AAA in KAT/DYKAT processes: first- and second-generation asymmetric syntheses of (+)- and (-)-cyclophellitol.

Kinetic resolutions and kinetic asymmetric transformations (KAT) as well as dynamic kinetic resolutions and dynamic kinetic asymmetric transformations (DYKAT) are important synthetic protocols. The feasibility of KAT and DYKAT processes for asymmetric allylic alkylations (AAA) is explored utilizing a single substrate--conduritol B tetraesters. Both processes can be performed resulting in excellent enantioselectivity. The impact of nucleophile and leaving group on the effectiveness of each is outlined. The ability to differentiate the various hydroxyl groups is also described. For this purpose, 4-tert-butyldimethylsiloxy-2,2-dimethylbutyric acid was developed as a nucleophile. The utility of effecting KAT/DYKAT processes through the Pd-catalyzed AAA reaction is demonstrated by efficient syntheses of both enantiomers of the potent glycosidase inhibitor cyclophellitol.

Is nephroureterectomy necessary in all cases of upper tract transitional cell carcinoma? Long-term results of conservative endourologic management of upper tract transitional cell carcinoma in individuals with a normal contralateral kidney.

OBJECTIVES: To evaluate the endoscopic management of upper urinary tract transitional cell carcinoma (TCC) as a first-line treatment in patients with a normal contralateral kidney. METHODS: During an 11-year period, 21 patients diagnosed with upper tract TCC were treated with conservative endourologic techniques using either neodymium:yttrium-aluminum-garnet laser or electrocautery at our institution. The 21 patients were followed up for a mean of 6.1 years (range 1 to 11.6). RESULTS: A total of 8 renal pelvic tumors and 13 ureteral tumors were found. All tumors were Stage T1 or less and grade 3 or less. All tumors were less than 2 cm in the greatest dimension (range 0.4 to 2). Of the 21 patients, 7 (33%) had one local recurrence and 1 (4.7%) developed two local recurrences. Of the 13 ureteral tumors, 6 (46%) recurred; 1 (12%) of the 8 renal pelvic tumors recurred. No recurrent tumor was shown to have an increase in grade. Of the 21 target renal units, 17 (81%) were preserved; 4 (19%) of 21 patients required nephroureterectomy because of tumor recurrence. Overall, 11 patients in the series died, 10 of non-TCC etiology and 1 secondary to invasive bladder TCC that developed after treatment for upper tract TCC. No patients died as a result of conservative management of their upper tract TCC. CONCLUSIONS: Endourologic techniques and conservative treatment of upper tract TCC is an evolving field; however, in properly selected patients, endoscopic treatment can be safely and effectively used as a first-line treatment for upper tract TCC.

Quality vascular surgical care: the importance of innovation and change in an era of dwindling reimbursement.

BACKGROUND: Reductions in vascular surgery reimbursement emphasize the need to decrease cost while maintaining quality. Hospital solvency is essential if we are to preserve acceptable levels of nursing/support personnel and acquire new diagnostic and treatment programs. METHODS: Care processes for patients undergoing carotid, aortic, or dialysis access surgery were retrospectively analyzed and new quality- and cost-oriented treatment algorithms and clinical pathways were developed and implemented using case management principles. Preoperative risk stratification, length of stay, costs, complications, outcomes, and patient satisfaction were compared before and after these revisions in the care process. Statistical analyses were done using the Wilcoxon Rank sum test and Fisher exact test. RESULTS: Significant reductions in length of stay, intensive care use, and cost of treatment and diagnosis were achieved without adversely affecting morbidity, mortality, or patient satisfaction. CONCLUSION: Use of algorithm, clinical pathway, and case management principles resulted in a marked improvement in the "bottom line" for vascular surgical procedures in our academic medical center.

Retroperitoneal approach for aortic surgery: is it worth it?

