Biomedical subjects

Kevin E Behrns

Publications and source records attributed to Kevin E Behrns.

6 recordsLinked to original sources

PubMed2003

Fundoplication improves disordered esophageal motility.

Patients with gastroesophageal reflux disease (GERD) and disordered esophageal motility are at risk for postoperative dysphagia, and are often treated with partial (270-degree) fundoplication as a strategy to minimize postoperative swallowing difficulties. Complete (360-degree) fundoplication, however, may provide more effective and durable reflux protection over time. Recently we reported that postfundoplication dysphagia is uncommon, regardless of preoperative manometric status and type of fundoplication. To determine whether esophageal function improves after fundoplication, we measured postoperative motility in patients in whom disordered esophageal motility had been documented before fundoplication. Forty-eight of 262 patients who underwent laparoscopic fundoplication between 1995 and 2000 satisfied preoperative manometric criteria for disordered esophageal motility (distal esophageal peristaltic amplitude < or =30 mm Hg and/or peristaltic frequency < or =80%). Of these, 19 had preoperative manometric assessment at our facility and consented to repeat study. Fifteen (79%) of these patients had a complete fundoplication and four (21%) had a partial fundoplication. Each patient underwent repeat four-channel esophageal manometry 29.5 +/- 18.4 months (mean +/- SD) after fundoplication. Distal esophageal peristaltic amplitude and peristaltic frequency were compared to preoperative data by paired t test. After fundoplication, mean peristaltic amplitude in the distal esophagus increased by 47% (56.8 +/- 30.9 mm Hg to 83.5 +/- 36.5 mm Hg; P < 0.001) and peristaltic frequency improved by 33% (66.4 +/- 28.7% to 87.6 +/- 16.3%; P < 0.01). Normal esophageal motor function was present in 14 patients (74%) after fundoplication, whereas in five patients the esophageal motor function remained abnormal (2 improved, 1 worsened, and 2 remained unchanged). Three patients with preoperative peristaltic frequencies of 0%, 10%, and 20% improved to 84%, 88%, and 50%, respectively, after fundoplication. In most GERD patients with esophageal dysmotility, fundoplication improves the amplitude and frequency of esophageal peristalsis, suggesting refluxate has an etiologic role in motor dysfunction. These data, along with prior data showing that postoperative dysphagia is not common, imply that surgeons should apply complete fundoplication liberally in patients with disordered preoperative esophageal motility.

Adult↗

PubMed2002

A scientist revisits the atrophy-hypertrophy complex: hepatic apoptosis and regeneration.

In 1898, Cantlie demonstrated his deep insight into the AHC when he wrote. "It is theoretically possible to tie the vessels of one side at the gate of the liver...leaving the other side to do the work. That one-half of the liver can hypertrophy, so as to perform the function of the whole, is attested by pathological study...I commend this subject to all those who are working on the surgery of the liver; and I believe that if, in the hands of future observers, the statements I have made receive closer investigation, surgery of the liver will be advanced a step." More than 100 years later, his foresight is coming to fruition, but the understanding of the AHC remains rudimentary. Further insight into the cellular and molecular mechanisms that initiate hepatocyte replication after contralateral atrophy may allow the development of novel therapeutic treatments or adjuncts.

Animals↗

PubMed2002

Cholestasis induces murine hepatocyte apoptosis and DNA synthesis with preservation of the immediate-early gene response.

BACKGROUND: Major hepatic resection in patients with unrelieved obstructive jaundice carries an increased risk of postoperative liver failure. We hypothesized that cholestasis induces hepatocyte apoptosis and impairs hepatic regeneration by inhibiting up-regulation of the known immediate-early response genes, nuclear factor kappa B (NF-kappaB) and activating protein-1 (AP-1). The aim of this study was to determine whether the immediate-early gene response in hepatic regeneration remains intact in extrahepatic cholestasis. METHODS: Eight-week-old BALB/c mice underwent either sham operation (SO) or common bile duct ligation (BDL). Two-thirds partial hepatectomy (PH) was performed at 4 and 7 days, with remnant liver harvested 0, 15, 30, or 60 minutes after PH. Serum analysis for markers of cholestasis and histopathology was obtained. Proliferating cell nuclear antigen and terminal deoxyuridine triphosphate nick end labeling (TUNEL) immunohistochemistry for detection of DNA synthesis and apoptosis, respectively, was performed 4, 7, or 10 days after SO or BDL. Liver samples from 0, 15, 30, or 60 minutes after PH were analyzed for NF-kappaB and AP-1 DNA binding activity by using electrophoretic mobility shift assays. RESULTS: Increased serum bilirubin level and hematoxylin-eosin-stained liver sections confirmed cholestasis in BDL mice. BDL induced marked DNA synthesis and hepatocyte apoptosis in prehepatectomy liver at both 4 and 7 days. Substantially higher basal levels of both NF-kappaB and AP-1 binding activity were present in BDL compared with SO mice. Fold induction of NF-kappaB and AP-1, however, was similar between BDL and SO mice. Cholestasis induced hepatocyte DNA synthesis and apoptosis. Basal NF-kappaB and AP-1 DNA binding activity was increased in BDL mice, but fold induction of these immediate-early genes did not differ from controls. CONCLUSIONS: Although basal NF-kappaB and AP-1 DNA binding is increased in cholestasis, the immediate-early gene response to PH remains intact in BDL mice.

