Quantification of perioperative changes in von Willebrand factor and factor VIII during elective orthopaedic surgery in normal individuals.

von Willebrand's disease (VWD) patients undergoing major surgery are prophylactically treated to promote haemostasis. There is variability in perioperative clinical practice; however, most guidelines suggest replacing the deficient factor to a level of 1.0 IU mL(-1) (or 100%). A review of the literature reveals a paucity of well constructed descriptive data quantifying the changes in coagulation that occur in response to surgical stress. The aim of this study was to quantify the changes in haemostatic variables occurring in response to elective orthopaedic surgery in normal individuals. Eligible subjects >18 years of age undergoing total hip or knee replacement were recruited. Blood samples were drawn at five time points: baseline, preoperatively, 30 min after surgical incision, 30 min postoperatively, postoperative day (POD) 1. Analyses included t-tests and repeated measures anova. Overall 30 patients, 21 women and 9 men, with a mean age of 65 were included in the final analysis. All von Willebrand factor (VWF) variables were seen to significantly decrease intraoperatively and increase postoperatively. VWF multimers showed a statistically significant decrease in high molecular weight multimers intraoperatively and an increase postoperatively. On subgroup analysis, age, gender and anaesthesia type were significantly correlated with changes in VWF parameters. Data presented in the current study establish a physiological baseline for VWF parameters in the normal population and demonstrate mean VWF/factor VIII levels greater than 1.0 IU mL(-1) intraoperatively. As such, current management in VWD patients does not appear to mimic the normal physiological response to surgery.

Cefazolin use in patients who report a non-IgE mediated penicillin allergy: a retrospective look at adverse reactions in arthroplasty.

BACKGROUND: A large number of patients presenting for total hip and knee arthroplasty report an allergy to penicillin. the reported incidence of cross reactions with cephalosporins in patients with penicillin allergy ranges from 3% to 18%. Perioperative antibiotic prophylaxis practices range from using cephalosporins to substituting clindamycin or vancomycin. the purpose of this study was to determine whether cefazolin can be used safely in the perioperative setting in patients with reported non-IgE mediated reactions to penicillin. METHODS: We retrospectively reviewed all primary total hip and knee arthroplasty (2012) and revision (278) cases done at a canadian university hospital from 2007 to 2010. We calculated the prevalence of reported penicillin allergy, the specific reaction reported, and the observed reaction rate in penicillin allergic patients given cefazolin. RESULTS: The prevalence of reported penicillin allergy was 9.9%. there was a wide range of reported reactions, with 25% IgE mediated and 75% non-IgE mediated. Only 27% of patients reporting penicillin allergies were given cefazolin. there were no adverse reactions when non-IgE mediated penicillin allergy patients received cefazolin. CONCLUSION: surgical patients with reported non-IgE allergic reactions to penicillin have a low chance of adverse reaction to perioperative administration of cefazolin. Only a fraction of surgical patients with reported non-IgE mediated reactions to penicillin receive cefazolin perioperatively.

Puboperineales: muscular boundaries of the male urogenital hiatus in 3D from magnetic resonance imaging.

PURPOSE: The aims of this report are 1) to extend our previous two-dimensional magnetic resonance imaging study to create a three-dimensional image of the pelvic floor, including the puboperinealis, the most anteromedial component of the levator ani; 2) to clarify the historical controversy about this particular component of the levator ani; and 3) to present clinical implications of this muscle with respect to urinary continence and radical prostatectomy. MATERIALS AND METHODS: We reused the axial magnetic resonance imaging series from 1 of 15 men in a previous series. Analyze AVWTM allowed creation of three-dimensional images. Further, a movie clip of all three-dimensional images was developed and placed at the manuscript-dedicated Web site: http://www.mayo. edu/ppmovie/pp.html. RESULTS: Our three-dimensional images show how the puboperinealis portion of the levator ani flanks the urethra as it courses from the pubis to its insertion in the perineal body. CONCLUSIONS: The puboperinealis corresponds to muscles previously designated as the levator prostatae, Wilson's muscle, pubourethralis, and levator urethrae, among others. The images suggest that the puboperinealis is the muscle most responsible for the quick stop phenomenon of urination in the male. Our study supports the suggestion that weakening of the puboperinealis by transection, traction injury, or denervation may affect urinary continence after radical prostatectomy.

