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Biomedical subjects

A El-Yazigi

Publications and source records attributed to A El-Yazigi.

8 recordsLinked to original sources

Water contamination and esophageal cancer at Gassim Region, Saudi Arabia.

Between January 1980 and December 1982, 183 patients with histologically confirmed carcinoma of the esophagus who were referred to a tertiary referral hospital were studied. Thirty-two (17%) patients were referred from Gassim Region at the north central part of Saudi Arabia. In contrast, only 5% of total cancer patient referrals were from this area. A case-control study showed a significant regional difference within Saudi Arabia and the most referrals from Gassim area. A prospective case-control study showed persistently high numbers of referrals from that region during 1983-1987. When patients from Gassim Region were compared with those referred from other locations, no statistical differences were noted between the two groups except for the source of drinking water. Water analysis from Gassim area showed a high solid content with elevated levels of calcium, magnesium, and to a lesser extent, chromium iron, cadmium, and cobalt. Traces of petroleum oil were found in five of six water samples from Gassim during 1983, compared with 3 of 49 samples from other areas. Mutagenicity tests on water specimens form Gassim Region indicated the presence of possible carcinogens. It is being suggested that the high prevalence of esophageal cancer in this region may be related to contamination of water by impurities such as petroleum oils. Malnutrition, particularly vitamin A deficiency, as well as other factors may have promoted such malignancies.

Age Factors

Capillary gas chromatography and thermionic N-P-specific detection of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in stability and pharmacokinetic studies.

An expedient, rapid, and sensitive capillary gas chromatographic method for the analysis of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in plasma is described. Separation of the underivatized nitrosourea compounds was performed on a 0.33-mm-i.d., 25-m fused-silica, SE-30 capillary column, and detection was carried out using a thermionic N-P-specific detector. The compounds were extracted from plasma with benzene with a yield of greater than 87%. The assay was linear in the ranges of 0.001 to 0.5 and 0.5 to 25 micrograms/ml for CCNU or 0.003 to 0.50 and 0.5 to 25 micrograms/ml for BCNU, with correlation coefficients from 0.9914 to 0.9999 and coefficients of variation (CV) of less than 3.3%. Other antineoplastic agents did not interfere in the assay. The method was employed to study the pharmacokinetics of BCNU in rabbits. The plasma concentration-time curves were fit to a two-compartment model with a mean (SE) alpha, beta, and total-body clearance of 2.898 (0.913) hr-1, 0.1228 (0.0179) hr-1, and 7.211 (2.862) liters/hr.kg, respectively. Further, the stability of BCNU and CCNU in solution was examined at different temperatures. Both compounds were stable in benzene or acetone (4 to 37 degrees C) but labile in plasma even if refrigerated. The apparent rate constants for degradation of BCNU and CCNU were 0.09921 and 0.02853 hr-1 at 4 degrees C and 5.998 and 2.553 hr-1 at 37 degrees C, respectively.

Animals

Analysis of oxprenolol in formulations by high-performance liquid chromatography.

A simple, accurate, and rapid high-performance liquid chromatographic method for the analysis of oxprenolol in commercial formulations is described. The analysis was performed on a cyano radial compression cartridge, with 0.0539 M, pH 3 phosphate buffer-acetonitrile-methanol (76: 15.6:8.4) as the mobile phase. The flow rate was 5 mL/min, with detection at 272 nm; the mobile phase was employed for extraction. The assay was applied to the content uniformity test of three oxprenolol hydrochloride tablet formulations of different strengths and the contents of a 2-mg dry ampule for intravenous/intramuscular injection. The percent of label claim for each formulation tested was within 91.7-110%. The applicability of this assay to the analysis of some other beta-blocking drugs was investigated. It was found that under the above conditions, atenolol, metoprolol, oxprenolol, and propranolol can be fully resolved in less than 3 min.

Adrenergic beta-Antagonists

Concentrations of Ag, Al, Au, Bi, Cd, Cu, Pb, Sb, and Se in cerebrospinal fluid of patients with cerebral neoplasms.

