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Biomedical subjects

G J Lane

Publications and source records attributed to G J Lane.

At least 19 recordsLinked to original sources

alpha-Glutathione-s-transferase as a new sensitive marker of hepatocellular damage in biliary atresia.

Early identification of patients likely to deteriorate post-hepatic portoenterostomy for biliary atresia (BA) would be beneficial. alpha-Glutathione-s-transferase (alpha-GST) is a serologic marker of reactive hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosol concentration, and short half-life. We evaluated whether serum alpha-GST in post-surgical BA patients correlates with liver function (LF) and investigated its potential as a medium- to long-term marker of prognosis. Postoperative BA patients (n = 30; mean age: 11.8 +/- 3.7 years) were divided into three groups based on average LF over the 3 months prior to this study. Group I (n = 8) were jaundice-free and had normal LF. Group II (n = 12) had moderate liver dysfunction, and group III (n = 10) had severe liver dysfunction. Serum alpha-GST was determined using a specific ELISA. Tissue alpha-GST was determined immunohistochemically, using liver needle-biopsy specimens. Bile lakes were found in 5 group II patients and 5 group III patients. Serum alpha-GST was significantly higher in group II (20.7 +/- 8.4 ng/ml) than in groups I (4.7 +/- 1.3 ng/ml) and III (8.0 +/- 1.2 ng/ml) (P < 0.0001) and was highest in group II subjects with bile lakes. In control liver specimens alpha-GST distribution was weak but uniform throughout normal liver lobule hepatocytes. In group II there was strong staining in centrilobular hepatocytes, and in group III alpha-GST was only found in regenerative nodules. We conclude that alpha-GST may be a more sensitive indicator of hepatocellular damage in BA because its distribution is correlated to the proportion of functioning liver tissue present. This is the first report of this relationship, which has great implications for group II subjects because a sudden shift in concentration of alpha-GST may be a better predictor of impending hepatic dysfunction than conventional LF tests.

Adolescent↗

Histology of the neobladder mucosa after sigmoidocolocystoplasty.

PURPOSE: The aim of this study was to examine the histopathology of neobladder mucosa biopsy specimens obtained routinely as part of postsigmoidocolocystoplasty (SCP) follow-up. METHODS: One hundred cases of SCP (mean age at surgery, 10.6 years) performed by the authors were examined for the presence of dysplasia or malignant changes in the mucosa of the neobladder using H&E and proliferating cell nuclear antigen (PCNA) staining. RESULTS: No dysplastic or malignant changes were identified in any case. Metaplasia was found in 5 cases and hyperplasia in 2. There were no major differences found on H&E and PCNA staining of specimens obtained after different periods of follow-up post-SCP; follow-up was short term (up to 5 years) in 44 cases, medium term (from 5 to 10 years) in 48 cases, and long term (over 10 years) in 8 cases. PCNA staining was significantly more intense in subjects who stopped regular bladder irrigations (BI) post-SCP and in subjects in whom bladder stones developed (P < .05; Welch's t test), compared with subjects who continued BI and subjects in whom bladder stones did not develop. CONCLUSIONS: After SCP, patients are advised to continue BI. Regular biopsies should be part of routine follow-up, especially in subjects with bladder stones.

Adolescent↗

Pyloromyotomy versus atropine sulfate for infantile hypertrophic pyloric stenosis.

PURPOSE: Atropine sulfate (atropine) and pyloromyotomy were compared for managing infantile hypertrophic pyloric stenosis (IHPS). METHODS: From 1996 to 1998, cases of IHPS treated surgically (pyloromyotomy; n = 20) or medically (atropine; n = 14) at separate institutions were compared retrospectively with regard to status on presentation, physical symptoms and signs, progress, and costs. Atropine was given orally, then intravenously if ineffective. Refractory cases were referred for pyloromyotomy. RESULTS: All subjects were matched for clinical and physiological status on admission. Oral atropine alone was effective in 11 cases, was converted to intravenous atropine in 2 cases, and was terminated in 1 case because of hematemesis. Two cases were referred for pyloromyotomy. All pyloromyotomies were successful. Atropine took on average, 2.6 days to take effect. The difference in time taken for normalization of pyloric muscle thickness between the 2 groups was not significant. Average time to return to full feeding was longer in the atropine group (P<.01). Costs were lower in the atropine group (P<.01). There were 2 wound infections in the pyloromyotomy group, but no adverse effects of atropine. There were no recurrences in either group. CONCLUSION: This study provides reasonable evidence to support a trial of atropine in IHPS.

