Association of serum caffeine concentrations with serum glucose levels in caffeine-drug users and non-users - results of German National Health Surveys

The purpose of this study was to explore the association of serum caffeine concentrations with serum glucose levels in caffeine-drug users and non-users, aiming at the chronic effects of caffeine on glucose metabolism in comparison with known acute effects of caffeine. Eight hundred and fourteen caffeine-drug users and 623 non-users were identified from German National Health Surveys. Their serum caffeine concentrations and glucose levels were measured. The associations of caffeine concentrations with glucose levels were established by correlation analysis and multivariable regression analysis in caffeine-drug users and non-users separately. Antidiabetic therapy was considered. Caffeine concentrations were closely positively correlated to serum glucose levels in caffeine-drug users (Spearman r = 0.117, p = 0.001; partial r = 0.102, p = 0.020) particularly in women (Spearman r = 0.155, p < 0.001; partial r = 0.150, p = 0.005) although the correlation was weak as shown by multivariable regression analysis. The serum glucose levels were significantly higher (5.403 +/- 0.033 vs. 5.306 +/- 0.037 mmol/l) whereas the magnesium level was significantly lower (0.8941 +/- 0.0026 vs. 0.9024 +/- 0.0030 mmol/l) in caffeine-drug users than in non-users. No associations of caffeine concentrations with serum glucose levels were found in any groups of caffeine-drug non-users in our study. Whereas acute intake of caffeine-drugs may impair glucose metabolism, chronic intake of caffeine exclusively from diet has little effects on glucose metabolism and therefore may not contribute to the risk reduction of type 2 diabetes that was found in recent coffee consumption studies.     

Pattern of regional cerebral blood-flow changes induced by acute heroin administration--a perfusion MRI study

PURPOSE: Although both the subjective and physiological effects of abused psychotropic substances have been characterized, less is known about their effects on brain function. We examined the actions of intravenous diacetylmorphine (heroin), the most widely abused opioid, on regional cerebral blood flow (rCBF), as assessed by perfusion-weighted MR imaging (PWI) in a double-blind and placebo-controlled setting. MATERIAL AND METHODS: Eight male subjects dependent of diacetylmorphine (mean age 36 years, range: 26 to 44 years), who had participated in a clinical diacetylmorphine maintenance program, underwent PWI with gadolinium injection. At two sessions separated by 2-7 days, the participants were examined 80 s after intravenous administration of either diacetylmorphine or saline. rCBF in four regions of interest (amygdala, vermis of the cerebellum, anterior cingulated cortex and thalamus) was compared with heroin versus placebo. RESULTS: In the cerebellum, thalamus and cingulated cortex, there were no significant differences in perfusion values between diacetylmorphine and placebo. In the amygdala, perfusion values were 0.8+/-0.4 and 0.5+/-0.2 on the left, and 0.9+/-0.4 and 0.6+/-0.3 on the right, with diacetylmorphine and with placebo, respectively (t-test results were P=0.044 and P=0.033 on the left and right sides, respectively). Other differences in perfusion values between the drug and placebo did not reach statistical significance. CONCLUSION: Perfusion MRI demonstrated differences in brain hemodynamics induced by drug intake.     

Intrahepatic cholestasis of pregnancy: the severe form is associated with common variants of the hepatobiliary phospholipid transporter ABCB4 gene

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is characterised by troublesome maternal pruritus, raised serum bile acid levels and increased fetal risk. Mutations of the ABCB4 gene encoding the hepatobiliary phospholipid transporter have been identified in a small proportion of patients with cholestasis of pregnancy. In a recent prospective study on 693 patients with cholestasis of pregnancy, a cut-off level for serum bile acid (> or =40 micromol/l) was determined for increased risk of fetal complications. OBJECTIVES: To investigate whether common combinations of polymorphic alleles (haplotypes) of the genes encoding the hepatobiliary ATP-binding cassette (ABC) transporters for phospholipids (ABCB4) and bile acids (ABCB11) were associated with this severe form of cholestasis of pregnancy. METHODS: For genetic analysis, 52 women with bile acid levels > or =40 micromol/l (called cases) and 52 unaffected women (called controls) matched for age, parity and geographical residence were studied. Gene variants tagging common ABCB4 and ABCB11 haplotypes were genotyped and haplotype distributions were compared between cases and controls by permutation testing. RESULTS: In contrast with ABCB11 haplotypes, ABCB4 haplotypes differed between the two groups (p = 0.019), showing that the severe form of cholestasis of pregnancy is associated with the ABCB4 gene variants. Specifically, haplotype ABCB4_5 occurred more often in cases, whereas haplotypes ABCB4_3 and ABCB4_7 were more common in controls. These associations were reflected by different frequencies of at-risk alleles of the two tagging polymorphisms (c.711A: odds ratio (OR) 2.27, p = 0.04; deletion intron 5: OR 14.68, p = 0.012). CONCLUSION: Variants of ABCB4 represent genetic risk factors for the severe form of ICP in Sweden.     

