Biomedical subjects

D Bunnag

Publications and source records attributed to D Bunnag.

At least 73 records · Page 4Linked to original sources

PubMed1990

Mefloquine antimalarial prophylaxis in pregnancy: dose finding and pharmacokinetic study.

1. A dose finding pharmacokinetic study was performed in 20 Karen women in the third trimester of pregnancy receiving antimalarial prophylaxis with mefloquine. Ten received 250 mg mefloquine base weekly and ten received identical tablets of 125 mg base/week. 2. Both dose regimens were well tolerated. Malaria was prevented effectively, there were no serious adverse effects, all pregnancies proceeded normally, and there were no abnormalities in the babies followed up to 2 years. 3. The median time from dose administration to peak whole blood mefloquine concentration was 6 (range 3-24) h. Mean (+/- s.d.) peak and trough concentrations in the seventh week were 722 +/- 279 and 488 +/- 155 ng ml-1 with the 250 mg/week dose, and 390 +/- 81 and 185 +/- 53 ng ml-1 with the 125 mg/week dose regimens respectively. These blood concentration values are lower than those reported previously in non-pregnant adults. 4. One and two compartmental models were fitted to the whole blood concentration-time data. Mean (+/- s.d.) clearance (CL/F) was 0.78 +/- 0.27 ml min-1 kg-1, and the apparent terminal elimination half-life (t1/2) was 11.6 +/- 7.9 days. 5. Further studies to determine the oral bioavailability of mefloquine are needed, but these results suggest that clearance may be increased in late pregnancy. These preliminary results of good efficacy without significant toxicity are encouraging, and a more extensive evaluation of mefloquine antimalarial prophylaxis in pregnancy is now warranted.

Birth Weight↗

PubMed1990

Quinine resistant falciparum malaria treated with mefloquine.

Twenty eight adult male patients with acute uncomplicated falciparum malaria which showed RI or RII responses to quinine sulfate at the dosage of 600 mg 8 hourly for 7, 10 or 14 days were treated with a single dose of mefloquine (Lariam); 25 patients received 1000 mg, 2 received 750 mg and 1 received 500 mg. The initial response was good; there was no RII or RIII response. Three patients were lost to followup. Of 25 patients who stayed in the Bangkok Hospital for Tropical Diseases where there was no malaria transmission for 28-65 days, only one patient in the 1000 mg group had recrudescence on day 21. The cure rate was 96%. Our prospective study suggests that mefloquine was effective in the treatment of quinine resistant falciparum malaria and the risk of cross-resistance between quinine and mefloquine in P. falciparum in vivo is very low.

Administration, Oral↗

PubMed1990

Characterization of a monoclonal antibody that neutralizes the hyaluronidase activity of Russell's viper venom.

Three monoclonal antibodies (WPN1, WPN2 and WPN3) raised against a partially purified fraction of Russell's viper venom (RVV) were characterized. All three monoclonal antibodies reacted with crude RVV when tested by ELISA, but only two (WPN1, WPN2) neutralized its hyaluronidase activity. WPN1 was the more potent and was effective at an antigen: antibody ratio of 1:3. Furthermore, WPN1 was shown to recognize only the 14,000 MW component of crude RVV. This has been identified in a previous study to be hyaluronidase. This antibody was also found to recognize some components of Calloselasma rhodostoma venom which also possesses potent hyaluronidase activity. The potential therapeutic role of antibodies that neutralize the hyaluronidase component of snake venoms should be investigated further.

Antibodies, Monoclonal↗

PubMed1990

Fecal egg output in relation to worm burden and clinical features in human opisthorchiasis.

A study of the relation of fecal egg excretion to worm burden and clinical features was carried out in 45 opisthorchiasis patients who had no signs of biliary obstruction. The fecal egg excretion was consistent and correlated with the worm burden. Although there was no definite association between clinical signs and intensity of infection, mild hepatomegaly and thickened wall or dilatation of the gallbladder were found more commonly in heavily infected patients. Eosinophilia was observed more often than previous reports. Concomitant parasitic infections were found in 82% of the patients. After praziquantel treatment, egg counts increased greatly during the first few days then decreased to very low levels in 7 days.

