PubMed Health⌕ Search

Biomedical subjects

D Bunnag

Publications and source records attributed to D Bunnag.

At least 127 records · Page 7Linked to original sources

Evaluation of selected anthelmintic compounds for activity against Opisthorchis viverrini.

In vitro and in vivo experiments were employed in the screening of potential anthelmintic agents against Opisthorchis viverrini infection in hamsters. A few selected groups of compounds tested included those that are commercially available as well as those that are still being tested by various pharmaceutical firms. The compounds tested in the present study were praziquantel, amoscanate, albendazole, flubendazole, metrifonate, metronidazole and benzodiazepine derivatives. Results from both in vitro and in vivo experiments showed that at the dosages employed, praziquantel was the only one that gave complete cure, as judged from faecal egg examination and worm recovery at the time of sacrifice. It was therapeutically effective against different developmental stages of O. viverrini including the metacercariae. Moreover, the drug was also effective as a chemoprophylactic agent when given 6 to 12 hr prior to being exposed to infective metacercariae. Other compounds tested were considerably less active although some might have permanently damaged the fluke reproductive capacity, while others were able to suppress egg-laying capacity only temporarily. Together, results suggests that the ineffectiveness of most agents tested in this study is not related to their inability to attain concentrations high enough to kill or damage the flukes in the biliary system but is most likely due the inherent lack of capacity to kill the flukes.

Albendazole↗

Opisthorchis viverrini infection: pathogenesis and clinical features.

The pathological changes are more or less related to the intensity and the duration of the infection, and are commonly seen in older patients with a large number of flukes. The pathogenesis is due to the mechanical irritation by the flukes and some toxic substances produced by them. Lesions are mainly confined to the biliary system. There is hyperplasia of the epithelial cells lining the bile ducts. In heavy and severe infections there are obstruction of the biliary tract, bile retention, extensive hyperplasia of the biliary system, with glandular proliferation of papillomatous and adenomatous type, cholangitis, periductal infiltration with eosinophils, round cells and fibrosis in the portal areas, necrosis and atrophy of hepatic cells. The bile ducts are dilated and in late cases saccular or cystic formations may develop into large cysts. The gallbladder may enlarge and contain white bile. The liver profile is generally normal. The majority of cases are symptomless. Clinical features vary from mild to severe. The symptoms and signs are vague gastro-intestinal symptoms, flatulence, anorexia, lassitude, weight loss, dull pain at the right hypochondrium, hot cutaneous sensation of the abdomen, and enlargement of the liver with some tenderness. In few cases the manifestations are severe. There is relapsing cholangitis, the patient is seriously ill and may succumb to septic shock. Cholangiocarcinoma, gallstones and obstructive jaundice are not unusual associations.

Bile Ducts↗

Opisthorchis viverrini: clinical experience with praziquantel in Hospital for Tropical Diseases.

Praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]++ +isoquinolin- 4-one, EMBAY 8440, Biltricide) has been used in 4853 patients with Opisthorchis viverrini infection. 786 patients were treated as inpatients with extensive clinical evaluation and the rest were out-patients. A cure rate (evaluated with 5 faecal samples) of 100% was obtained in groups given 6 X 25 mg/kg on 2 days and 3 X 25 mg/kg on 1 day, while in groups given 2 X 25 mg/kg, 1 X 25 mg/kg and 1 X 40 mg/kg all on 1 day the cure rates were 88, 44 and 91%, respectively. With one sample evaluation the parasitological cure rate was 96% in further 96 patients excreting the geometric mean (GM) of 5394 eggs per gram (EPG) and receiving 1 X 40 mg/kg. Another 68 patients with an egg output of 26044 (GM/EPG) and treated with 1 X 50 mg/kg showed a cure rate of 97% by similar evaluation. Side effects were mild and transient and were more frequent in higher dosage groups. They included anorexia, nausea, vomiting, abdominal pain, epigastric pain, rumbling in the abdomen, diarrhoea, lassitude, myalgia, headache, dizziness, sleeplessness, sleepiness, "hot sensation", shortness of breath, and skin rash in a few cases. Headache (30.7%) was most common in the 6 X 25 mg/kg group. In 53 patients with severe jaundice the side effects were similar. There was no evidence of toxicity. Remarkable was one patient treated with 1 X 50 mg/kg who expelled 5636 O. viverrini worms, most of which were elongated and damaged. When a single dose is prescribed it should be given at bed time to reduce the side effect of sedation.

