Showing papers by "Mahidol University published in 1991"

Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria.

Abstract: The protective effect of African IgG antibodies against Plasmodium falciparum malaria was investigated by passive transfer in Thai patients. Sera from 333 African adults were collected in the Cote d'Ivoire and subjected to extensive screening. One hundred fifty-three samples were discarded for safety reasons, and IgG was extracted from those remaining under conditions allowing their use by the intravenous (iv) route. Eight Thai patients with P. falciparum parasitemia were treated by iv inoculation of the IgG: six with a 100 mg/kg dose given over three days, one with a single 20 mg/kg dose, and one with a single 200 mg/kg dose. To ensure a safety margin of at least 48 hours, subjects were chosen among patients having a recrudescent parasitemia following quinine treatment failure at the RI level. At that stage, symptoms were mild or absent and parasitemia was low but increasing (range 4, 200-9,000/microliters). The IgG pool exerted a profound, stage-specific, but non-sterilizing effect on each of the strains tested, and proved to be safe. Asexual parasitemia decreased by a mean 728-fold (range 46-1,086), while gametocytes were unaffected. Clearance of parasites and symptoms was as fast or faster than with drugs, and was consistent in the eight patients treated, suggesting that target antigens were equally expressed in geographically remote isolates. In peripheral blood smears, no mature forms were seen at any time during the followup, which does not support the hypothesis that reversal of cytoadherence occurred. After the disappearance of the transferred antibodies, recrudescent parasites from three patients were found to be susceptible to the same extent (mean decrease of 1,310-fold) to the same IgG preparation, indicating that selection of parasites able to escape the effect of antibodies had not occurred. No adverse side-effects were detected during the followup, which lasted one year.

Melioidosis: the tip of the iceberg?

Abstract: For nearly 80 years clinical melioidosis has been considered a rare disease. This bacterial infection is caused by Pseudomonas pseudomallei, a saprophyte found in soil and surface water of endemic areas. Consequently, those who have most contact with soil, the rural poor, are likely to be at greatest risk of infection. Since the diversity of clinical manifestations necessitates the isolation and identification of the causative organism for a definitive diagnosis of melioidosis and the population at greatest risk within endemic areas rarely have access to an appropriate level of health care, the disease has probably been underrecognized. Melioidosis is now known to be an important cause of human morbidity and mortality in Thailand, and this may be true throughout Southeast Asia, which is usually regarded as the main endemic area for the disease. In Australia, melioidosis causes a smaller number of human infections, while disease among livestock has important economic and possible public health implications. Sporadic reports of the infection indicate its presence in several other tropical regions: in the Indian subcontinent, Africa, and Central and South America. Clinical melioidosis may be highly prevalent in these areas, but underdiagnosed as a result of a lack of awareness of the clinical and microbiological features of the disease, or simply because of a lack of health care facilities. Furthermore, during the last two decades the importation and transmission of melioidosis within nontropical zones have been documented. The causative organism is not difficult to grow, and modern antibiotics have improved disease prognosis. Further studies are needed to determine the true worldwide distribution and prevalence of melioidosis so that improved therapeutic and preventive measures can be developed and applied.

Microvascular sequestration of parasitized erythrocytes in human falciparum malaria: a pathological study.

Abstract: Thirty-nine falciparum malaria autopsy cases from the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand were divided into two groups that had had either cerebral malaria (CM) or non-cerebral malaria (NCM). We then studied significant pathological differences between these groups in order to investigate the correlation between parasitized erythrocyte (PRBC) sequestration in small blood vessels in the brain, heart, lungs and small intestines. We found that the percentage of PRBC sequestration in the organs which we studied was higher in the CM patients than in the NCM patients. The difference of PRBC sequestration among the organs of two groups was significant (P less than 0.05). In the CM group, the average percentage of PRBC sequestration in the brain was significantly higher than in the heart, lungs and small intestines (P less than 0.05). No statistically significant difference was found between PRBC sequestration in the brains, hearts, lungs and small intestines in the NCM group (P greater than 0.05). Our study indicates that severity of malaria in the CM patients depends on PRBC sequestration, especially in the brain. A combination of functional disturbances of the other organs, in addition to the cerebral pathology, may augment the severity of the disease.