BACKGROUND: Previous reports suggest that earlier hospital discharges and reduced postoperative complications occur when a retroperitoneal approach is used for aortic surgery. Other publications refute this concept. In an effort to determine the most cost efficient method for aortic surgery in our institution, while maintaining high standards of care and outcome, we compared the retroperitoneal approach to the conventional transperitoneal aortic operation. PATIENTS AND METHODS: Between December 1995 and April 1998, 120 patients underwent aortic surgery by either the transperitoneal (n=60) or retroperitoneal approach (n=60). All patients were enrolled prospectively in a vascular registry and retrospectively reviewed. Patients were randomly assigned to one of three vascular surgeons. A clinical pathway for elective aortic surgery was developed and applied to both groups. Patients were evaluated with respect to demographics, comorbidities, preoperative risk stratification, conduct of the operative procedure, length of stay, complications, cost, clinical outcomes and patient satisfaction. The indications for aortic surgery were similar in both groups - 64% for aneurysm disease and 36% for occlusive disease. Both symptomatic and asymptomatic aneurysms were included and size ranged from 4.4 to 14cm. All aortic reconstructions were done in the standard manner using knitted Dacron velour prostheses in either the aortic tube, bi-iliac or bi-femoral configuration. Statistical analysis of means and medians was accomplished using the Wilcoxin Rank-sum test and percentages were compared using Fisher's Exact test. P values less than 0.05 indicate statistical significance. RESULTS: There were no statistically significant differences in patient demographics. The incidence of atherosclerotic coronary artery disease, obstructive pulmonary disease, diabetes, hyperlipidemia, tobacco abuse, distal lower extremity occlusive disease and the results of chemical myocardial stress evaluations were similar in both groups. Comorbidities of pre-existing renal insufficiency/failure and morbid obesity were increased in the retroperitoneal group. Five patients in the retroperitoneal group represented redo aortic surgery and there were no redo procedures in the transperitoneal group. Length of operative procedures and blood replacement requirements for both groups were similar. The transperitoneal group required 2-3l more intraoperative intravenous (IV) crystalloid than the retroperitoneal group (P<0.0001). Statistically significant reductions in ICU days, postoperative ileus and total lengths of stay were observed in the retroperitoneal group (P<0.0001). This resulted in substantial reductions in hospital costs for the retroperitoneal group (P<0.01). Postoperative complications were similar for both groups except for statistically significant increases in pulmonary edema (P<0.01) and pneumonia (P<0.001) in the transperitoneal group. Cardiac arrhythmias, primarily atrial dysrhythmias, were more frequent in the transperitoneal group but this failed to reach statistical significance (P<0.16). Combined thirty day mortality was 0.9%. Time of recovery to full activity and patient satisfaction substantially favored the retroperitoneal group. CONCLUSION: Our clinical pathway and algorithm for aortic surgery was easily followed by those patients in the retroperitoneal approach group and resulted in decreases in ICU time, postoperative ileus, volume of intraoperative crystalloid and total length of stay. The patients in the transperitoneal group often failed to progress appropriately on the pathway. Reduced hospital costs associated with aortic surgery using the retroperitoneal approach has increased the profitability for this surgery in our institution by an average of $4000 per case and has increased the value (quality/cost) of this surgery to our patients and our institution.

Suggested treatment protocol for improving patency of femoral-infrapopliteal cryopreserved saphenous vein allografts.

