The Australian Diabetes,Obesity and Lifestyle Study (AusDiab)--methods and response rates

The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) addresses the urgent need for data on diabetes prevalence, risk factors and associated conditions in Australia. Here we describe the methods used and the response rates obtained. AusDiab was a population-based cross-sectional survey of national diabetes mellitus prevalence and associated risk factors in people aged > or =25 years, conducted between May 1999 and December 2000 in the six states and the Northern Territory of Australia. The study involved an initial household interview, followed by a biomedical examination that included an oral glucose tolerance test (OGTT), standard anthropometric tests, blood pressure measurements and the administration of questionnaires. Of the 20347 eligible people (aged > or =25 years and resident at the address for > or =6 months) who completed a household interview, 11247 (55.3%) attended for the biomedical examination. Of those who completed the biomedical examination 55.1% were female. Comparisons with the 1998 Australian population estimates showed that younger age responders were under-represented at the biomedical examination, while the middle-aged and older age groups were over-represented. Weighting of the AusDiab data for age and gender have corrected for this bias. AusDiab, which is the largest national diabetes prevalence study undertaken in a developed nation to have used an OGTT, provides a valuable national resource for the study of the prevalence and possible causes of diabetes, as well as identifying possible risk factors that may lead to diabetes. Furthermore, it generates the baseline data for a prospective 5-year cohort study. The data will be important for national and regional public health and lifestyle education and health promotion programs.     

The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no significant effect on cancellous or cortical bone measurements. CONCLUSIONS: Chronic alcohol consumption significantly reduced bone formation. Exercise had no effect on the bone and did not attenuate any of the negative effects of alcohol. The results suggest that alcohol consumption weakens the skeleton and increases the incidence of endurance-exercise-related bone injuries. Thus, individuals who are participating in endurance exercise and consuming alcohol may be at greater risk for exercise-related skeletal injuries. Further investigation of the potential for alcohol to induce detrimental effects on the hearts of individuals participating in endurance exercise is indicated.     

Establishing a laparoscopic gastric bypass program

OBJECTIVE: To evaluate the outcomes for laparoscopic Roux-en-Y gastric bypass in a newly developed bariatric surgery program. METHODS: A prospective analysis of the initial 100 patients who underwent laparoscopic Roux-en-Y gastric bypass at a community based teaching hospital between December 2000 and October 2001 was performed. Study endpoints included operative time, early (less than 7 days) and late complication rates, hospital length of stay (LOS), time to initiation of oral diet, and percentage of excess body weight loss. RESULTS: There were 91 women and 9 men with a mean age of 39 years (range 21 to 57). Mean preoperative weight was 126.4 kg (range 92.3 kg to 214 kg), with a mean preoperative body mass index of 47.4 (range 37.3 to 75.7). Ninety (90%) patients had at least one significant medical comorbidity (median = 6 per patient). Mean operative time was 2.4 hours (range 1.0 to 6.5; 3.0 hours for the first 50 patients and 1.8 hours for the last 50 patients). Three patients required conversion to open gastric bypass, all due to equipment failure (two harmonic scalpel failures and one linear stapler malfunction). Seven patients had early complications, 3 with anastomotic hemorrhage requiring transfusion, 3 with intestinal leaks requiring reoperation, and 1 with transected nasogastric tube. Eleven patients had late complications: 5 patients with small bowel obstruction, all due to herniation through the transverse colon mesentery (these occurred early in the series, prompting a change in technique, with no subsequent occurrences), 3 with gastrojejunostomy strictures requiring endoscopic dilation, 2 superficial wound infections, and 1 port-site incisional hernia. No complications occurred in the last 40 patients. No deaths occurred. Median hospital stay was 2 days (range 1 to 37); 3 days in the first 50 cases and 1 day in the last 50 cases. The median number of days to the start of an oral diet was 1 day. Average excess body weight loss was 34% (median follow-up 4 months). CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass is a technically challenging procedure that can be safely integrated into a bariatric treatment program with good results. Improved outcomes, shorter operative times, and fewer complications are associated with increased surgical experience.     

Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II)

The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in cultured cells, has been associated with generation of the promutagenic lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects. One possible source of this base may be 8-oxo-7,8- dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool, from which it is incorporated into DNA. To promote such incorporation, the metals would have to inhibit specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the nucleotide pool. The present study was designed to test such inhibition in vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein and Escherichia coli MutT protein. In the presence of Mg(II), the natural activator of 8-oxo-dGTPases, all four metals were found to inhibit both enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 microM for Cu(II), 30 +/- 8 microM for Cd(II), 376 +/- 71 microM for Co(II) and 801 +/- 97 microM for Ni(II). For MutT, they were 60 +/- 6 microM for Cd(II), 102 +/- 8 microM for Cu(II), 1461 +/- 96 microM for Ni(II) and 8788 +/- 1003 microM for Co(II). Thus, Cu(II) and Cd(II) emerged as much stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be generally more sensitive to metal inhibition than MutT. Interestingly, in the absence of Mg(II), the activity of the enzymes could be restored by Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the other metals being much less or non-effective. The difference in sensitivity to metal inhibition between the two enzymes may reflect the differences in the amino acid ligands, especially the cysteine ligand, outside their evolutionarily conserved Mg(II)-binding active sites, which might indicate predominantly non-competitive or uncompetitive mechanism of the inhibition. The overall results suggest that inhibition of 8-oxo- dGTPases may be involved in the mechanisms of induction of the 8- oxoguanine lesion in DNA by the metal ions studied, especially the non- redox-active Cd(II) cation.      

Localized muscular mucormycosis in a child with acute leukemia

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.      

Factor VIII-von Willebrand factor requires calcium for facilitation of platelet adherence

The role of divalent cations in platelet adherence to deendothelialized human arteries in flowing blood was investigated in an annular perfusion chamber. Spreading of platelets on the subendothelium was impaired below 30 microM of free Ca2+ ions (Ca2+). When Ca2+ was replaced by Mg2+, adherence was unchanged in perfusates without exogenous factor VIII-von Willebrand factor (FVIII-vWF), but the ability of FVIII-vWF to support platelet adherence was lost. Binding of FVIII-vWF to the vessel wall was independent of divalent cations, but bound FVIII-vWF was only able to mediate adherence after exposure to Ca2+. Pretreatment of FVIII-vWF with the calcium chelator EGTA (10 mM) resulted in loss of the ability to facilitate platelet adherence, while the ristocetin cofactor activity remained intact. Full restoration of the ability to mediate platelet adherence could only be obtained by prolonged dialysis against Ca2+ in the millimolar range. These data indicate that divalent cations have at least two separate roles to play in supporting platelet adherence: (1) platelet spreading on the subendothelium requires Ca2+ or Mg2+; (2) FVIII-vWF should be exposed to Ca2+ to obtain its optimal biologic activity in supporting platelet adherence.