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Biomedical subjects

K T Oldham

Publications and source records attributed to K T Oldham.

At least 55 records · Page 3Linked to original sources
PubMed1989

Long-term radiographic follow-up of the Nissen fundoplication in children.

This study examined 46 children 5-9 years (mean 6.7) after Nissen fundoplication surgery for gastroesophageal reflux (GER). Eleven were deceased and ten of the 35 families declined objective evaluation. The remaining 25 children (71%) had a barium swallow examination. In 16 of the 25 patients the fundoplication was intact. In 2 patients a small portion of the fundoplication was displaced above the diaphragm. In 5 patients there was residual esophageal disease. In 3 patients (one with esophageal disease), with a hiatus hernia prior to surgery, despite immediate postoperative reduction, the barium swallow examination done for this study revealed recurrent hiatus hernia but no GER. Long-term results of the Nissen fundoplication reveal success in eliminating clinically significant gastroesophageal reflux. Those patients with esophageal disease prior to the surgery need close interval follow-up to monitor continuing problems.

Child↗
PubMed1989

Failure of antioxidant therapy (polyethylene glycol-conjugated catalase) in acute pancreatitis.

Previous studies have demonstrated that intravenous catalase infusion protects against the formation of pancreatic edema in cerulein-induced acute pancreatitis; however, polyethylene glycol (PEG)-conjugated catalase given as a bolus was not protective. Using radiolabeled catalase and PEG-catalase in subtherapeutic tracer doses, the pancreas tissue distributions of each were determined in rats with and without pancreatitis. Rats with cerulein-induced pancreatitis developed tissue concentrations of catalase within the pancreas that were three times those of PEG-catalase. The relatively low levels of PEG-catalase in the pancreas outside of the vascular compartment suggest that the failure to prevent edema formation may result from inability of PEG-catalase to reach extravascular sites of injury because of the large molecular size.

Acute Disease↗
PubMed1989

Bacteremia-induced suppression of alveolar surfactant production.

Sepsis is characterized by Adult Respiratory Distress Syndrome (ARDS)-like pulmonary dysfunction largely attributed to alveolar capillary endothelial cell injury which causes increased microvascular permeability and interstitial edema formation. In addition, quantitative and qualitative abnormalities of the pulmonary surfactant system may be important features of some clinical and experimental lung injuries. This study was designed to investigate the relationship of bacteremia and endotoxemia to pulmonary surfactant production in vivo. A technique for estimation of pulmonary surfactant phospholipid synthesis measuring incorporation of a stable isotope precursor [( 2-13C]acetate) into dipalmitoylphosphatidylcholine (DPPC) in alveolar lavage fluid was developed. Male 350 g Sprague-Dawley rats had placement of central venous catheters. After overnight recovery, sublethal bacteremia (Escherichia coli, 1 x 10(8) organisms, iv) and sublethal endotoxemia (Difco; 10 mg/kg, iv) were induced. Both were associated with lung microvascular permeability increases consistent with capillary endothelial injury. Eight-hour infusions of [2-13C]acetate were given. After sacrifice, bronchoalveolar washings and lung tissue were obtained and [2-13C] incorporation into lavage and lung DPPC was measured by gas chromatography mass spectroscopy. Endotoxin-treated animals had a 21.5% reduction in label incorporation into DPPC [1.215 +/- 0.145 APE (%) sham versus 0.954 +/- 0.144 APE (%) experimental, P greater than 0.05] and bacteremic animals had a 56.9% diminution of [2-13C]acetate incorporation [1.215 +/- 0.145 APE (%) sham versus 0.524 +/- 0.56 APE (%) experimental, P less than 0.05]. Bacteremia-induced dysfunction of alveolar type II epithelial cells manifested as diminished alveolar surfactant phospholipid production may be a contributing factor to sepsis-induced respiratory failure.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

Successful separation of a conjoined biliary tract in a set of omphalopagus twins.

