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P Colombani

Publications and source records attributed to P Colombani.

At least 37 records · Page 2Linked to original sources

Effects of L-carnitine supplementation on physical performance and energy metabolism of endurance-trained athletes: a double-blind crossover field study.

A double-blind crossover field study was performed to investigate the effects of acute L-carnitine supplementation on metabolism and performance of endurance-trained athletes during and after a marathon run. Seven male subjects were given supplements of 2 g L-carnitine 2 h before the start of a marathon run and again after 20 km of the run. The plasma concentration of metabolites and hormones was analysed 1 h before, immediately after and 1 h after the run, as well as the next morning after the run. In addition, the respiratory exchange ratio (R) was determined before and at the end of the run, and a submaximal performance test was completed on a treadmill the morning after the run. The administration of L-carnitine was associated with a significant increase in the plasma concentration of all analysed carnitine fractions (i.e. free carnitine, short-chain acylcarnitine, long-chain acylcarnitine, total acid soluble carnitine, total carnitine) but caused no significant change in marathon running time, in R, in the plasma concentrations of carbohydrate metabolites (glucose, lactate, pyruvate), of fat metabolites (free fatty acids, glycerol, beta-hydroxybutyrate), of hormones (insulin, glucagon, cortisol), and of enzyme activities (creatine kinase, lactate dehydrogenase). Moreover, there was no difference in the result of the submaximal performance test the morning after the run. In conclusion, acute administration of L-carnitine did not affect the metabolism or improve the physical performance of the endurance-trained athletes during the run and did not alter their recovery.

Adult↗

Diabetes as a complication of tacrolimus (FK506) in pediatric renal transplant patients.

Three cases of insulin-requiring diabetes mellitus associated with tacrolimus (FK506) therapy in pediatric renal transplant patients are presented. New-onset diabetes mellitus has been reported with tacrolimus therapy post liver and kidney transplants in up to 12% of adult patients, but is thought to be rare in pediatrics. Although insulin requirement with tacrolimus therapy has been occasionally reported in adolescent patients post liver transplant, only a single case in a pediatric kidney transplant recipient has been previously documented. These cases illustrate the significant diabetogenic effect of tacrolimus in pediatric renal transplant patients. As the use of tacrolimus becomes more prevalent in pediatric kidney transplantation, pediatric nephrologists should be aware of this potential complication.

Adolescent↗

The role of cyclosporine-induced autoreactive T lymphocytes in solid organ allograft survival and chronic rejection.

Cyclosporine (CsA) has profound but paradoxical effects on the immune system. CsA can facilitate the induction of transplantation tolerance in some animal systems but it inhibits the clonal deletion of MHC class II autoreactive T cells. The present studies evaluated whether the autoreactive T cells participate in the induction of facilitated graft acceptance after CsA treatment by recognizing and eliminating activated allograft responsive T cells that express MHC class II determinants. Transfer of autoreactive T cells into naive Lewis rats pretreated with cyclophosphamide significantly prolonged the survival of heterotopic cardiac allografts from MHC-disparate BN strain donors. Following transfer of the autoreactive T cells, there was a marked reduction in the frequency of alloreactive T lymphocytes responsive to donor alloantigens. The role of MHC class II autoreactive CD8+ V beta 8.5+ T cells in facilitated graft acceptance was also supported by the findings that (1) treatment with anti-MHC class II antibody abrogated prolonged allograft survival after CsA therapy and (2) V beta 8.5+ lymphocytes infiltrate the allograft during CsA therapy but are absent in the graft in non-CsA-treated control animals. Although these data are consistent with the hypothesis that autoreactive T cells prolong cardiac allograft survival after CsA treatment, the autoaggressive cells failed to inhibit the development of chronic rejection of both heart and skin allografts. These data suggest either that the autoreactive T cells do not inhibit immune mechanisms responsible for chronic graft rejection or that the autoaggressive lymphocytes may participate in and exacerbate chronic rejection of allografts. Taken together, the induction of MHC class II autoreactive T cells may provide a common fundamental mechanism explaining the paradoxical effects of CsA.

