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Biomedical subjects

Nadia Khan

Publications and source records attributed to Nadia Khan.

At least 19 recordsLinked to original sources
PubMed2006

Re-examining the efficacy of beta-blockers for the treatment of hypertension: a meta-analysis.

BACKGROUND: In a recently published meta-analysis, investigators asserted that beta-blockers should not be used to treat hypertension. Because the pathophysiology of hypertension differs in older and younger patients, we designed this meta-analysis to clarify the efficacy of beta-blockers in different age groups. The primary outcome was a composite of stroke, myocardial infarction and death. METHODS: We identified randomized controlled trials that evaluated the efficacy of beta-blockers as first-line therapy for hypertension in preventing major cardiovascular outcomes. Both authors independently evaluated the eligibility of all trials. Trials enrolling older (mean age at baseline > or = 60 years) patients were separated from those enrolling younger (mean age < 60 years) patients. Data were pooled using a random effects model. RESULTS: Our analysis incorporated data from 145 811 participants in 21 hypertension trials. In placebo-controlled trials, beta-blockers reduced major cardiovascular outcomes in younger patients (risk ratio [RR] 0.86, 95% confidence interval [CI] 0.74-0.99, based on 794 events in 19 414 patients) but not in older patients (RR 0.89, 95% CI 0.75-1.05, based on 1115 events in 8019 patients). In active comparator trials, beta-blockers demonstrated similar efficacy to other antihypertensive agents in younger patients (1515 events in 30 412 patients, RR 0.97, 95% CI 0.88-1.07) but not in older patients (7405 events in 79 775 patients, RR 1.06, 95% CI 1.01-1.10), with the excess risk being particularly marked for strokes (RR 1.18, 95% CI 1.07-1.30). INTERPRETATION: beta-blockers should not be considered first-line therapy for older hypertensive patients without another indication for these agents; however, in younger patients beta-blockers are associated with a significant reduction in cardiovascular morbidity and mortality.

Adrenergic beta-Antagonists↗
PubMed2006

A relationship-based framework of spirituality for individuals with HIV.

Twenty HIV-positive individuals (10 male, 10 female) participated in interviews on their spiritual life. Interview themes suggest that the HIV diagnosis facilitated a relationship-based framework of spirituality. Relationships that formed this framework were: relationship with God/Higher Power, renewed engagement with life, and relationship with family. Within ''relationship with God/Higher Power,'' subthemes included gratitude for God's benevolent influence, spiritual struggles, and building connections with their Higher Power. Self care, transformation of life goals, and accepting mortality were subthemes for ''renewed engagement with life.'' Subthemes within ''relationship with family'' included finding a sense of purpose, finding support through families, and families as a source of strain. Overall, results suggest that interventions that integrate spirituality need to consider a notion of spirituality that goes beyond church attendance, prayer, and Bible reading. These interventions must include the positive aspects of spirituality and spiritual struggles that individuals with HIV may experience.

Adaptation, Psychological↗
PubMed2006

Surgical management of tuberculum sellae meningioma: role of selective extradural anterior clinoidectomy.

A retrospective analysis of 32 patients with tuberculum sellae meningiomas who underwent surgery via a unilateral pterional approach was performed. A selective extradural anterior clinoidectomy (SEAC) technique was added in 20 patients. All patients had visual dysfunction preoperatively. Macroscopically complete removal with Simpson grade II was performed in 28 patients (87.5%). The postoperative visual function improved in 25 (78.1%), did not change in 3 (9.4%), and worsened in 4 patients (12.5%). The SEAC technique was effective, especially for removal of the tumour extending into the sellae/pituitary stalk (9 patients), the optic canal (4 patients) and hypothalamus (4 patients) with preservation of the visual and endocrinological function. These results were superior to those of surgery without SEAC technique. This technique is therefore recommended for complete resection of the tuberculum sellae meningiomas extending to the surrounding anatomical structures as the SEAC procedure reduces the risk of intraoperative optic nerve injury considerably.

Adolescent↗
PubMed2005

Role of human cripto-1 in tumor angiogenesis.

