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Biomedical subjects

K E Wells

Publications and source records attributed to K E Wells.

At least 37 records · Page 2Linked to original sources
PubMed1997

The clinical relevance of sentinel lymph nodes identified with radiolymphoscintigraphy.

BACKGROUND: The purpose of this case report is to illustrate the utility of radio-guided mapping of sentinel lymph nodes (SLN's) as demonstrated by the technique's successful identification of nodes containing metastatic disease that would have been left behind if only the visual-oriented vital blue dye mapping technique had been used. METHOD: The patient underwent preoperative lymphoscintigraphy and intra-operative lymphatic mapping using vital blue dye and radiolymphoscintigraphy using the Neoprobe (handheld gamma probe). Nodes which were blue and/or "hot" (i.e., radioactive counts were three times the background count) were considered SLN's. RESULTS: Four SLN's were harvested, all of which were "hot" but only one of which was both "hot" and blue. Pathology revealed that the two SLN's positive for metastatic disease were not blue. CONCLUSION: While the blue dye lymphatic mapping technique provides the surgeon with a visual road map in the identification of SLN's, the Neoprobe increases the success rate of localization when compared to vital blue dye mapping due to the reliable migration of radiocolloid to the SLN's in the regional basin. Radiolymphoscintigraphy also increases the accuracy and efficiency of the SLN harvest by providing a directed dissection to the level of the nodes in the basin. The Neoprobe increases the yield of SLN's, some of which are clinically relevant since they contain metastatic disease.

Coloring Agents↗
PubMed1996

Sex hormones affect the calcium signaling response of human arterial cells to LDL.

The present study was designed to examine the role of calcium-dependent signal transduction as a common link between the atherogenic effect of LDL and the mitigating influence of sex hormones in aortic endothelial (EC) and smooth muscle cells (SMC). Human aortic EC and SMC were pre-incubated for 48 hr in media containing no hormone, 17-beta-estradiol (20 ng/ml) or testosterone (300 ng/ml). Low density lipoprotein (N-LDL) or its minimally oxidized species (Ox-LDL) was added to the media at different concentrations (0, 2, 5, 10, 20, and 40 micrograms protein/ml), and changes in cytosolic calcium [Ca+2]i were measured by spectrofluorometric analysis using a Fura 2-AM indicator. Cell viability was determined with a 51chromium release assay. In EC, exposure to N-LDL resulted in a weak and unsustained increase in [Ca+2]i, (max. 21.9 +/- 4.6%) while a more marked rise was seen in SMC (max. 79.1 +/- 11.5%; P < 0.005). There was an amplified response to the more atherogenic Ox-LDL in both EC (max. 130.9 +/- 22.9%) and SMC (max. 240.5 +/- 14.2%; P < 0.0002). Estrogen was associated with a lower resting level of [Ca+2]i in both cell types, and resulted in a significant, dose-dependent inhibition of cytosolic calcium mobilization in SMC exposed to Ox-LDL (P < 0.05). Alternatively, testosterone increased cytosolic calcium response in SMC exposed to either N-LDL (P < 0.05) or Ox-LDL (P < 0.05). Similar trends were seen in EC, but failed to reach statistical significance. These changes could not be attributed to cell toxicity. Sex hormones may modulate the atherogenic potential of LDL by influencing intracellular, calcium-dependent signaling mechanisms.

Analysis of Variance↗
PubMed1996

The role of composite sequential bypass in the treatment of multilevel infrainguinal arterial occlusive disease.

BACKGROUND: In this study, the efficacy of composite sequential bypass is compared to that of standard in situ bypass, and to alternate prosthetic graft systems which have been used for the treatment of multilevel infrainguinal arterial occlusive disease in the absence of suitable autogenous vein. PATIENTS AND METHODS: A retrospective review of graft patency and limb salvage included 197 patients undergoing 211 bypass procedures consisting of in situ femoral-tibial (IS; n = 119); composite sequential (CS; n = 35), prosthetic femoropopliteal with single (PFP-1; n = 30) or no vessel runoff (PFP-O; n = 9), and prosthetic femoral-tibial (PFT; n = 18) bypass. RESULTS: By life-table analysis, IS bypass provided superior primary (P < 0.005) and secondary (P < 0.0005) patency over the other groups. CS bypass was similar to PFP-1, with a 2-two year primary patency of 35% and 44% (NS), respectively, and limb salvage rates of 60% and 80% (P = 0.01). PFP-O and PFT bypass procedures did considerably worse, with a 1-year patency of 19% and 22%, respectively, and associated limb salvage rates of 25% and 41% (NS). CONCLUSIONS: Composite sequential bypass is an acceptable procedure for infrainguinal arterial reconstruction when absence of autogenous vein prevents either in situ or secondary vein graft bypass procedures.

Arterial Occlusive Diseases↗
PubMed1996

Calcium-dependent second-messenger regulation of low-density lipoprotein oxidation by human aortic smooth muscle cells.

