Sudden Vision Loss Secondary to Optic Nerve Infiltration as a Presenting Symptom of Metastatic Lung Adenocarcinoma.

Purpose: To report a rare case of left-sided metastatic optic nerve infiltration and right-sided choroidal mass with exudative retinal detachment caused by EGFR exon 19 deletion positive non-small-cell lung adenocarcinoma that responded to targeted therapy with osimertinib (EGFR-TKI). Our patient demonstrated an excellent response with reduced size of the metastatic choroidal mass of the right orbit and improved visual acuity, in addition to systemic disease control. Case: A 66-year-old male patient with a history of diabetes mellitus, hypertension, and tobacco use presented with sudden vision loss in the left eye secondary to optic nerve infiltration and subacute vision loss in the right eye secondary to exudative retinal detachment from a choroidal metastasis. He was found to have a right lung mass, multiple metastatic pulmonary nodules, and liver and bone metastases. Biopsy from a mediastinal lymph node confirmed the diagnosis of metastatic lung adenocarcinoma. He was found to have exon 19 deletion on next-generation sequencing. We treated him with local radiation therapy to the left eye and systemic osimertinib (EGFR-TKI). Conclusion: To our knowledge, our case is the first report of a patient who initially presented with acute vision loss and was found to have metastatic retrobulbar optic nerve infiltration in one eye and metastatic choroidal lesion with exudative retinal detachment in the fellow eye secondary to lung adenocarcinoma. Due to the rarity of this condition, literature regarding effective treatment is scarce. Our patient demonstrated significant improvement in visual acuity and resolution of exudative retinal detachment in the right eye following osimertinib treatment and radiation therapy to the left eye. Further investigation into the role of tyrosine kinase inhibitors and radiation therapy in treating intraocular metastasis involving the optic nerve is needed.

Effects of a learning trial on self-regulation of exercise.

Heart rate (HR) and ratings of perceived exertion (RPE) are common exercise intensity regulatory strategies, however, some individuals are unable to use these strategies effectively. Alternative or conjunctive strategies may aid in the transition to self-guided programs. The purpose of the present study was to examine the value of a brief, field-based exercise intensity learning trial on self-regulation of intensity during a weeklong exercise program. Forty-two males were randomly assigned to either a paced learning trial (P) or non-paced control (NP), and then one of three intensity feedback groups: HR, HR + RPE, or no feedback (CONT). The paced trial consisted of an 800-m trial at 75 % of maximal heart rate reserve (MHRR) on day one. Subjects then completed four 800-m trials each day for four days and received feedback on deviation from target HR (THR) after each 800-m trial. Four-way MANOVA (pacing x feedback x trials x days) was used to assess the influence of the learning trial on THR deviation scores across the week. The pacing x feedback x trials interaction was significant (Pillai's Trace = 0.36, approximately F (6,70) = 2.56, p = 0.03) and thus, the influence of the learning trial was assessed within feedback group. There were no significant differences in THR deviation scores for P vs. NP within the HR or HR + RPE feedback groups. However, P was significantly more accurate then NP (p < 0.05) within the CONT feedback groups during each trial averaged across the week (T (1) = - 2.6 vs. 5.3; T (2) = 2.6 vs. 14.2; T (3) = 4.6 vs. 16.2; T (4) = 5.3 vs. 20.5 beats . min (-1)). These results demonstrate that a brief intensity learning trial, in the absence of HR or HR+RPE feedback, provided for accurate self-regulation of vigorous exercise training. These results would support the efficacy of a brief intensity learning trial within the context of transitioning an individual to a self-guided exercise program.

Childhood inattention-overactivity, aggression, and stimulant medication history as predictors of young adult outcomes.

