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Michael A Palese

Publications and source records attributed to Michael A Palese.

10 recordsLinked to original sources
PubMed2006

Alternatively spliced neuronal nitric oxide synthase mediates penile erection.

A key role for nitric oxide (NO) in penile erection is well established, but the relative roles of the neuronal NO synthase (nNOS) versus endothelial forms of NOS are not clear. nNOS- and endothelial NOS-deficient mice maintain erectile function and reproductive capacity, questioning the importance of NO. Alternatively, residual NO produced by shorter transcripts in the nNOS(-/-) animals might suffice for normal physiologic function. We show that the beta splice variant of nNOS elicits normal erection despite a decrease in stimulus-response characteristics and a 5-fold increased sensitivity to the NOS inhibitor, l-NAME. Residual nNOSbeta generates only 10% of the normal NO level in vitro but produces citrulline and diaphorase staining reflecting in vivo NOS activity in pelvic ganglion nerves that is comparable to WT animals. Thus, alternatively spliced forms of nNOS are major mediators of penile erection and so may be targets for therapeutic intervention.

Alternative Splicing↗
PubMed2005

Impact of delay to nephroureterectomy for patients undergoing ureteroscopic biopsy and laser tumor ablation of upper tract transitional cell carcinoma.

OBJECTIVES: To investigate whether a delay in nephroureterectomy for patients with transitional cell carcinoma of the upper urinary tract owing to ureteroscopic biopsy and/or laser tumor ablation affects postoperative disease status. METHODS: Of 155 patients diagnosed with upper tract transitional cell carcinoma at our institution from 1993 to 2003, 121 underwent nephroureterectomy. We compared the postoperative disease status of patients who underwent nephroureterectomy on the basis of positive cytology findings and filling defect on contrast imaging (no ureteroscopy; n = 34) to patients who underwent nephroureterectomy after ureteroscopic biopsy (n = 75) and patients who underwent nephroureterectomy after ureteroscopic biopsy and laser tumor ablation (n = 12). RESULTS: At a mean follow-up of 38.7 months, 29 (85.3%) of 34 patients who underwent nephroureterectomy on the basis of contrast imaging and urinary cytology alone were disease free compared with 61 (81.3%) of 75 patients who underwent ureteroscopic biopsy before nephroureterectomy (P = 0.18). The mean time from biopsy to nephroureterectomy for these 75 patients was 28 days, and the mean follow-up after nephroureterectomy was 40.1 months. Finally, 10 (83.3%) of 12 patients who underwent ureteroscopic biopsy and laser tumor ablation before nephroureterectomy were disease free at a mean follow-up of 37.2 months. The mean time from ureteroscopic biopsy to nephroureterectomy in this group was 196 days. No significant difference was found in the postoperative disease status between patients undergoing nephroureterectomy after ablation and those who proceeded to nephroureterectomy after endoscopic biopsy or those who did not undergo ureteroscopy before nephroureterectomy (P = 0.16). CONCLUSIONS: Ureteroscopy with biopsy and/or tumor ablation before nephroureterectomy did not adversely affect the postoperative disease status.

Aged↗
PubMed2005

Robot-assisted laparoscopic dismembered pyeloplasty: a combined experience.

