Toward elimination of Haemophilus influenzae type B carriage and disease among high-risk American Indian children

OBJECTIVES: This report describes the epidemiology of Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal colonization among Navajo and White Mountain Apache children younger than 7 years in an era of widespread immunization. METHODS: We conducted active surveillance for invasive H influenzae disease from 1992 to 1999 and an oropharyngeal carriage study from 1997 to 1999. The predominant vaccine used was PedvaxHib. RESULTS: The average annual incidence of invasive Hib disease among children younger than 24 months was 22 cases per 100,000. Of 381 children younger than 7 years, only 1 (0.3%; 95% confidence interval = 0.0%, 1.3%) was colonized with Hib; 370 (97%) had received 2 or more doses of Hib conjugate vaccine. CONCLUSIONS: Among Navajo and White Mountain Apache children, Hib conjugate vaccines have led to a sustained reduction in invasive Hib disease and a reduction in oropharyngeal Hib carriage. The disease incidence among children younger than 24 months remains 20 times higher than in the general US population. Hib elimination will require additional characterization of colonization and disease in these high-risk populations.     

Kinetics and localization of brain phosphate activated glutaminase.

The cellular concentration of phosphate, the main activator of phosphate activated glutaminase (PAG) is rather constant in brain and kidney. The enzyme activity, however, is modulated by a variety of compounds affecting the binding of phosphate, such as glutamate, calcium, certain long chain fatty acids, fatty acyl CoA derivatives, members of the tricarboxylic acid cycle and protons (Kvamme et al. [2000] Neurochem. Res. 25:1407-1419). Therefore, the kinetic and allosteric properties of the enzyme are essential for regulating the enzyme activity in situ, especially because the enzymically active pool of PAG is assumed to have an external localization in the inner mitochondrial membrane, being exposed to cytosolic variation in the content of effectors. This has largely been overlooked. A hypothetical model for the allosteric interactions based on the sequential induced fit allosteric model by Koshland et al. ([1966] Biochemistry 5:365-385) is presented. Furthermore, it has been generally accepted that there exist only two isoforms of PAG, the kidney PAG that is similar to brain PAG, and the liver PAG. Therefore, the immunoreactivity of brain cells against kidney PAG antibodies has been considered a measure of PAG protein. Gomez-Fabre et al. ([2000] Biochem. J. 345:365-375) recently found, however, that a PAG mRNA from human breast cancer ZR75 cells is present in human brain and liver, but not in the kidney. We observed only traces of PAG immunoreactivity in cultured astrocytes and cultured neuroblastoma cells, regardless whether antibodies against the C- and N-termini of kidney PAG or antibodies against liver PAG were used, but considerable enzyme activity, demonstrating hitherto unknown isoforms of PAG (Torgner et al. [2001] FEBS Lett. 268(Suppl 1):PS2-031).     

Development of SNP and microsatellite markers for goldsinny wrasse (<Emphasis Type="Italic">Ctenolabrus rupestris</Emphasis>) from ddRAD sequencing data

Wrasse (Labridae) species have been used as parasite cleaners in Atlantic salmon farming since the 1980s. However, their use has recently escalated, with millions now being introduced into salmon cages each year. Most fish are of wild origin, their exploitation potentially impacting native populations. Genetic information is urgently required to inform management decisions. We identified 174 microsatellite and 149 SNP markers from ddRAD sequence data. From these, 17 and 48 microsatellite and SNP markers, respectively, were validated by genotyping 150 goldsinny wrasse collected from five locations along the Norwegian and Swedish coasts. Two to 30 alleles were identified at the microsatellite loci, while gene diversity (H _e ) ranged 0.101–0.907. All SNP loci were biallelic, with averaged H _e per locus ranging between 0.063 and 0.495.     

Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) prevent vaccine serotype (VT) invasive disease; nonvaccine serotype (NVT) disease increases modestly. The impact of PCV on nasopharyngeal (NP) colonization is essential to understanding disease effects. METHODS: We conducted a community-randomized controlled trial with catch-up vaccination through age 2 years investigating the effect of 7-valent PCV (PnCRM7) on NP colonization among American Indian infants and their unvaccinated contacts. Infants receiving blinded vaccine at 2, 4, 6, and 12-15 months of age had NP cultures obtained at age 7, 12, and 18 months. Serotype-specific colonization was detected by immunoblot. RESULTS: We enrolled 566 vaccinated and 286 unvaccinated children from 511 households and collected 5157 specimens, of which 3525 (68.4%) had pneumococcus. PnCRM7 vaccinees were less likely to be colonized with VT (odds ratio [OR], 0.40 [95% confidence interval {CI}, 0.23-0.67]) but were more likely to be colonized with NVT pneumococci (OR, 1.67 [95% CI, 1.02-2.78]). PnCRM7 vaccinees were less densely colonized with VT strains than control vaccinees (OR, 0.61 [95% CI, 0.38-0.99]). Day care-attending unvaccinated children in PnCRM7 communities were less likely to have VT colonization than those in control communities (OR, 0.27 [95% CI, 0.07-1.07]). CONCLUSIONS: PnCRM7 reduces the risk of VT acquisition and colonization density but increases the risk of NVT acquisition among vaccinees and their household contacts.     

