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Biomedical subjects

T M Davis

Publications and source records attributed to T M Davis.

At least 109 records · Page 6Linked to original sources
PubMed1993

Glucose turnover in severe falciparum malaria.

To investigate glucose metabolism in acute falciparum malaria, [3-3H]glucose turnover was measured in 18 normoglycemic adult Thais (eight males, 10 females; median age, 28 years) with severe infections. Eleven patients were studied before quinine treatment, 15 while receiving quinine, and 10 during convalescence. In paired studies conducted before and after initial intravenous quinine, plasma glucose level decreased from a median (95% confidence limits) of 5.5 (3.0 to 6.6) to 4.6 (2.5 to 6.1) mmol/L (P < or = .027, n = 8), and plasma insulin level increased 9.3 (-3.2 to 30.0) mU/L (P = .02). Glucose turnover decreased during the 4-hour quinine infusion from 3.04 (2.12 to 4.23) to 1.89 (1.20 to 2.54) mg/kg.min-1 (P < .004), as did the metabolic clearance rate for glucose (2.87 [1.88 to 7.83] to 2.50 [1.43 to 4.55) mL/kg.min-1; P = .008). Glucose turnover and clearance measured both after initial quinine treatment and in convalescence were similar (P = .234 and .344, respectively; n = 7). In the series as a whole, there was an inverse association between pretreatment turnover and the simultaneous plasma glucose level (rs = -.76, P < .01; n = 11), a stronger inverse relationship between glucose clearance and plasma glucose level (rs = -.88, P < .001), and a positive association between pretreatment turnover and oral temperature (rs = .65, P < .025; n = 10). These data suggest that, as in other severe illnesses, glucose turnover is high in untreated patients, but that glycolysis by mature parasite forms may accelerate glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Platelet-activating factor and lipid metabolism in acute malaria.

Platelet-activating factor (PAF) contributes to a range of pathophysiological responses in severe illness. To examine PAF metabolism in acute malaria, venous blood was drawn from 10 untreated adults with falciparum malaria, from 8 with untreated vivax malaria, and from 10 controls. Plasma lyso-PAF, produced from PAF through the enzyme acetylhydrolase (AH), was bioassayed, after acetylation to PAF, by platelet [14C]-serotonin release. AH activity was measured by hydrolysis of [3H]-acetyl-PAF. Amounts of plasma lyso-PAF were lower in falciparum (median [range] 24 [9-221] ng/ml) and vivax (35 [7-236] ng/ml) infected patients than in controls (399 [212-504] ng/ml; P < 0.01), and correlated significantly with serum total and HDL-cholesterol (P < 0.001). Plasma AH activities were similar in the control, falciparum and vivax malaria groups. These data suggest that in malaria plasma lyso-PAF values fall together with other blood lipids, but independently of changes in AH activity. This may reflect a generalised decrease in lipid and phospholipid synthesis. However, the reduction of plasma lyso-PAF concentrations in our patients was much greater than that of serum lipoproteins. This is consistent with conversion of lyso-PAF to PAF or with increased PAF-receptor interactions. These two possibilities would have pathophysiological implications.

Acute Disease↗
PubMed1993

Interactions among primaquine, malaria infection and other antimalarials in Thai subjects.

