Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

A multicenter phase 3 trial of lobeline sulfate for smoking cessation.

OBJECTIVE: To evaluate the safety and efficacy of sublingual lobeline sulfate for smoking cessation. METHODS: A multicenter (3 sites), double-blind, parallel, placebo-controlled, phase 3 smoking cessation trial of sublingual formulation of lobeline sulfate. A total of 750 smokers (250 per site) were randomized to either treatment (lobeline sulfate) or placebo with individual smoking cessation counseling lasting up to approximately 10 minutes. RESULTS: Efficacy revealed no statistical significance (P = 0.62) for lobeline sulfate as a smoking cessation aid. CONCLUSION: Sublingual formulation of lobeline sulfate does not appear to be an effective smoking cessation aid.

Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women.

CONTEXT: Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. OBJECTIVE: This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. DESIGN, SETTING, AND PARTICIPANTS: Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20-24.9 kg/m(2)), overweight (n = 31; BMI 25-29.9 kg/m(2)), and obese (n =32; BMI >or=30 kg/m(2)). INTERVENTION: For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. MAIN OUTCOME MEASURES: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. RESULTS: Increasing BMI was associated with increased follicular fluid insulin (P < 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P < 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. CONCLUSIONS: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients.

A randomized, controlled trial to assess the efficacy and safety of a transdermal delivery system of nicotine/mecamylamine in cigarette smokers.

AIMS: To determine the efficacy and safety of nicotine transdermal therapy co-administered with the nicotine antagonist, mecamylamine, compared to a nicotine transdermal patch alone (21 mg nicotine + 6 mg mecamylamine, 21 mg nicotine + 3 mg mecamylamine, and 21 mg nicotine + 0 mg mecamylamine). DESIGN: Multi-center (n = 4), double-blind, randomized, parallel group, repeat-dose study. SETTING: Clinical laboratory. PARTICIPANTS: A total of 540 subjects were enrolled into the study-135 from each of four sites; 180 patients in each of three treatment arms. INTERVENTION: Treatment was administered for the first 6 weeks of the 8-week study. Patients were instructed to continue smoking for the first 2 weeks of treatment. MEASUREMENTS: The primary efficacy parameter was 4-week continuous abstinence after the quit date, confirmed with an expired carbon monoxide of < 10 parts per million. FINDINGS: Analysis of the 4-week continuous abstinence for the intent-to-treat population showed overall rates of 29% (nicotine + 6 mg mecamylamine), 29% (nicotine + 3 mg mecamylamine) and 23% (nicotine only) using the slip definition which allows smoking in the first 2 weeks after the quit date. Statistical analyses revealed no significant treatment differences. Analyses using the strict definition (no smoking after the quit date) yielded similar non-significant group differences (29%, 27%, 26%). CONCLUSION: If adding mecamylamine to nicotine replacement therapy (NRT) improves the chances of success at stopping smoking, the results of this study suggest that the effect is very small.

Sensitivity and specificity of a reagent-impregnated test strip in identifying smokeless tobacco users.

This study was designed to determine the sensitivity and specificity of a reagent-impregnated test strip in identifying habitual snuff users and tobacco chewers. Urine specimens were obtained from smokeless tobacco users and controls and blind tested on-site using a reagent-impregnated test strip. Samples also were sent to our university hospital lab for cotinine and nicotine analysis by gas chromatography (GC). The test strip results were compared with GC results and self-reported use of snuff and chewing tobacco. A total of 61 subjects enrolled in the study: 26 snuff users, 25 tobacco chewers, and 10 nonconsumers of nicotine. Using GC assessment of nicotine and cotinine (>or=200 ng/ml) as the standard, we found the sensitivity of the test strip to be 96% (25/26) for snuff users and 96% (24/25) for tobacco chewers. When compared with self-report, the sensitivity of the test strip was 92.3% (24/26) for snuff users and 84% (21/25) for tobacco chewers. The specificity for nonusers of nicotine was 100% (10/10) for both the self-report and GC conditions. These results suggest that a reagent-impregnated test strip is a rapid, valid, and user-friendly means of differentiating smokeless tobacco users from nonconsumers of tobacco. The intensity of the pink color on the test strip is proportional to the amount of nicotine or its metabolites present in urine and therefore offers a semiquantitative measure of nicotine consumption.

Efficacy of the nicotine inhaler in smoking reduction: A double-blind, randomized trial.