BACKGROUND AND PURPOSE: The need for advanced laparoscopic skills limits the implementation of laparoscopic pyeloplasty to centers with extensive experience. The introduction of robotic technology into the field of minimally invasive surgery has facilitated complex surgical dissection and genitourinary reconstruction. We report our experience with robot-assisted laparoscopic pyeloplasty using the daVinci Surgical System at three New York City medical centers. PATIENTS AND METHODS: A retrospective review of all robot-assisted laparoscopic Anderson-Hynes dismembered pyeloplasty cases in 18 female and 17 male patients between April 2001 and January 2004 was performed. The average patient age was 39.0 years (range 15-69 years). All patients had symptoms or radiographic evidence of ureteropelvic junction (UPJ) obstruction. Robotic assistance with the daVinci Surgical System was employed after preparation of the UPJ with a standard laparoscopic approach. RESULTS: The mean operative time and suturing time was 216.4 +/- 52.9 minutes and 63.0 +/- 14.2 minutes, respectively. The average estimated blood loss was minimal at 73.9 +/- 58.3 mL. The mean length of hospitalization was 69.4 hours (range 28-310 hours). The average use of intravenous morphine was 28.4 mg (range 0-162 mg). There were no intraoperative complications or open conversions. A mean follow-up of 7.9 months revealed a success rate of 94%, with two patients requiring further treatment. CONCLUSIONS: This combined multi-institutional series reveals that robot-assisted pyeloplasty with the daVinci Surgical System is safe and reproducible. These intermediate results appear comparable to those of open and laparoscopic pyeloplasty repairs.

Adolescent↗
PubMed2004

Abnormal selective cytology results predict recurrence of upper-tract transitional-cell carcinoma treated with ureteroscopic laser ablation.

BACKGROUND AND PURPOSE: Endoscopic management of transitional-cell carcinoma (TCC) of the upper urinary tract remains associated with a significant rate of recurrence. We evaluated the impact of selective upper-tract cytology findings on tumor recurrence and renal salvage rate after ureteroscopic laser tumor ablation. PATIENTS AND METHODS: From 1993 though 2003, 38 patients with upper-tract TCC underwent ureteroscopic laser tumor ablation. Cytology specimens were collected from the upper urinary tract prior to ablation. "Abnormal cytology" was defined as the presence of malignant or atypical cells. Patients with abnormal cytology results were compared with patients with those having negative findings for tumor recurrence and renal salvage rates using the X (2) test. RESULTS: Of the 38 patients, 26 (68.4%) experienced at least one recurrence at a mean follow-up of 37.2 months. Pretreatment upper-tract cytology results were available in 34 of these patients: 17 (50%) were negative, and 17 were abnormal. Sixteen of the patients (94.1%) with abnormal cytology results had tumor recurrence after ablation, compared with 8 of the 17 (47.1%) with negative cytology findings (P = 0.0026). Twelve patients (31.5%) underwent nephroureterectomy during follow-up: 8 of the 17 (47.1%) with abnormal cytology, and 4 of the 17 (23.5%) with negative cytology (P = 0.15). CONCLUSION: Abnormal selective cytology results were associated with a significantly higher rate of tumor recurrence and a trend toward increased renal loss in patients with upper-tract TCC treated with ureteroscopic ablation. These findings suggest a prognostic value for upper-tract cytology analysis in patients undergoing endoscopic therapy.

Adult↗
PubMed2003

Phosphorylated endothelial nitric oxide synthase mediates vascular endothelial growth factor-induced penile erection.

The objective of the present study was to evaluate whether vascular endothelial growth factor (VEGF)-induced penile erection is mediated by activation of endothelial nitric oxide synthase (eNOS) through its phosphorylation. We assessed the role of constitutively activated eNOS in VEGF-induced penile erection using wild-type (WT) and eNOS-knockout (eNOS(-/-)) mice with and without vasculogenic erectile dysfunction. Adult WT and eNOS(-/-) mice were subjected to sham operation or bilateral castration to induce vasculogenic erectile dysfunction. At the time of surgery, animals were injected intracavernosally with a replication-deficient adenovirus expressing human VEGF145 (10(9) particle units) or with empty virus (Ad.Null). After 7 days, erectile function was assessed in response to cavernous nerve electrical stimulation. Total and phosphorylated protein kinase B (Akt) as well as total and phosphorylated eNOS were quantitatively assessed in mice penes using Western immunoblot and immunohistochemistry. In intact WT mice, VEGF145 significantly increased erectile responses, and in WT mice after castration, it completely recovered penile erection. However, VEGF145 failed to increase erectile responses in intact eNOS(-/-) mice and only partially recovered erectile function in castrated eNOS(-/-) mice. In addition, VEGF145 significantly increased phosphorylation of eNOS at Serine 1177 by approximately 2-fold in penes of both intact and castrated WT mice. The data provide a molecular explanation for VEGF stimulatory effect on penile erection, which involves phosphorylated eNOS (Serine 1177) mediation.

