Pulmonary manifestations of uncomplicated falciparum and vivax malaria: cough, small airways obstruction, impaired gas transfer, and increased pulmonary phagocytic activity.
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Despite recognition of acute respiratory distress syndrome in both falciparum and vivax malaria, disease-related changes in pulmonary function have not been defined, and underlying mechanisms are not well understood. Respiratory symptoms, pulmonary function, pulmonary phagocytic cell activity, and longitudinal changes were examined in 26 adults with uncomplicated falciparum, vivax, and ovale malaria after treatment. Self-limiting cough occurred in both falciparum (36%) and vivax or ovale (53%) malaria. In infection with each malaria species, admission measures of airflow and gas transfer were lower than predicted, and mean lung (99m)technetium-sulfur-colloid uptake was significantly increased. Changes were most evident in falciparum malaria, with treatment resulting in initial worsening of airflow obstruction and gas transfer. Altered pulmonary function in malaria is common and includes airflow obstruction, impaired ventilation, impaired gas transfer, and increased pulmonary phagocytic activity, and its occurrence in both vivax and falciparum malaria suggests that there may be common underlying inflammatory mechanisms. (+info)
In vivo evaluation of 99mTc-DTPA and 99mTc-sulphur colloid as tracers in colonic drug delivery systems using gamma scintigraphy in volunteers.
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PURPOSE: The suitability of 99mTc-diethylenetriaminepenta- acetic acid (DTPA) and 99mTc-sulphur colloid (99mTc-SC) as tracers in gamma scintigraphy for the evaluation of colon-specific drug delivery systems was assessed in healthy volunteers. METHOD: Sodium chloride core tablets containing either 99mTc-DTPA or 99mTc-SC were prepared and compression coated with two different quantities of guar gum. The compression-coated tablets were subjected to gamma scintigraphic studies for colonic drug delivery in healthy human volunteers. RESULTS: The tablets containing 99mTc-DTPA did not release the tracer in stomach and small intestine, and on entering the colon disintegrated completely whereas the tablets containing 99mTc-SC remained intact in stomach, small intestine and in colon as well. The study showed that DTPA is a suitable tagging agent for 99mTc in the evaluation of guar gum based colonic drug delivery systems containing water-soluble drugs. CONCLUSION: In the present investigation guar gum was applied externally as a compression coat over the radiolabelled core. Since the core consisted of water-soluble material (sodium chloride), it is possible that the release of the tracer from the 99mTc-DTPA containing formulations is a combined effect of enzymatic action and diffusion of the salt. The failure of disintegration of 99mTc-SC containing formulations might be due to its interference with the disintegration or the part diffusion observed with 99mTc-DTPA cores. The results of the study showed that DTPA is a suitable tagging agent for 99mTc in the evaluation of colonic drug delivery systems containing water-soluble drugs by gamma scintigraphy. (+info)
Lung clearance of 99mTc-DTPA in systemic lupus erythematosus.
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The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99mTc-DTPA is increased in SLE patients with active disease. (+info)
A Bayesian regression model for plasma clearance.
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Nonlinear Bayesian regression permits curve fitting to a group of subjects simultaneously rather than individually. We evaluated this approach for interpreting plasma clearance curves with the goal of reducing curve-fitting failures and dealing objectively with problem datasets that may arise in clinical settings. METHODS: (99m)Tc-Diethylenetriaminepentaacetic acid plasma clearance curves from 79 subjects were analyzed. The data typically comprised 7-9 samples obtained from 5-10 to 180-240 min after injection. A 2-compartment model was fitted by Bayesian regression to yield compartmental hyperparameters V1, L21, and L12 corresponding to the volume of the compartment into which tracer was injected and the transfer rates from compartment 1 to compartment 2 and from compartment 2 to compartment 1, respectively. This also yielded a clearance estimate for each subject. RESULTS: Estimated hyperparameters were V1 = 8.9 L, L21 = 0.026 min(-1), and L12 = 0.040 min(-1). Conventional methods led to fitting failures in 2 of the 79 subjects but there were no failures with the Bayesian method. The hyperparameters were used to calculate the glomerular filtration rate for each subject from a single plasma sample with a root-mean-square error of 7.3 mL/min, which was not significantly different from the widely used Christensen-Groth formula. CONCLUSION: Fewer fitting failures were encountered than with conventional methods, offering an objective means of dealing with problem data. This conceptually simple model can be used directly to calculate clearance from a single plasma sample. It requires only the 3 parameters described above, whereas the Christensen-Groth method requires 6 parameters. (+info)
Liquid gastric emptying in the pig: effect of concentration of inhaled isoflurane.
