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Biomedical subjects

D McLain

Publications and source records attributed to D McLain.

33 records · Page 2Linked to original sources
PubMed1994

Renal masses simulating primary renal cell carcinoma in patients with advanced malignancies.

Most patients who present with a large solid renal mass and evidence of advanced malignancy will have primary renal cell carcinoma but a small subset with similar features have different and more treatable malignancies. We identified 7 patients with clinical and radiological findings suggestive of metastatic renal cell carcinoma who were ultimately diagnosed as have non-Hodgkin's lymphoma (5), germ cell tumor (1) or transitional cell carcinoma (1). Two of these patients presented with abdominal pain, gross hematuria and a flank mass. Computerized tomography was interpreted as showing renal cell carcinoma in all patients, although lymphoma and sarcoma were included in the differential diagnoses in 2. With the correct diagnosis and appropriate therapy, 4 of the 7 patients are currently disease-free. We emphasize the need for histological documentation in such patients in view of curative therapy available for possible underlying neoplasms simulating renal cell carcinoma.

Adult↗
PubMed1994

Phase I trial of cisplatin, WR-2721, and the murine monoclonal antibody R24 in patients with metastatic melanoma: clinical and biologic effects.

The therapeutic and biologic effects of murine monoclonal antibodies in patients with malignancies have been widely investigated. Attempts to enhance results by combining these agents with cytotoxic drugs are now under study. A Phase I trial was performed to assess the toxicity and biologic effects of escalating doses of R24 (0-40 mg/m2/day 1-5, 8-12), an antibody that binds to the ganglioside GD3 present on melanoma cells, administered in combination with cisplatin (120 mg/m2) and WR-2721 (740 mg/m2) on day 1. Twenty-three patients with metastatic malignant melanoma were treated and are evaluable. The true maximum tolerated dose of R24 given as part of this combination was not reached. The toxicity of the regimen was moderate and included fever and urticaria, which were attributed to R24. Severe but reversible renal failure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicity was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients receiving only cisplatin and WR-2721. No significant enhancement of natural killer, lymphokine-activated killer, and antibody-dependent cellular cytotoxicity lytic activity or significant changes from baseline in lymphocyte subsets secondary to R24 were seen. In 4 of 10 patients tumor localization of mouse monoclonal antibody was found and appeared greatest at higher R24 doses and during week 1 of therapy. Human anti-mouse antibody responses developed by day 22 in 17 of 19 patients treated with R24, and the coadministration of cisplatin did not appear to abrogate this response. Finally, the half-life and Cmax of cisplatin were not affected by R24. In summary, the combination was well tolerated, responses were few, and significant biologic interactions or immunomodulation were not observed.

Adult↗
PubMed1994

Phase I trial of subcutaneous recombinant macrophage colony-stimulating factor: clinical and immunomodulatory effects.

PURPOSE: Recombinant human macrophage colony-stimulating factor (rM-CSF) has been demonstrated to control the growth, differentiation, and function of mononuclear phagocytes. Preclinical studies have indicated antitumor effects, and therefore a phase I trial of rM-CSF in patients with malignancy was initiated. The toxicity and hematologic and immunologic effects were investigated. PATIENTS AND METHODS: rM-CSF was administered as a subcutaneous injection on days 1 through 5 and 8 through 12. Cycles were repeated every 28 days. Cohorts of four to seven patients received rM-CSF at dose levels from 0.1 to 25.6 mg/m2/d. Forty-two patients received 88 cycles of rM-CSF. All patients had metastatic solid tumors refractory to standard therapy. RESULTS: The toxicity of rM-CSF was mild. Dose-limiting toxicity included thrombocytopenia (two patients) and iritis (one patient) occurring at a dose of 25.6 mg/m2/d. Hematologic studies demonstrated dose-related monocytosis occurring routinely at doses > or = 3.2 mg/m2/d, and thrombocytopenia. Immunologic studies demonstrated enhanced secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) by monocytes after in vitro stimulation with lipopolysaccharide, and increased expression of TNF-alpha mRNA at higher rM-CSF dose levels. Pharmacokinetic studies demonstrated that the systemic clearance rate of M-CSF increases during week 1 of therapy, resulting in lower blood levels of M-CSF during the second week of therapy. CONCLUSION: rM-CSF can be safely administered to patients, and has biologic activity on peripheral-blood monocytes.

Adult↗
PubMed1994

Pleiotropic effects of cytokines: clinical and preclinical studies.

Cytokines have diverse and pleiotropic effects including immunologic, hematopoietic and pro-inflammatory activities. A total of 135 patients have been treated in a series of phase I clinical trials utilizing five different recombinant cytokines: granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), interleukin 3 (rhIL-3) interleukin 4 (rhuIL-4), and interleukin 6 (rhIL-6). The toxicity, maximum tolerated dose and biologic activities were determined. Hematopoietic, immunologic and pro-inflammatory effects were noted during therapy with these agents. Prominent effects on lymphocyte and monocyte functional activities were demonstrated. The diversity of biologic effects in vivo demonstrates the pleiotropic nature of the cytokines investigated and the difficulties encountered in their in vivo evaluation.

