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Biomedical subjects

M Saeed

Publications and source records attributed to M Saeed.

At least 19 recordsLinked to original sources
PubMed2006

Lack of association of VEGF promoter polymorphisms with sporadic ALS.

The authors tested the association of three vascular endothelial growth factor (VEGF) promoter polymorphisms with sporadic ALS (SALS) to verify the results of a previous study and to investigate their modifier effects on the subphenotypes of SALS in a large family-based and case-control cohort of North American white subjects (N = 1,603). They did not find any association of the VEGF promoter polymorphisms with SALS or its subphenotypes, suggesting that they do not have a direct causal role in ALS.

Adult↗
PubMed2006

Paraoxonase cluster polymorphisms are associated with sporadic ALS.

BACKGROUND: Paraoxonases (PONs) are involved in the detoxification of organophosphate pesticides and chemical nerve agents. Due to a reported possible twofold increased risk of ALS in Gulf War veterans and the associations of PON1 polymorphisms with the neurologic symptom complex of the Gulf War syndrome, the authors investigated the association between sporadic ALS (SALS) and PON gene cluster variants in a large North American Caucasian family-based and case-control cohort (N = 1,891). METHODS: Clinically definite and probable ALS was diagnosed according to the revised El Escorial criteria, exclusion of family history of ALS, and SOD1 mutation analysis. Single nucleotide polymorphism (SNP) genotyping was done using TaqMan assays on ABI7900HT. Data were analyzed using SPSS, Haploview, FBAT, and THESIAS. RESULTS: A haploblock of high linkage disequilibrium (LD) spanning PON2 and PON3 was associated with SALS. The SNPs rs10487132 and rs11981433 were in strong LD and associated with SALS in the trio (parents-affected child triad) model. The association of rs10487132 was replicated in 450 nuclear pedigrees comprising trios and discordant sibpairs. No association was found in case-control models, and their haplostructure was different from that of the trios with overall reduced LD. Resequencing identified an intronic variant (rs17876088) that differentiated between detrimental and protective SALS haplotypes. CONCLUSION: This study demonstrates evidence of significant association of variants in the Paraoxonase gene cluster with sporadic ALS and is compatible with the hypothesis that environmental toxicity in a susceptible host may precipitate ALS.

Adult↗
PubMed2005

MRI in guiding and assessing intramyocardial therapy.

Cardiovascular intervention, using MRI guidance, is challenging for clinical applications. Real-time imaging sequences with high spatial resolution are needed for monitoring intramyocardial delivery of drug, gene, or stem cell therapies. New generation MR scanners make local intramyocardial and vascular wall therapies feasible. Contrast-enhanced MRI is used for assessing myocardial ischemia, infarction, and scar tissue. Active (microcoils) and passive (T1 and T2* mechanisms) tracking methods have been used for visualization of endovascular catheters. Safety issues related to potential heating of endovascular devices is still a major obstacle for MRI-guided interventions. Fabrication of MRI-compatible interventional devices is limited. Noninvasive imaging strategies will be critical in defining spatial and temporal characteristics of angiogenesis and myocardial repair as well as in assessing the efficacy of new therapies in ischemic heart disease. MRI contrast media improve the capability of MRI by delineating the target and vascular tree. Labeling stem cells enables MRI to trace distribution, differentiation, and survival in myocardium and vascular wall. In the long term, MRI in guiding and assessing intramyocardial therapy may circumvent the limitations of peripherally administered cell therapy, X-ray angiography, and nuclear imaging. MRI represents a highly attractive discipline whose systematic development will foster the implementation of new cardiac and vascular therapies.

Cardiomyopathies↗
PubMed2005

Development of monoclonal antibodies to 4-hydroxyestrogen-2-N-acetylcysteine conjugates: immunoaffinity and spectroscopic studies.

