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W Rayford

Publications and source records attributed to W Rayford.

At least 19 recordsLinked to original sources
PubMed2006

Prostate specific antigen isoforms and human glandular kallikrein 2--which offers the best screening performance in a predominantly black population?

PURPOSE: Free prostate specific antigen, complexed PSA and human glandular kallikrein 2 have independently been tested against the gold standard of total PSA for prostate cancer screening in largely white populations. With the incidence of prostate cancer much higher in black men, we sought to evaluate these markers simultaneously in a predominantly black population. MATERIALS AND METHODS: A total of 138 men, of whom 108 were black, underwent ultrasound guided biopsy of the prostate for tPSA levels greater than 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn before biopsy and analyzed for tPSA, fPSA, cPSA and hK2 concentrations using standard methods (hK2 assay is for research use only, not for use in diagnostic procedures). The areas under the receiver operator characteristic curves were determined for each marker as well as biomarker combinations. Additionally, each parameter's specificity, positive and negative predictive values, and theoretical screening efficiency were assessed at or above the 95% sensitivity level. RESULTS: A total of 43 (31.1%) men had prostate cancer by biopsy. While the AUC for %fPSA was statistically the highest (0.822, p <0.001), cPSA offered the highest specificity (31.6%) and positive predictive power (31.7%) of any of the tested biomarkers at comparable sensitivity (greater than 95%). The calculated efficiency of cPSA (51.4%) was also higher than the other markers. Nearly 20% of biopsies would be avoided using cPSA vs standard tPSA screening methods. CONCLUSIONS: Comparing the major PSA isoforms and hK2, cPSA alone appears to offer superior diagnostic discrimination for cancer detection in a predominantly black population.

Black or African American↗
PubMed2004

Early detection of prostate cancer in African-American men through use of multiple biomarkers: human kallikrein 2 (hK2), prostate-specific antigen (PSA), and free PSA (fPSA).

Recent studies have reported enhanced prostate cancer detection in Caucasians with serum human glandular kallikrein 2 (hK2) in combination with total- (tPSA) and free-prostate-specific antigen (fPSA). The purpose of this study is to validate these findings in an African-American patient cohort. A total of 137 African-American men were found by routine screening to have tPSA levels above 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn prior to biopsy of the prostate and Hybritech PSA, FPSA and hK2 (for research use only, not for use in diagnostic procedures) concentrations were determined on Beckman Coulter's Access immunoanalyzer. These independent variables and the ratios of percent fPSA (%fPSA), hK2/tPSA, hK2/fPSA, and hK2*tPSA/fPSA were compared between cancer and non-cancer groups. In all, 49 of 137 men had prostate cancer. hK2 and its calculated ratios outperformed tPSA on receiver operator characteristic (ROC) analysis, but %fPSA had statistically the highest area under the curve (AUC) at 0.801. When restricting the analysis to only the tPSA range of 4.0-10 ng/ml, hK2/fPSA yielded the highest AUC (0.721). The ratio of hK2/fPSA was also found to increase the positive predictive value (PPV) of the %fPSA ranges less than 10 and 10-25%. %fPSA offered the best performance and highest specificity in prostate cancer detection in African-American males over the entire range of tPSA. hK2/fPSA may offer modest improvement in the tPSA range of 4.0-10 ng/ml. Furthermore, hK2/fPSA can enhance the PPV of low %fPSA values. Therefore, the use of multiple biomarkers may ultimately increase the specificity of prostate cancer screening in African-American men.

Black or African American↗
PubMed2003

Complexed PSA performance for prostate cancer detection in an African-American population.