Blood Cell Count↗
PubMed1993

Phase I trial of recombinant granulocyte-macrophage colony-stimulating factor in patients with lung cancer: clinical and immunologic effects.

Recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) may enhance the functional activity of monocytes and macrophages in vitro and in vivo and thereby have antitumor activity. A phase I trial using rhuGM-CSF was performed; the trial included 17 patients with unresectable and/or metastatic lung cancer. rhuGM-CSF was administered as a continuous infusion for 14 days at four dose levels: 60 micrograms/m2, 125 micrograms/m2, 250 micrograms/m2, and 500 micrograms/m2. Dose-limiting toxicity was pulmonary and occurred at 500 micrograms/m2, with the maximal tolerated dose (MTD) identified as 250 micrograms/m2. The hematologic effects of rhuGM-CSF included leukocytosis with significant correlations between dose level and the numbers of neutrophils, monocytes, eosinophils, and lymphocytes. Bronchoalveolar lavage was performed for 14 patients, and no effect on alveolar macrophage numbers was detected. Tumor biopsies were obtained in two patients, and no changes in macrophage infiltrates were detected with use of immunohistochemical studies. Serum levels of GM-CSF reached a steady state during week one and decreased or were undetectable during week two. No evidence of tumor regression was seen. rhuGM-CSF when administered as a continuous infusion was well tolerated and appears to modulate monocyte numbers and function in vivo.

Adult↗
PubMed1993

Interleukin-2: use in solid tumors.

Recombinant interleukin-2 (rIL-2) is a cytokine that has a central immunoregulatory role in controlling T cell function and growth. Clinical trials of rIL-2 regimens in various solid tumors have been initiated, and 337 patients at the Cleveland Clinic Foundation have been treated in a sequence of trials. The studies have involved rIL-2 or polyethylene-glycol conjugated rIL-2 (PEG-IL-2) as single agents, combinations of rIL-2 with recombinant interferon alpha, IL-4, or doxorubicin, and trials of rIL-2 with tumor infiltrating lymphocytes (TILs). These studies are summarized and involve Phase I or Phase II investigations in patients with renal cell carcinoma (191 patients), malignant melanoma (49 patients) or miscellaneous solid tumors (97 patients). Response rates in each category, respectively, were 12%, 20% and 2%. Toxicity varied depending on the regimen and generally reflected the dose and schedule of rIL-2 being employed. This series of clinical studies demonstrates the role of rIL-2 in various malignancies and documents the activity in patients with malignant melanoma and renal cell carcinoma. Additional studies to investigate potential mechanisms of antitumor activity and response determinants are underway.

Clinical Protocols↗
PubMed1993

Phase I study of WR-2721 and carboplatin.

Because WR-2721 reduces the toxicity of cisplatin and carboplatin in preclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short relative to that of carboplatin, WR-2721 was administered in two divided doses. This schedule produced acceptable toxicity in 24 patients treated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In the subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopenia (platelets < 50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were similar to those reported for carboplatin alone. These results suggest that WR-2721 might increase the maximum tolerated dose of carboplatin from 400 to 500 mg/m2.

Adult↗
PubMed1993

Immunomodulatory effects of recombinant interleukin-3 treatment on human alveolar macrophages and monocytes.

The purpose of these studies was to examine the effects of in vivo and in vitro recombinant IL-3 treatment on alveolar macrophage and monocyte activities associated with antitumor and antimicrobial properties. Alveolar macrophages and blood monocytes from 6 patients receiving IL-3 (125-500 micrograms/m2/day) subcutaneously were isolated before therapy and at various times during the 15 days of therapy. Results indicated that tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6) secretion were enhanced from monocytes of all patients and from alveolar macrophages of patients receiving 500 micrograms/m2/day IL-3. Constitutive cytokine gene expression was present before therapy, but further enhancement was not detectable during therapy, suggesting a rapid time course of cytokine gene transcription and translation. Serum neopterin levels were elevated 2-5 fold in all patient compatible with the presence of augmented monocyte/macrophage activity. Peak levels of neopterin did not coincide with peak levels of cytokine secretion. In vitro studies of IL-3-treated normal alveolar macrophage and monocyte population demonstrated that IL-3 significantly augmented TNF and IL-6 secretion in monocytes, but not in alveolar macrophages. These differences in alveolar macrophage cytokine secretion observed after in vivo and in vitro IL-3 treatment may reflect the involvement of other cell populations in IL-3 modulation of alveolar macrophages in vivo. Monocytes, in contrast were comparably activated by IL-3 whether presented in vitro or in vivo.

Biopterins↗
PubMed1983

Artistic development in the dancer.

The life of the artist who devotes himself or herself to dance as a career can be divided into seven stages. Each stage seems to have specific physical problems and challenges as well as success in technical and artistic achievement.

Adolescent↗
PubMed1975

A new consideration in athletic injuries. The classical ballet dancer.

