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Biomedical subjects

M Darwish

Publications and source records attributed to M Darwish.

At least 19 recordsLinked to original sources
PubMed2005

Tacrolimus (FK506) versus cyclosporine microemulsion (neoral) as maintenance immunosuppression therapy in kidney transplant recipients.

The effects of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine (Neoral) on graft survival, function, and metabolic profile were evaluated in 69 patients receiving Neoral (group 1) and 54 patients receiving FK506 (group 2) for maintenance immunosuppression following kidney transplantation. Recipient and donor demographics and induction therapy were comparable, except for a higher number of sensitized patients in group 2 (n = 13). Acute rejection timing, severity, and infection rates and types were similar in both groups. During hospitalization, at 6 months, and at 1 year following transplantation, no significant differences were noted between groups in fasting glucose, serum cholesterol levels, triglyceride levels, or need for insulin or antihypertensive therapy. Mean serum creatinine levels on discharge (1.42 mg/dL +/- 0.14 vs 1.68 mg/dL +/- 0.3), at 1 month (1.45 mg/dL +/- 0.1 vs 1.39 mg/dL +/- 0.11), 3 months (1.46 mg/dL +/- 0.09 vs 1.32 mg/dL +/- 0.14), and 1 year (1.29 mg/dL +/- 0.08 vs 1.19 mg/dL +/- 0.09), but not at 6 months (1.42 +/- 0.37 vs 1.10 +/- 0.07; P = .001), were comparable between groups. The 1-year patient and graft survival rates were 98.3% for group 1 and 94.5% for group 2. When evaluated for acute rejection, infection, and metabolic differences, we conclude that both tacrolimus and cyclosporine are effective and safe calcineurin inhibitors for short-term use in kidney transplantation. A similar study is proposed to evaluate the long-term effects of both agents.

Adult↗
PubMed2004

Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study.

AIMS: To characterize the population pharmacokinetics of indometacin in preterm infants with symptomatic patent ductus arteriosus and to investigate the influence of various factors on the response to treatment. METHODS: Data were collected from 35 infants (gestational age 25-34 weeks; postnatal age 1-77 days) in neonatal units in Belfast and Copenhagen. Infants received an initial course of up to three doses of intravenous indometacin (0.1-0.2 mg kg(-1)) as considered appropriate by the treating physician. For those infants who did not respond to therapy or in whom the ductus reopened, a second course was sometimes given. Population analysis of the 185 plasma concentrations obtained was conducted using NONMEM and pharmacokinetic and demographic differences between responders and nonresponders were compared. RESULTS: The concentration-time course of indometacin was best described by a one-compartment model. The final population parameter estimates of clearance (CL) and volume of distribution (V) (standardized to the median weight of 1.17 kg) were 0.00711 l h(-1) and 0.266 l, respectively. CL increased from birth by approximately 3.38% per day and V by approximately 1.47% per day. Concomitant digoxin therapy resulted in a 30% decrease in V. Interindividual variability in CL and V was 41% and 21%, respectively. Interoccasion variability for CL was 43%. Residual variability corresponded to a standard deviation of 0.148 mg l(-1). Closure occurred in 75% of infants with a plasma concentration > or = 0.4 mg l(-1) 24 h after the last dose. CONCLUSIONS: Dosing regimens for indometacin should take into account the weight and postnatal age of the infant and any concomitant digoxin therapy. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indometacin that should increase the probability of achieving a 24 h plasma concentration > or = 0.4 mg l(-1). Although the pharmacokinetic estimates will be affected by both interindividual and within-individual variation, it is anticipated that this approach will decrease the variability of exposure and optimize treatment outcome.

Cardiovascular Agents↗
PubMed2003

Gender differences in the regulation of 3 alpha-hydroxysteroid dehydrogenase in rat brain and sensitivity to neurosteroid-mediated stress protection.

