Biomedical subjects

T M Crombleholme

Publications and source records attributed to T M Crombleholme.

105 records · Page 6Linked to original sources

PubMed1989

Appendicovesicostomy: a new technique for bladder diversion during reconstruction of cloacal exstrophy.

Urinary tract diversion in the reconstruction of cloacal exstrophy presents a difficult problem. Many methods have been used, but none has been found to be ideal. We describe a simple technique that incorporates the ileocecal plate in the bladder augmentation, and uses the appendix as a conduit for urinary diversion. This technique offers the advantages of primary closure, effective urinary drainage without tubes, and simplicity of bowel reconstruction with preservation of maximal absorptive surface.

Appendix↗

PubMed1989

Biliary appendico-duodenostomy: a nonrefluxing conduit for biliary reconstruction.

Biliary conduits constructed during operations for choledochal cysts or biliary atresia are frequently complicated by reflux of gastrointestinal contents, stasis, and obstruction with resulting cholangitis. We have used the appendix as a biliary conduit for cases of biliary atresia and choledochal cyst, adapting the urologic technique of a tunneled, nonrefluxing anastomosis for reconstruction of the biliary tree--biliary appendico-duodenostomy (BAD). From our preliminary experience with this technique, it appears promising.

Anastomosis, Surgical↗

PubMed1989

Studies in fetal wound healing. IV. Hyaluronic acid-stimulating activity distinguishes fetal wound fluid from adult wound fluid.

Recent clinical and experimental evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Our initial experience with human open fetal surgery reinforces experimental observations that the fetal wounds heal without the scarring, inflammation, and contraction that often accompany adult wounds. In this study we examine fetal wound fluid in an attempt to elucidate the control mechanisms that endow the fetus with unique healing properties. The extracellular matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. We establish that wound fluid from the fetus contains high levels of hyaluronic acid-stimulating activity that may underlie the elevated deposition of hyaluronic acid in the fetal wound matrix. In contrast there was no hyaluronic acid-stimulating activity present in adult wound fluid. Hyaluronic acid, in turn, fosters an extracellular environment permissive for cell motility and proliferation that may account for the unique properties observed in fetal wound healing.

Age Factors↗

PubMed1989

Neonatal model of heterotopic heart transplantation in pigs.

To investigate the long-term success of heart transplantation in newborn infants who have complex congenital heart disease, we have developed a model of heterotopic heart transplantation in immature pigs. We chose the heterotopic technique because it is simple, does not require cardiopulmonary bypass or heparin, allows for significant size disparity between the recipient and donor hearts, and allows for experimental comparisons between the two hearts. Small newborn piglet hearts are harvested, prepared, and then transplanted into the left chest of larger weanling pigs to augment or substitute for the native left ventricle. Preliminary data from transplants into 49 pigs suggest that the technique is technically possible, the pigs can be immunosuppressed over the long term, and the donor heart can contribute hemodynamically. Experimentally, the model is well designed for the investigation of issues critical for the long-term success of heart transplantation in infants and children, including growth and development, optimal long-term immunosuppression, differences in immunotolerance, and the study of coronary obliterative disease. Clinically, the model has potential applicability in congenital heart anomalies if one native functioning atrium and ventricle are present.

Animals↗

PubMed1988

Prenatal diagnosis and management of bilateral hydronephrosis.

This report reviews the management of the fetus with congenital hydronephrosis (CH), a challenging diagnostic and therapeutic problem. Experimental models of obstructive uropathy have produced histologic changes similar to those seen in kidneys of human neonates with congenital hydronephrosis. Relief of obstruction in utero in these models has been shown to prevent some of the dysplastic changes caused by obstruction. These studies have formed the theoretical basis for in utero decompression to restore amniotic fluid dynamics to prevent death from pulmonary hypoplasia, and reverse or arrest dysplastic morphogenesis. The development of prognostic criteria has greatly aided in selection of appropriate fetuses for intervention. These criteria include: (1) Na less than 100 mEq/l; (2) Cl less than 90 mEq/l; (3) osmolarity less than 210 mosmol; (4) sonographic appearance of the fetal kidneys; (5) amniotic fluid status; (6) urine output at fetal bladder catheterization. All fetuses should have ultrasonography to exclude other anomalies, and karyotype analysis to exclude chromosomal abnormality. If amniotic fluid volume is normal, the pregnancy is followed with serial ultrasound examinations. If oligohydramnios develops, a prognostic evaluation is performed, including fetal bladder catheterization. If the fetus has poor residual renal function, on the basis of prognostic criteria, appropriate counseling may be given. If the fetus has good residual renal function, depending on lung maturity, it can be delivered early for corrective surgery. If diagnosed prior to lung maturity in utero, decompression by either vesicoamniotic shunting or open fetal surgery may be attempted in the highly selected case.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Early experience with open fetal surgery for congenital hydronephrosis.

