Biomedical subjects

K Hassan

Publications and source records attributed to K Hassan.

At least 19 recordsLinked to original sources

PubMed2006

Acetabular fractures in the UK. What are the numbers?

We have established a nationwide directory of the specialist surgical units and their Lead Consultants with expertise in acetabular fracture surgery throughout the UK. Our directory has facilitated an estimation of the total numbers of operative acetabular fracture cases managed annually in the UK, as reported by those actually providing this specialist service. Previously the total number of acetabular injuries admitted and operated on in the UK was not known and there was no directory of acetabular surgeons in the UK. The introduction and accuracy of the OPCS codings will have massive financial implications for the DoH at a local and national level in the planning and provision of adequate health care resources. We have performed a questionnaire study to validate the DoH data for acetabular fracture surgery. Data was compiled using the ICD-10 for diagnosis of fracture of the acetabulum, and the OPCS-4 codes for the surgical procedures used for fracture fixation for the year 2003-2004. The Department of Health (DoH) data identified 44 units that had OPCS-4 coding for acetabular fracture fixation. We had a 95% (42 out of 44 units) response to our questionnaire. A total of 9 units contacted had actually performed no surgery, whereas the DoH coded these as having performed a maximum of 35 cases. The DoH data showed a total of 1825 admissions to 311 NHS hospitals for acetabular fractures, including 258 operative cases performed in 44 NHS hospitals in the UK. Our study has found that 748 acetabular fracture fixation cases were performed at 33 NHS hospitals in the UK in this study period. The total difference between the DoH operated cases and those confirmed by our study was 490. The hospital care for an operative acetabular fracture case may cost approximately 14,830, pounds if the actual numbers are under-reported to or by the DoH are 490, then approximately 7,266,700 pounds has been lost by these centres due to incorrect proportioning of resources.

Acetabulum↗

PubMed2006

Prevalence of repetitive and reward-seeking behaviors in Parkinson disease.

We surveyed 297 patients with Parkinson disease (PD) with systematic screens and rigorous definitional criteria. Pathologic hypersexuality lifetime prevalence was 2.4%. Compulsive shopping was 0.7%. Combined with our pathologic gambling data, the lifetime prevalence of these behaviors was 6.1% and increases to 13.7% in patients on dopamine agonists.

Aged↗

PubMed2006

Thromboprophylaxis for acetabular injuries in the UK What prophylaxis is used?

Due to chronic underfunding and the absence of a comprehensive and coordinated national approach to the management of acetabular trauma throughout the UK, patients can incur prolonged recumbancy. We have performed a postal questionnaire to establish the current clinical practice in the specialist pelvic and acetabular units throughout the UK, with respect to time to surgery from injury, thromboprophylaxis, and surveillance. We have identified 21 units, and 37 surgeons in the NHS who deal with acetabular trauma. The mean time to surgery from injury in the UK is 8.5 days (range 2-19 days). Mechanical thromboprophylaxis was used in 67% (14) of the units. No unit routinely uses prophylactic IVC filters. Chemical thromboprophylaxis is routinely used in 100% (21) of the units. Ninety-five percent (20) used prophylactic doses of LDH or LMWH. Clinical surveillance alone for thromboembolism is employed in 90% (19) of the units. Only 2 (10%) units routinely perform radiological surveillance with ultrasound Doppler, pre-operatively. Currently there is no published directory of dedicated pelvic and acetabular surgeons in the UK. There is no general consensus on the approach to thromboprophylaxis and surveillance in acetabular trauma in the UK. There is no consensus approach to thromboprophylaxis and surveillance in the literature.

Acetabulum↗

PubMed2006

Prospective prevalence of pathologic gambling and medication association in Parkinson disease.

The authors prospectively screened 297 patients with Parkinson disease (PD), who attended a tertiary clinic, using a modified South Oaks Gambling Scale. Lifetime prevalence of pathologic gambling (PG) was 3.4% and on any dopamine agonist was 7.2%. PG was associated with earlier PD onset and with dopamine agonists but not with agonist subtype or doses. We found no association with a potent D3 receptor agonist.

Aged↗

PubMed2006

Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease.

BACKGROUND AND AIMS: The OCTN1 (SLC22A4 1672C-->T) and OCTN2 (SLC22A5 -207G-->C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn's disease (CD), but their contribution in children has not been examined. METHODS: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. RESULTS: All SNPs were in strong linkage disequilibrium (D' >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p = 0.02) and UC (28.2% v 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9(th) centile) at diagnosis (weight: 87.9% v 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4% (p<0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). CONCLUSIONS: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.

