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Biomedical subjects

S Abbas

Publications and source records attributed to S Abbas.

At least 19 recordsLinked to original sources
PubMed2006

Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus.

Oncogene-expressing human papillomavirus type 16 (HPV16) is found in a subset of head and neck squamous cell carcinomas (HNSCC). HPV16 drives carcinogenesis by inactivating p53 and pRb with the viral oncoproteins E6 and E7, paralleled by a low level of mutations in TP53 and allelic loss at 3p, 9p, and 17p, genetic changes frequently found in HNSCCs of nonviral etiology. We hypothesize that two pathways to HNSCC exist: one determined by HPV16 and the other by environmental carcinogens. To define the critical genetic events in these two pathways, we now present a detailed genome analysis of HNSCC with and without HPV16 involvement by employing high-resolution microarray comparative genomic hybridization. Four regions showed alterations in HPV-negative tumors that were absent in HPV-positive tumors: losses at 3p11.2-26.3, 5q11.2-35.2, and 9p21.1-24, and gains/amplifications at 11q12.1-13.4. Also, HPV16-negative tumors demonstrated loss at 18q12.1-23, in contrast to gain in HPV16-positive tumors. Seven regions were altered at high frequency (>33%) in both groups: gains at 3q22.2-qter, 5p15.2-pter, 8p11.2-qter, 9q22-34.1, and 20p-20q, and losses at 11q14.1-qter and 13q11-33. These data show that HNSCC arising by environmental carcinogens are characterized by genetic alterations that differ from those observed in HPV16-induced HNSCC, and most likely occur early in carcinogenesis. A number of genetic changes are shared in both tumor groups and can be considered crucial in the later stages of HNSCC progression.

Adult↗
PubMed2005

Oral water soluble contrast for the management of adhesive small bowel obstruction.

BACKGROUND: Adhesions are the leading cause of small bowel obstruction. Most adhesive small bowel obstructions resolve following conservative treatment but there is no consensus as to when conservative treatment should be considered unsuccessful and the patient should undergo surgery. Studies have shown that failure of an oral water-soluble contrast to reach the colon after a designated time indicates complete intestinal obstruction that is unlikely to resolve with conservative treatment. Other studies have suggested that the administration of water-soluble contrast is therapeutic in resolving the obstruction. OBJECTIVES: The aims of this review are:1. To determine the reliability of water-soluble contrast media and serial abdominal radiographs in predicting the success of conservative treatment in patients admitted with adhesive small bowel obstruction.2. To determine the efficacy and safety of water-soluble contrast media in reducing the need for surgical intervention and reducing hospital stay in adhesive small bowel obstruction. SEARCH STRATEGY: The search was conducted using MeSH terms: ''Intestinal obstruction'', ''water-soluble contrast'', "Adhesions" and "Gastrografin", and combined with the Cochrane Collaboration highly sensitive search strategy for identifying randomised controlled trials and controlled clinical trials. SELECTION CRITERIA: 1. Prospective studies (to evaluate the diagnostic potential of water-soluble contrast in adhesive small bowel obstruction);2. Randomised clinical trials (to evaluate the therapeutic role). DATA COLLECTION AND ANALYSIS: 1. Studies addressing the diagnostic role of water-soluble contrast were critically appraised and data presented as sensitivities, specificities and positive and negative likelihood ratios. Results were pooled and summary receiver operating characteristic (ROC) curve was constructed. 2. A meta-analysis of the data from therapeutic studies was performed using the Mantel -Haenszel test using both the fixed effect and random effects model. MAIN RESULTS: The appearance of water-soluble contrast in the caecum on an abdominal radiograph within 24 hours of its administration predicts resolution of an adhesive small bowel obstruction with a pooled sensitivity of 0.96, specificity of 0.96. The area under the curve of the summary ROC was 0.98. Four randomised studies dealing with the therapeutic role of Gastrografin were included in the review, water-soluble contrast did not reduce the need for surgical intervention (odds ratio 1.29, P = 0.36). Meta-analysis of two studies showed that water-soluble contrast reduced hospital stay compared with placebo (weighted mean difference = - 2.58) P = 0.004. AUTHORS' CONCLUSIONS: Published literature strongly supports the use of water-soluble contrast as a predictive test for non-operative resolution of adhesive small bowel obstruction. Although Gastrografin does not cause resolution of small bowel obstruction, it does appear to reduce hospital stay.