The enzyme 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) is involved in the generation of neuroactive steroids through ring-A-reduction of hormonal precursors. We examined the developmental regulation of, gender differences in, and effects of hormonal manipulations on the expression of 3 alpha-HSD in the rat hippocampus. High levels of 3 alpha-HSD mRNA were found on postnatal day 7, coinciding with the stress hyporesponsive period in the rat. Gender differences in 3 alpha-HSD expression were documented during puberty, but not in adulthood. Adrenalectomy and gonadectomy, and supplementation with individual steroid hormones influenced 3 alpha-HSD expression in a gender-specific mode. We also demonstrate that the manifestation of behavioral and endocrine consequences of early life stress depends on the individual's gender and gonadal status. Males are liable to aftereffects of neonatal maternal deprivation, regardless of their adult gonadal status. In females, however, anxiogenic aftereffects of neonatal stress become apparent only after gonadectomy. These data suggest that (i) transient increase of neurosteroid biosynthesis may contribute to stress hyporesponsiveness during early infancy; (ii) gonadal steroids regulate 3 alpha-HSD expression in the hippocampus in a sex-specific mode; (iii) physiological sex steroid secretions in females may mask behavioral consequences of adverse early life events, and (iv) concomitant treatment with the neurosteroid THP counteracts behavioral and endocrine dysregulation induced by neonatal stress in both genders.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

Exposure to a novel stimulus reduces anxiety level in adult and aging rats.

Male Wistar rats aged 3, 15 and 24 months were isolated and housed individually for 72 h prior to being subjected to inanimate objects (two objects per rat, each 1.5 cm in diameter and 4 cm in length, made of surgical gauze). Following the exposure to the objects, rats were subsequently tested in an elevated plus-maze. The inanimate objects induced locomotor activity, chewing and transportation of the object. This changed to social interaction and play-like behavioral activity in rats of all ages that were kept in small groups with a latency of 1 to 2 min. One hour after the start of exposure, the animals were tested in the elevated plus-maze to measure anxiety behavior. It was found that all age groups spent significantly more time in the open arm of the elevated plus-maze than the corresponding controls. Latencies to first entry into open arms were also significantly lowered. The number of entries to the open or to the dark arm, however, did not show statistical difference, indicating that the novel object-induced activity failed to exert influence on gross motor activity in the elevated plus-maze. In conclusion, the stimulation elicited by the exposure to novel stimulus (inanimate objects) resulted in a significant reduction of anxiety level both in adult and in aging rats.

Aging↗
PubMed2001

Field investigations of brucellosis in cattle and small ruminants in Syria, 1990-1996.

The authors present the epidemiological status of brucellosis in cattle and small ruminants in Syria from 1990 to 1996, based on laboratory findings at the Brucellosis Centre, Damascus. Initial investigations using the Rose Bengal plate test, the complement fixation test and a miniaturised variant of the slow agglutination test were conducted throughout the country in 1990 and 1991, revealing an overall herd seroprevalence rate of 3.14% in cattle herds and 2.94% in small ruminant flocks. Although partially biased by previous vaccination of young female cattle with S19 vaccine, these figures indicate that brucellosis in cattle is widespread, particularly in the urban governorates (provinces) of Damascus, Aleppo and Suwaydah. Brucellosis seroprevalence in sheep and goats was relatively high in the governorates of Damascus, Aleppo and Dara'a. The results of a second series of investigations, performed between 1992 and 1996, show that herd seroprevalence in cattle decreased steadily from 17.48% in 1992, to 2.59% in 1996, in the Government-owned farms, while seroprevalence increased in the private sector during the same period. The difference may be explained by the restriction of brucellosis vaccination to public farms (although this was far from systematic), combined with partial application of a 'test-and-slaughter' policy. In sheep and goats, brucellosis seroprevalence fluctuated in the two sectors, but was higher in the private sector where husbandry is principally extensive. Bacteriological investigations led to the isolation of Brucella melitensis biovars 2 and 3 in sheep and B. abortus biovar 9 in cattle. Although no specific methodology was employed, particularly with regard to sampling, this study is significant as the first international report of the distribution of brucellosis in Syria. Further, well-structured studies are required, the results of which could be used to plan an appropriate national control programme for brucellosis.

Abortion, Veterinary↗
PubMed2000

Effect of zaleplon on digoxin pharmacokinetics and pharmacodynamics.