Adult↗

Laparoscopic surgery in newborn infants.

BACKGROUND: Thanks to various technical innovations and advances in instrumentation, laparoscopic surgical intervention is now possible for certain congenital anomalies in children. To test the applicability of laparoscopic surgery in neonates, we reviewed our personal experience of neonatal laparoscopic surgery, focusing on cardiopulmonary function, surgical procedures, problems with devices, and degree of associated surgical stress. METHODS: We performed 65 laparoscopic procedures in neonates. Their ages ranged from 2 to 30 days old, and their body weights ranged from 1,980 to 4,780 g. All 65 laparoscopic procedures were carried out without mortality or serious morbidity. RESULTS: As complications, we encountered four cases of hypothermia due to rapid insufflation of carbon dioxide (CO(2)). We also found that relative hypercapnea (increase in end-tidal CO(2) as high as 61 mmHg) developed unless hyperventilation and a relatively high peak insufflation pressure were maintained during pneumoperitoneum. No cardiac depression developed at this insufflation pressure. Fluid and electrolyte balance during our cases of newborn laparoscopic surgery, as well as the doses and volumes of fluid and electrolytes administered, were identical to those required for open surgery. Interleukin-6 (IL-6) was measured serially to estimate the degree of associated surgical stress and was found to be significantly lower in neonates who had received laparoscopic procedures than in those who had received open procedures. CONCLUSION: Laparoscopic surgery can be carried out safely even in neonates.

Heart Function Tests↗

Mast cells and gut nerve development: implications for Hirschsprung's disease and intestinal neuronal dysplasia.

BACKGROUND/PURPOSE: In Hirschsprung's disease (HD), the aganglionic bowel is characterized by the presence of hypertrophic nerve trunks and increased numbers of adrenergic and cholinergic nerve fibers. Intestinal neuronal dysplasia (IND), if associated with HD, occurs proximal to the aganglionic segment in HD, and is characterized by dysplasia of parasympathetic nerves, hyperganglionosis, and giant ganglia. However, the cause of such abnormalities in HD and IND is unclear. Recent reports that mast cells (MC) have been observed in direct contact with nerve fibers generally, suggest that MC are essential for nerve growth and repair. MC synthesize, store, and release nerve growth factor (NGF). NGF supports the development and functional maintenance of sympathetic and cholinergic neurons. The aim of this study was to examine the colonic distribution of MC with respect to nerves in HD and HD associated with IND. METHODS: MC and NGF were examined immunohistochemically in ganglionic, transitional, and aganglionic segments of colon from 20 patients with HD (five patients associated with IND) and 15 age-matched controls. MC were counted in each of five random fields using light microscopy (x100). RESULTS: Interestingly, aganglionic and IND segments had large numbers of MC in all layers compared with ganglionic segments in HD patients and controls (P< .0001). The number of MC in transitional segments was significantly less compared with ganglionic segments in HD patients and controls (P< .01). MC stained positively for NGF, and some were found in contact with abnormal hypertrophic nerve trunks in HD and giant ganglia in IND. CONCLUSIONS: MC may cause hypertrophic nerve trunks and giant ganglia by releasing NGF and also may be an important factor in the excessive development of cholinergic and adrenergic nerve fibers in HD and IND.

Colon↗

Does probiotics administration decrease serum endotoxin levels in infants?

PURPOSE: The aim of this study was to examine whether administration of probiotics to infants can change the ratio of intestinal flora and thereby decrease serum endotoxin produced by potentially pathogenic microorganisms. METHODS: Nine infants including five with of biliary atresia, two with omphalocele, one each with Hirschsprung's disease and imperforate anus were studied. All patients were stable, and no antibiotics were given during this study. A probiotic mixture consisting of Streptococcus faecalis, Clostridium butyricum and Bacillus mesentericus was administered orally to each infant at 2 g/day for 2 weeks. Fecal aerobic and anaerobic bacterial cultures, serum endotoxin level, and other biochemical parameters were examined. RESULTS: In fecal cultures, anaerobic bacteria including Bifidobacterium increased significantly whereas Escherichia coli, Streptococcus, and Klebsiella tended to decrease. The ratio of anaerobic to aerobic bacteria increased five times as a result of administration of probiotics, and serum endotoxin levels decreased. CONCLUSIONS: Probiotics affect intestinal bacterial flora by increasing anaerobic bacteria and decreasing the population of potentially pathogenic microorganisms. A decrease in luminal endotoxin may result in less endotoxin translocation or bacterial translocation.

