Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

A method for calculation of true coincidence summing correction factors for extended sources.

In gamma-ray spectrometry, true coincidence summing correction factors for an extended sample can be calculated from full-energy-peak and total efficiencies as if the sample were a point source, if the so-called linear-to-square- (LS) curve, introduced by Blaauw and Gelsema, is known and properly applied. A method is described for obtaining the efficiencies and the corresponding LS-curve for an arbitrary cylindrical sample from calibration measurements in a reference geometry. The approach is aimed at the analysis of samples measured on p-type HPGe detectors in environmental gamma-ray spectrometry and was successfully verified against experimental data.     

Limitations of CT during PET/CT.

Our aim was to determine the diagnostic limitations of low-dose, unenhanced CT scans performed for anatomic reference and attenuation correction during PET/CT. METHODS: The Radiology Information System at our oncologic hospital was queried during the 9-mo period from July 2002 to April 2003 for patients with PET/CT scans and diagnostic enhanced CT within 2 wk of each other. One radiologist interpreted the CT portion of the PET/CT (CT(p)) unaware of the PET results and the associated enhanced diagnostic CT (CT(d)). A medical student compared this interpretation with the official report of the CT(d) and listed all discrepancies between reports. A separate radiologist compared CT(p) and CT(d) images and classified true discrepant findings as due to lack of intravenous contrast, arm-position artifact, lack of enteric contrast, low milliamperage (mA), and quality of lung images. RESULTS: Among 100 patients, the most common malignancies were lymphoma (n = 37), cancer of the colorectum (n = 31), and esophageal cancer (n = 15). Among 194 true discrepancies in which findings were missed at CT(p), causes were as follows: (a) lack of intravenous contrast (128/194, 66%), (b) arm-down artifact (17/194, 9%), (c) quality of lung images (26/194, 13%), (d) lack of enteric contrast (15/194, 8%), and (e) low mA (8/194, 4%). Discrepancies were seen most commonly in detecting lymphadenopathy and visceral metastases. CONCLUSION: Most missed findings on the unenhanced CT portion of the PET/CT scans were due to technical factors that could be altered. Discrepant findings would have led to altered management in only 2 patients, suggesting a role for limited repeat imaging to reduce radiation and use of valuable resources.     

Determining client need in a multi-state fetal alcohol syndrome consortium: from training to practice

Background  

A multi-state consortium was developed in the US to conduct baseline data collection and intervention research on fetal alcohol syndrome. Each state employed support specialists whose job it was to reduce or eliminate alcohol consumption in women who were at high risk for drinking alcohol during their pregnancy. The purpose of this paper is to report how support specialists in three primarily rural/frontier states were trained to assess client need and how client need was actually assessed in the field.     

Is chronic nitrate therapy associated with a different clinical presentation of acute coronary syndrome?

BACKGROUND: Nitrate therapy can induce ischemic preconditioning with a consequent increase in tolerance to ischemia. In the context of acute coronary syndromes (ACS), nitrates may result in a different presentation. with greater protection. OBJECTIVES: To investigate in a population of patients with ACS whether previous chronic use of nitrates results in a different presentation of ACS. METHODS: We studied 287 patients (65 +/- 13 years, 66% male) admitted to our department in the first six months of 2005 with ACS (with and without ST-segment elevation). Of these, 8% were under nitrate therapy at the time of admission. In this group, 27% presented ACS without ST-segment elevation, while in the group without nitrates this value was 58% (p = 0.005). By univariate analysis, the use of nitrates was a predictor of the preferential occurrence of non-ST-segment elevation ACS (OR 0.27, 95% CI 0.10-0.71). After correction for the potential influence of variables (age, gender, previous revascularization and smoking) by multivariate logistic regression, nitrate therapy remained a borderline predictor of clinical presentation as non-ST-segment elevation ACS (OR 0.37, 95% CI 0.13-1.04, p = 0.059). CONCLUSIONS: Previous use of nitrates was associated with a tendency to present as non-ST-segment elevation ACS. This finding may be explained by the hypothesis that nitrates induce pharmacological preconditioning, reducing the transmural extent of myocardial infarction.     

The effect of combined Angiotensin-converting enzyme inhibition and calcium antagonism on allograft coronary vasculopathy validated by intravascular ultrasound.

BACKGROUND: Hypertension is a potential risk factor for allograft coronary vasculopathy. We evaluated the efficacy of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, and their combined use, on the development of coronary vasculopathy in hypertensive heart transplant recipients. METHODS: Eighty-two heart transplant recipients underwent serial intravascular ultrasound (IVUS) analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for the development of coronary vasculopathy. Patients were divided into 4 groups. Nineteen normotensive recipients received no treatment, control (Group A). Hypertensive patients were treated with either ACE inhibitors (Group B, n = 37), calcium antagonists (Group C, n = 16), or both (Group D, n = 10). RESULTS: We found a significant reduction in IVUS indices of coronary vasculopathy in heart transplant recipients who used a combination of an ACE inhibitor and a calcium antagonist compared with recipients who used either drug alone (p < 0.05). This synergistic efficacy was independent of the baseline indices evaluated in a multivariate regression analysis model and was noted despite comparable mean arterial pressure among the 3 hypertensive groups at 1 year, thus suggesting the presence of a synergistic anti-proliferative effect beyond the anti-hypertensive efficacy. CONCLUSIONS: The combined use of an ACE inhibitor and a calcium antagonist is more effective than the individual use of either drug alone on the development of coronary vasculopathy in cardiac transplant recipients. Large randomized clinical trials are warranted to evaluate such a synergistic efficacy.