Adolescent↗

PubMed1990

Pharmacokinetics of mefloquine in combination with sulfadoxine-pyrimethamine and primaquine in male Thai patients with falciparum malaria.

The pharmacokinetics of mefloquine (M) were studied in 59 male Thai patients with falciparum malaria. Mefloquine was administered alone (750 mg orally; group 1), or with primaquine (PQ, 45 mg; group 2), or in combination with sulfadoxine (1.5 g) + pyrimethamine (75 mg) (MSP; group 3), or as MSP + PQ (group 4). All patients in groups 1, 2 and 4 initially responded to treatment, but two patients from group 1 had RI recrudescent infections. One patient in group 3 failed to respond to treatment and was considered to have RII resistance, while a further patient from this group had RI recrudescence. The pharmacokinetic parameters for group 1 and group 3 were not significantly different. Co-administration of primaquine alone had no significant effect on the pharmacokinetics of mefloquine, but there was a statistically significant decrease in the terminal elimination half-life of mefloquine for group 4 relative to that for group 3.

Adolescent↗

PubMed1989

Electron microscopic study of phagocytosis in human spleen in falciparum malaria.

The ultrastructure of the spleen of a patient who died of natural infection of Plasmodium falciparum was studied with emphasis on phagocytosis. Parasitized erythrocytes were shown to interact with the heterogenous populations of phagocytic cells. Phagocytosis occurred predominantly in macrophages than endothelial cells and immature forms of parasites were preferentially phagocytosed. Splenic trapping, pitting and destruction of both infected and noninfected erythrocytes were demonstrated. Other forms of interaction between phagocytic cells and parasitized erythrocytes observed include complex interdigitation, association of loose and tight phagosomes, and preferential sites of adherence, the significance of which need further investigation.

Adolescent↗

PubMed1989

Development of in vitro microtest for the assessment of Plasmodium vivax sensitivity to chloroquine.

An in vitro microtest to assess P. vivax sensitivity to chloroquine has been developed using a medium mixture which contained RPMI, Waymouth (GIBCO) and 15% (vol/vol) human serum group AB. The rate of success was highest in samples which were not washed by centrifugation before culturing in microtest plates predosed with varying concentrations of chloroquine. Evaluation of the effective concentration of chloroquine using a program for probit analysis of log dose/response test proved superior to simply using the percentage of schizont maturation.

Adolescent↗

PubMed1989

The optimum dose of Puag-Haad in the treatment of taeniasis.

Forty-two per cent of 24 patients with Taeniasis saginata were cured by two-gram dose of a crude aqueous extract of the wood Artocarpus lakoocha, Puag-Haad, while eighty per cent of 25 patients were cured by three-gram dose which is comparable to the results of five-gram dose but had less side-effect. Thus, the three-gram dose of Puag-Haad is recommended in the treatment of taeniasis.

Adult↗

PubMed1989

A new intestinal fluke, Plagiorchis harinasutai n.sp.

Dilution-sedimentation examination of stool specimens from four opisthorchiasis patients treated with praziquantel led to the discovery of six Plagiorchis worms. This is the first known report of plagiorchis infection in man in Thailand. The morphological features differed from those of previously described Plagiorchis species indicating that these worms belong to a new species, which we designated as Plagiorchis harinasutai n.sp. in honour of Professor Chamlong Harinasuta, former Dean of the Faculty of Tropical Medicine, Mahidol University, Bangkok. The holotype is held at the Museum and Reference Centre. Paratypes are held in the Bangkok School of Tropical Medicine, Faculty of Tropical Medicine, Mahidol University.

Adult↗

PubMed1989

Determination of quinine and quinidine in biological fluids by high performance liquid chromatography.

