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Biomedical subjects

Stephen C Jacobs

Publications and source records attributed to Stephen C Jacobs.

14 recordsLinked to original sources
PubMed2006

Finasteride targets prostate vascularity by inducing apoptosis and inhibiting cell adhesion of benign and malignant prostate cells.

BACKGROUND: This study investigated the effects of finasteride, a 5alpha-reductase inhibitor, clinically used for the treatment of benign prostatic hyperplasia (BPH) on prostate tumor vascularity, apoptosis, and cell adhesion in situ and in vitro. METHODS: Prostate specimens from BPH patients treated with finasteride for 1-12 months (n = 13), or without finasteride treatment (n = 14), were evaluated for apoptosis (TUNEL assay), microvessel density (Factor VIII), and prostate specific antigen (PSA) immunoreactivity. In vitro, the effect of finasteride was investigated in benign prostate cells, BPH-1, and its tumorigenic derivatives, CAFTD-01 and CAFTD-03, using Hoechst staining and cell adhesion assays. RESULTS: A significant increase in the apoptotic index, and reduced microvessel density and PSA expression were detected in prostates from finasteride-treated patients, compared to controls (P < 0.01). In vitro finasteride led to a significant decrease in prostate epithelial cell adhesion (P < 0.05). CONCLUSIONS: Finasteride can induce prostate apoptosis and reduce tissue vascularity by inhibiting epithelial cell adhesion. This evidence supports that finasteride has apoptotic and anti-angiogenic effects against benign and malignant prostate.

Apoptosis↗
PubMed2006

Complete urinary tract extirpation: the University of Maryland experience.

OBJECTIVES: Complete urinary tract extirpation (CUTE) involves simultaneous bilateral nephroureterectomy, cystectomy or cystoprostatectomy, and the creation of a urinary diversion, if needed. Case reports of this operation have been published, but to our knowledge, this is the largest case series yet reported. We sought to evaluate the characteristics and outcomes of patients who underwent CUTE. METHODS: From 1994 to 2005, 9 patients underwent CUTE at our institution. We performed a retrospective chart review of these patients. The data reviewed included demographics, operative time, length of stay, complications, recurrences, and overall survival. RESULTS: Nine patients who underwent CUTE were identified. The mean patient age at the operation was 61 years. Five patients were men. The mean operative time was 356 minutes. Two patients required a blood transfusion. The length of stay averaged 10.8 days (range 6 to 47). Four patients had functioning renal allografts before and after surgery. Three patients needing dialysis received renal allografts postoperatively. The overall survival rate at a mean follow-up of 31 months was 86%. CONCLUSIONS: Although this report presented a small number of patients, it has illustrated that CUTE can be performed safely and allow definitive surgical treatment of patients with complex genitourinary pathologic findings.

Female↗
PubMed2004

Laparoscopic kidney donation from patients older than 60 years.

BACKGROUND: The current study seeks to determine if the efficacy and safety of laparoscopic donor nephrectomy holds true when performed in patients older than 60 years of age. STUDY DESIGN: Medical records of 42 renal donors older than 60 years were reviewed compared with younger controls carefully matched for gender, race, nephrectomy side, auxiliary recipient procedures, and date of surgery. RESULTS: Preoperative baseline serum creatinine was identical in both groups (0.9 +/- 0.2 mg/dL) although controls had a slightly higher (NS) creatinine clearance (106.9 +/- 19.1 versus 100.0 +/- 35.5 mL/m). Operatively, there was no substantial difference between groups in operative time, warm ischemia time, estimated blood loss, number or size of ports used, and length of incision needed for removal of kidney. Intraoperative and postoperative complication rates were also equivalent between old and young donors. Postnephrectomy serum creatinine was identical. There was no increased length of hospitalization for older donors and they tended to require less morphine sulfate patient-controlled anesthesia. Recipient renal function was slightly better in the younger kidneys early and the difference became statistically significant at 6 to 12 months, but the magnitude of the improvement is not clinically important. CONCLUSIONS: Laparoscopic donor nephrectomy may be performed safely in patients older than 60 years of age. There was no increase in complication rates or length of hospital stay. Older donors did not have a greater increase in serum creatinine after donation compared with donors younger than 40 years of age, nor did recipients of these older kidneys have clinically significantly higher serum creatinine than recipients of kidneys from donors less than 40 years old.