Omphalopagus twins were separated in the first 48 hours of life. Preoperative evaluation did not disclose either their conjoined intestines or their conjoined biliary tract; intraoperative evaluation, including an operative cholangiogram, was required to determine if separation was possible. The intestines were divided to give each infant an equal share, and an hepaticoenterostomy was constructed in each of the twins.

Bile Ducts↗
PubMed1989

Reversal of mortality for congenital diaphragmatic hernia with ECMO.

Extracorporeal Membrane Oxygenation (ECMO) has been available to neonates with respiratory failure at the University of Michigan School of Medicine since June 1981. In order to evaluate the impact of this type of pulmonary support, a retrospective analysis of 50 neonates with posterolateral congenital diaphragmatic hernia (CDH) who were symptomatic during the first hour of life and were treated between June 1974 and December 1987 was carried out. The patients were divided into two groups, those treated before June 1981 (16 patients) and those treated after June 1981 (34 patients). Overall survival improved from 50% (eight of 16 patients) during the pre-ECMO era to 76% (26 of 34 patients) during the post-ECMO period (p = 0.06). During the period after June 1981, 21 neonates were unresponsive to conventional therapy and were therefore considered for ECMO. Failure of conventional therapy was defined as acute clinical deterioration with an expected mortality of greater than 80% based on an objective formula previously reported. Six patients were excluded on the basis of specific contraindications to ECMO. Thirteen of 15 infants (87%) supported with ECMO survived. Three patients treated before 1981 met criteria for ECMO; all three died while receiving treatment using conventional therapy. These survival differences are significant (p less than 0.01). In addition, the survival of 87% for the infants treated with ECMO versus the expected mortality of greater than 80% for these same patients when treated with conventional therapy is highly significant (p less than 0.005). Based on this data, ECMO appears to be a successful, reliable, and safe method of respiratory support for selected, critically ill infants with CDH.

Evaluation Studies as Topic↗
PubMed1989

Neutrophil-dependent, oxygen-radical mediated lung injury associated with acute pancreatitis.

Cerulein-induced acute pancreatitis in rats is associated with a reversible lung injury that is characterized by alveolar capillary endothelial-cell injury, increased microvascular permeability, interstitial edema formation, and intraalveolar hemorrhage and fibrin deposition. The role of mediators in this injury was analyzed using gravimetric data, microvascular permeability indices, electron microscopy, and a quantitative morphometric analysis. Neutrophil depletion induced by a specific antibody was highly protective against lung injury. Interruption of the complement pathway (using low dose Naja naja cobra venom factor) also protected against lung injury. Catalase and superoxide dismutase were also protective. The iron chelator deferoxamine and the hydroxyl radical scavenger, dimethylsulfoxide, were not protective against acute lung injury. These data suggest that complement, neutrophils, and neutrophil-derived (H2O2-dependent) oxygen products mediate lung injury that occurs secondary to cerulein-induced pancreatitis. In contrast to other models of neutrophil-dependent, oxygen-radical-mediated lung injury, this lung injury does not appear to be an iron-dependent and hydroxyl-radical mediated injury. We postulate that the process of acute pancreatitis leads to complement activation followed by neutrophil recruitment, sequestration, and adherence to alveolar capillary endothelial cells. Ultimately lung injury appears to result from local endothelial-cell injury secondary to neutrophil-generated oxygen products that may be myeloperoxidase dependent.

Acute Disease↗
PubMed1989

Evidence for neutrophil-related acute lung injury after intestinal ischemia-reperfusion.