PURPOSE: Cryopreserved saphenous vein allografts are used for femoral-infrapopliteal bypass graft purposes when adequate autogenous vein is unavailable. Anticoagulation, immunosuppression therapy, or both have been suggested means for improving allograft patency. Immunosuppression has significant cost and morbidity and has produced variable results. Our successful treatment of luminal surface hypercoagulability associated with certain endovascular procedures prompted the use of an anticoagulation protocol prospectively to improve graft patency and limb salvage for patients receiving femoral-infrapopliteal cryopreserved saphenous vein allografts. METHODS: Between September 1995 and October 1999, 24 patients (15 men and nine women) were enrolled in a prospective clinical trial for salvage of 26 severely ischemic lower limbs with femoral-infrapopliteal cryopreserved saphenous vein allograft bypass grafts. All patients were treated with a protocol (aspirin, low-dose heparin, low molecular weight dextran 40, dipyridamole, and warfarin), and no immunosuppressive agents were used. The cryopreserved saphenous vein allografts were matched to patients by ABO and Rh compatibility. Indications for revascularization were ischemic rest pain (n = 8), nonhealing ulcer (n = 13), or focal gangrene (n = 5), and no usable autogenous vein was available. Follow-up ranged from 2 to 35 months (mean, 19 months). We studied the location and type of outflow anastomosis, specific outflow vessel, morbidity, death, secondary procedures (digital/transmetatarsal amputation), and complications related to the treatment protocol. Life table analyses of primary graft patency and limb salvage were compared with other current reported data. RESULTS: Primary graft patency with Kaplan-Meier life table analysis was 96% at 6 months, 87% at 12 months, and 82% at 18 and 24 months. There were no reoperations for acute graft occlusion. One graft underwent late segmental aneurysmal degeneration and rupture. There were no procedure-related deaths or bleeding complications. During late follow-up, anticoagulation was discontinued in three patients (12%) because of gastrointestinal bleeding. Limb salvage was 88% at 6 months and 80% at 12, 18, and 24 months. Patients returned to ambulatory status that was limited only by their other comorbidities. CONCLUSION: Femoral-infrapopliteal bypass graft for limb salvage with a cryopreserved saphenous vein allograft can be an acceptable alternative when autogenous vein is not available. Our treatment protocol substantially improved allograft patency and limb salvage when compared with current published data.

Benefit of adjuvant radiation therapy for localized prostate cancer with a positive surgical margin.

PURPOSE: Positive surgical margins are common after radical prostatectomy, and the role of adjuvant therapy in such cases is controversial. We determined the benefit of postoperative external beam radiation therapy in patients with margin positive prostate cancer with respect to biochemical progression or cancer recurrence. To decrease confounding factors that may affect the likelihood of biochemical progression our study was limited to men with organ confined cancer and a single positive margin. MATERIALS AND METHODS: We retrospectively evaluated the records of a nested matched cohort of 76 patients with pathological stage T2N0 prostate cancer and a single positive margin who underwent adjuvant radiation therapy within 3 months of radical prostatectomy. There was a positive margin at the prostatic apex in 35 cases, prostatic base in 18, posterior prostate in 11, urethra in 7, and prostatic apex and urethra in 5. These patients were matched 1:1 with 76 controls who did not receive adjuvant radiation therapy. Neither group received androgen deprivation therapy. Patients and controls were matched exactly for the margin positive site, age at surgery, preoperative serum prostate specific antigen, Gleason score and DNA ploidy. Biochemical relapse was defined as posttreatment PSA greater than 0.2 ng./ml. RESULTS: Overall there was significant estimated improvement plus or minus standard error in 5-year clinical and biochemical progression-free survival in 88%+/-5% versus 59%+/-11% of patients treated with adjuvant radiation therapy versus no radiation therapy (p = 0.005). No patient who received radiation therapy had local or distant recurrence, while 16% of controls had recurrence (p = 0.015). When stratified by site of margin positivity, the 5-year estimated clinical and biochemical progression-free rate in 18 cases and controls with a positive base margin was 95%+/-15% and 65%+/-13%, respectively (p = 0.02). The rate in 35 cases and cases with a positive apex margin was 95%+/-5% and 64%+/-15%, respectively (p = 0.07). Limited sample size precluded analysis of the other sites. CONCLUSIONS: Patients with localized prostate cancer and a singe positive surgical margin appear to have a lower rate of biochemical relapse at 5 years when adjuvant radiation therapy is administered. Definitive evidence of the beneficial effect of adjuvant radiation therapy for patients with involved surgical margins awaits conclusion of randomized clinical trials.

Combined carotid endarterectomy with transluminal angioplasty and primary stenting of the supra-aortic vessels.

