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P M Colombani

Publications and source records attributed to P M Colombani.

At least 19 recordsLinked to original sources
PubMed1996

Modulation of multidrug resistance with antisense oligodeoxynucleotide to mdr1 mRNA.

BACKGROUND: P-glycoprotein (pgp), a 170-kDa adenosine triphosphate-dependent membrane drug efflux pump encoded by the mdr1 gene, mediates cross-resistance in tumor cells to structurally unrelated cancer drugs. We investigated the capacity for modulating multidrug resistance by selectively inhibiting synthesis of Pgp using an antisense oligodeoxynucleotide complementary to the initiation codon of mdr1 messenger RNA. METHODS: By continuous culture of K562 in 100 nM vincristine, a resistant cell line, K562/VCR100, was derived with high expression of Pgp (95.9% of cells) and an IC50 40-fold greater than that of the parental cell line. The K562/VCR100 cells were treated with 10 microM of 15-mer antisense and sense phosphorothioate oligodeoxynucleotides. Modulation of multidrug resistance was analyzed using a daunorubicin/tritiated thymidine incorporation assay and flow cytometric assessment of cellular rhodamine 123 accumulation. RESULTS: Treatment of K562/VCR100 with the antisense oligodeoxynucleotide led to a doubling in daunorubicin growth inhibition at 1 microgram/ml and a tripling of growth inhibition at 0.6 micrograms/ml (p < 0.0023); a 58% reduction in the daunorubicin IC50 (p < 0.02); and an increased rate of rhodamine-123 accumulation (p = 0.02) compared with treatment with sense oligodeoxynucleotide or media controls. CONCLUSIONS: These results suggest that antisense oligodeoxynucleotides may serve as a useful adjunct in the treatment and prevention of multidrug resistance during cancer chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Chest wall constriction after too extensive and too early operations for pectus excavatum.

BACKGROUND AND METHODS: Since 1990 we have evaluated 12 children and teenagers in whom severe cardiorespiratory symptoms have developed due to failure of chest wall growth after very extensive pectus excavatum operations (removal of five or more ribs) at very early ages (< 4 years). RESULTS: Apparently these extensive procedures have removed or prevented growth center activity, which resulted in restriction of chest wall growth with marked limitation of ventilatory function. The forced vital capacity ranged from 30% to 50% of predicted and the forced expiratory volume in 1 second from 30% to 60%. All patients are symptomatic with mild exercise and cannot compete in running games. Our protocol for critical evaluation includes exercise pulmonary function studies and axial computed tomographic reconstruction. CONCLUSIONS: This report is an alert to recognize such patients and also to recommend delay in operative repair in small children until at least 6 to 8 years of age. The younger the patient the more limited the chest wall resection for pectus excavatum should be. Five of these patients have had a chest cavity expansion operation with encouraging early results.

Adolescent↗
PubMed1996

Liver transplantation in infants younger than 1 year of age.

OBJECTIVE: The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS: The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS: Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS: Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults.

Biliary Atresia↗
PubMed1994

P-glycoprotein status of favorable-histology Wilms' tumor predicts treatment outcome.

Patients with advanced-stage favorable-histology (FH) Wilms' tumor have a 4-year relapse-free survival rate of 70% to 90% after resection and chemotherapy of actinomycin D, vincristine, and doxorubicin. These three agents are actively pumped out of cells by P-glycoprotein (Pgp). The authors studied whether Wilms' tumor expresses Pgp and if the degree of Pgp expression correlates with treatment outcome. At the time of diagnosis, eight blinded paraffin-embedded FH and four anaplastic (ANA) Wilms' tumor sections were immunogold-labeled with a Pgp monoclonal antibody (17F9). Four of the FH-tumor patients had had relapse (FH+) according to the National Wilms' Tumor Study-3 protocol. Negative-relapse FH-tumor patients (FH-) had at least 6 years of follow-up. All 12 Wilms' tumors stained positive for Pgp. Both differentiated tubular structures and blastemal elements expressed Pgp. By the pathologist's score and the computerized cell image analysis, the degree of Pgp staining was greater at the time of diagnosis in FH+ tumors than in FH- tumors (P < .03; Mann-Whitney test). There was no statistically significant difference between ANA and FH+ or FH- tumors. These results show that both FH and ANA Wilms' tumors express Pgp, with higher levels of Pgp expression found in FH patients who had relapse. Current chemotherapeutic protocols, using Pgp-sensitive agents, may not be optimal for all FH Wilms' tumor patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Criteria for safe cost-effective pediatric trauma triage: prehospital evaluation and distribution of injured children.

