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Biomedical subjects

A Rook

Publications and source records attributed to A Rook.

At least 19 recordsLinked to original sources
PubMed1999

Extracorporeal photopheresis alone and with interferon-alpha2a in chronic hepatitis C patients who failed previous interferon therapy.

Extracorporeal photopheresis (ECP) is approved for treatment of cutaneous, T-cell lymphoma. Evidence suggests that ECP can induce an immune response against tumor antigens expressed by malignant T lymphocytes. We theorized that if HCV-infected PBMCs express viral antigens, ECP could demonstrate antiviral activity by eliciting an immune response against these antigens. Fifteen cirrhotic patients with genotype-1 HCV, who had previously relapsed or not responded to interferon-alpha (IFN-alpha) therapy were stratified by their HCV RNA titer into one of three treatment groups: (1) ECP alone, (2) ECP + 3 MIU IFN-alpha2a subcutaneously three times a week and (3) ECP + 6 MIU IFN-alpha2a subcutaneously three times a week. All patients received treatment for 24 weeks. Group 1 had no significant decrease in HCV RNA. Two patients in group 2 had undetectable HCV RNA at the end of treatment. One patient in group 3 had undetectable HCV RNA at the end of treatment. However, HCV RNA was detected in all three patients during follow-up. ECP alone or with IFN-alpha was well tolerated. ECP alone demonstrated no clear antiviral activity. The combination of ECP and IFN-alpha resulted in an end-of-treatment response (ETR) in three of 10 patients. All responders had elimination of serum HCV RNA by three months, although no patient had a sustained response. More intensive therapy for a longer duration may result in sustained responses. A multicenter trial is now underway.

Antiviral Agents↗
PubMed1998

Radiotherapy for unilesional mycosis fungoides.

PURPOSE: To evaluate the treatment outcome and natural history of patients with the diagnosis of unilesional mycosis fungoides, treated according to a prospective radiotherapy protocol in our institution since July 1975. METHODS AND MATERIALS: A total of 325 patients with the diagnosis of mycosis fungoides have been referred to the Department of Radiation Oncology at Allegheny University of Health Sciences from July 1975 through September 1996. Of these, 18 patients (5%) were classified as having unilesional mycosis fungoides and were irradiated with a curative intent using local electron fields. One patient received 22 Gy; 1 patient received 40 Gy, and the rest of the patients 30.6 Gy. Daily fractions ranged from 1.8 to 2.0 Gy. Treatments prior to radiation consisted of topical steroids and/or antifungal creams in the majority of patients, with temporary partial responses. One patient had received 2 years of topical mechlorethamine (HN2) and another patient had received topical carmustine solution (BCNU) without response prior to irradiation. RESULTS: The responses were measured clinically; posttreatment skin biopsy was not performed routinely unless there was clinical evidence of disease persistence. Complete response rate was 100%; all treated lesions cleared completely within 4 to 8 weeks after the completion of radiation. With a median follow-up of 43 months (range 12 to 240 months), 2 relapses have occurred, 2 and 71 months after the completion of radiation. Both relapses were confined to the skin and were remote from the original site. Both relapses responded to topical application of HN2. There have been no recurrences in the irradiated field nor systemic dissemination. No long-term side effects were found related to treatment, and all the patients are currently alive and without evidence of disease. Actuarial relapse-free and overall survival at 10 years are, respectively, 86.2% and 100%. CONCLUSION: Unilesional mycosis fungoides has a long natural history, is possibly the earliest manifestation of a malignant process, and local treatments, including local radiotherapy, result in long-term disease-free intervals and, possibly, cure. Total skin electron beam radiotherapy is not indicated for this disease entity.

Adult↗
PubMed1998

Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2.

