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Biomedical subjects

A G Coran

Publications and source records attributed to A G Coran.

At least 37 records · Page 2Linked to original sources

Confirmation of translocated gastrointestinal bacteria in a neonatal model.

PURPOSE: The hypothesis that enteric bacteria translocate from the gastrointestinal (GI) tract to extraintestinal sites has been extensively studied. However, definitive evidence that spontaneous bacterial translocation and dissemination from the GI tract to extraintestinal sites occur in a neonatal model has been lacking. The aim of this study was to confirm this phenomenon by tracking enterally administered, plasmid-labeled bacteria to extraintestinal sites. MATERIALS AND METHODS: Escherichia coli 07:K1 (E. coli K1) with and without a nontransferable, ampicillin resistance plasmid (pGEM-7) were used in this study. Newborn New Zealand white rabbit pups were separated into three treatment groups: transformed E. coli K1 (E. coli K1 + pGEM-7, n = 20), nontransformed E. coli K1 (n = 12), and control pups (no bacteria, n = 7). Pups were enterally fed 10% Formulac solution supplemented with a suspension of bacteria respective to their group. After the pups fed twice daily for 2 days, representative tissue specimens from the small bowel (SB), mesenteric lymph nodes (MLNs), spleen (SPL), and liver (LIV) were aseptically harvested and tested for culture growth in ampicillin-supplemented medium. RESULTS: Positive growths of plasmid-induced ampicillin-resistant bacteria were detected in tissue specimens harvested from rabbits fed transformed E. coli K1, but were not detected in the other groups. CONCLUSION: This experiment demonstrated conclusively that transformed E. coli K1 fed to healthy rabbit pups spontaneously translocated from the intestinal lumen and subsequently disseminated to the mesenteric lymph nodes, spleen, and liver.

Animals↗

The effect of phospholipids and mucin on bacterial internalization in an enterocyte-cell culture model.

A primary component of the intestinal mucous layer that functions as a barrier to luminal bacteria is mucin, a high-molecular-weight glucoprotein. In addition, the mucous layer also contains other important elements such as phospholipids (PLs), which may effect bacterial translocation (BTL). It has been reported that mucin inhibits Escherichia coli translocation; however, the effect of PLs on intestinal permeability is still controversial. We have recently reported that the concentration of mucous PLs is higher in neonatal as compared to adult rabbits. The functional significance of these biochemical differences on BTL remains to be determined. The aim of this study was to evaluate the effect of PL and mucin composition on BTL in a human enterocyte-cell culture model. Human enterocyte Caco-2 cells were seeded in 24-well tissue-culture plates and grown for 14 days to confluence. The monolayers were pretreated with phosphate buffered saline as control, 10 mg/ml or 20 mg/ml mucin, 0. 5 mM or 1.0 mM PL mixture based on neonatal (NPL) and adult (APL) composition, and 10 mg/ml mucin with 0.5 mM either APL or NPL mixtures 30 min before a 120-min incubation period at 37 degrees C with 10(8) colony forming units (CFU) of E. coli C25. Non-internalized bacteria were killed by the addition of gentamicin. Internalized bacteria were quantified by counting CFU from enterocyte-cell lysates grown on MacConkey's agar. Mucin inhibited bacterial internalization, while both compositions of PLs promoted it. Mucin added to the PL solution also diminished the stimulatory effect of PLs on bacterial internalization. These results indicate that the increased concentration of PLs found in the intestinal mucous layer of neonates, and/or the alteration in the balance between PLs and mucin, may play a role in the increased BTL seen in neonates.

Animals↗

The effect of mucin on bacterial translocation in I-407 fetal and Caco-2 adult enterocyte cultured cell lines.

