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Biomedical subjects

A Karim

Publications and source records attributed to A Karim.

At least 55 records · Page 3Linked to original sources
PubMed2001

CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop.

Escherichia coli ILT-1, Klebsiella pneumoniae ILT-2, and K. pneumoniae ILT-3 were isolated in May 1999 in Paris, France, from a rectal swab of a hospitalized 5-month-old girl. These isolates had a clavulanic acid-inhibited substrate profile that included expanded-spectrum cephalosporins. The MICs of cefotaxime were higher for E. coli ILT-1 and K. pneumoniae ILT-2 than for K. pneumoniae ILT-3, while the opposite was found for the MICs of ceftazidime. Genetic and biochemical analyses revealed that E. coli ILT-1 and K. pneumoniae ILT-2 produced the CTX-M-18 beta-lactamase, while K. pneumoniae ILT-3 produced the CTX-M-19 beta-lactamase. The amino acid sequence of the CTX-M-18 beta-lactamase differed from that of the CTX-M-9 beta-lactamase by an Ala-to-Val change at position 231, while CTX-M-19 possessed an additional Pro-to-Ser change at position 167 in the omega loop of Ambler class A enzymes. The latter amino acid substitution may explain the CTX-M-19-mediated hydrolysis of ceftazidime, which has not been reported for other CTX-M-type enzymes. The bla(CTX-M-18) and bla(CTX-M-19) genes were located on transferable plasmids that varied in size (ca. 60 and 50 kb, respectively) but that showed similar restriction patterns.

Amino Acid Sequence↗
PubMed2001

Molecular epidemiology of the integron-located VEB-1 extended-spectrum beta-lactamase in nosocomial enterobacterial isolates in Bangkok, Thailand.

Over a 21/2-month period in 1999, 37 ceftazidime-resistant nonrepetitive enterobacterial isolates were collected from 37 patients in a Bangkok hospital, Thailand. Eighty-one percent of these strains expressed a clavulanic acid-inhibited extended-cephalosporin resistance profile. An identical extended-spectrum beta-lactamase (ESBL), VEB-1, was found in 16 unrelated enterobacterial isolates (Escherichia coli, n = 10; Enterobacter cloacae, n = 2; Enterobacter sakazakii, n = 1; and Klebsiella pneumoniae, n = 3) and in two clonally related E. cloacae isolates. The bla(VEB-1) gene was located on mostly self-conjugative plasmids (ca. 24 to 200 kb) that conferred additional non-beta-lactam antibiotic resistance patterns. Additionally, the bla(VEB-1) gene cassette was part of class 1 integrons varying in size and structure. The bla(VEB-1)-containing integrons were mostly associated with bla(OXA-10)-like and arr-2-like gene cassettes, the latter conferring resistance to rifampin. These data indicated the spread of bla(VEB-1) in Bangkok due to frequent transfer of different plasmids and class 1 integrons and rarely to clonally related strains. Plasmid- and integron-mediated resistance to rifampin was also found in enterobacterial isolates.

Anti-Bacterial Agents↗
PubMed2001

How feasible is it to conform to the European guidelines on administration of activated charcoal within one hour of an overdose?

OBJECTIVES: The European and American position statement on the use of activated charcoal recommends its administration within an hour of ingestion of a charcoal binding poison. But in reality, this time limit is difficult to follow for the majority of poisoned patients. This study aimed to examine the treatment of acutely poisoned patients with activated charcoal in an accident and emergency (A&E) department. METHODS: 63 patients who had taken potentially serious overdoses and required hospital admission from a London teaching hospital A&E department were identified over a six month period. The patients' case notes were analysed for age, sex, substances taken, and the timing of their management within the A&E department. RESULTS: Median time of arrival after overdose was 136 minutes, and only 15 patients presented within an hour. Ten of these 15 patients were given activated charcoal, and only four of the 10 received it within the one hour limit. Sixteen patients received charcoal outside the time limit. Subanalysis of the individual cases given charcoal shows that triaging is fast (median five minutes), but a significant time delay occurs after this before charcoal is administered (median 21 minutes). CONCLUSIONS: These results are likely to be exaggerated in rural hospitals and demonstrate the difficulty of adhering to the recommended guidelines, unless activated charcoal can be safely administered to appropriate patients in the prehospital environment.

Adolescent↗
PubMed2001

A pharmacokinetic study of intramuscular (i.m.) parecoxib sodium in normal subjects.

