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Biomedical subjects

T M Krummel

Publications and source records attributed to T M Krummel.

At least 73 records · Page 4Linked to original sources
PubMed1993

Fetal tissue repair and wound healing.

The fibrosis and scar formation that characterize adult wound healing are also the cause of clinical problems; scar contracture, hypertrophic scar, and pulmonary and hepatic fibrosis are only a few examples. Studies of fetal wound healing can provide an insight into the initiation and regulation of a scarless repair process akin to regeneration. Studies of fetal repair have already suggested mechanisms that might favorably alter adult healing. Topical application of hyaluronic acid to wounds in adult diabetic rats leads to enhanced epithelial migration. It has been recognized that the addition of TGF-beta to fetal wounds causes an adultlike healing response with fibrosis and inflammation. A subsequent study using neutralizing antibody to TGF-beta in adult wounds showed enhanced healing with a more normal dermal architecture with fewer macrophages, fewer blood vessels, and less collagen. As our understanding of regenerative tissue repair increases, the opportunities to modulate adult fibrotic conditions should expand.

Adult↗
PubMed1993

Video-assisted thoracoscopic excision of intrathoracic masses in children: report of two cases.

Video-assisted thoracoscopy was used to remove a bronchogenic cyst in a 6-year-old boy and a foregut duplication cyst in a 2-year-old girl. Access ports were placed along the site of a proposed thoracotomy incision and chest tube exit site. Thoracoscopic excision was uneventful, and each child left the hospital on the second postoperative day. Video-assisted thoracoscopy has a role in the evaluation and the definitive treatment of intrathoracic masses in children.

Bronchogenic Cyst↗
PubMed1992

In vivo degradation of fetal wound hyaluronic acid results in increased fibroplasia, collagen deposition, and neovascularization.

Fetal tissue repair occurs without acute inflammation, prominent fibroplasia, or marked neovascularization. The fetal wound extracellular matrix is rich in hyaluronic acid (HA), while collagen is deposited in an organized normal dermal pattern. In various biologic systems, including regeneration and development, the controlled accumulation and subsequent degradation of hyaluronic acid is associated with distinct cellular and matrix events. Therefore, it is hypothesized that the abundance of hyaluronic acid in fetal wounds may influence cellular and/or matrix events such that tissue repair is highly organized and adult-like scarring does not occur. To test this hypothesis, the hyaluronic acid content of fetal rabbit wounds was reduced by specific degradation with Streptomyces hyaluronidase. Control wounds were treated with either enzyme buffer (n = 12) or denatured enzyme solution (n = 8) and exhibited a normal fetal healing response with scattered peripheral fibroblasts, a matrix of hyaluronic acid, and no infiltrating collagen. In marked contrast, the hyaluronidase-treated wounds (n = 14) demonstrated increased fibroblast infiltration, collagen deposition, and capillary formation. A significant reduction in the hyaluronic acid content of the hyaluronidase-treated wounds was confirmed biochemically. Since the degradation of hyaluronic acid resulted in an altered healing response, this study demonstrates that hyaluronic acid affects the cellular and matrix events in fetal healing and may be partially responsible for the unique qualities of this regenerative repair process.

Animals↗
PubMed1992

Scarless wound healing in the mammalian fetus.

Fetal wound healing is a remarkable process that is fundamentally different than postnatal healing. Healing of primarily closed, linear wounds occurs rapidly and without scarring. In late gestational age fetal sheep, a transition to adult-like healing occurs as evidenced by minimal scar formation. Acute inflammation is not involved, fibroblast recruitment and proliferation is minimal, the matrix of the wounds is enriched with HA and collagen deposition is highly organized so that scarring is minimal or nonexistent. Open wounds in several species do not contract, an observation that may be because of an inhibitor of contraction in amniotic fluid. The underlying mechanisms that regulate fetal wound repair are currently not well understood. An altered supply or activity of growth factors may be instrumental. Fibroblasts may preferentially produce HA secondary to a factor present within the fetal system, and HA may influence cellular and matrix events within the wound. As greater knowledge of the biologic factors of scarless healing in the fetus is gained, applications to abnormal adult healing may be developed. As the age of fetal surgery is approaching, it is essential to understand the injury response in these new patients.

Adult↗
PubMed1991

Hyaluronic acid is a major component of the matrix of fetal rabbit skin and wounds: implications for healing by regeneration.

