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Biomedical subjects

S Malik

Publications and source records attributed to S Malik.

At least 19 recordsLinked to original sources
PubMed2003

Respiratory disease due to parainfluenza virus in adult leukemia patients.

Reports of human parainfluenza viruses (HPIV) in patients with leukemia have been limited to a few cases or as a portion of general surveys. In order to expand the knowledge of these infections in this patient group, the frequency and clinical course of HPIV infections was determined among 1,787 patients with leukemia treated at The University of Texas M.D. Anderson Cancer Center between July 1994 and December 1997. HPIV was isolated from 47 (6.2%) of the 770 patients who were cultured for respiratory viruses. HPIV type 3 accounted for 39 of the 47 HPIV infections. Twenty-six patients developed pneumonia, and the associated mortality was 27%. Multivariate analysis revealed that a low absolute lymphocyte count and pneumonia were associated with increased mortality. Concurrent respiratory and other infections were associated with an increased frequency of pneumonia. Only five patients with pneumonia received antiviral therapy and four of them survived the infection. HPIV infection in leukemic patients is frequently associated with pneumonia and the mortality rate from pneumonia is substantial among lymphopenic patients.

Adolescent↗
PubMed2003

An evaluation of topical and local anesthesia in phacoemulsification.

OBJECTIVE: To assess the comparative efficacy of topical and local anesthesia in phacoemulsification. MATERIAL AND METHODS: The medical records of 186 men and women between the ages of 45-85 years, who underwent elective cataract surgery by phacoemulsification technique, under the care of one surgeon, over a period of one year, from March 1999-March 2000 were reviewed. RESULTS: Of 186 patients who underwent small incision, self-healing phacoemulsification cataract surgery, 124 received topical and 62 local anesthesia. The most common cataract types were nuclear sclerosis. The duration of surgery with topical anesthesia was shorter. Sutures and eye padding were more frequently applied for procedures done under local anesthesia. Uncorrected visual acuity in the first post-op week was between 20/20-20/50 for 53.6% of the cases done under topical compared to 30.9% in local anesthesia. A similar trend was noted in the visual acuity one month post operatively. CONCLUSION: The uncorrected visual acuity improves faster and the duration of surgery is shorter when topical anesthesia is used.

Administration, Topical↗
PubMed2002

Adult onset pigmentary orthochromatic leukodystrophy with ovarian dysgenesis.

Pigmentary type of orthochromatic leukodystrophy (POLD) is an adult-onset leukodystrophy, characterized pathologically by the presence of glial and microglial cytoplasmic pigment inclusions. The complete phenotype, genotype and pathogenetic mechanisms in POLD have not been elucidated. We followed for 18 years a woman with autopsy-proven POLD, who presented with 'frontal' dementia and spasticity. Her further course was marked by progressive mutism, apraxia and seizures. Her sister had died of the same disease after a much more rapidly progressing course. These sisters had primary infertility with pathologic evidence of streak ovaries. Diagnosis was confirmed in both cases by post-mortem examination. POLD is a rare cause of adult-onset leukodystrophy presenting with dementia. Ovarian dysgenesis is extremely rare in the absence of demonstrable chromosomal abnormalities and extends the clinical spectrum of POLD.

Adult↗
PubMed2002

Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.

Adult↗
PubMed2002

Comparative analysis of knowledge, attitudes and perceptions about induced abortions among medical and non-medical students of Karachi.

OBJECTIVE: To determine the knowledge, attitudes and perceptions regarding induced abortions among university students of Karachi and compare these aspects among medical and non-medical students. STUDY DESIGN: Cross sectional opinion survey. METHODS: The study is a cross sectional opinion survey of medical and non-medical students from four educational institutions of Karachi using a pretested questionnaire. RESULTS: Of the 381 students interviewed, 201 were medical and 180 were non-medical. More medical students were aware of the correct definition of induced abortion. An encouraging finding was the awareness of our study population about the only legally acceptable circumstance for induced abortion in Pakistan, that is, if conceptus is a risk to maternal health (p<0.001). More medical students cited complications that were technical like uterine perforation (p<0.001), cervical trauma (p<0.001), DIC (p<0.001), and sepsis (p<0.001). More medical students thought induced abortion to be a health issue (p=0.001) as compared to non-medical students. Most of the medical students felt the need to modify Pakistan's law regarding abortion (p=0.008) especially for fetal anomalies (13.9%) and rape (7%). CONCLUSION: Though medical students were more knowledgeable about induced abortions as compared to the non-medical population, there is a need to improve awareness regarding induced and unsafe abortions and their consequences.

