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Biomedical subjects

T Solomon

Publications and source records attributed to T Solomon.

At least 19 recordsLinked to original sources

Polymorphisms of the gene coding for copper/zinc superoxide dismutase (SOD1) in patients with Japanese encephalitis.

Japanese encephalitis is the commonest form of encephalitis globally. Most cases develop characteristic encephalitis but some also present with flaccid paralysis. The paralysis is secondary to damage at the alpha motor neurone, the site that is also damaged in amyotrophic lateral sclerosis (ALS). The gene coding for superoxide dismutase 1 (SOD1) is thought to be involved in ALS and may also be linked to susceptibility to Japanese encephalitis. To investigate this possibility, polymorphisms in the SOD1 gene were investigated, in 61 cases of Japanese encephalitis, 61 matched controls and 171 population controls, in Vietnam. Novel polymorphisms, found only in three of the cases and one of the population controls, may be involved with susceptibility to Japanese encephalitis and potentially to other flavivirus infections that lead to damage to the cells of the anterior horn. Further research on this possible association is required.

Adolescent↗

Neurovirulence and host factors in flavivirus encephalitis--evidence from clinical epidemiology.

Japanese encephalitis virus (JEV) and West Nile virus (WNV) provide some of the most important examples of emerging zoonotic viral encephalitides. For these flaviviruses, only a small proportion of those infected develop clinical features, and these may range from a non-specific flu-like illness to a severe fatal meningoencephalitis, often with Parkinsonian features, or a poliomyelitis-like flaccid paralysis. The factors governing the clinical presentations, and outcome of flavivirus infections are poorly understood, but studies have looked at viral virulence determinants and the host immune response. Previous studies on JEV have suggested that the distribution of the four genotypes across Asia may relate to the differing clinical epidemiology (epidemic disease in the north, endemic disease in the south). However, new data based on the complete nucleotide sequence of a virus representing one of the oldest lineages, and phylogenetic analyses of all JEV strains for which genetic data are available, suggest that the distribution is best explained in terms of the virus' origin in the Indonesia-Malaysia region (where all genotypes have been found), and the spread of the more recent genotypes to new geographical areas. Clinical studies have shown that innate immunity, as manifested by interferon alpha levels, is important in JEV and other flaviviruses, but treatment with interferon alpha did not improve the outcome. A failure of the humoral immune response, is associated with death from encephalitis caused by JEV and WNV. Cellular immunity has been less well characterized, but CD8+ and CD4+ T cells are thought to be important.

Animals↗

Pathological evaluation, clinical chemistry and plasma cholecystokinin in neonatal and young miniature swine fed soy trypsin inhibitor from 1 to 39 weeks of age.

The potential toxicity of dietary soy trypsin inhibitor (TI) was evaluated in neonatal miniature swine. From 1 to 6 weeks of age, two groups of male piglets were artificially reared in an Autosow and automatically fed either TI or control liquid diet. From 6 to 39 weeks of age, these two groups were fed either TI or control chow diet. A third group, sow control (SC), suckled from birth to 6 weeks of age, were also weaned to control chow from 6 to 39 weeks of age. Clinical chemistry and plasma cholecystokinin (CCK) determined at 6, 18, 30 and 39 weeks of age, and serum amylase activity with gross and histopathological analyses of major organs at 6 and 39 weeks of age are reported. TI had no effect on plasma CCK, serum amylase activity, or numerous clinical chemistry values. TI-fed piglets had a larger relative liver weight at 6 weeks of age. Relative pancreas weight decreased with age but was not affected by TI. Gross and histopathological analyses of major organs, except the spleen, were within normal limits. Increased incidence of extramedullary hematopoiesis was noted in the spleen of the TI group at 6 but not at 39 weeks of age. There was no consistent pattern in immunohistochemical foci for secretin, gastrin releasing polypeptide or CCK, and no change in DNA, RNA, mitotic index or nuclear density of pancreatic cells. At 6 weeks of age, TI increased pancreatic protein and amylase activity but not trypsin or chymotrypsin activity. None of the effects suggested that this dose of TI was toxic to either the neonatal or sexually mature miniature male swine.

Administration, Oral↗

Autosomal recessive limb girdle myasthenia in two sisters.

Limb girdle myasthenic syndromes are rare genetic disorders described under the broad heterogeneous group known as congenital myasthenic syndromes and present with mixed features of myasthenia and myopathy. The familial limb girdle myasthenia has been described as one with selective weakness of pectoral and pelvic girdles, showing a positive response to edrophonium chloride. A report of two sisters affected by this disorder is presented.

Adolescent↗

Liquid chromatographic determination of total and beta-N-oxalyl-L-alpha,beta-diaminopropionic acid in lathyrus sativus seeds using both refractive index and bioelectrochemical detection.

