Functional sphincter ani externus reconstruction for treatment of fecal stress incontinence using free latissimus dorsi muscle transfer with coaptation to the pudendal nerve: preliminary experimental study in dogs

The external anal sphincter (EAS) is a skeletal muscle capable of voluntary contraction to prevent accidental defecation. Current reconstructive options for a severely damaged EAS using local muscle flaps are not always adequate for functional repair. The present preliminary experimental model was designed to assess the feasibility of a neuromicrovascular latissimus dorsi muscle transfer for functional external spincter muscle reconstruction. In nine mongrel dogs, the anal sphincter muscles were totally resected, leaving a mucosal canal in place. A segmental latissimus dorsi muscle was shaped around the anal canal in a circular fashion, with coaptation to the pudendal nerve, and vessel anastomosis at the ischiorectal fossa. Functional evaluation was performed using electromyogram, sphincter manometry, video documentation, and histologic examination with standard and immunohistochemical staining. After 8 months, the remaining three eligible dogs were continent. Muscle function was verified by means of electromyogram, sphincter manometry, and a video record. Histologic and immunohistochemical examination confirmed the functional results, showing only minor zones of fatty and fibrous degeneration. Transplantation of a segmental latissimus dorsi muscle with vascular anastomosis and coaptation to the pudendal nerve has proved to be successful in restoring (voluntary) anal continence experimentally in dogs. Its feasibility for perfect orientation as a neosphincter seems to be superior to any pedicled muscle flap. However, these preliminary results deserve further investigation prior to considering application in humans.     

Influence of a platelet concentrate on prosthetic bone ingrowth in a rabbit model

Recent studies have shown that an increase in bone ingrowth by addition of osteogenic growth factors can reduce micro motion and gross implant motion and contribute to joint implant stability through osseointegration. Platelet-rich plasma (PRP) has the potential to provide growth factors that may be conducive to osteointegration at the bone-implant interface. This study analyzed the influence of PRP on bone ingrowth upon a beaded metal implant in distal femurs of 22 rabbits. Rabbit limbs were randomly assigned to receive an implant plus PRP or plain implant. Half of the specimens were randomly assigned to a 2-week group (n = 20) or a 5-week group (n = 20). Histologic and histomorphometric comparison between implant alone and implant plus PRP, at 2 and 5 weeks, was performed. In both the 2- and 5-week comparisons, there was no statistical difference (p > .05) in bone ingrowth between the control and PRP group, despite a slight increase in trabecular bone growth in PRP groups. This study suggests that PRP is not a major contributing factor to bone ingrowth at the bone-implant interface. This supports growing evidence in the literature that PRP can lead to variable bone growth stimulation in vivo.     

A novel lymphatic mapping technique to improve localization and staging of early colon cancer during laparoscopic colectomy

Encouraging results from our previous studies of sentinel lymph node (SLN) mapping in colorectal cancer (CRC) prompted investigation of its feasibility and accuracy during laparoscopic colectomy for early CRC. Between 1996 and 2000, 14 patients with clinically localized colorectal neoplasms underwent colonoscopic tattooing of the primary site and SLN mapping. In each case 0.5 to 1 cm3 of isosulfan blue dye was injected submucosally via the colonoscope. The blue-stained lymphatics were visualized through the laparoscope and followed to the SLN, which was marked with a clip, and laparoscopic colectomy was completed in the routine fashion. All lymph nodes were examined by hematoxylin and eosin (H&E) staining; in addition each SLN was subjected to focused examination by multisectioning and immunohistochemical staining using cytokeratin antibody. In all 14 patients the primary neoplasm and an SLN were identified laparoscopically. An average of 13.5 total lymph nodes and 1.7 SLNs per patient were identified. The SLN correctly reflected the tumor status of the nodal basin in 93 per cent of the cases. In four cases with unexpected lymphatic drainage, the extent of mesenteric resection was altered. In two cases (14%), nodal involvement was micrometastatic, confined to an SLN, and identified only by immunohistochemical staining. Lymphatic mapping caused no complications and added only 10 to 15 minutes to the overall operative time. Comparison of results in this group with results for a matched group of 14 patients undergoing SLN mapping during open colon resection showed that the laparoscopic technique had similar rates of accuracy and success. These preliminary findings indicate that colonoscopic/laparoscopic SLN mapping during laparoscopic colon resection is a feasible and technically simple means of identifying the primary colorectal neoplasm and its SLN. Focused pathologic examination of this node can upstage CRC and thereby may improve selection of patients for adjuvant chemotherapy.     

