Biomedical subjects
A Michael
Publications and source records attributed to A Michael.
Aetiology and clinical signs of bacterial meningitis in children admitted to Goroka Base Hospital, Papua New Guinea, 1989-1992.
Children aged 1-59 months admitted to Goroka Base Hospital with signs suggestive of meningitis were recruited to determine what proportion of such children have clinical or bacterial meningitis and to investigate the bacterial aetiology. A laboratory classification of definite, probable, possible, indeterminate and no meningitis was established. Thirty per cent of 697 children had a final clinical diagnosis of meningitis, 12% had culture-proven bacterial meningitis (case fatality rate 34%) and 10% had probable or possible meningitis. Inability to feed, vomiting, drowsiness, "staring eyes" and haemoglobin < 9 g/dl in addition to the classical signs of meningitis were associated with increased mortality. Isolates from cerebrospinal fluid were 62 pneumococci, 22 Haemophilus influenzae type b (Hib) and one Neisseria meningitidis. Including blood culture-proven and antigen-proven Hib disease, Hib and pneumococci accounted for 44% and 46% of bacterial meningitis, respectively, and 23% of pneumococci were intermediately resistant to penicillin. Inability to feed, bulging fontanelle, convulsions in young children, neck stiffness, fever and "staring eyes" were all independently associated with bacterial meningitis. Conjugate Hib vaccine must be given to infants as early as possible. Conjugate pneumococcal vaccines, maternal immunization with 23-valent vaccine and pneumococcal protein vaccines are under investigation for prevention of pneumococcal disease.
Day-old vaccination with live-in-oil vaccines: Newcastle disease (ND) and infectious bursal disease (IBD) in chicks and ND in turkey poults.
One-day-old broiler chicks were vaccinated with live Newcastle disease (ND) vaccine incorporated in oil alone or in killed-in-oil ND vaccine. Incorporation of live vaccine in oil emulsions was carried out just prior to vaccination. Live-in-oil ND vaccine containing 106.0 median embryo lethal doses (ELD50/dose induced the same protection following challenge and the same level of antibody at 42 days post-vaccination as did commercial killed-in-oil ND vaccine containing about 250 times as much antigen (108.4 ELD50/dose). Incorporation of live ND vaccine in killed-in-oil vaccine contributed markedly to protection rates and antibody levels, as compared to those obtained following vaccination with killed-in-oil vaccine only. One-day-old turkey poults also showed the advantage of incorporation of live ND vaccine in killed-in-oil vaccine when challenged 3 months post-vaccination. One-day-old broiler chicks, vaccinated with live ND and infectious bursal disease vaccine (IBD) incorporated in killed-in-oil combined ND + IBD vaccine, showed better protection against challenge with IBDV and higher antibody levels to NDV as compared to vaccination with killed-in-oil vaccine alone.
Bacterial and viral etiology of severe infection in children less than three months old in the highlands of Papua New Guinea.
OBJECTIVE: Determine the bacterial and viral etiology of severe infection in young Papua New Guinean infants as part of a multicenter study in four developing countries aimed at improving case management guidelines. METHODS: Between March, 1991, and April, 1993, children aged <3 months were recruited at the outpatient department of Goroka Base Hospital, Papua New Guinea (PNG). Children with pre-defined inclusion criteria were enrolled, a history was taken and clinical examination was performed. Blood and urine were collected from children with signs suggestive of severe disease together with eye, umbilical and pernasal swabs as appropriate. Nasopharyngeal aspirates (NPAs) were collected from children with and without signs of severe disease for identification of viruses and Chlamydia trachomatis by direct fluorescent antibody staining. RESULTS: 3280 infants were triaged and 2168 enrolled, among whom 968 had signs suggestive of severe disease. Group A Streptococcus (Streptococcus pyogenes) and Staphylococcus aureus were the most important bacterial pathogens isolated from children < 1 month old with severe infections, and Streptococcus pneumoniae, S. pyogenes and Staphylococcus aureus were most important in older children. Of 292 eye swabs 19 (7%) grew Neisseria gonorrhoeae. Of 116 umbilical swabs 51 (44%) grew S. pyogenes and 45 (39%) grew Staphylococcus aureus. Respiratory syncytial virus was the most important viral cause of acute lower respiratory infection. CONCLUSIONS: S. pyogenes, S. pneumoniae and Staphylococcus aureus are important causes of severe infection in young children in the PNG highlands. It is necessary to improve access to clean water, promote hand-washing in the hospital and at home and investigate further the use of maternal immunization for the prevention of severe disease in young infants.