OBJECTIVES: Complexed prostate-specific antigen (cPSA) has been shown to improve the differentiation of benign and malignant disease compared with total PSA (tPSA) in studies evaluating predominantly white populations of men. We sought to evaluate the diagnostic performance of cPSA relative to tPSA in a population of African-American men. METHODS: Consecutive African-American men scheduled for prostate biopsy were enrolled prospectively at the Louisiana State University Medical Center, New Orleans. Serum was collected before the biopsy procedure and tested with the Immuno 1 tPSA and cPSA methods. Receiver operating characteristic curve analysis was performed and the area under the curve was calculated for tPSA and cPSA. RESULTS: A total of 156 patients were evaluated, 51 (32.7%) of whom were diagnosed with prostate cancer. The median PSA value for men with prostate cancer was 4.96 ng/mL and for those with benign disease was 3.93 ng/mL. The receiver operating characteristic analysis indicated that the area under the curve for cPSA (0.679) was statistically greater than that achieved for tPSA (0.642, P = 0.004). Using cutoff values for cPSA of 2.3 ng/mL and for tPSA of 2.85 ng/mL provided a specificity of 31.4% and 26.7%, respectively, at a sensitivity for prostate cancer detection of 95%. This was not statistically significant (P = 0.18). CONCLUSIONS: cPSA offers modest improvement in prostate cancer detection compared with tPSA in African-American men, but not at the clinically relevant 95% sensitivity level. Additional work is needed to improve prostate cancer detection in this high-risk cohort of patients.

Adenocarcinoma↗
PubMed2003

cPSA and fPSA elimination in African-American men.

In all, 22 African-American males undergoing radical prostatectomy for prostate adenocarcinoma had serum drawn for tPSA, cPSA, and total protein concentrations prior to, during, and after operation to determine the respective elimination rates. African-American cPSA was found to fit best a simple first-order exponential elimination kinetic, with a half-life of 44.6 h. fPSA followed a two-compartment elimination with an alpha-phase elimination of 0.50 h and a beta-phase half-life of 4.2 h. Our results suggest higher rates of elimination for both cPSA and fPSA in an African-American male population with respect to Caucasians and may account for differences in PSA values between races.

Adenocarcinoma↗
PubMed2001

Calcitonin is a prostate epithelium-derived growth stimulatory peptide.

Locally secreted growth factors and neuropeptides may play an important role in sustaining the growth of hormone-independent prostate cancer. Our previous studies have shown that calcitonin-like immunoreactive peptide (CTI) is secreted by primary prostate cells in culture, and its secretion from malignant prostate cells is significantly higher than benign cells. Exogenously added calcitonin (CT) induces DNA synthesis in serum-starved prostate cancer LNCaP and PC-3M cells. Present studies extended these findings by cloning cDNAs for CT and CT receptor (CT-R) from prostate cancer cells and studying the expression of CT and CT-R mRNA in prostate cancer cell lines and primary prostate tumor specimens. The results have shown that PC-3 cells expressed CT, and not CT-R, mRNA, whereas CT-R, but not CT, mRNA was expressed by LNCaP cells. Conditioned media from PC-3 cells induced DNA synthesis of LNCaP cells, and this mitogenic response was abolished by anti-CT serum. Highly aggressive PC-3M cells co-expressed CT and CT-R mRNAs. CT also induced a twofold increase in DNA synthesis of primary prostate cells and anti-CT serum caused a 56% decline. In-situ hybridization histochemistry of archival prostate specimens has selectively localized CT and CT-R mRNA in basal epithelium of benign and low grade PC specimens, and these mRNAs were not detected in either luminal epithelium or stroma. In contrast, CT and CT-R mRNA were detected throughout the luminal epithelium of moderate and high-grade PC specimens. Most epithelial cells of low and moderately differentiated tumors expressed either CT or CT-R mRNA, suggesting that CT may serve as a paracrine factor. In contrast, CT and CT-R mRNAs were co-expressed by most tumor cells in advanced PC specimens. The cells expressing CT-R mRNA in primary tumors also co-expressed PCNA. These results, when combined with mitogenic actions of CT on primary prostate cells as well as PC cell lines, strongly support the role for CT in sustaining the growth of cancer cells.

Calcitonin↗
PubMed2001

Practice patterns in the diagnosis and treatment of erectile dysfunction among family practice physicians.

