Biomedical subjects
Publications and source records attributed to B Khan.
Three cases of Brucella endocarditis with aortic root abscess are reported. Two patients were successfully managed by a combination of medical therapy and surgery. The third patient died suddenly 36 hours after admission to hospital.
To study potential effects of hepatic cholesterol concentration on secretion of very-low-density lipoprotein (VLDL) by the liver, male rats were fed on unsupplemented chow, chow with lovastatin (0.1%), or chow with lovastatin (0.1%) and cholesterol (0.1%) for 1 week. Livers were isolated from these animals and perfused in vitro, with a medium containing [2-14C]acetate, bovine serum albumin and glucose in Krebs-Henseleit buffer, and with an oleate-albumin complex. With lovastatin feeding, the hepatic concentrations of cholesteryl esters and triacylglycerols before perfusion were decreased, although free cholesterol was unchanged. However, hepatic secretion of all the VLDL lipids was decreased dramatically by treatment with lovastatin. Although total secretion of VLDL triacylglycerol, phospholipid, cholesterol and cholesteryl esters was decreased, the decrease in triacylglycerol was greater than that in free cholesterol or cholesteryl esters, resulting in secretion of a VLDL particle enriched in sterols relative to triacylglycerol. In separate studies, the uptake of VLDL by livers from control animals or animals treated with lovastatin was measured. Uptake of VLDL was estimated by disappearance of VLDL labelled with [1-14C]oleate in the triacylglycerol moiety, and was observed to be similar in both groups. During perfusion, triacylglycerol accumulated to a greater extent in livers from lovastatin-fed rats than in control animals. The depressed output of VLDL triacylglycerols and the increase in triacylglycerol in the livers from lovastatin-treated animals was indicative of a limitation in the rate of VLDL secretion. Addition of cholesterol (either free cholesterol or human low-density lipoprotein) to the medium perfusing livers from lovastatin-fed rats, or addition of cholesterol to the diet of lovastatin-fed rats, increased the hepatic concentration of cholesteryl esters and the output of VLDL lipids. The concentration of cholesteryl esters in the liver was correlated with the secretion of VLDL by the liver. These data suggest that cholesterol is an obligate component of the VLDL required for its secretion. It is additionally suggested that cholesteryl esters are in rapid equilibrium with a small pool of free cholesterol which comprises a putative metabolic pool available and necessary for the formation and secretion of the VLDL. Furthermore, the specific radioactivity (d.p.m./mumol) of the secreted VLDL free cholesterol was much greater than that of hepatic free cholesterol, suggesting that the putative hepatic metabolic pool is only a minor fraction of total hepatic free cholesterol.
We previously reported isolation of DNA probe which specifically recognizes Plasmodium falciparum and developed a simple method for its use. The sensitivity and specificity of this DNA probe method have now been extensively field tested in comparison with those of conventional microscopic examination of blood films in two separate studies in Malindi, Kenya, involving a total of 1179 patients. In the second study, which used improved techniques, sensitivity of the DNA probe was 89% when compared to microscopy. We conclude that the DNA probe method compares favorably with conventional microscopy in detecting parasite densities as low as 25 parasites per microliter of blood. A significant advantage of the DNA probe method is that it utilizes a standardized procedure which can simultaneously and reproducibly analyze a large number of samples without opportunity for significant reader bias.
Administration of lovastatin to male, Sprague-Dawley rats by addition of the drug to the normal chow diet caused a two-fold increase in the activity of the hepatic mitochondrial outer carnitine palmitoyltransferase, but lovastatin apparently did not affect the sensitivity of the outer carnitine palmitoyltransferase to inhibition by malonyl-CoA. There was also no effect of lovastatin on the activity of the hepatic mitochondrial inner carnitine palmitoyltransferase. Feeding of cholestyramine to rats did not affect either the mitochondrial outer carnitine palmitoyltransferase or the mitochondrial inner carnitine palmitoyltransferase.
58 children aged 1 to 10 years who had pure Plasmodium falciparum infections acquired on the coast of Kenya were treated with chloroquine 25 mg/kg given over 3 d and erythromycin 10 mg/kg 4 times a day given for 7 d. After 4 weeks follow-up, 62% had recurrent infections and 11% failed to clear their parasitaemia (1 had an RIII pattern of resistance). Of 38 children treated with chloroquine 25 mg/kg alone, 55% had recurrences and 21% failed to clear (including 1 RIII). In vitro microtests classified 74% of isolates from initial infections and 91% of isolates from recurrent infections as resistant. Erythromycin does not improve chloroquine treatment in children with infections due to P. falciparum having low to moderate levels of chloroquine resistance.