The fetus with severe bilateral hydronephrosis and associated oligohydramnios in the second trimester is doomed at birth by ongoing pulmonary and renal damage. Since decompression with percutaneously placed catheters anesthetic, surgical, and tocolytic techniques for open fetal anesthetic, surgical, and tocolytic techniques for open fetal urinary tract decompression in animals, and have now applied those techniques to a small group of five patients. One had bilateral ureterostomies and the subsequent four had marsupialization of the bladder. All pregnancies proceeded to cesarean delivery at 32 to 35 weeks' gestation. There was no long-term maternal morbidity, and two mothers have since experienced normal pregnancies. Three fetuses had return of normal amniotic fluid dynamics, and all three had adequate pulmonary function at birth, suggesting that fatal pulmonary hypoplasia associated with early severe oligohydramnios had been reversed. Two neonates died at birth with pulmonary hypoplasia. One had no amniotic fluid even after decompression, and the other had some amniotic fluid after decompression but a tiny chest cavity due to the long period of severe oligohydramnios before decompression. Of the three surviving infants, one had normal renal function when she died of unrelated causes at 9 months of age. One has normal renal function at 23 months and the third had failing renal function at 2 1/2 years and has grown and developed normally, but will require renal transplantation. We have now developed selection criteria that would exclude from treatment the two fetuses who died of pulmonary hypoplasia and the one who developed renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987

Perinatal management of the fetus with an abdominal wall defect.

The antenatal diagnosis of abdominal wall defects has allowed improved perinatal management. For fetuses with associated anomalies, the options of elective termination or minimal intervention can be offered. Our ability to predict the extent of bowel damage in gastroschisis based on the ultrasound findings enables us to offer early delivery to those fetuses who are at high risk. The data are not clear at the present time whether cesarean section offers any advantage. These fetuses should, however, be delivered at a center which is capable of providing high level medical and surgical care to these potentially ill infants. Initial resuscitation of these neonates requires early insertion of an intravenous line and a nasogastric tube, the administration of antibiotics, sterile coverage of the eviscerated bowel, and careful attention to temperature instability. Neonates with gastroschisis should be operated on as soon as they are stable, whereas infants with omphalocele can be investigated for associated anomalies prior to surgery. Primary fascial closure is performed whenever possible. Where this is not possible, a staged repair using a silastic chimney achieves closure within 3-6 days. Skin coverage alone or nonoperative management is reserved for the few cases with giant omphalocele, associated anomalies, or poor operative risk. Decisions about primary versus delayed closure, while usually dictated by clinical judgement, can be aided by indirect measurement of intraabdominal pressure. Postoperative ventilation, and consideration of long-term nutritional needs, are also important parts of the perioperative management.

Abdominal Muscles↗

PubMedDate not supplied

The current status and future potential of fetal intervention: image is everything.

Fetal imaging is integral to the past, present, and future of fetal intervention. In the early history of fetal intervention, the role of prenatal ultrasound was primarily to identify a fetal lesion, provide a correct anatomic diagnosis, and exclude other anatomic defects. We now depend on ultrasound, and other imaging studies, not only to provide anatomic information, but to provide prognostic, physiologic and functional information prior to, during, and after surgery for optimal selection and management of fetal surgery patients. In the future improvements in imaging and non-invasive technology will drive further expansion of indications and therapeutic options for fetal intervention.

Fetal Diseases↗

PubMedDate not supplied

Hyaluronic acid-dependent pericellular matrices in fetal fibroblasts: implication for scar-free wound repair.

