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Biomedical subjects

D M McCarthy

Publications and source records attributed to D M McCarthy.

At least 109 records · Page 6Linked to original sources
PubMed1984

Validation of Fourier amplitude ratio to quantitate valvular regurgitation.

It has previously been shown that patients with valvular regurgitation can be identified by the ratio of left and right ventricular amplitude values obtained from first harmonic Fourier analysis of the gated blood pool scan. The present study was designed to validate the accuracy of this technique for quantifying the amount of valvular regurgitation. In a blinded analysis of 19 patients who underwent cardiac catheterization, there was a close correlation between the radionuclide and hemodynamic determination of the amount of regurgitation (r = 0.84). The interobserver agreement for calculating the radionuclide data was also high (r = 0.88). These results suggest that the Fourier ventricular amplitude ratio is an accurate and reproducible technique for quantifying valvular regurgitation by gated blood pool scanning.

Adult↗
PubMed1984

Detection of sclerosing adenosis of the breast on a thallium scan.

Uptake of thallium in a patient with sclerosing adenosis of the breast was detected. Although thallium has been reported to accumulate in primary carcinoma of the thyroid, lung, and liver, detection of a breast lesion on a thallium scan has not been previously reported.

Coronary Disease↗
PubMed1984

Granulocytic cryopreservation: further studies on the pathogenesis of impaired cellular function.

The effects of different methods of purifying peripheral blood granulocytes on their functional capacity after cryopreservation have been studied. The standard method of isolating granulocytes by centrifugation through Lymphoprep sensitizes cells to damage induced by subsequent cryopreservation. Some of this damage occurs during addition of cryoprotectant and we describe how to add and remove dimethyl sulphoxide without impairing cell function. The granulocytic function that suffers most during cryopreservation is granulocyte migration. This impairment may be partially due to uncontrolled entry into the cell of calcium. In contrast the bactericidal capacity in vitro is not so greatly reduced and ability to reduce nitroblue tetrazolium redox dye even less so.

Blood Bactericidal Activity↗
PubMed1984

Haematological reconstitution and severity of graft-versus-host disease after bone marrow transplantation for chronic granulocytic leukaemia: the influence of previous splenectomy.

Eighteen patients with chronic granulocytic leukaemia (CGL) were treated by chemoradiotherapy and transplantation of bone marrow (BMT) collected from their HLA-identical sibs; engraftment with donor marrow occurred in all cases. Ten of the patients had been subjected to splenectomy before BMT; recovery after BMT of granulocyte, lymphocyte and platelet numbers in the peripheral blood was more rapid in these patients than in the eight patients who retained their spleens. Acute graft-versus-host disease occurred in 12 of the 15 evaluable patients and appeared to be more severe in those who lacked their spleens at the time of transplant. Of the 12 patients surviving at follow-up times ranging from 59 to 207 weeks, six had been subjected to splenectomy before BMT and six retained their spleens. We conclude that engraftment was more rapid in the splenectomized patients and splenectomy might have increased the chance of eradicating the leukaemia, but these considerations must be balanced against the short-term and long-term risks associated with splenectomy.

Adolescent↗
PubMed1984

Chemotherapy and autografting for chronic granulocytic leukaemia in transformation: probable prolongation of survival for some patients.

Between June 1977 and July 1983 51 patients with Ph1-positive chronic granulocytic leukaemia (CGL) in transformation were treated either by chemotherapy or by chemoradiotherapy followed by autografting with haemopoietic stem cells collected from their peripheral blood at the time of diagnosis. Forty-eight patients were restored to a second chronic phase. The median duration of survival after autografting was 26 weeks (range 2-152 weeks). Twenty-one patients with relatively long durations of second chronic phase were treated again by autografting as consolidation or when transformation recurred; this selected group of patients survived longer than the 30 patients treated by autografting only once (medians 52 v. 13 weeks respectively, P less than 0.01). There was no significant influence of the patients' age, splenectomy status, type of transformation, treatment pre-autograft or number of nucleated cells autografted on the duration of survival. Three patients treated in myeloid blastic transformation were restored to partially Ph1-negative haemopoiesis. We conclude that this approach to the management of CGL in transformation can offer benefit for a minority of patients and that further chemotherapy and autografting for patients still in second chronic phase may be valuable.

Adolescent↗
PubMed1984

Transfusion of circulating stem cells.

