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Biomedical subjects

A Karim

Publications and source records attributed to A Karim.

At least 19 recordsLinked to original sources
PubMed2001

Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1.

Six non-clonally related enterobacterial isolates producing a same extended-spectrum beta-lactamase CTX-M-15 were isolated in 1999 from patients hospitalized in a New Delhi hospital. CTX-M-15 differed from CTX-M-3 by an asparagine to glycine substitution in position ABL238. Its gene was located on large plasmids varying in size. In each case, a same insertion sequence ISEcp1 was identified upstream of the 5' end of bla(CTX-M-15). Typical -35 and -10 promoter sequences of Enterobacteriaceae were identified in the 3' end of ISEcp1. The location of ISEcp1 upstream of plasmid-mediated CTX-M-type beta-lactamase genes may contribute to their spread or/and their expression.

Amino Acid Sequence↗
PubMed2001

Two atropisomers of tricarbonyl[eta6-6-chloro-3-(3-chloro-2-methylphenyl)-2,4,8-trimethyl-1,2,3,4-tetrahydro-2,4-dibora-1,3-diazanaphthlene]-chromium(0).

The structures of two atropisomers of the title compound, [Cr(C16H18B2Cl2N2)(CO)3], are reported. For both compounds, the Cr(CO)3 moiety is bound to the C6 aromatic ring of the molecule; the existence of atropisomers resulting from the non-equivalence of both faces of the C6 aromatic ring is a consequence of the 3-chloro-2-methylphenyl ring being nearly perpendicular to the mean plane of the 2,4-dibora-1,3-diazanaphthalene ring. The orientation of the Cr(CO)3 tripod relative to the C6 aromatic ring is such that it is nearly eclipsed in one isomer (2.4 degrees rotation from being eclipsed with C--N, C--Cl and C--H) and slightly twisted (16.2 degrees ) from an eclipsed conformation in the other.

Journal Article↗
PubMed2001

Combinatorial study of surface pattern formation in thin block copolymer films.

Surface pattern formation in diblock copolymer films is investigated as a function of film thickness h and molecular mass M. Smooth films are observed for certain h ranges centered about multiples of the lamellar thickness L0, and we attribute this effect to an increase in the surface chain density with h in the outer brushlike copolymer layer. We also observe apparently stable labyrinthine surface patterns for other h ranges, and the average size of these patterns is found to scale as lambda approximately L0(-2.5). Hole and island patterns occur for h ranges between those of the labyrinthine patterns and the smooth regions, and their size similarly decreases with L0 and M.

Journal Article↗
PubMed2001

Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia.

Activation of coagulation induces a proinflammatory response in in vitro and animal experiments. Inhibition of the tissue factor-dependent pathway of coagulation inhibits cytokine release and prevents death in gram-negative sepsis models in primates. This study investigated the influence of blocking the coagulation system by tissue factor pathway inhibitor (TFPI) on endotoxin-induced inflammatory responses in healthy humans. Eight men were studied in a double-blind, randomized, placebo-controlled cross-over study. They received a bolus intravenous injection of 4 ng/kg of endotoxin, followed by a 6-h continuous infusion of either TFPI (0.2 mg/kg/h after a bolus of 0.05 mg/kg) or placebo. Endotoxin induced-activation of coagulation was prevented completely by TFPI. In contrast, TFPI did not influence leukocyte activation, chemokine release, endothelial cell activation, or the acute phase response. Thus, complete prevention of coagulation activation by TFPI does not influence activation of inflammatory pathways during human endotoxemia.

Acute-Phase Reaction↗
PubMed2001

A novel MVMp-based vector system specifically designed to reduce the risk of replication-competent virus generation by homologous recombination.

Recent work highlights the potential usefulness of MVM-based vectors as selective vehicles for cancer gene therapy (Dupont et al, Gene Therapy, 2000; 7: 790-796). To implement this strategy, however, it is necessary to develop optimized methods for producing high-titer, helper-free parvovirus stocks. Recombinants of MVMp (rMVMp) are currently generated by transiently co-transfecting permissive cell lines with a plasmid carrying the vector genome and a helper plasmid expressing the capsid genes (replaced with a foreign gene in the vector genome). The resulting stocks, however, are always heavily contaminated with replication-competent viruses (RCV), which precludes their use in vivo and particularly in gene therapy. In the present work we have developed a second-generation MVMp-based vector system specifically designed to reduce the probability of RCV generation by homologous recombination. We have constructed a new MVMp-based vector and a new helper genome with minimal sequence overlap and have used the degeneracy of the genetic code to further decrease vector-helper homology. In this system, the left homologous region was almost completely eliminated and the right sequence overlap was reduced to 74 nt with only 61% homology. We were thus able to substantially reduce ( approximately 200 x), but not completely eliminate, generation of contaminating viruses in medium-scale rMVMp preparations. Since the remaining sequence homology between the new vector and helper genomes is weak, our results suggest that contaminating viruses in this system are generated by nonhomologous recombination. It is important to note, unlike the autonomously replicating helper viruses produced from the first-generation vector/helper genomes, the contaminating viruses arising from the new packaging system cannot initiate secondary infection rounds (so they are not 'replication-competent viruses'). Our findings have important implications for the design of new MVMp-based vectors and for the construction of trans-complementing packaging cell lines.

Animals↗
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↗
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↗