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Biomedical subjects

T C Jones

Publications and source records attributed to T C Jones.

At least 37 records · Page 2Linked to original sources
PubMed1995

Planning for the future: moving to the multispecialty group organizational structure.

Physicians in a Southeastern community were finding themselves ill equipped to deal with many of the requirements of insurance companies, state governments and managed care organizations. One medical practice was considering moving toward becoming a multispecialty group and adding physicians to keep with their objective of having a "growing practice." This case study is centered around the efforts of the physicians' involvement in the strategic planning process of growing their practice.

Delivery of Health Care↗
PubMed1994

Future uses of granulocyte-macrophage colony-stimulating factor (GM-CSF).

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used extensively to restore hematopoietic system function after damage by diseases such as myelodysplastic syndrome or by cytotoxic anti-cancer agents used during cancer chemotherapy or prior to bone marrow transplantation. The clinical benefits of this approach have included fewer infections, fewer hospital days and less antibiotic use. In the future, the use of GM-CSF will be focused on special situations within these general areas, plus new directions that were not previously given sufficient attention. Examples of focused approaches include the use of GM-CSF in the control of fungal or protozoal disease and to take advantage of anti-tumor effects of myeloid cell activation. The anti-microbial effects will also be explored in patients who are not neutropenic but have serious infections which may be benefited by increased stimulation to myeloid cell function. The use will also be focused on mobilization of peripheral blood progenitor cells and in cycling of normal hematopoietic and malignant cells. The new directions will include use of GM-CSF by local application in healing of cutaneous ulcers, rapid wound closure and skin grafting. Because of its potent effects on immunologic mechanisms of antigen presentation, it will be used in several ways as a vaccine adjuvant. This adjuvant action will be directed at enhancing immunologic responses to antimicrobial antigens and anti-tumor antigens. The future of GM-CSF as a tool for hematopoietic and immunologic stimulation with resulting important clinical benefits is clear.

Adjuvants, Immunologic↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor in combination with pentavalent antimony for the treatment of visceral Leishmaniasis.

The efficacy of GM-CSF was investigated in 20 neutropenic patients (< 1500 neutrophils/microliters) with acute visceral leishmaniasis due to Leishmania chagasi. Patients were randomized to receive either GM-CSF, 5 micrograms/kg daily (intravenously or subcutaneously), or placebo for ten days, in combination with pentavalent antimony, 10-20 mg/kg daily for 20 days. Neutrophil counts were significantly greater on days 5 and 10 of treatment in the GM-CSF group compared with the placebo group (p < 0.02). Eosinophil and monocyte counts were also significantly increased in the GM-CSF group at day 10 (p < or = 0.03). Interestingly, at day 30, platelet counts were significantly increased in the GM-CSF group on days 5 and 10 (p = 0.04 and 0.02, respectively). Patients in the GM-CSF group experienced fewer secondary bacterial or viral infections than placebo patients. Infections occurred in only three patients given GM-CSF compared with eight patients given placebo (p < 0.04). All patients had complete resolution of disease symptoms at three months. Few adverse events were recorded. GM-CSF given subcutaneously at a dose of 5 micrograms/kg daily for ten days was well tolerated, reversed neutropenia rapidly and reduced the number of secondary infections in patients with leishmaniasis.

Adolescent↗
PubMed1994

Recombinant human granulocyte-macrophage colony-stimulating factor reverses neutropenia and reduces secondary infections in visceral leishmaniasis.

Twenty-four patients with acute visceral leishmaniasis and leukopenia (< 1500 neutrophils/mm3) due to Leishmania chagasi were studied, 4 in an open-label pilot study and 20 in a double-blind, placebo-controlled trial. Patients received granulocyte-macrophage colony-stimulating factor (GM-CSF), 5 micrograms/kg daily, or placebo for 10 days, plus 10-20 mg/kg pentavalent antimony daily for 20 days. In GM-CSF recipients, neutrophil counts increased threefold and fourfold over baseline at 5 and 10 days, respectively, and were significantly higher than those in placebo recipients (P < .02). Eosinophil and monocyte counts were significantly increase in GM-CSF recipients at 10 days (P < or = .03). Secondary infections occurred in 3 GM-CSF and in 8 placebo recipients (P = .04). All patients had complete resolution of their leishmaniasis at 3 months. Few adverse events were recorded. GM-CSF, 5 micrograms/kg daily for 10 days, was safe, rapidly reversed neutropenia, and reduced the number of secondary infections in patients with leishmaniasis.

