Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey

 The behavioral effects of GBR 12909, a selective dopamine uptake inhibitor, were determined in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of stimulus termination and a second-order schedule of IV drug self-administration. Intermediate doses of GBR 12909 increased FI response rate markedly, and the highest dose decreased response rate below control values. The 5HT uptake inhibitors, alaproclate and fluoxetine, and the 5HT agonist, quipazine, attenuated the behavioral-stimulant effects of GBR 12909, whereas the 5HT_2A/2C antagonist, ritanserin, enhanced the behavioral-stimulant effects of the lowest dose. GBR 12909 reliably maintained self-administration, and ritanserin increased response rate maintained by the highest dose. The dopamine agonist, quinpirole, increased FI response rate in only one of three subjects, and ritanserin enhanced the behavioral-stimulant effects of quinpirole in that subject. The dopamine agonist, apomorphine, only decreased FI response rate, and ritanserin did not alter its behavioral effects. The pharmacological profile of GBR 12909 administered alone and in combination with selective 5HT drugs in the present study was similar to that obtained previously with cocaine, further demonstrating that 5HT can reliably modulate the behavioral effects of psychomotor stimulants with prominent dopaminergic actions. Received: 9 July 1996 / Final version: 22 November 1996     

AIDS in the black community: The plague, the politics, the people

This paper was originally developed by Calu Lester, the founder of KWICFAN, which took a novel approach to grass roots AIDS education in the black community. Calu died of AIDS before completing the work and the paper was completed by Larry L. Saxxon, who was both a friend of Calu's and an AIDS program consultant.

The paper presents a critical perspective of black America's response to the AIDS epidemic. The findings are frightening. Denial within the black community, coupled with a lack of support from the agencies responsible for funding AIDS education, has created a potential epidemiological nightmare. IV drug use continues to be a critical problem of frightening magnitude, allowing an efficient vehicle of HIV transmission. Most sadly of all, the social conditions that create and perpetuate the problematic drug abuse patterns still continue in black America. Black people are clearly becoming the new face of AIDS.     

Surveillance of Treated and Untreated Funguria in a University Hospital

Study Objective . To determine the influence of treatment on the microbiologic outcome of funguria. Design . Retrospective case series. Setting . A 300-bed tertiary care teaching hospital in a large metropolitan area. Subjects . 141 hospitalized patients, 18 years of age or older, with at least one urine culture positive (≥ 10² cfu/ml) for fungi. Interventions . Retrospective review of medical records to determine the microbiologic outcome of funguria. Main Results . Funguria developed rapidly in individuals with known predisposing factors. Urinalysis did not routinely detect the presence of fungi or pyuria. Symptoms such as fever, dysuria, and frequency were generally absent. Funguria persisted whether it was due to Candida albicans or non-albicans species. There were no statistical differences in the microbiologic outcomes of treated and untreated funguria. Conclusions . Funguria is a rapidly developing, often benign and persistent process. Minimizing predisposing risks, such as removing indwelling urinary catheters, is beneficial in its management. Pharmacologic treatment of funguria due to C. albicans or non-albicans species does not influence the microbiologic outcome.     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

Ethics and Economics in Search of a Common Language

Book reviewed in this article: The Needs of Strangers . By Michael Ignatieff. The Health Economy . By Victor Fuchs. Just Health Care . By Norman Daniels     

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

Impact of smoking on cancer stage at diagnosis.

BACKGROUND: Studies evaluating the relationship between smoking and cancer spread are limited. METHODS: We studied the relationship between cancer stage at diagnosis (local, regional, or metastatic) and smoking history (current, previous, or nonsmoker). For lung cancer, patterns of spread were also studied. RESULTS: In a tumor registry for eastern North Dakota, northwestern Minnesota, and northern South Dakota, 11,716 cases were identified from 1986 to 2001. Current smokers (relative risk [RR], 2.11; 95% confidence interval, 1.93 to 2.32; P <.001) and previous smokers (RR, 1.56; 95% confidence interval, 1.42 to 1.72; P <.001) had an increased risk of metastatic disease at diagnosis. Current smokers (RR, 1.39; 95% confidence interval, 1.29 to 1.51; P <.001), but not previous smokers, also had an increased risk of regional disease. An increase in metastatic disease was most evident for prostate cancer (RR, 1.53; P =.003). An increase in regional disease was most evident for head and neck (RR, 3.53; P <.001), prostate (RR, 1.83; P =.030), and breast cancer (RR, 1.22; P =.005). Compared with previous smokers, current smokers with metastatic lung cancer were more likely to have involvement of the brain (33.6% v 23.0%; P =.004), bone marrow, adrenal gland, and pericardium (24.7% v 15.9%; P =.004). CONCLUSION: Previous or current smoking is a risk factor for increased cancer stage in a wide range of malignancies. Further study is required to determine whether this association is causal.