Role of interleukin 6 in the growth of myeloma-derived cell lines.

The role of interleukin 6 (IL-6) in the growth of five multiple myeloma-derived cell lines was characterized. The U266 and RPMI 8226 cell lines demonstrated increased DNA synthesis when cultured with exogenous IL-6, expressed IL-6 cell surface receptors (IL-6Rs) and expressed mRNA for IL-6R. However, these cells did not secrete detectable IL-6 protein, and a neutralizing antibody to IL-6 did not inhibit their growth. Three other myeloma-derived cell lines ARH-77, IM-9 and HS-Sultan did not respond to exogenous IL-6, secrete IL-6 or express cell surface IL-6Rs. The IL-6 responsive cell lines bore late B-cell surface antigens (Ags), CD38 and PCA-1, whereas those lines which were non-IL-6 responsive strongly expressed B1 (CD20) and B4 (CD19) Ags, representing earlier stages in B-cell differentiation. Finally, the two IL-6 responsive cell lines did not express Epstein-Barr virus (EBV) proteins; in contrast, EBV encoded proteins typically expressed during latency could be detected in the three non-IL-6 responsive lines, confirming infection with virus. These studies clarify the heterogeneity observed in the myeloma cell line phenotype and biology and suggest that the U266 and RPMI 8226 cell lines, which express IL-6 cell surface receptors and are IL-6 responsive, may be useful for further study of IL-6 signal transduction in and related IL-6 mediated growth of myeloma in vivo. In contrast, those cell lines which are IL-6-independent provide a model for further study of EBV transformation and IL-6-dependent growth mechanisms in malignancy.     

A nationwide survey of excessive daytime sleepiness in Parkinson's disease in France

To determine the prevalence of excessive daytime sleepiness (EDS) and that of dozing and sudden onset of sleep episodes (SOS) while driving in ambulatory patients with Parkinson's disease (PD) in France, a national sample of private and public neurologists was asked to recruit the first 10 consecutive nondemented PD patients. Each patient completed a questionnaire including the Epworth Sleepiness Scale (ESS) and the likelihood of dozing off and experiencing SOS episodes behind the wheel. Clinical and demographic data were collected. One thousand six hundred and twenty‐five patients with PD were included in the survey. Twenty‐nine percent of the patients suffered from EDS (ESS score ≥10) but only 0.8% declared a high chance of dozing while driving and 0.5% reported totally unpredictable SOS episodes while driving. Risk factors for EDS were male gender, reduced activity of daily living, and a high daily levodopa equivalent dosage. Risk factors for SOS episodes while driving were an ESS score ≥10, male gender, and low Hoehn and Yahr staging. EDS is common in ambulatory patients with PD and is a major risk factor for dozing and for SOS episodes behind the wheel in patients who drive. © 2007 Movement Disorder Society     

The emerging role of induced hypothermia in the management of acute stroke.

Current treatment of acute stroke remains unsatisfactory. This review presents experimental and clinical data which suggest that mild induced hypothermia could be a potent and practicable neuroprotective treatment of acute ischaemic stroke and intracerebral haemorrhage. Hypothermia, if proven to be safe, effective and widely practicable in patients with acute stroke, could have an enormous positive impact on reducing the burden of stroke worldwide. Critical issues that will need to be considered in a well designed randomised controlled trial of induced hypothermia in acute stroke patients are discussed.     

Reduced blood clearance and increased urinary excretion of N-nitrosodimethylamine in patas monkeys exposed to ethanol or isopropyl alcohol.

Low concentrations of N-nitrosodimethylamine are metabolized in rodent and human liver by cytochrome P450IIE1, an activity competitively inhibitable by ethanol. In rodents coadministration of ethanol with N-nitrosodimethylamine results in increased tumorigenicity in extrahepatic organs, probably as a result of reduced hepatic clearance. To test this concept in a primate, the effects of ethanol cotreatment on the pharmacokinetics of N-nitrosodimethylamine were measured in male patas monkeys. Ethanol, 1.2 g/kg given p.o. before i.v. N-nitrosodimethylamine (1 mg/kg) or concurrently with an intragastric dose resulted in a 10-50-fold increase in the area under the blood concentration versus time curves and a 4-13-fold increase in mean residence times for N-nitrosodimethylamine. Isopropyl alcohol, 3.2 g/kg 24 h before N-nitrosodimethylamine, also increased these parameters 7-10-fold; this effect was associated with persistence of isopropyl alcohol and its metabolic product acetone, both IIE1 inhibitors, in the blood. While no N-nitrosodimethylamine was detected in expired air, trace amounts were found in urine. Ethanol and isopropyl alcohol pretreatment increased the maximum urinary N-nitrosodimethylamine concentration 15-50-fold and the percentage of the dose excreted in the urine by 100-800-fold. Thus ethanol and isopropyl alcohol greatly increase systemic exposure of extrahepatic organs to N-nitrosodimethylamine in a primate.     

The Veterans Affairs Learners' Perceptions Survey: the foundation for educational quality improvement.