Although the intestinal mucosa forms a crucial barrier between the host and the environment, bacterial translocation (BT) occurs frequently in neonates and may be a source of sepsis. The intestinal mucous gel layer is thought to be a vital component of the gut barrier and is composed, in part, of a family of glycoproteins known as mucins. Our aim was to study the effects of mucin on BT in an enterocyte cell-culture model using a fetal (I-407) and an adult (Caco-2) intestinal cell line. I-407 and Caco-2 cells were grown to confluence on porous filters in a two-chamber Transwell system. The integrity of the monolayers was confirmed by transepithelial electrical resistance (TEER) and permeability using the macromolecule dextran blue. Cells were treated with mucin (40 mg/ml) prior to inoculation of 1 x 10(6) Escherichia coli C25. The magnitude of BT was determined quantitatively by culturing the samples from the basal chamber of the wells and was expressed as log 10 [Colony Forming Units (CFU)/ml]. Statistical analysis was performed by the Mann-Whitney U test with statistical significance at P < 0.05. Mucin inhibited BT across both fetal and adult cultured enterocyte monolayers; however, the inhibitory effect was less on the fetal cells compared to the adult cells. Dextran-blue studies showed that monolayers were intact throughout the experiments. Despite 98% inhibition of BT, mucin had a statistically significant effect on post-bacterial inoculation TEER in Caco-2 cells and no effect in I-407 cells. The ability of mucin, a mucous-barrier glycoprotein, to inhibit BT across immature intestinal enterocytes, as in the neonate, may be diminished compared to mature adult enterocytes.

Adult↗

Prenatal diagnosis of congenital cystic adenomatoid malformation and its postnatal presentation, surgical indications, and natural history.

BACKGROUND/PURPOSE: Regression of a cystic adenomatoid malformation (CAM) in a fetus is well described. Little, however, is known about the postnatal course of these infants. This study attempts to correlate the prenatal course of CAMs with postnatal symptoms, radiological manifestations, and need for surgery. METHODS: The clinical course of patients with a CAM diagnosed prenatally were retrospectively reviewed. Inclusion in the study required a prenatal ultrasound scan documenting a CAM. RESULTS: Over 10 years, 14 patients with a CAM were diagnosed prenatally. Six (43%) showed a partial in utero regression. Four patients were symptomatic at birth and underwent a resection as newborns. Ten patients were asymptomatic at birth, and eight of these had normal chest x-rays. Elective resection has been performed in 3 of these 10, and two additional children are scheduled to undergo an excision near 1 year of age. The remaining five patients have undergone follow-up nonoperatively for a mean of 36 +/- 15 months. Of the seven asymptomatic patients not undergoing immediate surgery, only one has shown a slight postnatal regression, despite five of these showing regression in utero. None have become symptomatic. CONCLUSIONS: The results suggest that regression of a CAM on prenatal ultrasound scan is common, but this process does not continue after birth. A normal chest x-ray does not indicate complete regression of a CAM; a computed tomography (CT) scan is required to evaluate such patients, and will generally demonstrate a CAM. Asymptomatic patients with a CAM may be followed up nonoperatively with no apparent adverse effects. The decision and timing of an excision in an asymptomatic patient remains controversial among pediatric surgeons.

Cystic Adenomatoid Malformation of Lung, Congenita↗

An analysis of the morbidity and mortality of short-bowel syndrome in the pediatric age group.

Twenty-two children with short-bowel syndrome (SBS) were treated at the C. S. Mott Children's Hospital in the University of Michigan Medical Center between June 1983 and May 1993. Definition of SBS was loss of 70% or more of the total small bowel. Seventeen of these children are currently alive, a 77% survival rate. Patients were followed for a mean of 1,148 days. The mean age of SBS development was 71 days of life. The only predictive indicator of patient survival was direct bilirubin levels. Sixty-seven percent of the children died if they had a direct bilirubin of > 4 mg/dl > or = 6 months duration.

Child↗

Specialty networking in pediatric surgery: a paradigm for the future of academic surgery.