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and possible antitumor activity of a ligand fusion-protein, DAB389IL-2, in a phase I trial. This was a multicenter, open-label, dose-escalation trial. Patients with preserved organ function and histologically confirmed relapsed cutaneous T-cell lymphoma (CTCL), other non-Hodgkin's lymphomas (NHL), or Hodgkin's disease (HD) were eligible if their cancer was shown to express the interleukin (IL)-2 receptor by an immunohistochemical assay for the p55 or the p75 subunit. Patients received up to eight courses of DAB389IL-2 given as a short intravenous infusion daily for 5 days with subsequent courses every 21 days. The maximum tolerated dose (MTD) and tumor response was determined according to standard criteria. Seventy-three patients (44 men/29 women), aged 16 to 81 years (mean, 50.7) with CTCL (n = 35), NHL (n = 17), and HD (n = 21) were enrolled. The patients were extensively treated, failing 0 to 15 previous therapies (median, 4). Patients received one to six courses (mean, 3.3) of DAB389IL-2 over a range of 3 to 31 micrograms/kg/day. The dose-limiting toxicity was asthenia, establishing the maximum tolerated dose of 27 micrograms/kg/day. Approximately half of all patients had significant titers of antibody to diphtheria toxin or to DAB389IL-2 at the time of enrollment compared with 92% with titers at the end of treatment. The presence of antibody did not preclude clinical response. There were five complete (CR) and eight partial (PR) remissions in patients with CTCL with one CR and two PR occurring in NHL. The median time to response was 2 months and the duration of response was 2 to 39+ months. No responses were documented in patients with HD. DAB389IL-2 is well tolerated with an MTD of 27 micrograms/kg/day. This ligand fusion-protein showed antitumor effects in patients with IL-2 receptor expressing CTCL and NHL. Additional trials in these diseases are warranted.

Adolescent↗
PubMed1998

Antitumor activity of DAB389IL-2 fusion toxin in mycosis fungoides.

BACKGROUND: DAB389IL-2 is a novel fusion toxin that retargets the cytotoxic A-chain of diphtheria toxin to interleukin-2 (IL-2) receptor-expressing tumors. OBJECTIVE: The purpose of this phase I trial was to study the toxicity, maximum tolerated dose, and clinical efficacy of DAB389IL-2 in IL-2 receptor expressing lymphoproliferative malignancies, including cutaneous T-cell lymphoma. METHODS: DAB389IL-2 was administered intravenously daily for 5 days every 3 weeks. Dose escalation occurred between patient groups. Patients were monitored for laboratory and clinical toxicity, kinetics, immune response, and clinical efficacy. RESULTS: Thirty-five patients with cutaneous T-cell lymphoma (including 30 patients with mycosis fungoides) were treated. Previously, conventional therapy had not worked for 34 of the patients. Thirteen patients (37%) achieved an objective response, including a complete response in five patients (14%). Complete response was achieved in patients with extensive erythroderma and tumor stage mycosis fungoides. Adverse events consisted of reversible fever/chills, hypotension, nausea/vomiting, and elevation of hepatic transaminase. Doses of less than 31 microg/kg per day were well tolerated. Clinical responses were observed at all dose levels. CONCLUSION: DAB389IL-2 is well tolerated at doses of less than 31 microg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule.

Adult↗
PubMed1997

Interleukin-2 fusion protein: an investigational therapy for interleukin-2 receptor expressing malignancies.

DAB389IL-2 is an interleukin-2 receptor (IL-2R) specific fusion protein with a molecular weight of 58 kD containing the enzymatic and translocation domains of diphtheria toxin (DT) and human IL-2. This fusion protein is able to direct the cytocidal action of the DT enzymatic region only to cells which bear the IL-2R. The human IL-2R exists in three forms: low, intermediate and high affinity. The high-affinity form is believed to be the biologically relevant form on mature, activated T-lymphocytes, B-lymphocytes and monocytes. DAB389IL-2 is able to bind selectively to the high-affinity IL-2R in a concentration-dependent manner, and once bound is internalised via receptor-mediated endocytosis. Upon acidification of the formed vesicle, the enzymatic portion of the fusion protein is believed to pass into the cytosol where it ultimately inhibits protein synthesis by inactivation of elongation factor-2, resulting in cell death. The constitutive expression of the IL-2R on certain leukaemic and lymphomatous cells of T and B cell origin has been reported to occur in patients with chronic lymphocytic leukaemia, cutaneous T cell lymphoma (CTCL), Hodgkin's disease and non-Hodgkin's lymphomas (NHLs). A multicentre DAB389IL-2 dose-escalation study of patients with IL-2R expressing lymphomas has been conducted. A 10-fold range of doses were evaluated on a five-daily dose schedule. Patients received up to six courses, with an additional two courses permitted for patients with partial responses that appeared to be still improving after six courses. Most adverse experiences were transient and mild. Preliminary assessment of response indicated five complete responses (CR, duration ongoing at 20, 11, 7, 5 and 4 months) and seven partial responses (PR, duration 3-20 months) in the 35 patients with CTCL. One CR (duration > 20 months) in a patient with NHL (Lennett's lymphoma) and two PR (duration 9 and 2 months) in 17 patients with B-cell NHL have been observed. Based on the mode of action of DAB389IL-2, its safety profile, and the patient responses associated with the phase I/II clinical trials, a phase III programme in CTCL patients has been initiated and plans for additional trials in NHL patients are targeted for 1996.

