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Biomedical subjects

J Grosfeld

Publications and source records attributed to J Grosfeld.

At least 19 recordsLinked to original sources

Dioecy in Fitzroya cupressoides (Molina) I.M. Johnst. and Pilgerodendron uviferum (D. Don.) Florin (Cupressaceae).

The aim of this study was to determine the dioecious or monoecious condition of Fitzroya cupressoides and Pilgerodendron uviferum. The study area lies west of the Nahuel Huapi National Park in northern Patagonia (Argentina), where these species form mixed stands. One hundred individuals of each species were studied over three successive years. The nature and position in the crown of their reproductive organs were recorded. Results showed that both species are dioecious. This feature has been confirmed on trees of these species growing in other sites within their natural distribution area in Argentina and Chile.

Argentina↗

Is the grass greener? Early results of the Nuss procedure.

BACKGROUND/PURPOSE: Minimal access surgery (MIS, Nuss Procedure) is gaining acceptance rapidly as the preferred method for pectus excavatum repair. This shift in operative management has followed a single institution's evaluation of the procedure. This report describes an additional experience with the Nuss procedure. METHODS: Twenty-one patients with pectus excavatum underwent repair by the Nuss Procedure. The patients ranged in age from 5 to 15 years (average, 8.2 years). There were 19 boys and 2 girls. RESULTS: In 1 patient (age 5 years) the MIS procedure was aborted because of persistence of chest wall asymmetry. The other 20 patients had completion of their procedure without intraoperative complication. The operating times ranged from 45 to 90 minutes; however, there was an additional anesthetic set-up time (average, 45 minutes). All cases utilized a single support bar (11 to 17 inches). Patients underwent extubation in the operating room and were admitted to a ward bed with an epidural catheter in place for pain control and received intravenous analgesia. The hospital stay ranged from 4 to 11 days and averaged 4.9 days. Early postoperative complications included ileus (n = 1), bilateral pleural effusion (n = 2), atelectasis (n = 1), fungal dermatitis (n = 1), pneumothorax (n = 1), and flipped pectus bar (n = 2). Delayed complications included flipped pectus bar (n = 2), marked pectus carinatum requiring bar removal (n = 1), mild carinatum (n = 1), mild bar deviation (n = 1), progressive chest wall asymmetry (n = 3) with 1 requiring bar removal and open pectus repair, pleural effusion (n = 1), and chronic persistent pain requiring bar removal (n = 1). The length of follow-up is 3 to 20 months with an average of 12.3 months. CONCLUSIONS: The Nuss Procedure is quick, minimally invasive, and a technically easy method to learn; however, our data indicate there is a significant learning curve. Although previous reports suggest that few complications occur, we believe further assessment of patient selection regarding age, presence of connective tissue disorder, and severe chest wall asymmetry are still needed. Long-term follow-up also will be required to assure both health professionals and the public that this is the procedure of choice for patients with pectus excavatum.

Adolescent↗

Evaluation of small intestine submucosa and acellular dermis as diaphragmatic prostheses.

