Reduced incidence and severity of accelerated graft atherosclerosis in cardiac transplant recipients treated with prophylactic antilymphocyte globulin.

Allograft coronary artery disease (ACAD) is the major factor limiting long-term survival of cardiac transplant recipients (CTRs). Although cyclosporine based triple drug immunosuppression has not decreased the occurrence of ACAD, some preliminary data suggests that prophylactic antilymphocyte preparations may reduce the incidence of this problem. All CTRs at Henry Ford Hospital have uniformly received prophylactic Minnesota Antilymphocyte Globulin (ALG), thereby providing a unique opportunity to investigate this hypothesis. One hundred three CTRs were followed for a median duration of 34 months with annual angiograms begun one year after transplant. Patients who died without an angiogram were considered to have ACAD based on autopsy results or if their death was clinically suspicious. Ninety-two patients underwent at least one angiogram. Fourteen patients had abnormal angiograms. Nine patients were identified as having ACAD by non-angiographic criteria. Five had autopsy proven disease, 3 died suspiciously, and 1 underwent successful re-transplantation for ACAD. By Kaplan-Meier analysis, the risk of developing ACAD was 12% in 1 year, 16% in 2 years, 22% in 3 years, 26% in 4 years, and 29% in 5 years. Risk of ACAD increased with older recipient's age, higher triglyceride levels, and diabetes, but was not affected by active CMV infection, number of acute rejection episodes, and HLA mismatching. These results suggest that prophylactic ALG reduces the occurrence of ACAD.     

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.     

Postural responses to lateral perturbation in healthy subjects and ankle sprain patients.

The purpose of this study was to investigate postural responses of healthy subjects and patients with recent ankle sprains following a perturbation that created sway in the frontal plane. EMG data were taken from the posterior tibialis (PT) (not monitored in patients), peroneal longus (PL), and tibialis anterior muscles (TA). Subjects stood on a platform that provided a rotational perturbation (approximately 70 degrees.s-1) in the frontal plane. This perturbation had the effect of everting and loading one limb while inverting and unloading the contralateral limb. An initial response in the PT of the loaded limb and the PL of the unloaded limb was noted at approximately 50 ms following the perturbation. This was followed by a bilateral response in the TA at 60 ms. The amplitude of the TA muscle was significantly greater in the loaded limb. For ankle sprain patients a bilateral TA response and a PL response in the unloaded limb was noted at approximately 65 ms. TA response amplitude ratios between the loaded and unloaded limbs were similar to that of the healthy subjects. These data suggest that ankle sprain patients use a modified postural response following lateral perturbation as a compensation for the injury.     

Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

Ethnic Differences in Bone Mineral Density Between Inuit and Caucasians in North Greenland Are Caused by Differences in Body Size

Data on bone mineral density (BMD) in living Inuit are limited and BMD measurements in Arctic Inuit using Dualenergy X-ray Absorptiometry (DXA) are lacking. Ethnicity may be important for bone mass. The aim of this study was to validate DXA in rural Arctic Greenland, to measure BMD in Greenland Inuit and Caucasians, and to estimate the importance of ethnicity for BMD. We measured the BMD in 80 healthy subjects living in Ilulissat and Saqqaq in North Greenland twice in both distal forearms and in both heels using peripheral DXA (pDXA). Participants were stratified by origin (Inuit[settlement])/Caucasians, n = 33 [19]/28), gender (men/women, n = 37/43), and age (30-39/40-49, n = 32/48). Caucasians were bigger than Inuit (men/women, height p < 0.001/p < 0.001; weight p = 0.01/ p = 0.026), but had similar BMI (p = 0.42/0.70). Triplicate pDXA measurements showed individual CV% = 0.16-1.79%; overall CV% = 1.1% (forearm)/1.0% (heel). Data followed the normal distribution (p = 0.65-0.99) with identical variances between Inuit and Caucasians (p = 0.12-0.63). Mean BMD in right forearm/left forearm/right heel/left heel was: Inuit men 0.570/0.568/0.549/0.536 g/cm2; Inuit women 0.484/0.474/0.473/0.464 g/cm2; Caucasian men 0.580/0.570/0.646/0.638 g/cm2; Caucasian women 0.495/0.496/0.552/0.553 g/cm2. An ethnic difference in heel BMD (p < 0.001) disappeared when adjusted for weight (p = 0.30). No difference was found in forearm BMD. In conclusion, pDXA is feasible and reliable in rural Greenland. Ethnic differences in BMD are small and may reflect differences in body size.     

Tibial hypo-/aplasia with preaxial syn- and polydactyly

Summary Tibial hypo-/aplasia with preaxial syn- and polydactyly is a rare autosomal dominant condition. Fewer than 20 cases have so far been described. One is presented here.