Intrapulmonary shunt after cardiopulmonary bypass: the use of vital capacity maneuvers versus off-pump coronary artery bypass grafting

OBJECTIVES: It has been proved in human subjects and animals that atelectasis is a major cause of intrapulmonary shunting and hypoxemia after cardiopulmonary bypass. Animal studies suggest that shunting can be prevented entirely by a total vital capacity maneuver performed before termination of bypass. This study aimed to test this theory in human subjects and to evaluate possible advantages of off-pump coronary artery bypass grafting. METHODS: Twenty-four patients scheduled for coronary artery bypass grafting were randomly assigned to receive no total vital capacity maneuver (control group, n = 12) or standard total vital capacity maneuvers (TVCM group, n = 12). Additionally, 12 consecutive patients undergoing off-pump coronary artery bypass grafting (off-pump group) were studied. Systemic and central hemodynamics, the pattern of breathing, and ventilatory mechanics were evaluated after induction of anesthesia, after sternotomy, after cardiopulmonary bypass and skin closure, and 4 hours after extubation. RESULTS: The use of total vital capacity maneuvers reduced (P <.05) intrapulmonary shunting after termination of cardiopulmonary bypass. However, shunting increased (P <.05) in all groups (control group, 8.2% +/- 3.3% vs 25.6% +/- 8.1%; TVCM group, 8.7% +/- 3.4% vs 24.4% +/- 8.5%; and off-pump group, 7.8% +/- 2.8% vs 14.0% +/- 5.3%) after extubation, but the increase was significantly (P <.05) less pronounced in the off-pump group. Furthermore, pulmonary compliance decreased (P <.05) in all groups except the off-pump group after extubation. Duration of hospital and intensive care unit stay was significantly shorter (P <.05) in the off-pump group than in the other groups. CONCLUSION: The development of intrapulmonary shunting and hypoxemia after coronary artery bypass grafting can be substantially reduced by performance of total vital capacity maneuvers while patients are mechanically ventilated. However, off-pump coronary artery bypass surgery is superior in preventing shunting and hypoxemia after bypass grafting in the immediate and early postoperative periods, probably leading to substantially shorter intensive care unit and hospital stays.     

Consensus guidelines for sustained neuromuscular blockade in critically ill children

BACKGROUND: The United Kingdom Paediatric Intensive Care Society Sedation, Analgesia and Neuromuscular Blockade Working Group is a multidisciplinary expert panel created to produce consensus guidelines on sedation, analgesia and neuromuscular blockade in critically ill children and forward knowledge in these areas. Neuromuscular blockade is recognized as an important element in the care of the critically ill and adult clinical practice guidelines in this area have been available for several years. However, similar clinical practice guidelines have not previously been produced for the critically ill pediatric patient. METHODS: A modified Delphi technique was employed to allow the Working Group to anonymously consider draft recommendations in up to three Delphi rounds with predetermined levels of agreement. This process was supported by a total of four consensus conferences and once consensus had been achieved, a systematic review of the available literature was carried out. RESULTS: A set of consensus guidelines was produced including six key recommendations. An evaluation of the existing literature supporting these recommendations is provided. CONCLUSIONS: Multidisciplinary consensus guidelines for maintenance neuromuscular blockade in critically ill children (excluding neonates) have been successfully produced and are supported by levels of evidence. The Working Group has highlighted the paucity of high quality evidence in these important clinical areas and this emphasizes the need for further randomized clinical trials in this area.     