BACKGROUND/PURPOSE: The repair of large congenital diaphragmatic defects in the neonate continues to be a challenge. Polytetrafluoroethylene (PTFE) is the synthetic material most widely used for reconstruction in instances of partial and complete diaphragmatic agenesis. Recurrent hernia is a frequent complication, because this material does not grow with the infant. This study evaluates two novel materials; small intestine submucosa (SIS; Cook Biotech, Lafayette, IN), and acellular dermis (AlloDerm; Lifecell Corp, The Woodland, TX) for diaphragm reconstruction in growing animals. METHODS: Sprague-Dawley rats (100 g, n = 87) were anesthetized and underwent laparotomy. The control group (n = 18) underwent a sham laparotomy with a left subcostal incision and closure. The other two groups underwent central excision of the left hemidiaphragm (50% loss) and reconstruction with either a SIS (n = 35) or AlloDerm (n = 19) patch sutured circumferentially with 6-0 prolene. Seventy-two animals survived the operation, and were killed at five separate time intervals (2 weeks, 1, 2, 3, and 4 months). Chest radiographs were performed monthly and before death. Radiographs were reviewed in a blinded fashion by two observers as were the necropsies, and rib deformity was noted if present. Histological examination of the diaphragm patch was performed in each animal. RESULTS: There was no evidence of rib deformity noted on gross examination at necropsy or on chest radiograph in either experimental group. At necropsy, all patches were intact without hernia, eventration, or contraction. Histology findings initially showed acute and chronic inflammatory changes in both patch materials that lessened at the 2-month time interval. Both prosthetic patches began to thin at 3 months and was most prominent in the SIS rats. At 4 months, both SIS and AlloDerm remained viable without evidence of necrosis. Each patch showed evidence of fibroblastic incorporation and small capillary ingrowth. These changes were more prominent in the AlloDerm group. There was no evidence of skeletal muscle ingrowth. CONCLUSIONS: These data indicate SIS and AlloDerm may be useful materials for prosthetic repair in instances of partial or total agenesis of the diaphragm. Further investigation in a large animal model over a longer duration is indicated.

Animals↗

Interleukin-11 improves survival and reduces bacterial translocation and bone marrow suppression in burned mice.

PURPOSE: Major burns are associated with a high mortality, an increased rate of bacterial translocation, and bone marrow suppression. This study evaluates the effect of interleukin-11 (IL-11), a bone marrow-derived growth factor on survival, intestinal cytoarchitecture, bacterial translocation, and bone marrow suppression in a highly lethal murine burn model with a lethal dose greater than 50. METHODS: C3H/HeJ 8 to 10-week-old mice underwent a standardized 32% total body surface area (TBSA) scald burn using a burn template. Mice were divided equally between groups receiving IL-11 (125 micrograms/kg, twice daily, subcutaneously [SC]) and 0.1% same-volume Bovine Serum Albumin (BSA) (0.2 mL, twice daily, sc). Animals were evaluated for mesenteric lymph node bacterial counts, intestinal mucosal villus height, number of mucosal crypt cell mitoses per 100 crypts, and peripheral platelet and total lymphocyte counts. Survival was calculated to 7 days postburn. RESULTS: At 24 hours postburn, IL-11-treated mice had significantly less enteric bacteria cultured from mesenteric lymph nodes (P < .001), increased intestinal crypt cell mitoses (P = .002) and intestinal villus height (P = .002), increased peripheral platelet (P = .002) and lymphocyte counts (P = .004), and an improved survival compared with BSA controls (P = .003). CONCLUSION: These data show that IL-11 improves survival, intestinal cytoarchitecture, reduces bacterial translocation, and reduces bone marrow suppression after a 32% TBSA burn in mice. These data imply that IL-11 cytokine therapy may be a useful adjunct in extensive burn injury.

Animals↗

Contamination of the pleural surfaces in childhood sarcoma. Use of colloidal P-32 to reduce radiation dose to the whole lung.

Children with pulmonary sarcomas who have diffuse contamination of the pleural cavity present a difficult management problem for the radiation oncologist. Doses required to control even microscopic disease exceed lung tolerance. We report on the use of intracavity colloid P-32 in an attempt to treat the pleural surface and spare normal lung parenchyma and tissues of the chest wall. Three children--18 months, 12 years, and 3 years of age--had spillage of pulmonary sarcomas into the chest cavity. All children were treated with systemic chemotherapy. Initially, 0.5 mCi of technetium sulfur colloid (99mTc-sulfur colloid) was instilled into the pleural space to ascertain even distribution of isotope. This was then followed by installation of 5.0 mCi of colloidal P-32. Uniform distribution was then confirmed by bremsstrahlung scanning. All three patients are in complete remission 3.5 years, 3 years, and 1 year after treatment, respectively. The major toxicity was asymptomatic pleural thickening, which could be confused with disease. This was confirmed histologically to be fibrous in the first patient. The process diminished or stabilized with time in all 3 patients over the period of observation. In this small series, intrapleural colloidal P-32 appeared to be safe and well tolerated and would be expected to be less toxic than wide-field external beam in the treatment of spilled pulmonary sarcomas.

