PubMed Health⌕ Search

Biomedical subjects

Randall B Meacham

Publications and source records attributed to Randall B Meacham.

At least 19 recordsLinked to original sources
PubMed2006

Penile rehabilitation after radical prostatectomy: important therapy or wishful thinking?

On the basis of data accumulated thus far, it is reasonable to discuss the implementation of a "penile rehabilitation" program with patients undergoing radical prostatectomy. Central to discussions of penile rehabilitation after radical prostatectomy is evidence demonstrating significant fibrotic changes in the corpus cavernosum that occur postoperatively. Several studies have been published evaluating the efficacy of various pro-erectogenic agents. The limited data regarding intracavernous injections and vacuum constriction devices suggest that an increased percentage of treated patients experienced a return of natural erections compared with patients who received no treatment. Longer, prospective, randomized, placebo-controlled studies will be needed to confirm the utility of these treatments. Data from contemporary studies evaluating the chronic use of oral phosphodiesterase type 5 inhibitors suggest a beneficial effect on endothelial cell function among men suffering from erectile dysfunction due to a variety of causes. Limited data suggest that this effect might be seen among post-prostatectomy patients, implying a possible role for these agents in enhancing the return of sexual function in such individuals.

Journal Article↗
PubMed2005

Oxalate toxicity in cultured mouse inner medullary collecting duct cells.

PURPOSE: Oxalate, a metabolic end product and a major constituent of the majority of renal stones, has been shown to be toxic to renal epithelial cells of cortical origin. However, to our knowledge it is unknown whether inner medullary collecting duct (IMCD) cells, which are physiologically exposed to higher concentrations of oxalate, also behave in a similar manner. MATERIALS AND METHODS: A line of IMCD cells was exposed to oxalate (0.2 to 10 mM) for various time points. Trypan blue, and hematoxylin and eosin stains were used to assess cell morphology and membrane integrity. The production of reactive oxidative species was determined using the nitro blue tetrazolium reaction and crystal violet staining was used to measure cell density. RESULTS: Exposure of IMCD cells to oxalate produced time and concentration dependent changes in the light microscopic appearance of the cells. Long-term exposure to oxalate resulted in alterations in cell viability with net cell loss following exposure to concentrations of 2 mM and greater. Free radical production was time and concentration dependent. Crystal formation occurred in less than 1 hour and cells in proximity to crystals lost membrane integrity. Compared to IMCD cells LLC-PK1 and HK2 cells showed significant toxicity starting at lower oxalate concentrations (0.4 mM and above). CONCLUSIONS: To our knowledge the results provide the first direct demonstration of toxic effects of oxalate in IMCD cells, a line of renal epithelial cells of the inner medullary collecting duct, and suggest that cells lining the collecting duct are relatively resistant to oxalate toxicity.

Animals↗
PubMed2005

The molecular basis of erectile dysfunction: from bench to bedside.

Erectile dysfunction is a common problem affecting many men across all age groups. Its etiology is multifactorial. Hormonal, vascular, neurogenic, lifestyle, and psychological entities have all been implicated as causative agents. The molecular basis underlying its etiology and progression is complex and still challenges researchers in the field. Nonetheless, newly discovered common pathways and targets of its pathogenesis have opened a new era for both prevention and active treatment of the disease. This review describes some of the known molecular mechanisms contributing to erectile dysfunction and discusses the future of gene therapy for the disease.

Journal Article↗
PubMed2004

Mitogen Activated Protein kinase signal transduction pathways in the prostate.

The biochemistry of the mitogen activated protein kinases ERK, JNK, and p38 have been studied in prostate physiology in an attempt to elucidate novel mechanisms and pathways for the treatment of prostatic disease. We reviewed articles examining mitogen-activated protein kinases using prostate tissue or cell lines. As with other tissue types, these signaling modules are links/transmitters for important pathways in prostate cells that can result in cellular survival or apoptosis. While the activation of the ERK pathway appears to primarily result in survival, the roles of JNK and p38 are less clear. Manipulation of these pathways could have important implications for the treatment of prostate cancer and benign prostatic hypertrophy.