Adenoviridae↗
PubMed2002

Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection.

In the penis, nitric oxide (NO) can be formed by both neuronal NO synthase and endothelial NOS (eNOS). eNOS is activated by viscous drag/shear stress in blood vessels to produce NO continuously, a process mediated by the phosphatidylinositol 3-kinase (PI3kinase)/Akt pathway. Here we show that PI3-kinase/Akt physiologically mediates erection. Both electrical stimulation of the cavernous nerve and direct intracavernosal injection of the vasorelaxant drug papaverine cause rapid increases in phosphorylated (activated) Akt and eNOS. Phosphorylation is diminished by wortmannin and LY294002, inhibitors of PI3-kinase, the upstream activator of Akt. The two drugs also reduce erection. Penile erection elicited by papaverine is reduced profoundly in mice with targeted deletion of eNOS. Our findings support a model in which rapid, brief activation of neuronal NOS initiates the erectile process, whereas PI3-kinase/Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection.

Androstadienes↗
PubMed2002

Laparoscopic retroperitoneal lymph node dissection after chemotherapy.

OBJECTIVES: To assess the operative feasibility, clinical outcomes, and complications of laparoscopic retroperitoneal lymphadenectomy (RPLND) after chemotherapy. METHODS: A retrospective review of clinical records from 7 patients who underwent laparoscopic RPLND after chemotherapy was performed. Five patients presented with nonseminomatous germ cell tumor after orchiectomy. One patient was diagnosed with pure seminoma and one with epididymal small cell cancer. All 7 patients received multiagent chemotherapy for clinical Stage IIA or higher disease, followed by laparoscopic RPLND for findings of a residual retroperitoneal mass on computed tomography or a prechemotherapy mass size greater than 3.0 cm. The mean tumor diameter was 3.07 cm before chemotherapy and 1.91 cm after chemotherapy. A modified laparoscopic left (n = 3), right (n = 3), and bilateral (n = 1) template was used. None of the patients had received radiotherapy before surgery. RESULTS: Postchemotherapy laparoscopic RPLND was successfully completed in 5 (71.4%) of 7 patients. Two patients required a conversion to open surgery. The overall complication rate was 57.1% (4 of 7), with a major complication incidence of 42.8% (3 of 7). No mortalities were recorded. Of the 5 patients who presented with nonseminomatous germ cell tumor after orchiectomy, 3 were found to have retroperitoneal lymph nodes consistent with mature teratoma, 1 had necrotic tissue, and 1 had residual viable tumor. CONCLUSIONS: Laparoscopic RPLND is a feasible operation in patients after systemic chemotherapy. This technique remains challenging at this time and should be reserved for patients with limited residual disease and should only be performed at institutions with considerable laparoscopic expertise.

Adult↗
PubMedDate not supplied

A castrated mouse model of erectile dysfunction.

