Showing papers by "Mahidol University published in 1988"

Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations.

Abstract: Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. Chloroquine was rapidly absorbed after either intramuscular or subcutaneous administration (5 mg of base per kilogram every 12 hours), producing high peak blood concentrations but transient hypotension in 5 of 18 patients (28 percent). Intermittent intravenous infusion (5 mg of base per kilogram over 4 hours, repeated every 12 hours) also produced wide fluctuations in chloroquine levels, suggesting incomplete distribution from a small central compartment. Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.

Bioethics in Thailand: The Struggle for Buddhist Solutions

Abstract: The Thai concern for bioethics has been stimulated by the departure of Thai medicine from its long tradition through the introduction of Western medical models. Bioethics is now being taught to Thai medical students emphasizing moral insights and principles found within Thai culture. These are to a large extent Buddhist themes. Veracity is always a duty for people in general and medical personnel in particular. Falsehoods and deception cannot be morally justified simply on the grounds that we think it is good for another. Buddhism also prohibits killing. The doctrine of kamma holds that joys and sorrows are the result of one's own past actions. Kamma must run its course or will be manifest in a future life. Mercy-killing also violates the Buddhist psychology. A physician who kills subconsciously transfers his aversion to suffering to the one who embodies the suffering. Buddhist justice is understood in terms of impartiality and equal treatment. Compassion goes beyond justice to self-giving and self-denial. It is central to the path to the attainment of highest human fulfillment.

Defective production of and response to IL-2 in acute human falciparum malaria.

Abstract: Patients with acute Plasmodium falciparum malaria have defective cell-mediated immune responses to malaria-specific Ag (MA). This immunologic defect may partially explain the difficulty with which natural immunity to falciparum malaria develops and may have important implications for the efficacy of potential malaria vaccines in endemic areas. To investigate the basis of this immune defect, we have examined the capacity of PBMC from patients with acute falciparum malaria to produce IL-2 and to express I1-2R in response to Ag stimulation. The effect of exogenous IL-1 and IL-2 on lymphocyte proliferation was studied. Soluble IL-2R levels were measured in acute and convalescent sera. Our results showed that no detectable IL-2 was produced and no IL-2R were expressed by PBMC in response to MA during the acute infection. IL-2 production and IL-2R expression were also depressed when PBMC were exposed to streptococcal Ag. The specific immune defect was not reconstituted by the addition of graded doses of purified human IL-1 or IL-2 and could not be attributed to suppressor adherent cells. In contrast to the absence of IL-2 and cell-bound IL-2R, circulating soluble IL-2R was elevated in acute sera. These findings suggest that the lack of IL-2, through either a defect in its production or inhibition of its activity, may be the basis of the Ag-specific immune unresponsiveness in acute P. falciparum malaria.

Drug treatment and prevention of malaria.

Abstract: Recommendations for the treatment and prevention of malaria vary considerably. There are two reasons for this: first, many recommendations are empirical, or based on studies performed before the development of modem techniques of drug measurement and modem concepts of pharmacokinetics; second, falciparum malaria has rapidly developed alarming resistance to the antimalarial drugs. Recent studies of the pharmacokinetic properties of the antimalarial drugs (reviewed by White 1985) have led to changes in recommendations for treatment, partictdarly in severe infections. The revised recommendations attempt to improve efficacy and reduce toxicity by providing blood concentration profiles that rapidly reach concentrations considered to be efficacious, do not \"overshoot\" into the toxic range, and maintain these concentrations during the acute phase of the disease. However, more information is needed on the relationship between plasma (or whole blood) concentrations and the response to antimalarial treatment, so that the ratio of toxicity risk to therapeutic benefit can be optimized. Advice on antimalarial prophylaxis remains confused. The demise of chloroquine in ever larger areas of the tropics has produced a void in the prophylactic armamentarium. There is no simple alternative, and there is consequently considerable variation in the advice given to travellers visiting areas endemic for drug-resistant falciparum malaria. The Cinchona Alkaloids

Utilization of [U-14C]Fructooligosaccharides in Man as Energy Resources

Abstract: Utilization of fructooligosaccharides, 1F-(β-fructofuranosyl)n-1-sucrose, which are not digestible in the small intestine but are fermentable by intestinal microorganisms in man, was investigated by a radiorespirometric study and an anaerobic incubation of [U-14C]fructooligosaccharides with feces.About 49% and 55% of the administered radioactivity were detected in expired 14CO2 after 24 and 48h, respectively.In the anaerobic incubation, the saccharides were catabolized to 14CO2 (9.6%), microbial cell constituents (10.4%), and 14C-volatile fatty acid (acetic acid, 24.1%; propionic acid, 20.2%; butyric acid, 11.4% and valeric acid, 2.2%).Complemental interpretation of the two studies allowed quantitation of the catabolic pathway of fructooligosaccharides in man, and utilization of the oligosaccharides was estimated to be 1.5kcal/g.