This study examined the contributions of childhood symptom dimensions and aspects of methylphenidate (MPH) treatment to the prediction of young adult outcomes in boys who were referred to a child psychiatry outpatient clinic. They were diagnosed with hyperkinetic reaction of childhood/minimal brain dysfunction, and given MPH for an average of 30 months. Including significant effects and statistical trends, childhood Inattention-Over-activity was uniquely associated with fewer than 10% of adult outcomes such as schizotypic features, impairment on the Global Assessment Scale (GAS), and unemployment. Childhood aggression was uniquely associated with 38% of adult outcomes such as lifetime diagnoses of major depression, drug abuse disorder, and antisocial personality disorder; MMPI PD, PA, and SC scores; and six additional measures of adult impairment and life circumstances-extending external validation of the two-factor model to young adulthood. For 20 young adult outcomes (63%), aspects of childhood treatment with MPH had no lasting effects. For one adult outcome (3%), a lasting negative effect of childhood drug treatment was found; better initial response to medication was associated with not graduating from high school. For 11 young adult outcomes (34%), however, aspects of childhood MPH treatment had positive effects that lasted long after treatment was discontinued. Higher dosage was associated with fewer diagnoses of alcoholism or suicide attempts. Better response to medication was associated with lower MMPI D scores and better social functioning. Longer medication duration was associated with fewer schizotypic features, lower MMPI MA scores, higher WAIS Performance and Full Scale IQs, and better WRAT Reading and Arithmetic performance.

The effects of blood lactate concentration on perception of effort during graded and steady state treadmill exercise.

Studies have reported that ratings of perceived exertion (RPE) are a valid tool for exercise prescription when blood lactate concentration (BLC) is used as the intensity criterion. However, few have studied the relationship between RPE and BLC during commonly used graded exercise tests (GXTs) and simulated exercise training. The purpose of this study was to determine if the RPE: BLC relationship is transferable across GXTs and a steady state exercise trial (SST). Thirteen healthy males (25+/-5.3yrs) completed two maximal treadmill tests (Bruce and Balke protocols) followed by a SST which consisted of approximately 8 minutes of exercise at each of two intensities (approximately 40% and 70% maximal heart rate reserve). BLCs and other physiological measures were compared at matched RPEs across the GXTs and SST trial at each exercise intensity using a two-way repeated measures ANOVA. There were no significant differences in BLC at a matched RPE across the exercise trials at the lower exercise intensity with the BLCs being 1.5+/-0.3, 1.6+/-0.6 and 1.3+/-0.3 mM, respectively. However, at the higher exercise intensity BLCs were significantly lower during the Balke GXT compared to the Bruce GXT and SST (1.8+/-0.6, 2.8+/-1.8 and 3.0+/-0.8 mM, p < 0.05). These results suggest that the RPE: BLC relationship may be protocol dependent during graded exercise testing as it was only transferable from the Bruce GXT to the exercise training setting at intensities in the typical prescription range of 50-85% of VO2max.

Rate of HIV-1 RNA rebound upon stopping antiretroviral therapy.

OBJECTIVE: To determine the rate of plasma HIV-1 RNA rebound in patients stopping highly active antiretroviral therapy (HAART) after achieving undetectable viral load. DESIGN: Sequential plasma HIV RNA levels were measured in six patients during the 21 days following withdrawal from HAART. METHODS: Plasma samples were obtained from six patients who chose to withdraw from HAART because of lipodystrophy, narcotic overdose, insomnia and/or high blood pressure. Longitudinal plasma viral load was determined in triplicate upon stopping therapy. RESULTS: All patients had plasma viral loads below 50 HIV RNA copies/ml at the time of stopping therapy and had had levels below 500 copies/ml for a median of 390 days (range 39-542 days). Plasma HIV rebound upon stopping therapy was rapid (median increase 0.2 log/day; range 0.15-0.42 log/day) and initially appeared to follow first-order kinetics. Plasma HIV RNA levels returned to greater than 500 copies/ml within 6 to 15 days (median 10 days) and approached or exceeded pre-therapy levels in all patients within 21 days of stopping therapy. Extrapolating backwards to the time at which individuals stopped therapy suggested that patients had tens of thousands of total body plasma HIV RNA copies despite having 'undetectable' plasma HIV RNA. CONCLUSIONS: HIV RNA in plasma rebounds within days of stopping antiretroviral therapy. A considerable burden of total body plasma HIV RNA likely remains even during effective HAART therapy.

Bone fluoride concentrations in beluga whales from Canada.

Beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary have been reported to have dental and bone abnormalities. To determine whether these lesions could be caused by high exposure to fluorides, we measured bone fluoride levels in eight beluga whales stranded on the shores of the St. Lawrence Estuary (Quebec, Canada), and in nine beluga whales killed by Inuit hunters in the Hudson Bay (North Western Territories, Canada). In both groups, fluoride concentrations were higher than those found in terrestrial mammals intoxicated by fluorides. Unexpectedly, fluoride concentration was significantly higher in beluga whales from the Hudson Bay (mean +/- SD: 10.365 +/- 1.098 ppm) than in beluga whales from the St. Lawrence Estuary (4.539 +/- 875 ppm) and was positively correlated with age in the latter population. Differences in diet might explain the differences in fluoride concentrations found between these two populations.

Physical fitness and clustering of risk factors associated with the metabolic syndrome.

PURPOSE: The purposes of this study were to 1) assess the prevalence of clustering of metabolic markers of the MS in a defined population and 2) determine the association between CRF and such clustering in a large group of adult men (N = 15,537) and women (N = 3,899). METHODS: Metabolic markers of the MS included systolic blood pressure (BP) > or = 140 mm Hg, serum triglycerides > or = 150 mg x dL(-1), fasting blood glucose > or = 110 mg x dL(-1), and elevated central adiposity (waist circumference > 100 cm). Cardiorespiratory fitness was defined as total time on a maximal treadmill exercise test. The cohort was grouped by the number of metabolic abnormalities and level of CRF. Associations between CRF and the number of metabolic abnormalities were assessed using proportional odds logit models. RESULTS: Among men, the age-adjusted cumulative odds ratio for abnormal markers of the MS was 3.0 (95% C.I. 2.7-3.4; P < 0.001) for the least-fit men when compared with moderately-fit ones, and 10.1 (95% C.I. 9.1-11.2; P < 0.001) when compared with the most-fit men. Among women, the age-adjusted cumulative odds ratio was 2.7 (95% C.I. 2.1-3.5; P < 0.001) for the least-fit women when compared with moderately-fit ones, and 4.9 (95% C.I. 3.8-6.3; P < 0.001) when compared with the most-fit women. CONCLUSIONS: These cross-sectional results suggest that low CRF is associated with an increased clustering of the metabolic abnormalities associated with the MS in both adult men and women and support the need for future prospective analyses.

Evaluation of a new standardized ramp protocol: the BSU/Bruce Ramp protocol.

BACKGROUND: Because of recent technological advances, exercise testing laboratories now have the ability to use ramp protocols with treadmill exercise tests. Since the Bruce protocol is the most widely used treadmill protocol in clinical laboratories, a standardized ramp treadmill protocol was developed that corresponds to the speed and grade settings of the Bruce protocol at each 3-minute time interval. The purpose of this study was to evaluate the utility of using subject demographic and exercise test data to predict peak oxygen uptake (VO2peak) for tests conducted with the BSU/Bruce Ramp protocol. METHODS: Maximal exercise tests were performed by 698 men and women using the BSU/Bruce Ramp protocol. Peak oxygen uptake was measured during all tests. Stepwise multiple regression analyses were used to predict VO2peak (mL.kg-1.min-1) from maximal treadmill test time and selected variables including age, gender, physical activity habits, and body weight. RESULTS: Maximal test time was found to be the most potent predictor of VO2peak, accounting for 86% of the variance in peak aerobic power, with a standard error of estimate of 3.4 mL kg min-1. A multiple regression equation including age, gender, physical activity habits, and body weight resulted in a slightly improved prediction (R2 = 0.88; standard error of estimates = 3.1 mL kg min-1). CONCLUSIONS: Peak oxygen uptake values can be predicted with reasonable accuracy from the BSU/Bruce Ramp protocol. The BSU/Bruce Ramp would be an excellent choice for laboratories desiring to use a ramp treadmill protocol because of the design of the protocol with identical workloads at equivalent time periods (3, 6, 9, 12, 15, 18, 21 minutes) as the commonly used Bruce protocol.

Caffeine consumption habits do not influence the exercise blood pressure response following caffeine ingestion.

