Ten‐year follow‐up study of Japanese patients with obsessive–compulsive disorder

Aim

Obsessive–compulsive disorder (OCD) is a well‐known chronic illness. This study retrospectively investigated 10‐year outcomes and associated clinical factors in Japanese OCD patients. We focused on the impact of several sociocultural factors, including medical expenses and insurance systems specific to each country, on the differences or biases in follow‐up procedures of OCD.

Methods

Seventy‐nine patients diagnosed with OCD who received a standardized combination of treatments for 10 continuous years were divided into three groups according to their improvement rates on the Yale–Brown Obsessive–Compulsive Scale after 10 years of treatment.

Results

A survival analysis revealed that the rate of patients achieving full remission increased every year. Following 10 years of treatment, 56% of OCD patients experienced ‘full remission’ for at least 1 year. Consequently, 48% exhibited full remission, and 37% exhibited partial remission at the end‐point of this study. We identified several factors that were predictive of poorer outcomes, including lower Global Assessment of Functioning Scale scores and the presence of hoarding symptoms or involvement behaviors. In addition, improvement rates after 1 year significantly predicted better 10‐year outcomes.

Conclusion

Our findings highlight the transcultural nature of long‐term outcomes of OCD treatment, which appear to be independent of sociocultural differences.

     

Comparative study of direct polymerase chain reaction, microscopic examination and culture-based morphological methods for detection and identification of dermatophytes in nail and skin samples

The positive rates of dermatophytes isolated and identified by conventional methods are rather low. Moreover, clinical isolates sometimes show atypical morphology, and in such cases microscopic methods are not applicable for identification. The present study was performed to assess the utility of specific polymerase chain reaction (PCR)-based methods for Trichophyton rubrum and Trichophyton mentagrophytes as diagnostic tools for dermatophytoses. Both conventional morphological identification and specific PCR methods based on the nuclear ribosomal internal transcribed spacer (ITS)1 DNA sequence were performed to identify dermatophyte species from clinical specimens of patients who visited Kawasaki Social Insurance Hospital between 16 May and 17 August 2005. Specific PCR methods were also directly applied to clinical specimens, and the results of the two methods were compared. The clinical samples examined consisted of 126 skin scale specimens and 80 nail specimens. The positive rates of culture isolation from clinical specimens were 67% and 33% for skin scale and nail specimens, respectively. In contrast, PCR analysis yielded a positive rate of 100% for clinical isolates from both skin scales and nails, and rates of 95% and 99% were obtained by direct application to clinical specimens. The results of the present study indicated that specific PCR is highly advantageous as a diagnostic tool for detection and identification of dermatophytes on direct application to skin scale or nail specimens.     

Pseudomyxoma Peritonei with High Carcinoembryonic Antigen (CEA) Level: Report of Two Cases

Two cases of pseudomyxoma peritonei with high serum carcinoembryonicantigen (CEA) are reported. CEA levels in serum increased incorrelation with the accumulation of ascites. Systemic chemotherapywith anticancer agents such as 5-fluorouraciI (5-FU), cyclophosphamide,mitomycin C (MMC) and chromomycin A_a showed no effect on reducingeither the production of mucinous materials or the CEA level,but repeated intraperi-toneal instillation of large amountsof MMC reduced them in one case. In the other case, the CEAlevel returned to normal after removal of the tumor. These resultssuggest that CEA may be a useful indicator of the effect oftreatment and of the prognosis of pseudomyxoma peritonei.     

Anterior lumbar interbody fusion: changes in area of the dural tube, disc height, and prevalence of cauda equina adhesion in magnetic resonance images

OBJECTIVE: Many investigators have reported satisfactory outcome in anterior lumbar interbody fusion (ALIF) performed for lumbar disc herniation or "multiply operated back" (MOB), but without comparing preoperative and postoperative dural tube area and cauda equina adhesion in magnetic resonance imaging (MRI). We conducted this study to determine these data in ALIF performed for lumbar disc herniation and MOB. METHODS: Thirty-two patients who underwent ALIF, involving 38 discs, were studied. In MRI obtained before and after surgery (interval 9-48 months, mean 19.2 months), cross-sectional areas of the lumbar dural tube were measured from axial T2-weighted images using a computer-linked digitizer. At 30 disc levels operated on, the cauda was identified in images; cauda equina adhesions were classified according to Matsui et al (grade I-III). Clinical improvement was scored. RESULTS: Bony union was observed in radiographs of all patients. Preoperative and postoperative cross-sectional areas of the lumbar dural tube were 1.32 +/- 0.4 and 1.87 +/- 0.5 cm, respectively, and expansion ratio was 1.43 +/- 0.4. Recovery did not correlate with expansion ratio. Positive correlation was noted between expansion ratio and disc height ratio. At 30 disc levels where cauda equina was identified, 22 represented grade I and 8 represented grade II. At three of the latter, prior surgery had been performed via a posterior approach. CONCLUSIONS: No significant difference was noted in occurrence of grade II adhesions between primary ALIF and ALIF performed for MOB. Dural tube expansion was accomplished even without exposure of the tube, and cauda equina adhesion was uncommon in primary ALIF.     

