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Biomedical subjects

J B Mitchell

Publications and source records attributed to J B Mitchell.

At least 109 records · Page 6Linked to original sources
PubMed1996

Maximal accumulated oxygen deficit of resistance-trained men.

The primary purpose of the study was to compare maximal accumulated oxygen deficit (MAOD) in resistance-trained (RT), endurance-trained (ET), and untrained men (UT). A secondary purpose was to determine the influence of leg muscle mass (MM) on MAOD by examining the relationship between MM and MAOD and by comparing MAOD expressed relative to MM between the groups. MAOD was determined during 2-4 min of constant-load fatiguing cycling. MM, estimated via anthropometric measurements, was higher (p < .05) for RT (mean +/- SE; 25.5 +/- 3.4 kg) compared to ET (20.3 +/- 3.5) and UT (21.6 +/- 3.4). MAOD in liters O2eq was larger in RT (4.75 +/- 0.3) compared to UT (3.07 +/- 0.3) and ET (3.75 +/- 0.3). A significant positive correlation was observed between MAOD (LO2eq) and MM (kg) for RT only (RT, r = .85; ET, r = .55; UT, r = .20). Based on the correlational and mean MM data, the higher MAOD (LO2eq) in RT relative to ET and UT is predominantly the result of their larger leg muscle mass.

Adult↗
PubMed1996

Adaptation to eccentric exercise: effect on CD64 and CD11b/CD18 expression.

The primary purpose of the study was to examine circulating neutrophils and monocytes and their plasma membrane expression of CD64, CD11b, and CD18 after two bouts (B1 and B2) of eccentric exercise. Subjects (n = 10) performed 25 forced-lengthened contractions of the forearm flexors on two occasions separated by 3 wk. Blood samples were obtained before exercise and at 1.5, 6, 12, 24, 48, 72, and 96 h of recovery. CD64, CD11b, and CD18 expression was determined via direct immunofluorescence and used as an indicator of neutrophil and monocyte activation. Creatine kinase activity (B1 = 1,390, B2 = 108 U/l), myoglobin (B1 = 163, B2 = 41, ng/dl), and muscle soreness and tenderness were higher (P < 0.01) after B1 compared with B2. Neutrophils at 6, 12, and 96 h were higher (P < 0.05) for B1 vs. B2. CD11b expression on neutrophils was 2.7-fold higher at 72 h for B1 vs. B2. CD64 expression on neutrophils at 72 and 96 h was 1.4- and 1.9-fold higher, respectively, for B1 vs. B2. At 72 and 96 h, CD18 and CD64 expression on monocytes was 1.3-fold higher for B1 vs. B2. The observed changes were not significantly correlated with changes in creatine kinase activity or myoglobin. In conclusion, the adaptation to eccentric arm exercise was associated with a reduction in circulating neutrophils and a lower state of neutrophil and monocyte activation.

Adaptation, Physiological↗
PubMed1996

What role do neurologists play in determining the costs and outcomes of stroke patients?

BACKGROUND AND PURPOSE: Despite growing concern over the large numbers of specialists in the United States, little information is available on how stroke treatment varies by the specialty of the attending physician. This study compares the costs and outcomes of acute stroke patients by physician specialty, especially between neurologists and other specialists. METHODS: We selected a random sample of Medicare patients aged 65 years and older admitted with cerebral infarction between January 1 and September 30, 1991, identified from the principal diagnosis on Medicare Provider Analysis and Review records. All Medicare claims for these patients were extracted from the date of admission through 90 days. The attending physician was identified as that physician billing for routine hospital visits during the first 7 days of the stay. RESULTS: Neurologists treating stroke patients were significantly more expensive than other physicians but obtained better outcomes. Ninety-day mortality rates for patients treated by neurologists were significantly lower than those for other specialists. These cost and outcome differences persisted even after adjustment for patient age, comorbidity, hospital teaching status, and other characteristics. Compared with other attending physicians, neurologists were significantly more likely to order diagnostic cerebrovascular tests (especially brain MRI scans), more likely to prescribe warfarin, and more likely to discharge patients to inpatient rehabilitation facilities. CONCLUSIONS: Systematic triaging to neurologists based on clinical characteristics unmeasured by administrative data might explain these observed differences between neurologists and other physicians. Alternatively, these specialists may have been better able to identify the mechanism of stroke, information that then affected the course of treatment. Given current pressures to substitute generalists for specialists, however, more research is needed on these stroke treatment differences.