Journal Article↗
PubMed2004

Laparoscopic varicocele ligation: are there advantages compared with the microscopic subinguinal approach?

OBJECTIVES: To compare the operative time, outcome, complications, and patient costs between laparoscopic varicocele ligation (LVL) and subinguinal microscopic varicocelectomy (SMV) in two patient cohorts. Varicocele therapy is a controversial issue, with no single approach adopted as the best therapeutic option. LVL has been considered more expensive and of no proven benefit compared with SMV. METHODS: We compared two groups of patients who underwent surgical correction of varicocele at our institutions during a 6-year period. Group 1 included postpubertal adolescents who underwent LVL and group 2 included adults seen at an infertility practice who underwent SMV. The outcome measures selected included operative time, direct hospital costs to the patient, and negative outcomes. RESULTS: We identified a total of 72 patients, 36 (mean age 13.8 years) in group 1 and 36 (mean age 34.1 years) in group 2. Group 1 had no persistent or recurrent varicoceles compared with 4 patients in group 2. Three men in group 2 required emergency room evaluation and no patient did so in group 1. No hydroceles developed in group 2, but three developed in group 1. CONCLUSIONS: LVL resulted in shorter operative times and fewer negative outcomes compared with SMV. This translated into lower direct patient costs for LVL. For those who have mastered laparoscopic techniques, LVL should be considered a safe, cost-effective option in the correction of varicoceles.

Adolescent↗
PubMed2004

Experimental varicocele induces testicular germ cell apoptosis in the rat.

PURPOSE: We evaluated the impact of experimentally created varicocele on ipsilateral and contralateral testicular germ cells in the rat. MATERIALS AND METHODS: Experimental left varicocele was created by partial ligation of the left renal vein in 17 adult male Sprague-Dawley rats. An additional 5 rats that underwent laparotomy and renal vein handling without ligation served as sham surgical controls. Five rats that underwent no surgical or other intervention served as a control group. Rats were sacrificed 7 (5), 14 (5) or 28 (7) days following varicocele creation. Germ cell apoptosis was quantified using a TUNEL assay. The results of this assay are expressed as the number of apoptotic germ cell nuclei per seminiferous tubular cross section. The presence of apoptosis was confirmed by cellular ultrastucture evaluation using transmission electron microscopy. RESULTS: Control and sham animals were found to have a mean of 0.05 and 0.15 apoptotic germ cells per seminiferous tubular cross section, respectively. Rats sacrificed 7, 14 and 28 days after varicocele creation were found to have 0.15, 0.23 and 0.27 apoptotic germ cells per tubule in the ipsilateral testis, and 0.14, 0.16 and 0.17 apoptotic germ cells per tubule in the contralateral testis, respectively. Compared with control animals a statistically significant increase in the number of apoptotic germ cells per tubular cross section was noted 14 days following varicocele creation in the ipsilateral testis (p <0.05). CONCLUSIONS: The creation of experimental varicocele generated an increase in germ cell apoptosis in the ipsilateral testis at 14 days compared with control animals.

Animals↗
PubMed2004

Effects of oxalate on IMCD cells: a line of mouse inner medullary collecting duct cells.

Oxalate, a metabolic end product and a major constituent of the majority of renal stones, has been shown to be toxic to renal epithelial cells of cortical origin. However, it is unknown whether inner medullary collecting duct (IMCD) cells that are physiologically exposed to higher concentrations of oxalate also behave in a similar manner. In the present study, we examined the effects of oxalate on IMCD cells. IMCD cells from the mouse were maintained in DMEM/F12 media supplemented with fetal bovine serum and antibiotics. Exposure of IMCD cells to oxalate produced time- and concentration-dependent changes in the light microscopic appearance of the cells. Long-term exposure to oxalate resulted in alterations in cell viability, with net cell loss after exposure to concentrations of 2 mM or greater. The production of free radicals was directly related to the exposure time and the concentration of oxalate. Crystal formation occurred in less than 1 h and cells in proximity to crystals would lose membrane integrity. Compared with IMCD cells, LLC-PK1 cells as well as HK-2 cells showed significant toxicity starting at lower oxalate concentrations (0.4 mM or greater). These results provide the first direct demonstration of toxic effects of oxalate in IMCD cells, a line of renal epithelial cells of the inner medullary collecting duct, and suggest that the cells lining the collecting duct are relatively resistant to oxalate toxicity.