Animals↗

PubMed2002

Transforming growth factor-beta1 induces hepatocyte apoptosis by a c-Jun independent mechanism.

BACKGROUND: During hepatic regeneration, transforming growth factor (TGF)-beta1 messenger RNA increases after the initial cycle of DNA synthesis, and it may control hepatocyte growth by inducing apoptosis. TGF-beta1 also induces c-Jun, a potential proapoptotic transcription factor. We hypothesized that autocrine expression of activated TGF-beta1 (Ad5aTGF-beta1) would increase c-jun expression in rat liver and limit hepatic regeneration by inducing apoptosis. METHODS: Male rats (175 to 200 g) received portal venous injections with adenoviruses expressing either luciferase (Ad5Luc), as a control, or Ad5aTGF-beta1 at a dose of 6 x 10(9) plaque-forming units. Livers were harvested 24 or 48 hours after injection and nuclear extracts and total RNA isolated. TGF-beta1 expression was confirmed by Northern blot analysis in all TGF-beta1-injected rats. RESULTS: A 2.5-fold increase in c-jun mRNA expression was detected in Ad5aTGF-beta1-infected rats compared with control rats. Transcriptional activity was assessed with an AP-1-responsive-reporter gene that increased 3-fold in rat primary hepatocytes infected with Ad5aTGF-beta1. C-Jun N-terminal kinase activity also increased 6- to 7-fold in Ad5aTGF-beta1-treated rats 24 and 48 hours after injection. Ad5aTGF-beta1-injected rats demonstrated increased AP-1 binding activity compared with Ad5Luc rats. Hepatocytes infected in vitro with Ad5aTGF-beta1 demonstrated increased apoptosis compared with Ad5Luc-infected hepatocytes (47% vs 27%) 36 hours after infection. Dual adenoviral infection with Ad5aTGF-beta1 and a dominant-negative c-Jun (Ad5TAM67) decreased AP-1-induced Ad5Luc activity but not hepatocyte apoptosis (46% with dominant-negative c-Jun and 47% without). CONCLUSIONS: These data demonstrate that TGF-beta1 induces c-Jun, but c-Jun is not proapoptotic in hepatocytes.

Adenoviridae↗

PubMed2002

Primary splenic lymphoma complicated by hematemesis and gastric erosion.

Gastrosplenic fistula resulting from erosion of a primary splenic lymphoma is a rare cause of massive upper gastrointestinal hemorrhage associated with benign peptic ulcer disease, gastric Crohn's disease, gastric adenocarcinoma, and primary gastric and splenic lymphomas. Upper intestinal hemorrhage can be successfully treated with splenic artery embolization, followed by splenectory and gastric resection.

Adult↗

PubMedDate not supplied

Gallbladder function before and after fundoplication.

No study has reported an association between gastroesophageal reflux disease (GERD) or its therapies and gallbladder function. We compared pre- and postoperative gallbladder function in patients undergoing fundoplication to determine the following: (1) whether patients with chronic GERD have preexisting gallbladder motor dysfunction; (2) whether medical or surgical therapy alters gallbladder function; and (3) whether division of the hepatic branch of the anterior vagus nerve is detrimental to gallbladder motility. Nineteen patients with documented GERD consented to a preoperative cholecystokinin-stimulated technetium hepatobiliary (CCK-HIDA) scan to quantify the gallbladder ejection fraction (GBEF). All patients underwent laparoscopic Nissen fundoplication. One month after fundoplication, 12 patients completed a repeat CCK-HIDA scan for determination of GBEF, with comparison to the preoperative GBEF. Among patients with preoperative GERD, 11 (58%) of 19 met the scintigraphic criteria for gallbladder dysfunction (GBEF <35%), which is a ratio comparable to that in patients undergoing a CCK-HIDA scan for presumed biliary dyskinesia during the same time period (31 [60%] of 53; P = NS, chi-square test) and exceeds the rate of abnormal GBEF reported in healthy volunteers (3%). Six of seven patients with a low preoperative GBEF who underwent repeat evaluation postoperatively had normalization of the GBEF (P < 0.05, paired t-test). In the 12 patients who underwent postoperative CCK-HIDA scanning, there was no association between preservation or division of the hepatic branch of the anterior vagus nerve and postoperative gallbladder dysfunction (P = NS, chi-square test). Unexpectedly, 58% of patients with GERD demonstrated gallbladder motor dysfunction prior to fundoplication, with improvement to normal occurring in most of those studied postoperatively. These data support controlled trials to determine the effect of chronic GERD and antisecretory therapy on gallbladder and global gastrointestinal smooth muscle function. Preservation of the hepatic branch of the anterior vagus nerve during fundoplication offered no clear benefit with regard to early postoperative gallbladder function.

Adult↗