Severe mental illness and HIV-related medical and neuropsychiatric sequelae

Medical and neuropsychiatric sequelae of HIV infection present a spectrum of diagnostic and treatment challenges to mental health clinicians. Both HIV and the many opportunistic infections that manifest in patients due to their immunocompromised state also can affect the central nervous system (CNS). Thus, mental health clinicians need to be familiar with the diagnosis and management of HIV-related medical and psychiatric complications. This article provides an overview of the CNS-related manifestations resulting from HIV disease, including HIV-related dementia, psychotic disorders, delirium, CNS opportunistic infections and tumors, systemic abnormalities, psychoactive substances, and the adverse effects of certain medical treatments. Treatment strategies for individuals with HIV disease and comorbid severe mental illness are outlined and recommendations for future research are offered.     

A rotating disk of gas and dust around a young counterpart to beta Pictoris

beta Pictoris is the best known example of a main-sequence star encircled by a tenuous disk. Optical and infrared images of beta Pic suggest that the disk is composed of dust grains which have been interpreted as the debris generated by the disruption of the asteroid-sized remnants of planet-formation processes. The star itself is relatively old, with an age in excess of 100 Myr. Here we present high-resolution millimetre-wave images of continuum and molecular-line emission from dust and gas surrounding a much younger star, MWC480: the stellar properties of MWC480 are similar to those of beta Pic, but its age is just 6Myr. The morphology of the circumstellar material and a comparison with the predictions of kinematic modelling indicate the presence of a rotating disk, gravitationally bound to the star. Moreover, the mass of the disk is greater than the minimum required to form a planetary system like our own. We therefore suggest that the disk around the young star MWC480 could be a progenitor of debris disks of the type associated with older stars such as beta Pic, and so holds much promise for the study of both the origin of debris disks and the early stages of the formation of planetary systems.     

Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings

PURPOSE: To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors. PATIENTS: A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques. RESULTS: Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002). CONCLUSION: Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.     

Onychomycosis. Baseline results of an observational study

The investigators present an analysis of baseline quality-of-life and patient-management approaches from an observational study of 150 patients being treated by podiatric physicians and dermatologists for onychomycosis. The majority (73%) made the initial office visit specifically because of their onychomycosis. Both men and women indicated that they had substantial physical discomfort as well as concerns related to appearance. Women reported significantly more problems than did men as a result of their onychomycosis. Physicians reported that 54% of patients suffered from toenail discomfort, 36% had pain while walking, 40% reported that their condition limited wearing of shoes, and 67% were embarrassed by the condition. The results of this study suggest that the treatment approach of podiatric physicians is more likely to address the palliative concerns of patients with onychomycosis, while the approach of dermatologists is more likely to attempt a definitive cure.     

Computational dosimetry and treatment planning for boron neutron capture therapy

The longitudinal, expert, all data (LEAD) procedure has been employed as a criterion for the assessment of the procedural validity of diagnostic instruments. This study evaluated the procedure's concurrent, discriminant and predictive validity. Interview and questionnaire data obtained from 100 individuals in a substance abuse treatment program were used to assess current and lifetime substance use disorders and common comorbid disorders. An experienced, doctoral-level clinician formulated LEAD diagnoses for each patient, based on an initial interview, ongoing clinical contact and the results of the research assessment and all available clinical records. LEAD-derived substance use diagnoses showed good concurrent, discriminant and predictive validity. The validity of comorbid diagnoses obtained using the LEAD procedure was generally fair to good. Comparison with diagnoses based only on the clinician's unstructured initial interview showed that the availability of additional data enhanced diagnostic validity. Diagnoses derived by a research technician using the Structured Clinical Interview for DSM-III-R showed validity comparable to that of LEAD diagnoses. To enhance its diagnostic validity, applications of the LEAD standard should include a structured interview. Other variations in the application of the LEAD standard, including a longer evaluation period, may also enhance its performance as a diagnostic criterion measure.     

RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist

The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described.     

Assessment of cerebral blood flow and CO2 reactivity after controlled cortical impact by perfusion magnetic resonance imaging using arterial spin-labeling in rats

We measured CBF and CO2 reactivity after traumatic brain injury (TBI) produced by controlled cortical impact (CCI) using magnetic resonance imaging (MRI) and spin-labeled carotid artery water protons as an endogenous tracer. Fourteen Sprague-Dawley rats divided into TBI (CCI; 4.02 +/- 0.14 m/s velocity; 2.5 mm deformation), sham, and control groups were studied 24 hours after TBI or surgery. Perfusion maps were generated during normocarbia (Paco2 30 to 40 mm Hg) and hypocarbia (PaCO2 15 to 25 mm Hg). During normocarbia, CBF was reduced within a cortical region of interest (ROI, injured versus contralateral) after TBI (200 +/- 82 versus 296 +/- 65 mL.100 g-1.min-1, P < 0.05). Within a contusion-enriched ROI, CBF was reduced after TBI (142 +/- 73 versus 280 +/- 64 mL.100 g-1.min-1, P < 0.05). Cerebral blood flow in the sham group was modestly reduced (212 +/- 112 versus 262 +/- 118 mL.100 g-1.min-1, P < 0.05). Also, TBI widened the distribution of CBF in injured and contralateral cortex. Hypocarbia reduced cortical CBF in control (48%), sham (45%), and TBI rats (48%) versus normocarbia, P < 0.05. In the contusion-enriched ROI, only controls showed a significant reduction in CBF, suggesting blunted CO2 reactivity in the sham and TBI group. CO2 reactivity was reduced in the sham (13%) and TBI (30%) groups within the cortical ROI (versus contralateral cortex). These values were increased twofold within the contusion-enriched ROI but were not statistically significant. After TBI, hypocarbia narrowed the CBF distribution in the injured cortex. We conclude that perfusion MRI using arterial spin-labeling is feasible for the serial, noninvasive measurement of CBF and CO2 reactivity in rats.     

The experiences of Sudanese unaccompanied minors in foster care.

Sudanese unaccompanied minors were separated from their parents in childhood and lived apart from their families in refugee camps for close to a decade before being resettled in the United States. This phenomenological study examines the refugees’ experiences of living in American foster families after living in peer groups in the camps. Interviews with 18 young adults, 7 years after resettlement, revealed that nearly all of the youth struggled with parental authority initially, and nearly half of them changed placements because of relationship difficulties with their foster parents. Misunderstandings based on cultural differences often exacerbated conflicts. However, 15 of 18 youth currently had a positive relationship with at least 1 foster parent, sometimes with a parent from their second or third placement. Changing foster families is often considered a failure in the child welfare system, but several Sudanese youth reported that having supportive relationships helped them during the acculturation process whether those relationships developed during the first or last placement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)