Many smokers are not ready to quit but are interested in changing their smoking behavior, particularly if such a change is associated with a reduction in health risk. The present study evaluated the efficacy of the nicotine inhaler in reducing smoking. Exploratory studies assessed whether reduction in smoking was associated with reduction in markers of disease risk. A total of 429 healthy smokers (smoking at least 20 cigarettes/day) were randomly assigned to either nicotine-containing or placebo inhalers, which subjects were allowed to use ad libitum for up to 1 year. The nicotine inhaler was significantly superior to placebo in achieving reduction in daily cigarette consumption by at least 50% after 4 months, compared with baseline (18% vs. 8%, p = .004). Active treatment promoted smoking cessation: 8% of subjects in the nicotine group and 1% in the placebo group were abstinent at month 15. Throughout the study, smoking reduction, per se, independent of treatment group, was associated with a statistically significant decrease in exhaled carbon monoxide and serum cotinine and thiocyanate. Smoking reduction also improved established risk markers for cardiovascular disease over 4 months. The incidence of adverse events did not differ significantly between the active and placebo groups. The most common treatment-related adverse events were throat irritation and cough. In conclusion, the nicotine inhaler can help smokers who are unable or unwilling to quit to reduce daily cigarette consumption, which may be a health benefit on its own and may further promote quitting.

A formative evaluation of the potential role of nurse practitioners in a central London HIV outpatient clinic.

In-house audit demonstrated that 49% (173/352) of patients attending routine HIV outpatient care are asymptomatic and have needs that could potentially be met by other health care professionals. We therefore evaluated the potential development and acceptability of nurse practitioner roles in contributing to HIV outpatient care. Data were collected through 26 consultation observations, 25 patient interviews, 2 patient focus groups, 22 provider interviews and 8 provider focus groups. Service users were key members of the evaluation team. With increasing HIV incidence and the change in focus of doctor-patient consultations from acute to chronic disease management, there are concerns about the sustainability of easily available routine HIV outpatient appointments using the same model of care that has prevailed over the past 20 years. Nurse practitioner models of care were considered acceptable for asymptomatic patients, including those who do not have complex issues related to highly active antiretroviral therapy (HAART). Key considerations for the role include training, supervision, referral pathways, and a clear understanding of the limitations of nursing practice. There is an emphasis on the need to consider 'new ways of working' throughout the service, rather than merely substituting or transferring clinical roles between professionals. Funding pending, nurse practitioner roles are planned for implementation in late 2004. Evaluation will determine impact on service utilization, health and economic outcomes.

Developmental history of the Glover-Nilsson smoking behavioral questionnaire.

OBJECTIVE: To develop a simple, easily administered pencil-and-paper questionnaire to determine the degree to which behavioral patterns play a role in smoking dependence. METHODS: A modified Delphi technique was used to identify initial questions and to eliminate obvious duplications. Phase 2 utilized multiple statistical methods (principal components analysis, cluster analysis, stepwise multiple linear regression, cross tables, Mantel-Haenzel c2-test, and a Gamma test) to evaluate and reduce the number of questions from 18. RESULTS: These analyses yielded an 11-item questionnaire that can potentially assess behavioral dependence. CONCLUSION: It is hoped that the GN-SBQ will assist physicians, health care providers, and tobacco interventionists in identifying aspects of smoking addiction that are behavioral in nature. The need for future research is discussed.

Treating nicotine dependence.

This article reviews the biology of nicotine addiction and the most effective treatments for nicotine dependence. Nicotine elevates dopamine levels in the brain, which is associated with drug reinforcement and dependence. Nicotine abuse leads to nicotine dependence. The most effective pharmacological adjuncts for treating nicotine dependence are nicotine replacement therapy and bupropion SR. When these are combined with behavioral counseling, the best treatment outcomes are observed.

The development of a highly informative mouse Simple Sequence Length Polymorphism (SSLP) marker set and construction of a mouse family tree using parsimony analysis.

To identify highly informative markers for a large number of commonly employed murine crosses, we selected a subset of the extant mouse simple sequence length polymorphism (SSLP) marker set for further development. Primer pairs for 314 SSLP markers were designed and typed against 54 inbred mouse strains. We designed new PCR primer sequences for the markers selected for multiplexing using the fluorescent dyes FAM, VIC, NED, and ROX. The number of informative markers for C57BL/6J x DBA/2J is 217, with an average spacing of 6.8 centiMorgans (cM). For all other pairs of strains, the mean number of informative markers per cross is 197.0 (SD 37.8) with a mean distance between markers of 6.8 cM (SD 1.1). To confirm map positions of the 224 markers in our set that are polymorphic between Mus musculus and Mus spretus, we used The Jackson Laboratory (TJL) interspecific backcross mapping panel (TJL BSS); 168 (75%) of these markers had not been previously mapped in this cross by other investigators, adding new information to this community map resource. With this large data set, we sought to reconstruct a phylogenetic history of the laboratory mouse using Wagner parsimony analysis. Our results are largely congruent with the known history of inbred mouse strains.

