PubMed Health⌕ Search

Biomedical subjects

A Afzal

Publications and source records attributed to A Afzal.

14 recordsLinked to original sources
PubMed2006

Proliferating endothelial cell-specific expression of IGF-I receptor ribozyme inhibits retinal neovascularization.

Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells, retinal pigment epithelial cells, Müller cells and endothelial cells. Endothelial cell proliferation is a common feature of proliferative retinopathies and involves abnormal growth of blood vessels within and on the surface of the retina. In an effort to inhibit the formation of these aberrant blood vessels, we cloned an IGF-IR ribozyme into an expression vector that limits expression of the ribozyme to proliferating endothelial cells. An endothelin enhancer and Cdc6 promoter chimera drives expression of the IGF-IR ribozyme. This promoter limited retinal expression of the reporter gene to proliferating endothelial cells in two mouse models of proliferative retinopathy. In addition, expression of the IGF-IR ribozyme by this promoter inhibited aberrant retinal angiogenesis in both models while preserving normal vessels. These results demonstrate the feasibility of IGF-IR ribozyme expression in a selective manner for safer treatment of abnormal angiogenesis associated with retinopathy.

Animals↗
PubMed2003

Reduction in preretinal neovascularization by ribozymes that cleave the A2B adenosine receptor mRNA.

Adenosine modulates a variety of cellular functions by interacting with specific cell surface G protein-coupled receptors (A1, A2A, A2B, and A3) and is a potential mediator of angiogenesis through the A2B receptor. The lack of a potent, selective A2B receptor inhibitor has hampered its characterization. Our goal was to design a hammerhead ribozyme that would specifically cleave the A2B receptor mRNA and examine its effect on retinal angiogenesis. Ribozymes specific for the mouse and human A2B receptor mRNAs were designed and cloned in expression plasmids. Human embryonic kidney (HEK) 293 cells were transfected with these plasmids and A2B receptor mRNA levels were determined by quantitative real-time RT-PCR. Human retinal endothelial cells (HRECs) were also transfected and cell migration was examined. The effects of these ribozymes on the levels of preretinal neovascularization were determined using a neonatal mouse model of oxygen-induced retinopathy (OIR). We produced a ribozyme with a Vmax of 515+/-125 pmol/min and a Kcat of 36.1+/-8.3 min(-1) (P< or =1x10(-5)). Transfection of HEK293 cells with the plasmid expressing the ribozyme reduced A2B receptor mRNA levels by 45+/-4.8% (P=5.1x10(-5)). Transfection of HRECs reduced NECA-stimulated migration of cells by 47.3+/-1.2% (P=7x10(-4)). Intraocular injection of the constructs into the mouse model reduced preretinal neovascularization by 53.5+/-8.2% (P=4.5x10(-5)). Our results suggest that the A2B receptor ribozyme will provide a tool for the selective inhibition of this receptor and provide further support for the role of A2B receptor in retinal angiogenesis.

Animals↗
PubMed2003

Long term benefits of hypnotherapy for irritable bowel syndrome.

BACKGROUND AND AIMS: There is now good evidence from several sources that hypnotherapy can relieve the symptoms of irritable bowel syndrome in the short term. However, there is no long term data on its benefits and this information is essential before the technique can be widely recommended. This study aimed to answer this question. PATIENTS AND METHODS: 204 patients prospectively completed questionnaires scoring symptoms, quality of life, anxiety, and depression before, immediately after, and up to six years following hypnotherapy. All subjects also subjectively assessed the effects of hypnotherapy retrospectively in order to define their "responder status". RESULTS: 71% of patients initially responded to therapy. Of these, 81% maintained their improvement over time while the majority of the remaining 19% claimed that deterioration of symptoms had only been slight. With respect to symptom scores, all items at follow up were significantly improved on pre-hypnotherapy levels (p<0.001) and showed little change from post-hypnotherapy values. There were no significant differences in the symptom scores between patients assessed at 1, 2, 3, 4, or 5+ years following treatment. Quality of life and anxiety or depression scores were similarly still significantly improved at follow up (p<0.001) but did show some deterioration. Patients also reported a reduction in consultation rates and medication use following the completion of hypnotherapy. CONCLUSION: This study demonstrates that the beneficial effects of hypnotherapy appear to last at least five years. Thus it is a viable therapeutic option for the treatment of irritable bowel syndrome.

