Call 911: psychiatry and the new Emergency Medical Treatment and Active Labor Act (EMTALA) regulations.

The Emergency Medical Treatment and Active Labor Act (EMTALA), enacted in 1986 as part of the Consolidated Omnibus Budget Reconciliation Act of 1985, aims to prevent "patient dumping" by requiring hospitals to screen and stabilize patients who come to an emergency room seeking medical attention. For many reasons, recovery under EMTALA is rare, especially when psychiatric treatment is called for. New regulations of EMTALA went into effect on November 10, 2003.

Dissociation of photoreceptors from whole heads of the fruit fly, Drosophila melanogaster.

Photoreceptor cells that were mostly free of extracellular material and suitable for most electrophysiological study procedures were dissociated from whole heads of the fruit fly, Drosophila melanogaster, by a simple "smash" technique employing gentle chopping by a razor blade through Parafilm sheets. A variety of commonly available proteolytic and glycolytic digestion enzymes were tested as additions to the basic dissociation procedure described. With the aid of Nomarski interference contrast optics, periodic acid-Schiff staining, and fluorescent labeling and microscopy methods, it was determined that proteolytic enzymatic digestion does little to enhance the dissociation procedure, and instead, often damages the cells that one is attempting to recover.

Translating safety, efficacy and compliance into economic value for controlled release dosage forms.

Advanced controlled release (CR) dosage forms are relative newcomers to pharmaceutical markets, and few studies relate their efficacy, safety or compliance benefits to economic value. This literature review was undertaken to assess the cost effectiveness of CR dosage forms using such measures as purchase costs, total treatment costs, and economic value of improved therapeutic outcomes compared with those with non-CR dosage forms. Three therapeutic areas were examined: cardiovascular therapy, pain management and estrogen replacement therapy.

Recombinant human TNF-alpha: preclinical studies and results from early clinical trials.

The application of recombinant DNA technology to the production of tumor necrosis factor has resulted in the availability of large quantities of a highly purified protein product. This product has been evaluated extensively in preclinical studies, which have documented a direct cytostatic and cytotoxic effect on human tumor cells, as well as a variety of immunomodulatory effects on various immune effector cells, including neutrophils, macrophages, and T cells. In addition, a number of anti-infective and metabolic effects have been documented.

A phase II study alternating alpha-2a-interferon and gamma-interferon therapy in patients with chronic myelogenous leukemia.

Patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) were treated with a combination of alpha-interferon and gamma-interferon. Recombinant alpha-2a-interferon (Roferon-A, Hoffmann-LaRoche, Inc., Nutley, NJ) and recombinant gamma-interferon (Genentech, Inc.

A phase II trial of recombinant human interferon-gamma and recombinant tumor necrosis factor in patients with advanced gastrointestinal malignancies: results of a trial terminated by excessive toxicity.

Recombinant human tumor necrosis factor and recombinant human interferon-gamma are two representatives of a novel class of antineoplastic agents. Evaluation of these agents in vitro has suggested that the combination would be more effective than either agent alone. A prior phase I study demonstrated that the maximum tolerated dose for each agent was 150 micrograms/m2/day for 5 days when administered concomitantly.

The extracellular domain of HER2/neu is a potential immunogen for active specific immunotherapy of breast cancer.

The proto-oncogene HER2/neu encodes a protein tyrosine kinase (p185HER2) that is homologous to the human epidermal growth factor receptor. Amplification and/or overexpression of HER2/neu occurs in multiple human malignancies and appears to be integrally involved in progression of some breast and ovarian cancers. Because of this fact, HER2/neu is an intriguing target for specific cancer therapeutic strategies.

Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma.

Recombinant human interferon gamma (rIFN-gamma) was used for the treatment of 16 patients with various stages of cutaneous T-cell lymphoma (CTCL). All patients had been previously treated with standard topical and/or systemic therapies, and some had received experimental treatment with retinoids, recombinant human interferon alfa-2a (rIFN-alpha 2a), or radiolabeled monoclonal antibodies; most patients had an advanced stage of disease. Objective partial responses (PRs) were noted in five patients (31%) and lasted 3 months to greater than 32 months (median, 10 mo).