PURPOSE: The U.S. Department of Veterans Affairs (VA) supports 8,700 resident positions nationally to enhance quality of care for veterans and to educate physicians. This study sought to establish a yearly quality indicator to identify and follow strengths and opportunities for improvement in VA clinical training programs. METHOD: In March 2001, the VA Learners' Perceptions Survey, a validated 57-item questionnaire, was mailed to 3,338 residents registered at 130 VA facilities. They were asked to rate their overall satisfaction with the VA clinical training experience and their satisfaction in four domains: faculty/preceptor, learning, working, and physical environments using a five-point Likert scale. Questionnaires were received from 1,775 residents (53.2%). A full analysis was conducted using 1,436 of these questionnaires, whose respondents were categorized in four training programs: medicine (n = 706), surgery (n = 291), subspecialty (n = 266), and psychiatry (n = 173). RESULTS: On a scale of 0 to 100, residents gave their clinical training experience an average score of 79. Eighty-four percent would have recommended VA training to peers, and 81% would have chosen VA training again. Overall, 87% were satisfied with their faculty/preceptors, 78% with the learning environment, and 67% with the working and physical environments. The survey was sensitive to differences in satisfaction among the trainee groups, with residents in internal medicine (IM) the least satisfied. CONCLUSION: The VA Learners' Perceptions Survey is the first validated survey to address comprehensive satisfaction issues in clinical training. The survey highlights strengths and opportunities for improvement in VA clinical training and is the first step toward improving education.     

Sources of cortical rhythms change as a function of cognitive impairment in pathological aging: a multicenter study.

OBJECTIVE: The present study tested the hypothesis that cortical electroencephalographic (EEG) rhythms. change across normal elderly (Nold), mild cognitive impairment (MCI), and Alzheimer's disease (AD) subjects as a function of the global cognitive level. METHODS: Resting eyes-closed EEG data were recorded in 155 MCI, 193 mild AD, and 126 age-matched Nold subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. RESULTS: Occipital delta and alpha 1 sources in parietal, occipital, temporal, and 'limbic' areas had an intermediate magnitude in MCI subjects compared to mild AD and Nold subjects. These five EEG sources presented both linear and nonlinear (linear, exponential, logarithmic, and power) correlations with the global cognitive level (as revealed by mini mental state examination score) across all subjects. CONCLUSIONS: Cortical EEG rhythms change in pathological aging as a function of the global cognitive level. SIGNIFICANCE: The present functional data on large populations support the 'transitional hypothesis' of a shadow zone across normality, pre-clinical stage of dementia (MCI), and AD.     

Transvaginal sonography of cervical width and length during pregnancy.

Transvaginal ultrasonography has been proposed as a reliable method of assessing dimensions of the cervix. The purpose of the current investigation was to establish normative data for cervical width and length during pregnancy. This information may be helpful in predicting patients at risk for preterm birth. A transvaginal 5 or 7.5 MHz transducer was used on 132 consecutive low-risk pregnant women undergoing evaluation for gestational dating purposes. Even in cases of patient obesity or an empty bladder, high resolution was possible and permitted cervical measurement in all but one case. The external cervical width at the vaginal fornices was found to increase with advancing gestation (R = 0.512, P < 0.005). The cervical length from internal os to external os was found not to change with advancing gestation (R = 0.11, P = 0.30). Using these normative data, investigation is recommended to determine whether measuring cervical width and length is useful in predicting preterm labor and delivery.     

The effects of a carbonated carbohydrate drink on gastric emptying, gastrointestinal distress, and exercise performance.

To determine the effect of a carbonated carbohydrate (CHO) drink on gastric function and exercise performance, eight male cyclists completed four 120-min bouts of cycling. Each bout consisted of a 105-min ride at 70% VO2max followed by a 15-min self-paced performance ride. During each trial, one of four test solutions was ingested: carbonated CHO (C-10%), noncarbonated CHO (NC-10%), carbonated non-CHO (C), and noncarbonated non-CHO (NC). Following the performance ride, the subjects had their stomach contents removed by aspiration. There were no significant differences in gastric emptying (GE) except for Trial C-10%, which averaged 13.3% less than NC. However, there was no difference in the perception of gastrointestinal comfort between this trial and any other. Average power output during the performance ride was not significantly different between carbonated and noncarbonated trials, or between CHO-fed and no-CHO trials; however, the subjects worked at a greater intensity when fed CHO. Finally, acid base status did not change when a carbonated drink was ingested. This indicates that adding carbonation to a sport drink does not significantly alter gastric function, the perception of GI comfort, or exercise performance.     

Influence of murine mast cell growth factor (c-kit ligand) on colony formation by mouse marrow hematopoietic progenitor cells.

Purified natural and recombinant murine mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with other cytokines for effects in vitro on colony formation by multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells from BDF1 mouse bone marrow. Both preparations stimulated Epo-dependent CFU-GEMM and enhanced Epo-dependent BFU-E colony numbers and size. MGF had some stimulating activity for CFU-GM. When used in combination with plateau concentrations of pokeweed mitogen mouse spleen cell conditioned medium or granulocyte-macrophage colony stimulating factor (CSF), MGF enhanced in greater than additive fashion colony formation by CFU-GM. MGF also enhanced the size of colonies formed, an enhancement greatest for colonies containing granulocytes and macrophages. MGF did not enhance Macrophage-CSF stimulated colony numbers or size. MGF seems to be an early acting cytokine with preferential effects on the growth of more immature hematopoietic progenitor cells.