Cerebrovascular Disorders↗
PubMed1996

Using physician claims to identify postoperative complications of carotid endarterectomy.

OBJECTIVE: This study develops a methodology for identifying complications following carotid endarterectomy, using physician claims data. DATA SOURCES/STUDY SETTING: We selected a random 20 percent sample of Medicare patients undergoing carotid endarterectomy in 1991 (n = 8,345) and extracted all of their claims. STUDY DESIGN: Project neurologists identified the following services as indicative of complications following carotid endarterectomy if they were provided within 30 days of surgery: head CT, head MRI, and surgical exploration of the neck for hemorrhage, thrombosis, or infection. DATA COLLECTION/EXTRACTION METHODS: Total costs were calculated from all claims associated with the hospitalization and the 30-day postoperative period. Outcomes included mortality (obtained from Medicare eligibility files), length of stay, discharge to an institution, and readmission to an acute care hospital (the latter obtained from claims data). PRINCIPAL FINDINGS: Surgical complications were identified in one out of every ten endarterectomy patients (10.3 percent). Patients with complications were significantly more likely to die within 30 days of surgery (8.9 percent, compared with 1.1 percent of those not experiencing complications). They also were significantly more likely to be discharged to an institutional setting (24.9 percent versus 2.9 percent), and more likely to be readmitted to acute care hospitals (26.8 percent versus 8.2 percent). Patients with postoperative complications also were significantly more expensive: $22,187 versus $10,892. CONCLUSION: Our findings suggest that physician claims could be used by PROs or similar entities as a screening tool to identify potential problem hospitals or problem surgeons. First, however, the methodology would need to be clinically validated.

Aged↗
PubMed1996

Radiation sensitisation by nitric oxide releasing agents.

Previous studies have shown that nitric oxide (NO) sensitises hypoxic cells to ionising radiation. In the present study, four different nitric oxide (NO) donor agents were evaluated for both NO release and hypoxic radiosensitisation. The S-nitrosothiol NO donor agents, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to release sustained NO concentrations (microM) and significantly radiosensitise hypoxic cells. The extent of hypoxic radiosensitisation by both of these agents at 1.0 mM concentration was similar to that obtained with molecular oxygen. In contrast, neither 3-morpholinosydnonimine (SIN-1) nor sodium nitroprusside (SNP) released detectable NO concentrations and neither agent enhanced the hypoxic radiation response to the extent of that observed for GSNO or SNAP. NO-mediated hypoxic cell radiosensitisation by NO donor drugs may offer a new approach for clinical consideration, particularly if such agents can be selectively delivered to hypoxic cells.

Animals↗
PubMed1995

Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli.

Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H2O2). Murine neutrophils and activated macrophages, however, produce NO, H2O2, and other reactive oxygen species to kill microorganisms, which suggests a paradox. In this study, we treated bacteria (Escherichia coli) with NO and H2O2 for 30 min and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H2O2-mediated killing, as evaluated by a clonogenic assay. The combination of NO/H2O2 induced DNA double strand breaks in the bacterial genome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing. NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells. The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H2O2 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H2O2 cytocidal mechanism. Our results suggest a possible mechanism of modulation of H2O2-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO.

Catalase↗
PubMed1995

Nitric oxide protects against alkyl peroxide-mediated cytotoxicity: further insights into the role nitric oxide plays in oxidative stress.