Malaria during pregnancy in an area of unstable endemicity

Abstract: A prospective study of malaria during pregnancy was conducted between September 1986 and December 1989 in an area of unstable (mesoendemic) malaria transmission on the Thai-Burmese border. Antenatal clinics were set up in camps for displaced persons of the Karen ethnic minority and 1358 pregnant women were enrolled at a mean estimated gestational age of 23 weeks (standard deviation 5.7 weeks) and were followed weekly until delivery. Malaria developed in 505 women (37.2%); 80.2% of infections were Plasmodium falciparum, 17.1% were P. vivax, and 2.7% were mixed. Primigravidae were infected more commonly than multigravidae: 153/322 (47.5%) compared with 318/953 (33.3%) (P less than 0.001). The incidence of malaria declined from the 20th week of gestation (12%) towards term (4.4%). Most infections were detected before symptoms developed, and there were no deaths associated with malaria. Despite this, malaria was associated with an overall 123 g reduction in birthweight (95% confidence interval [CI] 34-212 g). This reduction was largely accounted for by lower birthweights of babies born to infected primigravidae (mean reduction 151 g, 95% CI 21-282 g) and women in their 2nd and 3rd pregnancies (mean reduction 185 g, 95% CI 84-286 g). The incidence of anaemia requiring treatment was higher in women who developed malaria, 149/420 (35.4%) compared with 191/670 (28.5%), and was proportional to the number of parasitaemic episodes. Thus, despite regular antenatal clinic attendance with prompt detection and treatment of malaria (the currently employed antimalarial strategy in areas with multidrug-resistant P. falciparum), malaria still had a significant adverse effect on pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction.

Abstract: OBJECTIVES--To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN--13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING--Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS--Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS--The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION--The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke.

Antibodies against dengue viral proteins in primary and secondary dengue hemorrhagic fever.

Abstract: Antibodies against dengue viral proteins were demonstrated in sera from dengue-infected patients by polyacrylamide gel electrophoresis, Western blotting, and enzyme immunoassay. Primary dengue cases showed low titers of IgG class antibodies to envelope (E) proteins and two non-structural proteins, NS3 and NS5, in sera collected during the convalescent phase. Secondary dengue- infected patients always demonstrated IgG antibodies to E proteins in sera collected during the acute phase, and high titers of IgG antibodies to many other proteins, including NS1, NS3, NS5, and C proteins in sera collected during the convalescent phase. Appearance of antibodies to E, NS3, and NS5 could be detected within five days after the onset of fever. These three dengue viral proteins and their corresponding antibodies may be involved in the immunopathologic mechanism underlying this disease. For diagnostic purposes, identifying the non-structural proteins such as NS3 and NS5 may be the best means for early confirmation of the disease.

Clinical trial of artesunate and artemether on multidrug resistant falciparum malaria in Thailand. A preliminary report.

Abstract: A 5-day course of oral artesunate at total doses of 1200, 600, 650 mg and intramuscular artemether 480 mg proved effective (90-100% cured) in the treatment of multidrug resistant falciparum malaria in Thailand Shorter courses yielded high recrudescence rates The fever clearance and parasite clearance times were short The side effects were mild and transient including occasional abnormal electrocardiograms and pain at the injection site Slight reduction of neutrophil leucocytes and reticulocytes was observed Further studies of artesunate and artemether should be carried out to find the optimum dosage regimen and to clarify the hematological effects

Plant anticancer agents, XLVIII. New cytotoxic flavonoids from Muntingia calabura roots.

Abstract: From a cytotoxic Et2O-soluble extract of Muntingia calabura roots, twelve new flavonoids were isolated, constituting seven flavans 1-7, three flavones 8, 10, and 12, and two biflavans 9 and 11. The structures of compounds 1-12 were established by the interpretation of spectral data, with the nmr assignments of these constituents being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. This is the first report of the occurrence of 7,8-di-O-substituted flavans, biflavans, and flavones. Most of the isolates demonstrated cytotoxic activity when tested against cultured P-388 cells, with the flavans being more active than the flavones. Furthermore, certain of these structurally related flavonoids exhibited somewhat selective activities when evaluated with a number of human cancer cell lines.

