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Biomedical subjects

R Persad

Publications and source records attributed to R Persad.

At least 19 recordsLinked to original sources
PubMed2006

Reactive oxygen species and erectile dysfunction: possible role of NADPH oxidase.

Erectile dysfunction (ED) is a widespread condition, the incidence of which is increasing globally. ED is also indicative of underlying vasculopathy and represents a predictor of more serious cardiovascular disorders. Understanding the aetiology of ED may therefore provide invaluable pointers to the pathobiology of other cardiovascular diseases (CVDs) and syndromes. It follows, too, that therapeutic interventions that are successful in treating ED may, ipso facto, be effective in treating the early stages of conditions that include atherosclerosis, angina, plaque rupture and diabetic angiopathy. One common pathological denominator in both CVD and ED is oxidative stress, that is, the overproduction of reactive oxygen species (ROS), in particular, superoxide (O(2)(*-)) and hydrogen peroxide (H(2)O(2)). In this review, therefore, we consider the aetiology and pathobiology of O(2)(*-) in promoting ED and focus on NADPH oxidase as an inducible source of O(2)(*-) and H(2)O(2). Therapeutic strategies aimed at reducing oxidative stress to improve erectile function are also discussed.

Animals↗
PubMed2005

Prostasomes--their effects on human male reproduction and fertility.

The prostate is a glandular male accessory sex organ vital for normal fertility. It provides the prostatic component of seminal plasma which nourishes and protects sperm following ejaculation. Prostasomes are small (40-500 nm) membrane-bound vesicles produced by epithelial cells lining the prostate acini and are a component of prostatic secretions. Although the existence of these particles has been known for many years, their full function and relevance to reproductive health are largely unknown. Proteomic studies have shown a wide range of proteins (enzymes, structural proteins and novel, unannotated proteins) present in or on the surface of prostasomes providing them with a diverse nature. Interestingly prostasomes are able to fuse with sperm, this event and the associated transfer of proteins lies at the heart of many of their proposed functions. Sperm motility is increased by the presence of prostasomes and their fusion prevents premature acrosome reactions. Prostasomes have been shown to aid protection of sperm within the female reproductive tract because of immunosuppressive, antioxidant and antibacterial properties. Clinically these functions imply a role for prostasomes in male factor infertility. However, the very functions that promote fertility may have negative connotations in later life; recent work has suggested that prostasomes are involved in prostate cancer. Clearly more work is needed to clarify the role of these novel particles and their impact on men's health.

Cytoplasmic Vesicles↗
PubMed2005

The use of Raman spectroscopy to differentiate between different prostatic adenocarcinoma cell lines.

Raman spectroscopy (RS) is an optical technique that provides an objective method of pathological diagnosis based on the molecular composition of tissue. Studies have shown that the technique can accurately identify and grade prostatic adenocarcinoma (CaP) in vitro. This study aimed to determine whether RS was able to differentiate between CaP cell lines of varying degrees of biological aggressiveness. Raman spectra were measured from two well-differentiated, androgen-sensitive cell lines (LNCaP and PCa 2b) and two poorly differentiated, androgen-insensitive cell lines (DU145 and PC 3). Principal component analysis was used to study the molecular differences that exist between cell lines and, in conjunction with linear discriminant analysis, was applied to 200 spectra to construct a diagnostic algorithm capable of differentiating between the different cell lines. The algorithm was able to identify the cell line of each individual cell with an overall sensitivity of 98% and a specificity of 99%. The results further demonstrate the ability of RS to differentiate between CaP samples of varying biological aggressiveness. RS shows promise for application in the diagnosis and grading of CaP in clinical practise as well as providing molecular information on CaP samples in a research setting.

Adenocarcinoma↗
PubMed2004

Contemporary update of cancer control after radical prostatectomy in the UK.