Endogenously formed nitric oxide (NO) possesses diverse properties such as regulating physiological functions, exerting specific toxic effects, and protecting against various toxic substances. Recent studies suggest that in the presence of reactive oxygen species, NO can serve as an antioxidant. We show here that NO delivered from the NO donor compound, PAPA/NO (NH2(C3H6)(N[N(O)NO](C3H7)), protects Chinese hamster V79 lung fibroblasts from the cytotoxicity of t-butyl hydroperoxide and cumene hydroperoxide. In contrast, the other end products of PAPA/NO degradation in aqueous solution, NH2(C3H6)NH(C3H7) and nitrite, did not protect. The NONOate DEA/NO releases NO six times faster than PAPA/NO, yet did not afford protection, which implies that NO must be present throughout the alkyl hydroperoxide exposure. Measurements of NO concentrations released from PAPA/NO suggest that micromolar levels protect against cytotoxicity induced by alkyl hydroperoxides. These findings demonstrate that the flux of NO sustained over the duration of the peroxide exposure determines protection and not the total of NO delivered. These results suggest that concentrations of NO produced in the microenvironment of endothelial cells are high enough to protect cells from Fenton-type-mediated toxicity and support the premise that NO may exert a salutary effect in certain diseases associated with membrane damage.

Alkylating Agents↗
PubMed1995

Protection from radiation-induced chromosomal aberrations by the nitroxide Tempol.

BACKGROUND: The nitroxide Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a stable, free radical that exhibits protection from ionizing radiation damage and from oxidative stress mediated through exposure of cells to superoxide or hydrogen peroxide. Radiation protection has been observed in both in vivo and in vitro models. To understand the mechanism of Tempol-mediated radioprotection better, the production of radiation-induced chromosome aberrations was evaluated. This study analyzed Tempol-mediated radioprotection of human peripheral blood lymphocytes (PBLs). METHODS: Peripheral blood lymphocytes were exposed to control (0mM), 10 mM (Tp10), and 50 mM (Tp50) concentrations of Tempol for 20 minutes before irradiation with 0, 150, 300, and 450 cGy. One quarter ml whole blood was cultured in F12 medium and phytohemagglutinin at 37 degrees C for 49, 54, 59, and 64 hours. Colcemide was added to each sample for the last 5 hours before harvest. Cells were harvested, treated with hypotonic solution, and fixed before dropping on cold clean slides. Mitotic indices and frequency of dicentric, ring, and triradial chromosomal aberrations were determined at 1000x magnification for each treatment group at each collection point. RESULTS: Treatment of cells with Tempol alone did not induce the chromosomal aberration frequency above that for unirradiated controls. Radiation dose response curves for total chromosome aberration production revealed radioprotection for Tempol treatment for both 10 and 50 mM exposures. Tempol protection factors (assessed at 0.2 aberrations/cell level) for Tp 10 and Tp 50 were 2.2 and 2.8, respectively. CONCLUSIONS: Tempol protects against radiation-induced chromosome aberrations in human PBLs. This finding is consistent with and lends support to previous studies in which Tempol was reported to enhance cell survival and reduce radiation-induced DNA double strand breaks.

Cell Survival↗
PubMed1995

Effects of chronic intermittent cold stress on pituitary adrenocortical and sympathetic adrenomedullary functioning.

Basal and stress-induced pituitary-adrenocortical (PA) and sympathetic adrenomedullary (SAM) function was investigated in rats exposed to chronic intermittent cold stress (4 degrees C for 4 h a day for 21 days; CHR). We found that basal plasma levels of corticosterone (B), corticosteroid-binding-globulin, ACTH, epinephrine (E) and norepinephrine (NE) were similar in CHR and control (CTL) animals. In contrast, activity of the adrenal catecholamine-synthesizing enzyme tyrosine hydroxylase, but not phenylethanolamine-N-methyl transferase, was significantly elevated in CHR compared to CTL. Following exposure to a heterotypic stressor (20 min restraint), plasma levels of B were significantly higher in CHR than CTL, but the stress-induced levels of E and NE were not different between groups. These data suggest that, although basal PA function is not altered by exposure to chronic intermittent cold stress, components of the SAM system are affected by this paradigm, and that co-ordinate facilitation of both PA and SAM responses to a novel stressor is not a necessary consequence of exposure to chronic intermittent stress.