A single-center, double-blind, placebo-controlled, randomized study was conducted to determine the pharmacokinetics, safety, and tolerability of single, rising intramuscular (i.m.) doses and the single maximum tolerated dose of parecoxib sodium, a prodrug of the novel COX-2 selective anti-inflammatory analgesic drug valdecoxib, in 56 healthy male volunteers, ages 18 to 45 years inclusive. Cohorts of up to 6 subjects in each dose schedule were administered either parecoxib sodium (1 mg, 2 mg, 5 mg, 10 mg, 20 mg, or 40 mg) or matching placebo. Following i.m. administration, serial blood samples for measurement of plasma concentrations of parecoxib, valdecoxib, and valdecoxib metabolite (M1) were collected at predetermined intervals (from 15 minutes prior to dose and through 96 hours postdose). Urine collections were obtained for drug assay (from -12 to 0 hours, 0 to 12 hours, and 12 to 24 hours postdose). After i.m. administration, peak plasma concentrations of parecoxib were reached within 15 minutes and then declined rapidly as prodrug was converted to the active moiety, valdecoxib. Change in plasma concentrations of valdecoxib, which declined more slowly (t(1/2) = 5.4-9.9 hours), reflected transformation to several metabolites, one of which was the minor active metabolite M1. As measured by the AUC(0-infinity), Cmax, and XU(0-24) of valdecoxib, parecoxib sodium demonstrated dose proportionality when administered in the range of 1 mg to 40 mg of parecoxib. All single i.m. doses up to the maximum of 40 mg of parecoxib, as well as concentrations of up to 20 mg/ml, were well tolerated.

Adolescent↗
PubMed2001

Hypertension control in a community health centre at Riyadh, Saudi Arabia.

OBJECTIVE: This study was carried out to determine the degree of control of hypertension and the most commonly used drugs for hypertensive patients attending our community health center. METHODS: A cross sectional study carried out by randomly examining the case notes of patients attending our primary care clinics. RESULTS: Case notes of 3747 patients were examined, 2064 (55%) females (mean age 23.76 years) and 1683 (45%) males (mean age 24.63 years). Prevalence of hypertension was 3% (108 patients), 3% (63 patients) and 3% (45 patients) for females and males respectively. Majority of patients 16 (35%) males and 32 (51%) females had blood pressure of 141-160/90-100 mmHg. Seventeen (37%) males and 15 (24%) female patients had blood pressure < 140/90 mm Hg. Among 108 hypertensive patients, 29 (65%) males and 44 (69%) females were on single drug. The most commonly used drugs were ACE inhibitors (35%), calcium channel blockers (17.5%) and beta- blockers (14%). CONCLUSION: This study like some other studies shows that control of hypertension falls short of recommended goals. There is need to adopt a strategy that incorporates health education about life style and proper protocol as this has been found useful in other studies.

Adolescent↗
PubMed2001

Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption.

Celecoxib pharmacokinetics was evaluated after single and multiple oral dosing; after dosing in a solution and as a solid; with and without food; and after administration into different sites of the GI tract using dog. After oral dosing in a solution, celecoxib was rapidly absorbed and reached maximum concentrations by 1 h; absorption was delayed another 1 to 2 h when administered as a solid. The absolute bioavailability of celecoxib was higher when given as a solution (64--88%) compared with capsule (22--40%). The absorption of celecoxib given in a capsule was delayed by food, although systemic exposure increased by 3- to 5-fold. The systemic availability of celecoxib given intragastrically in solution was similar to that obtained following direct instillation into the duodenum, jejunum, or colon through a chronic intestinal access port. Collectively, these data suggest that celecoxib is a highly permeable drug that can be absorbed throughout the GI tract and that dissolution may be a rate-limiting factor for absorption from solid dosage forms. Unlike dogs, celecoxib given to humans with a high fat meal exhibits only a slight increase in AUC(0--infinity) (11%) that is not clinically significant with regard to safety or efficacy. In humans, a lower dose and a longer GI residence time may promote the opportunity for absorption of a poorly soluble drug such as celecoxib that can be absorbed throughout the GI tract. This would minimize the effect of food on absorption; as such, patients with arthritis can be given celecoxib with or without food.

Adult↗
PubMed2001

Prevalence of smoking among high school students.