Adult↗

Roentgenographically controlled healing of gallbladder lesions in opisthorchiasis after praziquantel treatment.

In a study, gallbladder lesions due to Opisthorchis viverrini infection were controlled roentgenographically after treatment with praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a] isoquinolin- 4-one, EMBAY 8440, Biltricide). The place of study was the Khon Kaen Hospital, Northeast Thailand. Included in the study were 20 patients with impairment of gallbladder function; 7 of them were males and 13 females. Their age ranged from 27 to 60 years (mean 47.4), eggs per gram (EPG) ranged from 800 to 30,000 (geometric mean 4321). The laboratory parameters were within normal limits. Praziquantel 3 X 25 mg/kg per kg body weight was given on Day 0 and all patients were parasitologically cured within 60 days. Oral cholecystography was performed to evaluate the function and size of the gallbladder and intravenous cholangiography for the common bile duct on Days 0, 14, 60, 120 and 180. The results were: (a) very large and severe dysfunction of gallbladder seen in three patients returned to normal in 60, 60 and 180 days; (b) moderate dysfunction was present in 13 patients, all but one returned to normal: 6 in 14 days, 1 in 21 days, 2 in 60 days, 1 in 120 days and 2 in 180 days. The only patient who showed no change had diabetes mellitus and moderate dysfunction of the gallbladder for one year prior to treatment; (c) mild dysfunction: all 4 patients were normal in 14 days. The common bile duct was enlarged in 3 patients (1.2, 1.3, 1.5 cm); no significant changes were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Paragonimus heterotremus and other Paragonimus spp. in Thailand: pathogenesis, clinic and treatment.

Six species of Paragonimus have been reported in Thailand: P. siamensis in cat, bandicoot and rat; P. bangkokensis in mongoose; P. harinasutai in cat and dog (experiment); P. macrochis in bandicoot and rat; P. westermani in tiger and P. heterotremus in cat, dog and man. It is interesting to note that in 1965 two immature P. heterotremus worms were recovered for the first time in man, namely in subcutaneous swellings in a boy; in 1981 nine mature P. heterotremus worms were expectorated after praziquantel treatment. P. heterotremus has been postulated to be the main cause of human paragonimiasis in Thailand. The clinical manifestation of paragonimiasis heterotremus is similar to paragonimiasis westermani. In the 1960's and 1970's bithionol was used to treat paragonimiasis, the cure rate was only 50-60%, and side effects including urticaria, rash, abdominal pain, nausea, vomiting, diarrhoea and dizziness were common. In the past 4 years, niclofolan and praziquantel (2-cyclohexyl-carbonyl-1,2,3,6,7,11b-hexahydro - 4H - pyrazino [2,1-a]isoquinolin-4-one, EMBAY 8440, Biltricide) have been used. A single dose of 2 mg/kg body weight of niclofolan yielded 100% cure rate. Praziquantel at dosages of 3 X 25 mg/kg body weight daily for one day and two days gave 80% and 100% cure rates, respectively. The eggs disappeared in 2-3 weeks with improvement of symptoms and signs, but radiologically lesions took a few months or more to clear, depending on size and severity. Side effects in the niclofolan group were higher; in the praziquantel group side effects were minimal and no toxic effects were detected.

Anthelmintics↗

Efficacy of praziquantel on fasciolopsiasis.

