Hemophilia and the family system.
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Adult↗
Biomedical subjects
R Simon
Publications and source records attributed to R Simon.
The biology of tumor growth in the non-Hodgkin's lymphomas. A dual parameter flow cytometry study of 220 cases.
Dual parameter flow cytometry studies (cell DNA content and electronic cell volume) were performed in 220 cases of non-Hodgkin's lymphoma. All cases were characterized as B or T cell malignancies, based on immunologic surface marker characteristics. Aneuploidy by flow cytometry was more common among the B cell lymphomas than among the T cell lymphomas, and was most common among the large B cell lymphomas and B cell lymphomas of intermediate size. Ploidy index distributions showed a prominent hyperdiploid peak, as well as tumor cell populations with near-tetraploid DNA contents. In serial studies, a decrease in ploidy index was observed in association with clinical and histologic transformation in one case. The highest S fractions were observed among the large and intermediate B cell lymphomas and among the aggressive T cell lymphomas. In clinical samples consisting of mixtures of diploid and aneuploid populations, the data on the aneuploid components could often be separated from other components of the mixture in multiparameter studies on the basis of the larger electronic cell volumes of the aneuploid cells. In each case, the aneuploid large cell component almost invariably had a higher S fraction than the residual component(s) of the mixture. Overall, the data are consistent with a model of clonal selection and clonal evolution in the lymphomas in which early cytogenetic abnormalities that involve little or no change in total cell DNA content are followed by cell tetraploidization that is associated with cytogenetic instability and chromosome loss over the course of time.
Aneuploidy↗
Importance of prognostic factors in cancer clinical trials.
The importance of prognostic factors in the design, analysis, and reporting of clinical trials is discussed. For many kinds of cancer, the variability in prognosis among patients is greater than the size of treatment differences usually seen. Consequently, failure to understand and adequately account for patient heterogeneity easily leads to unreliable claims and inefficient trials. Identified prognostic factors are generally of sufficient importance to demand attention in design and analysis, but rarely are sufficiently explanatory to render randomization unnecessary. Improvement in knowledge of prognostic factors is important for sharpening the focus and for improving the reliability, efficiency, and interpretability of clinical trials. Problems in the conduct of prognostic factor studies are also discussed, and the calculation of the proportion of variability explained by logistic regression models is illustrated for two examples.
Bone Marrow↗
Age-related renal, hematologic, and hemostatic abnormalities in FH/Wjd rats.
This longitudinal study compared the renal morphologic changes and hemostatic defects of FH/Wjd rats at different ages. A second aim was to determine whether the bleeding tendency becomes intensified in older animals by the concomitant renal disease. Results indicated that reduced capacity for platelet 14C-serotonin release (P less than 0.01) was found for each age group studied in comparison with Wistar controls. The nephropathy of old FH/Wjd male rats was more severe than that in either FH/Wjd females or age-matched Wistars of both sexes. The mesangial lesions showed abundant deposits of factor VIII-related antigen, fibronectin, and immunoglobulins, but not C3, along with tightly packed or loose electron-dense material. Polyethylene glycol precipitation and platelet aggregation tests detected small amounts of circulating immune complex-like material. Old FH/Wjd rats did not develop edema, and the glomerular filtration rate remained normal despite the persistent proteinuria, hematuria, and arterial hypertension characteristic of this strain. Our data indicated that the congenital platelet dysfunction does not become more severe in older animals and that the nephropathy seems unrelated, does not appear to be mediated by immune complexes, and, in contrast to the focal segmental glomerulosclerosis of persons, the lesions progress without a parallel impairment of renal function.
Aging↗
The effect of nitroglycerin and isosorbiddinitrate on myocardial perfusion and hemodynamics in patients with and without coronary disease.
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Blood Flow Velocity↗
[Hemodynamics in ischemia: diastolic phase].
The diastolic portion of the cardiac cycle can be divided into sequential phases: isovolumic ventricular relaxation; rapid ventricular filling; slow, or passive, ventricular filling; and atrial contraction. Contraction and relaxation are to some extent interrelated; however, relaxation is not simply a passive reversal of events during systole. Rather, relaxation is an energy-consuming process which involves dissociation of calcium from the actin-myosin-complex and reuptake of calcium by the sarcoplasmic reticulum. Left ventricular diastolic function is determined by the interrelationship of several/factors, including some intrinsic to the left ventricular chamber (completeness of left ventricular relaxation, time course of left ventricular contraction, and elastic and viscous properties of the myocardium) and others extrinsic to the left ventricle (pericardial and pleural pressure, right ventricular contraction, and coronary perfusion pressure). Acute ischemia alters diastolic left ventricular function by: slowing isovolumic relaxation, delaying left ventricular filling and altering passive elastic properties of the myocardium. Slowing of isovolumic relaxation is measured as a fall in the maximal rate of left ventricular pressure decline (peak negative dP/dt) and as an increase in the time constant (T) of left ventricular pressure fall. Delayed left ventricular filling is manifested regionally as a reduced rate of septal and posterior wall thinning (by echocardiography) and globally as a reduced rate of chamber filling (by gated radionuclide angiography).(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure↗
[Calcium antagonists: effect on peripheral and coronary hemodynamics].
