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Showing papers by "Mahidol University published in 1993"


Journal ArticleDOI
TL;DR: The two artemisinin compounds had the broadest time window of action and may be particularly suitable for the treatment of severe malaria.

291 citations


Journal ArticleDOI
TL;DR: In a prospective electrocardiographic study of Karen patients with acute uncomplicated falciparum malaria, mefloquine had no cardiac effects, but halofantrine induced consistent dose-related lengthening of the PR and QT intervals in all 61 patients treated.

262 citations


Journal ArticleDOI
TL;DR: The density of gibbon populations may be estimated by listening for the loud duetted songs of monogamous territorial groups but this method requires a correction factor which must be estimated from the frequency of singing of an adequate number of known study groups.
Abstract: The density of gibbon populations may be estimated by listening for the loud duetted songs of monogamous territorial groups. This method requires a correction factor which must be estimated from the frequency of singing of an adequate number of known study groups. The correction factor and its error were estimated for pileated gibbons (Hylobates pileatus) in Khao Soi Dao Wildlife Sanctuary in southeastern Thailand. Among 30 groups studied, 47% sang per day, on average, but the variation between days and the variation in singing frequency between groups were large. Weather conditions, especially windiness, explained some variation in singing. During an area-wide survey of groups in the sanctuary, unexplained variation in singing from day to day accounted for approximately half of the sample error of group density estimated from 1-day listening samples. Error due to day-to-day variability can be reduced by listening for more than one day at each site. Correction factors based on the cumulative proportion of groups heard during longer (2-5-day) sample periods of listening were closer to 1.0, therefore leaving less room for error and bias of the correction factor. © 1993 Wiley-Liss, Inc.

203 citations


Journal ArticleDOI
TL;DR: Although the overall effect of bed nets on patent parasitaemia was marginal, they were associated with a significant reduction in maternal malaria-associated anaemia and this suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent.
Abstract: A prospective comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border. Women in 3 adjacent study sites were allocated at random to receive either a single size permethrin-impregnated bed net (PIB), a non-impregnated bed net (NIB), or to a control group who used either their own family size non-impregnated bed net (FNIB) or no net. In one study site, but not the other 2, PIB significantly reduced parasite densities and, together with FNIB, reduced the incidence of malaria in pregnancy from 56% to 33% (relative risk = 1.67, confidence interval = 1.07-2.61, P = 0.03, allowing for parity). Anaemia proved a more sensitive marker of bed net antimalarial efficacy than parasite rates. The incidence of anaemia (haematocrit < 30%) at all study sites was significantly lower at delivery in the PIB (27%) and FNIB groups (21%) than in the NIB group (41%) or those using no net (56%). This suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent. Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a reduction in birth weight. Infant mortality was high (16%) and strongly associated with prematurity, low birth weight and maternal anaemia. PIB were well tolerated and had no apparent adverse effect on the pregnancy or infant development. Although the overall effect of bed nets on patent parasitaemia was marginal, they were associated with a significant reduction in maternal malaria-associated anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

165 citations


Journal ArticleDOI
TL;DR: High-dose halofantrine is better tolerated and more effective than mefloquine for the treatment of uncomplicated falciparum malaria in this area, however, evidence of possible cardiotoxicity will need to be investigated fully before a role can be established for hal ofantrine in the treatmentof multidrug-resistant malaria.

