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R Phelps

Publications and source records attributed to R Phelps.

At least 19 recordsLinked to original sources
PubMed2003

Lichen planus and the vulvovaginal-gingival syndrome.

Lichen planus is a dermatologic disease that affects both skin and mucosa. Here we report five cases of lichen planus that presented as the oral component of the vulvovaginal-gingival syndrome. Four of the cases were associated with biopsy-proven oral lichen planus, and all five patients had oral lesions that clinically resembled lichen planus. Three patients were taking medications that are associated with lichenoid drug reactions; four patients were postmenopausal; and all five patients had desquamative vulvovaginitis. Clinicians may see these patients when they show persistent signs and symptoms of oral lichen planus. We report five case histories and review the 127 cases found in the literature to make the practicing clinician aware of this unusual clinical entity. The hepatitis C virus association and drug-induced lichenoid mucositis are topics that are addressed. In addition, clarification of the issues surrounding the premalignant potential of oral lichen planus is provided with evidence, rationale, and data from the literature to support the position that true oral lichen planus has no inherent predisposition to become malignant.

Adult↗
PubMed2002

Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood.

BACKGROUND: The detection of disseminated tumor cells in peripheral blood is limited by the presence of very few tumor cells within a large number of blood cells. Therefore, tumor cell detection calls for enrichment systems with effective depletion of blood cells and high tumor cell recovery. METHODS: We compared the new density gradient centrifugation method OncoQuick with the standard method of Ficoll. The enriched cell fractions were quantified. Tumor cell spiking experiments examined the recovery of tumor cells as detected by immunocytochemistry and cytokeratin-20 reverse transcriptase-polymerase chain reaction (RT-PCR). Clinical application of OncoQuick was evaluated in 37 peripheral blood samples of patients with gastrointestinal carcinomas. RESULTS: The depletion of mononuclear cells (MNCs) in the enriched cell fraction after OncoQuick centrifugation was 632-fold, with an average cell number of 9.5 x 10(4), compared with Ficoll, with a depletion factor of 3.8 and a mean number of 1.6 x 10(7) MNCs. The mean tumor cell recovery rates were 87% for OncoQuick and 84% for Ficoll. The increased depletion of MNCs with OncoQuick centrifugation further simplified immunocytochemical evaluation by reducing the number of cytospins and increasing the tumor cell density. Due to the reduced number of co-enriched MNCs by OncoQuick, the blood volume, which could be analyzed in one RT-PCR reaction, was increased up to 30 ml. Examination of peripheral blood samples from 37 patients with gastrointestinal tumors showed a cytokeratin-20 detection rate of 30% and a significant correlation with the presence of distant metastases (P < 0.02). CONCLUSIONS: OncoQuick significantly reduced the co-enriched number of MNCs, with a high tumor cell recovery rate. Processing blood from tumor patients with OncoQuick increased the chance of detecting circulating tumor cells.

Cell Count↗
PubMed2001

A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies.

Fabry disease results from deficient alpha-galactosidase A (alpha-Gal A) activity and the pathologic accumulation of the globotriaosylceramide (GL-3) and related glycosphingolipids, primarily in vascular endothelial lysosomes. Treatment is currently palliative, and affected patients generally die in their 40s or 50s. Preclinical studies of recombinant human alpha-Gal A (r-halphaGalA) infusions in knockout mice demonstrated reduction of GL-3 in tissues and plasma, providing rationale for a phase 1/2 clinical trial. Here, we report a single-center, open-label, dose-ranging study of r-halphaGalA treatment in 15 patients, each of whom received five infusions at one of five dose regimens. Intravenously administered r-halphaGalA was cleared from the circulation in a dose-dependent manner, via both saturable and non-saturable pathways. Rapid and marked reductions in plasma and tissue GL-3 were observed biochemically, histologically, and/or ultrastructurally. Clearance of plasma GL-3 was dose-dependent. In patients with pre- and posttreatment biopsies, mean GL-3 content decreased 84% in liver (n=13), was markedly reduced in kidney in four of five patients, and after five doses was modestly lowered in the endomyocardium of four of seven patients. GL-3 deposits were cleared to near normal or were markedly reduced in the vascular endothelium of liver, skin, heart, and kidney, on the basis of light- and electron-microscopic evaluation. In addition, patients reported less pain, increased ability to sweat, and improved quality-of-life measures. Infusions were well tolerated; four patients experienced mild-to-moderate reactions, suggestive of hypersensitivity, that were managed conservatively. Of 15 patients, 8 (53%) developed IgG antibodies to r-halphaGalA; however, the antibodies were not neutralizing, as indicated by unchanged pharmacokinetic values for infusions 1 and 5. This study provides the basis for a phase 3 trial of enzyme-replacement therapy for Fabry disease.