Improving the interface between primary and secondary care: a statement from the European Working Party on Quality in Family Practice (EQuiP)

A group from the European Working Party on Quality in Family Practice (EQuiP), working with over 20 European colleges of primary care, has assessed what, in their view, is needed to improve the quality of care at the interface between general practice and specialists. Experiences and ideas from a wide range of people were gathered through focused group discussions. From these it was clear that, for real improvement at the interface of care, changes are needed in the system of care and in the ways that doctors view their roles and their performance. All providers of care need to be able to see the care system from the patients' perspective if they are to help their patients make sense of and benefit from an increasingly complex system. This paper outlines the EQuiP recommendations on how cooperation between general practitioners and specialists might be improved. This includes strategic perspectives and both targets for improvement and methods for teaching, training and development that are all independent of country and health care system. The 10 targets for development identified by the group are: leadership, initial shared care approaches, task division, mutual guidelines, patient perspective, informatics, education, team building, quality monitoring systems, and cost effectiveness. Working towards these targets could provide an effective approach to improving the cooperation between the interfaces of care. Getting effective leadership is a necessary first step as implementation of such a strategy will involve significant change. Responsibility lies primarily with the medical profession.     

Synthesis of transmitter glutamate and the glial-neuron interrelationship

Glutamate in glutamatergic neurons exists in a cytosolic pool, as well as a transmitter pool, which is assumed to be localized in synaptic vesicles. Transmitter glutamate released from glutamatergic neurons is taken up by both neurons and glial cells, giving rise to a flux of glutamate from neurons to astrocytes In astrocytes, glutamine is formed from glutamate by the glial-specific enzyme glutamine synthetase (EC 6.3.1.2). Glutamine diffuses back to neurons, where glutamate is formed by phosphate-activated glutaminase (EC 3.5.1.2). However, this cycle is not stoichiometric, and glutamine obtained from glial cells cannot replenish all transmitter glutamate lost from neurons. 2-Oxoglutarate is another putative precursor for transmitter glutamate. Net synthesis of citric acid cycle intermediates is dependent on carbon dioxide fixation to pyruvate, catalyzed by pyruvate carboxylase (EC 6.4.1.1). Since this enzyme is exclusively glial, a net flow of citric acid cycle intermediates from glial cells to neurons probably exists. The quantitative contribution of each transmitter precursor may not be the same in different regions of the brain and may vary with the metabolic state of the neuron. The pool of transmitter glutamate is most likely regulated by the activity of glutamate-forming enzymes in the nerve terminal, and/or by uptake/release of glutamate and glutamate precursors through the synaptosomal plasma membrane.     

Influence of vasoactive intestinal contractor on the feline pulmonary vascular bed

Pulmonary vascular responses to vasoactive intestinal contractor (VIC) (endothelin-B) were investigated in the feline pulmonary vascular bed under constant and natural flow conditions. Injection of VIC, 0.3 nmol/kg i.v., increased pulmonary arterial and left atrial pressures and cardiac output and caused a biphasic change in pulmonary vascular resistance. VIC and endothelin-1 (ET-1) caused a similar pattern of response and under constant flow conditions, VIC increased lobar arterial pressure in a dose-related manner and was similar in potency and duration of action to ET-1. The thromboxane mimic, U46619, was far more potent than VIC, and a monocyclic ET-analog had no activity in the pulmonary vascular bed. The present data show that VIC has significant vasoconstrictor activity in the pulmonary vascular bed of the cat.     

Evidence for compartmentalization of glutamate in rat brain synaptosomes using the glutamate sensitivity of phosphate-activated glutaminase as a functional test

The glutamate content of rat brain synaptosomes was measured by high performance liquid chromatography to be 39 micromol/g protein. If uncompartmentalized this glutamate (4 mM) would inhibit phosphate-activated glutaminase considerably. Since the action of any endogenous effector on the enzyme is assumed to be negligible following disruption of the synaptosomes, due to dilution with the incubation medium, the inhibition by glumate and activation by phosphate were compared in intact and disrupted synaptosomes. The inhibition by endogenous glutamate in intact synaptosomes was found to correspond to less than that of 0.5 mM of added glutamate to disrupted synaptosomes, indicating that the major fraction of synaptosomal glutamate is compartmentalized.