Child↗

Antiangiogenic therapy of transgenic mice impairs de novo tumor growth.

Angiogenesis is activated during multistage tumorigenesis prior to the emergence of solid tumors. Using a transgenic mouse model, we have tested the proposition that treatment with angiogenesis inhibitors can inhibit the progression of tumorigenesis after the switch to the angiogenic phenotype. In this model, islet cell carcinomas develop from multifocal, hyperproliferative nodules that show the histological hallmarks of human carcinoma in situ. Mice were treated with a combination of the angiogenesis inhibitor AGM-1470 (TNP-470), the antibiotic minocycline, and interferon alpha/beta. The treatment regimen markedly attenuated tumor growth but did not prevent tumor formation; tumor volume was reduced to 11% and capillary density to 40% of controls. The proliferation index of tumor cells in treated and control mice was similar, whereas the apoptotic index was doubled in treated tumors. This study shows that de novo tumor progression can be restricted solely by antiangiogenic therapy. The results suggest that angiogenesis inhibitors represent a valid component of anticancer strategies aimed at progression from discrete stages of tumorigenesis and demonstrate that transgenic mouse models can be used to evaluate efficacy of candidate antiangiogenic agents.

Adenoma, Islet Cell↗

Is there a place for the Kasai procedure in biliary atresia?

The survival of infants with biliary atresia has improved significantly during the past two decades as a result of modification of the Kasai hepatoportoenterostomy procedure complemented by advances in liver transplantation. Recent reports suggest that the long-term success rate of the Kasai procedure is 40%. Failures are salvaged by liver transplantation. Advances in organ preservation, the use of reduced-sized grafts, and newer immunosuppressive agents (cyclosporine, FK 506) have strongly influenced these improved results. Unfortunately, liver transplantation is associated with a high complication rate, the risk of opportunistic infection, and an increased rate of malignancy due to immunosuppression. Until immunotolerance can be achieved, the Kasai procedure remains the procedure of choice for infants with biliary atresia. Liver transplantation is a life-saving complementary procedure for patients who fail to drain bile following the Kasai procedure, who are older than 3 to 4 months of age at diagnosis, or who have advanced cirrhosis. In the current era, the overall survival should exceed 80%.

Biliary Atresia↗

The combination of antiangiogenic agents to inhibit primary tumor growth and metastasis.

Neovascularization is a critical component for the growth of tumors and is a dominant feature in diseases such as diabetic retinopathy and hemangiomas in infancy. Angiogenesis inhibition is a potentially important therapeutic modality. We have previously reported that AGM-1470 is a fungal-derived angiogenesis inhibitor that suppresses primary tumor growth and metastases and is also nontoxic. alpha-Interferon, an angiogenesis inhibitor, is effective in the treatment of life-threatening hemangiomas. We therefore attempted to treat murine primary tumors and metastases with a combination of AGM-1470 and alpha/beta-interferon. Treatment began after solid tumors formed. Six-week-old syngeneic C57BI/6 mice were treated for 21 days with either AGM-1470, or alpha/beta-interferon or AGM-1470 + alpha/beta-interferon. The combination of the angiogenesis inhibitors AGM-1470 and alpha/beta-interferon suppressed tumor growth by 80% compared with controls (P < or = .001). AGM-1470 and alpha/beta-interferon inhibited pulmonary metastatic tumor growth greater than sevenfold (P < or = .001) compared with controls. These effects were better than either inhibitor alone, and the combined effect was additive. Combination of angiogenesis inhibitors may be useful in the treatment of tumors and other angiogenesis-dependent diseases.