BACKGROUND: We postulated that the response of vascular smooth muscle cells (SMCs) to oxidized low-density lipoprotein (LDL) may be modulated through calcium and 3', 5' cyclic adenosine monophosphate (Ca+2-cAMP) second-messenger activity. METHODS: Changes in cytosolic calcium [Ca+2]i in aortic SMCs exposed to native (N-) and oxidized (Ox-) LDL were measured with a Fura 2-AM indicator. The influence of cAMP on this response was determined by incubating the cells with either forskolin or 8-bromo-cAMP (stimulatory) or galanin (inhibitory). The cells were then activated by an initial preincubation with N- or Ox-LDL, and the subsequent cellular oxidation of N-LDL was measured. The effect of cAMP mediators alone or in conjunction with calcium antagonism was studied. RESULTS: Exposure of SMCs to Ox-LDL resulted in a marked elevation of [Ca+2]i(306 +/- 12 nmol/L) compared with that in the control group (192 +/- 15 nmol/Liter; p < 10(-6)). This response was augmented by cAMP stimulation (406 +/- 8 nmol/L; p < 10(-6)) but reduced by cAMP inhibition (247 +/- 8 nmol/L; p < 10(-6)). The activation of intracellular signaling by initial Ox-LDL priming increased the subsequent oxidation of N-LDL (0.40 +/- 0.02 nmol malondialdehyde versus 0.24 +/- 0.02 nmol MDA control; p < 10(-4)). This response was enhanced by cAMP (0.45 +/- 0.03 nmol MDA; p < 10(-4)) and inhibited by galanin (0.26 +/- 0.02; p < 10(-4)). The cAMP effect was reversed by the blockade of calcium mobilization via membrane channels and reticular release. CONCLUSIONS: Oxidized LDL-induced Ca+2-cAMP signaling modulates the cellular oxidation of N-LDL. This finding suggests a mechanism through which the scavenger uptake of modified LDL may potentially be regulated.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder with a high spontaneous mutation rate and no effective treatment, hence development of genetic based therapies is an important goal. We report that expression of a recombinant human minidystrophin cDNA, compatible with current viral vectors, can significantly reduce the myopathic phenotype in transgenic mdx mice, even when expressed at only 20-30% of endogenous dystrophin levels at the sarcolemma. To the extent that data obtained in mouse studies are applicable to DMD, the virtual elimination of morphological and biochemical abnormalities in the mdx mouse supports the use of this cDNA in somatic gene therapy protocols for DMD.

Animals↗
PubMed1995

Psychological and rheumatic symptoms of women requesting silicone breast implant removal.

In this case series, we describe the psychological and rheumatic symptoms of 52 women requesting breast implant removal. Main outcome measures include psychological evaluation with the Brief Symptom Inventory and the Beck Depression Inventory. Clinical evaluation was performed using a rheumatic symptom survey. Results noted elevation of all Brief Symptom Inventory subscales (highest in Somatization and Obsessive-Compulsive), and the Beck Depression Inventory showed mild depression. Rheumatic survey noted a mean of 12 of 23 symptoms. In conclusion, psychological distress and mild depression are noted in this group, who also may experience rheumatic symptoms of connective tissue disease. There was a moderate positive correlation between rheumatic symptoms and psychological distress.

Breast Implants↗
PubMed1994

Local increase in hyaluronic acid and interleukin-2 in the capsules surrounding silicone breast implants.

Connective tissue disease-like illness has been associated with silicone breast implants. However, no data are currently available on the immunopathology of the capsule surrounding the breast implants. Sera from women with breast implants were collected and assayed for interleukin-6 (IL-6), IL-2, and hyaluronic acid. Capsular biopsies were stained with a probe for HYA or with monoclonal antibodies specific for human macrophages (CD68), T cells (CD4), IL-6, and IL-2. Control specimens consisted of breast biopsies from women undergoing reduction mammoplasty. Our results revealed an increased local amount of hyaluronic acid in the capsule of patients with breast implants compared with control breast tissue. The HYA was localized extracellularly in areas containing fibrosis and cellular infiltrates. The infiltrating cells were determined to be primarily macrophages and T cells. No IL-6 was localized in any of the tissue sections. In contrast, large amounts of IL-2 were found in regions of infiltrating lymphocytes. No significant increase in IL-6, IL-2, or hyaluronic acid was found in the sera. The role of hyaluronic acid and cytokines in the inflammatory response in the capsules of silicone breast implants is discussed.

Breast↗
PubMed1994

Extramammary Paget's disease of the scrotum.

This case report describes a patient with extramamary Paget's disease of the scrotum. Treatment consisted of excision and primary closure with local advancement flaps. A review of the literature and treatment of extramammary Paget's disease are discussed.

Aged↗
PubMed1994

The use of lymphoscintigraphy in melanoma of the head and neck.

