Hypogonadotropic hypogonadism discovered in a patient with cerebellar ataxia

We present the case of a male patient who presented progressive cerebellar ataxia since childhood who developed partial hypogonadotropic hypogonadism discovered when searching for a cause of low fecundity. The association of these two entities has been described in several rare syndromes: Homes ataxia, Boucher-Neuhauser syndrome and Richards-Rundle syndrome. The genetic background of these three syndromic associations defined solely on the basis of clinical manifestations remains to be elucidated, leading to uncertain diagnosis. The present case suggests the syndromic entity could be associated with autosomal recessive spinocerebellar ataxia with hypogonadotropic hypogonadism which includes several genotypic entities.     

Modulation of inflammation by kininogen deficiency in a rat model of inflammatory arthritis

OBJECTIVE: To compare inflammatory peripheral arthritis in wild-type and high molecular weight kininogen (HK)-deficient rats, both on the genetically susceptible Lewis background. METHODS: By backcrossing Brown-Norway HK-deficient rats with Lewis rats for 6 generations, 2 new strains were produced, wild-type F6 and HK-deficient F6, each with a 98.5% Lewis genome. Inflammatory arthritis was induced by intraperitoneal injection of peptidoglycan-polysaccharide (PG-PS), and the clinical, histopathologic, and biochemical responses were compared in both strains. RESULTS: Eighteen days after PG-PS injection, rats with normal concentrations of HK showed weight loss and marked increase in hind ankle diameter with severe synovial inflammation and cartilage abnormalities. In contrast, HK-deficient rats showed no weight loss (P < 0.05), no increase in hind ankle diameter (P < 0.05), and an absence of inflammatory changes (P < 0.05), as measured by the histologic and morphometric Mankin grading system for synovial and cartilage injury. CONCLUSION: Plasma HK is a key mediator of acute and chronic inflammatory arthritis in genetically susceptible Lewis rats.     

Facial surface analysis by 3D laser scanning and geometric morphometrics in relation to sexual dimorphism in cerebral--craniofacial morphogenesis and cognitive function

Over early fetal life the anterior brain, neuroepithelium, neural crest and facial ectoderm constitute a unitary, three-dimensional (3D) developmental process. This intimate embryological relationship between the face and brain means that facial dysmorphogenesis can serve as an accessible and informative index of brain dysmorphogenesis in neurological and psychiatric disorders of early developmental origin. There are three principal challenges in seeking to increase understanding of disorders of early brain dysmorphogenesis through craniofacial dysmorphogenesis: (i) the first, technical, challenge has been to digitize the facial surface in its inherent three-dimensionality; (ii) the second, analytical, challenge has been to develop methodologies for extracting biologically meaningful shape covariance from digitized samples, making statistical comparisons between groups and visualizing in 3D the resultant statistical models on a 'whole face' basis; (iii) the third, biological, challenge is to demonstrate a relationship between facial morphogenesis and brain morphogenesis not only in anatomical-embryological terms but also at the level of brain function. Here we consider each of these challenges in turn and then illustrate the issues by way of our own findings. These use human sexual dimorphism as an exemplar for 3D laser surface scanning of facial shape, analysis using geometric morphometrics and exploration of cognitive correlates of variation in shape of the 'whole face', in the context of studies relating to the early developmental origins of schizophrenia.     

Estimating patient time costs associated with colorectal cancer care

BACKGROUND: Nonmedical costs of care, such as patient time associated with travel to, waiting for, and seeking medical care, are rarely measured systematically with population-based data. OBJECTIVES: The purpose of this study was to estimate patient time costs associated with colorectal cancer care. METHODS: We identified categories of key medical services for colorectal cancer care and then estimated patient time associated with each service category using data from national surveys. To estimate average service frequencies for each service category, we used a nested case control design and SEER-Medicare data. Estimates were calculated by phase of care for cases and controls, using data from 1995 to 1998. Average service frequencies were then combined with estimates of patient time for each category of service, and the value of patient time assigned. Net patient time costs were calculated for each service category, summarized by phase of care, and compared with previously reported net direct costs of colorectal cancer care. RESULTS: Net patient time costs for the 3 phases of colorectal cancer care averaged dollar 4592 (95% confidence interval [CI] dollar 4427-4757) over the 12 months of the initial phase, dollar 2788 (95% CI dollar 2614-2963) over the 12 months of the terminal phase, and dollar 25 (95% CI: dollar 23-26) per month in the continuing phase of care. Hospitalizations accounted for more than two thirds of these estimates. Patient time costs were 19.3% of direct medical costs in the initial phase, 15.8% in the continuing phase, and 36.8% in the terminal phase of care. CONCLUSIONS: Patient time costs are an important component of the costs of colorectal cancer care. Application of this method to other tumor sites and inclusion of other components of the costs of medical care will be important in delineating the economic burden of cancer in the United States.     