164 citations


Journal ArticleDOI
TL;DR: Observations are consistent with the hypothesis that a predominance of mature parasites in the peripheral blood reflects a greater sequestered biomass, and thus more severe disease, in severe falciparum malaria.
Abstract: Admission blood films from 72 patients who died of severe falciparum malaria (50 Thai adults, 22 Gambian children) were matched retrospectively for parasitaemia with equal numbers of survivors. The peripheral blood parasites from fatal cases were more mature than those from survivors. Tiny rings (TR) comprised > 50% of parasites in 47/72 (65%) survivors but only 12/72 (17%) of fatal cases (P 10(4) MTS/microL, 30 (81%) died. These findings were confirmed in a prospective study of 279 adult Thai patients admitted sequentially with acute falciparum malaria. Only 4 of the 19 fatal cases (21%) had > 50% TR, compared with 130 of 260 (50%) survivors, whereas > 20% MTS were found in 10/19 (53%) fatal cases, compared with 28/108 (27%) severe malaria survivors, and 26/155 (17%) patients with moderately severe malaria (P = 0.001). As a predictor of fatal outcome, the finding of either > 10(4) MTS/microL or > 5 x 10(5) parasites/microL in severe malaria had a sensitivity of 90% (95% confidence interval [CI] = 75-97%) and a specificity of 72% (95% CI = 59-86%). These observations are consistent with the hypothesis that a predominance of mature parasites in the peripheral blood reflects a greater sequestered biomass, and thus more severe disease. Simple microscopical assessment of parasite maturity on an admission blood slide provides important pathophysiological and prognostic information in severe falciparum malaria.

158 citations


Journal ArticleDOI
TL;DR: It is proposed that understanding the patients' self-concepts and patterns of self-other relationships is essential for an objective understanding of the Patients' experience of illness, and can profoundly affect the quality of the physician-patient relationship and medical care.

146 citations


Journal ArticleDOI
TL;DR: Increased expression of the Gγ‐globin gene and higher production of haemoglobin F. which could reduce the overall globin chain imbalance, were also associated with homozygosity for the Xmn I cleavage site and thus with less severe anaemia, however, this effect was not seen inXmn I site heterozygotes.
Abstract: Genetic factors determining the difference in severity of anaemia in beta-thalassaemia/HbE disease were studied in 90 patients who had haemoglobin levels, at steady state, ranging from 4.2 to 12.6 g/dl. Co-inheritance of alpha-thalassaemia 2 and haemoglobin Constant Spring could significantly decrease the severity of the disease. Inheritance of a beta-thalassaemia chromosome with Xmn I cleavage site at position -158 of the G gamma-globin gene which was linked to the haplotype -+-++ or ++-++, was associated with a milder anaemia. Two copies of these alleles were necessary to produce a significant clinical effect. Increased expression of the G gamma-globin gene and higher production of haemoglobin F, which could reduce the overall globin chain imbalance, were also associated with homozygosity for the Xmn I cleavage site and thus with less severe anaemia. However, this effect was not seen in Xmn I site heterozygotes. Whether the effects of the Xmn I polymorphism, HbF concentration and G gamma/A gamma ratio act separately or through common mechanisms in reducing anaemia remains to be ascertained.

111 citations


Journal ArticleDOI
TL;DR: Kinetic properties of the purified recombinant DHFR were similar to those reported for wild type bifunctional TS-DHFR.

105 citations


Journal ArticleDOI
TL;DR: Investigation of the possibility that protection might be achieved through an inability of red blood cells (RBC) with the AS genotype to form rosettes with RBC infected by Plasmodium falciparum found no evidence to support this hypothesis.
Abstract: The mechanisms by which the hemoglobin genotype AS protect against severe malaria are not fully understood. We have investigated the possibility that protection might be achieved through an inability of red blood cells (RBC) with the AS genotype to form rosettes with RBC infected by Plasmodium falciparum. No evidence was obtained to support this hypothesis because RBC with the AS genotype formed rosettes with wild isolates of P. falciparum as readily as RBC with the AA genotype. However, the previous finding that parasitized RBC form rosettes more readily with RBC belonging to group A or B than with RBC belonging to group O was confirmed even in fresh clinical isolates.

