Enhancement of rat sciatic nerve regeneration by fibronectin and laminin through a silicone chamber

In this study, the authors examined the effects of fibronectin and laminin on sciatic nerve regeneration in rats. Sixty-eight Sprague-Dawley rats underwent bilateral sciatic nerve transections and silicone tubulizations, with a 10-mm gap between the proximal and distal nerve stumps. Thirty rats (n=30) received 10 microg of fibronectin injection into the right sciatic nerve chamber, while saline was injected into the left nerve chamber, serving as the control. Another 30 rats (n=30) were given 6 microg of laminin injection into the right nerve chambers and saline into the left chambers. At 1, 3, and 4 months postoperatively, electrophysiologic and histologic examinations, including nerve morphometry, were performed. Eight additional rats, receiving fibronectin (n=4) and laminin (n=4) injections, were used for horseradish peroxidase (HRP) tracing at 3 months postoperatively. Results from the study showed that fibronectin- and laminin-treated groups had significantly higher motor nerve conduction velocity and evoked muscle action potential amplitude of the anterior tibial muscle than the control group (p<0.01). Nerve diameter and the number of myelinated axons from the groups receiving fibronectin and laminin applications were greater than the controls (p<0.01). Also, a greater number of HRP-labeled motor neurons were found in the ventral horns and dorsal root ganglia of the fibronectin- and laminin-treatment groups compared to the controls. The authors conclude that local applications of fibronectin and laminin into the nerve chambers can significantly improve axonal regeneration and maturation of injured rat sciatic nerves.     

The effect of vascular endothelial growth factor on the healing of ischaemic skin wounds.

The effect of exogenous vascular endothelium growth factor (VEGF) on wound healing in an ischaemic skin flap model was evaluated in this study. Seventy-two Sprague-Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. The study was divided into two parts. In Part I, VEGF protein levels were determined from the incisional and H-shaped ischaemic wounds at 12 and 24 h, postoperatively. In Part II, tensile strength and immunohistochemical stains were examined to determine the level of microvessel density (MVD) at 1 and 2 weeks, postoperatively in simple incisional wounds, ischaemic wounds, and ischaemic wounds following 1 ml (1 microg/ml) exogenous VEGF injections into the subcutaneous tissue. The results showed a significantly higher level of VEGF protein in the ischaemic wounds than the incisional wounds. Tensile strength was statistically higher in the incisional wound group and in the ischaemic flap wounds with VEGF treatment compared to the ischaemic flaps with no treatment at 1 week, postoperatively (p>0.05). MVD data indicated that ischaemic wound repair with VEGF treatment had significantly higher MVD than the normal incisional wounds and ischaemic wounds without treatment. We conclude that exogenous application of VEGF can increase early angiogenesis and tensile strength in the ischaemic wound.     

The Clinical Conundrum of Corticotropin-independent Autonomous Cortisol Secretion in Patients with Bilateral Adrenal Masses

Background Management of patients with bilateral adrenal masses and corticotropin (ACTH)-independent Cushing syndrome (CS) or subclinical CS is problematic. We report our experience with adrenal venous sampling (AVS) in the evaluation of 10 patients with bilateral masses who had ACTH-independent CS or subclinical CS. Patients and Methods Ten patients (9 women, 1 man, mean age 56.4 years) with bilateral adrenal masses and ACTH-independent CS (n = 3) or subclinical CS (n = 7) underwent AVS. Autonomous cortisol secretion was documented in all cases with suppressed serum ACTH concentrations and lack of cortisol suppression with dexamethasone administration. Adrenal venous sampling was performed on the second day of dexamethasone administration. Cortisol and epinephrine levels were measured from each adrenal vein (AV) and from a peripheral vein (PV). Results Mean (± SD) maximal diameter of the adrenal masses on computed tomography was 3.3 ± 1.3 cm (range: 1.2–6.0 cm). Successful catheterization was confirmed with AV:PV epinephrine gradients. A cortisol AV:PV gradient >6.5 was consistent with a cortisol-secreting adenoma in 11 adrenal glands; 5 patients had clinically important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol-secreting adenomas, and 2 had ACTH-independent macronodular adrenal hyperplasia. Adrenal venous sampling-guided adrenalectomy was completed in all 10 patients—2 patients had total bilateral adrenalectomy and 2 others had subtotal bilateral adrenalectomy. During a mean follow-up of 36.1 months (range: 0.7–123 months), CS or clinically important cortisol secretory autonomy did not recur. Conclusions Adrenal venous sampling contributed to the localization of autonomous hypercortisolism in the setting of ACTH-independent CS or subclinical CS in patients with bilateral adrenal masses. Presented at the Annual Meeting of the International Association of Endocrine Surgeons, Montreal, Canada, August 26–29, 2007. J. A. Carney is an Emeritus Member of the Department of Laboratory Medicine and Pathology.     

