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Biomedical subjects

T F Tracy

Publications and source records attributed to T F Tracy.

54 records · Page 3Linked to original sources
PubMed1993

Growth-related gene expression in early cholestatic liver injury.

BACKGROUND: Extrahepatic biliary obstruction initiates cholestasis, bile duct proliferation, periportal fibrosis, and, eventually, lethal biliary cirrhosis. Little is known about the genetic regulation of the cellular proliferation and differentiation that begins with the onset of bile duct obstruction. To focus this and future gene expression studies, we sought to determine the time frame for growth-related gene expression and questioned whether the in vivo expression of the protooncogenes H-ras and c-myc was altered after bile duct obstruction. METHODS: Female Fisher rats underwent ligation and division of the common bile duct or sham laparotomy. RESULTS: After obstruction, serum bilirubin and gamma-glutamyl transpeptidase rose to 24% and 30%, respectively, of maximum levels by 10 days after ligation. Morphologic evidence of proliferation of bile duct epithelial cells was first evident after 3 days. After hybridization to c-DNA probes, densitometry for H-ras and beta-actin revealed an immediate and parallel increase in steady-state levels of expression after 24 hours of cholestasis. Levels of c-myc messenger RNA were elevated during the first 3 days of cholestasis; however, at 7 and 10 days c-myc expression was depressed 16% and 60%, respectively. CONCLUSIONS: These profiles of expression show an oncogene response induced by early cholestasis. These data showed that elevations in H-ras and c-myc steady-state expression accompany the proliferative response of bile duct epithelial cells. Decreased levels of c-myc after initial elevation infer that ductal proliferation may continue independently of its steady-state expression, a response usually seen in vitro rather than in in vivo proliferation.

Actins↗
PubMed1993

Congenital hemangiopericytoma: an unusual vascular neoplasm of infancy.

BACKGROUND: Hemangiopericytoma is an uncommon tumor of infants, which originates from the vascular pericytes. Although generally considered to benign, metastases can occur. METHODS: Five cases of congenital hemangiopericytoma were seen in infants; all were found in females. The mean age at diagnosis was 7 weeks (range, birth to 10 weeks). The lesions were located in the neck, the parotid, the axilla, and the retroperitoneum. One neck lesion was detected prenatally by ultrasonography. Each lesion was resected. The diagnosis of congenital hemangiopericytoma was established only after histologic examination. RESULTS: No evidence of recurrence has been found in four of the children. However, intrathoracic and intracranial metastases developed in one child with a neck lesion 28 months after the original resection, and the child was treated with chemotherapy, but she died of progressive disease. CONCLUSIONS: We advocate the consideration of congenital hemangiopericytoma in the newborn infant with a vascular mass. Because congenital hemangiopericytoma is unresponsive to steroid therapy, unlike other vascular malformations, resection is the treatment of choice. Long-term postoperative follow-up is essential for the early detection of metastases.

Axilla↗
PubMed1993

Somatostatin analogue (octreotide) inhibits bile duct epithelial cell proliferation and fibrosis after extrahepatic biliary obstruction.

Extrahepatic biliary obstruction leads to bile duct epithelial cell proliferation. Somatostatin and its analogue, octreotide, have been shown to inhibit DNA synthesis and proliferation in hepatocytes. We investigated the effect of octreotide on the biliary epithelial cell proliferative responses to biliary obstruction. Male Sprague-Dawley rats underwent common bile duct ligation and subcutaneous injection of either saline or octreotide (6 micrograms/kg) twice daily for 7 days. Morphometric analysis of hepatocytes, bile duct epithelial cells, and periportal connective tissue was performed by computerized point counting. Hepatocyte volume was preserved with octreotide treatment, which also significantly decreased bile duct proliferation and periportal extracellular matrix deposition in response to biliary obstruction compared with saline treated, duct-ligated animals. These results indicate that octreotide prevents the morphological changes that accompany extrahepatic biliary obstruction.

Animals↗
PubMed1992

Prolonged extracorporeal support for nonneonatal respiratory failure.