A simple, specific, rapid and sensitive High Performance Liquid Chromatography (HPLC) method has been developed to measure plasma level of quinine and quinidine. The drugs were extracted successively from plasma at basic pH with chloroform and quantified on a revers-phase Z-module C18 HPLC column with fluorescence detector (excitation 340 nm, emission 425 nm). The isocratic mobile phase used was the mixture of 0.05 M ammonium formate and acetonitrile (93.5:6.5, v/v), adjusted pH to 2.0 with ortho-phosphoric acid. The limits of quantitation for these compounds were as low as 4 ng/ml of plasma, using a 0.25 ml specimen. Calibration curves were linear (R squared = 0.9994) in the range 0-7,000 ng/ml. An interassay reproducibility was 6.8%, 0.3% and 1.2% at the concentrations of 250 ng, 4,000 ng and 8,000 ng of quinine, respectively. Inter-assay coefficient of variation of quinidine was 1.8%, 2.7% and 3.7% at the concentrations of 250 ng, 1,500 ng and 3,000 ng, respectively. Recovery of quinine and quinidine were 76% and 81%, respectively. The method has been used in the analysis of quinine and quinidine in healthy volunteers receiving quinine or quinidine intravenously. The method is now being used to assay samples from field studies with satisfactory results.

Chromatography, High Pressure Liquid↗

PubMed1989

Human pathology of Opisthorchis viverrini infection: a comparison of adults and children.

The pathology of human opisthorchiasis in 22 adults (20 to 68 years) and 7 children (7 to 15 years) at autopsy is described. The changes of the liver in adults and children are similar and are summarized as follows: Enlargement of the liver was a common finding. Pericholangitis was observed in most cases. The pathology was confined to the large and medium-sized bile ducts where the flukes inhabited. The small interlobular bile ducts had minimal or unremarkable changes. Dilatation of the bile ducts with hyperplasia, desquamation and proliferation of the bile duct epithelial cells, glandular formation and fibrous connective tissue infiltration of the walls were the most common features. The pathological changes were well established within 7 to 15 years. Dilatation of the gallbladder, chronic cholecystitis and carcinoma were found only in adults. Eight of ten cases were cholangiocarcinoma and two were hepatocellular carcinoma.

Adolescent↗

PubMed1989

Determination of mefloquine in biological fluids using high performance liquid chromatography.

A simple, specific and sensitive High Performance Liquid Chromatography (HPLC) method for determination of whole blood of mefloquine has been developed. WR 184806 was used as internal standard, using a two step extraction procedure followed by revers phase HPLC. Acetonitrile and dichloromethane were used as extraction solvents. Octanesulphonic acid was used as an ionpairing reagent. Detection of extracted mefloquine and internal standard was achieved at 222 nm. Calibration curves for mefloquine in whole blood showed linearity with correlation coefficients of 0.9999. The limitation of detection using a 1 ml sample was 50 ng/ml. Recovery of mefloquine varied from 61% to 81%. Due to the very similar behavior of the internal standard during extraction, changes in recovery are of minor importance. Good accuracy and precision were obtained (intra-assay coefficient of variation ranged between 1.8% and 5%; inter-assay coefficient of variation were less than 10% at 100 ng/ml and less than 6% at 1,000 ng/ml). The assay employs a rapid and simple two-step extraction which requires a small sample volume. The low limit of detection of mefloquine and the short retention time make the method suitable for routine analysis of mefloquine.

Antimalarials↗

PubMed1988

A comparison of the pharmacokinetics of mefloquine in healthy Thai volunteers and in Thai patients with falciparum malaria.

We have studied the kinetics of a single oral dose of mefloquine (750 mg) in 12 Thai patients with falciparum malaria and have compared the results with those of a previous study in 12 healthy Thai volunteers. All the patients responded to treatment with a mean parasite clearance time of 66.6 h and a mean fever clearance time of 54.1 h. There was no significant difference in peak plasma concentration, time to peak, area under the curve or apparent volume of distribution between patients and controls. However, the terminal half-life (t1/2) and mean residence time (MRT) were shorter in the patients (12.2 vs 16.7 days for t1/2 and 15.5 vs 21.4 days for MRT). We conclude that there are changes in the disposition of mefloquine related to malaria, although the exact basis of the changes is not clear.

