Possible predictors of response to clonazepam augmentation therapy in patients with protracted depression

INTRODUCTION: Clonazepam has been shown to be an effective supplementary treatment for depression. Thus, it would be useful to determine which patient characteristics are associated with response to clonazepam. AIMS: The purpose of this study was to examine the possible predictors of response to clonazepam in the treatment of depression. METHOD: A retrospective cohort analysis was carried out in 120 patients with protracted depression who were being treated with clonazepam. RESULTS: A variety of clinical factors, including age, gender, type of depression, frequency of episodes, family history; and daily dose of clonazepam, were analyzed as possible predictors of response to clonazepam. A Weibull regression analysis showed that the factors that best predicted improvement with clonazepam augmentation were negative family history of psychiatric illness (e(coef) = 0.378), daily clonazepam dose of 2.5-4.0 mg (e(coef) = 0.160), and unipolar depression (e(coef) = 0.147). CONCLUSIONS: These factors should be considered when clonazepam augmentation therapy is selected for protracted depression.     

The loss of HBeAg without precore mutation results in lower HBV DNA levels and ALT levels in chronic hepatitis?B virus infection

Background  The aim of this study was to investigate the correlation between precore (PC)/basal core promoter (BCP) mutations and the viral loads or activity of hepatitis in patients with chronic hepatitis B virus (HBV) infection. Methods  HBV genotypes, PC mutations, BCP mutations, HBV DNA levels, and serological markers of HBV were analyzed in all the patients with chronic HBV infection seen in Fujita Health University Hospital from June 2004 to November 2008 (n = 215). Results  HBV genotype was C in 169 patients, B in 16, A in 3, F in 1, and unclassifiable in 5. Among the patients with genotype C, the prevalence of PC wild type was significantly lower in hepatitis B envelope antigen (HBeAg)(−) patients than in HBeAg(+) patients (9.5% versus 49.0%, P < 0.0001). Among HBeAg(−) patients, the patients with PC wild type had significantly lower serum viral loads and alanine aminotransferase (ALT) levels compared with those with PC mutant (P < 0.001). Among HBeAg(−) patients, the patients with genotype B had lower serum viral loads compared with those with genotype C (3.6 ± 0.9 versus 4.6 ± 1.6, P < 0.05), and the prevalence of BCP wild type was significantly higher in those with genotype B than in those with genotype C (58.3% versus 10.8%, P < 0.05). Conclusions  Among HBeAg(−) patients with genotype C, the patients with PC wild type had significantly lower viral loads and ALT levels than those with PC mutant. This suggests that the patients with PC wild type may have better prognosis than those with PC mutant among HBeAg(−) patients with genotype C.     

Is omeprazole or misoprostol superior for improving indomethacin-induced delayed maturation of granulation tissue in rat gastric ulcers?

BACKGROUND AND AIMS: Proton pump inhibitors (PPI) and prostaglandin (PG) preparations are believed to both prevent NSAID-induced gastric ulcers and promote the delayed healing of gastric ulcers by NSAIDs, but it remains unclear which of these drugs is superior. The aim of this study was to clarify which achieved better healing of NSAID-induced gastric ulcers, not only with respect to epithelialization but also repair of the submucosal tissues. METHODS: We used acetic acid to induce gastric ulcers in rats, and compared the changes between a control group, NSAID group, NSAID + PPI group and NSAID + PG group. After removing the stomach of each animal, an ulcer index was calculated and the collagen content and type III collagen content of granulation tissue were measured. We also studied fibroblast dynamics, including proliferation, collagen synthesis, differentiation into myofibroblasts, and apoptosis. RESULTS: Indomethacin prevented re-epithelialization of the ulcers, interfered with fibroblast function, and also delayed the replacement of type III collagen. Omeprazole promoted epithelialization, but could not fully reverse the influence of indomethacin on granulation tissue maturation. A concomitant dose with misoprostolreversed it completely. CONCLUSIONS: From our point of view in this study in the use of experimental ulcers, it was thought that compensation of PG should have priority to gastric acid inhibition in terms of healing of NSAID-induced gastric ulcer.     

Neutral endopeptidase expressed by decidualized stromal cells suppresses akt phosphorylation and deoxyribonucleic acid synthesis induced by endothelin-1 in human endometrium

Endothelin-1 (ET-1) in human endometrium has been proposed to have a potential paracrine role, for its receptors are also present within this tissue. In addition, the expression of ET-1 varies during the menstrual cycle, and therefore, ET-1 may be involved in the cyclic change of the human endometrium, such as proliferation and decidualization. However, neither the inactivation of ET-1 in the endometrium nor the paracrine effect of ET-1 on endometrial cells has been determined. We investigated the production of ET-1 and the presence of neutral endopeptidase (NEP), which cleaves and inactivates ET-1, in primary cultured human endometrial cells. We found primary cultured endometrial epithelial cells, not stromal cells, to be the major source of ET-1. Western blot analysis and RT-PCR demonstrated that NEP was predominantly expressed by endometrial stromal cells. We also demonstrated that ET-1 stimulated the phosphorylation of Akt and DNA synthesis in endometrial stromal cells via the ET(A) receptor and phospahtidylinositol-3 kinase signaling pathways. The effect of ET-1 was regulated by NEP expressed by stromal cells. We also found that conditioned medium containing ET-1 from endometrial epithelial cell culture stimulated phosphorylation of Akt via the ET(A) receptor. In conclusion, ET-1 has a paracrine effect of Akt phosphorylation and cell proliferation on endometrial stromal cells, which occurs via the ET(A) receptor and phospahtidylinositol-3 kinase signaling pathways, and is regulated by cell-surface NEP.     