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Due to increased chloroquine resistance, the antifolate/sulpha drug combinations are becoming increasingly important in the chemotherapy of falciparum malaria. However, point mutations in the dihydrofolate reductase gene lead to resistance to the antifolate drugs. We therefore investigated the prevalence of the 6 reported point mutations in this gene among field isolates of Plasmodium falciparum from Kenya, to determine if the mutations correlated with resistance to pyrimethamine and the biguanides cycloguanil and chlorcycloguanil. We used a mutation-specific polymerase chain reaction technique to test for these reported mutations in 21 Kenyan isolates and 4 reference lines. We also amplified and directly sequenced the dihydrofolate reductase coding sequence from these parasites to confirm the results and test for other possible mutations. Of the reported mutations, we found S108N, which is the central mutation of pyrimethamine resistance, and mutations N51I and C59R, which modulate the levels of resistance and may confer decreases in response to cycloguanil that are folate and p-aminobenzoic acid dependent. No isolate possessed the paired point mutations S108T and A16V, or I164L and S108N, which have been associated with cycloguanil resistance in previous studies. These results provided supportive evidence for the combined use of a cycloguanil-class drug (e.g., chlorproguanil) and a sulpha drug (e.g., dapsone) against P.falciparum malaria in Kenya.
A randomized 14-day study in vivo compared the response of Plasmodium falciparum malaria to amodiaquine (35 mg/kg) and sulfadoxine-pyrimethamine (sulfadoxine, 25 mg/kg) in symptomatic outpatients at 2 sites in northern and western Kenya during 1993. Of the 239 patients recruited, 181 (76%) completed the study [84 (46%) on amodiaquine and 97 (54%) on sulfadoxine-pyrimethamine]. There were no significant differences in the parasitological, clinical or haematological responses between the 2 drug groups in both areas, with 18.5% resistance to amodiaquine versus 9.5% for sulfadoxine-pyrimethamine in the north and 35.1% against amodiaquine versus 34.5% for sulfadoxine-pyrimethamine in the west. In both sites defervescence was significantly more rapid with amodiaquine (P < 0.05) and true clinical failure (symptomatic illness with recurrent parasitaemia) was unusual (9%). As high-level resistance to chloroquine is widespread, both drugs are valuable alternatives. However, the significantly higher levels of resistance in the west may be a sign of the increased drug pressure in this holoendemic area and send an important warning concerning resistance to sulfadoxine-pyrimethamine.
BACKGROUND: Although upper gastrointestinal endoscopy is generally a safe procedure, it is known to be associated with arterial oxygen desaturation, resulting in rare serious cardio-pulmonary events. OBJECTIVE: To determine the severity of oxygen desaturation during nonsedated upper gastrointestinal endoscopy and study the effect of various variables on oxygen saturation. METHODS: 126 patients underwent nonsedated upper gastrointestinal endoscopy (82 diagnostic, 44 therapeutic). Arterial oxygen saturation (SaO2) was monitored using a pulse oximeter. RESULTS: Baseline SaO2 was mean (SD) 97.8 (1.8%). It remained > 95% in 60.2% of patients during the procedure, whereas mild oxygen desaturation (SaO2 90%-94%) occurred in 23.7% and severe oxygen desaturation (SaO2 < 90%) occurred in 15.8% of patients. Six patients (4.7%) required supplemental oxygen administration sometime during the procedure. Desaturation occurred in patients undergoing diagnostic and therapeutic procedures but was severe in the latter group (p < 0.002). Patients aged more than 60 years (p < 0.001), hemoglobin < 10 g/dL (p < 0.001), history of smoking (p < 0.001), and underlying chronic obstructive airway disease (p < 0.001) were significantly related to oxygen desaturation. However, on multivariate analysis, no significant correlation was observed with hemoglobin value. CONCLUSION: Therapeutic intervention during nonsedated upper gastrointestinal endoscopy, old age, smokers and chronic obstructive airways disease are independent risk factors for oxygen desaturation. We recommend continuous monitoring of SaO2 in these high-risk patients undergoing upper gastrointestinal endoscopy.
BACKGROUND: Pre-operative tissue diagnosis with colonoscopy is not always possible in patients with colonic lesions. OBJECTIVE: To study the usefulness and efficacy of percutaneous ultrasound-guided aspiration biopsy of colonic lesions. METHODS: Fifty consecutive patients with colonic lesions in whom colonoscopic brush cytology and biopsy were either negative or the lesion was not accessible on colonoscopy on two attempts, underwent percutaneous ultrasound-guided fine-needle aspiration biopsy. The results were compared with surgical findings. RESULTS: Fine-needle aspiration biopsy revealed adenocarcinoma in 40 patients; one had lymphoma, 2 had tuberculosis, 2 had abscess and 5 patients had negative aspiration. Forty-eight patients (excluding 2 with tuberculosis) underwent laparotomy and the diagnoses on aspiration biopsy were confirmed. Of the 5 negative aspirations, 3 had adenocarcinoma, one had tuberculosis and one intussusception. Thus, we had sensitivity of 91.8%, specificity of 100%, predictive value of positive results 100%, predictive value of negative results 20%, and percentage of false negative results 8.1%. Two patients developed complications--hemorrhage into the peritoneum and sepsis due to perforation at the site of aspiration; both survived after surgery. CONCLUSION: Percutaneous ultrasound-guided aspiration biopsy may be attempted for diagnosis of colonic lesions in situations where it may be the only means of obtaining a cytological diagnosis before surgery.