Administration, Oral↗
PubMed2005

Imaging patients with "post-cholecystectomy syndrome": an algorithmic approach.

AIM: To assess the role of ultrasound (US), magnetic resonance cholangiopancreatography (MRCP) and liver function tests (LFTs) in the evaluation of selected patients presenting with late post-cholecystectomy syndrome (PCS) who were referred for endoscopic retrograde cholangiopancreatography (ERCP). MATERIALS AND METHODS: In a retrospective study a final group of 42 patients with PCS referred for diagnostic ERCP underwent MRCP and abdominal US. ERCP and MRCP images were assessed for bile duct diameters and the presence of strictures and stones. A common bile duct (CBD) diameter of < 10mm was considered normal, whereas > or = 10mm was considered abnormal on US. Findings were correlated to LFTs with contingency table results performed for single techniques and combination of methods. RESULTS: In total 14 stones and one stricture were seen. US had a high negative predictive value (86.4%). MRCP had a sensitivity of 100% and specificity of 88.0%. ERCP is the most accurate test but failed in 11 patients, five of whom had a stone. The accuracy of US and LFTs increases to 93.8% if test results agree in either negative or positive outcome. CONCLUSION: US and LFTs are first-line tests in PCS. If the CBD on US is > or = 10mm, but no cause is identified, MRCP should be performed. If US and LFTs are normal then MRCP is not necessary. The availability of LFTs raises the diagnostic value of imaging.

Adult↗
PubMed2004

[An example of simulation for a better understanding of PK/PD relationship of antibiotics].

The interpretation of PK/PD indices is specific to each class of antibiotics. In order to illustrate this, we developed a multidisciplinary tutorial program based on simulation of clinical cases. Three drugs were included in this software: tobramycin, vancomycin and azithromycin. From the dosage regimen proposed by the user, the model simulates a plotting of antibiotic plasma concentrations vs. time (tobramycin, vancomycin and azithromycin) and tissue concentrations (azithromycin). Peak and trough concentrations are calculated at steady-state. A commentary is provided to evaluate the efficacy of treatment and to assist the user in improving his prescription of tobramycin or vancomycin. T(> MIC) (time the concentration remains above the MIC) and AUC(24) (area under the concentration-time curve) are calculated in plasma and tissues for azithromycin. In order to create a link between theoretical pharmacokinetics and clinical practice, we propose this model as a simulation of antibiotic monitoring. We put the emphasis on interactivity and simulation, leading to applied reasoning and decision making. It illustrates (i) the influence of pharmacokinetic parameters, location of infection and bactericidal kinetics on the use of three different classes of antibiotics, (ii) the role of route of administration, dosing and intervals between administrations on therapeutic response and (iii) the influence of erratic administrations on clinical efficacy.

Anti-Bacterial Agents↗
PubMed2003

Mitogen-activated protein (MAP) kinases mediate PMMA-induction of osteoclasts.

Inflammatory osteolysis induced by implant-derived wear debris is associated with infiltration of various cell-types to the implant-bone interface leading to abundant secretion of pro-inflammatory cytokines and activation of proteinases that together lead to propagation of the localized inflammatory response and periprosthetic bone erosion. Tumor necrosis factor family members are considered to be direct mediators of inflammation and osteolysis. These cytokines exert their osteoclastic effects via activation of the transcription factor NF-kappaB and certain MAP kinases, including c-Jun, Erks and p38, all known to be essential for the development of osteoclasts. We have recently documented that the osteoclastogenic cytokines TNF and RANKL play a pivotal role in the development of inflammatory osteolysis. We have also found that PMMA particles stimulate osteoclastogenesis, at least in part, by induction of RANKL, TNF, and by activation of the transcription factor NF-kappaB. More importantly, our data indicate that inhibitors of the osteoclastogenic factors, TNF and RANKL abrogate particle-induced osteoclastogenesis. In the current study, we investigated if PMMA particles activate MAP kinases, and the potential role of these kinases as mediators of osteolysis. Using kinase assays, we show that in osteoclast precursors, PMMA particles markedly and rapidly activate p38 and ERK MAP kinases. This activation was specific, evident by complete blockade with specific inhibitory compounds. Similarly, we show that PMMA particles activate the JNK pathway, which is known to be involved in inflammatory and osteoclastogenic events. We also show that p38 MAP kinase regulates PMMA-activation of NF-kappaB, thus providing a possible mechanism for particle action in osteoclast precursors. Finally, we provide evidence that specific inhibitors of MAP kinases are capable of inhibiting PMMA-stimulated osteoclastogenesis. These data provide evidence that MAP kinases are potent mediators of particle-induced osteoclastogenesis.