Common features of Bacillus thuringiensis toxins specific for Diptera and Lepidoptera.

Abstract: The complete nucleotide sequence of a cloned gene encoding a 130-kDa crystal protein of Bacillus thuringiensis (B.t.) subspecies israelensis has been determined. The recombinant protein (Bt8) was purified and shown to be a mosquito-specific toxin with a LC50 value of 43 ng/ml to third-instar larvae of Aedes aegypti. Bt8 is processed by proteases or midgut extracts of mosquito larvae into toxic fragments of 68-78 kDa. Deletion mapping indicated that the active fragment of Bt8 is localized in the N-terminal half of the protoxin molecule. The deduced amino acid sequence of Bt8 has been compared with that of Bt2, a Lepidoptera-specific toxin, previously cloned from Bacillus thuringiensis berliner. Highly homologous amino acid stretches are present in the C-terminal half of the proteins. The N-terminal parts show much less sequence homology but they display a strikingly similar distribution of hydrophilic and hydrophobic amino acids. In addition, Bt8 and Bt2 show a significant immunological cross-reaction. The data indicate that although these B.t. delta endotoxins exhibit a different insect-host specificity, they are structurally related and might use a similar mechanism to interact with insect cell membranes.

Factors contributing to fatal snake bite in the rural tropics: analysis of 46 cases in Thailand

Abstract: Records of 46 cases of fatal bites by identified snakes from 15 provincial hospitals throughout Thailand contained sufficient information for detailed analysis. Bungarus Candidus and Calloselasma rhodostoma were each responsible for 13 deaths, Naja kaouthia for 12, Vipera russelli for 7 and B. fasciatus for one. Major causes of death among elapid victims were respiratory failure (26) and complications of prolonged mechanical ventilation (10), and among viper victims shock (12), intracranial haemorrhage (9), complications of local wound necrosis (7) including tetanus (2), and renal failure (2). Factors contributing to fatal outcome included inadequate dose of antiyenom (15 cases), misidentification of the snake leading to use of the wrong antivenom (12), problems associated with mechanical ventilation (10), and delayed arrival in hospital after traditional (herbal) treatment (10). Similar problems have been identified in other tropical countries. Education of medical staff and the patient population at highest risk could reduce snake bite mortality.

Foods as a source of enteropathogens causing childhood diarrhea in Thailand.

Abstract: Foods obtained in markets in Bangkok were cultured for bacterial enteric pathogens and examined for their similarity to strains isolated from children under 5 years of age in Bangkok in 1986. Salmonella was isolated from 17%, Campylobacter from 12%, and enterotoxigenic Escherichia coli (ETEC) from 3% of 510 foods examined. Campylobacter was isolated from 13.5%, ETEC from 13%, and Salmonella from 12% of 1,230 children under 5 years of age with diarrhea. Eighty-eight percent of children infected with Salmonella were infected with serotypes isolated from foods of animal origin. Six percent of children with Salmonella were infected with the same serotype containing plasmids with identical endonuclease restriction patterns as isolates from food. Eighty-seven percent of children with Campylobacter were infected with the same serotypes and biotypes found in food of animal origin. Thirty-one percent of heat-labile enterotoxin (LT) producing ETEC from foods containing genes coding for LT II, but LT II ETEC was not isolated from children. Twenty-one percent of ETEC isolated from foods vs. 53% isolated from children were resistant to 2 or more antibiotics (P less than 0.01). Salmonella and Campylobacter, but not ETEC, isolated from foods were similar to strains isolated from children. Foods of animal origin are an important source of Salmonella and Campylobacter in Thailand.

Deep vein thrombosis after hip surgery among Thai.

Abstract: • A pilot study was done during April 1984 through June 1986 to determine the incidence of postoperative deep vein thrombosis (DVT) among 50 Thai patients who underwent hip surgery, which mainly consisted of total hip replacement (19 patients) and repair of hip fracture (29 patients). Most patients were in the sixth to seventh decade of life, and the male-to-female ratio was 32:18. Most patients were of normal or low weight, few had known risk factors for DVT, and all but three had general anesthesia. Venography performed on the operated on legs on the seventh to tenth postoperative days showed that only two patients had DVT, one in the calf and another in the calf and thigh veins. The low incidence of DVT in the Thai population even after such extensive surgery, which is associated with a high (40% to 70%) frequency of DVT in the Western world, suggests that routine prophylactic anticoagulant measures are not presently needed in this country. ( Arch Intern Med 1988;148:1349-1353)

Characterization of humoral immune response in the serum and bile of patients with opisthorchiasis and its application in immunodiagnosis.

