Association between human rhinovirus C and severity of acute asthma in children.

A new and potentially more pathogenic group of human rhinovirus (HRV), group C (HRVC), has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups. Children with acute asthma (n = 128; age 2-16 yrs) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed, and respiratory viruses and HRV strains were identified in a nasal aspirate. The majority of the children studied had moderate-to-severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n = 76) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n = 34; p = 0.018), and all other children (n = 50; p = 0.016). Of the 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC. HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously known HRV groups and other viruses.

The fate of patients who undergo "preoperative" ERCP to clear known or suspected bile duct stones.

BACKGROUND: There is debate as to whether recurrent biliary complications are more common in patients who do not have elective cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) management of common bile duct (CBD) stones. The aim of this study was to determine the fate of patients with intact gallbladders who have had CBD stones removed at ERCP, and to assess their risk of recurrent biliary symptoms. METHODS: We retrospectively identified all patients in our large tertiary center population with intact gallbladders who had an ERCP for CBD stones from December 1999 to March 2002. We determined which patients had subsequent elective cholecystectomy, and the outcomes of patients who did not have elective surgery. RESULTS: 309 patients had CBD stones at ERCP during the study period, of which 139 had intact gallbladders at the time of ERCP. Of these 139 patients 59 had subsequent elective cholecystectomy, 11 by open operation and 48 laparoscopically. Of these 139 patients, 27 had cholecystectomy planned; 47 patients were managed with a wait-and-see strategy, 30 of whom were poor surgical candidates. Of these 47 patients in whom a wait-and-see policy was adopted, 9 (19%) developed complications including recurrent pain and/or abnormal liver function tests (LFTs), recurrent biliary colic, and pancreatitis. Eight of these nine patients were from the poor surgical candidate group. Sphincterotomy had been performed at initial ERCP in all patients. CONCLUSIONS: Over half of our population of 139 patients with CBD stones at ERCP and intact gallbladders had actual or planned elective cholecystectomy. For those patients in whom a decision to wait-and-see was made, almost 20% developed complications. Elective cholecystectomy after a finding of choledocholithiasis is supported by many and is a common strategy in our experience. Recurrent biliary complications are relatively common in those who do not undergo elective cholecystectomy, especially those patients who represent a high operative risk.

Supply and demand for liver transplant surgery: are we training enough surgeons?

The purpose of our study is to determine whether the current level of transplant fellow training is sufficient to meet the future demand for liver transplantation in the United States. Historical data from the Nationwide Inpatient Samples (NIS) for the years 1998 through 2003 were used to construct an estimate of the annual number of liver transplant procedures currently being performed in the United States, and the number projected for each year through 2020. Estimates for the current and future number of surgeons performing liver transplant procedures were also constructed using the same database. The NIS database was used because current national transplant registries do not include information on the number of surgeons performing liver transplant procedures. Using historical data derived from the NIS database, we project that the estimated number of liver transplant procedures per surgeon will remain relatively stable through 2020, with each surgeon performing an average of 12.9 procedures in 2020 compared to 12.9 currently. We conclude that the relationship between demand for liver transplantation in the United States and the supply of liver transplant surgeons will remain stable over the next 15 years.

Serial viral infections in infants with recurrent respiratory illnesses.

To better understand the viral aetiology of recurrent and prolonged illnesses, nasal secretions were prospectively collected from 285 infants at increased risk of developing asthma. Of these, 27 infants had recurrent (at least five) moderate-to-severe respiratory illnesses (MSIs). The viral aetiology of the 150 MSIs and 86 scheduled visits was analysed by molecular diagnostics. The demographic and clinical data were compared with infants who had 0-4 MSIs. Frequently ill infants had higher exposure to other children and more wheezing illnesses than less symptomatic children. Viruses were detected in 136 (91%) out of 150 MSIs, 14 (67%) out of 21 mild illnesses and 29 (45%) out of 65 asymptomatic visits. Human rhinovirus was the most common aetiological agent (61, 43 and 35% in MSIs, mild illnesses and asymptomatic visits, respectively). Mixed viral infections were generally associated with more severe illnesses (27, 0 and 5%, respectively). Among the 27 frequently ill infants, only eight (5.3%) out of 150 MSIs were prolonged (> or =2 weeks duration). Considering all samples, detection of the same virus strain > or =2 weeks apart was unusual (5.3% of all 244 positive findings). Human rhinovirus infections occur early, pervasively and repetitively in these high-risk infants. Infants with prolonged or recurrent respiratory illnesses most often have a series of infections rather than persistent infection with one virus strain.