97 citations


Journal ArticleDOI
TL;DR: A Thai village with dengue transmission was surveyed for Aedes aegypti and Ae.
Abstract: A Thai village with dengue transmission was surveyed for Aedes aegypti (L.) and Ae. albopictus (Skuse) larvae at the end of the rainy season. All containers (1,819) in 186 households were surveyed, recording the presence of larvae, container type, level of water, kind of cover, and location. The number of positive containers was proportional to the total number of containers in a household. Standard water jars (≍200 liters) contributed 57% and small water jars (<100 liters) contributed 16% of the total infested containers. Each of the other 10 container types contributed ≤10% of the total infested containers and were not statistically different from each other. Containers inside houses were infested significantly more often than were those outdoors, those under elevated houses or roofs, or those in bathrooms. Unexpectedly, standard water jars located outdoors that were covered with commercial metal lids were infested significantly more often than were uncovered jars.

Journal ArticleDOI
TL;DR: In three patients with falciparum malaria, humoral and cellular immune responses to blood-stage antigens during the acute infection and convalescence were similar to those of individuals whose spleens were intact, suggesting that the spleen may not be essential for the processes leading to parasite clearance in partially immune, splenectomized patients.
Abstract: The spleen plays a central role in host defense against malaria in animals. Its role in human malaria is less well established. The spleen may contribute to protection against human malaria by mediating humoral or cellular immune responses or by clearing both rheologically and immunologically altered host erythrocytes. This report describes Plasmodium falciparum and Plasmodium vivax infections that occurred after splenectomy in one nonimmune and three partially immune Thai adults. The clinical course was uncomplicated for all four patients, and parasite clearance was delayed only in the nonimmune patient. In three patients with falciparum malaria, humoral and cellular immune responses to blood-stage antigens during the acute infection and convalescence were similar to those of individuals whose spleens were intact. These findings suggest that the spleen may not be essential for the processes leading to parasite clearance in partially immune, splenectomized patients. Further studies on the course of malarial infections in splenectomized patients are crucial for clarifying the role of the spleen in host defense against human malaria.

Journal ArticleDOI
TL;DR: The inherent resistance of P. pseudomallei biofilms to conventional antibiotics may explain the lack of success in the treatment of the chronic manifestations of this bacterial infection.
Abstract: We have examined the resistance of Pseudomonas pseudomallei biofilm cells to ceftazidime and cotrimoxazole. A large number of these biofilm cells remained viable at 12 and at 24 h, except in the biofilm treated with 200 times the MIC of ceftazidime. The inherent resistance of P. pseudomallei biofilms to conventional antibiotics may explain the lack of success in the treatment of the chronic manifestations of this bacterial infection.

Journal ArticleDOI
TL;DR: An investigation of the impact of housing conditions and household crowding in the context of one developing country, Thailand finds that subjective aspects of housing and of crowding, especially housing satisfaction and a felt lack of privacy, have detrimental effects on health.


Journal Article
TL;DR: The study demonstrated the rate, nature and predisposing factors of infection in SLE which may lead to better anticipation and diminution of morbidity and mortality related to infection in hospitalized patients with SLE.
Abstract: A review of 1,069 total admissions of 537 systemic lupus erythematosus (SLE) patients during a 10-yr period at Ramathibodi Hospital showed that 220 episodes which occurred in 137 patients (25.5%) were motivated by infection. Skin was the most common site (23%) with Herpes zoster being the most common organism (15.5%) found in our lupus patients. However, if we considered only major infections, pulmonary tuberculosis, salmonella septicemia and urinary tract infection by E. coli would be the most frequent complications respectively. In the absence of immunosuppressive therapy, infections coincided with the initial manifestation of SLE in 25 patients and were associated with exacerbation of the disease in 20 patients. Mean SLEDAI score in these patients was 8.8, suggesting that active lupus link together with infection. Steroid therapy influenced the rate of opportunistic infections (p = 0.006). Infections were determined to be the cause of death in 23 of 77 patients (29.9%). Opportunistic pathogens played an equal role as other common bacterial organisms in these fatal cases. SLE patients who died from infections were treated with cyclophosphamide in higher proportion than those with no infectious complication (p = 0.025). Our study demonstrated the rate, nature and predisposing factors of infection in SLE which may lead to better anticipation and diminution of morbidity and mortality related to infection in hospitalized patients with SLE.