The effects of calcium channel blocking drugs, so-called calcium antagonists, on the human heart and circulation are a composite of various direct (cardiac) and indirect (peripheral vascular) actions. When injected into the coronary circulation, calcium antagonists produce a direct negative inotropic effect on the human myocardium that is characterized by a depression of DP/DT and left ventricular ejection fraction, an increase in end-diastolic pressure and a decrease in systolic pressure. When administered intravenously, sublingually or orally, all calcium antagonists cause a fall in systemic vascular resistance and a drop in systemic arterial pressure, but their actions on cardiac function are less uniform. In particular, a baroreceptor-mediated reflex increase in betaadrenergic tone that is triggered by the fall in blood pressure and depends in degree on the compound and the route of administration, may counterbalance or override the direct negative inotropic effect. As a result, myocardial contractility and ventricular performance can be depressed, unchanged, or even enhanced by calcium antagonists, depending on the underlying status of myocardial function. In the coronary circulation, calcium antagonists, whether administered directly or indirectly (systemically), elicit relaxation of vascular smooth muscle and vasodilatation that is associated with an increase in global coronary blood flow. In contrast to the effects of other vasodilating drugs, however, flow is found to be enhanced not only in myocardial regions supplied by normal coronaries but also in poststenotic areas, at rest as well as with rapid atrial pacing. Although not entirely understood, this latter phenomenon may be of particular interest for the treatment of patients with coronary disease and angina pectoris.
Animals↗
Intracoronary nifedipine in human beings: magnitude and time course of changes in left ventricular contraction/relaxation and coronary sinus blood flow.
Eight patients, all men, having at least 75% stenosis of the proximal, middle or both segments of the left anterior descending coronary artery, underwent intracoronary drug studies at the time of cardiac catheterization after saphenous vein bypass grafting. Nifedipine, 0.1 mg dissolved in saline solution, was infused into a left anterior descending graft that was the primary blood supply to each patient's anterior left ventricular wall and septum. High fidelity left ventricular pressure and its first derivative, dP/dt, and aortic pressure were sampled synchronously with coronary sinus blood flow by the thermodilution technique. The time constant of isovolumic pressure decay (T) was derived. In five patients, percent systolic shortening and mean shortening velocity were determined from myocardial markers implanted into the midwall of the myocardium at the time of cardiac surgery. In response to nifedipine, left ventricular systolic pressure decreased and end-diastolic pressure increased up to 60 seconds. Both positive and negative dP/dt also decreased up to 60 seconds, whereas coronary sinus blood flow increased up to 5 minutes. T was increased at 1 minute but returned to baseline by 3 minutes. Percent systolic shortening and mean shortening velocity were decreased at 1 minute but returned to control level by 3 minutes. Thus, although both left ventricular systolic and diastolic function were depressed by intracoronary administration of nifedipine, coronary sinus blood flow was augmented and remained increased long after changes in left ventricular contraction and relaxation had subsided. These temporal differences are consistent with animal studies showing a differential depressant effect of nifedipine on calcium uptake in smooth muscle and cardiac muscle.
Adult↗
[Explosion of intestinal gas during surgery].
Two cases of colonic gas explosion during surgery are reported. The treatment of the lesions required a partial colectomy in one case and a total colectomy in the other case. The different factors involved in such accidents are discussed. Three factors are necessary to trigger off an explosion of intestinal gases: the presence of combustible gases (hydrogen, methane), the presence of combustive gases (oxygen, nitrous oxide) and an initiating heat source (endoscopic or surgical electrocautery). The mannitol used for bowel cleansing undergoes partial colonic bacterial fermentation increasing the intraluminal concentration of hydrogen. During anaesthesia the oxygen-nitrous oxide mixture increases the intestinal concentration of these two major combustive gases. Electrocautery provides the spark triggering the explosion. The use of mannitol for colonic preparation should be questioned; the use of electrocautery to open the colon is advised against.
Aged↗
Early apocrine change in hyperplastic cystic disease.
