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Biomedical subjects

C Chin

Publications and source records attributed to C Chin.

At least 73 records · Page 4Linked to original sources

Susceptibility of three laboratory strains of Aedes albopictus (Diptera: Culicidae) to Japanese encephalitis virus from Taiwan.

The susceptibility of 3 laboratory strains of Aedes albopictus (Skuse) (Sanhsia [SH], Yungho [YH], Liyang [LY], and 1 strain of Culex tritaeniorhynchus Giles from northern and central Taiwan were compared for susceptibility to the MQ1-2 strain of Japanese encephalitis (JE) virus. The median infective dose (MID50) by intrathoracic inoculation was 0.23, 0.76, 1.60, and -0.03 log10 WMICLD50 (50% weanling mice intracranial lethal dose) with Ae. albopictus SH, YH, LY, and Cx. tritaeniorhynchus, respectively. After feeding on a sweetened blood-virus mixture, the oral MID50 was 2.03, 4.32, and 4.98 log10 WMICLD50 for SH, YH, and LY, respectively, and 1.02 log10 WMICLD50 for Cx. tritaeniorhynchus. The SH Ae. albopictus strain transmitted virus to normal mice after 14 d. with an average transmission rate of 45%. Based on these results, the SH strain was the most susceptible and important potential vector among 3 Ae. albopictus strains for the sympatric MQ1-2 strain of JE.

Aedes↗

Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy.

PURPOSE: To compare the efficacy of dolasetron and ondansetron in controlling nausea and vomiting in the first 24 hours; to evaluate the efficacy when dexamethasone is added to either drug in the first 24 hours; and to extend these comparisons over 7 days in patients receiving moderately emetogenic chemotherapy. PATIENTS AND METHODS: This was a multicenter, double-blind, randomized study with six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive patients. In arm 1, dolasetron (2.4 mg/kg) was given intravenously (I.V.) prechemotherapy, followed 24 hours later by oral dolasetron (200 mg once daily) for 6 days. Arms 2 and 3 consisted of dolasetron and dexamethasone 8 mg I.V., followed 24 hours later by oral dexamethasone (8 mg once daily) in one arm, and oral dexamethasone and dolasetron in the other, also for 6 days. In arms 4, 5, and 6, ondansetron (32 mg I.V. or 8 mg orally twice daily) was administered in a similar manner to arms 1, 2, and 3 before and 24 hours after chemotherapy. Mean nausea severity (MNS) was assessed on a visual analog scale (VAS) in a daily diary. RESULTS: Of 703 patients enrolled, 696 were eligible. There were 343 dolasetron- and 353 ondansetron-treated patients; 57% of dolasetron-treated patients had complete protection in the first 24 hours versus 67% of patients who received ondansetron (P = .013). MNS was also more pronounced on the dolasetron arm (P = .051). Sixty-seven percent of patients who received added dexamethasone in the first 24 hours had complete protection, compared with 55% without dexamethasone (P < .001). MNS was significantly reduced with the addition of dexamethasone (P < .001). At 7 days, dolasetron and ondansetron had equivalent complete protection rates (36% and 39%, respectively). With the addition of dexamethasone, 48% of patients compared with 28% had complete protection (P < .001). MNS was significantly improved with added dexamethasone (P < .001). CONCLUSION: At the doses used, dolasetron was significantly less effective than ondansetron at controlling nausea and vomiting in the first 24 hours in patients receiving moderately emetogenic chemotherapy, but there was no demonstrable difference between both drugs over 7 days. The addition of dexamethasone significantly improved the efficacy of both drugs in the first 24 hours and over 7 days.

Administration, Oral↗

Generation and characterization of organ-tropism mutants of Japanese encephalitis virus in vivo and in vitro.

Using gamma-ray irradiation, a pair of virulent (RP-9) and attenuated (RP-2ms) variants of Japanese encephalitis virus (JEV) were generated from a Taiwanese isolate, NT109. The two variants differed in plaque morphology, virus adsorption, and growth properties in BHK-21 cells: (i) RP-2ms produced smaller plaques than RP-9; (ii) RP-2ms adsorbed less efficiently to host cells but yielded a higher virus titer (burst size); and (iii) RP-2ms virions were mostly accumulated intracellularly, whereas RP-9 was released extracellularly. In addition, in an in vitro binding assay, the envelope (E) protein of RP-9, but not that of RP-2ms, bound specifically to a cellular protein of 57-kDa derived from BHK-21 cells. When injected into mice intracerebrally, RP-2ms was much less virulent than RP-9, with 50% lethal doses of > 10(7) and 0.4 plaque forming units, respectively. Moreover, when inoculated intraperitoneally, their organ tropism differed in that the main target organ for RP-2ms was liver, whereas that for RP-9 was brain. These results suggest that RP-2ms was less neurovirulent and less neuroinvasive from peripheral routes. Molecular analysis of the virus structural proteins detected only two differences between RP-9 and RP-2ms: one in E protein, Glu-138 in RP-9 and Lys-138 in RP-2ms, and the other in prM, Tyr-43 in RP-9 and His-43 in RP-2ms. Since the N-terminal 92 amino acids of prM are cleaved and not present in mature JEV virions, the single-amino-acid change of the E protein at position 138 may account for the difference between the mutants in the in vitro binding assay. Such mutation in E protein, or perhaps in conjunction with the prM mutation, may be responsible, in part, for the phenotypic differences observed in vitro and in vivo between the two mutants.

