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At least 433 records · Page 24Linked to original sources
PubMed1994

Cell culture as a tool for identifying nutritional disease therapies.

Cell culture methodologies can be used to help develop therapies for the treatment of polytrauma. An overview is presented of research with the L6 myoblast cell line that led to the discovery of the truncated insulin-like growth factor (IGF) variant, des(1-3)IGF-I and that gave an explanation of the enhanced potency of this growth factor. Subsequent efforts to develop an even more potent variant also utilized cultured cells as indicator bioassays. Such experiments not only provided mechanistic information on IGF action but also directed attention towards IGF variants that were later shown to be more potent in vivo at reversing catabolic conditions.

Animals↗
PubMed1987

Biliary bacteria, antibiotic use, and wound infection in surgery of the gallbladder and common bile duct.

That clinical risk groups predict postoperative infection in biliary operations has recently been challenged. To reevaluate the risk of infection, we studied 215 patients stratified by clinical risk factors. Of 100 patients having simple "low-risk" cholecystectomy, 11 had positive bile cultures (90% pure), and one with sterile bile got a staphylococcal wound infection (WI). Among 92 "high-risk" patients with acute cholecystitis, obstructive jaundice, or choledochal stones, 42 had positive bile cultures (44% pure, 12% anaerobes). One of 52 patients who received preoperative cefazolin got a staphylococcal WI, but ten of 40 patients without antibiotic therapy developed WIs, nine caused by organisms that also grew from the bile. Of 23 patients with obstructive cholangitis, 22 had positive bile cultures (88% mixed, 23% anaerobes). Despite antibiotic therapy, four developed WIs caused by these organisms. The concept of clinical risk factors is validated.

Adult↗
PubMed2006

Twenty years of systemic therapy for breast cancer.

The past 2 decades of systemic therapy for breast cancer have been a period of monumental change, in terms of both theory and technology. Adjuvant therapy developed from two strands of research--one in systemic chemotherapy and one in hormonal therapy--both of which were aided by the application of higher statistical methodology to clinical trials. The agent with the single greatest public health impact in oncology has been tamoxifen, but problems with tamoxifen therapy led to the development of the aromatase inhibitors, and further research led to the use of hormonal therapy in a chemopreventive capacity. The evolution of systemic chemotherapy for breast cancer has been an interplay between theory-driven approaches and new agents. By the late 1980s, accumulating data revealed that overexpression of HER2 (erbB2) played an important role in a substantial portion of breast cancers, which prompted the development of trastuzumab (Herceptin), an agent targeting HER2-positive disease. Determining HER2 status proved essential to assessing patient eligibility for trastuzumab therapy. Decoding of the human genome and application of bioinformatics further revolutionized the possibilities in breast cancer treatment.

Antibodies, Monoclonal↗
PubMed2001

[Expectations of patients with rheumatism from new therapies].

The expectation of patients with rheumatism concerning newly developed therapies are described on the basis of the experience of the patients' self-help movement. Most important are the wishes of the patients for healing and for treatment which is safe and without adverse effects. The measures necessary for better implementation of research results in the treatment of patients are described.

Antirheumatic Agents↗
PubMed2003

Novel immunotherapeutic strategies for invasive fungal disease.

Infectious diseases still represent a major cause of mortality in man. Failure of the immune system to eradicate pathogens may result in serious invasive infections. Increasing numbers of immunocompromised patients, ineffective treatment and the emergence of drug-resistant pathogens represent the underlying problems. The focus of this review is on the pathogenesis of systemic fungal disease and the development of novel immunotherapeutic approaches. A comprehensive understanding of host-pathogen interactions is required for manipulation of immune responses to direct anti-fungal immunity. The potential of growth factor- and antibody-based therapeutics for invasive fungal disease are discussed. Recent advances in antibody technology may provide new strategies for developing antibody-based anti-fungal therapies. Development of fungal disease is related primarily to impaired host defense mechanisms, which emphasizes the importance of immunorestorative therapy in immunocompromised individuals. Controlled comparative clinical research is needed to evaluate the efficacy of novel immunotherapies, which provide prospects for the future management of invasive fungal disease.

Adoptive Transfer↗
PubMed1997

Botulinum toxin: chemistry, pharmacology, toxicity, and immunology.

The seven serotypes of botulinum toxin (BTX) produced by Clostridium botulinum exert their paralytic effect by inhibiting acetylcholine release at the neuromuscular junction. Each of these zinc endopeptidases cleaves one or more proteins involved in vesicle transport and membrane fusion. The extent of paralysis depends on both doses and volume; the duration of paralysis is further dependent on the serotype employed. Restoration of neuromuscular function follows axon terminal sprouting. The two major commercial preparations of BTX-A appear to differ in their relative potencies, despite a common unit labeling system. Adverse effects are a consequence of the drug's mechanism of action, and can usually be tolerated or mitigated through dosing changes. Patients who are pregnant or lactating, or who have a neuromuscular disease, may not be appropriate candidates for BTX therapy. Development of resistance to BTX-A therapy, characterized by absence of any beneficial effect and by lack of muscle atrophy following the injection, is an important clinical issue. The incidence of antibody-mediated resistance, as determined by the mouse lethality assay, is reported between 3% and 10%. Use of the smallest possible effective dose and longer treatment intervals may reduce the likelihood of antibody development. Other serotypes may benefit those who have developed antibody resistance.