Intestinal ischemia-reperfusion injury is a common and important clinical event associated with the activation of an endogenous inflammatory response. Some of the mediators of this response may be involved in the pathogenesis of multiple organ system failure. The purpose of this study was to determine whether remote organ dysfunction--specifically, acute lung injury--occurs after intestinal ischemia-reperfusion injury. After an ischemia-reperfusion event in rat intestine, whole lungs were obtained for measurement of tissue adenosine triphosphate (ATP) and myeloperoxidase values, and evaluation of histologic condition. In addition, lung microvascular permeability was assessed by determination of the rate at which iodine 125-labeled bovine serum albumin sequestration in the extravascular compartment occurred. Lung tissue ATP levels were no different in sham-operated animals than in those that had undergone 120 minutes of intestinal ischemia. Within 15 minutes of gut reperfusion, however, lung ATP decreased from 3.82 +/- 0.27 to 1.53 +/- 0.90 x 10(-7) moles/50 mg tissue, p less than 0.05. Neutrophil accumulation in the lungs, estimated by tissue myeloperoxidase determination, increased sevenfold (0.13 +/- 0.02 to 0.97 +/- 0.25 units/gm, p less than 0.05) after 120 minutes of ischemia and 15 minutes of reperfusion. Lung microvascular permeability increased threefold after 120 minutes of intestinal ischemia and 120 minutes of reperfusion (0.10 +/- 0.01 vs. 0.35 +/- 0.05 [lung/blood counts per minute], p less than 0.05). Intestinal ischemia followed by reperfusion is associated with acute lung injury characterized by increased microvascular permeability, histologic evidence of alveolar capillary endothelial cell injury, reduced lung tissue ATP levels, and the pulmonary sequestration of neutrophils. These data confirm an acute lung injury associated with intestinal ischemia-reperfusion and suggest a possible pathogenic role for the neutrophil.

Acute Disease↗
PubMed1989

Late results of fundoplication for gastroesophageal reflux in infants and children.

The Nissen fundoplication (NFP) for the management of severe gastroesophageal reflux (GER) in infants and children has become one of the most frequently performed operations in pediatric surgical centers in the United States. Short-term outcome, morbidity, and mortality are consistently favorable in several large series. The long-term success of this procedure is presumed but has not been established objectively. To examine the late results of this operation, 46 infants and children were carefully evaluated more than 5 years after NFP (mean, 6.7 years). Evaluation included parental interview, physical examination, upper gastrointestinal series, and esophageal pH monitoring. The mean age at the time of operation was 4.13 years. Fifty-seven percent of the patients had significant neurologic impairment, and 80% had at least one serious additional medical problem. Twenty-four percent of the children died during the period of follow-up--all but one death related to serious underlying medical problems. Of the 35 survivors, 26 (74.3%) have no symptoms; five (14.3%) have mild symptoms potentially referable to GER that necessitate little if any treatment; four (11.5%) have had symptomatic recurrence of GER necessitating repeat fundoplication. Three of these patients now have no symptoms. Forty-five percent of the patients had at least one postoperative complication. NFP provides efficacious, long-term treatment of GER in infants and children, with acceptable morbidity. Mortality in this group of children is related primarily to associated diseases rather than to GER.

Adolescent↗
PubMed1988

The role of oxygen radicals in immune complex injury.

In this review we will summarize our current understanding of the mediation of immune complex induced tissue injury. Comparisons will be made between the mediation of IgG versus IgA immune complex injury with emphasis on the role that reactive oxygen products derived from leukocytic phagocytic cells play in the initiation of the tissue injury.

Animals↗
PubMed1988

The development of necrotizing enterocolitis following repair of gastroschisis: a surprisingly high incidence.

