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Biomedical subjects

Franklin C Lowe

Publications and source records attributed to Franklin C Lowe.

At least 19 recordsLinked to original sources

The management of chronic prostatitis in men with HIV.

Prostatitis is a common urologic diagnosis. Although treatment algorithms are available for this poorly understood entity, several adaptations must be made in order to accommodate the therapeutic needs of HIV-positive patients. The most important consideration when treating HIV-infected patients for prostatitis is their current immune status, whether they are immunocompromised or not (non-progressive disease or reconstituted with highly active antiretroviral therapy). A treatment algorithm for those with chronic bacterial prostatitis (Category II), chronic nonbacterial prostatitis (Category IIIA), and prostatodynia (Category IIIB) is presented in this article. In the HIV-positive patient population, there is a greater likelihood for atypical pathogens including fungi, tuberculosis, anaerobes, and viruses. Because the HIV-infected patient is at increased risk for the development of prostatic abscess and urosepsis than the general population, increased monitoring and evaluation and longer-term appropriately directed antimicrobial therapy are required.

Adrenergic alpha-Antagonists↗

Treatment of benign prostatic hyperplasia in patients with cardiovascular disease.

Pharmacological management is the most common therapeutic approach for patients with benign prostatic hyperplasia and alpha-adrenoceptor antagonists are the most commonly prescribed initial treatment. Although all of the alpha-adrenoceptor antagonists produce similar improvements in symptom scores and urinary flow rates, they have different adverse effect profiles, especially with respect to the cardiovascular system. The older alpha-adrenoceptor antagonists, terazosin and doxazosin, were initially approved for the treatment of hypertension and are associated with higher rates of dizziness, syncope and hypotension than the newer agents, tamsulosin and alfuzosin. The older alpha-adrenoceptor antagonists are also involved in more interactions and have a greater number of precautions concerning their usage with other cardiovascular medications. Of the newer alpha-adrenoceptor antagonists, tamsulosin has a lower rate of dizziness than alfuzosin. However, both of these agents are superior to doxazosin and terazosin in that no dose escalation or titration is needed for them.

3',5'-Cyclic-GMP Phosphodiesterases↗

Approach to management of clinically localized prostate cancer in patients with human immunodeficiency virus.

OBJECTIVES: To evaluate the approach to management of localized prostate cancer (PCa) in patients with human immunodeficiency virus (HIV) in the highly active antiretroviral therapy era. METHODS: A retrospective analysis was performed on 10 HIV-positive patients who recently presented with elevated prostate-specific antigen levels and clinically localized PCa. RESULTS: At the diagnosis of PCa, the average patient was 54.0 years old, had been HIV positive for 8.75 years, had a CD4 count of 417, a prostate-specific antigen level of 9.2 ng/mL, and a Gleason score of 6. Eight of the patients had risk factors for PCa--either African-American descent (n = 6) or a positive family history (n = 2). The treatment was laparoscopic radical prostatectomy in 1, potency-preserving androgen deprivation in 1, cryosurgery in 1, brachytherapy in 2, observation in 2, and external beam radiotherapy in 3. CONCLUSIONS: Screening of all HIV-positive men should be initiated at age 40 if they have either a positive family history of prostate cancer or are of African-American descent. Asymptomatic HIV-positive patients should be offered all therapeutic PCa treatment options.

Adenocarcinoma↗

Evidence suggesting PSA cutpoint of 2.5 ng/mL for prompting prostate biopsy: review of 36,316 biopsies.

OBJECTIVES: To determine whether a prostate-specific antigen (PSA) level of 2.0, 2.5, or 4.0 ng/mL is the most appropriate cutpoint for determining the need for prostate biopsy. It has been suggested that the PSA cutpoint of 4.0 ng/mL is inappropriate because the rate of prostate cancer detection is similar in patients with lower PSA values. Some investigators have recommended a 2.6-ng/mL cutpoint. Others have recommended a cutpoint of 2.0 ng/mL. METHODS: A total of 36,316 prostate biopsies submitted to DIANON Systems from January 1, 1997 through December 31, 2001 were reviewed. These biopsy specimens also had DIANON PSA test results available that had been performed within 6 months of the biopsy date. These biopsies were stratified according to the PSA level within the 6 months before the time of biopsy, and the prostate cancer detection rate was determined for the stratified PSA levels. RESULTS: The detection rate of prostate cancer varied according to the PSA level. The incidence of prostate cancer was similar for the groups with less than 2.0 ng/mL and 2.0 to 2.5 ng/mL (18.67% and 21.89%, respectively). Also, the groups with 2.5 to 4.0 ng/mL and 4.0 to 10.0 ng/mL had similar cancer detection rates (27.48% and 30.08%, respectively). CONCLUSIONS: The prostate cancer detection rate for a PSA level between 2.5 and 4.0 ng/mL was similar (27.48%) to that for the PSA range of 4.0 to 10.0 ng/mL (30.08%). The absolute cutpoint used to determine the need to evaluate a patient for prostate cancer by biopsy is not clear; however, many studies have suggested that 2.5 ng/mL may be a more appropriate cutpoint than 4.0 ng/mL.