1. The pharmacokinetics of rac-primaquine (45 mg base) and its principal plasma metabolite, carboxyprimaquine have been investigated in healthy Thai adults prior to and following a single oral dose of mefloquine (10 mg kg-1). 2. Primaquine was rapidly absorbed, attaining peak plasma concentrations (median and range) of 167 (113-532) micrograms l-1 in 2 (1-4) h. Thereafter, concentrations declined rapidly with an apparent terminal half-life of 6.1 (1.7-16.1) h and an oral clearance (CLpo) of 33.1 (17.6-49.3) l h-1. Administration of mefloquine had no effect on the values of any of these parameters at the 5% level of significance [Cmax 229 (114-503) micrograms l-1; tmax 3 (2-4) h; t1/2,z 3.9 (1.7-13.5) h; CLpo 34.0 (21.7-49.0) l h-1]. 3. The carboxylic acid metabolite of primaquine achieved maximum concentrations (median and range) of 890 (553-3634) micrograms l-1 at 6 (3-16) h. Thereafter, plasma concentrations of carboxyprimaquine declined to 346 (99-918) micrograms l-1 at 24 h. AUC (0,24 h) was 12737 (6837-27388) micrograms l-1 h. Administration of mefloquine had no effect on the plasma concentrations of this metabolite [Cmax 1035 (174-3015) micrograms l-1; tmax 8 (2-24) h; AUC(0,24) 13471 (2132-17863) micrograms l-1 h]. 4. The effect of falciparum malaria and treatment with quinine (10 mg salt kg-1 p.o.) on the pharmacokinetics of primaquine (45 mg base p.o.) has been investigated in adult Thai patients during and after infection with falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

A comparison of the pharmacokinetic and pharmacodynamic properties of quinine and quinidine in healthy Thai males.

1. Eight healthy Thai males, aged 19-27 years, received quinine or quinidine dihydrochloride 10 mg kg-1 body weight by intravenous infusion over 1 h. At least 1 week later, the alternative alkaloid was administered. 2. The terminal elimination half-time of quinidine was shorter than that of quinine (median [range]; 5.7 [5.0-10.0] vs 9.9 [8.8-15.1] h, P < 0.01), the volume of distribution at steady state (Vss) for quinidine was larger than that for quinine (3.5 [2.5-5.6] vs 3.1 [1.8-4.1] 1 kg-1; P = 0.02) and quinidine was less bound to plasma proteins (% free drug: 22.8 [15.4-47.2] vs 9.4 [7.3-15.0]%, P < 0.01). Total clearance was greater for quinidine (7.7 [3.9-11.4] vs 3.4 [1.8-4.6] ml min-1 kg-1, P < 0.01) but not for clearance of unbound drug (32.2 [14.6-50.4] vs 29.9 [20.2-50.9] ml min-1 kg-1 respectively, P > 0.2). 3. Side-effects, including transient hypotension after quinidine in two cases, were mild. 4. Both drugs produced prolongation of the rate-corrected QT interval (QTc), with similar rates of elimination from the cardiac conduction 'effect' compartment (keo; 4.14 [0.03-15.33] h-1 for quinine, 3.74 [1.63-13.14] h-1 for quinidine, P > 0.19). Using a linear concentration-response model, the intercept ('threshold') for quinidine effect was lower than that for quinine (P = 0.004) but the slopes (change in QTc for a given change in free drug concentration) were similar (P = 0.56).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose.

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Measures of capillary permeability in acute falciparum malaria: relation to severity of infection and treatment.

Capillary permeability was investigated in 32 Thai patients aged 14-49 years who had acute falciparum malaria with use of three distinct techniques: quantitation of the urinary albumin/creatinine ratio (ACR), estimation of the transcapillary escape rate of radiolabeled albumin (TER), and retinal photography/fluorescein angiography. Fourteen patients had uncomplicated infections and 18 were severe cases. The severely ill patients had significantly higher ACRs (median, 4.8 mg/mmol; 95% confidence limits, 2.4-19.9 mg/mmol) and TERs (median, 8.3%/h; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 1.0-8.8 mg/mmol; TER: median, 5.9%/h; 95% confidence limits, 3.8-10.6%/h; P = .014 and .042). Both variables were significantly associated with biochemical indices of disease severity including total serum bilirubin levels (rs greater than or equal to 0.398, P less than .025 in each case), but there were no significant differences between ACRs and TERs among comatose and noncomatose patients with severe infections (P greater than or equal to .08). Retinopathy (hemorrhages, cotton-wool spots, capillary nonperfusion, and/or extravasation of fluorescein) was found in eight severely ill patients and in two uncomplicated cases. Fluorescein leakage was evident in six patients. Although fluorescein leakage had the strongest parametric correlation with the presence of coma relative to both ACR and TER in the full patient series (r = 0.58, P less than .01), multiple linear regression analysis indicated that concentrations of plasma lactate (t = 2.998, P = .006) and serum creatinine (t = 2.200, P = .036) were the factors responsible for this association. These data do not support a role for tissue edema in the pathogenesis of cerebral malaria but reveal an association between markers of disease severity and a generalized increase in systemic capillary permeability.

