Risk of thiamine deficiency and Wernicke's encephalopathy after gastrointestinal surgery for cancer.

BACKGROUND: Cancer patients submitted to gastrointestinal surgery are at risk of thiamine deficiency (TD) and Wernicke's encephalopathy (WE). Although permanent neurological damage and death could be prevented by a timely replacement therapy, they often remain undiagnosed and untreated. We hypothesized that WE remains unrecognized because most cases may manifest several months after hospital discharge. METHODS: WE frequency was investigated in a sample of cancer patients who underwent gastrointestinal surgery, by using the diagnostic criteria proposed to improve diagnosis among alcoholics. Patients were evaluated at discharge through the examination of medical records and 6 months after by telephonic interview. RESULTS: Forty-five patients were selected. Signs of WE resulted in 4.4% at discharge. At 6 months, 21 patients were interviewed. Among them, 90.4% had signs of WE. The number of affected patients was significantly higher 6 months after discharge than at discharge (90.4 vs 9.5%, p < 0.0001). CONCLUSIONS: Further studies with larger samples are needed to establish the prevalence of TD and related WE in cancer patients after gastrointestinal surgery. This study suggests that the problem is understated. Even in absence of symptoms of TD, the use of prophylactic thiamine supplementation should be taken in consideration, as consequences of misdiagnosis can be severe.

Disulfiram for binge eating disorder: an open trail.

OBJECTIVE: To evaluate the efficacy and safety of disulfiram for treatment of binge eating disorder. METHOD: Two hundred and fifty milligrams per day of disulfiram was administered to 12 patients affected by binge eating disorder for 16 weeks; the number of binge eating episodes per week and the number of participants who reported side effects were evaluated. RESULTS: Nine participants (75.0%) completed the trial, while the other 3 (25.0%) discontinued prematurely. Disulfiram significantly decreased the mean frequency of binge eating episodes per week from 7.9±1.2 to 0.9±0.6 (p<.001). All patients (100.0%) reduced the frequency of binge eating episodes, and 7 participants (58.3%) achieved remission of binge eating. Eleven participants (91.7%) reported side effects [drowsiness (N=9), headache (N=7), dysgeusia (N=3), tachycardia (N=3), dizziness (N=2), and nausea (N=2)]. DISCUSSION: While disulfiram reduced the frequency of binge eating episodes, side effects were observed in the majority of participants. Longer-term placebo-controlled studies are warranted to exclude the contribution of a placebo response from these results and to evaluate drugs with similar pharmacological activity but improved tolerability.

Twenty-four novel mutations in Wilson disease patients of predominantly Italian origin.

Herein we report the results of mutation analysis of the ATP7B gene in a group of 134 Wilson disease (WD) families (268 chromosomes) prevalently of Italian origin. Using the SSCP and sequencing methods we identified 71 disease-causing mutations. Twenty-four were novel, while 19 more mutations already described, were identified in new populations in this study. A known mutation G591D showed a regional distribution, since it was only detected in 38.5% of the analyzed chromosomes in WD patients originating from Apulia, a region of South Italy. Detection of new mutations in the ATP7B gene increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.

The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease.

BACKGROUND: It has recently been demonstrated that the Wilson disease (WD) protein directly interacts with the human homolog of the MURR1 protein in vitro and in vivo, and that this interaction is specific for the copper transporter. The aim of the present study was to clarify the role of MURR1 in the pathogenesis of WD as well as in other WD-like disorders of hepatic copper metabolism of unknown origin. METHODS: Using the single-strand conformation polymorphism (SSCP) method followed by sequencing, we analyzed the 5' untranslated region (UTR) and three exons of the MURR1 gene in three groups of patients: 19 WD: patients in whom no mutations were detected in the ATP7B gene, 53 WD: patients in whom only one mutation in the ATP7B gene was found, and 34 patients in whom clinical and laboratory data suggested a WD-like disorder of hepatic copper metabolism of unknown origin. RESULTS: We detected in these patients six rare nucleotide substitutions, namely one splice-site consensus sequence and one missense and four silent nucleotide substitutions. All substitutions except one were found in the heterozygous state. No difference in the frequencies of the various substitutions was observed between patients and controls. CONCLUSIONS: These data suggest that the MURR1 gene and its protein product are unlikely to play a primary role in the pathogenesis of Wilson disease. More extensive studies with larger numbers of clinically homogeneous patients should be carried out to establish whether nucleotide alterations in the MURR1 gene may have a role in causing WD or WD-like disorders or act as modifying factors in the phenotype variability in WD.