OBJECTIVE: Smoking is the single and most important preventable cause of morbidity and morality worldwide. This study was carried out to ascertain the prevalence of smoking among high school students in Alkharj and the influencing factors for smoking. METHODS: This study was carried out by means of a Questionnaire. The study was conducted by the Department of Family and Community Medicine in AlKharj Military Hospital, Kingdom of Saudi Arabia. The participants were students of age 15 years and above in randomly selected Alkharj high schools. RESULTS: Out of 819 correspondence 166 (20%) were current smokers, 134 (16%) were ex-smokers. Five hundred and nineteen (64%) were non-smokers. The average starting age for current smokers was 13.8 years (13 years-15 years). 105 (63%) of current smokers smoked less than 10 cigarettes per day (light smokers). the influence of friends 96 (58%) and the presence of smoking in the family 53 (32%) were the 2 most important factors influencing the rate of smoking in current smokers. Ninety-five percent of smokers know that smoking is harmful and 60% know that smoking is harmful for others. One hundred and one (61%) of current smokers, have tried to quit smoking but failed. CONCLUSION: The prevalence of smoking is high among school students in Alkharj. Most current smokers know the harmful effects of smoking. A collaborative effort is needed by all concerned to reduce the number of school students who smoke.

Adolescent↗
PubMed2000

Lipotoxic heart disease in obese rats: implications for human obesity.

To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-alpha. Levels of ceramide, a mediator of apoptosis, were 2-3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids.

Age Factors↗
PubMed2000

Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.

Inhibition of the tissue factor pathway has been shown to attenuate the activation of coagulation and to prevent death in a gram-negative bacteremia primate model of sepsis. It has been suggested that tissue factor influences inflammatory cascades other than the coagulation system. The authors sought to determine the effects of 2 different doses of recombinant tissue factor pathway inhibitor (TFPI) on endotoxin-induced coagulant, fibrinolytic, and cytokine responses in healthy humans. Two groups, each consisting of 8 healthy men, were studied in a double-blind, randomized, placebo-controlled crossover study. Subjects were studied on 2 different occasions. They received a bolus intravenous injection of 4 ng/kg endotoxin, which was followed by a 6-hour continuous infusion of TFPI or placebo. Eight subjects received 0.05 mg/kg per hour TFPI after a bolus of 0.0125 mg/kg (low-dose group), and 8 subjects received 0.2 mg/kg per hour after a bolus of 0.05 mg/kg (high-dose group). Endotoxin injection induced the activation of coagulation, the activation and subsequent inhibition of fibrinolysis, and the release of proinflammatory and antiinflammatory cytokines. TFPI infusion induced a dose-dependent attenuation of thrombin generation, as measured by plasma F1 + 2 and thrombin-antithrombin complexes, with a complete blockade of coagulation activation after high-dose TFPI. Endotoxin-induced changes in the fibrinolytic system and cytokine levels were not altered by either low-dose or high-dose TFPI. The authors concluded that TFPI effectively and dose-dependently attenuates the endotoxin-induced coagulation activation in humans without influencing the fibrinolytic and cytokine response. (Blood. 2000;95:1124-1129)

Adult↗
PubMed2000

[Colonization by methicillin-resistant Staphylococcus aureus is a predictive factor for the resistance phenotype of an infectious strain of S. aureus].

OBJECTIVE: To assess the predictive value of a previous colonization with methicillin-resistant Staphylococcus aureus for the resistance pattern of a bacteriological specimen significantly positive to S. aureus. STUDY DESIGN: Retrospective study of patients' files. PATIENTS: Patients admitted for at least 48 hours in a surgical intensive care unit from April 1, 1996 to December 31, 1997. METHODS: Collection of patients' characteristics and chronology of positive microbiological specimens with methicillin-susceptible (MSSA) or -resistant (MRSA) S. aureus from medical and laboratory records. During the study period, screening for nasal or perineal colonization with MRSA was systematically performed on admission and weekly thereafter. RESULTS: The files of 540 patients were reviewed. MSSA and MRSA infections occurred in 7% (39/540) and 4% (20/540) of the patients respectively. By opposition with MSSA infections, MRSA infections occurred more frequently in patients previously colonized with MRSA (13 infections in 63 colonized patients [21%] versus 7 infections in 477 non-colonized patients [2%], odds ratio = 18, confidence interval: 6-51, P < 0.0001). The median delay between colonization and infection was 5 days. The positive and negative predictive values for previous colonization with MRSA to predict infection with MRSA in presence of a bacteriological specimen significantly positive with S. aureus were 81 and 84%, respectively. CONCLUSION: The probabilistic use of a glycopeptide in presence of a bacteriological specimen significantly positive with S. aureus should be limited to patients already colonized with MRSA, in order to decrease the abusive administration of these antibiotics.