Extracorporeal membrane oxygenation (ECMO) is effective for newborns with pulmonary failure unresponsive to conventional therapy. However, ECMO for the older child and adult has been controversial and not widely utilized. Over 4 years, 24 patients (aged 4 months to 16 years; 11 boys, 13 girls) underwent venoarterial ECMO (duration, 7 to 19 days) for respiratory failure. The diagnoses were: viral pneumonia (7), hydrocarbon aspiration (6), sepsis with adult respiratory distress syndrome (ARDS) (2), bacterial pneumonitis (2), tracheal stenosis (1), bilateral pulmonary contusion (1), diaphragmatic hernia with ARDS (1), ketoacidosis with ARDS (1), pulmonary artery injection of hydrocarbon (1), drowning (1), and epiglottis with barotrauma (1). Pre-ECMO blood gas ranges (and means) were PO2 18 to 65 (46), and PCO2 47 to 112 (65). Nineteen patients received dopamine, dobutamine, or other inotrope for associated cardiac and/or renal failure. Cannulation for ECMO was through neck or groin vessels in 17, and sternotomy in 7. ECMO flow rates were 150 to 250 mL/kg/min, to maintain PO2 greater than 100 and PCO2 less than 40. Nine patients (41%) survived ECMO, with eight long-term survivors, (4 hydrocarbon aspiration or injection, 1 pulmonary contusion, 1 viral pneumonia, 1 ARDS, 1 barotrauma), three of whom have mild neurological deficit. All patients with sternotomy, and 8 of 15 with neck and/or groin cannulation, required 1 to 5 explorations for hemorrhage while on ECMO. All survivors had primarily pulmonary failure; patients with combinations of pulmonary, cardiac, and renal failure did not survive. ECMO can be life-saving in the child with isolated pulmonary failure, but its efficacy in patients with multiorgan failure is uncertain.

Adolescent↗
PubMed1991

Congenital tracheal stenosis with unilateral pulmonary agenesis.

Cogenital tracheal stenosis with unilateral pulmonary agenesis is a rate and frequent fetal combination. In an 8-year period, 5 infants (ages 2 to 6 months) with these anomalies were treated. The presenting signs and symptoms consisted of wheezing, stridor, and tachypnea and included frank respiratory failure requiring emergency therapy in several patients. The operative repair consisted of segmental resection and anastomosis in one patient, and rib-cartilage tracheoplasty in the other four. Two infants died, one of cerebral hypoxia, and the other of aortotracheal fistula. Long-term follow-up in the three survivors is satisfactory.

Abnormalities, Multiple↗
PubMed1991

Cholestasis without cirrhosis alters regulatory liver gene expression and inhibits hepatic regeneration.

Partial hepatectomy (PH) initiates cellular signals for regeneration. Sequential expression of nuclear and cytosolic protooncogenes accompanies the restoration of normal liver function and architecture. Although cirrhosis is known to inhibit liver regeneration, the effects of noncirrhotic cholestasis on hepatocellular proliferation, differentiation, and regulatory gene expression are unknown. To examine this, 25 male Fisher rats underwent common bile duct ligation and division. A 47% +/- 5% PH was performed 10 days after common bile duct ligation and division when histologic analysis revealed cholestasis without cirrhosis. Despite early elevations of total hepatic DNA and RNA values, cholestatic livers demonstrated a significant threefold suppression of expected hepatocyte mitotic indexes 48 and 72 hours after PH, compared with livers after PH alone. Weight restoration in cholestatic livers was 11% +/- 5.2% compared with 40% +/- 4.3% in control livers (+/- SEM; p less than 0.001) 5 days after PH. Analysis of regenerating liver messenger RNA with complementary DNA probes revealed an abnormal, sustained elevation of K-ras expression in cholestatic livers through all time points. Cholestasis blunted but did not obliterate normal sequential elevations in H-ras found in control livers. The expression of c-myc was inhibited threefold with cholestasis 72 hours after PH. These results are the first indication that cholestasis alone inhibits hepatocyte proliferation and the expression of c-myc that normally precedes the first wave of mitosis. This implies that cholestasis without cirrhosis may alter programmed liver gene expression, inhibiting normal hepatic regeneration.

Animals↗
PubMed1991

Complement activation during prolonged extracorporeal membrane oxygenation.