Anxiety↗
PubMed2001

The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation.

Increased reactive oxygen species generation by the leukocytes of the obese may be responsible for increased oxidative injury to lipids and proteins and, hence, atherosclerosis. We have investigated whether reactive oxygen species generation by leukocytes and other indexes of oxidative damage in the body fall with short-term dietary restriction and weight loss. Nine nondiabetic obese subjects (body mass index, 32.5-64.4 kg/m(2)), not taking any antioxidants, were put on a 1000-Cal diet. Fasting blood samples were taken at 0, 1, 2, 3, and 4 weeks and at 12 weeks after the cessation of dietary restriction. Blood samples were also obtained at 1 and 2 h after administration of 75 g oral glucose at 0 and 4 weeks. Mononuclear cells (MNC) and polymorphonuclear leukocytes (PMN) were isolated, and reactive oxygen species generation was measured. Plasma concentrations of thiobarbituric acid-reactive species (TBARS), 13-hydroxyoctadecadienoic acid (13-HODE), 9-hydroxyoctadecadienoic acid (9-HODE), carbonylated proteins, o-tyrosine, and m-tyrosine as indexes of oxidative damage to lipids, proteins and amino acids, respectively, were measured. Antioxidant vitamins were measured as indexes of antioxidant reserves. Plasma tumor necrosis factor-alpha concentrations were also measured. Mean weight loss was 2.4 +/- 0.6 kg at week 1, 2.5 +/- 1.7 kg at week 2, 3.9 +/- 0.8 kg at week 3, and 4.5 +/- 2.8 kg at week 4 (P < 0.05). Reactive oxygen species generation by PMN fell from 236.4 +/- 95.8 to 150.9 +/- 69.0, 125.9 +/- 24.3, 96.0 +/- 39.9, and 103.1 +/- 35.7 mV at weeks 1, 2, 3, and 4, respectively (P < 0.001). It increased 3 months after the cessation of dietary restriction to 270.0 +/- 274.3 mV. Reactive oxygen species generation by MNC fell from 187.8 +/- 75.0 to 101.7 +/- 64.5, 86.9 +/- 42.8, 63.8 +/- 14.3, and 75.1 +/- 32.2 mV and increased thereafter to 302.0 +/- 175.5 mV at 1, 2, 3, 4, and 16 weeks, respectively (P < 0.005). Reactive oxygen species generation by PMN and MNC increased in response to glucose; the relative increase was greater at 4 weeks than that at week 0 due to a fall in the basal levels of reactive oxygen species generation. Consistent with the fall in reactive oxygen species generation, there was a reduction in plasma TBARS from 1.68 +/- 0.17 micromol/L at week 0 to 1.47 micromol/L at 4 weeks (P < 0.05). The 13-HODE to linoleic acid ratio fell from a baseline of 100% to 56.4 +/- 36.1% at 4 weeks (P < 0.05), and the 9-HODE to linoleic acid ratio fell from a baseline of 100% to 60.5 +/- 37.7% at 4 weeks (P < 0.05). Carbonylated proteins fell from 1.39 +/- 0.27 microgram/mg protein at week 0 to 1.17 +/- 0.12 microgram/mg protein at week 4 (P < 0.05); o-tyrosine fell from 0.42 +/- 0.03 mmol/mol phenylalanine at week 0 to 0.36 +/- 0.02 mmol/mol phenylalanine at 4 weeks (P < 0.005), and m-tyrosine fell from 0.45 +/- 0.04 mmol/mol phenylalanine at week 0 to 0.40 +/- 0.03 mmol/mol phenylalanine at 4 weeks (P < 0.05). The basal concentrations of TBARS, 9-HODE, 13-HODE, carbonylated proteins, o-tyrosine, and m-tyrosine in the obese were significantly greater than those in normal subjects. On the other hand, tumor necrosis factor-alpha concentrations did not change during this 4-week period, nor was there any change in antioxidant vitamins. This is the first demonstration of 1) an increase in reactive oxygen species-induced damage in lipids, proteins, and amino acids in the obese compared with normal subjects; and 2) a decrease in reactive oxygen species generation by leukocytes and oxidative damage to lipids, proteins, and amino acids after dietary restriction and weight loss in the obese over a short period.

Adult↗
PubMed2000

Fever in acute pulmonary embolism.