Adolescent↗
PubMed2000

Hardness and ultrasonic characteristics of the human crystalline lens.

PURPOSE: To evaluate the relationship between hardness of the human crystalline lens and its acoustic characteristics. SETTING: St. George's Hospital Medical School, University of London, London, United Kingdom. METHODS: Cataractous lenses from patients who had extracapsular cataract surgery were studied for hardness and ultrasonic characteristics. Lens hardness was assessed with an automated guillotine. Ultrasound velocity and attenuation were measured with a scanning acoustic macroscope using the pulse transmission reflection method. RESULTS: Thirty-seven lenses from 37 patients (mean age 75.5 years) were evaluated. Lens hardness was associated with ultrasound attenuation (r = 0.65, P <.0001) and attenuation frequency gradient (r = 0.67, P <.0001). The correlation of hardness with mean ultrasound velocity was not significant (r = 0.22, P =.2). CONCLUSIONS: The attenuation of ultrasound waves by the human crystalline lens correlated with its hardness. Ultrasonography can be used to evaluate lens hardness.

Aged↗
PubMed2000

Tumor-selective gene transduction and cell killing with an oncotropic autonomous parvovirus-based vector.

A recombinant MVMp of the fibrotropic strain of minute virus of mice (MVMp) expressing the chloramphenicol acetyltransferase reporter gene was used to infect a series of biologically relevant cultured cells, normal or tumor-derived, including normal melanocytes versus melanoma cells, normal mammary epithelial cells versus breast adenocarcinoma cells, and normal neurons or astrocytes versus glioma cells. As a reference cell system we used normal human fibroblasts versus the SV40-transformed fibroblast cell line NB324K. After infection, we observed good expression of the reporter gene in the different tumor cell types, but only poor expression if any in the corresponding normal cells. We also constructed a recombinant MVMp expressing the green fluorescent protein reporter gene and assessed by flow cytometry the efficiency of gene transduction into the different target cells. At a multiplicity of infection of 30, we observed substantial transduction of the gene into most of the tumor cell types tested, but only marginal transduction into normal cells under the same experimental conditions. Finally, we demonstrated that a recombinant MVMp expressing the herpes simplex virus thymidine kinase gene can, in vitro, cause efficient killing of most tumor cell types in the presence of ganciclovir, whilst affecting normal proliferating cells only marginally if at all. However, in the same experimental condition, breast tumor cells appeared to be resistant to GCV-mediated cytotoxicity, possibly because these cells are not susceptible to the bystander effect. Our data suggest that MVMp-based vectors could prove useful as selective vehicles for anticancer gene therapy, particularly for in vivo delivery of cytotoxic effector genes into tumor cells.

Adenocarcinoma↗
PubMed2000

The influence of reduced liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue factor pathway inhibitor.

OBJECTIVES: Recombinant tissue factor pathway inhibitor (rTFPI) has been shown to be an effective treatment in animal models of sepsis and is under investigation for human use. Reduced liver blood flow during septic shock may substantially alter the pharmacokinetics of rTFPI because clearance of rTFPI approaches liver blood flow. The aim of this study was to examine the effect of exercise-induced reduction in liver blood flow on the pharmacokinetics and pharmacodynamics of rTFPI. METHODS: This was a two-way, open-label, randomized crossover study in eight healthy male volunteers. The subjects in both treatment groups received a continuous intravenous infusion of rTFPI (0.2 mg/kg/h) concurrently with intravenous sorbitol (50 mg/min) for 4 hours. Sorbitol was used as a biomarker for liver blood flow. The subjects were randomized to remain supine or to exercise on a bicycle ergometer for 30 minutes starting at the beginning of the third hour of the infusion. RESULTS: Exercise reduced liver blood flow (mean +/- SEM) from 1.44 +/- 0.06 L/min to 0.40 +/- 0.03 L/min. The average clearance of rTFPI decreased from 0.73 +/- 0.04 L/min in the supine position to 0.25 +/- 0.02 L/min during exercise. This decrease in rTFPI clearance resulted in an 80% (95% confidence interval [CI], 60% to 102%) increase in plasma rTFPI levels during exercise. The average maximal prothrombin time and activated partial thromboplastin time values during exercise were 1.4 (95% CI, 0.4 to 2.5) and 4.4 (95% CI, 2.7 to 6.1) seconds higher compared with the supine steady-state level. CONCLUSIONS: Reduction in liver blood flow by exercise markedly increased rTFPI concentrations and induced a slight but variable prothrombin time and activated partial thromboplastin time increase at the rTFPI dose studied.