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.

Prospective analysis of intraoperative frozen needle biopsy of solid renal masses in adults.

PURPOSE: We prospectively determined the accuracy of intraoperative needle biopsy of solid renal masses. MATERIALS AND METHODS: A total of 103 patients diagnosed with a solid renal mass and scheduled for surgery were prospectively evaluated. Radical or partial nephrectomy was performed, and biopsy of the surgical specimen was done twice through the tumor using an 18 gauge biopsy gun. Biopsy specimens of 106 tumors were sent for frozen sectioning, stained with hematoxylin and eosin, and reviewed by 2 independent pathologists blinded to each other and whole tissue specimens. Biopsy results were compared to whole tissue specimens. RESULTS: Specimens were obtained from 60 radical and 46 partial nephrectomy cases. Malignant neoplasms were present in 91 cases (86%). Overall, 15 cases (14%) were benign, of which 11 were oncocytomas. If lesions 4 cm. or less only were included in analysis, the incidence of benign lesions increased to 22%. Overall accuracy of the 2 pathologists was 76 and 80%. Nondiagnostic rates were 11 and 17%. Both observers incorrectly diagnosed 4 malignant lesions (5%) as benign, and incorrectly diagnosed 3 and 5 benign lesions (21 and 36%), respectively, as malignant. Analysis of values for both observers yielded a sensitivity of 77 and 84%, specificity 60 and 73%, positive predictive value 94 and 96%, and negative predictive value 69 and 73%. CONCLUSIONS: Overall frozen needle biopsy was accurate in more than 75% of cases and showed an excellent positive predictive value for carcinoma of more than 94%. Unfortunately, there was a large degree of inaccuracy for benign lesions and we do not recommend the routine use of intraoperative frozen needle biopsy to guide surgical decision making.

Management of acquired rectourinary fistulas: outcome according to cause.

PURPOSE: Acquired rectourinary fistulas, an infrequent complication of pelvic conditions, remain a therapeutic problem for which neither a widely accepted classification nor long-term outcome data are available. This study was designed to provide a new etiologic classification system and examine the success of various surgical therapies. It also looked at the need for permanent fecal or urinary diversion or radical excision depending on the cause of the fistula, i.e., benign vs. malignancy-related. METHODS: A retrospective analysis was made of 41 patients treated for acquired rectourinary fistulas between 1980 and 1995. Acquired rectourinary fistulas were classified as 1) benign but caused by Crohn's disease, trauma, perirectal sepsis, or iatrogenic injury; and 2) malignancy-related fistulas secondary to neoplasm, radiation, surgery, or combined tumor and treatment effects. Surgical interventions were classified as repair, excision, fecal diversion, and urinary diversion. RESULTS: Thirty-seven males and 4 females with acquired rectourinary fistula were identified with a mean age of 62 (range, 28-90) years. Nineteen patients had fistulas involving their urethras, and 22 patients had fistulas involving the bladder. Eight patients were not treated surgically; one was not treated because of an advanced malignancy, three because of patient preference, three because of sepsis, and one because of a poor general condition. Of the remaining 33 patients, nine had benign fistulas of which two were the result of Crohn's disease, two were the result of trauma, two were from an iatrogenic response, and three were from perirectal sepsis. Twenty-four patients had malignancy-related fistulas, and five patients had neoplasm at their fistula sites. The remaining 19 patients had malignancy-related fistulas that were the result of cancer treatments. Of the 19 malignancy-related fistulas, 5 were from radiation, 9 were from surgical trauma, and 5 were from radiation and surgical trauma. Forty-nine percent of the patients had undergone attempts at fistula treatment before referral. A resolution of symptoms after initial and reoperative surgery occurred more often in patients with benign fistulas (44 and 100 percent; mean, 1.8 surgeries per patient) compared with malignancy-related fistulas (21 and 88 percent; mean, 2.1 surgeries per patient). The rates of permanent fecal, urinary, and fecal plus urinary diversion were also lower for benign fistulas (11, 0, and 33 percent) compared with malignancy-related fistulas (13, 8, and 54 percent). Permanent diversion was avoided in 56 percent of the benign fistulas but in only 25 percent of the malignancy-related fistulas. The rates of excisional and radical (ileal conduit) surgery were lower for benign fistulas than for malignancy-related fistulas (44 and 11 percent vs. 50 and 54 percent). CONCLUSION: Successful management of rectourinary fistulas typically requires aggressive reoperative therapy with permanent diversion more often required for malignancy-related fistulas. Better outcomes can be anticipated for benign fistulas.