Abortion, Induced↗
PubMed2001

Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis.

Mutation of the adenomatous polyposis coli (APC) gene and the subsequent dysregulation of beta-catenin are well-documented abnormalities in familial adenomatous polyposis (FAP), as well as sporadic polyposis. Intriguingly, overexpression of the integrin-linked kinase (ILK) has been shown to modulate beta-catenin subcellular localization and function. However, the significance of this finding for human carcinogenesis remains unclear. Here, we report the increased biochemical activity and expression of ILK protein in polyps from FAP patients. Furthermore, dramatic increases in ILK immunoreactivity were observed in all abnormal crypts from sporadic polyps, when compared with the normal appearing crypts within the same resected specimens. As sulindac and aspirin are the two most important therapeutic/chemopreventative agents demonstrated in colorectal carcinogenesis, in both humans and animals, further investigation revealed that these non-steroidal anti-inflammatory drugs (NSAIDs) target ILK and ILK-mediated events in vivo. These include inhibition of, both the biochemical activation of ILK, inhibition of serine 9 GSK3beta phosphorylation and the enhancement of TCF-4 transcriptional activity. In conclusion, ILK protein hyperexpression appears to be an early event in colonic polyposis. Additionally, ILK signaling is shown to undergo modulation by sulindac (and aspirin) for the first time, indicating that it is likely to be one of the targets affected by these agents in vivo.

Adenomatous Polyposis Coli↗
PubMed2001

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗
PubMed2001

Narcolepsy associated with other central nervous system disorders.

The authors identified patients with the coexistence of narcolepsy and another CNS disorder seen between 1975 and 1998 at their institution. Eighteen patients were identified, nine with narcolepsy commencing within 1 year before or after the other disorder. Seven patients (39%) had hypothalamic-pituitary syndromes. When they occur together, narcolepsy and other CNS disorders frequently emerge at about the same time, suggesting a causative relationship. Hypothalamic-pituitary pathology was the most common association.

Brain↗
PubMed2001

Measurement of the electric form factor of the neutron through d-->(e-->,e(')n)p at Q2 = 0.5 (GeV/c)(2).

We report the first measurement using a solid polarized target of the neutron electric form factor G(n)(E) via d-->(e-->,e(')n)p. G(n)(E) was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia ( 15ND3). The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility in quasifree kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find G(n)(E) = 0.04632+/-0.00616(stat)+/-0.00341(syst) at Q2 = 0.495 (GeV/c)(2).

Journal Article↗
PubMed2001

Acetoxy-4-methylcoumarins confer differential protection from aflatoxin B(1)-induced micronuclei and apoptosis in lung and bone marrow cells.

The ability of various acetoxy derivatives of 4-methylcoumarins to inhibit the genotoxic changes due to aflatoxin B(1) (AFB(1)) is reported here. Several 4-methylcoumarins (test compounds), such as 7,8-diacetoxy-4-methylcoumarin (DAMC), monoacetoxy-4-methylcoumarin (MAC), 5-N-acetyl-6-acetoxy-4-methylcoumarin (NAMC) and 7,8-dihydroxy-4-methylcoumarin (DHMC) were separately administered intraperitoneally (i.p.) to male wistar rats followed by AFB(1) administration i.p. or intratracheally (i.t.) (2-8 mg/kg b.wt.) and another dose of the test compound. The animals were sacrificed 26h after AFB(1) administration. From animals receiving AFB(1) i.p., bone marrow (BM) cells were isolated and stained with Mayer's haematoxylin and eosin. Micronuclei (MN) in BM were scored by light microscopy. From animals receiving AFB(1) i.t., bronchoalveolar lavage (BAL) was obtained, lung cells (LG) were isolated and stained with fluorochrome 6-diamidino-2-phenylindole (DAPI) for the analysis of MN, apoptotic bodies (AP) and cell cycle variations. Rats were separately treated with the vehicle DMSO to serve as the proper control. AFB(1) caused significant dose-dependent induction of MN in BM as well as LG. AP were observed in LG of rats receiving AFB(1) and was found to correlate with MN induction. DAMC injection caused significant decrease in AP due to AFB(1) in LG and MN in both BM and LG. The effectiveness of MAC was approximately half that of DAMC, thereby indicating that number of acetoxy groups on the coumarin molecule determine the efficacy. The fact that NAMC had no effect either on MN or AP indicate that neither acetoxy group at C-6 nor the N-acetyl group at C-5 facilitate the transfer of acetyl group to P-450 required for inhibition of AFB(1)-epoxidation. DHMC, the deacetylated product of DAMC had no normalizing effect on the induction of MN and AP. These findings confirm our earlier hypothesis that DAMC-mediated acetylation of microsomal P-450 (catalysing epoxidation of AFB(1)) through the action of microsomal transacetylase is responsible for the protective action of DAMC. The relative number and position of acetoxy groups on the coumarin nucleus determine the specificity to the transacetylase necessary for the chemopreventive action.