Lymphoscintigraphy has been shown to be of assistance in defining the lymphatic drainage pattern of melanoma. In this study, lymphoscintigraphy was performed on 25 patients with primary melanoma (stages I and II at diagnosis) of the head and neck to determine whether the lymphatic drainage seen on lymphoscintigram was the same as the surgeon's expected lymphatic drainage. The lymphoscintigrams were discordant in 21 of the patients (84 percent) with drainage to a lymphatic basin not predicted clinically. Based on the discordant lymphoscintigram, a change in surgical therapy occurred in 13 of 21 patients (62 percent). Of the 25 patients, 18 underwent prophylactic node dissections and 7 did not. Of the nodal basins removed, 27 of 38 nodal bases (71 percent) were seen on lymphoscintigraphy. Melanoma metastatic to lymph nodes was removed from nodal basins identified by the lymphoscintigram, but not predicted clinically, in two patients (8 percent). Historical anatomical patterns of lymph drainage and the clinical impression of experienced surgeons cannot reliably predict the pattern of lymphatic drainage in patients with melanoma of the head and neck.

Adolescent↗
PubMed1994

The health status of women following cosmetic surgery.

A retrospective study was performed to determine the frequency of new symptoms and diseases after silicone breast implantation. Questionnaires were mailed to 826 women who made up a breast implant group (n = 516) and a control group who had undergone blepharoplasty (n = 124), liposuction (n = 111), or rhinoplasty (n = 75). Responses were obtained from 370 women (45 percent); however, 68 of these patients (18 percent) were considered ineligible. The overall response rate was 59 percent for the breast implant group and 46 percent for controls. The 302 eligible women included patients with silicone breast implants (n = 222) and controls (n = 80). Women with implants were significantly younger than controls, the median age of women with breast implants being 37 years compared with 46.5 years for controls (p < 0.0001). We compared the incidence of 23 symptoms and 4 connective-tissue diseases after cosmetic surgery in the two groups. The symptoms of swollen glands under arms (p < 0.05) and tender glands under arms (p < 0.01) were statistically more frequent in the breast implant group. The symptom change in skin color was more common in the controls (p < 0.001). The Bonferroni correction for multiple (27) endpoints adjusts the 5 and 1 percent significance cutoff points to 0.00185 and 0.00037, respectively, leaving only change of skin color significant at the 5 percent level on the adjusted data. No cases of scleroderma or lupus were found, and the incidence of arthritis was not significantly different between the implant and control groups.

Adult↗
PubMed1994

Independent localization of dystrophin N- and C-terminal regions to the sarcolemma of mdx mouse myofibres in vivo.

Dystrophin has been proposed to associate with the skeletal muscle membrane by way of a glycoprotein complex that interacts with its C-terminal domains. Transfection of mdx mouse myotubes in culture or myofibres in vivo with recombinant genes encoding human dystrophin deletion mutants shows, however, that not only the C terminus of dystrophin but also its N-terminal actin-binding domain can locate independently to the muscle sarcolemma. This observation suggests that lack of sarcolemma-associated dystrophin in Duchenne muscular dystrophy (DMD) muscle may result from enhanced degradation of truncated mutation products rather than their inability per se to associate with the sarcolemma.

Animals↗
PubMed1993

Chronic pressure ulcer carcinomas.

Carcinomas arising from chronic pressure ulcers, Marjolin's ulcers, are an uncommon occurrence. They are virulent cancers that require aggressive surgical treatment. We present 3 such cancers including the first report of a squamous cell carcinoma arising in a distal extremity pressure ulcer. Carcinomas arising in chronic pressure ulcers behave more aggressively than other types of Marjolin's ulcers and, therefore, they need to be treated more aggressively. Extensive surgical excisions with wide surgical margins are necessary and elective lymph node dissections should be considered for optimal therapy.

Adult↗
PubMed1992

Human dystrophin expression corrects the myopathic phenotype in transgenic mdx mice.

Duchenne and the less severe Becker form of muscular dystrophy (DMD,BMD) result from genetic deficiency in the level and/or activity of the protein dystrophin. The recent availability of cDNA based minigenes encoding recombinant dystrophin polypeptides has raised the possibility of somatic gene transfer as a therapeutic approach to treat dystrophin deficiency. In this respect, the mdx mouse provides a useful model of DMD exhibiting features characteristic of both the early myopathic and later fibrotic phases of the human disease. Using a mutated human cDNA, compatible in size with virus-based somatic gene transfer vectors, the pathophysiological consequences of restoring dystrophin expression have been examined in transgenic mdx mice. Transgene expression was correlated with a marked reduction of the skeletal myofibre necrosis and regeneration which is a major feature of the dystrophin-deficient phenotype in young mdx mice. The cDNA construct which is based on a very mild BMD phenotype thus encodes a highly functional dystrophin molecule whose reduced size renders it an attractive candidate for development as a therapeutic gene transfer reagent.

Animals↗
PubMed1992

Treatment of the primary in malignant melanoma of the skin.

Surgical excisional therapy of malignant melanoma is the primary method of treatment for malignant melanoma. The exact size of the excisional therapy depends on the depth and location of the tumor. At the University of South Florida (Tampa, FL), tumors less than 0.76 mm in depth are resected with a 1-cm margin and tumors greater than 0.76 mm in depth are resected with a 3-cm margin. The location of the tumor also determines the exact margin of excision. Maximal reconstructive efforts following general principles of plastic and reconstructive surgery are noted and used for producing an optimal functional and aesthetic result.

Esthetics↗