Showing papers by "Sasithon Pukrittayakamee published in 1990"

Erythrocyte sequestration and anemia in severe falciparum malaria: analysis of acute changes in venous hematocrit using a simple mathematical model.

Abstract: Microvascular erythrocyte sequestration, the characteristic pathological feature of falciparum malaria, was evaluated using a mathematical model in 46 patients with severe infections. From admission radioisotopic circulating red cell volumes and simultaneous venous hematocrits, the model-derived sequestrum hematocrit (mean [95% confidence limits]: 0.70 [0.43-0.97], n = 29) was twice that of peripheral blood (0.33 [0.30-0.36]). Serial reticulocyte and radiolabeled erythrocyte counts indicated that small numbers of cells enter the circulation during initial therapy. The mean fall in hematocrit over 84 h in 26 nontransfused patients conformed to a three-term equation. A first-order decline (t1/2 2.0 h [0.6-3.4]) suggested an average 7.5% plasma volume expansion through rehydration. A zero-order 6.3% (3.1-9.5) fall (t1/2 25.7 h [21.2-30.2]) occurred contemporaneously with a fall in mean parasitemia from 4.5% (3.6-5.4); from these data the model-derived average sequestered erythrocyte volume (4.8% of the admission hematocrit) was similar to the peripheral parasite burden. A second, first-order fall (t1/2 1,047 h [278-1,816]) indicated loss of uninfected erythrocytes with mean lifespan 62 d. Predicted total plasma volume expansion during initial therapy (21.2%) was similar to radioisotopic estimates in 11 patients (17.3% [2.0-33.1]). Application of the model to individual patient data showed wide variations in relative proportions of circulating and sequestered parasitized cells. The model provides evidence of the nature and fate of all parasitized erythrocytes in malaria.

Quinine induces reversible high-tone hearing loss.

Abstract: Serial audiometry was performed in ten patients receiving quinine treatment for acute falciparum malaria. Quinine reduced high tone auditory acuity in all patients, resulting in flattening of the audiograms. The effect was rapid in onset, usually unnoticed (although tinnitus was reported in seven patients), and resolved completely after treatment was completed.

A Safe and Effective Consecutive-Infusion Regimen for Rapid Quinine Loading in Severe Falciparum Malaria

Abstract: Recommended initial treatment of severe chloroquine-resistant falciparum malaria consists of a 4-h loading infusion of 20 mg of quinine dihydrochloride (salt)/kg of body weight. To achieve and maintain therapeutic blood quinine concentrations (10 mg/l) safely and rapidly, a consecutive-infusion regimen (7 mg of salt/kg of body weight over 30 min followed by 10 mg of salt/kg of body weight over 4 h) based on pharmacokinetic parameters in cerebral malaria has been suggested. This regimen was evaluated in 16 adults (6 male, 10 female; mean age, 25.9 years) with severe falciparum malaria. Plasma quinine concentrations (mean +/- SE) were 8.7 +/- 1.2 mg/l at 30 min and 11.0 +/- 1.8 mg/l at 4.5 h. There was no electrocardiographic evidence of serious cardiotoxicity during the 4.5-h infusion period, and systolic blood pressure fell by greater than 10 mm Hg in only one patient. Parasite clearance in 13 surviving patients (median count on admission, 438 x 10(3)/microliters; range, 500-122 x 10(4) took an average of 71 h (range, 9-115). This regimen is safe, effective, and suitable for use in an intensive care unit.

Glucose metabolism in quinine-treated patients with uncomplicated falciparum malaria.

Abstract: SUMMARY To investigate host and drug effects on glucose metabolism in acute falciparum malaria, 10 previously untreated, fasting Thai males with uncomplicated infections were given a 2-h intravenous glucose infusion (5 mg/kg ideal body weight min) with an infusion of quinine dihydrochloride (10 mg/kg body weight) during the second hour. Eight patients were restudied in convalescence. Fasting plasma glucose (mean ± SD) and insulin (geometric mean (— SD to + SD)) were higher during acute illness (5.5 ± 1.0 mmol/l and 6.2 (5.0–7.7) mU/l) than in convalescence (4.2 ± 0.25 mmol/l and 3.7 (2.1–6.7) mU/l; P 0.5). Basal plasma free fatty acid concentrations were increased in acute illness (0.68 ±.24 vs 0.21 ± 0.12 mmol/l, P < 0.001) but fell to low levels at 2 h in both studies. These data suggest tissue insulin resistance and augmented quinine-stimulated insulin secretion in acute falciparum malaria, factors which are likely to influence the clinical situation in which malaria-associated hypoglycaemia occurs.

The pituitary-thyroid axis in severe falciparum malaria: evidence for depressed thyrotroph and thyroid gland function

Abstract: Abnormal thyroid function is strongly associated with mortality in severe non-thyroidal illness. We have assessed the pituitary-thyroid axis serially in 18 Thai adults with severe falciparum malaria and in 18 matched controls. The admission total serum thyroxine (T4) concentrations of the patients (median [range]: 64 nmol/litre [less than 30-91]) were significantly lower than those of controls (81 nmol/litre [61-133]; 2P less than 0.01), and remained depressed until after fever and parasite clearance. Two patients who died in hospital had admission serum T4 concentrations less than 35 nmol/litre. The admission basal serum thyrotropin (TSH) levels of the patients (0.9 mU/litre [less than 0.2-3.1]) were similar to those of controls (1.3 mU/litre [less than 0.2-3.7], 2P greater than 0.1) and remained normal throughout fever and parasitaemia. Thirty-minute TSH increments during a thyrotropin-releasing hormone test on admission were reduced in 13 patients with severe malaria (4.1 mU/litre [0.7-8.1]) relative to those in convalescence (7.1 mU/litre [1.7-14.4], n = 10, 2P less than 0.01) and controls (5.6 mU/litre [3.3-12.9], n = 9, 2P less than 0.05). These findings suggest that thyrotroph and thyroid gland function are depressed during acute, severe malaria. As these changes may be an adaptation to accelerated catabolism, the role of thyroid replacement in such patients is uncertain.

Synergy of antithrombin III concentrate and antivenom in preventing coagulopathy in a rat model of Malayan pit viper envenoming.

Abstract: The effects of unrefined equine antivenom and antithrombin III (AT-III) concentrate on the coagulopathy induced by systemic envenomation by Malayan pit viper (Calloselasma rhodostoma; MPV) venom were investigated in a rat model. 37 rats received an intramuscular injection of MPV venom and serial blood samples were taken from the femoral vein for simple whole blood clotting tests and measurement of AT-III activity. 30 min after venom injection, treatment (antivenom, AT-III or both) was given intravenously. 6 rats were untreated and all developed uncoagulable blood and AT-III depletion 90-210 (median 180) min after venom injection. A combination of high dose AT-III concentrate (0.5 units/g) and antivenom (20 micrograms/g) prevented abnormal clotting (P less than 0.001), whereas AT-III alone, antivenom alone, or a combination of low dose AT-III (0.25 units/g) and antivenom did not (P less than 0.05). These results suggest that the coagulation abnormality in MPV envenomation is secondary to activation of the coagulation cascade at several levels, and that treatment with antivenom alone may not be sufficient to reverse or prevent this phenomenon.

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

Abstract: 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.