To establish a mouse model for the study of venoocclusive erectile dysfunction, we investigated erectile function in wild-type (WT), castrated (CAST), and castrated mice receiving immediate testosterone replacement (TEST). Adult C57BL6 mice ( approximately 30 g) underwent electrical stimulation of the cavernous nerve in vivo (parameters: 16 Hz frequency, 5 ms duration, 4V stimulatory voltage) with intracavernosal pressure (ICP) monitoring. A total of 55 mice (5 WT, 25 CAST, and 25 TEST) were evaluated. CAST and TEST (5.0 mg/pellet, 60-day release) mice were divided into groups of 5 and evaluated at 24 hours, 72 hours, 1 week, 2 weeks, and 4 weeks. Penile tissue was immunohistochemically stained for alpha-actin (marker for smooth muscle cells) and CD-31 (marker for endothelial cells). Stained slides were analyzed using Image Pro-plus software. In secondary studies, a Doppler flow meter was employed to evaluate penile blood flow. ICP measurements (mm Hg) were significantly decreased in CAST mice at 24 hour-, 72 hour-, 1 week-, 2 week-, and 4-week time points compared with WT mice (41.9 +/- 14.9, 19.1 +/- 4.2, 17.5 +/- 8.2, 14.2 +/- 4.4, and 10.0 +/- 3.8, respectively, vs 50.2 +/- 2.8), but TEST animals maintained or had an increase in ICP in comparison with WT mice (48.0 +/- 1.4, 52.3 +/- 1.3, 60.8 +/- 7.6, 80.5 +/- 2.1, and 81.5 +/- 1.2, respectively). Mean systemic arterial pressure remained approximately 80 mm Hg irrespective of treatment. CAST mouse penis specimens revealed decreased alpha-actin and CD-31 immunoreactivity only at the 4-week interval, compared with WT and TEST specimens. Doppler ultrasound flow rates (centimeter per second), taken before, during, and immediately after cavernous nerve stimulation, were WT 45.4 +/- 7.3, 30.6 +/- 5.2, 55.3 +/- 8.2 vs CAST (2 weeks) 22.2 +/- 2.5, 25.0 +/- 1.5, 23.1 +/- 2.0 vs TEST (2 weeks) 30.5 +/- 6.5, 25.7 +/- 2.0, 45.2 +/- 4.5. This prominently showed that intrapenile flow was not reduced normally during erectile stimulation in CAST mice. This is the first described mouse model of castration-induced veno-occlusive erectile dysfunction. Erectile response abnormalities as measured by ICP and Doppler ultrasound studies in CAST mice may be attributed to hypogonadal effects on erectile tissue function. Morphologic changes in the cavernosal tissue of CAST mice coincide with these abnormalities to some extent. This study defines an androgen-dependent mechanism of veno-occlusive erectile function in the mouse. The castrated mouse model can be applied in future studies of veno-occlusive erectile dysfunction.

Actins↗
PubMedDate not supplied

Robot-assisted laparoscopic dismembered pyeloplasty.

OBJECTIVE: Advanced laparoscopic skills limit the implementation of laparoscopic pyeloplasty to centers with extensive experience. The introduction of robotic technology into the field of minimally invasive surgery has facilitated complex surgical dissection and genitourinary reconstruction. We report our experience with robot-assisted laparoscopic pyeloplasty using the da Vinci Robotic Surgical System at 3 New York City medical centers. METHODS: A review of all robot-assisted laparoscopic Anderson-Hynes dismembered pyeloplasty cases in 38 patients (21 females, 17 males) between April 2001 and January 2004 was performed. All patients had symptoms or radiographic evidence of ureteropelvic junction obstruction. Robotic assistance with the da Vinci Robotic Surgical System was used after preparation of the ureteropelvic junction with a standard laparoscopic approach. RESULTS: The average patient age was 39.3 years (range, 15 to 69). The mean operative time and suturing time were 225.6+/-59.3 minutes and 64.2+/-14.6 minutes. The average estimated blood loss was minimal at 77.3+/-55.3 mL. The mean length of hospitalization was 69.6 hours (range, 28 to 310). The average use of intravenous morphine was 26.5 mg (range, 0 to 162). No intraoperative complications occurred, and open conversions were not necessary. A mean follow-up of 12.2 months revealed a success rate of 94.7% with 2/38 patients requiring further treatments. CONCLUSIONS: This combined multi-institutional series reveals that robot-assisted pyeloplasty with the da Vinci Surgical System is safe and reproducible. These intermediate results appear comparable to results with open and laparoscopic pyeloplasty repairs.

Adult↗