Adolescent↗
PubMed2001

Mohs micrographic surgery of a plexiform fibrohistiocytic tumor.

BACKGROUND: Plexiform fibrohistiocytic tumor (PFT) is a rare mesenchymal neoplasm first described by Enzinger and Zhang in 1988. Clinically it is characterized by slow growth, frequent local recurrences, and rare systemic metastasis. These tumors occur chiefly in children and young adults and are most commonly located on the shoulders and forearms. OBJECTIVE: To present a case report of an incompletely excised PFT, its complete resection using simple excision and Mohs micrographic surgery, and review of the literature. METHODS: An 11-year-old Hispanic girl was evaluated for the treatment of an incompletely excised plexiform fibrohistiocytic neoplasm located in the right axilla. Mohs micrographic surgery (MMS) was chosen because of the ill-defined borders and the need for tissue conservation. The patient underwent a two-stage, six section, micrographically controlled excision. Upon completion of the MMS a 2 mm final stage, taken as a peripheral and deep section around and underneath the cleared area, was submitted for paraffin embedding. Residual plexiform histiocytic tumor was found at the margin of resection in one location. Reevaluation of the Mohs slides demonstrated the possible presence of tumor at one deep focus. The tumor was reexcised with a 5 mm margin and repeat hematoxylin and eosin staining showed no residual tumor. There has been no evidence of recurrence in 4 years. RESULTS: Complete resection of the PFT and absence of tumor recurrence 4 years later. CONCLUSION: Over the past few years the list of neoplasms for which MMS is the treatment of choice has steadily grown. PFT is a recently described locally aggressive mesenchymal neoplasm with potential for distant metastasis. To our knowledge this is the first time MMS has been used to resect this tumor. To ensure the chance of complete extirpation we recommend the harvest of an additional stage for hematoxylin and eosin staining, as is done in some aggressive squamous cell carcinomas.

Axilla↗
PubMed2000

Acquired dermal melanocytosis in an African-American: A case report.

We report an unusual case of acquired dermal melanocytosis occurring in a 57-year-old African-American woman. Macular pigmentation over the patient's cheeks, back, and sclerae developed over the course of 18 months without identifiable antecedent. The patient was taking only hormone replacement therapy and was generally healthy. Histologic examination of the skin revealed dendritic melanocytes and melanophages in the mid- to upper dermis. We briefly review the literature surrounding acquired dermal melanocytosis and continue discussion regarding its pathogenesis.

Black People↗
PubMed1999

Considerations for ethical practice in managed care.

How does one maintain an ethical practice while facing the requirements and limits of a health care system that is dominated by managed care? Psychologists are increasingly raising such questions about ethical issues when working in or contracting with managed care organizations. The authors review the process involved in ethical decision making and problem solving and focus on 4 areas in which ethical dilemmas most commonly arise in a managed care context: informed consent, confidentiality, abandonment, and utilization management-utilization review. The need for sustained and organized advocacy efforts to ensure patient access to quality health care is discussed, as is the impact of managed care's competitive marketplace on professional relationships. Hypothetical examples of typical dilemmas psychologists face in the current practice environment are provided to illustrate systematic ethical decision making.

Codes of Ethics↗
PubMed1998

Locally administered vascular endothelial growth factor cDNA increases survival of ischemic experimental skin flaps.