Fetal fibroblasts are intrinsically different from postnatal fibroblasts. We studied the differences in expression, size, and assembly of pericellular matrices in human fetal and postnatal fibroblasts, as well as the effect of fetal fibroblast-conditioned media as a source of migration stimulating factor on pericellular matrix formation. Fibroblasts in their fifth to fifteenth passages were cultured for 24 hours before analysis. Streptomyces hyaluronidase (0.1 U/ml), monoclonal mouse anti-human CD-44std, or anti-human CD-4 antibodies were added and incubated for 1 hour (at 4 degrees and 37 degrees C) before analysis of the pericellular matrices with the use of a particle exclusion technique. The pericellular matrix/cell body ratio of fetal fibroblasts was significantly larger than that of newborn (p < 0.002) and adult (p < 0.001) fibroblasts. Hyaluronidase disrupted the pericellular matrices in all three cell lines. Assembly of the pericellular matrices was blocked by anti-human CD-44std antibody but not by anti-human CD-4 antibody at both 4 degrees and 37 degrees C. Incubation of fibroblast cell lines in fetal fibroblast-conditioned media did not increase pericellular matrix/cell body ratio but did increase the percentage of fibroblasts expressing a detectable pericellular matrix in adult (p < 0.01), newborn (p < 0.001), and fetal (p < 0.005) fibroblasts. We conclude that fibroblasts produce hyaluronic acid-dependent pericellular matrices which require interaction with a hyaluronic acid-binding protein for assembly. Large pericellular matrices are one intrinsic factor characterizing a unique fetal fibroblast phenotype.

Journal Article↗

PubMedDate not supplied

Recombinant adenoviral mediated gene transfer in ischemic impaired wound healing.

Chronic nonhealing wounds represent a large clinical problem resulting in severe disabilities and large healthcare expenditures. Despite the scope of this problem, effective new therapies are lacking. The deficiency of growth factors in chronic wounds has brought attention to the topical application of growth factors, but initial clinical trials have resulted in only modest improvements in healing despite large, repetitive doses. The modest improvement in healing observed in these trials show that growth factors can improve chronic wound healing, but a better means of growth factor delivery is needed. We hypothesized that gene therapy using a recombinant adenoviral vector could be used to induce transgene production directly by cells in the wound. An adenovirus containing the beta-galactosidase reporter transgene (Ad-LacZ) was used in the ischemic rabbit ear model to test this hypothesis. Ad-LacZ resulted in efficient transgene delivery to cells participating in the wound healing response, with expression up to 2 weeks. However, wound reepithelialization was impaired in Ad-LacZ treated wounds compared to vehicle control wounds. Adenoviral mediated gene transfer is a promising efficient means of growth factor delivery to chronic wounds. However, selection of the proper transgene with appropriate biologic activity in wound healing may be essential to overcome the potential adverse effects of adenoviral infection.

Adenoviridae↗

PubMedDate not supplied

Adenoviral-mediated gene transfer in wound healing: acute inflammatory response in human skin in the SCID mouse model.

The use of an adenoviral vector as a means of therapeutic protein delivery for the treatment of impaired wound healing is a potentially effective application of current gene transfer techniques. This study was designed to investigate the ability of adenovirus to mediate gene transfer in healing wounds in human skin in vivo. The human skin/severe combined immunodeficient mouse chimera model was used to study both the response of human tissue to adenoviral infection and the nature of the acute inflammatory response. The effects of adenoviral infection and transgene expression on the rate and quality of human wound healing were then investigated. Cell- and species-specific monoclonal antibodies were used to characterize the resident skin cell types participating in wound repair, the inflammatory response, and the proliferative potential of adenovirus-treated compared to control skin. Our studies show that, following wounding, normal skin architecture is restored in the presence of adenoviral infection equivalent to noninfected controls. Despite an increased acute inflammatory response after adenovirus injection, no difference in the healing capabilities of wounded skin was observed, suggesting that adenovirus-mediated gene transfer for growth factor-mediated acceleration of wound healing may be feasible.

Adenoviridae Infections↗

PubMedDate not supplied

Adenoviral-mediated gene transfer in wound healing.

