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Mani Menon

Publications and source records attributed to Mani Menon.

At least 55 records · Page 3Linked to original sources
PubMed2004

Robotics in urology.

PURPOSE OF REVIEW: Robotic urologic surgery, an exciting and new emerging frontier in the field of urology, has tremendous potential to progress in the future. It is important, therefore, that urologists keep abreast of the new technologies, their limitations, and the possibility of incorporating them in day-to-day surgery. There are a substantial number of reports on performing complex urological procedures with robotic assistance in humans that document their safety, efficacy and feasibility. RECENT FINDINGS: Most of the recent reports pertaining to robotic surgery have been in the domain of localized cancer of the prostate (radical prostatectomy), bladder cancer (radical cystectomy and urinary diversion for muscle invasive bladder cancer), kidney surgery (nephrectomy, donor nephrectomy and pyeloplasty), and adrenal surgery. There are also a few anecdotal reports. SUMMARY: With the potential advantages and latent qualities of robotic assistance in minimally invasive surgery over conventional surgery, robot-assisted surgeries may be developed to the next level and lead to a future revolution of the way surgery is performed. Robot-assisted radical prostatectomy in the management of localized cancer of the prostate is one such example. The impact of robotics is therefore very promising. However, controlled clinical trials and comparisons from various centers are needed. Other important concerns are the cost and training implications. Future application may also allow integration of pre- and intraoperative imaging in the management of urological diseases. In the not too distant future, newer robotic instruments will be added to the armamentarium for performing different urological procedures.

Adrenalectomy↗
PubMed2004

Long-term survival probability in men with clinically localized prostate cancer: a case-control, propensity modeling study stratified by race, age, treatment and comorbidities.

PURPOSE: We used a propensity risk scoring approach to model long-term survival for men with clinically localized prostate cancer. We developed comprehensive lookup tables for estimating survival probability stratified by patient age, race, readily available clinical variables, comorbidities and treatment type. MATERIALS AND METHODS: We retrospectively identified a cohort of 1611 men with clinically localized prostate cancer (patients) and 4538 age, race and comorbidity matched controls. Based on demographic and clinical variables propensity risk scoring was used to develop smoothed survival prediction models for patients and controls. Based on these models tables were created to provide 10-year overall survival estimates. The tables are stratified by patient age, race, comorbidity, prostate specific antigen, cancer grade, and treatment type when applicable. RESULTS: Mean patient age was 67.0 years and median baseline prostate specific antigen was 8.5 ng/ml. Of the patients 68% had biopsy cancer grade 2, 39% were black, 29% received conservative treatment, 43% underwent radical prostatectomy and 27% were treated with radiation therapy. Crude and cancer specific 10-year survival rates were 67% and 93%, respectively. Validation C-index values were 0.63 for the cancer specific model and 0.69 for the overall survival model. CONCLUSIONS: These lookup tables provide physicians and patients with realistic estimates of 10-year survival and allow them to compare the impact of cancer vs noncancer factors on patient mortality.

Adult↗
PubMed2004

Biochemical recurrence and survival prediction models for the management of clinically localized prostate cancer.

A number of new predictive modeling techniques have emerged in the past several years. These methods, which have been developed in fields such as artificial intelligence research, engineering, and meteorology, are now being applied to problems in medicine with promising results. This review outlines our recent work with use of selected advanced techniques such as artificial neural networks, genetic algorithms, and propensity scoring to develop useful models for estimating the risk of biochemical recurrence and long-term survival in men with clinically localized prostate cancer. In addition, we include a description of our efforts to develop a comprehensive prostate cancer database that, along with these novel modeling techniques, provides a powerful research tool that allows for the stratification of risk for treatment failure and survival by such factors as age, race, and comorbidities. Clinical and pathologic data from 1400 patients were used to develop the biochemical recurrence model. The area under the receiver operating characteristic curve for this model was 0.83, with a sensitivity of 85% and specificity of 74%. For the survival model, data from 6149 men were used. Our analysis indicated that age, income, and comorbidities had a statistically significant impact on survival. The effect of race did not reach statistical significance in this regard. The C index value for the model was 0.69 for overall survival. We conclude that these methods, along with a comprehensive database, allow for the development of models that provide estimates of treatment failure risk and survival probability that are more meaningful and clinically useful than those previously developed.