Urological complications after kidney-pancreas transplantation.

PURPOSE: Urological complications are common after kidney-pancreas transplantation. Predictors of urological complication after transplantation have not been established. We studied the impact of urological complications on allograft function. In addition we evaluated age at transplantation, diabetic years before transplantation and preoperative bladder function as predictors of allograft pancreatitis, postoperative retention and urine leaks. MATERIALS AND METHODS: Urological complications in 65 cases (38 men, 27 women, mean diabetic years 21 +/- 6, mean age 33 +/- 7 years) who had transplants between December 1987 and January 1995 were reviewed. Preoperative urodynamics in 50 patients (77%) and voiding cystourethrogram in 40 (62%) were analyzed. Kidney-pancreas transplantation was completed using bladder drainage techniques. RESULTS: Mean followup was 44 +/- 27 months (median 40, range 1 to 93). Urological complications in 51 patients (79%) included urinary tract infection in 59%, hematuria in 26%, allograft pancreatitis in 19%, duodenal leaks in 17%, ureteral lesions in 9% and urethral lesions in 6%. Eleven duodenal leaks (8 leaks in less than 1 month) required surgical treatment. Nine leaks recurred in 7 patients. Allograft pancreatitis occurred 32 times (range 1 to 9) in 12 patients. Three patients had ureteral obstruction and 3 had ureteral leaks. Preoperative urodynamics included detrusor hyperreflexia in 8 patients, detrusor areflexia in 19, indeterminate in 5 and normal in 18. The 1-year patient, kidney and pancreatic allograft survival rates were 92, 91 and 86%; 2-year survival rates were 89, 88 and 80%, and 5-year survival rates were 61, 59 and 55%, respectively. CONCLUSIONS: Urological complications were common after transplantation but did not adversely affect allograft survival in our series. Age at transplantation, diabetic years preceding transplantation and preoperative bladder function were not significantly correlated with allograft pancreatitis, postoperative urinary retention or urine leaks. A prospective analysis of postoperative bladder function should be completed to improve understanding and possibly reduce morbidity of urological complications after transplantation.

Synthesis and structure of chiral macrocycles containing 2,2'-bipyridine subunits.

A series of macrocyclic receptors has been prepared containing bipyridine groups linked to two amino acids. Variations in both the amino acid and the linking spacer have been made. The structure of the resulting macrocycles has been investigated using 1H NMR spectroscopy and X-ray crystallography. The use of L-valine leads to an open conformation for the macrocycle in which the 2-propyl substituents are directed perpendicular to the plane of the ring leaving the bipyridine and amide groups accessible for binding to a metal or complementary substrate. Proline-based macrocycles take up a twisted arrangement with the linking chain stretched across the face of the bipyridine which takes up a trans conformation. The metal ion binding properties of these derivatives have been investigated and shown to occur only to the valine macrocyles which have the two pyridine rings preorganized for complexation. These macrocycles have also been shown to bind to phenolic hydroxyl groups by using hydrogen-bond donors and acceptors from the amide groups in the linking chain.

Ocular hemodynamic effects of acute ethanol ingestion.

PURPOSE: Because the protean biological effects of ethanol include acute alterations in both cortical function and circulatory control, we investigated the effect of acute alcohol consumption on retrobulbar hemodynamics and contrast sensitivity in healthy human volunteers. SUBJECTS AND METHODS: Twelve young adults received orange juice with and without ethanol in a double-masked fashion. The ethanol dose was sufficient to raise blood alcohol to 0.07 +/- 0.003 g/dl. Retrobulbar hemodynamics were assessed at baseline and twice at elevated blood alcohol by color Doppler imaging. RESULTS: Acute elevation of blood alcohol lowered intraocular pressure from 13.0 +/- 0.7 to 10.7 +/- 0.7 mm Hg (p < 0.05). In contrast, elevated blood alcohol left peak systolic velocity, end-diastolic velocity and the resistance index constant in three retrobulbar arteries (ophthalmic, central retinal and posterior ciliary). For example, in the central retinal artery, peak systolic velocity, end-diastolic velocity and the resistance index averaged 11.0 +/- 1.3 cm/s, 2.8 +/- 0.4 cm/s and 0.75 +/- 0.03 before ethanol, as compared with 10.5 +/- 1.0 cm/s, 2.9 +/- 0.3 cm/s and 0.72 +/- 0.03 after ethanol (all p = NS). Alcohol ingestion also failed to alter either visual acuity or contrast sensitivity, as assessed under both photopic and mesopic conditions. CONCLUSIONS: Although ethanol has widespread cognitive and cardiovascular effects, at blood levels near legal definitions of intoxication we found it ineffective in altering either retrobulbar hemodynamics or contrast sensitivity.