Administration, Oral↗

Serum IFN-inducible protein-10: a new clinical prognostic predictor of hepatocyte death in biliary atresia.

PURPOSE: The aim of this study was to determine whether chemokines such as serum IP-10 levels in patients with biliary atresia (BA) correlate with liver function and histology and assess its value as a medium to long-term prediction of prognosis in postoperative BA patients. METHODS: Thirty postoperative BA patients (mean age, 10.8+/-3.5 years) and eight normal controls (mean age, 10.3+/-3.3 years) were studied. The BA patients were divided into three groups according to liver function. Group I (n = 8) was jaundice free, had normal liver function and no evidence of severe cholangitis or portal hypertension. Group II (n = 12) had moderate liver dysfunction. Group III (n = 10), had severe liver dysfunction. Hepatic histology was assessed using conventional needle biopsy. Serum IP-10 levels were determined using a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of IP-10 in group III (458.0+/-240.0 pg/mL) were significantly higher than those in group II (233.6+/-126.9 pg/mL; P < .0001). Levels in group II were also significantly higher than those in group I (144.8+/-23.4 pg/mL; P < .05), but there was no significant difference between group I and controls (107.9+/-34.0 pg/mL). Liver biopsy findings showed a progression of fibrosis and mononuclear cell infiltration from group I to group III. There was intimal hyperplasia and swelling of endothelial cells of branches of the hepatic artery in the portal area in group III. CONCLUSION: Because IP-10 levels correlate closely with histological findings in postoperative BA patients, it would appear to play a specific role in hepatocyte death and hepatic artery changes, thus providing important information about progressive fibrosis in BA patients that facilitates treatment decision making and prediction of prognosis.

Biliary Atresia↗

Long-term postsurgical outcome of biliary atresia.

BACKGROUND/PURPOSE: A successful Kasai procedure is effective in creating biliary drainage and radically altering the natural history of infants with biliary atresia (BA). Since its introduction in the 1950s, long-term follow-up would appear to show that only 30% to 50% of patients have a good long-term prognosis despite initially good surgical outcome. The authors reviewed their experience in treating BA from 1968 to 1997 to assess long-term outcome. MATERIALS AND METHODS: The records of 163 patients treated surgically for BA from 1968 to 1997 were reviewed. Forty-eight (29%) were alive at the end of 1997, of whom, 14 had received liver transplants (LT). Surviving patients who had not undergone transplantation were divided into two groups according to clinical condition: group A, normal liver function without cholangitis (CG) and portal hypertension (PH) and group B, liver dysfunction with CG or PH. The study period was divided arbitrarily into three periods, 1968 to 1975 (period I, n = 34); 1976 to 1985 (period II, n = 81); 1986 to 1997 (period III, n = 48). RESULTS: Thirty-four patients were alive without LT at the end of 1997. There were eight patients (mean age, 16.3+/-4.8 years) in group A, and 26 patients (mean age, 14.3+/-7.6 years) in group B. Recently, four group A patients (mean age, 19.3+/-1.9 years) shifted to group B because of sudden deterioration in condition involving severe CG with multiple bile lakes (n = 2), uncontrollable intestinal bleeding (n = 1), and liver atrophy (n = 1). Survival deteriorated with length of follow-up. There were three survivors from 34 patients treated in period I, 16 survivors from 81 patients treated in period II (three had LT), and 29 survivors from 48 patients treated in period III (11 had LT). CONCLUSIONS: Although satisfactory bile drainage can be obtained with portoenterostomy, our data suggest that liver function can deteriorate progressively, with a possible turning point in late adolescence, indicating that as the length of follow-up increases, clinical assessment should be regular and comprehensive. The timing of LT in postoperative BA patients with deteriorating liver function is a vital management issue.

