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Biomedical subjects

M Aslam

Publications and source records attributed to M Aslam.

At least 37 records · Page 2Linked to original sources

Atmospheric perfluorocarbons.

Collectively, man-made emissions of a few greenhouse gases may cause about the same amount of global warming as increasing carbon dioxide. Among the most potent of these non-CO2 greenhouse gases are the perfluorocarbons that have extraordinarily long atmospheric lifetimes of 10,000 to more than 50,000 yr. We report atmospheric concentrations over two decades, between 1978 and 1997, of the three most abundant perfluorocarbons--CF4, C2F6, and C3F8--and delineate the sources that account for the present abundances and trends. We show that C2F6 and C3F8 are present at only 2.9 and 0.2 pptv, respectively. CF4 is the most abundant perfluorocarbon at 74 pptv (in 1997) of which about 40 pptv are from natural emissions, 33 pptv from aluminum manufacturing, and 1 pptv from the semiconductor industry. The increasing trend of CF4 has slowed in recent years due to the major reductions in the emission rate per ton of aluminum produced. The effect of the falling emission factor is partially offset by increased production and increasing use by the semiconductor industry.

Air Pollutants↗

Modulation of oesophago-UOS contractile reflex: effect of proximal and distal esophageal distention and swallowing.

Upper oesophageal sphincter (UOS) tone is influenced by intraoesophageal pressure events. Our aim was to test the hypothesis that UOS tone is responsive to simultaneous inhibitory and stimulatory signals originating from the oesophagus and compare effect of proximal and distal oesophageal air distention on oesophageal balloon-stimulated UOS contraction. We studied 16 healthy volunteers, ages 19-80 years in two stages. We induced UOS contraction by distending various size balloons intraoesophageally and studied response of contracted UOS to oesophageal air distentions and swallowing. Intraoesophageal injections of 60-ml room air resulted in UOS pressure augmentation (31%), relaxation (64%) and no effect in the remaining 5% of instances. The majority of air injections into the oesophageal segment proximal to the distended balloon were followed by relaxation of the contracted UOS, whereas, the majority of oesophageal air distentions distal to the balloon resulted in augmentation of UOS contraction (P < 0.01). Swallowing resulted in complete relaxation of the UOS. In conclusion, UOS contractile response to oesophageal balloon distention is overridden by further augmentation or relaxation as a result of oesophageal air distention and swallowing. Contractile and inhibitory responses of the contracted UOS to generalized oesophageal distention is region-specific.

Adult↗

Reliability of pre-operative biopsies in the histological grading of colorectal adenocarcinomas.

BACKGROUND: Management of colorectal cancer depends on many patient and tumour variables. Decisions are sometimes based on the histological grade of tumour as assessed by initial biopsy. This retrospective study looked at the reliability of grading colorectal cancer from pre-operative biopsies. METHODS: 118 patients with a diagnosis of colorectal cancer, who had adequate pre-operative biopsies, were included in the study. A single consultant histopathologist re-examined all the preoperative biopsy slides, but was blinded to the final grading of the resection specimen. RESULTS: Of the 118 resection specimens, 41 were graded well-differentiated, 52 moderately differentiated and 25 poorly differentiated. When compared with postoperative grading, 37 (31%) initial biopsies were undergraded, 49 (43%) were correctly graded and 32 (26%) were overgraded. CONCLUSIONS: These results suggest that the histological grading of pre-operative specimens is inaccurate and should be used with caution to determine treatment. The difficulty with grading pre-operative biopsies in colorectal cancer may be owing to a lack of specific criteria such as is used in, for example, breast cancer.

Adenocarcinoma↗

Lipoprotein (a) and glycaemic control in Pakistani subjects with diabetes mellitus.

