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Biomedical subjects

S Tawfik

Publications and source records attributed to S Tawfik.

14 recordsLinked to original sources
PubMed2006

Haemoglobin A1c (HbA1C) in non-diabetic and diabetic vascular patients. Is HbA1C an independent risk factor and predictor of adverse outcome?

BACKGROUND: Plasma Haemoglobin A1c (HbA1c) reflects ambient mean glycaemia over a 2-3 months period. Reports indicate that patients, with and without diabetes, with an elevated HbA1c have an increased risk of adverse outcome following surgical intervention. Our aim was to determine whether elevated plasma HbA1c level was associated with increased postoperative morbidity and mortality in patients undergoing vascular surgical procedures. METHODS: Plasma HbA1c was measured prospectively in 165 consecutive patients undergoing emergency and elective vascular surgical procedures over a 6-month period. Patients were categorized into four groups depending on whether their plasma HbA1c was < or =6%, 6.1-7%, 7.1-8% or >8% and clinical data was entered into a prospectively maintained database. Patients were also classified by diabetic status with suboptimal HbA1c in a patient without diabetes being >6 to < or =7% and suboptimal HbA1c in a patient with diabetes being >7%. Patients with plasma HbA1c >7% were reclassified as having undiagnosed diabetes mellitus. Composite primary endpoints were all cause 30-day morbidity and mortality and all cause 6-month mortality. Composite secondary endpoints were procedure specific complications, adverse cardiac events, stroke, infection and mean length of hospital stay. RESULTS: Of the 165 patients studied, 43 (26.1%) had diabetes and the remaining 122 (73.9%) did not. The mean age was 72 years and 59% were male. Suboptimal HbA1c levels were found in 58% patients without diabetes and in 51% patients with diabetes. In patients without diabetes those with suboptimal HbA1c levels (6-7%) had a significantly higher incidence of overall 30-day morbidity compared to patients with HbA1c levels < or =6% (56.5 vs 15.7%, p<0.001). Similarly, for patients with diabetes those with suboptimal HbA1c levels (HbA1c >7%) had a significantly higher incidence of 30-day morbidity compared to those with HbA1c levels < or =7% (59.1% vs 19%, p=0.018). Multivariate analysis revealed that a plasma HbA1c level of >6 to < or =7% was a significant independent predictor of overall 30-day morbidity in patients without diabetes undergoing vascular surgical procedures. No difference in mortality, composite secondary endpoints, procedure specific complications, stroke or mean length of hospital stay was observed between any of the groups in the study. CONCLUSION: Suboptimal HbA1c levels may hold prognostic significance in patients without diabetes undergoing vascular surgery.

Aged↗
PubMed2001

Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due to the mutations in the AIRE (autoimmune regulator) gene. APECED patients develop several autoimmune endocrine disorders and are characterized by the high titer autoantibodies to organ-specific antigens such as the steroidogenic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED patients of Eastern and Central European origins and one Egyptian patient. From 54 analyzed APECED chromosomes, eight mutations were detected, four of which (T16M, W78R, IVS1_IVS4, 30-53dup23bp) are novel. The most prevalent reason for APECED in these populations was the occurrence of R257X (36 chromosomes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogenic P450 cytochromes by the immunoblotting of E. coli expressed antigens in the 18 APECED patients showed that 67%, 44%, and 61% of the Eastern and Central European APECED patients had autoantibodies to P450c17, P450c21, and P450scc, respectively.

Autoantibodies↗
PubMed2001

Development of an Arabic battery for remediation of selective auditory attention disorder in children.

A battery of Arabic speech material was developed for remediation of selective auditory attention disorder (SAAD) in children and standardized on 40 normal children aged from 6 to 12 years. This battery included: the Word Intelligibility by Picture Identification (WIPI) test, newly developed sentences for speech discrimination in noise, bisyllabic words and monosyllabic words. The tests were recorded against a background noise of either multitalker babble or stories. Variables affecting the results of the new battery, namely age, type of speech material and type of background noise, were studied. A significant positive correlation was found between the age of the child and the test scores. The WIPI test was the easiest test, giving the highest scores. The monosyllabic words test was the most difficult, yet normal children gave mean scores around 92%. The type of background noise showed a non-significant effect on the test scores. Results of two cases with SAAD are also presented.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Ferrous sulphate interacts with captopril.