Adolescent↗
PubMed1992

Effects of treatments by calcium and sex hormones on vertebral fracturing in osteoporosis.

Lateral radiographs of the thoracic and lumbar spine were taken periodically in 49 patients with osteoporosis. Thirty patients were postmenopausal, and 19 nonmenopausal with osteoporosis due to steroids, male hypogonadism, alcoholism, thyrotoxicosis or unknown cause. Patients were studied before, during and after treatment with high calcium alone, or with combined calcium and sex steroids. Calcium was given as effervescent calcium lactate gluconate, and sex hormones as oestradiol valerate, testosterone oenanthate, or methenolone oenanthate. A total of 964 films covering 409 patient-years were available for measurement. On each vertebra, deformity due to loss of anterior height was measured and assigned to one of four grades. For the time interval between each consecutive pair of films, a patient's vertebral fracture rate score was calculated and expressed per thousand patient-years. In comparison with the corresponding pretreatment fracture rate score, both the postmenopausal and the nonmenopausal groups who had not received sex hormones previously, failed to show significant changes (p = 0.144; p = 0.017) on high calcium alone during mean periods of 4.3 and 2.8 years respectively. If the first 2 years on high calcium were excluded for the postmenopausal group, they still failed to show a reduction in fracture rate score (observed for a mean period of 5.0 years; p = 0.04). When treated with combined calcium and sex hormones, both postmenopausal and nonmenopausal groups showed a lower fracture rate score of 20 and 207 respectively when compared with the pretreatment levels of 1500 and 1697 (in mean treatment periods of 3.2 and 4.4 years; p less than 0.001 in each case). When given high-dose calcium alone, but after treatment with sex hormones as well, the postmenopausal group showed no change in fracture rate score from pretreatment (in a mean of 3.1 years; p = 0.069); however the nonmenopausal group still showed a significant reduction in fracture rate score from 1697 to 42 over a mean period of 2.3 years (p = 0.001). The postmenopausal group, after stopping all treatment, showed a higher fracture rate score of 1286 (in a mean of 2.6 years) than did those on combined calcium and sex hormones, in whom the fracture rate score was 20 (in a mean of 3.2 years; p = 0.008). A subgroup of 11 patients with osteoporosis of both the menopausal and nonmenopausal types, had data both before (in a mean of 5.5 years) and during (for a mean of 2.5 years) treatment with calcium alone; the fracture rate scores were 1473 and 918 (p = 0.247).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

AIDS in Thailand.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Disposition of oral quinine in acute falciparum malaria.

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-1.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 alpha 1 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.

Administration, Oral↗
PubMed1991

Erythrocyte survival in severe falciparum malaria.

Erythrocyte survival was studied in 17 Thai patients (10 males, 7 females; aged 13-57 years) with severe falciparum malaria. To ensure radioisotopic labelling of cells before bone marrow recovery and survival analysis under near-steady state conditions, 51Cr labelling of autologous erythrocytes was performed at the time of admission (0 h) and calculation of mean cell lifespan (MCL) was based on semilogarithmic plots of corrected counts from 60 h onwards. Five patients received blood transfusions, all within 48 h of admission. The overall mean (+/- S.D.) MCL was short (44.1 +/- 21.7 days). Nontransfused patients had similar MCL values (43.6 +/- 20.4) to those of transfused patients (45.5 +/- 27.3 days, p greater than 0.8). Patients with and without palpable splenomegaly had MCL values which were not significantly different (54.1 +/- 28.8 vs. 37.2 +/- 12.3 days respectively, p greater than 0.1). There was no association between admission haematocrit or peripheral parasitaemia and MCL (p greater than 0.2 in each case), but there was an inverse correlation between total serum bilirubin and MCL (r = -0.49, p less than 0.025). There is accelerated destruction of non-parasitised erythrocytes in severe malaria resulting in a mean MCL that is half that found previously in healthy Thai volunteers (89.6 +/- 13.1 days, p less than 0.001) and significantly shorter than that reported previously in Thai patients with uncomplicated P. falciparum infections studied after parasite clearance (56.8 +/- 10.2 days, p less than 0.05).