BACKGROUND: The purpose of this study was to determine if the BP response during walking following caffeine ingestion differed between those who regularly consume caffeine and those who do not. METHODS: A double-blind cross-over experimental design was used. Data were collected in a research laboratory with a clinical exercise testing room. Eight regular caffeine users and eight men who did not habitually consume caffeine were studied. Each subject consumed of a beverage once with and once without 4.5 mg caffeine/kg fat-free mass added to the drink. Following consumption each subject walked at three intensities of exercise (30, 50, and 70% of VO2peak). Measures of BP were obtained by the auscultatory technique. RESULTS: Caffeine consumption resulted in significant increases in both systolic BP and diastolic BP at rest and during exercise. The elevation during exercise was 7-8 mmHg at all three exercise intensities for systolic BP; however, for diastolic BP there was only a significant elevation (4 mmHg) at the highest exercise intensity. No differences were noted between those men who regularly consume and those who regularly abstain from caffeine. There was a wide range in the resting BP response to caffeine (combined SBP and DBP ranged from 10-39 mmHg) suggesting that there are marked differences in sensitivity to caffeine, irrespective of individuals' consumption habits. CONCLUSIONS: Consideration should be given to caffeine intake prior to exercise in patients for whom an additional increase in BP during exercise would not be desirable.

Increased expression of activated matrix metalloproteinase-2 by human endothelial cells after sublethal H2O2 exposure.

Basement membranes form a boundary between intravascular and extravascular compartments that is remodeled by matrix metalloproteinases (MMP) expressed by endothelial cells. These cells are at risk of exposure to reactive oxygen intermediates generated as a consequence of interactions with drugs, x-radiation, activated neutrophils, or cancer cells. Herein we have investigated the hypothesis that endothelial cells alter their expression of MMP after sublethel exposure to H2O2 and that this leads to degradation of adjacent basement membranes. Cultured human umbilical vein endothelial cells were treated with concentrations of H2O2 ranging from 1.5 to 32 microM or with 2 x 10(-6)M phorbol myristate acetate (PMA). After 24 hours, the cells were placed into serum-free medium for an additional 24 hours. This conditioned medium or cell lysates were studied by matrix degradation assays, gelatin zymography, immunoblots, and Northern analysis. H2O2-treated or PMA-treated cells, or their serum-free conditioned medium, caused a 2-fold increase in degradation of [3H]-proline-labeled endothelial basement membranes or purified type IV collagen compared to untreated cells. Endothelial cells constitutively expressed gelatinases at Mr 96,000 and 72,000, consistent with MMP-9 and inactive MMP-2. H2O2 exposure caused increased expression of these MMP and appearance of Mr 64,000 to 66,000 gelatinases corresponding to activated MMP-2. In cell lysates, H2O2 or PMA treatment led to increased expression of membrane-type MMP-1, an activator of latent MMP-2. The results suggest that oxidants such as H2O2 may stimulate MMP expression and influence the remodeling of vascular basement membranes by endothelial cells.

Validity of rating of perceived exertion during graded exercise testing in apparently healthy adults and cardiac patients.

PURPOSE: Recent exercise guidelines recommend a generalized rating of perceived exertion (RPE) range of 12 to 16 (15-point Borg scale) as the perceptual range associated with a physiological training effect. However, whether an individual who selects an RPE within the generalized range during an graded exercise test or exercise training, is actually within the correlated physiological range (50 to 85% maximum oxygen consumption [VO2max]) has not been studied in large samples of apparently healthy individuals or cardiac patients. The purpose of the present study was to assess the validity of the generalized RPE recommendations in a large heterogeneous group of apparently healthy subjects and cardiac patients. METHODS: Subjects included apparently healthy adults (N = 463) and cardiac patients (N = 217) who presented for a sign-symptom limited maximal graded exercise test (SSLMGXT). Ratings of perceived exertion associated with relative exercise intensities of 60 and 80% of maximal heart rate reserve (MHRR) and peak exercise were selected for analyses. RESULTS: Significant interindividual variability in RPE was observed at both relative exercise intensities (6 to 20 RPE range at 60% MHRR; 8 to 20 RPE range at 80% MHRR) for both populations. Thirty-nine percent of healthy subjects and 32% of cardiac patients reported an RPE outside an 11 to 14 range at 60% of MHRR, whereas 32% of healthy subjects and 52% of cardiac patients reported an RPE outside of a 14 to 17 range at 80% of MHRR. Peak RPE was higher for the apparently healthy subjects compared with the cardiac patients (18.8 +/- 1.2 versus 16.5 +/- 1.8; P < 0.01). CONCLUSIONS: These results challenge the applicability of the generalized RPE recommendations described in recent exercise guidelines under typical clinical exercise testing conditions. The basis for the generalized RPE recommendations warrant further investigation. Those who desire to use RPE as a marker of relative exercise intensity during SSLMGXT should take into consideration the large interindividual variability in these measures.