Catechol estrogen quinones (CEQ) derived from oxidation of the catechol estrogens 4-hydroxyestrone (4-OHE1) and 4-hydroxyestradiol (4-OHE2) can conjugate with glutathione (GSH), a reaction that prevents damage to DNA and can provide biomarkers of exposure to CEQs. Monoclonal antibodies (MAb) to 4-OHE1(E2)-2-N-acetylcysteine [4-OHE1(E2)-2-NAcCys] were developed and characterized by immunological and spectroscopic studies. The NAcCys conjugate is the hydrolytic product of the corresponding conjugate with GSH, followed by N-acetylation of cysteine. MAbs were produced by immunizing mice with 4-OHE1(E2)-2-NAcCys attached to an appropriate linker that was conjugated to keyhole limpet hemocyanin (KLH). Hybridoma cell lines were screened using 4-OHE1(E2)-2-NAcCys conjugated to ovalbumin (OA). There is no immunological cross-reactivity between KLH and OA. Hence, positive hybridoma cell lines secreting antibody against 4-OHE1(E2)-2-NAcCys could be rapidly identified using OA-4-OHE1(E2)-2-NAcCys. An affinity column was developed and used to purify MAb against 4-OHE1(E2)-2-NAcCys. The purified MAb was immobilized on an agarose bead column. This column was used to capture and preconcentrate the hapten of interest out of urine samples. A number of structurally related standards were used to estimate the selectivity and specificity of the chosen MAb. Capillary electrophoresis (CE) with field-amplified sample stacking in absorbance detection mode and laser-induced low temperature luminescence measurements were used to identify and quantitate the 4-OHE1(E2)-2-NAcCys conjugates and related compounds released from the affinity column. Femtomole detection limits have been demonstrated. Future prospects in clinical diagnostics for testing human exposure to CEQ by urine analysis are briefly addressed.

Acetylcysteine↗
PubMed2003

Cotton leaf curl disease is associated with multiple monopartite begomoviruses supported by single DNA beta.

For bipartite begomoviruses (family Geminiviridae) trans-replication of the DNA B component by the DNA A-encoded replication-associated protein (Rep) is achieved by virtue of a shared sequence, the "common region", which contains repeated motifs (iterons) which are sequence-specific Rep binding sites and form part of the origin of replication. Recently cotton leaf curl disease (CLCuD), a major constraint to cotton production on the Indian subcontinent, has been shown to be caused by a monopartite begomovirus ( Cotton leaf curl Multan virus [CLCuMV]) and a novel single-stranded DNA satellite molecule termed CLCuD DNA beta. The satellite molecule is trans-replicated by CLCuMV but does not possess the iteron sequences of this virus. We have investigated the ability of CLCuD DNA beta to interact with three further clones of monopartite begomoviruses, isolated from cotton, that have distinct Rep binding specificities. All three cloned viruses were capable of trans-replicating the satellite molecule and inducing CLCuD symptoms in cotton, indicating that the interaction between begomovirus and DNA beta is relaxed in comparison to the interaction between DNA A and DNA B components. Field surveys across all the cotton growing regions of Pakistan indicate that dual and multiple infections are the norm for CLCuD with no evidence of synergism. Despite the diversity of begomoviruses associated with CLCuD, only a single class of DNA beta has been detected, suggesting that this satellite has the capacity to be recruited by unrelated begomoviruses.

Animals↗
PubMed2002

[MR contrast media for cardiovascular imaging].