The pharmacokinetics and pharmacodynamics of digoxin alone and digoxin plus zaleplon were studied. Healthy, nonsmoking men between 18 and 45 years of age were given a single oral dose of digoxin 0.375 mg daily on days 1 through 9. On days 10 through 14, the subjects received digoxin 0.375 mg plus oral zaleplon 10 mg daily. Blood samples were obtained on days 3, 5, 8, 9, and 14, and serum digoxin concentration data were analyzed by model-independent pharmacokinetic methods. Blood pressure, heart rate, PR interval, and QTc interval were recorded to determine the effect of zaleplon on digoxin pharmacodynamics. A total of 20 men completed the study. Maximum serum digoxin concentration and area under the serum digoxin concentration-versus-time curve from 0 to 24 hours met bioequivalence test criteria. There were no significant differences in QTc or PR interval between days 9 (digoxin alone) and 14 (digoxin plus zaleplon), and there were no clinically important changes from baseline to the study's end in vital signs, physical examination findings, or ECG results for individual subjects. Eighteen percent of the subjects who received digoxin alone and 35% of those who received digoxin plus zaleplon reported one or more adverse effects; all were mild and resolved quickly. Zaleplon had no significant effects on selected pharmacokinetic and pharmacodynamic properties of digoxin.

Acetamides↗
PubMed2000

Psychomotor effects of zaleplon and thioridazine coadministration.

OBJECTIVE: To assess the potential pharmacokinetic and pharmacodynamic interaction of zaleplon and thioridazine administered concomitantly in healthy volunteers. METHODS: A three-period, double-blind, randomized crossover study of the psychomotor effects of single oral doses of zaleplon 20 mg alone, thioridazine 50 mg alone, or the two drugs administered concomitantly was performed in 12 healthy subjects. Pharmacodynamic testing was performed before, and at 1, 2, 4, and 8 h after drug administration. Critical flicker fusion (CFF), tapping rate (TR), reaction time (RT) with dominant and nondominant hands, and digit symbol substitution test (DSST) were used to assess psychomotor performance. RESULTS: Pharmacokinetic results showed that coadministration of zaleplon and thioridazine did not alter the pharmacokinetic profile of either drug. In both CFF and TR tests, values for change from baseline with combined treatment were not significantly different from those with thioridazine at any time point, indicating no pharmacodynamic interaction. RT test values with coadministered treatment were significantly different from those with thioridazine alone at 1 h after administration, indicating additivity. Supra-additivity was observed in DSST results at 1, 2, and 4 h. There was no interaction at 8 h. CONCLUSION: The results of single-dose administration showed an additive pharmacodynamic interaction between zaleplon and thioridazine at 1 h in one of four tests and supra-additivity for 4 h in another test. This interaction is relatively short in duration due to the short half-life of zaleplon.

Acetamides↗
PubMed2000

Pharmacokinetics, pharmacodynamics, and relative pharmacokinetic/pharmacodynamic profiles of zaleplon and zolpidem.

OBJECTIVE: This study compared the pharmacokinetics, pharmacodynamics, and pharmacokinetic/pharmacodynamic (PK/PD) profile of zaleplon, a new pyrazolopyrimidine hypnotic, with those of zolpidem and placebo. METHODS: This was a double-blind, 5-period crossover study in which healthy volunteers with no history of sleeping disorder were randomized to 10- or 20-mg oral doses of zaleplon, 10- or 20-mg oral doses of zolpidem, or placebo. The pharmacokinetic characteristics of the active drugs were estimated using a noncompartmental method and NONMEM. Pharmacodynamic characteristics were determined using psychophysical tests, including measures of sedation, mood, mental and motor speed, and recent and remote recall. Results of these tests were used to compare the drugs' relative PK/PD profiles. RESULTS: Ten healthy male and female volunteers, aged 23 to 31 years, took part in the study. The apparent elimination half-life of zaleplon (60.1+/-8.9 min) was significantly shorter than that of zolpidem (124.5+/-37.9 min) (P < 0.001). Zaleplon produced less sedation than zolpidem at the 2 doses studied (P < 0.001). The sedation scores of the zaleplon groups returned to baseline in less time than those of the zolpidem groups (4 vs 8 hours; P < 0.05). Zaleplon had no effect on recent or remote recall, whereas zolpidem had a significant effect on both measures (P < 0.05). CONCLUSIONS: In this study in 10 young, healthy volunteers, zaleplon was eliminated more rapidly, produced no memory loss, and caused less sedation than zolpidem at the same doses.