Adolescent↗
PubMed1991

Calcium and phosphate metabolism in acute falciparum malaria.

1. Mineral homeostasis was investigated in 172 Thai adults with acute falciparum malaria at presentation (87 males, 85 females; mean age 30 years), and prospectively in a subgroup of 10 severely ill patients. 2. Mild, asymptomatic hypocalcaemia (corrected plasma calcium concentration 1.79-2.11 mmol/l) was found in 61 cross-sectional study patients (35.5%), with no difference between those with uncomplicated (2.16 +/- 0.10 mmol/l, mean +/- SD, n = 89) and severe (2.18 +/- 0.15 mmol/l, n = 83, P = 0.36) infections. Six prospectively studied patients were hypocalcaemic during treatment; simultaneous serum intact parathormone concentrations were inappropriately low (less than 5.0 pmol/l), but rose in three patients to high levels (11.8-16.4 pmol/l) on the fifth day. 3. Plasma phosphate concentration was decreased (less than 0.80 mmol/l) on admission in 74 patients (43.0%) and increased (greater than 1.45 mmol/l) in 15 (8.7%). Severe phosphate depletion (plasma phosphate concentration less than 0.30 mmol/l) occurred in 14 patients, of whom 11 had severe infections. Serum phosphate concentrations in the prospective study patients on admission (0.59 +/- 0.23 mmol/l) correlated significantly with the simultaneous renal threshold phosphate concentration (0.68 +/- 0.33 mmol/l; r = 0.607, P less than 0.025) and both parameters rose in parallel during treatment. 4. Plasma magnesium concentrations were normal (0.75-1.05 mmol/l) in 108 patients (62.8%); 45 cases (26.1%) had hypermagnesaemia and 19 (11.0%) had hypomagnesaemia. 5. These data suggest that mild hypocalcaemia is common in malaria regardless of disease severity; a depressed parathormone response may contribute. Despite malaria-associated haemolysis, hypophosphataemia is also common, but can be severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

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

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.

Acute Disease↗
PubMed1991

Clinical correlates of in vitro Plasmodium falciparum cytoadherence.

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.

Adult↗
PubMed1991

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

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.

Acute Disease↗
PubMed1991

Cortical bone metastases.

The bone scans and radiographs of 27 patients with solitary or multiple cortical bone metastases were retrospectively studied. Thirty-six cortical metastases were identified in 32 appendicular long bones. Origin of the tumors included lung, breast, kidney, pancreas, larynx, uterus, and site unknown. Cortical metastases have hitherto been reported as individual cases or in small numbers. The large number reported herein suggests that the occurrence of these lesions may be more common than previously expected. A cortical metastasis was the only evidence of metastatic disease in eight of the 27 patients.

Aged↗
PubMed1991

Peripheral gangrene in nonfatal pediatric cerebral malaria: a report of two cases.

Two Thai girls aged 10 and 13 years from the same rural area were admitted to Paholpolpayuhasena Hospital, Kanchanaburi, Thailand during the rainy season of 1989 with cerebral malaria. After several days of conventional treatment, both developed gangrene involving the feet and toes, but the lesions healed and no other complications were seen. In the absence of convincing clinical and laboratory evidence of vasculitis or coagulopathy, it seems likely that host factors (dehydration, sluggish peripheral circulation, platelet activation, subclinical intravascular coagulation) combined with strain-specific parasite factors (tissue sequestration of mature forms, rosette formation) may predispose to peripheral microvascular occlusion sufficient to produce infarction of tissue in susceptible children. However, despite the apparently ominous appearance of such lesions in a comatose child, the prognosis seems good.

Adolescent↗