Journal Article
TL;DR: The estimated safe and adequate daily carnitine intake for adults is 150-500 mumol/day whereas pharmacological doses of carnitines are required for the treatment of hereditary carnitINE deficiency, and organic acidurias.

Journal ArticleDOI
TL;DR: Both phyllanthin and hypophyllanthin were found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB cells, suggesting an interaction with the P-glycoprotein.
Abstract: Complete 1H-nmr data and unambiguous assignments of the 13C-nmr spectra of phyllanthin [1] and hypophyllanthin [2] were obtained through extensive nmr studies, including homonuclear COSY, homonuclear decoupling, APT, HETCOR, nOe difference, selective INEPT, and COLOC experiments. The absolute configuration of hypophyllanthin [2] was determined by cd. Neither of these lignans demonstrated significant cytotoxic activity when evaluated with a battery of cultured mammalian cells, but both were found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB cells. In addition, 1 was found to displace the binding of vinblastine with membrane vesicles derived from this cell line, suggesting an interaction with the P-glycoprotein.

Journal ArticleDOI
TL;DR: Three diarylheptanoids exerted significant anti-inflammatory activity in the assay of carrageenin-induced hind paw edema in rats and were identified by high-field 1H-NMR.
Abstract: Bioassay-guided fractionation of a hexane extract of the rhizomes of Curcuma xanthorrhiza Roxb. (Zingiberaceae) led to the isolation of three non-phenolic diarylheptanoids, identified mainly by high-field 1H-NMR as trans-trans-1,7-diphenyl-1,3-heptadien-4-one (alnustone), trans-1,7-diphenyl-1-hepten-5-ol, and trans,trans-1,7-diphenyl-1,3-heptadien-5-ol. The latter is reported for the first time as a plant constituent. Germacrone, curzerenone, and cinnamaldehyde were also isolated and identified. The three diarylheptanoids all exerted significant anti-inflammatory activity in the assay of carrageenin-induced hind paw edema in rats.

Journal ArticleDOI
TL;DR: The results are in line with the conclusion that parasite-associated proliferation in target cell populations is, at least in part, responsible for the influence of OV on liver tumor development.
Abstract: Administration of hepatocarcinogenic nitrosamines before or after infection with the liver fluke, Opisthorchis viverrini (OV), results in marked development of cholangiocellular and hepatocellular precancerous and cancerous lesions in the hamster liver. The promoting effects of OV are believed to be exerted either mechanically, chemically or immunologically. To test the influence of possible mechanical effects, Syrian hamsters were initiated with a single i.p. injection of dimethylnitrosamine (DMN) 20 mg/kg and subjected 2 weeks later either to a sham operation or to complete ligation of the extrahepatic bile duct to the left lateral lobe. At the end of week 40, the animals receiving DMN-initiation and ligation had a 60.9% incidence of cholangiofibrosis, 21.7% of mucous cystadenomas and 39.1% of cholangiocarcinomas, whereas the group given DMN alone only developed cholangiofibrosis, limited to 5% of the animals. In the latter case neither cystadenomas nor cholangiocarcinomas were observed. The incidence of hepatocellular nodules did not differ between the two groups and no tumorous lesions developed in either the ligated or the untreated groups without DMN pretreatment. Complete ligation of the bile duct itself led to a series of events; obstruction of bile flow being followed by dilatation, cyst formation, and necrosis of the bile duct epithelium and surrounding affected areas leading to regenerative proliferation. The results are in line with the conclusion that parasite-associated proliferation in target cell populations is, at least in part, responsible for the influence of OV on liver tumor development.