A comparison of sustained-release bupropion and placebo for smokeless tobacco cessation.

OBJECTIVE: To evaluate the potential efficacy of bupropion sustained release when used in combination with minimal counseling for moist snuff cessation in males. METHODS: A double-blind, placebo-controlled 3-month trial. The active treatment group (n = 35) received bupropion SR at 150 mg/qd day for the first 3 days, then beginning day 4 through day 49 (7 weeks) 150 mg/ b.i.d. The placebo group (n= 35) received 1 tablet qd for 3 days and beginning day 4 through day 49, 1 tablet/b.i.d. RESULTS: Bupropion 300 mg/day (150 b.i.d.) produced significantly higher quit rates for smokeless tobacco cessation at the end of treatment (7 weeks) than placebo (p = 0.04) with an OR of 2.73. CONCLUSION: Bupropion SR appears to be effective for smokeless tobacco cessation.

A postal survey to identify and describe nurse led clinics in genitourinary medicine services across England.

BACKGROUND: Nurses in genitourinary medicine (GUM) services are progressively extending their roles to conduct "comprehensive care" nurse led clinics. In such roles the nurse coordinates the first line, comprehensive care of patients presenting with sexual health conditions and issues. OBJECTIVES: To identify and describe comprehensive care nurse led clinics in GUM services across England. METHODS: A postal questionnaire consisting of 17 closed response questions was sent to 209 GUM services across England. A second questionnaire was sent to non-responders to increase the response rate. Data were single entered and analysed using SPSS. RESULTS: Of the 190 GUM clinic respondents (91% response rate), 44 (23%) reported providing some form of comprehensive care nurse led clinic, 90% of which were initiated since 1995. Key results show staff development featured as the main reason for initiating such services and there was general consistency in the aspects of care undertaken by these nurses. There was evidence of guideline development specific to nurse led care and some patient group direction use for supplying medication. The level of support from medical staff while nurse led clinics were being conducted varied between services. Few services have conducted any audit or research to monitor/evaluate nurse led care. There was little consistency in the clinical experience and educational prerequisites to undertake comprehensive care nurse led clinics. Continuing professional development opportunities also varied between services. CONCLUSIONS: The steady growth of comprehensive care nurse led clinics indicates that the skills of GUM nurses are being recognised. Nurses working in advanced practice roles now require courses and study days reflecting these changes in practice. Locally agreed practice guidelines can define nursing practice boundaries and ensure accountability, as will the development of patient group directions to supply medication. Monitoring and evaluation of nurse led clinics also require attention.

Sexual health clinics for women led by specialist nurses or senior house officers in a central London GUM service: a randomised controlled trial.

OBJECTIVES: To assess the care process and clinical outcomes for two different models of GUM clinic for women: one led by specialist nurses and the other by senior house officers (SHOs). METHOD: An open randomised controlled trial was carried out in a central London genitourinary medicine (GUM) women's clinic. Of 1172 women telephoning for an appointment, 880 were randomised to provide 169 eligible patients in the specialist nurse arm and 178 in the SHO arm. Of the eligible patients a total of 224 attended their appointment. The clinical records of the randomised women were audited for adequacy of care according to local guidelines. 30 key variables were objectively assessed and recorded on a standard audit form. An overall unitary index score (%) was calculated for each patient. The main variables associated with the outcome of specialist nurse and SHO decision making (diagnostic test request, preliminary diagnosis, and treatment provided) were then analysed independently. RESULTS: The median documentation audit scores for specialist nurses (n=103) and SHOs (n=121) were 92% and 85% respectively (p<0.0001). The specialist nurses' documentation was significantly (p<0.05) more complete than the SHOs' for five variables: details of menstrual cycle, physical examination, medication instructions given to patients, health promotion discussion, and provision of condoms. Specialist nurses performed equally to the SHOs with regard to requesting the correct diagnostic tests, providing the correct preliminary diagnosis, and providing the correct treatment. CONCLUSIONS: A model of care using trained GUM nurses working within agreed protocols can provide comprehensive patient care for female patients that is equal to care provided by SHOs. Our results raise important issues regarding advanced GUM nursing education and training, protocol development, and accountability.

A comparison of a nicotine sublingual tablet and placebo for smoking cessation.