AIMS: To measure lipoprotein (Lp)(a) levels in people with diabetes mellitus (DM) and to see if there is any difference in Lp(a) levels between diabetics with good glycaemic control and those with poor glycaemic control. METHODS: Sixty subjects with DM and thirty healthy individuals were studied. Fasting blood samples were analyzed for glucose, glycosylated hemoglobin, Serum total cholesterol, triglycerides, low density lipoproteins, high density lipoproteins and Lp(a). RESULTS: A non significant difference was found between the lipid profile of normal individuals and subjects with DM with a good glycemic control. Lp(a) levels were significantly raised in diabetics. The difference in Lp(a) levels between well controlled and poorly controlled diabetics was non significant. In the control group 23.4% of individuals had high risk levels of Lp(a) while it was 46.7 % for people with DM. CONCLUSION: Glycaemic control improves lipid profile positively in diabetics and may even lead to near normalization of lipoprotein concentrations. Diabetics have elevated levels of Lp(a) and the difference in Lp(a) levels between well controlled and poorly controlled diabeticsts is non-significant.

Adult↗

Hypoxia and pulmonary acclimatisation at 4578 m altitude: the role of acetazolamide and dexamethasone.

OBJECTIVES: To quantify the changes in ventilatory response and arterial blood gases in healthy male volunteers on acute ascent to 4578 meters altitude along with evaluating the role of acetazolamide and dexamethasone prophylaxis in acclimatisation. METHODS: Forty four lowlander male subjects participated as two groups in the study. Twenty four lowlander healthy male adults (age mean +/- SE 27.8 +/- 1.24 years) comprised the non-acclimatised group. They were sub grouped in a double blind fashion into four. Each subgroup (n=6) received placebo (multivitamin) or acetazolamide (250 mg) or dexamethasone (4 mg) or combined regimen of the two drugs twice daily for 5 days commencing 24 hours before ascent. The volunteers reached the altitude of 4578 meters within a span of one day. The second group (acclimatised) comprised of age and height matched twenty volunteers who had arrived 4 and 8 weeks earlier at the same altitude. Arterial PO2, PCO2, SO2 and minute respiratory rate pH were measured. The pulmonary functions (FVC, %FEV1 PEF, FEF(25-75%) and MVV) were recorded by Compact Spirometer (Vitalograph). Pre and post ascent measurements were carried out in non-acclimatised group whereas one measurement of the same parameters were made in acclimatised group. RESULTS: The study revealed a significant increase in respiratory rate min-1 after 24 hours of ascent along with reduction in PaO2 and SaO2. The gradual increase in PaO2 and SaO2 and reduction in PaCO2 was observed after 4 weeks at the same altitude. The reduction in FVC, %FEV1, PEF, FEF(25-75%) and MW were recorded in our subjects after 24 hours of acute ascent. Nevertheless, all pulmonary parameters in volunteers having 8 weeks of stay at 4578 m altitude, were found equivalent to the non-acclimatised group. The greater increase in minute respiratory rate, PaO2, SaO2 and pulmonary functions was found in volunteers taking acetazolamide. CONCLUSION: It is concluded that hyperventilation and increase in lung volumes are the adaptive pulmonary responses which help in improving levels of PaO2 and SaO2. The acetazolamide-dexamethasone prophylaxis appears beneficial in promoting pulmonary acclimatisation during hypobaric hypoxia.

Acclimatization↗

Norm and associated radiation hazards in bricks fabricated in various localities of the North-West Frontier Province (Pakistan).

The activity concentrations of natural gamma-emitting radionuclides and associated radiation hazards due to 40K, 226Ra and 232Th have been measured in baked brick samples, collected from six highly populated areas of the North-West Frontier Province (NWFP) of Pakistan. For the detection, analysis and data acquisition, a high purity germanium (HPGe) detector coupled with a high resolution multichannel analyser (MCA) was used. The range of the average values of the activity concentrations due to 40K, 226Ra and 232Th were found to be 680.3 +/- 22.2-784.4 +/- 30.7 Bq kg(-1), 36.9 +/- 3.5-51.9 +/- 3.3 Bq kg(-1) and 52.5 +/- 3.6-67.6 +/- 3.1 Bq kg(-1), respectively. Radium equivalent (Ra(eq)) activities and various hazard indices were also calculated to assess the radiation hazards. All the brick samples showed Ra, activities within the limit (370 Bq kg(-1)) set by the Organization for Economic Cooperation and Development (OECD) countries. The results of different criterion formulae also complemented each other in this study. The derived data have been compared with the reported values for other countries of the world.