Adolescent↗

Laparoscopic extramucosal pyloromyotomy versus open pyloromyotomy for infantile hypertrophic pyloric stenosis: which is better?

BACKGROUND/PURPOSE: The aim of this study was to evaluate the advantages or disadvantages of laparoscopic pyloromyotomy compared with open transumbilical fold pyloromyotomy. METHODS: Thirty consecutive laparoscopic extramucosal pyloromyotomies (LP) performed from 1994 to 1997 were compared with 30 consecutive open pyloromyotomies (OP) performed during the same period with regard to age at operation, body weight, thickness of hypertrophied pyloric muscle, operating time, time of return to full feeding, frequency of postoperative emesis, surgical complications, and degree of surgical stress reflected by interleukin-6 (IL-6). LP was performed according to conventional techniques, and OP was performed using a transumbilical fold approach. RESULTS: The groups were matched for age at operation, preoperative clinical and physical status, laboratory data, and size of the hypertrophied pylorus assessed by ultrasonography. There was a learning curve with LP; the average operating time required for the first 10 cases was significantly longer than the time required for OP, but later cases took just as long as OP cases. Time taken to full feeding was significantly shorter in the LP group than the OP group (LP, 38 hours v OP, 64 hours). One case was converted from LP to OP because of mucosal perforation. The incidence of postoperative emesis was significantly higher in the OP group than in the LP group (OP, 25% v LP, 3%). The mean length of hospitalization was significantly shorter in LP (P < .01). The intraoperative peak values of IL-6 in LP were significantly lower than those in the OP group (P < .01). CONCLUSIONS: The advantages of LP are improved cosmesis, decreased surgical stress with earlier postoperative recovery, and shorter hospitalization. Because LP uses reusable devices, and the mean period of hospitalization is shorter, average operating costs could be reduced, representing a net saving in total hospital charges.

Eating↗

Hyaluronic acid: a specific prognostic indicator of hepatic damage in biliary atresia.

BACKGROUND/PURPOSE: Hepatic fibrosis can progress in biliary atresia (BA) and is associated with capillarization of hepatic sinusoids. The significance of serum hyaluronic acid (HA) as a noninvasive indicator of histological sinusoidal endothelial cell (SEC) damage and hepatic fibrosis in BA, is investigated. METHODS: A total of 28 postoperative BA patients (mean age, 11.0+/-3.7 years) and 20 normal controls (mean age, 10.5+/-2.8 years) were studied. BA patients were divided into group I, good liver function (n = 8); group II, moderate liver dysfunction (n = 10); and group III, severe liver dysfunction (n = 10). Serum HA was determined using a one-step sandwich enzyme immunoassay, and liver histological damage was confirmed immunohistochemically using an antibody against factor VIII-related antigen (FVIIIRAg), which is specific for detecting damaged SEC. RESULTS: Serum HA was significantly higher (P < .0001) in group III (84.6+/-36.5 ng/mL) than in group I (15.9+/-6.9 ng/mL) or group 11 (28.7+/-10.7 ng/mL). Although immunoreactive products of FVIIIRAg were abundant in group III, they were not detected in SEC from group II. CONCLUSION: Serum HA may be of value for monitoring postoperative BA patients as a noninvasive indicator of SEC damage and progressive hepatic fibrosis.

Adolescent↗

Modified soave pull-through for Hirschsprung's disease: intraoperative internal sphincterotomy.

BACKGROUND/PURPOSE: Anorectal achalasia (AA) may persist after pull-through (PT) for Hirschsprung's disease (HD), which may cause postoperative enterocolitis (POE) and constipation. The authors modified the Soave PT (modified Soave PT, MSPT) to eliminate AA, and present their results. METHODS: This was a 16-year retrospective review of 43 patients with histologically proven HD of the rectosigmoid or sigmoid colon treated by MSPT. The MSPT involves excision of the posterior rectal cuff and an intraoperative internal sphincterotomy, allowing the PT colon to fit nicely. RESULTS: Mean age at MSPT was 16.7 months (16 were < or =3 months old [37%]; 7 were neonates [16%]). Mean follow-up was 9.2 years. Six of 43 cases (14%) had preoperative enterocolitis; only 2 of 43 (5%) had single episodes of POE. At review, 37 of 43 were older than 4 years; 29 (78%) had normal bowel function (14 had experienced soiling after MSPT, which resolved after a mean of 6.4 years); and 8 (21%) had problematic bowel function: 3 had occasional soiling, 1 had soiling only before defecation, 3 (8%) had constipation requiring laxatives or enemas, and 1 had significant soiling. CONCLUSION: MSPT is safe and may contribute to a reduction in the incidence of POE and constipation.

