 ms. There was no correlation between QRS width and extent of intra-VMD. Intensive medical therapy was associated with a significant reduction in intra-VMD (85 +/- 23 ms vs. 39 +/- 19 ms; P <.001). Significant hemodynamic improvement in cardiac index, filling pressures, and systemic and pulmonic vascular resistance was seen only in patients with intra-VMD., Conclusion: A substantial subset of patients admitted with ADHF and hemodynamic derangements demonstrate evidence of intra-VMD, which is reduced at follow-up and independent of underlying QRS width. Nevertheless, the presence of significant intra-VMD is associated with a more reversible hemodynamic profile.

Some studies have suggested that genetic variability in the glycoprotein (GP) IIIa gene modulates expression of platelet GPIIb/IIIa (alpha(2b)beta(3)). We sought to determine as to whether combinations of genetic variants within the GPIIIa gene (haplotypes) influenced the expression of GPIIIa RNA and protein levels in human platelets. Three promoter polymorphisms, Pl(A1/A2) genotype and platelet receptor densities were determined in 207 acute coronary syndrome (ACS) patients. Allele-specific quantitative reverse transcription-polymerase chain reaction of platelet RNA from Pl(A1/A2) heterozygotes identified a greater expression of Pl(A2) bearing transcripts among heterozygotes. Among the patients studied, the ratio of Pl(A1)/Pl(A2) RNA expression was significantly influenced by promoter haplotype (P < 0.01). However, this effect reflected carriership of rare not common haplotypes (P = 0.2). There was a threefold variation between subjects in the number of GPIIb/IIIa receptors expressed per platelet, although no association between receptor density and the Pl(A2) (P = 0.93) or promoter polymorphisms was demonstrated (-468A, P = 0.52; -425C, P = 0.59; -400A, P = 0.52). Among common haplotypes, Pl(A1)/Pl(A2) RNA expression was negatively correlated with adjusted GPIIb/IIIa receptor density (P = 0.04). The overall trend towards higher expression of Pl(A2) bearing message in Pl(A1/A2) heterozygotes, and the existence of rare haplotypes with more pronounced changes indicate the existence of cis-acting genetic factors that remain to be identified.

The intravenous Glycoprotein (GP) IIb/IIIa antagonists are potent antiplatelet agents that are particularly effective in patients who undergo percutaneous coronary intervention (PCI). Questions remain about their benefit in the setting of primary PCI, as well as in patients with acute coronary syndromes who do not undergo PCI. The dosing of these drugs is critical to their efficacy and for some agents may not yet be optimized. Differences in the level of platelet inhibition achieved with previous and current dosing strategies of these agents are discussed. In addition, the pharmacology of GPIIb/IIIa antagonists is more complex than initially appreciated. These drugs appear to have partial agonist properties and as a result may be prothrombotic at lower doses. Recent evidence also suggests that at least some of the GPIIb/IIIa antagonists may have anti-inflammatory as well as anti-thrombotic activity. Future research should clarify these issues. Because of the observed inter-individual variation in the response to GPIIb/IIIa antagonists, future trials of these agents should also look at individual tailoring of the dose to an optimum level of platelet inhibition. No definite clinical predictors of this inter-individual variation have been identified, but the Pl(A) polymorphism in GPIIIa appears to be associated with an adverse response to treatment with the oral GPIIb/IIIa antagonists in particular.

Saint James' Hospital is a 650-bed tertiary referral hospital. An audit was performed of acute transmural myocardial infarctions for the years 1996 to 1999 inclusive. On average there were 2043 cardiology admissions annually, 9.8% of all hospital admissions. Acute transmural myocardial infarction was diagnosed in 178 patients annually, and was less common during the summer. The figure of 72% receiving revascularisation therapy (thrombolysis 67%, primary angioplasty 5%) compares favourably with 35% in 1992. The main reason for not receiving thrombolysis was late presentation (15%) with contraindications present in only 5%. The case fatality rate was 16% confirming the higher mortality in clinical practice than that of thrombolytic trials. The prescription of aspirin or warfarin (99%) and betablockers (67%) was in line with international trials. The use of angiotensin converting enzyme inhibitors (34%) and statins (28%) is similar to other studies but less than would be expected according to trial evidence.