Aged↗
PubMed2003

Physical and functional interaction of androgen receptor with calmodulin in prostate cancer cells.

Ca(2+) and calmodulin (CaM) play a critical role in proliferation and viability of a wide variety of cells, including prostate cancer cells. We examined two prostate cancer cell lines, androgen-sensitive LNCaP and androgen-independent PC-3. Proliferation of LNCaP cells was six to eight times more sensitive to the inhibitory effect of the CaM antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) than were PC-3 cells. Because LNCaP cell proliferation is sensitive to stimulation by androgen, we assessed the physical and functional interaction between androgen receptor (AR) and CaM. We observed tight binding of AR to CaM when LNCaP cell extracts were subjected to CaM-affinity column chromatography. AR binding to CaM was Ca(2+)-dependent and was inhibited by pretreatment of the cell extracts with W-7. Using immunofluorescence staining and confocal microscopy, we demonstrated colocalization of AR and CaM in the nucleus of LNCaP cells. Furthermore, the functional relevance of AR-CaM interactions in intact cells was revealed by the observation that W-7 was as effective as Casodex, an antiandrogen, in blocking AR-regulated expression of prostate-specific antigen in LNCaP cells. AR seems to interact with CaM directly because purified human AR could bind to CaM-agarose, and CaM could be detected in AR-immunoprecipitate prepared from purified soluble proteins. These studies provide direct evidence for physical and functional interaction between AR and CaM and suggest the potential usefulness of CaM antagonists in blocking AR activity in prostate cancer.

Calmodulin↗
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

Synchronized prostate cancer cells for studying androgen regulated events in cell cycle progression from G1 into S phase.

Androgen-ablation is a most commonly prescribed treatment for metastatic prostate cancer but it is not curative. Development of new strategies for treatment of prostate cancer is limited partly by a lack of full understanding of the mechanism by which androgen regulates prostate cancer cell proliferation. This is due, mainly, to the limitations in currently available experimental models to distinguish androgen/androgen receptor (AR)-induced events specific to proliferation from those that are required for cell viability. We have, therefore, developed an experimental model system in which both androgen-sensitive (LNCaP) and androgen-independent (DU145) prostate cancer cells can be reversibly blocked in G(0)/G(1) phase of cell cycle by isoleucine deprivation without affecting their viability. Pulse-labeling studies with (3)H-thymidine indicated that isoleucine-deprivation caused LNCaP and DU145 cells to arrest at a point in G(1) phase which is 12-15 and 6-8 h, respectively, before the start of S phase and that their progression into S phase was dependent on serum factors. Furthermore, LNCaP, but not DU145, cells required AR activity for progression from G(1) into S phase. Western blot analysis of the cell extracts prepared at regular intervals following release from isoleucine-block revealed remarkable differences in the expression of cyclin E, p21(Cip1), p27(Kip1), and Rb at the protein level between LNCaP and DU145 cells during progression from G(1) into S phase. However, in both cell types Cdk-2 activity associated with cyclin E and cyclin A showed an increase only when the cells transited from G(1) into S phase. These observations were further corroborated by studies using exponentially growing cells that were enriched in specific phases of the cell cycle by centrifugal elutriation. These studies demonstrate usefulness of the isoleucine-deprivation method for synchronization of androgen-sensitive and androgen-independent prostate cancer cells, and for examining the role of androgen and AR in progression of androgen-sensitive prostate cancer cells from G(1) into S phase.

Androgens↗
PubMed2003

Vattikuti Institute prostatectomy: surgical technique and current results.

The Vattikuti Urology Institute has been developing a robotic prostatectomy system for the management of prostate cancer. This technique is based on the scientific foundations of Walsh's anatomic prostatectomy. Two hundred fifty patients with clinically localized prostate cancer have undergone this technique. Preoperative, operative, and postoperative parameters were collected, and functional outcomes using previously validated quality-of-life instruments were evaluated. The mean operating time for these patients was 2.5 hours (165 and 135 minutes with and without lymphadenectomy, respectively), and the average blood loss was 150 mL. The median specimen Gleason score was 7, and the mean tumor volume was 7 mL. Four patients had a positive surgical margin (three unifocal, one multifocal). Ninety-five percent of the patients were discharged within 23 hours, and the mean catheterization time was 4.2 days. The complication rate was 4%. Approximately 78% of the patients had intact erectile response and 96% achieved continence by the sixth month after surgery. The robotic prostatectomy system is a safe and effective operation for the management of prostate cancer.