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An animal model of gastric emptying may have use in the study of gastric physiology and pharmacoscintigraphy. The pig has anatomy and physiology similar to that of humans. Our aim was to develop a model of gastric emptying in the pig. It was not possible to perform this study in conscious pigs; therefore, an anesthetic model was developed. METHODS: Fifteen studies were performed on 4 pigs (age, 2-6 mo; weight, 20-100 kg). After acclimatization and training, pigs were fasted overnight before the study. Pigs were anesthetized using inhaled isoflurane without the use of injected premedication agents. An orogastric tube was inserted for the administration of a liquid meal, which consisted of (99m)Tc-diethylenetriaminepentaacetic acid either in water (nonnutrient) or with dextrose (nutrient meal). The pig was laterally positioned to enable right lateral dynamic acquisition to be performed. Anesthesia was maintained at 2% +/- 0.5% isoflurane in 4 studies and 0.8% +/- 0.5% in 11 studies (4 nutrient, 7 nonnutrient). RESULTS: With 2% +/- 0.5% isoflurane, there was delayed gastric emptying with a mean 50% emptying time (+/-SEM) of 141 +/- 14 min. With 0.8% +/- 0.5% isoflurane, the liquid meal emptied in an exponential manner similar to that of humans, with mean 50% emptying times (+/-SEM) of 30 +/- 7 min (nutrient) and 31 +/- 4 min (nonnutrient). CONCLUSION: The results indicate that high-dose anesthesia inhibits gastric emptying, but with low-dose anesthesia a useful pig model of liquid gastric emptying can be developed. (+info)
A comparison of bedside renal function estimates and measured glomerular filtration rate (Tc99mDTPA clearance) in cancer patients.
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BACKGROUND: The aim of this study was to compare measured glomerular filtration rate (GFR) with estimates of GFR derived from the population pharmacokinetic methods of Martin and Wright, and the creatinine clearance (CrCl) estimates of Cockcroft and Gault, and Jelliffe. PATIENTS AND METHODS: GFR was determined by technetium-99m diethyl triamine penta-acetic acid (Tc99DTPA) clearance in adult cancer patients. Height, actual body weight and serum creatinine were measured, and GFR and CrCl estimates calculated. RESULTS: One hundred and twenty-two patients were included. The mean measured GFR was 87 ml/min (range 30-174 ml/min). The mean bias (mean percentage error) was 2, 1, -10 and -17%, and the mean precision (mean absolute percentage error) was 18, 19, 21 and 23% for the Wright, Martin, Cockcroft and Gault, and Jelliffe formulas, respectively. The Martin formula significantly underestimates GFR for females (mean bias -10%) and overestimates GFR for males (mean bias 8%) (P <0.001 for bias of males versus females). The Wright and Martin formulas significantly overestimate GFR <50 ml/min (mean bias 39 and 30%; P = 0.03 and 0.05, respectively) and all formulas underestimate GFR >100 ml/min (mean bias -18, -16, -24 and -32% for Wright, Martin, Cockcroft and Gault, and Jelliffe formulas, respectively; P <0.001). CONCLUSIONS: All the assessed estimates for renal function were found to have significant limitations. (+info)
Pharmacokinetics and gamma scintigraphy evaluation of two enteric coated formulations of didanosine in healthy volunteers.