AIMS: To determine if iron binds strongly to captopril and reduces captopril absorption. METHODS: A variety of in vitro experiments was conducted to examine iron binding to captopril and a randomized, double-blind, placebo controlled, cross-over study design was used to assess the in vivo interaction. Captopril (25 mg) was coingested with either ferrous sulphate (300 mg) or placebo by seven healthy adult volunteers. Subjects were phlebotomized and had blood pressure measured at 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 12 h post ingestion. A 1 week washout period was used. RESULTS: The coingestion of ferrous sulphate and captopril was associated with a 37% (134 ng ml(-1) h, 95% CI 41-228 ng ml(-1) h, P = 0.03) decrease in area under the curve (AUC) for unconjugated plasma captopril. There were no substantial changes in Cmax (mean difference; -32; 95% CI -124-62 ng ml(-1) (P = 0.57)) or in tmax (mean difference; 0; 95% CI -18-18 min (P = 0.65)) for unconjugated captopril when captopril was ingested with iron. There was a statistically insignificant increase in AUC for total plasma captopril of 43% (1312 ng ml(-1) h, 95% CI -827-3451 ng ml(-1) h P = 0.27) when captopril was ingested with iron. The addition of ferric chloride to captopril resulted in the initial rapid formation of a soluble blue complex which rapidly disappeared to be replaced by a white precipitant. The white precipitate was identified as captopril disulphide dimer. There were no significant differences in systolic and diastolic blood pressures between the treatment and placebo groups. CONCLUSIONS: Co-administration of ferrous sulphate and iron results in decreased unconjugated captopril levels likely due to a chemical interaction between ferric ion and captopril in the gastrointestinal tract. Care is required when coprescribing captopril and iron salts.

Adult↗
PubMed1997

Effects of intravenous infusion of lidocaine on its pharmacokinetics in conscious instrumented dogs.

In this study, potential alterations in hepatic blood flow, plasma protein binding, hepatic tissue binding, and enzyme activities induced by LD iv infusion of lidocaine (LD) were evaluated using a chronically instrumented dog model. Four conscious female mongrel dogs (19.0-23.5 kg) were each given, on days 1 and 10, a 5-min infusion of a mixture of unlabeled LD at approximately 2 mg/kg and 14C-labeled LD at approximately 25 microCi and, on day 8, a 12-h constant rate iv infusion of LD (approximately 76 microg/kg/min). During LD infusion, there was a 11-79% increase in total hepatic blood flow, mainly due to a 1.6-9.2-fold increase in hepatic arterial flow. Despite similar blood clearance (27.5 +/- 6.0 mL/min/kg vs 27.5 +/- 3.5 mL/min/kg), volume of distribution at steady state (1.38 +/- 0.08 L/kg vs 1.36 +/- 0.17 L/kg), and free fraction values of LD between days 1 and 10 (p > 0.05), intrinsic clearance values were consistently reduced (1224 +/- 859 mL/ min/kg vs 285 +/- 104 mL/min/kg; p = 0.034). Furthermore, hepatic tissue uptake of LD and/or its metabolites was less on day 10 than on day 1 (39.7 +/- 14.5 micromol vs 30.1 +/- 15.1 micromol; p = 0.072). The extent of N-dealkylation of LD to MEGX was unaltered, whereas sequential biotransformation of MEGX was impaired. Hence, these findings suggested that LD infusion led to a reduction of hepatic intrinsic clearance, although the change was not significant enough to alter its conventional kinetic parameters.

Animals↗
PubMed1996

Nonlinear pharmacokinetics of mibefradil in the dog.

The pharmacokinetics of mibefradil in the dog was evaluated in this study. Single intravenous (1 mg/kg) and three oral doses (1, 3, 6 mg/kg) of mibefradil were administered to three dogs according to a randomized complete block design, where dogs were blocks and treatments randomly assigned to each block. Systemic plasma clearance, volume of distribution at steady-state and half-life after intravenous administration were as follows: ClS = 18.4 +/- 1.2 mL/min/kg, VSS = 9.7 +/- 3.8 L/kg, and T1/2 = 9.5 +/- 3.4 h. Oral plasma clearance decreased with an increase in dose, from 101.8 +/- 18.8 mL/min/kg at 1 mg/kg to 21.7 +/- 4.3 mL/min/kg at a 6 mg/kg dose (p < 0.05). Half-life values did not change significantly with an increase in oral dose in all the animals studied (10.6 +/- 1.5 h at 1 mg/kg to vs 13.4 +/- 3.5 h at 6 mg/kg). Dose-normalized AUC ratios between the oral and intravenous treatments increased from 0.18 +/- 0.03 at 1 mg/kg to 0.87 +/- 0.21 at a 6 mg/kg dose (p < 0.05). The nonlinear kinetic behavior of mibefradil is consistent with an increase in gut absorption and/or reduction in elimination after higher oral doses. Although both dogs and humans exhibit nonlinear pharmacokinetics after oral administration, there are substantial differences in the clearance and volume of distribution values between these two species. Even though these differences can, in part, be accounted for by the difference in plasma protein binding, the use of the dog as an animal model for human mibefradil pharmacokinetics need to be qualified.

Animals↗
PubMed1996

Mechanisms of nonlinear pharmacokinetics of mibefradil in chronically instrumented dogs.