A therapeutic study with praziquantel (2-cyclohexylcarbonyl - 1,2,3,6,7, 11b - hexahydro - 4H - pyrazino [2,1-a] isoquinolin-4-one, EMBAY 8440, Biltricide) was carried out in a primary school in Central Thailand. 72 children harbouring Fasciolopsis buski were randomized and were then given single dose of 40, 25 and 15 mg/kg bwt, respectively. Unwanted side effects were mild and transient. They were more frequent after the higher dosages. F. buski flukes with damaged tegument were excreted in stools. Cure rates in all regimens were 100%. The authors recommend a single dose of 15 mg/kg of praziquantel at bed time for the treatment of fasciolopsiasis.

Adolescent↗

Radiological findings in pulmonary paragonimiasis heterotremus.

The routine chest roentgenogram of pulmonary paragonimiasis heterotremus were evaluated in 93 Thai and Laotian patients. They were 44 males and 49 females; the ages ranged from 12 to 79 years; the history of illness ranged from 4 months to 14 years and the egg output per day was 400 to 300,000. Twelve patients, 12.9% had normal roentgenologic films and 81 patients (87.1%) had abnormalities with 316 lesions; 22.2% had one lesion and 77.7% had multiple lesions. The common lesions were cystic formation, multiple or single and linear infiltration. Both lower lobes of the lungs and the left upper lobe were the common sites but any part of the lung may be affected. There were correlation between the duration of illness, number of eggs output per day and the extent of the lesions. The longer the duration of illness or the higher number of eggs output per day the more extensive lesions in the X-ray films have been observed.

Adolescent↗

Alterations of the surface tegument of Opisthorchis viverrini exposed to praziquantel in vitro and in vivo.

The in vitro and in vivo effects of praziquantel on the ultrastructural surface of Opisthorchis viverrini were investigated using scanning electronmicroscopy. For the in vitro study, adult flukes were collected from experimentally infected hamsters, and were incubated for various time intervals at 37 degrees C in Earle's basal medium containing praziquantel at final concentrations of 0.01-100 micrograms/ml. For the in vivo study, flukes were collected from the biliary system of experimentally infected hamsters that had been treated 4 hours previously with 350 mg of praziquantel per kg body weight (mg/kg). Flukes were also obtained from the feces of a patient with opisthorchiasis who had been given praziquantel once at a dose of 40 mg/kg 4-6 hours previously and from the bile of a patient at the time of operation 24 hours after praziquantel treatment. Scanning electronmicroscopic analyses of the surface teguments of flukes exposed to praziquantel either in vitro or in vivo showed similar changes. Tegumental bubbles of different sizes appeared on the surface; they later ruptured and resulted in the formation of crater-like lesions. These lesions might be so extensive as to result in the peeling of the entire areas. On occasions, "micronodules" appeared later in these areas and those at the periphery of the lesions; these micronodules may represent an attempt by the worm to regenerate new tegument. The possibility that these ultrastructural changes may represent a generalized response of the tegumental surface to an obnoxious agent was discussed.

Animals↗

An economical regimen of human diploid cell strain anti-rabies vaccine for post-exposure prophylaxis.

Vaccine regimens using 0.1 ml human diploid cell strain vaccine (HDCSV) given intradermally (id) in single and multiple sites, or with aluminum hydroxide adjuvant given subcutaneously (sc), were compared with the regimens of HDCSV and Semple vaccine currently suggested by WHO. Some groups were also given human rabies-immune globulin (HRIG). Neutralising antibody titres were monitored for 3 months. Antibody was detected earliest in subjects given 0.1 ml HDCSV id at each of eight sites. The highest antibody titres from day 14 onwards were found after intramuscular (im) administration of HDCSV, but the multiple-site id regimen, which requires only one quarter of the volume of vaccine required for the im regimen, gave similar results, provided that a booster was given on day 91. This finding suggests that a treatment schedule based on this regimen would be suitable for post-exposure prophylaxis. Adjuvanted vaccine gave similar results to the same amount of antigen given id. Semple vaccine produced the lowest titres. HRIG, given at the high dose of 40 IU per kg, suppressed the antibody response to some of the regimens.