Microvascular surgery has emerged as an attractive area for recent advances in the field of gene therapy. The present study investigated the survival of ischemic, experimental skin flaps after treatment with the gene encoding vascular endothelial growth factor (VEGF). In 30 Sprague-Dawley rats, anterior abdominal skin flaps supplied by the epigastric artery and vein were created. Ten animals were treated with a mixture of liposomes and the cDNA encoding the 121-amino acid isoform of VEGF. Another 10 animals were treated with control plasmid DNA and liposome transfection medium; a third group of 10 animals was given physiologic saline. Each solution was injected directly into the femoral artery distal to the origin of the epigastric pedicle supplying the flap. Four days after injection, the pedicle was ligated and blood flow in the flap was approximated using dye fluorescence. Seven days later, the amount of viable tissue within the flap was measured by planimetry. After the animals were killed, specimens from both the operated and nonoperated sides of the abdomen were harvested for immunohistologic evidence of VEGF protein expression. Average dye fluorescence indices of the three groups (VEGF cDNA, control plasmid, and saline) 2 hours after pedicle ligation were 35.9, 23.9, and 53.9 percent, respectively (p < 0.05). Compared with the two control groups, flaps receiving VEGF cDNA had significantly greater tissue viability at the end of 7 days: 93.9 versus 28.1 percent for the control plasmid DNA group and 31.9 percent for the saline group (p < 0.05). Immunohistochemical staining documented increased deposition of VEGF protein in flaps that were infused with the VEGF cDNA versus saline alone (p < 0.05). The results indicated that the survival of ischemic tissues can be enhanced by administration of a cDNA encoding VEGF, a protein known to be important in the process of angiogenesis and wound healing.

Animals↗
PubMed1996

Correlation of in vitro drug sensitivity testing results with response to chemotherapy and survival: comparison of non-small cell lung cancer and small cell lung cancer.

Clinical protocols for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) were devised to prospectively select individualized chemotherapy based on in vitro drug sensitivity testing (DST) of cell lines derived from the patient's SCLC tumor cell lines or the patient's fresh NSCLC tumor. DST data derived from SCLC tumor cell lines were available for 33/115 (29%) patients. The DST-selected chemotherapy regimen was administered to 21 (18%) patients, or 64% of patients with DST. In SCLC< the DST-selected chemotherapy was administered either during weeks 13-24 following 12 weeks of etoposide/cisplatin, or at relapse after complete response to etoposide/cisplatin. Several parameters of in vitro drug sensitivity were significantly associated (two-sided P < 0.05) with clinical response to primary therapy and also with response to the DST-selected chemotherapy regimen, but were not associated with survival (P = 0.24). Five patients treated with their DST-selected chemotherapy attained a complete or partial response, compared to 5 of 68 who received an empiric regimen (P = 0.057). A total of 36/165 (22%) NSCLC patients had DST successfully completed. These results directed management for 21/96 (22%) patients who eventually received chemotherapy, or 58% of patients with DST. Response to chemotherapy for the patients treated prospectively with their DST-selected chemotherapy regimen (2/21; 9%) was not significantly different than the response rate for patients treated empirically with etoposide/cisplatin (10/69; 14%) in the absence of in vitro results to direct chemotherapy (P = 0.73). There was no difference in survival by treatment group for the NSCLC patients. The correlation between in vitro and clinical response was not significant for any individual drug or for all drugs considered together, illustrating the poor predictive value of in vitro testing with currently available chemotherapy in NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

MYC family DNA amplification in 126 tumor cell lines from patients with small cell lung cancer.

We identified 126 tumor cell lines established from patients with small cell cancer at the NCI-Navy Medical Oncology Branch from 1977 through 1992. Extensive clinical information was available on 96 patients from whom these cell lines were established. These patients comprised approximately one fourth of the 407 patients treated on prospective therapeutic clinical trials during the same time period. The proportion of tumor cell lines established from previously untreated patients with both limited and extensive stage small cell lung cancer increased during the 16 years of the study (P = 0.008). MYC family DNA amplification was present in 16 of 44 (36%) tumor cell lines established from previously treated patients compared to 7 of 52 (11%) of tumor cell lines established from untreated patients (P = 0.009). MYC DNA amplification in tumor cell lines established from patients previously treated with chemotherapy continued to be associated with shortened survival (P = 0.001). The initiation of a policy to obtain tumor tissue for the purpose of selecting chemotherapeutic agents given to individual patients was associated with an increase in the proportion of patients from whom tumor cell lines could be established for both extensive and limited stage patients (P = 0.0001 and 0.05, respectively).