Animals↗

Comparison of growth, neovascularization, and enzymatic function of fetal intestinal grafts in the omentum and renal capsule.

Fetal tissues are less immunogenic and may be a useful donor source for organ transplantation. This report compares the fate of fetal small bowel segments transplanted in the omentum and renal capsule of recipient syngeneic rats. Two-centimeter segments of fetal jejunum and ileum were obtained from 26 donor 19-day gestational age rat fetuses and transplanted into the subrenal capsule (n = 35) and omentum (n = 40) in syngeneic Fisher rats (weight, 150 g) as free grafts. No immunosuppression was used. At 2 weeks posttransplantation, the recipient rats underwent laparotomy and the grafts were evaluated for viability, growth, enzymatic function, and revascularization. Viable grafts were identified in 27 of 35 renal capsule grafts and 34 of 40 omental grafts. The order of magnitude of fetal growth in the omentum for jejunum was 16 +/- 10 versus ileum 23 +/- 9 (NS). However, in the renal capsule, ileal growth (15 +/- 6) was significantly greater than jejunum (8 +/- 5; P less than .01). Growth for both jejunal and ileal segments was greater in the omentum (P less than .02). The lumen of all omental grafts remained patent; however, 26 of 27 renal grafts had cystic dilatations and areas of obstruction. Microfil casts of the specimens showed vascular connections (neovascularization) between the graft and omentum, a normal serosal vascular pattern, and many submucosal capillary-like vessels. Maltase activity was measured in fetal grafts and compared with control pups bred on the same date as the donor animals. The grafts had a higher maltase level 33.4 +/- 34.6 mumol/min/g than controls 8.3 +/- 2.0 (P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Infants with cystic fibrosis: pulmonary function at diagnosis.

Meconium ileus (MEC), failure to thrive (FTT), and a combination of FTT and pulmonary symptoms (COMB) are the most frequent symptoms of cystic fibrosis (CF) at the time of diagnosis. The purpose of this study was to compare to normal controls (NC) the pulmonary function of CF infants at the time of diagnosis, when grouped by these symptoms. The measurements of pulmonary function included oxygen saturation (SaO2), functional residual capacity (FRC), mixing index (MI), total respiratory system compliance (Crs), and maximal flow at FRC (VmaxFRC). Compared to NC (n = 33), the MEC group (n = 5) had a higher MI (54 vs. 42%) and no difference in SaO2, Crs or VmaxFRC. There were no significant differences between FTT (n = 8) and NC groups although there was a tendency for Crs to be lower in the FTT group (5.1 vs. 6.8 ml/cm H2O). When compared to all other groups, the COMB group (n = 11) had significantly lower SaO2, MI, Crs, and VmaxFRC. The normal lung function in the MEC group is consistent with the normal anatomy reported in CF infants dying secondary to meconium ileus. Longitudinal evaluation of the infants in this study, following initiation of care as patients with a diagnosis of CF, may allow us to determine whether symptoms at diagnosis remain an important determinant of lung function in infancy.

Cystic Fibrosis↗

An evaluation of the role of surgery in metastatic neuroblastoma.

The role of surgery was evaluated in 320 patients with metastatic neuroblastoma (Children's Cancer Study Group [CCSG] stage IV, excluding IV-S) enrolled in two CCSG treatment protocols between June 1978 and November 1982. The regimens consisted of combination chemotherapy, radiation therapy, and surgery. Two hundred seventy-seven surgical procedures were performed in 214 of the 320 eligible patients. Surgical intervention at the primary site was performed at initiation of therapy in 86 patients. There was a slight survival advantage when complete resection of the primary tumor was achieved (P = .09). Delayed surgery was performed in 89 patients. Gross complete resection of primary tumor was feasible in 57 of these patients (64.0%). However, survival analysis showed that resolution of metastases had a more important impact on subsequent length of survival than resectability at the delayed procedure (P = .005).

