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Biomedical subjects

M M Ziegler

Publications and source records attributed to M M Ziegler.

At least 91 records · Page 5Linked to original sources
PubMed1985

Early diagnosis of experimental necrotizing enterocolitis using proton nuclear magnetic resonance.

The purpose of this study was (1) to confirm an experimental model of aminophylline-induced necrotizing enterocolitis (NEC); and (2) to determine whether nuclear magnetic resonance (NMR) imaging, based upon proton relaxation values (T1, T2), could detect NEC during its early pathogenesis. Sixty male weanling Lewis rats (avg wt = 75 g) were randomly assigned to one of three experimental groups: (A) superior mesenteric artery (SMA) occlusion (1 min) + aminophylline treatment (40 mg/kg); (B) SMA occlusion; and (C) sham midline laparotomy (control). All surviving animals were sacrificed at 48 hr postoperation and a specimen of ileum was removed for light microscopy (LM), electron microscopy (EM), and NMR analysis. Percentage water content was determined for representative specimens. Mortality occurred only in experimental group A animals (18.2%; P less than 0.05), who had received aminophylline. Microscopy of ileum from sacrificed animals of this group showed changes ranging from mild cellular disruption to severe hemorrhagic necrosis. Early ultrastructural changes consistent with NEC were detectable with EM before LM. Proton relaxation results obtained with NMR showed significant prolongation of T1 (252.5 +/- 4.4 msecs; P less than 0.001) and T2 (69.3 +/- 1.4 msecs; P less than 0.025) during the first stages of NEC. NMR may indeed enable early, safe diagnostic imaging of NEC in infants receiving aminophylline, or those who are otherwise at increased risk for development of this disease.

Aminophylline↗
PubMed1985

Intestinal ischemia: reduction of mortality utilizing intraluminal perfluorochemical.

This study reports an assessment of a method of intestinal protection by the intraluminal administration of an oxygenated perfluorochemical, perfluorotributylamine, or gaseous oxygen in an attempt to provide oxygen for mucosal cells rendered ischemia. A model of acute arterial or acute arteriovenous ischemia was produced in adult female rats. All control ischemic animals died within 12 hours. To assess intestinal protection, the mortality rates in the experimental groups were compared with the 100 percent control mortality. Gaseous oxygen and oxygenated perfluorochemical administered intraluminally reduced mortality significantly in the acute arterial model but not in rats with arteriovenous occlusion. Electron microscopy demonstrated preservation of villi after 1 and 2 hours of occlusion in the oxygen-treated groups. Light microscopy revealed massive destruction in control animals with preserved architecture in both the gaseous oxygen and oxygenated perfluorochemical groups. These results demonstrate that the intraluminal delivery of oxygen to bowel rendered ischemic by arterial occlusion may significantly decrease anatomic bowel disruption and improve animal survival. Such techniques have a potential clinical application to facilitate salvage of ischemic intestine and to augment intestinal preservation.

Animals↗
PubMed1985

Resolution of intractable cholestasis associated with total parenteral nutrition following biliary irrigation.

Although the protracted use of total parenteral nutrition (TPN) in infants is known to predispose to cholestasis, which in certain instances may not be reversible, failure to understand the pathogenesis of this condition has hindered the development of an effective medical treatment. That surgical treatment may reverse this process in selected patients is the subject of the present report. Two premature infants and one term infant, with short bowel syndrome acquired in infancy, developed conjugated hyperbilirubinemia following institution of balanced TPN. Infectious and metabolic etiologies for the jaundice were ruled out. No excretion of 99mTc-labeled DISIDA from the biliary tree was demonstrable 24 hours following injection by nuclear scintigraphy, despite the absence of extrahepatic biliary obstruction by abdominal sonography. When all conventional medical methods of managing the problem failed, exploration was performed. Intraoperative cholangiography showed normal intrahepatic and extrahepatic biliary ducts in each instance. Irrigation of the biliary tree with normal saline solution was then performed. In all cases, liver biopsies were obtained that were consistent with TPN-associated cholestasis and in all cases, jaundice resolved promptly following operation. We conclude that intractable cholestasis associated with TPN, regardless of its etiology, is a functional abnormality of biliary excretion that may respond in selected patients to irrigation of the biliary tree with radiographic dye and/or normal saline solution.

Biliary Tract↗
PubMed1985

Management of esophageal atresia and tracheoesophageal fistula in the neonate with severe respiratory distress syndrome.

