Association study of novel human serotonin 5-HT(1B) polymorphisms with alcohol dependence in Taiwanese Han.

BACKGROUND: Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders, such as depression, anxiety, migraine, substance abuse, and alcoholism. The human serotonin receptor 1B, encoded by the HTR1B gene, is a presynaptic serotonin autoreceptor that plays a role in regulating serotonin synthesis and release. Because the linkage of antisocial alcoholism to the HTR1B gene was recently reported in two populations, it was of interest to identify genetic variants at the HTR1B locus and study their association with alcoholism in the Taiwanese Han population. METHODS: We sequenced DNA from Taiwanese Han to screen for genetic variation in the coding, promoter, and partial 3' untranslated regions of the HTR1B locus of 158 alcohol-dependent cases with withdrawal symptoms and 149 control subjects, who either never drank or drank only occasionally and in low quantities. RESULTS: Seven variants were identified. Positive associations were found between variant A-161T and alcohol dependence at both the allelic and genotypic level. In addition, an expression study showed that the A-161T variant affected reporter gene activity. CONCLUSIONS: Our results support an association between HTR1B and alcohol dependence. The HTR1B A-161T polymorphism may be valuable both as a functional and as an anonymous genetic marker for HTR1B.     

Inter-carpal soft tissue entrapment. A possible explanation for chronic dorsal wrist pain

This retrospective study evaluates the surgical treatment of a group of patients with unknown chronic dorsal wrist pain. The cause of their symptoms was interpreted as a painful entrapment of fibrous tissue in the radio-carpal and inter-carpal joints during specific movements. Between 1997 and 2001, 30 patients were treated by surgical excision of this tissue and 26 patients were traced for follow-up. Twenty-three patients were symptom free, or experienced major benefit from surgery. Wrist function measurements using the VAS scale showed improvement in 24 patients. Microscopic examination of the removed specimen shows fibrous tissue with non-specific changes. Inter-carpal soft tissue entrapment can explain the typical clinical findings in some patients with unknown chronic dorsal wrist pain. After careful selection, surgical excision of all entrapped tissue in the radio-carpal and mid-carpal joint may give relief of pain and improvement of wrist function.     

Endogenous opioid receptor genes and alcohol dependence among Taiwanese Han

BACKGROUND: Nonselective opioid antagonists reduce alcohol consumption under various experimental situations, and several association studies have examined possible roles of opioid receptor mu (OPRM), delta (OPRD), and kappa (OPRK) genes in the development of alcohol dependence. METHODS: We examined 20 single nucleotide polymorphisms (SNPs) across the OPRM, OPRD, and OPRK genes in 158 alcohol-dependent subjects and 149 controls. Differences in allele frequency and genotype distribution between case subjects and controls, as well as the deviation from Hardy-Weinberg equilibrium, were examined using Fisher's exact tests. RESULTS: No significant difference in either allele or genotype frequency was found between case subjects and controls for each of the SNPs. CONCLUSIONS: Our findings do not support a possible role of the opioid receptor genes for the proclivity to alcohol dependence in the Taiwanese Han.     

Levodopa-responsive aromatic L-amino acid decarboxylase deficiency

We report three siblings, who were treated empirically with levodopa combined with carbidopa. There was an immediate therapeutic response. Biochemical investigation surprisingly showed the clinical phenotype to be caused by aromatic L-amino acid decarboxylase deficiency. Molecular characterization showed a homozygous point mutation (c.387 G-->A) in exon 3. Kinetic studies showed the mutation to decrease the binding affinity for the substrate. This, combined with structural modeling suggesting alteration of active site configuration, provided an explanation for the therapeutic response to levodopa.     

Prevertebral muscle involvement in nasopharyngeal carcinoma

PURPOSE: The purpose of this study is to evaluate the prevalence and prognostic significance of prevertebral muscle involvement in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between July 1990 and December 2001, 521 newly diagnosed patients with NPC treated at Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were examined with magnetic resonance imaging (MRI) for evidence of prevertebral muscle involvement before treatment. Patients were staged according to the 1997 American Joint Committee on Cancer staging classification of NPC based on the physical exams and MRI findings. All patients received radiotherapy with or without chemotherapy. The association between clinical prevertebral muscle involvement and posttreatment outcomes (overall survival, locoregional recurrence, and distant metastasis) were evaluated using Cox regression model to adjust for other prognostic factors. RESULTS: Of 521 patients treated at KF-SYSCC, 181 (35%) patients were found to have prevertebral muscle involvement, one-third in those with Stage II/III tumors and two-thirds in those with Stage IV tumor. In multivariate analysis accounting for all previously known prognostic factors, prevertebral muscle invasion was associated with an increased risk for any recurrence (adjusted relative risk, 2.01; p<0.001), locoregional recurrence (adjusted relative risk, 2.69; p<0.001), and distant metastasis (adjusted relative risk, 2.25; p<0.001), and with a borderline significant increased risk for overall survival (adjusted relative risk, 1.44; p=0.10). CONCLUSIONS: Prevertebral muscle involvement is an independent prognostic factor for NPC recurrence.     

Non-muscle invasive transitional cell carcinoma of the distal ureter and bladder with lung metastasis: A case report and literature review

INTRODUCTIONNon-muscle invasive transtitional cell carcinoma (TCC) with metastases is exceedingly rare.PRESENTATION OF CASEWe report the case of a 78-year old man with an incidental finding of a non-muscle invasive TCC of the left distal ureter during treatment for Duke's B Colon cancer. Following laparoscopic nephro-ureterectomy (LNU) he had two further superficial recurrences in the bladder over a 14-month period which underwent transurethral resection (TUR). On surveillance imaging for his colorectal cancer follow-up a lung nodule was detected and video-assisted thoracic surgical (VATS) resection of the lesion showed it to be TCC in origin. He was referred to oncology for chemotherapy and remains clinically well.DISCUSSIONA Literature search found only three other such cases and the ureteric TCC is the most likely source of the metastasis.CONCLUSIONThis occurrence is exceedingly rare.     

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

AIM Infantile-onset inflammatory bowel disease(IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10(IL-10) and interleukin-10 receptors(IL-10R) in Asian children with IO-IBD. METHODS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10 R genes in patients with presenting clinical features of Crohn's disease(CD).RESULTS Six [13%; CD = 3, ulcerative colitis(UC) = 2, IBDunclassified(IBD-U) = 1] of the 48 children(CD = 25; UC = 23) with IBD have IO-IBD. At final review [median(range) duration of follow-up: 6.5(3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy(IBD-U), after standard immunosuppression(CD), and after total colectomy(UC)]. Three patients were on immunosuppression:one(UC) was in remission while two(both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea(100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease(0% vs 19%, P = 0.31), requiring biologics therapy(50% vs 36%, P = 0.40), surgery(50% vs 29%, P = 0.27), or achieving remission(50% vs 64%, P = 0.40). No mutations in either IL10 or IL10 R in the three patients with CD and the only patient with IBD-U were identified.CONCLUSION The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10 R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.     

Complementary and alternative medicine (CAM) practices and dietary patterns in children with inflammatory bowel disease in Singapore and Malaysia

Background

The use of complementary and alternative medicine (CAM) has been associated with adverse effects and self-imposed dietary restrictions. The prevalence of its use in Asian children with inflammatory bowel disease (IBD) is unknown. We aimed to determine the prevalence, types, and factors associated with the use of CAM among children with IBD from Singapore and Malaysia, and to ascertain if dietary restriction was prevalent in patients who used CAM.

A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy

Purpose: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. METHODS AND MATERIALS: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. RESULTS: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. CONCLUSION: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.