BACKGROUND: Human cripto-1 (CR-1) promotes cell transformation and increases migration and invasion of various mouse and human epithelial cell lines. We investigated whether CR-1 also stimulates angiogenesis. METHODS: We used human umbilical vein endothelial cells (HUVECs) to measure in vitro migration with fibronectin-coated Boyden chambers, invasion with Matrigel-coated Boyden chambers, proliferation with a tetrazolium salt, and differentiation with an in vitro Matrigel assay. We investigated new blood vessel formation in vivo by use of Matrigel-filled silicone cylinders implanted under the skin of nude mice and by use of a breast cancer xenograft model with CR-1-transfected or control Neo-transfected MCF-7 human breast cancer cells. We also used a blocking anti-CR-1 monoclonal antibody to investigate the role of CR-1 in angiogenesis in vivo and in vitro. All statistical tests were two-sided. RESULTS: CR-1 stimulated HUVEC proliferation, migration, and invasion and induced HUVEC differentiation into vascular-like structures on Matrigel. In vivo, recombinant CR-1 protein induced microvessel formation in Matrigel-filled silicone cylinders, and microvessel formation was statistically significantly inhibited with a blocking anti-CR-1 monoclonal antibody (CR-1 and antibody = 127% of microvessel formation compared with that in untreated control cylinders and CR-1 alone = 259%; difference = 132%, 95% confidence interval [CI] = 123% to 140%; P<.001). Tumors formed by CR-1-transfected MCF-7 cells in the cleared mammary fat pad of nude mice had higher microvessel density than tumors formed by control Neo-transfected MCF-7 cells (CR-1-transfected cells = 4.66 vessels per field and Neo-transfected cells = 2.33 vessels per field; difference = 2.33 vessels per field, 95% CI = 1.2 to 2.8; P = .004). CONCLUSION: CR-1 appears to have an important role in the multistep process of angiogenesis.

Animals↗
PubMed2005

Cripto-1: an oncofetal gene with many faces.

Human Cripto-1 (CR-1), a member of the epidermal growth factor (EGF)-CFC family, has been implicated in embryogenesis and in carcinogenesis. During early vertebrate development, CR-1 functions as a co-receptor for Nodal, a transforming growth factor beta (TGFbeta) family member and is essential for mesoderm and endoderm formation and anterior-posterior and left-right axis establishment. In adult tissues, CR-1 is expressed at a low level in all stages of mammary gland development and expression increases during pregnancy and lactation. Overexpression of CR-1 in mouse mammary epithelial cells leads to their transformation in vitro and, when injected into mammary glands, produces ductal hyperplasias. CR-1 can also enhance migration, invasion, branching morphogenesis and epithelial to mesenchymal transition (EMT) of several mouse mammary epithelial cell lines. Furthermore, transgenic mouse studies have shown that overexpression of a human CR-1 transgene in the mammary gland under the transcriptional control of the mouse mammary tumor virus (MMTV) promoter results in mammary hyperplasias and papillary adenocarcinomas. Finally, CR-1 is expressed at high levels in approximately 50 to 80% of different types of human carcinomas, including breast, cervix, colon, stomach, pancreas, lung, ovary, and testis. In conclusion, EGF-CFC proteins play dual roles as embryonic pattern formation genes and as oncogenes. While during embryogenesis EGF-CFC proteins perform specific and regulatory functions related to cell and tissue patterning, inappropriate expression of these molecules in adult tissues can lead to cellular proliferation and transformation and therefore may be important in the etiology and/or progression of cancer.

Epidermal Growth Factor↗
PubMed2005

Eosinophil activation in Wegener's granulomatosis: a harbinger of disease progression?

PURPOSE: To investigate the relation between eosinophil activation in tissue from patients with an active, limited form of Wegener's granulomatosis (WG) affecting the eye and subsequent systemic disease activity. METHODS: Analysis of ocular specimens obtained from 10 patients was performed. Sections were probed with antibodies to assess the presence of major basic protein (MBP) and eosinophil cationic protein (ECP). RESULTS: Four of the 10 specimens demonstrated the presence of MBP and ECP. WG progressed to the complete form in two of these patients, who received no or inadequate treatment. The other two, treated with cyclophosphamide for one year, did not progress to the complete form of WG during observation after therapy. CONCLUSIONS: Activated eosinophils in sclera or conjunctiva of patients with ocular limited WG may predict progression to complete WG.

Adult↗
PubMed2005

Moyamoya syndrome associated with hemolytic anemia due to Hb Alesha.