Journal ArticleDOI
TL;DR: In vitro mammalian cell growth assays showed compound 13 to be one of the least cytotoxic 9-anilinoacridines (50% inhibitory concentration, 15 microM), and the antimalarial drug pyronaridine inhibited the decatenation activity of P. falciparum DNA topoisomerase II.
Abstract: An in vitro investigation of the structure-activity profiles for a range of 9-anilinoacridines on drug-resistant Plasmodium falciparum is reported. C-3, 6-diamino substitution, low lipophilicity, and high pKa values substantially increased the activities of the 9-anilinoacridines tested. There appeared to be no correlation between DNA binding and antimalarial activity. 3,6-Diamino-1'-amino-9-anilinoacridine (compound 13) was the most active compound tested; it had a 50% inhibitory concentration of 25 nM. In vitro mammalian cell growth assays showed compound 13 to be one of the least cytotoxic 9-anilinoacridines (50% inhibitory concentration, 15 microM). Both compound 13 and the antimalarial drug pyronaridine inhibited the decatenation activity of P. falciparum DNA topoisomerase II at concentrations of 10 and 11 microM, respectively.

Journal ArticleDOI
TL;DR: The parasitic diseases of the liver and lung are caused by trematodes or flukes--Opisthorchis viverrini, O. felineus, Fasciola hepatica, and Paragonimus westermani--and the drug of choice except in falcioliaisis.

Journal ArticleDOI
TL;DR: The high biomnass of a stubterranean mammal, CGianongs badius, has not been doctumented elsewhere in Asia; this species probably influiences the forest dynamics and ecology of small carnivores in this area.
Abstract: Density and biomass of four ungulate species, elephant (Elephas maximus) and seven other mammal species were estimated in an area of about 50 km2 in a dry tropical forest in Huai Kha Khaeng Wildlife Sanctuary, western Thailand. Density estimations employed line transects, using either direct sightings or indirect signs. Total biomass of these ungulates and elephant was 1450 kg km–2 which was lower than that found in a well protected and managed area of similar forest, Nagarahole National Park, in India. This is due to the intensive poaching activity and the lack of wildlife management in this study site. Three species of ungulate, banteng (Bos javanicus), gaur (Bos gaurus) and sambar deer (Cervus unicolor), contributed over 70% of the estimated herbivore biomass. This situation is similar to that found in other parts of Asia. The high biomass of a subterranean mammal, Cannomys badius, has not been documented elsewhere in Asia; this species probably influences the forest dynamics and ecology of small carnivores in this area.

Journal ArticleDOI
TL;DR: P. insidiosum infection should be considered in thalassaemic patients with leg ulcers or arterial occlusion of the lower limbs, with periodic acid Schiff and Gomori's methenamine silver staining.
Abstract: Six thalassaemic patients had a distinct clinical syndrome characterized by progressive ischemia of the lower extremities, with ascending arteritis and thrombosis of the main arteries of the lower limbs. With periodic acid Schiff and Gomori's methenamine silver staining a large number of hyphae were revealed in the arterial wall and the outer part of the thrombus. Pythium insidiosum was isolated from 3 patients. The clinical course of the disease was progressive gangrene of the extremities and the patients invariably died when the infectious process reached the bifurcation of the aorta. There is no effective antimicrobial agent for the syndrome and radical amputation was the only method to ensure survival of the patients. P. insidiosum infection should be considered in thalassaemic patients with leg ulcers or arterial occlusion of the lower limbs.