Humans↗
PubMed2003

Robotic radical prostatectomy and the Vattikuti Urology Institute technique: an interim analysis of results and technical points.

We have performed >350 robotic radical prostatectomies in the last 2 years. A single surgeon (MM) performed 250 of these procedures using a technique developed at our institution, the Vattikuti Urology Institute. This article summarizes the technical highlights and interim results of the Vattikuti Institute Prostatectomy (VIP) technique. We prospectively collected baseline demographic data, such as age, race, body mass index (BMI), serum prostate-specific antigen values, prostate volume, Gleason score, percentage cancer, TNM clinical staging, and comorbidities. Urinary symptoms were measured with the International Prostate Symptom Score, and sexual health with the Sexual Health Inventory of Males. In addition, patients received the Expanded Prostate Inventory Composite at baseline and at 1, 3, 6, 12 and 18 months after the procedure via mail. Data collection is complete on 200 of the first 250 patient cases. Gleason score >or=7 was noted in 40% of patients. The average BMI was high (28), and 86% patients were classified as pathologic stage pT2a to pT2b. The mean operative time was 160 minutes and the mean blood loss was 153 mL. No patient required blood transfusion. At 6 months, 82% of the men who were <60 years of age and 75% of those >60 years of age had return of sexual function, and 64% and 38%, respectively, had sexual intercourse. At 6 months, 96% patients were continent.

Adenocarcinoma↗
PubMed2003

An operative and anatomic study to help in nerve sparing during laparoscopic and robotic radical prostatectomy.

OBJECTIVE: To provide a detailed description of the steps involved in a laparoscopic radical prostatectomy in relation to the complex neurovascular anatomy of the male pelvis. AIM AND HYPOTHESIS: We aimed at delineating the neurovascular anatomy to assist in nerve preservation during laparoscopic and robotic radical prostatectomies. METHODS: A team of urologists and an anatomist performed anatomic dissections of 12 male cadavers using a combination of laparoscopic equipment, magnification, and open surgical dissection. Each step involved in laparoscopic prostatectomy was reviewed in relation to the possible impact the step could have on the neurovascular bundles. RESULTS: Dissections were performed systematically to mimic various steps of laparoscopic and robotic prostatectomy. The neurovascular bundles were identified and correlated with video images of actual surgery. This enabled us to construct computer simulations and show the actual nerves on the operative pictures. We specially unraveled the relationship between neurovascular bundles and lateral pelvic and Denonvillier's fascias, both of which enclose and hide these important structures. The course of the bundles was traced from its origin at pelvic plexus to its distal course along the urethra. We also showed the important relationship between pelvic plexus ganglions and seminal vesicles to illustrate the vulnerability of these nerves to thermal, electrical and/or crush injury during seminal vesicle and prostatic pedicle dissections. The importance of additional fine neural plexus along the posterior and antero-lateral surface of the prostate was shown by both gross anatomical and microscopic images. The distal precarious location of the bundles was illustrated by dissections showing anteriorly lifted prostate.These anatomico-operative correlations have not been published for laparoscopic and robotic prostatectomies, which differ significantly in its visual angles, magnifications and sometimes three-dimensional (3D) visualization from its open counter part. CONCLUSION: Laparoscopic and robotic radical prostatectomy provides exposure and visualization of male pelvis not previously appreciated. It is only through a careful reexamination of the anatomy of the male pelvis, in the context of this new procedure, that the improvements in visualization and exposure benefit the surgeon. Our work provides a detailed map relating to operative steps to aid the surgeon in the performance of a nerve sparing robotic and laparoscopic radical prostatectomy.

Fascia↗
PubMed2003

Vattikuti Institute Prostatectomy: a single-team experience of 100 cases.