Phase I study of a combination of recombinant tumor necrosis factor-alpha and recombinant interferon-gamma in cancer patients.

Combinations of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) demonstrate synergistic antiproliferative activity in vitro. Therefore, we initiated a clinical study of recombinant TNF-alpha (rTNF-alpha) and rIFN-gamma combination therapy in humans. Twenty-five patients with metastatic cancer received both rTNF-alpha and rIFN-gamma by intramuscular injection for 5 consecutive days every 2 weeks for a total of 4 weeks.

Phase I trial of recombinant human gamma-interferon and recombinant human tumor necrosis factor in patients with advanced gastrointestinal cancer.

Recombinant human gamma-interferon and recombinant human tumor necrosis factor are two representatives of a new class of antineoplastic agents. In vitro studies have suggested synergistic cytotoxic activities when the agents are combined. We report a phase I study of these two agents when administered daily for 5 consecutive days every 2 weeks in patients with advanced gastrointestinal cancers.

Recombinant interferon-gamma in the treatment of recurrent nasopharyngeal carcinoma.

The etiologic relationship of the Epstein-Barr virus (EBV) to nasopharyngeal carcinoma prompted this study of the efficacy of interferon-gamma (IFN-gamma), which possesses antiviral and antitumor activity, in the treatment of recurrent carcinoma. Fourteen patients received recombinant IFN-gamma in daily intramuscular doses of 5-10 X 10(6) U/m2. Of 13 patients evaluable for response, five had a minor response; disease was stable in two and had progressed in six.

Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.

Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied.

Intravenous recombinant tumor necrosis factor in the treatment of AIDS-related Kaposi's sarcoma.

Tumor necrosis factor (TNF) has demonstrated antitumor activity against a variety of tumors and is particularly cytotoxic to capillary endothelial cells, which are the presumed cell of origin of Kaposi's sarcoma. We evaluated the toxicity and clinical antitumor and antiretroviral effects of recombinant TNF administered at a once weekly dose of 100 micrograms/m2 intravenously for 8 weeks in five men with AIDS-related Kaposi's sarcoma and without prior opportunistic infection. One patient was removed from study at week 4 due to rapid progression of Kaposi's sarcoma, another patient with stage IV disease and a pretreatment CD4 count of 11 developed fever, hypotension, and pneumonia at week 7 and died 8 days after discontinuing recombinant TNF.

Intralesional recombinant tumor necrosis factor-alpha for AIDS-associated Kaposi's sarcoma: a randomized, double-blind trial.

The effect of recombinant tumor necrosis factor-alpha (rTNF), injected directly into the tumor, was evaluated in a Phase I/II study of 27 patients with AIDS-associated Kaposi's sarcoma (KS). The maximally tolerated intralesional dose was less than 100 micrograms/m2 and the recommended intralesional dose was 25 micrograms/m2. In a double-blind, randomized, placebo-controlled study, rTNF reduced the cross-sectional area of 15 of 16 (94%) of the injected KS lesions and caused complete disappearance of 3 of 16 (19%) lesions.

Recombinant interferon gamma in hairy cell leukemia, multiple myeloma, and Waldenstrom's macroglobulinemia.

Fifteen patients with multiple myeloma, five with hairy cell leukemia, and five with Waldenstrom's macroglobulinemia were treated with recombinant interferon gamma (rINF-gamma) to determine the antitumor activity of this agent. The rIFN-gamma was administered by daily intramuscular injection at doses ranging from 0.125 to 0.

A phase I trial of intravenously-administered recombinant tumor necrosis factor-alpha in cancer patients.

We report a phase I clinical investigation of 30-minute and four-hour intravenous (IV) infusions of recombinant tumor necrosis factor (rTNF)-alpha. Thirty-nine patients with disseminated cancer received escalating doses of rTNF-alpha for five consecutive days every 2 weeks for a total duration of 8 weeks. Dose escalations followed a modified Fibonacci scale with a minimum of four patients entered at each dose level: 5, 10, 25, 50, 75, 100, 150, 200, and 250 micrograms/m2/d.