Pharmacogenetics refers to the genetic factors that influence the response to a drug, often involving genetic variations in drug metabolizing enzymes. The pharmacogenetics of antiplatelet agents is in its infancy and largely reflects variations in drug targets or related genes. One particular gene variant, the PlA2 polymorphism of the glycoprotein (GP) IIb/IIIa receptor, is now emerging as a probable determinant of the response to antiplatelet agents including GPIIb/IIIa antagonists. This variant may in part explain the heterogeneity in the response to GPIIb/IIIa antagonists. The PlA2 genotype appears to be associated with an adverse outcome in patients treated with an oral GPIIb/IIIa antagonist and may be a factor in the observed failure of these agents in unselected populations. However, there are preliminary indications that other antiplatelet agents may have an enhanced effect in PlA2 subjects. Further clinical trials in particular are required to definitively characterize the pharmacogenetic effect of PlA2. Other polymorphisms are also likely to contribute to the pharmacogenetics of antiplatelet agents, but these await investigation.

EEG spectral analyses were conducted from 19 scalp locations for patients with mild (n=40), moderate (n=25), and severe (n=43) traumatic brain injury (TBI), 15 days to 4 years after injury. Severity of TBI was judged by emergency hospital admission records (Glasgow Coma Score and duration of coma and amnesia). Highest-loading EEG variables on each factor that differed significantly between severe and mild TBI by univariate t-test were entered into a multivariate discriminant analysis, yielding 16 variables. Discriminant analysis between mild and severe TBI groups showed classification accuracy of 96.39%, sensitivity 95.45%, and specificity 97.44%. The EEG discriminant score also measured intermediate severity in moderate TBI patients. Results were cross-validated in 503 VA patients. Significant correlations between EEG discriminant scores, emergency admission measures, and post-trauma neuropsychological test scores validated the discriminant function as an index of severity of injury and a classifier of the extremes of severity.

This qualitative, exploratory-descriptive study describes self-management strategies of long-term survivors of dialysis. Data were collected via long, semi-structured interviews with 18 individuals, 10 male and 8 female, who had been on dialysis for more than 15 years. Of these, 10 participants were Caucasian, 4 were African-American, and 4 were Hispanic. Respondents ranged in age from 38 to 63 years. Interviews were audio-recorded, and verbatim transcriptions of interviews were analyzed according to a content analytic procedure, with movement from specific to general. Six broad patient self-management strategies were identified: impression management, selective symptom report/management, vigilant oversight of care, self-proposal of treatments, active self-advocacy, and independent adoption of treatments/use of alternative therapies. For the individuals interviewed, self-management was largely constituted as management of the health care system and health care providers who represent it. Although the small sample size and the exploratory-descriptive methodology limit generalizability, valuable insights into techniques for self-management were derived. Such insights pave the way for future research into characteristics that distinguish dialysis patients who have the potential to be effective self-managers. More importantly, understanding of successful self-management by individuals on dialysis lays the groundwork for development of interventions to help other patients develop similar positive self-management strategies.

From 1979 to 1996, the Survey of Consumer Attitudes response rate remained roughly 70 percent. But number of calls to complete an interview and proportion of interviews requiring refusal conversion doubled. Using call-record histories, we explore what the consequences of lower response rates would have been if these additional efforts had not been undertaken. Both number of calls and initially cooperating (vs. initially refusing) are related to the Index of Consumer Sentiment (ICS), but only number of calls survives a control for demographic characteristics. We assess the impact of excluding respondents who required refusal conversion (which reduces the response rate 5-10 percentage points), respondents who required more than five calls to complete the interview (reducing the response rate about 25 percentage points), and those who required more than two calls (a reduction of about 50 percentage points). We found no effect of excluding any of these respondent groups on cross-sectional estimates of the ICS using monthly samples of hundreds of cases. For yearly estimates, based on thousands of cases, the exclusion of respondents who required more calls (though not of initial refusers) had an effect, but a very small one. One of the exclusions generally affected estimates of change over time in the ICS, irrespective of sample size.

The present study evaluates the precision of outlying percentile estimates, with age- and sex-associated variations and facilitates decisions needed to revise the current NCHS 1977 Growth Charts with regard to 1) the inclusion of 3(rd) and 97(th) percentiles and 2) the selection of survey data for the construction of the revised growth charts. Simulation was performed to obtain data with distribution characteristics similar to those of The Third National Health and Nutritional Examination Survey (NHANES III) (1988-1991) data. NHANES III consists of a two-phase, 6-year, complex stratified multistage probability cluster, cross-sectional survey conducted from 1988 through 1994 to represent the US noninstitutionalized population. Phase I of the survey consisted of 679 boys and 622 girls in age groups 3, 8, 13, and 18 years. Weight and stature, the body mass index (BMI) (weight/stature(2); kg/m(2)) was calculated. The results show that 1) the precision of the percentile estimates is greater for stature than for weight and BMI, 2) percentiles during the pubertal period are less precise than those during the prepubertal and postpubertal periods for weight and BMI but there is little difference for stature, and 3) percentile estimates are more precise for girls than boys for weight and BMI, but not for stature. The present findings suggest that pooling of NHANES III and earlier National Center for Health Statistics (NCHS) survey data is necessary to achieve reasonable precision for the 3(rd) and 97(th) percentile estimates. Am. J. Hum. Biol. 12:64-74, 2000. Copyright 2000 Wiley-Liss, Inc.

