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Biomedical subjects

E R Farmer

Publications and source records attributed to E R Farmer.

At least 19 recordsLinked to original sources
PubMed1992

Induction of cutaneous graft-versus-host disease by administration of cyclosporine to patients undergoing autologous bone marrow transplantation for acute myeloid leukemia.

Cutaneous graft-versus-host disease (GVHD) has been reported after administration of cyclosporine (CSP) after autologous bone marrow transplantation (ABMT) with unpurged marrow in patients with lymphoma. To determine whether GVHD can be induced after ABMT with chemopurged marrow in acute myeloid leukemia (AML), we administered intravenous CSP for 28 days (beginning on the day of ABMT) to 19 patients with AML (12 in first remission [CR1], six in CR2, and one in CR3) who received busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) and ABMT with 4-hydroperoxycyclophosphamide (4HC)-treated marrow. In this dose-escalation trial, CSP daily doses were 1 mg/kg in seven patients, 2.5 mg/kg in eight patients, or 3.75 mg/kg in four patients. Skin biopsies were obtained weekly after ABMT or on appearance of rash and were graded for GVH changes. Overall, 15 of 19 patients (79%) had cutaneous histopathologic grade 2 GVHD at a median of 33 days (range, 14 to 49) after ABMT; in 10, cutaneous manifestations were present at time of positive biopsy. The frequency, time to onset, and duration of GVHD were similar among the three CSP dosage groups. No patients had hepatic or gastrointestinal dysfunction attributable to GVHD or required specific therapy for GVHD. Positive biopsies for GVHD were seen in seven of eight patients who received full-course, full-dose CSP and 8 of 11 patients who had CSP discontinued or dosage reduced because of renal insufficiency. Three patients (one with positive biopsy) died with ABMT-related complications. Seven patients (four CR1, three CR2) relapsed with AML at a median of 411 days (range, 178 to 549) after ABMT; six of seven had positive biopsies for cutaneous GVHD. Nine patients (seven CR1, one CR2, and one CR3) are alive without relapse at a median of 501+ days (range, 252+ to 811+) after ABMT; eight of nine had cutaneous GVHD. Short-course CSP can induce autologous GVHD in recipients of chemopurged marrow autografts for AML, but randomized prospective trials are needed to determine whether this immunologic reaction is associated with alterations in leukemic relapse rate and disease-free survival after ABMT in AML.

Adolescent↗
PubMed1992

Thalidomide for the treatment of chronic graft-versus-host disease.

BACKGROUND: Allogeneic bone marrow transplantation is an accepted therapy for hematologic cancer, aplastic anemia, and inherited immunodeficiencies. Chronic graft-versus-host disease (GVHD) is the principal complication in patients surviving more than 100 days. Thalidomide has been shown experimentally to be effective in treating GVHD. METHODS: We treated 23 patients with chronic GVHD refractory to conventional treatment and 21 patients with "high-risk" chronic GVHD (identified as having at least two of the following three risk factors: chronic GVHD that has evolved from acute GVHD, lichenoid skin or mucous-membrane changes, and hepatic dysfunction. Such patients have a high mortality rate.) with thalidomide in a dose that produced a plasma level of 5 micrograms per milliliter two hours after administration. Therapy was continued for three months after a complete response or for six months after a partial response. RESULTS: The overall actuarial survival of all enrolled patients was 64 percent. Survival was 76 percent among the patients receiving salvage therapy for refractory GVHD and 48 percent among those with high-risk GVHD. A complete response was observed in 14 patients, a partial response in 12 patients, and no response in 18. Side effects were minor, most notably sedation in almost all patients. CONCLUSIONS: In this preliminary trial, thalidomide appeared to be safe and effective for the treatment of chronic GVHD. A trial comparing thalidomide with prednisone in patients with newly diagnosed chronic GVHD will be required to demonstrate its relative efficacy.