OBJECTIVES: To examine the philosophies and practices of the family practitioner (FP) regarding the diagnosis and treatment of erectile dysfunction (ED). METHODS: A prospective study by questionnaire of a group of FPs was performed. The Spearman correlation coefficient and proportional odds regression analysis were used to measure the relationship between the continuous variable and ordinal-scale variables. The Goodman-Kruskal gamma test was used to measure the strength of the association between the ordinal-scale variables. RESULTS: Eighty-five FPs completed the questionnaire. All respondents had at least occasional discussions with their patients about ED. History taking, physical examination, and laboratory data were the most common tools used for diagnosis. Eighty-two percent of the FPs reported being either comfortable or somewhat comfortable in making a diagnosis of ED; 93% believed that only selected patients required more extensive diagnostic workups for ED. Sildenafil was the most commonly used agent. All physicians referred patients with ED to urologists at least occasionally. Most referred only after unsuccessful trials with sildenafil. The relationship between the degree of managed care penetration and the percentage of patients with ED referred for evaluation to a urologist was not statistically significant (P = 0.402). The relationship between the number of years in practice and the percentage of patients referred to a urologist for treatment or evaluation was found to be a negative, but statistically significant, relationship (P = 0.003). CONCLUSIONS: FPs are now diagnosing and treating ED on a routine basis. Referrals to urologists are likely to be made when they are no longer comfortable treating the problem.

Adult↗
PubMed2000

Predictive value of preoperative tests in discriminating bilateral adrenal hyperplasia from an aldosterone-producing adrenal adenoma.

In primary hyperaldosteronism, discriminating bilateral adrenal hyperplasia (BAH) from an aldosterone-producing adenoma (APA) is important because adrenalectomy, which is usually curative in APA, is seldom effective in BAH. We analyzed the results from our most recent 7-yr series to evaluate the predictive value of preoperative noninvasive tests compared with adrenal vein sampling (AVS). Forty-eight patients with hypertensive hyperaldosteronism underwent bedside testing, computed tomography (CT) imaging, and AVS. Those in whom the results of AVS indicated APA underwent adrenalectomy. Twelve (30%) and 14 (34%) of 41 patients with APA had paradoxical falls with ambulation in plasma aldosterone concentration (PAC) and 18-hydroxycorticosterone (18-OH-B), respectively. Twenty-nine (70%) and 26 (65%) APA patients had a rise in PAC and 18-OH-B, respectively, as did all 8 BAH patients. Significant identifiers of BAH were supine PAC values less than 15 ng/dL (P: = 0.04), an increase greater than 60% (P: = 0.02) in PAC with ambulation, and supine 18-OH-B values less than 60 ng/dL (P: = 0.04). CT imaging alone was not predictive for BAH or APA. In our population, patients with a positive bedside test result (e.g. a fall in PAC and/or 18-OH-B) and a unilateral adrenal nodule on CT (10 of 41 patients) could have proceeded directly to adrenalectomy for APA. However, a positive bedside test result with a negative CT or a negative bedside test result regardless of CT findings required AVS to confirm the diagnosis and site of disease.

Adenoma↗
PubMed1999

Renal cancer in families with hereditary renal cancer: prospective analysis of a tumor size threshold for renal parenchymal sparing surgery.

