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Biomedical subjects

T M Krummel

Publications and source records attributed to T M Krummel.

At least 91 records · Page 5Linked to original sources
PubMed1988

Multifocal ganglioneuroblastoma coexistent with total colonic aganglionosis.

Neuroblastoma and Hirschsprung's disease are considered aberrations of neural crest cell growth, migration, or differentiation. Their coexistence, however, is rare. We present the case of an only child with total colon Hirschsprung's disease diagnosed shortly after birth, who was found to have noncontiguous ganglioneuroblastomas without metastases at age 16 months. The spectrum of neural crest anomalies, long segment Hirschsprung's disease and multifocal neuroblastoma, in this child is unique and previously unreported.

Adrenal Gland Neoplasms↗
PubMed1988

Transforming growth factor beta (TGF-beta) induces fibrosis in a fetal wound model.

The adult cellular response to tissue injury is characterized by acute inflammation followed eventually by fibroblast proliferation and collagen synthesis. Fetal tissue responses to injury differ markedly from those of the adult; an early acute inflammatory response is absent, few fibroblasts participate, and no collagen is deposited. The object of the present study was to analyze the effects of transforming growth factor beta (TGF-beta), an important regulatory molecule in adult healing events, on the fetal tissue response following wounding. Fetal cellular and extracellular matrix responses to injury were evaluated by placing subcutaneous wound implants containing TGF-beta (0.01 to 10 ng) in fetal rabbits at 24 days gestation (term = 31 days). Histologic responses one to seven days later were compared with fetal and adult control implants without TGF-beta. The histology of the adult implant was characterized by an early acute inflammatory response: by day 7 fibroblasts and collagen were predominant. In contrast, control implants removed from fetal rabbits had no histologic evidence of acute inflammation or fibroblast penetration and no collagen was deposited. When implants containing 1.0 ng TGF-beta were removed from fetal rabbits at seven days, a grossly fibrotic reaction was observed: histology confirmed marked fibroblast penetration with collagen deposition. Fetal implants containing 0.01 ng or 10 ng TGF-beta showed few fibroblasts but had increased numbers of inflammatory cells compared with controls. These observations demonstrate that the fetal response becomes adultlike with fibroblast proliferation and collagen accumulation when TGF-beta is added, thus documenting the responsiveness of the fetal system to adult repair signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

Fetal response to injury in the rabbit.

Fetal, neonatal, and adult tissue response to a standardized injury was studied using subcutaneous wound implants, linear incisions, and punch wounds in New Zealand white rabbits. In the fetus, sutured incisions healed by primary intention without antecedent inflammation. However, neither contraction nor healing by secondary intention was seen in punch or unsutured wounds. Healing both by primary and secondary intention following inflammatory infiltration was observed uniformly in neonatal and adult rabbits. Wound implants were extensively infiltrated with collagen in the adults studied; however, no collagen was seen in fetal implants and collagen hydroxyproline content could not even be detected by high performance liquid chromatography techniques; rather, a matrix rich in hyaluronic acid was found. The fetal tissue response to injury differs from the adult, proceeding in the absence of a classical inflammatory stimulus and lacking contractile capabilities. The deposition of extracellular matrix rich in hyaluronic acid but devoid of collagen suggests that the fetal response to injury may be a process more closely resembling regeneration or growth rather than repair by scar deposition.

Animals↗
PubMed1987

Auxiliary transplantation of the fetal liver. II. Functional evaluation of an intraabdominal model.

To evaluate the use of the fetal liver as an auxiliary graft, we have developed a model of intraabdominal heterotopic transplantation of late gestational fetal lamb livers into weanling lambs. Thirty-eight transplants have been performed of which 31 were technically successful. Twenty-three grafts functioned for intervals of 5 to 22 days after transplantation. Grafts were functionally evaluated by analysis of total bile acid and bilirubin excretion. To determine whether host liver excretory function would influence function of the graft, common bile duct ligated recipients were compared with recipients with normal host liver function. We found that (1) intraabdominal auxiliary transplantation of the fetal lamb liver is technically feasible; (2) the fetal liver graft is capable of rapid adaptation and can assume a significant portion of host excretory function; and (3) excretory function of the fetal liver is proportional to the functional demands of the host. Auxiliary transplantation of the fetal liver is a promising alternative to current methods of liver transplantation.

