Biomedical subjects
Ridwan Shabsigh
Publications and source records attributed to Ridwan Shabsigh.
Third International Conference on the Management of Erectile Dysfunction: Linking Pathophysiology and Therapeutic Response.
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Erectile dysfunction.
Erectile dysfunction (ED) is a highly prevalent and often undertreated condition. It may be a symptom of underlying, chronic illness and can have a negative impact on quality of life, psychosocial health, and relationships. The aging of the population, as well as the introduction of new treatment options, such as sildenafil, has led to increased public awareness of this disorder. New oral therapeutic agents are on the horizon. This article provides an overview of the physiology of erection, the pathophysiology of ED, and modern patient evaluation. Management options, including traditional therapeutic approaches as well as the new generation of oral agents, are also presented.
Human hormone-refractory prostate cancers can harbor mutations in the O(2)-dependent degradation domain of hypoxia inducible factor-1alpha (HIF-1alpha).
PURPOSE: Androgen ablation, the preferred therapy for advanced prostate cancer, reduces blood flow and induces hypoxia in androgen-dependent tissues. Given the transient effectiveness of this therapy, we must consider whether a hypoxia-resistance mechanism might be involved in the development of therapeutic resistance by prostate cancer cells. The transcription factor protein, hypoxia-inducible factor 1alpha (HIF-1alpha), helps increase the expression of gene products that enable cells to survive conditions of hypoxic stress. Enhanced HIF-1alpha expression during hypoxia results from a drastic reduction of its degradation rate within a critical region of the protein referred to as the "oxygen-dependent degradation (ODD) domain". We sequenced HIF-1alpha cDNAs amplified from human prostate cancer cell lines and from hormone resistant prostate cancer specimens to determine whether prostate cancer cells might harbor mutations within the HIF-1alpha ODD domain. METHODS: HIF-1alpha cDNAs were RT-PCR amplified from three prostate cancer cell lines (LNCaP, PC-3, and DU145), from five different human hormone-resistant prostate cancers and one normal prostate, all microdissected, and were sequenced to determine whether the HIF-1alpha gene products were wildtype or mutant. One specimen containing a hormone-resistant prostate tumor that expressed a mutated HIF-1alpha cDNA was further microdissected into benign and tumorous regions and DNAs extracted from these regions were directly amplified by PCR and sequenced to determine whether the HIF-1alpha mutation was specific to the tumor. RESULTS: Although the HIF-1alpha cDNAs of all cell lines, the normal prostate, and three of the tumors were found to have a wildtype sequence, HIF-1alpha cDNAs amplified from two hormone-resistant tumors had nucleic acid substitutions that resulted in significant amino acid changes within the ODD domain of the HIF-1alpha protein. Analysis of the DNA extracted from a benign or tumorous region of one of these specimens showed that only the wildtype (nonmutated) form of the HIF-1alpha gene was amplified from the normal DNA whereas only the mutated form of the HIF-1alpha gene was amplified from the tumor. CONCLUSIONS: Some human hormone-refractory prostate cancers have mutations in a critical regulatory domain of the HIF-1alpha protein. We believe that these mutations might enable expression of this protein under inappropriate conditions and contribute to the development of therapeutic resistance by the cancer cells. This hypothesis is currently being tested.
The epidemiology and definition of female sexual disorders.
Female sexual dysfunction (FSD) is a multifactorial condition that has anatomical, physiological, medical, psychological, and social components. Similar to erectile dysfunction in men, FSD is highly prevalent and often undertreated. Due to the development of successful treatment for male erectile dysfunction, FSD is receiving increased attention. Only a few studies dealing with epidemiology of female sexual dysfunction are available in the literature. However, research efforts in the field are increasing. This overview presents currently used classification systems, recently updated definitions, as well as prevalence data on the different entities of female sexual disorders.
Female sexual dysfunction: state of the art.
Female sexual dysfunction, a common, multifactorial, and often undertreated medical condition, attracted the attention of the medical community with the successful introduction of medical therapy for male erectile dysfunction. This review discusses the updated classification systems and definitions, epidemiologic aspects, and new pathophysiologic and therapeutic implications of this sexual disorder.
Depression, antidepressant therapies, and erectile dysfunction: clinical trials of sildenafil citrate (Viagra) in treated and untreated patients with depression.
Erectile dysfunction (ED) and depression are highly prevalent conditions and frequently occur concomitantly in predisposed individuals. Men with ED and depression are also likely to have other comorbid conditions, including diabetes, hypertension, and heart disease. Because ED is also a common adverse effect of some medications for these conditions, patients are frequently noncompliant with treatment. Sildenafil citrate (Viagra) is effective in treating ED of a broad range of etiologies, suggesting that it may be equally beneficial in patients with ED that is associated with depressive symptoms and in those with ED resulting from serotonergic reuptake inhibitor (SRI) antidepressant treatment. We review the results of 3 randomized, placebo-controlled trials and a retrospective analysis of data pooled from 10 clinical trials that examine the efficacy of sildenafil in treating ED associated with depression and as an adverse effect of SRI treatment. The results suggest that sildenafil is efficacious as a first-line treatment for ED in men with untreated minor depression, in men with ED that is refractory to successful SRI treatment of depression, and in those whose depression was successfully treated but who developed ED as a consequence of SRI treatment. Given the complex interrelations among ED, depression, and other comorbid conditions, the key to proper management is a comprehensive evaluation, including sexual function, and an accurate differential diagnosis.
Hormonal factors in female sexual dysfunction.
Female sexual dysfunction is a common, multifactorial medical condition, which can have a major impact on self-esteem, quality of life, mood and relationships. Hormonal imbalances may contribute to sexual dysfunction, in particular sexual arousal disorder. Androgens for the treatment of decreased libido, especially in postmenopausal women, have gained increased popularity despite preliminary and controversial results. The absence of precise definitions of androgen deficiency, unknown 'normal' ranges for androgens, and nuances in the sensitivity of the various assays have made research on androgens and libido in women difficult to interpret. This review presents the role of estrogen and androgens in sexual function and their potential roles as therapeutic agents for female sexual dysfunction.
Economic aspects of medical erectile dysfunction therapies.
The introduction of safe and effective oral therapies has changed the significance of erectile dysfunction (ED) forever. Seldom has a new drug changed the landscape of pharmacotherapy in so many ways as sildenafil (Viagra, Pfizer). This article highlights the various oral, intracavernosal and intraurethral therapies currently available for ED and evaluates the socio-economic impact of each method.
Sexual dysfunction is common and overlooked in female patients with hypertension.
Our objective was to investigate sexual activity, behavior, dysfunction, and satisfaction in hypertensive women. Sixty-seven patients with a mean age of 60.4 years completed a detailed questionnaire. Of these women, 81.3% had a sex partner; 42.6% had untreated sexual dysfunction with a duration of more than 5 years in 70.9% and a duration of more than 10 years in 41.7%; 5.3% initiated sexual activity; 36.6% reported less sexual activity than desired; and 54.8% reported sexual activity as important. Our study revealed highly prevalent untreated sexual dysfunction of long duration. It also showed low frequency of sexual activity in spite of the high availability of partners. There was low frequency of initiation of sexual activity. In spite of the high prevalence of sexual dysfunction, more than a third of patients reported sexual activity to be less than desired, and more than half of patients reported sexual activity as important.