123rc/medical_text huggingface dataset:
Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet-activating factor antagonist. To determine if alterations in regional coronary vascular resistance could occur in the type of myocardial ischemia present in severe angina pectoris, regional perfusion and function were studied in 35 conscious sedated dogs. A stenosis producing severe hypokinesia of the perfused segment was created for 2 h on the left anterior descending coronary artery and 10 episodes of 1 min of high demand ischemia (atrial pacing at a rate sufficient to induce dyskinesia in the hypoperfused segment) were superimposed before reperfusion. The dogs were randomized into three treatment groups: control (n = 13), dipyridamole (n = 10) or WEB-2086 (n = 12), an antagonist of the effects of the endogenous platelet-activating factor. During stenosis, residual endocardial blood flow in the ischemic but nonnecrotic area averaged 0.72 +/- 0.14, 0.38 +/- 0.13 and 0.68 +/- 0.17 ml/min per g in the control, WEB-2086 and dipyridamole groups, respectively. Twenty-four hours after reperfusion, endocardial blood flow in the ischemic area was significantly lower in control dogs (1.04 +/- 0.15 ml/min per g) than in dogs treated with WEB-2086 (1.44 +/- 0.28 ml/min per g; p less than 0.03) or dipyridamole (3.00 +/- 0.83 ml/min per g; p less than 0.01). Accordingly, in control dogs, endocardial coronary vascular resistance in the ischemic area was increased after reperfusion from 85 +/- 11 to 124 +/- 27 mm Hg/(ml/min per g) (p less than 0.05) after 24 h. In contrast, coronary vascular resistance in the ischemic area remained unchanged in dogs receiving WEB-2086 (77 +/- 8 to 79 +/- 9 mm Hg/(ml/min per g); p = NS) and it decreased significantly in dogs receiving dipyridamole (72 +/- 8 to 44 +/- 8 mm Hg/(ml/min per g); p less than 0.01). Regional function after 24 h remained depressed in all three groups. These data indicate that low flow, high demand ischemia induces alterations in the subendocardial microvasculature. Such alterations in regional coronary vascular resistance might play a role in several forms of ischemic heart disease such as in severe angina, but they appear susceptible to improvement by therapeutic interventions that influence granulocyte and platelet activation.
The relationship between sex hormones and high-density lipoprotein cholesterol levels in healthy adult men. The objective of this study was to clarify the complex and uncertain relationship between endogenous sex hormones and high-density lipoprotein (HDL) cholesterol levels in healthy men. Fifty-five healthy adult men were consecutively recruited from an ongoing cross-sectional study of cardiovascular disease risk factors from a lipid research clinic at the University of Washington, Seattle. Subjects receiving medication were excluded. Multiple linear regression analysis identified several factors that correlated highly significantly with HDL cholesterol levels, including alcohol intake; frequency of strenuous exercise; age; levels of total cholesterol, low-density lipoprotein cholesterol, and triglyceride; and carbohydrate intake. Nearly 80% of the heterogeneity in HDL cholesterol levels could be accounted for by these factors. Despite finding significant correlations with factors known to influence HDL cholesterol levels, no correlation with estradiol level, testosterone level, or the ratio of estradiol to testosterone levels was apparent. In conclusion, endogenous sex hormones do not appear to influence HDL cholesterol levels in healthy adult men. Alternatively, a large proportion of the heterogeneity in HDL levels in this group of men can be accounted for by environmental factors. The disparity between this conclusion and others may be partially due to differences in accounting for these confounding variables.
Racial and ethnic modifiers of the salt-blood pressure response. The relation between sodium and blood pressure is a centuries-old question. A substantial body of epidemiological and experimental data has accumulated that strongly implicates NaCl as having a causal role in the genesis of arterial hypertension. Prospective studies that have been performed in diverse populations that have manipulated NaCl exposure by diet or infusion have repeatedly documented an NaCl pressor effect. Further, similar studies in biracial populations have also demonstrated a greater prevalence of "salt sensitivity" in blacks compared with whites. The reasons for this observation are not entirely clear; however, intrinsic or hypertension-induced renal abnormalities that limit natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion transport disturbances, differential exposure to psychological stressors, greater insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been suggested as possibly playing a role. Salt sensitivity appears to be a widespread phenomenon. However, it is critically important to determine what factors account for racial differences in salt sensitivity. Moreover, the prevalence of salt sensitivity in the general population is unknown. Current definitions of salt sensitivity are varied and unidirectional. In comparison with bidirectional criteria (blood pressure increase with salt loading and blood pressure decrease with salt restriction), they are probably inadequate to identify salt-sensitive individuals who manifest less extreme blood pressure change after dietary sodium or plasma volume manipulations. More sensitive criteria for diagnosing salt sensitivity will facilitate a better understanding of racial and ethnic differences in the prevalence of salt sensitivity.