PURPOSE: Patients with hereditary forms of renal cancer are at risk for new tumors and metastases. Renal parenchymal sparing surgery has been performed to preserve renal function and quality of life, and prevent metastases. We evaluated a 3 cm. threshold for performing renal parenchymal sparing surgery in patients with von Hippel-Lindau disease and hereditary papillary renal cancer. MATERIALS AND METHODS: Patients with von Hippel-Lindau disease or hereditary papillary renal cancer and renal cancer were identified by screening affected kindred and by kindred history. Patients with small tumors were followed with serial imaging studies until the largest renal tumor was 3 cm., when renal parenchymal sparing surgery was performed. Renal tumors greater than 3 cm. were resected without delay. Parenchymal sparing techniques were used when possible in each group. RESULTS: The 3 cm. surgical threshold was evaluated in 52 patients with von Hippel-Lindau disease (group 1) at a median followup of 60 months (range 6 to 205). None of these patients had metastatic disease and none has required renal transplantation or dialysis. In 44 patients with von Hippel-Lindau disease (group 2) renal tumors larger than 3 cm. developed. Median followup from the initial radiological diagnosis of renal cancer in this group was 66.5 months (range 0 to 321). Patients in group 1 underwent parenchymal sparing surgery instead of nephrectomy more frequently than those in group 2 (46 of 48 operations or 96% versus 45 of 72 or 63%, Fisher's exact test p <0.0001). In contrast to patients in group 1, metastatic renal cancer developed in 11 of the 44 in group 2 (25%) (Fisher's exact test p <0.0001). A total of 23 patients with hereditary papillary renal cancer were also identified. Median followup in these cases was 44 months (range 0 to 237). Ten patients had tumors less than 3 cm. No patient with tumors less than 3 cm. and 2 of the 13 (15%) with larger tumors had metastases. CONCLUSIONS: Using a 3 cm. renal tumor diameter as an indication for renal surgery no patient with renal cancer and von Hippel-Lindau disease or hereditary papillary renal cancer had metastatic disease regardless of the number of tumors. Using a lesion size of 3 cm. as a threshold for performing renal parenchymal sparing surgery may help to prevent metastatic disease, unnecessary renal damage due to frequent surgery and renal dialysis or transplantation.

Adolescent↗
PubMed1999

Management of hereditary pheochromocytoma in von Hippel-Lindau kindreds with partial adrenalectomy.

PURPOSE: In patients with von Hippel-Lindau disease multiple bilateral adrenal pheochromocytoma can develop, which has traditionally been treated with adrenalectomy. Partial adrenalectomy can preserve normal adrenal function and avoid the morbidity associated with medical adrenal replacement. We demonstrate whether adrenal function could be preserved by partial adrenalectomy in patients with von Hippel-Lindau disease. MATERIALS AND METHODS: From 1995 to 1998, 13 consecutive von Hippel-Lindau disease patients with pheochromocytoma underwent 14 partial and 6 complete unilateral adrenalectomies. Function of residual normal adrenal and recurrence of adrenal pheochromocytoma were determined at followup. RESULTS: Of the patients 2 had undergone unilateral adrenalectomy and 1 had undergone complete and partial adrenalectomy previously. Following surgery residual normal adrenal tissue consisted of 1 partial adrenal in 3 patients, bilateral partial adrenal in 5, partial and complete adrenal gland in 1, 1 complete adrenal gland in 3 and no adrenal tissue in 1. Three patients with residual adrenal tissue were placed on medical adrenal replacement until adrenocorticotropic hormone stimulation testing demonstrated adrenocortical function. In 2 patients 1 adrenal and 2 extra-adrenal new pheochromocytomas developed 11 and 152 months, respectively, after partial adrenalectomy. No morbidity related to pheochromocytoma was observed during followup. CONCLUSIONS: Partial adrenalectomy can preserve adrenal function in patients with a hereditary form of pheochromocytoma.

Adolescent↗
PubMed1997

Muscarinic cholinergic receptors promote growth of human prostate cancer cells.

BACKGROUND: Recent evidence suggests that muscarinic receptors induce mitogenesis in cells capable of undergoing cell proliferation. Human prostate gland is innervated by the autonomic nervous system and muscarinic receptors have been localized in the prostate gland. METHODS: Effects of carbachol (a stable analog of acetyl choline) on DNA synthesis of LNCaP cells (a human prostate cancer cell line) and primary prostate cells was examined. The DNA synthesis in the cultured cells was assessed using techniques of 3H-thymidine incorporation and bromodeoxyuridine (BrdU) incorporation immunocytochemistry. RESULTS: Carbachol induced a significant increase in BrdU- and 3H-thymidine incorporation of LNCaP cells. The effect of carbachol was completely reversed by atropine, a selective muscarinic antagonist. Subtypes of muscarinic receptors mediating carbachol-induced DNA synthesis were identified using selective receptor subtype antagonists. Pirenzepamine and gallamine did not affect carbachol action on LNCaP cells but diphenylpyralamine, an M3 receptor antagonist, completely blocked carbachol-induced DNA synthesis. Carbachol also stimulated DNA synthesis in primary prostate cells. Prostate carcinoma (PC)-derived primary prostate cells displayed a dramatically greater response to carbachol (a ten-fold increase in DNA synthesis) as compared to benign prostate hypertrophy (BPH)-derived cells (a two-fold increase in DNA synthesis). CONCLUSIONS: M3 receptors stimulate the proliferation of LNCaP cells, BPH-derived and PC-derived primary prostate cells. A dramatically higher response to carbachol by PC-derived prostate cells suggests that M3 receptors may be up-regulated in PC. M3 receptors may play a significant role in PC tumors growth and androgen-independent tumor progression.