Adolescent↗
PubMed1992

A comparison of wound healing after epithelial resection by ultrasonic surgical aspiration and ablation by the carbon dioxide laser.

The ultrasonic surgical aspirator (USA) offers unique surgical options in the treatment of vulvar intraepithelial diseases. Clinical observations have shown results that equal those achieved with the use of the carbon dioxide laser with regard to patient satisfaction and incidence of recurrent disease. The purpose of this study was to compare the USA to the carbon dioxide laser in the laboratory with respect to ease of use, adequacy of epithelial removal, amount of tissue damage, and timing of wound healing. The backs of ten Hartley guinea pigs were marked with eight 1-cm2 patches placed 2 cm apart. Each instrument was used to ablate or resect the area within four patches on each animal's back to the level of the mid-dermis (0.5-1.0 mm). At time intervals from 0 hr to 28 days, the eight 1-cm patches were removed and evaluated histologically. The USA was easier to control and maintain within the 1-cm2 patch than the laser was. On histologic evaluation, the USA demonstrated less adjacent epithelial damage. The peak inflammatory response, depth of collagen denaturation, reepithelialization, and healing at 28 days were similar in both groups. The study indicates that the ultrasonic surgical aspirator is effective in epithelial removal and allows rapid wound healing with minimal scarring.

Animals↗
PubMed1992

Clinical, laboratory, and histopathologic indicators of the development of progressive acute graft-versus-host disease.

Graft-versus-host disease (GvHD) is the major cause of morbidity and mortality following bone marrow transplantation (BMT). The goal of this study of 69 cyclosporin-treated, allogeneic BMT patients was to identify early clinical, laboratory, or histopathologic indicators of the development of progressive, fatal GvHD. Peak values within 100 d of allogeneic BMT for total bilirubin, stool volume in a day, clinical stage of cutaneous GvHD (based on extent of rash), and overall clinical stage of GvHD (based on a combination of graft-versus-host reactions in the skin, liver, and gastrointestinal tract) were most useful (p less than 0.05, by logistic regression) in identifying those patients with clinically progressive and fatal GvHD. Peak values for each of these parameters were reached an average of 40 d or less after BMT. Each unit increase in peak clinical stage of rash (e.g., stage 2 versus stage 3) was associated with an odds ratio incremental risk of 5.8 for clinical progression of GvHD, and each tenfold increase in peak total bilirubin (e.g., 2 mg/dl versus 20 mg/dl) or stool output in a day (e.g., 100 cm3/d versus 1000 cm3/d) was associated with an incremental risk of 8.4 and 10.6, respectively, for a fatal outcome from GvHD. Number of exocytosed lymphocytes and dyskeratotic epidermal keratinocytes (DEK) per linear millimeter of epidermis, the presence of follicular involvement, and the degree of dermal perivascular lymphocytic infiltration in 121 skin biopsy specimens were not associated with the development of progressive or fatal GvHD. Pretransplant total body irradiation was associated (p = 0.03, by Mann-Whitney U testing) with an increased number of DEK in skin biopsy specimens taken less than 20 d after BMT. This study demonstrates that monitoring of total bilirubin, stool output, extent of rash, and overall clinical stage of GvHD is most useful during the first 40 d after BMT in formulating the prognosis of early acute GvHD in allogeneic BMT patients receiving cyclosporin.

Acute Disease↗
PubMed1992

Cutaneous manifestations of the eosinophilia-myalgia syndrome.

We report the cutaneous manifestations of the eosinophilia-myalgia syndrome in 10 patients, with specific reference to their clinical course, histopathological features, and immunogenetic studies. Cutaneous manifestations could be classified into three groups: morphoea-like sclerosis, urticarial and papular lesions, and generalized sclerosis. Despite this polymorphic clinical presentation, the histopathological abnormalities in all cases were strikingly similar, and consisted of superficial and deep perivascular lymphocytic dermal infiltrates, mucin deposition, and fascial inflammation (often in the absence of sclerosis). Immunoperoxidase studies revealed increased numbers of factor XIIIa- and MAC 387-positive cells in the inflammatory infiltrate. Immunogenetic studies demonstrated that 77% (7/9) of patients possessed the HLA-DR3 or HLA-DR4 phenotypes. Mean follow-up of 24 months after discontinuation of L-tryptophan revealed the presence of persistent severe disabling disease in 30% of patients.

