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Biomedical subjects

J B Lynch

Publications and source records attributed to J B Lynch.

At least 19 recordsLinked to original sources
PubMed1992

Epidermal growth factor receptor distribution in burn wounds. Implications for growth factor-mediated repair.

Epidermal growth factor (EGF) along with several related peptide growth factors has been shown both in vivo and in vitro to accelerate events associated with epidermal wound repair. EGF and transforming growth factor alpha act by binding to a common EGF receptor tyrosine kinase thereby initiating a series of events which ultimately regulate cell proliferation. This study examined the immunohistochemical localization of EGF receptor (EGF-R) in burn wound margins, adjacent proliferating epithelium, and closely associated sweat ducts, sebaceous glands, and hair follicles. Tissue specimens removed during surgical debridement were obtained from full and partial thickness burn wounds in 32 patients with total body surface area burns ranging from 2 to 88%. In the early postburn period (days 2-4), prominent staining for EGF-R was found in undifferentiated, marginal keratinocytes, adjacent proliferating, hypertrophic epithelium, and both marginal and nonmarginal hair follicles, sweat ducts, and sebaceous glands. During the late postburn period (days 5-16), EGF-R was depleted along leading epithelial margins; however, immunoreactive EGF-R remained intensely positive in the hypertrophic epithelium and all skin appendages. Increased detection of immunoreactive EGF-R and the presence of [125I]EGF binding in the hypertrophic epithelium correlated positively with proliferating cell nuclear antigen distributions. Thus, the presence of EGF-R in the appropriate keratinocyte populations suggests a functional role for this receptor during wound repair. Dynamic modulation in EGF receptor distribution during the temporal sequence of repair provides further evidence that an EGF/transforming growth factor alpha/EGF-R-mediated pathway is activated during human wound repair.

Burns↗
PubMed1991

Electron transfer associated with oxygen activation in the B2 protein of ribonucleotide reductase from Escherichia coli.

Each of the two beta peptides which comprise the B2 protein of Escherichia coli ribonucleotide reductase (RRB2) possesses a nonheme dinuclear iron cluster and a tyrosine residue at position 122. The oxidized form of the protein contains all high spin ferric iron and 1.0-1.4 tyrosyl radicals per RRB2 protein. In order to define the stoichiometry of in vitro dioxygen reduction catalyzed by fully reduced RRB2 we have quantified the reactants and products in the aerobic addition of Fe(II) to metal-free RRB2apo utilizing an oxygraph to quantify oxygen consumption, electron paramagnetic resonance to measure tyrosine radical generation, and Mössbauer spectroscopy to determine the extent of iron oxidation. Our data indicate that 3.1 Fe(II) and 0.8 Tyr122 are oxidized per mol of O2 reduced. Mössbauer experiments indicate that less than 8% of the iron is bound as mononuclear high spin Fe(III). Further, the aerobic addition of substoichiometric amounts of 57Fe to RRB2apo consistently produces dinuclear clusters, rather than mononuclear Fe(III) species, providing the first direct spectroscopic evidence for the preferential formation of the dinuclear units at the active site. These stoichiometry studies were extended to include the phenylalanine mutant protein (Y122F)RRB2 and show that 3.9 mol-equivalents of Fe(II) are oxidized per mol of O2 consumed. Our stoichiometry data has led us to propose a model for dioxygen activation catalyzed by RRB2 which invokes electron transfer between iron clusters.

Electron Transport↗
PubMed1989

Enhancement of wound healing by topical treatment with epidermal growth factor.

Experimental studies in animals have demonstrated that the topical application of epidermal growth factor accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns. We conducted a prospective, randomized, double-blind clinical trial using skin-graft-donor sites to determine whether epidermal growth factor would accelerate the rate of epidermal regeneration in humans. Paired donor sites were created in 12 patients who required skin grafting for either burns or reconstructive surgery. One donor site from each patient was treated topically with silver sulfadiazine cream, and one was treated with silver sulfadiazine cream containing epidermal growth factor (10 micrograms per milliliter). The donor sites were photographed daily, and healing was measured with the use of planimetric analysis. The donor sites treated with silver sulfadiazine containing epidermal growth factor had an accelerated rate of epidermal regeneration in all 12 patients as compared with that in the paired donor sites treated with silver sulfadiazine alone. Treatment with epidermal growth factor significantly decreased the average length of time to 25 percent and 50 percent healing by approximately one day and that to 75 percent and 100 percent healing by approximately 1.5 days (P less than 0.02). Histologic evaluation of punch-biopsy specimens taken from the centers of donor sites three days after the onset of healing supported these results. We conclude that epidermal growth factor accelerates the rate of healing of partial-thickness skin wounds. Further studies are required to determine the clinical importance of this finding.

Administration, Topical↗
PubMed1989

Mössbauer and EPR studies of the binuclear iron center in ribonucleotide reductase from Escherichia coli. A new iron-to-protein stoichiometry.