We recently observed the development of necrotizing enterocolitis (NEC) in two consecutive newborn infants after gastroschisis repair. Because this association was unexpected, a retrospective review of our 11-year experience was performed using a multivariant computer analysis. The cohort consisted of 54 newborns with gastroschisis. All infants with omphalocele were excluded. Ten of 54 infants (18.5%) developed NEC as defined by classical clinical findings and pneumatosis intestinalis. Twenty-one distinct episodes of NEC occurred with up to three episodes (mean, 2.1) per patient. Twenty of the 21 episodes were successfully treated nonoperatively. Two infants developed pneumoperitoneum, one of whom underwent laparotomy upon which no perforation or intestinal infarction was found. Eight of the ten patients survived--a survival rate no different than for the remainder of the study group. Neither of the two deaths was attributable to NEC. The NEC was atypical in that no significant relationship was established with known predisposing conditions such as prematurity or low Apgar scores. Suspected risk factors such as time of feeding, type of closure, type of formula, total parenteral nutrition (TPN), and composition of TPN were not statistically related. Significant associations included concurrent TPN associated cholestatic liver disease in nine of the ten infants, antecedent intestinal surgery other than abdominal wall closure in five of the ten infants, and delay in initiation of enteral feedings (greater than 30 days) in eight of ten infants. In addition, the NEC occurred significantly later (range, 32 to 79 days; mean, 52 days) in the clinical course than usual; in fact, three of ten infants were rehospitalized with NEC following discharge. We conclude that a relationship exists between NEC and gastroschisis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1988

Pancreatitis-induced acute lung injury. An ARDS model.

Cerulein-induced acute pancreatitis in rats is associated with acute lung injury characterized by increased pulmonary microvascular permeability, increased wet lung weights, and histologic features of alveolar capillary endothelial cell and pulmonary parenchymal injury. The alveolar capillary permeability index is increased 1.8-fold after a 3-hour injury (0.30 to 0.54, p less than 0.05). Gravimetric analysis shows a similar 1.5-fold increase in wet lung weights at 3 hours (0.35% vs. 0.51% of total body weight, p less than 0.05). Histologic features assessed by quantitative morphometric analysis include significant intra-alveolar hemorrhage (0.57 +/- 0.08 vs. 0.12 +/- 0.02 RBC/alveolus at 6 hours, p less than 0.001); endothelial cell disruption (28.11% vs. 4.3%, p less than 0.001); and marked, early neutrophil infiltration (7.45 +/- 0.53 vs. 0.83 +/- 0.18 PMN/hpf at 3 hours, p less than 0.001). The cerulein peptide itself, a cholecystokinin (CCK) analog, is naturally occurring and is not toxic and in several in vitro settings including exposure to pulmonary artery endothelial cells, Type II epithelial cells, and an ex vivo perfused lung preparation. The occurrence of this ARDS-like acute lung injury with acute pancreatitis provides an excellent experimental model to investigate mechanisms and mediators involved in the pathogenesis of ARDS.

Animals↗
PubMed1988

Activation of complement by hydroxyl radical in thermal injury.

Complement activation resulting from local burn injury of skin and other soft tissues can be linked to systemic complications, such as intravascular hemolysis, neutrophil activation, and acute lung injury. This study was designed to clarify the relationship between cutaneous thermal injury, oxygen radical formation, and complement activation in vivo. A model for "selective" venous sampling from the area of a partial-thickness cutaneous burn over 25% to 30% of the total body surface in the rat was developed. Interventions involving oxygen radical scavengers, antioxidant enzymes, xanthine oxidase inhibitors, an iron chelator, complement depletion, and neutrophil depletion were used to probe the nature of the oxygen products involved in complement activation. Plasma from the area of burn was examined for total hemolytic complement activity, content of C5a-related chemotactic peptide, and relationship of oxygen products to appearance of this peptide. Xanthine oxidase inhibitors, hydroxyl radical scavengers, and complement depletion diminished the generation of C5a activity at the burn site, whereas neutrophil depletion was without effect. These data suggest that C5a activity may be related to oxygen products from xanthine oxidase. The catalase sensitivity and iron dependency of C5a generation suggest that hydroxyl radical may be related to complement activation and C5a appearance. This is the first report to directly link oxygen radical generation and complement activation in vivo.

Animals↗
PubMed1988

Oxygen free radical activity during live E. coli septic shock in the dog.