The purpose of this study was to describe the prevalence, severity, and patterns of noncompliance with prescribed medications among hemodialysis patients; and to identify patient, disease and/or treatment characteristics associated with noncompliance. Demographic and medical history information were collected from chart reviews and patient interviews. Compliance data were collected via self-report, pill count, and a medication event monitoring system (MEMS, Product of Aprex, a division of Apria Healthcare; Costa Mesa, CA). A total of 135 hemodialysis patients from 11 dialysis facilities in a large Midwestern metropolitan area participated. Overall, medication compliance rates were very low. Of the patient, disease, and treatment characteristics considered, only race was found to be associated with patient noncompliance; African-American patients had higher rates of noncompliance with both monitored medications. The results of this study confirm that noncompliance with medication regimens continues to be an unremitting problem for hemodialysis patients and that demographic, medical history, and treatment characteristics do not adequately explain this behavior. Also, estimates of patient compliance as measured by self-report, pill count, and microelectronic monitoring are disparate enough to suggest that relying exclusively on patients' self-report of compliance might be insufficient.

A contemporary focus on outcomes assessment has provided affirmation that patient functional status is both an important outcome of medical care and an important predictor of longer term outcomes such as morbidity and/or mortality. Monitoring functional status among end-stage renal disease (ESRD) patients is particularly critical because the cycle of physical deconditioning experienced by renal patients is both insidious and malignant. Over the past several years, patient self-report instruments have been used with increasing frequency to assess functioning. Among ESRD patients, such self-reports have reliably predicted mortality and some morbidity. Additionally, renal patients' self-reported functioning is also correlated with the results of several commonly performed laboratory tests. Based on these findings, measures of self-reported functional status might be considered a practical adjunct to regular patient assessments. They could be routinely used for purposes that might include: identifying the particular areas of functioning and well-being that need improvement; screening for subtle changes in health status; establishing physical status baselines; and corroborating the effectiveness of physical activity interventions. Overall, ESRD patients' self-report of their functioning appears to secure, synthesize, and standardize data about patient health status that is unavailable through any other mechanism. Such information may be essential to medicine's primary missions of promoting health and preserving life.

Hemodialysis patients' compliance with their therapeutic regimens, including dietary and fluid restrictions, dialysis treatments and medications, is generally suboptimal. Recently, the mean age of the dialysis population has increased. Since impaired cognitive function, which sometimes accompanies aging, interferes with the ability to comprehend instructions, elderly dialysis patients might be at greater risk for noncompliance than are their younger counterparts. In this project, 135 hemodialysis patients (68 patients > 65 years of age and 67 patients < or = 65 years) were studied. Rates of noncompliance with oral antihypertensives and phosphate binders, as tracked by a medication event monitoring system (MEMS), are reported here. More than 42% of older patients (> 65) and 47% of younger patients (< or = 65) were repeated noncompliers with antihypertensives, missing at least 20% of the prescribed doses. Similarly, 65% of older patients and 80% of younger patients exhibited repeated noncompliance with phosphate binders. Almost 30% of older patients and more than 32% of younger patients missed their antihypertensives completely on 20% or more of the prescribed days. Only 18% of the older subjects, but 33% of younger patients missed taking their phosphate binders for 20 or more percent of the prescribed days. Rates of noncompliance were found to differ between the two populations of patients in that younger patients made significantly more dosing errors with their antihypertensives and missed taking their phosphate binders on more days than did their older counterparts.

Three hundred fifty-nine chronic dialysis patients (85 employed and 274 nonemployed) were surveyed to identify/verify those characteristics which differentiate between employed versus nonemployed status. Education emerged as a significant correlate of employment, as noted by previous investigators, whereas, unlike previous research, neither mode of dialysis, length of time on dialysis, number of comorbid conditions, nor cause of renal failure (eg, diabetes) were associated with employment status. Measures of functional status (MOS SF-20 and Karnofsky) were positively associated with employment. Furthermore, patients' perceptions that their health limited the type and amount of work that they could do were negatively associated with employment. In addition, using a series of de novo items, we found subjects' beliefs about dialysis patients' ability to work to be a "self-fulfilling prophecy" with regard to employment status. That is, patients who themselves believed that dialysis patients should work and had this notion reinforced by significant others were more likely to be employed. Interestingly, 21 percent of unemployed patients reported that they were both able to work and wanted to return to work. Because it is consistently reported that only a small percentage of dialysis patients are employed, targeting the patients who are both willing and able to work for vocational rehabilitation might significantly increase the numbers of employed dialysis patients.

