Identifying incident cases of parkinsonism among veterans using a tertiary medical center.

To better understand the impact of incident Parkinson's disease (PD) on the Veteran's Health Administration (VHA) and to develop methods applicable to future epidemiological research, we performed a medical record review study at a tertiary referral VHA medical center. Searching the local data base, we identified 782 veterans with diagnostic codes for PD or secondary parkinsonism (SP) between 1998 and 2000. Based on structured medical record review, a movement disorders specialist confirmed diagnoses for incident parkinsonism cases. Among the 782, 191 incident parkinsonism cases were identified (100 PD, 75 SP, and 16 Parkinson's Plus). Incident PD cases were older at diagnosis (74.5 vs. 70.4 yr; P < 0.05) and more likely to be white (81% vs. 62; P < 0.07) than incident SP cases. Diagnostic codes were insufficient to distinguish between incident PD and SP (positive predictive value, 57% and 39%, respectively), and VHA sources failed to identify 21% of confirmed deaths among the incident PD cohort by November 2004. Although the large number of incident cases identified suggests PD is an important cause of disability among elderly VHA users, observed limitations of VHA sources for identifying incident PD cases and determining their vital status should be considered when designing future studies.     

Longitudinal predictors of continued tobacco use among patients diagnosed with cancer

Even though continued smoking by cancer patients adversely affects survival and quality of life, about one third of patients who smoked prior to their diagnosis continue to smoke after their diagnosis. The implementation of smoking cessation treatments for cancer patients has been slowed by the lack of data on correlates of tobacco use in this population. Thus, this longitudinal study assessed demographic, medical, addiction, and psychological predictors of tobacco use among 74 head, neck, and lung cancer patients. Multivariable binary logistic regression analyses, with outcome categorized as smoker or nonsmoker, indicated that the likelihoodthat patients would be a smoker was associated with lower levels of perceived risk and a higher level of quitting cons. Multivariable nominal logistic regression, with outcome classified as continuous smoker, continuous quitter, relapser, or follow-up quitter, indicated that: (a) patients categorized as continuous smokers reported significantly lower quitting self-efficacy than follow-up quitters and continuous quitters, (b) relapsers reported a significantly lower level of quitting self-efficacy than either follow-up quitters or continuous quitters, and (c) continuous smokers exhibited a significantly lower level of risk perceptions than continuous abstainers. These findings can be useful for the development and evaluation of treatments to promote smoking cessation among cancer patients. Support for this study was provided by National Institutes of Health Grants CA57708, CA06927, CA88610, CA95678, and CA76644.     

Computed tomography in gunshot wounds to the neck: Can we predict vascular injury?

The purpose of this study was to evaluate the ability of helical computed tomography (CT) to detect arterial injuries in gunshot wounds to the neck. In a blinded retrospective review, 54 helical CT scans of the cervical spine were evaluated for bullet/bone fragments, subcutaneous air, bullet path, hematoma, spine fractures, and pharyngoesophageal compromise. The distance of fragments to a major vessel was calculated. CT findings that correlated significantly with major arterial injury included the presence of fragments (bullet/bone) close to a major vessel (2.5 mm) and spine fractures. Visualizing fragments <5 mm from a vessel or a transcervical bullet trajectory predicted 12 of 13 major arterial injuries. We conclude that CT clearly depicts anatomic damage. Specific findings, such as the location of fragments and bullet trajectory adjacent to a vessel and spine fractures, indicate a higher probability of vascular damage, thus directing more definitive evaluation.     

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.     

The effects of aerobic conditioning and/or caloric restriction in overweight men and women

The purpose of this study was to compare the effects of exercise and/or caloric restriction for 12 wk on body composition, maximal aerobic power (VO2max), and serum lipids and lipoproteins in overweight individuals. Forty-eight males and 48 females (means age = 36.6 yr), 120-140% of ideal body weight, were randomly assigned to groups (N = 12 each) of diet-exercise (DE), diet (D), exercise (E), and sedentary control (C). The dietary regimen consisted of 1,200 kcal X d-1, while exercise consisted of 5 d X wk-1 of 30 min of walk/running. For the males, body weight (BW) and fat weight loss in the DE group (-11.8 and 23%, respectively) were significantly greater than in the D group (-9.1 and -18%), with both groups significantly greater than for E and C. In the females, BW and fat weight loss for DE (-10.4 and -24%) were significantly greater than for D (-7.8 and -20%), with both groups significantly greater than E and C. Both DE and D males and females had a decrease in fat-free weight of -4.5 and -2.4%, respectively. In both sexes, the increase in VO2max-BW (ml X kg -1 X min-1) in DE (25%) was significantly greater than for E (15%), D (11%), and C (0%), with differences between E and D nonsignificant. However, increases in absolute VO2max (1 X min-1) and VO2max-fat-free weight (ml X kg-1 X min-1) were similar (P greater than 0.05) for DE and E (14%) but significantly greater compared to D and C (2%).(ABSTRACT TRUNCATED AT 250 WORDS)