Animals↗
PubMed1992

[A case with delayed-onset radiation pneumonitis suspected to be induced by oral etoposide].

Radiation pneumonitis usually occurs within 1-3 months after the completion of radiation therapy. A 63-year-old male with primary lung cancer treated by radiation therapy developed radiation pneumonitis 5 months after the completion of radiation therapy. He received 60 Gy to the lung tumor in a conventional fractionation schedule, and then two courses of intravenous chemotherapy using cis-diamine-dichloroplatinum (II) (110-140 mg) and etoposide (140-175 mg). Oral etoposide was initiated for bone metastases on the 104th day after the completion of radiation therapy at a daily dose of 20 mg, to a total dose of 1075 mg. He complained of fever and exertional dyspnea 5 months after the completion of radiation therapy. Chest radiography showed homogeneous infiltrates in the irradiated lung. These clinical signs and symptoms were refractory to antibiotic therapy, but steroid therapy resulted in marked improvement. The development of radiation pneumonitis was suspected to be induced by oral etoposide, which was given before the onset of radiation pneumonitis. These data suggest that etoposide induces a recall phenomenon, as has been demonstrated with such drugs as adriamycin and actinomycin-D.

Administration, Oral↗
PubMed1975

Wiskott-Aldrich syndrome with 18-year survival. Treatment with transfer factor.

An 18-year-old boy with Wiskott-Aldrich syndrome has severe symptoms of thrombocytopenia, recurrent infections, and atopic eczema. We believe he is the fifth oldest patient described with Wiskott-Aldrich syndrome. Recently, a malignant lymphoma of the histiocytic type appeared in the skin, while he was receiving transfer factor. To our knowledge, he is the only reported patient with lymphoma in the skin, but four other patients with Wiskott-Aldrich syndrome have developed malignant lymphoreticular lymphoma during transfer factor therapy. Detailed immunologic studies show failure to make a sustained antibody response to various antigens, lack of delayed hypersensitivity responsiveness, and failure of proliferative response to antigens in in vitro cultures. The IgE and IgA levels were high, and the IgM and IgG levels were low. Although clinical improvement followed transfer factor therapy, development of the malignant lymphoma was not prevented.

Adolescent↗
PubMed2001

Childhood acute lymphoblastic leukaemia--current status and future perspectives.

The current cure rate of 80% in childhood acute lymphoblastic leukaemia attests to the effectiveness of risk-directed therapy developed through well-designed clinical trials. In the past decade there have been remarkable advances in the definition of the molecular abnormalities involved in leukaemogenesis and drug resistance. These advances have led to the development of promising new therapeutic strategies, including agents targeted to the molecular lesions that cause leukaemia. The importance of host pharmacogenetics has also been recognised. Thus, genetic polymorphisms of certain enzymes have been linked with host susceptibility to the development of de novo leukaemia or therapy-related second cancers. Furthermore, recognition of inherited differences in the metabolism of antileukaemic agents has provided rational selection criteria for optimal drug dosages and scheduling. Treatment response assessed by measurements of submicroscopic leukaemia (minimal residual disease) has emerged as a powerful and independent prognostic indicator for gauging the intensity of therapy. Ultimately, treatment based on biological features of leukaemic cells, host genetics, and the amount of residual disease should improve cure rates further.

Child↗
PubMed1999

Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy.

PUVA-bath therapy developed into a first line topical PUVA therapy, and gel and cream preparations have been described as alternative modes of topical 8-MOP application. Because bath-PUVA can be difficult to manage, topical PUVA therapy using 8-MOP gel or cream preparations may become an important alternative when treating localised skin diseases. However, controlled comparisons of efficacy with this alternative topical PUVA therapy are lacking. We therefore compared the efficacy of PUVA-cream therapy with PUVA-bath therapy in 12 patients with recalcitrant dermatoses of the palms and soles using a left/right trial design. These patients responded well to both treatment modalities, meaning that both could be used successfully to treat recalcitrant dermatoses of the palms and soles.

Administration, Cutaneous↗
PubMed2001

A murine model of smoke inhalation.

The United States has one of the world's largest per capita fire death rates. House fires alone kill >9,000 Americans annually, and smoke inhalation is the leading cause of mortality from structural fires. Animal models are needed to develop therapies to combat this problem. We have developed a murine model of smoke inhalation through the design, construction, and use of a controlled-environment smoke chamber. There is a direct relationship between the quantity of wood combusted and mortality in mice. As with human victims, the primary cause of death from smoke inhalation is an elevated blood carboxyhemoglobin level. Lethal (78%) and sublethal (50%) carboxyhemoglobin levels were obtained in mice subjected to varying amounts of smoke. Mice exposed to wood smoke demonstrated more dramatic pathology than mice exposed to cotton or polyurethane smoke. A CD-1 model of wood smoke exposure was developed, demonstrating type II cell hypertrophy, cytoplasmic blebbing, cytoplasmic vacuolization, sloughing, hemorrhage, edema, macrophage infiltration, and lymphocyte infiltration. The bronchoalveolar lavage fluid of smoke-exposed mice demonstrated a significant increase in total cell counts compared with those in control mice. These findings are comparable to the lung tissue response observed in human victims of smoke inhalation.