In a 10-year period, 22 neonates with esophageal atresia (EA) and tracheoesophageal fistula (TEF) required high pressure ventilatory support soon after birth because of respiratory distress syndrome (RDS). Eleven of the 22 or 50% survived overall, but if the 5 patients who died before definitive surgical repair could be attempted are excluded, 11 of 17 or 65% survived. More importantly, 4 of 7 (57%) patients who had gastrostomy performed first survived while 7 of 10 (70%) who had fistula ligation performed first survived. The difficulties with intraoperative management of those who had gastrostomy performed first were even more impressive. Our experience leads us to conclude that patients with EA and TEF with severe RDS who require high pressure ventilation preoperatively represent a group of patients who require special consideration. The danger to such patients with increased pulmonary resistance is not gastric distention but sudden loss of intragastric pressure. In the presence of poor lung compliance, the upper gastrointestinal tract functions in continuity with the tracheobronchial tree. A sudden loss of intragastric pressure, as with placement of a gastrostomy tube, results in an acute loss of effective ventilating pressure. Resuscitation of such a patient is not possible until leakage from the esophagus is controlled by ligation of the fistula or transabdominal occlusion of the distal esophagus. Placement of a Fogarty catheter into the fistula via a bronchoscope is effective but may not be feasible in every case. Early thoracotomy and ligation of the fistula in patients with progressive RDS provides immediate improvement in ventilatory efficiency and relief of gastric distention.

Airway Resistance↗
PubMed1985

Rational selection of adjuvant chemotherapy after cytoreduction surgery for murine neuroblastoma.

Improving the prognosis of advanced neuroblastoma remains an important yet unachieved goal of pediatric oncology, a fact which may be related to an insufficient analysis of the role played by cytoreductive surgery. Utilizing strain A mice bearing C-1300 syngeneic neuroblastoma, tumor biology and host immunocompetence were studied after cytoreduction surgery and adjuvant chemotherapy. Cell kinetic analysis in the residual tumor demonstrated an increase of the proliferative fraction 18 to 42 h after operation, but the same peak proliferation was delayed in bone marrow cells to 24 to 96 h. The potential for drug distribution to the tumor after cytoreduction surgery was assessed by injecting Na251CrO4 and measuring tumor uptake. There were two significant (P less than 0.05) peaks of activity at 6 h and 3 days, suggesting local edema and neovascularity, respectively. Injection of both cell cycle specific and nonspecific adjuvant chemotherapeutic agents in a dosage of one-fourth of their 50% lethal dose at 24 or 72 h following surgical cytoreduction did not induce any antitumor activity at either injection time. However, when cyclophosphamide was given in this dose, the C-1300 tumor growth was impaired, an effect which was largely abrogated by first subjecting the tumor bearer to thymectomy and irradiation. The transfer of spleen cells from adjuvant cyclophosphamide-treated mice to tumor-inoculated normal mice significantly delayed tumor appearance when comparison was made with animals treated by operation alone, and such recipients also exhibited a more prolonged survival. These data suggest that the antitumor activity of cyclophosphamide following cytoreduction surgery of C-1300 neuroblastoma is mediated by both pharmacological and immunological mechanisms.

Animals↗
PubMed1984

Cloning of the luciferase structural genes from Vibrio harveyi and expression of bioluminescence in Escherichia coli.

The DNA encoding the luciferase alpha and beta subunits in the luminous marine bacterium Vibrio harveyi (strain 392) is contained within a 4.0-kilobase HindIII fragment. DNA from V. harveyi was digested with HindIII, and the resulting fragments were inserted into the HindIII site of plasmid pBR322. The recombinant plasmids were introduced by transformation into Escherichia coli RR1. The colonies were supplied with n-decanal, the substrate for the bioluminescence reaction, and 12 colonies (of ca. 6000 total) were observed to luminesce brightly. One of the recombinant plasmids, pTB7, has been studied in detail. The high level of expression of bioluminescence in pTB7 was the result not of native V. harveyi promoters but rather of a promoter in pBR322 which is within the tetracycline resistance gene but oriented in the direction opposite to the transcription of the tetracycline gene. Using antiluciferase antibody to probe proteins transferred from sodium dodecyl sulfate-polyacrylamide gels to nitro-cellulose paper, we have shown that the E. coli transformants produce luciferase that cross-reacts with antiluciferase antibody and is the same molecular weight as V. harveyi luciferase. No alpha subunit could be detected by using antiluciferase antibody in lysates of a subclone, pTB104, which is identical with pTB7 except for deletion of the beta-subunit gene. Thus, the alpha subunit may be unstable and be degraded unless it is associated with beta. The bioluminescence emission spectra of V. harveyi and of E. coli transformants carrying pTB7 are indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1984

Taurine deficiency in the severe hepatic dysfunction complicating total parenteral nutrition.

