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Biomedical subjects

R M Barton

Publications and source records attributed to R M Barton.

At least 19 recordsLinked to original sources

An in vivo comparison of topical agents on wound repair.

Selection of the ideal antiseptic or antimicrobial treatment for contaminated wounds remains a controversial decision. Clinical decisions are often made on the basis of in vitro studies and personal preference. Although topical solutions are widely used, their comparative in vivo effects on wound healing are largely unreported.A porcine wound model was used to compare five commonly used topical agents-5% mafenide acetate (Sulfamylon solution), 10% povidone with 1% free iodine (Betadine), 0.25% sodium hypochlorite ("half-strength" Dakin), 3% hydrogen peroxide, and 0.25% acetic acid-with a control group. Reepithelialization, angiogenesis, neodermal regeneration, fibroblast proliferation, collagen production, and bacterial colony counts were analyzed at 4 and 7 days after wounding (n = 4). Reepithelialization was not significantly influenced among the various treatment modalities tested. Sulfamylon and Dakin solutions significantly increased neodermal thickness (p < 0.05), whereas hydrogen peroxide and acetic acid significantly inhibited neodermal formation (p < 0.001). All treatments except hydrogen peroxide significantly increased fibroblast proliferation. Sulfamylon and Betadine significantly enhanced angiogenesis (p < 0.05). Sulfamylon proved most effective in maintaining an aseptic environment while concomitantly increasing angiogenesis, fibroblast proliferation, and dermal thickness compared with control. These data show that selection of a particular topical treatment can affect various aspects of wound repair in an animal model. These results suggest that the selection of topical treatments in the clinical setting should be carefully tailored to match unique wound situations and therapeutic endpoints.

Administration, Topical↗

Prenylated prelamin A interacts with Narf, a novel nuclear protein.

Prelamin A is farnesylated and methylated on the cysteine residue of a carboxyl-terminal CaaX motif. In the nucleus, prelamin A is processed to lamin A by endoproteolytic removal of the final 18 amino acids, including the farnesylated cysteine residue. Using the yeast two-hybrid assay, we isolated a novel human protein, Narf, that binds the carboxyl-terminal tail of prelamin A. Narf has limited homology to iron-only bacterial hydrogenases and eukaryotic proteins of unknown function. Narf is encoded by a 2-kilobase mRNA expressed in all human cell lines and tissues examined. The protein is detected in the nuclear fraction of HeLa cell lysates on Western blots and can be extracted from nuclear envelopes with 0.5 M NaCl. When a FLAG epitope-tagged Narf is expressed in HeLa cells, it is exclusively nuclear and partially co-localizes with the nuclear lamina. The farnesylation status of prelamin A determines its ability to bind to Narf. Inhibition of farnesyltransferase and mutation or deletion of the CaaX motif from the prelamin A tail domain inhibits Narf binding in yeast two-hybrid and in vitro binding assays. The prenyl-dependent binding of Narf to prelamin A is an important first step in understanding the functional significance of the lamin A precursor.

Amino Acid Sequence↗

Synergistic interaction between cisplatin and tamoxifen delays the emergence of cisplatin resistance in head and neck cancer cell lines.

The interaction between cisplatin (cDDP) and tamoxifen (TAM) was evaluated in the human head and neck squamous-carcinoma cell lines UM-SCC-10B and UM-SCC-5. Synergy between cDDP and TAM was demonstrated in the UM-SCC-10B cell line. Concordant with the synergistic effect between cDDP and TAM, the rate of development of resistance to cDDP was delayed when selections were performed in the presence of TAM. However, in the UM-SCC-5 cell line, TAM was neither synergistic nor did it delay the development of cDDP resistance. The difference with respect to the synergistic interaction of cDDP with TAM and the effect on the development of cDDP resistance in the UM-SCC-10B and UM-SCC-5 cell lines was not related to any significant difference in the accumulation of the cDDP analog [3H]-cis-dichloro(ethylenediamine)platinum(II) (DEP), drug sensitivity [concentrations inhibiting colony formation by 50% (IC50 values) were 6.5 and 7.2 microM for cDDP and 3.5 and 3.2 microM for TAM, respectively], the number of estrogen and progesterone receptors (negative in both cell lines), the number of antiestrogen binding sites (404 +/- 85 and 353 +/- 24 fmol/mg protein, respectively), or the affinity of TAM for these binding sites (1.7 and 1.5 nM, respectively). Importantly, however, we demonstrated that TAM can delay the emergence of resistance to cDDP in head and neck carcinomas and that this effect is linked to the nature of the interaction between cDDP and TAM.

Binding Sites↗

Induction of the growth arrest and DNA damage-inducible gene GADD153 by cisplatin in vitro and in vivo.

