Effect of thyrotropin-induced desensitization of bovine thyroid adenylate cyclase on the nucleotide regulatory protein

The stimulation of adenylate cyclase by TSH was decreased 50-60% in crude membranes prepared from homogenates of bovine thyroid slices that had previously been incubated for 2 h with the hormone. The diminished response was not associated with any significant change in the binding capacity or affinity for 125I-labeled TSH. The apparent affinities of the desensitized adenylate cyclase for TSH or GTP were not different from those of the enzyme prepared from thyroid slices that had been incubated without TSH. Decreased adenylate cyclase responses to NaF, cholera toxin, or guanyl-5'-yl-imidodiphosphate were also observed in the desensitized membrane, whereas the enzyme responses to prostaglandin E1, GTP, or forskolin were not decreased. However, desensitization caused no decrease in the cholera toxin-catalyzed ADP ribosylation of the 40,000 mol wt polypeptide guanine nucleotide-binding component of the adenylate cyclase. The desensitized membranes showed basal adenylate cyclase activity similar to that of the control membranes using adenyl-5'-yl-imidodiphosphate as substrate in the absence of a nucleotide-regenerating system. These results suggest that the in vitro TSH-induced desensitization of thyroid adenylate cyclase reflects an alteration in the activation processes of the nucleotide regulatory protein.     

System for Rapid Assessment of Pneumonia and Influenza-Related Mortality—Ohio, 2009–2010

Rapid mortality surveillance is critical for state emergency preparedness. To enhance timeliness during the 2009–2010 influenza A H1N1 pandemic, the Ohio Department of Health activated a drop-down menu within Ohio’s Electronic Death Registration System for reporting of pneumonia- or influenza-related deaths approximately 5 days postmortem. We used International Classification of Diseases—Tenth Revision (ICD-10) codes, available 2–3 months postmortem as the standard, and assessed their agreement with drop-down-menu codes for pneumonia- or influenza-related deaths. Among 56 660 Ohio deaths during September 2009–March 2010, agreement was 97.9% for pneumonia (κ = 0.85) and 99.9% for influenza (κ = 0.79). Sensitivity was 80.2% for pneumonia and 73.9% for influenza. Drop-down menu coding enhanced timeliness while maintaining high agreement with ICD-10 codes.     

A prospective study of visceral leishmaniasis in an endemic area of Brazil

The epidemiology, clinical patterns, and risk factors for visceral leishmaniasis were prospectively studied in an endemic area of Brazil. The prevalence of disease was 3.1% for children less than 15 years of age, and the annual incidence was 4.3 cases per 1,000 children. The number of children with disease fluctuated yearly and seasonally, and distribution of the disease varied within the endemic area. Risk factors included young age (median, three years) and malnutrition before the onset of disease. Intestinal parasitism, recent migration into the area, and house location within the area did not influence the progression of infection to disease. Serological testing indicated that 7.5% of children were infected with Leishmania each year and that the ratio of disease to infection was 1:18.5 for the whole area and 1:6.5 for the section with the highest prevalence of disease. Early diagnosis and therapy altered clinical patterns of the disease.     

Defining an exacerbation of pulmonary disease in cystic fibrosis

Despite the importance of pulmonary exacerbations in CF in both clinical and research settings, both published evidence and consensus are lacking concerning the criteria used to define an exacerbation. The use of hospitalization as a surrogate measure presupposes uniformity among clinicians in diagnosis and treatment of exacerbations. Our aims were to evaluate consensus among clinicians about the variables considered helpful in diagnosing an exacerbation requiring treatment. A comprehensive list of symptoms, signs, and investigations used to define exacerbations was compiled from published trials. A written self-administered questionnaire included the list in age-appropriate groups to survey opinion about the helpfulness of each item, and the estimated proportion of patients admitted within a month of diagnosis of an exacerbation. This was sent to all clinicians managing CF patients in Australia. There were replies from 59/91 clinicians (65%), 41/60 (68%) from those managing children and 18/31 (58%) from those managing adults. Responses of those managing children and adults differed for 7/32 variables (Mann-Whitney test, P < 0.05). Clinic grouping did not show greater consensus among responses of pediatricians (Kruskal-Wallis test, P = 0.362). Consensus, >74% or <26% of respondents rating a variable helpful/very helpful, was found in only 50% of variables listed. Estimated admission rate within a month of diagnosis was 61% (30-100%) for those managing adults and 48% %5-100%) for pediatricians. A lack of consensus was found among clinicians managing CF about the variables considered in diagnosing an exacerbation. The estimated proportion admitted within a month of diagnosis was very variable. This demonstrated inhomogeneity in approach to diagnosis and management of an exacerbation suggests a significant heterogeneity of clinical care.     

Therapy of metabolic disorders with intravenous (IV) access ports and long term intravenous L-carnitine therapy

With the expansion of newborn screening to include many organic acidurias and fatty acid oxidation defects, effective therapies of these disorders will be needed. Currently severe disorders such as methylmalonic and propionic aciduria. conventional therapy with diet and oral L-camitine often prove ineffective in preventing failure to thrive and recurrent metabolic decompensations. L-carnitine provides a natural pathway for removal of the toxic metabolites in these disorders and is life saving therapy but, with poor oral absorption (25%), it is difficult to supply adequate carnitine to meet the metabolic needs of these patients. Long term intravenous L-carnitine therapy, administered through a subcutaneous venous access port in 5 patients with organic acidurias [propionic aciduria (2), methylmalonic aciduria (2), 3 methylglutaconic aciduria(1)] resulted in improved growth, lower frequency of metabolic decompensations and increased tolerance of natural protein in the diet. An added benefit was the ability to initiate fluid. electrolytes, and antibiotics during metabolic decompensations at home thus averting hospitalizations.     

Association between fruit and vegetable intake and change in body mass index among a large sample of children and adolescents in the United States

OBJECTIVE: To assess whether intake of fruits and vegetables was associated with change in body mass index (BMI) among a large sample of children and adolescents in the United States. DESIGN: Prospective cohort study of children and adolescent who were 9-14 y of age in 1996, when the study began. SUBJECTS: The subjects included 8203 girls and 6715 boys in an ongoing cohort study who completed at least two questionnaires between 1996 and 1999. MEASUREMENTS: Fruit and vegetable intake was assessed in 1996-1998 with a validated food frequency questionnaire designed specifically for children and adolescents. The outcome measure was change in age- and gender-specific z-score of BMI (kg/m(2)). Self-reported weight and height, which were used to calculate BMI, were collected annually from 1996 to 1999. RESULTS: During 3 years of follow-up, annual changes in BMI were slightly greater among the boys than the girls. After controlling for Tanner stage of development, age, height change, activity and inactivity, which are known or suspected predictors of change in BMI, among the girls there was no relation between intake of fruits, fruit juice, or vegetables (alone or combined) and subsequent changes in BMI z-score. Among the boys, intake of fruit and fruit juice was not predictive of changes in BMI, however, vegetables intake was inversely related to changes in BMI z-score (beta per serving=-0.003). However, after adjusting for caloric intake, the magnitude of the effect was diminished and no longer significant. CONCLUSION: Our results suggest that the recommendation for consumption of fruits and vegetables may be well founded, but should not be based on a beneficial effect on weight regulation.