Aluminum Silicates↗

Solution structures of complement components by X-ray and neutron scattering and analytical ultracentrifugation.

The short consensus/complement repeat (SCR) domain (also known as the complement control protein domain) is the most abundant domain type in the complement system. Crystal and NMR structures for proteins that contain single and multiple SCR domains have now been published. These contain inter-SCR linkers of between three and eight residues, and the structures show much variability in inter-SCR orientations. X-ray and neutron scattering, combined with analytical ultracentrifugation and constrained modelling based on known subunit structures will yield a medium-resolution structure for the protein of interest. The fewer parameters that are associated with the structure of interest, the more defined the structure of interest becomes. These solution studies have been applied to several SCR-containing proteins in the complement system, most notably Factor H with 20 SCR domains, a complement receptor type 2 fragment with two SCR domains, and rat complement receptor-related protein (Crry) which contains five SCR domains. The results show great conformational variability in the inter-SCR orientation, and these will be reviewed. Even though the rotational orientation cannot be modelled, it is nonetheless possible to measure the degree of extension of the multi-SCR proteins and, from this, to obtain functionally useful results.

Animals↗

An unusual complication of penile prosthesis following urethroplasty.

We report a case of an adult who had undergone transpubic urethroplasty for a 5-cm long posterior urethral stricture. A malleable penile prosthesis (AMS 600R) was implanted 19 months later for the trauma-related impotence. The patient was discovered to develop a complete obliteration of the urethra after removal of infected penile prosthesis 18 months later. Perineal urethroplasty cured his restricture. Suggestions are made to prevent urethral restricture if penile prosthesis is required after urethroplasty.

Device Removal↗

Pictorial review: MRI of the sternum and sternoclavicular joints.

The sternum and sternoclavicular joints are difficult to evaluate with plain radiographs. The value of CT in assessing lesions of the sternum and sternoclavicular joints has been well documented, but the potential role of MRI has not been emphasized. We present the MRI techniques, normal appearances and a spectrum of abnormalities, and emphasize the role of MRI as a useful radiological investigation for the sternum and sternoclavicular joints.

Bacterial Infections↗

Folded-back solution structure of monomeric factor H of human complement by synchrotron X-ray and neutron scattering, analytical ultracentrifugation and constrained molecular modelling.

Factor H (FH) is a regulatory cofactor for the protease factor I in the breakdown of C3b in the complement system of immune defence, and binds to heparin and other polyanionic substrates. FH is composed of 20 short consensus/complement repeat (SCR) domains, for which the overall arrangement in solution is unknown. As previous studies had shown that FH can form monomeric or dimeric structures, X-ray and neutron scattering was accordingly performed with FH in the concentration range between 0.7 and 14 mg ml(-1). The radius of gyration of FH was determined to be 11.1-11.3 nm by both methods, and the radii of gyration of the cross-section were 4.4 nm and 1.7 nm. The distance distribution function P(r) showed that the overall length of FH was 38 nm. The neutron data showed that FH was monomeric with a molecular mass of 165,000(+/-17,000) Da. Analytical ultracentrifugation data confirmed this, where sedimentation equilibrium curve fits gave a mean molecular mass of 155,000(+/-3,000) Da. Sedimentation velocity experiments using the g*(s) derivative method showed that FH was monodisperse and had a sedimentation coefficient of 5.3(+/-0.1) S. In order to construct a full model of FH for scattering curve and sedimentation coefficient fits, homology models were constructed for 17 of the 20 SCR domains using knowledge of the NMR structures for FH SCR-5, SCR-15 and SCR-16, and vaccinia coat protein SCR-3 and SCR-4. Molecular dynamics simulations were used to generate a large conformational library for each of the 19 SCR-SCR linker peptides. Peptides from these libraries were combined with the 20 SCR structures in order to generate stereochemically complete models for the FH structure. Using an automated constrained fit procedure, the analysis of 16,752 possible FH models showed that only those models in which the 20 SCR domains were bent back upon themselves were able to account for the scattering and sedimentation data. The best-fit models showed that FH had an overall length of 38 nm and is flexible. This length is significantly less than a predicted length of 73 nm if the 20 SCR structures had been arranged in an extended arrangement. This outcome is attributed to several long linker sequences. These bent-back domain structures may correspond to conformational flexibility in FH and enable the multiple FH binding sites for C3 and heparin to come into close proximity.