Unmet needs in the diagnosis and treatment of dyslipidemia in the primary care setting in Germany

OBJECTIVES AND METHODS: DETECT is a cross-sectional study of 55,518 unselected consecutive patients in 3188 representative primary care offices in Germany. In a random subset of 7519 patients, an extensive standardized laboratory program was undertaken. The study investigated the prevalence of cardiovascular disease, known risk factors (such as diabetes, hypertension and dyslipidemia and their co-morbid manifestation), as well as treatment patterns. The present analysis of the DETECT laboratory dataset focused on the prevalence and treatment of dyslipidemia in primary medical care in Germany. Coronary artery disease (CAD), risk categories and LDL-C target achievement rates were determined in the subset of 6815 patients according to the National Cholesterol Education Program (NCEP) ATP III Guidelines. RESULTS: Of all patients, 54.3% had dyslipidemia. Only 54.4% of the NCEP-classified dyslipidemic patients were diagnosed as 'dyslipidemic' by their physicians. Only 27% of all dyslipidemic patients (and 40.7% of the recognized dyslipidemic patients) were treated with lipid-lowering medications, and 11.1% of all dyslipidemic patients (41.4% of the patients treated with lipid-lowering drugs) achieved their LDL-C treatment goals. In conclusion, 80.3% of patients in the sample with dyslipidemia went undiagnosed, un-treated or under-treated.     

Improved neovascularization of PEGT/PBT copolymer matrices in response to surface modification by biomimetic coating

PEGT/PBT (polyethylene glycol terephthalate/polybutylene terephthalate) copolymer matrices with three different surface coatings [calcium-phosphate (Ca-P), collagen, and gas plasma] were placed into dorsal skinfold chambers of 24 balb/c mice. Untreated PEGT/PBT matrices served as the controls. The basal surfaces of the implants directly contacted the striated skin muscle. Neovascularization of the implants was analyzed by intravital fluorescence microscopy. Microcirculatory observations were performed in the surrounding skin muscle, at the border zone of the implant, and in the center of the implant. The functional vessel density (FVD; mm/mm2), as the length of perfused microvessels per observation area, was measured by computer-assisted analysis. The FVD served as the parameter of neovascularization. At the end of the protocol, histological observation of hematoxylin/eosin-standard-stained sections was performed by light microscopy. The FVD in the center of the implant on day 8 was only observed in gas-plasma-coated (8.8 +/- 10.2 mm/mm2) and Ca-P-coated implants (0.8 +/- 2.0 mm/mm2). None of the other groups showed perfused microvessels in the center of the implant on day 8 (p < 0.05). The FVD values in the center of the gas-plasma-coated and the Ca-P-coated implants were 20.7 +/- 8.2 and 19.2 +/- 15.5 mm/mm2 as compared with 7.1 +/- 17.4 and 7.7 +/- 5.9 mm/mm2 for collagen-coated and untreated implants on day 16. The histological examination confirmed the profound microvascular ingrowth into the matrix pores of the gas-plasma-treated and the Ca-P-coated copolymer matrices in the center of the implants. The study showed that the ingrowth of microvessels into PEGT/PBT matrices can be accelerated by Ca-P coating and gas plasma treatment in the dorsal skinfold chamber in mice.     