The influence of processing factors and non-atopy-related maternal and neonate characteristics on yield and cytokine responses of cord blood mononuclear cells.

RATIONALE: Several studies have evaluated the associations between cord blood cellular responses and atopic diseases in children, but the results of these studies are inconsistent. Variations in blood processing factors and maternal and infant characteristics are typically not accounted for and may contribute to these inconsistencies. METHODS: Cord blood samples were obtained from 287 subjects participating in the Childhood Origins of ASThma project, a prospective study of children at high risk for the development of asthma/allergies. Mononuclear cells were stimulated with phytohaemagglutinin (PHA), phorbal myristate acetate/ionomycin or a suspension of killed staphylococcus, and IFN-gamma, IL-10 and IL-13 were quantitated by ELISA. Cell yields and cytokine production were related to processing factors and maternal and infant characteristics. RESULTS: The strongest relationships between independent variables and cell yield or cytokine responses occurred with the season of birth. The highest median cell yields were seen in fall, and the lowest in summer (difference of 47%, P=0.0027). Furthermore, PHA-induced IL-5 and IL-13 responses were approximately 50% higher in spring and summer than in fall or winter (P<0.0001). Clots in the cord blood samples were associated with a reduced median cell yield (42% reduction, P<0.0001), and an increased PHA-induced IL-10 secretion (27% increase, P=0.004). CONCLUSIONS: These data suggest that season of collection, and to a lesser extent clotting in samples, affect cord blood mononuclear cell yield and cytokine responses. Careful documentation and analysis of processing and environmental variables are important in understanding biological relationships with cytokine responses, and also lead to greater comparability among studies using these techniques.

Endogenous acyl ghrelin is involved in mediating spontaneous phase III-like contractions of the rat stomach.

In humans and dogs, it is known that motilin regulates phase III contractions of migrating motor complex (MMC) in the fasted state. In rats, however, motilin and its receptor have not been found, and administration of motilin failed to induce any phase III-like contractions. Ghrelin was discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) from the rat stomach. Ghrelin promotes gastric premature phase III (phase III-like contractions) in the fasted state in rats. We hypothesized that endogenous ghrelin regulates spontaneous phase III-like contractions in rats. Strain gauge transducer was sutured on the antrum and a catheter was inserted into the jugular vein. We studied the effects of i.v. administration of ghrelin and a GHS-R antagonist on gastric phase III-like contractions in conscious rats. Plasma level of ghrelin was measured by a radioimmunoassay. Ghrelin augmented spontaneous phase III-like contractions and a GHS-R antagonist significantly attenuated the occurrence of spontaneous phase III-like contractions. During the phase I period, plasma ghrelin level increased to its peak then returned to basal level, subsequently phase III-like contractions were observed. These results suggest that endogenous ghrelin regulates gastric phase III-like contractions in rats.

Laparoscopic distal pancreatectomy with splenic preservation.

BACKGROUND: The technique of distal pancreatectomy has been well described, both with en bloc resection of the spleen and with splenic preservation. Splenic preservation during pancreatic tail resection is desirable when oncologically appropriate, yet it is technically challenging, particularly with laparoscopic approaches. Skeletonization of the splenic artery and vein is associated with longer operative times and greater potential for bleeding. The authors report their experience with splenic preservation during laparoscopic pancreatic resection using ligation of the splenic vessels and preservation of the short gastric vessels. METHODS: A retrospective chart review was performed for all patients who underwent attempted laparoscopic pancreatic resection at Duke University Medical Center from July 2002 to October 2005. Charts were analyzed for demographic information, length of hospital stay, conversion, splenic preservation, and postoperative complications. RESULTS: A total of 12 laparoscopic distal pancreatic resections were attempted for three men and nine women with a mean age was 55.8 years (range, 33-74 years). All 12 patients underwent distal pancreatectomy, 8 with splenic preservation. The spleen was removed from three patients using splenic hilar lesions that prevented splenic salvage. One patient required splenectomy secondary to more than 50% ischemia of the spleen. No patients with preoperatively diagnosed malignancy underwent splenic salvage. The final pathologic diagnosis included neuroendocrine tumors (n = 2), cystic serous (n = 4) and mucinous (n = 2) neoplasms, intraductal papillary mucinous neoplasm (IPMN) (n = 1), pancreatitis (n = 2), and adenocarcinoma (n = 1). Two patients underwent conversion to open surgery for thickened parenchyma secondary to chronic pancreatitis (17%). There were no other conversions. There were three chemical leaks (25%) diagnosed by elevated drain amylase and low volume output, which were managed with intraoperatively placed drains removed at the initial postoperative clinic visit. There were three higher volume leaks (25%) that required extended or percutaneous drainage, with eventual removal. The average blood loss was 215 ml (range, 50-700 ml). The average operative time was 3 h and 41 min (range, 2 h 15 min to 5 h 58 min). The average length of hospital stay was 4 days (range, 2-7 days). CONCLUSION: Splenic preservation should be performed when technically possible to decrease the morbidity of laparoscopic distal pancreatectomy. The choice to ligate the splenic vessels allows for shorter operative times with minimal perioperative morbidity and blood loss while maintaining the spleen.