OBJECTIVE: To review retrospectively a 4-year experience with pediatric surgical networking at a major academic medical center in the Midwest. BACKGROUND: The growth of managed care in the United States during the past decade has had a major impact on the practice of medicine in general, but especially on academic medicine. In some academic medical centers, the loss of market share has not only affected clinical activity but has also compromised the educational and research missions of these institutions. METHODS: At the authors' institution, a networking strategy in pediatric surgery was established in 1993 and implemented on July 1, 1994. In 1994, one new satellite practice was established; over the next 4 years, four additional practices were added, including one in another state. To assess the impact on financial status, clinical activity, education, and academic productivity, the following parameters were analyzed: gross and net revenue, surgical cases, clinic visits, ranking of the pediatric surgery residency, publications, grant support, and development and endowment funds. RESULTS: Gross and net revenue increased from $3,273,000 and $302,000 in 1993 to $10,087,000 and $2,826,000, respectively, in 1998. Surgical cases and clinic visits increased from 1240 and 3751 in 1993 to 5872 and 11,604, respectively, in 1998. At the medical center's children's hospital, surgical cases and clinic visits increased from 1240 and 3751 to 2592 and 4729 during the same time period. During this 4-year period, the faculty increased from 4 to 11. Since 1997, the National Resident Matching Program has provided data on how pediatric surgery residency candidates ranked a training program. In 1997, this program received the second-most one to five rankings; in 1998, it tied for first. This exceeds the faculty's perception of previous years' rankings. Publications increased from 26 in 1993 to a peak number of 62 in 1996; in 1997 and 1998 the publications were 48 and 37, respectively. External grant support increased from $139,882 in 1993 to a total of $6,109,971 in 1998. Development and endowment funds increased from $103,559 in 1993 to $2,702,2777 in 1998. CONCLUSIONS: Pediatric surgical networking at the authors' institution has had a markedly positive impact on finances, clinical activity, education, and academic productivity during a 4-year period. The residency training program appears to have improved in popularity among candidates, probably because of the increased referral of complex cases to the medical center from the various networking satellites. External grant support and basic laboratory research significantly increased, most likely because of the greater number of faculty with protected time for research recruited. Development and endowment funds dramatically grew because of the excellent fiscal health of the pediatric surgical program. This experience may serve as a model for other academic surgical specialties.

Academic Medical Centers↗

The association of large ovarian cysts with cloacal exstrophy.

BACKGROUND/PURPOSE: Cloacal exstrophy can now be managed with excellent survival rates and reasonable long-term outcomes with many of these patients living into their late teens and early adulthood. In this report, the authors describe for the first time the association of large ovarian cysts with cloacal exstrophy. METHODS: From 1974 to 1996, 12 patients with cloacal exstrophy have been treated at C.S. Mott Children's Hospital. Massive ovarian cysts developed in four of these. These patients represent the subjects of this study. RESULTS: All four patients have been followed up beyond puberty and massive ovarian cysts have developed, which have caused significant morbidity. Three patients have required surgical intervention. All the patients had reached menarche before the development of the cysts. In all cases, the presentation was severe pelvic pain. Urinary tract obstruction from the large pelvic cysts developed in three of the four. The cysts were bilateral in three of four patients and measured 8 to 10 cm in diameter on ultrasound scan or computed tomography (CT). Cyst aspiration was attempted in two cases and was unsuccessful. Three of the four patients have required bilateral salpingo-oophorectomy. The indications for surgery were uncontrollable pelvic pain in one and urinary obstruction and uncontrollable pelvic pain in two. Surgical findings demonstrated massive thin-walled cysts with essentially no normal ovarian tissue in association with duplicated mullerian structures. The pathology findings were corpus luteal cyst in two and mucinous cystadenoma in one. The fourth patient with an 8- x 10-cm unilateral cyst is being followed up. CONCLUSIONS: The authors have described, for the first time, the association of massive ovarian cysts with cloacal exstrophy. These cysts can lead to severe pelvic pain and urinary tract obstruction. Bilateral oophorectomy has been required in most of these patients.

Adolescent↗

Firearm ownership in households with children.

