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Biomedical subjects

S Niazi

Publications and source records attributed to S Niazi.

At least 19 recordsLinked to original sources

Long-term outcome and objective changes of anorectal function after biofeedback therapy for faecal incontinence.

BACKGROUND: In the short-term, biofeedback therapy improves symptoms and anorectal function in patients with faecal incontinence but whether there is long-term improvement is incompletely understood. AIM: To prospectively evaluate bowel symptoms and anorectal function, both immediately and 12 months after biofeedback therapy. METHODS: A total of 105 consecutive patients (male/female = 12/93) with faecal incontinence, unresponsive to supervised medical treatment were enrolled in biofeedback training consisting of biweekly pelvic muscle strengthening exercises, anal squeeze and sensory-motor coordination training, and reinforcement sessions at 3, 6 and 12 months. Anorectal manometry, saline continence test, stool diaries and bowel satisfaction scores were used to assess improvement. RESULTS: 94/105 (male/female = 10/84) completed training and 11 dropped out. Sixty completed 1-year assessment. At 1-year, 63% reported no episodes of incontinence. Biofeedback decreased (P < 0.001) stool frequency and number of incontinence episodes and increased (P < 0.001) bowel satisfaction score, anal resting and squeeze pressures, squeeze duration and ability to retain saline infusion increased (P < 0.001), both immediately and at 1 year. Sensory thresholds decreased (P < 0.001). CONCLUSIONS: Biofeedback therapy produced sustained improvement in bowel symptoms and anorectal function. Because it is safe, inexpensive compared with other surgical interventions, and effective, biofeedback should be offered to incontinent patients unresponsive to medical therapy.

Adolescent↗

The gene for cherubism maps to chromosome 4p16.

Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of approximately 22 cM.

Adolescent↗

Influence of water deprivation on the disposition of paracetamol.

The effect of acute (96 h) water deprivation on the disposition of paracetamol (acetaminophen) has been examined in male Sprague-Dawley rats. Plasma and urinary concentrations of the drug and its two major metabolites, the glucuronide and sulphate, were determined by a sensitive and specific high performance liquid chromatographic assay. Following an intravenous dose of 100 mg kg-1 of paracetamol, no significant changes were found in the elimination rate constant (k), the mean residence time (MRT), total plasma clearance (Cl) and the apparent volume of distribution at steady-state (Vss). However, rats deprived of water for 96 h excreted a larger percentage of the administered dose as the glucuronide conjugate (15.3 vs 7.9%) and a smaller percentage as unchanged paracetamol (7.3 vs 20.7%) in the urine. In addition, there was a significant two-fold increase in the partial metabolic clearance to paracetamol glucuronide. Water deprivation also led to a significant reduction in the renal clearance of paracetamol accompanied by an increase in the renal clearance of the glucuronide.

Acetaminophen↗

Influence of short-term water deprivation on antipyrine disposition.

The effects of acute (96 h) water deprivation on the disposition kinetics of antipyrine and hepatic cytochrome P-450 content were investigated in male rats. The disposition kinetics of antipyrine in rats deprived of water for 96 h was altered significantly: the total body clearance and steady-state volume of distribution decreased by 27.1 and 22.4%, respectively, as compared to control rats. There was no significant change in the disposition rate constant as a result of simultaneous changes in the volume of distribution and clearance. There was a 51.4% decrease in the hepatic cytochrome P-450 content in water-deprived rats. These results suggest that the pharmacokinetic changes observed in acute water deprivation with a model drug, antipyrine, are related to a decrease in total body water and to a reduced amount and/or activity of the hepatic microsomal oxidative enzymes.

Animals↗

Unbound plasma salicylate concentration in rheumatoid arthritis patients.

This study was designed to investigate the relationship of free plasma salicylate to total plasma salicylate and to determine the clinical utility of monitoring the free plasma salicylate concentration. Analysis of 46 patient samples indicated a close correlation between the free and total plasma concentration and that there is no additional advantage to monitoring the free plasma salicylate concentration. Also this study re-emphasizes the unique pharmacokinetic characteristics of salicylate, whereby the amount of free plasma salicylate increases disproportionately with increased total plasma salicylate concentration.

Adult↗

High-performance liquid chromatographic determination of aspirin and its metabolites in plasma and urine.

A simple quantitative method for the rapid determination of aspirin and its metabolites, salicylic acid, salicyluric acid, and gentisic acid, in plasma and urine using o-toluic and o-anisic acids, respectively, as internal standards was developed. Plasma proteins were precipitated by the addition of acetonitrile and, after centrifugation, the supernatant fluid was injected directly onto a reverse-phase column. The mobile phase consisted of an isocratic mixture of water, methanol, and glacial acetic acid (64:25:1, v/v/v) and the separated components were detected at 238 nm using a UV detector. Concentrations greater than or equal to 0.5 microgram/ml could be quantitated for aspirin or its metabolites in plasma. The peak heights and peak height ratios to the internal standard, o-toluic acid, were linear for the concentration range of 0.5-200 micrograms/ml. The aspirin metabolites in urine were isolated by extracting the acidified urine with either and then reextracting the material into an aqueous buffer solution at pH 7.0. Twenty microliters of the buffer extract was directly injected onto the column. The separated components were detected and quantitated at 305 nm. Concentrations greater than or equal to 5 micrograms/ml of salicyluric acid, salicylic acid, and gentisic acid could be determined accurately. The peak heights and peak height ratios to the internal standard, o-anisic acid, were found to be linear for the concentration range of 5-200 micrograms/ml in urine.

Animals↗

Stability of aspirin in different media.