Carcinoma, Small Cell↗
PubMed1996

Silicone does not potentiate development of the scleroderma-like syndrome in tight skin (TSK/+) mice.

Several reports have implicated an association between the development of connective tissue disorders and exposure to silicone in breast implant patients. These connective tissue disorders include local or systemic scleroderma-like syndrome and have been characterized by fibrosis as well as the presence of circulating autoantibodies. Whether silicone does potentiate the development of a scleroderma-like syndrome is still to be defined. The purpose of the present study was to determine the effect of silicone on the tight skin (TSK/+) mouse which develops a scleroderma-like syndrome and on its normal pa/pa TSK/- littermate. Groups of six TSK and five of their normal pa/pa littermates were injected subcutaneously with low molecular weight silicone (LMW-PDMS), high molecular weight silicone gel (HMW-PDMS), incomplete Freunds' adjuvant (IFA) or Hank's balanced salt solution (HBSS) in the dorsal neck area and ventrally in the upper chest region. Serum was obtained prior to and 1 month after injection of silicone, IFA, or control HBSS. Antibody levels to bovine serum albumin (BSA), RNA polymerase (RNAP) and topoisomerase I were determined. Mice were then euthanized and strips of skin from the injection sites as well as samples of kidney and liver were studied histologically. No significant pathological changes were observed in TSK/- mice 1 month following injection with HBSS, LMW-PDMS or HMW-PDMS. Skin samples from TSK/+ mice which received LMW-PDMS showed hyperplasia of the dermis and peri-panniculus carnosus tissue and infiltrates of macrophages containing lipid-like vacuolated materials. Lipid vacuoles were observed throughout the deeper dermis as multiple loculated vacuoles. TSK mice which received HMW-PDMS showed similar thickening of the dermis and the peri-panniculus carnosus connective tissue. There were no significant differences in the histologic characteristics of the silicone-injected TSK/+ mice compared to those that received HBSS or IFA. No detectable changes in the kidney, spleen, or liver samples taken from TSK/+ or TSK/- mice injected with HBSS, IFA or silicone (LMW-PDMS, HMW-PDMS) preparations were noted. Baseline circulating antibody levels to BSA, RNAP and topoisomerase were significantly higher in TSK/+ mice compared to the control TSK/- littermates. Administration of silicone (LMW-PDMS or HMW-PDMS) did not significantly alter circulating antibody levels to BSA, RNAP and topoisomerase in either the TSK/+ or the TSK/- mice. The results of this study indicate that silicone administration does not potentiate the development of the scleroderma-syndrome characterized by skin lesions and presence of circulating antibodies in the TSK/+ model.

Animals↗
PubMed1996

Development of scleroderma-like syndrome in Tsk/+ mice is not enhanced by silicone administration.

The possible role of silicone in the pathogenesis of a scleroderma-like syndrome is still unresolved. It has been proposed that silicone escaping from breast implants potentiates the progression of the disease. To clarify whether silicone enhances development of fibrotic skin lesions and autoantibodies, we tested its effect on tight skin (TSK/+) mice. TSK/+ mice spontaneously develop skin fibrosis and characteristic autoantibodies which resemble human scleroderma. The results of the present study indicate that silicone administration does not enhance development of skin fibrosis nor synthesis of autoantibodies to RNA polymerase and topoisomerase in TSK/+ mice.

Animals↗
PubMed1996

Pseudoxanthoma elasticum and pregnancy.

Reports of complications of pseudoxanthoma elasticum occurring during pregnancy have dissuaded some women with the disorder from attempting to conceive for fear of exacerbating the disease. The actual risks of serious complications during pregnancy, however, may be overstated. We report a 40-year-old woman with pseudoxanthoma elasticum who delivered a healthy male infant after an uneventful pregnancy. At the time of delivery, the placenta was noted to be heavily calcified. The effects of pregnancy on pseudoxanthoma elasticum and the effects of maternal pseudoxanthoma elasticum on a developing fetus are reviewed, with a review of the relevant medical literature.