Biopsy material from 42 cases of florid hyperplastic cystic disease of the breast were reviewed and were found to have foci of apocrine metaplasia. This appearance was limited to the ductular epithelium of hyperplastic lobules. It is believed that this scattered change is an initial feature in relation to the genesis of apocrine-lined and fully developed cysts.
Breast↗
Size and motion of the tricuspid annulus.
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Humans↗
Effects of nitroglycerin on left ventricular diastolic properties in man.
The effects of nitroglycerin (NTG) on left ventricular (LV) isovolumic relaxation and diastolic function were studied in 12 patients with coronary artery disease: in 6 patients after 0.8 mg sublingual (sI) NTG and in 6 patients after 0.15 mg intracoronary (ic) NTG. From high-fidelity LV pressure peak positive and negative dP/dt, LV systolic (LVSP) and end-diastolic pressure (LVEDP) were measured. The time constant T of isovolumic pressure decay was derived from P = a X exp(-t/T) + c. From simultaneous diastolic pressures and volumes, pressure-volume curves were obtained throughout diastole. In an additional 14 patients, the effects of 0.15 mg ic NTG on coronary sinus blood flow (CSBF) and end-diastolic (ED) and end-systolic septal thickness (ESST) were evaluated. SI NTG produced an increase in heart rate and a decrease in LVSP, LVEDP and negative dP/dt. These effects were associated with a decrease in T and a downward shift of the pressure-volume relation. In contrast, ic NTG caused no change in heart rate, LVSP and LVEDP. The LV pressure-volume relation was not altered although T decreased. Ic NTG produced an early rise in CSBF and a sustained increase in EDST and ESST. Data indicate that sI NTG increases the speed of isovolumic relaxation and improves diastolic function, but these actions are not reflected by negative dP/dt due to its dependence on multiple hemodynamic factors. Ic NTG accelerates isovolumic relaxation, but has no measurable effects on later diastolic function. The increase in positive dP/dt may be explained by an engorgement of the coronary vasculature resulting in stretching of the myocardial fibers.
Blood Pressure↗
[Constrictive pericarditis: results and problems of conservative and surgical treatment].
34 patients (pts.) with chronic constrictive pericarditis (CCP) were investigated by right and left heart catheterization and were followed at Hannover Medical School between 1975 and 1981. 12 pts. in NYHA stage II were treated medically (group I); 22 pts. (group II) in NYHA stages III or IV underwent surgery (pericardectomy). 7 pts. of group I and 12 pts. of group II underwent cardiac catheterization twice; the time interval between the two studies was at least 12 months, averaging 34 +/- 16 months in group I and 34 +/- 19 months in group II. 2 pts. of group I underwent pericardectomy after the second investigation. In group I the mortality was 16.7% (2 out of 12 pts.), both pts. being in stage IV. Hospital mortality in group II amounted to 20.8% (5 out of 24 pts.); late mortality was 4.2% (1 out of 24 pts.). However, 2 of 5 pts. who died in hospital had also undergone aortic and/or mitral valve replacement, and one was on chronic hemodialysis. Additional disorders of liver, lung, and/or kidney function or aortic and/or mitral valve replacement increased the operative risk considerably. Cardiac catheterization performed in 7 out of 12 pts. of group I yielded slight but significant hemodynamic deterioration under conservative management, and 2 of these pts. required surgery after reinvestigation. Cardiac catheterization performed postoperatively in 12 pts. of group II demonstrated normal hemodynamics, especially a decrease in right and left atrial and ventricular enddiastolic pressures (p less than 0.001) and an improvement in cardiac index (p less than 0.05) and stroke index (p less than 0.01). These observations suggest the following conclusions: Pts. in NYHA stage II can be treated medically as long as additional disorders are absent. Hemodynamic deterioration, however, is unpredictable, and approximately one third of pts. may deteriorate rapidly. Therefore, careful clinical observations and repeated hemodynamic studies are necessary. Pericardectomy is still associated with a rather high mortality, depending on additional disorders of liver, lung, and/or kidney function, which accumulate in pts. with long histories of right heart failure. On the other hand, late postoperative results are favorable. When the patient has liver, lung, and/or kidney damage or a long history of cardiac insufficiency, or is advanced in age, operation should be performed even in NYHA stage II because of the increasing operative risk attending higher stages of cardiac insufficiency.
Adult↗
Variation in the lipid composition of rabbit muscle sarcoplasmic reticulum membrane with muscle type.