Bone marrow collected from all species including man contains specific cells, putative pluripotential stem cells, capable of reestablishing hemopoiesis in a syngeneic or genetically identical member of the same species which has been treated with whole body irradiation. The question of whether similar pluripotential stem cells are present in the circulation in all animals is not yet resolved. In mice, reconstitution of hemopoiesis can be achieved by transfusion of peripheral blood cells only. The same result can be obtained in dogs and probably in baboons. In dogs, experiments with fresh and cryopreserved blood mononuclear cells have confirmed a dose-response relationship--below a certain number of mononuclear cells failure of hemopoietic reconstitution can be predicted. In man, isolated anecdotal case reports suggest that pluripotential stem cells in the circulation may or may not be valuable in repopulating a bone marrow defective as a result of primary disease or following chemotherapy. Indirect evidence from in vitro culture of circulating myeloid progenitor cells suggests but does not prove that pluripotential stem cells circulate in normal man. Pluripotential stem cell numbers are probably greatly increased in the circulation in patients with chronic granulocytic leukemia: such cells can be collected, cryopreserved, and used at a later date as "bone marrow autografts". Whether circulating stem cells can be collected and used in an analogous manner for patients with other leukemias or other neoplasms is not yet established.

Adolescent↗
PubMed1984

Specific uptake of 1,25-dihydroxycholecalciferol by human chronic myeloid leukemia cells.

We have examined mononuclear cell preparations from patients with chronic myeloid leukemia [CML] for binding of and response to 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. Whole cells specifically took up [3H]-1,25-(OH)2D3 with high affinity (Kd 3.6 X 10(-11) M) and low capacity. Subcellular fractionation of labeled cells showed that binding was restricted to cytosols and nuclei. Sucrose gradient centrifugation of cells preincubated with [3H]-1,25-(OH)2D3 revealed a single 3.6S peak which was totally displaced with 100-fold excess nonradioactive hormone. However, we were unable to demonstrate specific binding of 1,25-(OH)2D3 by postlabeling standard cytosol preparations. In addition, cytosols prepared from a mixture of CML cells and 1,25-(OH)2D3 receptor-positive T47D (human breast cancer) cells had less than 10% of the binding measured in T47D cytosol alone. However, the levels of binding in T47D cytosols were not reduced if the receptors were occupied with [3H]-1,25-(OH)2D3 prior to the addition of the CML cytosols. Thus, CML cells appear to contain both the receptor for 1,25-(OH)2D3 and an unknown substance which prevents its detection following the preparation of cytosol. Cells from patients with CML in the chronic phase specifically bound more 1,25-(OH)2D3 [18.0 +/- 3.2 (S.E.) fmol/10(7) cells] than did those in acute myeloid transformation [7.2 +/- 1.5] or than did cells from patients with acute myeloid leukemia [2.6 +/- 0.8]. Only cells from the first group of patients responded to the addition of 1,25-(OH)2D3 by differentiating along the monocyte-macrophage pathway. We conclude that the differentiation-induction effect of 1,25-(OH)2D3 is likely to depend on adequate levels of receptor and that intact cells rather than cytosol preparations should be studied before cells of a particular tissue are designated as receptor negative.

Calcitriol↗
PubMed1983

Relation between site of origin of ventricular tachycardia and relative left ventricular myocardial perfusion and wall motion.

To assess the relation between the site of origin of ventricular tachycardia (VT) and relative myocardial perfusion and wall motion, 18 patients with a history of recurrent sustained VT underwent cardiac catheterization, invasive electrophysiologic study with endocardial mapping, and resting radionuclide ventriculography. In addition, 6 patients had exercise and redistribution thallium-201 scintigraphy, whereas the remaining 12 patients had resting thallium scans. The site of origin of VT (determined by catheter and intraoperative endocardial mapping) was correlated with relative myocardial perfusion (thallium) and left ventricular (LV) wall motion. All patients had significant (greater than 50% narrowing) coronary artery disease and 16 had LV aneurysms. Twenty sites of origin of VT (28 morphologies) were identified in these 18 patients. Of the 9 patients with multiple VT morphologies, the VT originated at disparate sites in 2 patients. All 18 patients had thallium defects at rest and 3 patients had additional reversible (ischemic) defects on exercise. Of the 20 sites of origin of VT, 16 were at the periphery of the thallium defect, 1 was adjacent to it, and 3 were in the center of it. In the 16 patients with LV aneurysm, there were 18 sites of origin: 15 at the border of the aneurysm, 1 adjacent to it, and 2 within it. The data suggest that in patients with VT and coronary artery disease the site of origin is usually the periphery of a resting thallium defect, and in patients with LV aneurysm the site is the border of the aneurysm.