Despite a significant increase of the number of radical prostatectomies (RPs) to treat organ-confined prostate cancer, there is very limited documentation of its oncological outcome in the UK. Pathological stage distribution and changes of outcome have not been audited on a consistent basis. We present the results of a multicentre review of postoperative predictive variables and prostatic-specific antigen (PSA) recurrence after RP for clinically organ-confined disease. In all, 854 patient's notes were audited for staging parameters and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment as well as patients with incomplete data and follow-up were excluded. Median follow-up was 52 months for the remaining 705 patients. The median PSA was 10 ng ml(-1). A large migration towards lower PSA and stage was seen. This translated into improved PSA survival rates. Overall Kaplan-Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probability for PSA ranges <4, 4.1-10, 10.1-20 and >20 ng ml(-1) was 0.82, 0.73, 0.59 and 0.20, respectively (log rank, P<0.0001). PSA recurrence-free survival probabilities for pathological Gleason grade 2-4, 5 and 6, 7 and 8-10 at 5 years were 0.84, 0.66, 0.55 and 0.21, respectively (log rank, P<0.0001). Similarly, 5-year PSA recurrence-free survival probabilities for pathological stages T2a, T2b, T3a, T3b and T4 were 0.82, 0.78, 0.48, 0.23 and 0.12, respectively (log rank, P=0.0012). Oncological outcome after RP has improved over time in the UK. PSA recurrence-free survival estimates are less optimistic compared to quoted survival figures in the literature. Survival figures based on pathological stage and Gleason grade may serve to counsel patients postoperatively and to stratify patients better for adjuvant treatment.

Humans↗
PubMed2004

Case selection for radical prostatectomy in the UK.

INTRODUCTION: Radical prostatectomy is an increasingly popular treatment option for clinically localised prostate cancer, yet PSA outcome figures are rare in the UK. This makes it difficult to establish appropriate criteria for case selection. We conducted an audit of PSA recurrence of 5 large centres in the south of England and investigated the use of pre-operative PSA to improve case selection and outcome. METHOD: 854 patients notes were audited for pre-operative staging parameters and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment as well as patients with incomplete data and follow-up were excluded. RESULT: Median follow-up was 52 months for the remaining 663 patients. Median PSA was 10 ng/ml. A large improvement of PSA recurrence free survival rates was observed from 1988 to 1998 as a result of change in case selection and stage migration. Overall Kaplan-Meier PSA recurrence free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. Five-year PSA recurrence free survival probability for PSA ranges <4 ng/ml, 4.1-10 ng/ml, 10.1-20 ng/ml and >20 ng/ml was 0.82, 0.73, 0.59 and 0.20, respectively (Wilcoxon, p < 0.0001). A simulation of biochemical recurrence free survival for patient cohorts with stepwise reduced inclusion PSAs suggests an improved outcome for patients with a pre-operative inclusion PSA of <12 ng/ml. Further reduction of the inclusion PSA does not improve outcome. CONCLUSION: Intermediate PSA recurrence free survival has improved over time in England. PSA recurrence free survival estimates are less optimistic compared to frequently quoted American figures. A reduced pre-operative PSA cut-off for case selection may be used to improve outcome.

Adenocarcinoma↗
PubMed2004

Current trends in the management of radical retropubic prostatectomy: is short-stay RRP feasible in the United Kingdom?

BACKGROUND: Our aim was to review UK practice in the management of radical retropubic prostatectomy and identify opportunities to reduce LOS to American levels. METHODS: A survey was conducted of BAUS members regarding LOS and postoperative management. RESULTS: Out of 551 surveys 126 were returned. Mean LOS in the UK is 5.2 days. Opiate analgesia, PCA and postoperative epidural may delay discharge. Diet and mobilization are commenced at 1.7 and 2.1 days, respectively. CONCLUSION: Care pathways can safely reduce LOS to 2 days. Protocols to reduce LOS in the UK should be assessed and their impact on cost and quality-of-life evaluated.

Health Care Costs↗
PubMed2004

Transient atypical monocytosis mimic acute myelomonocytic leukemia in post-chemotherapy patients receiving G-CSF: report of two cases.

Granulocyte colony-stimulating factor (G-CSF) is now widely used in patients with malignant disorders receiving intensive chemotherapy to increase leukocyte count and to upregulate phagocyte function during neutropenia. Monocytosis associated with G-CSF has been reported in anecdotal literature. We report two cases of pseudoleukemia secondary to G-CSF administration. Both patients initially presented with myelodysplastic syndrome with chromosome 7 abnormalities that evolved into acute myeloid leukemia. Case one had deletion 7q while case two initially had monosomy 7 and subsequently developed a balanced translocation between the short (p) arm of chromosome 1 and long (q) arm of chromosome 15. Following the induction chemotherapy and G-CSF administration, both of these patients developed pseudoleukemia. Patient 1 had white blood cell (WBC) count of 26 x 10(9)/l with 72% monocytes, while patient two had WBC of 14.1 x 10(9)/l with 30% monocytes. In both patients the monocytosis resolved after the discontinuation of G-CSF therapy. In summary, patients treated with G-CSF should be followed closely. In those cases with pseudoleukemia discontinuation of the drug with no supplemental chemotherapy is probably enough to control the atypical monocytosis.

