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Biomedical subjects

D H Teitelbaum

Publications and source records attributed to D H Teitelbaum.

67 records · Page 4Linked to original sources

Small-bowel transplantation permits survival in rats with lethal short-gut syndrome.

The functional integrity of transplanted bowel would most convincingly be demonstrated if transplantation after an otherwise lethal intestinal resection permitted survival and growth. In this experiment, we proposed to define the extent of bowel resection necessary for lethality and to show that transplantation allows salvage of these animals. Adult Brown-Norway rats (250 g) underwent extensive small-bowel resection (SBR) (ligament of Treitz to ileocecal valve) (n = 5), cecectomy only (CEC) (n = 3), SBR plus CEC (n = 6), or SBR plus CEC and syngeneic transplantation of 25 cm of jejunum (n = 6). All animals with SBR or CEC alone survived and grew; all animals with SBR plus CEC died within 2 weeks (mean, 6.4 days); and 6 of 6 animals with SBR plus CEC and transplant survived and grew. The difference in survival between the lethally resected rats and those with an intestinal transplant was highly significant (P less than 0.01). Dietary intake was similar in all groups. We conclude that in the rat, extensive small-bowel resection alone is not sufficient to be lethal; most of the small bowel and the cecum must be resected to obtain a lethal model. We have also shown that transplantation of small bowel into rats with an otherwise lethal extent of bowel resection will allow the animals to survive and grow. These results suggest the need for caution in correlating survival after intestinal transplantation in the rat with transplant function, since the preservation of too much native gut might permit survival even if the transplant has no nutritional function.

Animals↗

Leakage of intraluminal low molecular weight polyethylene glycol as a marker of small bowel transplant rejection.

To facilitate early detection of small bowel allograft rejection, we correlated transluminal leakage of low molecular weight polyethylene glycol (PEG) with the development of allograft rejection. Vascularized allogeneic and syngeneic jejunal transplants were performed in rats, without immunosuppression. A control group underwent creation of jejunal Thiry-Vella fistulas of similar length. Jejunal segments were perfused with a physiologic solution containing [3H]-PEG-900. At the end of an equilibrium period, an urinary bladder aspirate was collected and [3H]-PEG-900 measured by scintillation counting. Results are expressed as disintegrations per minute per 100 microL urine. Histologic examinations were performed at all experimental time points. Two days following transplantation, urinary PEG levels were elevated in both allogeneic and syngeneic groups (3943 +/- 935 and 4007 +/- 1164, respectively). Four days after the transplant, syngeneic urine PEG levels decreased to 581 +/- 159, and were not significantly different (P greater than .05) from Thiry-Vella controls (635 +/- 145). Syngeneic levels remained at this low level for the rest of the experiment. The allogeneic group continued to show significantly higher levels (P less than .05) compared with syngeneic and Thiry-Vella groups from day 4 until the end of the experiment. These elevated levels most likely represented the development of rejection, preceding the first significant histologic signs of rejection, which were found at six days post-transplant. Detection of transluminal leakage of low molecular weight PEG may be a useful adjunct in monitoring for small bowel transplant rejection.

Animals↗

The pathophysiology of Hirschsprung's-associated enterocolitis: importance of histologic correlates.

To more clearly define the pathophysiology of Hirschsprung's-associated enterocolitis (HAEC), this study comprehensively evaluates the gastrointestinal tissue of a group of infants with clinical HAEC. A pathologic grading system that demonstrates a progressive sequence of histologic changes specific for HAEC is established. The grading system correlates closely with clinical enterocolitis and may prove to be a useful method for early detection of infants at risk for the development of clinical HAEC. A significant alteration of intestinal mucins with an increase in neutral mucins and a decrease in acidic-sulfomucins was identified in HAEC tissue specimens. Enterocyte-adherent organisms were present in 39% of HAEC tissue specimens. The pathogenesis of HAEC may result from an alteration in intestinal mucins that may allow for the subsequent adherence of enteropathogenic organisms to enterocytes. The enterocyte-adherent organisms have the potential to induce an enterocolitic process and may contribute to both the intestinal and systemic manifestations of HAEC.

Enterocolitis↗

The piebald-lethal murine strain: investigation of the cause of early death.

Forty-eight piebald-lethal (PL) mice with distal aganglionosis and 42 normal littermates (LM) were studied to determine the cause of early death. PL mice were noted to be smaller than their LM and to have normal albumin and immunoglobulin levels for the first 30 days of age. As PL mice aged, a significant decline in albumin with a concomitant rise in immunoglobulin levels was demonstratable. Systemic sepsis with enteric organisms was found in 10% of sacrificed PL mice and in 38% of spontaneously dying PL animals. Histologic examination of PL aganglionic and ganglionic colon demonstrated no evidence of enterocolitis. Ganglionic colon of PL mice contained a flattened, thinned mucosa. The early death of PL mice is related to generalized debilitation from prolonged distal colonic obstruction resulting in a decrease in immunologic integrity and an increased susceptibility to sepsis.