Gut Microbiota Prevents Sugar Alcohol-Induced Diarrhea

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual’s susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.     

Pharmacokinetics,metabolism and pharmacodynamic s of a benzimidazole angiotensin II type 1 receptor antagonist in the beagle dog and cynomologus monkey

1. The pharmacokinetic s and disposition of E4177, an angiotensin II (Ang II) type 1 receptor antagonist, were studied in the beagle dog and cynomologus monkey following intravenous (i.v.) and oral (p.o.) administration. The relationship between the plasma concentrations of E4177 and Ang II receptor blockade were investigated in both species.

2. Single 0.3?mg kg i.v. doses of E4177 in dog and monkey were eliminated rapidly. The elimination half-lives were 1.9 and 2.0 h, and the systematic plasma clearance values were 9.1 and 12.9 ml/min/kg respectively.

3. The oral bioavailabilityof single doses of 0.3-3?mg/kg of E4177 was > 60% in both dog and monkey. The absorption by both species was rapid, with peak plasma levels observed within 1 h, and the areas under the concentration versus time curve to infinity were proportional to the dose.

4. The apparent volumes of distributionat the steady-state were 1.0 and 1.2 l/kg in dog and monkey respectively. Tissue penetration was probably limited by the relatively high binding to plasma proteins (approximately 92.0 and 98.6% in the dog and monkey respectively).

5. Faecal excretion was the major eliminationpathway for radioactivity(approximately 90% of the dose) in both species after 1?mg/kg p.o. administration of ¹⁴C-E4177. Unchanged E4177 was the major radioactive component in the urine and faeces (0-24 h) of both species, accounting for approximately 85% of dose. In monkey, a minor metabolitein excreta and plasma was identified as the phase I metabolite M1, which is produced from E4177 by methyl- hydroxylation. M1 was not detected in dog. 6. The unbound plasma concentration versus blockade of the exogenous Ang IIinduced vasopressor response was also determined after an i.v. administrationof E4177 to dog and monkey. The relationship between the unbound E4177 concentration and the effect was highly significant in both species. The IC₅₀ of the dog and monkey were not significantly different: 2.6 and 2.7 ng/ml respectively.     

SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus

A vaccine for severe acute respiratory syndrome (SARS) is being intensively pursued against its re-emergence. We generated a SARS coronavirus (SARS-CoV) spike protein-expressing recombinant vaccinia virus (RVV-S) using highly attenuated strain LC16m8. Intradermal administration of RVV-S into rabbits induced neutralizing (NT) antibodies against SARS-CoV 1 week after administration and the NT titer reached 1:1000 after boost immunization with RVV-S. Significantly, NT antibodies against SARS-CoV were induced by administration of RVV-S to rabbits that had been pre-immunized with LC16m8. RVV-S can induce NT antibodies against SARS-CoV despite the presence of NT antibodies against VV. These results suggest that RVV-S may be a powerful SARS vaccine, including in patients previously immunized with the smallpox vaccine.     

Current state of therapeutic development for rare cancers in Japan,and proposals for improvement

This article discusses current obstacles to the rapid development of safe and effective treatments for rare cancers, and considers measures required to overcome these challenges. In order to develop novel clinical options for rare cancers, which tend to remain left out of novel therapeutic development because of their paucity, efficient recruitment of eligible patients, who tend to be widely dispersed across the country and treated at different centers, is necessary. For this purpose, it is important to establish rare cancer registries that are linked with clinical studies, to organize a central pathological diagnosis system and biobanks for rare cancers, and to consolidate patients with rare cancers to facilities that can conduct clinical studies meeting international standards. Establishing an all‐Japan cooperative network is essential. Clinical studies of rare cancers have considerable limitations in study design and sample size as a result of paucity of eligible patients and, as a result, the level of confirmation of the efficacy and safety shown by the studies is relatively low. Therefore, measures to alleviate these weaknesses inherent to external conditions need to be explored. It is also important to reform the current research environment in order to develop world‐leading treatment for rare cancers, including promotion of basic research, collaboration between industry and academia, and improvement of the infrastructure for clinical studies. Collaboration among a wide range of stakeholders is required to promote the clinical development of treatment for rare cancers under a nationwide consensus.