The extracellular matrix (ECM) of fetal rabbit wounds contains an abundance of the glycosaminoglycan hyaluronic acid (HA) but is devoid of excessive collagen. Thus, fetal wounds heal without scarring, such that tissue repair grossly resembles regeneration. To obtain further insight into the process of fetal wound healing, the ECM of normal fetal rabbit skin was analyzed, thus providing a comparative endpoint for the ECM of healing fetal wounds. Similarities between the matrices would support the theory of healing by regeneration. The glycosaminoglycan (GAG) component of fetal rabbit skin from 24- and 29-day gestational age fetuses was extracted and then quantitated using an alcian blue binding assay. The extracted GAG was characterized by cellulose acetate electrophoresis and HA was identified by its selective digestion by Streptomyces hyaluronidase. The mean GAG content, measured as ng GAG per mg dry weight skin, was 260 +/- 200 for the 24-day group (n = 28) and 280 +/- 220 for the 29-day group (n = 26). The only GAG identified at both times of gestation was HA. This study has demonstrated that HA is the predominant GAG present in fetal rabbit skin and its quantity is stable during the period studied late in gestation. A major component of the ECM of both wounded and normal fetal skin is HA, indicating a close compositional similarity. These observations provide biochemical support for the hypothesis that the reparative process of injured tissue in the fetal rabbit proceeds in an attempt to reconstitute normality, i.e. regeneration.

Animals↗
PubMed1991

Analysis of skin grafting techniques in the fetal rabbit.

The experimental model reported here was developed initially to examine the possibility of in utero coverage of congenital soft tissue defects using several types of reconstructive techniques. To pursue this, full-thickness skin grafts, pedicle flaps, and skin "islands" were fashioned on the backs of fetal rabbits; equivalent adult control wounds were also created. While all pedicle flaps and skin islands remained viable, none of the full-thickness grafts survived in the fetus. All adult control flaps, skin islands, and skin grafts were viable. Angiogenesis is crucial to full-thickness skin graft survival. These observations suggest that the death of full-thickness fetal skin grafts may be related to a failure of neovascularization in the graft bed. Further analysis using this model may help elucidate the factors involved in fetal angiogenesis. Additionally, this model may permit testing of putative angiogenic factors applied under a full-thickness skin graft; graft survival offers an easy, objective, and quantifiable means of data analysis.

Animals↗
PubMed1991

Yolk sac tumor of the liver.

A primary yolk sac tumor of the liver in a 16-mo female is presented. The fine needle aspiration biopsy (FNAB) cytology of this lesion is illustrated and discussed. This case supports continued exploration of the use of FNAB in childhood abdominal masses.

Biopsy, Needle↗
PubMed1990

Fetal skin organ culture.

The fetal response to cutaneous injury has been investigated in a variety of models; most have studied the differences between fetal and adult healing mechanisms in vivo and in cell culture. Further disclosure of the cellular and biochemical events requires a model that can be manipulated to study single factors influencing fetal tissue repair without the complex interactions that occur in vivo, but in a system that more closely approximates normal skin than cell culture models. This paper presents a method for the organ culture of fetal skin and its advantages as a model to help elucidate fetal healing mechanisms. Skin sections (1 x 1 cm) excised from the backs of fetuses of New Zealand white rabbits on day 27 gestation (term = 31 days) were placed eccentrically in 65-mm culture dishes and fed daily with 2.5 mL of DMEM containing 10% fetal calf serum, antibiotics, and 10 mM ascorbic acid. A separate group, treated similarly, received 4-mm punch wounds to assess the in vitro response to wounding. The specimens were incubated at 37 degrees C in humidified room air on a rocker platform to provide alternate exposure of the skin to air and medium. Gross observation at 3 weeks showed cells extending into the central wound, indicating that viable cells were proliferating and/or migrating from the tissue. Skin was examined histologically and was viable over the 3-week period studied. Organ culture, by maintaining tissue in the natural extracellular matrix, allows cell-to-cell contact and communication to be maintained while allowing controlled environmental manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Operative techniques in the fetal rabbit.