Aedes↗

Reversible cardiomyopathy in a child with Addison's disease.

An 11-year-old boy in acute adrenal crisis was subsequently diagnosed with Addison's disease and presumably had an unrecognized preceding chronic adrenal insufficiency. His adrenal insufficiency and hypovolemic shock were promptly diagnosed and treated in the emergency room. However, 24 h later, signs of congestive heart failure developed and an echocardiogram revealed cardiomyopathy. He responded to i.v. dopamine and his cardiomyopathy resolved over some days. Acute adrenal insufficiency and actual ventricular dysfunction had not been described in humans until last year; this is the second reported case of cardiomyopathy in a patient with acute adrenal insufficiency.

Acute Disease↗

Identification of immunodominant, group-specific and subcomplex-specific, continuous epitopes in the core regions of Japanese encephalitis virus using synthetic peptides.

Two flaviviruses, Japanese encephalitis (JE) virus and Dengue (DEN) virus which have high pathogenicity for humans, continue to pose a serious public health problem in tropical and subtropical countries of the world. In order to identify the immunodominant B-cell epitopes for diagnostic application, we have prepared a series of 15-mer synthetic peptides from JE virus core protein based on computer analysis. Four linear, immunodominant epitopes corresponding to amino acids 91-105 (P78), 1-15 (P73), 8-22 (P74), and 34-48 (P75) of JE virus core proteins were identified by employing an enzyme-linked immunosorbent assay (ELISA), using high-titered immune sera from JE-vaccinated children. P78 was found to be the most immunodominant. The sero-specificity of these peptides was tested by binding to seroconverted samples from JE and DEN-1 patients. P78 and P74 belonged to group-specific epitopes which reacted with both JE and DEN-1 patient sera. P73 and P75 belonged to subcomplex-specific epitopes which reacted only with JE but not with DEN-1 patient sera. The study suggests that these peptides corresponding to the immunodominant epitopes of JE virus core protein might have the potential to be used as peptide-based diagnostic reagents for the detection and differentiation of JE and DEN antibody responses.

Adult↗

A highly attenuated strain of Japanese encephalitis virus induces a protective immune response in mice.

A pair of virulent (RP-9) and attenuated (RP-2ms) mutants of Japanese encephalitis virus (JEV) were generated from a Taiwanese isolate NT109. The mutants differed in several aspects in vitro and in vivo. RP-2ms exhibited smaller plaque than RP-9 on BHK-21 cells, and when intracerebrally injected, RP-2ms was much less neurovirulent than RP-9. As peripherally inoculated, RP-2ms lost neuroinvasiveness while RP-9 penetrated blood-brain barrier, replicated in mouse brain, and killed all the mice. Single RP-2ms immunization completely protected C3H and ICR mice from a lethal challenge with RP-9; the sera from such mice contained antibodies against JEV envelope and nonstructural 1 proteins, indicating RP-2ms had replicated in the mice Neutralizing activity against NT109 in such sera was further demonstrated by plaque reduction neutralization test. In addition, significant lymphoproliferation was detected in spleen cells from the RP-2ms-immunized mice, and cytotoxic activity in these cells specific for the MHC-matched, JEV-infected cells, but not mock cells, was also observed. Altogether, these results demonstrate that RP-2ms, a highly attenuated JEV strain, can induce a protective immunity in mice.

Aedes↗

Pharmacokinetics of the active metabolite (MDL 74,156) of dolasetron mesylate after oral or intravenous administration to anesthetized children.