A further improved chromatographic method for the simultaneous determination of the total amount of ODAP, selectively the amount of its neurotoxic form, beta-ODAP, and free L-glutamate in raw Lathyrus sativus (grass pea) seed samples is described using post-column refractive index in combination with bioelectrochemical detection. The biosensor is based on crosslinking horseradish peroxidase (HRP) and an Os-containing mediating polymer with poly(ethyleneglycol)(400) diglycidyl ether (PEGDGE), forming an inner hydrogel layer and then immobilising L-glutamate oxidase (GlOx) as an outer layer on top of a graphite electrode. Addition of polyethylenimine (PEI) to the hydrogel is believed to have sensitivity and stability enhancing effect on the biosensor. The double-layer approach in the biosensor construction avoided direct electrical wiring of GlOx and resulted in a higher sensitivity of 4.6 mA/M cm2 with respect to beta-ODAP and a wider linear range (1-250 microM) for both L-glutamate and beta-ODAP when compared with a single-layer approach where GlOx, HRP, and Os-polymer are crosslinked together. The limit of detection for the chromatographic-biosensor system was found to be 2 microM with respect to beta-ODAP and 0.7 microM with respect to L-glutamate. The refractive index detection on-line with the biosensor enabled full control of the chromatographic system for the determination of the total amount of ODAP, selectively the amount of beta-ODAP and L-glutamate. Ten grass pea samples have been collected from Lathyrism prone areas of Ethiopia to test the applicability of the presently developed analytical system for real sample analysis. The toxin levels of grass pea collections were determined in an aqueous extracts and ranged from 0.52 to 0.76%, dry mass basis. Comparison of results of an established spectrophotometric assay and that of the present system has shown an extraordinary degree of agreement as revealed by parallel "t" test (90% confidence limit). The present system has operational stability of more than 50 h. Analysis time per sample is 10 min after extraction for 90 min.

Amino Acids, Diamino↗

Acute management of dengue shock syndrome: a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour.

Dengue hemorrhagic fever is an important cause of morbidity among Asian children, and the more severe dengue shock syndrome (DSS) causes a significant number of childhood deaths. DSS is characterized by a massive increase in systemic capillary permeability with consequent hypovolemia. Fluid resuscitation is critical, but as yet there have been no large trials to determine the optimal fluid regimen. We undertook a randomized blinded comparison of 4 fluids (dextran, gelatin, lactated Ringer's, and "normal" saline) for initial resuscitation of 230 Vietnamese children with DSS. All the children survived, and there was no clear advantage to using any of the 4 fluids, but the longest recovery times occurred in the lactated Ringer's group. The most significant factor determining clinical response was the pulse pressure at presentation. A comparison of the colloid and crystalloid groups suggested benefits in children presenting with lower pulse pressures who received one of the colloids. Further large-scale studies, stratified for admission pulse pressure, are indicated.

Adolescent↗

Dengue and other emerging flaviviruses.

Flaviviruses are among the most important emerging viruses known to man. Most are arboviruses (arthropod-borne) being transmitted by mosquitoes or ticks. They derived from a common ancestor 10-20000 years ago and are evolving rapidly to fill new ecological niches. Many are spreading to new geographical areas and causing increased numbers of infections. Traditionally, three clinical syndromes are recognized: fever-arthralgia-rash, viral haemorrhagic fever, and neurological disease, though for some flaviviruses the disease pattern is changing. Dengue, the most important flavivirus, is transmitted between humans by Aedes mosquitoes. Recent work is elucidating the pathogenesis of its most severe form, dengue haemorrhagic fever. Yellow fever, which has epidemiological similarities to dengue, was under control in the mid-20th century, but is once again increasing. Japanese encephalitis virus is numerically the most important cause of epidemic encephalitis; its geographical area is expanding despite the availability of vaccines. Other mosquito-borne neurotropic flaviviruses with clinical and epidemiological similarities are found across the globe. These include St Louis encephalitis virus, Murray Valley encephalitis virus, and West Nile virus, which recently reached the Americas for the first time. In cooler northern climates ticks are more important vectors. Tick-borne encephalitis virus occurs across large parts of Eastern Europe and the Commonwealth of Independent states. The tick-borne haemorrhagic flaviviruses, Omsk haemorrhagic fever and Kyasanur Forrest disease are localized in small areas.

Americas↗

Late presentation of Nipah virus encephalitis and kinetics of the humoral immune response.

Nipah virus is a newly discovered paramyxovirus transmitted directly from pigs to humans. During a large encephalitis outbreak in Malaysia and Singapore in 1998-9, most patients presented acutely. A 12 year old child is described who developed encephalitis 4 months after exposure to the virus. She was diagnosed by a new indirect IgG enzyme linked immunosorbent assay (ELISA), which is also described. The late presentation and IgG subclass responses had similarities to subacute sclerosing panencephalitis. Nipah virus should be considered in patients with encephalitis even months after their possible exposure.