Recombinant interferon alpha and gamma in combination as treatment for metastatic renal cell carcinoma.

Fifty-three patients with metastatic-renal cell carcinoma received treatment with combinations of recombinant alpha (rIFN-alpha-2a) and gamma (rIFN-gamma) interferons on three different treatment schedules. On treatment schedule A, 13 patients received i.m.

Therapy of chronic myelogenous leukemia with recombinant interferon-gamma.

Recently, we reported that recombinant interferon-alpha (rIFN-alpha) can induce hematologic remissions and cytogenetic improvement in newly diagnosed Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) patients. Although IFN-gamma is a structurally distinct molecule, this agent suppresses in vitro hematopoietic progenitor cells in a fashion similar to that of IFN-alpha. Therefore, we initiated a study of rIFN-gamma at doses of 0.

ELISA for quantitation of tumor necrosis factor-alpha in serum.

A sensitive and precise ELISA has been developed for the quantitation of recombinant Tumor Necrosis Factor-Alpha (rTNF-alpha) in undiluted sera. Affinity purified rabbit antibody was used as capture antibody and mouse monoclonal antibody labelled with horseradish peroxidase was used as the second antibody in a sandwich ELISA. The assay range was from 50 to 2000 pg/ml and the relative standard deviation was 8% or less for both interassay and intra-assay precision studies.

Acquired Bernard-Soulier syndrome. Evidence for the role of a 210,000-molecular weight protein in the interaction of platelets with von Willebrand factor.

A patient with a lymphoproliferative disorder developed bleeding associated with a prolonged bleeding time and a selective defect of platelet aggregation in response to ristocetin. The patient's purified IgG was shown to inhibit aggregation of washed normal platelets by ristocetin and von Willebrand factor (F VIII:vWF). By Western blotting, it was shown that antibody bound specifically to an antigen of Mr 210,000 present on normal platelets but missing on platelets from patients with congenital Bernard-Soulier syndrome (BSS).

Sequential infusions of methotrexate and 5-fluorouracil in advanced cancer: pharmacology, toxicity, and response.

Preclinical studies have suggested that synergistic antitumor toxicity occurs when methotrexate (MTX) is administered prior to 5-fluorouracil (FUra). A protocol of sequenced, overlapping infusions of MTX and FUra was designed to achieve 5 microM MTX serum levels lasting 36 h and 1 to 5 microM FUra levels lasting 24 h, with leucovorin started at the end of the MTX infusion. Thirty-nine patients with metastatic neoplasms received a total of 127 treatment courses; two-thirds of the patients had received prior treatment with radiation therapy or chemotherapy; most of the latter treatment regimens included MTX or FUra.

The seeding of a transplanted murine leukemia and its influence on hemopoietic stem cells and immune function of the host.

A butylnitrosourea-induced murine T-cell leukemia, L40, was transplanted in BDF1 mice; 1 X 10(3) cells killed all recipients after conditioning with 400 rad, whereas 1 X 10(5) were needed with normal recipients. No leukemic cells could be detected by transplantation or cytogenetic analysis in the femur or the spleen at day 6 after L40 inoculation and, at day 11, leukemic cells were found in one out of two experiments, more if the host had been irradiated. Up to day 17, when leukemic cells were present, the CFU-S and CFU-C content of the femur was normal, but later a loss was observed with an increase in the enlarging spleen.

Chromosome changes in butylnitrosourea (BNU)-induced mouse leukemia.

G-banding analysis was carried out in 45 mice after exposure to the leukemogen butylnitrosourea (BNU). Of 27 animals without clinical signs of leukemia, 2 had chromosomal rearrangements (7%) while, of 18 leukemic mice, 5 showed abnormal karyotypes (28%). The chromosomal abnormalities were not random and showed preferential changes of chromosomes Nos.