Adult↗
PubMed1992

A morphologic, pathologic, and virologic study of anogenital warts in men.

BACKGROUND AND DESIGN: Infection with human papillomavirus (HPV) in the anogenital region is associated with benign papillomas (condyloma acuminatum), subtle verrucous changes, subclinical infection, and malignant lesions. Although both men and women are affected, much of the investigation has been directed toward women in the study of cervical and vulvar carcinoma. The current investigation focuses on HPV infection in men. This study was undertaken to correlate the clinical spectrum of disease in our population of male patients with histopathologic features, immunoperoxidase staining for viral capsid antigen, and viral typing. Genital lesions from 26 patients were examined and tested prospectively over a 1-year period. RESULTS: The 26 lesions examined demonstrated variable morphologic features with regard to location, size, surface characteristics, and color. Histopathologic features were consistent with the diagnosis of venereal warts, but not necessarily diagnostic. Three of five standard histopathologic criteria were present in only 71% of the specimens. Despite the morphologic variability and the indeterminant histopathologic findings, 20 of 23 lesions positive for the genital tract HPV types tested contained HPV types 6 and/or 11. CONCLUSIONS: We conclude that the morphologic appearance of anogenital warts does not necessarily correlate with HPV type. Histopathologic study is helpful in excluding other diagnoses but may be indeterminant in the diagnosis of venereal warts. All men with anogenital warts should be counseled, treated, and undergo follow-up regardless of HPV type.

Adolescent↗
PubMed1992

Growth retardation and depigmentation of hair after high-dose busulfan and congenic hematopoietic cell transplantation in mice.

Busulfan, a myeloablative but non-immunosuppressive alkylating agent, is used extensively in clinical bone marrow transplantation (BMT), but the effects of high-dose administration have not been previously evaluated in preclinical BMT settings with young murine recipients. We compared the survival and growth of C57BL/6 mice given graded single doses of busulfan (10-100 mg/kg) or total body irradiation (TBI; 900 cGy) at age 9 days and hematopoietic cell transplantation (HCT; transplantation of congenic bone marrow and spleen cells) 24 h later. The 30-day survival was 87-100% in mice transplanted after 10-40 mg/kg busulfan and 79% after TBI, but fell to 54% and 33%, respectively, after 80 mg/kg and 100 mg/kg busulfan, suggesting that this latter dosage range represents the LD50 for single-dose busulfan in young C57BL/6 mice given stem cell rescue. The weights of 10-week-old mice given HCT after lower doses of busulfan ranged from 87% of control at 10 mg/kg to 64-69% of control in mice conditioned with 35-65 mg/kg busulfan or TBI. Impairment of weight gain was most striking (approximately 50% of control) in mice transplanted after 80-100 mg/kg busulfan. Despite retardation of somatic growth, the brain weights of busulfan-conditioned mice remained at least 90% of control, and there were no obvious neuropathological alterations in the brains of these animals. All mice treated with at least 20 mg/kg busulfan or TBI lost hair by 3-4 weeks after transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Development and field-test validation of an assay for DNA repair in circulating human lymphocytes.

