Epidural catheter replacement rates with dural puncture epidural labor analgesia compared with epidural analgesia without dural puncture: a retrospective cohort study.

BACKGROUND: Lumbar epidural analgesia (LEA) is commonly used for labor analgesia but up to 13% of epidural catheters fail and require replacement. Combined spinal-epidural analgesia is associated with a lower catheter failure rate. Few data exist regarding catheter replacement rates after dural-puncture epidural (DPE). We conducted a retrospective analysis comparing catheter failure rates between epidural and DPE techniques. METHODS: This retrospective single-center trial reviewed all labor neuraxial analgesia procedures among 18 726 women across five years, and identified 810 DPE and 2667 LEA procedures. Catheter failure rates, consisting of replacement or requirement of general anesthesia for cesarean delivery, were compared. Propensity score matching was used to balance the groups. RESULTS: Dural-puncture epidural was associated with significantly fewer catheter failures compared with LEA (74/759 vs. 49/759, odds ratio 0.64, 95% CI 0.44 to 0.93, P=0.02). Sensitivity analysis excluding cases of general anesthesia confirmed this relationship. Risk factors identified for catheter failure included age, body mass index, and nulliparity. Dural-puncture epidural was associated with a longer mean time to catheter replacement (918 min vs. 609 min, P=0.04). Kaplan-Meier and Cox multivariate analyses confirmed this relationship. There was no significant difference in the requirement for epidural analgesia supplementation, but DPE required supplementation significantly later than LEA. There was no difference in the rate of headache or epidural blood patch between groups. CONCLUSIONS: Dural-puncture epidural is associated with fewer catheter failures and replacements than LEA, without an increase in the rate of post-dural puncture headache or epidural blood patch.

Low-dose intravenous dexmedetomidine reduces shivering following cesarean delivery: a randomized controlled trial.

BACKGROUND: Intravenous dexmedetomidine 30 µg reduces shivering after cesarean delivery but can result in sedation and dry mouth. We hypothesized that prophylactic administration of 10 µg of IV dexmedetomidine would reduce the patient-reported severity of shivering after cesarean delivery, without an increased incidence of side effects. METHODS: After institutional review board approval and informed written consent, women undergoing scheduled cesarean delivery with spinal or combined spinal-epidural anesthesia were randomized to receive either intravenous normal saline or dexmedetomidine 10 µg immediately after delivery. The primary outcome was a patient-rated subjective shivering score using a 10-cm visual analog scale at 30 and 60 min after arrival in the Post-Anesthesia Care Unit. Secondary outcomes included subjective scores for pain, nausea, itching, dry mouth, and sedation, as well as 24-h medication administration and investigator-rated observations of shivering, vomiting, pruritus, and sedation. Repeated measures ANOVA with Tukey-Kramer multiple-comparison test was applied for primary outcomes. RESULTS: One hundred patients were enrolled, and 85 completed the study and were included in analysis. The mean ±â€¯SD shivering score in the dexmedetomidine group was significantly lower by repeated measures analysis than among controls across the first 60 min (P=0.0002), and individually at both 30 and 60 min (placebo 1.8 ±â€¯2.6 vs. dexmedetomidine 0.6 ±â€¯1.4 at 30 min; 1.2 ±â€¯2.1 vs. 0.3 ±â€¯0.6 at 60 min; both P <0.01). Patient-rated and observer-rated side effects did not significantly differ between groups. CONCLUSIONS: Prophylactic administration of intravenous dexmedetomidine 10 µg after delivery reduces shivering without notable side effects.

Successful reinsertion of the artificial urinary sphincter after removal for erosion or infection.

We present 5 cases involving reinsertion of an artificial urinary sphincter after either erosion or infection. All 5 patients now have socially acceptable urinary continence.

Femoral nerve neuropathy after the psoas hitch procedure.

We report the first 3 cases of femoral nerve neuropathy after a psoas hitch vesicopexy, a technique commonly used with ureteroneocystostomy. The condition in 2 patients resolved with conservative therapy, and the third patient required reoperation with removal of an offending suture. All 3 patients recovered completely with no residual neurologic deficit. Urologists who use the psoas hitch must be familiar with this potential complication to prevent its occurrence.