Acetylation↗
PubMed2001

Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription complex.

The X-ray structure of a ternary complex of Negative Cofactor 2 (NC2), the TATA box binding protein (TBP), and DNA has been determined at 2.6 A resolution. The N termini of NC2 alpha and beta resemble histones H2A and H2B, respectively, and form a heterodimer that binds to the bent DNA double helix on the underside of the preformed TBP-DNA complex via electrostatic interactions. NC2beta contributes to inhibition of TATA-dependent transcription through interactions of its C-terminal alpha helix with a conserved hydrophobic feature on the upper surface of TBP, which in turn positions the penultimate alpha helix of NC2beta to block recognition of the TBP-DNA complex by transcription factor IIB. Further regulatory implications of the NC2 heterodimer structure are discussed.

Amino Acid Sequence↗
PubMed2001

New antioxidant and antimicrobial ellagic acid derivatives from Pteleopsis hylodendron.

Bioassay-guided isolation of two new compounds, 3,4-methylenedioxy-3'-O-methyl-4'-O-glucoside ellagic acid (1) and the pteleoellagic acid derivative (2), from the stem bark of Pteleopsis hylodendron is reported along with 3,4-methylenedioxy-3'-O-methyl ellagic acid (3), 3,3'-di-O-methyl ellagic acid (4) and 3,3',4'-tri-O-methyl ellagic acid (5), which were obtained for the first time from this plant. The structures of these compounds were elucidated with the help of spectroscopic studies. Compounds 1 and 4 were found to have significant antioxidant activity, while compounds 1-4 showed antibacterial activity against different pathogenic bacteria.

Anti-Bacterial Agents↗
PubMed2001

Triterpenes from Mimusops elengi.

Pentacyclic triterpenes (1) and (2) have been isolated from Mimusops elengi and assigned structures 3beta,6beta,19alpha,23-tetrahydroxy-urs-12-ene and 1beta-hydroxy-3beta-hexanoyllup-20 (29)-ene-23, 28-dioic acid, respectively, on the basis of spectroscopic studies including 2D-NMR. The compound 1 showed moderate inhibiting activity against beta-glucuronidase enzyme

Animals↗
PubMed2001

Angiogenic growth factor messenger ribonucleic acids in uterine natural killer cells.

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.

Angiogenesis Inducing Agents↗
PubMed2001

Effects of duration and time of food availability on photoperiodic responses in the migratory male blackheaded bunting (Emberiza melanocephala).

