Theophylline improves hypoglycemia unawareness in type 1 diabetes

Iatrogenic hypoglycemias and the subsequent occurrence of hypoglycemia unawareness are well-known complications of intensive insulin therapy in type 1 diabetic patients that limit glycemic management. From a pharmacological point of view, the adenosine-receptor antagonist theophylline might be beneficial in the management of hypoglycemia unawareness. Theophylline stimulates the release of catecholamines and reduces cerebral blood flow, thereby facilitating stronger metabolic responses to and a prompter perception of decreasing glucose levels. To test the effect of theophylline on responses to hypoglycemia, we performed paired hyperinsulinemic-hypoglycemic clamp studies in 15 diabetic patients with hypoglycemia unawareness and 15 matched healthy control subjects. In random order, we concurrently infused either theophylline or placebo. Measurements included counterregulatory hormones, symptoms, hemodynamic parameters, and sweat detection using a dew-point electrode. Additionally, middle cerebral artery velocities (V(MCA)) using transcranial Doppler were monitored as an estimate of cerebral blood flow. When compared with placebo, theophylline significantly enhanced responses of plasma epinephrine, norepinephrine, and cortisol levels in both diabetic patients and control subjects. Because of the theophylline, sweat production started at approximately 0.3 mmol/l higher glucose levels in both groups (P < 0.01), and symptom scores in diabetic patients approached those in control subjects. Theophylline decreased V(MCA) in both groups (P < 0.001), but significantly greater in diabetic patients (P < 0.01), and prevented the hypoglycemia-induced increase of V(MCA) that occurred during the placebo studies. We conclude that theophylline improves counterregulatory responses to and perception of hypoglycemia in diabetic patients with impaired awareness of hypoglycemia.     

Participants' perception of impact of a workshop on their preventive practices

A 90-minute interactive workshop, offered to small groups on request, was developed to help physicians include evidence-based preventive interventions in their practices. Between 25 September 1996 and 10 December 1997, 593 family physicians throughout the Province of Quebec (Canada) participated in one of the 40 workshops presented in all the regions of Quebec. Almost all participants (98%) completed the self-administered questionnaire. Their opinion of the achievement of three workshop objectives were evaluated using a seven-point Likert scale (-3 to +3)as their perception of the direct impact of the workshop on their practice. The workshop objectives were reached to a high degree: 2.1 (sd 0.90) for prescribing a proper check-up for adults; 1.83(sd 1.02) for explaining to the patient the reasons motivating his/her choice to include or exclude certain tests; 2.09 (sd 0.93)for using concrete and useful tool facilitating the integration of preventive measures in his/her professional practice. Female physicians and those under 40 perceived that the objectives were reached to a greater degree. Participants indicate their intention to modify their practice according to the clinical practice guidelines presented in the workshop.     

Trypanosoma brucei gambiense African trypanosomiasis: differences between men and women in severity of disease and response to treatment

To compare the characteristics of women and men with Trypanosoma brucei gambiense trypanosomiasis, all 3231 cases treated in Nioki hospital, Democratic Republic of Congo, from 1982 to 2000 were reviewed for demographic information, date and mode of diagnosis, pre-treatment cerebrospinal fluid (CSF) examination, treatment given and its adverse effects, and whether a diagnosis of relapse was made during post-treatment follow-up. Women had a higher apparent incidence of Gambian trypanosomiasis than men (1768 cases in females, 1463 in males), due to selective migration of males out of endemic foci and potentially to a higher exposure among females. Women presented with a less-advanced disease than men: 27% (384/1431) of women had CSF trypanosomes and 72% (1024/1431) had an abnormal CSF white cell count, while corresponding figures in men were 39% (431/1115) and 82% (910/1115) (P < 0.001 for both comparisons), presumably because of differences in health-seeking behaviour. Men (61/718, 8.5%) were more likely to relapse after melarsoprol treatment than women (41/857, 4.8%) (P = 0.004), even after adjustment for other independent risk factors in multivariate analysis. The cause of this higher risk of treatment failure among men treated with melarsoprol remains unclear.     

Dietary and nondietary determinants of vitamin K biochemical measures in men and women

Few epidemiological studies that rely on the food frequency questionnaire (FFQ) for dietary assessment have measured biomarkers of vitamin K intake to independently confirm associations between self-reported dietary vitamin K intake and disease risk. Associations were examined between two sensitive biomarkers of vitamin K status, plasma phylloquinone and serum percent undercarboxylated osteocalcin (%ucOC), and self-reported usual phylloquinone intake as estimated from a FFQ. The influence of other dietary and nondietary factors on plasma phylloquinone concentrations was also examined. Dietary phylloquinone intake was estimated using a FFQ in 369 men and 468 women of the Framingham Offspring Study. The prevalence of high %ucOC concentrations (>/= 20%), suggestive of a low vitamin K status, was 44% in men and 54% in women, respectively. After multivariate adjustment, the odds of a high %ucOC was 2.5 greater for women (odds ratio: 2.5; 95% confidence interval [CI]: 1.2-5.1) and almost three times greater for men (odds ratio: 2.8; 95% CI: 1.3-5.9) in the lowest dietary phylloquinone intake quintile category compared to the highest quintile category. Fasting triglyceride concentrations, smoking status and season were associated with plasma phylloquinone concentrations, independent of dietary phylloquinone intake. Phylloquinone and green vegetable intake was linearly associated with plasma phylloquinone, after adjustment for potential confounding factors. There were limitations in the use of the FFQ to predict plasma phylloquinone, evident in an observed plateau effect and required nondietary adjustment factors. Despite these caveats, these findings support the use of a FFQ for a relative assessment of vitamin K status in population-based studies.     

