Pathological gambling is linked to reduced activation of the mesolimbic reward system

By analogy to drug dependence, it has been speculated that the underlying pathology in pathological gambling is a reduction in the sensitivity of the reward system. Studying pathological gamblers and controls during a guessing game using functional magnetic resonance imaging, we observed a reduction of ventral striatal and ventromedial prefrontal activation in the pathological gamblers that was negatively correlated with gambling severity, linking hypoactivation of these areas to disease severity.     

Sexually dimorphic link between dopamine D2 receptor gene and neuroticism-anxiety

Prior theory-driven research probing the association between dopaminergic candidate genes and human personality has focused on the trait of novelty seeking. Here, we examined the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and two other personality traits, neuroticism-anxiety and agentic extraversion. We found no significant associations for agentic extraversion. However, for men, but not for women, we observed a strong and specific association between low neuroticism-anxiety and the A1+ allele of the DRD2 TaqI A polymorphism across two independent samples and across two alternative personality scales. We conclude that new theoretical models are needed to account for these and other recent reports of associations between neuroticism-anxiety and brain dopamine, which cannot be interpreted within the traditional framework.     

Altered hetero- and homeometric autoregulation in the terminally failing human heart

OBJECTIVE AND METHODS: To further investigate length-dependent force generation in human heart, nonfailing (donor hearts, NF) and terminally failing (heart transplants, dilated cardiomyopathy, DCM) left ventricular myocardium was studied under various preload (4-40 mN/mm2) or length conditions. In addition, morphological studies (van Giesson Trichrome staining, electron microscopy) were performed. RESULTS: In NF, a biphasic increase in force of contraction (FOC) was observed after elevating the preload (4-40 mN/mm2): there was an immediate fast increase (FOCf,), followed by a slow increase over several minutes (FOCs), which was paralleled by an increase in the systolic fura-2 transient. In DCM, FOCf, FOCs and the systolic fura-2 transient were blunted and diastolic tension was increased at increasing muscle length. Only in NF, a stretched induced increase in diastolic fura-2 ratio was observed. In DCM, no obvious interstitial fibrosis and no difference in basement membrane structure and attachment were observed. CONCLUSIONS: Since FOCf has been attributed to the Frank-Starling mechanism, whereas FOCs represents a length-dependent increase in the intracellular Ca2+-transient, the impaired length-dependent force generation in failing myocardium results from a dysregulation of both myofibrillar Ca2+-sensitivity as well as the intracellular Ca2+-homeostasis. Interstitial fibrosis may have only minor impact on force generation in human end-stage heart failure.     

Correlation between HRCT findings,pulmonary function tests and bronchoalveolar lavage cytology in interstitial lung disease associated with rheumatoid arthritis

A prospective study correlating high-resolution computed tomography (HRCT), lung function tests (PFT) and bronchoalveolar lavage (BAL) cytology in patients with interstitial lung disease (ILD) associated with rheumatoid arthritis (RA). Fifty-three RA patients with suspected ILD (19 men, 34 women) underwent 71 HRCT (14 of 53 with sequential HRCT, mean follow-up 24.3 months). The HRCT evaluation by two observers on consensus included a semi-quantitative characterisation of lesion pattern and profusion on representative anatomical levels. Fifty-two HRCT were followed by PFT and BAL. Agreement or discordance of HRCT-, PFT- and BAL findings were analysed with Pearsons correlation, score and McNemars test. Tobacco-fume exposure was estimated in pack years. Smoking/non-smoking groups were compared with Students t test. In 49 of 53 patients, HRCT was suggestive of ILD associated with RA (66 of 71 HRCT). Reticular lesions were found in 40 of 53 patients, in 15 of 40 presenting as mixed pattern with ground-glass opacities (GGO). Pure reticular patterns predominated in patients with long duration of ILD (p>0.01). Pure GGO were not observed. Lesion profusion was highly variable and correlated moderately negative with diffusion capacity (mean 88.2% (SD±20.9%); r=–0.54; p<0.001) and very weak with vital capacity and FEV1 (mean values 92.2% (SD±18.3%); r=–0.27; p<0.05 and 89.8% (SD±17.5%); r=–0.31; p<0.01). In patients with GGO, BAL differentials tended towards neutrophilia (=0.39; p=0.04; McNemar test p>0.2), but not towards lymphocytosis (=0.10; p=0.23; McNemar test p>0.2). Differences in smoking history were not significant (p>0.1). The HRCT appears most appropriate for the detection and follow-up of ILD associated with RA. The PFT and BAL correlate only partially with lesion profusion or grading on HRCT, but they contribute valuable information about dynamic lung function and differential diagnoses (pneumonia, medication side effects).     

