PubMed Health⌕ Search

Biomedical subjects

E Darracott Vaughan

Publications and source records attributed to E Darracott Vaughan.

35 records · Page 2Linked to original sources
PubMed2004

Dietary L-arginine supplementation improves the glomerular filtration rate and renal blood flow after 24 hours of unilateral ureteral obstruction in rats.

PURPOSE: Unilateral ureteral obstruction (UUO) results in a significant change in renal blood flow (RBF) and glomerular filtration rate (GFR) by 24 hours. The intake of L-arginine, a substrate of nitric oxide (NO) synthase (NOS), can augment NO production. NO can maintain renal function through its vasodilatory action. Therefore, we examined the effect of dietary arginine supplementation on renal function in UUO. MATERIALS AND METHODS: GFR and RBF were measured by inulin and para-aminohippurate clearance, respectively, in control rats and in rats 24 hours after UUO. Rats were given arginine with or without the concomitant administration of N-nitro-L-arginine methyl ester. Urinary nitrate/nitrite (NO2/NO3) was measured by the Griess reaction and urinary cyclic guanosine monophosphate was determined by enzyme-linked immunosorbent assay. The expression of renal inducible NOS was determined by immunohistochemistry. RESULTS: Urinary NO2/NO3 was significantly increased after 2 weeks of arginine, confirming increased NO production. In control rats GFR and RBF were not significantly different in untreated vs arginine treated groups. In contrast, arginine treatment significantly increased GFR in the obstructed kidney (0.06 +/- 0.01 to 0.14 +/- 0.02 ml per minute per 100 gm) and the contralateral kidney compared with control UUO. RBF was also significantly increased by arginine. The increases in renal function with arginine were blunted by a NOS inhibitor in obstructed and contralateral kidneys. Inducible NOS expression was increased in obstructed and contralateral kidneys. CONCLUSIONS: This study demonstrates that L-arginine supplementation can improve renal function in acute UUO. This finding suggests that NO system may be a future site of pharmacological intervention for UUO.

Animals↗
PubMed2004

Pathophysiology of unilateral ureteral obstruction: studies from Charlottesville to New York.

PURPOSE: More than 30 years ago the decreased renal blood flow and glomerular filtration rate characteristic of unilateral ureteral obstruction (UUO) was described. In the ensuing time, much has been learned about the involvement of nitric oxide (NO) and transforming growth factor-beta (TGF-beta) in the pathophysiology of UUO. MATERIALS AND METHODS: We measured renal blood flow and glomerular filtration rate in dogs and rats, and assessed the effect of altering the availability of NO on these parameters. In rats and mice we used an antibody to TGF-beta, NO synthase gene deletion and inducible nitric oxide synthase gene therapy to assess the role of TGF-beta and NO in renal fibrosis. RESULTS: Results of our studies suggest 2 strategies that have the potential to be incorporated into clinical trials. The first would be replenishment of the NO system with arginine (or a NO donor) to decrease renovascular resistance and increase renal nitric oxide. Either in addition to the first strategy or separately, interstitial fibrosis could be targeted. Strategies for inhibiting fibrosis include antibody to TGF-beta, use of antisense oligonucleotides to TGF-beta, use of drugs that inhibit other pro-fibrotic mediators or gene therapy to inhibit fibrosis. CONCLUSIONS: While these studies have primarily centered on acute UUO, the findings in this model of renal injury may potentially be transferable to other entities that are characterized by decreased renal function and increased renal fibrosis such as different forms of interstitial nephropathy or diabetic glomerulopathy.

Animals↗
PubMed2004

Jay Y. Gillenwater.

Explore the source record for details and available documents.

History, 20th Century↗
PubMed2004

A meta-analysis of trials of transurethral needle ablation for treating symptomatic benign prostatic hyperplasia.

