NCT00530933 (http://www.clinicaltrials.gov).

No abstract

Sacral nerve stimulation can maintain a persistent clinical benefit in the long term for the majority of patients. Some patients will experience deterioration in their symptoms over time, for reasons yet unknown.

Summary. Development of autoantibody against coagulation factor V (FV) is a rare clinical condition with hemorrhagic complications of varying severity. The aim of this study was to establish the pathomechanism of an acquired FV deficiency and characterize the FV inhibitor responsible for the clinical symptoms. A 78-year-old female was admitted to hospital with severe gastrointestinal bleeding. General clotting tests and determination of clotting factors were performed by standard methods. FV antigen and FV containing immune complexes were measured by ELISA. The FV molecule was investigated by Western blotting and by sequencing the f5 gene. The binding of patient's IgG to FVand activated FV (FVa) was demonstrated in an ELISA system and its effect on the procoagulant activity of FVa was tested in clotting tests and in a chromogenic prothrombinase assay. Localization of the epitope for the antibody was performed by blocking ELISA. FV activity was severely suppressed both in plasma and platelets. FV antigen levels were normal by ELISA using polyclonal anti-FV antibody or monoclonal antibody against the connecting region of FV, but depressed when HV1 monoclonal antibody against the C2 domain in the FV light-chain was used as capture antibody. The FV molecule was found intact. An IgG reacting with both FV and FVa was present in the patient's plasma and its binding to FV was inhibited by HV1 antibody. FV-containing immune complexes were detected in the patient's plasma and platelet lysate. The patient's IgG inhibited the procoagulant function of FVa. An anti-FV IgG was present in the patient's plasma and platelets. The autoantibody reacted with an epitope in the C2 domain of FV light chain and neutralized the procoagulant function of FVa.Keywords: factor V, factor V inhibitor, hemorrhagic diathesis, platelets.Human coagulation factor V (FV) is a single-chain glycoprotein with a Mr of 330 kDa. Its plasma concentration is approximately 20 nmol L À1 (7 mg mL À1 ) [1]. Approximately 25% of whole blood FV is compartmentalized in the a-granules of platelets and becomes secreted during activation [1,2]. The principal site of FV biosynthesis is the liver [3,4], but it is still unclear whether platelet FV originates from the uptake of exogenous FV via endocytosis by megakaryocytes or megakaryocytes themselves can synthesize FV [5][6][7]. Single chain FV has a structure consisting of three homologous A domains and two homologous C domains connected by a heavily glycosylated B domain in the order of A1-A2-B-A3-C1-C2 [8,9]. The gene for human FV has been localized to chromosome 1q21-25, it spans approximately 80 kilobases of DNA and consists of 25 exons and 24 introns [10]. Proteolytic cleavage of FV by a-thrombin results in the removal of B-domain and converts the pro-cofactor into active cofactor (FVa) that enhances factor Xa (FXa) À catalyzed activation of prothrombin by several thousand-fold [11,12]. FVa contains a heavy chain (HC; Mr 105 kDa) and a light chain (LC; Mr 71 or 74 kDa) associated via calcium bond [13]. The HC is ...

We have shown that it is safe and reasonable to offer fistulotomy to appropriate patients despite previous surgery and within the tertiary setting. By so doing, a very high rate of healing can be achieved in patients who have previously failed. The additional risk of impairment of continence is around one in five, and in the majority will represent only minor incontinence.

Summary The 6 month prospective, randomized study compared the steroid‐sparing potential of two tacrolimus‐based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid‐resistant acute rejection and with serum creatinine concentrations <160 μmol/l. The incidence of biopsy‐confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4–6 was low in all groups, both for patients on steroid‐free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid‐free patients with month 6 median serum creatinine levels of 119.5 μmol/l (Tac/MMF), and 115.1 μmol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 μmol/l (Tac/MMF/S) and 132.8 μmol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus‐based regimens allowed the safe discontinuation of steroids in low‐risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.

Two cases of neoesophago-tracheal fistula are described. After esophagectomy for cancer a fistula developed between the trachea and the pulled-up stomach probably because of the ischaemic effect of the tracheostomy tube. At single stage repairs, the fistulae were divided and the gastric defects were closed directly. In one case, tracheal resection and anastomosis was necessary. The defect on the membranous trachea in both cases was patched with an autologous fascia lata graft. A left pectoralis major muscle flap was interposed between the suture lines to prevent recurrence of the fistula. Treatment of this potentially life-threatening and rare condition yielded excellent results.

A disturbed glucose homeostasis was observed in gastrectomized patients most prominently in the Roux-en-Y group. Also, cholecystokinin and somatostatin response differed significantly in favor of duodenal passage preservation after total gastrectomy. Cholecystokinin levels close to physiologic found at APwPDP reconstruction may contribute to a physiologic satiation in reconstructions with preserved duodenal passage after total gastrectomy.