The development of fetal surgical techniques has made the antenatal correction of congenital defects possible. These techniques have evolved from trials with animal models, permitting increasingly sophisticated operations with low morbidity and mortality. Experimental models range from large animals offering longer gestations but with single pregnancies and high cost, to smaller animals offering multiple pregnancies at reduced cost but with shorter gestations. This paper describes operative techniques in the fetal rabbit and its advantages as a fetal surgical model. Experience with the pregnant rabbit has shown it to be a suitable surgical model for several reasons. Pregnancies are multiple, increasing cost effectiveness and permitting operation on up to eight fetuses per litter without fetal loss. Techniques that promote fetal survival include local housing of does several days prior to operation and preoperative sedation. Spontaneous mask ventilation provides ease of anesthetic administration and titration. Overall surgery is well tolerated with a low incidence of intraoperative complications. Rabbit models have been used in the study of transamniotic fetal feeding, abdominal wall defects, and wound healing. These techniques have resulted in postoperative fetal viability approaching 90%, with negligible maternal mortality in over 4000 fetal operations, thereby making the rabbit a manageable cost-effective model of fetal surgery.

Animals↗
PubMed1989

Hypophosphatemia in a pediatric patient after major hepatic resection.

Hypophosphatemia was noted in a 20-month-old infant following major hepatic resection. The hypophosphatemia appeared to be related in part to renal wasting of phosphate, although this condition was transient. Prompt recognition and treatment prevented serious sequelae of this disorder.

Female↗
PubMed1989

Transthoracic Nissen fundoplication for gastroesophageal reflux in patients with severe kypho-roto-scoliosis.

Transthoracic Nissen fundoplication was used for the correction of gastroesophageal reflux in five mentally retarded patients with severe kypho-roto-scoliosis. This deformity may result in a gastroesophageal junction so high above the left costal margin that transabdominal fundoplication is extremely difficult. Operative morbidity was minimal. One wrap disruption occurred that required reoperation. Results have been satisfactory 6 to 24 months postoperatively.

Adolescent↗
PubMed1989

Double aortic arch associated with esophageal atresia and tracheoesophageal fistula.

Esophageal atresia (EA) with tracheoesophageal fistula (TEF) is commonly associated with significant cardiovascular anomalies. Mortality is higher with cardiovascular abnormalities, especially those undiagnosed prior to surgical repair of the EA/TEF. Advances in cardiac imaging techniques, most notably echocardiography, have made noninvasive evaluation of the heart and great vessels easy to perform and reliable. Thus, the preoperative cardiovascular anatomy of these infants should be routinely assessed prior to surgical correction. A case of EA/TEF associated with an unsuspected double aortic arch is described. Although a wide variety of cardiovascular lesions have been associated with EA/TEF, coexistence of a double aortic arch has not been previously reported. Preoperative recognition of this anomaly would have altered the surgical approach, and perhaps reduced the postoperative morbidity and mortality.

Abnormalities, Multiple↗
PubMed1989

Analysis of transforming growth factor beta receptor binding in embryonic, fetal, and adult rabbit fibroblasts.

Adult wound repair traits including inflammation, fibroplasia, and collagen deposition are not seen at fetal wound sites. This observation raised questions about regulatory mechanisms extant in fetal healing. Transforming growth factor beta (TGF-beta) is an important regulatory polypeptide known to orchestrate fibroplasia and collagen synthesis during adult wound repair. Previous studies have suggested that the wounded rabbit fetus is capable of responding with these adult characteristics if provided with exogenous TGF-beta. In order to test whether the observed in vivo effects of TGF-beta in the rabbit fetus might be due to a direct effect on the fibroblast, TGF-beta receptor binding characteristics of early passage cultured embryonic (14 days' gestation), fetal (24 days' gestation), and adult rabbit fibroblasts were studied by flow cytometry. Experiments were carried out using fluorescein-conjugated TGF-beta (F-TGF-beta) with analysis on an EPICS V flow cytometer. F-TGF-beta was incubated with each of the three fibroblast types at 37 degrees C after which time the cells were washed twice and analyzed with a minimum of 10(5) cells for each data point. F-TGF-beta bound rapidly and reversibly to the embryonic, fetal, and adult fibroblasts with saturation being achieved at 1 nmol/L for fetal and adult cells, and 8 nmol/L in the embryonic fibroblasts. Saturating concentrations of F-TGF-beta yielded mean channel numbers (a function of relative amounts of F-TGF-beta-bound) of 172, 114, and 97 for embryonic, fetal, and adult cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Use of intraoperative ultrasound during hepatic resection in pediatric patients.