This study assessed the efficacy and safety of a nicotine sublingual tablet in smoking cessation in a randomized, double-blind, placebo-controlled outpatient trial conducted between January 1996 and May 1997. Two hundred and forty-one adult smokers (> or = 10 cigarettes/day for at least 3 years) used nicotine 2-mg sublingual tablet (n = 120) or placebo (n = 121) for up to 6 months (a 3-month treatment period followed by a 3-month tapering period). Subjects who scored <7 on the Fagerström Tolerance Questionnaire used 1 tablet/h (up to maximum of 20/day), whereas subjects who scored (7 used 2 tablets/h (up to maximum of 40/day). Brief counseling was provided at baseline and at all visits. Self-reported abstinence was measured from week 2 onwards, confirmed by expired carbon monoxide (CO) levels <10 ppm at each visit (1, 2, 3 and 6 weeks and 3, 6 and 12 months). After 6 weeks of treatment, CO-validated abstinence rates were 48% in the active group and 23% in the placebo group (p < 0.0001). At the 3-, 6- and 12-month visits, abstinence rates (active vs. placebo) were 33% vs. 17% (p = 0.0046), 21% vs. 11% (p = 0.0304) and 18% vs. 10% (p = 0.0606). Adverse events were mild and transient and reflected those reported with existing nicotine replacement formulations. We concluded that the nicotine 2-mg sublingual tablet was effective as a smoking cessation aid.

Patient group directions in nurse-led sexual health clinics.

BACKGROUND: This article details an audit of the supply of medications by specialist nurses at a genitourinary medicine clinic. CONCLUSION: The use of patient group directions resulted in a reduced number of prescriptions being required from doctors, thus saving time for them, the nurses and patients.

The Allen Cognitive Level Test and social competence in adult psychiatric patients.

OBJECTIVES: The purpose of this study was to investigate the relationship between cognitive disability and social skills in an acute care adult inpatient psychiatric population (n = 55). METHOD: Independent ratings of patient's social skills were made during a semistructured interview using the Social Interaction Test (SIT), followed by measurement of cognitive disability using the revised Allen Cognitive Level Test (ACL-90). Reliability of the assessments was established. RESULTS: Significant correlations were found between the ACL-90 and SIT scores: patients with greater cognitive disability had poorer social skills. ACL-90 scores were not related to gender or diagnosis. A gender difference was found for SIT scores with women having better social skills than men. CONCLUSION: These findings suggest there is a relationship between cognitive disability and social skills in adult psychiatric inpatients. Implications for occupational therapy treatment include better integration of the grading of the cognitive and social requirements of tasks to achieve optimal functioning.

Immunochemical quantitation, size distribution, and cross-reactivity of lepidoptera (moth) aeroallergens in southeastern Minnesota.

With an immunochemical method, we analyzed outdoor air samples during a 3-year period for concentrations of the predominant local species of moth, Pseudaletia unipuncta (Haworth). Airborne particulates were collected on fiberglass filter sheets with an Accu-Vol sampler located 1.5 m above ground on the southeastern Minnesota prairie. Filter eluates analyzed by RIA inhibition contained concentrations of moth protein peaking in June and August to September of each year, with levels comparable to reported immunochemically measured levels of pollen and mold allergens. These peaks also corresponded with total numbers of moths captured in light traps. Moth-allergen activity was distributed in particle sizes ranging from 0.8 to greater than 4.1 micron when sized samples were obtained by use of an Andersen cascade impaction head. By RIA inhibition, there was cross-reactivity between P. unipuncta and insects of different genera, families, and orders, but not with pollens or molds. Forty-five percent of 257 patients with immediate positive skin tests to common aeroallergens had positive skin tests to one or more commercially available whole body insect extracts. Of 120 patients with allergic rhinitis believed to be primarily caused by ragweed sensitivity, 5% also had elevated specific IgE to moths. We conclude that airborne concentrations of Lepidoptera can be measured immunochemically and that moths may be a seasonal allergen in the United States.

The shelf life of chilled sheep livers packed in closed tubs.

Livers incubated at 30°C in closed tubs developed floras dominated by Enterobacteriaceae. At chiller temperatures, floras were ultimately dominated by psychrotrophic lactobacilli. Tub-packed livers can have an extended shelf life similar to that reported for vacuum-packed liver.

Relação dos tipos de invertebrados depositados na Coleção de Entomologia Sistemática do INPA - Manaus, até dezembro de 1982

Summary In this article are listed all types of invertebrates deposited in the Systematic Entomology Collection, Division of Entomology of INPA, Manaus, until 31 December, 1982.

Resumo Neste trabalho são listados todos os tipos de invertebrados depositados na Coleção de Entomologia Sistemática, Divisão de Entomologia, do INPA, Manaus, até dezembro de 1982.