BACKGROUND: Dolasetron mesylate is a selective 5-HT3 receptor antagonist under investigation as an antiemetic in children. Published studies indicate that its antiemetic activity results from the active metabolite (MDL 74,156), which is produced within 10 minutes of administration of dolasetron mesylate. METHODS: The pharmacokinetics of MDL 74,156 and the safety and tolerability of dolasetron mesylate were studied after a single oral or intravenous dose of 1.2 mg.kg-1 dolasetron mesylate to healthy children from 2 to 12 years of age. Oral dolasetron was administered to 12 children 1 to 2 hours before anesthesia. Intravenous dolasteron was administered to 18 children at induction of anesthesia. Serial blood samples were collected for 24 hours after dosing to measure the plasma concentration of MDL 74,156. Indexes of liver and kidney function were determined, and electrocardiograms and adverse events were recorded.

Administration, Oral↗

Characterization of the NTPase activity of Japanese encephalitis virus NS3 protein.

Japanese encephalitis (JE) virus NS3 protein and two N-terminally truncated (delta 1-148 and delta 1-323) forms of NS3 were engineered and expressed in E. coli as fusion proteins with a histidine tag at the N terminus. The purified recombinant proteins his-NS3 and his-NS3(delta 1-148) were found to possess NTPase activity which was stimulated by single-stranded RNA, whereas NS3(delta 1-323) did not. The requirements for MgCl2 and MnCl2 and the salt and pH ranges necessary for optimal activity of the enzyme were determined and shown to be slightly different from those of the NTPases of other flaviviruses. Poly(U) and poly(C) were better than poly(A) at stimulating the NTPase activities, in contrast to other flaviviral NTPases. The substrate preference was in the order GTP > ATP >> UTP > CTP. Interestingly, we found that Ca2+ could not substitute for Mg2+; on the contrary, it inhibited NTPase activity. The removal of the N-terminal 148 amino acids enhanced NTPase activity, but further deletion of the region (amino acids 148-323) completely abolished the activity. Therefore, amino acids 148-323 contain a critical region required for NTPase activity.

Acid Anhydride Hydrolases↗

Risk factors for ill-health in a remote desert-dwelling aboriginal community in Western Australia.

BACKGROUND: Living in small, isolated groups may promote health for Aborigines if traditional lifestyles are followed, but overall health risks in such communities are inadequately documented. AIM: To document health status of a remote Aboriginal community with reference to nutrition, cardiovascular risks, renal disease and infections and to identify areas where health might be improved. METHODS: All residents of a small community in the Great Sandy Desert underwent medical examinations, anthropometry and measurement of blood pressure. Investigations included cholesterol, triglycerides, glucose, insulin, creatinine, lipoprotein (a), apolipoprotein E phenotype, angiotensin-converting enzyme genotype, urinalysis, stool microscopy (children), liver function tests and full blood examination. RESULTS: Children (n = 26) were undernourished while 14% of adults (n = 51) were underweight, 22% overweight and 40% of women and 13% of men were obese with central obesity in 90% of women and 48% of men. Fifteen per cent of the group were hypertensive. Insulin levels were increased in 55% of subjects, total cholesterol in 21% and triglycerides in 56%, while HDL was decreased in 78%. Angiotensin-converting enzyme and apolipoprotein E typing and lipoprotein (a) did not suggest increased cardiovascular risk. Proteinuria was present in 39% of subjects, haematuria in 49% and definite or possible urinary tract infections in 30%. Faecal parasites were prevalent and a history of infections, including sexually transmitted diseases, was common. CONCLUSIONS: Increased cardiovascular risk, nutritional disorders, renal disease and infections are major problems in this community which had relocated several years previously from a mission environment closer to western influences, including alcohol.

Adolescent↗

Arterial switch and resection of hepatic hemangioendothelioma.

We report on the management of a neonate undergoing arterial switch for transposition of the great arteries and concomitant resection of a hepatic infantile hemangioendothelioma. A preoperative aortogram demonstrated the arterial supply of the hepatic hemangioendothelioma. Pulmonary artery hypertension and myocardial ischemia were noted after separation from cardiopulmonary bypass. Resection of the hepatic malformation produced an immediate reduction in pulmonary hypertension and resolution of the myocardial ischemia. The patient had an uneventful postoperative recovery.

Female↗

Cardiomyopathy induced by phenylpropanolamine.

A 14-year-old girl had evidence of an acute cardiomyopathy after a minimal overdose of phenylpropanolamine. She had myocardial dysfunction, ventricular dysrhythmia, and secondary pulmonary edema without any associated systemic hypertension. The cardiomyopathy resolved after several days.

Adolescent↗

HeT-A, a transposable element specifically involved in "healing" broken chromosome ends in Drosophila melanogaster.