Amino Acid Sequence↗

Structural studies in solution of the recombinant N-terminal pair of short consensus/complement repeat domains of complement receptor type 2 (CR2/CD21) and interactions with its ligand C3dg.

Human complement receptor type 2 (CR2, CD21) is a cell surface receptor that binds three distinct ligands (complement C3d, Epstein-Barr virus gp350/220, and the low-affinity IgE receptor CD23) via the N-terminal two of fifteen or sixteen short consensus/complement repeat (SCR) domains. Here, we report biophysical studies of the CR2 SCR 1-2 domain binding to its ligand C3dg. Two recombinant forms of CR2 containing the SCR 1-2 and SCR 1-15 domains were expressed in high yield in Pichia pastoris and baculovirus, respectively. Circular dichroism spectroscopy showed that CR2 SCR 1-2 receptor possessed a beta-sheet secondary structure with a melting temperature of 59 degrees C. Using surface plasmon resonance, kinetic parameters for the binding of either CR2 SCR 1-2 or the full-length SCR 1-15 form of CR2 showed that the affinity of binding to immobilized C3d is comparable for the SCR 1-15 compared to the SCR 1-2 form of CR2. Unexpectedly, both the association and dissociation rates for the SCR 1-15 form were slower than for the SCR 1-2 form. These data show that the SCR 1-2 domains account for the primary C3dg binding site of CR2 and that the additional SCR domains of full-length CR2 influence the ability of CR2 SCR 1-2 to interact with its ligand. Studies of the pH and ionic strength dependence of the interaction between SCR 1-2 and C3d by surface plasmon resonance showed that this is influenced by charged interactions, possibly involving the sole His residue in CR2 SCR 1-2. Sedimentation equilibrium studies of CR2 SCR 1-2 gave molecular weights of 17 000, in good agreement with its sequence-derived molecular weight to show that this was monomeric. Its sedimentation coefficient was determined to be 1.36 S. The complex with C3d gave molecular weights in 50 mM and 200 mM NaCl buffer that agreed closely with its sequence-derived molecular weight of 50 600 and showed that a 1:1 complex had been formed. Molecular graphics views of homology models for the separate CR2 SCR 1 and SCR 2 domains showed that both SCR domains exhibited a distribution of charged groups throughout its surface. The single His residue is located near a long eight-residue linker between the two SCR domains and may influence the linker conformation and the association of C3d and CR2 SCR 1-2 into their complex. Sedimentation modeling showed that the arrangement of the two SCR domains in CR2 SCR 1-2 is highly extended in solution.

Amino Acid Sequence↗

Differential effect of amino acids on nitrate uptake and reduction systems in barley roots.