Adolescent↗

PubMed2005

The Healthgrid White Paper.

Over the last four years, a community of researchers working on Grid and High Performance Computing technologies started discussing the barriers and opportunities that grid technologies must face and exploit for the development of health-related applications. This interest lead to the first Healthgrid conference, held in Lyon, France, on January 16th-17th, 2003, with the focus of creating increased awareness about the possibilities and advantages linked to the deployment of grid technologies in health, ultimately targeting the creation of a European/international grid infrastructure for health. The topics of this conference converged with the position of the eHealth division of the European Commission, whose mandate from the Lisbon Meeting was "To develop an intelligent environment that enables ubiquitous management of citizens' health status, and to assist health professionals in coping with some major challenges, risk management and the integration into clinical practice of advances in health knowledge." In this context "Health" involves not only clinical procedures but covers the whole range of information from molecular level (genetic and proteomic information) over cells and tissues, to the individual and finally the population level (social healthcare). Grid technology offers the opportunity to create a common working backbone for all different members of this large "health family" and will hopefully lead to an increased awareness and interoperability among disciplines. The first HealthGrid conference led to the creation of the Healthgrid association, a non-profit research association legally incorporated in France but formed from the broad community of European researchers and institutions sharing expertise in health grids. After the second Healthgrid conference, held in Clermont-Ferrand on January 29th-30th, 2004, the need for a "white paper" on the current status and prospective of health grids was raised. Over fifty experts from different areas of grid technologies, eHealth applications and the medical world were invited to contribute to the preparation of this document.

Computer Communication Networks↗

PubMed2005

A multi-resolution approach for content-based image retrieval on the Grid--application to breast cancer detection.

OBJECTIVES: Hospitals and medical centers are producing more and more data that need to be processed. Those data are confidential, heterogeneous, and limited to the geographic site where they have been produced. Unless properly anonymized, they cannot be distributed on wide area networks. METHODS: Grid technologies allow the globalization of storage and processing resources, and enable large-scale experimentations on distributed data. They constitute a promising tool to treat the different data and analyze the knowledge they contain, while offering secured access and high-performance computing capacities to the different users. Our aim is to evaluate the possibilities of grid technologies for handling medical data. RESULTS AND CONCLUSIONS: In this paper, we focus on a breast cancer diagnosis assistance tool, based on distributed and incremental knowledge construction and a content-based image retrieval system. We analyze the different scenarios of uses of such a tool. We further propose an algorithm that indexes mammographic images for content-based query purposes. This algorithm is tested on images of different resolutions in order to reduce the indexation time and we analyze its performance with experiments on the grid.

Algorithms↗

PubMed2004

The presence of erythropoietin receptors in the human peripheral nervous system.

Erythropoietin (EPO) is a well-known hematopoietic factor and a major determinant of tissue oxygenation. EPO receptors have been identified on a wide variety of non-erythroid cell types including human central nervous system and peripheral nervous system of animal models. The presence or function of EPO receptors in human peripheral nervous system is unknown. By examining nerve segments from radicular and autonomic nerves using immunohistochemical methods, we demonstrated the presence of EPO receptors on myelin sheath of radicular nerves in the human peripheral nervous system.

Humans↗

PubMed2001

Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study.

BACKGROUND: Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease. The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis. METHODS AND RESULTS EPIDEMIOLOGY: Progression of intima-media thickness (IMT) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a randomly sampled cohort of utility employees age 40 to 60 years (n=480). Coculture: The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima. Mouse models: The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein (0.2% by weight) and LDL receptor-null mice to Western diet or Western diet plus lutein. IMT progression declined with increasing quintile of plasma lutein (P for trend=0.007, age-adjusted; P=0.0007, multivariate). Covariate-adjusted IMT progression (mean+/-SEM) was 0.021+/-0.005 mm in the lowest quintile of plasma lutein, whereas progression was blocked in the highest quintile (0.004+/-0.005 mm; P=0.01). In the coculture, pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner (P<0.05). Finally, in the mouse models, lutein supplementation reduced lesion size 44% in apoE-null mice (P=0.009) and 43% in LDL receptor-null mice (P=0.02). CONCLUSIONS: These epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.

Adult↗

PubMed2001

Mitogen-activated protein kinase phosphatase 1 activity is necessary for oxidized phospholipids to induce monocyte chemotactic activity in human aortic endothelial cells.