BACKGROUND: Although fever has been reported in several case series of acute pulmonary embolism (PE), the extent to which fever may be caused by PE, and not associated disease, has not been adequately sorted out. Clarification of the frequency and severity of fever in acute PE may assist in achieving an accurate clinical impression, and perhaps avoid an inadvertent exclusion of the diagnosis. PURPOSE: The purpose of this investigation is to evaluate the extent to which fever is caused by acute PE. METHODS: Patients participated in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). Temperature was evaluated among patients with angiographically proven PE. A determination of whether other causes of fever were present was based on a retrospective analysis of discharge summaries, PIOPED summaries, and a computerized list of all discharge diagnoses. RESULTS: Among patients with PE and no other source of fever, fever was present in 43 of 311 patients (14%). Fever in patients with pulmonary hemorrhage or infarction was not more frequent than among those with no pulmonary hemorrhage or infarction, 39 of 267 patients (15%) vs 4 of 44 patients (9%; not significant). Clinical evidence of deep venous thrombosis was often present in patients with PE and otherwise unexplained fever. CONCLUSION: Low-grade fever is not uncommon in PE, and high fever, although rare, may occur. Fever need not be accompanied by pulmonary hemorrhage or infarction.

Acute Disease↗
PubMed2000

Reversible cardiomyopathy associated with Addison's disease.

Myocardial involvement in Addison's disease has been described previously. A 36-year-old man presented with cardiomyopathy and was found to have Addison's disease. The patient's myocardial function improved after steroid therapy for Addison's disease. This is the only case report of reversible cardiomyopathy associated with Addison's disease in an adult patient.

Addison Disease↗
PubMed2000

Myocarditis and pericarditis with tamponade associated with disseminated tuberculosis.

Tuberculous involvement of the myocardium is relatively rare. Tuberculous pericarditis with tamponade and myocarditis in a young woman with no evidence of immunosuppression and disseminated tuberculosis is described. Three distinct forms of myocardial involvement are recognized: nodular tubercles (tuberculomas) of the myocardium; miliary tubercles of the myocardium; and an uncommon diffuse infiltrative type. The myocardium is involved by a hematogenous route, by lymphatic spread or contiguously from the pericardium. The diagnosis can be made by endomyocardial biopsy if clinical suspicion is strong and echocardiographic findings are suggestive. Antituberculosis drugs may be curative. With an increasing prevalence of tuberculosis, the possibility of potentially lethal myocardial tuberculosis is important to consider.

Adult↗
PubMed1999

Racial differences in patients with heart failure.

BACKGROUND AND HYPOTHESIS: Limited data exist regarding racial differences in heart failure. The objective of this prospective study was to document racial differences in the baseline demographics and patterns of health care utilization and outcomes in patients with heart failure. METHODS: The data on 163 consecutive patients (113 black, 50 white) admitted with a diagnosis of heart failure confirmed by pulmonary congestion on chest x-ray were prospectively evaluated. Patient demographics, physical examination findings at admission, comorbid conditions, and medications at admission and discharge were analyzed. Follow-up was performed to document visits to the physician's office after discharge and readmission rate during a 6-month time period. RESULTS: Compared with whites, blacks were younger in age (mean age 63.8 +/- 13.7 years vs. 70.8 +/- 13.1, p = 0.003), and had a higher prevalence of hypertension (86 vs. 66%, p = 0.004), left ventricular hypertrophy (24 vs. 8%, p = 0.02), ejection fraction < 40% (64 vs. 43%, p = 0.03), and readmission rate (33 vs. 18%, p = 0.05). Whites had a higher prevalence of atrial fibrillation (42 vs. 21%, p = 0.006) and more frequently followed up with their cardiologists as outpatients (58 vs. 39%, p = 0.04). CONCLUSION: Significant racial differences exist in patients with heart failure with regard to age, incidence, etiologic factors, left ventricular hypertrophy, left ventricular function, and clinical follow-up. It is important to consider these racial differences in the evaluation and management of patients with heart failure.

Aged↗
PubMed1999

Heart transplant for dilated cardiomyopathy associated with polymyositis.

Cardiac involvement is one of the most significant factors in the poor clinical outcome of polymyositis. The case of a 39 year old African American woman with polymyositis, cardiomyopathy, and severe heart failure who had orthotopic heart transplantation is described. Review of the literature reveals that cardiac manifestations of polymyositis are frequent and include conduction system abnormalities, myocarditis, cardiomyopathy, coronary artery atherosclerosis, valvar disease, and pericardial abnormalities.

