Treatment regimen and hypnotic self-administration

RATIONALE AND OBJECTIVES: Previous studies have shown that insomniacs self-administer hypnotics at high nightly rates. This study determined whether prior experience with different treatment regimens (i.e., instructions and capsule availability) would alter the previously observed high hypnotic self-administration rates. METHODS: Sixty-four healthy men and women with (n = 32) and without (n = 32) insomnia, 21-55 years, self administered placebo or triazolam (0.25 mg) after different prior treatment regimens. They received one of three different treatment regimens enforced for 11 nights: a capsule each night, a capsule as needed, or a capsule every third night. On 14 subsequent nights they choose to self-administer a capsule or not, placebo during 1 week and triazolam (0.25 mg) the other (counterbalanced in order). RESULTS: Insomniacs self-administered more capsules than normals and triazolam was self-administered more than placebo. For both groups, treatment regimen had a minimal effect on capsule self-administration. During the treatment phase, triazolam improved self-ratings of sleep relative to placebo. During the choice phase, nightly variations in self-rated sleep predicted self-administration of a capsule on the following night, regardless of whether the capsule was active drug or placebo. CONCLUSIONS: The data of this study are consistent with the view that hypnotic self-administration by insomniacs is therapy-seeking behavior and not drug abuse.     

Comparison of micafungin MICs as determined by the Clinical and Laboratory Standards Institute broth microdilution method (M27-A3 document) and Etest for Candida spp. isolates

Micafungin Etest and Clinical and Laboratory Standards Institute (CLSI) MICs were compared for 337 Candida spp. isolates. The performance of Etest for testing the susceptibilities of Candida spp. to micafungin was evaluated by the assessment of both categorical (CA) and essential (EA) agreements. The CA was evaluated 2 ways: (i) by the ability of Etest to separate resistant (nontreatable) from susceptible (treatable) isolates by using the newly adjusted species-specific micafungin clinical breakpoints (CBPs) that are available for most of the common species tested and (ii) by the ability to separate wild type (WT) from non-WT isolates or those harboring FKS mutations (with reduced echinocandin susceptibility) by using micafungin epidemiologic cutoff values (ECVs). Etest and CLSI MICs were in EA when the MICs were within 2 log(2) dilutions. Based on agreement percentages, our data indicated that Etest is suitable to test micafungin for most of the Candida species evaluated (overall EA 94.7%; overall CA according to CBPs 97.2% and according to ECVs 97.3%). However, the number of resistant isolates was small, so further evaluations are needed with a higher number of such isolates including more resistant or those with known mechanisms of resistance (non-WT).     

Colonic Perforation in Graft Versus Host Disease: A Case Report

Graft versus host disease (GVHD) is a phenomenon that occurs after allogeneic bone marrow transplants. Gastrointestinal (GI) manifestations of acute GVHD are common, but severe GI GVHD complications, such as bowel perforation, occur rarely and necessitate surgical intervention. To our knowledge, there are no recorded cases of colonic perforation resulting from GVHD with negative cultures for infectious agents such as cytomegalovirus. We present a case of large bowel perforation due to GVHD.     

Effects of sarpogrelate hydrochloride in a patient with chronic graft-versus-host disease: a case report

Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogenic bone marrow transplantation. Even with aggressive treatment, cGVHD is associated with a significant degree of morbidity and mortality. cGVHD resembles autoimmune disorder, particularly systemic sclerosis (SSc). Sarpogrelate hydrochloride (SH) is an antagonist of the 5-hydroxytryptamine2A (5HT2A) receptor and has been reported to be effective in the treatment of systemic sclerosis (SSc) patients with Raynaud phenomenon. We used SH to treat a cGVHD patient, and we measured plasma PDGF and total TGF-beta levels. After SH treatment, his plasma PDGF and total TGF-beta levels decreased, and he noticed improvement in his skin pigmentation. In the present case, SH may have improved the skin lesion by inhibiting the synthesis of PDGF and TGF-beta.     

Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.