Adult↗
PubMed1995

Hypopigmented variant of mycosis fungoides: demography, histopathology, and treatment of seven cases.

BACKGROUND: Hypopigmented macules have been described infrequently as a presenting form of mycosis fungoides (MF). OBJECTIVE: This study was designed to clarify general characteristics of a hypopigmented MF variant. METHODS: Seven new cases were investigated with the use of descriptive epidemiology techniques. Demographic parameters, histopathology, and treatment outcomes were analyzed. These data were combined with those from prior reports to develop a broad composite view of this disease process. RESULTS: The median ages in our series were 36 years for disease onset and 39 years at biopsy diagnosis. All patients had brown or black skin. Histologic findings consistently showed a lack of epidermal atrophy and moderate to profound exocytosis. Treatment with PUVA induced rapid and complete repigmentation in six of seven patients. CONCLUSION: On the basis of our experience and a literature review, the hypopigmented variant of MF occurs in a younger population than typical forms of the disease and affects persons with dark skin almost exclusively. Microscopic features include lack of epidermal atrophy and moderate to extreme epidermotropism of infiltrating mononuclear cells. The treatment of choice appears to be PUVA.

Adult↗
PubMed1994

Integrated clinical and basic studies related to circumventing non-small cell lung cancer drug resistance.

Consideration of a range of clinical and basic studies conducted at the National Cancer Institute which explore the nature of the tumor biology of lung identify the limitations of using chemotherapy for the treatment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable information about the biology of lung cancer and some of its clinical consequences have been elucidated. In contrast to previous works from our group, this presentation will focus principally on studies of the nature of drug resistance with non-small cell cancer. An alternative combined modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still confined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic laser therapy can be effective in this application. To deal with the underlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical intervention with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may involve the combined modalities of laser ablation of accessible dysplastic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more remote areas of the lung epithelium.

Antineoplastic Agents↗
PubMed1994

Correlation of liver and skin histopathology with serology in a patient with cutaneous vasculitis and hepatitis C infection.

A strong body of evidence supports a viral etiology for many forms of vasculitis. Recent literature supports the association of the hepatitis C virus (HCV) with essential mixed cryoglobulinemia. We describe a case of cutaneous vasculitis associated with simultaneous active hepatic inflammation demonstrated by skin and liver biopsies. Immunofluorescence, hepatitis C serology, and study of the cryoprecipitate all confirmed HCV infection and deposition of immune complexes. Treatment with interferon alpha-2b was extremely effective as compared with prednisone and colchicine. This case provides further evidence that active hepatic infection with HCV may be a cause of cryoglobulinemia and cutaneous vasculitis. It also suggests that further studies of antiviral therapy for vasculitis should be explored.

Female↗
PubMed1994

Calcitonin elevation in small cell lung cancer without ectopic production.

To determine the relative contribution of ectopic calcitonin (CT) production versus nonectopic secretion of CT in patients with small cell lung cancer (SCLC), serum and urine immunoreactive CT (iCT) levels of 86 different subjects were measured by radioimmunoassay (RIA) using two polyclonal antisera (Ab3b and Ab4). The subjects included 49 previously untreated patients with SCLC, 17 smokers, and 20 nonsmokers. Serum and urine iCT values were highest in the patients with SCLC, intermediate in the smokers, and lowest in the nonsmokers (p < 0.0003). Sixteen of the 49 patients with SCLC had tumor cell lines available for determination of CT mRNA expression by RNase protection assay (RPA) and iCT production by RIA. CT mRNA was detected in nine of 16 subjects and iCT in eight of 16. The tumor cell lines of seven patients had undetectable CT by both RPA and RIA, and of these, five had elevated urine or serum iCT values compared with those of nonsmokers, and two had levels above all values in the smoker group. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor samples detected iCT in two of four tumors from patients whose tumor cell lines had CT mRNA by RPA and iCT by RIA, but in none of six whose tumor cell lines had undetectable CT mRNA. Thus, increased iCT values in some patients with SCLC are likely due to sources other than CT production by tumor cells.

Adult↗