Short-term cardiopulmonary bypass activates the complement system, possibly resulting in pulmonary dysfunction from granulocyte aggregation and pulmonary endothelial damage. These effects may be inhibited by steroids. Prolonged extracorporeal membrane oxygenation (ECMO) is used for newborn respiratory failure, but the effects of ECMO on complement activation are unknown. Twenty-one newborn infants with respiratory failure treated with ECMO were randomly assigned to group I (control, no steroids) or group II (30 mg/kg intravenous methylprednisolone before ECMO). Depletion assays of C3 and C5 were performed in each group at intervals before and during ECMO (declining values indicate complement activation). The groups were compared for complement levels, survival, time on ECMO and on the ventilator, and total hospitalization time. Steroids significantly shortened the time on ECMO and time on the ventilator after ECMO but did not affect survival or total hospitalization time. Steroids also enhanced activation of C3 and C5. Complement activation occurs during ECMO. Steroid administration paradoxically causes earlier complement activation but shortens ECMO and ventilator times. Complement activation during ECMO is of questionable significance. The benefits of steroids during ECMO may be mediated through other mechanisms.

Birth Weight↗
PubMed1991

Acquired tracheal stenosis in infants and children.

Acquired tracheal stenosis in childhood is frequently difficult to manage because of poor healing, infection, and scarring. In a 10-year period, 62 patients (4 weeks to 14 years of age) were treated for acquired tracheal stenosis. The causes of stenosis were endotracheal intubation (44 patients), caustic aspiration (6 patients), recurrent infection (5 patients), bronchoscopic perforation (4 patients), and gastric aspiration (3 patients). The subglottic or upper trachea was involved in 47 patients, mid portion in 8, and distal or carinal area in 7. Fifty children underwent tracheostomy as part of the therapy, and 12 were managed without tracheostomy. Therapy was individualized, frequently sequentially, utilizing rigid or balloon dilatation (20 patients), bronchoscopic electrocoagulation resection (44 patients), steroid injection (48 patients), T tube stent (8 patients), resection with anastomosis (12 patients), cricoid split (3 patients), and rib cartilage graft (12 patients). Most patients required several techniques and repeated procedures to eventually achieve decannulation. Seven patients (11%) died of unrelated causes. Forty-four of 55 surviving patients (80%) are without tracheostomy, although 14 have required continued endotracheal treatment after tracheostomy removal (dilatation, endotracheal resection). This series demonstrates that acquired tracheal stenosis in childhood is a common, difficult problem, but manageable with the use of a variety of techniques. Resection and grafting procedures should be reserved for cases in which less complex modalities fail.

Adolescent↗
PubMed1990

Complex hemangiomas of infants and children. Individualized management in 22 cases.

Large hemangiomas in infants and children are rare but can be life-threatening if they involve vital structures or produce thrombocytopenia or congestive heart failure. During a 6-year period, 22 infants and children, aged newborn to 7 years, were treated for complex, symptomatic hemangiomas. The lesions were located in the liver in seven, face or parotid gland in five, neck in four, extremity in two, and mediastinum, chest wall-spinal cord, trachea, and retroperitoneum in one patient each. The diagnosis was suggested by physical examination in all patients and was confirmed by radiologic examination in most patients. The treatment was individualized, usually progressed from less to more invasive, and included observation, prednisone therapy, arterial ligation, and resection. All children were eventually cured, with minimal morbidity. Children with life-threatening hemangiomas can be successfully managed with the use of a variety of techniques.

Angiography↗
PubMed1990

Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns.

Extracorporeal membrane oxygenation (ECMO) is becoming an accepted therapeutic modality for newborn respiratory failure, but there is little information available regarding the prognostic determinants with this technique. One hundred thirty-five newborns treated with ECMO over a 4-year period were critically analyzed with regard to the influence that birth weight, gestational age, age at initiation of ECMO, best blood gases before ECMO, number of hours on ECMO, renal failure, intracerebral hemorrhage, and long-distance air transport had on survival. Infants with meconium aspiration and those undergoing long-distance transfer showed significant differences in blood gases before ECMO, with survivors having more normal pH and carbon dioxide tension values. Intracerebral hemorrhage and renal failure that developed during ECMO were grave prognostic signs, with few survivors in either group. These data show that ability to ventilate patients before ECMO, giving normal carbon dioxide tension and pH values, is an important prognostic sign in infants with meconium aspiration and undergoing long-distance transfer for ECMO, whereas renal failure and intracerebral hemorrhage are usually lethal complications of ECMO. Each center performing ECMO should continually reevaluate this invasive technique and its results and complications.