Reliability of perceived exertion during graded exercise testing in apparently healthy adults.

PURPOSE: Ratings of perceived exertion (RPE) are widely used for monitoring individuals during graded exercise testing. Studies of the reliability of RPEs across various exercise conditions have produced mixed results. The purpose of this study was to assess the reliability of RPEs during graded exercise testing by comparing the perceptual-physiological relationship between the Bruce and Balke treadmill protocols throughout a broad range of relative exercise intensities. METHODS: Thirty-eight middle-aged men and women completed two maximal treadmill graded exercise testing separated by 48 hours. Test order was randomly assigned. RPEs were compared across protocols and between gender at selected exercise intensities using a series of two-way analysis of variances with repeated measures. RESULTS: A comparison of RPEs (Borg 15-point scale) during the graded exercise testing revealed significant protocol and gender differences at 40%, 60% and 80% of maximal heart rate reserve. RPEs were significantly higher during the Balke protocol compared to the Bruce at each intensity (45% = 9.5 +/- 2.0 vs. 8.3 +/- 1.6; 60% = 12.7 +/- 2.4 vs. 11.1 +/- 2.3; 80% = 15.7 +/- 2.2 vs. 14.1 +/- 2.0). In addition, men rated each intensity significantly higher than the women (P < 0.05). CONCLUSIONS: The results from the present study confirm that the perceptual-physiological relationship observed during graded exercise testing varies as a function of the treadmill protocol employed and that these differences extend throughout the exercise training intensity range (40--80% of maximal heart rate reserve) recommended for healthy adults. The perceptual differences between the protocols could not be accounted for by any of the physiological measures assessed within the study. These results have implications when using RPEs from exercise testing for exercise prescription purposes.

Differential regulation of matrix metalloproteinases in human cancer cells by exogenous factors.

Matrix degradation by cancer cells is an important attribute of malignant behaviour. We have postulated that during invasion and metastasis, matrix metalloproteinase (MMP) production by cancer cells is modulated by microenvironmental factors. To determine this, we screened human cancer cell lines of diverse histogenesis for their secreted MMP profile following exposure to a diversity of soluble and insoluble agents. Enzymatic changes were observed in the presence of phorbol ester (TPA) and hydrogen peroxide (H2O2). More specifically, we observed: (a) increased secretion and/or activation of gelatinases A (MMP-2) and B (MMP-9) after exposure of 8 cell lines to 10(-6) M TPA; (b) increased activation of interstitial collagenase (MMP-1) caseinolysis after stimulation of 3 cancer cell lines with 10(-7) M TPA; and (c) increased activation of MMP-2 after exposure of 2 cell lines to 0.5 mM H3O2. In functional assays, exposure of lung Calu-6 carcinoma cells to 0.5 mM H2O2 and PC-3 cells to TPA, increased their ability to degrade radiolabelled endothelial cell-derived and osteoblast-like-derived basement membranes, respectively. RNA hybridization studies confirmed and further documented these observations. We conclude that modulation of MMP activity in human cancer cells is a common phenomenon regardless of lineage. Modulatory mechanisms such as increased de novo pro-enzyme synthesis and/or release, and enhanced proenzyme activation may be involved. Furthermore, our results provide evidence that extracellular matrix degradation by human cancer cells during invasion and metastasis may be stimulated by soluble matrix-derived factors in a cell type-specific fashion.

Evaluation of lipid profile measurements obtained from the Cholestech L.D.X analyzer.