A method for measuring nucleotide excision repair in response to UV irradiation and chemical-induced DNA damage has been developed, validated, and field tested in cultured human lymphocytes. The methodology is amenable to population-based screening and should facilitate future epidemiological studies seeking to investigate associations between DNA repair proficiency and cancer susceptibility. The impetus for such endeavors derives from the suggestion that the high incidence of skin cancer in the genetic disorder xeroderma pigmentosum is manifested as a result of the reduced capacity of patients' cells to repair DNA damaged by UV-mimetic agents. For the assay, damaged, nonreplicating, recombinant plasmid DNA harboring a chloramphenicol acetyltransferase (cat) reporter gene is introduced into lymphocytes by using a DEAE-dextran/DNA complex short-term transfection conditions. Excision repair of the damaged bacterial cat gene is monitored proportionately as a function of reactivated CAT enzyme activity following a 40-h repair/expression incubation period. The validity of the approach was indicated by the ability of the assay to discriminate xeroderma pigmentosum virus-transformed lymphocyte cell lines of both severe (complementation groups A and D) and moderate (complementation group C) excision repair deficiencies from repair-proficient cell lines. Similar results were observed when a mitogen-stimulated peripheral blood lymphocyte culture from an xeroderma pigmentosum A patient was assayed concurrently with mitogen-stimulated peripheral blood lymphocytes obtained from healthy individuals. Adaptation of this DNA repair assay as a field test in a pilot-tested select group of basal cell carcinoma patients and cancer-free controls led to the preliminary identification of a specific subset at risk for this disease as a consequence of significant reduction to the repair of photochemically (UV)-damaged plasmid DNA.

Adult↗
PubMed1991

Israel Zeligman.

Explore the source record for details and available documents.

Baltimore↗
PubMed1991

Primary cutaneous mucoepidermoid carcinoma: report of a case.

Primary mucoepidermoid carcinomas of the skin are extremely rare tumors. We describe a primary cutaneous mucoepidermoid carcinoma arising in the right ear (posterior mid helix) of a 66-year-old white man. The tumor was 0.6 cm in diameter, ulcerated and nonencapsulated. No other tumors were found in the patient. Histologically the tumor showed the characteristics of a "low grade" mucoepidermoid carcinoma, consisting of lobules of polygonal cells with vesicular nuclei. In the center of the lobules were large vacuolated cells (goblet cells). Transitions between the two cell populations were present throughout the tumor. An epidermal attachment of the tumor, as well as epidermal dysplasia, predominantly at the acrosyringium was present, consistent with the theory of sweat duct histogenesis of these tumors. Immunoperoxidase staining showed positivity for epithelial membrane antigen, keratin and carcinoembryonic antigen. The latter was predominantly positive in the goblet cells. Cutaneous metastasis of mucoepidermoid carcinomas with epidermal attachment has been reported. Our case showed only ear involvement and follow-up at 8 months has revealed no evidence of recurrence. These findings are consistent with the diagnosis of primary cutaneous mucoepidermoid carcinoma.

Aged↗
PubMed1991

PUVA therapy for chronic cutaneous graft-vs-host disease.

Chronic graft-vs-host disease (GVHD) is an immunologic disorder frequently occurring as a late sequelae of allogeneic bone marrow transplantation and characterized in the skin with lichenoid or sclerodermoid lesions. Systemic immunosuppressive agents such as corticosteroids or cyclosporine are usually required to control the disease. Therapy with psoralen and UVA (PUVA) has recently been shown to be effective for skin and oral mucosa in a few cases of GVHD. We present our experience with PUVA in six patients, five with lichenoid and one with sclerodermoid GVHD. None of these patients had significant systemic involvement. All five patients with lichenoid GVHD showed clinical improvement after PUVA therapy. Three of these patients had complete clearance of skin lesions. Clinical clearance of the disease was accompanied by microscopic clearance. The patient with sclerodermoid GVHD did not respond to therapy. No significant complications or exacerbation of systemic disease occurred. We confirm that PUVA is an effective and safe therapy for the cutaneous manifestations of lichenoid chronic GVHD. We postulate that PUVA therapy clears chronic lichenoid GVHD by selective cytotoxicity for the activated lymphoid cells in the inflammatory infiltrate.

Adolescent↗
PubMed1991

Disseminated hypopigmented keratoses.