BACKGROUND: Carotid endarterectomy (CEA) is the standard of care for patients with high-grade carotid artery stenosis who are acceptable surgical candidates. Focal occlusive lesions of the origin of aortic arch vessels can be effectively and safely treated with balloon angioplasty and primary stenting. The purpose of this study was to retrospectively review results of carotid endarterectomy for high-grade carotid bifurcation stenosis combined with intraoperative retrograde transluminal angioplasty and primary stenting of a hemodynamically significant stenosis at the origin of a proximal ipsilateral aortic arch vessel. METHODS: Between October 1994 and August 1998, 592 patients underwent CEA. Six patients were found to have hemodynamically significant tandem lesions affecting one of the aortic arch vessels and the ipsilateral ICA for an overall incidence of 1%. Age ranged from 63 to 78 years (mean 74.7). Four of 6 (67%) patients had asymptomatic lesions, and 2 of 6 (33%) had symptoms of cerebral ischemia. Five patients had tandem lesions affecting the proximal left common carotid artery and the left ICA. One patient had a tandem lesion affecting the innominate artery and the right ICA. Carotid duplex imaging and arch and cerebral arteriography was performed in all six patients. Arteriography confirmed high-grade stenoses in both the ICA and ipsilateral proximal aortic arch vessel. The range of stenoses in the ICA was 70 to 95% (mean 80.8%) measured arteriographically. The range of stenoses at the origin of the aortic arch vessels was 75-90% (mean 79.2%). All six patients underwent combined retrograde transluminal balloon angioplasty and primary stenting of the ipsilateral CCA or innominate artery with temporary occlusion of the ICA for cerebral protection. The endovascular procedure was then followed with standard surgical endarterectomy using an inline shunt. RESULTS: All six procedures were successfully completed. There were no periprocedural strokes or other morbidities. Follow-up ranged from 6 to 43 months (mean 23.6) and showed no evidence of recurrent stenosis by carotid duplex imaging. No TIAs or strokes related to the surgically corrected lesions were noted during the follow-up period. One patient suffered a right hemispheric stroke secondary to a high-grade right carotid stenosis which occurred two months after her procedure surgically correcting tandem lesions on the opposite side. CONCLUSIONS: Carotid endarterectomy with balloon angioplasty and primary stenting of an ipsilateral hemodynamically significant aortic arch trunk vessel stenosis can be safely and successfully accomplished and avoids the need for an intra/extrathoracic bypass procedure.

Visualizing substructural fingerprints.

Substructural fingerprints have proven very useful for chemical library and diversity analysis, but their high dimensionality makes them poorly suited to principal components analysis and to standard nonlinear mapping methods. By using a combination of optimizable K-dissimilarity selection (OptiSim) and a modified stress function that suppresses effects of distances that fall beyond a characteristic horizon, it is possible to relax principal components analysis coordinates into more consistently meaningful projections from fingerprint space into two dimensions. The nonlinear maps so obtained are useful for characterizing combinatorial libraries, for comparing sublibraries, and for exploring the distribution of biological properties across structural space.

Economic considerations for aortic surgery: retroperitoneal approach--is it worth it?