Adrenal Medulla↗
PubMed1995

Nitric oxide (NO) protects against cellular damage by reactive oxygen species.

Since the discovery of nitric oxide (NO) as an endogenously formed radical, its effect on numerous physiological processes has been intensively investigated. Some studies have suggested NO to be cytotoxic while others have demonstrated it protective under various biological conditions. Though NO shows minimal cytotoxicity to a variety mammalian cell cultures, it does modulate the toxicity of some agents such as reactive oxygen species. Often, NO is generated in the presence of these reactive oxygen species in response to foreign pathogens or under various pathophysiological conditions. We will show that NO can play a protective role under oxidative stress resulting from superoxide, hydrogen peroxide and alkyl peroxides. It was found by measuring the time-concentration profiles of NO released from various NO donor compounds that only microM levels of NO were required for protection against the toxicity of these reactive species. It was found that there are several chemical reactions which may account for these protective effects such as NO preventing heme oxidation, inhibition of Fenton-type oxidation of DNA, and abatement of lipid peroxidation. Taken together, NO at low concentrations clearly protects against peroxide-mediated toxicity.

Animals↗
PubMed1995

A diffusing sphere which delivers homogeneous laser light for use in photodynamic therapy.

Photodynamic therapy (PDT) exploits the selective uptake of a photosensitizer in tumors and other hyperproliferative target tissues, as well as the ability to direct the treatment light beam to a specific region. Since the photodynamic effect depends on light dose, tissue optical properties and photosensitizer concentration, uniform delivery of light is crucial to attain optimal photodynamic effect. Many commonly used methods for delivering laser light during photodynamic therapy, such as a free fiber or microlens, require fiber and laser adjustments to obtain a highly uniform beam. In this study, we test the ability of a diffusing sphere to improve the uniformity of a light field coming from an argon laser coupled to a free fiber, in which no attempt has been made to optimize beam characteristics. Light fields from the free fiber, a microlens and the diffusing sphere are compared for uniformity via light intensity readings. An in vivo comparison between the sphere and the free fiber is also made in guinea pigs given Photofrin-II. The diffusing sphere decreases problems with shielding, allows quick and easy application of light by simply applying the device over the desired treatment area, and optimizes the desired photodynamic effect by producing ad highly uniform beam of light with no necessity to optimize light delivery by vibrating, looping or re-cleaving fibers.

Animals↗
PubMed1995

Neurophysiological consequences of nitroxide antioxidants.

Nitroxides are antioxidant compounds that have been shown to provide radioprotection in vivo and in vitro. Radioprotection in vivo is limited by toxicity, which appears to be neurologic in nature. To further evaluate the toxicity of these compounds, three representative nitroxides, Tempol, Tempamine, and Tempo, were examined in slices of guinea pig hippocampus. Each nitroxide increased the population spike and caused potentiation of excitatory postsynaptic potential--spike coupling. Repetitive activity and epileptiform activity were observed at the highest concentrations of Tempo and Tempamine. Tempol was the least toxic compound in this system, followed by Tempamine and Tempo. Additional studies are necessary to further define the effects of nitroxides on the central nervous system and to develop strategies to mitigate these effects.

Animals↗
PubMed1995

Suppression of LH secretion in food-restricted lactating females: effects of ovariectomy and bromocryptine treatment.

