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Biomedical subjects

Manit Arya

Publications and source records attributed to Manit Arya.

At least 19 recordsLinked to original sources
PubMed2006

Tissue microarrays and their relevance to the urologist.

PURPOSE: We review important aspects of TMA methodology and discuss its wide range of clinical applications with particular emphasis on key clinical studies. We also provide an update on recent and projected uses of this technology to help the urologist improve care in oncology patients. MATERIALS AND METHODS: A directed MEDLINE literature review of TMAs was performed. Important publications that have shaped our understanding of TMAs were selected for review. They were augmented by manual searches and our personal bibliographic collections. RESULTS: The TMA is a high throughput molecular biology technique that can significantly accelerate the processing of a large number of tissue specimens with excellent quality, good reliability and the preservation of original tissue. TMA studies demonstrate their accuracy and reliability compared to those of standard histological techniques and correlate with clinicopathological information to determine disease progression and prediction of the clinical outcome. CONCLUSIONS: This review represents an overview and update for the urologist on TMAs and their clinical applications in urological oncology. In the future it is anticipated that the outcomes of this method will be used to assist in the diagnosis, prognosis and development of novel therapies in individual patients.

Biomarkers, Tumor↗
PubMed2006

Management of detrusor-external sphincter dyssynergia.

Detrusor-external sphincter dyssynergia (DSD) is a debilitating problem in patients with spinal cord injury. DSD carries a high risk of complications, and even life expectancy can be affected. The mainstay of treatment is the use of antimuscarinic medication and catheterization, but in those for whom this is not possible external sphincterotomy has been the traditional management route. External sphincterotomy, however, is associated with significant risks, including hemorrhage, erectile dysfunction and the need for repeat procedures, and over the last decade alternatives have been investigated, such as urethral stents and botulinum toxin injection. We present a review of DSD, including the current management strategies and prospects for future treatment.

Adrenergic alpha-Antagonists↗
PubMed2006

The overactive bladder: review of current pharmacotherapy in adults. Part 1: pathophysiology and anticholinergic therapy.

Overactive bladder is a syndrome characterised by urinary urgency, with or without urge incontinence, and usually with frequency and nocturia. It affects millions of people of all ages worldwide and causes significant morbidity, especially in terms of health-related quality of life. It poses a huge economic burden on health resources. Managing such patients involves a thorough history, physical examination and the use of pertinent investigations before the initiation of treatment. Therapy consists of lifestyle changes, bladder training, anticholinergics, second-line agents such as resiniferatoxin instillation or botulinum toxin injections into the bladder in refractory cases and, finally, in intractable cases, surgery. In the first part of this review of pharmacotherapy for the treatment of this condition, the focus is on the pathophysiological factors potentially involved in overactive bladder and covers the wide range of currently available first-line anticholinergic agents. Treatment algorithms are suggested on the basis of current literature.

Administration, Cutaneous↗
PubMed2006

The overactive bladder: review of current pharmacotherapy in adults. Part 2: treatment options in cases refractory to anticholinergics.

In the first part of this review the potential pathophysiological factors involved in the overactive bladder were outlined, and the wide range of first-line anticholinergic pharmacotherapies available for such patients were reviewed. The second part will focus on the intravesical instillation of resiniferatoxin and injections of botulinum toxin into the bladder to treat overactive bladder and detrusor overactivity. Resiniferatoxin has been shown to increase bladder capacity and improve incontinence in patients with neurogenic and non-neurogenic detrusor overactivity. Botulinum toxin has successfully been used to treat neurogenic and idiopathic detrusor overactivity, with improvements observed in bladder capacity, decreases in detrusor pressures on filling and voiding, and increased volumes at first contraction. Further validation is required for both treatments, in the form of large randomised controlled trials, before their use can be considered routine, with particular focus on dosing required.

Administration, Intravesical↗
PubMed2005

Current challenges in Wilms' tumor management.

Wilms' tumor is a renal cancer that predominantly affects children during the first 2 years of life. The continuing success of clinical trials in Wilms' tumor patients over the past 30 years has led to an overall survival of 85%, and treatment-related morbidity has been reduced. Less-aggressive chemotherapeutic regimes are available for patients with validated good prognostic factors, such as low stage and favorable histology. It is becoming increasingly apparent that treatment can be optimized through stratification of patients according to tumor stage and histology. Established treatments for Wilms' tumor include perioperative vincristine and actinomycin, with or without doxorubicin or radiotherapy. Relapsed patients have the option of salvage chemotherapy with ifosfamide, carboplatin and etoposide, as well as high-dose chemotherapy regimes and autologous hemopoietic stem-cell rescue. Further research is required to refine these regimes and identify further the role of additional prognostic factors in this childhood disease. In this article we discuss the most-debated issues and advances that have been made in the management of Wilms' tumor.

Antineoplastic Agents↗
PubMed2005

Bladder carcinoma: understanding advanced and metastatic disease with potential molecular therapeutic targets.