Moyamoya angiopathy is a well-known complication of sickle cell disease but has rarely been observed in other hemoglobinopathies. The authors describe a previously unreported association of hemolytic anemia due to a rare unstable hemoglobinopathy with abnormal oxygen affinity (Hb Alesha) and moyamoya syndrome in a 10-year-old girl. At age 4 she had recurrent migraine-with-aura-like symptoms. Cranial MRI, Doppler, and EEG examinations were not conclusive. Deterioration of her neurologic symptoms prompted a renewed EEG examination at 10 years of age, which revealed a re-buildup phenomenon. MRI and MR angiography now showed moyamoya angiopathy with stenotic and occlusive lesions of both internal carotid and middle cerebral arteries. Conventional angiography confirmed these findings. Reperfusion with three extra-intracranial bypasses terminated the transient ischemic attacks. The authors suggest that chronic hypoxemia may be the cause of occlusive moyamoya angiopathy in Hb Alesha and possibly other unstable hemoglobinopathies with altered oxygen affinity.

Anemia, Hemolytic↗
PubMed2005

Awake surgery for glioma resection in eloquent areas--Zurich's experience and review--.

Awake surgery was performed in a series of 21 patients with gliomas in eloquent areas with the use of intraoperative electrical mapping. Gross total removal was performed in 18 patients. There was no operative mortality. Postoperative findings included no change in symptoms and signs in 10 patients, improvement of the preoperative deficit in 11 patients. Four patients had improved Karnofsky performance status (KPS) scores after surgery, 17 patients were stable, and no patient had lower KPS score. Extensive radical resection of gliomas prolongs the overall survival and improves the patient's quality of life. However, surgical resection of gliomas located within the sensorimotor or language areas remains a neurosurgical challenge in reducing eloquent neurological sequelae. Awake surgery with intraoperative functional mapping is a safe approach to maximize the extent of tumor removal and to minimize the resultant neurological deficits in the treatment of glioma involving the eloquent cortex.

Adult↗
PubMed2004

Antidepressant medication use among First Nations peoples residing within British Columbia.

Very little is known about antidepressant medication use among First Nations people in Canada. This information would be useful to begin estimating the prevalence of conditions treated with this class of medications and planning appropriate programs. Antidepressant medication claims for First Nations people residing within British Columbia were extracted from the Non-Insured Health Benefits pharmacy database. During 2001, 9.8% (95% CI = 9.81, 9.79) of the population filled a prescription for antidepressant pharmacotherapy, claimant mean age was 40.3 years and the female:male ratio was approximately 3:1. The most common medications were Paxil, Apo-Amitriptyline, Effexor, and Celexa. Use of this medication class is common and more research is needed in this area of study.

Adult↗
PubMed2004

Moyamoya angiopathy with dolichoectatic internal carotid arteries, patent ductus arteriosus and pupillary dysfunction: a new genetic syndrome?

We report on 2 children with moyamoya angiopathy and bilateral dolichoectatic internal carotid arteries in combination with iris hypoplasia with bilateral fixed dilated pupils and a history of patent ductus arteriosus. Both were symptomatic with moyamoya angiopathy and underwent bilateral extracranial-intracranial (EC-IC) bypass operations for cerebral revascularization. This is the first report on moyamoya angiopathy and bilateral dolichoectatic internal carotid arteries with simultaneous occurrence of ocular and cardiovascular malformations. There have been descriptions of cerebral vascular abnormalities in combination with either congenital heart disease or ocular abnormalities but not with both presenting together. The combination of these separate congenital developmental defects may not be purely coincidental: we propose that the 2 probands are affected with a not yet recognized clinical syndrome of probably genetic etiology.

Carotid Artery, Internal↗
PubMed2004

Students, stress and coping strategies: a case of Pakistani medical school.