Class III antiarrhythmic activity of novel substituted 4-[(methylsulfonyl)amino]benzamides and sulfonamides.

The synthesis and Class III antiarrhythmic activity of a series of 4-[(methylsulfonyl)amino]benzamides and sulfonamides are described. Selected compounds show a potent Class III activity and are devoid of effects on conduction both in vitro (dog Purkinje fibers) and in vivo (anesthetized dogs). Compounds having a 2-aminobenzimidazole group were found to be the most potent, and one compound having this heterocycle (5, WAY-123,398) was selected for further characterization. Compound 5 was shown to have good oral bioavailability and a favorable hemodynamic profile to produce a 3-fold increase of the ventricular fibrillation threshold and to terminate ventricular fibrillation, restoring sinus rhythm in anesthetized dogs. Voltage-clamp studies in isolated myocytes show that 5 is a potent and specific blocker of the delayed rectifier potassium current (IK) at concentrations that cause significant prolongation of action potential duration.

Structures of 3 beta-tetrahydropyranyloxy-5 alpha-cholesta-20(21),24-diene and 3 beta-tetrahydropyranyloxy-21-nor-5 alpha-ergost-24-en-20-one.

3 beta-Tetrahydropyranyloxy-5 alpha-cholesta-20(21),24-diene: C32H52O2, Mr = 468.77, orthorhombic, P2(1)2(1)2(1), a = 6.710 (4), b = 11.361 (4), c = 37.812 (11) A, V = 2882 (2) A3, Z = 4, Dx = 1.08 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 4.60 cm-1, F(000) = 1040, T = 224 K, final R = 0.088 for 1729 unique observed reflections. 3 beta-Tetrahydropyranyloxy-21-nor-5 alpha-ergost- 24-en-20-one: C32H52O3, Mr = 484.77, triclinic, P1, a = 6.640 (2), b = 9.589 (2), c = 12.202 (3) A, alpha = 111.33 (2), beta = 101.22, gamma = 90.27 (2) degrees, V = 707.4 (3) A3, Z = 1, Dx = 1.14 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.8 cm-1, F(000) = 268, T = 225 K, final R = 0.058 for 2208 unique observed reflections. The configuration at C(17) of these synthetic sterol derivatives, which had been uncertain, is unambiguously established to be 'normal' (possessing a 17 alpha-H).

Renal plasmacytoma: Mayo Clinic experience and review of the literature.

Extramedullary plasmacytoma arising in the kidney is rare. Only 8 cases have been reported. Recently, we noted the ninth case, the second case seen at the Mayo Clinic. Clinically, the tumor mimics a renal cell carcinoma or a transitional cell carcinoma of the renal pelvis.

Spontaneous renal rupture during pregnancy.

Spontaneous rupture of the renal parenchyma or renal pelvis during pregnancy has been previously reported in 16 cases. In the case we describe in this report, the patient initially had right flank pain and nausea for 48 hours, which progressed to severe abdominal symptoms that necessitated exploratory laparotomy. Cystoscopic placement of a ureteral stent relieved the obstruction and allowed spontaneous healing of the renal pelvis. Dilatation of the urinary collecting system commonly occurs during pregnancy. Spontaneous rupture of the renal parenchyma or renal pelvis, however, is unusual and often associated with diseased kidneys. Our case is the 8th one of spontaneous rupture of the renal collecting system with no identifiable underlying pathologic condition and the 17th case of spontaneous renal rupture overall.

Morbidity of pancreas transplantation during cadaveric renal transplantation.