Subcapsular hepatic hematoma with right hepatic vein thrombosis: a complication of shock wave lithotripsy

Extracorporeal shock wave lithotripsy (ESWL) is a well-established, safe and effective therapeutic modality for surgical treatment of urolithiasis. Hematoma is a rare complication of ESWL and, when it occurs, typically involves the kidney. We report the case of a 71-year-old woman who developed severe, persistent abdominal pain after ESWL for a 9-mm stone at the ureteropelvic junction. Post-treatment CT scan demonstrated a 13 × 6–cm subcapsular hepatic hematoma. A follow-up CT scan showed expansion of the hematoma and development of hepatic vein thrombosis. This finding, along with persistent abdominal pain and rising liver transaminases, led to surgical intervention. The patient''s symptoms resolved and liver function returned to baseline following liver decompression.     

Outcome of Invasive and Noninvasive Intraductal Papillary-Mucinous Neoplasms of the Pancreas (IPMN): A 10-year Experience

BACKGROUND: Intraductal papillary-mucinous neoplasms (IPMN) were officially introduced into the TNM classification in 1996. Based on a two-center database, we reevaluated histopathological findings, clinicopathological pattern, predictive markers for malignancy, and outcome. METHODS: Between 1996 and 2006, a total of 1424 pancreatic resections were performed in the University Hospitals Dresden and Mannheim. Pathologists of both institutions reviewed the IPMN diagnoses and other with cystic or solid tumor diagnoses. All possible markers, such as diabetes, jaundice, etc., were analyzed for prediction of malignancy. We performed a survival analysis based on the morphologic classification to determine the prognosis of IPMN. RESULTS: There were 43 patients of primarily diagnosed IPMN along with 1174 patients with diagnoses, such as ductal adenocarcinoma. In 207 patients, the diagnoses revealed other cystic or small solid tumors. A histopathological review of the latter patients revealed 54 IPMNs, resulting in a total of 97 IPMN patients (29 noninvasive, 68 invasive). All IPMN patients had a median survival of 36 months. Recurrence occurred more frequently in invasive IPMN. Predictive markers of malignancy were pain, preoperative weight loss, jaundice, and elevated CA 19.9. The strongest independent prognostic factor was invasive growth. The survival analysis revealed excellent prognosis for noninvasive IPMN. CONCLUSIONS: Since the introduction of IPMN in 1996, even specialized centers have had to deal with a learning curve. By reevaluating all cystic or small solid tumors, centers can improve and their patients' treatment can be optimized. Because the preoperative diagnostic methods are not sensitive enough to differentiate between benign and malignant lesions, surgery is advocated for all main duct IPMN, because they have a high malignant potential. For branch duct IPMN, surgery is advocated if the lesion is symptomatic, >3 cm, or has enlarged nodules.     