Adolescent↗
PubMed1993

Intervention treatment of established neutropenia with human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients undergoing cancer chemotherapy.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was given to 60 patients, in a double-blind, non-prophylactic study of already established chemotherapy-induced leucopenia, for 5 days by continuous intravenous infusion and twice or once daily by subcutaneous injection. Four patients were randomized to rhGM-CSF (3) or placebo (1) at each dose (1.3, 1.7, 5.5, 11, or 22 micrograms of protein/kg). Leucocyte recovery was significantly enhanced compared with controls, in a dose-dependent manner except for 22 micrograms/kg which was ineffective with a worse experience of side effects in some patients. Most adverse events occurred in equal proportions in the treated and placebo cases. Fourteen patients developed infection and were treated with antibiotics in addition to rhGM-CSF. They were joined by a further 18 febrile patients and treated with rhGM-CSF in a subsequent open-label trial. The survival from infection was related to white blood cell (WBC) count: 19 of 32 responded with increased numbers of leucocytes (WBC count above 1.5 x 10(9)/1) after 5 days of GM-CSF. Sixteen of the 19 leucocyte 'responders' recovered from infection, two died from the underlying disease and one from persistent infection. Six of the 13 patients who did not have a leucocyte response died with persistent infection. These data indicate that rhGM-CSF enhances the leucocyte count following chemotherapy and in this way saves critically ill neutropenic patients from fatal infections.

Adult↗
PubMed1993

The effects of rhGM-CSF on macrophage function.

Markers of monocyte/macrophage activity are numerous, and offer an insight on the potential effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). These include anti-microbial effects, anti-tumour effects, inflammation and wound healing enhancing effects, antigen presenting effects and effects on the haematopoietic microenvironment. The actions of rhGM-CSF on monocytes/macrophages relevant to enhanced antimicrobial activity include increased phagocytosis, increased oxidative metabolism, increased numbers of Fc receptors, release of chemotactic factors and stimulation of mechanisms for killing intracellular viruses, fungi, bacteria and protozoa. Markers of macrophage anti-tumour activities can be divided into two types: those associated with antitumour antibodies, antibody-dependent cell cytotoxicity (ADCC) and those associated with synthesis and secretion of cytolytic substances by activated macrophages. In addition, rhGM-CSF has actions on fibroblasts and kerotinocytes consistent with an important role in wound healing. Moreover, the clinical use of rhGM-CSF to enhance antibody responses in conditions of inadequate immunisation is currently being investigated. Furthermore, rhGM-CSF appears to have a role in stimulating haemopoietic recovery following cytotoxic chemotherapy or radiation damage to bone marrow tissue.

Granulocyte-Macrophage Colony-Stimulating Factor↗
PubMed1993

Clinical experience with Escherichia coli rHuGM-CSF.

The use of rHuGM-CSF has resulted in patient benefit as shown by reduced infections (MDS and AA), reduced days in intensive care (ABM transplant), better adherence to cancer chemotherapy protocols, and the ability to use full doses of antiviral drugs in AIDS and cytomegalovirus retinitis. The adverse reactions are significant when high doses are used, therefore high doses should be avoided (there is a plateau in the dose-effective biological responses). At recommended doses, GM-CSF is well tolerated and is a valuable adjunctive therapy in the management of patients with conditions of dysmyelopoiesis and myeloid hypoplasia associated with myelotoxic therapy, or after bone marrow transplantation.