MR contrast media improve the diagnostic capability of MRI and MRA. They are used in the discrimination of viable and non-viable myocardium, transmural and non-transmural infarction, occlusive and reperfused infarction and for measurement of myocardial perfusion. Currently, clinical studies are almost completely restricted to the use of extracellular non-specific MR contrast media (i. e., Gd-DTPA, Gd-DTPA,-BMA, Gd-BOPTA, Gd-D03A). However, the feasibility of using intravascular, necrosis specific or intracellular MR contrast media or endogeneous substrates as specific MR contrast media in cardiovascular imaging has been demonstrated in experimental and a few clinical studies. Intravascular contrast media (i. e., MS-325 or NC100150 Injection) allow assessment of microvascular integrity and performance of MR angiography. Necrosis specific contrast media (i. e., Gadophrin-2) have been used for sizing the extent of infarcted myocardium while intracellular contrast media (i. e., Mn-DPDP) delineate viable myocardium. Endogenous contrast media (i. e., Deoxyhemoglobin, Na (+) or K (+)) have been tested for detecting the alterations in concentrations of these ions in infarcted myocardium and for perfusion measurements. Furthermore, intravascular MR contrast media may be useful for MRA and MRI guided cardiovascular interventions.

Contrast Media↗
PubMed2002

Entonox as an analgesic agent during panretinal photocoagulation.

BACKGROUND/AIMS: Panretinal photocoagulation (PRP) reduces the risk of visual loss in proliferative diabetic retinopathy but some patients cannot tolerate PRP because of pain. Inhaled Entonox was evaluated as an analgesic during PRP. METHODS: A randomised, crossover, double masked pilot study was performed. Patients inhaled either air or Entonox and half the PRP was applied. The treatment was completed with the alternate inhaled gas. Patients graded pain experienced during both stages of the treatment using a visual analogue scale. Pain scores were compared using a paired t test. RESULTS: 20 patients participated. Mean pain scores from the Entonox and air treatments were 2.94 (SD 2.73) versus 3.73 (SD 3.20) respectively (p<0.03). CONCLUSION: Entonox can be used as a safe and effective analgesic agent during PRP treatment.

Administration, Inhalation↗
PubMed2002

MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring.

Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.

Artificial Intelligence↗
PubMed2001

Sequential magnetic resonance monitoring of pulmonary flow with endovascular stents placed across the pulmonary valve in growing Swine.

BACKGROUND: Patients with endovascular stent implantation for the treatment of right ventricular outflow tract obstruction are often left with incomplete relief of the obstruction and significant pulmonary regurgitation. A noninvasive and reproducible method for monitoring such patients is desirable. MRI in the presence of a stent, however, has to overcome the problem of potential metallic artifacts. METHODS AND RESULTS: Under x-ray fluoroscopic guidance, endovascular nitinol stents were placed across the pulmonary valve in 6 young pigs to induce pulmonary regurgitation. Five additional pigs served as controls. Initial MRI was performed after 2 days (13.5+/-1.8 kg) and follow-up after 3 months (32+/-2.9 kg). Pulmonary flow volumes and regurgitant fraction were quantified by velocity-encoded cine (VEC) MRI through (VEC-TS) and distal to (VEC-DS) the stent. VEC-TS was compared with VEC-DS and volumetric measurements of left and right ventricular stroke volumes provided by cine MRI ("gold standard"). Antegrade and retrograde pulmonary flow volumes by VEC-TS were slightly but significantly less than those with VEC-DS and cine MRI. Excellent correlations (r>0.97) for phasic pulmonary flow volumes as measured by VEC-TS and VEC-DS were shown. Pulmonary regurgitant fraction increased from 32.8+/-15% to 49.6+/-17% (P<0.05) over the course of 3 months with VEC-TS. CONCLUSIONS: MRI demonstrates the progression of pulmonary regurgitation in growing swine. VEC MRI has the ability to quantify pulmonary blood flow inside the lumen of nitinol stents. MRI appears to be ideally suited for monitoring patients with endovascular nitinol stents in the pulmonary artery or pulmonary valve position.

Alloys↗
PubMed2001

Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media.