BACKGROUND: Planned reductions in reimbursement for all forms of vascular surgery dictate a need for the development of more cost efficient, yet quality oriented, treatment programs. We are faced with an increasingly older patient population with multiple comorbidities. In this environment it will become extremely difficult to accomplish aortic surgery in a way which will be profitable for our hospitals. More than 100,000 aortic surgeries are performed annually in the United States. Previous reports suggest that earlier hospital discharges and reduced postoperative complications occur when a retroperitoneal approach is used for aortic surgery. Other publications refute this concept. In an effort to determine the most cost efficient method for aortic surgery in our institution, while maintaining high standards of care and outcome, we compared the retroperitoneal approach to the conventional transperitoneal aortic operation. PATIENTS AND METHODS: Between December 1995 and April 1998, 120 patients underwent aortic surgery by either the transperitoneal (n = 60) or retroperitoneal approach (n = 60). All patients were enrolled prospectively in a vascular registry and retrospectively reviewed. Patients were randomly assigned to one of three vascular surgeons. A clinical pathway for elective aortic surgery was developed and applied to both groups. Patients were evaluated with respect to demographics, comorbidities, preoperative risk stratification, conduct of the operative procedure, length of stay, complications, cost, clinical outcomes and patient satisfaction. The indications for aortic surgery were similar in both groups--64% for aneurysm disease and 36% for occlusive disease. Both symptomatic and asymptomatic aneurysms were included and size ranged from 4.4 cm to 14 cm. All aortic reconstructions were done in the standard manner using knitted Dacron velour prostheses in either the aortic tube, bi-iliac or bi-femoral configuration. Statistical analysis of means and medians was accomplished using the Wilcoxin Rank-sum test and percentages were compared using Fisher's Exact test. P values less than 0.05 indicate statistical significance. RESULTS: There were no statistically significant differences in patient demographics. The incidence of atherosclerotic coronary artery disease, obstructive pulmonary disease, diabetes, hyperlipidemia, tobacco abuse, distal lower extremity occlusive disease and the results of chemical myocardial stress evaluations were similar in both groups. Comorbidities of preexisting renal insufficiency/failure and morbid obesity were increased in the retroperitoneal group. Five patients in the retroperitoneal group represented redo aortic surgery and there were no redo procedures in the transperitoneal group. Length of operative procedures and blood replacement requirements for both groups were similar. The transperitoneal group required 2-3 liters more intraoperative intravenous (i.v.) crystalloid than the retroperitoneal group (p < 0.0001). Statistically significant reductions in ICU days, postoperative ileus and total lengths of stay were observed in the retroperitoneal group (p < 0.0001). This resulted in substantial reductions in hospital costs for the retroperitoneal group (p < 0.01). Postoperative complications were similar for both groups except for statistically significant increases in pulmonary edema (p < 0.01) and pneumonia (p < 0.001) in the transperitoneal group. Cardiac arrhythmias, primarily atrial dysrhythmias, were more frequent in the transperitoneal group but this failed to reach statistical significance (p < 0.16). Combined thirty day mortality was 0.9%. Time of recovery to full activity and patient satisfaction substantially favored the retroperitoneal group. CONCLUSION: Our clinical pathway and algorithm for aortic surgery was easily followed by those patients in the retroperitoneal approach group and resulted in decreases in ICU time, postoperative ileus, volume of intraoperative crystalloid and total length of stay. The patients in the transperitoneal group often failed to progress appropriately on the pathway. Reduced hospital costs associated with aortic surgery using the retroperitoneal approach has increased the profitability for this surgery in our institution by an average of $4000 per case and has increased the value (quality/cost) of this surgery to our patients and our institution. This was accomplished in an academic environment with surgical residency training where cost containment has historically been difficult.

Mobile atheroma of the aortic arch and the risk of carotid artery disease.

BACKGROUND: Mobile atheromas of the aortic arch are associated with otherwise unexplained strokes and transient ischemic attacks (TIA). They are associated with increased perioperative strokes in patients undergoing coronary artery bypass surgery. Peripheral embolization is an additional risk. Transesophageal echocardiography (TEE) accurately identifies mobile atheroma. Anticoagulant therapy may have therapeutic considerations in the management of this condition. However, the risk of significant carotid artery disease associated with mobile atheromas is unknown. METHODS: Between March 1994 and July 1998, 40 patients with mobile atheromas by TEE and evidence of embolization were studied. All patients were captured prospectively in a vascular registry and were retrospectively reviewed. Carotid artery disease was evaluated using carotid duplex imaging in an accredited vascular laboratory. All patients with significant carotid disease, 70% or greater stenosis, underwent arteriography. Patients with significant carotid artery stenosis then underwent carotid endarterectomy. All patients with mobile atheromas were maintained on anticoagulation. RESULTS: Forty patients with mobile atheromas of the aortic arch were diagnosed with TEE. All 40 patients had evidence of embolization. Patient age ranged from 57 to 73 years (mean 68.4). There were 22 men and 18 women. Twenty of 40 (50%) patients presented with symptoms of TIA. Eleven of 40 (28%) patients presented with diffuse atheroembolization (lower extremity embolization and renal insufficiency). Six of 40 (15%) patients presented with a completed stroke. Three of 20 (7%) patients presented with acute extremity ischemia secondary to a peripheral embolus. Twenty-three of 40 (58%) of patients had significant carotid artery stenosis, 70% or greater stenosis. These 23 patients underwent both arteriography and carotid endarterectomy without complication. All patients were treated with anticoagulation and have remained anticoagulated. Clinical follow-up between 2 to 48 months (mean 18) has demonstrated no further evidence of systemic embolization in these 40 patients. Repeat TEE was performed in 6 of 40 patients. These follow-up studies no longer visualized mobile atheromas. CONCLUSIONS: Mobile atheromas are recognized sources for embolization. Routine carotid duplex imaging should be performed in patients found to have mobile atheromas of the aortic arch. Carotid endarterectomy appears to be safe in patients who have combined carotid artery stenosis and mobile atheromas. Anticoagulation may have therapeutic considerations in the management of this condition.