Antineoplastic Agents↗
PubMed1992

The side-effect profile of GM-CSF.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic molecule which displays a broad range of haematopoietic activities, has become available for clinical evaluation in various patient groups. It has been shown to be effective in preventing or reversing neutropenia. Adverse effects of GM-CSF, however, are dose related. Appropriate dose, route and schedules for GM-CSF in various clinical settings have recently been defined, the usual range being 5-10 micrograms/kg/day either by 4-6 h intravenous infusion or by subcutaneous injection. At such doses, adverse effects are predominantly mild-to-moderate in nature, occur in 20-30% of patients and usually comprise fever, myalgia, malaise, rash and injection site reaction. Early trials using very high doses of GM-CSF were often associated with marked adverse effects, which in rare cases proved severe (pericarditis and thrombosis). Similarly, a so-called "first-dose reaction", defined as a syndrome of hypoxia and hypotension after the initial but not subsequent doses of GM-CSF, was observed in certain predisposed patients following doses above 10 micrograms/kg/day. Subsequent trials have established that intravenous bolus or short infusions of GM-CSF are more likely to promote adverse effects. Certain patient groups, for example those with myelodysplastic syndrome, acute myeloid leukaemia, inflammatory disease, autoimmune thrombocytopenia or malfunctional immunological responsiveness, require careful clinical monitoring in order to avoid potential complications following the administration of GM-CSF. With the current appropriate administration and doses of GM-CSF, the benefit:risk ratio has been greatly improved.

Dose-Response Relationship, Drug↗
PubMed1992

Special features of the clinical use of oral terbinafine in the treatment of fungal diseases.

Terbinafine (Lamisil) is an antifungal drug, belonging to a class of drugs called the allylamines, which has recently become available for clinical use. This is a report of four special features which emerged during evaluation of the systemic use of orally administered terbinafine in the treatment of 2500 patients during the last 5 years. These features include: (i) distribution of terbinafine in skin, hair and nail tissue; (ii) use in short-duration treatment of chronic tinea pedis and onychomycosis; (iii) use in patients with serious infections often associated with local or generalized immunological defects; and (iv) tolerability and safety of the drug. The diffusion of terbinafine into thickened, chronically infected tissue and into nails, and its recognized fungicidal action are the most likely features responsible for its success in the treatment of chronic fungal diseases, including those with immunological defects. Terbinafine is well tolerated, particularly when compared with other available systemic antifungal drugs.

Administration, Oral↗
PubMed1991

Carboxyl-terminal truncation of apolipoprotein B results in gradual loss of the ability to form buoyant lipoproteins in cultured human and rat liver cell lines.

Apolipoprotein B has an obligatory role in the production of chylomicrons, VLDL, and LDL. Familial hypobetalipoproteinemia is a codominant disorder characterized by reduced levels of apo B containing lipoproteins in plasma. We have previously described mutations of the apo B gene in persons with hypobetalipoproteinemia that predict truncated forms of apo B designated apo B29 (1305 amino acid residues) and apo B39 (1799 residues). Apo B39 was present in the VLDL and LDL fractions of plasma, but apo B29 was not detected in the lipoprotein or infranatant fractions of plasma. Here we have investigated the regions of apo B necessary for apo B containing lipoprotein secretion by expression of constructs designed to express truncated forms of apo B. Apo B13 (583 residues), apo B17 (784 residues), apo B23 (1084 residues), apo B29 (1306 residues), and apo B41 (1880 residues) were transiently expressed in HepG2 cells, and apo B23 and apo B41 were stably expressed in McArdle 7777 cells. Lipoprotein (d less than 1.25 g/mL) and infranatant (d greater than 1.25 g/mL) fractions of conditioned medium were analyzed by immunoprecipitation and SDS-PAGE. The distribution between lipoprotein and infranatant fractions varied: apo B41 was found solely in the lipoprotein fraction; apo B29, apo B23, and apo B17 were present in both fractions, but with stepwise truncation, progressively more apo B was recovered in the infranatant; apo B13 was only in the infranatant. These results demonstrate that deletion from the carboxyl terminal of apo B41 results in a gradual loss of the ability of the truncated proteins to form buoyant lipoprotein particles.

Animals↗
PubMed1991

Transfer of processing in repetition priming: some inappropriate findings.

Transfer effects in repetition priming were found with both picture and word naming, but varied with the type of prime list. Unmixed lists of word or picture primes produced equivalent intra-modal and cross-modal repetition priming in both picture-naming (Experiment 1) and word-naming (Experiment 5) tasks. However, mixing word and picture primes resulted in greater intra-modal than cross-modal priming for both picture-naming (Experiment 2) and word-naming (Experiment 6) tasks. This mixed-list difference between intra-modal and cross-modal priming was reduced by blocking prime types at input (Experiment 3). These findings suggest that differences in priming as a function of prime stimulus format should be cautiously interpreted when mixed prime lists are used.