The inability to assess the extent of tumour damage immediately following treatment is a major clinical obstacle to improving the management of cancer patients. Normally, the effectiveness of chemotherapy or radiation therapy cannot be determined for at least several weeks after treatment. We studied the increase in mRNA of the growth arrest and DNA damage-inducible gene GADD153 in human 2008 ovarian carcinoma cells in vitro and in vivo to determine whether treatment-induced increases in the level of GADD153 mRNA could be used as a marker of the extent of tumour damage. GADD153 mRNA was increased in a transient, dose-dependent manner by cisplatin (DDP) when the tumour cells were grown both in vitro and as tumour xenografts in nude mice. The magnitude of induction of GADD153 mRNA did not vary significantly between different 2008 xenografts treated with equal doses of DDP, and GADD153 mRNA induction correlated with the degree of in vitro cytotoxicity for two different schedules of drug exposure. DDP increased GADD153 mRNA levels in melanoma and head and neck xenograft models as well. We conclude that the increase in GADD153 mRNA can be used to detect tumour injury at time points as short as 24 h after administration of DDP.

Animals↗

Is aggressive surgical management justified in the treatment of Merkel cell carcinoma?

Since its original description in 1972, we have seen and personally treated a group of 15 patients with Merkel cell carcinoma at the Vanderbilt Medical Center and the Nashville VA Hospital. We will review the demographics, management, and clinical course of this extremely lethal but initially benign appearing cutaneous malignancy. The majority of lesions occur on the head and neck, followed by the extremities and trunk. Location of the primary tumor has no effect on outcome. Despite a high mortality in our series (10 of 15), early recognition and aggressive surgical therapy may be the only way to prolong survival. No other adjuvant therapy has proved effective.

Aged↗

Rigid internal fixation vs. traditional techniques for the treatment of mandible fractures.

Treatment results were compared between mandibular fractures repaired with vitallium miniplates versus intermaxillary fixation (IMF) and wire osteosynthesis in 79 patients treated over a 4-year period. The postoperative courses of 35 patients treated with 46 plates were compared to those of 44 individuals treated with traditional reduction techniques. The plated group contained nine complications (26%) versus ten (23%) in the non-plated group. This difference was not statistically significant, despite the presence of more severe fractures in the plated group. Major complications (nonunions, malocclusions) were noted in only three (8%) of the plated group; there were six complications (14%) in the non-plated group. We conclude that the plating of mandibular fractures incurs no greater overall risk of complications than traditional methods of fixation, and a lower risk of major complications, and that the advantages of plate fixation, including decreased time of intermaxillary fixation and cost effectiveness, make this the method of choice in complex mandibular fractures, even in a high-risk population.

Adult↗

Multivariate analyses of cognitive and cognitive style variables based on hemisphere specialization theory predictive of success in a college developmental studies program.

Right and left cerebral hemisphere and limbic scores derived from the Herrmann Brain Dominance Profile, Scholastic Aptitude Test Verbal and Mathematics scores, and High School Grade Point Average were correlated with grades in college developmental courses in reading, English, and mathematics for 146 students. Pearson correlations ranged from -.27 to .42. Multiple correlations with seven predictors ranged from .45 to .55, and from .14 to .37 for the profile scores alone. Discriminant analyses yielded hit-rates (predictive of classification of success and failure/actual classification) of 69%/72% in Reading, 76%/75% in English, and 66%/71% in Mathematics.

Achievement↗

Use of sonography in the early detection of suppurative flexor tenosynovitis.

Eighteen patients with swollen fingers suggesting acute suppurative tenosynovitis were studied by ultrasonography. All patients received intravenous antibiotics. Twelve patients required surgical drainage. Eleven of 12 patients had sonographic evidence of both a swollen tendon and fluid in the flexor sheath. Eleven of the 12 patients operated on had purulent fluid in the flexor sheath. Four of the operative cases were culture positive and four were culture negative. All six patients treated only with antibiotics had swollen tendons, but five of the six had no sonographic evidence of fluid in the flexor sheath. All patients had a full recovery. Sonographic evidence of fluid in the flexor sheath is a useful sign in the early diagnosis of acute suppurative flexor tenosynovitis.

Adult↗

Comparative study of vascularized and nonvascularized tendon grafts for reconstruction of flexor tendons in zone 2: an experimental study in primates.

Vascularized tendon grafts were compared with nonvascularized tendon grafts in a primate experimental model. In four monkeys, seven vascularized extensor hallucis longus grafts were placed in the foot's digital fibroosseous canal and these were compared with eight nonvascularized tendon grafts similarly placed in the opposite extremities. The juncture techniques and postoperative protocols were identical for both tendon groups. All tendons were explored 5 months after insertion. The vascular pedicle was patent in all vascularized tendons. Three tendon ruptures occurred in nonvascularized tendons and only one rupture occurred in a vascularized tendon. The digits with vascularized tendons demonstrated a significantly better simulated total active motion (117 degrees versus 128 degrees, p less than 0.05) than digits with nonvascularized tendons. The difference was even more significant when a localized tenolysis of the proximal juncture of the tendon graft was performed (215 degrees versus 138 degrees, p less than 0.01). This study supports the concept that vascularized tendon grafts may be advantageous in scarred tendon beds.