Simultaneous transplantation of the pancreas is an option for diabetic patients undergoing kidney transplantation to attempt to halt progression of diabetic complications, but the additional risk imposed by the procedure is unclear. Our aim was to determine the morbidity attributable to pancreas transplantation during simultaneous pancreas and kidney transplantation. We compared the first posttransplant year of 18 consecutive recipients of combined pancreas and kidney transplantation to 18 consecutive recipients of kidney transplantation alone. All patients received cadaver donor allografts between 1986 and 1989, and had type I diabetes mellitus with chronic renal failure. There were no differences in patient survival (94% both groups) or satisfactory renal allograft function (89% pancreas/kidney group, 83% kidney group) up to 18 months after transplantation. Eighty-eight percent of pancreas allografts were functioning satisfactorily at 18 months. There was a mean (+/- SD) of 1.5 +/- 1.0 acute rejection episodes per patient for the pancreas/kidney group compared to 0.8 +/- 6 for the kidney-only group (P less than 0.02). Cytomegalovirus infection and wound complications were each encountered more often after pancreas/kidney transplantation than kidney transplantation alone, and together with rejection accounted for a difference in days of hospitalization during the first year (71 +/- 34 vs. 27 +/- 13, P less than 0.001). We conclude that simultaneous pancreas transplantation during cadaver donor kidney transplantation accounted for more frequent rejection episodes, CMV infections, and wound complications. These complications resulted in more hospitalization for patients undergoing simultaneous pancreas/kidney transplantation than kidney transplantation alone.

Intravesical condyloma acuminatum with progression to verrucous carcinoma.

Condyloma acuminatum is a common form of venereal disease. Most patients with condylomata acuminata suffer from only the local cosmetic and irritative effects of the lesions. Few patients have progression to aggressive, regionally distributed lesions that can be life-threatening. We describe a forty-three-year-old white woman who had a seventeen-year history of scleroderma with extravesical and intravesical condylomata acuminata. During two years of conservative management with transurethral excision, electrocoagulation, and intravesical chemotherapy, the disease progressed to involve the entire bladder and resulted in obstructive renal insufficiency that required anterior exenteration and urinary diversion. The natural history of the disease is described, and the relevant literature is reviewed.

Histologic diagnosis of rejection by using cystoscopically directed needle biopsy specimens from dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder.

To determine the histologic features of rejection and to identify nonrejection causes of human pancreatic allograft dysfunction, we analyzed 31 needle biopsy specimens (17 pancreatic, 14 duodenal) obtained under cystoscopic direction from 15 dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder. Eight allografts undergoing rejection showed the most common histologic features of rejection to be diffuse mixed inflammatory infiltrates of pancreatic acinar tissue and duodenum wall. Diffuse infiltration of pancreatic acinar tissue by neutrophils was the earliest histologic change in rejection. Seven dysfunctional allografts not undergoing rejection ("nonrejection") showed a normal pancreas or various changes including acinar dilation with inspissation of secretions, fibrosis, cytomegalovirus inclusions, and enzymatic necrosis. The histologic changes in the duodenum paralleled those in the pancreas in both rejection and nonrejection allografts. We conclude that the histologic features of rejection in pancreatoduodenal allografts are distinctive. The changes seen in biopsy specimens accurately reflect the state of the graft and can be used to diagnose rejection and to identify other causes of graft dysfunction. Biopsy samples from the duodenum as well as the pancreas are diagnostically useful. The biopsy findings can be used to guide the clinical management of rejection and in the development of other noninvasive tests for rejection.

Pancreas transplantation at Mayo: II. Operative and perioperative management.

Better perioperative and operative management techniques have contributed to an improvement in the success rate of pancreas transplantation. Because of a shortage of donor organs, the criteria for acceptability of the allograft have been liberalized, and the development of techniques such as combined liver and pancreas procurement has increased allograft availability. Major advances have been made in organ preservation. Currently, pancreas allografts can routinely be stored for 18 to 24 hours. The technique of pancreaticoduodenal transplantation with a duodenocystostomy for the exocrine drainage is widely used. Experience with anesthetic and intensive-care unit management of these patients is accumulating. With the evolution of pancreas transplantation and with the help of the excellent transplant centers in our area, we developed a pancreas transplantation protocol and performed transplantation based on this protocol in 16 recipients at the Mayo Clinic from October 1987 through December 1988.