Effects of a long-distance run on cardiac markers in healthy athletes.

BACKGROUND: Running a marathon is a stressful event for athletes. Limited research exists on the role of cardiac markers during such a strenuous event. The aim of this study was to investigate detailed changes in cardiac markers before and after a long-distance run. METHODS: We studied 25 male and 2 female runners (age 34-64 years) who were running the Visé-Maastricht-Visé marathon. Blood samples were drawn just before and immediately after finishing the marathon. An additional blood sample was collected 24 h later. RESULTS: Running the marathon led to a significant increase in cortisol. This returned to baseline values 24 h after the marathon. There was a slight increase in brain natriuretic peptide (BNP); however, this was not statistically significant. On the contrary, the N-terminal fragment of BNP (NT-pro-BNP) was significantly increased immediately after the run and was normalized 24 h later in 26 out of 27 runners (96%). The magnitude of the transient elevations in BNP and NT-pro-BNP increased with the age of the athletes. Furthermore, in 9 out of 27 runners there was a significant increase in troponin T. However, in all these runners this increase was transient and troponin-T levels returned to baseline values 24 h after the marathon. CONCLUSIONS: Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress. The transient increases in BNP, NT-pro-BNP and troponin T are more likely to reflect myocardial stunning than cardiomyocyte damage. It seems that the magnitude of the increase in BNP could serve as a marker of the biological age of the myocardium.     

Endotoxin promotes synergistic lethality during concurrent Escherichia coli and Candida albicans infection.

Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens. To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E. coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed. E. coli (2 x 10(7) colony-forming units (CFU)) plus C. albicans (6 x 10(7) CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E. coli or C. albicans alone (20 and 3%, respectively, P less than 0.01). Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P less than 0.05), endotoxemia (3653 +/- 3187 versus 2 +/- 2 endotoxin units (EU), P less than 0.01), and bacteremia (4.2 +/- 2.3 versus 1.1 +/- 2.1 log(CFU/ml), P less than 0.01) compared to animals receiving saline alone. In a separate series of experiments, purified E. coli 0111:B4 LPS was administered in place of viable E. coli. The simultaneous injection of 200 micrograms E. coli LPS and C. albicans (6 x 10(7) CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E. coli 0111:B4 LPS or C. albicans alone (21 and 3% respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Attempted suicide in bipolar disorder pedigrees: evidence for linkage to 2p12.

BACKGROUND: We are interested in identifying susceptibility genes that predispose subjects to attempted suicide. METHODS: We conducted a secondary analysis of genome-wide linkage data from 162 bipolar pedigrees that incorporated attempted suicide as a clinical covariate. RESULTS: The strongest covariate-based linkage signal was seen on 2p12 at marker D2S1777. The logarithm of odds (LOD) score at marker D2S1777 rose from 1.56 to 3.82 after inclusion of the suicide covariate, resulting in significant chromosome-wide empirically derived p-values for the overall linkage finding (p = .01) and for the change in LOD score after the inclusion of the covariate (p = .02). CONCLUSIONS: The finding on chromosome 2 replicates results from two previous studies of attempted suicide in pedigrees with alcohol dependence and in pedigrees with recurrent early-onset depression. Combined, these three studies provide compelling evidence for a locus influencing attempted suicide on 2p12.     

Cerebral hemodynamic and metabolic profiles in fulminant hepatic failure: relationship to outcome.

The purpose of this retrospective study was to examine the potential role of cerebral hemodynamic and metabolic factors in the outcome of patients with fulminant hepatic failure (FHF). Based on the literature, a hypothetical model was proposed in which physiologic changes progress sequentially in five phases, as defined by intracranial pressure (ICP) and cerebral blood flow (CBF) measurements. Seventy-six cerebral physiologic profiles were obtained in 26 patients (2 to 5 studies each) within 6 days of FHF diagnosis. ICP was continuously measured by an extradural fiber optic monitor. Global CBF estimates were obtained by xenon clearance techniques. Jugular venous and peripheral artery catheters permitted calculation of cerebral arteriovenous oxygen differences (AVDO2), from which cerebral metabolic rate for oxygen (CMRO2) was derived. A depressed CMRO2 was found in all patients. There was no evidence of cerebral ischemia as indicated by elevated AVDO2s. Instead, over 65% of the patients revealed cerebral hyperemia. Eight of the 26 patients underwent orthotopic liver transplantation-all recovered neurologically, including 6 with elevated ICPs. Of the 18 patients receiving medical treatment only, all 7 with increased ICP died in contrast to 9 survivors whose ICP remained normal (P < 0.004). Hyperemia, per se, was not related to outcome, although it occurred more frequently at the time of ICP elevations. Six patients were studied during brain death. All 6 revealed malignant intracranial hypertension, preceded by hyperemia. In conclusion, the above findings are consistent with the hypothetical model proposed. Prospective longitudinal studies are recommended to determine the precise evolution of the pathophysiologic changes.     

Quality of life in patients with seasonal affective disorder: summer vs winter scores.

OBJECTIVE: To compare perceived quality of life (QoL) in patients diagnosed with seasonal affective disorder (SAD) during the winter and summer months. METHODS: Twenty-six patients who were enrolled in an ongoing multicentre study in Canada completed 2 measures of QoL (the 20-item Medical Outcomes Study Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire, [Q-LES-Q]) during the winter, when suffering from depression, and again during the summer months. RESULTS: Both general and health-related QoL scores were significantly improved in patients with SAD during the summer months, with scores for the most part falling within normal range. CONCLUSIONS: Perceived QoL in patients with SAD is markedly impaired during the winter months but shows a substantial rebound during the summer months. The findings of this study provide further evidence that SAD is a distinct diagnostic entity.     

Epidermal growth factor receptor inhibition modulates the nuclear localization and cytotoxicity of the Auger electron emitting radiopharmaceutical 111In-DTPA human epidermal growth factor.

(111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. METHODS: Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. RESULTS: Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean +/- SD: 35 +/- 4 vs. 24 +/- 5 foci per nucleus, respectively). In clonogenic assays, a significant reduction in the surviving fraction was observed when (111)In-DTPA-hEGF (5 ng/mL, 6 MBq/microg) was combined with gefitinib (1 microM ) compared with (111)In-DTPA-hEGF alone (42.9% +/- 5.7% vs. 22.9% +/- 3.6%, respectively; P < 0.01). CONCLUSION: The efficacy of (111)In-DTPA-hEGF depends on internalization and nuclear uptake of the radionuclide. Nuclear uptake, DNA damage, and cytotoxicity are enhanced when (111)In-DTPA-hEGF is combined with gefitinib. These results suggest a potential therapeutic role for peptide receptor radionuclide therapy in combination with tyrosine kinase inhibitors.