Effects of milnacipran on binge eating - a pilot study

Selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors are effective in the treatment of bulimia nervosa. There have been relatively few studies of the efficacy of specific serotonin and norepinephrine reuptake inhibitors in the treatment of eating disorders. Twenty-five outpatients with binge eating episodes, diagnosed as anorexia nervosa, binge-eating/purging type, bulimia nervosa/purging type, or bulimia nervosa/non-purging type, were treated with milnacipran and 20 patients completed the 8-week study. Symptom severity was evaluated using the Bulimic Investigatory Test, Edinburgh (BITE) self-rating scale before administration of milnacipran and after 1, 4, and 8 weeks treatment. The scores improved after 8 weeks, especially drive to, and regret for, binge eating. Milnacipran was more effective in patients without purging and in younger patients, while there was no difference in the efficacy of milnacipran among subtypes of eating disorders.     

Four cases of therapy-related leukemia in multiple myeloma

We have experienced 4 cases of therapy-related leukemia (TRL) in 119 patients with multiple myeloma (MM) who had received combination chemotherapy including alkylating agents between 1988 and 1998. All 4 cases were acute myelogenous leukemia, 3 were males and 1 was female. Median age at diagnosis of MM was 60 years, and median time to TRL from diagnosis of MM was 5.5 years. The chromosome abnormalities were found in 3 of those cases. All 4 cases were resistant to antileukemic chemotherapy, and median survival time from TRL was only 5.5 months. The TRL in MM is thought to be a more important problem, because recently the treatment for this disease has become more intensive, including high-dose chemotherapy supported by autologous stem cell transplantation.     

Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model

To ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the antitumor effects of trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSA and vorinostat both displayed strong antitumor activities in 50% of NSCLC cell lines, suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified National Cancer Institute program. In addition, pathway analysis was done with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the support vector machine model was validated by an additional nine cell lines, resulting in a prediction value of 100% with respect to determining response to TSA and vorinostat. Our results suggested that (a) HDAC inhibitors may be promising anticancer drugs to NSCLC and (b) the nine-gene classifier is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients.     

Critical assessment of the methylphenidate transdermal system

Introduction of the methylphenidate transdermal system (MTS) provides a different way of delivery for the most widely prescribed agent used to treat attention-deficit hyperactivity disorder (ADHD). The MTS delivery system provides good absorption of the active ingredient. Maximal plasma concentration of methylphenidate occurs from seven to nine hours after patch placement. Onset of action in pharmacodynamic studies has been registered at the two-hour mark after patch placement. As a result of the transdermal delivery system, the effect of first-pass metabolism is greatly diminished. Removal of the patch is associated with a biexponential decrease in methylphenidate levels. Recommended placement of the MTS is on a patient's hip, with a suggested application time of nine hours. Efficacy was demonstrated at all time points measured in ADHD, from 2-12 hours. Most adverse events reported were mild to moderate in severity; the most frequent adverse events reported were disturbances in sleep and appetite.     

Tumor doubling time and local immune response to hepatic metastases from colorectal cancer

BACKGROUND AND OBJECTIVES: A number of studies have investigated the role of tumor-infiltrating lymphocytes in cancer, yet the local immune response to hepatic colorectal cancer metastasis remains unclear. As the tumor doubling time (DT) of hepatic colorectal cancer metastases is a good index of tumor growth, we examined the correlation between tumor DT and the local immune response by phenotype in hepatic colorectal cancer metastases. METHODS: Tumor DT and local immune response were examined in 20 patients with hepatic colorectal cancer metastases by analyzing tumor-infiltrating lymphocytes using flow cytometry or immunohistochemical studies. Tumor proliferative activity was also investigated by determining the expression levels of Ki-67 and proliferating cell nuclear antigen (PCNA). RESULTS: Locally abundant populations of CD83(+) dendritic cells (DCs) and CD8(+) T cells were positively related to longer tumor DT (P < 0.05), as were abundant CD8(+) T cells having interferon-gamma-producing potentials (P < 0.05). There was no significant correlation between tumor cell expression levels of Ki-67 or PCNA and tumor DT. CONCLUSIONS: Longer DT tumors have increased local populations of CD8(+) T cells and CD83(+) DCs even in hepatic colorectal cancer metastases.     