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AIMS: The aims of the study were to evaluate the bioavailability of didanosine from the encapsulated enteric coated beads (1 x 200 mg; enteric beads) and enteric coated mini-tablets (4 x 50 mg; enteric tablet) formulations relative to the chewable/dispersible buffered tablets (2 x 100 mg; buffered tablet), and to study their rate of gastrointestinal transit. METHODS: This was a single-dose, randomized, three-way crossover study in 18 healthy male volunteers. A 200 mg dose of didanosine was given in each period and each formulation contained a gamma radiation-emitting isotope. Pharmacokinetic parameters determined were Cmax, tmax, AUC(0, infinity ) and t1/2. Bioequivalence was assessed using the confidence interval (CI) of 0.80, 1.25 for Cmax and AUC(0, infinity ). Scintigraphic images were recorded and gastrointestinal transit profiles were generated. RESULTS: The point estimate and 90% CI of the ratio of Cmax for the enteric beads and enteric tablet relative to the buffered tablet was 0.71 (0.59, 0.85) and 0.55 (0.46, 0.66), respectively. The tmax was significantly different for the enteric beads (median, 1.33 h) and the enteric tablet (median, 2.83 h) than for the buffered tablet (median, 0.67 h). The AUC(0, infinity ) satisfied the bioequivalence criteria, and the point estimate and 90% CI of the ratio were 1.02 (0.91, 1.15) and 0.92 (0.82, 1.04) for the enteric beads and enteric tablet, respectively. The AUC(0, infinity ) values appeared to be less variable with the enteric beads (% CV = 19%) than with the enteric tablet (% CV = 33%). The t1/2 values were not significantly different between formulations, and the mean values ranged from 1.82 to 1.92 h. Inspection of the individual scintigraphy profiles and concentration-time curves suggested that didanosine was absorbed throughout the small intestine. Gastrointestinal transit parameters were higher for both enteric formulations than for the buffered tablet, indicating slower transit of the enteric formulations. Between the enteric formulations, gastric emptying was slower for the enteric beads than for the enteric tablet; however, plasma didanosine concentrations were observed sooner for the enteric beads, suggesting that the enteric coat for the beads dissolved more rapidly. CONCLUSIONS: The enteric beads and enteric tablet formulations of didanosine were equivalent to the buffered tablet in their extent of absorption. Although the gastric emptying of the enteric tablet was faster, based on the rapid uncoating and the lower variability in AUC, the enteric beads were chosen for further clinical development. (+info)
The mean transit time and functional image in asialoglycoprotein receptor scintigraphy: a novel modality for evaluating the regional dynamic function of hepatocytes.
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In this study, we attempted to evaluate the regional dynamic function of hepatocytes by introducing unique parameters in (99m)Tc-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99m)Tc-GSA) scintigraphy. (99m)Tc-GSA scintigraphy provides valuable information for the receptor population density. However, the conventional indices are the results of the analyses of 2 fixed points and, as a result, it is not possible to accurately estimate the regional dynamic function. METHODS: We performed (99m)Tc-GSA scintigraphy 100 times on a total of 54 pediatric patients. The average age at examination was 7.4 +/- 5.8 y. Ninety-one of the 100 scintigraphy cases were available for this study. We converted the time-activity curve for the liver of (99m)Tc-GSA to a horizontal mirror image curve, and, on the basis of the height-over-area method, calculated the mean transit time (MTT) in each pixel and depicted the functional image as unique parameters, which were thus compared with the conventional indices. For these parameters, we used the time-activity curve for only the liver. RESULTS: The whole liver MTT showed a significant correlation with both the clearance (y = 590.3x + 10.3; r = 0.51; P < 0.0001) and the receptor (y = -1,836.2x + 2,038.8; r = -0.66; P < 0.0001) indices. On the basis of the MTT in each pixel, we could depict the functional image of the liver. In actual clinical situations, the functional image was quite useful for making a visual evaluation of the dynamic distribution of (99m)Tc-GSA. The functional image indicated that, even at an extremely early stage of biliary atresia, the hepatic functional reserve might be exacerbated earlier in the right lobe than in the left lobe. CONCLUSION: The MTT and the functional image enable us to elucidate the regional dynamic function of hepatocytes both quantitatively and visually. In addition, this diagnostic modality can be used at virtually all medical institutions using a modified analytic program already in public use. (+info)