Adolescent↗

Sodium homeostasis in infants with biliary drainage procedures.

We studied biliary excretion of sodium and chloride in 17 infants with external bile drainage through a "biliostomy" and describe four additional children who became ill from sodium depletion following external biliary drainage procedures for biliary tract anomalies. In the 17 infants, the mean +/- SD bile sodium concentration was 122 +/- 15 mEq/L. The mean +/- SD serum sodium concentration was low (132 +/- 7 mEq/L) (normal, 138 to 145 mEq/L). The mean +/- SD bile volume was 388 +/- 317 mL/day at one year following surgery (range, 40 to 1,000 mL/day). In the four children, clinical manifestations of sodium depletion (lethargy, anorexia, dehydration, and malnutrition) necessitated hospital admission. At that time, the serum sodium concentration ranged from 109 to 129 mEq/L, and the simultaneous urinary sodium concentration ranged from 0 to 5 mEq/L. Although dietary sodium was normal, biliary losses exceeded dietary intake, resulting in salt and water depletion despite renal conservation. Children with biliary drainage procedures are at risk for sodium depletion and should be monitored closely and supplemented accordingly until biliostomy closure is performed.

Bile↗

VATER association: analysis of growth and development.

The growth and development of 15 patients with VATER association were prospectively followed for 1-4 years. Prenatal growth retardation was frequent but at least 50% of children with early growth deficiency demonstrated long-term catch-up growth. Mental development was normal in 12 of 15 children but 8 of 13 children had delayed motor skill development. Early postnatal growth deficiency was an indicator of children at risk for developmental problems. Parents should be reassured that most children with VATER association display normal development.

Abnormalities, Multiple↗

Preoperative evaluation of pediatric abdominal tumor volumes by computerized tomography.

The volumes of two neuroblastomas and two Wilms' tumor masses were calculated by computerized tomography (CT) within 48 hours of surgical removal of the tumor. True volumes of the tumor masses were obtained by volume displacement. CT was very accurate in predicting volume with an error ranging from 1.5% to 7.5%. This accurate method of evaluating tumor volume will allow precise monitoring of the response of nonoperable tumors to chemotherapy and radiotherapy.

Abdominal Neoplasms↗

A new look at the neonatal bowel-contrast studies with metrizamide (Amipaque).

Metrizamide is the first water-soluble radiographic contrast agent which, because it is nonionic, can be used in isotonic solution and gives good visualization of the desired body structure. Its only major disadvantage is that it is very expensive. Metrizamide can be used to study the neonatal bowel in clinical situations where all the other existing contrast agents are contraindicated. The results of 55 metrizamide studies of the bowel in infants are reviewed. In necrotizing enterocolitis metrizamide aids in confirming or rejecting the diagnosis, identifying patients for surgery, and in evaluating the response to surgery. Metrizamide can identify the etiology in unusual cases of bowel obstruction. Metrizamide correctly identified a thoracic origin of free peritoneal air in four cases and a bowel origin in two cases. It identified bowel perforation in two patients in the absence of pneumoperitoneum. In six patients, the metrizamide study identified the cause for a gasless abdomen. It is concluded that metrizamide has a valuable role to play in evaluating a variety of neonatal bowel disorders.

Drug Evaluation↗

Lung CT for detection of metastases: solid tissue neoplasms in children.

The results of 73 computed tomographic studies of lung and pleura in 52 children with solid-tissue tumors have been analyzed. In nine children computed tomography provided information not evident by chest radiograph or whole lung tomography. In four of these cases computed tomography demonstrated lung nodules not seen on chest radiography or whole lung tomography; in another four cases it revealed pleural involvement with tumor; and in one case it revealed calcium in a nodule. In two children computed tomography missed lung mestastases seen by lung tomography and chest radiography.

Child↗