BACKGROUND/PURPOSE: Increased morbidity and mortality rates in children injured by firearms has been well documented during this past decade. The aim of this study was to determine the socioeconomic factors affecting firearm ownership in families with children living in suburban/rural versus inner-city environments, and to identify predictors of firearm ownership in these families. METHODS: Parents of children less than 19 years old seen in a suburban (n = 751) or inner-city hospital (n = 406) anonymously completed a questionnaire regarding firearm ownership. RESULTS: Firearm ownership was 54% in rural locations, versus 18% among inner-city residents (P< .05). Firearm ownership in white households was 45% versus 20% in African-American households (P< .05). Mean number of all types of firearms in white households was 3.38 versus 1.78 in black households (P< .001). Firearm ownership was 19% in the less than $20,000 income bracket, significantly lower than households with greater incomes, and was significantly lower in households in which parents had the least education (19.7%) versus those with college degrees (38.5%; P< .05). Firearm owners of rifles and shotguns significantly more often cited hunting, collection, and target shooting as reasons for owning firearms, in contrast to revolver owners who cited protection and collection as reasons for firearm ownership (P < .05). CONCLUSIONS: Firearm ownership is higher in rural, caucasian versus inner-city African-American residents and is significantly less in households with lower income and educational levels. Significant predictors for firearm ownership were number of parents in households, educational level of parents, and population of residence.

Adult↗

Changes, with age, in the phospholipid content of the intestinal mucus layer of the newborn rabbit.

BACKGROUND/PURPOSE: The high incidence of bacterial translocation in newborns is thought to be caused, in part, by the immaturity of the intestinal mucosal barrier. Recently, intestinal mucus phospholipids (PL) have been reported to be important factors in the function of this mucosal barrier. The aim of this study was to quantify changes, with age, in the intestinal mucus PL of the newborn rabbit. METHODS: Mucus was gently scraped from the small intestinal mucosal surface of rabbits of different ages (0, 7, 14, and 28 days old and adult; n = 6 for all groups). PL was extracted from the mucus and was separated by two-dimensional thin-layer chromatography. The isolated phospholipid spots were quantified for their phosphorus content. RESULTS: Total PL content of the mucus decreased significantly with age (day 0, 21+/-2; day 7, 16+/-4; day 14, 9+/-3; day 28, 2+/-1; adult, 1+/-1 micromol/g wet mucus; P = .0001). Phosphatidylcholine and phosphatidylethanolamine levels in the adult rabbits were significantly lower in comparison with the 0-, 7-, and 14-day-old pups (P < .05). In contrast, lysophosphatidylcholine and lysophosphatidylethanolamine were significantly higher in the 28-day-old and adult rabbits in comparison with the 0-, 7-, and 14-day-old pups (P < .05). Phosphatidylinositol + phosphatidylserine levels in 7-day-old rabbits was significantly higher compared with adult rabbits. There was no significant difference in the composition of sphingomyeline between groups. CONCLUSION: Significant changes in the content and composition of the intestinal mucus phospholipids were observed during the first month of life in rabbits.

Aging↗

Long-term outcome for infants and children with sacrococcygeal teratoma: a report from the Childrens Cancer Group.

BACKGROUND/PURPOSE: Sacrococcygeal teratomas (SCT) are a relatively uncommon tumor affecting neonates, infants, and children. This study was designed to determine the effect of therapy on the long-term outcome of neonates and children with sacrococcygeal teratomas (SCT). METHODS: The authors conducted a retrospective review of children with SCT treated at 15 Childrens Cancer Group institutions from 1972 to 1994. RESULTS: One hundred twenty-six children presented with SCT diagnosed prenatally (n = 32), at birth (n = 79), or later in infancy (n = 15). For neonates, complete resection was performed except in two babies with lethal associated defects. All others (n = 15) underwent resection at the age of diagnosis. Six had a sacral mass identified at birth but had delayed surgery (1.5 to 11 months) and of these, two were malignant. Resection was via sacral (n = 96) or abdominosacral (n = 28) approach. Histology showed mature teratoma (MT, 69%), immature teratoma (IT, 20%), or endodermal sinus tumor (EST, 11%) at presentation. Seven neonates (5.6%) died of perioperative complications, whereas the remaining 117 were available for long-term follow-up. Between 6 and 34 months postresection, recurrent disease developed in 9 of 80 MT patients (11%) followed-up for a mean of 5 years. Recurrent disease was MT (n = 2) and EST (n = 7). The recurrent EST patients were treated with adjuvant chemotherapy. Six are alive with mean follow-up of 114 months, whereas one with metastatic disease was lost to follow-up. Recurrence (MT) developed in only 1 of 24 IT patients, and all are alive and well at mean follow-up of 39 months. Patients presenting with EST (n = 13) underwent excision, with two dying from non-EST causes. Six EST patients received no chemotherapy, with two of the six (33%) experiencing recurrence within 11 months and both disease free after salvage chemotherapy. The remaining five EST patients received adjuvant chemotherapy; four are alive and one died of metastatic disease. Of the 18 EST patients followed-up after resection (presentation, 11, recurrent teratoma, 7), 16 (89%) are free of disease with a mean follow-up of 91 months. CONCLUSIONS: (1) Benign teratomas have a significant recurrence rate mandating close follow-up for more than 3 years. (2) Surgical resection alone is adequate therapy for nonmetastatic malignant tumors. (3) Survival for malignant lesions with metastases is excellent with modern chemotherapy.