Adolescent↗

Do patients with cerebral malaria have cerebral oedema? A computed tomography study.

Computed tomography of the brain in 10 patients with severe cerebral malaria, 5 of whom died, showed evidence of cerebral oedema in only 2 fatal cases. Small areas of altered density were seen in 4 cases; these were not associated with focal neurological signs and were still visible in convalescent scans in 2 survivors. 4 patients, including 1 of the fatalities, had completely normal scans. Cerebral oedema may occur in severe cerebral malaria but is not a consistent feature of living patients and cannot, therefore, always be the cause of their coma.

Acute Disease↗

Attempts to induce protective immunity in hamsters against infection by a liver fluke of man (Opisthorchis viverrini).

The development of acquired resistance in opisthorchiasis was studied in hamsters experimentally infected with Opisthorchis viverrini. The induction of protective immunity was attempted by first exposing adult female golden Syrian hamsters to 1, 2 or 3 doses of infective metacercariae obtained from naturally infected cyprinoid fishes and then reinfecting them with 80 metacercariae. In other experiments, animals that were infected with 50 metacercariae were treated with praziquantel prior to being rechallenged in order to eliminate the flukes that had developed from the first infection. The effect of long-term chronic infections was also studied. Faecal egg counts were determined at weekly intervals from 4-5 weeks onwards. The animals were killed 2-3 months after the last infection for worm recovery, and terminal faecal egg output/g faeces/worm was calculated. The data showed that prior infection of animals with O. viverrini did not induce significant protective immunity against reinfection by the same parasite. Lack of protection was also noted in animals reinfected several times with small doses of metacercariae. However, under certain circumstances, prior infection could result in a significant reduction in the faecal egg output due to subsequent infection.

Animals↗

Quinine loading dose in cerebral malaria.

In cerebral malaria, the use of currently recommended doses of intravenous quinine may result in subtherapeutic plasma concentrations during the critical first 24 hours of treatment. A loading dose of quinine (20 mg/kg quinine dihydrochloride, equivalent to 16.7 mg/kg base, infused over 4 hours) proved a rapid and safe method of achieving plasma concentrations above the high minimum inhibitory concentrations for Plasmodium falciparum prevalent in Eastern Thailand.

Adolescent↗

Preliminary field trial of a radioimmunoassay for the diagnosis of malaria.

A radioimmunoassay (RIA) has been developed for the detection of Plasmodium falciparum in infected blood. The assay is based on the ability of solubilized, infected red blood cells (RBC) (P. falciparum "antigen") to combine with anti-P. falciparum antibodies and thus prevent the subsequent interaction of the latter with "antigen"-coated microtiter plates. A preliminary trial was carried out in Thailand to determine the usefulness of the RIA for the immunodiagnosis of malaria. Blood samples from malarious and non-malarious patients were examined both by standard microscopy and by RIA. Efficient solubilization of the parasites proved to be a major requirement for the successful performance of the RIA. Sonication or freezing and thawing, which were perfectly satisfactory for the solubilization of cultured, infected RBC, were found to be totally inadequate when applied to RBC taken from patients. However, parasites in RBC from patients could be solubilized efficiently by treatment with detergents (e.g., NP40, Triton X-100, etc.). Of the 108 blood samples tested, 23 were found positive for falciparum parasitemia by microscopy and 39 by RIA. One sample from a patient with patent falciparum parasitemia and three with patent vivax parasitemia were negative by RIA. Ten of the samples positive only by RIA belonged to patients with recent malarial infection, as shown by microscopy. Thus, the RIA detected almost all of the patients with microscopic evidence of falciparum malaria. The proportion of false positives in the RIA test was low.

Detergents↗

Human serum proteins indicative for the nutritional status and serum proteinase inhibitors in uncomplicated falciparum malaria.