Quality of life of living kidney donors in Germany: a survey with the Validated Short Form-36 and Giessen Subjective Complaints List-24 questionnaires

BACKGROUND: Most studies evaluating the impact of kidney donation on donors' quality of life (QOL) have limitations such as small cohort size, unmatched references, use of nonstandardized and nonvalidated questionnaires, or low response rates. METHODS: We performed a study on donors' QOL that was designed to avoid these limitations. All available living renal donors in our department in the last 18 years were included in the study. QOL was assessed with two validated, standardized questionnaires (Short Form-36, Giessen Subjective Complaints List [Giessener Beschwerdebogen]-24) and compared with gender- and age-matched references. In addition, specific questions relating to kidney donation were asked. RESULTS: The response rate (89.8%) is one of the highest reported for studies on QOL of living kidney donors. Most donors had an equal or better QOL than the healthy population. Donors' willingness to donate again (93.4%) or recommend living-donor kidney transplantation (92.4%) was high, irrespective of complications. A small number of donors experienced financial drawbacks or occupational disadvantages. Donors aged 31 to 40 years were found to be at risk of QOL deterioration after organ donation. Donor and recipient complications had a significant impact on donors' QOL. One third of the donors found that the psychologic care preceding and after kidney donation was insufficient. CONCLUSIONS: Our findings support the practice of living-donor kidney transplantation as a good means to meet the persisting organ shortage. Further effort must be put into minimizing donor and recipient complications. The specific demands of younger donors should be further elucidated. In addition to medical follow-up, living kidney donors should also be offered lifelong psychologic counseling.     

Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma

Background The clinical staging of renal cortical tumors traditionally has not evaluated the potential effect of histological subtypes on survival. Evidence suggests that conventional clear cell renal cell carcinoma (RCC) and nonconventional clear cell RCC (chromophobe and papillary) have different metastatic potential. Using a large renal tumor database, we examined the effect of tumor histology on the pattern of metastasis and patient survival. Methods All patients with nonmetastatic renal cortical tumors undergoing partial or radical nephrectomy were identified from a renal tumor database between July 1989 and July 2002. Kaplan-Meier and Cox regression tests were used for statistical analysis. Results Analysis revealed 1057 patients: 794 with conventional clear cell RCC, 157 with papillary RCC, and 106 with chromophobe RCC. Metastasis occurred in 95 conventional clear cell RCC, 9 papillary RCC, and 6 chromophobe RCC. Metastasis occurred in 95 conventional clear cell RCC, 9 papillary RCC, and 6 chromophobe RCC with a median follow-up of 34.6, 43.0, and 33.2 months, respectively. Using log-rank analysis, chromophobe and papillary RCC were associated with an improved disease-free survival at 5 years (P=.009 and .015, respectively). Multivariate analysis revealed tumor size, stage, and chromophobe histology as significant variables for disease progression. Conclusions Renal cortical tumors have distinct histological subtypes with varying degrees of metastatic potential. Conventional clear cell RCC, which comprises two thirds of renal cortical tumors presenting with localized disease, has a less favorable outcome when compared with papillary and chromophobe RCC. Controlling for size and stage, chromophobe, and not papillary, RCC was a significant variable for disease progression compared with conventional clear cell RCC. Knowledge of renal cortical tumor histological subtype is critical for projecting prognosis, tailoring follow-up strategies, and designing clinical trials. Presented at the 56th Annual Cancer Symposium, Society of Surgical Oncology, San Diego, CA, March 5–9, 2003.     

Enhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferens

Galantamine, a mild acetylcholinesterase inhibitor and an allosteric ligand of nicotinic receptors, enhanced in a concentration-dependent manner the amplitude of purinergic twitch contractions of the electrically stimulated rat vas deferens (0.2 Hz, 1 ms, 60 V). Other acetylcholinesterase inhibitors also increased the twitches, showing a hierarchy of potencies of galantamine>physostigmine>tacrine>rivastigmine=donepezil. The potentiations seem to be unrelated to the ability to inhibit acetylcholinesterase, since the hierarchy of potencies to block the enzyme in vas deferens was tacrine>physostigmine>rivastigmine>donepezil>galantamine. Acetylcholine also increased the twitches; such effect was produced by a low range of concentrations of acetylcholine (10(-10)-10(-7) M). This facilitatory effect of acetylcholine on twitches was significantly potentiated by galantamine (10(-7)-10(-6) M), but not by rivastigmine or donepezil. A striking enhancement of twitches was also caused by charybdotoxin, a blocker of high-conductance Ca2+-activated K+ channels, and by 4-aminopyridine, a non-specific blocker of K+ channels; in addition, apamin, a blocker of small-conductance Ca2+-activated K+ channels, induced a lower potentiation. The antagonist mecamylamine (10(-7)-10(-6) M) reduced by 80% the potentiation by galantamine, indicating the involvement of nicotinic receptors. Therefore, it is suggested that, besides an inhibition of acetylcholinesterase, some additional mechanisms, such as blockade of Ca2+-dependent K+ channels, or activation of nicotinic receptors of nerve terminals, might be involved in twitch potentiation. These results are relevant in the context of the clinical use of galantamine to improve cognition and behaviour in patients with Alzheimer's disease.     

Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model

Abstract. Rasagiline is an antiapoptotic compound with neuroprotective potential. We examined its neuroprotective effect alone and in combination with the putative glutamate release blocker riluzole in the G93A model of familial amyotrophic lateral sclerosis (fALS). Endpoints of experimental treatment were survival and motor activity. The drug had a significant dose-dependent therapeutic effect on both preclinical and clinical motor function and survival of the animals. We also found that the combination of rasagiline with riluzole is safe and increases survival by about 20 % in a dosedependent manner. Therefore, we conclude that the combination of rasagiline and riluzole is a promising clinical combination for the improvement of current neuroprotective treatment strategies of ALS.