Rosette formation of Plasmodium falciparum-infected erythrocytes from patients with acute malaria.

Abstract: Noninfected erythrocytes form rosettes around those infected with trophozoites and schizonts of Plasmodium falciparum in vitro. These rosettes are thought to contribute to the microvascular obstruction which underlies the pathophysiology of severe falciparum malaria. To determine whether the percentage of infected erythrocytes forming rosettes for a parasite isolates in vitro correlates with the in vivo severity of disease, we studied the rosette formation behavior of 35 isolates of P. falciparum from patients with uncomplicated, severe, and cerebral malaria. There was a wide variation in the degree of rosette formation (0 to 53%). Four parasite isolates formed rosettes well (30 to 53%), and seven isolates formed rosettes poorly or not at all (0 to 5%), while the majority of the isolates formed rosettes to various degrees between these two extremes. In this relatively small sample of patients, we were unable to demonstrate a significant association between in vitro rosette formation and patients with cerebral malaria or conscious patients with significant renal (serum creatinine greater than 200 mumol/liter) or hepatic dysfunction (serum bilirubin greater than 50 mumol/liter and aspartate aminotransferase greater than 50 Reitman-Frankel units). However, there was an inverse relationship between rosette formation and cytoadherence (r = -0.575, P less than 0.01) which could not be explained on the basis of steric hindrance. This finding suggests that cytoadherence and rosette formation properties are intrinsic to the parasites, with isolates having a greater propensity for one or the other but not both. Further studies are required to establish the occurrence and pathophysiological role of rosette formation in vivo.

Depot‐medroxyprogesterone acetate (dmpa) and risk of edometrial cancer

Abstract: The use of depot-medroxyprogesterone acetate (DMPA), a long-acting progestational contraceptive, in relation to risk of epithelial ovarian cancer was examined in a hospital-based case-control study conducted in Mexico and Thailand. Women with histologically confirmed epithelial ovarian cancer (n = 224) diagnosed between 1979 and 1988 were compared with hospital controls (n = 1,781) matched on age, hospital and year of interview. Overall, 9.8% of cases and 12.9% of controls had ever used DMPA. The relative-risk (RR) estimate in women who had ever used DMPA, controlling for the confounding effects of number of live births and oral contraceptive use, was 1.07 (95% CI 0.6, 1.8). No consistent patterns of increasing or decreasing risk were noted according to duration of use, time since first or most recent use or age at first use of DMPA. These results suggest that the risk of epithelial ovarian cancer is not altered by the use of DMPA.

Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults.

Abstract: One hundred and fifty-two adult patients with pharyngotonsillitis were enrolled in the randomized double blind study to assess the efficacy of Andrographis paniculata. The patients were randomized to receive either paracetamol or 3 g/day of Andrographis paniculata or 6 g/day of Andrographis paniculata for 7 days. The baseline characteristics of the patients among the three groups were not different. The efficacy of paracetamol or high dose Andrographis paniculata was significantly more than that of low dose Andrographis paniculata at day 3 in terms of the relief of fever and sore throat. The clinical effects were not different at day 7. Minimal and self limiting side effects were found in about 20 per cent in each group.

Alpha 1-acid glycoprotein (orosomucoid) and plasma protein binding of quinine in falciparum malaria.

Abstract: 1. Plasma concentrations of alpha 1-acid glycoprotein (AAG) and plasma protein binding of quinine were measured in 97 Thai adults with acute falciparum malaria. There was a linear relationship between log AAG and percentage quinine binding (r = 0.71, P less than 0.001) in vivo, which was similar to that observed in vitro; the slopes and intercepts of the regression lines at AAG concentrations of 1 g l-1 were -8.94 and -8.41, and 7.2% and 10.9%, respectively. 2. Hill plots from these data suggest a single high affinity quinine binding site on each molecule of AAG. 3. Plasma AAG concentrations were consistently raised in acute malaria, and were higher in patients with cerebral malaria [2.03 (0.51) g l-1, mean (s.d.)], and conscious patients with severe malaria [1.93 (0.53) g l-1] than in patients with uncomplicated infections [1.55 (0.58) g l-1], P = 0.008. Plasma protein binding of quinine was correspondingly higher and thus the proportion of free drug was lower in the severe groups; 5.5 (2.4)% compared with 7.2 (1.9)%, P = 0.03. 4. Following recovery from malaria, plasma AAG concentrations fell by an estimated 0.05 g l-1 day-1 to levels that were approximately half (median 45%) the admission value at 28 days. 5. AAG is the principal binding protein for quinine in plasma. Changes in plasma concentrations of this acute phase reactant account for the increased plasma protein binding of quinine in acute malaria.