OBJECTIVES: To investigate the short- and long-term effectiveness of transurethral needle ablation (TUNA) of the prostate for clinical benign prostatic hyperplasia (BPH), using a meta-analysis of all clinical studies involving TUNA. METHODS: Data were extracted from two randomized trials, two non-randomized observational protocols and 10 single-arm studies conducted on TUNA, according to a determined protocol. The meta-analysis was based on the change in the mean score at the end of study from that at baseline. The estimation of the effects from the meta-analysis used a multilevel model including random effects for the studies. RESULTS: In all studies the patients recruited had severe lower urinary tract symptoms and a mean International Prostate Symptom Score (IPSS) of > 20 before treatment. The effect of TUNA was to halve the mean IPSS at 1 year after treatment and, although there was a slight tendency for the IPSS to increase in all arms from year 1 to year 5, this decrease by half was maintained at 5 years. The maximum urinary flow rate (Q(max)) also increased by approximately 70% from baseline to 1 year and in virtually all studies the mean Q(max) approached or exceeded 15 mL/s. Although there was a tendency for Q(max) to decline slightly over time, the mean Q(max) 5 years after treatment was > 50% over baseline. CONCLUSIONS: This meta-analysis shows that TUNA is an effective and minimally invasive treatment for men with clinical BPH, even when the symptoms are severe. There is a significant improvement in symptoms and flow rate after 1 year which persists for at least 5 years. TUNA therapy would appear to be an alternative to surgery and an attractive option for men who do not wish to undergo long-term medical therapy, are poor candidates for surgery or are concerned about the side-effects of TURP.

Aged↗
PubMed2004

Liposome-mediated transfer of nitric oxide synthase gene improves renal function in ureteral obstruction in rats.

BACKGROUND: The protective effect of nitric oxide has been demonstrated in several renal disease models. We augmented renal nitric oxide production by transfer of the inducible nitric oxide synthase (iNOS) gene into rat kidney in controls and in unilateral ureteral obstruction (UUO). METHODS: The human iNOS gene was inserted into a pcDNA 3.1-backbone plasmid with the FLAG epitope (FLAG-iNOS). In vitro, transduction of FLAG-iNOS was confirmed by Western blot and Griess reaction. In vivo, we transfected either FLAG-iNOS or control plasmid (CMV-LacZ), using cationic liposomes. Urinary nitric oxide metabolites and immunohistochemistry confirmed iNOS transduction. Renal function was also assessed. RESULTS: In vitro, increased iNOS expression was demonstrated in human embryonic kidney (HEK293) cells, along with increased release of nitric oxide metabolites, NO(2)/NO(3). In vivo, FLAG-iNOS was detected by polymerase chain reaction (PCR) up to 35 days after the transfection. Urine collection documented increased urinary NO(2)/NO(3). Immunohistochemistry localized iNOS to collecting ducts, distal tubules, and glomerulus of the injected kidney. Renal function measured up to 21 days after transfection in control animals was not significantly different between the two groups. In contrast, renal function after 24 hours of UUO was significantly improved in FLAG-iNOS-treated animals. CONCLUSION: This study demonstrates the feasibility of liposome-mediated iNOS gene transfer into the kidney. Furthermore, the improvement of renal function in UUO demonstrates that the transfected iNOS gene is active and suggests that decreased iNOS activity contributes to the decreased renal function in UUO. This iNOS construct may have therapeutic utility in the pathophysiologic sequelae of UUO and other renal diseases.

Cells, Cultured↗
PubMed2004

Liposome-mediated gene therapy in the kidney.

Gene therapy directed to the kidney has been attempted to improve renal disorders such as inherited kidney diseases and common renal diseases that cause interstitial fibrosis, tubular atrophy, and glomerulosclerosis. Viral and non-viral vectors have been tried and been modulated to obtain sufficient transgene expression. However, gene delivery to the kidney is usually difficult because of characteristics of renal cell biology. Among non-viral vectors, the liposome system is a promising procedure for kidney-targeted gene therapy. Using cationic liposome, tubular cells were effectively transduced by retrograde injection of liposome/cDNA complex. Although transgene expression was reportedly modest using cationic liposomes, this method improved renal disease models such as carbonic anhydrase II deficiency and unilateral ureteral obstruction. In contrast, HVJ-liposome system is an effective transfection method to glomerular cells using intra-renal arterial infusion and improved glomerular disease models such as glomerulonephritis and glomerulosclerosis. In addition, intra-renal pelvic injection of DNA by HVJ-liposome system showed transgene expression in interstitial fibroblasts. In kidney-targeted gene therapy, liposome-mediated gene transfer is an attractive method because of its simplicity and reduced toxicity. In spite of modest transgene expression, several renal disease models were successfully modulated by liposome system. Although one limitation of liposome-mediated gene delivery is the duration of transgene expression, the liposome/cDNA complex can be repeatedly administered due to the absence of an immune response.

Animals↗
PubMed2004

The impact of technological advances on the evolution of 3D conformal brachytherapy for early prostate cancer.