Entrapment and oxidation of low density lipoproteins (LDL) in the sub-endothelial space is a key process in the initiation of atherosclerotic lesion development. Functional changes induced by oxidized lipids in endothelial cells are early events in the pathogenesis of atherosclerosis. Oxidized-l-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC), a major component of minimally modified/oxidized-LDL (MM-LDL) mimics the biological activities assigned to MM-LDL both in vitro in a co-culture model as well as in vivo in mice. We hypothesized that ox-PAPC initiates gene expression changes in endothelial cells that result in enhanced endothelial/monocyte interactions. To analyze the gene expression changes that oxidized lipids induce in endothelial cells, we used a suppression subtractive hybridization procedure to compare mRNA from PAPC-treated human aortic endothelial cells (HAEC) with that of ox-PAPC-treated cells. We report here the identification of a gene, mitogen-activated protein kinase phosphatase 1 (MKP-1), that is rapidly and transiently induced in ox-PAPC-treated HAEC. Inhibition of MKP-1 using either the phosphatase inhibitor sodium orthovanadate or antisense oligonucleotides prevents the accumulation of monocyte chemotactic activity in ox-PAPC-treated HAEC supernatants. Furthermore, we show that decreased monocyte chemotactic activity in HAEC treated with sodium orthovanadate or MKP-1 antisense oligonucleotides is due to decreased MCP-1 protein. Our results implicate a direct role for MKP-1 in ox-PAPC-induced signaling pathways that result in the production of MCP-1 protein by ox-PAPC-treated HAEC.

Aorta↗

PubMed2001

Loss of Fhit expression is a predictor of poor outcome in tongue cancer.

Abnormalities of FHIT, a candidate tumor suppressor gene located at 3pl4.2, have been found frequently in multiple tumor types, including head and neck squamous cell carcinoma. To determine the role of FHIT in tongue cancers, Fhit expression was determined by immunohistochemistry studies in tissue samples from 41 patients with stages II-IV squamous cell carcinomas of the tongue. All of the patients underwent curative surgical treatment with a median of 83 months of follow-up care. We found that 28 (68%) of the 41 tumor specimens demonstrated a lack of or significantly decreased staining for Fhit. Fhit expression tended to be stronger in well-differentiated tumor areas than it was in poorly differentiated areas, although this trend was not statistically significant. There was no significant correlation between Fhit expression and a patient's age or sex or the histological grade or clinical stage of disease. As expected, clinical stage and nodal involvement correlated with prognosis. Interestingly, patients whose tumors demonstrated low levels of or no Fhit expression had a significantly shorter time of disease-free survival than those whose tumors had high Fhit expression (P = 0.035, by log-rank test). This prognostic value of Fhit was independent of other clinical parameters, including stage of disease and nodal status. We conclude that Fhit plays an important role in the development of squamous cell carcinomas of the tongue and that loss of Fhit expression may be an independent prognostic indicator for clinical outcome in patients with this tumor type.

Acid Anhydride Hydrolases↗

PubMed2001

Successful pregnancy in a patient with polycystic kidney disease and advanced renal failure without prophylactic dialysis.

Pregnancies in women suffering from advanced chronic renal failure are frequently associated with deterioration of maternal renal function, premature births and low birth weights. Prophylactic dialysis is sometimes instituted since this intervention ameliorates the uremic milieu and improves maternal status and fetal uterine environment. This report describes a successful pregnancy and delivery in a hypertensive woman with advanced chronic renal failure due to polycystic kidney disease without accelerating the natural deterioration of renal function and without instituting prophylactic dialysis. The infant was delivered at full term with a normal birth weight. Thirty months after delivery, growth and development of the child were normal and the rate of deterioration of maternal renal function, assessed by 1/creatinine, was unaffected by pregnancy. Conservative management and effective control of blood pressure may be sufficient to achieve successful pregnancy outcome when women with advanced chronic renal failure become pregnant.

Acute Kidney Injury↗

PubMed2001

Adverse events following vaccination in premature infants.