Adult↗
PubMed1991

Recombinant human GM-CSF: present clinical results and potential use in oncologic and hematologic disorders.

The human recombinant GM-CSF (hrGM-CSF) is a glycosylated hematopoietic growth factor, derived from CHO cells (Schering Plough/Sandoz) used in these studies. The hrGM-CSF can be given intravenously (i.v.) in 4- to 24-h infusions or subcutaneously (scx) once or twice a day. Many patients (more than a thousand) have been treated with the hrGM-CSF in various pathologies, in association with anti-cancer chemotherapy, after bone marrow transplants or for myelodysplasias, refractory anemias, some neutropenias and infections. The reversion of neutropenia is dose-dependent with either a sc or i.v. administration. Recommended doses are from 5.0 to 10.0 micrograms/kg/per day. When the product is given sc the effect is delayed by one day but is more prolonged than with the i.v. route. The treatment duration has been investigated in different studies: a minimal duration of 5 days seems appropriate. When given in association with high doses of cytotoxic chemotherapeutic agents 10 to 14 days are required. In bone marrow transplants (autologous or allogenic with T-cell depletion), the hrGM-CSF has been shown to significantly reduce the time necessary for engraftment. Contrary to some fears, it was not shown that hrGM-CSF increased the risk of blastic transformation in myelodysplastic syndromes. In association with cytosine-arabinoside a certain number of partial and complete responses have been obtained. The toxic effects of the product are also dose-dependent. At doses greater than 11 micrograms/kg per day, there is a risk of stimulating inflammatory phenomena whereas at lower doses, more moderate side effects (myalgia, fever, injection site reaction) occur in only 30% of the cases. The GM-CSF will certainly be important in the future in haematology, oncology and for the treatment of infectious diseases.

Bone Marrow Transplantation↗
PubMed1989

Clinical efficacy and tolerability of terbinafine (Lamisil)--a new topical and systemic fungicidal drug for treatment of dermatomycoses.

Terbinafine (Lamisil) is the newest compound within a class of antimycotic drugs called allylamines. It is active against a broad range of dermatophytes and yeasts and exerts its fungicidal action by inhibiting squalene epoxidation during sterol synthesis in fungal membranes. Effective therapy (complete cure or mycological cure with minimal signs and symptoms) has been observed in 70-90% of 1200 patients treated topically with 1% cream for tinea corporis/cruris, tinea pedis, cutaneous candidiasis and pityriasis versicolor. Cure in patients treated systemically (125 mg b.i.d. orally) has been documented to be 75-90% in tinea corporis and chronic tinea pedis (plantar type), 60-70% in cutaneous candidiasis, and 90-100% in onychomycosis. Particularly noteworthy is the low rate of relapse of infection after cure of chronic dermatophyte infections, since frequent relapse is a recognized problem with presently available antifungal drugs. Terbinafine is ineffective when used systemically for pityriasis versicolor. Side-effects following oral administration of the recommended dose of 125 mg b.i.d. include gastrointestinal symptoms (3-4%), allergy (1%), and miscellaneous mild non-specific symptoms (1%). No significant haematological, hepatic or renal effects have been observed. Based on the drug's fungicidal action and the early appearance of negative cultures in these studies, a short duration therapy is predicted to be effective.

Administration, Oral↗
PubMed1987

Epidemiology of American cutaneous leishmaniasis due to Leishmania braziliensis braziliensis.

A five-year prospective study of cutaneous leishmaniasis in an endemic area of Brazil revealed an annual incidence of disease of 8.1 per 1000 inhabitants and a prevalence of 14.9%. The disease fluctuated as a series of mini-epidemics. Most disease occurred in individuals who were 10-30 years of age. Mucosal disease occurred in 2.7% of patients with primary lesions and occurred a median of six years after this lesion. Disease was more common in males, in those with either large or multiple antecedent skin lesions, and in those with incomplete antimony therapy for the primary lesions. An ELISA was positive in 85% of those tested during the first two years after the primary lesion and remained positive for five to 40 years in 27% of patients. Skin testing was positive in 96% of patients with recent lesions and remained positive in 70% of patients. All patients with mucosal disease had positive serological and skin tests.

Adolescent↗