Bromodeoxyuridine↗
PubMed1997

Renal cancer: preoperative evaluation with dual-phase three-dimensional MR angiography.

PURPOSE: To evaluate the use of dual-phase three-dimensional magnetic resonance (MR) angiography in the preoperative staging of renal cancer. MATERIALS AND METHODS: MR angiography was performed in 18 patients before performance of partial (n = 7), radical (n = 10), or laparoscopic (n = 1) nephrectomy to treat renal cancer. Dynamic, three-dimensional MR angiograms were obtained with gadoteridol enhancement, breath holding, and a three-dimensional spoiled gradient-echo sequence. Images were obtained at 15-second intervals to achieve opacification of arteries and veins. Source, maximum intensity projection, and multiplanar reconstruction images were evaluated. Imaging results were compared with surgical findings. RESULTS: Renal arterial phase MR angiograms depicted 30 of 31 (97%) surgically confirmed renal arteries, with one false-positive result (an artery that arose from an early-branching single main renal artery, interpreted as a separate accessory artery). Renal venous phase MR angiograms depicted all seven instances of renal vein involvement, including extension to the inferior vena cava in two patients. Collateral vessels around the tumor, including prominent gonadal veins in three patients, were demonstrated. Additional findings included adenopathy and adrenal and pulmonary metastases. CONCLUSION: Dual-phase MR angiography of the kidney may be a useful technique in depicting renal vessels before nephrectomy.

Carcinoma, Renal Cell↗
PubMed1994

Calcitonin stimulates growth of human prostate cancer cells through receptor-mediated increase in cyclic adenosine 3',5'-monophosphates and cytoplasmic Ca2+ transients.

Our recent study has shown that a calcitonin (CT)-like immunoreactive substance(s) is secreted by cultured prostate cells, and secretion of this material is significantly higher in malignant than in benign prostate cells. To test the hypothesis that prostatic CT may serve as a paracrine/neuroendocrine factor, the present study investigated for the presence of CT receptors in the prostate gland. Signal transduction mechanisms activated by CT were examined, and the study also tested its effects on prostate cell proliferation, as assessed by [3H]thymidine incorporation. The results show that high affinity binding sites for [125I]salmon CT were present in plasma membrane fractions of human prostate tissue specimens and the prostate cancer LnCaP cell line. The maximal binding for CT receptors was 564 +/- 163 fmol/mg protein, and the apparent dissociation constant (Kd) was 2.89 +/- 0.58 nM. CT induced a dose-dependent increase in cAMP generation in LnCaP cells. The effect of CT on cytoplasmic Ca2+ transients of LnCaP cells was examined by videofluoromicroscopy. CT (100 nM) induced a rapid and sharp increase in cytoplasmic Ca2+ concentrations in LnCaP cells. The CT-induced increase in cytoplasmic Ca2+ transients appeared to be biphasic (spike and plateau), and this increase was 4- to 10-fold during the initial phase. The profile of this response is characteristic of the activated Ca2+/phospholipid second messenger system. CT also caused a dose-dependent increase in [3H]thymidine incorporation by LnCaP cells. These results suggest that a locally secreted CT-like peptide(s) induces mitogenic responses in prostate cancer cells. This action seems to be mediated through activation of signaling mechanisms, leading to the accumulation of two different second messengers, cAMP and calcium. Activation of dual second messenger systems by CT receptors suggests that the peptide hormone may play an important role in rapidly growing cell populations during the process of tumor formation.

Adenocarcinoma↗