Acetamides↗
PubMed1999

Zaleplon pharmacokinetics and absolute bioavailability.

The pharmacokinetics and absolute oral bioavailability of zaleplon were assessed to evaluate the extent of presystemic metabolism of this new nonbenzodiazepine hypnotic agent. A partially randomized, single-dose, four-period crossover study was conducted in 23 healthy subjects. Subjects received 1 and 2.5 mg intravenous (i.v.) infusions of zaleplon during the first and second periods, respectively, and then were randomly assigned to receive a 5 mg oral dose or 5 mg i.v. infusion of zaleplon in a crossover design during the final two periods. Zaleplon pharmacokinetics were determined in 20 subjects (ten men and ten women) after the two 5 mg treatments. The oral and i.v. doses of zaleplon administered in this study were safe and well-tolerated. Following i.v. administration, zaleplon had a moderate to high systemic clearance (mean +/- S.D., 0.94 +/- 0.20 L/h/kg), rapid elimination (half-life, t1/2 = 1.05 +/- 0.13 h), and a steady-state volume of distribution of 1.27 +/- 0.25 L/kg, indicating substantial distribution into extravascular tissues. Zaleplon was rapidly absorbed after oral administration, and the mean apparent elimination t1/2 was similar to that obtained after i.v. infusion. The absolute bioavailability was 30.6 +/- 10.2%.

Acetamides↗
PubMed1999

Rapid disappearance of zaleplon from breast milk after oral administration to lactating women.

Five lactating mothers were administered the therapeutic dose of zaleplon (10 mg) orally in an open-label, single-dose, pharmacokinetic study. Plasma and breast milk were sampled through 8 hours after dose administration for subsequent determinations of zaleplon and its major, though inactive, plasma metabolite 5-oxo-zaleplon. Zaleplon concentrations peaked in plasma and milk approximately 1 hour after dosing and then disappeared rapidly. The mean terminal half-life was slightly greater than 1 hour. Milk concentrations "mirrored" plasma concentrations closely with no discernible delay between peak times. The average milk-to-plasma (M/P) concentration ratio for zaleplon was approximately 0.50 over the time course. 5-oxo-zaleplon was undetectable in all but one milk sample. The maximum exposure of an infant to zaleplon during a feeding at peak milk concentrations was estimated to range from 1.28 micrograms to 1.66 micrograms, corresponding to 0.013% to 0.017% of the maternal dose or 0.320 microgram/kg to 0.415 microgram/kg for a 4 kg infant. The results indicate that zaleplon taken by a nursing mother is transferred through breast milk to her infant in very small quantities that are unlikely to be clinically important.

Acetamides↗
PubMed1998

Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo.

PURPOSE: This study evaluated the relationship of dose, plasma concentration, and time to the pharmacodynamics of zaleplon and zolpidem, 2 structurally distinct benzodiazepine receptor agonists. METHOD: Ten healthy male volunteers received single oral doses of placebo, 10 mg zaleplon, 20 mg zaleplon, 10 mg zolpidem, and 20 mg zolpidem in a double-blind, 5-condition crossover study, with 48 hours elapsing between trials. Plasma drug concentrations and pharmacodynamic effects were measured during the 8 to 24 hours after administration. RESULTS: Kinetics of zaleplon and zolpidem were not significantly related to dose. However, zaleplon had more rapid elimination (apparent elimination half-life [t1/2] of 1 hour) and higher apparent oral clearance (approximately 4300 mL/min) than zolpidem (t1/2, 2.0 to 2.2 hours; apparent oral clearance, 340 to 380 mL/min). Active treatments produced pharmacodynamic effects consistent with benzodiazepine agonist activity: self- and observer-rated sedation, impairment of digit symbol substitution test (DSST) performance, impaired memory, and increased electroencephalographic activity in the beta frequency range. The overall order of agonist potency was as follows: placebo < 10 mg zaleplon < 20 mg zaleplon < 10 mg zolpidem < 20 mg zolpidem; on a number of measures, 20 mg zaleplon was comparable to 10 mg zolpidem. Quantitative effects of zolpidem 20 mg far exceeded those of other treatments. Dynamic effects of both drugs were significantly related to plasma concentration. CONCLUSIONS: Benzodiazepine agonist effects of zaleplon and zolpidem were dose and concentration dependent. At the usual clinically effective hypnotic dose (10 mg of either drug), agonist effects of zolpidem exceeded those of zaleplon.