Adult↗
PubMed2000

Gram staining of protected pulmonary specimens in the early diagnosis of ventilator-associated pneumonia.

We evaluated prospectively the use of Gram staining of protected pulmonary specimens to allow the early diagnosis of ventilator-associated pneumonia (VAP), compared with the use of 60 bronchoscopic protected specimen brushes (PSB) and 126 blinded plugged telescopic catheters (PTC) obtained from 134 patients. Gram stains were from Cytospin slides; they were studied for the presence of microorganisms in 10 and 50 fields by two independent observers and classified according to their Gram stain morphology. Quantitative cultures were performed after serial dilution and plating on appropriate culture medium. A final diagnosis of VAP, based on a culture of > or = 10(3) c.f.u. ml-1, was established after 81 (44%) samplings. When 10 fields were analysed, a strong relationship was found between the presence of bacteria on Gram staining and the final diagnosis of VAP (for PSB and PTC respectively: sensitivity 74 and 81%, specificity 94 and 100%, positive predictive value 91 and 100%, negative predictive value 82 and 88%). The correlation was less when we compared the morphology of microorganisms observed on Gram staining with those of bacteria obtained from quantitative cultures (for PSB and PTC respectively: sensitivity 54 and 69%, specificity 86 and 89%, positive predictive value 72 and 78%, negative predictive value 74 and 84%). Increasing the number of fields read to 50 was associated with a slight decrease in specificity and positive predictive value of Gram staining, but with a small increase in its sensitivity and negative predictive value. The results obtained by the two observers were similar to each other for both numbers of fields analysed. Gram staining of protected pulmonary specimens performed on 10 fields predicted the presence of VAP and partially identified (using Gram stain morphology) the microorganisms growing at significant concentrations, and could help in the early choice of the treatment of VAP. Increasing the number of fields read or having the Gram stain analysed by two independent individuals did not improve the results.

Adolescent↗
PubMed2000

Molecular epidemiology of an outbreak due to IRT-2 beta-lactamase-producing strains of Klebsiella pneumoniae in a geriatric department.

In February 1998, 195 patients in the geriatric department of a French hospital were screened for the presence of co-amoxiclav-resistant Klebsiella pneumoniae. Eleven co-amoxiclav-resistant isolates obtained all produced an identical IRT-2 beta-lactamase. These K. pneumoniae isolates were clonally related and harboured a c. 55 kb non-conjugative plasmid encoding a non-class-1 integron-located blaIRT-2 gene. This study underlines that geriatric departments may be a reservoir for antibiotic-resistant strains and that IRT beta-lactamase-producing strains may be nosocomial pathogens.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2000

A ruthenium(II) complex with p-cymene and (S)-2-(anilinomethyl)pyrrolidine

The title compound, [(S)-2-(anilinomethyl)pyrrolidine-N, N']-chloro(eta(6)-para-cymene)ruthenium(II) chloride, [RuCl-(C(10)H(14))(C(11)H(16)N(2))]Cl, has been synthesized by the reaction of [RuCl(2)(p-cymene)](2) (p-cymene is para-isopropyltoluene) with (S)-2-(anilinomethyl)pyrrolidine in triethylamine/2-propanol. The Ru atom is in a pseudo-tetrahedral environment coordinated by a chloride ligand, the aromatic hydrocarbon is linked in a eta(6) manner and the amine is linked via its two N atoms. The chloride anion is involved in hydrogen bonding with the diamine moieties through N-H.Cl interactions, with N.Cl distances of 3.273 (4) and 3.352 (4) A.

Journal Article↗
PubMed2000

Heterogeneity of AmpC cephalosporinases of Hafnia alvei clinical isolates expressing inducible or constitutive ceftazidime resistance phenotypes.

Ten unrelated Hafnia alvei clinical isolates were grouped according to either their low-level and inducible cephalosporinase production or their high-level and constitutive cephalosporinase production phenotype. Their AmpC sequences shared 85 to 100% amino acid identity. The immediate genetic environment of ampC genes was conserved in H. alvei isolates but was different from that found in other ampC-possessing enterobacterial species.

Amino Acid Sequence↗