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Biomedical subjects

M L Murphy

Publications and source records attributed to M L Murphy.

At least 127 records · Page 7Linked to original sources

The changing management of childhood Hodgkin's disease.

Between 1929 and September 1974, 211 children under 15 years of age with biopsy-proven Hodgkin's disease were treated at Memorial Sloan-Kettering Cancer Center. For analysis these patients were placed into three historical groups which displayed the most marked changes in diagnostic workup and therapy. They are as follows: Pre-1959-80 patients with "clinical" staging, local field radiation therapy, palliative chemotherapy; 1960-1969-86 patients with lymphangiographic staging, extended field radiation therapy, palliative chemotherapy; 1970-September 1974-45 patients with "contemporary" staging, including laparotomy, involved field radiation therapy, and/or multiple drug chemotherapy. Twenty-seven children with Stage IV disease at diagnosis or those with recurrent disease received this multiple drug regimen. This consisted of Adriamycin, followed by combined prednisone, procarbazine, and vincristine, then cyclophosphamide. Drug cycles were repeated every 3-4 months for a period of about 24 months. Twenty-five achieved remission, 20 complete and 5 partial. The median duration of complete remission was 18 plus months. This multidisciplinary management of Hodgkin's disease has shown early, encouraging results. Longer followup is needed to determine that this improvement in survival will persist into adulthood.

Adolescent↗

Non-Hodgkin's lymphoma in children.

In a study of non-Hodgkin's lymphoma in children, 104 children were treated and followed at Memorial Sloan-Kettering Cancer Center from 1964 throughout June 1974. Forty-three patients, previously treated and untreated, received a nonspecific group of various chemotherapeutic agents and attained an 11% disease-free survival rate. A second group of 18 previously untreated patients, who received a chemotherapeutic regimen consisting of cyclophosphamide alone, achieved a 33% disease-free survival rate. The last group, 43 previously untreated patients (77% of whom had far advanced disease and 86% of whom had diffuse histological types) who received a new and intensive multiple-drug regimen (the LSA2-L2 protocol) consisting of induction, consolidation, and maintenance phases, has maintained an 81% disease-free survival rate after a median observation time of 21+ months. Although nervous system involvement and recurrence or metastases at any time are poor prognostic factors, initial marrow involvement and the amount of bulky disease are no longer considered negative prognosticators when intensive treatment is initiated immediately after diagnosis, is continued for 2--3 years, and includes radiation therapy to sites of bulky disease and CNS prophylaxis. The LS2-L2 treatment is effective in accomplishing the dual aims of not only increasing the numbers of disease-free patients but also prolonging their survival.

Adolescent↗

Mitochondrial function, oxygen extraction, epicardial S-T segment changes and tritiated digoxin distribution after reperfusion of ischemic myocardium.

This study examines the effect of 2 hours of reperfusion on transiently ischemic myocardium in pigs. Indexes of myocardial viability measured were mitochondrial function, oxygen extraction, epicardial S-T segment change and distribution of tritiated digoxin. Results were as follows: (1) Mitochondrial function was markedly impaired in the reperfused area after 60 minutes or more of coronary occlusion. The defect would seem to be a block in electron flow near site I, which can be partially bypassed with succinate. (2) An apparent inability of the reperfused myocardium to extract oxygen did not improve with 2 hours of reperfusion. (3) Epicardial S-T segment mapping suggested that necrosis occurred during reperfusion. (4) There was an altered distribution of tritiated digoxin in the reperfused area. The results show that reperfusion for 2 hours did not improve myocardial viability after 60 minutes or more of ischemia.

Adenosine Triphosphate↗

Altered refractory periods in patients with short P-R intervals and normal QRS complex.

To evaluate the refractory periods of the atrioventricular (A-V) conducting system in patients with a short P-R interval and normal QRS complex, 57 patients with a P-R interval of 110 to 280 msec were studied with His bundle recording and premature atrial stimulation at similar cycle lengths of 660 to 720 msec. In 13 patients with a short P-R interval (120 msec or less) the mean value for the functional refractory period of the A-V node was 368 plus or minus 36 msec (standard deviation), which was significantly lower (P smaller than 0.01) than the mean value of 415 plus or minus 50 msec in 36 patients with a normal P-R interval (between 120 and 200 msec) and the mean value of 492 plus or minus 57 msec in 8 patients with an increased P-R interval (200 msec or greater). Patients with a short P-R interval had a mean value for the effective refractory period of the A-V conducting system of 247 plus or minus 26 msec, which was significantly lower (P smaller than 0.01) than the mean values of 297 plus or minus 51 msec in patients with a normal P-R interval and 369 plus or minus 87 msec in patients with an increased P-R interval. The results identify a characteristic conduction abnormality that is compatible with a partial A-V nodal bypass or dual A-V nodal conduction pathways. The relation between the duration of the P-R interval and the regractory period may aid understanding of the clinical significance of the scalar electrocardiogram.