PURPOSE: To analyze the outcomes of the first 100 patients undergoing robotic radical prostatectomy by a single surgical team. PATIENTS AND METHODS: From August 2001 to May 2002, we performed robotic radical prostatectomy in 100 patients with localized prostate cancer. The mean age was 60 +/- 0.67 years (SEM), the body mass index 27.5 +/- 0.35, the preoperative prostate specific antigen concentration 7.2 +/- 0.86 ng/mL, and follow-up 5.5 +/- 0.24 months. Thirty-eight patients also underwent pelvic lymph node dissection. We used the da Vinci surgical system and a subperitoneal approach (the Vattikuti Institute Prostatectomy; VIP). This is a prospective outcomes analysis of these patients. RESULTS: The mean operating time was 195 +/- 5.0 minutes, and the mean blood loss was 149 +/- 11.8 mL. No patient required blood transfusion. The stages of the cancers were pT(2a) in 21, pT(2b) in 64, pT(3a) in 5, pT(3b) in 9, and pT(3b)N(1) in 1. The positive surgical margin rate was 15%. At 1, 3, and 6 months, the continence rates were 37%, 72%, and 92%, respectively, and the potency rates were 11%, 32%, and 59%. CONCLUSION: The VIP is a safe operation with excellent operative parameters, low morbidity, and good surgical margins. The early functional results are promising.

Adult↗
PubMed2003

Vattikuti Institute prostatectomy: technique.

PURPOSE: We have performed more than 250 radical prostatectomies using the da Vinci (Intuitive Surgical, Mountain View, California) surgical system. Our initial cases were done using the classic Montsouris approach. However, after gaining familiarity with the robot we modified our technique to reflect our experience with open radical retropubic prostatectomy. We detail the Vattikuti Institute prostatectomy technique that we currently use. MATERIALS AND METHODS: The robotic technique requires 2 teams, namely a skilled laparoscopic team at the patient and a skilled open surgeon at the console. Dissection is started anterior to the bladder and it continues extraperitoneally. The endopelvic fascia is opened and the dorsal vein complex is secured. The apex of the prostate is dissected free, releasing the neurovascular bundles at the apex. The bladder neck is then incised, and the seminal vesicles and vasa are transected. Posterior dissection is done within the posterior layer of Denonvilliers' fascia, preserving the neurovascular bundles and lateral prostatic fascia. The apex is transected and frozen sections are obtained from the parietal margins. Vesicourethral anastomosis is formed with 2 continuous sutures. RESULTS: In the last 100 cases mean operative time was 2.5 hours and average blood loss was 150 ml. (range 25 to 525 cc.). Median specimen Gleason score was 7 and mean tumor volume was 7 cc. Four patients had a positive surgical margin, which was focal in 3. Of the patients 95% were discharged home within 23 hours. Mean catheterization time was 4.2 days. CONCLUSIONS: Vattikuti Institute prostatectomy is a precise and safe minimally invasive technique of radical retropubic prostatectomy.

Humans↗
PubMed2002

Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants.

In a previous study we demonstrated that oxalate induced free radical injury can promote calcium oxalate stone formation. In the present study, we tested whether the antioxidants vitamin E, superoxide dismutase (SOD), catalase and desferoxamine (DFO) can provide protection against oxalate toxicity in LLC-PK(1) cells. LLC-PK(1) cells were exposed to oxalate (1.0 mM) or oxalate+calcium oxalate monohydrate crystals (COM, 500 microg) for 3, 6, and 9 h. Cellular injury was assessed by lactate dehydrogenase (LDH) release. Malondialdehyde (MDA) content, catalase and glutathione peroxidase activities were also measured. The effect of vitamin E (200 microM), DFO (1.0 mM), SOD (400 U), and catalase (400 U) on oxalate-exposed cells was tested. LLC-PK(1) cells exposed to oxalate showed a significant increase in LDH release and MDA content, which was further elevated when COM crystals were added. Cellular glutathione peroxidase and catalase activities were decreased on exposure to oxalate. The addition of vitamin E, SOD, catalase and DFO significantly reduced the release of LDH and restored glutathione peroxidase and catalase activities towards the control level. The increased formation of MDA on oxalate or oxalate+COM toxicity was restored towards normalization by antioxidants and antioxidant enzymes. The protection rendered by vitamin E was greater than that of SOD, catalase and DFO. We conclude that oxalate associated free radical injury may promote stone formation by providing cellular debris for crystal nucleation and aggregation and augment crystal attachment to other tubular cells. Antioxidant administration may prevent calcium oxalate nucleation and retention in the renal tubules by preventing oxalate mediated peroxidative injury.