Journal ArticleDOI
TL;DR: It is suggested that a causal relationship may exist between use of combined oral contraceptives and squamous‐cell cervical carcinoma, and women who have used these products for 4 or more years, and who most recently used them within the past 8 years, should receive high priority for cervical cytologic screening.
Abstract: Data from a hospital-based case-control study collected in 11 participating centers in 9 countries were analyzed to determine whether use of combined oral contraceptives alters risk of invasive squamous-cell cervical cancer. Information on prior use of oral contraceptives, screening for cervical cancer, and suspected risk factors for this disease were ascertained from interviews of 2361 cases and 13,644 controls. A history of smoking and anal and genital warts was obtained, and blood specimens were collected for measurement of antibodies against herpes simplex and cytomegalo viruses, from selected sub-sets of these women, as was a sexual history from interviews of husbands. The relative risk of invasive squamous-cell cervical carcinoma was estimated to be 1.31, with a 95% confidence interval that excluded one, in women who ever used combined oral contraceptives. Risk of this disease increased significantly with duration of use after 4 to 5 years from first exposure, and declined with the passage of time after cessation of use to that of non-users in about 8 years. No sources of bias or confounding were identified that offered plausible explanations for these findings. The strength of these results, and their consistency with those from other studies, suggest that a causal relationship may exist between use of combined oral contraceptives and squamous-cell cervical carcinoma. Women who have used these products for 4 or more years, and who most recently used them within the past 8 years, should receive high priority for cervical cytologic screening.

Journal ArticleDOI
15 Dec 1993-Blood
TL;DR: Protection against malaria inThalassemia is caused by both reduced parasitemias and altered adherence properties of the infected thalassemic RBCs that promote enhanced clearance of the parasite from the circulation.

Journal Article
TL;DR: Both drugs produced prolongation of the rate-corrected QT interval (QTc), with similar rates of elimination from the cardiac conduction 'effect' compartment (keo) and the slopes (change in QTc for a given change in free drug concentration) were similar (P = 0.56).
Abstract: 1. Eight healthy Thai males, aged 19-27 years, received quinine or quinidine dihydrochloride 10 mg kg-1 body weight by intravenous infusion over 1 h. At least 1 week later, the alternative alkaloid was administered. 2. The terminal elimination half-time of quinidine was shorter than that of quinine (median [range]; 5.7 [5.0-10.0] vs 9.9 [8.8-15.1] h, P 0.2). 3. Side-effects, including transient hypotension after quinidine in two cases, were mild. 4. Both drugs produced prolongation of the rate-corrected QT interval (QTc), with similar rates of elimination from the cardiac conduction 'effect' compartment (keo; 4.14 [0.03-15.33] h-1 for quinine, 3.74 [1.63-13.14] h-1 for quinidine, P > 0.19). Using a linear concentration-response model, the intercept ('threshold') for quinidine effect was lower than that for quinine (P = 0.004) but the slopes (change in QTc for a given change in free drug concentration) were similar (P = 0.56).(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: Dog bites represent 5.3% of injuries seen in the emergency room, the majority occur on the street, are inflicted by stray dogs and are interpreted by the victim as unprovoked, and children and teenagers account for 55% of the victims.

Journal Article
TL;DR: The increased binding of neutrophil and platelet to endothelial cell may explain neutropenia and thrombocytopenia in DHF patients.
Abstract: Adhesion to endothelial cells by blood cells was assessed by measuring the cell number of each blood cell component in the supernatant after exposing blood cells to dengue-infected endothelial cells for 0, 10, 20 and 30 minutes. White blood cells, neutrophils, lymphocytes, platelets, and large lymphocytes or large unstained cells (LUC) preferentially bound to dengue-infected endothelial cells as compared to the control endothelial cells. P values were 0.0096 for total leukocytes and platelets, 0.006 for lymphocytes, and 0.001 for neutrophils and LUC. Monocytes basophils and eosinophils had no interaction with dengue-infected endothelial cells. The increased binding of neutrophil and platelet to endothelial cell may explain neutropenia and thrombocytopenia in DHF patients.

Journal ArticleDOI
TL;DR: The data show that blood concentrations of the active antimalarial metabolite cycloguanil are reduced in late pregnancy and that the currently recommended dose of proguanil could be inadequate for antimalaria prophylaxis in pregnant women.
Abstract: Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery.