A comparative study of the bone-restorative efficacy of anabolic agents in aged ovariectomized rats

Introduction The study was designed to compare the bone anabolic effects of basic fibroblast growth factor (bFGF), a selective agonist for prostaglandin E receptor subtype EP4, and parathyroid hormone (PTH) in aged ovariectomized (OVX) rats with severe cancellous osteopenia. Methods Groups of aged OVX rats were maintained untreated for 1 year postovariectomy (15 months of age) to develop severe tibial cancellous osteopenia. These animals were then treated with bFGF or the EP4 agonist (EP4) for 3 weeks. Other groups of aged OVX rats were treated with EP4 or PTH alone for 11 weeks, or sequentially with bFGF or EP4 for 3 weeks followed by PTH for 8 weeks. Cancellous and cortical bone histomorphometry were performed in the right proximal tibial metaphysis and tibial diaphysis respectively. Results Treatment with bFGF for 3 weeks markedly increased serum osteocalcin, osteoid volume, and osteoblast and osteoid surfaces to a greater extent than EP4. Basic FGF, but not EP4 or PTH, induced formation of osteoid islands within bone marrow. EP4 stimulated cancellous bone turnover, but failed to restore lost cancellous bone in the severely osteopenic proximal tibia after 11 weeks of treatment. In contrast, EP4, much like PTH, increased cortical bone mass in the tibial diaphysis by stimulating both periosteal and endocortical bone formation. Treatment of aged OVX rats with PTH alone tended to partially reverse the severe tibial cancellous osteopenia, whereas sequential treatment with bFGF and PTH increased tibial cancellous bone mass to near the level of vehicle-treated control rats. These findings indicate that bFGF had the strongest stimulatory effect on cancellous bone formation, and was the only anabolic agent to induce formation of osteoid islands within the bone marrow of the severely osteopenic proximal tibia. Therefore, bFGF may be more effective for the reversal of severe cancellous osteopenia. PTH and EP4 increased cortical bone mass to nearly the same extent, but cancellous bone mass was greater by two-fold in PTH-treated OVX rats than in EP4-treated OVX rats. Conclusion These findings in aged OVX rats suggest that PTH is more efficacious than EP4 for augmentation of cancellous bone in the severely osteopenic, estrogen-deplete skeleton.     

Predicting Stricture in Morbidly Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass: A Logistic Regression Analysis

Gastrojejunostomy stricture after Roux-en-Y gastric bypass occurs in 3 to 27% of morbidly obese patients in the USA. We questioned whether preoperative patient characteristics, including demographic attributes and comorbid disease, might be significant factors in the etiology of stricture. In this study from November 2001 to February 2006 (51 months), at a high-volume bariatric center, of the 1,351 patients who underwent laparoscopic gastric bypass, 92 developed stricture (6.8%). All but two were treated successfully by endoscopic dilation. All patients stopped nonsteroidal anti-inflammatory medications 2 weeks prior to surgery and did not restart them. The operative procedure included the use of a 21-mm transoral circular stapler to create the gastrojejunostomy; the Roux limb was brought retrogastric, retrocolic. In an effort to reduce our center’s stricture rate, late in the study, U-clips used at the gastrojejunostomy were replaced by absorbable sutures, and postoperative H₂ antagonists were added to the treatment protocol. The change to absorbable polyglactin suture proved to be significant, resulting in a lower stricture rate. The addition of H₂ antagonists showed no significant effect. Following the retrospective review of the prospective database, univariate and multivariate logistic regression analyses identified factors associated with the development of stricture. Gastroesophageal reflux disease and age were each shown to be statistically significant independent predictors of stricture following laparoscopic gastric bypass. Presented at the 2006 Annual Meeting of the Society for Surgery of the Alimentary Tract, May 20–24, Los Angeles, CA (poster presentation).     

The evolution and genesis of supraventricular waltz & duet

Objective. This study documents and traces the evolution of triple rhythm (Waltz) linking the great veins, corresponding systemic or pulmonary venous sinuses and pectinated right or left atrium in frog, turtle, snake and human hearts. Alternating rhythm (duet) between systemic and pulmonary veins has also been documented in these hearts. Material Studied. The hearts of six dead hammer-head sharks were examined with the naked eye. Air-breathing, fresh-water fish (three Channa striata and three Indian catfish) were anaesthetised with ketamine and their pharynx insufflated with oxygen. Six frogs, three turtles, and two snakes were anaesthetised, intubated and ventilated. Contractions of the exposed hearts of these animals were correlated with their electrocardiograms using superimposed videos. The human heart was observed carefully during surgery through median sternotomy or anterolateral thoracotomy by visual inspection especially during instillation of or recovery from cardioplegia. Digital videos were taken and studied in slow motion replay later. Observations. In the air-breathing fish, Channa striata and Indian catfish and presumably the shark, the cardinal veins and thin walled sinus venosus do not contract. In the frog, turtle, and snake there is sequential contraction of the systemic veins, systemic venous sinus and pectinated right atrium. Likewise, there is waltz on the arterial side. There is a duet between systemic and pulmonary veins, contractions of the former preceding the latter in the frog, turtle and snake. The observations are similar in the human heart except that the inferior vena cava does not contract. Conclusions. There is sequential contraction of the superior vena cava, the systemic venous sinus and the pectinated part of the right atrium in the human heart. Likewise, there is a waltz linking the terminal pulmonary veins, pulmonary venous sinus and pectinated part of the left atrium in the human heart. This waltz or triple rhythm, as well as a duet between the systemic and pulmonary veins are seen in frog, turtle and snake. The duet is also observable in the human heart, during recovery from cardioplegia. It is likely that the waltz and duet are conducted by a neurogenic mechanism. Clinical Implications. The understanding, preservation and restoration of the mechanism sustaining supraventricular waltz and duet is relevant to surgical and interventional procedures for control of atrial arrhythmia, Fontan circulation, technique for cardiac transplantation and planning atriotomies.     

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.     

Abdominal computed tomography for postoperative abscess: Is it useful during the first week?

While classic teaching dictates computed tomography (CT) for postoperative abdominal or pelvic abscess in the first week is of low yield, little evidence supports intentional delays in imaging for suspected abscess. This retrospective review examined all CT scans obtained for clinical suspicion of abscess between 3 and 30 days after abdominal or pelvic operation over a 3-year period. Scans were grouped into those obtained between 3 and 7 days after surgery (EARLY) and those obtained after day 7 (LATE). Diagnostic yield was compared between EARLY and LATE groups. Of 262 CT examinations (EARLY, n=106; LATE, n=156), 71 studies (27%) demonstrated abscess. There was no significant difference in the diagnostic yield of CT for abscess between EARLY and LATE groups (23% [24 of 106] versus 30% [47 of 156], P=0.18). Of patients with an abscess, 63% (45 of 71) underwent percutaneous or operative drainage (EARLY 75% [18 of 24], LATE 57% [27 of 47], P=0.15). Abdominal CT for postoperative abscess can be expected to be diagnostic in a substantial proportion of cases in the first week, the majority of which lead to percutaneous or operative drainage. Postoperative CT for intra-abdominal abscess should be obtained as clinically indicated, regardless of interval from surgery. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States Government.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.