The compositions of sarcoplasmic reticulum (SR) membranes from rabbit caudofemoralis, tibialus, and soleus muscles (fast, mixed, and slow twitch, respectively) were analyzed. Compared to caudofemoralis (fast twitch) SR, soleus (slow twitch) SR contained a significantly greater percentage of cholesterol, phosphatidylinositol, and sphingomyelin and a lesser percentage of phosphatidylcholine. Correlations between properties reported for the SR isolated from different muscle types and our analyses of the compositions are discussed. We suggest that the greater cholesterol content and the greater sphingomyelin to phosphatidylcholine ratio present in soleus SR contribute to decreased bilayer fluidity and, hence, decreased Ca2+-ATPase activity.
Adenosine Triphosphatases↗
Comparison of four-combination chemotherapy programs in metastatic breast cancer: comparison of multiple drug therapy with cytoxan, 5-FU and prednisone versus cytoxan and adriamycin, versus cytoxan, 5-FU and adriamycin, versus cytoxan, 5-FU and prednisone alternating with cytoxan and adriamycin.
In 126 postmenopausal women with metastatic breast cancer, four chemotherapeutic combination programs were tested. Patients were stratified and randomized to one of the four programs: (1) fluorouracil, cytoxan and prednisone (CFP): (2) fluorouracil, cytoxan and Adriamycin (CAF); (3) cytoxan and Adriamycin (CA); or (4) alternating combinations of CFP-CA. Objective response rates were 17% for 18 patients on CFP, 25% for 40 patients on CAF, 42% for 41 patients on CA and 63% for 19 patients on CFP-CA. CFP-CA provided a significantly higher response rate than either CFP or CAF. The response rate of CA was intermediate. The duration of remission and survival were similar for all four groups. When progression or relapse following remission was demonstrated, patients were rerandomized to either adrenalectomy or tamoxifen. There were no responders either in the 15 patients undergoing adrenalectomy or the 11 patients receiving tamoxifen. In a crossover study, nine adrenalectomized patients received tamoxifen and four tamoxifen-treated patients underwent adrenalectomy. None responded. It appears that response rates to hormonal modalities are reduced in patients previously treated by combination chemotherapy.
Adrenalectomy↗
Diagnostic criteria for schizophrenia: reliabilities and agreement between systems.
We compared the joint frequencies and reliabilities of the following sets of criteria for the diagnosis of schizophrenia: the New Haven Schizophrenia Index: the Carpenter, Strauss, Bartko (4-, 5-, 6-, and 7-item) system; DSM-III; Research Diagnostic Criteria (RDC; full and chronic); the Feighner system; and the 1975 criteria of Taylor and Abrams. The systems, of essentially equal reliability, varied sevenfold in their rates of diagnosing schizophrenia. Patients in whom schizophrenia was diagnosed by the lower-rate systems were likely to receive the same diagnosis by the higher-rate systems. This tends not to be the cases when an affective syndrome is present.
Adult↗
Thiabendazole (TBZ), an immunohemomodulator. I. Effects on lymph node and spleen.
Previous studies in our laboratory with Thiabendazole (TBZ) indicated that the drug significantly augmented cellular immune responses in mice. The purpose of the present and companion study was to determine which of the cell populations in primary and secondary lymphoid organs and in bone marrow were affected by the in-vivo administration of TBZ. Two major changes in lymph nodes and/or spleens of TBZ-treated mice were detected by histological and quantitative planimetric analysis: (1) expansion of T and B lymphocyte compartments and (2) increase in extramedullary hemopoiesis. The effect on T cells and on hemopoiesis were observed only when TBZ was administered with the thymus-dependent neoantigen, dinitrofluorobenzene (DNFB). The effect on B cells appeared to be antigen-independent. Increased extramedullary hemopoiesis in TBZ + DNFB-treated mice was preceded by a significant increase in pluripotent hemopoietic stem cell activity in bone marrow, as measured by the CFU-S assay. This study indicates that TBZ has significant effects on the development and differentiation of both lymphoid and hemopoietic cells.
Adjuvants, Immunologic↗
Thiabendazole (TBZ), an immunohemomodulator. II. Effects on thymocytes and prothymocytes.
The purpose of this study was to document the effects of TBZ on the early stages of T cell maturation. The method utilized to quantify presumptive thymocyte progenitors in the bone marrow used the enzyme terminal deoxynucleotidyl transferase (TdT) as a marker. Shifts in thymocyte populations were determined by quantitative planimetry, immunofluorescence for TdT and tritiated thymidine incorporation. When given alone, TBZ produced a marked increase in the number of large, mitotically active lymphoblasts in the thymus cortex. When given with DNFB, a thymus-dependent neoantigen, TBZ produced a significant increase in TdT-positive bone marrow cells. In a companion study, TBZ + DNFB were found to stimulate T cells in lymph node and spleen. Hence, the results indicate that under appropriate conditions, TBZ can stimulate all stages of T cell differentiation in mice.
Adjuvants, Immunologic↗