Aged↗
PubMed2004

Time trends in case selection, stage and prostate-specific antigen recurrence after radical prostatectomy: a multicentre audit.

OBJECTIVES: To report an audit of preoperative staging variables, case selection, stage migration and prostate-specific antigen (PSA) recurrence at five large centres in the south of England. To establish PSA outcome values after radical prostatectomy for clinically localized prostate cancer in the UK, and enable appropriate patient counselling. PATIENTS AND METHODS: The notes of 854 patients were audited for preoperative staging variables and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment, and with incomplete data and follow-up, were excluded. RESULTS: The median follow-up was 52 months for the remaining 663 patients; the median PSA level was 10 ng/mL. There was a large migration towards lower PSA and stage; this translated into improved PSA survival rates. The overall Kaplan-Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probabilities for PSA levels of < 4, 4.1-10, 10.1-20 and > 20 ng/mL were 0.82, 0.73, 0.59 and 0.20, respectively (Wilcoxon, P < 0.001). The PSA recurrence-free survival probabilities for biopsy Gleason grade 2-4, 5 and 6, 7 and 8-10 at 5 years were 0.70, 0.61, 0.55 and 0.21, respectively (Wilcoxon, P < 0.001). Similarly, the 5-year PSA recurrence-free survival probabilities for clinical stages T1a and 1b, T1c, T2a and T2b were 0.79, 0.62, 0.57 and 0.44, respectively (Wilcoxon, P = 0.0012). CONCLUSION: With better case selection the intermediate oncological outcome has improved over time in the UK. PSA recurrence-free survival estimates are less optimistic than the frequently quoted American values. The present values may be used to help in counselling British patients before radical prostatectomy.

Adenocarcinoma↗
PubMed2004

Do height-related variations in insulin-like growth factors underlie the associations of stature with adult chronic disease?

Tall people, particularly those with long legs, have an increased risk of developing cancer but a reduced risk of cardiovascular disease and type II diabetes. We examined associations of stature and body mass index with IGF-I, IGF-II, and IGF binding protein (IGFBP)-2 and IGFBP-3 in 274 men aged 50-70 yr to investigate whether variations in growth factor levels underlie associations of anthropometry with a number of adult diseases. Height and leg and trunk length were not strongly associated with circulating levels of IGF-I, IGF-II, or IGFBP-3. The molar ratio of IGF-I/IGFBP-3 increased with increases in the leg/trunk length ratio (P = 0.06). IGFBP-2 was positively associated with leg length and inversely associated with trunk length. Mean levels of IGFBP-2 (in nanograms per milliliter) across quartiles of increasing leg length were 504.4 493.6, 528.7, and 578.8 (P(trend) = 0.06), and for trunk length were 615.2, 507.2, 498.6, 488.5 (P(trend) < 0.01), suggesting that variations in IGFBP-2, or a factor influencing its levels in the circulation, may contribute to biological mechanisms underlying height-disease associations. We conclude that whereas growth-influencing exposures during childhood, which may operate through effects on IGF-I levels, have long-term influences on disease risk, they do not necessarily program IGF-I levels throughout life. The associations of anthropometry with IGFBP-2 merit additional investigation.

Aged↗
PubMed2003

Are diet-prostate cancer associations mediated by the IGF axis? A cross-sectional analysis of diet, IGF-I and IGFBP-3 in healthy middle-aged men.

We examined the association of diet with insulin-like growth factors (IGF) in 344 disease-free men. Raised levels of IGF-I and/or its molar ratio with IGFBP-3 were associated with higher intakes of milk, dairy products, calcium, carbohydrate and polyunsaturated fat; lower levels with high vegetable consumption, particularly tomatoes. These patterns support the possibility that IGFs may mediate some diet-cancer associations.

Adult↗
PubMed2002

Use of bacille Calmette-Guérin in superficial bladder cancer.

Intravesical bacille Calmette-Guérin (BCG) has been used by urologists for several years after its first reported use as a cancer therapy in the 1930s. Morales in 1976 described the usage of BCG as a once weekly intravesical instillation for six weeks; this is a treatment regimen that still exists today. Its success as a treatment depends on it being used appropriately. It is employed: (1) to treat carcinoma in situ or occasionally residual papillary tumours; (2) to reduce the number and frequency of recurrent high grade superficial tumours; and (3) to prevent disease progression (although this remains a controversial point, on which there is no consensus view). Unfortunately, the more widespread use of BCG is often limited due its high side effect profile. Present research is directed towards reducing its side effect profile, improving its efficacy, and understanding its exact mechanism of action, which is not fully understood.

BCG Vaccine↗