Adult↗
PubMed2004

Laparoscopic donor nephrectomy: the University of Maryland 6-year experience.

PURPOSE: We determined whether the results of laparoscopic donor nephrectomy warranted expansion of the availability of the technique. MATERIALS AND METHODS: Donor and recipient charts for 738 consecutive laparoscopic living donor nephrectomies have been reviewed. RESULTS: Renal donors were 69% white race and 57% female. Age range was 18 to 74 years. Neither age nor obesity alone were exclusionary criteria. Nephrectomy was left sided in 96%. Donors with body mass index greater than 33 had longer operative times. The extraction site changed from umbilical to suprapubic during the series. Warm ischemia time was 169 seconds. Conversion to open nephrectomy occurred in 1.6% of cases and blood transfusion was required in 1.2%. Major intraoperative complications occurred in 6.8% and major postoperative complications occurred in 17.1% of cases. Hospitalization lasted 64.4 hours. Postoperative donor creatinine was 1.5 times the preoperative level. Recipient serum creatinine averaged 2.0 mg% at 1 week and 1.6 mg% at 1 year. Delayed graft function occurred in 2.6%. However, 9.1% of recipients did not achieve a serum creatinine less than 3.0 mg% within 7 days. The endovascular stapler also created 37 extra arteries for implantation. CONCLUSIONS: Risks of laparoscopic donor nephrectomy to the donor must not be minimized. Rapid conversion to open surgery to control bleeding may be necessary. Nonvascular intraoperative injuries require recognition. Slow bowel function recovery prolongs hospitalization and may indicate unrecognized pancreatitis or small bowel herniation. Surgical technique and complication management have improved. Laparoscopic donor nephrectomy is now routine but still requires an intense level of attention to prevention of complications.

Adolescent↗
PubMed2003

The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

5-alpha Reductase Inhibitors↗
PubMed2003

Pleural injury during laparoscopic renal surgery: early recognition and management.

PURPOSE: Injury to the diaphragm is an uncommon yet recognized complication of several laparoscopic procedures, including laparoscopic renal surgery. As these procedures increase in popularity and use, laparoscopic surgeons should be aware of techniques for avoiding this complication as well as methods of identifying pleural injury and managing it appropriately. We report our experience with the detection and intraoperative management of pleural injury sustained during laparoscopic renal surgery and its subsequent treatment. MATERIALS AND METHODS: From July 1993 to April 2001 at 4 institutions 1,765 patients underwent laparoscopic renal surgery for benign and malignant disease as well as for live renal donation. We retrospectively reviewed the charts and interviewed the primary surgeons to determine the etiology of pleural injury, intraoperative detection and management, and possible future prevention. RESULTS: Pleural injury occurred in 10 cases (0.6%). In 2 cases injury involved inadvertent trocar placement through the pleural cavity. These cases were managed by intraoperative chest tube placement. In 8 cases the diaphragm was injured in iatrogenic fashion during kidney dissection, including during splenic mobilization in 2, liver mobilization in 2, ascending colon mobilization in 1, dissection of the upper renal pole in 2 and dissection of a large renal cyst off of the diaphragm in 1. In all patients injury was detected intraoperatively and repaired via laparoscopy. In 1 patient residual pneumothorax postoperatively necessitated tube thoracostomy. CONCLUSIONS: Pleural injury sustained during laparoscopic surgery is an uncommon but potentially serious complication of laparoscopic renal procedures. The experienced laparoscopic surgeon can identify and repair the injury intraoperatively, minimizing patient morbidity postoperatively.

Diaphragm↗
PubMed2002

Risk group stratification in patients undergoing permanent (125)I prostate brachytherapy as monotherapy.