This study was conducted to determine whether the inhibition of nitrate reductase activity (NRA; EC 1.6.6.1) in barley (Hordeum vulgare L. var. CM-72) roots by the amino acids (glutamic, aspartic, glutamine and asparagine) is a direct effect or indirect due to inhibition of the NO(3)(-) uptake system. Roots of 8-day-old intact seedlings were supplied with the amino acids (I mM) individually either with NO(3)(-) (0.1 or 10 mM) or roots were pretreated with the amino acids and then supplied with NO(3)(-) only. Nitrate uptake was determined by following NO(3)(-) depletion from the uptake solution containing 0.1 mM NO(3)(-). All the amino acids inhibited the increase in NO(3)(-) uptake similarly (50-60%) when the roots were supplied with 0.1 mM NO(3)(-). Pretreatment with glutamic and aspartic acids was more inhibitory (70-80%) than with glutamine and asparagine (30%). The amino acids partially inhibited (35%) the induction of NRA in roots supplied with 0.1 mM NO(3)(-); however, no inhibition occurred at 10 mM NO(3)(-). Likewise, pretreatment with glutamic or aspartic acid inhibited the induction of NRA at 0.1 mM NO(3)(-) but not at 10 mM NO(3)(-). In contrast, pretreatment with glutamine or asparagine had no effect on the subsequent induction of NRA, even at 0.1 mM NO(3)(-). The results suggest that, at low NO(3)(-) supply, the inhibition of induction of NRA by the amino acids is a result of the lack of substrate availability due to inhibition of the NO(3)(-) uptake system.

Journal Article↗

Fecal incontinence after minor anorectal surgery.

PURPOSE: Fecal leakage after open lateral internal anal sphincterotomy for chronic anal fissure is common, but underreported. The aim of this study was to prospectively assess the physiologic and morphologic effects of sphincterotomy, comparing continent and incontinent patients after surgery. This group was further compared with an unselected group of patients presenting with incontinence after hemorrhoidectomy. METHODS: Between January 1997 and June 1999, 23 patients were prospectively followed up through internal sphincterotomy with conventional and vector volume anorectal manometry, parametric assessment of the rectoanal inhibitory reflex, and endoanal magnetic resonance imaging. Fourteen continent patients were compared with 9 incontinent postoperative cases, 9 patients referred with incontinence after hemorrhoidectomy, and 33 healthy volunteers without anorectal disease. RESULTS: Significant differences were noted between continent and incontinent postsphincterotomy cases for all resting conventional and vector volume parameters and for some squeeze parameters. Although there was a significant reduction in postoperative high pressure zone length at rest, there were no differences between the postoperative groups. There was an increase in sphincter asymmetry of 6.7 percent (+/- 3.5 percent) in incontinent postsphincterotomy patients and a decrease of 2.8 percent (+/- 3.2 percent) in continent cases. Significant differences were noted for resting parameters between incontinent postsphincterotomy and posthemorrhoidectomy patients, with a higher resting sphincter asymmetry in the latter group. The area under the rectoanal inhibitory curve was smaller in postsphincterotomy incontinent patients when compared with continent cohorts over the distal and intermediate sphincter zones at rest with a reduced latency of inhibition. There was no difference in the magnetic resonance images of the sphincterotomy site between incontinent and continent postsphincterotomy cases and no posthemorrhoidectomy case had evidence of sphincteric damage. CONCLUSION: There are complex significant differences in the postoperative physiology of patients undergoing lateral internal sphincterotomy who become incontinent when compared with those who maintain continence. These physiologic changes are not reflected in detectable morphologic sphincteric differences. It is unknown whether these changes predict for long-term incontinence, and it is suggested that postoperative incontinence after minor anorectal surgery is not necessarily related either to a preexisting sphincter defect or inadvertent intraoperative sphincter injury.

Adult↗

Rectoanal inhibition and rectocele: physiology versus categorization.