Animals↗
PubMed2001

Commercially available 5'-DMT phosphoramidites as reagents for the synthesis of vinylphosphonate-linked oligonucleic acids.

[reaction: see text]. Commercially available cyanoethyl phosphoramidites derived from T, d(C), d(A), and d(G) were hydrolyzed (1H-tetrazole, MeCN/H2O) to give the corresponding H-phosphonates in excellent yields. Palladium(0)-catalyzed cross-coupling of each of these with the thymidine-derived vinylbromide 2 afforded the corresponding vinylphosphonate-linked dimers TT, d(C)T, d(A)T, and d(G)T in modest to good yields. The TT dimer was further elaborated to give a 5'-DMT-TT-3'-CEP building block, and this was used in the automated synthesis of the TpTTpT tetramer.

Amides↗
PubMed1999

Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatographic assay for the novel bio-reductive anti-tumor agent RH1 in human and mouse plasma.

A HPLC assay and solid-phase extraction technique from human plasma has been developed and validated for the experimental anticancer agent, RH1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone) which is currently being evaluated by the CRC phase I/II committee. A 500 mg amino propyl solid-phase extraction cartridge was used to isolate RH1 from human plasma. Analysis was performed on a reversed-phase chromatography system using a 15 cm cyanopropyl column and isocratic elution with a 10% methanol-90% water (double distilled) solution. The lower limit of quantitation for RH1 was found to be 0.00375 microg/ml (3.75 ng/ml+/-8.3%) in water and following extraction from plasma. Recovery of >80%(+/-11.9%) was achieved over a five-day validation study. This method was used to carry out pre-clinical studies in BDF mice (standard strain of hybrid mice) at three dose levels (2, 5 and 10 mg/kg of RH1 in 0.9% (w/v) saline via an intraperotoneal injection). Standard Version of PC Winnonlin pharmacokinetic modelling software was used to model the data. A none-compartmental model was used to describe the disposition of RH1 in mice plasma. RH1 was rapidly eliminated from plasma with a mean plasma clearance of 23.4 ml/min, mean volume of distribution of 321.6 ml and mean t(1/2) alpha and beta decays of 4.8 and 9.6 min, respectively. RH1 in human and mouse whole blood and plasma was found to be stable up to 2 h.

Animals↗
PubMed1999

Development and validation of a high-performance liquid chromatographic assay using solid-phase extraction for the novel antitumor agent pancratistatin in human plasma.

The stability of the experimental anti-tumour agent pancratistatin in human plasma has been investigated. A solid-phase extraction technique and an HPLC assay with external standards have been developed and validated. Extraction was performed using C18 cartridges and HPLC, analysis was performed on a 15 cm Hypersil BDS column using isocratic elution with 13% acetonitrile and aqueous solution of 1% (w/v) acetic acid. The lower limit of quantification for pancratistatin in 5% DMF-95% water was found to be 0.58 ng/ml (+/-10.58%) and 2.3 ng/ml (+/-9.2%) following extraction from human plasma. Mean recovery of 89.4% (+/-4.73%) was obtained over the concentration range 0.0023-9.45 microg/ml for a five day validation study. Pancratistatin was stable at room temperature in light or dark for at least 15 days, in the refrigerator at 4 degrees C for at least 16 days and in the freezer at -20 degrees C or -80 degrees C for at least 28 days. Under all conditions monitored, % recovery of pancratistatin from human plasma was greater than 95% and no evidence of degradation had occurred. There also was no loss of pancratistatin after three cycles of freezing and thawing.