Prediction of stone composition from plain radiographs: a prospective study.

BACKGROUND AND OBJECTIVES: Stone composition, as reflected in radiographic appearance, is important to help choose between SWL and percutaneous/endoscopic procedures. Predicting a stone's composition accurately from a plain radiograph would be a useful tool in clinical decision-making. However, the ability of physicians to predict composition has not been adequately assessed. A prospective study was designed to quantify the accuracy of a panel of physicians who routinely deal with stones in classifying stone composition solely from radiographs. MATERIALS AND METHODS: A panel of six members was created to review 100 plain-film radiographs from patients with renal stones of known composition. The panel consisted of two urologists, two radiologists, and two nephrologists, all of whom have expertise in stone disease. If the composition guessed was at least 40% of the total stone composition, the response was deemed correct. RESULTS: Overall, there was an average 39% correct response score among the six panelists. When the stones were divided by size, 35% were <1 cm, and 65% were larger. The accuracy of chemical composition determination did not improve with greater stone size, nor was there a difference in accuracy for pure and mixed stones. The most frequently misclassified stone was calcium phosphate, with only 14% being correctly diagnosed. CONCLUSIONS: With a random sampling of plain radiographs, a panel of physicians specializing in stone disease correctly diagnosed the composition of renal calculi less than half of the time without being given clinical information.

Value of an endovascular suite in the operating room.

The purpose of this study is to describe the advantages and value of an endovascular suite in the operating room from a vascular surgeon's perspective. All endovascular procedures were performed in a specially equipped operating room by vascular surgeons using digital fluoroscopic imaging equipment. Between January 1, 1994 and August 31, 1996, intraoperative balloon angioplasties were attempted by vascular surgeons in 102 patients with insertion of 22 stents. Angioplasties were performed for stenoses in 50 arterial bypasses and 25 iliac, 17 femoral and 10 popliteal arteries proximal or distal to arterial grafts. Sixty-two procedures were performed concomitantly with a surgical bypass and 40 were performed as the sole procedure (30 percutaneous, 10 open) in patients who had previously undergone a bypass. There were five technically unsatisfactory results which were converted to surgical procedures and one postoperative hematoma that required surgical repair. Ninety of the 102 grafts remained patent more than 1 month after the procedure. Establishment of an endovascular operating room suite enables vascular surgeons to perform adjunctive endovascular procedures concomitantly with vascular surgery and treat unexpected findings in the operating room amenable to endovascular intervention without requesting other interventionalists to participate on an emergent basis.

Speech dysfunction due to trazodone--fluoxetine combination in traumatic brain injury.