BACKGROUND: The Cholestech L.D.X analyzer has the capability of performing a lipid profile in approximately 5 minutes. The purpose of this study was to determine analytical performance capability of the L.D.X to perform lipid profile measurements. METHODS: Forty subjects gave two finger capillary samples and one venous serum which were analyzed in duplicate by two technicians, on two different L.D.X analyzers. A local pathology laboratory was used as the standard for accuracy comparisons. Two controls with known values were provided by the manufacturer to assess within-day precision. Day-to-day precision was determined by analyzing high (240 mg/dL-1 total cholesterol (TC) and 60 mg/dL-1 high-density lipoprotein [HDL]) and low (200 mg/dL-1 TC and 35 mg/dL-1 HDL) human serum samples on 10 different days. RESULTS: Analysis of variance procedures revealed no significant differences between the two technicians or the two analyzers, nor among the fingerstick, venous serum, or reference measures for any of the analytes. The total error of measurement of TC, triglycerides, and HDL measurements were 6.3 to 16.2%, 14.8 to 30.8%, and 11.5 to 26.8%, respectively. In comparison to the National Cholesterol Education Program (NCEP) desirable, borderline-high, and high classifications obtained from the reference laboratory the L.D.X TC results were correctly classified in 92.5% of the cases. L.D.X triglyceride classifications of desirable, borderline hypertyglyceridemia, and distinct hypertriglyceridemia matched 100% with the classifications obtained from the reference laboratory. CONCLUSIONS: Although the Cholestech L.D.X analyzer did not consistently meet NCEP standards for acceptable total measurement error of TC, HDL, and triglyceride analyses, it seems capable of providing reasonable lipid profile measures in both a screening setting and a clinician office where the goal is correct classification of patients' results.

Magnetic cross-relaxation and chemical exchange between microporous solid and mobile liquid phases.

Nuclear magnetic spin-lattice relaxation rates are reported as a function of magnetic field strength, pH, and temperature for water protons in Sephadex gels. The water proton rates report the relaxation profile characteristic of the solid at high pH values. At lower pH values, the relaxation rate is limited by a slow chemical exchange process that makes the relaxation rate independent of magnetic field at low field strengths. In cases where the proton exchange rate does not limit the total relaxation rate, the magnetic field dependence of the relaxation rate is given by a power law of the type R = Av-B, where B is 0.75 except at pH 11 where the data are better represented with B = 0.5. The exchange events important for the water proton relaxation are represented as a two-stage process in which water within the pores of the gel exchanges protons and magnetization with the solid spin system rapidly compared with the rate at which the water within the pores exchanges with the bulk water phase.

Postprandial lipemia in obese men with abdominal fat patterning.

OBJECTIVE: The purpose of this study was to assess differences in measures of postprandial triglyceride (TG) clearance between obese men with abdominal fat patterning (OAF) and men of desirable weight (DW). It was hypothesized that the OAF men would have impaired postprandial TG clearance. EXPERIMENTAL DESIGN: A comparative design was used. SETTING: Data were collected in a research laboratory with access to blood analysis instrumentation. PARTICIPANTS: Fourteen healthy, physically active, normolipemic men (7 OAF and 7 DW) were studied. INTERVENTIONS: Each subject consumed an oral fat load (78 grams of fat) and blood samples were collected every hour for 8 hours. MEASURES: Measures of postprandial lipemia included: incremental TG area, total TG area, time to peak TG concentration, maximal change in TG concentration, and time to return to baseline TG concentration. RESULTS: OAF men had significantly greater total area under the TG curve (24.7 +/- 1.09 vs 16.1 +/- 1.3 mmol-L(-1).8 hours, p = 0.003) and greater maximum TG change (2.0 +/- 0.3 vs 1.2 +/- 0.2 mmol-L-1, p = 0.03) following the oral fat load. Additionally, the total area under the TG curve was positively correlated with baseline TG concentrations (r = 0.53) and inversely correlated with baseline HDL2 concentrations (r = 0.64). Baseline HDL2 concentrations were inversely correlated with time to return to TG baseline (r = 0.57). CONCLUSIONS: Normal fasting lipoprotein profiles and regular physical activity do not preclude OAF men from having pronounced postprandial lipemia.

Similar abnormalities of idiotype and immunoglobulin light chain expression and of cell-mediated cytotoxicity in HIV-infected humans and simian immunodeficiency virus (SIV)-infected rhesus macaques.