Adult↗
PubMed1983

1,25-dihydroxyvitamin D3 inhibits proliferation of human promyelocytic leukaemia (HL60) cells and induces monocyte-macrophage differentiation in HL60 and normal human bone marrow cells.

1,25-dihydroxyvitamin D3 induces monocyte-macrophage differentiation and inhibits proliferation of cells from the human promyelocytic leukaemia cell line HL60. Similarly human bone marrow progenitor cells differentiate preferentially along the monocyte-macrophage pathway when incubated in the presence of 1,25-dihydroxyvitamin D3. We suggest that the inhibition of growth which occurs after addition of the vitamin to HL60 might be paralleled in vivo by inhibition of proliferation of leukaemic cells; also we speculate that the vitamin may be involved in the control of both monocyte-macrophage and osteoclast production in vivo.

Animals↗
PubMed1983

Predictors of the success or failure of medical therapy in patients with chronic recurrent sustained ventricular tachycardia: a discriminant analysis.

To identify predictors of the success or failure of medical therapy in chronic recurrent sustained ventricular tachycardia, univariate and multivariate statistical techniques were used to retrospectively analyze data in 84 patients with this arrhythmia. By univariate analysis, four factors were associated with successful medical treatment: age less than 45 years, ejection fraction greater than 50%, hypokinesia as the only contraction abnormality and the absence of organic heart disease. Four other findings, the induction of ventricular tachycardia with a single ventricular extrastimulus, an HV interval greater than 60 ms, the presence of a left ventricular aneurysm and Q waves on a baseline electrocardiogram, correlated with medical failure. However, none of these variables alone accurately predicted treatment results in more than 75% of cases. By discriminant analysis, a function incorporating eight variables was constructed which correctly classified 81% of patients. Moreover, three-quarters of the patients could be classified into groups with a high or low probability of success where accuracy increased to 90%. When the discriminant function was tested prospectively in 31 similar patients, 25 (81%) fell into the groups with a high or low probability of success. In the latter group, of 20 patients predicted to fail medical therapy, 19 (95%) did fail a complete trial of medical therapy. The overall accuracy remained a high 92%. In clinical application this function would allow patients with a high probability of responding to medical therapy to be selected for serial electrophysiologic drug testing. In patients with a low probability of responding to medical therapy, serial studies could be avoided and alternate forms of therapy explored.

Anti-Arrhythmia Agents↗
PubMed1983

Antigenic expression and proliferative status of multilineage myeloid progenitor cells (CFU-GEMM) in normal individuals and patients with chronic granulocytic leukaemia.

We assayed the number of multilineage myeloid progenitor cells (CFU-GEMM) in the blood and marrow of patients with newly diagnosed chronic granulocytic leukaemia (CGL). The mean number of CFU-GEMM in the blood was increased 600-fold and CFU-GEMM in the marrow was doubled in the CGL patients compared with normal. A complement-fixing monoclonal antibody with HLA-DR specificity inhibited the proliferation of CFU-GEMM from CGL blood to a greater extent than that of comparable cells in normal marrow. Using a hydroxyurea 'suicide' method we found that the proportion of CFU-GEMM in proliferative cycle was higher in CGL blood than in normal marrow. We conclude that (1) CFU-GEMM numbers are greatly increased in the blood of patients with CGL, (2) CFU-GEMM express HLA-DR antigens on their surface, and (3) the apparently increased expression of the antigen on CFU-GEMM from CGL blood in comparison with CFU-GEMM from normal marrow may parallel the relatively higher proportion of CGL CFU-GEMM in cell cycle.

Antibodies, Monoclonal↗
PubMed1983

Fractionation of whole body irradiation before bone marrow transplantation for patients with leukaemia.

Thirty patients in various stages of acute leukaemia or chronic granulocytic leukaemia (CGL) were treated with cytotoxic drugs followed by whole body irradiation (TBI) administered in 200 cGy fractions twice daily to a total of 1000 or 1200 cGy. The immediate toxicity of fractionated TBI administered in this way was negligible and patients required only minor premedication and little treatment subsequently for complications attributable to TBI. Fourteen (47%) patients have died, ten of the 12 transplanted with active disease, and four of the 18 subjected to transplantation in remission of acute leukaemia or in chronic phase of CGL. Though the duration of follow-up is still short, no patient in the latter group (follow-up of survivors ranging from six to 146 weeks) has yet relapsed with any evidence of recurrent leukaemia. We conclude that this method of fractionating TBI reduced toxicity for the patient without necessarily reducing its antileukaemic effect.

Acute Disease↗
PubMed1983

Ranitidine or cimetidine.

Ranitidine, a new H2-receptor blocking antihistamine, is pharmacokinetically similar to cimetidine, but its potency is about eightfold greater. The clinical response to ranitidine is more prolonged, largely because of potency and not kinetic advantage. Increased potency has not meant greater clinical efficacy: duodenal ulcer healing, at 4, 6, or 8 weeks of therapy, does not differ between ranitidine and the cheaper cimetidine. Compliance and overall safety appear excellent for both drugs at this time. The safety record and side effects of cimetidine, but not ranitidine, are well established. So far, side effects of ranitidine are minimal, and in some cases anecdotal, but they cannot be ignored. Emerging information suggests that, although the incidence and severity of certain side effects may prove different for ranitidine than cimetidine, the pattern of side effects is similar with both drugs.

Cimetidine↗
PubMed1983

Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome.

In the present study we explored whether the presence or absence of symptoms could provide a reliable way of assessing the adequacy of control of gastric secretion in patients with Zollinger-Ellison syndrome who were treated medically. Over a 5-yr period, 26 Zollinger-Ellison syndrome patients were entered into a prospective study which examined the presence or absence of symptoms that are associated with gastric hypersecretion, the presence of absence of upper gastrointestinal pathology, and the degree of control of gastric acid secretion. During their last admission, 15 of the 26 patients (58%) were symptomatic, but post-drug gastric acid secretion for the 2 h before the next dose of medication was not significantly different from that in asymptomatic patients. This lack of correlation between the presence or absence of symptoms and post-drug gastric acid secretion was evident for the group as a whole, as well as for 8 to 12 patients who underwent multiple admissions. Of 23 patients who underwent upper gastrointestinal endoscopy of x-ray, or both, on their last admission, 12 had pathology. Post-drug gastric acid secretion was less in patients without pathology than in those with pathology. Furthermore, in patients in whom post-drug gastric acid secretion was less than or equal to 10 mEq/h, the criterion of acceptable control used in this study, pathology did not occur. These findings demonstrate that the presence or absence of symptoms cannot be used to assess the adequacy of medical control of gastric acid secretion in patients with Zollinger-Ellison syndrome. In our opinion, maintenance of post-drug gastric acid secretion less than or equal to 10 mEq/h for the 2 h before the next dose of medication is an acceptable criterion for long-term control of gastric secretion in patients with Zollinger-Ellison syndrome.

Adult↗
PubMed1983

Fourier amplitude ratio: a new way to assess valvular regurgitation.

The stroke-volume ratio determined from the equilibrium gated blood-pool study has been utilized to assess valvular regurgitation, but it is difficult to get reproducible results using generally available equipment. We have developed a new approach utilizing the Fourier amplitude ratio of the left and right ventricles, which is easily implemented and reproducible. Initial clinical experience shows that 17 patients with valvular regurgitation were clearly distinguished from 30 patients without valve disease.

Aortic Valve Insufficiency↗
PubMed1983

Fourier analysis of a gated blood-pool study during atrial flutter.

First-harmonic Fourier analysis of a gated blood-pool study is based on the assumption that the cardiac chambers contract once per cardiac cycle. In atrial arrhythmias this condition may not exist for the atria. We recently studied a patient with atrial flutter and 2:1 atrioventricular conduction. There were predictable alterations in the first-harmonic Fourier phase and amplitude images. The observed changes from first-harmonic Fourier analysis were: (a) very low atrial amplitude values, and (b) absence of identifiable atrial regions on the phase image.

Aged↗
PubMed1982

Marrow transplantation for patients in the chronic phase of chronic granulocytic leukaemia.

In 1979 two patients with Philadelphia (Ph1)-chromosome-positive chronic granulocytic leukaemia (CGL) were treated with chemoradiotherapy and transplantation of bone marrow from their respective identical twins. Subsequently twelve patients with Ph1-positive CGL in chronic phase were treated with chemoradiotherapy followed by transplantation of bone marrow from their HLA-identical sibs. Two of the fourteen patients have died of complications of the transplant procedure; twelve patients are alive and well. All the survivors have normal or nearly normal blood counts; there is no evidence of recurrent leukaemia or Ph1-positive cells in any patient after follow-up periods ranging from 97 to 1112 days. Bone-marrow transplantation should be considered in the management of any young patient with CGL who has a suitable marrow donor.

Adolescent↗