57Fe-enriched ribonucleotide reductase subunit B2 from Escherichia coli strain N6405/pSPS2 has been characterized by Mössbauer and EPR spectroscopy in its native diferric state and in a new differous form. The native protein exhibits two Mössbauer doublets in a 1:1 ratio with parameters that are in excellent agreement with those reported for the wild-type protein (Atkin, C. L., Thelander, L., Reichard, P., and Lang, G. (1983) J. Biol. Chem. 248, 7464-7472); in addition, our studies show the absence of adventitiously bound iron. The iron content in the present samples approached 4 per B2 subunit, and the tyrosyl radical content exceeded 1 per B2 subunit. The higher values are attributed to the use of a new epsilon 280 for the protein and more efficient methods for iron extraction. We thus propose that subunit B2 has two binuclear iron clusters, each associated with its own tyrosyl radical, in contradistinction from the prevailing model. Reduction of the native protein with dithionite or reconstitution of the apoprotein with Fe(II) afforded a protein complex with Mössbauer parameters, delta EQ = 3.13 mm/s and delta = 1.26 mm/s at 4.2 K, and a low field EPR signal associated with an integer spin system. These spectral properties resemble those of methane monooxygenase in its diferrous form. Upon exposure to O2, the reduced subunit B2 readily converts to the diferric state and yields active enzyme.

Dithionite↗
PubMed1988

Hepatitis B surface antigen associated nephrotic syndrome.

Hepatitis B virus (HBV) has been reported in association with the nephrotic syndrome from different parts of the world, but its role as a cause of the pathological findings of nephrotic syndrome is still controversial. We report seven nephrotic children with positive hepatitis B markers in which members of their families were also positive for the markers but without clinical, renal or hepatic involvement. Four showed haematuria at onset and three developed hypertension later in the course of the disease. Only two were responsive to steroid therapy. Renal biopsy was performed in four, of whom three showed membranous nephropathy and the other showed mesangioproliferative glomerulonephritis. Four patients developed end-stage renal disease. We conclude that in our environment HBV, when detected in children with nephrotic syndrome, should not be considered as a chance finding, but may have a definite role in its pathogenesis. Moreover, the prognosis of HBV-associated nephrotic syndrome appears poor.

Child↗
PubMed1987

Latissimus dorsi flap: a valuable resource in lower arm reconstruction.

Lower arm reconstruction of soft tissue defects and after ablation for cancer leaves the reconstructive surgeon few alternatives. We have used latissimus dorsi muscle (n = 1) and musculocutaneous flaps (n = 3) with good functional and cosmetic results. Defects in one patient with traumatic amputation, another with extravasation of doxorubicin, and two with cancer were closed without complications to donor site, recipient site, or flap. Skin paddle size averaged 182 sq cm in the three musculocutaneous flaps. Mean follow-up was six months.

Aged↗
PubMed1987

Radiation dermatitis.

Even in this era of modern radiotherapy, injuries associated with the medical and industrial use of radiation devices will continue to pose a difficult problem for the reconstructive surgeon. It must be borne in mind that the single most serious hazard to surgery in irradiated tissue is the lodgement of bacteria in tissue rendered avascular by the radiation and the secondary necrosis from the infection itself. The basic principles of wound management must be augmented by thorough knowledge of the use of well-vascularized muscle and musculocutaneous flap to provide adequate, blood-rich, soft-tissue coverage.

Female↗
PubMed1986

Pectoralis major musculocutaneous flaps: long-term follow-up of hypopharyngeal reconstruction.

We have reviewed our experience with 25 patients who have undergone major head and neck resections and required hypopharyngeal pectoralis major flap reconstruction. Six patients were alive 1 year following reconstruction and five patients consented to evaluation of flap function with endoscopy, with biopsy, barium swallow, and esophageal manometrics. The patients were older (61 +/- 6 years) and the flaps were large (42 +/- 9 cm2). Barium studies were the most useful method of evaluating these patients. Postoperative stricture and laryngeal aspiration were found in two patients. Biopsy of the flap demonstrated loss of keratin in the overlying epidermis, while the gross appearance was more like the surrounding mucosa. A review of dietary intake in these cases revealed that two patients weighed less than their preoperative weights, while another refused oral feedings despite a good functional result. Three of five patients preferred gastrostomy feedings to oral alimentation.

Aged↗
PubMed1986

Split jejunal free-tissue transfer in oropharyngoesophageal reconstruction.