Eight terminally deleted Drosophila melanogaster chromosomes have now been found to be "healed." In each case, the healed chromosome end had acquired sequence from the HeT DNA family, a complex family of repeated sequences found only in telomeric and pericentric heterochromatin. The sequences were apparently added by transposition events involving no sequence homology. We now report that the sequences transposed in healing these chromosomes identify a novel transposable element, HeT-A, which makes up a subset of the HeT DNA family. Addition of HeT-A elements to broken chromosome ends appears to be polar. The proximal junction between each element and the broken chromosome end is an oligo(A) tract beginning 54 nucleotides downstream from a conserved AATAAA sequence on the strand running 5' to 3' from the chromosome end. The distal (telomeric) ends of HeT-A elements are variably truncated; however, we have not yet been able to determine the extreme distal sequence of a complete element. Our analysis covers approximately 2,600 nucleotides of the HeT-A element, beginning with the oligo(A) tract at one end. Sequence homology is strong (greater than 75% between all elements studied). Sequence may be conserved for DNA structure rather than for protein coding; even the most recently transposed HeT-A elements lack significant open reading frames in the region studied. Instead, the elements exhibit conserved short-range sequence repeats and periodic long-range variation in base composition. These conserved features suggest that HeT-A elements, although transposable elements, may have a structural role in telomere organization or maintenance.

Animals↗

Fate of the atrioventricular endocardial cushions in the developing chick heart.

To determine the fate of the atrioventricular endocardial cushions in cardiac development, we used staining methods for extracellular fibronectin, which is abundant in the endocardial cushions, and actin, which is abundant in the myocytes. White Leghorn chick embryo hearts were harvested at Hamburger and Hamilton stages 26 to 36, and serial sections of the atrioventricular valve region were stained. Before atrioventricular valve formation, fibronectin and actin staining reveal separation between the fibronectin-rich endocardial cushions and the actin-rich myocardial layer. The developing mitral valve leaflets at all of the observed stages contain a fibronectin-rich matrix but no actin-rich myocytes. In contrast, the tricuspid band includes both fibronectin matrix and actin-rich cells. We conclude that the mitral valve leaflets in the chick form predominantly from the endocardial cushion tissue, and the tricuspid band receives contributions from both the endocardial cushions and surrounding myocardium.

Actins↗

Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise.

BACKGROUND: Silent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear. METHODS AND RESULTS: Sixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p = 0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 +/- 148 from 296 +/- 154 seconds (p = 0.005). Although less frequent with diltiazem administration (45 versus 54 patients, p less than 0.03), exercise-induced ST depression was more often asymptomatic (98% versus 72% of patients, p less than 0.0001). CONCLUSIONS: Diltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease.

Activities of Daily Living↗

Role of diltiazem in the treatment of silent myocardial ischemia.

Silent myocardial ischemia is a frequent finding when Holter monitoring is done in patients with advanced coronary disease. Silent ischemia is associated with a worse prognosis in patients with stable or unstable angina, survivors of myocardial infarction, and populations at risk for coronary disease. Whether medical therapy for silent ischemia improves prognosis is not known. In a randomized, placebo-controlled, multicenter trial of 60 patients with documented coronary disease, positive exercise tests, and ischemic episodes on Holter monitoring, long-acting diltiazem reduced ischemic episodes by 50% compared to placebo, from a mean of 5.6 to 2.8 (p less than 0.0001). Efficacy was maintained over 24 h and diltiazem also significantly improved exercise test parameters. Three smaller studies also demonstrated that diltiazem effectively reduces ambulatory ischemia; however, results with nifedipine are conflicting, with several studies showing no benefit. In contrast, beta-blockers reliably reduce ischemic episodes. The role of medical therapy for silent ischemia will be clarified only when its effect upon morbidity and mortality are determined.

Adult↗

Multidisciplinary home rehabilitation. A practical model.

The home is the most natural setting for rehabilitation. At home, the patient and family become active team members and the plan of care is created and carried out in the environment in which the patient will live. Home rehabilitation enhances the patient's autonomy, independence, and community reintegration.

Aged↗

Usefulness of sustained-release diltiazem for stable angina pectoris.

Sustained-release diltiazem, 120 and 180 mg twice daily, was assessed in a multicenter, double-blind, randomized, placebo-controlled trial in 65 stable angina patients with exercise-induced ST depression. Exercise testing was performed 12 +/- 1 hours after the last dose at the end of each of the 3 treatment weeks. Both dose levels of drug reduced spontaneous angina (p less than 0.001) and increased exercise duration (p less than 0.01) and time to 1-mm ST depression (p less than 0.001). No differences were noted between the 2 dose levels. Rate-pressure product at maximal exercise was similar for the 3 groups. Only 1 patient terminated the study because of adverse drug effects; severe adverse effects occurred in 1 placebo and 1 low-dose period. Sustained-release diltiazem is safe and efficacious monotherapy for patients with stable angina.

Adult↗