Animals↗
PubMed2004

p42/p44 Mitogen-activated protein kinase signal transduction pathway: a novel target for the treatment of hormone-resistant prostate cancer?

Prostate cancer is the second leading cause of cancer deaths in men. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is no cure once the disease has spread beyond the prostate. Androgen withdrawal remains the only treatment for these men with clinically advanced disease; however, most of these men, who initially respond to hormone ablation therapy, fail and the disease progresses. There is at present no effective treatment for hormone-independent prostate cancer. Several lines of evidence suggest a role of p42/p44 mitogen-activated protein kinase (p42/p44 MAP kinase) signal transduction pathways in prostate cancer. At the molecular level, a variety of genetic alterations lead to an epigenetic mechanism by which a feedback autocrine loop between membrane receptors and associated ligands serves as an essential component of the growth, proliferation, and metastasis of prostate cancer at an advanced and androgen-independent stage. Peptide growth factors are known to exert their effects by a complex array of mechanisms primarily mediated by the p42/p44 MAP kinase signal transduction pathway. Thus, we hypothesized that MAP kinase signal transduction pathways could serve as new and novel targets in prostate cancer therapy. In this article we provide an overview of the role played by MAP kinase signal transduction in the prostate.

Humans↗
PubMed2004

p42/p44 Mitogen-activated protein kinase signal transduction pathway regulates interleukin-6 expression in PC3 cells, a line of hormone-refractory prostate cancer cells.

The mechanisms that regulate prostate cancer growth and proliferation are not fully understood. IL-6, a multifunctional cytokine, has been shown to play an important role in prostate cancer biology. Functional role of MAP-kinase signal transduction pathways in prostate biology has not been evaluated in detail. In the present study we evaluated the effects of modulation of p42/44 MAP kinase signal transduction pathway on IL-6 expression and secretion by PC3 cells, a line of hormone refractory prostate cancer cells. Results presented, herein, demonstrate that modulation of p42/44 MAP kinase activity results in partial inhibition of synthesis and secretion of IL-6. These data suggest that modulation of p42/p44 may result in regulation of other survival pathways as well.

Base Sequence↗
PubMed2003

Male infertility.

Explore the source record for details and available documents.

Case Reports↗
PubMed2003

Androgen replacement therapy in the aging male.

Beginning around age 40 years, men experience a decrease in testosterone level-referred to as "andropause"-and the pathophysiologic changes that accompany this decrease. Androgen replacement therapy, typically used for the treatment of senile hypogonadism, is evolving as a potential treatment of various other conditions related to testosterone loss, such as osteoporosis, sarcopenia, and even psychological symptoms. As with any treatment modality, certain patient factors are more predictive of success with minimal adverse effects, and consideration must be given to concomitant conditions. This article will provide a review of recent studies examining the effects of androgen supplementation and evaluate the purported benefits and potential risks of this therapy. Further research is anticipated to elucidate the most appropriate candidates, as well as other potential indications, for this treatment.

Journal Article↗
PubMed2002

Apoptosis: its importance in spermatogenic dysfunction.

Apoptosis, spontaneous programmed cell death, has recently generated great interest in several areas of investigation, including infertility. Selective sperm cell death also seems to be a component of normal spermatogenesis. A better understanding of this process may lead to the development of new strategies to treat intrinsic testicular failure.

Apoptosis↗