Antineoplastic Agents↗
PubMed1992

Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy.

BACKGROUND: This original cohort of patients with erythrodermic cutaneous T-cell lymphoma (CTCL) was reported to have clinical improvement with photopheresis during the 12 months of the original study. No long-term follow-up data have been available to examine the impact of this therapy on the disease. OBJECTIVE: Our purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL patients treated with photopheresis and to compare these results with historical controls. METHODS: Files of patients from the original photopheresis study centers were reviewed and their current status was documented. RESULTS: The median survival of the treated patients was 60.33 months from the date of diagnosis and 47.9 months from the date of the start of photopheresis therapy. A complete remission has been maintained in four of the six patients who achieved complete responses in the original study. The best responses were seen in patients with a lower CD4/CD8 ratio in the peripheral blood at the start of therapy. CONCLUSION: Photopheresis can influence the natural history of erythrodermic CTCL by inducing remissions and prolonging survival with minimal toxicity.

CD4-CD8 Ratio↗
PubMed1990

A controlled trial of intralesional recombinant interferon-gamma in the treatment of keloidal scarring. Clinical and histologic findings.

Interferon-gamma (IFN-gamma) suppresses the synthesis of collagen by fibroblasts in vitro and the synthesis of collagen in vivo in animal models. Therefore, recombinant human IFN-gamma was examined for its ability to clinically modify keloids. Subjects were treated by injection of either 0.01 or 0.1 mg of recombinant human IFN-gamma into one lesional site and diluent alone into another lesional site three times per week for 3 weeks. Keloids were measured and photographed before beginning therapy and weekly thereafter. Three days after the final injection, biopsies were performed on treated and control sites. Six of eight subjects who finished the course of treatment demonstrated reduction in size at the treated site with an average reduction in height of 30.4% vs 1.1% for control sites. Lesions treated with recombinant human IFN-gamma demonstrated alterations in both the epidermis and dermis. The epidermis showed thinning of the suprapapillary plates, compact hyperkeratosis, focal or diffuse parakeratosis, exocytosis of lymphocytes, and an increased quantity of mucin. The dermis contained a diminished quantity of thickened collagen bundles and active fibroblasts and an increased number of inflammatory cells and quantity of mucin. These results suggest the feasibility of using IFN-gamma in the treatment of abnormal fibrosis. Dose-ranging studies are required to establish whether IFN-gamma can fulfill a true clinical need in the treatment of keloidal scarring.

Adolescent↗
PubMed1989

[Family groups and family self-help groups for schizophrenic patients. Concepts, establishment, problems in implementation].

In Münster/W.-Germany the effect of therapeutical work with relatives of young schizophrenic patients is investigated in a government supported prospective study. In this paper we reveal therapeutical concepts and difficulties dealing with the formation and guidance of the relatives groups. After a personal interview about one third of the relatives was interested in relatives groups (151 relatives of 99 patients). Relatives of younger patients with a shorter duration of illness were somewhat more interested. During the one-year-period of group-work about one third of the relatives left the groups. The motivation for a regular participation dependent on the symptoms of the patients. A special training produced better motivation for taking part in long-term self-help-groups.

Adult↗
PubMed1982

Acrokeratoelastoidosis.

A case of acrokeratoelastoidosis (AKE) is reported. A review of the literature has established that at least three clinicopathological entities have been reported under this term. Two of the entities show a combination of hyperkeratosis with fragmentation of dermal elastic tissue, which justifies the designation AKE. The first, for which the term familial AKE is perhaps appropriate, though many cases have been sporadic, begins in childhood or early adult life, and there is no evidence that trauma or light exposure are factors in its production. The second is a more variable clinical syndrome occurring in middle or late adult life, and both physical trauma and light exposure appear to be concerned in its induction. The third syndrome to be reported under the designation AKE shows no abnormality of elastic tissue and appears to be a separate entity.

Child↗
PubMed1979

Results of retransplantation in individuals who received two successive cadaver kidneys.

At the Royal Victoria Hospital in Montreal, 22 patients received two successive cadaver renal transplants. The results were analysed to determine which factors have the best predictive value for success or failure in renal retransplantation. The fate of a second cadaver renal allograft was found to be about the same as the first if the initial transplant has been lost because of rejection and not technical failure. The duration of survival of the initial transplant serves as the best guide to potential outcome of retransplantation after rejection of the initial graft.

Adolescent↗