PURPOSE: For 30 years, we have consecutively performed rectal mucosal punch biopsy to diagnose Hirschsprung's disease. The aim of this study was to evaluate the safety of our technique. METHODS: Patients with suspected Hirschsprung's disease who underwent punch biopsy, including our original "K-PUNCH" method using an S-moid forceps and non-specific blood-collecting tube at our department and branch hospital between April 1986 and March 2016 were included in the present study. Our punch biopsy technique is characterized by excellent visibility and a direct grasping sensation. The backgrounds and complications of the patients were retrospectively investigated. RESULTS: During this period, 954 patients (median age 4 months; range 1 day-73 years) underwent punch biopsy. Although there were no cases of severe complications (i.e., rectal perforation, infection or full-thickness biopsy), one (0.1%) of the 954 cases in the early period showed liver dysfunction and required transfusion due to bleeding. In addition, inappropriate specimens were obtained in 37 patients (3.9%). CONCLUSION: Punch biopsy including the "K-PUNCH" method is considered safe and feasible and is associated with a low rate of complications and inappropriate specimen harvesting among patients of all ages. Comorbidities, including the potential for hemorrhage, should always be considered.
OBJECTIVES: Acetylcholinesterase (AChE) staining has become the gold standard for definitively diagnosing Hirschsprung disease (HD), although some pitfalls have been reported. We reevaluated a large series at our institute in order to validate the accuracy of AChE staining for detecting HD. METHODS: A retrospective study of the rectal mucosal specimens of all of the children with suspected HD during a 13-year period was performed. The specimens were stained according to the modified Karnovsky-Roots method for AChE staining. The final diagnosis, prognosis, and management after the histopathological diagnosis were analyzed with a questionnaire sent to the patient's original hospital. RESULTS: Three hundred and fifty-eight specimens were collected. One hundred twenty-two (34%) specimens were diagnosed as HD, 198 (55%) as nonHD, 25 (7%) as "undetermined," and 13 (4%) as "inappropriate." The non-HD group contained 190 (96%) specimens with a normal appearance and 8 (4%) specimens with suspected intestinal neuronal dysplasia (IND). Three hundred and six of 358 questionnaires were returned. The final diagnosis showed that no specimens first diagnosed as HD were identified as non-HD and vice versa, for a sensitivity and specificity of 100%. Four cases were finally diagnosed as chronic idiopathic intestinal pseudo-obstruction (CIIP) in the non-HD group. All of the patients with HD underwent radical surgery. Most non-HD patients were managed conservatively, although some continued to have constipation. CONCLUSIONS: AChE staining is an accurate tool for differentiating between HD and non-HD with high sensitivity and specificity. CIIP can be included in cases of non-HD; therefore, careful follow-up is mandatory.
The mesolimbic system is thought to be involved in the reinforcing action of many addictive drugs and the release of dopamine modulated by neuronal nicotine cholinergic receptors (nAChRs). Several investigations suggested that nAChRs on dopaminergic terminals play an important role in the development of some long-lasting adaptations associated with drug abuse. A majority of high-affinity nicotine binding sites in the brain have been showed in heteropentameric alpha4 (alpha4) and beta2 subunit (beta2) of nAChRs. Therefore, we conducted a genetic association analysis of the alpha4 gene (CHRNA4) and beta2 gene (CHRNB2) with methamphetamine (METH)-use disorder (191 cases and 753 controls). We first evaluated the linkage disequilibrium (LD) structure of these genes and selected 7 and 5 tagging SNPs (tag SNPs) on CHRNA4 and CHRNB2, respectively. Some tag SNPs were significantly associated with total METH-use disorder and METH-induced psychosis; however, these associations were no longer statistically significant after Bonferroni's correction for multiple testing. In conclusion, our results suggest that neither CHRNA4 nor CHRNB2 plays a major role in Japanese METH-use disorder.
Several lines of evidence suggest that nicotinic cholinergic dysfunction may contribute to the cognitive impairments in schizophrenia. The majority of high affinity nicotine binding sites in the human brain have been implicated in heteropentameric alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptors; therefore, these two neuronal nicotinic acetylcholine receptors genes (CHRNA4 and CHRNB2) are considered to be attractive candidate genes for the pathophysiology of schizophrenia. To represent these two genes in a gene-wide manner, we first evaluated the linkage disequilibrium structure using our own control samples. Thirteen SNPs (7 SNPs for CHRNA4 and 5 SNPs for CHRNB2) were selected as tagging SNPs. Using these tagging SNPs, we then conducted genetic association analysis of case-control samples (738 schizophrenia and 753 controls) in the Japanese population. No significant association was detected in the allele/genotype-wise or haplotype-wise analysis. Our results suggest that CHRNA4 and CHRNB2 do not play a major role in Japanese schizophrenia.
BACKGROUND: Changes in serum lipid concentrations during the administration of interferon to patients with chronic hepatitis C virus (HCV) infection have not been fully investigated. The present study was designed to compare changes in serum lipid concentrations before, during and after interferon therapy in responders and non-responders to treatment. METHODS: In total, 101 patients with chronic HCV positive hepatitis were enrolled in this study. High dose interferon alpha was given on alternate days for 6 months. Six months after the end of treatment patients were assessed for the presence or absence of HCV RNA to determine the results of interferon treatment. The time courses of changes in serum lipid concentrations were measured in all patients. RESULTS: The total cholesterol level increased gradually during and after interferon therapy, and its pattern of change coincided with that of serum cholinesterase activity. Pretreatment serum cholesterol concentrations did not differ between responders and non-responders to interferon therapy. The serum triglyceride concentration, conversely, showed a sharp increase during interferon administration and returned to its basal level after the end of treatment. Responders to interferon therapy tended to have higher pretreatment triglyceride concentrations than did non-responders. CONCLUSIONS: We clarified that serum cholesterol and triglyceride levels showed different patterns of change during interferon therapy.