Animals↗

Long microvenous allografts in rabbit femoral arteries and veins.

In this study the patency of long microvenous allografts in rabbits with and without immunosuppressive drug therapy was investigated. Eighty-two microvenous autografts (controls) and allografts were transplanted into rabbit femoral vessels. Veno-venous autograft controls were 100% patent at 3 weeks. Rejection of non-immunosuppressed veno-venous allografts consistently produced occlusion between 15-20 days. Thrombus filled the lumen, and a leucocyte invasion destroyed the graft wall. In contrast vein allografts into arteries were 100% patent at 3 weeks; this was reduced to 50% at 4 weeks. Low (5 mg/kg/day) and high (20 mg/kg/day) doses of hydrocortisone over 21 days improved the 3 week patency in veno-venous allografts to 28.5% and 57.0% respectively. Cyclosporin A (15 mg/kg/day) over 8 or 22 days significantly increased the patency rate of veno-venous allografts to 100%. Only cyclosporin A treated rabbits maintained allografts of normal vein morphology to 3 weeks.

Animals↗

Acute suppurative tenosynovitis of the hand: diagnosis with US.

The sonographic findings in seven patients with surgically proved acute tenosynovitis of the hand (bacterial in six cases, of presumed viral origin in one) were reviewed. In the six patients with bacterial tenosynovitis the affected flexor tendon was larger than that of the contralateral normal digit. In five patients hypoechoic areas were identified surrounding the flexor tendon that proved to be pus at surgery. Sonography failed to depict a small amount of pus in the tendon sheath in one patient. The affected tendon of the single patient with tenosynovitis thought to be of viral origin was normal in size, but a focal tendon sheath fluid collection was detected that proved to be sterile at surgery. Sonography appears to be a useful imaging technique in the early diagnosis of acute suppurative tenosynovitis of the hand.

Acute Disease↗

Protein metabolism and fibrosis in experimental canine obstructive lymphedema.

Obstructive lymphedema is a pathologic condition resulting in the accumulation and stagnation of serum proteins in the lymphatics and interstitial spaces. In a canine model of obstructive lymphedema, one limb was rendered lymphedematous, and various biochemical parameters were determined in this and an unaffected control limb. Both lymph and interstitial fluid had significantly decreased acid proteinase activity (comprising mostly cathepsin D-like enzymes) and neutral proteinase activity (comprising metallo, sulfhydryl, and serine proteinases, and collagenase). Possible reasons for these decreases could be: (1) saturation of macrophages and their surrounding environment with whole or partially digested proteins, or (2) elevation in the levels of circulating inhibitors like alpha 2-macroglobulin. The lymphedematous skin was significantly thicker than control skin and had elevated levels of collagen. However, unlike some fibrotic conditions, the relative proportions of types I, III, and V collagen, as determined by pepsin solubilization and neutral salt fractionation of the collagen fibrils, were similar to those found in normal skin. It is speculated that a decrease in the breakdown of collagen by collagenase and a continuing synthesis of collagen by fibroblasts led to an imbalance in favor of collagen deposition in the skin.

Animals↗

The implications of local recurrence of breast cancer as the first site of therapeutic failure.

Sixty patients who had ipsilateral chest wall recurrence of breast cancer and no detectable distant metastases were evaluated retrospectively to determine the implications of chest wall recurrence as the first site of therapeutic failure. Mean time intervals between treatment of the primary breast cancer and discovery of local recurrence, between treatment of local recurrence and distant metastases, and between treatment of local recurrence and death in order and, respectively, in years for pathologic Stages I, II, and III patients were 6.2, 4.3 and 2.1; 4.2, 3.5, and 1.2; and 7.2, 6.0, and 2.5. Surgical resection resulted in the best local control. All patients eventually died of metastatic breast cancer, one as late as 23 years after treatment of the local recurrence. No Stage I patients recurred before two years. An arbitrary delay of two years before recommending breast reconstruction to avoid masking local recurrence seems unjustified for pathologic Stage I patients.

Breast Neoplasms↗

Carcinoma of the ampulla of Vater.

A retrospective study of 56 patients with carcinoma of the ampulla of Vater revealed a resectability rate of 79.0 per cent and an operative mortality of 2.3 per cent. Although 55 per cent of those undergoing pancreaticoduodenectomy had complications postoperatively, these were usually self-limiting and did not require operative intervention. The five year survival rate was 23 per cent. The most significant pathologic determinant of long term survival was the nodal status at the time of exploration. Local recurrence after resection for cure was common as the first site of treatment failure and raises the question of the value of a more aggressive surgical approach or adjuvant radiation therapy to the surgical fields. The reason for a local recurrence appeared to be failure to remove all microscopic disease at the initial operation. Multifocal origin within the biliary tract could have contributed to the local recurrence. However, residual disease within the remaining pancreas after pancreaticoduodenectomy was a problem in only one patient. When disease was locally advanced, short term palliation was best accomplished by pancreaticoduodenectomy. However, survival beyond two years was no different from that of those treated by simple biliary bypass.

Adult↗