Comparison of pramipexole and modafinil on arousal, autonomic, and endocrine functions in healthy volunteers

The noradrenergic locus coeruleus is a major wakefulness-promoting nucleus of the brain, which is also involved in the regulation of autonomic and endocrine functions. The activity of the locus coeruleus is believed to be tonically enhanced by a mesocoerulear dopaminergic pathway arising from the ventral tegmental area of the midbrain. Both modafinil, a wakefulness-promoting drug, and pramipexole, a D(2)/D(3)receptor agonist with sedative properties, may act on this pathway, with modafinil increasing and pramipexole decreasing locus coeruleus activity. The aim of this study was to compare the two drugs on alertness, autonomic and endocrine functions in healthy volunteers. Pramipexole (0.5mg), modafinil (200mg), and their combination were administered to 16 healthy males in a double-blind, placebo-controlled design. Methods included tests of alertness (pupillographic sleepiness test, critical flicker fusion frequency, visual analogue scales), autonomic functions (resting pupil diameter, light and darkness reflex responses, heart rate, blood pressure, salivation, core temperature), and endocrine functions (blood concentrations of prolactin, growth hormone, and thyroid stimulating hormone). Data were analysed by ANOVA. Pramipexole reduced alertness, caused pupil dilatation, increased heart rate, reduced prolactin and thyroid stimulating hormone, and increased growth hormone level. Modafinil caused small increases in blood pressure and core temperature, and reduced prolactin levels. The sedative effect of pramipexole and the autonomic effects of modafinil are consistent with altered activity in the mesocoerulear pathway; the pupil dilatation following pramipexole suggests reduced dopaminergic excitation of the Edinger-Westphal nucleus.     

Non-invasive measurement of organ density in a rat simulated microgravity model

BACKGROUND: Spaceflight has caused serious concerns to the health and well-being of astronauts, both while in space and post-mission on Earth. The deleterious health effects due to microgravity are not well understood and though these effects may be caused by multiple factors, fluid shifts within the body may play a major role. HYPOTHESIS: We believe that 45 degrees C HDT will cause significant changes in organ density as measured by spiral computed tomography in a 1-h experimental time period. METHODS: There were 20 male Fischer 344 rats that were randomly selected to be in an experimental or control group. The experimental group (n = 12) was subjected to a 45 degrees head down tilt microgravity exposure (45 degrees HDT) for 1 h, and the control group (n = 8) remained in the prone position for the same amount of time. At the end of 1 h, the density of the brain, lungs, heart, liver, and left and right kidneys were measured using spiral computed tomography (SCT) while the rats remained in their experimental positions. RESULTS: With the exception of the right kidney, we demonstrated that there was a significant change (p < 0.05) in the densities of all tested organs in the 45 degrees HDT group when compared with the control group. The brain showed the largest percent increase at 45.6% while the lungs showed the least amount of change at 8.7%. CONCLUSIONS: We conclude there are significant increases in organ density, as measured by SCT, in male 45 degrees HDT rats compared with prone controls.     

The spectrum of HIV-related disease in rural Central Thailand

To determine the spectrum of HIV-related illnesses presenting to a rural primary and secondary healthcare facility in Central Thailand, a cross-sectional study was conducted. Routinely collected data were extracted from outpatient medical notes for all adult HIV-infected new attenders of the Manorom Christian Hospital Infectious Disease Clinic. Data concerning inpatient admissions of HIV-infected individuals were collected from ward admission books and discharge summaries. Complete data were available for 229 outpatients, 70% of whom were men. The median age at presentation was 31 years for men and 30 years for women. The majority of the outpatients were married (69%) and infected heterosexually (91%). The commonest conditions requiring admission were cryptococcal meningitis (15%), bacterial pneumonia (12%), extrapulmonary tuberculosis (12%), Pneumocystis carinii pneumonia (7%), cerebral toxoplasmosis (4%) and pulmonary tuberculosis (3%). Of the patients presenting for the first time, 32% had AIDS-defining illnesses. Presentations with some conditions, such as tuberculosis and septicemia, were fewer than expected. The common opportunistic infections among HIV-infected adults in this rural region are treatable and preventable. Most patients present with advanced disease and earlier diagnosis, through improved access to voluntary counseling and testing, would enable them to receive appropriate preventive therapies and antiretrovirals as they becomes available. The high prevalence of cryptococcal disease suggests that prophylactic anti-fungal therapy may be of value in this area. Septicemia and tuberculosis may be under-diagnosed, highlighting the need for improved diagnostic laboratory facilities or treatment based upon validated clinical algorithms. Community care and palliative care services for HIV-infected individuals will increasingly be required in this region.     

Integrating Cognitive-Behavioral Psychotherapy for Persons with Schizophrenia into a Psychiatric Rehabilitation Program: Results of a Three Year Trial

Emerging models of cognitive-behavioral treatment (CBT) offer promising new intervention strategies in the psychotherapy of schizophrenia. These models, however, have not been integrated into community support programs and evaluated in comparison to standard community treatments. This study examined differences in outcomes of clients who received long-term day treatment program services (DTP) compared to clients who received individual CBT that was included as part of their DTP treatment. Twenty-four clients were randomly assigned to DTP treatment or CBT/DTP treatment. Data on standardized measures of psychosocial functioning, symptomatology and rehospitalizations were collected over the course of three years of treatment. Analysis of variance with repeated measures was conducted to evaluate the effects of type of treatment (CBT/DTP and DTP) and time (dependent variable scores taken at the end of treatment years one, two and three) on the three outcome variables. Results indicate significant improvement for the CBT/DTP group compared to the DTP group in the patterns of change over time for psychosocial functioning and symptomology. In addition to this significant group/time interaction the time factor was also significant for both variables. For rehospitalizations the time factor was significant and the group/time factor was nonsignificant. Implications for service delivery to persons with schizophrenia and suggestions for future research are discussed.