The application of gene transfer strategies to wound healing is not an obvious use of this technology until one considers the important role of cytokines and growth factors in the normal wound healing response. Several gene transfer strategies have been proposed, from in vitro retroviral-mediated gene transfer with autologous transplantation, to in vivo plasmid based gene transfer as retroviral gene transfer. The limitations of these approaches have been efficiency of gene transfer, transgene expression and biologic response. Adenoviral-mediated gene transfer in wound healing is a relatively new application of this vector. The advantage of the adenovirus as a gene transfer vector lies in its ability to transduce nondividing cells of all types at very high efficiency without integration into the host cell's genome. The disadvantage of adenovirus as a vector is the relatively short duration of transgene expression and the inflammatory response it elicits. In the setting of wound healing brief duration of high levels of transgene may be all that is necessary to favorably influence wound healing. Secondly, as wound healing is fundamentally an inflammatory response, the inflammation elicited by the adenovirus may not be detrimental as long as the transgene is a growth factor with significant vulnerary effects such as platelet-derived growth factor-B. This review summarizes the current state of adenoviral-mediated gene transfer in experimental models of impaired wound healing which have laid the groundwork for proposed phase I clinical trials of adenoviral-mediated gene transfer of platelet-derived growth factor-B in chronic venous leg ulcers and chronic nonhealing diabetic foot ulcers. Adenoviral-mediated gene transfer is a useful tool in the study of the role of specific cytokines and growth factors in normal and impaired wound healing. Adenoviral-mediated gene transfer may hold significant promise for clinical application as a means of efficient growth factor delivery in correcting impaired wound healing.

Adenoviridae↗

PubMedDate not supplied

Salvage of a fetus with congenital high airway obstruction syndrome by ex utero intrapartum treatment (EXIT) procedure.

A fetus with congenital high airway obstruction syndrome (CHAOS) due to complete tracheal atresia was referred at 31 weeks of gestation after 12 weeks of massive hydrops. The fetus was delivered by the ex utero intrapartum treatment procedure allowing sufficient time while on placental support for bronchoscopy to confirm tracheal atresia and tracheostomy to secure the airway. His postnatal course was complicated by severe capillary leak syndrome secondary to hydrops, diaphragmatic paralysis, tracheobronchial malacia, and the need for chronic ventilatory support. The infant's tracheobronchial malacia resolved by 5 months of age and normal diaphragmatic function was restored at 9 months allowing him to be weaned from mechanical ventilation. He underwent tracheal reconstruction at 17 months of age. At follow up at 32 months of age he has a patent airway and is the first long-term survivor with CHAOS.

Adult↗

PubMedDate not supplied

Decompression of fetal axillary lymphangioma to prevent dystocia.

BACKGROUND: Lymphangiomas are commonly diagnosed by prenatal ultrasound. These anomalies are most often cervical, but occasionally present in the axilla, thorax and abdomen. We present a case in which intrauterine drainage was followed by an uneventful vaginal delivery. CASE: A 30-year-old G4P3 female was referred to our ultrasound unit at 36 weeks of gestation for evaluation of a large cystic chest wall mass. Ultrasound demonstrated a large septated mass along the left chest wall up to the apex of the axilla of the fetus. The left arm was held in 90 degrees abduction due to the mass. Because of concern about shoulder dystocia at delivery the cystic mass was aspirated under ultrasound guidance and the patient underwent an uneventful induction of labor. CONCLUSIONS: Intrauterine decompression of large axillary lymphangiomas may obviate concern about a shoulder dystocia and avoid the need for cesarean sections.

Adult↗

PubMedDate not supplied

Pitfalls of the 'double bubble' sign: a case of congenital duodenal duplication.

The 'double bubble' sign in prenatal diagnosis is most often associated with duodenal atresia. However, other causes of upper intestinal obstruction and cystic abdominal masses need to be considered. One possible diagnosis that can mimic the 'double bubble' sign of duodenal atresia is duodenal duplication, but little information is available to guide sonologists in the prenatal diagnosis of this rare congenital anomaly. In this case report we describe the successful prenatal diagnosis of duodenal duplication, by relying on the early gestational age of presentation, the lack of polyhydramnios, the failure to consistently demonstrate a 'double bubble' on transverse images, and the presence of a normal distal bowel pattern.

Adult↗