A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

Neuropharmacology and Drug Interactions in Clinical Practice

Summary: Absorption, distribution, and clearance are key pharmacokinetic principles. These parameters can be highly variable among patients and among compounds, and are factors that must be considered in the wide variability in response to medications. Current antiepileptic drugs (AEDs) present many challenges in their administration. However, understanding and utilizing pharmacokinetic principles can assist the clinician in the appropriate optimization of AEds.     

The effects of illicit drug use and HIV infection on sex hormone levels in women.

Drug use and HIV infection may affect sex hormone levels in women. One hundred and ninety-six women with and without a history of illicit drug use (50 HIV-negative and 148 HIV-infected), with regular menses, who never used antiretrovirals, were evaluated. Luteinizing hormone levels were significantly higher in women with a CD4 cell count <200/microl (p < 0.002). Current methadone use was associated with lower levels of total testosterone (p = 0.03) and higher levels of prolactin (p = 0.002); mean estradiol levels were 43% lower in women who used intravenous drugs (p < 0.001). Alcohol and crack cocaine use was not associated with sex hormone levels. Age, race, body mass index and degree of HIV immunosuppression were also associated with differences in sex hormone levels.     

Significance of Anticardiolipin Antibodies on Short and Long Term Allograft Survival and Function following Kidney Transplantation

The significance of anticardiolipin antibodies (ACAs) prior to renal transplantation is unclear. We studied a cohort of 337 patients who underwent renal transplantation from 1996 to 2001. Follow-up continued until allograft loss, patient death or 31 December 2002. The primary outcome was a composite endpoint of death-censored allograft loss or a 25% reduction in estimated glomerular filtration rate (GFR) from 1-month post-transplant. Secondary outcomes were allograft loss, a 25% reduction in GFR, acute rejection and creatinine at 1 year. IgG and IgM ACA titers were positive (> or =15) in 18.1% of recipients. There were no significant differences at baseline between recipients, except coumadin therapy in those with positive ACA titers (20% vs. 7.4%). Post-transplant, there was no increase in the primary outcome in ACA-positive patients, even after adjustment for anticoagulation with coumadin (HR = 1.42 [0.68, 2.96]). There was no difference in secondary outcomes between those with or without positive titers. Two of five patients with very high titers (>50) who were not anticoagulated had early graft loss. A positive ACA titer prior to kidney transplantation was not associated with inferior renal outcomes after transplantation, although more research is required to address the prognostic significance of very high ACA titers.     

Overview of contemporary families.

Perceptions and definitions of the term family have always been varied and complex. Hence, an overview of contemporary families is presented here from several perspectives. First, families as they have been perceived by nursing and social science theorists are reviewed. Demographic changes in the family over the last two decades are then presented, followed by an examination of issues faced by families as they change over time. Finally, families as they exist within varying cultural and social contexts are discussed. Emphasis is placed on the need for health care providers to be flexible in defining and working with individual patients and their families.     

Antisocial personality disorder, HIV risk behavior and retention in methadone maintenance therapy

In a sample of 55 consecutive methadone maintenance admissions to our clinic, 42% were diagnosed with antisocial personality disorder (ASPD) using the National Institute of Mental Health Diagnostic Interview Schedule NIMH DIS. Individuals with ASPD exhibited greater risk for HIV infection as defined by more sexual contacts, needle use and equipment sharing. Data at 1 year follow-up were obtained on this group of patients. The objective was to compare the ASPD and non-ASPD groups with regards to demographics, drug abuse history, outcome and retention in treatment. There were no significant differences between the groups on any demographic or treatment outcome variables. Survival analysis indicated that there were no group differences in treatment retention. In conclusion, although there were no differences in treatment outcome between ASPD and non-ASPD groups it is possible that ASPD patients who drop out of treatment will be at higher risk for contracting and spreading HIV within the IV drug using population. These data also suggest that in this population the diagnosis of ASPD using primarily behavioral traits as measured in the NIMH-DIS-III, has little utility in predicting treatment outcome.     

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.     

Anti-interleukin-1 reactive cells in Hodgkin's disease

Constitutional symptoms (or B-symptoms) of Hodgkin's disease may be mediated by interleukin 1 (IL-1), a product of macrophage-histiocytes. To further study this relation, the authors examined the cells that reacted with anti-human IL-1 antibody in biopsy specimens from 140 untreated patients with Hodgkin's disease (72 asymptomatic patients and 68 with B-symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Anti-IL-1 reactive cells were observed in 62 cases. A positive staining reaction was observed in three types of cells: Reed-Sternberg and related (R-S) cells (33 cases); small to medium cells of undetermined origin (18); and granulocytes (11). The staining was negative in 78 cases, including 42 with B-symptoms. The majority of tumors (27/33) with positively stained R-S cells were from asymptomatic patients. Most tumors (14/18) with positively stained small to medium sized cells were from patients with B-symptoms. Large numbers of granulocytes were positively stained in five asymptomatic patients and six with B-symptoms. The immunohistochemical demonstration of IL-1-bearing cells in tumors does not correlate with the manifestation of constitutional symptoms in Hodgkin's disease.     

Effect of high terrestrial altitude and supplemental oxygen on human performance and mood.

Sustained exposure to high terrestrial altitudes is associated with cognitive decrement, mood changes, and acute mountain sickness (AMS). Such impairment in aviators could be a safety hazard. Thirteen male soldiers, ages 19-24, ascended in 10 min from sea level to 4,300 m (simulated), and remained there 2.5 d. Four times per day, subjects completed a test battery consisting of nine cognitive tests, a mood scale, and an AMS questionnaire. During one test session per day, subjects breathed 35% oxygen instead of ambient air. Analysis revealed transient deficits on altitude day 1 for three cognitive tasks. Most tasks displayed a persistent training effect. Sick subjects' moods were more negative and their performance improvement less. On altitude day 1, oxygen administration improved performance on two cognitive tests and one mood subscale. Following rapid ascent to 4,300 m, performance is most affected during the first 8 h. Individuals affected by AMS tend to improve more slowly in performance and have more negative moods than those who feel well.