The pathogenesis of AIDS in simian immunodeficiency virus (SIV)-infected rhesus macaques models the pathogenesis of human AIDS. We investigated whether certain immunological abnormalities associated with HIV infection and implicated in disease progression also occur in SIV infection. We observed striking parallels between the rhesus macaque humoral immune response to SIV and unusual features of the human humoral immune response to HIV infection. Anti-SIV envelope antibodies from SIV-infected macaques exhibited skewed kappa/lambda L chain usage relative to the ratio of kappa/lambda L chain usage detected on total plasma Ig. In addition, the same idiotope conserved on human anti-HIV gag, pol and env antibodies was detected with a similar distribution pattern on macaque anti-SIV env, gag and pol antibodies. Skewed Ig L chain representation and selection of a highly conserved possible dominant regulatory idiotope on antibodies against key neutralizing antigens raise the possibility that the progressive failure of the humoral immune response to SIV and HIV involves skewed oligoclonal humoral immunity. We also found that SIV-infected macaques, like HIV-infected humans, have elevated levels of CD8+ lymphocyte-mediated cytotoxicity. Cytotoxicity against human B cells was higher in CD8+ effector lymphocytes from SIV-infected macaques than in those from uninfected macaques (P < 0.05). Cell-mediated cytotoxicity against human NK cell targets was not elevated in effector lymphocytes from the SIV-infected macaques, suggesting that CTL activity was selectively elevated. Two out of seven SIV-infected macaques tested had CD8+ cytotoxic lymphocytes that selectively killed activated uninfected CD4+ macaque lymphocytes. Oligoclonal B cell responses and persistently elevated CD8+ lymphocyte-mediated cytotoxicity are consistent features of primate retroviral infections leading to AIDS. Understanding immune predispositions to these features triggered by HIV and SIV may advance new prophylactic and therapeutic strategies.

Development of a pre-employment testing program in medical group practices.

Pre-employment testing requires rigorous groundwork which many managers may not be willing to do, nor pay a professional to do for them. The benefits, though, have been documented in a number of studies which have shown pre-employment testing to be a beneficial and cost-efficient part of the selection process. Pre-employment testing will not supplant traditional selection processes such as interviewing and reference checks, but rather will enhance the selection process and reduce costs associated with turnover, as this professional paper discusses.

Evaluation of the ACSM submaximal ergometer test for estimating VO2max.

The purpose of this investigation was to assess the reliability and validity of maximal oxygen uptake estimates (ESTmax) from the ACSM submaximal cycle ergometer test. Subjects included 15 men and 15 women aged 21-54 yr who performed two submaximal tests and one maximal cycle ergometer test to determine maximal oxygen uptake (VO2max). During the submaximal tests, heart rates (HR) were recorded from a radio telemetry monitor. ESTmax was predicted for both submaximal trials by extrapolating HR to an age-predicted maximal HR. Correlation coefficient and standard error of measure (SEmeas) for ESTmax between submaximal trials were r = 0.863 and SEmeas = 0.40 l.min-1, while a t-test revealed no significant difference between trials. Although trial means were not significantly different, large variation in individual cases was evident by the high SEmeas (0.40 l.min-1) and by a large SEmeas expressed as a percentage of the mean (13%). The mean of the two ESTmax significantly overestimated measured VO2max with percent error, total error, and mean error equal to 25.7%, 0.89 l.min-1, and 0.63 l.min-1, respectively. The standard error of estimate expressed as a percentage of the mean was equal to 16% and 15% for both ESTmax. In summary, the ACSM protocol failed to be reliable as represented by the large differences found between submaximal trials. Furthermore, the protocol significantly overestimates VO2max and should not be used when an accurate assessment of VO2max is required.

Oxygen sensors based on luminescence quenching: interactions of pyrene with the polymer supports.

Oxygen quenching of pyrene has been studied in a diverse series of polymers. Most measurements were made using homo- or copolymers containing a poly(dimethylsiloxane) region. Systematic variations in the polymer properties have been made in order to delineate the structural features important for satisfactory use as supports for oxygen sensors. In particular, quenching behavior was examined as a function of the type and amount of copolymer cross-linkers; these were added to produce domains of different polarity and rigidity that would segregate the sensor molecule. A domain model (Xu, W.; et al. Anal. Chem. 1994, 66, 4133-4141) was used to explain the variations in oxygen-quenching properties as a function of additives and cross-linkers. The relative affinity of the different domains for the pyrene and the efficacy of the domains for oxygen quenching controls the overall behavior of the sensing response.