Fiber-Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

Background

Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA-PD) have a more aggressive disease course than those with idiopathic PD (iPD).

Objective

The objective of this study was to investigate fiber-specific white matter (WM) differences in nonmedicated patients with early-stage GBA-PD and iPD using fixel-based analysis, a novel technique to assess tract-specific WM microstructural and macrostructural features comprehensively.

Methods

Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA-PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses.

Results

Patients with GBA-PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal-thalamo-cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal-thalamo-cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA-PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α-synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores.

Conclusions

We report reduced fiber-specific WM density and bundle cross-sectional size in patients with GBA-PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α-synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Therapeutic effect of laparoscopic sleeve gastrectomy on obstructive sleep apnea and relationship of type 2 diabetes in Japanese patients with severe obesity

Aims/IntroductionObstructive sleep apnea (OSA) is among the most important obesity‐related diseases, and offers the potential for accelerated the early onset and progression of type 2 diabetes. The aim of the present study was to clarify the therapeutic effect of laparoscopic sleeve gastrectomy on OSA in severely obese Japanese patients, and to find correlations between OSA improvements and β‐cell function (BCF).Materials and MethodsBetween September 2013 and December 2019, 61 patients who underwent laparoscopic sleeve gastrectomy were enrolled. The apnea–hypopnea index (AHI) was used to diagnose OSA. The tongue area, uvula area and other parameters were measured using cone‐beam computed tomography. Regarding BCF parameters, the homeostasis model assessment of β‐cell function, insulinogenic, Matsuda and disposition indexes were used to evaluate the improvement in BCF. Improvement of OSA was defined as AHI <15.ResultsThe improvement rate of OSA was 51.8% (29/56). The change in AHI was significantly correlated with the excess weight loss percentage (ρ = 0.501), changes in tongue area (ρ = 0.350) and uvula area (ρ = 0.341). Multivariate analysis showed that preoperative AHI and postoperative hemoglobin A1c were independent prognostic factors of OSA non‐improvement. The homeostasis model assessment of β‐cell function (P < 0.001), the insulinogenic index (P < 0.001) and the disposition index (P = 0.019) of patients with AHI of <15 were significantly higher than those in patients with AHI of ≥15.ConclusionsLaparoscopic sleeve gastrectomy is a promising procedure for severely obese patients with OSA. BCF recovery was found to be significantly higher in patients with OSA improvement.     

In vivo activities of new rifamycin derivatives against mycobacteria

Therapeutic effects of new rifamycin derivatives, 3'-hydroxy-5'-(4-alkylpiperazinyl) benzoxazinorifamycins, KRM 1648, 1657, 1668, 1674 and 2312 (kindly supplied by Kanegafuchi Chem. Ind. Co. Japan), were evaluated on experimental tuberculosis and Mycobacterium avium complex infection in mice. I. Experimental tuberculosis in mice Male ddY mice were inoculated via tail vein with ca. 1 x 10(9) CFU of M. tuberculosis H37Rv suspended in 0.2 ml medium. Treatment of the mice with the new rifamycin derivatives or rifampicin (RFP: as a control drug) was performed by daily oral administration of 10 mg/kg of the drugs, starting at the 24th hour of infection and continuing until the 40th day of infection. Therapeutic effect of each drug was assessed by mortality of the treated mice. All control mice which did not receive any drug died within the 20th day (in Exp. 1) and the 22nd day (in Exp. 2) of infection, while 25% (in Exp. 1) and 40% (in Exp. 2) of RFP-treated mice and 100% (in Exp. 1 and 2) of mice treated with any of the KRMs survived on the 40th day of infection. II. Experimental M. avium complex infection in mice Female beige mice (8-12 weeks old) were inoculated via tail vein with ca. 1 x 10(8) CFU of M. avium complex strain 31F093T, a mouse-virulent strain, suspended in 0.2 ml medium. Treatment of the mice with each drug (daily oral administration of 20 mg/kg) was started 24 hours after the inoculation, and was continued throughout 12 weeks of infection.(ABSTRACT TRUNCATED AT 250 WORDS)