PURPOSE: Patients undergoing prostate brachytherapy (PB) as monotherapy are often selected on the basis of favorable pretreatment factors. However, intermediate and high-risk prostate cancer patients are commonly offered PB as monotherapy without the addition of external beam radiotherapy (EBRT) or hormonal therapy. This series reports the outcome of patients undergoing PB as monotherapy who were stratified into low, intermediate, and high-risk groups with extended follow-up. METHODS AND MATERIALS: A total of 102 patients with clinically localized prostate cancer underwent PB alone as monotherapy. EBRT or hormonal therapy was not part of their initial treatment. Prostate-specific antigen (PSA) relapse-free survival (PRFS) was determined in accordance with the American Society for Therapeutic Radiology and Oncology consensus statement. Patients were stratified as at favorable risk (Stage T1-2a, pretreatment PSA < or =10.0 ng/mL, and Gleason score < or =6), intermediate risk (one prognostic indicator with a higher value), or unfavorable risk (> or =2 indicators with higher values). The median follow-up period for patients in this series was 7 years (range 2.1-9.7). The median age at treatment was 71 years (range 54-80), and the median prescribed dose of (125)I was 145 Gy. RESULTS: Forty patients experienced a biochemical relapse at a median of 1.9 years (range 0.4-4.2). The 5-year actuarial PRFS rate for patients with favorable, intermediate, and unfavorable risk was 85%, 63%, and 24%, respectively (p <0.0001). All but 1 patient had the relapse within the first 5 years of treatment. When stratifying patients on the basis of their pretreatment PSA level, the 5-year PRFS rate for men with a PSA < or =10 ng/mL vs. >10 ng/mL was 78% vs. 35%, respectively (p = 0.0005). Furthermore, the 5-year PRFS rate for men with a Gleason score of < or =6 vs. > or =7 was 74% vs. 33%, respectively (p = 0.0001). No difference was found between Stage T1-T2a and Stage T2b or higher (64% vs. 54%, respectively; p = 0.353). CONCLUSION: On the basis of risk stratification, PB as monotherapy produces comparable PRFS to EBRT and surgery at 7 years of follow-up. PB as monotherapy is particularly ineffective in patients with unfavorable risk factors, and additional therapy is warranted.

Aged↗
PubMed2002

Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer.

PURPOSE: Prostate brachytherapy (PB) entails the placement of radioactive sources throughout the entire prostate gland to treat localized cancer. Typically, the target volume in PB encompasses the entire prostate gland because of the inability to localize the cancer and the multifocal nature of this malignancy. However, because of the unique biochemical nature of the prostate gland, recent advances in magnetic resonance spectroscopic imaging (MRSI) of the prostate have allowed precise delineation of the cancer location within the prostate gland. This report reveals our initial experience of MRSI-guided PB. METHODS: A MRSI study was obtained in 15 localized prostate cancer patients before their scheduled PB. The results of this study were used to internally map 7 x 7 x 9-mm volumes of prostate tissue to assign cancerous areas a higher dose of radiation. Such tumor-bearing areas had a low citrate/(choline+creatine) ratio consistent with cancer. On the basis of the anatomic MRI and MRSI correlation, three-dimensional coordinates were assigned to the locations of MRSI-defined cancer. The entire target volume was treated to a standard prescription dose using I-125 or Pd-103. Abnormal citrate regions, termed the biologic tumor volume, were prescribed a dose of 130% of the target volume dose to dose escalate in the abnormal citrate regions while respecting the normal radiation tolerances of the surrounding areas. Three-dimensional treatment planning was used to perform the implant. RESULTS: Of the 15 prostate cancer patients evaluated, all had successful three-dimensional MRSI acquisition before their scheduled PB procedure. In 14 of the 15 patients planned with MRSI, the data were successfully incorporated into their treatment planning and were used to increase the radiation dose prescription to 130% in the MRSI-defined volumes. In 1 patient, MRSI revealed significant background artifact that made a focal boost impractical. Postimplant dosimetry confirmed a median V100 of 95% (range 72%-100%) in the 15 evaluated patients for the prescription dose. Furthermore, the median BTV100 for the abnormal citrate region was 90% (range 80-100%) as determined by postimplant dosimetry. Urethral and rectal dose-volume histograms were within normal limits. Morbidity was comparable with that for conventionally treated patients. CONCLUSION: MRSI offers a promising new approach for the delivery of ionizing radiation in PB. Although this series was small and with a short follow-up, MRSI-guided implants are feasible and warrant further investigation as a means of improving the therapeutic ratio in PB [corrected].

