Background: Alcohol withdrawal profoundly affects the hypothalamic-pituitary-adrenocortical (HPA) system. We investigated whether a family history of alcoholism modulates HPA response to pharmacologic intervention during detoxification in alcohol-dependent patients.Methods: Sixteen family history negative (FH-N) and 19 family history positive (FH-P) alcohol-dependent patients were admitted for withdrawal. All 35 patients were investigated 1 week after remission of withdrawal symptoms; 17 patients were also tested during acute withdrawal. Dexamethasone 1.5 mg was given orally at 11 PM, followed by 100 mug corticotropin-releasing hormone (hCRH) administered intravenously at 3 PM the following day. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were determined at 0, 30, 45, 60, and 75 min after CRH.Results: During withdrawal, cortisol but not ACTH secretion was increased in patients compared with 19 control subjects matched for age and gender. After withdrawal, cortisol was normal in FH-P but still increased in FH-N patients versus control subjects, and ACTH was marginally decreased in FH-P patients only. Both hormones were increased in FH-N versus FH-P patients.Conclusions: Recovery from alcohol withdrawal-induced impairment of HPA system regulation occurs earlier in FH- P than FH-N patients, indicating that the efficacy of central neuroadaptation to this ethanol-related stimulus may be related to genetic factors. (C) 2003 Society of Biological Psychiatry.

Purpose: We investigated the outcome of nephron sparing surgery in patients with low grade and low stage (Robson stage II or less) renal cell carcinoma.Materials and Methods: We retrospectively reviewed the records of 185 patients treated with nephron sparing surgery and 209 matched for patient age and sex, and tumor stage and grade who were treated with radical nephrectomy, Kaplan-Meier survival curves were constructed for progression and survival end points. Multivariate-analysis was performed to determine the tumor characteristics independently correlated with progression and cancer death.Results: No significant difference was observed with respect to progression-free, crude or cancer specific survival between the nephron sparing surgery and radical nephrectomy groups. Less than 5% of the patients treated with conservative nephron sparing surgery had local recurrence. Tumor size was a strong independent predictor of outcome, whereas Robson stage was not. Patients treated with radical nephrectomy had a significant cancer specific and progression-free survival advantage when controlling for tumor diameter and grade. However, no difference was observed in patients with primary tumor diameters of 4 cm, or less.Conclusions: Robson staging is inaccurate in predicting tumor behavior. Patients with tumors larger than 4 cm. and a normal contralateral kidney may be best served by radical nephrectomy rather than elective nephron sparing surgery. However, nephron sparing surgery may result in an outcome similar to that of radical nephrectomy for low grade, low stage renal cell carcinomas of 4 cm. or smaller.

Voxel-based morphometry has recently been used successfully to detect gray matter volume reductions in schizophrenic patients. The aim of the present study was to confirm the findings on gray-matter changes and to complement these by applying the methodology to CSF-differences. Also, we wanted to determine whether a correlation exists between a clinically defined parameter of disease severity and brain morphology in schizophrenic patients. We investigated 48 schizophrenic patients and compared them with 48 strictly age- and sex-matched controls. High-resolution whole-brain MR-images were segmented and analyzed using SPM99. In a further analysis, the covariate effect of the global assessment of functioning-score (GAF) was calculated. Main findings were (i) left-dominant frontal, temporal, and insular GM-reductions and (ii) GM-increases in schizophrenic patients in the right basal ganglia and bilaterally in the superior cerebellum; (iii) CSF-space increases in patients complementary to some GM-reductions; (iv) a correlation between the GAF-score and local GM-volume in the left inferior frontal and inferior parietal lobe of schizophrenic patients. This study confirms and extends some earlier findings on GM-reduction and detected distinct GM-increases in schizophrenic patients. These changes were corroborated by complementary CSF-increases. Most importantly, a correlation could be established between two particular gray matter-regions and the overall disease severity, with more severely ill patients displaying a local GM-deficit. These findings may be of potentially large importance for both the future interpretation and design of neuroimaging studies in schizophrenia and the further elucidation of possible pathophysiological processes occurring in this disease.

Functional and structural abnormalities in the thalamus as well as a generalized phospholipid membrane disorder have been implicated in the pathogenesis of schizophrenic psychosis. To determine whether thalamic neuronal abnormalities and altered membrane-associated metabolites can be detected in schizophrenic patients, we used in vivo proton magnetic resonance spectroscopy (1H-MRS) in 32 acutely-ill, medicated schizophrenic patients and 17 age-matched controls. Thalamic and white matter metabolite concentrations (myo-inositol (mI), choline-containing compounds (Cho), total creatine (Cr) and N-acetylaspartate (NAA)) were estimated and corrected for atrophy (CSF) and gray and white matter contributions (GM, WM) by use of image-based voxel segmentation. Thalamic NAA was significantly reduced in schizophrenic patients, whereas Cho and mI were significantly increased in the parietal white matter. White matter Cr was significantly elevated in patients and correlated positively with the brief psychiatric rating scores (BPRS). Regional metabolite levels were inversely associated with GM and WM content reaching significance for mI and Cr in the thalamus and Cho and NAA in the white matter. Reduced NAA in the left thalamus of schizophrenic patients confirms and extends previous spectroscopic data and agrees well with histologic and imaging findings of reduced neuronal density and volume. Elevated Cho in line with 31P-MRS studies suggests increased myelin degradation thus further supporting a generalized membrane disorder in schizophrenic patients. In addition, we demonstrate the need to correct metabolite concentrations for regional tissue composition in studies employing patients with altered brain morphology.

Several lines of evidence suggest a dysregulation of the adrenocortical (HPA) system with hypersecretion of CRH is associated with suicidal behavior. However, controversial results have emerged from the determination of corticotropin-releasing hormone (CRH) concentrations in the lumbar cerebrospinal fluid (CSF) of suicide attempters probably due to methodological differences. We simultaneously measured CRH concentrations in the CSF and in the plasma of 41 psychiatric in-patients with different diagnoses (affective disorder, schizophrenia, personality disorders, adjustment disorder, substance abuse) and eight neurological control subjects. We also measured plasma cortisol concentrations because data from animal experiments suggest that cortisol may influence CSF CRH concentrations. The major finding was that patients who attempted suicide prior to admission had significantly lower CSF CRH concentrations than psychiatric patients without suicidal behavior. CRH concentrations were significantly higher in the CSF than in plasma in both, psychiatric patients and neurological control subjects. There was no significant difference between suicide attempters and patients with acute suicidal ideations. The latter group showed a trend towards lower CSF CRH concentrations compared with the neurological control subjects. Patients with affective disorder alone as well as patients with multiple diagnoses, but not schizophrenic patients, showed significantly lower CSF CRH concentrations than neurological control subjects. Plasma CRH and plasma cortisol concentrations did not differ among diagnostic groups or between suicide attempters vs. non-attempters. Further studies with more homogeneous samples, drug-free patients and with simultaneous assessment of various parameters of the HPA system are warranted.