Amaryllidaceae Alkaloids↗
PubMed1999

Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatography assay for the novel antitumour agent CT2584 in human plasma.

A HPLC assay and solid-phase extraction technique from human plasma has been developed and validated for the novel anticancer agent CT2584, 1-(11-dodecylamino-10-hydroxyundecyl)-3,7-dimethylxanthine, which has recently completed a phase I trial at the Christie Hospital, Manchester under the auspices of the CRC phase I/II committee. Following addition of CT2576, 1-(11-octylamino-10-hydroxylundecyl)-3,7-dimethylxanthine, as internal standard, a solid-phase extraction cartridge (100 mg cyanopropyl) was used to isolate the drug CT2584 from human plasma. Analysis was performed by reversed-phase chromatography. CT2576 was used as internal standard at a concentration of 4 microg ml(-1) for the quantification of CT2584 from plasma for the duration of this work. The lower limit of quantification for the drug CT2584 in buffer using this assay was found to be 0.0122 microM (0.008 microg ml(-1)) and 0.048 microM (0.027 microg ml(-1)) when extracted from human plasma.

Antineoplastic Agents↗
PubMed1997

Serum IgE levels in patients with allergic problems and healthy subjects.

Total serum IgE levels were estimated in 219 patients with various allergic disorders (119 with bronchial asthma, 68 with allergic rhinitis and 32 with urticaria) and 240 healthy age matched subjects. Serum IgE levels were significantly (P < 0.001) higher in healthy males (mean 181 IU/ml) than females (mean 99 IU/ml). Higher levels were found in the age group 15 to 24 years and lowest in over 55 years. Males had higher IgE levels than females at any given age. Mean IgE levels were significantly (p < 0.001) higher in all three groups of patients than in healthy subjects. Among all age groups, the difference in mean IgE levels between allergic subjects and controls was significant. Positive skin test reactivity (to pollen and dust allergens) was found in 60% patients with asthma, 51% with allergic rhinitis, 46% with urticaria and in 4.5% healthy subjects. Patients with positive skin test had higher mean IgE levels as compared to those with negative skin test, but the difference was insignificant.

Adolescent↗
PubMed1996

"IR-Spectroscopy" - computer-program for the interpretation of infrared spectra.

A computer-program "IR-Spectroscopy" for the interpretation of infrared spectra of organic compounds is described. It contains the following basic items for preprocessing and execution of the computer based interpretation process: handling of the rule-base CorTab, routines for automatic rule generation and interpretation modules on the basis of the programming languages PROLOG and C.

Journal Article↗
PubMed1996

Obsessive-compulsive disorder and rheumatic chorea: is there a connection?

There is increasing evidence to suggest basal ganglion involvement in the aetiopathogenesis of obsessive-compulsive disorder (OCD). Twenty subjects with rheumatic chorea were assessed for presence of OCD and evaluated on Leyton's Obsessional Inventory. Four subjects had OCD. The study group had markedly higher scores on all the scales of Leyton's Obsessional Inventory. The findings implicate that caudate dysfunction is not sufficient on its own to explain the presence of obsessive-compulsive behaviour and that additional basal ganglion regions/rostral connections also have to be involved to produce co-morbidity.

Adolescent↗
PubMed1996

Reduction of Myocardial Infarct Size in the Rabbit by a Carbohydrate Analog of Sialyl Lewis(x).

BACKGROUND: Available data suggest that the accumulation of neutrophils within the myocardium following an ischemic event plays an important role in the pathogenesis of myocardial ischemia/reperfusion injury. It is of interest, therefore, to develop pharmacologic agents designed to inhibit neutrophil adhesion to the endothelium. METHODS AND RESULTS: A synthetic carbohydrate analog to the P-selectin ligand sialyl Lewis(x) (sLe(x)) was evaluated for its ability to protect the myocardium from ischemia/reperfusion injury. Open chest anesthetized rabbits were subjected to 30 minutes occlusion of the left circumflex artery followed by 5 hours of reperfusion. Vehicle or sLe(x) analog (10 mg/kg) was administered intravenously before the onset of reperfusion and every hour during the reperfusion period. Myocardial infarct size in rabbits treated with the sLe(x) analog (10 mg/kg) was administered intravenously before the onset of reperfusion and every hour during the reperfusion period. Myocardial infarct size in rabbits treated with the sLe(x) analog was significantly reduced when compared to rabbits treated with vehicle (28 +/- 9% vs 57 +/- 10% of the area at risk, p <.05). The compound did not alter circulating neutrophil counts or myocardial oxygen demand as determined by the rate-pressure product. Furthermore, neutrophil accumulation within the ischemic region was decreased by 44% (P <.05) in the hearts of animals receiving sLe(x) analog as compared to vehicle. CONCLUSIONS: Carbohydrate derivatives of sLe(x) may be effective in reducing the degree of myocardial injury after ischemia/reperfusion.