Laparoscopic partial nephrectomy for hilar tumors: technique and results

BACKGROUND: Laparoscopic partial nephrectomy for hilar tumors is a cutting edge procedure for which little data is available in the current literature. OBJECTIVE: To describe our technique and results of laparoscopic partial nephrectomy for renal hilar tumors. DESIGN, SETTING, AND PARTICIPANTS: Between April 2000 and September 2006, 94 partial laparoscopic nephrectomies were performed at our institution. A total of 18 (19.1%) patients had hilar tumors. A hilar tumor was defined as a lesion suspicious for renal cell carcinoma in contact with a major renal vessel on preoperative cross-sectional imaging. In 3 (16.7%) of the patients, the indication for nephron-sparing surgery was imperative. Mean tumor size was 3cm (range, 2-4.5). Eight (44.4%) surgeries were performed with renal artery perfusion for cold ischemia; the remaining surgeries were performed under warm ischemia. INTERVENTION(S): After occluding the renal artery and controlling the renal vein by using separate rubber band tourniquets, we excised the tumor mass including delicate mobilization away from the blood vessels. Although we used to insert a ureteral stent at the beginning of our experience with laparoscopic partial nephrectomies, we no longer do so. All surgeries were performed by a single urologist (G.J.). MEASUREMENTS: Operative time, ischemia time, blood loss, renal function using the Cockroft formula as well as renal scans, operative and post-operative complications, pathology parameters. RESULTS AND LIMITATIONS: All surgeries were completed laparoscopically. Mean surgical time was 238min (range, 150-420). Mean ischemia times were 42.5min (range, 27-63) and 34.1min (range, 24-56) for the cold and warm ischemia groups, respectively. Estimated intraoperative blood loss was 165ml (range, 50-500). There were two (11%) entries into major vessels during tumor excision, namely a segmental renal artery in one patient and a segmental renal vein in another. Both of these occurrences were managed laparoscopically. One patient necessitated laparoscopic reexploration for urine extravasation in the immediate postoperative period. All postoperative nuclear scans (available in 12 of 18 patients) showed functional kidney moiety. Mean split renal function was 38.6% (range, 24-50) on the operated side. Histopathological examination confirmed renal cell carcinoma in 14 (77.8%) of the patients. One (7.1%) patient had a positive surgical margin on the surface that was adjacent to the renal artery. In a median follow-up of 26 mo (range, 1-59), no local recurrence or systemic progression occurred. CONCLUSION: Laparoscopic partial nephrectomy for hilar tumors is a feasible and safe procedure in the hands of experienced laparoscopic surgeons. Oncological results seem excellent, but further follow-up is needed for accurate long-term assessment of this surgical approach.     

A key role for beta-cell cytosolic phospholipase A(2) in the maintenance of insulin stores but not in the initiation of insulin secretion.

Cytosolic phospholipase A(2) (cPLA(2)) is a Ca(2+)-sensitive enzyme that has been implicated in insulin secretion in response to agents that elevate beta-cell intracellular Ca(2+) ([Ca(2+)](i)). We generated clones of the MIN6 beta-cell line that stably underexpress cPLA(2) by transfection with a vector in which cPLA(2) cDNA had been inserted in the antisense orientation. Reduced expression of cPLA(2) was confirmed by Western blotting. The insulin content of cPLA(2)-deficient MIN6 cells was reduced by approximately 90%, but they showed no decrease in preproinsulin mRNA expression. Measurements of stimulus-dependent changes in [Ca(2+)](i) indicated that reduced expression of cPLA(2) did not affect the capacity of MIN6 cells to show elevations in Ca(2+) in response to depolarizing stimuli. Perifusion experiments indicated that cPLA(2) underexpressing MIN6 pseudoislets responded to glucose, tolbutamide, and KCl with insulin secretory profiles similar to those of cPLA(2) expressing pseudoislets, but that secretion was not maintained with continued stimulus. Analysis of the ultrastructure of cPLA(2)-deficient MIN6 cells by electron microscopy revealed that they contained very few mature insulin secretory granules, but there was an abundance of non-electron-dense vesicles. These data are consistent with a role for cPLA(2) in the maintenance of insulin stores, but they suggest that it is not required for the initiation of insulin secretion from beta-cells.     

Baseline characteristics and treatment preferences of oral surgery patients.

PURPOSE: Patient preferences for treatment choices may depend on patient characteristics. Using standard gamble (SG) and willingness to pay (WTP), this study compares preferences for treatment of mandibular fracture among patients in a low-income urban area. PATIENTS AND METHODS: Surveys of African-American and Hispanic adults receiving treatment at King/Drew Medical Center for either mandibular fracture (n = 98) or third molar removal (n = 105) were used to investigate differences in patient characteristics across treatment groups (third molar vs fracture) and treatment preference (wiring vs surgery). RESULTS: The fracture patients were willing to pay more to restore function without scarring or nerve damage than were the third molar patients. Patients who chose surgery were willing to accept a greater risk of possible nerve damage or scarring than those who chose wiring. Among 15 potential predictors of SG and WTP studied in 4 subgroups defined by actual treatment and treatment preference, significant predictors varied, with associations for education and clinical experience for SG and associations with income and psychosocial predictors for WTP. CONCLUSIONS: SG and WTP capture different domains of health values in patients. There is considerable heterogeneity in relationships among patient characteristics and patient preferences across subgroups defined by actual treatment and treatment preferences.