In an effort to maximize staff utilization, all pediatric trauma patients were triaged by emergency room personnel to one of two tiers, based on information reported by prehospital providers over radiotelephones. A total of 952 patients less than 15 years of age were evaluated during a 1-year period. The triage criteria had a sensitivity of 86% in predicting which trauma patients would require operating room and/or pediatric intensive care, while maintaining a specificity of 90%. Fifteen patients died; however, by TRISS methodology there were no unexpected deaths and four unexpected survivors. All eventual deaths were initially captured from field data by the severely injured triage criteria. The study data suggest that physician-controlled two-tiered field triage criteria can safely serve to maximize staff utilization in the emergency room.

Child↗
PubMed1994

Choledochal cyst disease. A changing pattern of presentation.

OBJECTIVE: The authors compared the presentation, treatment, and long-term outcome of children and adults with choledochal cysts. SUMMARY BACKGROUND DATA: The typical patient with choledochal cyst disease has been the female infant with the triad of jaundice, an abdominal mass, and pain. However, the recent experience of the authors suggested that the disease currently is recognized more commonly in adults. METHODS: Forty-two patients (11 children, 32 adults) with choledochal cyst disease were treated primarily at this institution between 1976 and 1993. Patients presentation, clinical evaluation, and operative treatment were obtained from existing records. Long-term follow-up was obtained by records, physician, or direct patient contact. RESULTS: One child--but no adults--had the classic triad of jaundice, abdominal mass, and pain. Children were more likely to have two of the three signs or symptoms (82% vs. 25%; p = < 0.05). Adult patients most commonly had abdominal pain and were thought to have pancreatitis (23%) or acute biliary tract symptoms, prompting cholecystectomy (50%). The type of choledochal cyst seen in children and adults was similar; the fusiform extrahepatic (Type I) was most common (50%), and the combined intrahepatic and extrahepatic (Type IVA) was the next most prominent (33%). For both children and adults, treatment consisted of excision of the cyst and biliary reconstruction with a hepaticojejunostomy. There was no surgical mortality. Gallbladder or cholangiocarcinoma was identified in three adults (9.7%), two of which were manifest on presentation. Long-term follow-up revealed one patient with a biliary stricture and three patients with Type IVA cysts who had intrahepatic stones. CONCLUSIONS: Children and adults differ in presentation of choledochal cysts, with adults commonly having acute biliary tract or pancreatic symptoms. Surgical treatment with cysts excision and biliary bypass is safe and effective in children and adults with excellent long-term results that minimize the development of malignancy.

Adolescent↗
PubMed1992

Atypical thrombotic and septic complications of totally implantable venous access devices in patients with cystic fibrosis.

The use of vascular access systems in patients with cystic fibrosis (CF) is well accepted, with lower overall complications and maintenance costs than percutaneous silastic catheters. We report our 6 year experience with 22 infusaports in 15 CF patients. Our patients had indwelling catheters for an average of 539 days per catheter (range, 14-2,224 days). These infusaports were used for home antibiotic therapy, blood sampling, and total parenteral nutrition. The overall complication rate was relatively low, 1 in every 1,483 catheter days. Infectious complications were extremely infrequent at a rate of 1 in 5,929 catheter days. The rate of mechanical complications was 1 in 1,976 catheter days. However, superior vena caval syndrome or deep venous thrombosis was associated with 3 of 22 catheters (13.6%). Due to this high incidence of major thrombotic events with the attendant risk of pulmonary embolism, all patients with CF using infusaports and without evidence of liver disease or bleeding problems receive aspirin prophylaxis.

Adolescent↗
PubMed1992

Diagnosis and management of congenital vascular rings: a 22-year experience.

