Ethnicity and psychiatric comorbidity among alcohol-dependent persons who receive inpatient treatment: African Americans,Alaska natives,Caucasians, and Hispanics

This study examined ethnic and gender differences of psychiatric comorbidity among alcohol dependent men and women from four ethnic groups: Alaska Native, Caucasians, African Americans, and Hispanics. The data were obtained through individual standardized interview; DSM-III-R diagnoses were obtained via a computer algorithm. The subjects included 1177 Caucasians, 361 African Americans, 93 Hispanics and 486 Alaska Natives. Significant ethnic differences were found in relation to age of onset of alcohol and multiple substance dependence and psychiatric comorbidity. Ethnic differences were also noted with regard to the health care utilization.     

Investigations of host defence in patients with sickle cell disease

Parameters of host defence were investigated in 30 patients with sickle cell disease (SCD). A newly devised perfusion system was used to study the kinetics in whole blood of leucocyte adherence, phagocytosis, killing and solubilization of a mixture of Staph. aureus and Str. pneumoniae, and secretion of lactoferrin. A skin window technique was used to examine the accumulation of leucocytes at inflammatory foci and their subsequent rate of movement through a filter. Serum concentrations of C3, C4, total haemolytic complement and immunoglobulins were also measured. The rate of neutrophil migration into filters was slightly reduced in patients with SCD. The proportion of monocytes that emigrated from the skin windows and their rate of migration were markedly diminished. The adhesion of neutrophils and their ability to kill staphylococci were also reduced, particularly in patients of the haemoglobin (Hb) SS and Hb S-beta-thalassaemia genotypes. Neutrophil function was mostly impaired in patients with the greatest frequency of bacterial infection. The rate of clearance of pneumococci was related to the concentration of type specific immunoglobulin G but not M. Serum concentrations of immunoglobulins and complement were normal. We were unable to define a defect of host defence of sufficient magnitude to explain the susceptibility of these patients to severe infection.     

Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice

Motor incoordination, immune deficiencies, and an increased risk of cancer are the characteristic features of the hereditary disease ataxia-telangiectasia (A-T), which is caused by mutations in the ATM gene. Through gene targeting, we have generated a line of Atm mutant mice, Atm(y/y) mice. In contrast to other Atm mutant mice, Atm(y/y) mice show a lower incidence of thymic lymphoma and survive beyond a few months of age. Atm(y/y) mice exhibit deficits in motor learning indicative of cerebellar dysfunction. Even though we found no gross cerebellar degeneration in older Atm(y/y) animals, ectopic and abnormally differentiated Purkinje cells were apparent in mutant mice of all ages. These findings establish that some neuropathological abnormalities seen in A-T patients also are present in Atm mutant mice. In addition, we report a previously unrecognized effect of Atm deficiency on development or maintenance of CD4(+)8(+) thymocytes. We discuss these findings in the context of the hypothesis that abnormal development of Purkinje cells and lymphocytes contributes to the pathogenesis of A-T.     

Postprandial thermogenesis at rest and postexercise before and after physical training in lean, obese, and mildly diabetic men.

To determine the independent impact of physical training on postprandial thermogenesis at rest and after 1 hour of cycling at 100 W, 10 lean (15% +/- 1% body fat), 10 obese (33% +/- 2% fat), and six obese diet-controlled, type II diabetic men (34% +/- 4% fat) underwent 12 weeks of vigorous cycle ergometer training (4 h/wk at approximately 70% of maximum oxygen consumption [VO2max]) while maintaining body weight and composition. Body weight was held constant by refeeding the energy expended in each training session. Cardiorespiratory fitness increased by approximately 27%, but body weight and fat did not change. Before and at least 4 days after the last exercise session, energy expenditure was measured for 3 hours under four conditions: (1) rest, no meal; (2) rest, after a 720-kcal mixed meal; (3) postexercise after 1 hour cycling, no meal; and (4) postexercise, meal after exercise. The thermic effect of food was calculated as postprandial minus postabsorptive energy expenditure at rest and postexercise (kcal/3 h). Before and after training, the thermic effect of food during rest was lower in obese than in lean men, and lower in diabetic than in obese men (P less than .05). Thermogenesis was improved after short-term exercise in obese and diabetic men compared with that at rest, but was not normalized (P less than .05 for lean v obese, diabetic men). A significant effect of training on thermogenesis was due to a small but significant increase after training for diabetic men under the postexercise condition. Thus, while short-term exercise enhances but does not normalize thermogenesis in obese and diabetic men, long-term exercise training leading to increased cardiorespiratory fitness, in the absence of changes in body composition, leads to a small increase in thermogenesis in diabetic men, which manifests only after a short period of exercise.     