Animals↗
PubMedDate not supplied

Prevalence of the intron 22 inversion of the factor VIII gene and inhibitor development in Polish patients with severe hemophilia A.

INTRODUCTION: Patients with severe hemophilia A often develop inhibitors (antibodies) against transfused factor VIII. MATERIAL/METHODS: One hundred thirteen Polish patients with severe hemophilia A, who had been treated on demand with cryoprecipitate until 1992 and exclusively with factor VIII concentrates after 1995, were examined for intron 22 inversion by Southern blotting and the presence and magnitude of inhibitor activity in blood as determined by the Bethesda assay. The patients' ages ranged 4--67 years (mean: 33.7+/-12.4 years, median: 32 years). RESULTS: The number of patients with the inversion amounted to 57, while in 56 patients the mutation types were unknown; 47 patients had a distal and 10 patients a proximal type of inversion. Thirteen patients with inversions (22.8%) were found to have inhibitor in their blood. Most patients (14 out of 15) who developed inhibitors in the course of cryoprecipitate therapy were high responders. Conversely, 4 of 5 patients treated between 1992 and 1995 with both cryoprecipitate and intermediate-purity factor VIII concentrates were low responders. One multitransfused patient who had remained inhibitor-free on cryoprecipitate therapy developed inhibitor after receiving a large dose of factor VIII concentrate during surgery. None of these 5 patients developed inhibitors during their 12--40 years of treatment with cryoprecipitate, suggesting that it was less immunogenic than factor VIII concentrates. CONCLUSIONS: The prevalence of the intron 22 inversion mutation of the factor VIII gene in Polish hemophiliacs is similar to that in other European countries. Treatment regimens with either cryoprecipitate or virus-inactivated plasma-derived factor VIII concentrates may affect inhibitor formation in hemophilia A patients.

Adolescent↗
PubMed1979

Cimetidine-induced neutropenia: a possible dose-related phenomenon.

Neutropenia associated with high-dose cimetidine therapy developed in a patient in whom earlier therapy, as well as rechallenge with low-dose cimetidine, did not result in neutropenia. As other factors cannot be implicated, a dose-related toxicity of cimetidine appears likely. Although the mechanism of cimetidine-induced neutropenia is unknown, it may involve the previously demonstrated ability of histamine H2 receptor antagonists to block the histamine-induced initiation of DNA synthesis in bone marrow stem cells.

Adult↗
PubMed1976

Yersinia enterocolitica septicemia with septic arthritis.

We report a case of Yersinia enterocolitica septicemia with septic arthritis. Gentamicin administration controlled the septicemia but failed to eradicate the organisms in the joint, in spite of a synovial fluid level four times its minimal inhibitory concentration after four days of therapy. Development of azotemia necessitated change of antibiotic therapy to chloramphenicol, which eradicated the infection. While Y enterocolitica infection in the United States is uncommon, it must be added to the list of organisms causing suppurative arthritis and septicemia in susceptible hosts. Septic arthritis must be distinguished from the much more common reactive theumatic polyarthritis associated with Y enterocolimica infection, for which antibiotic therapy is neither needed nor helpful.

Adolescent↗
PubMed1995

Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956.

ras oncogenes are present in several types of cancers but are most frequently described in colon and pancreatic carcinomas. Consequently, ras is being targeted for drug development as a means to develop therapies for these types of cancer. The ras protein is posttranslationally modified by the addition of a farnesyl group, followed by cleavage of the COOH-terminal 3 amino acids and methylation of the prenylated cysteine. Because the posttranslational addition of farnesyl is obligatory not only for the remaining modifications to take place but also for ras control of cell growth, inhibitors of farnesylation are being developed as potential antitumor agents. In this report, a new peptidomimetic inhibitor of farnesyl transferase is described. This compound, B956, and its methyl ester B1086, inhibit the formation of colonies in soft agar of 14 human tumor cell lines expressing different ras oncogenes at concentrations between 0.2 and 60 microM. Higher concentrations of B956 (10-80 microM) were required to inhibit colony formation by 5 tumor cell lines without ras mutations. B956/B1086 at 100 mg/kg also inhibited tumor growth by EJ-1 human bladder carcinoma, HT1080 human fibrosarcoma, and to a lesser extent by HCT116 human colon carcinoma xenografts in nude mice. Furthermore, inhibition of tumor growth by B956 is shown to be correlated with inhibition of ras posttranslational processing in the tumor. Thus, peptidomimetic inhibitors of ras farnesylation have the potential to be developed as therapy for ras-dependent tumors.

Alkyl and Aryl Transferases↗