The etiology of the severe hepatic dysfunction associated with total parenteral nutrition (TPN) remains unknown, but recent studies suggest that taurine deficiency may be associated with the development of cholestasis in experimental animals. That taurine deficiency might also play a role in the development of the severe hepatic dysfunction in human infants receiving TPN as their sole nutritional intake is the subject of the present report. Serial plasma aminograms were obtained from three children with severe hepatic dysfunction associated with TPN, in whom progressive disease led to death after 20, 13, and 14 months. All three children underwent massive intestinal resection for necrotizing enterocolitis, leaving 30, 44, and 17 cm of viable small bowel, respectively. Balanced TPN was given as 20 to 25 g/kg/d dextrose, 1.5 to 2.5 g/kg/d crystalline amino acids, and 2 to 3 g/kg/d fat emulsion; enteral feedings were attempted but were poorly tolerated. Mild cholestasis progressed to severe hepatic dysfunction manifested by hyperbilirubinemia, increased serum transaminases, hypoproteinemia, and abnormal coagulation profiles. Liver histology revealed extensive fibrosis, fatty replacement, and coarse cholestasis, necrosis not being prominent. Serial plasma aminograms revealed markedly elevated plasma levels of methionine (1353, 1168, and 113 nm/mL), low levels of 1/2 cystine (68.4, trace, and 17 nm/dL), and undetectable levels of taurine; plasma levels of branched-chain amino acids were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1984

Morbidity and mortality of short-bowel syndrome acquired in infancy: an update.

The advent of total parenteral nutrition (TPN) has made survival beyond infancy possible for large numbers of patients who have sustained massive small intestinal loss due to a variety of intraabdominal catastrophes. However, the quantity and quality of life have been limited by the development of late sequelae due both to the protracted use of TPN and the long-term complications of foreshortening of the gut. To determine to what extent the morbidity and mortality of short-bowel syndrome (SBS) may have improved over the last 10 years, we reviewed our experience since 1973 with patients losing more than 50% of total small intestinal mass in infancy. The etiologies of SBS in the 16 study patients were necrotizing enterocolitis (6), midgut volvulus (5), multiple atresias (3), gastroschisis (1), and congenital SBS (1). Overall survival was 81%; total small intestinal length (SIL) at the time of diagnosis was 44.2 +/- 7.9 cm in survivors and 30.3 +/- 7.8 cm in nonsurvivors, probability values not significant. Although no patient survived without an ileocecal valve whose total SIL was greater than 20 cm, the three deaths in this series were not related directly to the SIL, but to end-stage liver disease resulting from TPN-associated cholestasis. Among the survivors, adaptation to enteral feedings required 13.8 +/- 2.5 mo, during which time weaning from TPN occurred; weight at adaptation was 6.87 +/- 1.32 kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1984

Immunodepression secondary to malnutrition: assay by lymphocyte subset analysis using monoclonal antibodies and the cell sorter.

It has been well documented that the hospitalized child frequently is malnourished, and the considerably greater morbidity and mortality of such children, in large part, is due to the associated secondary immunodepression. To assess the mechanism of such immunodepression in acute and chronically malnourished subjects, we chose an experimental murine model of malnutrition. Immune function was assayed by lymphocyte subset population and mixed lymphocyte culture (MLC) assessment, determining whether an alteration of the T helper (TH) to T suppressor-cytotoxic (TS-C) lymphocyte ratio is the mechanism that produces immunoincompetence in malnutrition. Ten-week-old A/J mice were rendered acutely or chronically malnourished by graded protein restriction using a 2.5% protein diet. These animals were studied before and after protein depletion with the fluorescent activated cell sorter (FACS) and the MLC. FACS cell populations were defined by the monoclonal antibodies to THY 1.2, LYT 1 (TH), and LYT 2 (TS-C) antigens. MLC reactivity was assessed with A/J v C 57 BL/6 mouse lymphocytes and expressed as a stimulation index (S.I.). Results are expressed in Table 1, and suggest that these malnourished animals were significantly immunodepressed as measured in the MLC reaction. However, the mechanism of this depression is not mediated by an inversion of the TH/TS-C ratio. These data contrast with those previously reported for the immunodepression of the burned or traumatized patient in which the TH/TS-C ratios are reversed; these data suggest that a different, as yet to be elucidated, mechanism exists for the immunodepression of malnutrition.