Adolescent↗

PubMed1988

The hyaluronidase activities of some Southeast Asian snake venoms.

The hyaluronidase activities of venoms of snakes indigenous to Southeast Asia were investigated. With the exception of the venom of the Malayan krait Bungarus candidus, the elapid venoms had either little or no hyaluronidase activities, whereas the viperid venoms possessed considerable activity. A component of Russell's viper venom with hyaluronidase activities had a mol. wt of approximately 14,000. Neither MP4, a monoclonal antibody raised against the purified Russell's viper venom hyaluronidase toxin, nor a monospecific polyclonal antivenom neutralized the hyaluronidase activities of this purified hyaluronidase component of crude Russell's viper venom. The Russell's viper venom hyaluronidase activities was labile on heating and storage. The significance of these observations to envenomation and antivenom production is discussed.

Animals↗

PubMed1988

Analysis of Opisthorchis viverrini antigens by immunoprecipitation and polyacrylamide gel electrophoresis.

Antigenicity of adult Opisthorchis viverrini, metacercariae and eggs was investigated by radio-immunoprecipitation and polyacrylamide gel electrophoresis using sera from patients with opisthorchiasis and from hamsters experimentally infected with O. viverrini metacercariae. 125I-labelled aqueous somatic extract and in vitro metabolic products of adult worms, and the extracts of metacercariae and eggs were immunoprecipitated, electrophoresed and autoradiographed and major antigens were characterized. Although components with Mr of greater than 116, 89, 78 and 20 kD appeared to be specifically associated with the somatic extract of adult fluke, the 89 kD protein was the most prominent component found in the in vitro culture fluid of adult worms and the metacercarial extract. Hamsters, experimentally infected with O. viverrini, also showed the presence of antibody reactive with the 89 kD component within 15 days of infection. The potential of this antigen in immunodiagnosis is discussed.

Animals↗

PubMed1988

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

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.

Animals↗

PubMed1988

Detection of antibodies against Opisthorchis viverrini in patients before and after treatment with praziquantel.

Levels of antibody in sera of 78 patients with opisthorchiasis, 30 patients with other liver diseases, 10 patients with schistosomiasis and 30 healthy individuals were compared using three serodiagnostic tests, namely indirect haemagglutination (IHA), enzyme-linked immunosorbent assay (ELISA) and lectin immuno test (LIT). The geometric mean reciprocal titer in sera of opisthorchiasis patients was significantly higher than patients with other diseases, patients with schistosomiasis and healthy individuals (p less than 0.00001). After treatment with praziquantel, the antibody titers were decreased and became lowest 120 days after treatment. A statistically significant decrease from the pre-treatment sample was observed only at 120 days after infection and not earlier and only with ELISA (p = 0.03) and not with IHA and LIT (p greater than 0.05). Even with ELISA, significant decrease in antibody titer was apparent only when the pre-treatment sera had high enough antibody titer. ELISA was therefore better than the other two tests for the assessment of cure provided that the titer of pre-treatment sera was high.

Animals↗

PubMed1988

Incidence of bacteremia in patients with opisthorchiasis during recurrent cholangitis.

A total of 257 haemocultures were performed in 50 patients with opisthorchiasis when they presented signs and symptoms of biliary tract infection. 19 patients showed positive haemoculture. There are no significant relationship between the age of the patient and the incidence of positive haemoculture. Septic shock occurred in 5 patients, one patient died. Out of 221 aerobic cultures, 14% were positive and of the 36 anaerobic cultures 11% were positive. The most common organism was Staphylococcus followed by Klebsiella and Bacillus spp. Anaerobic bacterias were Streptococcus spp. Clostridia spp. was not found in this study. Most organisms were sensitive to cefotaxime, cephalothin, kanamycin and chloramphenicol, and the least sensitive to ampicillin.

Adult↗