Mapping disease incidence in suburban areas using remotely sensed data

A method using remotely sensed data was developed to map the incidence of Q fever in the vicinity of Cayenne, French Guiana. A satellite image was processed to map land cover and generate a population density index, which was used to determine areas of high disease incidence during the 1996-2000 period. A comparison with results obtained using population census data showed strong concordance between the two incidence maps. All high-incidence areas identified using population census data were also detected using remotely sensed data. This demonstrates the potential of remote sensing as a new tool for rapid mapping of disease incidence in epidemiologic surveys.     

Pulse protein feeding pattern restores stimulation of muscle protein synthesis during the feeding period in old rats

Muscle loss during aging could be related to a lower sensitivity of muscle protein synthesis to feeding. To overcome this decrease without increasing protein intake, we proposed to modulate the daily protein feeding pattern. We showed that consuming 80% of dietary proteins at noon (pulse pattern) improved nitrogen balance in elderly women. The present study was undertaken in rats to determine which tissues are the targets of the pulse pattern and what mechanisms are involved. Male Sprague-Dawley 11- and 23-mo-old rats (n = 32 per age) were fed 4 isoproteic (18% protein) meals/d for 10 d. Then half of the rats at each age were switched to a 11/66/11/11% repartition of daily proteins (pulse pattern) for 21 d. On d 21, rats were injected with a flooding dose of L-(13)C-valine (50 atom% excess, 150 micromol/100 g body) and protein synthesis rates were measured in liver, small intestine and gastrocnemius muscle in either the postabsorptive or the fed state. Epitrochlearis muscle degradation rates and plasma amino acid concentrations were measured at the same times. The pulse pattern had the following effects: 1) it significantly increased liver protein synthesis response to feeding and postprandial plasma amino acid concentrations at both ages; 2) it restored a significant response to feeding of gastrocnemius muscle protein synthesis in old rats; and 3) it had no effect in small intestine or on muscle breakdown. Thus, using a pulse pattern could be useful in preventing the age-related loss of muscle by increasing feeding-induced stimulation of muscle protein synthesis.     

Improved smoking cessation in smokers given ultrasound photographs of their own atherosclerotic plaques

BACKGROUND: We examined whether making smokers aware that they had developed peripheral atherosclerosis would improve smoking cessation. METHODS: Smokers selected from the general population were randomly allocated to undergo high-resolution B-mode ultrasonography of their carotid and femoral arteries. All smokers received quit-smoking counseling. Smokers with > or =1 atherosclerotic plaque were given two photographs of a plaque with a relevant explanation. Quit rates were assessed by telephone 6 months later. RESULTS: Seventy-nine smokers did not undergo ultrasonography (A). Among the 74 smokers submitted to ultrasonography, 20 had no plaque (B) and 54 had > or =1 plaque (C). Quit rates were, respectively, 6.3, 5.0, and 22.2% in groups A, B, and C. Quit rates were higher in smokers submitted to ultrasonography (B + C vs A; P = 0.031) and in those receiving photographs (C vs A + B; P = 0.003). Smoking cessation was independently associated with intervention C (OR = 6.2; 95% CI = 1.8-21) and a white-collar job but not with age or gender. CONCLUSIONS: Providing smokers with photographs demonstrating atherosclerosis on their own person was an effective adjunct to physician's advice to quit smoking. Since ultrasonography is used increasingly often in clinical practice for cardiovascular risk stratification, this can provide an additional opportunity and means to deter smokers from smoking.     

Long-term fate of human telencephalic progenitor cells grafted into the adult mouse brain: effects of previous amplification in vitro

We assessed the developmental potential of human telencephalic progenitor cells, with and without previous amplification in vitro, following grafting into the nonlesioned adult mouse CNS. Cell suspensions, shown to contain neuroepithelium-like and neuroblast-like cells, were injected into the subventricular zone (SVZ) and the striatum. These two regions were selected for comparative studies because one, the SVZ, is mitotically active, whereas the other, the striatum, is mitotically inactive. In situ hybridization with a human-specific Alu probe showed that the cells survived for up to 30 weeks in both targets and migrated away from the injection site. Fresh cells continued to proliferate and gave rise to very extended grafts before differentiating into neurons and glia. We further show that, when grown in vitro prior to grafting, human cells acquired new properties: Their proliferation was very limited, and they differentiated more rapidly. This study therefore provides new information about the use of these cells, which are a potential tool for both cellular and gene therapy.