Percutaneous cervical oesophageal cannulation in the dog for the performance of prolonged oesophageal pH and manometric studies.

Traditional methods for obtaining oesophageal access in experimental animals are unsuitable for prolonged (24 h) oesophageal pH evaluation, a procedure that is commonly employed in the assessment of human patients suspected of having gastroesophageal reflux disease. In the present study, we describe a six-year experience with a technique of percutaneous oesophagostomy for the performance of serial 24 h oesophageal pH and manometric studies involving 62 dogs and a total of 208 oesophageal cannula placement procedures. The results indicate a considerable improvement over previously described techniques with respect to simplicity of surgical technique, associated morbidity, oesophagostomy management, animal conditioning, and avoidance of chemical and excessive physical restraints in animals undergoing oesophageal pH and manometric evaluation.

Impaired gastric motor activity after abdominal surgery in rats.

Postoperative ileus (POI) is a transient bowel dysmotility that occurs following abdominal surgery. Several mechanisms have been proposed such as neural reflex and inflammatory changes. We focused on gastric motility after abdominal surgery in rats. To investigate the time course of gastric motility after surgery, gastric motility was continuously recorded before, during and after surgery. After laparotomy, terminal ileum was manipulated for 10 min. Gastric motility was recorded by a strain gauge transducer implanted on the serosal surface of the stomach. To investigate whether peripheral sympathetic nerve is involved in the pathogenesis of POI, effects of guanethidine and celiac ganglionectomy were tested on the postoperative gastric motility. Although isoflurane anaesthesia reduced the gastric motility to 40%, the motility recovered immediately when isoflurane was withdrawn. Intestinal manipulation reduced the postoperative gastric motility for 3-24 h after surgery, compared with preoperative levels. Guanethidine administration and celiac ganglionectomy restored the impaired gastric motility. Feeding increased the gastric motility in each group. It is suggested that the pathogenesis of postoperative gastric ileus induced by intestinal manipulation involves viscero-sympathetic pathways. Intestinal manipulation causes impaired gastric motility via inhibitory sympathetic efferent pathway. Feeding may improve the postoperative gastric motility.

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Magnitude of abdominal incision affects the duration of postoperative ileus in rats.

BACKGROUND: The pathogenesis of reduced postoperative ileus (POI) in laparoscopic gastrointestinal (GI) surgery still remains controversial. The aim of this study was to investigate the effect of surgical incision on postoperative ileus. METHODS: The effects of length, depth, and site of the incision on GI transit were compared using the geometric center of 51Cr in rats. The inhibitory mechanism of abdominal incision on GI transit also was studied. RESULTS: The findings showed that 5 cm of abdominal skin and the 5-cm back muscle incision had no significant effect on GI transit. However, the 5-cm abdominal muscle-fascia incision and a 5-cm laparotomy significantly delayed GI transit. Gastrointestinal transit after a 5-cm laparotomy was significantly delayed, as compared with that of a 1-cm laparotomy regardless whether intestinal manipulation was performed or not. Guanethidine and yohimbine, but not propranolol, significantly improved the impaired GI transit after a 5-cm laparotomy. CONCLUSIONS: The results suggest that the longer and deeper abdominal incision more profoundly inhibits GI transit. The inhibitory effect of abdominal incision is mediated via the activation of the somatosympathetic reflex and alpha-2 adrenoceptors.

Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats.

BACKGROUND AND AIMS: The role of sensory neurones in colitis was studied by chemical denervation of primary sensory neurones as well as antagonism of the vanilloid receptor-1 (VR-1) in rats prior to administration of dextran sulphate sodium (DSS) to induce colitis. METHODS: Neonatal rats were chemically denervated by subcutaneous administration of capsaicin; controls received capsaicin vehicle only. When animals reached maturity, colitis was induced by administration of 5% DSS in drinking water for seven days. Additionally, normal adult rats were treated with a VR-1 antagonist capsazepine (CPZ) or vehicle twice daily via an enema from day 0 to day 6 of the DSS regimen. Control rats were treated with an enema infusion of vehicle and 5% DSS, or without either an enema infusion or DSS in drinking water. For both groups of rats, severity of inflammation was quantitated by disease activity index (DAI), myeloperoxidase (MPO) activity, and histological examination. RESULTS: DSS induced active colitis in all control rats with resultant epithelial ulceration, crypt shortening, and neutrophil infiltration. Both neonatal capsaicinised rats and normal adult rats treated with CPZ enemas exhibited significantly lower levels of DAI, MPO, and histological damage compared with vehicle treated rats (p< 0.05). CONCLUSIONS: Neonatal capsaicinisation and local administration of CPZ prevents intestinal inflammation in a well established model of colitis indicating that primary sensory neurones possessing VR-1 receptors are required in the propagation of colonic inflammation.