OBJECTIVE: Assess the perception of stress amongst medical students and their coping strategies. METHODOLOGY/STUDY DESIGN: A cross sectional study using a semi-structured self administered questionnaire was carried out over four weeks, using a small sample of students of all categories and classes of a medical college. RESULTS: A total of 264 students out of 300 (88%) filled in the questionnaire. Inability to cope, helplessness, increased psychological pressure, mental tension and too much workload are 'stress factors' for students. A considerable majority (> 90%) think that they have been stressed at one time or another. Ninety-four per cent of males have experienced stress. The senior students of the fourth and final year feel more stressed (95% and 98% respectively). Low moods, inability to concentrate, loss of temper are most common symptoms. Females report more symptoms. Academics and exams are the most powerful stressors. Sports, music, hanging out with friends, sleeping or going into isolation are various coping mechanisms. Stress can affect the academic performance. If needed, students prefer to talk to a peer. They demand more recreational activities on campus, revised schedule of academics and exams, better counselling facilities and improvement in student-teacher relationship. CONCLUSION: The prevalence of perceived stress seems to be high among medical students, which tends to affect not only their academic performances but also all aspects of health. Review of academics and exam schedules, more leisure time activities, better interaction with the faculty and proper guidance, advisory services and peer counselling at the campus could do a lot to reduce the stress.

Adaptation, Psychological↗
PubMed2004

Tobacco cessation pharmacotherapy use among First Nations persons residing within British Columbia.

The rate of tobacco use is higher among First Nations (FN) peoples than among other Canadians. Cessation pharmacotherapy agents reduce tobacco use, but the appropriateness and effectiveness of these agents among FN smokers are not entirely clear. Rates of tobacco cessation pharmacotherapy use among FN smokers are unknown; such information would be useful for program planners and would indicate appropriateness of use. To examine cessation pharmacotherapy use, we extracted claims for nicotine gum, nicotine patch, and bupropion SR (Zyban) from the Non-Insured Health Benefits pharmacy database for FN persons living within British Columbia during 2001. A total of 3.8% (95% CI=3.6-4.0) of FN claimants filled a prescription for at least one tobacco cessation pharmacotherapy agent; 61.7% were female, and their mean age was 38.1 years. Most claims (60.5%) were for bupropion, followed by nicotine patch (40.7%) and nicotine gum (4.7%). A total of 4.6% of claimants used both nicotine patch and bupropion,.8% used nicotine gum and nicotine patch, and.5% used nicotine gum and bupropion. Pharmacotherapy agents appear to be used less often by FN smokers than by other Canadian smokers for several possible reasons. Additional research is needed related to FN populations and cessation pharmacotherapy use in terms of cultural appropriateness, barriers to use, and effectiveness.

Adult↗
PubMed2004

The 2004 Canadian Hypertension Education Program recommendations for the management of hypertension: Part I--Blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the assessment of the diagnosis, cardiovascular risk and identifiable causes for adults with high blood pressure. OPTIONS: For persons in whom a high blood pressure value is recorded, the assignment of a diagnosis of hypertension is dependent on the appropriate measurement of blood pressure, the level of the blood pressure elevation and the duration of follow-up. In addition, the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases should be assessed to determine the urgency, intensity and type of treatment. For persons diagnosed as having hypertension, defining overall risk of adverse cardiovascular outcomes requires an assessment of concomitant vascular risk factors, including laboratory testing, a search for target organ damage and an assessment for modifiable causes of hypertension. Home and ambulatory blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: The identification of persons at increased risk of adverse cardiovascular outcomes; the quantification of overall cardiovascular risk; and the identification of persons with potentially modifiable causes of hypertension. EVIDENCE: Medline searches were conducted from November 2001, one year before the period of the last revision of the Canadian recommendations for the management of hypertension, to October 2003. Reference lists were scanned, experts were polled, and the personal files of subgroup members and authors were used to identify other studies. Identified articles were reviewed and appraised using prespecified levels of evidence by content experts and methodological experts. VALUES: A high value was placed on the identification of persons at increased risk of cardiovascular morbidity and mortality, and persons with identifiable and potentially modifiable causes of hypertension. BENEFITS, HARMS AND COSTS: The identification of persons at higher risk of cardiovascular disease will permit counselling for lifestyle maneuvers and introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. The identification of specific causes of hypertension may permit the use of cause-specific interventions. For certain subgroups of patients and specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The document contains recommendations for blood pressure measurement, diagnosis of hypertension and assessment of cardiovascular risk for adults with high blood pressure. These include the accurate measurement of blood pressure, criteria for diagnosis of hypertension, and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory blood pressure monitoring, and the role of echocardiography for those with hypertension. VALIDATION: All recommendations were graded according to strength of evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Only the recommendations that achieved high levels of consensus are reported. These guidelines will be updated annually.