Abdomen↗
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

Ileoproctostomy with J-pouch: use of the Swenson pull-through for reconstruction after proctocolectomy for ulcerative colitis.

Continence can be preserved by several operations following proctocolectomy for ulcerative colitis. The Swenson procedure, used for congenital megacolon, may be applied for reconstruction following proctocolectomy for other colonic disease. Rectal eversion and resection to the dentate line obviates the need for mucosectomy and permits ileoanal anastomosis with excellent exposure. Two girls, 9 and 11 years of age, underwent proctocolectomy, formation of an ileal J-pouch, and a Swenson pull-through with ileoanal anastomosis. One year following closure of diverting ileostomies, both children have 2 to 3 continent bowel movements daily with very rare nocturnal soiling. Anal manometry is normal. The application of this method for ileoanal anastomosis may broaden the choice of operations for selected children requiring proctocolectomy.

Child↗
PubMed1985

The postoperative response of the term and preterm newborn infant to sodium administration.

Twenty surgical newborn infants aged less than 5 days were selected for study to determine the quantity of sodium administered during operation and the subsequent 48 hours, and to determine their response to this sodium load. There were 6 preterm infants with gestational age 35 weeks or less and 14 full-term infants aged more than 35 weeks. Measurements calculated at 12 hourly intervals for 48 hours after operation included sodium intake, sodium excretion, fractional excretion of sodium, and serum sodium. No special guidelines were utilized for fluid management. The mean sodium intake during the 48-hour study period for the term infants was 15.7 mEq/kg, of which 46% was given during the first 12 hours, and for the premature infants was 17.1 mEq/kg, of which 56% was given during the first 12 hours. In the two groups of patients, the amount of sodium given during the first 12 hours was 470% and 480% of their estimated maintenance requirements, respectively. The mean sodium output during the first 12 hours was low in the term group (1.2 mEq/L) and the premature group (1.3 mEq/L), and subsequently increased reaching maximum levels of 2.3 and 2.1 mEq/L, respectively, by 36 hours. The fractional excretion of sodium exceeded 1.0% in 53% of the term and 94% of the preterm infants. During the study period, the mean serum sodium levels exceeded 145 mEq/L (hypernatremia) in 64% of the term and 67% of the preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluid Therapy↗
PubMed1984

The early evaluation of survivors after extracorporeal membrane oxygenation for neonatal pulmonary failure.

Excluding mortality data, there is little information regarding patients' development after extra corporeal membrane oxygenation (ECMO). In six of nine neonates surviving ECMO for predictably fatal pulmonary failure, examination 15 to 21 months afterward showed (1) physical growth and development, normal in six; (2) chest x-ray, normal pulmonary parenchyma; (3) average arterial blood gases, PO2 80, Pco2 35, pH 7.35; (4) echocardiogram, normal, without evidence of pulmonary hypertension; (5) cerebrovascular dopplers, normal ophthalmic artery flow in five patients, retrograde in one; (6) CT scan, EEG, neurologic survey, normal in five, cerebral atrophy in one patient who had an air embolus during decannulation; (7) psychologic examination, normal in all. This early evaluation of ECMO survivors should encourage its further application in those newborns who would otherwise die.

Child Development↗
PubMed1984

Alveolar-arterial oxygen gradients versus the Neonatal Pulmonary Insufficiency Index for prediction of mortality in ECMO candidates.