Laparoscopic antireflux surgery in the lung transplant population.

BACKGROUND: Lung transplantation has emerged as a viable therapeutic option for patients with a variety of end-stage pulmonary diseases. As immediate posttransplant surgical outcomes have improved, the greatest limitation of lung transplantation remains chronic allograft dysfunction. Gastroesophageal reflux disease (GERD) with resultant aspiration has been implicated as a potential contributing factor in allograft dysfunction. GERD is prevalent in end-stage lung disease patients, and it is even more common in patients after transplantation. We report here on the safety of laparoscopic fundoplication surgery for the treatment of GERD in lung transplant patients. METHODS: Eighteen of the 298 lung transplants performed at Duke University Medical Center underwent antireflux surgery for documented severe GERD. The safety and benefit of laparoscopic fundoplications in this population was evaluated. RESULTS: The antireflux surgeries included 13 laparoscopic Nissen fundoplications, four laparoscopic Toupets, and one open Nissen (converted secondary to extensive adhesions). Two of the 18 patients reported recurrence of symptoms (11%), and two others reported minor GI complaints postoperatively (nausea, bloating). There were no deaths from the antireflux surgery. After fundoplication surgery, 12 of the 18 patients showed measured improvement in pulmonary function (67%). CONCLUSIONS: GERD occurs commonly in the posttransplant lung population. Laparoscopic fundoplication surgery, when indicated, can be done safely with minimal morbidity and mortality. In addition to the resolution of reflux symptoms, improvement in pulmonary function may be seen in this population after fundoplication. Lung transplant patients with severe GERD should be strongly considered for antireflux surgery.

A canine model of gastroesophageal reflux disease (GERD).

BACKGROUND: Although a variety of antireflux procedures and medications are used to treat gastroesophageal reflux disease (GERD), reliable large-animal models of GERD that can be used to objectively compare the efficacy of these treatments are lacking. METHODS: Esophageal manometry and 24-h gastroesophageal pH monitoring with event data were performed in 18 mongrel dogs with a cervical esophagopexy. We then calculated a modified DeMeester score: The Duke Canine reflux score (DCR). Thereafter, the animals underwent a 4-cm anterior distal esophageal myotomy, incision of the left diaphragmatic crus, and intrathoracic gastric cardiopexy. Postoperative 24-h pH and manometry were obtained 2 weeks later. RESULTS: The postoperative 24-h pH results showed a significant increase in the mean DCR score (5.9 +/- 4.5 vs 84.9 +/- 56.1, p < 0.0002), and manometry indicated a significant decrease in mean lower esophageal sphincter (LES) pressure (7.1 +/- 2.9 vs 3.2 +/- 2.5 mmHg, p < 0.0001). CONCLUSION: This technique reliably creates a canine model of GERD.

ERCP-related perforations: risk factors and management.

BACKGROUND AND STUDY AIMS: Perforations during endoscopic retrograde cholangiopancreatography (ERCP) are rare, and the management of these perforations is variable, with some patients requiring immediate surgery and others only conservative management. We reviewed all ERCP-related perforations at our institution to determine: a) their incidence; b) clinical outcomes; c) which management approaches gave the best results; and d) which factors predict a perforation. PATIENTS AND METHODS: All patients who underwent ERCP and suffered perforation were reviewed. To compare the length of hospital stay of the perforation group with that of patients suffering a different complication, patients who developed post-ERCP pancreatitis were also reviewed. To evaluate predictors of ERCP-related perforations, three groups were compared: group 1 (n = 49), normal ERCP/no complications; group 2 (n = 52), ERCP complicated by pancreatitis; and group 3 (n = 33), ERCP with perforation. RESULTS: Of 33 patients with confirmed ERCP-related perforations, only seven patients required surgical intervention. The overall length of hospital stay (6.5 +/- 3.5 days) was significantly longer (P = 0.003) than that of a random group of patients with the complication of post-ERCP pancreatitis (4.7 +/- 2.6 days). According to univariate analysis, risk factors included: sphincterotomy (odds ratio [OR] 9.0, 95 % confidence interval [CI] 3.2 - 28.1); sphincter of Oddi dysfunction (OR 3.8, 95 % CI 1.4 - 11.0); and dilated common bile duct (OR 4.07, 95 % CI 1.63 - 10.18, P = 0.003). In the multivariate logistic regression analysis, additional predictive factors included the duration of procedure (OR 1.021, 95 % CI 1.006 - 1.036), and biliary stricture dilation (OR 7.2, 95 % CI 1.84 - 28.11). CONCLUSIONS: (i) The incidence of ERCP-related perforations is very low (0.35 %). (ii) Esophageal, gastric and duodenal perforations usually require surgery, but sphincterotomy- and guide wire-related perforations rarely do so. (iii) Factors which carry increased risk of an ERCP-related perforation include suspected sphincter of Oddi dysfunction, greater age, a dilated bile duct, sphincterotomy, and longer duration of the procedure.

