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Biomedical subjects

M Leahy

Publications and source records attributed to M Leahy.

45 records · Page 3Linked to original sources
PubMed1983

Ligand-induced conformational changes in proteins.

The natures and roles of ligand-induced conformational changes are described in terms of the influence of the ligand on the equilibrium distribution of the protein structure among various conformational states. A very commonly observed conformational change is produced by a ligand binding into a cleft that lies between two domains and then closing the cleft through a hinge-like motion. Such a change in hexokinase serves to bring potential catalytic groups into the active site and to provide a binding site for the three phosphates of ATP. Flexibility in gene regulatory proteins such as the Escherichia coli catabolite activator protein and lac repressor may be important in the dual requirement for rapid diffusion of the proteins along the DNA as well as specific recognition of base sequences. A second role for flexibility in this class of proteins is to reduce their affinity for affinity for DNA, without reducing their capacity to discriminate among sequences.

Adenosine Triphosphate↗
PubMed1982

Heart failure in outpatients: a randomized trial of digoxin versus placebo.

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the severity of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P less than 0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound.

Adult↗
PubMed1970

Effects of rapidly and slowly permeating osmotica on metabolism.

Zea mays was exposed to solutions of low water potentials by addition of ethylene glycol or mannitol. Intact seedlings were treated for 1 hr at potentials between -10 and -20 atmospheres and then returned to high water potentials. Subsequent root extension was slow after mannitol treatment, but rapid when ethylene glycol had been used as the osmoticum. Cellular activity of excised roots was also affected much less by ethylene glycol than by mannitol. Processes studied included respiration, glucose uptake, and synthesis of methanol-insoluble compounds. These differences in response to various osmotica applied both during and after treatment at low water potentials.Ethylene glycol penetrated the tissues much more rapidly than mannitol. Rapid penetration of the osmoticum would minimize turgor loss and plasmolysis. Thus, the data suggest that adverse effects were induced by water loss or structural changes, or both, during plasmolysis, rather than by low water potentials, demonstrating the crucial importance of osmotic adjustment.

Journal Article↗
PubMedDate not supplied

Recombinant human granulocyte macrophage colony stimulating factor following alternating non cross resistant chemotherapy in Hodgkin's disease.

Fourteen patients with Hodgkin's disease (two previously untreated, 12 following relapse or with refractory disease) were treated with a combination chemotherapy regimen comprising chlorambucil, vinblastine, procarbazine, prednisolone, etoposide, vincristine and adriamycin administered on days 1-8. Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (mammalian glycosylated, Sandoz/Schering-Plough) was administered after alternate cycles of chemotherapy from day 10 for 7 days by continuous intravenous (i.v.) infusion in 12 patients in a dose finding study (dose: 2 micrograms/kg/day in four patients, 4 micrograms/kg/day in four patients and 8 micrograms/kg/day in four patients) and by daily subcutaneous (s/c) injections in two patients (8 micrograms/kg/day). There was a rapid peripheral leucocytosis following the rhGM-CSF, reaching a peak at 1-2 days in 12/14 patients. The initial leucocytosis was composed of neutrophils followed by a rise in immature myeloid cells. There was no difference observed in the duration or depth of the nadir following chemotherapy or in the rate of recovery of peripheral white cell counts between cycles with and without rhGM-CSF in patients treated with 2 and 4 micrograms/kg/day. At the dose of 8 micrograms/kg/day, 3/6 patients had a shorter nadir duration in the cycle with rhGM-CSF, compared with cycle without rhGM-CSF. There was no difference in frequency of infection in cycles with and without rhGM-CSF. Following chemotherapy, six patients achieved clinical remission, six partial remission and two had progressive disease.

Adult↗
PubMedDate not supplied

Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy.

Thirty-four patients with refractory or recurrent high grade non-Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be 'consolidated' with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment-related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended 'curative' therapy, of whom only four are alive and well 1 year later.

Adolescent↗
PubMedDate not supplied

Autologous stem cell transplantation in myeloma: the St James's Hospital experience, 1997-2003.

BACKGROUND: High-dose treatment with autologous stem cell transplantation (ASCT) has become the standard of care for patients with myeloma below the age of 65 years. AIMS: We report an audit of 60 patients (median age: 52.5 years) who underwent ASCT in the National Bone Marrow Transplant centre in St James's Hospital in Dublin between 1997 and 2003 inclusive. METHODS: Clinical and laboratory data were retrieved from patient medical records and hospital information management systems. RESULTS: Thirty-six patients had IgG, 11 IgA, 1 IgD, 9 light chain and 3 non-secretory MM. Fifty-seven (95%) patients received anthracycline-corticosteroid combination chemotherapy prior to autografting. There was no transplant-related mortality (TRM). Complete (CR) and Partial Responses (PR) were seen in 16 (29.6%) and 29 (53.7%) of those evaluable (n = 54 (90%)). The actuarial Progression-Free (PFS) and Overall Survival (OS) rates at five years are 13% and 55% respectively. CONCLUSION: Centre outcome is comparable to published international series and supports the use of ASCT in the treatment of this malignancy.

Aged↗
PubMedDate not supplied

Docetaxel.

Paclitaxel was the first taxoid to become available. It was found to be an active anticancer agent but with significant toxicity. Docetaxel is a semisynthetic taxoid and the next of a fast-expanding class of drugs. Studies suggest that docetaxel may be more effective and less toxic than paclitaxel.

Antineoplastic Agents, Phytogenic↗