Adult↗
PubMed2004

Constant-infusion H(2)15O PET and acetazolamide challenge in the assessment of cerebral perfusion status.

UNLABELLED: Assessing the baseline perfusion and perfusion reserve after acetazolamide (ACZ) challenge is a common method for the evaluation of patients with cerebrovascular disease. Most previous studies using H(2)(15)O PET applied the bolus injection technique. There is considerable discrepancy regarding the optimal time point of imaging after ACZ injection. The purpose of this study was to continuously monitor cerebral blood flow (CBF) after ACZ using constant-infusion H(2)(15)O PET. METHODS: Four patients with stenoses of an internal carotid artery and 6 with moyamoya disease were studied. H(2)(15)O was continuously infused, and data were recorded in 1-min frames. After equilibration of H(2)(15)O, 5 min of baseline data were acquired, and then 1 g of ACZ was administered intravenously and data collection continued for 10-22 min. Arterial blood was continuously drawn for absolute quantification of CBF. RESULTS: The arterial (15)O concentration remained generally stable during scanning, and the cerebellar blood flow fluctuations of the 5 baseline scans were small. The scan-to-scan difference was 6% (difference of 2 successive scans/mean). In the nonpathologic areas, the increase in CBF started 1-2 min after administration of ACZ. The largest fraction of the increase occurred from 0 to 10 min. The ratio of CBF in pathologic areas to CBF in cerebellum showed an initial decrease that stabilized after 5 min. CONCLUSION: A continuous-infusion protocol is a viable alternative to single bolus injections for the assessment of cerebral perfusion status. Such a protocol is advantageous when the time course of CBF after an intervention is not known. With continuous monitoring, the optimal time point for evaluation of a certain parameter can be chosen post hoc. Furthermore, the time course of CBF itself may allow the definition of new parameters for evaluating perfusion status in cerebrovascular patients, both for assessment before a revascularization procedure and for follow-up. A limitation of the present study is the relatively small number of patients with each type of cerebrovascular disease and the lack of healthy subjects.

Acetazolamide↗
PubMed2003

Identification, characterization, and gene expression profiling of endotoxin-induced myocarditis.

In septic shock, reversible cardiac dysfunction starts within 24 h. Myocardial depressant factors are thought to cause myocyte dysfunction, resulting in alterations of intrinsic cardiac function. Nitric oxide is a myocardial depressant factor candidate. Here we identify endotoxin-induced myocarditis (EIM) a previously uncharacterized pathophysiological entity. Features of EIM include differential patterns of inducible NO synthase (NOS2) mRNA induction in the left (LV) and right (RV) ventricles during the systemic response inflammatory syndrome (SIRS) and the presence of myocarditis with focal areas of aseptic necrosis in the RV 24 h after SIRS induction. Even though clinical data lead to the presumption of myocardial injury in sepsis, the underlying pathophysiological mechanisms have not been previously elucidated. Gene expression profiling was used to test the hypothesis of differential LV and RV responses in EIM, and revealed novel patterns of qualitative and quantitative expansion of transcription. Those genes are novel targets for drug development in SIRS and sepsis. Our results demonstrate spatial and temporal heterogeneity of myocardial responses in EIM. These findings justify the design of treatments to ameliorate tissue injury in the RV. Because the complexity of the inflammatory response increases substantially as time elapses, we suggest a stepwise and multitarget therapeutic approach for SIRS and sepsis. Our findings can help identify innate immune pathways that could become targets for immunotherapy in the treatment of disease caused by potential bioterrorism agents.

Animals↗
PubMed2003

A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src.

Human Cripto-1 (CR-1) is a member of the epidermal growth factor-Cripto FRL1 Cryptic family that has been shown to function as a coreceptor with the type I Activin serine-threonine kinase receptor ALK4 for the transforming growth factor beta-related peptide Nodal. However, CR-1 can also activate the mitogen-activated protein kinase and Akt pathways independently of Nodal and ALK4 by an unknown mechanism. Here, we demonstrate that CR-1 specifically binds to Glypican-1, a membrane-associated heparan sulfate proteoglycan, and activates the tyrosine kinase c-Src, triggering the mitogen-activated protein kinase and Akt signaling pathways. Finally, an active Src kinase is necessary for CR-1 to induce in vitro transformation and migration in mouse mammary epithelial cells.

Activin Receptors, Type I↗