Abstract: The humoral immune response in patients with opisthorchiasis was investigated using an enzyme-linked immunosorbent assay. IgG antibody reactive with Opisthorchis viverrini antigens was present in the serum of all patients. The infection also stimulated specific IgA and IgE antibody responses in most patients and, in practically all patients, there was a marked increase of total IgE. There was a moderate but significant correlation between serum IgG antibody level and severity of infection as judged from the quantity of eggs in the stool of the patients. There was also a significant elevation of antibody in the bile and serum of O. viverrini-infected patients who also had biliary obstruction. Analysis of paired samples from individual patients showed that while IgG was the predominant class of antibody in the serum of all patients, IgA was present at approximately the same level as IgG or higher in the bile of many patients. In addition to IgA and IgG antibodies, IgE antibody was also detectable in 50% of the bile samples. The high level of IgA antibody in the bile together with its presence in association with the secretory component suggested a selective transport and/or local production of IgA antibody by the hepatobiliary system of these patients.

Geographic distribution and biting behaviour of four species of the anopheles dirus complex . (diptera : culicidae) in thailand

Abstract: A cytogenetic analysis of the species status of members of the Anopheles dirus group, from natural populations, over a six-year period has produced biogeographic and behavioural data which are presented herein. Species A, B, C and D have quite distinct geographic distributions in Thailand. Species A is the only species in most of the mainland but is absent from the southern half of the peninsula. Species B is dominant in the far south of the peninsula giving way to species C on the north-east side and rarely occurring on the west side of the peninsula; it is unknown from the northern half or the rest of the country. Species C is known from the middle eastern side of the peninsula and from a site far to the north along the Burmese border. Species D occurs down the mountains along the Burmese/Thai border and along the north half of the western peninsula. Each species appears to have distinct times of biting during the night. They also appear to have differential seasonal abundance. These data together with the differing geographic distributions suggest some implications for Plasmodium transmission and that care should be taken to identify these genetic species during malariometric studies.

Impaired parasite growth and increased susceptibility to phagocytosis of Plasmodium falciparum infected alpha-thalassemia or hemoglobin Constant Spring red blood cells.

Abstract: In vitro multiplication of Plasmodium falciparum in hemoglobin H or hemoglobin Constant Spring red blood cells (from homozygotes or double heterozygotes) was significantly reduced as compared with that in normal erythrocytes. The parasitized genetically abnormal red blood cells showed further-more a high propensity for being phagocytosed by peripheral blood monocytes. Both impaired parasite growth and increased susceptibility to phagocytosis may be related to mechanisms for protection of the variants from P. falciparum infection.

Predictors for extraintestinal infection in Salmonella enteritis in Thailand

Abstract: To identify the risks and predictors for extraintestinal Salmonella infection (ETI) in infants and children with nontyphoidal Salmonella enteritis, we performed a retrospective review of 326 infants and children with diarrhea and rectal swab cultures positive for nontyphoidal Salmonella enteritis seen at Ramathibodi Hospital between 1981 and 1983 Nineteen patients had bacteremia The overall rate of bacteremia was 58% which was 243% of those having blood cultures taken Salmonella typhimurium was the most common cause of ETI and the most invasive among the common serotypes causing enteritis The clinical characteristics of the patients with high probabilities of having ETI were: younger than 6 months of age; high body temperature; and immunocompromising conditions The observed frequency of ETI in these patients was 219 to 263% compared with 0 to 07% in patients without those risk factors

Population genetic studies on the Anopheles minimus complex in Thailand.

Abstract: The population genetic studies on the Anopheles minimus complex revealed that An. minimus is a species complex evident by IK value were less than 0.0534 and 0.4163 for the morphotaxonomy and isozyme studies. There are two sibling species in the An. minimus species complex. The first is the typical minimus and its variations described by Harrison. Esterase-2 alleles 100 and 102 are predominant with a few other alleles of 96 and 104. It is exophagic and zoophilic. It is widely distributed in all provinces where minimus breeds. The second of the two sibling species is An. minimus species C, with 2 pale spots on the humeral dark band and Est-2 allele 98. It is found most frequently in Pu Toei District of Kanchanaburi Province, Thailand. An. minimus probably species B showing M1 + 2 wing vein entirely dark is found in China.