Five pediatric patients with primary liver tumors were evaluated preoperatively with ultrasound (US), computerized tomography (CT), and angiography, and tentative operative plans were formulated. Intraoperative US was subsequently used to examine these children, resulting in changes in operative strategy of all five patients despite their extensive preoperative evaluations. Intraoperative ultrasound appears to provide the most accurate assessment of both the extent of tumor and its vascular relationships. Thus, operative strategies may be precisely tailored on the basis of such information, allowing rational resection where appropriate, while futile attempts at removal of inoperable lesions may be averted.

Carcinoma, Hepatocellular↗
PubMed1989

Characterization and quantitation of wound matrix in the fetal rabbit.

Fetal response to injury has been characterized by the deposition of a matrix that is not primarily collagen. This study was designed to identify this matrix, in order to better understand the fetal mechanism of tissue repair. Silastic/polyvinyl alcohol sponge (PVA) wound implants were placed paravertebrally in 24-day gestation (31 days = term) fetal (n = 65) and adult (n = 43) rabbits and then harvested from one hour to 6 days post-wounding. Histologic analysis of the fetal wound matrix deposited in the PVA implants suggested the presence of glycosaminoglycans (GAG) rather than the collagen found in adult wound implants. To further analyze the fetal wound matrix, the GAG content was quantitated using an Alcian Blue dye-binding assay. Results showed significantly increased (p less than 0.05) GAG deposition on days 2-6 in the fetal wound compared to the adult wound. Fetal GAG levels were approximately three times those of the adult during this period. Separation of individual GAG species by cellulose acetate electrophoresis demonstrated that the GAG matrix of the fetal wound was composed predominantly of hyaluronic acid. This finding was confirmed by selective enzymatic digestion of separated GAG species using highly specific polysaccharidases. These observations of hyaluronic acid deposition in the fetal wound may be ascribed an important physiologic role by providing a more fluid and malleable matrix rather than a restrictive matrix composed of collagen. This new evidence coupled with earlier findings of the lack of an acute inflammatory response in the fetus further supports the hypothesis that the fetal response to injury is significantly different from the adult response.

Alcian Blue↗
PubMed1988

Cricoid split for subglottic stenosis in infancy.

Historically, tracheostomy has been used for infants with airway obstruction caused by congenital or acquired subglottic stenosis. Postoperative morbidity and mortality with this provisional operation led Cotton, in 1980, to substitute anterior cricoid split as the primary definitive procedure. Within the past three years, anterior cricoid split has been performed in 4 infants, aged 3 to 9 months, with acquired (3 patients) or congenital (1 patient) subglottic stenosis requiring ventilation through an endotracheal tube. Following cricoid split, the trachea is stented for 12 to 14 days by a nasotracheal tube, with extubation and rigid bronchoscopy in the operating room with the patient under anesthesia to confirm healing and patency. During an 18- to 24-month follow-up in these 4 patients, morbidity has been minimal, patency has persisted, and stridor has not recurred. Accordingly, a conclusive operation, cricoid split, rather than a temporizing tracheostomy may be employed for certain obstructive tracheal lesions early in life.

Cricoid Cartilage↗
PubMed1988

Use of the Greenfield filter in adolescents for deep vein thrombosis and pulmonary embolism.

Serious venous thromboembolic disease is now recognized more frequently in the pediatric age group. Caval interruption is indicated most commonly for prophylaxis against life-threatening or recurrent pulmonary embolism (PE) when anticoagulation is ineffective or contraindicated. Greenfield vena caval filters have been utilized locally in 415 adult patients with 97% long-term patency and 5% recurrent embolization. Its application in adolescents is reported herein. Standard adult (30-mm) vena caval filters were placed in ten patients, ages 13 to 18. Four filters were required following PE, six were used for deep venous thrombosis (DVT) when anticoagulation was contraindicated, and one was inserted prophylactically. In eight patients, filter insertion was accomplished with local anesthesia, while two underwent filter placement under general anesthesia administered for other procedures. One filter was misplaced into the right renal vein, requiring a second filter insertion. All patients have been followed from 1 to 11 years with yearly vascular duplex imaging and radionuclide venograms documenting caval patency without clinical embolic sequelae. This duplicates the adult experience in safety and efficacy. As recognition of venous thromboembolism becomes more frequent in the pediatric age group, safe caval interruption may be necessary for those excluded from or not responsive to anticoagulation. This technique may be extended to smaller patients with miniaturization of both filter and carrier.

Adolescent↗