The effects of the duration and time of food availability on stimulation of the photoperiodic responses (fattening and gain in body mass, and growth and development of testes) were investigated in the migratory blackheaded bunting (Emberiza melanocephala). Two experiments were performed. Experiment I examined the effects of a reduction in the duration of food supply in buntings that were subjected to long day lengths (16h:8h L:D) and received food ad libitum (group I) or for restricted durations, coinciding with the end of the lights-on period, of 8h (group II) and 4h (group III). Buntings of group I gained in body mass, whereas there was a mixed response in group II (half the birds gained and half lost body mass), and all birds of group III lost body mass. There was no effect on testis growth in groups I and II, but testes grew more slowly in group III. Experiment 2 investigated the effects of both the duration and the time of food availability. Of five groups of birds, group I was exposed to an 8h:16h L:D photoperiod, and groups II-V were exposed to 16h:8h L:D. Whereas birds of groups I and II received food ad libitum, those of groups III-V were fed only for 5 h, at zt 0-5 (group III), zt 5.5-10.5 (group IV) or zt 11-16 (group V), where zt = zeitgeber time and zt 0 refers to the beginning of the lights-on period. Apart from duration, the timing of food availability also had an effect on photoperiodic stimulation under the 16h:8h L:D photoperiod. Birds that were fed ad libitum fattened and gained in body mass, whereas among restricted feeding groups, only birds in the group fed during the first 5 h (zt 0-5, group III) showed a significant increase in body mass (albeit considerably lower than in the ad libitum group). Birds fed during the middle 5h (zt 5.5-10.5, group IV) showed an intermediate response, and those fed during the last 5h (zt 11-16, group V) lost body mass. Testicular growth was suppressed in birds that were fed for 5 h in the evening, but not in those fed for the same period in the morning or in the middle of the long day. Taken together, these results show that the duration of food supply and/or the time of day at which food is available affect photoperiodic stimulation of fattening and gain in body mass as well as the growth and development of gonads in the blackheaded bunting.

Animal Migration↗
PubMed2001

Ethnic classification in primary dental care and dental health services research: time to pause for thought.

'Ethnicity' is an important concept in dental health services research and in enabling general dental practitioners to gain insight into their patients values and expectations. Since more health services research is being undertaken in primary dental care settings it is becoming an important issue for dental professionals and researchers in primary care to be aware of. Ethnicity is thought to be related to dental health inequalities and access and is often used as a stratifying variable in many dental studies. The meaning and use of the term however differs among researchers and among the public. It is clear that researchers and professionals need to pause for thought when considering what this often bandied about term actually means and the impact of different definitions. This is illustrated using examples from the authors' own research and published papers in the medical and dental literature. There is also much debate about whether ethnicity--however defined--is an important predictor of differences in dental health in itself or is merely a marker for other factors such as social deprivation or the impact of 'place' on dental health. While the jury on this debate is out we suggest guidelines on the reporting of ethnicity should be outlined in the dental literature--perhaps updating those published in 1996 in the British Medical Journal.

Cultural Characteristics↗
PubMed2001

Chemoprevention of benzene-induced bone marrow and pulmonary genotoxicity.

Our earlier studies documented the ability of 7,8-diacetoxy-4-methylcoumarin (DAMC) to cause irreversible inhibition of cytochrome P-450 linked mixed function oxidases (MFO) mediated by membrane bound DAMC: protein transacetylase. Since P-450 catalyzed oxidation of benzene is crucial to its toxic effects, the action of DAMC and related analogues were considered promising in preventing the genotoxicity due to benzene. For this purpose rats were pretreated with various acetoxy-4-methylcoumarins (test compounds), which was followed by the administration of benzene either intratracheally (IT) or intraperitoneally (IP), and sacrificed 26 h after the injection of benzene. The incidence of micronuclei (MN) in bone marrow (BM) and lung (LG) were assessed by light and fluorescent microscopy, respectively. A dose-dependent induction of MN in BM and LG cells was observed in rats administered with benzene. A significant reduction in benzene-induced MN in BM and LG was observed as a result of DAMC administration to rats; a higher dose of DAMC resulted in greater inhibition of clastogenic action of benzene as revealed by MN incidence. 7,8-dihydroxy-4-methylcoumarin (DHMC), the deacetylated product of DAMC, demonstrated relatively lesser potency to inhibit the clastogenic action of benzene. This observation is consistent with the ability of DAMC to inhibit the formation of benzene oxide as well as to scavenge the oxygen radicals formed during the course of benzene metabolism. The fact that DHMC can only scavenge the oxygen radicals and is ineffective in inhibiting benzene oxidation in vivo explains the reduced capability of dihydroxy coumarin to prevent MN due to benzene. 7-Acetoxy-4-methylcoumarin (MAC) inhibits the MN due to benzene being roughly 50% of that produced by DAMC. DAMC is also effective in normalizing the cell cycle alterations produced by benzene in BM and LG. These observations further substantiate our hypothesis that the biological effects of acetoxy coumarins are mediated by the action of membrane bound transacetylase that catalyzes the acetylation of concerned proteins. Teratogenesis Carcinog. Mutagen. 21:181-187, 2001.

Animals↗