From January 1, 1981 to July 1, 1981, ten patients underwent immediate reconstruction utilizing split jejunal free-tissue transfers following resection of large oropharyngeal neoplasms. All 10 flaps were successfully transferred. Three patients were irradiated preoperatively and six patients were irradiated 2 to 3 weeks postoperatively. Nine patients were available for follow-up until their death from 10 to 39 months postoperatively (average 26 months). All but two patients died of their original tumor. Six of the nine patients had a good early functional result; taking semisoft or soft diets allowed them to maintain or gain weight. Three patients had poor early results with limited oral feedings due to repeated aspiration in two and severe gastroesophageal reflux in another. Postoperative graft biopsies were obtained in five patients, showing normal mucosa or mild chronic inflammation histologically even following irradiation. Postoperative barium studies showed varying degrees of graft peristalsis. Complication rates were acceptable, and donor-site morbidity was minimal. Neither preoperative nor postoperative radiation affected the viability of the grafts. Therefore, this technique should continue to find application as a reliable method of providing like tissue for reconstructing a variety of large oropharyngeal defects.

Aged↗
PubMed1985

Brown recluse spider bites. A comparison of early surgical excision versus dapsone and delayed surgical excision.

In a prospective study, 31 patients with brown recluse spider bites were treated by either immediate surgical excision or with the leukocyte inhibitor, dapsone, followed by delayed surgical excision. Patients were matched for age, gender, and lesion size and were excluded if the typical history and physical findings were not present. In patients treated with immediate surgical excision (N = 14), delayed wound healing (N = 5) and objectional scarring (N = 7) were common complications. However, pretreatment treatment with dapsone reduced the incidence of wound complications (N = 1) and objectional scarring (N = 1) (p less than 0.05), while reducing the need for surgical excision (N = 1). There were no severe drug reactions due to dapsone, although one patient had persistent G.I. upset. Pretreatment with dapsone not only reduced surgical complications but also improved the outcome of patients bitten by the brown recluse spider.

Adolescent↗
PubMed1985

Neurofibromas of the head and neck.

Ten patients ranging in age from 7 to 47 years have been treated for neurofibromas of the head and neck at Vanderbilt University Hospital during the last 14 years. Three of them had a positive family history of von Recklinghausen's disease; none has developed malignant degeneration. Serial subtotal excisions of the lesions was the primary treatment.

Adolescent↗
PubMed1985

Sacral pressure sores: treatment with island gluteus maximus musculocutaneous flaps.

We have used the island gluteus maximus musculocutaneous flap to cover sacral pressure sores. In this report, we describe the surgical anatomy, cadaveric dissections (n = 25), and postoperative follow-up (one to 40 months) in 13 clinical cases. Our results compare favorably with those of other previously reported series. Postoperative complications are few (n = 2) and late recurrence is acceptable (n = 1). Since the surgical anatomy is consistent and the operative technique simple, this procedure may be the treatment of choice for sacral pressure sores.

Adult↗
PubMed1979

Pectoralis major musculocutaneous flap: a new flap in head and neck reconstruction.

The pectoralis major musculocutaneous flap described by Ariyan has great potential in single stage reconstructions of the head and neck. The advantages of the flap are greater length, improved vascularity, bulk, and one-stage reconstruction of oropharyngeal defects. The flap was used successfully in eight patients to reconstruct large defects in the head and neck area. Experience to date indicates that this flap has greater versatility than the deltopectoral flap in one-stage head and neck reconstructions.

Adult↗
PubMed1979

Long-term experience with childhood thyroid carcinoma.

Twenty patients with well-differentiated thyroid carcinoma, 20 yr of age or younger have been treated at Vanderbilt University Hospital. The young patient with thyroid carcinoma frequently presents with far-advanced disease but enjoys an improved survival. Preoperative scintiscanning is useful in the evaluation of patients with childhood thyroid carcinoma. A new noninvasive scan is described and appears to be promising in the preoperative differentiation between benign and malignant thyroid lesions in children and young adults. There is a high instance of nodal metastases, but long-term follow-up would indicate that lobectomy and modified neck dissection are sufficient for most patients. However, total thyroidectomy can be performed safely in those patients with disease in both lobes. Additionalally, frozen section diagnoses were found to be helpful in diagnosing and staging thyroid carcinoma.

Adenocarcinoma↗
PubMed1979

Use of the free dorsalis pedis flap in head and neck repairs.

Many defects of the head and neck can be readily repaired with a free dorsalis pedis flap, and we report success with these flaps in 9 of 12 cases. A precise knowledge of the anatomy of the arterial supply of the flap is necessary. Preoperative arteriography is recommended if the dorsalis pedis artery is not easily palpable, or if an anomalous distribution of the artery along the dorsum of the foot is sus pected. However, the transfer of the flap should be delayed for two weeks after preoperative arteriography is performed. The one-stage soft tissue reconstruction with a free dorsalis pedis flap has been associated with minimal morbidity and good acceptance by patients. A delay procedure for the flap seems to enhance the chances of complete survival which is so necessary in the repair of intraoral and pharyngeal defects. Careful attention to details and close monitoring of the flap will minimize morbidity. In case of an early failure of a flap, a secondary reconstruction by a different flap can be done in the first 48 to 72 hours. Early postoperative radiotherapy has been well tolerated over these free flaps.

Aged↗