Between 1968 and 1990, we operatively treated 39 patients (19 boys, 20 girls) with congenital aortic arch anomalies. Median age was 7 months (range, 1.5 months to 23 years). Thirty-seven patients (95%) had respiratory symptoms. Barium swallow was diagnostic in 95%. Right arch with aberrant left subclavian artery and double aortic arch were the most common types (11 each). Treatment of an aortic diverticulum was documented in 19 patients; the aortic diverticulum was excised (9), managed by aortopexy (7), or left in situ (3). Postoperative recovery was rapid, with a median intensive care unit stay of 2 days, time to oral feeding of 1 day, and postoperative time to discharge of 7 days. Two deaths occurred: 1 infant had undergone emergent operation for control of hemorrhage from an aortotracheal fistula due to tracheostomy tube erosion, and the other had multiple associated congenital heart defects. Postoperative complications included bleeding (1), pneumonia (5), and chylothorax (4). One boy had persistent severe symptoms due to an untreated aortic diverticulum and underwent subsequent excision of the aortic diverticulum with complete relief of symptoms. Median length of follow-up was 12.5 months, with at least 97% of survivors completely or nearly completely free of symptoms from the vascular ring. These results suggest that early repair of congenital aortic vascular rings, including fixating or excising an associated serious aortic diverticulum, is safe and effective and allows for normal tracheal growth.

Adolescent↗
PubMed1992

Treatment of recurrent and refractory pediatric solid tumors with high-dose busulfan and cyclophosphamide followed by autologous bone marrow rescue.

PURPOSE: The purpose of this study was to determine the toxicities of and responses to high-dose busulfan and cyclophosphamide with autologous bone marrow transplant (ABMT) in patients with recurrent or refractory pediatric solid tumors. PATIENTS AND METHODS: We treated 18 patients (ages, 2 to 38 years; median, 14) who had tumors that were resistant to conventional chemotherapy and radiotherapy with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg. Seventeen patients received bone marrow purged with 4-hydroperoxycyclophosphamide; one received unpurged marrow. RESULTS: Despite extensive prior treatment, including radiotherapy in 16 patients, toxicity generally was acceptable. For seven patients with measurable disease, there were three partial responses of 2, 10, and 20 months' duration, three patients with stable disease (SD), and one early, toxic death. Of the 11 patients with no measurable disease at the time of transplantation, one patient with osteosarcoma continues in remission at 57+ months and one third of the patients survived for at least 16 months. Mucositis was the predominant nonhematopoietic toxicity. CONCLUSION: Although the high-dose busulfan and cyclophosphamide combination showed modest activity, changes in the preparative regimen should be considered to improve the response rate in refractory tumors.

Adolescent↗
PubMed1990

The ontogeny of the gut-associated lymphoid tissue in short bowel syndrome.

Newborns suffering from short bowel syndrome (SBS) after massive intestinal resection have numerous infectious complications, which may be due to immunoincompetence from the loss of gut-associated lymphoid tissue (GALT). This study examines the ontogeny of GALT in the rat with SBS. A total of 36 3-week-old rats were divided into two groups: I, sham operated (C, n = 16); and II (SBS, n = 20), with a 50% resection of small intestine with jejunoileostomy. At 4, 5, 6, and 10 weeks of age the animals were sacrificed and the GALT was assessed by video analysis and immunoperoxidase monoclonal antibodies, OX8 (CD8), W-3/25 (CD4), and MARA-2 (IgA). The data were expressed as positive staining lymphocytes per 10(4) microns2 (mean +/- SD). table; see text In the sham group there was an increase in all lymphocyte subsets over time. In the SBS group there was a rapid fall in OX8 and W-3/25 T-lymphocytes by 10 weeks, with no increase in IgA plasma cells at 6 and 10 weeks. This study demonstrates that in the massive bowel resection in the suckling rat decreases the T- and B-lymphocyte populations in the GALT. This lack of development may underlie the associated infectious complications and malabsorption in SBS.

Animals↗
PubMed1990

Superior mesenteric vein inflow for liver transplantation when the portal vein is occluded.

An alternative solution to the problem of liver transplantation in the patient with an occluded portal vein is described. It uses a bridge graft of donor iliac vein from the superior mesenteric vein at the base of the colonic mesentery. The graft is tunnelled over the pancreas and under the stomach to the region of the liver hilum to provide portal inflow. This procedure was employed successfully in four patients, with patency for more than 2 years in the patient with the longest follow-up. By this approach it is routinely possible to perform a transplant procedure in a recipient with an occluded portal vein.

Adult↗
PubMed1989

Neonatal diagnosis of a presacral mass in the presence of congenital anal stenosis and partial sacral agenesis.