Eight trained male cyclists who competed regularly in track races, were studied under control, alkalotic (NaHCO3) and placebo (CaCO3) conditions in a laboratory setting to study the effect of orally induced metabolic alkalosis on 60 s anaerobic work and power output on a bicycle ergometer. Basal, pre- and post-exercise blood samples in the three conditions were analysed for pH, pCO2, pO2, bicarbonate, base excess and lactate. All blood gas measurements were within normal limits at basal levels. There were significant differences in the amount of work produced, and in the maximal power output produced by the cyclists in the experimental condition when compared to the control and placebo conditions (P less than 0.01). The post-exercise pH decreased in all three conditions (P less than 0.05) and post-exercise pCO2 increased significantly in the alkalosis trial (P less than 0.01). In the alkalotic condition, the pre-exercise base excess and HCO3- levels were both higher (P less than 0.05) than the basal levels, suggesting that the bicarbonate ingestion had a significant increase in the buffering ability of the blood. Post-exercise lactate levels were significantly higher (P less than 0.05) after the alkalotic trial when compared to the other two conditions, immediately post-exercise and for the next 3 min. Post-exercise lactate levels were higher than basal or pre-exercise levels (P less than 0.001). This was true immediately post-exercise and for the next 5 min. The results of this study suggest that NaHCO3 is an effective ergogenic aid when used for typically anaerobic exercise as used in this experiment. We feel that this ergogenic property is probably due to the accelerated efflux of H+ ions from the muscle tissue due to increased extracellular bicarbonate buffering.

1. For any close-up photography, a single lens reflex type of camera should be used. 2. Magnification of an image can be increased either by lengthening the distance between the lens and the film or by adding supplementary lenses. 3. Photography of the eye presents special lighting problems, requiring the pretesting of exposures, and careful exposure control.

A study was performed to quantitate the adrenal medullary and cortical response to hemorrhage in awake animals bled at different rates and to relate these responses to simultaneous changes in blood glucose and serum insulin. A series of awake pigs were bled either slowly or rapidly of 30% of their calculated blood volume. Infusions of exogenous epinephrine were performed in an additional series of unbled animals and infusions of epinephrine plus hydrocortisone were similarly performed in an additonal series. Increase in blood glucose and epinephrine secretion rate following hemorrhage were found to be significantly dependent upon the rate of initial hemorrhage. Cortisol secretion was found to rise significantly during and following hemorrhage in both rapidly and slowly bled animals. Serum insulin levels remained at baseline levels during shock, despite the presence of significant hyperglycemia. In unbled animals infused with epinephrine at rates comparable to those measured in shock, elevations in blood glucose were markedly lower, shifting to the right of the dose-response curve during hemorrhage. Simultaneous infusions of cortisol and epinephrine resulted in a dose-response curve which did not differ significantly from that following infusion of epinephrine alone.

A 16-month study of foraging and ranging among gray langurs (Presbytis entellus) in the Nepal Himalaya revealed that these animals range over larger areas than other gray langurs so far studied and that they show great seasonal differences in foraging and ranging. A summer monsoon and winter dry season characterize the Himalayan climate. During summer, broadleaf forest provides the basic foraging substrate for the langurs, and when its resources fail during the winter dry season, they radically shift their diet and feed largely in meadow, range over wider areas, use their range more evenly and make longer day journeys. It is hypothesized that the ability of the langurs to make these changes in response to the dry season is vital to their survival at the study site.

During the course of an ongoing investigation of the effects of mother-infant separation on development in gray langur monkeys (Presbytis entellus), a series of 4 mothers of approximately 6-month-old infants were removed from their social groups and placed in a captive all-male group for 2-week periods. The male group contained 3 sexually mature animals and 1 juvenile and was within the range of variation observed in the wild. One of the introduced females came into estrus while with the male group. Agonistic behavior among the males increased during her introduction, but was resolved through dominance. There was no fighting and little threat. Agonistic behavior did not increase during the introductions of the other 3 females. These results are discussed and it is proposed that dominance can allow the survival of multi-male troops among gray langurs where (1) low population densities allow the formation of hierarchies, and (2) existing hierarchies are not disrupted by the simultaneous presence of several estrous females. It is predicted that these conditions will best be met where troop sizes are moderate and mating is not sharply seasonal.