Permanent implantation of I-125 and Pd-103 seeds is one of the widely used treatment options for the early stage prostate cancer with minimum normal tissue complications and long-term local control of the tumor. This is possible because of several technological advances made in the past decade to better understand the procedural aspects of implantations with the desired clinical outcome and with acceptable morbidities. In addition, with the widespread use of PSA testing, more widely disseminated information about prostate cancer and increased patient awareness, over 70% of patients are diagnosed early with localized disease and therefore are candidates for definitive local therapy. Delineation of soft tissue structures including the prostate, rectum, urethra and bladder has become more accurate with the use of imaging modalities including Ultrasound and MRI, with or without the CT. A re-evaluation of the dosimetric parameters of the radioactive sources has lead to a more precise estimate of the dose delivered to the prostate and the associated critical normal structures. Technological improvements in the post implant dosimetry have helped to understand the factors, which makes an implant a "good implant" or a "poor implant". Intraoperative treatment planning with on line dosimetry is emerging as one of the best approaches for prostate brachytherapy. In addition, better software is now available producing dose-volume histograms with 3D target and normal tissue reconstruction. The combination of seed implant followed by IMRT would provide scope for differentially boosting the regions under-dosed because of uncontrollable and unexpected reasons during the implant and unsuspected micro extensions of the tumor.

Brachytherapy↗
PubMed2003

Effect of UUO on D1aR expression reveals a link among dopamine, transforming growth factor-beta, and nitric oxide.

Interactions between transforming growth factor-beta (TGF-beta) and nitric oxide (NO) are important in the pathophysiology of unilateral ureteral obstruction (UUO). Dopamine (DA) is a vasoactive renal mediator active at the D(1A) receptor (D(1A)R), which has not been studied in UUO; therefore, we examined the interactions among DA, TGF-beta, and NO in UUO. In vivo, UUO was carried out in rats with or without concurrent treatment with 1D11, a monoclonal antibody to TGF-beta, for 14 days. In vitro, NRK-52E cells (normal rat kidney tubules) were treated with DA, and NO and TGF-beta release were examined. UUO resulted in a 70% decrease in the expression of renal D(1A)R, confirmed by both Western blot analysis and immunohistochemistry. 1D11 treatment restored expression to 60% of control values. DA treatment decreased NRK-52E release of TGF-beta by 80%; conversely, DA significantly increased NO release from NRK-52E cells. These results suggest that DA modulates the release of cytokines, which are involved in the fibrotic and apoptotic sequelae of UUO, and that these effects are independent of DA's known vasoactive properties.

Animals↗
PubMed2003

Renal hemodynamic and ureteral pressure changes in response to ureteral obstruction: the role of nitric oxide.

PURPOSE: Triphasic changes in renal blood flow and ureteral pressure after unilateral ureteral obstruction have long been known. The contribution of nitric oxide to the decline in renal blood flow and ureteral pressure in unilateral ureteral obstruction was studied in this model using arginine infusion and by studying the effect of 2 inhibitors of nitric oxide synthase (NOS). MATERIALS AND METHODS: Left ureteral obstruction was created in dogs. Renal blood flow and ureteral pressure were monitored. Groups 1 to 4 underwent unilateral ureteral obstruction and group 5 dogs underwent sham operation. Groups 2 to 5 received an infusion of arginine at hour 18 of obstruction that was sustained for 1 hour. In addition, NOS inhibitors were administered to dogs in groups 3 (N-monomethyl-L-arginine) and 4 (triamcinolone diacetate). RESULTS: Arginine administration at 18 hours of obstruction caused a significant increase in renal blood flow and ureteral pressure compared to sham operated animals. Triamcinolone diacetate eliminated the increase in renal blood flow and ureteral pressure, whereas N-monomethyl-L-arginine did not, reflecting the competitive nature of its inhibition of NOS. CONCLUSIONS: Arginine infusion 18 hours after unilateral ureteral obstruction led to increases in renal blood flow and ureteral pressure that were not seen in control animals. These results suggest that the nitric oxide system of the kidney is activated in unilateral ureteral obstruction. Since the addition of arginine is accompanied by an increase in renal blood flow and ureteral pressure, it further suggests that a lack of availability of substrate for NOS may explain the decrease in renal blood flow and ureteral pressure in obstruction. Providing substrate may be a way of maintaining renal blood flow in unilateral ureteral obstruction.

Animals↗
PubMed2003

Practice patterns among urologic surgeons treating localized renal cell carcinoma in the laparoscopic age: technology versus oncology.