Biopsy↗

Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: sexual function.

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), and sexual dysfunction, are common, highly bothersome conditions in older men, and the prevalence of both disorders increases with age. Sexual dysfunction manifests mainly as erectile dysfunction (ED), ejaculatory disorders, or decreased libido/hypoactive sexual desire (HSD). Whereas both reduced rigidity and reduced ejaculate volume are highly prevalent in ageing men, reduced rigidity and pain on ejaculation are considered to be most bothersome. Sexual dysfunction is much more prevalent in patients with LUTS/BPH than in men with no LUTS/BPH, even after controlling for confounding variables such as age or comorbidities. Hence LUTS/BPH is considered an independent risk factor for sexual dysfunction. Whether this is because of a common underlying pathology, or whether the considerable bother associated with LUTS/BPH leads to reduced sexual functioning, remains to be elucidated. Despite a decline in the frequency of sexual intercourse, as well as in overall sexual functioning, most ageing men report regular sexual activity and consider their sex life as an important dimension of their quality of life (QoL). However, most patients with LUTS/BPH experience a negative effect of their LUTS on their sex life. Hence, treatment of LUTS/BPH should aim to at least maintain or, if possible, improve sexual function. Current medical treatment of LUTS/BPH consists of monotherapy with alpha1-adrenoceptor (AR) antagonists, 5alpha-reductase inhibitors (RIs) or a combination of these. Whereas 5alpha-RIs increase the risk of ED, ejaculatory disorders and HSD, alpha1-AR antagonists can induce ejaculatory disorders, but do not provoke HSD or ED. Combined therapy carries the cumulative risk for sexual dysfunction associated with either type of drug. As already indicated, ED is generally perceived as more bothersome than ejaculatory disorders. In addition, alpha1-AR antagonists slightly improve overall sexual function, possibly by increasing blood flow in the penis through alpha1-AR blockade and/or to an increased overall QoL from the relief of LUTS. It can be concluded that alpha1-AR antagonists constitute a first-line therapy for LUTS/BPH because they combine good treatment efficacy with very few adverse effects on sexual function.

5-alpha Reductase Inhibitors↗

Prostate biopsy in the diagnosis of prostate cancer: current trends and techniques.

The advent of prostate specific antigen (PSA) screening and transrectal ultrasonography (TRUS) has had a significant impact on the detection of prostate cancer over the last 15 years. The mean age at diagnosis has decreased and the most common stage at diagnosis is now localized disease. TRUS guidance, spring-loaded biopsy needles, utilization of oral antibiotic prophylaxis, developments in local anesthesia, increases in the number of cores sampled and the use of site-specific containers have all made the prostate biopsy easier to perform and more accurate. The indications for an initial prostate biopsy have been strongly influenced by digital rectal examinations (DREs), PSA levels and the PSA-related parameters of velocity, density, and percent free. These parameters, along with abnormal histology, also dictate the need for a repeat biopsy. With the better, earlier, and more patient-friendly usage of the prostate biopsy, there has been a decrease in the mortality rate of prostate cancer.

Biopsy↗

Summary of clinical experiences with tamsulosin for the treatment of benign prostatic hyperplasia.

Tamsulosin, a uroselective alpha(1A)-adrenergic-receptor antagonist, has been shown to improve lower urinary tract symptoms associated with benign prostatic hyperplasia. It has a better side effect profile than earlier alpha-adrenergic-receptor antagonists, which were initially developed as antihypertensive agents. Clinical trials of 1 year or longer with tamsulosin show high tolerability for the 0.4 mg dose and no significant interaction with other antihypertensive medications.