Digestive System Surgical Procedures↗

Complications after sigmoidocolocystoplasty: review of 100 cases at one institution.

BACKGROUND/PURPOSE: The aim of this study was to review complications after sigmoidocolocystoplasty (SCP) performed at a single institution from 1984 to 1997. METHODS: The medical records of 100 patients who underwent SCP were reviewed retrospectively. RESULTS: Mean age at SCP was 10.8 years. Urinary control was improved in 75 cases and unchanged in 25. Post-SCP complications included death, abdominal wound infection or dehiscence, adhesive bowel obstruction, vesical calculi, vesicocolonic anastomosis stenosis, metabolic acidosis, and transient renal hypertension. Fifty-one patients underwent ureteric re-implantation (URI) at the time of, or before, SCP, and 7 had recurrence of VUR post-URI (spontaneous regression in 6); 3 patients had new onset of contralateral VUR post-URI (spontaneous regression in 2). Transient pleural effusion was seen after reinsertion of ventriculo-pleural shunts to ventriculo-thoracic in 12 cases, but there was no incidence of infection. Squamous metaplasia of the bladder mucosa was identified in 5 patients on routine mucosal biopsy results but resolved in all cases after regular bladder irrigation was commenced. Preoperative constipation or fecal incontinence was better managed after sigmoidectomy in approximately one third of cases (38%). CONCLUSIONS: SCP with or without URI can improve the quality of life of patients with neurogenic or small-capacity bladder, but it can be associated with long-term complications. Regular bladder irrigation is recommended to maintain bladder mucosa integrity.

Adolescent↗

Management of vesicoureteral reflux secondary to neurogenic bladder.

The authors encountered 108 cases of vesicoureteral reflex (VUR) in 231 cases of neurogenic bladder complicating spina bifida. Bladder compliance and percent volume (% vol.) were measured pre- and postoperatively and the patients were divided into four groups retrospectively according to the treatment. Ninety-five percent of low-grade VUR (grades I and II) disappeared spontaneously with conservative therapy or after augmentation cystoplasty without antireflux surgery; 92% of high-grade VUR (grade III or more) required ureteral reimplantation with or without bladder augmentation. Reflux did not recur in any case of ureteral reimplantation with bladder augmentation, however, it did recur in 20.4% of the cases of simple ureteral reimplantation without bladder augmentation. Percent volume and bladder compliance in cases of recurrence following simple ureteral reimplantation were significantly lower than in the successful cases. This study suggests that low-grade VUR can resolve spontaneously with conservative therapy or with a suitable maneuver to improve bladder compliance. High-grade reflux in cases of preserved bladder volume (% vol.>75%) and compliance (>7 ml/cmH2O) can be treated successfully with simple ureteral reimplantation, however, in cases of low volume (% vol.<60%) and low compliance (<4 ml/cmH2O), reimplantation with bladder augmentation is recommended.

Adolescent↗

Pedicled external spermatic fascia flap for urethroplasty in hypospadias and closure of urethrocutaneous fistula.

PURPOSE: To prevent the development of urethrocutaneous fistula after urethroplasty for hypospadias or recurrence after closure of a urethrocutaneous fistula, the authors developed a new simple technique wherein the readily available external spermatic fascia (ESF) surrounding the testis and cord is used as a pedicled blanket flap to cover the neourethra or the site of closure of a urethrocutaneous fistula. RESULTS: In three patients who had urethroplasty for hypospadias incorporating our ESF flap procedure, no urethrocutaneous fistula developed. It was also effective for closure of urethrocutaneous fistula in five patients, some of whom had had recurrent fistula formation.

Adult↗

Necrotizing enterocolitis and C-KIT.