BACKGROUND: Because ischemically injured myocardium is frequently composed of viable and nonviable portions, a method to discriminate the two is useful for clinical management. METHODS AND RESULTS: Ischemically injured myocardium was characterized with extracellular nonspecific (Gd-DTPA) and necrosis-specific (mesoporphyrin) MR contrast media in rats. Relaxation rates (R1) were measured on day 1 and day 2 by inversion-recovery echoplanar imaging. Spin-echo imaging was used to define contrast-enhanced regions and regional wall thickening. Gadolinium concentration, area at risk, and infarct size were measured at postmortem examination. DeltaR1 ratio (DeltaR1(myocardium)/DeltaR1(blood)) after administration of Gd-DTPA was greater in ischemically injured myocardium (1.20+/-0.15) than in normal myocardium (0.47+/-0.05, P<0.05), which was attributed to differences in gadolinium concentration and water content. The Gd-DTPA-enhanced region on day 2 was larger (32.8+/-0.9%) than true infarction as demonstrated by triphenyltetrazolium chloride (TTC) (24.6+/-1.4%, P<0.001, r=0.21). Bland-Altman analysis revealed that the Gd-DTPA-enhanced region overestimated true infarct size by 7.8+/-5.9%. On the other hand, the mesoporphyrin-enhanced region (26.9+/-1.8%, P=NS, r=0.87) and true infarct size were identical. The difference in the areas demarcated by the 2 agents is the peri-infarction. Systolic and diastolic MR images revealed no wall thickening in the mesoporphyrin-enhanced region (0.3+/-3.3%) but reduced thickening in the Gd-DTPA-enhanced rim (8.5+/-5.5%, P<0.05). CONCLUSIONS: The Gd-DTPA-enhanced region encompasses both viable and nonviable portions of the ischemically injured myocardium. The Gd-DTPA-enhanced area overestimated infarct size, but the mesoporphyrin-enhanced area matched true infarct size. The salvageable peri-infarction zone can be characterized with double-contrast-enhanced and functional MR imaging; the mismatched area of enhancement between the 2 agents shows residual wall thickening.

Animals↗
PubMed2001

Accuracy of segmented MR velocity mapping to measure small vessel pulsatile flow in a phantom simulating cardiac motion.

The purpose of this study was to investigate the accuracy of conventional, segmented, and echo-shared MR velocity mapping sequences to measure pulsatile flow in small moving vessels using a phantom with simulated cardiac motion. The phantom moved either cyclically in-plane, through-plane, in- and through-plane, or was stationary. The mean error in average flow was -2% +/- 3% (mean +/- SD) for all sequences under all conditions, with or without background correction, as long as the region of interest (ROI) size was equal to the vessel cross-sectional size. Overestimation of flow as a result of an oversized ROI was less than 20%, and independent of field of view (FOV) and matrix, as long as the offset in angle between the imaging plane and flow direction was less than 10 degrees. Segmented velocity mapping sequences are surprisingly accurate in measuring average flow and render flow profiles in small moving vessels despite the blurring in the images due to vessel motion. J. Magn. Reson. Imaging 2001;13:722-728.

Blood Flow Velocity↗
PubMed2001

Frequency-doubled Nd:YAG laser for the treatment of exudative diabetic maculopathy.

PURPOSE: To determine the clinical efficacy of frequency-doubled Nd:YAG (FD YAG) laser for the treatment of diabetic clinically significant macular oedema (CSMO). METHODS: A prospective pilot study was carried out on 55 eyes with CSMO. FD YAG laser exposures were applied in a focal or grid pattern. The results were evaluated by Snellen visual acuity, slit-lamp biomicroscopy, colour photography and fundus fluorescein angiography. RESULTS: At mean review of 5.3 months, macular oedema had resolved either completely or partly in 44 (80%) eyes, was unchanged in 10 (18%) eyes and progressed in 1 (2%) eye. Visual acuity improved in 11 (20%), stabilised in 40 (73%) and deteriorated in 4 (7%) eyes. CONCLUSION: FD YAG laser therapy is effective in the treatment of CSMO. It combines the ergonomic advantages of a solid-state laser with the benefits of its wavelength. A comparison between the clinical results of FD YAG and other lasers used in the treatment of CSMO is, however, required.

Adult↗