A prospective cohort study of cancer incidence following the diagnosis of Parkinson's disease.

BACKGROUND: Prior studies suggest a decreased risk of cancer among patients with Parkinson's disease (PD). METHODS: Matched cohort analysis among the 22,071 participants in the Physician's Health Study. A total of 487 incident cases of PD without preceding cancer were identified by self-report. Each PD case was matched by age to a reference participant who was alive and cancer free at the time of PD diagnosis. Both cohorts were followed for incident cancer. We used proportional hazards models to calculate adjusted relative risks (RR) for cancer. RESULTS: A total of 121 cancers were confirmed during a median follow-up of 5.2 years (PD) and 5.9 years (reference). Those with PD developed less cancer (11.0% versus 14.0%), with an adjusted RR of 0.85 [95% confidence interval (95% CI), 0.59-1.22]. Reduced risk was present for smoking-related cancers such as lung (RR, 0.32), colorectal (RR, 0.54), and bladder (RR, 0.68), as well as for most non-smoking-related cancers such as prostate cancer (RR, 0.74). In contrast, PD patients were at significantly increased risk (RR, 6.15; 95% CI, 1.77-21.37) for melanoma. PD patients who smoked were at reduced risk for smoking-related cancer (RR, 0.33; 95% CI, 0.12-0.92), whereas nonsmokers with PD were at increased risk (RR, 1.80; 95% CI, 0.60-5.39). This interaction was statistically significant (P(interaction) = 0.02). CONCLUSIONS: Our results suggest a decreased incidence of most cancers in patients with PD. PD patients had a significantly increased risk of malignant melanoma, a finding consistent with prior studies. We confirmed an interaction between smoking and the relationship of PD to smoking-related cancer that may fit the pattern of a gene-environment interaction.     

The relationship patterns questionnaire (RPQ): validation by using a representative sample

In this study the present form of the Relationship Patterns Questionnaire (RePat) will be presented as a successor of the Interpersonal Relationship Patterns Questionnaire (IRQ). Similar to the IRQ the RePat assesses the behavior of relationship concerning both one's own and the anticipated behavior of an important person on the basis of the SASB model and the CCRT method. In contrast to the IRQ, the RePat is much shorter and thus easier to use. The study describes the construction and the psychometric examination of the questionnaire by using a representative study (n = 2007, East = 1015, West = 992). The samples of East and West Germany show structural differences concerning its relationship patterns, which in our opinion are plausible for political and historical reasons. The clinical application and their implications for therapeutic interventions will be demonstrated by a single case using both the patient's and her partner's assessment of their relationship.     

Event-related fMRI of the somatosensory system using electrical finger stimulation

Cortical signal intensity changes due to brief (1 s) innocuous electrical stimuli applied to the second and fifth finger of the right hand were measured by means of fMRI at 1.5 T. The activation pattern in this event-related fMRI approach closely resembled that obtained in recent block-design studies. Activations were found in contralateral primary (SI) and bilaterally in secondary (SII) somato-sensory cortex as well as in posterior parietal cortex, insula, and supplementary motor area (SMA). In SI, the somatotopic organization of the hand area is demonstrated, more clearly to be seen in area 3b than in area 1 and 2. In conclusion, the feasibility to employ event-related somatosensory stimulation paradigms in fMRI studies is demonstrated.     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.     

Reversible findings of restricted diffusion in 5‐flourouracil neurotoxicity

A 35‐year‐old woman presented with neurotoxicity correlated to an i.v. regimen of 5‐fluorouracil as episodes of acute confusional state and abnormalities of symmetrically restricted diffusion in the periventricular white matter and corpus callosum. On discontinuing the medication, the areas of severely restricted diffusion had entirely resolved, with minimal residual T2 signal abnormality. In this case, immediate discontinuation of the chemotherapeutic agent apparently reversed the patient's symptoms and findings on MRI. The scant information available in the published literature regarding this phenomenon is reviewed with regard to 5‐fluorouracil.     

Effect of inhaled prostacyclin in combination with almitrine on ventilation-perfusion distributions in experimental lung injury

BACKGROUND: Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone. METHODS: Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences. RESULTS: All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution. CONCLUSIONS: The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.     

Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs

BACKGROUND: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model. METHODS: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19 degrees C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined. RESULTS: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group. CONCLUSIONS: Desflurane-based anesthesia yields hemodynamics during CPB with DHCA that are similar to those with fentanyl-based anesthesia. However, desflurane-based anesthesia improves neurologic and histologic outcomes of CPB-DHCA in comparison with outcomes with fentanyl-based anesthesia.