The simultaneous presentation of clinically symptomatic anal anomalies and roentgenographically demonstrated sacral dysgenesis should alert the pediatric surgeon to investigate for the presence of a presacral malformation. We report on such a case to illustrate a new radiographic technique that facilitates diagnosis and management of complex congenital malformations. A 1-day-old white boy presented with anal stenosis, a scimitar-shaped sacrum, and large anterior and posterior meningoceles. In addition, a distinct presacral tumor--a teratoma--was identified. These malformations were identified utilizing metrizamide myelography and three-dimensional reconstruction computed tomography (CT) scanning. The meningoceles and a tethered cord were successfully corrected utilizing a posterior approach. A diverting colostomy was performed and subsequently taken down. Two years postoperatively, the patient continues to do well. This case demonstrates that this triad of anomalies (presacral mass, sacral dysgenesis, and anorectal malformation), once considered, can be safely detected with modern radiologic techniques and can be expeditiously corrected during infancy before further deterioration occurs.

Abnormalities, Multiple↗
PubMed1989

Prediction of successful primary closure of congenital abdominal wall defects using intraoperative measurements.

To determine whether intragastric pressure (IGP) and central venous pressure (CVP) would reliably predict successful primary closure of congenital abdominal wall defects (omphalocele/gastroschisis) in newborn infants, we developed the following prospective intraoperative management protocol. Following a temporary trial of fascial closure, infants who had an IGP less than 20 mm Hg or an increase in CVP of less than 4 mm Hg were primarily closed. If IGP was greater than 20 mm Hg or if CVP increased by more than 4 mm Hg, the temporary closure of the abdomen was reopened and a prosthetic silo was placed. Ten infants who were less than 24 hours old and averaged 2.7 kg (range, 1.4 to 4.2 kg) and 37-weeks gestation (range, 32 to 41 weeks) were studied. Eight infants met criteria for primary closure. Their IGP averaged 14 +/- 4 mm Hg (+/- SD) (range, 8 to 19 mm Hg), and their increase in CVP averaged 1 +/- 2 mm Hg (range, -2 to 3 mm Hg). In the two infants who required staged repair, IGP averaged 25 +/- 1 mm Hg (+/- SD) (range, 24 to 25 mm Hg), and the increase in CVP averaged 7 +/- 1 mm Hg (range, 6 to 8 mm Hg). All patients were anesthetized with fentanyl (12.5 micrograms/kg) and paralyzed with metocurine (0.3 mg/kg) intraoperatively. There were no postoperative complications in either group of patients related to increased intraabdominal pressure, and all patients were extubated within 48 hours of the initial surgery. We conclude that the intraoperative measurement of changes in IGP and CVP can serve as a guide to the operative management of congenital abdominal wall defects and can reliably predict successful outcome following repair.

Abdominal Muscles↗
PubMed1989

Evolving management of pectus excavatum based on a single institutional experience of 664 patients.

Most pediatricians and family physicians believe that children with pectus excavatum require surgery only for cosmetic indications and then only in teenagers. We believe pectus excavatum should be repaired in childhood (1) to relieve structural compression of the chest and allow normal growth of the thorax; (2) to prevent pulmonary and cardiac dysfunction in teenagers and adults; and (3) to obviate the cosmetic impact that may cause a child to avoid sports and gymnastics. Preoperative CT scans now help select those children who need repair to prevent progressive deformities. Pulmonary function studies during vigorous exercise can document respiratory dysfunction in teenagers. These features are reversible if repair is completed before the pubertal growth spurt. The ideal age for repair is 4 to 6 years, which permits enough emotional maturity for a positive hospital experience and avoids later psychological effects. Repair at an earlier age has no operative advantages. Our operative technique consists of the removal of three to four overgrown costal cartilages, repositioning of the sternum with a transverse osteotomy, and internal support using the child's lowest normal ribs, avoiding any prosthetic support. To prevent recurrence in teenagers, we add a temporary bar beneath the sternum to prevent depression of the sternum from the weight of the chest-wall muscle mass. Six hundred sixty-four patients have been followed for 1 to 40 years; 95% have excellent long-term results and only 5% have mild to moderate recurrences. Our current techniques of patient selection and surgery will be presented.

Adolescent↗