Residual FDG uptake of primary thyroid lymphoma after treatment may overestimate residual lymphoma

Objective

To assess ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) images in primary thyroid lymphoma (PTL) patients before and after treatment.

Methods

We conducted a retrospective review of data for ten patients (four men, six women) of mean age 65 (range 48–88) years, with histopathologically confirmed malignant thyroid lymphoma who underwent pre-treatment and post-treatment ¹⁸F-FDG PET between January 2005 and December 2014. Thyroid uptake was assessed by the 5-point scale score based on maximum intensity projection images.

Results

Four of the ten patients were judged to have a complete metabolic response (scores 1–3) and four to have a partial metabolic response (PMR; scores 4–5). Three of the four PMR patients had a good outcome with a treatment-free interval and overall survival of at least 53.0 months, although two of these three patients showed residual FDG uptake in the thyroid for more than 2 years after completion of treatment. Two of the ten patients were considered to have progressive metabolic disease.

Conclusions

In patients with PTL, residual FDG uptake in the thyroid after treatment that corresponds to a PMR may not always indicate a poor outcome.

     

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer

Background

Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers.

Materials and methods

The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed.

Results

Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years.

Conclusion

Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5–10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.     

Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial

Laninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20 mg of laninamivir octanoate once daily for 2 days (LO-2), 20 mg of laninamivir octanoate once daily for 3 days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9 % (19/487) in the LO-2 group, 3.7 % (18/486) in the LO-3 group, and 16.9 % (81/478) in the placebo group (P < 0.001 for each of the laninamivir octanoate group). The relative risk reductions, compared with the placebo group, were 77.0 % [95 % confidence interval (CI) 62.7–85.8] and 78.1 % (95 % CI 64.1–86.7 %) for the LO-2 and LO-3 groups, respectively. The incidences of adverse events in the laninamivir octanoate groups were similar to that in the placebo group. The inhalation of 20 mg of laninamivir octanoate once daily for 2 or 3 days was well tolerated and effectively prevented the development of influenza in household contacts.     

Role of Social Support in the Relationship Between Financial Strain and Frequency of Exercise Among Older Japanese: A 19-year Longitudinal Study

BackgroundPrevious studies have reported that financial strain has deleterious effects on healthy behaviors. Moreover, social support is expected to mitigate these effects, but few studies have investigated the effects of exercise; thus, the investigation can deepen our understanding of the relationship between social support and physical activity/exercise. We examined the relationship between financial strain and frequency of exercise, and the role of social support in this relationship in old age.MethodsData came from a 19-year longitudinal study conducted between 1987 and 2006 of Japanese adults aged 60 or more with up to seven repeated observations. Frequency of exercise was assessed using a four-point scale. Financial strain was measured using the responses to three questions related to financial condition. This study considered both emotional and instrumental supports. Covariates included demographic and socioeconomic factors, health behaviors, and health condition.ResultsThe analysis included 3,911 participants. The results of a generalized estimation equation model showed that among females, greater financial strain in the previous wave was associated with reduced frequency of exercise (b = −0.018; 95% confidence interval, −0.032 to −0.004), and that as financial strain increased, those who received more instrumental support engaged in less exercise than those who received less support (b = −0.009; 95% confidence interval, −0.017 to −0.002). These relationships were not observed among males.ConclusionThis study provides evidence that financial strain is negatively correlated with frequency of exercise among older females. In addition, instrumental support is negatively correlated with frequency of exercise among females under financial strain.Key words: financial strain, social support, exercise, panel data analysis, old age     

Akaike's information criterion for a measure of linkage disequilibrium

 The extent and distribution of linkage disequilibrium (LD) in humans is a current topic especially for gene mapping of complex diseases. Akaike's information criterion (AIC) was applied to estimate LD and compared with other standard LD measures, D′ and r ². By comparison of an independent model (IM; linkage equilibrium) and a dependent model (DM; linkage disequilibrium), the parsimonious model is the one with the smaller AIC score. Therefore, the extent of LD by AIC is expressed as AIC(IM) — AIC(DM)(AIC(LD)). A total of 39 single-nucleotide polymorphisms on a 1.6-Mb region of chromosome 21q22 were identified, and genotyped in 192 Japanese individuals. All possible pairs were analyzed to estimate LD and the analyses were compared. AIC(LD) became highly positive as the D′ value increased and was negative at D′ values of around 0.2. Because a negative value of AIC(LD) implies linkage equilibrium, D′ values below 0.2 should be regarded as linkage equilibrium. The LD estimate by AIC yielded results similar to those obtained by r ², indicating that AIC(LD) would be useful for fine gene mapping. Received: July 3, 2002 / Accepted: October 2, 2002