Free radicals generated during purine catabolism or by activated granulocytes cause tissue injury by peroxidation of lipid membranes. In a canine model of sepsis initiated by intravenous live Escherichia coli, fluorescent products of lipid peroxidation (FP) were measured in serum. Four groups of five dogs infused with 10(9)E. coli/kg were analyzed--I: no further treatment; II: prior depletion of granulocytes with a cytotoxic antibody; III: pre-treatment with superoxide dismutase and catalase; and IV: resuscitation after bacterial infusion to maintain cardiac output greater than 80% of pre-bacteremic levels. In Groups I, II, and III, cardiac output fell to less than 50% of baseline within 1 hr and remained there throughout the study. FP in Groups I and II rose to greater than 200% of baseline (P less than .02 and less than .03). In Groups III and IV, FP did not rise significantly from baseline. The rise in serum FP and the prevention of this rise by-treatment with antioxidants indicate generation of oxygen radicals. Their presence had no effect on hemodynamic parameters. Granulocyte depletion did not alter appearance of FP; however, prevention of low cardiac output blocked FP formation. These data suggest that oxygen free radicals were generated by tissue ischemia, rather than by granulocytes, in this model of septic shock.

Animals↗
PubMed1987

Lung injury in acute pancreatitis: primary inhibition of pulmonary phospholipid synthesis.

Alterations in the pulmonary surfactant system are partly responsible for the respiratory insufficiency seen with acute pancreatitis. In this model of cerulein-induced pancreatitis in rats, we utilized a new stable isotope metabolic tracer technique to examine one aspect of the pulmonary surfactant system and its relationship to associated lung injury. We have demonstrated primary, early depression of lung phospholipid synthesis reflected in both lung tissue and alveolar washings. We suggest that this quantitative change in pulmonary surfactant synthetic rate may partly explain the occurrence of respiratory failure with acute pancreatitis.

Acute Disease↗
PubMed1987

Treatment of intestinal ischemia with oxygenated intraluminal perfluorocarbons.

Liquid perfluorocarbons are biologically inert compounds capable of dissolving up to 40 percent oxygen by volume. This remarkable and reversible oxygen solubility has encouraged investigations into therapeutic application in situations where tissue oxygen delivery is impaired. One such setting is intestinal ischemia. Identically prepared devascularized segments of rat intestine were treated with either intraluminal oxygenated perfluorocarbon (perfluorotributylamine) or physiologic saline solution. After timed sacrifice, blinded quantitative histologic evaluation for ischemic injury was performed. The perfluorotributylamine treatment groups had histologic scores indicative of less severe injury between 1 and 4 hours. These scores achieved statistical significance (p less than 0.05). We conclude that intraluminal oxygenated perfluorocarbons have a significant protective effect in this model of intestinal ischemia. This quantitative analysis is unique and is an important aspect of the preclinical evaluation of the perfluorocarbon preparations.

Animals↗
PubMed1987

The use of venovenous extracorporeal membrane oxygenation in sheep receiving severe smoke inhalation injury.

Smoke inhalation injury now represents the most frequent cause of death in burn patients, and accounts for 20-80 per cent of overall mortality. We have studied the use of extracorporeal membrane oxygenation (ECMO) to support sheep which have received lethal pulmonary smoke damage. The animals (n = 19) received inhalation injury induced by insufflation with smoke derived from burning cotton delivered with a bee smoker. The treatment group, those placed on ECMO at the time of injury (n=6), were systemically heparinized and placed on a venovenous perfusion circuit consisting of a roller pump, membrane oxygenator and heat exchanger. Blood flow rate in the circuit approximated 20-25 per cent of cardiac output. The animals remained on partial venovenous bypass until the termination of the experiment 96 h after injury. All animals in the treatment group survived. The control sheep (n = 7) received inhalation injury alone and had a 100 per cent mortality (P = 0.0015 ECMO vs. control). Ventilatory management of treatment and control groups followed an identical protocol. We have also studied a third group (n = 6) composed of animals receiving inhalation injury with systemic heparinization but not ECMO. This group had a 66 per cent mortality at 96 h. These studies suggest that partial venovenous ECMO may be a valuable form of adjunctive treatment in severe inhalation injury.

Animals↗