UNLABELLED: The aims of this study were to study the frequency, severity and types of adverse reactions following DPT/Hib (diphtheria and tetanus toxoids and pertussis/Haemophilus influenzae type B conjugate) immunization in very preterm infants and to identify possible risk factors. Case notes of 45 preterm babies vaccinated in the neonatal intensive care unit between January 1993 and December 1998 were studied retrospectively. Birthweight, gestational age, duration of ventilation, oxygen dependency, timing of vaccination, weight, corrected gestation at vaccination and apparent adverse effects were noted. Apparent adverse events were noted in 17 of 45 (37.8%) babies: 9 (20%) had major events, i.e. apnoea, bradycardia or desaturations, and 8 (17.8%) had minor events, i.e. increased oxygen requirements, temperature instability, poor handling and feed intolerance. Babies with major events were significantly younger (p < 0.05), had a lower postmenstrual age (p < 0.05) and weighed less (p < 0.05) at the time of vaccination compared with babies without major events. No differences in the mean birthweight, gestational age, duration of ventilation or oxygen dependency were found between the two groups. Age at vaccination of 70 days or less was significantly associated with increased risk (p < 0.01). Of 27 babies vaccinated at 70 days or less, 9 (33.3%) developed major events compared with none when vaccinated over 70 d. CONCLUSION: Vaccine-related cardiorespiratory events are relatively common in preterm babies. Problems were much more common if vaccine is administered at or before 70 d. These babies should therefore be monitored postvaccination. Further prospective studies are needed to clarify whether delaying vaccination offers protection against these adverse events.

Apnea↗

PubMed2000

Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication.

Cyclin B1 is a key molecule for G2-M-phase transition during the cell cycle and is overexpressed in various tumor types. However, the expression status of cyclin B1 in lung cancer and its clinical significance remain unknown. We used immunohistochemistry studies to examine the expression of cyclin B1 in 77 non-small cell lung cancer specimens from patients with histological stage I disease. All of the patients underwent curative surgical treatment. The median length of follow-up care is 8.2 years. High-level cyclin B1 expression (a cyclin B1 labeling index > or =15%) was observed in 17 of the 77 (22%) tumors. Patients whose tumors expressed a high level of cyclin B1 had a significantly shorter survival time than patients whose tumors expressed a low level of cyclin B1 (P = 0.02, log-rank test). Interestingly, overexpression of cyclin B1 was more frequently observed in tumors with squamous cell histology than in tumors with other histological cell types (P = 0.01, Fisher's exact test). A subgroup analysis revealed that cyclin B1 overexpression seems to be an adverse prognostic factor only in patients with squamous cell carcinoma (SCC) of the lung (P = 0.02, log-rank test). Our data indicate that cyclin B1 may be dysregulated in non-small cell lung cancer, particularly in the SCC subtype, and that a high level of cyclin B1 expression may be a prognostic marker for patients with early-stage SCC of the lung.

Aged↗

PubMed2000

The incidence of childhood inflammatory bowel disease in Wales.

UNLABELLED: A prospective study was undertaken throughout Wales over the period from 1 January 1995 to 30 March 1997, to determine the incidence of childhood inflammatory bowel disease (IBD). Thirty-eight (24 male) new cases of IBD were reported. Twenty (16 male) of the reported cases had Crohn's disease, 11 (5 male) had ulcerative colitis (UC) and 7 (3 male) indeterminate colitis. Crohn's disease occurred four times more often in boys than girls, whereas there was no sex difference in the incidence for UC and indeterminate colitis. The median age at presentation was 12 (range 1.5-16) years and there was no difference in the age of presentation or the duration of symptoms prior to diagnosis in any of the types of IBD. CONCLUSION: The overall incidence (95% confidence intervals) for IBD in Wales was 2.6 (1.87-3.48) cases per 100,000 per year. The incidence for Crohn's disease was 1.36 (0.86-2.04) cases per 100,000 per year, for UC 0.75 (0.39-1.28) cases per 100,000 per year and for indeterminate colitis 0.48 (0.2-0.92) cases per 100,000 per year.

Adolescent↗

PubMed2000

Short-term feeding of atherogenic diet to mice results in reduction of HDL and paraoxonase that may be mediated by an immune mechanism.