Unusually located left atrial papillary fibroelastoma with probable embolization to the spinal cord.

This report presents a patient with flaccid paraplegia, most probably secondary to embolization from a left atrial papillary fibroelastoma. The unique location of the tumor, attached to the ridge in the left atrium between the left atrial appendage and pulmonary vein, was well documented on transesophageal echocardiography, and the diagnosis was confirmed by histopathology. Although benign, these tumors may develop in all four cardiac chambers and result in pulmonary or systemic embolization. Paraplegia is a rare embolic complication.

Immediate and long-term outcomes after lateral pancreaticojejunostomy for chronic pancreatitis.

Lateral pancreaticojejunostomy (LPJ) is the recommended surgical treatment of intractable pain from chronic pancreatitis (CP) with obstruction and ductal dilatation. This study evaluated the etiology, morbidity, mortality, hospital costs, and quality of life (QL) for patients with LPJ for CP. Medical records of 60 patients undergoing LPJ for CP between 1988 and 1996 were reviewed. Long-term QL was assessed by the Short Form 36 Health Survey and analyzed against control populations of patients who underwent pancreatic debridement for necrosis and patients with laparoscopic cholecystectomy for cholelithiasis. CP etiologies included 52 per cent alcoholic, 28 per cent idiopathic, 13 per cent pancreatic divisum, and 7 per cent familial pancreatitis. Peri- and postoperative morbidity and mortality were 25 and 0 per cent respectively. Average hospital cost was $13,530 with mean postoperative hospital stay of 12.1 days. Overall physical and mental QL were diminished compared with both the debridement group and cholecystectomy group with particular detriments in areas of physical role (P < 0.05), bodily pain (P < 0.001), social function (P < 0.001), and mental health (P < 0.001). We conclude that LPJ for CP is a relatively safe procedure with low morbidity and mortality but results in a significantly diminished long-term QL relative to other surgical patients with pancreatic or biliary disease. This difference prevails in both physical and mental aspects of health.

Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience.

OBJECTIVE: To examine clinical outcomes in patients receiving neoadjuvant chemoradiation for locally advanced rectal adenocarcinoma. SUMMARY BACKGROUND DATA: Preoperative radiation therapy, either alone or in combination with 5-fluorouracil-based chemotherapy, has proven both safe and effective in the treatment of rectal cancer. However, data are lacking regarding which subgroups of patients benefit from the therapy in terms of decreased local recurrence and increased survival rates. METHODS: A retrospective chart review was performed on 141 consecutive patients who received neoadjuvant chemoradiation (5-fluorouracil +/- cisplatin and 4,500-5,040 cGy) for biopsy-proven locally advanced adenocarcinoma of the rectum. Surgery was performed 4 to 8 weeks after completion of chemoradiation. Standard statistical methods were used to analyze recurrence and survival. RESULTS: Median follow-up was 27 months, and mean age was 59 years (range 28-81). Mean tumor distance from the anal verge was 6 cm (range 1-15). Of those staged before surgery with endorectal ultrasound or magnetic resonance imaging, 57% of stage II patients and 82% of stage III patients were downstaged. The chemotherapeutic regimens were well tolerated, and resections were performed on 140 patients. The percentage of sphincter-sparing procedures increased from 20% before 1996 to 76% after 1996. On pathologic analysis, 24% of specimens were T0. However, postoperative pathologic T stage had no effect on either recurrence or survival. Positive lymph node status predicted increased local recurrence and decreased survival. CONCLUSIONS: Neoadjuvant chemoradiation is safe, effective, and well tolerated. Postoperative lymph node status is the only independent predictor of recurrence and survival.