Animals↗

Primary cutaneous neuroendocrine tumors. Diagnostic use of cytogenetic and MIC2 analysis.

Merkel cell carcinoma (MCC) is a primary cutaneous neoplasm most commonly involving older adults. The cell of origin is thought to be the Merkel cell, a cutaneous neurosecretory cell. However, other neuroectodermal tumors may present in the skin and may be difficult to distinguish from MCC, including peripheral neuroectodermal tumors (PNET) and metastatic small cell carcinoma. We examined a primary cutaneous tumor of an 18-year-old which was strongly positive for cytokeratin (CK), neuron-specific enolase (NSE), and 12E7, an antibody to the protein determined by the MIC2 gene. Electron microscopy showed paranuclear aggregates of filaments and no cytoplasmic processes. These findings were considered to be consistent with MCC. Cytogenetic analysis demonstrated 46,XX,der(1)t(1;3;22)(1qter-->pa34::3q28-->q11::22q 12--> qter),der(3)t(1;3)(3pter-->q11::1p35-->pter), der(22)t(3;22)(22pter-->q11::?3q29-->qter). This was confirmed by chromosome painting using probes for chromosomes 1, 3, and 22. Peripheral neuroectodermal tumors (PNETs) show a characteristic translocation involving the same breakpoint on chromosome 22 that was present in this tumor. PNETs can also be CK and NSE positive. The MIC2 gene codes for a surface glycoprotein that has been shown to be very strongly and reliably expressed in PNETs, but not in other small round blue cell tumors and not in small cell carcinoma of the lung. However, MIC2 expression has not been studied in MCC. We investigated the use of MIC2 analysis in the distinction of MCC from PNET. Five additional MCCs were stained with the monoclonal 12E7 antibody, and one additional tumor showed the strong membranous positivity reported in PNETs. Our data suggest that MIC2 analysis may be useful in differentiating between MCC and PNET. However, cases will remain for which the distinction is elusive and cytogenetic analysis may be helpful.

Adolescent↗

Proximal renal tubular acidosis secondary to FK506 in pediatric liver transplant patients.

We hereby report our experience with an index case of a pediatric liver transplant patient in whom FK506 administration was associated with the development of proximal renal tubular acidosis (RTA), as well the prevalence of acidosis and renal dysfunction in all pediatric liver transplant patients in our institution followed long term during a 6-year period. Data were grouped according to immunosuppressant regime: cyclosporine (CsA) only, FK506 only, or CsA with conversion to FK506. A 23-month-old female treated with FK506 after orthotopic liver transplantation (OLT) performed 15 months earlier presented with a 1-wk history of fever, watery diarrhea and metabolic acidosis. Although the acidosis did not improve following correction of her hydration status, administration of oral bicarbonate was effective. Discontinuation of this therapy resulted in acidosis. Since other indirect measurements of renal tubular function were normal, the patient was judged to have an isolated proximal RTA. In our group of pediatric liver transplant patients converted from CsA to FK506, FK506 administration was associated with a decline in serum bicarbonate (19 +/- 1 vs. 16 +/- 1 mEq/l, p < 0.02); neither blood urea nitrogen nor serum creatinine differed between the two groups. The number of rejection episodes/patient/month was comparable, allowing clinically relevant comparison of relative drug nephrotoxicities. We conclude that proximal RTA may be a relatively common treatable complication of FK506 administration in children.

Acidosis, Renal Tubular↗

Nonoperative management of solid organ injuries in children. Is it safe?