Aged↗
PubMed2002

Recruitment for a clinical trial of drug treatment for benign prostatic hyperplasia.

OBJECTIVES: To evaluate the effectiveness of various recruitment strategies for a 6-year multicenter clinical trial of medical therapy for benign prostatic hyperplasia, the Medical Therapy of Prostatic Symptoms Trial. METHODS: How participants learned about the trial was obtained during initial contact with clinical centers and at the first screening visit. The yield of randomized participants from the initial contact and first screening visit was calculated for each of the recruitment techniques. RESULTS: During a period of 28 months, 16,723 potential trial participants made an initial contact with the 17 clinical centers, and 2931 men were randomized. An average of four initial contacts were required for each first screen visit and six per randomized participant. Newspaper (29.9%) and mail (26.7%) were the two leading sources of randomized participants. Medical sources (9.6%), radio (8.8%), and newsletters (8.4%) were also important sources. All clinical centers achieved or exceeded their recruitment goals. CONCLUSIONS: Mass mail and newspaper were the most effective recruitment techniques to enlist the interest of men with urinary symptoms for a long-term trial of drug therapy for benign prostatic hyperplasia.

Humans↗
PubMed2002

Effect of doxazosin on stretch-activated adenosine triphosphate release in bladder urothelial cells from patients with benign prostatic hyperplasia.

OBJECTIVES: Recent data suggest that the bladder urothelium may have a sensory function by way of release of adenosine triphosphate (ATP) during stretch, which then acts as a sensory neurotransmitter. Because benign prostatic hyperplasia (BPH) can give rise to irritative (hypersensory) voiding patterns, we questioned whether the bladder urothelium from patients with BPH released more ATP during in vitro stretch and whether doxazosin, an alpha(1)-adrenoceptor blocker, affects this purinergic mechanism. METHODS: Bladder urothelial biopsies from patients with BPH (n = 4) and controls (n = 4) were cultured using established techniques. In vitro stretch was performed with a Flexcell 2000 device that uses vacuum to deform the cell growth surface to impart a stretch force. Doxazosin (5 microM and 20 microM) was added to cells, and supernatants were collected at various points for ATP assay. ATP was assayed using the luciferin-luciferase reaction. ATP data were normalized to the time 0 value and expressed as a percentage of the baseline value. RESULTS: After 96 hours of stretch, the BPH urothelial cells released significantly more ATP than did the control urothelial cells (62.6% +/- 11.2% versus 24.2% +/- 5.4%, P = 0.005) and nonstretched BPH urothelial cells (62.6% +/- 11.2% versus 15.1% +/- 5.1%, P = 0.004). The augmented release of ATP by stretched BPH bladder urothelial cells was completely blocked by treatment with 20 microM doxazosin. CONCLUSIONS: Irritative voiding secondary to BPH may arise from increased ATP release by bladder urothelium during stretch. Doxazosin inhibits ATP release by way of an unknown mechanism that may or may not involve the alpha1-adrenoreceptor. Treatment for hypersensory voiding symptoms secondary to BPH might also target the urothelial purinergic pathway.

Adenosine Triphosphate↗
PubMedDate not supplied

Laparoscopic donor nephrectomy: why not?

OBJECTIVES: Laparoscopic donor nephrectomy has undergone explosive worldwide growth as the method of choice for removal of living donor kidneys. However, the method does have some distinct disadvantages as well. The objective is to define real and potential difficulties with the generalized uncritical acceptance of this surgical technique. METHODS: The literature and personal experience at the largest laparoscopic donor program were reviewed and consolidated. Critical areas of technique and management were analyzed. RESULTS: Laparoscopic living donor nephrectomy has increased the pool of willing potential renal donors. In experienced has the recipient renal function results are equivalent to open nephrectomy. CONCLUSIONS: There are risks in performing the operation to the donor and to the allograft. These risks are potentially catastrophic and mitigate against any casual attitudes about embarking on a laparoscopic donor nephrectomy program.

Clinical Competence↗