New serotonin reuptake inhibitors are available for the treatment of affective disorders and sleep dysfunction in traumatic brain injury (TBI) patients. Commonly reported serotonergic side-effects include nausea, headache, dizziness, nervousness and orthostatic hypotension. Trazodone, a non-selective serotonin reuptake inhibitor, is often used in conjunction with fluoxetine, a selective serotonin reuptake inhibitor, in order to combat the insomnia associated with fluoxetine. Successful use of this combination is generally limited by the cumulative serotonergic side-effects of the two medications. This paper describes the first reported case of speech dysfunction as a complication of combined trazodone and fluoxetine use. A 43-year-old male suffered bilateral wrist fractures and a moderate TBI during a fall. Within 1 week of adding fluoxetine to trazodone the patient developed new-onset dysarthria and speech blocking. Upon discontinuation of fluoxetine, speech returned to normal. Possible mechanisms include inhibition of hepatic metabolism, unmasking of caudate nucleus injury, increased noradrenergic activity or previously unreported serotonergic effects. This case illustrates the importance of monitoring drug combinations for unexpected side-effects in the TBI population.

Ureteroscopy: current practice and long-term complications.

PURPOSE: We compared a current cohort of patients who underwent ureteroscopy to a cohort from the early 1980s to determine changes in success, indications and long-term complications of the procedure. MATERIALS AND METHODS: A chart review was performed of 194 patients who underwent 209 ureteroscopic procedures at our institution during 1992. This group was then statistically compared to 317 patients who underwent 346 ureteroscopies between 1982 and 1985. RESULTS: The current indications for ureteroscopy were calculus extraction (67% of the cases), diagnosis (28%) and stent manipulation (5%). These indications differed from those of the early series, in which 84% of all ureteroscopies were performed for calculus extraction and 16% for diagnosis. Overall ureteroscopic success rate increased from 86 to 96% (p < 0.001). Success of stone extraction improved from 89 to 95% (p = 0.08, distal success rate 95 to 97% and proximal success rate 72 to 77%). Success of diagnostic inspections increased from 73 to 98% (p < 0.001). In the early series failure was usually due to inability to traverse the ureter (54% of the cases), while currently failure is due almost exclusively to impassable ureteral strictures (63%). The overall complication rate decreased from 20 to 12% (p = 0.01) and the rate of significant complications decreased from 6.6 to 1.5% (p < 0.05). Clinical followup (mean 36 months) for all patients and radiological followup (mean 9.8 months) for 67% of eligible patients detected only 1 ureteral stricture. The remaining patients were asymptomatic after the ureteroscopic procedure. CONCLUSIONS: Improvements in ureteroscope design, accessories and technique have led to a significant increase in the success of diagnostic and therapeutic ureteroscopy while decreasing morbidity. Outpatient ureteroscopic stone extraction, particularly for distal ureteral calculi, is almost uniformly successful with low morbidity. The long-term complication rate of ureteroscopy is 0.5%.

Thrombolytic and endovascular treatment of peripartum iliac vein thrombosis: a case report.

This case report details the multidisciplinary treatment of peripartum left iliac vein thrombosis using percutaneous catheter-directed urokinase thrombolysis and balloon thromboplasty. Enhanced chances for long-term patency and the normalization of venous function make these minimally invasive procedures accepted options for the treatment of iliofemoral deep venous thrombosis in selected peripartum patients.

Transurethral microwave thermotherapy v sham treatment: double-blind randomized study.

Transurethral microwave thermotherapy (TUMT) is a single-session, 1-hour office-based treatment for benign prostatic hyperplasia. A randomized, double-blind study has been conducted at our institutions involving 115 patients who, after satisfying the entry criteria, were randomized in a 2:1 fashion to receive TUMT or a sham treatment. Three months' unblinding revealed both statistically and clinically significant improvement in the efficacy measures for the real treatment compared with the sham. The mean Madsen Symptom Score decreased 55% and the mean peak flow rate increased 58% in the TUMT-treated patients v 28% and 27% in the sham-treated patients (P < 0.001). Also, the TUMT-treated patients improved in mean AUA Symptom Score by 43% v 26% for sham-treated patients (P < 0.01). Reclassification of patients after therapy showed a greater shift to the mild category of AUA Symptom Score: 37% for TUMT patients v 6.5% for sham-treated patients. In addition, prostate-specific antigen elevation to >4 times baseline was noted 1 week after TUMT v no statistically significant change for sham-treated patients. This double-blind study demonstrates that thermotherapy's efficacy is not placebo related and that the mechanism of action is related to thermal ablation of transition zone adenoma.