The contraction of stunned myocardium: isovolumetric bulging and wasted ejection shortening in dog heart.

OBJECTIVE: The aim of the study was to assess the contraction of myocardium stunned by repetitive brief coronary occlusions by examining the response to alterations in loading and inotropy of systolic contraction on isovolumetric and ejection phase shortening. METHODS: Fourteen open chest anaesthetised dogs were used for the studies. After destruction of the sinus node, the heart was atrially paced and atrial extrasystoles were introduced followed by a short (400 ms) or long (700 ms) postextrasystole. The left anterior descending coronary artery was occluded for 5 min and reperfused for 10 min a total of eight times to produce stunned myocardium, followed by a final 60 min of reflow. Regional function was assessed with segment length sonomicrometers. RESULTS: With successive periods of occlusion there was an increase in the end diastolic segment length and a progressive decrease in total percent systolic shortening (baseline 22.3%, 1st reflow 14.5%, 8th reflow 7.9%) with some recovery after 60 min of reflow (12.0%). This was predominantly due to the development of bulging during isovolumetric systole (4.5%, -4.9%, and -8.3%, respectively) which diminished during 60 min recovery to -3.1%. Ejection shortening was relatively constant (17.8%, 19.4%, 16.3%, and 15.1%, respectively). Postextrasystolic potentiation resulted in an increased in total percent systolic shortening, but not to the baseline value, as slight isovolumetric bulging persisted. Similar changes were seen with the short and long postextrasystoles although the latter had a greater increase in ejection shortening. CONCLUSIONS: The decrease in function after repetitive occlusion and reflow is predominantly due to bulging during isovolumetric systole which persists after postextrasystolic potentiation in our model of stunned myocardium.     

Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons.     

A Novel Non-Invasive Adjuvant Biomechanical Treatment for Patients with Altered Rehabilitation after Total Knee Arthroplasty: Results of a Pilot Investigation

Background

Many factors contribute to suboptimal results after total knee arthroplasty (TKA) but little is known regarding the value of postsurgical rehabilitation after TKA. We examined the effects of an enhanced closed kinematic chain exercises program (AposTherapy) on gait patterns and clinical outcomes among patients with a lack of progress in their postsurgical rehabilitation.

Methods

Twenty-two patients were prospectively followed during the study. Gait spatiotemporal parameters were measured at the initial evaluation, after 15 minutes of therapy, and after 3 months of therapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the short form (SF) 36 health survey were completed by patients before treatment and after 3 months of treatment.

Results

The WOMAC and SF-36 scores improved significantly after 3 months of treatment. Gait velocity, single limb support, and step length of the operated leg improved significantly even after a single 15 minutes treatment. Normal gait velocity was observed in 36% of patients after 3 months of treatment.

Conclusions

A physiotherapy program that included enhanced closed kinematic chain biomechanical therapy was beneficial for patients who experienced a suboptimal rehabilitation course after TKA.     

Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins.

The consequences of Helicobacter pylori attachment to human gastric cells were examined by transmission electron microscopy and immunofluorescence microscopy. H. pylori attachment resulted in (i) effacement of microvilli at the site of attachment, (ii) cytoskeletal rearrangement directly beneath the bacterium, and (iii) cup/pedestal formation at the site of attachment. Double-immunofluorescence studies revealed that the cytoskeletal components actin, alpha-actinin, and talin are involved in the process. Immunoblot analysis showed that binding of H. pylori to AGS cells induced tyrosine phosphorylation of two host cell proteins of 145 and 105 kDa. These results indicate that attachment of H. pylori to gastric epithelial cells resembles that of enteropathogenic Escherichia coli. Coccoid H. pylori, which are thought to be terminally differentiated bacterial forms, are capable of binding and inducing cellular changes of the same sort as spiral H. pylori, including tyrosine phosphorylation of host proteins.