OBJECTIVE: The authors reviewed their experience with life-threatening blunt injuries in approximately 2900 children (0-14 years) admitted to the designated state pediatric shock trauma unit between 1990 and 1993. METHODS: During this time, the authors treated all severely injured children with a prospective, nonoperative protocol if they were hemodynamically stable after less than 40 mL/kg fluid replacement, had proven evidence of solid organ injuries and remained stable in the pediatric intensive care unit under surgical management. RESULTS: Twenty-eight children had computed tomography (CT) or operatively proven lacerations of the spleen, 25 had lacerations of the liver, 18 had lacerations of the kidney, 7 had lacerations of the pancreas, and 11 had two or more solid organ injuries. Three of the 28 children with injured spleens required laparotomy (two splenectomy, one splenorrhaphy). Two of the 25 children with liver injuries required laparotomy (one suturing, one partial resection). One of the 18 children with kidney injuries required laparotomy (nephrectomy), and 3 of the 7 children with pancreas injuries required laparotomy (two resection, one pseudocyst). There were three deaths after laparotomy (two head, one chest/abdominal). There were no deaths in the children managed nonoperatively, and there were no immediate or long-range complications. CONCLUSIONS: Comparison of the authors' data with the National Pediatric Trauma Registry shows similar results. The authors believe that nonoperative management of solid organ injuries under careful surgical observation in a pediatric intensive care unit is safe and appropriate.

Abdominal Injuries↗

[Prenatal screening for Down's syndrome: a simplified method].

Prenatal screening for Down's syndrome (DS) can be achieved by combining maternal age risks and maternal serum additional parameters (AFP, HCG, uE3) by computer assisted statistical analysis. Nevertheless this measure of risk is far from broad and practical application in Italy, due to cultural and organization difficulties. So we suggest a different technical approach, the age specific risk being multiplied by the HCG/AFP likelihood ratio. HCG and AFP can be tested by an automated Elisa assay, and calculations performed by a simple method, excluding computer and software package use. About 100 pregnancies were evaluated both by a modified version of the Wald test and the method described hereafter. Using the automated HCG and AFP Elisa Testing and Crossley statistical calculation a higher False Positive Rate was observed. On the other hand no different Detection Rate was observed for the two tests. On a retrospective study we found that 5 sera from affected pregnancies were correctly identified both by the modified Wald test and the other method. It is concluded that, despite different False Positive Rates, the choice of which test to use depends on evaluation of local resources, one test being easier-to-perform and more sensitive, the other one probably being more specific but more difficult to perform.

Adolescent↗

Intrahepatic hepatocyte transplantation following subtotal hepatectomy in the recipient: a possible model in the treatment of hepatic enzyme deficiency.

Orthotopic liver transplantation as treatment for hereditary enzyme deficiencies in the absence of cirrhosis suffers from significant operative risks, complications, and donor shortages. Transplantation of isolated hepatocytes (HTX) may offer opportunities for the treatment of these diseases and retain the recipient liver. Hepatocytes transplanted into the portal vein, spleen, or omentum lack an ideal growing environment for cell proliferation and maintenance. Therefore, we investigated a method combining 75% recipient hepatectomy with direct injection of hepatocytes into the remaining 25% of liver parenchyma to provide proliferative stimuli and a stable environment during and following liver regeneration. Recipient Gunn rats (glucuronyltransferase deficiency and hyperbilirubinemia) underwent hepatectomy before HTX by direct injection of 10(7) isolated hepatocytes into the remaining parenchyma. Inbred male Wistar and Gunn rats were used as normal and control hepatocyte donors and saline injection served as a sham transplant control. Isolation of donor hepatocytes was performed with a two-step collagenase digestive method (Seglen) with cell viability of 85% to 95%. Liver regeneration was complete by 2 weeks posttransplant. Four weeks following HTX, total serum bilirubin and qualitative bile analysis were performed. A significant decrease in total serum bilirubin levels was observed in Gunn rats receiving Wistar hepatocytes compared with those receiving Gunn hepatocytes and saline control. Bile analysis from HTX rats demonstrated a normal pattern containing bilirubin monoglucuronides and diglucuronides (conjugated bilirubin) in the rats receiving Wistar hepatocytes, whereas the control group receiving Gunn hepatocytes or saline injection demonstrated only unconjugated bilirubin. No differences in histological appearance were noted between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reduction of morbidity and mortality from biliary complications after liver transplantation.