In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. The knowledge about drug resistance in childhood leukemias and acute lymphoblastic leukemia (ALL) in general is limited. This is because of the lack of a suitable in vitro drug sensitivity assay, which is in part due to low in vitro ALL cell survival. We recently adapted the highly efficient 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay to test cells from ALL patients and showed that its results were comparable with those of the DiSC assay, up to now the most valid but laborious assay. In this study, in vitro drug sensitivity was assessed in cells from 82 children with leukemia, 79 of whom had ALL, with the MTT assay. Dose response curves were obtained for 6-mercaptopurine, 6-thioguanine (6-TG), prednisolone (Pred), daunorubicin (DNR), vincristine (VCR), cytosine arabinoside (Ara-C), L-asparaginase (L-Asp), mafosfamide, and mustine. A cytotoxic effect of methotrexate could be detected in only a few cases. Large interindividual differences in drug sensitivity were detected. Compared with leukemia cells from newly diagnosed patients, leukemia cells from relapsed patients were significantly more in vitro resistant to 6-TG, Pred, Ara-C, mafosfamide and mustine but not to DNR, VCR, and L-Asp. Improvements of culture medium and methods to increase MTT reduction were studied. From 10 components tested, addition of insulin and bovine serum albumin to serum-containing medium improved ALL cell survival. Addition of succinate did not increase the amount of MTT reduction. We conclude that the in vitro MTT assay highly facilitates large-scale studies on drug resistance of ALL patients that can lead to rational improvements in existing treatment protocols.
Reduction of the membrane fluidity of human breast cancer cells by tamoxifen and 17 beta-estradiol. The intracellular steady-state levels of methotrexate were previously shown to be reduced in estrogen receptor (ER)-negative human breast cancer MDA-MB-436 cells and ER-positive human breast cancer MCF7 cells following treatment with pharmacologically relevant concentrations of 17 beta-estradiol (E2). We now report that both E2 and tamoxifen (TMX) significantly decreased the fluidity of MCF7 and MDA-MB-436 cellular membranes. With E2 or TMX at concentrations greater than 1 microM, perturbations in membrane fluidity were accompanied by apparently non-ER-mediated cytotoxicity. Alterations in membrane structure may have contributed to the cytotoxicity of high-dose endocrine therapy and to the ability of E2 to inhibit methotrexate transport and cytotoxicity in some human breast cancer cells.
Late chronic hemolysis after valve replacement for aortic stenosis. Relation to residual hypertrophy and impaired left ventricular function. The relationship between intravascular hemolysis induced by aortic valve prosteses and patient status/left ventricular (LV) function (radionuclide cardiography) was examined in 63 patients of 65 who were alive ten to seventeen years after valve replacement (1965-1973) for aortic stenosis. Serum-lactic dehydrogenase (LDH) exceeded upper reference limit in 62 patients and S-haptoglobin (HAPTO) was reduced in 62. One patient with normal LDH had reduced HAPTO and elevated plasma-hemoglobin. Anemia was noted in 4 patients (6%). S-LDH was higher in men than in women (p less than 0.05), in patients with increased ECG hypertrophy score than in those with a normal score (p less than 0.05), in patients with NYHA class II-III than in those with class I (p less than 0.05), in patients with abnormal LV function than in those with a normal radionuclide study (p less than 0.05), in patients with a pathologic Q wave in the ECG than in those without (p less than 0.05), and in patients with a Starr Edwards cloth-covered (SECC) prosthesis than in those with other types (p = 0.07). ECG hypertrophy score correlated directly with LDH (r = 0.33, p = 0.008) and inversely with LV ejection fraction (r = -0.57, p less than 0.0001), peak ejection rate (r = -0.47, p less than 0.0001), and peak filling rate (r = -0.41, p less than 0.001). Multiple linear regression analysis revealed that LDH was accounted for by ECG hypertrophy score (p = 0.001), SECC prosthesis (p = 0.04), and male gender (p = 0.05). Hypertrophic malfunctioning left ventricles may be responsible for higher degrees of turbulent flow characteristics in the vicinity of prosthetic valves in the aortic position and, by inference, explain the increased tendency toward hemolysis in these patients.