Animals↗
PubMed2002

Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer.

Adenovirus-mediated suicide gene therapy may hold promise in the treatment of human cancer. We have developed a novel approach that utilizes a lytic, replication-competent adenovirus (Ad5-CD/TKrep) to deliver a cytosine deaminase/herpes simplex virus-1 thymidine kinase fusion gene to tumors. The cytosine deaminase and herpes simplex virus-1 thymidine kinase suicide genes render malignant cells sensitive to specific pharmacological agents and, importantly, sensitize them to radiation. The Phase I study described here represents the first gene therapy trial in which a replication-competent virus was used to deliver a therapeutic gene to humans. The indication is local recurrence of prostate cancer after definitive radiation therapy. An escalating dose (10(10), 10(11), and 10(12) viral particles) of the Ad5-CD/TKrep virus was injected intraprostatically under transrectal ultrasound guidance into 16 patients in four cohorts. Two days later, patients were given 5-fluorocytosine and ganciclovir prodrug therapy for 1 (cohorts 1-3) or 2 (cohort 4) weeks. There were no dose-limiting toxicities, and the maximum tolerated dose of the Ad5-CD/TKrep vector was not defined. Ninety-four percent of the adverse events observed were mild or moderate (grade 1/2) in nature. Seven of 16 (44%) patients demonstrated a >or=25% decrease in serum prostate-specific antigen, and 3 of 16 (19%) patients demonstrated a >or=50% decrease in serum prostate-specific antigen. Transgene expression and tumor destruction at the injection site were confirmed by sextant needle biopsy of the prostate at 2 weeks. Two patients were negative for adenocarcinoma at 1 year follow-up. Although Ad5-CD/TKrep viral DNA could be detected in blood as far out as day 76, no infectious adenovirus was detected in patient serum or urine. Together, the results demonstrate that intraprostatic administration of the replication-competent Ad5-CD/TKrep virus followed by 2 weeks of 5-fluorocytosine and ganciclovir prodrug therapy can be safely applied to humans and is showing signs of biological activity.

Adenoviruses, Human↗
PubMed2002

COM crystals activate the p38 mitogen-activated protein kinase signal transduction pathway in renal epithelial cells.

Interaction of calcium oxalate monohydrate (COM) crystals with renal cells has been shown to result in altered gene expression, DNA synthesis, and cell death. In the current study the role of a stress-specific p38 MAP kinase-signaling pathway in mediating these effects of COM crystals was investigated. Exposure of cells to COM crystals (20 microg/cm(2)) rapidly stimulated strong phosphorylation and activation of p38 mitogen-activated protein kinase (p38 MAP kinase) and re-initiation of DNA synthesis. Inhibition of COM crystal binding to the cells by heparin blocked the effects of COM crystals on p38 MAPK activation. We also show that specific inhibition of p38 MAPK by 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl) imidazole (SB203580) or by overexpression of a dominant negative mutant of p38 MAP kinase abolishes COM crystal-induced re-initiation of DNA synthesis. The inhibition is dose-dependent and correlates with in situ activity of native p38 MAP kinase, determined as mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP kinase-2) activity in cell extracts. In summary, inhibiting activation of p38 MAPK pathway abrogated the DNA synthesis in response to COM crystals. These data are the first demonstrations of activation of the p38 MAPK signaling pathway by COM crystals and suggest that, in response to COM crystals, this pathway transduces critical signals governing the re-initiation of DNA synthesis in renal epithelial cells.

Animals↗
PubMed2002

Resveratrol induces prostate cancer cell entry into s phase and inhibits DNA synthesis.