Animals↗
PubMed1983

A case of microgastria in association with splenic-gonadal fusion.

Microgastria is a rare congenital anomaly usually associated with asplenia. In this 2 1/2-year-old presenting with left hydrocele and inguinal hernia multiple accessory spleens were found in the inguinal-scrotal region compatible with splenic-gonadal fusion. 99mTc-sulfur colloid scanning is helpful in microgastria searching for the presence of splenic tissue and in splenic-gonadal fusion for the location of accessory heterotopic spleens.

Abnormalities, Multiple↗
PubMed1983

Situs inversus: the complex inducing neonatal intestinal obstruction.

Situs inversus (SI) complicating neonatal bowel obstruction presents a challenging complex, and to facilitate rational decision making for treatment, we have reviewed 23 cases of abdominal SI seen in our hospital over the last 25 years. Preoperative roentgenographic studies most always predicted SI, the specific patient groups including: 12 abdominal SI with dextrocardia, 10 abdominal SI with levocardia, and 1 with partial heterotaxia. Major intraabdominal anomalies produced surgical emergencies in 7 neonates in the first year, 6 of these 7 being in the first month of life. In these 7 patients, multiple anomalies occurred including 1 child with a rotational anomaly with reversible ischemia secondary to midgut volvulus, and 4 with a rotational anomaly without volvulus, all being treated with a modified Ladd procedure. One of these children had an unrecognized intraluminal duodenal membrane, 1 an operatively diagnosed intraluminal membrane, 1 had annular pancreas, and 1 had a discontinuous jejunal atresia. A preduodenal portal vein was present in 4 of the 7 children, a branch being divided in 1 and the full vein bypassed in 2 of the other 3 patients. Two patients had biliary atresia, one of whom also had a diaphragmatic hernia. Five of the 7 neonates had associated major congenial heart disease accounting for 2 of the 3 deaths in this series. This review emphasizes the protean nature of abdominal SI, especially as it may cause or contribute to neonatal intestinal obstruction; and it is this understanding which is a prerequisite to optimal operative management.

Child↗
PubMed1983

Rectosigmoid perforation and intestinal evisceration from transanal suction.

Transanal suction injuries were sustained in 1981 by five children when they sat upon uncovered swimming area drain sites. Tears of the rectosigmoid areas occurred in each with associated evisceration and loss of substantial amounts of small intestine because of mesenteric separation. These cases are reviewed.

Child, Preschool↗
PubMed1983

Influence of primary tumor site on lymphocyte antitumor activity.

Clinical Stage IV-S neuroblastoma involving a primary, the liver, bone marrow, and/or skin has a favorable prognosis despite a considerable tumor burden. In a pilot experiment utilizing mouse C 1300 neuroblastoma, we demonstrated that animals receiving tumor to IV-S sites had a prolonged survival. To analyze the role which liver modulation of tumor might play in an immunologically mediated host-antitumor response, we applied an in vitro lymphocyte blastogenesis assay. Host-tumor response as reflected by blastogenesis and as quantified by tritiated thymidine incorporation into DNA demonstrated that normal lymphocytes were stimulated to a greater degree by subcutaneous site tumor than by tumor from the liver (260.7 +/- 71.9 vs. -54.2 +/- 194.3 CPM, p less than 0.05). Sensitized lymphocytes harvested from liver tumor bearers demonstrated a greater response when admixed with subcutaneous tumor in vitro (771.9 +/- 300.4 vs. 45.9 +/- 277.5 CPM, p less than 0.05) and sensitized lymphocytes harvested from subcutaneous tumor bearing animals also demonstrated more in vitro blastogenesis to subcutaneous tumor (577.9 +/- 200.2 vs. 98.9 +/- 154.1 CPM, p less than 0.05). However, host lymphocytes were themselves comparably reactive whether they were harvested from liver tumor or subcutaneous tumor donors (771.9 +/- 300.4 vs. 577.9 +/- 200.2, p = NS). These data suggest that lymphocytes in contact with murine liver neuroblastoma respond less well than when in contact with subcutaneous site tumor, a form of afferent blockade which may account for the propensity of the liver to serve as a site for metastatic disease.

Animals↗