Basal glucose turnover inPsammomys obesus

The aim of this study was to examine wholebody glucose turnover and glucose uptake into individual tissues inPsammomys obesus. The animals were classi-fied according to the level of circulating glucose and insulin in the fed state: group A was normoglycaemic and normoinsulinaemic (glucose <8.0 mmol/l, insulin <150 mU/l), group B was normoglycaemic and hyperinsulinaemic (glucose <8.0 mmol/l, insulin 150 mU/l), and group C was hyperglycaemic and hyperinsulinaemic (glucose 8.0 mmol/l, insulin 150 mU/l). The animals were deprived of food for 6 h, after which they were anaesthetized and cannulated, using the jugular vein for infusions and the carotid artery for blood sampling. Whole-body glucose turnover was measured using a primed-continuous infusion of 6-[³H]-glucose and saline to quantitatively assess hepatic glucose production (HGP), glucose disposal (Rd), and the metabolic clearance rate of glucose (MCR). Following the 2-h infusion period, the glucose metabolic index (Rg) of individual tissues was measured using a fixed-dose bolus of 2-deoxy-[¹⁴C]glucose. Under the steady-state conditions of the experiment, HGP was assumed to be equal to Rd, and both variables were found to be significantly correlated to the fasting glucose concentration (r=0.534,P<0.05,n=19). On the other hand, MCR was found to be inversely correlated to the fasting plasma glucose concentration (r=0.670,P<0.01,n=19). When the animals were divided into three groups as described above, HGP in group C animals was significantly elevated compared with group A (20.8±2.6 vs 12.7±0.6 mg · kg^–1 · min^–1;P<0.05), and MCR showed a tendency to be lower in group C than group A, although the difference was not statistically significant. HGP and MCR were not significantly different between groups A and B. Measurement of the glucose metabolic index in individual tissues showed that group C animals had significantly higher Rg values in muscles and adipse tissues compared with those in group A (P<0.05). In addition, Rg in group B white gastrocnemius and soleus were significantly higher than in group A despite similar rates of HGP and levels of glycaemia. These findings suggest that an early increase in skeletal muscle glucose uptake and hyperinsulinaemia can be demonstrated in group BPsammomysobesus before significant hyperglycaemia.     

Telephone ownership and deaf people: implications for telephone surveys.

OBJECTIVES: This study was done to determine the prevalence of telephone ownership in different deaf populations and to explore its implications for telephone-based surveys. METHODS: Multivariate analyses, with adjustments for sociodemographics and health status, were done of National Health Interview Survey (NHIS) data from 1990 and 1991, the years in which the NHIS Hearing Supplement was administered. RESULTS: Prelingually deafened adults were less likely than members of the general population to own a telephone (adjusted odds ratio [AOR] = 0.35; 95% confidence interval [CI] = 0.15, 0.82), whereas postlingually deafened adults were as likely as members of the general population to own one (AOR = 1.00; 95% CI = 0.78, 1.28). CONCLUSIONS: Telephone surveys risk marginalizing prelingually deafened adults because of low telephone ownership and language barriers between the deaf and hearing communities.     

HIV-1 vaccine-induced immune responses which correlate with protection from SHIV infection: compiled preclinical efficacy data from trials with ten different HIV-1 vaccine candidates

The specific immune mechanisms necessary and/or sufficient to elicit HIV-vaccine protection remain undefined. Utilising the SHIV rhesus macaque model the immunogenicity as well as the efficacy of ten different HIV-1 vaccine candidates was evaluated. Comparison of the immune responses induced, with the ability of the vaccine to protect from SHIV infection provided a means to determine which type of immune responses were necessary for protection. Vaccine candidates included VLPs, DNA, subunit protein with novel adjuvant formulations, ISCOMs and pox-virus vectors. Protection from SHIV infection was achieved in approximately half of the animals which received a primary intravenous cell-free challenge. The presence of CTL in the absence of other effector responses did not correlate with protection from this route and type of challenge. Virus neutralising antibodies (Nab) appeared to be necessary but alone were insufficient for protection. If Ag-specific IFN-gamma and/or IL-4 as well as lymphoproliferative (LP) responses were found with the lack of a detectable IL-2 response, then protection was not observed. Immunity correlated with the magnitude of Nab responses, beta-chemokines and as well as balanced, qualitative T-helper responses.     