It has been shown that restricting food in lactating rats for the first 2 weeks postpartum at a level of 60% of the ad-libitum daily ration increases the length of lactational dioestrus by about 7 days but little is known about correlated changes in hormone levels. In the first experiment we report changes in LH, prolactin (PRL) and ACTH secretion in food-restricted and ad-libitum fed lactating rats at various stages of lactation. Our results demonstrate that food restriction during the first 2 weeks of lactation did not affect PRL or ACTH secretion, but decreased plasma LH levels despite comparable GnRH receptor density between food-restricted and ad-libitum fed females. In the second experiments we investigated a possible causal relationship between the increased secretion of progesterone seen in food-restricted females and the suppression of plasma LH levels, by determining the effects of bromocryptine treatment and ovariectomy on LH secretion in both ad-libitum fed and food-restricted lactating females. LH suppression in food-restricted lactating females was not affected by ovariectomy or bromocryptine treatment, although the latter treatment significantly increased GnRH receptor number. These data suggest that factors other than ovarian steroids, PRL or increased adrenocortical activity modulate LH secretion and the length of lactational dioestrus in food-restricted lactating females.

Adrenocorticotropic Hormone↗
PubMed1995

Black-white treatment differences in acute myocardial infarction.

Previous research has documented that black patients with acute myocardial infarction (AMI) are significantly less likely than white patients to receive cardiac procedures. This article seeks to expand this research by: controlling for the limited ability of low income elderly to pay for care; and adjusting for the impact of differential mortality. We selected a sample of 18,202 Medicare beneficiaries admitted during 1992 with AMI, and followed them for 90 days. Even after adjusting for other factors, black patients with AMI were less likely to undergo cardiac catheterization, and if catheterized, less likely to receive a revascularization procedure.

Black or African American↗
PubMed1995

Exercise-induced muscle damage: effect on circulating leukocyte and lymphocyte subsets.

The purpose of this study was to determine the effect of downhill and level running on circulating leukocyte and lymphocyte subsets and T lymphocyte activation. Using a random cross-over design, 10 runners completed two trials of 60 min of level running (0% grade; LR) and downhill running (-10% grade; DHR) at 70% of level VO2max. Blood samples were obtained preexercise and immediately postexercise (POST) and at 1.5, 12, 24, and 48 h of recovery. Creatine kinase activity peaked at 12 h of recovery from DHR and was not significantly altered following LR. The number of total T, CD16+, CD3+CD56+ cells were significantly higher POST DHR compared with LR. Leukocyte and neutrophil counts were significantly higher at 1.5 and 12 h of recovery from DHR compared with LR. The number of activated CD8+ cells (CD25+ CD8+) was significantly higher at 12 h of DHR compared to LR. Total T cells were significantly reduced at various time points during the 48 h of recovery from LR and DHR. In summary, DHR relative to LR resulted in a greater mobilization of lymphocytes (post), neutrophils (1.5-12 h of recovery) and activation of CD8+ cells at 12 h of recovery. In addition, reductions in circulating T lymphocyte subsets occurred following both conditions.

Adult↗
PubMed1995

Impact of Medicare payment reductions on access to surgical services.

OBJECTIVE: This study evaluates the impact of surgical fee reductions under Medicare on the utilization of surgical services. DATA SOURCES: Medicare physician claims data were obtained from 11 states for a five-year time period (1985-1989). STUDY DESIGN: Under OBRA-87, Medicare reduced payments for 11 surgical procedures. A fixed effects regression method was used to determine the impact of these payment reductions on access to care for potentially vulnerable Medicare beneficiaries: joint Medicaid-eligibles, blacks, and the very old. DATA COLLECTION/EXTRACTION METHODS: Medicare claims and enrollment data were used to construct a cross-section time-series of population-based surgical rates from 1985 through 1989. PRINCIPAL FINDINGS: Reductions in surgical fees led to small but significant increases in use for three procedures, small decreases in use for two procedures, and no impact on the remaining six procedures. There was little evidence that access to surgery was impaired for potentially vulnerable enrollees; in fact, declining fees often led to greater rates of increases for some subgroups. CONCLUSIONS: Our results suggest that volume responses by surgeons to payment changes under the Medicare Fee Schedule may be smaller than HCFA's original estimates. Nevertheless, both access and quality of care should continue to be closely monitored.

Black or African American↗