The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers

BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) could extend the duration of response of androgen sensitive prostate cancers to androgen deprivation. METHODS: We investigated the effect of new GHRH antagonists MZ-J-7-118 and MZ-J-7-138 and luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix or castration on androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancer models xenografted into nude mice. Animals bearing androgen-independent LuCaP-35V prostatic cancer model were also treated with MZ-J-7-118. RESULTS: Receptors for LHRH and GHRH were present in MDA-PCA-2b, LuCaP-35, and LuCaP-35V tumors. GHRH antagonists increased the inhibitory effect of surgical castration and LHRH antagonists on androgen sensitive MDA-PCa-2b and LuCaP-35 tumors. The time to relapse of androgen-dependent LuCaP-35 tumors was extended by GHRH antagonists. Growth of androgen-independent LuCaP-35V xenografts was also significantly inhibited by MZ-J-7-118. In MDA-PCa-2b tumors treatment with MZ-J-7-118 caused a significant decrease of VEGF and Cetrorelix or its combination with MZ-J-7-118 reduced EGF. The B(max) of EGF receptors was significantly reduced by Cetrorelix, MZ-J-7-118 and their combination. CONCLUSIONS: Our findings suggest that the use of a combination of antagonists of GHRH and LHRH could improve the therapy for androgen sensitive prostate cancer. Antagonists of GHRH could be also considered for treatment of androgen-independent prostate cancers.     

Role of amiodarone on the systemic inflammatory response induced by cardiac surgery: proinflammatory actions

PURPOSE: Amiodarone (AMIO), a widely used anti-arrhythmic drug, has been shown to reduce the incidence of atrial fibrillation after cardiac surgery and also to exert immunomodulatory actions in vitro and proinflammatory effects in vivo. The present study investigated the immunomodulatory properties of AMIO in the inflammatory response induced by cardiac surgery with cardiopulmonary bypass (CPB). METHODS: In this double-blind, placebo-controlled trial, 20 patients undergoing elective coronary artery bypass graft were randomized to receive placebo or AMIO 600 mg day(-1) orally for seven days before surgery and 45 mg hr(-1) intravenously for 48 hr postoperatively. Plasma levels of the proinflammatory markers C-reactive protein (CRP), fibrinogen (FBG), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and the antiinflammatory marker IL-10, were compared before and after surgery. RESULTS: Ninety-six hours after start of surgery, plasma levels of FBG had more than doubled (2.2 +/- 0.5-fold increase, P < 0.0001). Overall, FBG formation was significantly increased in the AMIO group (P = 0.048). Monocyte chemoattractant protein 1 secretion transiently increased four hours after start of surgery (6.6 +/- 4.5-fold increase) but rapidly declined thereafter, (P < 0.0001). There was a trend toward higher MCP-1 plasma concentrations in the AMIO group (P = 0.13). The plasma levels of CRP, TNF-alpha, IL-6 and Il-10 changed significantly over time, but were not altered by AMIO treatment. CONCLUSION: In the inflammatory response induced by cardiac surgery with CPB, our data suggest that AMIO treatment is associated with a selective trend toward proinflammatory actions.     

Splenectomy versus medical treatment for idiopathic thrombocytopenic purpura

BACKGROUND: Treatment strategies for idiopathic thrombocytopenic purpura (ITP) are still uncertain and its management is primarily empirical. The aim of this study was to investigate the role of splenectomy in the therapy of ITP and to evaluate whether medical or surgical treatment is superior. METHODS: Ninety-two patients with ITP were included in the study. All of these patients had medical therapy and 38 of them underwent splenectomy subsequently. Follow-up was completed in 91 patients after a median of 64 months. RESULTS: Side effects of medical therapy were noticed in 32 patients (35%), whereas after surgery only 2 patients (5%) had minor complications. A complete or partial remission was achieved in 35 patients (92%) after splenectomy, whereas this was achieved in only 27 patients (30%) after medical therapy. On multivariate analysis splenectomy and age were the only significant independent factors for complete and partial remission. CONCLUSIONS: Splenectomy is highly effective and safe in the treatment of ITP and is superior over medical therapy. These results should stimulate the discussion about splenectomy for ITP, possibly establishing evidence-based guidelines for surgical treatment in hematology.