Sertraline-induced anorgasmia reversed by nefazodone.
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The complete DNA sequence and genome organization of the avian adenovirus, hemorrhagic enteritis virus.
Hemorrhagic enteritis virus (HEV) belongs to the Adenoviridae family, a subgroup of adenoviruses (Ads) that infect avian species. In this article, the complete DNA sequence and the genome organization of the virus are described. The full-length of the genome was found to be 26,263 bp, shorter than the DNA of any other Ad described so far. The G + C content of the genome is 34.93%. There are short terminal repeats (39 bp), as described for other Ads. Genes were identified by comparison of the DNA and predicted amino acid sequences with published sequences of other Ads. The organization of the genome in respect to late genes (52K, IIIa, penton base, core protein, hexon, endopeptidase, 100K, pVIII, and fiber), early region 2 genes (polymerase, terminal protein, and DNA binding protein), and intermediate gene IVa2 was found to be similar to that of other human and avian Ad genomes. No sequences similar to E1 and E4 regions were found. Very low similarity to ovine E3 region was found. Open reading frames were identified with no similarity to any published Ad sequence.
Treating chronic fatigue with exercise. Exercise improves mood and sleep.
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Stimulation of multiple mitogen-activated protein kinase sub-families by oxidative stress and phosphorylation of the small heat shock protein, HSP25/27, in neonatal ventricular myocytes.
We investigated the activation of three subfamilies of mitogen-activated protein kinases (MAPKs), namely the stress-activated protein kinases/c-Jun N-terminal kinases (SAPKs/JNKs), the extracellularly responsive kinases (ERKs) and p38-MAPK, by oxidative stress as exemplified by H2O2 in primary cultures of neonatal rat ventricular myocytes. The 46 and 54 kDa species of SAPKs/JNKs were activated 5- and 10-fold, respectively, by 0.1 mM H2O2 (the maximally effective concentration). Maximal activation occurred at 15-30 min, but was still detectable after 2 h. Both ERK1 and ERK2 were activated 16-fold by 0.1 mM H2O2 with a similar time course to the SAPKs/JNKs, and this was comparable with their activation by 1 microM PMA, the most powerful activator of ERKs that we have so far identified in these cells. The activation of ERKs by H2O2 was inhibited by PD98059, which inhibits the activation of MAPK (or ERK) kinases, and by the protein kinase C (PKC) inhibitor, GF109203X. ERK activation was also inhibited by down-regulation of PMA-sensitive PKC isoforms. p38-MAPK was activated by 0.1 mM H2O2 as shown by an increase in its phosphorylation. However, maximal phosphorylation (activation) was more rapid (<5 min) than for the SAPKs/JNKs or the ERKs. We studied the downstream consequences of p38-MAPK activation by examining activation of MAPK-activated protein kinase 2 (MAPKAPK2) and phosphorylation of the MAPKAPK2 substrate, the small heat shock protein HSP25/27. As with p38-MAPK, MAPKAPK2 was rapidly activated (maximal within 5 min) by 0.1 mM H2O2. This activation was abolished by 10 microM SB203580, a selective inhibitor of certain p38-MAPK isoforms. The phosphorylation of HSP25/27 rapidly followed activation of MAPKAPK2 and was also inhibited by SB203580. Phosphorylation of HSP25/27 was associated with a decrease in its aggregation state. These data indicate that oxidative stress is a powerful activator of all three MAPK subfamilies in neonatal rat ventricular myocytes. Activation of all three MAPKs has been associated with the development of the hypertrophic phenotype. However, stimulation of p38-MAPK and the consequent phosphorylation of HSP25/27 may also be important in cardioprotection.
Stimulation of the p38 mitogen-activated protein kinase pathway in neonatal rat ventricular myocytes by the G protein-coupled receptor agonists, endothelin-1 and phenylephrine: a role in cardiac myocyte hypertrophy?