Some authors divide rectoceles into those with chronic evacuatory difficulty and normal genital position (type 1) and those with associated pelvic organ prolapse (type 2). This study assessed whether there are physiological differences between these two clinical rectocele types. Female patients were assessed by conventional anorectal manometry, vector manometry, parametric assessment of the rectoanal inhibitory reflex (RAIR), and defecography. Subjects included 33 volunteer controls without anorectal disease, 14 patients with type I rectocele, and 26 patients with type II rectocele. Significant differences were noted for resting pressure measurements (maximal resting anal pressure and vector volume) between rectocele types and between type I patients and controls. Significant differences were noted for squeeze parameters (maximal squeeze pressure and vector volume) only between rectocele types. There were minimal differences in parameters of the RAIR, with a reduced slope of inhibition in the proximal sphincter for both rectocele groups and a reduced maximal inhibitory pressure in the intermediate and distal sphincter of type 1 rectocele patients. There were no differences in transient excitation of the pressure wave during the RAIR reflex to account for pressure variations with no measured differences in rectocele depth (type 1, 2.87 +/- 0.7 cm; type 2, 2.84 +/- 1.4 cm) There are few physiological differences between the different clinical categories of rectocele patients based on the presence or absence of associated genital prolapse.

Adult↗

Multisorbent plasma perfusion in fulminant hepatic failure: effects of duration and frequency of treatment in rats with grade III hepatic coma.

Using the model of galactosamine-induced fulminant hepatic failure in the rat, the effects of multisorbent plasma perfusion over Asahi uncoated spherical charcoal, Plasorba (BR-350) resin, and an endotoxin removing adsorbent (polymyxin B-sepharose) were determined in Grade III hepatic coma animals by studying survival as influenced by timing, duration, and frequency of treatment. The effects of treatment on liver cell proliferation and endotoxin removal also were examined. The results demonstrate that duration and frequency of treatment are major contributing factors in the successful application of nonbiological membrane-based multisorbent liver support systems. Examination of the regenerative activity in the liver indicates an enhanced proliferative response following multisorbent plasma perfusion compared with untreated fulminant hepatic failure (FHF) paired controls. Utilizing an endotoxin removal adsorbent alone, a marked reduction in systemic levels of endotoxin in FHF was demonstrated compared with nonperfused FHF paired controls. Despite current emphasis on bioartificial liver support systems, plasma purification by multisorbent systems offers a simple method for the removal of circulating toxic metabolites in general together with specific toxin removal.

Animals↗

Radiological significance of building bricks in Pakistan.

Baked clay bricks samples were collected from both urban and rural areas of the North West Frontier Province of Pakistan and natural radioactivity due to 40K, 226Ra and 232Th has been measured in these samples. The specific absorbed dose rates due to natural radioactivity emanating from the walls, floors and ceilings of the typical model rooms made of these building bricks have been calculated applying the mesh size adaptive volume integral methodology. The occupancy factor, representing the weighted average of all the population in the country, was taken to be 0.3 in this study. The values of estimated annual effective dose rates for whole body were found to be 0.38 and 0.35 mSv.y(-1) for the two types of model rooms. These values are smaller than those predicted by UNSCEAR for normal background areas. Thus the building bricks analysed in this study do not pose any significant health problem to the population.

Background Radiation↗

Evaluation of body mass index for a reference Pakistani man and woman.

To strengthen the radiation protection infrastructure, a pilot study on physical characteristics for Reference Asian Man was carried out in Pakistan. Physical data on height and weight of Pakistani men and women were collected and compiled for all age groups to establish a Reference Pakistani Man/Woman which contributed toward the Reference Asian Man/Woman. A correlation between Age and Body Mass Index (BMI) of Pakistani MALES (i.e., rm = +0.89) and FEMALES (i.e., rf = +0.71) was observed. Average BMI of Pakistani males and females for the age group of 20-50 y was found to be 21.95 kg m(-2) and 21.20 kg m(-2), respectively. From recent literature and work of others BMI for Reference Asian Male (RAM) and Reference Asian Female (RAF) has been found to be 20.79 kg m(-2) and 20.81 kg m(-2). Results of our study fall within BMI ranges for male/female adults of Asian countries, i.e., 19.14-22.98 kg m(-2) and 19.38-22.71 kg m(-2), respectively. However, no significant sex specific difference has been noted.

Adolescent↗