Research environments that promote integrity

BACKGROUND: The body of empirical knowledge about research integrity and the factors that promote research integrity in nursing research environments remains small. OBJECTIVE: To propose an internal control model as an innovative framework for the design and structure of nursing research environments that promote integrity. METHODS: An internal control model is adapted to illustrate its use for conceptualizing and designing research environments that promote integrity. RESULTS: The internal control model integrates both the organizational elements necessary to promote research integrity and the processes needed to assess research environments. The model provides five interrelated process components within which any number of research integrity variables and processes may be used and studied: internal control environment, risk assessment, internal control activities, monitoring, and information and communication. DISCUSSION: The components of the proposed research integrity internal control model proposed comprise an integrated conceptualization of the processes that provide reasonable assurance that research integrity will be promoted within the nursing research environment. Schools of nursing can use the model to design, implement, and evaluate systems that promote research integrity. The model process components need further exploration to substantiate the use of the model in nursing research environments.     

Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma

RATIONALE: Genetic variation of the beta2-adrenoceptor (ADRB2) influences receptor function in vitro. There are reports that, in vivo, bronchodilator response is related to ADRB2 genotype, and that clinical outcomes during chronic therapy with beta2-agonist drugs are also influenced by genotype. Whether these features are related to single nucleotide polymorphisms or to combinations (haplotypes) is unclear. OBJECTIVES: Our aim was to measure bronchodilator response in patients with asthma stratified by ADRB2 haplotype. This was done after eliminating the confounding effect of prior drug treatment with inhaled beta2-agonists and corticosteroids. METHODS: ADRB2 haplotype was determined in 176 patients with asthma, of whom 161 harbored the six most common combinations. Treatment with inhaled beta2-agonists and inhaled corticosteroids was withheld for appropriate intervals. Spirometric changes 20 minutes after a single dose of albuterol (2.5 mg by nebulizer) were then recorded. RESULTS: There were no significant differences in bronchodilator response (% improvement in FEV(1)) with respect to any of the major ADRB2 haplotypes or genotypes. CONCLUSIONS: Genetic variation of the ADRB2 does not influence the immediate response to inhaled beta2-agonist. The confounding effect of tolerance resulting from regular beta2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with beta2-agonists.     

Sex differences in factors associated with childhood- and adolescent-onset wheeze

RATIONALE: Factors predicting the development of wheeze may differ between sexes and between childhood and adolescence. METHODS: A New Zealand birth cohort of 1,037 children was followed to age 26. For this analysis, those reporting recurrent wheezing at two or more assessments were classified as "wheezers." We examined risk factors for development of wheeze before age 10 (childhood) and subsequently (adolescent-onset) for males and for females separately using Cox regression modeling. RESULTS: Males more often developed childhood wheeze (p = 0.002) and females adolescent-onset wheeze (p < 0.001). Maternal atopy (asthma or hay fever) was a risk factor for childhood wheeze in both sexes (hazard ratio [HR], 1.48, p < 0.05 for males; HR, 2.37, p < 0.001 for females). Paternal atopy also influenced childhood wheeze, significantly for males (HR, 1.72; p = 0.01), and similarly but not significantly for females (HR, 1.70; p = 0.08). For adolescent-onset wheeze, neither maternal (HR, 1.41; p = 0.19) nor paternal history (HR, 0.73; p = 0.42) was a risk factor in males, but maternal history (HR, 2.08; p < 0.01) was a significant risk factor for females. When both age ranges were combined, providing greater power for analysis, paternal history was a stronger risk factor for wheeze in females (HR, 1.62; p = 0.02) than in males (HR, 1.35; p = 0.12). CONCLUSION: The influence of parental atopy on the development for wheeze differs between males and females and between childhood- and adolescent-onset wheeze.     

Recommendations for blood pressure measurement in humans and experimental animals: part 2: blood pressure measurement in experimental animals: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research

In experimental animals, as in humans, techniques for measuring blood pressure (BP) have improved considerably over the past decade. In this document, we present recommendations for measuring BP in experimental animals with the goal of helping investigators select optimal methods for BP monitoring in the research laboratory. The advantages and disadvantages of various BP measurement methods are discussed and specific recommendations are provided for selecting the optimal technique depending on the study objective. Although indirect techniques that permit only sporadic measurements of BP may be suitable for some purposes, methods for directly measuring BP are generally preferred because of their ability to monitor the highly dynamic nature of BP in a comprehensive fashion. Selection of the methods to be used should ultimately be guided by the study objectives to insure that the techniques chosen are appropriate for the experimental questions being explored.