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     

A clinically applicable method to preserve urine and bladder washing cells for flow cytometric monitoring of bladder cancer patients

We describe a method to fix exfoliated bladder cells that is suitable for followup of bladder cancer patients by deoxyribonucleic acid flow cytometry. After fixation with room temperature methanol plus acetic acid (20:1, volume:volume) urine and bladder washing samples from these patients can be stored at room temperature for 3 to 7 days and then assessed reliably for the presence of aneuploidy and the percentage of hyperdiploid cells. For those with active transitional cell carcinoma diagnostic accuracy comparing fresh to fixed specimens was improved from 58 to 92% with urine and from 50 to 100% with washing samples. For patients with a history of transitional cell carcinoma who currently are free of disease the false positive rate remains unchanged after fixation. The procedure described is suitable for use in the outpatient clinic and should permit shipping of samples without refrigeration to a central flow cytometry facility for analysis.     

Toward a VA women’s health research agenda: Setting evidence-based priorities to improve the health and health care of women veterans

The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the changing demographics and special health care needs of women, the VA Office of Research & Development recently sponsored the first national VA Women’s Health Research Agenda-setting conference to map research priorities to the needs of women veterans and position VA as a national leader in Women’s Health Research. This paper summarizes the process and outcomes of this effort, outlining VA’s research priorities for biomedical, clinical, rehabilitation, and health services research.     

Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament

The flow-independent viscoelastic and equilibrium behaviors of canine articular cartilage were examined with time after transection of the anterior cruciate ligament. The equilibrium, transient, and dynamic shear behaviors of cartilage were studied in biaxial compression-torsion testing at two time periods after transection of the anterior cruciate ligament and at two sites on the femoral condyle, in order to test for differences between sites of frequent and less frequent contact. Water content also was measured in cartilage at sites corresponding to the areas of mechanical testing. Transection of the anterior cruciate ligament produced significant decreases in all measured moduli of articular cartilage tested in equilibrium and dynamic shear and in equilibrium compression; the values for these moduli were 61, 56, and 77% of the control values, respectively, beginning at 6 weeks following transection of the anterior cruciate ligament. There was evidence of increased energy dissipation of cartilage in shear, with a 13 and 35% increase in tan δ at 6 and 12 weeks after transection of the anterior cruciate ligament, respectively. Changes in the viscoelastic relaxation function of cartilage in shear also were evident at 12 weeks after surgery. In all tissue, there was a significant increase in hydration of approximately 4% at 6 or 12 weeks after surgery. There was little difference between the material parameters for areas considered to be in frequent and less frequent contact, with the exception of hydration, which was greater for areas of less frequent contact. The observed changes in material properties demonstrate that relatively short periods of joint instability result in significant changes in the flow-independent viscoelastic behavior of articular cartilage, as well as in the intrinsic stiffnesses in compression and shear.     

Respiratory symptoms among elderly people in the New Forest area as assessed by postal questionnaire.

This study was carried out to estimate the prevalence of respiratory symptoms among people aged 65 years and older and assess the value of a postal survey in obtaining this information. A questionnaire was sent to 2011 subjects (957 men) drawn by age-stratified random sampling from the age-sex registers of four New Forest group practices (1:3.3 sample). A total of 1803 replied, a 96.2% response after excluding 136 who had died or moved from the area. The accuracy of replies was verified for 355 (20%) randomly selected subjects. Forty per cent had no respiratory symptoms. Exertional breathlessness was common (38%), increasing in prevalence with age but not with smoking history, and was the only symptom reported by 10% of subjects. Only 14.2% were current smokers; more of the subjects aged 85 years and over were lifelong non-smokers. Two hundred and ninety-six (16.4%) had chronic bronchitis, which was more common among smokers; 151 (8.4%) gave a history of asthma, of whom half (76) had active asthma, which was slightly less common among the very elderly subjects. Only 489 (27.1%) of subjects had seen their doctors with chest symptoms during the preceding 2 years.     

Hospital efforts in smoking control: remaining barriers and challenges.

BACKGROUND. This study reports the barriers and challenges for hospital tobacco control efforts after the institution of smoke-free policies. METHODS. Surveys of employees and inpatients of five hospitals in Augusta, Georgia, were conducted and evaluated 4 months after joint hospital implementation of smoke-free policies. A random sample of 1997 employees and a convenience sample of 517 inpatients returned usable surveys. RESULTS. Although attitudes to the hospital bans on smoking reflected strong support for smoke-free policies, four out of five hospitals reported significant implementation problems. Despite the bans, 49% of patients who were smokers continued to smoke while hospitalized, and almost one half of all hospitalized smokers had received no advice to quit smoking from a physician or a nurse since admission. Employees and patients both agreed that the smoke-free policies had benefited employees more than patients. CONCLUSIONS. Despite achieving a smoke-free status, there are many challenges that remain for comprehensive hospital tobacco-control efforts. Hospitals and health care professionals must remain particularly alert and attentive to the needs of patients and employees still addicted to tobacco.     

Multivesicular liposomes containing 1-beta-D-arabinofuranosylcytosine for slow-release intrathecal therapy

Optimal anticancer treatment with cell cycle-specific antimetabolites requires maintenance of a cytotoxic drug level for a prolonged period of time. We explored the use of multivesicular liposomes as a slow-release depot of 1-beta-D-arabinofuranosylcytosine for intrathecal administration. The intrathecal half-life of the liposome-encapsulated drug was 148 h, in contrast to the half-life of 2.7 h for the unencapsulated free drug, in a Sprague-Dawley rat model. The prolonged maintenance of a therapeutic drug level may increase efficacy, and the elimination of the very high peak level may decrease toxicity.