Nasopharyngeal carcinoma: result of treatment with cis-diamminedichloroplatinum II, 5 fluorouracil, and radiation therapy.

Abstract: Combined CT (CDDP + 5FU) and RT were given to 28 patients with NPC during July 1982–May 1985. Two, 1, 4, and 21 were in Stages I–IV (AJC), respectively. None had distant metastasis. Four did not complete the planned treatment, and one each had more or fewer CT courses than planned. The median duration of follow-up of surviving patients was 29 months (19–52, x 31.1). Objective response (CR + PR) at the primary lesion was 2728 (96.4%), whereas CR was 2328 (82%). CR + PR and CR of the regional nodes were 2122 (95.5%) and 1822 (82%) respectively. Remaining node in the 2 patients, who did not prematurely die were pathologically negative. Response at N site should therefore be 100% CR. Only patients with T 3 (15) and T 4 (313) lesions had residual disease at the T site after initial treatment. Salvage therapy was able to induce CR in all asymptomatic PR patients. There were 4 relapses, 2 at T, and 1 each at T+N and T+M sites. All M disease occurred in patients with huge and/or low cervical lymphadenopathy. Five patients died, one of an unrelated disease, and one each of T, M, T+N, and T+M diseases. The remaining 23 patients were still alive, and all except 3 were free of disease. Side effects, mainly from RT, were clinically acceptable. One had transient cervical myelitis. Myelosuppression was mild and of short duration. Activity of CT was seen at both T, and N sites after the upfront CT. Compared to our previous experience using RT alone, the result of this study suggested a positive role of CT in this disease. However, future prospective randomized trials are required to better define its role.

Living Arrangements and Family Formation

Abstract: Interviews were conducted in Thailand with 1679 ever-married women aged less than 45 and 994 of their husbands who were available to examine the relationships between household structure and family formation in a country where postnuptial residence expectations vary by ethnicity and residence. Strength of the relationship depends on the institutional context which defines parental roles and stakes in the marital choice and fertility behavior of their children. It is shown that postnuptial residence has been conceptualized far too simplistically: husband and wife often live apart after marriage and this pattern has been quite common for some time in Thailand. Marriage should not be used as a proxy for sexual relations the start of a permanent relationship coresidence or any of the other conventional marital functions. If investigators are interested in these dimensions of marriage they should collect information on them directly.

Population cytogenetics of the malaria vector Anopheles leucosphyrus group.

Abstract: Until recently, very little was known of Anopheles species complexes and their relationships to epidemiology and malaria transmission in Southeast Asia. During the past eight years, extensive studies on the genetics of natural populations of anopheline mosquitoes in this region, involving the interdisciplinary efforts of taxonomists, operational entomologists and biologists, have revealed groups of cryptic species of Anopheles vectors, particularly the An. leucos phyrus group. This species group comprise seventeen species and two subspecies widely distributed in the forested areas of Southeast Asia. Among these species. An. dirus Peyton and Harrison, has been shown by cytogenetic and morphological studies to be a complex of at least seven isomorphic species, provisionally designated species A, B, C, D, E, F and takasagoensis, on the Southeast Asian mainland. Cytological identification of these species is based on distinct banding patterns of salivary gland polytene chromosomes as well as heterochromatin differences in mitotic karyotypes. The five species found in Thailand (A-D, F) exhibit distinct geographic distributions. Species A is widespread throughout Thailand except in the south. Species B had been found in sympatry with species C in southern Thailand and both seem to show north-south clinal geographic variation. Species D is common on the west side of southern Thailand and along the Thai-Burmese border in sympatry with species A. Species F, An. nemophilous Peyton and Ramalingam, has been found in a population at the Thai-Malaysian border in this study although it was known to be common in southern and western Thailand and Peninsular Malaysia. Species E is known only from western India. The five species found in Thailand also exhibit seasonal variation in relative abundance and different nocturnal biting cycles. Chromosomal polymorphisms have been observed in mitotic and polytene chromosomes of An. dirus A and D. Species B and C also show heterochromatin variation in the sex chromosomes, but are monomorphic for the standard sequence in polytene chromosomes. These biological characteristics of the An. dirus complex may have implications for understanding the epidemiology of malaria in Southeast Asia. Recent cytogenetic studies of wild-caught samples of An. leucosphyrus from Sumatra, Kalimantan and southern Thailand have revealed the presence of two distinct species within this taxon. Species A is widely distributed in southern Thailand, East Malaysia and Kalimantan, while species B is confined to Sumatra. The two isomorphic species are vectors of human malaria within their range of distribution.(ABSTRACT TRUNCATED AT 400 WORDS)

Beta-thalassemia associated with alpha-thalassemia in Thailand.