Short-term feeding (up to 7 days) of an atherogenic diet to C57BL/6 low density lipoprotein receptor-deficient mice did not result in decreased hepatic paraoxonase (PON) mRNA but caused a dramatic decrease in plasma PON activity and mass. The decreased activity and mass were temporally related to an increase in plasma and high density lipoprotein (HDL) lipid hydroperoxides and to a decrease in HDL cholesterol and native apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II). As the native apoA-I protein disappeared from the circulation, higher molecular weight forms of apoA-I appeared, some of which contained epitopes recognized by an antibody (EO6) that recognizes oxidized phospholipids. After mice consumed an atherogenic diet for 1 or 3 days, switching the mice to a low fat chow diet for 3 days resulted in a return to baseline levels of lipid hydroperoxides but only a small return toward baseline for HDL cholesterol, with no significant increase in apoA-I mass or PON activity and mass. After mice consumed an atherogenic diet for 3 days, switching to the chow diet for 3 days did not significantly alter the high molecular weight forms of apoA-I or the signal generated by EO6. In marked contrast, after mice consumed an atherogenic diet for 7 days, switching to the chow diet for 3 days resulted in a dramatic increase in native apoA-I to baseline levels, with virtual disappearance of the high molecular weight forms of apoA-I, including the form recognized by EO6. After mice consumed an atherogenic diet for 7 days, switching to the chow diet for 3 days also resulted in significant increases in HDL cholesterol and PON mass and activity, although baseline levels were not reached. IgG and IgM antibodies were found to be associated with apoA-I in control animals, were minimally decreased after the 3-day atherogenic diet, were dramatically decreased after the 7-day atherogenic diet, and returned to near or above baseline levels after a return to the chow diet for 3 days. We conclude that the atherogenic diet rapidly induces lipid hydroperoxide formation and apoA-I oxidation with the formation of high molecular weight forms of apoA-I. Concomitant with these changes in apoA-I levels, HDL cholesterol and PON activity and mass declined without changes in mRNA levels for apoA-I or PON, suggesting increased clearance of these altered HDL particles. We further conclude that between the third and seventh day of the atherogenic diet, an as-yet-unidentified mechanism for clearing the high molecular weight forms of apoA-I is induced and that this mechanism may be related to the clearance of immune complexes.

Animals↗

PubMed2000

Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3.

Treatment of human artery wall cells with apolipoprotein A-I (apoA-I), but not apoA-II, with an apoA-I peptide mimetic, or with high density lipoprotein (HDL), or paraoxonase, rendered the cells unable to oxidize low density lipoprotein (LDL). Human aortic wall cells were found to contain 12-lipoxygenase (12-LO) protein. Transfection of the cells with antisense to 12-LO (but not sense) eliminated the 12-LO protein and prevented LDL-induced monocyte chemotactic activity. Addition of 13(S)-hydroperoxyoctadecadienoic acid [13(S)-HPODE] and 15(S)-hydroperoxyeicosatetraenoic acid [15(S)-HPETE] dramatically enhanced the nonenzymatic oxidation of both 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and cholesteryl linoleate. On a molar basis 13(S)-HPODE and 15(S)-HPETE were approximately two orders of magnitude greater in potency than hydrogen peroxide in causing the formation of biologically active oxidized phospholipids (m/z 594, 610, and 828) from PAPC. Purified paraoxonase inhibited the biologic activity of these oxidized phospholipids. HDL from 10 of 10 normolipidemic patients with coronary artery disease, who were neither diabetic nor receiving hypolipidemic medications, failed to inhibit LDL oxidation by artery wall cells and failed to inhibit the biologic activity of oxidized PAPC, whereas HDL from 10 of 10 age- and sex-matched control subjects did. We conclude that a) mildly oxidized LDL is formed in three steps, one of which involves 12-LO and each of which can be inhibited by normal HDL, and b) HDL from at least some coronary artery disease patients with normal blood lipid levels is defective both in its ability to prevent LDL oxidation by artery wall cells and in its ability to inhibit the biologic activity of oxidized PAPC.

Aorta↗

PubMed1999

Interaction between erythropoietin and peripheral polymorphonuclear leukocytes in hemodialysis patients.

The effect of erythropoietin (EPO) on the oxidative stress and inflammation caused by polymorphonuclear leukocytes (PMNLs) in chronic hemodialysis (HD) patients was investigated in vivo and in vitro. The studies were performed on isolated PMNLs from peripheral blood of healthy controls and HD patients before and following 6 weeks of EPO treatment. The oxidative stress was expressed by the rate of superoxide release from phorbol 12-myristate 13-acetate stimulated PMNLs, and the inflammatory state was evaluated by in vitro PMNL survival, in addition to white blood cell and PMNL counts of the enrolled subjects. Following 6 weeks of EPO treatment, in HD patients, the rate of superoxide release from PMNLs as well as WBC and PMNL counts fell significantly when compared with the pretreatment values. PMNLs from HD patients and healthy controls incubated in vitro with increasing amounts of EPO displayed a significant reduction in their rates of superoxide release and a significant improvement in survival. We have concluded that EPO interacts with PMNLs, attenuating their primed state in HD patients, thus reducing oxidative stress and the extent of inflammation. To the best of our knowledge, this attenuation of the primed state of PMNLs by EPO is a new finding.

Cell Survival↗