Journal Article↗
PubMed1993

Structure-function studies on selectin carbohydrate ligands. Modifications to fucose, sialic acid and sulphate as a sialic acid replacement.

The selectins are a family of carbohydrate-binding proteins that have been implicated in the initial interaction between leukocytes and the vascular endothelium. The three members of this family will bind to the sialyl-Lewisx epitope [Sia alpha 2-3 Gal beta 1-4 (Fuc alpha 1-3) GlcNAc] and related oligosaccharides. In this report, we examine the molecular details of that recognition using synthesized carbohydrates with specific modifications on the sialyl-Lewisx epitope. E- and L-Selectin require hydroxyl groups at the 2, 3 and 4 positions of the fucose residue. P-Selectin, however, requires only the 3-position hydroxyl group, while tolerating removal of the oxygen at positions 2 or 4 of fucose residue. Modifications of the glycerol side chain or the N-acetyl group of the sialic acid have little effect on the binding of any of the selectins. All three selectins bind efficiently to an oligosaccharide with a sulphate replacement for the sialic acid [sulpho-Lewisx, or SO4-3Gal beta 1-4 (Fuc alpha 1-3) Glc-ceramide]. For E-Selectin, binding to sulpho-Lewisx appears to be equivalent to binding to sialyl-Lewisx, while for L- and P-Selectin binding to the sulphated structure shows characteristics distinct from sialyl-Lewisx recognition. Taken together, these data indicate that, while all three selectins can recognize sialyl-Lewisx, E-, L- and P-Selectin each display distinct carbohydrate ligand preferences.

Carbohydrate Metabolism↗
PubMed1993

Family care of elderly problems.

This study was conducted to determine the elderly health problems and family care presented to them. The study was carried out in four MCH centers in Zagazig. The sample was composed of 275 women, having elderly members in their families, they were interviewed individually at the MCH center. The results showed that the main elderly physical problems were decline in daily activities, impairment of vision & digestive and urinary disorders. Psychological problems as mentioned by their families were agitation, depression and low body image. While the main identified socio-economic problems were loneliness and limited income. Regarding the family care presented to the elderly, the results showed that the low social class families had poor consideration as regards nutrition of elderly, regular physician visit, foot care, and personal hygiene. It is recommended to provide health education programs for the family about aging process, problems and needs of elderly people. As well as health education to the elderly themselves to motivate them to seek medical advice at regular intervals and integration of geriatric care in MCH centers.

Aged↗
PubMed1991

Structural requirements for the carbohydrate ligand of E-selectin.

The acute inflammatory response requires that circulating leukocytes adhere to, and then migrate through, the vascular wall at the site of injury or infection. Several receptors have been implicated in this adhesion and migration process, including the selectins, a family of carbohydrate-binding proteins. The ligand for one of these proteins, E-selectin (LECAM-2, ELAM-1) has been described by several groups to contain a polylactosamine structure bearing a terminal sialic acid residue and at least one fucose residue. We report here a more detailed investigation into the minimum structural requirements for carbohydrate recognition by E-selectin. Using both direct binding and inhibition studies we demonstrate that the sialyl Lewisx tetrasaccharides Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc, and Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]Glc are the smallest oligosaccharides recognized by the lectin. In addition, an oligosaccharide containing the sialyl Lewisa epitope is also recognized, but less avidly. We propose a structural model of functional groups necessary for recognition by E-selectin, based on these data and additional experiments on modifications of sialic acid and the reducing terminal saccharide.

Animals↗