Acoustic startle and prepulse inhibition in 40 inbred strains of mice

A high-throughput phenotype screening protocol was used to measure the acoustic startle response (ASR) and prepulse inhibition (PPI) in mice. ASRs were evoked by noise bursts; prepulses for PPI were 70 dB sound pressure level tones of 4, 12, and 20 kHz. Forty inbred strains of mice were tested (in most cases using 10 males and 10 females of each strain). The data on both the ASR and PPI had high internal and test-retest reliability and showed large differences among inbred strains, indicative of strong genetic influences. Previously obtained measures of hearing sensitivity in the same inbred strains were not significantly correlated with ASR or PPI measures.     

Quality of life after lobectomy for adult liver transplantation

INTRODUCTION: Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. METHODS: Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. RESULTS: Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P<0.007) and general health (P<0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications. CONCLUSIONS: Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.     

gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor

Ciliary neurotrophic factor (CNTF) exerts anorectic effects by overcoming leptin resistance via activation of hypothalamic neurons. However, the exact site of CNTF action in the hypothalamus has not yet been identified. Using Cre-loxP-mediated recombination in vivo, we have selectively ablated the common cytokine signaling chain gp130, which is required for functional CNTF signaling, in proopiomelanocortin (POMC)-expressing neurons. POMC-specific gp130 knockout mice exhibit unaltered numbers of POMC cells and normal energy homeostasis under standard and high fat diet. Endotoxin (LPS) and stress-induced anorexia and adrenocorticotropin regulation were unaffected in these animals. Strikingly, the anorectic effect of centrally administered CNTF was abolished in POMC-specific gp130 knockout mice. Correspondingly, in these animals, CNTF failed to activate STAT3 phosphorylation in POMC neurons and to induce c-Fos expression in the paraventricular nucleus. These data reveal POMC neurons as a critical site of CNTF action in mediating its anorectic effect.     

Using an asthma control questionnaire and administrative data to predict health-care utilization

OBJECTIVE: To examine the merits of the Asthma Therapy Assessment Questionnaire (ATAQ) control index together with prior asthma health-care utilization from administrative data in predicting future acute asthma health-care utilization. DESIGN: Prospective cohort study. POPULATION: A total of 4,788 adult asthma patients aged 17 to 93 years who completed a baseline evaluation and had at least 6 months of follow-up data. STATISTICAL METHODS: Classification and regression tree methodology to predict future risk of acute health-care utilization events. RESULTS: These results show that the ATAQ control index and administrative data are jointly useful for predicting future health-care utilization. The utility of the ATAQ control index in the presence of information about prior health-care utilization is to further stratify risk among the subset of younger individuals who did not have any prior acute health-care utilization. While administrative health-care utilization data served as the strongest predictor of future health-care utilization, the ATAQ control index helped to identify 1% of individuals without recent acute care that had approximately a sixfold elevated risk (95% confidence interval, 4.2 to 8.4) of future acute health-care utilization. This is an important result since only a small fraction of individuals with acute events in a given year will have had acute events in the previous year. CONCLUSION: These findings should assist the practicing clinician and organizations interested in population-based asthma disease management.     

The development and preliminary validation of a brief measure of chronic pain impact for use in the general population

From a biopsychosocial perspective, assessing chronic pain's psychological impact should involve at minimum the measurement of pain severity, functional interference, and pain-related emotional burden. This article details the development of a brief instrument, the 15-item Profile of Chronic Pain: Screen (PCP:S), designed to address these three key elements in a national (US) sample of over 2400 individuals recruited via random digit dialing. Retest reliability, internal consistency, and preliminary validity were excellent. The scales also demonstrated minimal social desirability response bias. A series of confirmatory factor analyses on several distinct samples revealed a stable, 3-factor solution reflecting pain severity, interference, and emotional burden. Finally, national norms were developed by gender and three age groups. In view of its strong psychometric properties, the PCP:S has the potential to serve as a brief, cost-effective assessment tool for identifying individuals whose chronic pain merits more detailed psychosocial evaluation.     

A phase I study of pegylated liposomal doxorubicin hydrochloride (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small-cell lung cancer

The purpose of this study was to determine the recommended phase II dose of liposomal doxorubicin (Caelyx ; Doxil in the United States) in combination with cyclophosphamide and vincristine for previously treated patients with good performance status with relapsed or refractory small-cell lung cancer. Twenty-one eligible patients were enrolled between November 1999 and September 2001 and received liposomal doxorubicin 25-40 mg/m2, cyclophosphamide 750-1000 mg/m2, and vincristine 1.2 mg/m2 intravenously (I.V.) every 21 days. At doses of liposomal doxorubicin 40 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V., 1 of 6 patients had dose-limiting neutropenia and fever in cycle 2 and 2 of 6 developed grade 3 hand-foot syndrome during cycle 3. Therefore, the recommended phase II doses are liposomal doxorubicin 35 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V. every 21 days. Antitumor activity was seen at all dose levels. This combination is well tolerated and has evidence of antitumor activity. A phase II evaluation is ongoing.     

Population implications of changes in lipid management in patients with coronary heart disease

Pharmacologic treatment and goal attainment rates from published literature indicate that lipid management has generally improved for patients with coronary heart disease. The population implications of these changes in lipid management are examined, suggesting that the challenge of lipid management may be shifting from a problem of no treatment to one of undertreatment.     

Infection control compliance issues and questions

This article uses the 2003 CDC infection control guidelines for dentistry as a framework for discussing representative questions and issues that continue to be raised by dental health care workers. Where applicable, additional supporting evidence will be incorporated to provide appropriate, useful information, to assist in understanding and complying with updated recommendations.     

Growth hormone therapy and quality of life in adults and children

A fundamental goal of growth hormone (GH) treatment for both adults and children is improvement in quality of life (QOL). Assessments of the therapeutic role of GH depend on its effectiveness in meeting this and other goals (including improved metabolic status in adults and improved growth in children) in relation to economic parameters. However, there are difficulties in interpreting data on GH treatment and QOL. These include controversy about appropriate definitions and measures for assessing QOL, disease adaptation, comorbid conditions, and potential patient selection bias.In GH-deficient adults who have completed linear growth, there is considerable evidence that GH exerts effects on body composition, serum lipids, and bone and mineral density. Several controlled trials have also examined the effect of GH treatment on QOL in GH-deficient adults. They generally indicate improvement in QOL with GH treatment, although there are inconsistencies in the data. Caveats include differing outcome measures and instruments, instruments that are not disease specific, variation in characteristics of patient samples and treatment protocols, evidence of a placebo effect, and some inconsistency among results. Open-label trials in adults also suggest improvement in QOL with GH treatment, although interpretation is limited by potential placebo effects and patient self-selection.Studies in children have generally addressed psychological status, and relatively few specifically focus on QOL. In children with classical GH deficiency, it is intuitive that GH treatment will improve QOL, although hard data are lacking. In children with idiopathic short stature, evidence for improved QOL as a result of GH treatment is not well developed. Translating changes in QOL, together with physiological and metabolic benefits, into economic cost-benefit or cost-effectiveness analyses are needed. In doing so, it will be important to consider subgroups of patients who may derive differential benefit from GH treatment. These analyses are central to the development of a framework for research, decision making, and policy for GH treatment.