Current selection criteria necessary for intelligent application of extracorporeal membrane oxygenation (ECMO) in hypoxic neonates remains controversial. Both the Neonatal Pulmonary Insufficiency Index (NPII) and serial alveolar-arterial oxygenation gradient measurements (A-a)Do2 have been recommended. Accordingly, an analysis of 50 consecutive severely hypoxic neonates was undertaken to assess the predictive value of (A-a)Do2 determinations and NPII in discriminating survivors from non-survivors. These infants with meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), or persistent pulmonary hypertension of the newborn (PPHN) required maximum mechanical ventilation for hypoxia. Pharmacologic manipulation of pulmonary vascular resistance was attempted in 83%. If postductal (A-a)Do2 remained greater than or equal to 620 torr despite 12 hours of maximum medical therapy, mortality was 100%; however, 35% of nonsurvivors were unfortunately excluded. (A-a)Do2 greater than or equal to 600 torr for 12 hours demonstrated 93.8% mortality, and only 12% of all mortalities were thus excluded. Among nonsurvivors successfully hyperventilated, the NPII could not predict mortality. Ideal selection criteria must exclude those who would otherwise survive without ECMO, yet allow early accurate identification of the neonate certain to die. It would appear that serial (A-a)Do2 determinations best permit this identification and thus orderly application of ECMO.

Extracorporeal Circulation↗
PubMed1983

Colitis cystica profunda: a pediatric case report.

A case of colitis cystica profunda in a 14-year-old male is presented. The clinical and pathologic management are reviewed. Differentiation from adenocarcinoma by careful histologic evaluation of the epithelium is fundamental in avoiding overtreatment.

Adolescent↗
PubMed1983

Use of extracorporeal membrane oxygenation for respiratory failure in term infants.

Eight infants with intractable respiratory failure were treated with extracorporeal membrane oxygenation. Intractable respiratory failure was defined as alveolar-arterial oxygen gradient of more than 620 torr for six to 12 hours that did not respond to hyperventilation and the use of tolazoline. Infants with overt sepsis, CNS damage, or other debilitating conditions were not considered for extracorporeal membrane oxygenation. Six of the eight infants survived after a mean extracorporeal membrane oxygenation time of 164 hours. Five of the six survivors were normal neurologically and developmentally when examined at 1 year of age.

Blood Gas Analysis↗
PubMed1982

Effects of dopamine agonists and antagonists on murine melanoma: correlation with dopamine binding activity.

The biosynthetic pathway melanin is present in many melanomas. Previous investigations have suggested that pharmacologic levels of intermediates in this pathway (L-dopa, dopamine, and their analogues) may inhibit macromolecular synthesis in some tissue culture melanoma cell lines and prolong survival in tumor-bearing mice. Recently, a potent antidopamine drug (pimozide) has been developed. This study was designed to investigate the effects of these drugs on murine melanomas and to correlate effects on macromolecular synthesis with competitive dopamine binding activity (receptors) and melanin synthesis. Three murine melanomas (F1, F10, B16) were studied. The amelanotic B16 cell line showed no inhibition by dopa, dopamine, or pimozide when assayed for 14C-leu or 3H-TdR incorporation. Using a competitive binding assay, only low levels of dopamine binding were present. The very melanotic F1 cell line showed no inhibition by dopa or dopamine, but pimozide inhibited 14C-leu and 3H-TdR incorporation in a dose-response fashion; 50% inhibition was noted at 10(-9) M concentration with no loss in cell viability as tested by trypan blue exclusion or cell counting. Competitive dopamine binding was present (19 pmoles per g of wet tissue) with a Kd of 0.2 nM, figures approximating those seen in normal dog caudate nucleus controls. The F10 line, with melanin production between the B16 and F1, was intermediate in terms of inhibition of 14C-leu and 3H-TdR incorporation and dopamine binding. Purified melanin did not bind and, thus, does not appear to explain these binding results. These data suggest that pimozide, a drug which is a potent dopamine antagonist, may inhibit 14C-leu and 3H-TdR incorporation in murine melanoma cells and that competitive dopamine binding (receptor) appears to correlate with this inhibition. This drug and the dopamine binding assay may be useful in the study of human melanoma.

Animals↗
PubMed1982

Clinical use of an extracorporeal membrane oxygenator in neonatal pulmonary failure.