We present two cases of asymptomatic, widespread keratotic eruptions in young female patients. Clinically, the lesions are well-demarcated, small, hypopigmented, flat-topped papules occurring on the trunk and extremities in a uniform distribution. Skin biopsy specimens from one patient revealed hyperorthokeratosis, papillomatosis, and a normal amount of melanin. We suggest that this is a newly recognized dermatologic entity that may be descriptively termed disseminated hypopigmented keratoses. Disseminated hypopigmented keratoses may be distinguished by clinical and histologic criteria from similar keratotic eruptions. Since the lesions of disseminated hypopigmented keratoses are both inconspicuous and asymptomatic, it is likely that the disorder is more prevalent than our two cases would suggest.

Adult↗
PubMed1990

Bone marrow graft engineering by counterflow centrifugal elutriation: results of a phase I-II clinical trial.

In an attempt to reduce the incidence and severity of acute graft-versus-host disease (GVHD), we have decreased the number of bone marrow (BM) lymphocytes in the donor marrow graft before bone marrow transplantation (BMT) using counterflow centrifugal elutriation (CCE). In a phase I-II clinical trial, 23 patients received lymphocyte-depleted BM allografts from their HLA-identical, mixed lymphocyte culture (MLC)-nonreactive sibling donors. The patients entered in the study were deemed to be at high risk for treatment failure on the basis of age (greater than 30 years; median, 39 years) and the result of our skin explant assay predictive of acute GVHD. Patients predicted not to develop acute GVHD by this assay were excluded from this study. All patients received a standard lymphocyte dose of 0.5 x 10(6) morphologic lymphocytes per kilogram ideal body weight (IBW) in the marrow graft and were maintained on cyclosporine A (CsA) immunosuppression for 170 days after BMT. Prompt hematopoietic recovery occurred in 22 of 23 patients with a median time to an absolute neutrophil count (ANC) greater than or equal to 500/microL of 21 days. Donor cell engraftment was subsequently verified by cytogenetic and/or DNA analysis in all of 21 evaluable patients. No patient developed systemic acute GVHD. Only five (22%) developed cutaneous GVHD (clinical stage 1) that required steroid treatment, including one patient who failed to engraft. The median follow-up of the patients enrolled in this study is 14 months (range, 5 to 20 months). Actuarial survival 1 year after BMT is 83%. Thus, in two consecutive clinical trials using CCE to deplete donor BM of alloreactive lymphocytes (1.0 x 10(6) versus 0.5 x 10(6) lymphocytes/kg), we have demonstrated that the procedure does not interfere with BM engraftment and is effective in decreasing the incidence and severity of acute GVHD. Furthermore, comparison of these studies has revealed a differential dose response relationship between the number of graft lymphocytes, protection of engraftment, and induction of acute GVHD. Although there appears to be a modest relationship between lymphocyte dose and time to hematopoietic recovery, the 50% reduction in lymphocyte dose from that used in our previous trial resulted in a marked decrease in acute GVHD without compromising engraftment.

Adult↗
PubMed1990

Distribution of lymphocytes bearing TCR gamma/delta in cutaneous lymphocytic infiltrates.

A monoclonal antibody to the recently characterized T lymphocyte expressing a T cell receptor bearing gamma and delta chains (TCR gamma/delta) was applied to 60 biopsy specimens spanning a wide range of diagnoses and containing a variable number of T lymphocytes. TCR gamma/delta+ cells were not enriched in the tissues examined, representing between 0-5% of the total CD3 positive T lymphocyte population. TCR gamma/delta+ cells were identified in 27 cases (45%). The distribution of the TCR gamma/delta-bearing cells was remarkable for preferential stratification at upper cutaneous levels, within the epidermis and papillary dermis in some cases of mycosis fungoides. Benign infiltrates lacked a similar pattern. The role of TCR gamma/delta+ cells is uncertain. The data do not reveal a consistent number or distribution of these cells in cutaneous infiltrates.

Antibodies, Monoclonal↗