Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe

A number of patients with type 2 diabetes are GAD antibody positive. A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in recently diagnosed drug-naive patients with type 2 diabetes that allows for the evaluation of GAD positivity in the context of anthropometric and biochemical characteristics. Of the 4,134 subjects enrolled in ADOPT for whom GAD status was obtained, 174 (4.2%) were GAD positive, with the prevalence of GAD antibodies being similar in North America (4.7%) and Europe (3.7%). Although BMI and age were similar, GAD-positive patients had a lower fasting insulin level, compatible with them being more insulin sensitive. The lower fasting insulin concentration was accompanied by a decreased early insulin response to oral glucose. However, when this insulin response was corrected for the degree of insulin sensitivity, GAD-positive and -negative patients had similar beta-cell function. Consistent with the difference in insulin sensitivity, GAD-positive patients had higher HDL cholesterol and lower triglyceride levels. In the GAD-positive individuals, the prevalence of the metabolic syndrome as defined by NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) was also lower (74.1 vs. 83.7%, P = 0.0009). These phenotypic differences may underlie a potential difference in the natural history of hyperglycemia and its clinical outcomes.     

Ancestry reported by white adults with cutaneous melanoma and control subjects in central Alabama

Background  

We sought to evaluate the hypothesis that the high incidence of cutaneous melanoma in white persons in central Alabama is associated with a predominance of Irish and Scots descent.     

Afterload reduction therapy in patients following intraatrial baffle operation for transposition of the great arteries

Patients with intraatrial baffle procedure for transposition of the great arteries (TGA) have diastolic dysfunction, decreased exercise capacity, stroke volume response and elevated systemic vascular resistance (SVR) during exercise. Angiotensin-converting enzyme (ACE) inhibitors improve exercise capacity in adults with congestive heart failure by improving diastolic function and decreasing SVR. We tested the hypothesis that ACE inhibitors decrease SVR and improve exercise capacity in patients after intraatrial baffle procedure for TGA. We studied the effects of enalapril in nine patients with TGA s/p intraatrial switch (mean age, 13.8 ± 3 years) 7 to 21 years (mean, 12 ± 4 years) after intraatrial baffle procedure. Enalapril (0.5 mg/kg/day, maximum dosage 20 mg bid) was administered for 12 months. Patients exercised using a cycle ergometer ramp protocol (0.25 W/kg/min) before enalapril (baseline), 1 month, 6 months, and 12 months after treatment initiation. Heart rate, blood pressure, cardiac output, respiratory rate, minute ventilation, oxygen consumption (VO2), total exercise time, work, and power were measured. SVR, cardiac index, and stroke volume index (SVI) were calculated. Two-tailed paired Student's t-test was used to compare data to those of normal control patients and the patients' baseline data. Patients had lower resting heart rate, cardiac index, maximum heart rate, cardiac index (CI), SVI, VO2, exercise time, work, and power and higher maximal SVR at baseline compared to normal control patients. There was no significant difference in total exercise time, work, power, VO2 (rest/peak), SVR, SVI, and CI after 12 months of therapy compared to patients' baseline values. We conclude that short-term (<1 year) use of enalapril does not improve exercise performance in patients with TGA in whom the intraatrial baffle procedure has been performed.     

Primary permanent arterialization of the portal vein in liver transplantation

Permanent total arterialization of the portal vein in liver transplantation has been described as a method of providing portal inflow after insufficient thrombectomy due to chronic occlusion of the portal-vein system. A specific problem is the restriction of the arterial inflow and its long-term adaptation after transplantation. We describe here the surgical techniques and clinical course of three patients who underwent portal-vein arterialization for liver transplantation. Two patients had an uneventful course. In one patient, a flow reduction by means of coil embolization of one arterial inflow branch was performed; thereafter, the patient recuperated well. Analysing the microcirculation of an arterialized graft in comparison with liver grafts with normal non-arterialized portal-vein inflow, we observed an increase in inter-sinusoidal distance and a decrease in sinusoidal red blood cell velocity. From a technical point of view, we recommend permanent portal-vein arterialization by an iliac artery graft interposition from the subdiaphragmatic aorta. The inflow to the portal vein can easily be reduced by the banding of the arterial graft interposition.     

Individueller Gesichtsschutz nach Frakturversorgung am Nasenbein und Jochbogen bei Profifußballern

Background. The treatment of sport accidents in professional athletes requires special treatment modalities, especially concerning quick rehabilitation. Case report. As early as 5 days after treatment of a nasal bone fracture under local anesthesia on an outpatient basis, an individual nasal shield out of silicone and acrylate could be manufactured from a facial impression for a professional soccer player. This shield enabled unlimited participation in the ensuing premier league matches 7 and 14 days after the accident. The same treatment was performed for another team member after closed reposition of a zygomatic arch fracture. Treatment modalities and manufacturing of the facial protection masks in these two cases are presented as examples.     