Hemodynamic effects of lobar pulmonary artery occlusion in a porcine sepsis model. We induced severe pulmonary hypertension and acute lung injury in 6 pigs by Pseudomonas aeruginosa infusion. We studied the effect of pulmonary artery catheter inflation of a pulmonary artery catheter balloon in the left lower lobar pulmonary artery was accompanied by a significant (p less than 0.05, paired t test) increase in pulmonary artery pressure, a decrease in left atrial pressure, a decrease in cardiac output, and a decrease in mean arterial pressure. No significant changes occurred when the catheter was advanced into the wedged position without balloon inflation. Balloon inflation had no significant effect on these variables before bacterial infusion. We conclude that with sufficiently severe pulmonary hypertension in association with diffuse lung injury, lobar pulmonary artery occlusion may cause alterations in cardiac output and left atrial pressure. This may confuse interpretation of pulmonary artery catheter measurements.
Cytoreductive hepatic surgery for neuroendocrine tumors. We retrospectively reviewed 37 patients who underwent hepatic resection between 1970 and 1989 to evaluate the role of cytoreductive hepatic surgery in patients with metastatic neuroendocrine tumors (carcinoid, 24; islet cell, 13). Seventeen resections were curative (no gross residual tumor); nine patients had symptomatic endocrinopathies and seven patients had symptoms caused by the primary tumor. Eight of nine patients with symptomatic endorcrinopathies obtained complete relief of symptoms; five are alive with no evidence of disease at 2 to 82 months (mean, 26 months). Six of seven patients with symptoms caused by the primary tumor obtained complete relief; five are alive with no evidence of disease at 5 to 28 months (mean, 14 months). One symptom-free patient underwent curative hepatic resection 5 years after abdominoperineal resection for a rectal carcinoid. Twenty resections were palliative (gross residual tumor); 16 patients had symptomatic endocrinopathies and 4 patients had symptoms caused by the primary tumor. Eight of 16 patients with symptomatic endocrinopathies obtained complete relief; five are alive at 2 to 30 months (mean, 11 months), with a mean duration of complete relief of 6 months (3 to 12 months). All four patients who underwent resection for symptoms caused by the primary tumor obtained complete relief; two are alive and symptom free at 10 and 101 months. Our experience suggests that curative surgery should be considered in all patients with completely resectable metastatic disease and that palliative surgery, despite the short duration of complete relief, should be considered in selected patients because it delays and may reduce the subsequent need for medical therapy.
Potential usefulness of combined thromboxane A2 and serotonin receptor blockade for preventing the conversion from chronic to acute coronary artery disease syndromes. Evidence suggests that unstable angina, non-Q-wave myocardial infarction and Q-wave myocardial infarcts represent a continuum, such that transient reduction in coronary blood flow associated with platelet aggregation and dynamic vasoconstriction at sites of coronary artery stenosis and endothelial injury lead to abrupt development of unstable angina. Factors potentially responsible for the conversion from chronic to acute coronary artery disease include endothelial injury at sites of stenosis. The endothelial injury may be the result of plaque fissuring or ulceration, hemodynamic factors (including systemic arterial hypertension or flow shear stress), infection, smoking, coronary arteriography or balloon angioplasty. Clinical and experimental animal studies suggest that interference with thromboxane and serotonin contributions to platelet aggregation and dynamic coronary artery constriction may prevent chronic coronary artery disease syndromes from converting to acute disease. To protect against this process may require both thromboxane and serotonin receptor antagonists or a combination of thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor antagonist. Further studies are needed to test this hypothesis.
Pseudo-abscess of the psoas bursa in failed double-cup arthroplasty of the hip. Seven psoas bursae filled with purulent fluid and inspissated debris were revealed at revision operations for failed resurfacing hip arthroplasties, an incidence of 5.8% in such revisions. Histological and microbiological investigations demonstrated that the psoas bursa collections resulted from the tissue response to polyethylene wear debris. None was due to infection.