The mechanisms of nonlinear pharmacokinetics after single- and multiple-dose treatments with a new calcium channel blocker, mibefradil, were studied. Four female, chronically instrumented dogs (22 +/- 2.1 kg) received a single i.v. dose (1 mg/kg), three single p.o. doses (1, 3 and 6 mg/kg) and a regimen of 3 mg/kg p.o. doses twice per day for 8 days; the order of treatment was randomized. Data on i.v. administration showed that hepatic clearance and systemic clearance values were similar (20.1 +/- 5.5 vs. 18.5 +/- 4.4 ml/min/kg, P > .05), suggesting that the liver is the main eliminating organ. The fraction of the administered dose absorbed from the gut after all p.o. treatments was approximately 60%, indicating that incomplete absorption and/or first-pass gut metabolism occurred. The fraction absorbed was not altered by dose or duration of treatment. The absolute bioavailability, however, was increased because of a dose- and duration of treatment-dependent reduction in hepatic elimination (absolute bioavailability changing from 0.25 +/- 0.18 at 1 mg/kg to 0.40 +/- 0.22 at 6 mg/kg and 0.48 +/- 0.14 after multiple dosing, P < .05). This change was mainly caused by a decrease of systemic clearance values from 15.6 +/- 9.7 to 9.0 +/- 1.3 and 7.0 +/- 3.5 ml/min/kg, respectively (P < .05). These data clearly indicate that the nonlinear pharmacokinetics of mibefradil after p.o. dosing are the result of an increase in bioavailability and a reduction in systemic clearance. Both changes are attributed to a reduction in the ability of the liver to eliminate the drug.

Administration, Oral↗
PubMed1991

SN10 auditory evoked potential revisited.

The slow brainstem response (SN10) was originally described as a slow negative wave occurring at a latency of 10 msec post stimulus onset. In the late 1970s and early 1980s it was considered to be promising for estimating hearing thresholds at low frequencies. However, there have been controversies regarding waveform description, recording stimulus parameters, and factors affecting the response. Consequently, the SN10 has not become a popular clinical test for estimating hearing thresholds electrophysiologically. However, recent observation of ABR waveforms using low-frequency stimuli and broad-band filtering indicate that the negative wave after wave V can be highly identifiable. This wave in many instances is the SN10. Therefore, this article was designed to review various aspects of the SN10 to make clinicians more aware of its possible applications in estimating low-frequency hearing thresholds.

Audiometry, Evoked Response↗
PubMed1990

Immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall in rheumatic fever.

An immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall was carried out on members of 15 multiplex families each having more than one sib affected with rheumatic heart disease. They comprised 30 parents and 61 sibs (32 with rheumatic disease and 29 without). Fifty healthy unrelated subjects served as controls. A history was taken and clinical examination carried out. Rheumatic activity was determined and HLA typing was carried out for nine A antigens, 15 B antigens, and six DR antigens. The immune response of lymphocytes to streptococcal polysaccharide antigen of the cell wall of group A beta haemolytic streptococci in vitro was studied by tritiated thymidine uptake. The results were statistically and genetically analysed. It was found that (a) all subjects with rheumatic disease were highly responsive to the streptococcal polysaccharide antigen of the cell wall, the sib pairs being mostly HLA identical; (b) all low responders had no rheumatic disease and their phenotypes were mostly different from those of the rheumatic member of their sib pair; (c) correlation of immune responsiveness (high or low) between HLA-identical sibs was significant, but insignificant between haplotype identical and non-identical sibs; (d) the gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall is recessive and closely linked to HLA. In conclusion, it was found that exposure to pharyngeal infection with group A beta haemolytic streptococci may lead to acute rheumatic fever in those with an inherited recessive gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall.

Adolescent↗
PubMed1987

The effect of linguistic background on staggered spondaic word and dichotic consonant vowel scores.

This study was undertaken to determine the effect of linguistic background on scores obtained by native and non-native subjects on two dichotic speech tests in American English, the staggered spondaic word (SSW) and the dichotic consonant-vowel (CV) tests. Thirty subjects whose native languages were either Hindi or Arabic were tested. Test findings were compared to results obtained from 10 native English-speaking subjects. The non-native English speakers showed abnormally high error scores on the SSW test while the native speakers performed with no errors on that test. Performance on the dichotic CV test was comparable for both the native English and the Hindi subjects, while the Arabic subjects performed significantly worse than the two other groups. These data indicate that tests of speech perception using English must be interpreted with caution when administered to non-native English speakers, and that neither the SSW nor the dichotic CV tests may be assumed to be free of linguistic bias.

Adult↗
PubMedDate not supplied

Performance of adults on directed listening tasks using a dichotic CV test.

The purpose of this study was to examine the response of adult subjects to directed listening tasks, using the dichotic consonant-vowel (CV) identification test. Twenty-five subjects, 20 to 36 years of age, were tested. Dichotic CV testing was administered utilizing the directed listening paradigm and free recall instructions. Results indicated that subjects showed right ear advantage in the directed right listening condition, and left ear advantage in directed left listening condition. Free recall listening conditions showed a right ear advantage. These results show a previously unreported maturational effect on dichotic CV testing. Implications of test findings are discussed.

Adult↗