Journal Article↗

Role of the newer alpha, -adrenergic-receptor antagonists in the treatment of benign prostatic hyperplasia-related lower urinary tract symptoms.

BACKGROUND: Although initially introduced for the management of hypertension, alpha(1)-adrenergic-receptor antagonists (alpha1-blockers) have become the standard of care for the medical management of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS). However, these agents have the potential to produce orthostatic hypotension and other blood pressure-related adverse effects in normotensive patients and in those receiving concurrent treatment with other antihypertensive agents. As a result, more "uroselective," less vasoactive alpha(1)-blockers have been developed. OBJECTIVE: This article reviews current information on the role of alpha(1)-blockers in the treatment of BPH-related LUTS. The focus is on tamsulosin and alfuzosin, newer "uroselective" agents in this class that have a decreased potential for cardiovascular adverse effects. METHODS: Relevant articles were identified through a search of the English-language literature indexed on MEDLINE and the proceedings of scientific meetings from 1976 to 2003. The search terms were benign prostatic hyperplasia treatment, alpha(1)-adrenergic-receptor blocker, uroselectivity, lower urinary tract symptoms, complications, and cardiovascular. RESULTS: Tamsulosin has selectivity for the a alpha(1) and alpha(1d) receptor subtypes. Alfuzosin, although not receptor subtype selective, is clinically "uroselective" and does not significantly affect vascular alpha-adrenergic receptors. Both agents are efficacious in relieving LUTS and have a decreased potential for such cardiovascular adverse effects as postural hypotension. Common adverse events with these agents include dizziness and asthenia. CONCLUSION: Based on the available data, "uroselective" alpha(1)-blockers should be considered over older, more vasoactive agents for the medical management of LUTS, particularly in patients with BPH and hypertension.

Adrenergic alpha-1 Receptor Antagonists↗

Long-term treatment with finasteride in men with symptomatic benign prostatic hyperplasia: 10-year follow-up.

OBJECTIVES: To evaluate the safety and efficacy of finasteride 5 mg during a 10-year period in men with enlarged prostates from a single center who participated in the double-blind and extension phases of the multicenter, Phase III, North American benign prostatic hyperplasia (BPH) trial. It is important that the long-term safety and efficacy of drugs intended for chronic administration in men with BPH be well understood. METHODS: The Phase III North American BPH trial involved a 1-year, placebo-controlled, double-blind study, followed by a 5-year open extension with finasteride 5 mg/day. The trial enrolled men with symptomatic BPH, an enlarged prostate on digital rectal examination, and no evidence of prostate cancer. Of the 46 patients originally enrolled from our institution, 43 were randomized to receive finasteride or placebo, of whom 41 (95%) completed the double-blind study and entered the 5-year extension. Thirty (73%) of these 41 patients completed the 5-year extension. Patients continued to be followed up by their physicians for an additional 5 years, for a total follow-up of at least 10 years. RESULTS: Twenty-four (56%) of the original 43 patients randomized to finasteride or placebo were judged as successfully treated during the 10-year finasteride follow-up (17 patients taking finasteride alone at 10 years and 7 patients who were taking finasteride alone when they discontinued during the 10-year follow-up for reasons not related to finasteride treatment). Altogether, 22 (51%) of the original 43 randomized patients continued finasteride treatment at 10 years (17 taking finasteride alone, 4 taking finasteride plus an alpha-blocker, and 1 taking finasteride for treatment of hematuria). Finasteride was well tolerated, with no new adverse experiences occurring with increasing duration of exposure to the drug. CONCLUSIONS: This long-term follow-up study has demonstrated that appropriately selected patients with symptomatic BPH and enlarged prostates are likely to have a long-term response to taking finasteride 5 mg daily.

5-alpha Reductase Inhibitors↗

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.

OBJECTIVES: To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important. METHODS: The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension. In total, 6-year finasteride data were available in 487 patients originally randomized to finasteride, and 5-year data were available on 238 patients originally randomized to placebo. RESULTS: After 6 years of treatment with finasteride 5 mg, the mean quasi-American Urological Association Symptom Score improved by 4.0 points, the median prostate volume decreased by 24%, and the mean maximal urinary flow rate increased by 2.9 mL/s (P <0.001 for all parameters). Long-term finasteride treatment was well tolerated, with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension. CONCLUSIONS: Treatment with finasteride leads to durable improvement in urinary tract symptoms, flow rate, and prostate volume, with no increase in the prevalence of drug-related adverse events over time.