Acetamides↗
PubMed1998

Prevalence of certain sexually transmitted viruses in Egypt.

The magnitude of Sexually Transmitted Diseases (STD) in the Eastern Mediterranean Region is not exactly known but considered to be not insignificant. A realistic estimate of the problem is necessary, to design an effective control program. This present study aimed to identify the most prevalent sexually transmitted viral agents among patients attending the STD clinic at Cairo Hospital for Skin and Venereal Diseases (El-Haud El-Marsoud). From persons attending this clinic whether complaining or visiting for screening, between October 1993 to April 1995, 95 cases were studied by history taking, clinical examination, bacteriological and serological examination for the detection of the most prevalent sexually transmitted organisms. Certain demographic and socio-economic factors interacting with sexual attitudes and practices were also studied. All the collected data for each patient were recorded. Antibodies (IgG) to cytomegalovirus (CMV) were detected in 86.3%, HBsAg in 10.5%, and antibodies to HBcAg were detected in 45.3%. Antibodies to HCV were detected in 8.4%, and antibodies to HIV in 5.3%.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Abdominal ultra sonographic findings detected in the course of a hepatitis survey in an Egyptian rural area.

The objective of this study was to determine the prevalence of abnormal findings detected by abdominal ultrasonography (US) in an Egyptian rural area. This study was a part of a community based cross sectional survey for virus hepatitis carried out at Kalama village in Nile Delta, 40 kilometers north of Cairo. People above 10 years of age living in a 10% systemic random sample of houses in the village were subjects of this study. A member of the team carried out US examination of the liver, biliary tree, spleen, kidneys, pancreas, para aortic areas and the pelvis. Examination included morphological assessment and organometry. All results are recorded on images by videoprinter. Abnormalities in abdominal US was detected in 34% of examined cases. Abnormal liver impressions were detected in 28.3% of cases. Ascites was detected in 13 cases (1.8%). Diseases of the gall bladder and kidneys were detected in 2.7% and 2.1%, respectively. US diagnosed pregnancy in 5 women, one of them had a blighted ovum. Some of these abnormalities were detected in subjects with no complaint. It is concluded that abdominal US may be a tool for early detection of asymptomatic disease.

Cholecystitis↗
PubMed1997

Ultra sonographic measurements of the normal liver and spleen among Egyptians 10-50 years old.

OBJECTIVE: To determine reference values of ultra sonographic (US) measurements of the normal liver, spleen, portal vein, right and left periportal thickness, gall bladder wall thickness and common bile duct diameter of Egyptians. DESIGN: Community-based cross sectional study. SETTING: Kalama village in Nile Delta, 40 kilometers north of Cairo. SUBJECTS: 10% systematic sample of people above 10 years of age. Selection criteria included normal clinical examination, normal liver functions by ALT, absence of hepatitis B and C virus markers and liver or spleen pathology by US. MEASUREMENTS: Organometery of the liver, spleen, portal vein, right and left periportal thickness, gall bladder wall thickness and common bile duct diameter by US. RESULTS: 217 subjects were admitted to the study out of 700 examined. All measured parameters increased with age till 20 years. There was no significant difference in measurements between males and females. The means, standard deviation and 95th percentiles of all measurements were higher than those recorded in other studies. CONCLUSION: Egyptian norms for US organometery of the liver, spleen, portal vein and gall bladder are different from those of other countries. We suggest that Egyptian sonologists use these norms in routine practice.

Adolescent↗