Animals↗

Neurological manifestations of dengue infection.

BACKGROUND: Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. METHODS: During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. FINDINGS: Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%) of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic fever, and with other strains previously isolated in southern Vietnam. INTERPRETATION: In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.

Adolescent↗

Comparison of PanBio Dengue Duo IgM and IgG capture ELISA and venture technologies dengue IgM and IgG dot blot.

BACKGROUND: A number of commercial ELISA for dengue diagnosis have recently become available, though direct comparison between these assays have not been published. OBJECTIVES: The Venture Technologies Dengue IgM and IgG Dot Blot assays and the PanBio Dengue Duo IgM and IgG Capture ELISA were compared. STUDY DESIGN: Paired sera from patients with dengue (n=20) and Japanese encephalitis (JE, n=10), and single sera from patients with typhoid (n=10), leptospirosis (n=10) and scrub typhus (n=10) were assayed according to the manufacturer's instructions. RESULTS: The Dot Blot IgM ELISA showed higher sensitivity than the PanBio IgM ELISA (100 vs. 95%), while the PanBio IgM ELISA showed higher specificity in JE (100 vs. 20%) and non-flavivirus infections (100 vs. 97%). Defining elevation of either IgM or IgG as a positive result, the Dot Blot and ELISA tests both showed 100% sensitivity in dengue infection, while the PanBio test showed superior specificity in JE (70 vs. 0%) and non-flavivirus infections (100 vs. 67%). CONCLUSIONS: Both assays are useful aids to the serological diagnosis of dengue infection. The clinical setting, user preference and local conditions will be important in determining which test is more appropriate.

Antibodies, Viral↗

Effects of dopamine and epinephrine infusions on renal hemodynamics in severe malaria and severe sepsis.

OBJECTIVE: To describe and compare the effects of dopamine and epinephrine in various doses on renal hemodynamics and oxygen transport in patients with severe malaria and severe sepsis. DESIGN: Prospective, controlled, crossover trial. SETTING: The intensive care unit of an infectious diseases hospital in Viet Nam. PATIENTS: Fourteen patients with severe falciparum malaria and five with severe sepsis. INTERVENTIONS: In an open, crossover design, we observed the effects on renal and systemic hemodynamics and oxygen transport of separate stepped infusions of epinephrine and dopamine. We measured renal blood flow (RBF) and cardiac output by the thermodilution method using fluoroscopically guided catheters. Creatinine clearance at each time point was calculated from the renal plasma flow and the renal arteriovenous difference in plasma creatinine. MEASUREMENTS AND MAIN RESULTS: Dopamine at a "renal" dose (2.5 microg/kg/min) was associated with a mean (95% confidence interval) fractional increase in the absolute renal blood flow index (RBFI) of 37% (13% to 61%) and in RBF as a fraction of cardiac output (RBF/CO) of 35% (10% to 59%; p = .007 and p = .014, respectively). The consequent 39% (14% to 64%) increase in renal oxygen supply (p = .002) was accompanied by a 32% (20% to 44%) decrease in the renal oxygen extraction ratio (p = .0003), leading to no net change in renal oxygen consumption. At higher doses (10 microg/kg/min), both RBF and RBF/CO were not significantly different from baseline values and decreased further as the dose was reduced again. There was no obvious explanation for this hysteresis. There was no change in renal oxygen consumption throughout the study. Because lactic acidosis developed, epinephrine was only given to eight of the 19 patients, and the full stepped epinephrine infusion was given to four patients. Epinephrine infusion was associated, both in absolute terms and when compared with dopamine, with a significant increase in renal vascular resistance (p = .0008 and .0005, respectively), a decrease in RBF/CO (p = .002 and .03), and a compensatory increase in the renal oxygen extraction ratio (p = .005 and .0001). RBFI and renal oxygen consumption remained constant throughout the epinephrine infusion profile. Neither epinephrine nor dopamine significantly affected creatinine clearance or urine output. Twelve patients (63%) were in established renal failure (plasma creatinine, >3 mg/dL) at the time of the study, although the presence or absence of renal failure did not significantly influence the effects of the study drugs. However, overall, the presence of renal failure was associated with a lower mean renal oxygen consumption, a lower mean renal oxygen consumption as a fraction of systemic oxygen consumption, and a higher mean renal vascular resistance. CONCLUSION: Although dopamine increased and epinephrine decreased fractional renal blood flow, there was no evidence that either drug produced either a beneficial or a deleterious effect on renal oxygen metabolism or function at any of the doses investigated.

Adult↗