Competition between native liver and graft in auxiliary liver transplantation in a rat model

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% +/- 55% of the intraoperative weight), whereas, the graft weight was only 76% +/- 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% +/- 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 +/- 126 vs 262 +/- 97 vs 216 +/- 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were 相似文献   

Death After Graft Loss: An Important Late Study Endpoint in Kidney Transplantation

Traditional study endpoints utilized in renal transplantation have included graft survival, and death with a functioning graft. We analyzed the risk factors for death after allograft loss (DAGL) among a total of 78564 primary renal transplants reported to the United States Renal Data System (USRDS) from 1988 to 1998. Cox models were used to investigate risk factors for DAGL. Of 15528 deaths, 10816 occurred before, and 4712 occurred after graft loss. Overall annual adjusted death rates were more than 3-fold higher after graft loss as compared to before graft loss (9.42% vs. 2.81%). By Cox model, dialysis for more than 2 years was associated with a more than 2-fold relative risk for DAGL (RR = 2.2, Cl = 1.88-2.53), while transplant time was not associated with DAGL. Infection related graft losses showed a strong association with DAGL (RR = 1.64, Cl = 1.31-2.07). Acute rejection and thrombosis as causes of graft loss were also significantly associated with the risk for DAGL (RR = 1.35, Cl = 1.23-1.47 and RR = 1.39, Cl = 1.39). Patient survival after graft loss is poor. The lack of association between DAGL and transplant time, as opposed to the strong relation to pretransplant dialysis time, would suggest the adverse effects of previous uremia-mediated damage may be contributing to this phenomenon, along with the adverse effects of loss of renal function.     

Long‐Term Renal Allograft Survival: Have we Made Significant Progress or is it Time to Rethink our Analytic and Therapeutic Strategies?

Impressive renal allograft survival improvement between 1988 and 1995 has been described using projections of half-lives based on limited actual follow up. We aimed, now with sufficient follow up available to calculate real half-lives. Real half-lives calculated from Kaplan-Meier curves for the overall population as well as subsets of repeat transplants and African Americans recipients were examined. Real half-lives were substantially shorter than projected half-lives. As a whole, half-lives have improved by about 2 years between 1988 and 1995 as compared to the earlier projected 6 years of improvement. The improvement seems to be driven primarily by the improvement in graft survival of re-transplants. First transplants showed a cumulative increase in graft survival of less than 6 months. Projected half-lives are a risky estimation of long-term survival especially when based on short actual follow up. First transplant survival has only marginally improved during the early years of post transplant follow up while no significant improvement in long-term survival could be detected between 1988 and 1995. Redirection of attention from early endpoints towards the process of long-term graft loss may be necessary to sustain early gains in the long term.     

InDuo, a novel combined insulin injection and blood glucose monitoring device - effective and save as other devices, and patient preference.

BACKGROUND AND AIM: Frequent blood glucose (BG) monitoring and insulin administration are necessary in intensive insulin regimes. A new integrated system, InDuo is a compact and portable combined insulin doser and BG monitor, designed to overcome some of the limitations of current insulin therapy. The aim of the study was to compare InDuo and a non-integrated system (HumaPen Ergo and Accu-Chek Sensor Meter) for efficacy and safety, and to evaluate patients preference. MATERIALS AND METHODS: The trial design was a multicentre, randomised, 12-week, open-label, comparative, two period crossover. One hundred and ten patients with diabetes, treated with a basal bolus regime, were included. The subjects were assigned to use either InDuo or the non-integrated system. After six weeks of treatment, the subjects were transferred to the alternative system. To assess efficacy, fasting plasma glucose (FBG), 7-point blood glucose profile, serum fructosamine and HbA1c were measured. Serum fructosamine and FBG were measured at baseline and at six and 12 weeks; HbA1c was measured at baseline and week 12. Safety endpoints were number and severity of hypoglycaemic episodes, adverse events and adverse device effects. Patient preference was assessed by a comparative device questionnaire at 12 weeks. RESULTS: Analysis with an ANOVA mixed model showed no difference after each treatment between serum fructosamine or between FBG levels. HbA1c decreased during the trial from 7.5 % +/- 1.2 to 7.1 % +/- 0.8 at 12 weeks. The safety profiles were similar for both treatments for hypoglycaemic episodes. The incidence of adverse events was also similar. There were 10 adverse device effects reported: eight for the Innovo device in the InDuo, one for the InDuo device and one for the Accu-Chek Sensor Meter. The comparative device questionnaire at 12 weeks showed patients strongly preferred InDuo to HumaPen Ergo and Accu-Chek Sensor Meter (all p < 0.0001). Of those preferring InDuo, more than 60 % classified their choice as very or extremely strong. Both memory functions in InDuo(R) (i. e., for insulin dosage and for blood glucose readings) were used by more than 70 % of the patients. CONCLUSION: Treatment with the InDuo system was as effective and safe as treatment with the non-integrated system. Almost 75 % preferred using InDuo to the non-integrated HumanPen Ergo and Accu-Chek Sensor Meter.