OBJECTIVES: To evaluate the effect of laparoscopy on practice patterns at a single institution in the treatment of renal cell carcinoma. Many now regard laparoscopic radical nephrectomy (LRN) as a standard of care in the management of localized renal cell carcinoma. As laparoscopy becomes more prevalent in the urologic community, practice patterns are changing. METHODS: We analyzed the renal cancer surgical database at the Weill Medical College of Cornell University from 1997 to 2002. We compared three groups, including open radical nephrectomy (ORN), open partial nephrectomy (OPN), and LRN. RESULTS: A total of 222 consecutive renal surgeries done for presumed malignancy were performed from 1997 to 2002. A total of 194 were assessable. Of these, 63 were OPNs, 51 were ORNs, and 80 were LRNs. When analyzed over time, during the latter half of 2000, 89% of all LRNs were performed on tumors less than 4 cm in size. More recently, in 2002, only 42% of LRNs were performed for tumors 4 cm or less in size. From 1997 to 2000, 30% of all OPNs were done on tumors greater than 4 cm compared with 28% from 2000 to 2002. Of 30 OPNs performed from 1997 to 2000, 21 (70%) were performed on small (4 cm or less) tumors compared with 24 (73%) of 33 from 2000 to 2002. CONCLUSIONS: From 2000 to 2002, the percentage of tumors less than 4 cm that were treated with LRN has increased with time. In the ORN cohort, the percentage of nephrectomies performed on small tumors (less than 4 cm) has decreased with time, and the trends in the OPN group have remained relatively stable. As an institution becomes more comfortable with laparoscopic techniques, technological concerns are likely to play less of a role in determining treatment algorithms among treating urologists.

Aged↗
PubMed2003

Long-Term Experience with 5-alpha-Reductase Inhibitors.

Finasteride, a 5-alpha-reductase inhibitor, dramatically suppresses the production of dihydrotestosterone in men; thus, attention has turned to this agent for the treatment of benign prostatic hyperplasia (BPH). A number of randomized clinical trials have studied finasteride's effects on prostate size, BPH symptoms, flow rate, and prostate-specific antigen (PSA) level. Although the decrease in symptoms with finasteride therapy has been modest compared with more invasive treatments, its use has resulted in sustained reductions in prostatic volume and PSA level with minimal adverse effects. Fewer surgeries for BPH, as well as a decreased incidence of acute urinary retention, have also been seen with finasteride therapy. More research is needed to maximize the effectiveness of such medical therapy for BPH.

Journal Article↗
PubMed2003

Long-Term Experience With 5-alpha-Reductase Inhibitors.

Finasteride, a 5-alpha-reductase inhibitor, dramatically suppresses the production of dihydrotestosterone in men; thus, attention has turned to this agent for the treatment of benign prostatic hyperplasia (BPH). A number of randomized clinical trials have studied finasteride's effects on prostate size, BPH symptoms, flow rate, and prostate-specific antigen (PSA) level. Although the decrease in symptoms with finasteride therapy has been modest compared with more invasive treatments, its use has resulted in sustained reductions in prostatic volume and PSA level with minimal adverse effects. Fewer surgeries for BPH, as well as a decreased incidence of acute urinary retention, have also been seen with finasteride therapy. More research is needed to maximize the effectiveness of such medical therapy for BPH.

Journal Article↗
PubMed2002

High expression of the Met receptor in prostate cancer metastasis to bone.

OBJECTIVES: Expression of the active Met receptor tyrosine kinase causes tumor metastasis in animal models. To begin to analyze whether Met expression might be related to the spread of prostate cancer cells, we investigated whether its expression correlates with prostate-specific antigen recurrence and whether its expression depends on the site of metastasis. METHODS: Ninety radical prostatectomy specimens with a Gleason sum of 6 or 7 and 86 specimens of bone, lymph node, and soft-tissue metastasis were immunohistochemically stained for Met, and a semiquantitative scoring system for Met in heterogeneously positive prostate cancers was applied. Met protein in prostate cancer cell lines was measured by Western blotting. RESULTS: With the exception of two lymph node metastases, all metastases and 51% of the primary prostate cancers expressed Met. Moreover, the bone metastases expressed significantly more Met than did the lymph node metastases. However, in prostate cancer with a Gleason sum of 6 or 7, Met was not a prognostic marker for prostate-specific antigen recurrence. In prostate cancer cell lines, Met expression correlated inversely with expression of the androgen receptor. CONCLUSIONS: The high expression of the Met receptor tyrosine kinase in bone metastasis renders Met a promising target for nuclear imaging and treatment of metastatic prostate cancer.

Bone Neoplasms↗