Adult↗
PubMed1999

Leukocytosis in acute pulmonary embolism.

PURPOSE: The purpose of this investigation is to assess the level of leukocytosis in acute pulmonary embolism (PE). BACKGROUND: Limited data exist regarding leukocytosis in acute PE. One reason that the prevalence of leukocytosis in acute PE is unknown, despite an extensive number of investigations of PE, may relate to the fact that acute PE is usually associated with other conditions that themselves may cause leukocytosis. METHODS: Hospital records of 386 patients with a diagnosis of acute PE were reviewed retrospectively. Patients with no other possible or definite cause of leukocytosis were analyzed separately. A diagnosis of PE was made by a high-probability interpretation of the ventilation/perfusion lung scan or pulmonary angiogram. RESULTS: Among patients with PE in whom other possible or defined causes for leukocytosis were eliminated, 52 of 266 (20%) had a WBC count > 10,000/mm3. None had a WBC count that was > or = 20,000/mm3. Patients with the pulmonary hemorrhage/infarction syndrome had an increased WBC count in 32 of 183 (17%) vs 20 of 83 (24%) in patients who did not have pulmonary hemorrhage/infarction syndrome (not significant). CONCLUSION: A modest leukocytosis may accompany (and possibly be caused by) PE. Its presence should not dissuade the clinician from objectively pursuing the diagnosis of PE.

Acute Disease↗
PubMed1999

Incidence of acute pulmonary embolism in a general hospital: relation to age, sex, and race.

PURPOSE: The purpose of this investigation is to determine the incidence of acute pulmonary embolism (PE) according to age, sex, and race in a tertiary care general hospital. BACKGROUND: Population-based investigations and autopsy studies have shown that acute PE occurs predominantly in middle-aged and elderly people. The incidence of PE according to age, race, and sex in a general hospital has been only sparsely studied. METHODS: Patients with PE diagnosed by a high-probability ventilation/perfusion lung scan or pulmonary angiography were identified in a tertiary care general hospital. The incidence of PE was determined according to age, sex, and race. RESULTS: The incidence of PE was 400 of 175,730 (0.23%; 95% CI, 0.21 to 0.25%). The incidence was linearly related to age (r = 0.94). Among patients >/= 50 years of age, the incidence of PE was higher among women (0.40% vs 0.29%; p < 0.01). The incidence was comparable among patients < 50 years of age. African Americans showed an incidence of 0.26%, and whites showed an incidence of 0. 21% (p < 0.05). CONCLUSION: Acute PE in a tertiary care hospital is more frequent than previously reported among short-term hospitals. Occasionally, young adults and adolescents had PE, although PE occurred primarily among middle-aged and elderly patients. Among patients >/= 50 years of age, the incidence of PE was higher among women. The incidence was not higher among women < 50 years of age, suggesting that childbirth and birth control pills had little impact. Only a trivial difference of the incidence of PE was observed among African Americans compared to whites.

Adolescent↗
PubMedDate not supplied

Exercise training in heart failure.

Patients with heart failure challenge the clinician with a constellation of difficult clinical, pathophysiologic, and psychologic issues. As a result, until recently, exercise training was not considered a safe and effective treatment strategy to be used in these patients. However, in the past 10 years, data from both randomized and nonrandomized trials showed that regular exercise training in patients with stable Class II and III heart failure can safely improve exercise tolerance, attenuate an overactivated sympathetic nervous system, partially reverse skeletal muscle abnormalities, and enhance health-related quality of life. These outcomes are achievable with a relatively moderate dose of physical activity, such as 30 to 60 minutes of walking or cycling 3 to 5 days per week at an intensity equivalent to 60% to 70% of peak oxygen consumption. Sufficiently powered trials are needed to assess morbidity, mortality, and cost-effectiveness endpoints relative to exercise training in patients with heart failure.

Cardiac Output↗
PubMedDate not supplied

Extrinsic compression of the left main coronary artery in pulmonary hypertension.

Compression of the left main coronary artery by a dilated pulmonary artery can be a life-threatening condition. It can present with angina, symptoms of left ventricular dysfunction, and sudden death. Diagnosis and treatment of this condition is very important. We demonstrate significant compression of the left main coronary artery on coronary angiography and thorax CT examinations.

Coronary Disease↗