Over a 4-yr period that began October 1, 1986, 103 orthotopic liver transplants were performed on 91 patients at the Johns Hopkins Hospital. Biliary reconstruction at the time of transplantation was performed in standard fashion by an appropriately trained member of the surgical team. Six (7%) patients developed biliary complications, which included three cases of common bile duct stricture and one case each of bile duct obstruction caused by biopsy-related hemobilia, biloma and a retained fragment of a T tube after removal. Five of the six patients were treated successfully by nonoperative interventional radiological procedures performed under local anesthesia with light intravenous sedation. Reoperative surgery (to remove the T-tube fragment from subcutaneous tissue) was required for only one patient, and no deaths (0 of 91) were attributable to biliary complications. All six patients are alive and well 6 to 33 mo after the operation with excellent liver function. Our findings would suggest that most biliary complications of orthotopic liver transplants are avoidable and that the few that do appear can usually be managed both safely and effectively by an interventional radiological approach.

Adult↗

Lymphocyte populations with different sensitivity to cyclosporin have different plasma membrane potentials.

Cyclosporin A (CsA), a clinically potent immunosuppressive agent, shows preferential biologic activity against certain lymphocyte subsets. To investigate this activity, we used flow cytometry to separate two distinct lymphocyte populations from unfractionated human peripheral blood lymphocytes, based on their different binding affinity for a biologically active fluorescent, dansylated cyclosporin (dans-CsA) derivative. The separate lymphocyte populations demonstrated different resting plasma membrane potentials. The two lymphocyte populations also had different levels of interleukin-2 (IL-2) receptors and shifted plasma membrane potential differently upon treatment with cyclosporin and lymphokine IL-2. The cell population that bound more dans-CsA contained the cells which possessed IL-2 receptors and responded to CsA and IL-2 with changes in membrane potential. The cell population that did not effectively bind dans-CsA lacked IL-2 receptors and did not respond to CsA or IL-2 with immediate membrane potential changes. Furthermore, stimulation studies of these separated two lymphocyte populations with phytohemagglutinin in the presence and absence of CsA revealed that only the population which binds a low level of dans-CsA shows a marked difference in membrane potential between the cells stimulated in the presence and absence of CsA. We concluded that ion flux changes caused by CsA affect the activation process of naive lymphocytes but not that of already stimulated ones. It can also be postulated that the ion flux changing property of CsA could constitute its primary or main mode of action.

Cell Membrane↗

Neonatal necrotizing enterocolitis: an update.

We reviewed 91 cases of neonatal necrotizing enterocolitis (NNEC), which continues to be a devastating disease occurring in 2% to 4% of all newborn intensive care unit admissions. Onset now occurs in older infants (11.9 days). The morbidity is significant (22%), with strictures (8%) and recurrences (8%) the primary problems. Recurrences are more likely to require surgical intervention and result in a high mortality. Early diagnosis of necrotic bowel before perforation, peritoneal contamination, and sepsis is difficult and contributes to the still high, but improved, overall mortality of 36%.

Enterocolitis, Pseudomembranous↗

Open lung biopsy in the immunocompromised pediatric patient.

Rapidly progressive pulmonary distress occurs as a secondary complication in immunocompromised pediatric patients. These patients usually develop a pattern of diffuse alveolar and/or interstitial infiltrates on chest x-ray and pursue a rapidly downhill course despite intensive respiratory support with the use of multiple and varied antimicrobial regimens. These patients are subjected to diagnostic open lung biopsies to establish a diagnosis. The diagnostic value of open lung biopsy and its current impact on therapy is not clearly established. This retrospective study attempts to determine the impact of open lung biopsy on diagnosis and therapeutic outcome. Between November, 1974, and October, 1982, 40 diagnostic open lung biopsies were performed on immunocompromised patients with clinically progressive respiratory disease. Adequate follow-up for complete evaluation was possible in 34 of these patients. Most of these patients had hematologic malignancies and all were on chemotherapeutic drugs at time of open lung biopsy. Open lung biopsy was considered helpful, ie, resulted in a change in antimicrobial therapy or substantiated preoperative therapy, in 17 of our 34 patients (50%). A "treatable" condition, amenable to antimicrobial therapy, was diagnosed in 16 of our patients (47%). Pneumocystis carinii pneumonitis (PCP) was the most common diagnosis in 11 (69%) of our "treatable" patients. The remaining five "treatable" patients had sarcoidosis (1), histiocytosis X (1), bacterial pneumonitis (1) and fungal pneumonitis (2). No diagnosis was achieved by open lung biopsy in ten (30%) of our patients. There were two complications attributable to open lung biopsy (6%), including one death. All PCP patients treated with trimethoprim sulfamethoxazole (T/S) survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