We examined the activation of the p38 mitogen-activated protein kinase (p38-MAPK) pathway by the G protein-coupled receptor agonists, endothelin-1 and phenylephrine in primary cultures of cardiac myocytes from neonatal rat hearts. Both agonists increased the phosphorylation (activation) of p38-MAPK by approximately 12-fold. A p38-MAPK substrate, MAPK-activated protein kinase 2 (MAPKAPK2), was activated approximately fourfold and 10 microM SB203580, a p38-MAPK inhibitor, abolished this activation. Phosphorylation of the MAPKAPK2 substrate, heat shock protein 25/27, was also increased. Using selective inhibitors, activation of the p38-MAPK pathway by endothelin-1 was shown to involve protein kinase C but not Gi/Go nor the extracellularly responsive kinase (ERK) pathway. SB203580 failed to inhibit the morphological changes associated with cardiac myocyte hypertrophy induced by endothelin-1 or phenylephrine between 4 and 24 h. However, it decreased the myofibrillar organization and cell profile at 48 h. In contrast, inhibition of the ERK cascade with PD98059 prevented the increase in myofibrillar organization but not cell profile. These data are not consistent with a role for the p38-MAPK pathway in the immediate induction of the morphological changes of hypertrophy but suggest that it may be necessary over a longer period to maintain the response.
Stimulation of "stress-regulated" mitogen-activated protein kinases (stress-activated protein kinases/c-Jun N-terminal kinases and p38-mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses.
"Stress-regulated" mitogen-activated protein kinases (SR-MAPKs) comprise the stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) and the p38-MAPKs. In the perfused heart, ischemia/reperfusion activates SR-MAPKs. Although the agent(s) directly responsible is unclear, reactive oxygen species are generated during ischemia/reperfusion. We have assessed the ability of oxidative stress (as exemplified by H2O2) to activate SR-MAPKs in the perfused heart and compared it with the effect of ischemia/reperfusion. H2O2 activated both SAPKs/JNKs and p38-MAPK. Maximal activation by H2O2 in both cases was observed at 0.5 mM. Whereas activation of p38-MAPK by H2O2 was comparable to that of ischemia and ischemia/reperfusion, activation of the SAPKs/JNKs was less than that of ischemia/reperfusion. As with ischemia/reperfusion, there was minimal activation of the ERK MAPK subfamily by H2O2. MAPK-activated protein kinase 2 (MAPKAPK2), a downstream substrate of p38-MAPKs, was activated by H2O2 to a similar extent as with ischemia or ischemia/reperfusion. In all instances, activation of MAPKAPK2 in perfused hearts was inhibited by SB203580, an inhibitor of p38-MAPKs. Perfusion of hearts at high aortic pressure (20 kilopascals) also activated the SR-MAPKs and MAPKAPK2. Free radical trapping agents (dimethyl sulfoxide and N-t-butyl-alpha-phenyl nitrone) inhibited the activation of SR-MAPKs and MAPKAPK2 by ischemia/reperfusion. These data are consistent with a role for reactive oxygen species in the activation of SR-MAPKs during ischemia/reperfusion.
[Bypass perforation by stent implantation: complication management. A case report].
We describe a case-report on an perforation of an aorto-coronary venous bypass graft, a complication induced by a stent-implantation. Perforations of coronary arteries are rare, however, for interventional cardiologists well-known complications. This case report is of special interest (1) because the perforation did not occur in a coronary artery but rather in an eight year old venous bypass graft and (2) because the perforation was induced by a stent-implantation. In addition, this case report describes in great detail the management of vessel perforation: several invasive methods contributed to minimize pericardial effusion and to stabilize the patient until surgical revision could be performed.
Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression.
BACKGROUND: It has been suggested that patients with unipolar depression show abnormal responses to negative feedback in the performance of cognitive tasks. Positron emission tomography (PET) has previously identified blood flow abnormalities in depressed patients during cognitive performance. We have also used PET to identify regions where there is differential neural response to performance feedback in normal volunteers. In this study we aimed to test the hypothesis that blood flow in these regions, the medial caudate and ventromedial prefrontal cortex, would be abnormal in depressed patients. METHODS: Six patients with unipolar depression and six matched controls were scanned using PET while performing cognitive tasks in the presence and absence of feedback. RESULTS: Compared with controls, depressed patients failed to show significant activation in the medial caudate and ventromedial orbitofrontal cortex. Blood flow was lower and a differential response, observed in normals, under different task and feedback conditions was not seen in the patients. DISCUSSION: The findings suggest that the behavioural response to feedback in depressed patients is associated with an abnormal neural response within the medial caudate and ventromedial orbitofrontal cortex, regions implicated in reward mechanisms. We argue that the observed abnormalities may depend on a combination of psychological factors, with both cognitive and emotive components.
European biotechnology firms approve of stock market mergers.
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Separating the microfuges.
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Cancer prognostic approved.
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All clear for HIV-targeting ribozyme in phase II.
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British Biotech fails to redeem itself.
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Europe proposes orphan drug legislation.
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