5-alpha Reductase Inhibitors↗

Evidence of increased prostate cancer detection in men aged 50 to 59: a review of 324,684 biopsies performed between 1995 and 2002.

OBJECTIVES: To analyze the age-specific detection rate of prostate cancer diagnosed from 324,684 biopsies submitted to a single laboratory and to assess the degree of prostate cancer in younger men. The advent of prostate-specific antigen (PSA) testing and increased prostate cancer screening has led to increased evaluations for prostate cancer. The initial stage and age at presentation in prostate cancer has shifted. METHODS: From 1995 through 2001, all prostate biopsies submitted to the laboratory were reviewed and analyzed for the diagnosis of prostate cancer, cancer detection rate, and age at diagnosis. RESULTS: The overall detection rate of prostate cancer increased by 15% from 29% to 34% for all biopsies submitted during the study period. For the age group 50 to 59 years, a 45% increase occurred in the detection of prostate cancer from a baseline of approximately 11% in 1995 to greater than 16% in 2001. For the age group 70 to 79 years, the detection of prostate cancer decreased from a baseline of 41% in 1995 to 36% in 2001. CONCLUSIONS: The increase in prostate cancer diagnosis among younger men in the United States has been significant. The increase is likely multifactorial and may be attributable to the impact of PSA and prostate cancer screening efforts. This has led to a greater number of younger men undergoing evaluation for prostate cancer. Thus, a heightened awareness regarding the diagnosis of prostate cancer among younger men is needed.

Adenocarcinoma↗

AIDS and the urologist.

The management of HIV infection has dramatically altered the natural history of the disease. Prevention of opportunistic infections and the development of HAART regimens altered the manifestations and conditions that urologists are being asked to evaluate and manage in this patient population.

Acquired Immunodeficiency Syndrome↗

Alfuzosin for the management of benign prostate hyperplasia.

Alfuzosin (UroXatral, Sanofi-Synthelabo) a quinazoline derivative, has well-documented alpha(1)-adrenoreceptor antagonist activity. These receptors are present in the smooth muscle located at the bladder base, proximal urethra, prostate and prostatic capsule as well as in vascular and nervous systems. Consequently, alfuzosin has the ability to reduce the tone of these areas, effectively decreasing bladder outlet resistance. A sustained-release formulation of alfuzosin is currently available in Europe and is FDA-approved in the US. The confirmed efficacy, proven bioavailability and good cardiovascular safety profile support the use of this drug for the management of lower urinary tract symptoms secondary to benign prostate hyperplasia (BPH). These findings have been confirmed in a large cohort of patients treated in general practice. Additionally, treatment with alfuzosin has demonstrated a favourable impact on quality of life of patients with BPH.

Adrenergic alpha-Antagonists↗

PC-SPES: herbal formulation for prostate cancer.

PC-SPES is a potent eight-herb formulation sold directly to consumers; it has promising efficacy in the treatment of prostate cancer (CaP). The product induces a castrate status in most, if not all, men, resulting in a 50% or greater prostate-specific antigen reduction in the great majority of men with androgen-dependent CaP and in more than one half of the men with androgen-independent CaP. The duration of response is not yet clear. The efficacy of PC-SPES appears to exceed that of androgen ablation alone, but is not necessarily separate from an estrogenic effect. Common side effects include gynecomastia, nipple tenderness, loss of libido, and impotency; uncommon side effects include a 4% incidence of thromboembolic phenomena, but also two reports of bleeding diatheses. The mechanisms of action may involve downregulation of the androgen receptor, induction of apoptosis by way of inhibition of the bcl-2 gene, and increased expression of p53. Two marker compounds in PC-SPES are baicalin and oridonin, both of which exhibit antiproliferative effects in CaP cell lines. Thousands of men are currently obtaining this nonprescription medicine, and physicians should ask patients specifically about its use. PC-SPES is of great interest in men with androgen-independent CaP, an area in which future research should be primarily directed.

Antineoplastic Agents, Phytogenic↗

Phytotherapy in the treatment of benign prostatic hyperplasia.

There are numerous plant extracts that have been used for the treatment of benign prostatic hyperplasia and lower urinary tract symptoms. While some extracts show promise, their efficacy has not been adequately proven in long-term, double-blind placebo-controlled trials monitored by an outside agency.

Drug Therapy, Combination↗