New techniques in the diagnosis and operative management of Siamese twins.

New techniques of 2-D sonography and radionucleotide Disofenin scanning allowed noninvasive evaluation of thoracoomphalopagus Siamese twins and successful separation at four days of age. Twin girls joined at the lower sternum and upper abdomen and weighing 15 lbs, were transferred at five hours of age after caesarian-section delivery. Scout films revealed high intestinal obstruction in twin A. 2-D sonography showed separate and normal hearts with different rates and attached pericardial sacs. Labeled Disofenin given intravenously to twin A was excreted exclusively in her gallbladder and bile ducts; vice versa for twin B. Because operation was necessary to correct jejunal atresia in twin A, further growth and development was not an option and the parents agreed to total correction. Sternal and pericardial separation and division of common midline-liver was followed by primary diaphragmatic defect repair and Dacron-cloth fascial reconstruction to upper abdominal wall and complete soft-tissue and skin closure in a ten-hour operation. Segmental jejunal resection and anastomosis with gastrostomy was added in baby A. The new tests greatly simplified definition of the anatomical relationships and implemented rapid correction in these newborn conjoint twins.

Electrocardiography↗

Organization and function of a regional pediatric trauma center: does a system of management improve outcome?

Since 1975, more than one thousand children with life-threatening injuries have been preferentially transported to our statewide Regional Pediatric Trauma Center by helicopter or city ambulance. Initial care is provided by emergency medical technicians with special instruction in the handling of pediatric trauma. More than half the children admitted to our service were injured in motor vehicle/pedestrian or motor vehicle/bicycle accidents. Have care and outcome improved? This system provides for excellent first aid at the scene and more rapid radio-directed transport to the trauma center where in-hospital management is provided by pediatric and surgical personnel experienced in the treatment of all aspects of childhood trauma. We have organized weekly trauma morbidity and mortality rounds and have established a trauma registry and index of severity. Pelvic fractures from blunt trauma had a mortality in this series of 1.4%, the lowest of any reported experience. Between January 1976 and December 1979, 46 children with coma of longer than 24 hours' duration were treated in the Pediatric Intensive Care Unit. The mortality rate was still high (38%) but employing intracranial monitoring and aggressive control of brain edema, 88% of the survivors had a good recovery without major motor or intellectual defects. The large volume of cases allows for development and evaluation of new techniques in trauma management and invaluable experience in the training of general surgical residents, pediatricians, and emergency physicians.

Adolescent↗

Upper extremity gangrene secondary to superior mesenteric artery infusion of vasopressin.

This patient demonstrates that peripheral vascular ischemia and gangrene may complicate the use of intraarterial vasopressin in the absence of catheter-related phenomena such as microemboli or catheter dislodgement. Discontinuation of vasopressin effectively reverses ischemic changes. Sympathetic blocking agents or direct-acting vasodilators may accelerate the reversal of the vasopressin induced ischemia. In the patient with a history of previous extremity cold injury, vasopressin may precipitate severe ischemia or gangrene by its direct effect at the arteriolar level in an extremity with already increased sympathetic vascular tone. Peripheral circulatory status must be assessed frequently during vasopressin infusion especially in patients with a history of frostbite.

Aged↗