High-performance liquid chromatography/fluorescence detection of S-methylglutathione formed by glutathione-S-transferase T1 in vitro

Glutathione-S-transferase T1 (GSTT1-1) is a major isoenzyme for the biotransformation of halomethanes. The enzyme activity is located, among other places, in human liver and erythrocytes and is subject to a genetic polymorphism. Metabolism of the halomethanes via GSTT1-1 yields S-methylglutathione (MeSG). A new HPLC assay for the enzymatic formation of MeSG was developed. The glutathione conjugate was derivatized with 9-fluorenylmethyl chloroformate, followed by reverse-phase HPLC with gradient elution and fluorescence detection. The limit of detection was as low as about 39 pmol MeSG on-column. Including derivatization and HPLC analysis, samples could be run at 42-min intervals, thus enabling a high sample throughput. The entire method was validated for analyte recovery (78.2%) and for variations in detector response with replicated injections (11.8%) and with analyses on each of 11 consecutive days (15.2%) with erythrocyte lysate incubations as the matrix. The time-, protein-, and substrate-dependences of the enzymatic catalysis with the model substrates methyl bromide (MeBr) and methyl chloride (MeCl) were studied. Due to its strong electrophilic character, MeBr caused a high level of spontaneous MeSG formation from glutathione in a protein-free medium and a substrate-trapping side reaction in the presence of proteins. Therefore, enzymatic MeSG formation rates may only be determined with MeBr concentrations of at least 3000 ppm in the presence of limited amounts of protein (e.g. 100 microl erythrocyte lysate). In contrast, MeCl showed a lower alkylating potential allowing enzymatic catalysis to be the dominant reaction in incubations with 10,000 ppm MeCl and 2 ml erythrocyte lysate.     

Femoro-distal ePTFE bypass grafting using femoro-crural patch prosthesis (FCPP). Results of a prospective clinical study

Femorodistal bypass using exclusively PTFE is known to have a poor prognosis, mostly because of the development of myointimal hyperplasia (MIH). Several vein patch techniques are established but the role of hemodynamics within the anastomotic site has only been explained insufficiently and is hardly considered clinically. In a prospective study, between 6/1992 and 7/1998 129 patients (89 m/40 f, mean age 65.2 +/- 10.0 years) with critical limb ischemia and no usable saphenous vein were included to undergo femorodistal ePTFE bypass grafting with a new, hemodynamically optimized distal end-to-side anastomosis. Patients were followed at 6-month intervals with clinical investigation and color-coded Doppler sonography. Primary and secondary graft patency (PPR, SPR), limb salvage, and patient survival were calculated according to Kaplan-Meier. With a median follow-up of 45 (range 6 to 72) months, PPR and SPR at 1, 3 and 5 years were 63.0, 35.7 and 27.6% and 74.5, 44.8%, and 37.6%, respectively. Limb salvage at 1, 3 and 5 years was 86.4%, 78.7% und 73.2%. There was no perioperative mortality. Graft infection occurred in 7 patients (5.2%). ePTFE bypass grafting represents a valuable option for infragenicular and crural reconstruction in the absence of autologous vein. The new anastomotic design was feasible and represents another adjunct to possibly improve patency of femorodistal bypass allografts.     

Ether--lipid (alkyl-phospholipid) metabolism and the mechanism of action of ether--lipid analogues in Leishmania

Ether-lipid (alkyl-phospholipid) analogues such as Miltefosine possess potent in vitro and in vivo anti-leishmanial activity and these compounds are currently undergoing clinical trials in humans. These analogues are also effective against Trypanosoma cruzi and Trypanosoma brucei subspecies but their mode of action is not known. Leishmania have high levels of ether-lipids and these are mainly found in the glycosylphosphatidylinositol-anchored glycolipids and glycoproteins present on the surface of the parasites. In Leishmania mexicana promastigotes we have studied both the initiating steps for the biosynthesis of ether-lipids, and key remodelling steps. The effect of Miltefosine and Edelfosine, on key enzymes involved in the metabolism of ether-lipids has been studied. The enzymes include dihydroxyacetonephosphate acyltransferase, sn-l-acyl-2-lyso-glycero-3-phosphocholine and sn-l-alkyl-2-lyso-glycero-3-phosphocholine acyltransferases. We confirm that the initiating steps in ether-lipid metabolism in Leishmania are present in glycosomes, and that Miltefosine or Edelfosine did not perturb these enzymes. The metabolism of the latter phosphatidylcholine base intermediates, which may be involved in the remodelling of acyl- and alkyl-glycerophospholipids, was also seemingly associated with glycosomes. Both Miltefosine and Edelfosine inhibited this microbody (glycosomal) located alkyl-specific-acyl-CoA acyltransferase in a dose-dependent manner with an inhibitory concentration of 50 microM. It is suggested therefore that a perturbation of ether-lipid remodelling could be responsible for the anti-leishmanial action of these drugs.