Resveratrol has an apoptotic effect on a variety of cancer cells. Changes in cell cycle regulatory processes contributing to the antiproliferative effect of resveratrol remain largely unknown. Our studies revealed that, in androgen-sensitive LNCaP cells, the effect of resveratrol on DNA synthesis varied dramatically depending on the concentration and the duration of treatment. In 1-h-treated cells, resveratrol showed only an inhibitory effect on DNA synthesis, which increased with increasing concentration (IC50 = 20 microM). However, when treatment duration was extended to 24 h, we observed a dual effect of resveratrol on DNA synthesis. At 5 to 10 microM it caused a 2- to 3-fold increase in DNA synthesis, and at > or =15 microM, it inhibited DNA synthesis. The increase in DNA synthesis was seen only in LNCaP cells, but not in androgen-independent DU145 prostate cancer cells or in NIH3T3 fibroblast cells. The resveratrol-induced increase in DNA synthesis was associated with enrichment of LNCaP cells in S phase, and a concurrent decrease in nuclear p21Cipl and p27Kip1 levels. Furthermore, consistent with the entry of LNCaP cells into S phase, there was a dramatic increase in nuclear Cdk2 activity associated with both cyclin A and cyclin E. Taken together, our observations indicate that LNCaP cells, treated with resveratrol, are induced to enter into S phase, but subsequent progression through S phase is limited by the inhibitory effect of resveratrol on DNA synthesis, particularly at concentrations above 15 microM. Therefore, this unique ability of resveratrol to exert opposing effects on two important processes in cell cycle progression, induction of S phase and inhibition of DNA synthesis, may be responsible for its apoptotic and antiproliferative effects.

Androgens↗
PubMed2002

Oxalate selectively activates p38 mitogen-activated protein kinase and c-Jun N-terminal kinase signal transduction pathways in renal epithelial cells.

Oxalate, a metabolic end product, is an important factor in the pathogenesis of renal stone disease. Oxalate exposure to renal epithelial cells results in re-initiation of the DNA synthesis, altered gene expression, and apoptosis, but the signaling pathways involved in these diverse effects have not been evaluated. The effects of oxalate on mitogen- and stress-activated protein kinase signaling pathways were studied in LLC-PK1 cells. Exposure to oxalate (1 mM) rapidly stimulated robust phosphorylation and activation of p38 MAPK. Oxalate exposure also induced modest activation of JNK, as monitored by phosphorylation of c-Jun. In contrast, oxalate exposure had no effect on phosphorylation and enzyme activity of p42/44 MAPK. We also show that specific inhibition of p38 MAPK by 4(4-(fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)imidazole (SB203580) or by overexpression of a kinase-dead dominant negative mutant of p38 MAPK abolishes oxalate induced re-initiation of DNA synthesis in LLC-PK1 cells. The inhibition is dose-dependent and correlates with in situ activity of native p38 MAP kinase, determined as MAPK-activated protein kinase-2 activity in cell extracts. Thus, this study not only provides the first demonstration of selective activation of p38 MAPK and JNK signaling pathways by oxalate but also suggests that p38 MAPK activity is essential for the effects of oxalate on re-initiation of DNA synthesis.

Animals↗
PubMed2002

Laparoscopic and robot assisted radical prostatectomy: establishment of a structured program and preliminary analysis of outcomes.

PURPOSE: The technique of laparoscopic radical prostatectomy is difficult to master and is associated with a steep learning curve. We hypothesized that a structured approach to establishing a laparoscopic prostatectomy program would diminish complications during the learning process and that robotic technology would be useful in learning the operation. MATERIALS AND METHODS: A structured laparoscopic radical prostatectomy program was introduced at the Vattikuti Urology Institute on October 23, 2000. One of 2 surgeons with a combined experience of more than 500 laparoscopic radical prostatectomies performed or supervised the first prostatectomies, training a third surgeon with extensive "open" surgical skills but no laparoscopic experience. The "trained" surgeon then started performing the operation independently with robotic assistance. The results of this approach were analyzed at the end of 12 months. RESULTS: We performed 48 laparoscopic radical prostatectomies and 50 robot assisted prostatectomies within the 12-month period. The preoperative and intraoperative demographical variables were comparable in both groups as were the operative times, changes in hemoglobin concentrations, durations of hospitalization, positive margin rates and overall complication rates. All measured parameters were comparable to the "best-in-class" values for laparoscopic radical prostatectomy reported in the literature. CONCLUSIONS: A structured approach minimizes complications during the establishment of laparoscopic radical prostatectomy program. Robotic assistance helps skilled "open" surgeons learn the technique of laparoscopic radical prostatectomy.

Humans↗