We measured the concentrations of nine trace elements in cerebrospinal fluid of 11 patients with malignant brain tumors, 11 with benign brain tumors, and 10 control patients, using flameless atomic absorption spectrophotometry. The mean and standard deviation for these concentrations (microgram/L) in the control group were 5.1 +/- 2.9 (silver), 326.6 +/- 171.2 (aluminum), 38.5 +/- 32.2 (gold), 36.6 +/- 23.7 (bismuth), 1.5 +/- 1.3 (cadmium), 39.8 +/- 24.7 (copper), 15.7 +/- 11.5 (lead), 20.9 +/- 3.8 (antimony), and 19.1 +/- 13.3 (selenium). Concentrations of silver and lead were markedly increased in patients with malignant cerebral neoplasms. The malignant-tumor/control patient concentration ratios were 2.31 for silver and 2.11 for lead. We observed no significant differences between the results for the benign tumor patients and the control group.

Adolescent

Simple methods for estimating percent disintegrated--time data.

Two techniques are described for the treatment of dissolution rates to estimate the percent disintegrated--time data for tablets and capsules. The first is an extension of an equation derived previously with the assumption of first-order disintegration and dissolution processes; whereas, the second involves the determination of the rate constant from the terminal segment of the curve and the use of numerical derivatives according to a disintegration kinetics-independent approach. The dissolution data of six commercial tablet and capsule formulations were treated according to the described techniques. Good agreement was found between the percent disintegrated--time data estimated by the second approach for an acetaminophen tablet and those obtained by a well-established model where a Weibull function was employed.

Acetaminophen

Theophylline absorption and disposition in rabbits: oral, intravenous, and concentration-dependent kinetic studies.

Theophylline pharmacokinetics following oral and intravenous administration were studied, and the absolute bioavailability of five commercially available products was determined using the rabbit as an in vivo model. Concentration-dependent clearance studies were performed by multiple constant-rate infusion and multiple bolus dose administration of aminophylline. Theophylline pharmacokinetics following the oral administration of these products obeyed the one-compartment open model adequately. However, the data obtained following rapid intravenous aminophylline administration in the rabbit fit either the one-compartment model (half-life = 2.8 hr and the volume of distribution = 4.4 hr and Vd(beta) = 0.708 liter/kg). There were no significant product-to-product differences in the time to peak (tmax), the rate constant of absorption (ka), or the percent of dose absorbed at 1 hr (F1); however, differences in the absolute bioavailability (F), dose-normalized peak serum concentration (Cmax(n)), and percent of dose absorbed at 6 hr (F6) were significant. There was no evidence of concentration-dependent clearance for theophylline in the rabbit in the serum concentration range studied, but the results of the multiple constant-rate infusion study suggest that total clearance decreases at higher serum theophylline concentrations.

Absorption

Disintegration-dissolution analysis of percent dissolved-time data.

A simple, graphical method is described for the disintegration--dissolution analysis of cumulative percent dissolved--time data. The technique is based on a biexponential equation with the assumption of first-order disintegration and dissolution according to a simple dissolution model. The dissolution data obtained for six commercial tablets and capsules adequately fit the developed equation. The described method is simple and can handle initial data points that are usually ignored by other techniques.

Capsules

Khellin determination in human serum and urine by high-performance liquid chromatography.

A rapid, sensitive, and specific high-performance liquid chromatographic method was developed for the determination of khellin in serum and urine using theophylline as the internal standard. Chromatography was performed on a reversed-phase C18 column with 65% (v/v) methanol as the mobile phase. The assay is capable of measuring khellin concentrations down to 100 ng/ml with a total procedure time of less than 20 min. Oral administration of 60 mg of khellin tablets to two healthy human males was carried out, and the serum samples were analyzed by the described method. Serum concentration-time profiles are presented.

Chromatography, High Pressure Liquid