Clinical correlates of in vitro Plasmodium falciparum cytoadherence.

Abstract: To determine whether isolates of Plasmodium falciparum have intrinsically different cytoadherent properties and whether these differences contribute to the clinical severity of human falciparum malaria, we studied the cytoadherence to C32 melanoma cells in vitro of 59 parasite isolates from patients with naturally acquired infections in Thailand. Parasitized erythrocytes adhere to these melanoma cells principally via the glycoprotein CD36, which is also expressed on most vascular endothelium. In vitro cytoadherence was significantly greater for isolates from patients with biochemical evidence of severe malaria. The cytoadherent properties of P. falciparum parasites may thus be a virulence factor in human falciparum malaria. However, there was no correlation between the degree of in vitro cytoadherence and cerebral symptoms, which suggests that other receptors and/or host factors may be important in the adherence of malaria parasites to cerebral vascular endothelium. The cytokines tumor necrosis factor, interleukin-1, and gamma interferon, which have been implicated in the pathogenesis of cerebral malaria and are known to promote intercellular adhesion in other systems, did not enhance the cytoadherence of P. falciparum isolates to C32 melanoma cells.

Establishment and characterization of a cholangiocarcinoma cell line from a Thai patient with intrahepatic bile duct cancer.

Abstract: A new human cholangiocarcinoma cell line (HuCCA-1) was established from cholangiocarcinoma (CCA) tissue fragments surgically removed from a Thai patient with intrahepatic bile duct cancer. The growth medium used for the primary cell culture was Ham's F12 supplemented with 10% fetal bovine serum (FBS) and 10 ng/ml epithelial growth factor (EGF). Approximately one month later, the cells were subcultured in Ham's F12 supplemented with only 10% FBS. The population doubling time was approximately 55 hr. Staining of the cells for cytokeratin and mucin confirmed that the cells were mucin-secreting tumor of epithelial cell origin. The supernatant fluid secreted a number of non-specific tumor markers including CA125 and traces of MCA and AFP. The ability of the HuCCA-1 cell line to synthesize specific marker that may have potential in the diagnosis of cholangiocarcinoma is now being investigated.

Intracranial pressure in childhood cerebral malaria

Abstract: Lumbar punctures were performed in 40 Gambian children with acute cerebral malaria aged between 18 months and 10 years. The mean opening pressure was elevated in 32 (80%) of the children, but was not significantly different in the 14 fatal cases compared with survivors: 110 (standard deviation 71) versus 131 (58) mm of cerebrospinal fluid respectively. Cerebral perfusion pressures were also similar in the 2 groups: 64 (20) mm Hg versus 64 (11) mm Hg respectively. There was no clear clinical evidence of raised intracranial pressure, and no evidence of deterioration immediately following lumbar puncture. Nevertheless brain swelling, and consequent brain-stem compression, may contribute to a fatal outcome in cerebral malaria--particularly in those children who die from sudden respiratory arrest. A prospective evaluation of osmotic agents in childhood cerebral malaria seems to be justified.

Disposition of oral quinine in acute falciparum malaria.

