Alcohol affects otolith-induced ocular counterrolling: dosage effects

Conclusion. Otolith function is significantly affected by alcohol ingestion and the higher the dosage, the greater the effect. Objective. To determine how the effect of a 5 oz (150 ml) dose of alcohol differs from an earlier study examining the effect of 3 oz (90 ml) on ocular counterrolling (OCR). Subjects and methods. Twenty subjects underwent OCR testing before and after drinking 5 oz of 80 proof vodka. Results. Blood alcohol levels (BAL) of the subjects ranged from 0.09 to 0.18%. Three measures of OCR were considered. Amplitude was significantly reduced post-alcohol; disconjugacy was significantly increased post-alcohol; smoothness was not significantly different pre- and post-alcohol. In contrast, the lower 3 oz study produced BAL of 0.04-0.09% and resulted in significantly reduced OCR amplitude, no significant change in disconjugacy, but a significant improvement in smoothness. The increase in BAL produced further impairment of amplitude and conjugacy but eliminated the benefit of smoothness.     

Trait anxiety and salivary cortisol during free living and military stress

INTRODUCTION: Accumulating evidence suggests that negative affect is associated with elevated cortisol. Limited research has investigated this association in young, highly functioning, and stress-resilient populations. METHODS: We examined the relation of trait anxiety with total and diurnal salivary cortisol during free-living conditions and during a stressful military exercise in 26 military men ages 19-30 yr (M = 21.6, SD = 2.3). Salivary cortisol was assessed at five time points over 2 consecutive days of free-living measurement, and three time points during a stressful military experience. Trait anxiety was measured with the trait portion of the Spielberger State-Trait Anxiety Inventory 1-3 wk prior to the military exercise. RESULTS: Total cortisol concentrations were similar between men reporting high or low anxiety during free-living conditions (8.6 +/- 3.2 vs. 7.4 +/- 2.8 nmol x L(-1), respectively, P > 0.05), and military stress (21.3 +/- 7.3 vs. 19.0 +/- 7.0 nmol x L(-1), respectively, P > 0.05). The diurnal cortisol profile differed significantly (P = 0.04) between these men during the free-living condition, but not the stressful military experience (P > 0.05). Specifically, during free living, men with low anxiety exhibited a diurnal cortisol pattern that peaked in the early morning, decreased precipitously during the midmorning, and continued to decrease throughout the day, reaching a nadir in the evening. By contrast, the cortisol pattern of high-anxiety men remained elevated and significantly higher than their low-anxiety counterparts during the midmorning, decreased more slowly throughout the day, and reached its lowest level in the evening. Results were not substantially altered following adjustment for sleep duration or wake time. CONCLUSION: These findings suggest that trait anxiety influences the diurnal cortisol pattern in young, apparently healthy men during free-living conditions, but does not predict the cortisol response to uncontrollable military stress.     

Selective loss of subpopulations of ventral mesencephalic dopaminergic neurons in the monkey following exposure to MPTP

Tyrosine hydroxylase immunohistochemical examination of the mesencephalon of severely parkinsonian MPTP-treated macaque fascicularis monkeys revealed a marked loss of substantia nigra pars compacta (SNc) neurons in both medial and central portions of the nucleus with a relative sparing of neurons in the dorsal-most portions of the substantia nigra. These animals also sustained 20–65% loss of neurons in the substantia nigra pars lateralis area, ventral tegmental area (A-10), and the retrorubral area (A-8 cell group, and the parabrachialis pigmentosus region). These animals all had extreme striatal dopamine depletions. A monkey which received several small doses of MPTP and yet remained asypptomatic for a motor disorder (although it had demonstrable behavioral performance deficits) had only a loss only ventral SNc neurons, with no appreciable cells in associated ventral mesencephalic dopamine areas and no loss of striatal dopamine. These data suggest that the effects of MPTP are not as selective as originally thought and, more importantly, indicate that MPTP-induced parkinsonism in the primate may be more analogous to idiopathic Parkinson's disease, where cells other than SNc cells are affected. Furthermore, the present findings suggest that only certain mesencephalic dopamine neurons are susceptible to MPTP-induced damage. The unique characteristics of these neurons need to be elucidated.     

A Randomized Phase 2 Trial of Neoadjuvant Chemotherapy in Resectable Pancreatic Cancer: Gemcitabine Alone Versus Gemcitabine Combined with Cisplatin

Background Survival after surgery for pancreas cancer remains low. This improves with adjuvant chemotherapy, but up to 30% patients do not receive the prescribed treatment. Neoadjuvant therapy may increase the proportion of patients who receive all treatment components, may downstage disease before surgery, and may provide early treatment of micrometastases. This randomized phase 2 study compares gemcitabine-based chemotherapy regimens to identify the most promising regimen for future study. Methods Fifty patients with potentially resectable pancreas lesions were enrolled onto the study. Twenty-four patients were randomized to gemcitabine (1000 mg/m²) every 7 days for 43 days; 26 patients were randomized to gemcitabine (1000 mg/m²) and cisplatin (25 mg/m²), 7 to the original schedule (omitting day 22) and 19 to a revised schedule due to neutropenia (omitting days 15 and 36). The primary outcome measure was resection rate. Results Patients who were allocated to gemcitabine received a median of 85% of the planned dose. Patients who were allocated to combination treatment received a median of 88% and 92% of the planned gemcitabine and cisplatin doses, respectively. There were 10 episodes of grade III/IV hematological toxicity in each group. Twenty-seven patients (54%) underwent pancreatic resection, 9 (38%) in the gemcitabine arm and 18 (70%) in the combination arm, with no increase in surgical complications. To date, 34 patients (68%) have died. Twelve-month survival for the gemcitabine and combination groups was 42% and 62%. Conclusions Chemotherapy can be safely administered before pancreatic surgery. Combination therapy with gemcitabine and cisplatin is associated with a high resection rate and an encouraging survival rate, suggesting that further study is warranted.     

Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis

Germ line mutations in the Adenomatous polyposis coli tumor suppressor gene cause a hereditary form of intestinal tumorigenesis in both mice and man. Here we show that in Apc(Min/+) mice, which carry a heterozygous germ line mutation at codon 850 of Apc, there is progressive loss of immature and mature thymocytes from approximately 80 days of age with complete regression of the thymus by 120 days. In addition, Apc(Min/+) mice show parallel depletion of splenic natural killer (NK) cells, immature B cells, and B progenitor cells in bone marrow due to complete loss of interleukin 7 (IL-7)-dependent B-cell progenitors. Using bone marrow transplantation experiments into wild-type recipients, we have shown that the capacity of transplanted Apc(Min/+) bone marrow cells for T- and B-cell development appears normal. In contrast, although the Apc(Min/+) bone marrow microenvironment supported short-term reconstitution with wild-type bone marrow, Apc(Min/+) animals that received transplants subsequently underwent lymphodepletion. Fibroblast colony-forming unit (CFU-F) colony assays revealed a significant reduction in colony-forming mesenchymal progenitor cells in the bone marrow of Apc(Min/+) mice compared with wild-type animals prior to the onset of lymphodepletion. This suggests that an altered bone marrow microenvironment may account for the selective lymphocyte depletion observed in this model of familial adenomatous polyposis.