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.     

Whole-heart cine MRI using real-time respiratory self-gating.

Two-dimensional (2D) breath-hold cine MRI is used to assess cardiac anatomy and function. However, this technique requires cooperation from the patient, and in some cases the scan planning is complicated. Isotropic nonangulated three-dimensional (3D) cardiac MR can overcome some of these problems because it requires minimal planning and can be reformatted in any plane. However, current methods, even those that use undersampling techniques, involve breath-holding for periods that are too long for many patients. Free-breathing respiratory gating sequences represent a possible solution for realizing 3D cine imaging. A real-time respiratory self-gating technique for whole-heart cine MRI is presented. The technique enables assessment of cardiac anatomy and function with minimum planning or patient cooperation. Nonangulated isotropic 3D data were acquired from five healthy volunteers and then reformatted into 2D clinical views. The respiratory self-gating technique is shown to improve image quality in free-breathing scanning. In addition, ventricular volumetric data obtained using the 3D approach were comparable to those acquired with the conventional multislice 2D approach.     

American Society of Nuclear Cardiology review of the ACCF/ASNC appropriateness criteria for single-photon emission computed tomograph myocardial perfusion imaging (SPECT MPI)

Conclusion  The ACCF/ASNC AC for SPECT MPI provides recommendations for the appropriate use of SPECT MPI. After the publication of the AC document in 2005, the AC has been used by nuclear cardiology practices with many clinical studies evaluating the list of indications in routine clinical practice. From these data. ASNC recommends minor but important changes to the indication list, suggesting the addition of 6 new indications and the modification of the definitions for “chest pain syndrome” and “CHD high risk.”. An objective review of existing indications focused on only those indications that had significant variability among the reviewers (n=20). These indications were reviewed in the presence of existing and new evidence-based data, and ASNC recommends that the grades for 6 indications be re-evaluated. The AC for SPECT MPI will require periodic review as new evidence becomes available or as clinical practice evolves. ASNC recognizes the importance of these criteria to improve the quality of patient care, and it will continue to play a key role in assembling the information for this ongoing review. From the current summary of evidence, ASNC consensus opinions, and ASNC recommendations in this document, ASNC strongly recommends that the AC guidelines be reviewed Prepared by the American Society of Nuclear Cardiology Quality Assurance Subcommittee for Quality in Imaging Standards. Reviewed by members of the American Society of Nuclear Cardiology Quality Assurance Committee. Approved by the American Society of Nuclear Cardiology Board of Directors, September 6, 20.     

Prospective evaluation of the effect on initial brain metastases from small cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating multidrug regimen

BACKGROUND:: During the 1980s reports describing the effect of systemic chemotherapyon brain metastases from chemosensitive tumours emerged, includinga few retrospective reports on small cell lung cancer (SCLC)patients. DESIGN:: Previously untreated SCLC patients with no other malignancy,but in some cases with mixed histological subtype, who had symptomaticbrain metastases verified by contrast enhanced CT-scan, weretreated with a multidrug combination chemotherapy regimen andno cranial irradiation. Radiotherapy was optional at cranialrelapse or progression at the discretion of the physician incharge. The intracranial effect was evaluated by 4-weekly CT-scanand neurological examination, according to a standardized scoringsystem. END POINTS:: Intracranial response, duration of response, neurological score,terminal CNS status, and survival. RESULTS:: 21 patients were included, corresponding to 8.6% of consecutiveSCLC patients at our institution. 8 patients died before follow-upleaving 13 evaluable for response. In the former group, allpatients had WHO performance status of 3–4 compared to6/13 in the latter group. Of the 13 evaluable patients, 1 hadearly progression in the CNS and 1 had no change. 11 had CT-scanverified response, with a median duration of 135 days. Mostpatients, including all complete responders, had improvementin their neurological score. 6 out of 11 responders died withoutactive CNS disease. The crude median survival was 111 days,whereas the median survival(early deaths excluded) was 197 days. CONCLUSION:: Systemic combination chemotherapy was effective for palliationof initial brain involvement in the majority of patients ina small consecutive series. The role of consolidating cranialirradiation in responders should be assessed by a randomizedtrial. small cell carcinoma, brain metastases, chemotherapy     

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.     

Neural classifier construction using regularization, pruning and test error estimation

In this paper we propose a method for construction of feed-forward neural classifiers based on regularization and adaptive architectures. Using a penalized maximum likelihood scheme, we derive a modified form of the entropic error measure and an algebraic estimate of the test error. In conjunction with optimal brain damage pruning, a test error estimate is used to select the network architecture. The scheme is evaluated on four classification problems.     

Vesico-anal influences in healthy intact humans: Quantificated by responses in the external anal sphincter following transcranial cortical stimulation

EMG responses in the external anal sphincter (EAS), the rectus abdominis muscle (RA), and the anterior tibial muscle (TA) were recorded following single magnetic transcranial cortical stimulations (TCCS) in seven healthy volunteers. The responses in the EAS differed from the responses in the other muscles. They had comparatively long durations ranging from 1 to 2 seconds, no inhibitory periods were observed, and there was no tendency for habituation to occur following a limited number of stimuli. The responses recorded in the EAS were used as test responses in order to evaluate the excitability changes in the EAS motoneurons occurring during bladder filling. Cystometries with filling rates of 15, 50 and 200 ml/min were done. During these cystometries TCCS were applied repeatedly, with constant strength, after each 50 ml of filling up to bladder capacity. The responses following TCCS changed in a highly reproducible way during bladder filling. After 100–200 ml of filling, the responses had longer latencies, diminished sizes, and shorter durations. When the filling reached a level 50–150 ml below capacity, the responses in most subjects again became greater and the latencies shorter. The changes were believed to be physiological. It was concluded that the EAS motoneurons are under both inhibitory and facilitatory influence during bladder filling in intact healthy humans. Facilitatory influences are often observed when the bladder is filled close to capacity. At lower bladder volumes the observed influence is always inhibitory. A decrease in the EMG activity of the EAS during filling cystometry should consequently not be regarded as a pathological response.     

Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat,and the effect of type I and type II corticosteroid receptor antagonists

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.