Acute Kidney Injury↗
PubMed1989

Changing spectrum of cholelithiasis and cholecystitis in infants and children.

Cholecystitis and cholelithiasis are infrequent in children and have been historically associated with adolescent pregnancy or hemolytic disorders; however, the incidence and spectrum of cholelithiasis seem to be changing. Between 1970 and 1988, 47 children 17 years of age or less underwent cholecystectomy for cholecystitis or cholelithiasis in our hospital. The patients were divided into chronologic groups: Group 1 encompassed 1970 through 1979 (15 patients) and group 2, 1980 through 1988 (32 patients). The groups were compared for age, sex, pregnancy, blood dyscrasia, family history, obesity, use of total parenteral nutrition (TPN), and incidence of choledocholithiasis with its sequelae. A significant increase in the number of patients with cholelithiasis was found. Infants and young children were affected more frequently in group 2, and many of these young patients had a history of TPN. Choledocholithiasis was also more common in group 2 and presented with life-threatening sequelae. Calculous biliary tract disease should be considered as a possible cause of abdominal pain in children. Timely operative intervention can prevent the increasingly common sequelae of childhood cholelithiasis.

Adolescent↗
PubMed1989

A critical analysis of extracorporeal membrane oxygenation for congenital diaphragmatic hernia.

Despite advances made in the care of infants with congenital diaphragmatic hernia (CDH), survival remains poor. New therapy, such as extracorporeal membrane oxygenation (ECMO), is controversial but may improve survival. Thirty-two newborns with CDH were treated. Thirteen infants were treated with jugular vein-carotid artery ECMO after CDH repair elsewhere; six (46%) survived. Three of the remaining 19 were moribund shortly after birth and first received ECMO, then underwent repair; two (67%) survived. The other 16 underwent CDH repair; 8 of 9 (89%) recovered with conventional therapy, and 4 of 7 (57%) survived when ECMO was used after conventional therapy failed. Overall survival was 63%. Parameters with which physicians may attempt to predict survival or the need for ECMO after repair--such as A-aDO2, ventilatory index versus PCO2, presence of a "honeymoon period" (PaO2 greater than 100 mm Hg after repair), or oxygenation index--were unreliable. ECMO can improve survival in infants with CDH, probably through reversal of pulmonary hypertension. Presently available methods of predicting survival after CDH repair with or without ECMO are not accurate, and thus no infant should be excluded from repair or ECMO support.

Extracorporeal Membrane Oxygenation↗
PubMed1987

Extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernias.

From 1981 through 1986, 8 newborns with congenital diaphragmatic hernia required herniorrhaphy in the first 8 hours of life. Extracorporeal membrane oxygenation (ECMO) was employed in 7 after they met local criteria predictive of 95% mortality. These criteria were an alveolar-postductal arterial oxygen gradient greater than 600 mm Hg for 12 hours or hemodynamic instability. Four of these 7 patients had unremitting hypoxemia after herniorrhaphy (no "honeymoon" period), 3 of whom survived. One additional patient died, producing a mortality of 29%. ECMO used for 68 to 241 hours (mean, 163 hours) provided reliable oxygenation in all. Deaths resulted from disseminated intravascular coagulation and bleeding, and bleeding and pulmonary failure after ligation of a patent ductus arteriosus. Complications occurred in 6 patients and included bleeding (3), hernia recurrence (3), and air embolism (1). Follow-up ranging from 1 year to 6 years after discharge of the 5 survivors shows normal growth and development in 4. The reported mortality without ECMO following congenital diaphragmatic herniorrhaphy in the first 8 hours of life ranges between 60 and 80%. While bleeding may present problems, survival of newborns with refractory hypoxemia after diaphragmatic repair has improved with ECMO.

Extracorporeal Circulation↗
PubMed1987

Mortality with extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernia in 93 infants.