Long-term experience with the double-cuff AMS 800 artificial urinary sphincter.

OBJECTIVES: To assess the efficacy and safety of the double-cuff artificial urinary sphincter over a long-term period. METHODS: Ninety-five patients charts were reviewed from December 1986 to November 1995. Data on the degree of urinary incontinence and complications were compiled and tabulated. RESULTS: There were 10 cuff erosions (10.5%) and one infection (1.1%) requiring removal of the double-cuff system, with one death from unrelated causes. Two patients in the erosion group had a double-cuff system reinserted at a later date. Eighty-six patients have a double-cuff system, with 97.6% remaining dry. CONCLUSIONS: A tandemly placed double-cuff artificial urinary sphincter is safe and effective in the treatment of severe postprostatectomy urinary incontinence.

Antitumor activity of ER-51785, a new peptidomimetic inhibitor of farnesyl transferase: synergistic effect in combination with paclitaxel.

Inhibitors of ras farnesylation have been extensively studied in the preclinical stage, and some of them are being developed in the clinic. Herein, we describe the antitumor activity of a new farnesyl transferase inhibitor, ER-51785. In vitro, ER-51785 selectively inhibited farnesyl transferase activity (IC50 = 77 nM) compared with geranylgeranyl transferase I activity (IC50 = 4200 nM). In cells, ER-51785 inhibited posttranslational processing of H-ras with IC50 = 28 nM, but not that of rap 1A at concentrations up to 50 microM. This compound also strongly inhibited colony formation of H-ras-transformed NIH 3T3 fibroblasts and EJ-1 bladder carcinoma cells. In vivo, ER-51785 showed potent tumor regression activity against EJ-1 xenografts but only modest activity against MIA PaCa-2 xenografts. Treatment of ER-51785 in combination with paclitaxel exhibited synergistic effects against colony formation and tumor growth of MIA PaCa-2 cells. The results presented herein support the idea that farnesyl transferase inhibitors alone and in combination with other chemotherapeutic agents have the potential to be developed as therapies for tumors expressing H-ras or K-ras oncogenes.

Office evaluation of the patient with an overactive urinary bladder.

Urinary incontinence affects between 13 and 17 million men and women in the United States, with an annual cost exceeding $26 billion. Overactive urinary bladder can be both neurologic (hyperreflexia) and nonneurologic (detrusor instability). The spontaneous involuntary detrusor contractions that occur with the overactive bladder often lead to urinary incontinence. Symptoms vary from patient to patient, with urgency, increased frequency, and urinary urge incontinence being the most bothersome complaints. Multiple components and interactions of the nervous system are required for appropriate storage and evacuation function of the bladder to occur normally. Thorough history taking and physical examination along with appropriate urodynamic testing are necessary for obtaining an accurate diagnosis and treatment planning. The quality of life for many patients with overactive bladder and the resulting incontinence can be dismal. Fortunately, most of these patients can be treated successfully.

Penile curvatures and aneurysmal defects with the Ultrex penile prosthesis corrected with insertion of the AMS700CX.

PURPOSE: We reviewed our series of patients with an AMS700 Ultrex penile prosthesis whose erectile deformities were corrected by replacement with AMS700CX cylinders. MATERIALS AND METHODS: Ultrex cylinders were replaced by AMS700CX cylinders in 7 men with erectile deformities. RESULTS: Deformities were corrected successfully in all 7 patients. The penis is completely straight in 6 patients, while a mild 30-degree ventral curvature is present in 1. CONCLUSIONS: Erectile deformities with the AMS700 Ultrex penile prosthesis can be repaired successfully by replacement with the AMS700CX cylinders.

Use of the artificial urinary sphincter in women.

Persistent urinary incontinence after failed surgical repair can be successfully treated with the artificial urinary sphincter. The English literature was reviewed from 1985 to 1996. Eleven articles and abstracts addressing placement of the artificial urinary sphincter in women were identified. Discussion includes two operative techniques. Success rates were in the range of 91%-99%. Erosion rates were 7%-29%. The artificial urinary sphincter is an effective treatment for women failing other procedures. Appropriate work-up and diagnosis for type III stress urinary incontinence is crucial.