Aging↗

Alteration in gastrointestinal peptide tissue levels in rejecting small bowel transplants.

Gastrointestinal (GI) peptide tissue levels were measured following intestinal transplantation in rats and evaluated as a possible early marker of transplant rejection. Vascularized syngeneic and allogeneic jejunal transplants were performed in rats without immunosuppressive therapy. Serial tissue samples of transplanted intestine were obtained from each group of animals. Baseline levels of peptides were determined in nontransplanted jejunum of the same animals. Results were correlated with histology at all experimental time points. Tissue levels of gut peptides (somatostatin, vasoactive intestinal peptide and substance P) were determined by two methods--immunoperoxidase staining and radioimmunoassay. Normal levels of gut peptides in syngeneic bowel were maintained up to 1 year after transplantation. Allogeneic bowel showed a progressive decline in gut peptide concentrations simultaneously with (or preceding) histologic evidence of rejection. The monitoring of GI peptide tissue levels may prove to be a useful method of detecting small bowel transplant rejection.

Animals↗

Hirschsprung's disease. Identification of risk factors for enterocolitis.

From 1975 to 1985, 80 infants and children were treated at a major pediatric hospital for Hirschsprung's disease, 19 (24%) of whom developed enterocolitis. In 9 neonates (18%) and 4 infants (29%) enterocolitis was present at diagnosis of Hirschsprung's disease, while 4 children acquired enterocolitis following a pull-through procedure. Significant risk factors for development of Hirschsprung's-associated enterocolitis (HAEC) were delay in diagnosis beyond 1 week of age and the presence of trisomy 21. HAEC did not occur more frequently in patients with long-segment aganglionosis, nor did an initial episode of HAEC confer a higher risk of recurrent enterocolitis. HAEC following a pull-through procedure was correlated with an anorectal stricture in three of four cases. Although neonates with HAEC had a low mortality rate (5%), their morbidity rate was 30% and their hospitalization was twice as long as neonates without enterocolitis.

Age Factors↗

Single plus double lumen intra-atrial [corrected] venous access in bone marrow transplant recipients.

BMT recipients require large volumes of fluids, drugs and PN. To reduce manipulation of central catheters and the risk of PN line sepsis, both single and double lumen intra-atrial [corrected] catheters were placed in ten BMT recipients through the internal jugular (double lumen) and cephalic or external jugular (single lumen) vein. Patients were observed for two to seven months. Two partially clotted catheters were cleared with intraluminal urokinase. Skin breakdown at two exit sites responded to local care. The nursing staff and patient tolerated the procedure well. During BMT, fluid administration of 4,900 +/- 150 milliliters a day was possible without interruption of PN. Line or catheter site infections did not occur. Use of three intra-atrial [corrected] lumens eased the care of BMT patients and eliminated PN interruption. Decreased line manipulation may also have led to fewer catheter related infections.

Bone Marrow Transplantation↗

Fibrolamellar carcinoma of the liver. Review of three cases and the presentation of a characteristic set of tumor markers defining this tumor.

This study demonstrates the unique clinical and histologic aspects of fibrolamellar hepatic carcinoma, a rare variant of hepatocellular carcinoma. Three cases are reviewed and an extensive study of immunologic and intracellular substances defining this tumor is presented. Length of survival was considerably longer than typical hepatoma. The cause of death generally is due to a lack of control of the primary tumor. Successful treatment appears to relate to the ability to perform a total excision of the primary hepatic tumor. Chemotherapy should be used only in the presence of metastatic disease. Surgical resection of metastatic disease, unlike the usual hepatocarcinoma, may have some beneficial use. Fibrinogen was found in all tumors. It is possible that this tumor produces fibrinogen to create its unique histologic appearance. Carcinoembryonic antigen is described for the first time in this tumor. Both deposits of alpha-1 antitrypsin and copper were found in most of the tissues studied. The presence and amounts of these substances differ markedly from the common type of hepatoma. This unique composition of intracellular components may both facilitate histologic diagnosis, particularly if the amount of tissue is limited, and give further insight into the etiology of this tumor.

Adolescent↗

Somatostatin modulation of peptide-induced acetylcholine release in guinea pig ileum.

The peptides caerulein, neurotensin, somatostatin, and substance P modulate the activity of intestinal neurons and alter gut motility. We examined the effects of these peptides on acetylcholine release from the myenteric plexus and intestinal contractility in vitro. Caerulein (1 X 10(-9) M), neurotensin (1.5 X 10(-6) M), and substance P (1 X 10(-7) M) significantly enhanced the release of [3H]acetylcholine from the myenteric plexus of the guinea pig ileum. This effect was inhibited by tetrodotoxin (1.6 X 10(-6) M). Somatostatin (10(-6) M) inhibited caerulein- and neurotensin-evoked release of acetylcholine but did not inhibit release induced by substance P. Caerulein, neurotensin, and substance P caused contraction of the guinea pig ileal longitudinal muscle. Somatostatin inhibited the contractions induced by caerulein and neurotensin. In contrast, substance P-induced contraction was not inhibited significantly by somatostatin. Thus, in the guinea pig ileum, caerulein-, neurotensin-, and substance P-induced contractility is due, at least in part, to acetylcholine release from the myenteric plexus. The ability of somatostatin to inhibit peptide-induced contractility is selective, and its mechanism may be attributed to inhibition of acetylcholine release.