Child, Preschool↗

Immediate and long-term results of surgical management of low imperforate anus in girls.

BACKGROUND: The majority of girls with imperforate anus are reported to have a malformation of the low variety. Despite this, much of the literature has focused on the more complex, high lesions. METHODS: This study reviews our experience with 44 girls with low imperforate anus from a 22-year period. RESULTS: The incidence of associated anomalies was 61%, which is higher than generally reported. All patients in the study had anal fistulae. Fifty-seven percent had perineal fistulae, 23% had fourchette fistulae, and 20% had vestibular fistulae. Cutback anoplasty was performed in 55%, Potts transfer anoplasty was used in 27%, and 18% of patients were treated with either limited posterior sagittal anorectoplasty or anterior sagittal anorectoplasty. Surgical complications were uncommon. Long-term follow-up was carried out by telephone survey. This showed 89% of the girls to be successfully toilet trained. However, 47% of patients experience at least occasional soilage or episodic fecal incontinence. CONCLUSIONS: Low imperforate anus can be successfully treated using a variety of procedures without colostomy. Most girls with low imperforate anus are successfully toilet trained, but problems with continence persist in a significant number of these patients.

Anus, Imperforate↗

The effect of epidermal growth factor on bacterial translocation in newborn rabbits.

PURPOSE: Epidermal growth factor (EGF), which is present in breast milk, has both trophic and maturational effects on intestinal mucosa. The aim of this study is to determine the effect of EGF on spontaneous intestinal bacterial translocation (BT) in formula-fed newborn rabbits, who have a high incidence of BT compared with breast-fed newborn rabbits. METHODS: Sixty-one rabbit pups were divided into three groups: EGF(-), n=24, EGF(+), n=22, and breast-fed animals, n=15. Both the EGF(-) and EGF(+) groups were gavage fed a standard artificial formula three times daily. EGF was administered subcutaneously three times daily (1.5 microg/g body weight per day) in the EGF(+) group. The breast-fed group was fed by their mothers ad libitum. At 7 days of age, all rabbits were killed, and the mesenteric lymph nodes (MLN), liver, and spleen were cultured qualitatively for bacterial growth, while the cecum and ileum were quantitatively cultured. To determine the effect of EGF on mucus-producing cells, goblet cell numbers in the small intestine were quantified histologically. RESULTS: There was no BT to MLN, spleen, or liver in the breast-fed group. The incidence of BT to MLN and spleen was significantly lower in the EGF(+) compared with EGF(-) group; (EGF[+]: MLN, 45%; spleen, 32%; Liver, 27%; EGF[-]: MLN, 79%; Spleen 67%; Liver 29%; in EGF[+] MLN and Spleen P<.05 vEGF[-]). There was no significant difference in cecal and ileal bacterial colonization between the EGF(+) and EGF(-) groups. The number of goblet cells in the small intestine was significantly lower in the EGF(-) group compared with the EGF(+) group as follows: EGF(+), 14+/-3; EGF(-), 9+/-3; breast-fed, 11+/-5 goblet cells per 100 epithelial cell nuclei; P=.013. CONCLUSIONS: (1) EGF caused a significant decrease in spontaneous bacterial translocation in formula-fed newborn rabbits and was associated with an increase in the goblet cell number of the small intestine. (2) These changes occurred in spite of the fact that no changes in small bowel bacterial colonization were observed. (3) These results suggest, but do not prove, that EGF may provide protection for neonates from gut origin infection by improving the mucosal barrier function through increased goblet cell production, thus decreasing the incidence of spontaneous bacterial translocation in the newborn.