This article is an expert review of bladder cancer genetics focusing on genetic changes and their significance in the pathogenesis and progression of bladder transitional cell carcinoma, in particular, muscle-invasive disease. Alongside the relevant genetic markers and their products, new therapeutic targets and agents that are being developed are presented.

Carcinoma, Transitional Cell↗
PubMed2005

Basic principles of real-time quantitative PCR.

Real-time quantitative PCR allows the sensitive, specific and reproducible quantitation of nucleic acids. Since its introduction, real-time quantitative PCR has revolutionized the field of molecular diagnostics and the technique is being used in a rapidly expanding number of applications. This exciting technology has enabled the shift of molecular diagnostics toward a high-throughput, automated technology with lower turnaround times. This article reviews the basic principles of real-time PCR and describes the various chemistries available: the double-stranded DNA-intercalating agent SYBR Green 1, hydrolysis probes, dual hybridization probes, molecular beacons and scorpion probes. Quantitation methods are discussed in addition to the competing instruments available on the market. Examples of applications of this important and versatile technique are provided throughout the review.

Benzothiazoles↗
PubMed2004

Allogeneic stem-cell transplantation for renal-cell cancer.

Metastatic renal-cell carcinoma (RCC) is resistant to chemotherapy, and patients with this disease have a poor outlook. Immunotherapy by use of cytokines and vaccines against tumour antigens has shown encouraging results in a small group of patients. Advances in the understanding of the graft-versus-tumour effect in haematological malignant disorders have led to the use of stem-cell transplantation for treatment of solid-organ malignant diseases such as RCC. Techniques of bone-marrow ablation have been superseded by safer conditioning regimens, with occasional complete remission and partial remission in some patients. Graft-versus-host disease, engraftment failure, and disease progression remain important obstacles to the widespread use of new techniques for metastatic RCC. Here, we summarise important issues surrounding immunotherapy for RCC, the problems encountered with use of immunotherapy, and the present use of non-myeloablative techniques for treatment of this disease.

Aged↗
PubMed2004

Allogeneic hematopoietic stem-cell transplantation: the next generation of therapy for metastatic renal cell cancer.

The management of metastatic renal cell carcinoma (mRCC) remains a therapeutic challenge; less than 10% of patients survive for longer than 5 years. The resistance of renal cancer to chemotherapy may be explained by high levels of the multidrug resistance gene, MDR1. Immune-based treatments for renal cancer have been explored because of their unusual susceptibility to immunological assault. However, response rates to cytokines such as interleukin-2 and interferon-alpha have ranged from only 10% to 20%, prompting other immunotherapy approaches, such as allogeneic stem-cell transplantation, to be investigated. Several clinical trials have provided evidence of partial or complete disease regression in refractory mRCC following nonmyeloablative stem-cell transplantation. This effect is because of a donor antimalignancy effect mediated by immunocompetent donor T cells, called graft-versus-tumor effect. Unfortunately, less than 30% of patients who could have this procedure will have a human-leukocyte-antigen-compatible sibling, and attention is focusing on alternative donors such as matched unrelated donors and partially mismatched related donors. Despite the improved safety of nonmyeloablative conditioning regimens, transplant-related toxic effects (particularly graft-versus-host disease) remain obstacles to the safe and effective use of this treatment. Regardless of these limitations, innovative approaches have attempted to harness the potential of the graft-versus-tumor effect in mRCC and other solid tumors.

Carcinoma, Renal Cell↗
PubMed2004

New phosphodiesterase inhibitors in the treatment of erectile dysfunction.

Sildenafil revolutionised the treatment of erectile dysfunction (ED) on its introduction in 1998. Not only is it effective, but is, perhaps even more importantly, an extremely acceptable manner in which to treat ED (i.e., oral pharmacotherapy), compared to the other treatments that were available at that time (e.g., intracavernosal injection). Whilst sildenafil remains the market leader for ED treatment, it does have some shortcomings: its clinical efficacy is diminished in 'difficult to treat' patient groups, such as diabetics, side effects, such as blue-tinged vision and headache, and the need to time the ingestion of sildenafil to 1 h prior to expected time of sexual intercourse. Recently, newer phosphodiesterase inhibitors ('sons of viagra') have become available, and potentially to improve upon, what has become regarded as the gold standard for ED treatment. This review article discusses the differences between vardenafil, tadalafil and sildenafil, in order to allow the clinician to make an informed decision as to which phosphodiesterase inhibitor to prescribe when dealing with the ever expanding number of patients seeking help for ED.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Peyronie's disease: an update of the medical management.

Peyronie's disease (PD) is characterised by penile plaque formation, pain, penile deformity and erectile dysfunction. It is a fibrotic disorder of the tunica albuginea with a poorly understood aetiology and epidemiology. PD may be classified into inflammatory (acute) and chronic stages. Medical treatment is usually instigated during the inflammatory phase of the disease. A review of the literature reveals a wide range of oral, intralesional and alternative therapies that are discussed in relation to established pathophysiological mechanisms of the disease. The advantages and disadvantages of each treatment are summarised. This review also discusses the ongoing therapeutic dilemmas of PD and suggests a treatment strategy based on an analysis of the urological literature.

Humans↗