Acetylcholine↗

Effects of caerulein on rat small and large intestinal fluid transport in vivo.

We have examined the effect of caerulein on intestinal fluid transport in vivo. Rat jejunal, ileal, and colonic segments were perfused with a physiologic buffer for a 60-min control period, followed by a 60-min period after caerulein, prostaglandin E2 (PGE2), or saline (0.9%, w/v) were given by intramuscular (i.m) injection. At a dose of 5 micrograms/kg caerulein had no effect on ileal fluid transport. Lower doses of caerulein (300 ng and 1 microgram/kg) also had no effect. PGE2 significantly (P less than 0.05) inhibited net ileal absorption by 94 +/- 24% from pre-dose levels. Caerulein (300 ng/kg) had no effect (P greater than 0.05) on jejunal or colonic fluid transport. Intestinal fluid accumulation assessed by the 'enteropooling' assay did not increase after 30 ng or 1 microgram/kg of caerulein, whereas in animals given PGE2 of (5 mg/kg) the fluid accumulation more than doubled (P less than 0.001): control 1.59 +/- 0.15 ml; cerulein (1 microgram/kg) 1.36 +/- 0.20 ml; and PGE2 4.7 +/- 0.50 ml. Serum levels of caerulein (after a 1 microgram/kg dose), measured by radioimmunoassay, were elevated up to 30 min after i.m. injection. The data indicate that caerulein has no direct effect on rat small or large intestinal fluid transport.

Animals↗

Inguinal herniorrhaphy in young infants: perianesthetic complications and associated preanesthetic risk factors.

STUDY OBJECTIVES: (1) To prospectively observe and tabulate all perianesthetic complications in young infants undergoing herniorrhaphy with general anesthesia and (2) to identify all major postnatal complications and determine which, if any, might be significant risk factors for perianesthetic complications. DESIGN: Prospective case control study. SETTING: Columbus, Ohio, Children's Hospital, a teaching and tertiary referral center. PATIENTS: One hundred two consecutive infants 60 weeks postconceptual age (PCA) or younger undergoing herniorrhaphy with general anesthesia. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: All perianesthetic complications occurring during anesthesia, in the postanesthesia care unit (PACU), during the remaining hospital stay, and within 30 days of anesthesia were recorded, and a detailed postnatal history was compiled. Fifty-five percent of 60 preterm infants [37 weeks gestational age (GA) or younger] and 50% of 42 term infants (older than 37 weeks GA) experienced at least one perianesthetic complication. Following discharge from the PACU, in-house complications were confined to the preterm group. Significant risk factors included a history of apnea, bradycardia, and ventilatory support for at least 24 hours after birth, mainly for respiratory distress syndrome. CONCLUSIONS: In a teaching hospital, prospectively observed perianesthetic complications can occur in more than 50% of infants 60 weeks PCA or younger undergoing herniorrhaphy with inhalation anesthesia. Infants younger than 49 weeks PCA with a significant preanesthetic risk factor should be monitored overnight for apnea and bradycardia.

Anesthesia, General↗

Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis.

BACKGROUND: Neonates are at high risk for the development of parenteral nutrition-associated cholestasis when receiving a prolonged course of total parenteral nutrition (TPN). Although this cholestasis is of unknown etiology, it may result from a lack of gastrointestinal hormone formation, including cholecystokinin, which normally occurs after enteral feedings. METHODS: Two groups of neonates were studied. The treatment group consisted of 21 consecutive, prospectively enlisted neonates receiving TPN for > 14 days. The nontreatment group consisted of 21 infants from the 2 years preceding the study who were matched to the treatment group by gestational age, diagnosis, and duration of TPN. The major outcome determinant was direct bilirubin. Cholestasis was defined as a direct bilirubin > 2.0 mg/dL and was considered severe if the direct bilirubin was > 5.0 mg/dL after other causes were ruled out. RESULTS: The mean direct bilirubin levels in the nontreated group progressively rose over time, whereas the mean direct bilirubin the treated group remained level. The incidence of infants with a direct bilirubin > 2.0 mg/dL was 24% and 43% in the CCK+ and CCK- groups, respectively, and was not significant (p = .14). The percentage of infants with a direct bilirubin > 5.0 mg/dL was 9.5% and 38% in the treatment and nontreatment groups, respectively, and was significant, p = .015. CONCLUSIONS: Levels of direct bilirubin were lower in the treated compared with the nontreated group. These findings suggest that cholecystokinin prophylaxis in high-risk neonates may help prevent the development of parenteral nutrition-associated cholestasis.

Bilirubin↗