Adult↗

Electrophysiology of atropine.

The effect of atropine on the refractory periods of the human atrium, A-V node, and His-Purkinje system was studied. The A-V node in man appears more sensitive to atropine than the atria as evidenced by a reduction in the effective and functional refractory periods of the A-V node without alteration of atrial conduction. Although atropine does not directly alter the refractory periods of the His-Purkinje system, atropine-induced facilitation of A-V nodal conduction results in block of premature atrial impulses in the His-Purkinje system, demonstrating an indirect effect of atropine on His-Purkinje conduction. Rarely, atropine may precipitate re-entrant atrial tachycardia (one patient) through facilitation of A-V nodal conduction.

Adult↗

Electrophysiological significance of rapid atrial pacing as a test of atrioventricular conduction.

Although rapid atrial pacing is frequently used as a test of atrioventricular conduction, no studies have compared this method with other conduction parameters. The purpose of this study was to compare the results of rapid atrial pacing with refractory period measurements utilizing the extrastimulus technique. Determination of the refractory periods of the atrium, A-V node, and His-Purkinje system were accomplished in 41 patients undergoing diagnostic cardiac catheterization, and the results compared with rapid atrial pacing to the point at which A-V Wenckebach occurred (WP). The results showed significant correlation (P less than 0.01) between the WP and functional refractory period (FRP) of the A-V node (r=0.89, FRP=865-2.6 WP), and significant correlation between the WP and the effective refractory period (ERP) of the total A-V conducting system(r=0.81, ERP=729-2.6 WP). The relationship between WP and the refractory periods also allowed prediction of the occurrence of physiological His-Purkinje block during introduction of premature atrial contractions and the site of the effective refractory period of the total A-V conducting system. This study establishes a close relationship between these methods and confirms the usefulness of rapid atrial pacing as a reliable test of A-V conduction in man.

Atrial Function↗

In-hospital mortality after acute myocardial infarction.

In order to determine if the risk factors contributing to mortality from acute myocardial infarction (MI) during the period of coronary care unit (CCU) observation are different from those in patients dying in the hospital after CCU discharge, the hospital records of 172 acute MI patients seen over an 18-month period were reviewed. Of the 32 deaths from acute MI, 25 per cent occurred suddenly outside the CCU. The risk factors identified in the 32 deaths were (1) anterior MI (2) Previous MI, (3) cardiac failure, (4) significant ventricular arrhythmia, (5) intraventricular conduction defects, and (6) murmur suggestive of papillary muscle dysfunction. These same risk factors were found to be far more frequent in the patients dying suddenly outside the CCU.

Adult↗

Hemodynamic and pathological results from experimentally induced left ventricular hypertrophy in the rabbit.

Many studies of ventricular structure and function of the hypertrophied cardiac muscle have been performed using a model of right ventricular hypertrophy because a reliable experimental model for the chronically hypertrophied left ventricle was not available. Adult rabbits underwent thoractomy with placement of an ameroid band on the proximal aorta. The ameroid band closed to a maximal extent at 9 days. Systolic gradients were measured at 3 weeks. 37 animals (group I) were sacrificed at an average of 7 weeks, and 5 (group II) at 18 weeks. Specific cardiac chambers were weighed. The average left ventricular weight expressed as a percentage of body weight of control animals was 0.13 +/- 0.01 compared to group I 0.17 +/- 0.04 (P = 0.001) and group II 0.23 +/- 0.04. Hemodynamic data revealed significant aortic outflow obstruction with systolic gradients averaging at least 50 mm Hg. Left ventricular end-diastolic pressures were elevated in 13 of 29 animals compatible with left ventricular failure. These results indicate that this technique affords a reliable experimental model for inducing biventricular hypertrophy which can be evaluated hemodynamically.

Animals↗

Observer agreement in evaluating coronary angiograms.