Erosion rate of the double cuff AMS800 artificial urinary sphincter: long-term followup.

PURPOSE: We reviewed the erosion rate of the double cuff artificial urinary sphincter. MATERIALS AND METHODS: Charts of 95 patients were evaluated for erosions and underlying etiology. RESULTS: Ten patients had erosion of the cuffs, for an erosion rate of 10.5%. Of the 10 erosions 4 (40%) were secondary to iatrogenic injuries. CONCLUSIONS: Addition of a second cuff to the artificial urinary sphincter remains a safe alternative for patients with severe urinary stress incontinence.

Peptidomimetic inhibitors of Ras farnesylation and function in whole cells.

The ras protooncogene is involved in regulation of cell growth. Mutations that activate the protein result in uncontrolled cell growth. Ras undergoes a series of posttranslational processing events, the first of which, farnesylation, is crucial for the function of the protein. Inhibitors of the farnesyltransferase enzyme are therefore potential candidates for the development of anticancer drugs. Tetrapeptides have been reported to be good inhibitors of this enzyme in vitro. We have synthesized analogs of the tetrapeptide Cys-Val-Phe-Met by replacement of the amino-terminal amide bonds. One inhibitor, B581, is permeable to the cell membrane. In the cell, it inhibits processing of two farnesylated proteins, H-ras and lamin A, but it does not inhibit processing of a geranylgeranylated protein, Rap 1A. Microinjection of B581 into frog oocytes inhibits maturation induced by activated, farnesylated H-ras but not maturation induced by activated, geranylgeranylated H-ras or by progesterone. These results demonstrate that this peptide mimic inhibits farnesylation selectively in the cell. The inhibition of farnesylation results in inhibition of H-ras function.

Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo.

It has recently been reported that Ki-Ras protein can be modified in vitro by farnesylation or geranylgeranylation. However, a previous analysis of Ki-Ras prenylation in vivo found only farnesylated Ki-Ras. In this report it is shown that under normal conditions, Ki-Ras is farnesylated in vivo and when cells are treated with the farnesyl transferase inhibitors B956 or B957, farnesylation is inhibited and Ki-Ras becomes geranylgeranylated in a dose dependent manner. These results have strong implications in the design of anticancer drugs based on inhibition of prenylation.

Synthesis and evaluation of some hydroxyproline-derived peptidomimetics as isoprenyltransferase inhibitors.

CA1A2X peptidomimetics containing a modified proline at position A2 were prepared and evaluated for their ability to inhibit farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) in enzymatic and cell-based assays. These compounds inhibited farnesylation of H-ras in vitro in the high nanomolar to low micromolar IC50 range.

The CAAX peptidomimetic compound B581 specifically blocks farnesylated, but not geranylgeranylated or myristylated, oncogenic ras signaling and transformation.

Recently developed CAAX peptidomimetic compounds have been shown to be potent and specific inhibitors of farnesyl protein transferase activity and to block the growth of Ras-transformed cells. However, whether this growth inhibitory action is specifically a consequence of blocking oncogenic Ras signaling has not been determined. To address this question, we have utilized mutants of the normally farnesylated oncogenic Ras protein (Ras-F) that are modified by alternative lipids, a geranylgeranyl isoprenoid (Ras-GG) or the fatty acid myristate (Myr-Ras), to determine the specificity of the CAAX peptidomimetic compound, B581. Like Ras-F, both Ras-GG and Myr-Ras are membrane-associated and transforming. Unexpectedly, NIH 3T3 cells transformed by each of the three Ras mutants underwent morphological alteration to a less transformed, but not normal, morphology. However, B581 inhibited the ability of only Ras-F-transformed cells, but not Ras-GG- or Myr-Ras- (or Raf-) transformed cells, to grow in soft agar. Furthermore, although all three lipid-modified versions of Ras stimulated mitogen-activated protein kinase activation, and both Jun and Elk-1 transcriptional activity, B581 inhibited only farnesylated Ras activation of these three downstream components of Ras signaling. Therefore, B581 prevents the growth of Ras-transformed cells by specifically antagonizing Ras-mediated signaling.