Aspirin rapidly hydrolyzes in various aqueous, organic, and biological media. The purpose of this investigation was to study the decomposition of aspirin in the media that comes in contact with it during analysis in biological fluids for pharmacokinetic studies. These media included water, water-polyethylene glycol 400, water-methanol-acetic acid, phosphate buffer, freshly drawn blood and plasma from control rats and rats deprived of water for 36 hr, and blood precipitated with acetonitrile. Studies were also conducted to determine the decomposition as a function of temperature and pH. Of the various solvent systems studied, aspirin was found most stable in water-polyethylene glycol (4:1, v/v),which provides an excellent medium for preparation of intravenous dosage forms. Phosphate buffer showed significant catalysis of aspirin hydrolysis. A more than fivefold increase in the hydrolysis of aspirin was noted when the temperature was raised to 37 degrees from 22.5 degrees. The hydrolysis of aspirin in rat blood was 13 times faster than that in plasma, with an average half-life in blood of approximately 13 min. This creates significant problems in aspirin disposition kinetic studies. Mixing the blood sample immediately after collection with twice the volume of acetonitrile and thn en centrifuging gives a plasma-acetonitrile mixture in which no lysis of blood cells is observed.

Animals↗

Simple reliable method for chronic cannulation of the jugular vein for pharmacokinetic studies in rats.

A simple method for the preparation and implantation of silicone cannulas into the rat jugular vein is described. The implanted cannula can be used to administer drugs and collect blood samples at intervals of less than or equal to 1 min without causing stress to the animal. If necessary, the animals can be exsanuinated within a few minutes using this cannula. With proper maintenance, the cannula is patent for weeks and could be used for repeated and crossover studies.

Animals↗

Effect of water deprivation on aspirin disposition kinetics.

Temporary water deprivation results in serious stress causing significant physiological, hormonal, and enzymatic changes in the body which can affect the disposition kinetics, toxicity, and activity of drugs. This study attempts to recognize the effect of water deprivation on drug disposition kinetics using aspirin. No significant effects were noted following 36-hr water deprivation in rats on the metabolism of aspirin; there was also no effect of heparinization on aspirin disposition kinetics. The disposition of salicylic acid, however, was altered significantly, with the half-life increased by approximately 72% concomitant with decreased total body clearance. The effect of two dose levels, 5 and 10 mg/kg, was also studied to elucidate nonlinearity in the disposition kinetic model. Almost complete urinary recovery of aspirin was obtained in the intact form or as metabolites. At the 10-mg/kg dose, the fraction of salicyluric acid excreted decreased significantly compared with the 5-mg/kg dose. However, the effect of water deprivation was uniform at the two dose levels without any effect on the excretion of salicyluric acid. It is suggested that, in view of the significant changes in the disposition characteristics of salicylates with water deprivation, due care must be exercised in adjusting doses giving proper consideration to body hydration levels.

Animals↗

Comparative pharmacokinetics of butylated hydroxyanisole and butylated hydroxytoluene in rabbits.

The widespread use of butylated hydroxyanisole (I) and butylated hydroxytoluene (II) as food antioxidants recently has been criticized by the Food and Drug Administration because of their pharmacological and toxicological effects. Interest also has arisen recently in the use of these compounds as anticancer agents. The purposes of this study were to evaluate the pharmacokinetics of I and II in rabbits and to compare their physicochemical properties with their disposition kinetics. It was found that I has a disposition half-life of approximately 1 hr, compared to 11 days for II. These differences are explained in terms of their lipid solubility and protein binding characteristics.

Animals↗

GLC determination of butylated hydroxyanisole in human plasma and urine.

A highly sensitive and specific GLC method was developed for the analysis of butylated hydroxyanisole, a commonly used antioxidant. Concentrations below 100 ng/ml could be detected in human plasma and urine. Preliminary pharmacokinetic studies demonstrated that, upon administration of 100 mg po, butylated hydroxyanisole was quickly absorbed and removed from the plasma with a high degree of intersubject variability.

Adult↗

Thermodynamics of mercaptopurine dehydration.

The hydrate form of mercaptopurine was shown to undergo peritectic decomposition of its water molecule, localized dissolution, and dehydration around 125 degrees. The anhydrate form was prepared by a thermal method, whose effectiveness was confirmed by X-ray diffraction, NMR spectroscopy, and differential scanning calorimetry. The activation energy for mercaptopurine dehydration calculated by various methods ranged from 45.74 to 63.04 kcal/mole. The dehydration enthalpy was calculated to be 8.27 kcal/mole by differential scanning calorimetry. The solution enthalpy for the hydrate was calculated to be 4.85 kcal/mole from its saturation solubility and differential scanning calorimetry. Anhydrate solubility in water was calculated based on initial dissolution rate data since the anhydrate converts to hydrate in aqueous media. The high degree of stability against interconversion of the hydrate and anhydrate forms and the higher solubility of the anhydrate suggest that use of the anhydrate might improve mercaptopurine bioavailability.

Desiccation↗

Binding of butylated hydroxyanisole to human albumin using a novel dynamic method.

To study the interaction of butylated hydroxyanisole with various body tissues, a fully automated dynamic method was developed for the determination of plasma protein binding constants at 37 degrees, using membrane filtration equipment designed for dissolution rate studies. Appropriate equations were derived for the calculation of the free drug concentration from comparative diffusion rates across sealed dialysis sacs. A monoexponential equation described the diffusion in the absence of proteins, and a biexponential equation was fitted to diffusion from the drug-protein complex. The Scatchard and double-reciprocal plots were developed for butylated hydroxyanisole. A high degree of reproducibility was obtained for the calculation of protein binding constants (K = 2.4 - 2.9 X 10(4) and n = 1.4 - 1.32). The magnitude of these binding-constants suggests that any change in protein binding can have a significant effect on the distribution of butylated hydroxyanisole throughout the body, such as may be brought about by the common variations in the amount ingested.

Anisoles↗