The professional ballet dancer presents all of the problems of any vigorous athlete. The problems include osteochondral fractures, fatigue fractures, sprains, chronic ligamentous instability of the knee, meniscal tears, impingement syndrome, degenerative arthritis of multiple joints and low back pain. Attention to minor problems with sound conservative therapy can avoid many major developments and lost hours. Observations included the extraordinary external rotation of at the hip without demonstrable alteration in the hip version angle and hypertrophy of the femur, tibia and particularly the second metatarsal (in female dancers). Careful evaluation of the range of motion of the extremities, serial roentgenographic examination, and systematic review of previous injuries, training programs and rehearsal techniques have been evaluated in a series of cases to provide the basis for advice to directors and teachers of the ballet.

Achilles Tendon↗
PubMedDate not supplied

Polyethylene glycol conjugated interleukin-2: clinical and immunologic effects in patients with advanced renal cell carcinoma.

Recombinant interleukin-2 (rIL-2) modified with monomethoxypolyethylene glycol (PEG IL-2) was utilized in patients with metastatic renal cell carcinoma in two separate multi-institutional trials. PEG IL-2 was administered as an I.V. bolus days 1, 8, 15, and 22 with cycles repeated every six weeks. The two trials employed different dose levels: A) 20 x 10(6) I.U./m2 day 1 followed by 12 x 10(6) I.U./m2 days 8, 15, 22; and B) 12 x 10(6) I.U./m2 days 1, 8, 15, 22. Thirty-five patients were entered and 31 were evaluable for response (A-15/18, B-16/17). Two of 31 patients had partial responses. Median therapy duration was four weeks (range 1-15), and dose reduction for grade III or IV toxicity was required in 14/35 patients (A-6/18, B-8/17). Toxicity (> or = grade III) seen included: hypotension 51%, dyspnea 17%, seizures 6%, and mental status changes 11%. No differences in response or toxicity between the two schedules were noted. Hematologic changes included lymphocytosis and eosinophilia in the majority of patients. PEG IL-2 given once weekly has significant toxicity, and may produce tumor regression in patients with renal cell carcinoma.

Adult↗
PubMedDate not supplied

Phase II trial of circadian infusion floxuridine (FUDR) in hormone refractory metastatic prostate cancer.

Circadian administration of chemotherapy has been reported to decrease toxicity and possibly enhance efficacy. Between March 1991 and December 1993, 18 evaluable patients with progressive, hormone-refractory metastatic prostate cancer were treated in this phase II trial of circadian infusion floxuridine (FUDR). The drug was delivered through a central venous catheter using a CADD-Plus computerized pump such that approximately 70% of the drug was administered between 3 and 9 p.m. and the rest (30%) was administered between 9 p.m. and 3 p.m. The dose of FUDR was 0.15 mg/kg/day x 14 days every 4 weeks. A total of 79 complete cycles was administered. Two of 18 evaluable patients (11.1%) had decreases in PSA lasting five and eight months. No objective responses or improvement in bone scans was noted. The major toxicity observed was diarrhea. Although circadian infusion FUDR is feasible and tolerable, it has limited activity in hormone refractory prostate cancer.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Phase 1 trial of subcutaneous IL-6 in patients with refractory cancer: clinical and biologic effects.

The authors evaluated the clinical and biologic effects of human recombinant interleukin-6 (rhIL-6) in patients with refractory cancer. A phase 1 trial using escalating doses of rhIL-6 (1-50 microg x kg(-1) x d(-1), Monday through Friday for 4 weeks) was performed in 30 patients. Toxicity was moderate and the maximum tolerated dose was determined to be 25 microg x kg(-1)x d(-1) based on cardiac and neurocortical toxicity in one patient each and thrombocytosis (platelets > 800,000/microL) in three patients. One patient with non-small-cell lung cancer had a partial response after three cycles of therapy. The biologic effects of rhIL-6 included anemia and dose-related thrombocytosis. Various proinflammatory activities were induced and included dose-related cyclical increases in peripheral blood monocytes and the CD14+/CD45RB+ +/- CD16C+ mononuclear cell populations. These increases were accompanied by increased levels of C-reactive protein, serum neopterin, and type I soluble tumor necrosis factor receptor. In contrast, rhIL-6 did not affect lymphocyte numbers or function (cytotoxicity, cytokine levels, immunoglobulin levels), with the possible exception of IL-2Ralpha mRNA induction in peripheral blood lymphocytes. rhIL-6 has pleiotropic proinflammatory actions in vivo and moderate toxicity when administered as long-term therapy.

Acute-Phase Reaction↗
PubMedDate not supplied

Dental needs related to primary cause for institutionalization.

One hundred and forty-seven dentate residents of a long-term care facility were examined to determine oral status and need for treatment. The assessment included dental caries (NIDR criteria), oral hygiene index-simplified, and missing teeth. Caries was further divided into "restorable" and "nonrestorable." Also, the primary cause for institutionalization was determined.

Adult↗