Pulmonary failure is the most frequent cause of mortality in newborns, accounting for 15,000 deaths yearly. It may be the result of the respiratory distress syndrome (RDS), meconium aspiration syndrome (MAS), or persistent fetal circulation (PFC), including infants with congenital diaphragmatic hernia (CDH). Early identification of patients with predictably fatal but potentially reversible respiratory failure refractory to conventional management protocols would permit orderly application of extracorporeal membrane oxygenation (ECMO) as a final resuscitative measure. Eight neonates with severe pulmonary failure manifested by A-a DO2 of greater than 620 torr for greater than 12 hr, persistent cardiovascular instability, and relentless progression of acidosis and hypoxemia were predicted to have a 100% mortality in spite of maximal medical therapy. Four patients presented with MAS and 4 others had PFC, including 2 with CDH. All were supported with ECMO using the internal jugular vein and common carotid artery for access to the right atrium and aortic arch. Following support for 77-313 hr, 6 were successfully weaned from ECMO and then from the ventilator. In these few patients the use of extracorporeal membrane oxygenation after exhaustion of standard therapy was accomplished safely and successfully without untoward short-term sequelae. Extracorporeal ventilatory support may purchase the critical time necessary for resolution of the underlying parenchymal disease, including the pulmonary hypertension associated with CDH.

Female↗
PubMedDate not supplied

Hyaluronic acid degradation products induce neovascularization and fibroplasia in fetal rabbit wounds.

Scarless fetal wound healing occurs with mild fibroplasia and neovascularization, while the wound is persistently enriched with hyaluronic acid. Conversely, adult wounds are characterized by prominent fibroplasia, neovascularization, and scar formation, and hyaluronic acid is a transient component of the early adult wound matrix. Our group has reported that enzymatic degradation of fetal rabbit wound hyaluronic acid results in marked increases in fibroplasia, collagen deposition, and neovascularization. This altered, adultlike healing response is hypothesized to have resulted from the generation of biologically active hyaluronic acid degradation products. Therefore, this study analyzes the fibrovascular inductive activity of hyaluronic acid degradation products. Fetal rabbit wounds were treated with hyaluronic acid degradation products generated by methods known to produce oligosaccharides with significant angiogenic activity. Implants from wounds treated with either of the control solutions (n = 4 for each control) had identical histologic features characterized by a mild mononuclear cell infiltrate but neither infiltrating fibroblasts nor collagen. In marked contrast, implants from wounds treated with hyaluronic acid degradation products contained infiltrating fibroblasts and collagen intermixed with numerous blood vessels. Quantitation of capillary ingrowth showed a sixfold increase in the neovascular response in wounds treated with hyaluronic acid degradation products compared with either controls (p < 0.05). This study shows that hyaluronic acid degradation products stimulate neovascularization and fibroplasia in fetal wounds. These observations suggest that a balance between hyaluronic acid accumulation and degradation has significant regulatory influence in fetal tissue repair.

Journal Article↗
PubMedDate not supplied

The role of transforming growth factor-beta in the conversion from "scarless" healing to healing with scar formation.

The objective of this study was to elucidate mediators responsible for conversion of "scarless" wound healing seen in wounded, day 14 fetal mouse limbs to healing with scar formation seen in wounded, day 18 fetal mouse limbs. Wounded, day 14 limbs were grown in a serum-free organ culture system in which either phosphate-buffered saline solution or human recombinant transforming growth factor beta-1 (1 microg/ml) was added daily. Wounded, day 18 limbs were also maintained in the same organ culture system with either phosphate-buffered saline solution or neutralizing antibody to transforming growth factor-beta (1 microg/ml) treatment. Limb cross sections were examined qualitatively with Masson's Trichrome stain and quantitatively by spectrophotometric analysis of Sirius Red and Fast Green dyes which bind to collagen and noncollagenous protein, respectively. Both qualitative and quantitative analyses showed the following: there was greater collagen deposition in day 18 versus day 14 limbs by 7 days after wounding, scar formation in day 18 limbs was attenuated by the addition of anti-transforming growth factor-beta, and there was the addition of transforming growth factor-beta-augmented collagenous scar formation in wounded regions of day 14 limbs. These results strongly suggest that transforming growth factor-beta present in the local wound environment is, at least in part, responsible for the conversion of "scarless" healing occurring in wounded, day 14 limbs to scar formation present in wounded, day 18 limbs.

Journal Article↗