Assigning the source of human campylobacteriosis in New Zealand: A comparative genetic and epidemiological approach

Integrated surveillance of infectious multi-source diseases using a combination of epidemiology, ecology, genetics and evolution can provide a valuable risk-based approach for the control of important human pathogens. This includes a better understanding of transmission routes and the impact of human activities on the emergence of zoonoses. Until recently New Zealand had extraordinarily high and increasing rates of notified human campylobacteriosis, and our limited understanding of the source of these infections was hindering efforts to control this disease. Genetic and epidemiological modeling of a 3-year dataset comprising multilocus sequence typed isolates from human clinical cases, coupled with concurrent data on food and environmental sources, enabled us to estimate the relative importance of different sources of human disease. Our studies provided evidence that poultry was the leading cause of human campylobacteriosis in New Zealand, causing an estimated 58–76% of cases with widely varying contributions by individual poultry suppliers. These findings influenced national policy and, after the implementation of poultry industry-specific interventions, a dramatic decline in human notified cases was observed in 2008. The comparative-modeling and molecular sentinel surveillance approach proposed in this study provides new opportunities for the management of zoonotic diseases.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

Controlled Release of Substituted Benzole and Naphthoic Acids Using Carbopol ® Gels: Measurement of Drug Concentration Profiles and Correlation to Release Rate Kinetics

Purpose. The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol^® matrices containing mesalamine or benzoic acid. Methods. Release rate experiments with Carbopol^® matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration. Results. The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93–95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices. Conclusions. The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol^® gel layer and drug diffusivity.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Hodgkin disease: contributions of chest CT in the initial staging evaluation

Chest radiographs and chest computed tomography (CT) scans were compared in 203 patients with newly diagnosed Hodgkin disease. The incidence of positive findings was tabulated from six intrathoracic lymph node groups, lung parenchyma, pericardium, pleura, and chest wall. The discordant cases were assessed to determine impact on clinical management. The CT scans provided additional evidence of disease involvement, ranging from 0% to 15% at each of the designated anatomic sites. Treatment was altered in 9.4% of all patients (19 of 203), including 13.8% (nine of 65) of those undergoing radiation therapy alone and 8.2% (ten of 122) of those undergoing combined-modality treatment. We conclude that routine chest CT examinations are valuable in the clinical management of those patients for whom radiation therapy is planned.     

Upper cervical ossicles in Down syndrome

Six patients with upper cervical spine ossicles and Down syndrome from a study population of 184 are described. The average age was 20.6 years at the time of diagnosis. Three of the patients were involved in tumbling. Radiographic anatomy of the ossicles and the dens, as well as serial radiographs in three of the six patients, suggest that this represents an avulsion of the upper end of the dens rather than an occipital vertebrae, ossiculum terminale, or os odontoideum, as previously described. The authors advocate restriction of high-risk activities for all patients with Down syndrome.     

Patterns of health-compromising behaviors among Minnesota adolescents: sociodemographic variations.

OBJECTIVES: This study compared prevalence rates of health-compromising behaviors among boys and girls from different ethnic backgrounds in early, middle, and late adolescence and compared co-occurrences of such behaviors across gender and ethnic groups. METHODS: The study population included 123 132 adolescents in grades 6, 9, and 12. Adolescents completed a classroom-administered statewide survey focusing on high-risk behaviors, including unhealthy weight loss, substance abuse, suicide risk, delinquency, and sexual activity. RESULTS: Prevalence rates of most health-compromising behaviors differed by gender, increased with age, and tended to be highest among American Indian youth and lowest among Asian Americans. Strong associations were found between substance abuse and delinquency across all ethnic groups. Substance abuse and delinquency were associated with suicide risk across most ethnic groups. Covariations with sexual activity and unhealthy weight loss behaviors showed more ethnic variation. CONCLUSIONS: Prevention interventions should take into account the tendency for health-compromising behaviors to co-occur and should be sensitive to demographic and socioeconomic differences in behavior patterns.