Animals↗

The lateral approach for open splenectomy.

BACKGROUND: Laparoscopic splenectomy (LS) has been used increasingly to treat children with hematologic disorders and has been reported to have advantages over open splenectomy performed through a standard vertical or subcostal incision. The authors perform open splenectomy (OS) through a lateral, muscle-splitting approach, and believe their approach is more reasonable in comparison with LS. METHODS: Thirty-nine consecutive open splenectomies performed between 1991 and 1995 were reviewed retrospectively and compared with recent reports of LS. The series included 24 boys and 15 girls with an average age of 9 years and average weight of 37.5 kg. Indications included immune thrombocytopenic purpura (n = 20), hereditary spherocytosis (n = 18), and sickle cell anemia (n = 1). The operation was performed with the child in the lateral decubitus position through a left upper abdominal muscle-splitting incision (off the 11th rib), sparing the rectus muscle. RESULTS: All 39 cases were completed without intraoperative complications with an average surgical time of 98.0 minutes (range, 30 to 302). The average surgical blood loss was 89 mL (range, 10 to 300). The children started feeding an average of 1.2 days (range, 0 to 4) postoperatively, were on a regular diet at an average of 2.0 days (range, 1 to 6) postoperatively, and had an average length of stay of 2.7 days (range, 1 to 6). There was no mortality or morbidity. CONCLUSIONS: Open lateral splenectomy is performed with shorter surgical times, less blood loss, an excellent cosmetic result, no complications, and a length of stay comparable to any of the published series on laparoscopic splenectomy in children. This approach provides a reasonable basis for comparison with laparoscopic splenectomy.

Adolescent↗

Enterocolitis.

Enterocolitis continues to be the major cause of morbidity and mortality in patients with Hirschsprung's disease. The exact etiology of Hirschsprung's-associated enterocolitis is not known. This review focuses on the clinical aspects, etiology, and therapy of Hirschsprung's-associated enterocolitis.

Enterocolitis↗

Surgical treatment of gastroesophageal reflux in children: a combined hospital study of 7467 patients.

OBJECTIVE: To review retrospectively the combined clinical experience with the surgical treatment of persistently symptomatic gastroesophageal reflux (SGER) in childhood from seven large children's surgery centers in the United States. DESIGN: During the past 20 years, 7467 children <18 years of age underwent antireflux operations for SGER at the seven participating hospitals. Fifty-six percent were neurologically normal (NN) and 44% were neurologically impaired (NI). The most frequent diagnostic studies were upper gastrointestinal series (68%), esophageal pH monitoring (54%), gastric emptying study (32%), and esophagoscopy (25%). The age at operation was under 12 months in 40% and 1 to 10 years in 48%. The type of fundoplication was Nissen (64%), Thal (34%), and Toupet (1.5%). A gastric emptying procedure was performed on 11.5% of NN patients and 40% of NI patients. Laparoscopic fundoplication was performed on 2.6% of patients. RESULTS: Good to excellent results were achieved in 95% of NN and 84.6% of NI patients. Major complications occurred in 4.2% of NN and 12.8% of NI patients. The most frequent complications were recurrent reflux attributable to wrap disruption (7.1%), respiratory (4.4%), gas bloat (3.6%), and intestinal obstruction (2.6%). Postoperative death occurred in 0.07% of NN and 0.8% of NI patients. Reoperation was performed in 3.6% of NN and 11.8% of NI patients. The results and complications were similar among the participating hospitals and did not seem related to the type of fundoplication used. CONCLUSION: The excellent results (94% cure) and low morbidity with gastroesophageal fundoplication with or without a gastric emptying procedure from a large combined hospital study indicate that operation should be used early for SGER in NN children and to facilitate enteral feedings and care in NI children.

Child↗