Association between seasonal affective disorder and the 5-HT2A promoter polymorphism, -1438G/A

Genes involved in serotonin metabolism are good candidates for the pathogenesis of seasonal affective disorder (SAD). A functional variant in the serotonin transporter promoter, 5-HTTLPR, has recently been shown to be associated with SAD and seasonality. The purpose of this study was to determine whether -1438G/A, a polymorphism in the 5-HT2A promoter, is associated with SAD and seasonality, and whether it has additive effects with 5-HTTLPR on seasonality. Sixty-seven individuals with SAD and 69 normal volunteers, all screened with the SCID and diagnosed according to DSM-III-R criteria, were genotyped for the -1 438G/A 5-HT2A promoter polymorphism. All had been previously genotyped for 5-HTTLPR and had been assessed for seasonality by the Global Seasonality Scale. There was a significant increase in the frequency of the -1438A variant allele of the 5-HT2A promoter polymorphism in SAD patients (0.47) compared to matched controls (0.36) (P < 0.01). The difference in genotype distribution was also significant (P < 0.05). We found no association between the -1438G/A polymorphism and seasonality scores, and there was no additive effect with 5-HTTLPR on seasonality. In conclusion, we have shown that the -1438G/A 5-HT2A promoter variant is associated with SAD but not with seasonality. We suggest that the association may instead be with the depressive symptoms of SAD. However, these results should be treated with caution until replicated because of the possibility of false-positive findings in case-control association studies.     

Periictal diffusion-weighted imaging in a case of lesional epilepsy

PURPOSE: Diffusion-weighted MR imaging (DWI) has been used for the early diagnosis of acute ischemic lesions in humans and in animal models of focal status epilepticus. We hypothesized that DWI may be a sensitive, noninvasive tool for the localization of the epileptogenic area during the periictal period. METHODS: A periictal DWI study was performed on a 35-year-old patient during focal status epilepticus with repetitive prolonged focal motor seizures originating from a lesion in the right frontal lobe. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps. RESULTS: On DWI, a single area of signal increase (decrease in ADC) was found in the region of focal electrocorticographic seizures that was mapped intraoperatively. CONCLUSIONS: Ictal/postictal DWI may be a useful technique for seizure localization in patients with lesional epilepsy.     

Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration

PURPOSE: To determine whether ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) treatment leads to long-term photoreceptor survival in hereditary retinal degeneration. METHODS: An autosomal dominant feline model of rod-cone dystrophy was used throughout the study with two normal animals. In the first experiment, intravitreal injections of a human CNTF analogue (Axokine; Regeneron Pharmaceuticals, Tarrytown, NY) were administered to one eye of each animal (n = 10) beginning on postnatal day 10 and were repeated every 4 weeks. Clinical and histopathologic examinations were performed at 5.5, 9.5, and 13.5 weeks. In the second experiment, animals (n = 17) were randomly assigned to receive intravitreal injections of either Axokine (at half the initial dose), human BDNF, or the vehicle for Axokine to one eye at 5.5 weeks. The same therapy was repeated every 4 weeks in each group. Clinical and histopathologic examinations were performed at 9.5, 13.5, and 17.5 weeks. Photoreceptor survival was assessed by cell counting. Apoptotic cells were identified by morphology and a modified TdT-dUTP terminal nick-end labeling (TUNEL) technique. In the third experiment, two normal animals were treated with Axokine as in the first experiment. Glial fibrillary acidic protein ((GFAP) immunohistochemistry was performed to assess glial cell reaction. RESULTS: In the first two experiments, Axokine significantly prolonged photoreceptor survival (P < 0.01) and reduced the presence of apoptotic cells (P < 0.05) and TUNEL-positive cells (P < 0.05). In the second experiment, results in the the BDNF- and sham-injected eyes were not significantly different from those in the untreated eyes. Minimal posterior subcapsular cataract and mild retinal folds were found in all Axokine-treated eyes in both dystrophic and normal animals. These complications were milder in the second experiment when injections were started later and at a reduced dose. GFAP immunolabeling was also increased in all Axokine-treated eyes. CONCLUSIONS: Axokine, but not BDNF, delays photoreceptor loss in this hereditary retinal degeneration. Repeated injections maintain the protective effect.     

Treatment of stage D2 hormone refractory carcinoma of the prostate with 5-fluorouracil and Roferon-A: a Southwest Oncology Group study

Based upon prior data suggesting that alpha-interferon possesses chemomodulatory activity, the Southwest Oncology Group conducted a study in which patients with hormone refractory, metastatic (stage D2) adenocarcinoma of the prostate were treated with 5-fluorouracil (5-FU) and Roferon-A. All patients had bidimensionally measurable disease. Treatment consisted of 5-FU 750 mg/m2/day by continuous i.v. infusion for 5 days with Roferon-A 9 million units subcutaneously ono days 1, 3 and 5. Roferon-A was continued three times weekly throughout treatment. Following a one week hiatus from 5-FU (week 2), 5-FU was continued at a dose of 750 mg/m2 i.v. bolus weekly. Nineteen patients were evaluable for toxicity. The most common toxicities were gastrointestinal and mucosal, hematologic and a flu-like syndrome. There were no deaths related to treatment. Among the 14 patients evaluable for response, the response rate was 0% (95% confidence interval, 0-18%). Thirteen of the 19 evaluable patients have died with a median survival of 9 months. The combination of 5-FU and Roferon-A does not have sufficient activity against advanced, hormone refractory prostate cancer to warrant further investigation.