Abstract: In Thailand alpha-thalassemia (thal), beta-thal, hemoglobin (Hb) E and Hb Constant Spring (Hb CS) are prevalent. The incidences are 20-30% for alpha-thal (3.5% for alpha-thal-1 and 16% for alpha-thal-2), 3-9% for beta-thal, up to 54% for Hb E and nearly 8% for Hb CS. Different combinations of these genes result in a spectrum of thalassemia syndromes ranging in severity from asymptomatic to intrauterine death. From the known gene frequencies the numbers of thalassemic patients per generation (total population of 50 million) are as follows: Hb Bart's hydrops fetalis 20,000; homozygous beta-thal 31,250; beta-thal/Hb E disease 162,500; Hb H disease (two genotypes) 200,000, making a total of 413,750. In addition, individuals may carry more than two of the abnormal genes leading to complex thalassemia syndromes such as alpha beta-thal, AE-Bart's and EF-Bart's diseases.

Detection with monoclonal antibody of Salmonella typhi antigen 9 in specimens from patients.

Abstract: Monoclonal antibodies were raised against Barber antigen (Ba) of Salmonella typhi 0901. Antibodies produced to antigen 9 of group D salmonellae were used in double- and triple-sandwich antibody enzyme-linked immunosorbent assays (ELISAs) for detecting antigen 9 in urine and plasma specimens from three groups of patients and 49 controls. The triple-antibody ELISA detected the antigen in urine samples from 11 of 18 (65%) patients with hemoculture-proven typhoid (group 1) and 12 of 39 (31%) patients with clinical features compatible with typhoid but whose hemocultures were negative (group 2). This ELISA was negative in three patients from whom Salmonella paratyphi A, Escherichia coli, and Klebsiella pneumoniae (group 3) were isolated by hemoculture and in all healthy controls. The double-antibody sandwich ELISA was positive in 41 and 15% of urine samples from patients in groups 1 and 2, respectively, and was negative with samples from two patients from group 3 and all controls. The sensitivity and specificity compared with those for healthy controls were 65 and 100%, respectively, for the triple-antibody ELISA. Although as little as 7.8 ng of homologous lipopolysaccharide could be detected, background in clinical specimens prevented accurate interpretation of the detection of this antigen in serum. Results were best with urine specimens. Images

Orientability of Crosslinked and of Chiral Liquid Crystalline Polymers

Abstract: Crosslinked liquid crystalline (l.c.) polymers can be reversibly oriented in the l.c. phase by small mechanical strains. This property makes it very interesting to investigate chiral l.c. phases with a helical superstructure (cholesteric and chiral smectic C*). These phases can e.g. be realized with new combined main chain / side group polymers. In order to give a high spontaneous polarization to the polymers in the chiral smectic C* phase, polymers with a dipole moment at the chiral center were synthesized.

Bionomics of Anopheles minimus and its role in malaria transmission in Thailand.

Abstract: The bionomics of Anopheles minimus, one of the main malaria vectors in Thailand, were conducted in Pakchong district, Nakhon Ratchasima province, from January 1984 to June 1985. The prevalence of An. minimus was influenced by monthly rainfall, relative humidity, temperature and wind velocity, with a major peak of density from September to November. An. minimus preferred to feed on animal rather than on human, tended to bite human more outdoors than indoors, and thus exhibiting zoophilic and exophilic behaviour. The biting activity of the mosquitoes on animal exhibited high densities throughout the night in all seasons, whereas on human they tended to be an early evening biter in the dry cool season, and early morning biter in the wet season, and thus increasing the chance of man-vector contact. The life expectancy of An. minimus varied from month to month, ranging from 2.7 to 11.5 days, with the longest longevity during the dry cool season. The natural malaria infection rate of this species was very low. Out of 1,518 dissected guts, only 0.4% were found infected with oocysts. There were no sporozoites detected in the 1,560 dissected salivary glands.

Identification of isomorphic malaria vectors using a DNA probe.

Abstract: About 7,000 recombinant clones, derived from chromosomally-identified families of wild-caught females of Anopheles dirus species D, were screened. The most promising clone was totally specific to species D when tested against single F1 females of all four species of the complex. In fresh specimens the clone was positive for DNA levels 150 times less than the normal DNA content of single individuals. Fresh adult males and females, larvae, and dried specimens have been successfully identified. The clone was sequenced; it is 124 bp long and appears to be repeated in the genome about 1.8 x 10(4) times.