The reliability of interpretation of coronary arteriography as a diagnostic tool was investigated in a sub-study of the VA Cooperative Study of Surgical Treatment for Coronary Arterial Occlusive Disease. Twenty-two physicians with varying levels of experience read 13 cine angiograms -- blind -- on two different occasions. Analysis of inter- and intraobserver variability showed that angiographic items about which observers were most inconsistent from one reading to the other had the largest interobserver disagreement as well. They were the distal portions of the left anterior descending and left circumflex arteries. Among the items on which there was most consistent agreement -- namely, the right main coronary artery and presence of ventricular aneurysm -- there was most often agreement between observers as well. When individual readers were evaluated, some observers were far more consistent in their own readings of all the angiographic items than others. This intraobserver agreement in turn correlated fairly well with how often they agreed with the other observers and with how much experience they reported having in reading coronary cineangiograms.

Angina Pectoris↗

Treatment of acute lymphoblastic leukemia in childreq with "prophylactic" intrathecal methotrexate and intensive systemic chemotherapy.

Sventy-five children under the age of 15 years, with acute lymphoblastic leukemia, were treated with a multiple drug chemotherapy regimen (L-2) and intrathecal methodtrexate. Remission was achieved in all except 1. Three died from infection early in remission and 1 was lost to follow-up. Of the remaining 70, relapse occurred in 19; in 3 children this was confined to the central nervous system (CNS) and in 1 was in both the CNS and bone marrow. Fifty-one children continue in complete remission from 14 to 54 months. Fourteen of these children have completed 3 years of chemotherapy and are disease free 2 to 18 months posttreatment. The results indicate that periodic administration on intrathecal methotrexate with no CNA irradiation, plus intensive systemic chemotherapy, can effectively control CNA leukemia and prolong the duration of complete remissions.

Adolescent↗

Non-Hodgkin's lymphoma in children: results of treatment with LSA2-L2 protocol.

The results obtained with very intensive treatment in previously untreated patients early in the disease are encouraging, and we hope will change the philosophy of most investigators that even in far advanced disease such as those with marrow metastases or multiple primary sites, one can still obtain complete regression at all tumour sites within 1 to 1 1/2 months from onset of therapy by combined treatment with multiple chemotherapeutic agents and radiation therapy to one or more sites.

Adolescent↗

Tritiated digoxin: studies in renal disease in human subjects.

Digoxin is excreted primarily in the urine as the unchanged glycoside: 60-80% can be recovered from the urine in 7 days after a single intravenous dose in the human subject. Definition of the role of the kidney in digoxin excretion, turnover and metabolism was studied in 57 patients with renal disease, transplant candidates and/or donors and recipients of renal transplants. A single dose of 3H digoxin was given to the subjects, frequent serum samples were obtained and all urine and stools were saved for 7 days. All specimens were extracted with chloroform and digoxin, and its metabolites were separated by column chromatography. Results reveal that the serum T1/2 and the dominant T1/2 of digoxin are prolonged in renal disease in direct proportion to the reduction in creatinine clearance (r = 0.833). The blood urea nitrogen (BUN) is also related to digoxin clearance (r = 0.742). The higher the BUN, the less digoxin excreted in the urine. Anephric patients excrete more digoxin in stool, but this does not compensate for the lack of renal excretion. Transplanted kidneys excrete digoxin in proportion to renal functional capacity, as do patients who have experienced unilateral nephrectomy. Peritoneal or hemodialysis is not effective in removing digoxin from the human subject and may lead to digitalis intoxication if K+ is allowed to fall to critical levels. Digoxin excretion is not volume related, as patients with nephritogenic diabetes insipidus excrete the drug normally with urine volumes of 12 liters a day. Digoxin doses in renal insufficiency should be dictated by knowledge of renal functional ability of the kidneys and after "normal" loading doses, and maintenance doses should be 1/4 to 1/2 those usually administered.

Adult↗

Impairment of mitochondrial function following reperfusion of acutely ischemic myocardium.

This study examines indices of respiratory function in mitochondria prepared from transiently ischemic myocardium that had been reperfused in order to evaluate the validity of performing early surgical revascularization procedures. Experiments were performed in pigs with temporary ligation (15-80 min) of an anterior descending coronary artery followed by a 2-hr reperfusion period. Mitochondria preparations were studied simultaneously from normal and reperfused mitochondria in malate and glutamate substrates using the polarographic method. Results revealed a marked decrease of oxygen consumption of mitochondria from reperfused myocardium with relative preservation of oxidative phosphorylation (near normal ADP/O ratio). These results are compatible with a block in electron transport, a theory which was further supported by the data obtained using dinitrophenol as an uncoupler. Additional studies suggested the block was located at site I in the electron transport chain since mitochondrial oxygen consumption, including ATP-linked oxygen consumption, was enhanced by the use of succinate in combination with glutamate. The abnormal mitochondrial function observed is probably due to ischemia persisting despite reperfusion.

Acute Disease↗