BACKGROUND/PURPOSE: In the gut, C-KIT is important for immune system homeostasis, and C-KIT+ cells are known to increase during inflammation. Recently the authors identified that spontaneous intestinal mucosal erosion develops in C-KIT-depleted W/Wv mice after day 14 of life at a high frequency, whereas genotypically normal litter mates do not. The authors hypothesized that a lack of C-KIT may be implicated in the development of necrotizing enterocolitis (NEC). METHODS: Bowel specimens were taken during surgery or postmortem from nine cases of NEC (mean gestational age, 32.0 weeks), six age-matched cases of enteritis, and 10 age-matched controls. Specimens were formalin fixed, paraffin embedded, and labeled with antibody to C-KIT. The number of C-KIT+ cells from five random fields per specimen were compared under light microscopy (200x). Results were expressed as the mean +/- SD and compared using the analysis of variance (ANOVA) test. RESULTS: In enteritis, the number of C-KIT+ cells in the lamina propria and submucosa was significantly higher than in controls (P<.01) indicative of their involvement in inflammation. However, in NEC, the number of C-KIT+ cells in the lamina propria and submucosa was significantly lower than in controls (P<.05) despite histological evidence of inflammation. CONCLUSION: A lack of C-KIT+ cells may exert a causal influence on the development of NEC.

Analysis of Variance↗

Abnormal distribution of intestinal pacemaker (C-KIT-positive) cells in an infant with chronic idiopathic intestinal pseudoobstruction.

BACKGROUND: Chronic idiopathic intestinal pseudoobstruction (CIIPO) is a rare syndrome with an obscure pathogenesis. The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor C-KIT that is critical for the development of the interstitial cells of Cajal, cells that are regarded as being the pacemaker cells of the gut. Thus, C-KIT immunopositive (C-KIT-) cells in the muscle layers of the bowel are considered to be intestinal pacemaker cells. METHODS: In this study, the distribution of intestinal pacemaker cells was examined for the first time using C-KIT immunohistochemistry in an infant with CIIPO. RESULTS: C-KIT+ cells were found lying on either side of the border between the two muscle layers (longitudinal and circular) of the bowel and dispersed unevenly throughout both muscle layers. Myenteric plexuses were not demarcated by C-KIT+ cells. In contrast, in controls, C-KIT+ cells were located distinctly between the two muscle layers of the small bowel and dispersed evenly throughout the muscle layers of the colon. Myenteric plexuses were clearly demarcated by C-KIT+ cells. CONCLUSIONS: This case demonstrates for the first time that there is abnormal distribution of intestinal pacemaker cells in CIIPO and provides new evidence that abnormal c-kit gene expression may be responsible for autonomic gut dysmotility. C-KIT immunohistochemistry may be an indispensable tool for diagnosing CIIPO.

Chronic Disease↗

Multiple bowel atresias after syngeneic fetal small bowel transplantation in rats.

PURPOSE: The aim of this study was the assessment of atresia formation after syngeneic fetal small bowel transplantation (SBTx) to clarify its pathogenesis. METHODS: Seventy Lewis rat fetuses (gestational age, 18 to 19 days) were obtained by hysterotomy, and a 30-mm long section of small bowel was excised from each fetus. Each bowel graft was then transplanted into the space between the peritoneum and the rectus abdominis in 70 adult Lewis rats to expose the grafts to ischemic stress. Transplantation was successful in 63 of 70 grafts (90%). Successfully transplanted bowel grafts were harvested for macroscopic and microscopic examination 10 days posttransplantation. RESULTS: Of the successfully transplanted grafts, only two (3%) were atresia free; 127 atretic segments were found in the remaining 61 grafts. Twenty-four grafts (38%) had a single atresia comprised of membranous stenosis (MS) in two, membranous atresia (MA) in 10, and blind ends (BEs) with or without a connecting tissue remnant in 12. Thirty-seven grafts (59%) had multiple atresias, comprised of MS, MA, or both in six, BEs alone in seven, and a combination of BEs with MS or MA in 24. CONCLUSIONS: Our model is the first to succeed in inducing experimentally membranous stenosis and a high incidence (59%) of multiple atresias. These results suggest that bowel ischemia is responsible for multiple bowel atresia formation.

Animals↗