Abstract: Plasma quinine concentrations following oral quinine sulphate 10 mg salt/kg have been measured by HPLC in 15 adult Thai patients with uncomplicated falciparum malaria. In 10 of the same patients the study was repeated in convalescence. In acute malaria plasma concentrations were approximately 50% higher than in convalescence; the mean acute peak plasma quinine concentration was 8.4 mg·l−1 compared to 5.7 mg·l−1 in convalescence. There was considerable variation in the rate of drug absorption, particularly in acute malaria. The mean time to peak plasma concentration was 5.9 h in acute malaria and 3.2 h in convalescence. The apparent clearance of oral quinine (CL/f) during the illness was 1.51 ml·kg−1·min−1, which was significantly lower than in convalescence — 2.67 ml·kg−·min−1. Estimated free quinine clearance was also lower in the acute phase: 30.6 compared to 49.0 ml·kg−1·min−1 in convalescence. Mean (SD) plasma protein binding of quinine was 94.7% in acute malaria and 92.8% in convalescence. Binding was significantly correlated with the plasma concentration of α1 acid glycoprotein (r=0.5), which was significantly higher in the acute phase; 1.48 g·l−1 compared to 1.05 g·l−1 during convalescence. Oral quinine sulphate was well absorbed in uncomplicated falciparum malaria. High blood concentrations following the administration of oral quinine in acute malaria are probably related to increased plasma protein binding, lower apparent volume of distribution, and a reduction in its systemic clearance.

Enterobiasis: a histopathological study of 259 patients.

Abstract: Enterobius worms or their eggs, or both, are present in preserved tissue sections or tissue specimens of 259 patients whose medical records are on file at the Armed Forces Institute of Pathology, Washington D.C., U.S.A. The most common site of infection (86.5%) was found to be the lumen of the appendix, where the worms provoke no reaction. Of the 259 patients 11 (4.2%) had worms and/or eggs in granulomas of the abdominal and pelvic peritoneum, and an equal number had granulomas on the peritoneum of the salphinx or on the surface of the ovary. There were also ectopic worms and/or eggs in granulomas on the peritoneum of the small and large intestines (2.7%). These Enterobius granulomas form around degenerating adult worms, around discrete eggs, around clusters of eggs, and, we believe, also around the tracks of migrating worms. Three patients (1.2%) had worms in perianal abscesses. A necrotic granuloma, removed from the lung of one patient, surrounded a degenerating adult worm. This suggests that the worm, carried to the lung as an embolus, impacted in a pulmonary arteriole. A stool specimen of one patient contains eggs of Enterobius, and that of another patient contains an adult Enterobius. This is the largest recorded histopathological study of enterobiasis in man.

False-negative Papanicolaou smears from women with cancerous and precancerous lesions of the uterine cervix.

Abstract: The occurrence from 1980 to 1989 of false-negative Papanicolaou smears in women with cancerous and precancerous lesions of the uterine cervix was studied. The 4,781 cases of cancer (2,814 invasive carcinomas and 593 carcinomas in situ) and precancerous lesions (418 severe dysplasias, 748 moderate dysplasias and 208 mild dysplasias) included 70 cases (1.5%) with false-negative smears. These 70 cases included 43 invasive carcinomas (61.4%), 17 carcinomas in situ and adenocarcinomas in situ (24.2%), and 10 dysplasias (14.4%); all were diagnosed histologically. The mean age of women with false-negative smears was 44.1 +/- 13.7 years. Review of the original cytologic samples showed a screening error in 41 cases (58.5%), an interpretation error in 2 cases (2.9%) and a sampling error in 27 cases (38.6%). Methods for eliminating false-negative smears are discussed.

Effect of steroids on cerebrospinal fluid penetration of antituberculous drugs in tuberculous meningitis

Abstract: Sixteen patients with oral isoniazid, pyrazinamide, rifampin, and intramuscular streptomycin for tuberculous meningitis were studied. The concentrations of isoniazid, pyrazinamide, rifampin, and streptomycin in cerebrospinal fluid (CSF) obtained 3 hours after administration were 2.40, 34.78, 0.29, and 3.78 micrograms/ml, respectively. The CSF concentrations of isoniazid and pyrazinamide were well above the minimum inhibitory concentration for Mycobacterium tuberculosis. Concentrations of rifampin and streptomycin were above the minimal inhibitory concentration initially but declined below the minimal inhibitory concentration at later times. The CSF penetration of isoniazid, pyrazinamide, rifampin, and streptomycin was about 89%, 91%, 5%, and 20%, respectively. In eight patients who received antituberculous drugs in combination with steroids, the mean CSF and serum concentrations, as well as CSF/serum ratios at various intervals of treatment, were not statistically different (p greater than 0.05) from those of the eight patients who did not receive steroids.