Neighborhood behavior: a useful concept for validation of "molecular diversity" descriptors.

When searching for new leads, testing molecules that are too "similar" is wasteful, but when investigating a lead, testing molecules that are "similar" to the lead is efficient. Two questions then arise. Which are the molecular descriptors that should be "similar"? How much "similarity" is enough? These questions are answered by demonstrating that, if a molecular descriptor is to be a valid and useful measure of "similarity" in drug discovery, a plot of differences in its values vs differences in biological activities for a set of related molecules will exhibit a characteristic trapezoidal distribution enhancement, revealing a "neighborhood behavior" for the descriptor. Applying this finding to 20 datasets allows 11 molecular diversity descriptors to be ranked by their validity for compound library design. In order of increasing frequency of usefulness, these are random numbers = log P = MR = strain energy < connectivity indices < 2D fingerprints (whole molecule) = atom pairs = autocorrelation indices < steric CoMFA fields = 2D fingerprints (side chain only) = H-bonding CoMFA fields.

Bioisosterism as a molecular diversity descriptor: steric fields of single "topomeric" conformers.

The comparative molecular field analysis steric field of a single "topomeric" conformer is introduced as a molecular diversity descriptor particularly useful for combinatorial chemistry involving variations around a fixed "core". Using this new descriptor, 736 commercially available thiols are divided into 231 bioisosteric clusters, whose compositions agree at least as well with medicinal chemical experience and intuition as do clusters derived from Tanimoto differences between 2D fragment occurrences. However, in practice topomeric steric fields complement 2D fingerprints, being the two most frequently useful descriptors yet found for neighborhood-based design of combinatorial libraries.

Long-term follow-up of endoscopically treated upper urinary tract transitional cell carcinoma.

OBJECTIVES: This report focuses on the long-term follow-up of patients with endoscopically treated upper tract transitional cell carcinoma (TCC) to determine the effectiveness of endoscopic therapy. METHODS: From May 1983 to April 1994, 44 patients with TCC of the upper urinary tract underwent conservative endourologic treatment with either electrocautery fulguration or neodymium:yttrium-aluminum-garnet laser at our institution. The mean follow-up period was 5 years (range, 3 months to 11 years). RESULTS: Renal pelvic tumor sizes ranged from 0.4 to 4.0 cm (mean, 1.5) and ureteral tumors from 0.2 to 1.0 cm (mean, 0.5). The majority of tumors were of pathologic grade 3 or less, and all were Stage T2 or less. Seventeen of 44 patients (38.6%) had local tumor recurrence (mean time to recurrence, 12.8 months; range 1.5 to 64). Mean recurrence time was 7.3 months for renal pelvic tumors and 17.8 months for ureteral tumors. Nineteen of 44 patients (43.2%) developed bladder tumors. The overall 5-year disease-free rate was 57%. No recurrent tumor was shown to have increased in grade, and one recurrent tumor was proved to have progressed in stage. Six patients (14%) ultimately required a nephroureterectomy for recurrence. There were no major complications as a result of endoscopic therapy. Six patients (14%) died of the effects of metastatic TCC, 5 of whom had known muscle invasive bladder TCC. CONCLUSIONS: Endourologic techniques and the conservative treatment of upper urinary tract TCC is an evolving field and can be safely and effectively used as a first-line treatment for upper tract TCC in selected patients.

Percutaneous antegrade endopyelotomy: review of 50 consecutive cases.

Between 1988 and 1993, 50 percutaneous antegrade endopyelotomies were performed for ureteropelvic junction obstruction at this institution. The success of the procedure was based on radiological parameters as well as patient symptomatology. The overall success rate of the procedure was 88%. Endopyelotomy was successful in 9 of 11 patients (82%) who presented after failing previous renal procedures. When endopyelotomy was used as the initial treatment modality the success rate was 90%. These results support the argument that endopyelotomy should be considered as first line therapy for most adults with ureteropelvic junction obstructions [corrected].