The serum proteins supposed to be indicative of the nutritional status, albumin, prealbumin and transferrin, as well as the serum proteinase inhibitors alpha 1-protease inhibitor (alpha 1-antichymotrypsin (Ach) and alpha 2-macroglobulin (alpha 2M) were measured in 14 Thai males suffering from uncomplicated falciparum malaria on the day of admission and after treatment with mefloquin on the 2nd, 28th and 63rd day. The same serum proteins had been determined from 31 healthy Thai males. Upon admission albumin and prealbumin concentrations had been lower and Ach higher in malaria patients compared with healthy Thai males. A significantly higher alpha 1 PI value was observed on the day of admission compared with the 28th day of the malaria patients. Only on the day of admission and only for the patients was a statistically significant negative linear regression found for albumin and prealbumin with Ach and a positive correlation for prealbumin with alpha 2 M as well as for albumin and transferrin correlated with alpha 1 PI. In well-nourished malaria patients the synthesis of the "acute phase reactants", alpha 1 PI and Ach, might be enhanced and in a reverse relationship the synthesis of albumin, pre-albumin and transferrin depressed.

Animals↗

A phase II clinical trial of mefloquine in patients with chloroquine-resistant falciparum malaria in Thailand.

A double-blind, randomized, dose-finding, phase II mefloquine trial was carried out in 147 adult male patients suffering from acute, uncomplicated, falciparum malaria and admitted to the Hospital for Tropical Diseases, Bangkok, between January 1980 and April 1981. Mefloquine was administered as a single oral dose of 500, 750, or 1000 mg (base) in the form of the hydrochloride. The clinical and parasitological responses were satisfactory with all three dosage regimens. The cure rates for the 1000-, 750-, and 500-mg doses were 100%, 92.5%, and 95% respectively, over an observation period of 63 days.The side-effects, which were transient and generally mild, included nausea, vomiting, and diarrhoea. No significant changes were noted in haematological or biochemical parameters in any of the three groups. Sinus bradycardia, which started 4-7 days after drug administration and lasted for a few weeks, was seen in 10 patients. It was symptomless and needed no treatment.Acute brain syndrome was observed in one patient on day 21 after receiving a 1000-mg dose of mefloquine.Mefloquine was well tolerated in one case of acute renal failure, in 10 cases of moderately severe malaria with jaundice, in 13 cases with glucose-6-phosphate dehydrogenase deficiency, and in one case of thalassaemia.Mefloquine showed no effect on either gametocytes of Plasmodium falciparum or tissue forms of P. vivax.Mefloquine hydrochloride was found to be an effective drug for the treatment of falciparum malaria and tended to produce a more rapid clinical and parasitological response at the highest tested dose of 1000 mg (base).

Adolescent↗

Field trial on the treatment of fasciolopsiasis with praziquantel.

Eight-five of 816 (10.7%) students attending a primary school in Central Thailand were examined and found infected with Fasciolopsis buski. All of students ate fresh water lily stems and most ate other fresh water plants including caltrop, water cress and morning glory. The 85 students were given praziquantel in randomized single doses of 15, 25 or 40 mg/kg body weight. Side effects were mild and transient and consisted of headache, dizziness, nausea, sleepiness, abdominal discomfort, anorexia, diarrhea, epigastric pain, vomiting and lassitude. Those receiving the highest dosages had more side effects than students in the other 2 groups. Large blisters were observed on the tegument of F. buski passed in feces and this was believed to be caused by the drug. The authors recommend a single dose of praziquantel in a dosage of 15 mg/kg of body weight for the treatment of parasitosis.

Adolescent↗

Clinical and laboratory evaluation of praziquantel in opisthorchiasis.

A total of 122 patients were treated with a single dose of praziquantel 40 mg per kilogramme body weight, with 96 patients completing the follow up period of 60 days. The parasitological cure rate was 95.8% by single faecal examination. These patients had mild clinical manifestations. The hematological, biochemical and the liver function tests were within the normal limits. High eosinophilia was observed in 84.5% but there were no significant difference after eradication of the flukes. No significant changes were observed in the laboratory investigation at day 60 post treatment.

Adolescent↗