The results of extracorporeal membrane oxygenation (ECMO) following repair of congenital diaphragmatic hernia (CDH) are analyzed for 93 neonates reported to the Neonatal ECMO Registry. Each infant was symptomatic at birth and developed life-threatening hypoxemia after herniorrhaphy. ECMO was used after neonates met criteria predictive of death in individual centers. These included (1) failure of medical therapy to reverse hypoxemia (35 neonates); (2) acute clinical deterioration making death appear likely (37 neonates); (3) AaDO2 greater than 600 for 8 hours (13 neonates); (4) oxygen index score of 51 for 4.8 hours (5 neonates); and (5) cardiac arrest (1 neonate). With ECMO, 52 infants (58%) survived and were discharged. Pre-ECMO arterial blood gas analysis was not predictive of outcome. Mortality was higher in small premature infants. ECMO corrected the hypoxemia, which usually causes death following congenital diaphragmatic herniorrhaphy. Unfortunately, 47 major bleeding complications occurred with 29 deaths. Therefore, improved survival may depend on new methods designed to prevent bleeding.

Cerebral Hemorrhage↗
PubMed1986

Selective low-dose streptokinase infusion in the treatment of acute transplant renal vein thrombosis.

A renal transplant recipient developed acute renal transplant vein thrombosis following surgery for a total hip replacement. As an alternative to standard surgical therapy, the patient was treated with selective intravenous low-dose infusion of streptokinase at doses of 5,000-20,000 units/h. The infusion was continued for 120 h with constant monitoring of PT, PTT, and fibrinogen levels. Therapy resulted in excellent preservation of renal function without complications. Low-dose selective infusion of streptokinase should be considered a potential alternative therapy for acute transplant renal vein thrombosis.

Acute Disease↗
PubMed1976

The effect of entrapment in liposomes on the in vivo distribution of [3H]methotrexate in a primate.

Entrapment of methotrexate (MTX) plus [3',5', 9(n)-3H]methotrexate into positively charged liposomes greatly alters the subsequent distribution of [3H]MTX in a cynomologous monkey (Macaca irus) after a single i.v. injection ([3H]MTX; refers to total radioactivity derived from purified [3H]MTX). When [3H]MTX is incorporated into small, sonically disrupted liposomes, the level of the entrapped [3H]MTX in the total plasma volume was still 50% of the total injected dose after 4 hr, which is 100 times greater than the level found when the same amount of free MTX (1 to 4 mg) plus [3H]MTX was injected. When entrapped in larger mechanicanically disperesed liposomes, however, the plasma levels of liposome-entrapped [3H]MTX at 4 hr was only 6-fold greater than free [3H]MT. The liposome-entrapped MTX (refers to MTX measured by dihydrofolate reductase assay) did not show detectable breakdown in the plasma whereas free MTX showed up to 97% breakdown. Increased clearance of [3H]MTX entrapped in mechanically dispersed liposomes was complemented by its much greater uptake into tissues, especially spleen, compared with sonically disrupted liposomes. There was over a 160-fold increased uptake by the spleen of liposome-entrapped [3H] MTX relative to free [3H]MTX, whereas for sonically disrupted liposomes the comparable ratio was 20. Although this liposome-entrapped MTX showed significant breakdown, it was less than that found after injection of free MTX. In certain tissues, especially the small intestine, a reduced uptake of liposome-entrapped [3H]MTX WAS FOUND. Uptake of liposome-entrapped [3H]MTX into liposomes led to a much lower renal clearance of [3H]MTX, especially in the case of sonically disrupted liposomes. Possible reasons for these effects and the relationship of our findings to those of others are discussed.

Animals↗
PubMedDate not supplied

Extracorporeal Life Support Organization 1994.

The annual report of the Extracorporeal Life Support Organization is presented for 1994. The aggregate experience of neonatal, pediatric pulmonary, and neonatal/pediatric cardiac patients treated with extracorporeal membrane oxygenation is presented for data collected to April 1994. In addition, the Registry now includes a large number of adult extracorporeal membrane oxygenation cases. Rates of survival for each patient group remained unchanged from previous years with 81% neonatal, 50% pediatric, and 44% cardiac survival. Complete data are available through 1992, with increasing case numbers each year as a basis for this growing registry.

Adult↗