Xanthine oxidase inhibition does not limit canine infarct size. BACKGROUND. Evidence supporting the role of xanthine oxidase in myocardial reperfusion injury is based on studies with pharmacological interventions used to inhibit enzyme function. Controversy exists, however, regarding the true role of xanthine oxidase in reperfusion injury. This study was performed to determine whether xanthine oxidase inhibition limits myocardial injury due to coronary artery occlusion and reperfusion. METHODS AND RESULTS. Anesthetized dogs underwent coronary artery occlusion (90 minutes) and reperfusion (6 hours). Oxypurinol (28 mg/kg) or amflutizole (30 mg/kg), chemically unrelated inhibitors of xanthine oxidase, or vehicle was infused intravenously 15 minutes before and 3 hours after reperfusion. Regional myocardial blood flow was determined with radiolabeled microspheres. Infarct size was determined with the tetrazolium method. Myocardial infarct size (percent of risk region) was less in oxypurinol-treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15%. Infarct size for the amflutizole-treated dogs, 40 +/- 21%, was not significantly different from that of the control group. There were no differences in rate-pressure product or collateral blood flow to account for differences in infarct size. Uric acid concentration in the coronary venous plasma increased after reperfusion in the dogs treated with vehicle but not in the drug-treated dogs. Xanthine oxidase inhibition was demonstrated in each of the drug treatment groups, but only oxypurinol limited the extent of myocardial injury. CONCLUSIONS. Previously reported cardioprotective effects of allopurinol, noted to occur only when the drug was administered chronically, may be related to a property of oxypurinol, a major metabolite of allopurinol. The beneficial effect of oxypurinol is unrelated to inhibition of superoxide formation during xanthine oxidase-catalyzed oxidation of xanthine and hypoxanthine.
Skeletal scintigraphy in coeliac disease. A patient with undiagnosed, long-standing coeliac disease had multiple hot spots on skeletal scintigraphy, similar to those observed in malignant disease metastatic to the skeleton. A gluten-free diet corrected the pathological laboratory values, and a repeat skeletal scintigram 15 months after the first one was normal. It is important to identify the secondary hyperparathyroidism of coeliac disease as a cause of multiple hot spots in skeletal scintigraphy--the finding resembles malignancy, but is due to a benign, curable condition.
Nasal and oral flow-volume loops in normal subjects and patients with obstructive sleep apnea. Because flow-volume loops (FVLs) are clinically useful in evaluating upper airway (UA) obstruction and the fact that patency of the nasopharyngeal ventilatory pathway is important to the prevention of obstructive sleep apnea (OSA), the present study examined the role of nasal compared with oral FVLs in evaluating patients with OSA. Fourteen obese male patients 56 +/- 3 yr of age with a mean apnea plus hypopnea index (AHI) of 51 +/- 9/h were studied along with 14 nonobese, healthy, age- and sex-matched control subjects whose mean AHI was 6 +/- 1/h. Nasal and oral FVLs obtained in the normal subjects indicated the nose behaved like a variable resistor, with flow limitation during inspiration but not during expiration. In the patient group, flow limitation was observed during expiration as well as inspiration indicating nondistensibility of the nasopharyngeal ventilatory pathway in the patients compared to the control subjects. A change in body position from upright to supine in the OSA group was associated with small reductions in expiratory but not inspiratory flow rates. The area under the nasal supine flow-volume loop (FVLANaSup) was found to be highly correlated with awake resting PaO2 (r = 0.80) and PaCO2 (r = -0.83) in the patient group. In addition, multiple linear regression analysis revealed that PaO2 and the area under the nasal FVLs independently contributed to the prediction of AHI with a multiple R of 0.89. These results suggest that limitations to ventilation via the nasopharynx may significantly influence both gas exchange and the frequency of sleep-disordered breathing in patients with OSA.
Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. The causes of chest pain in patients found to have angiographically normal coronary arteries during cardiac catheterization remain controversial. Cardiac sensitivity to catheter manipulation, pacing at various stimulus intensities and intracoronary injection of contrast medium was examined in several groups of patients who underwent cardiac catheterization. Right heart (especially right ventricular) catheter manipulation and pacing and intracoronary contrast medium provoked chest pain typical of that previously experienced in 29 (81%) of 36 patients with chest pain and angiographically normal coronary arteries and 15 (46%) of 33 symptomatic patients with hypertrophic cardiomyopathy. In contrast, only 2 (6%) of 33 symptomatic patients with coronary artery disease experienced their typical chest pain with these sensitivity tests (p less than 0.001). None of 10 patients with valvular heart disease but without a chest pain syndrome experienced any sensation with these tests. Cutaneous pain threshold testing demonstrated that patients with chest pain and normal coronary arteries had a higher pain threshold to thermal stimulation compared with patients who had coronary artery disease or hypertrophic cardiomyopathy. No relation existed between cardiac sensitivity and cutaneous sensitivity testing. Thus, patients who have chest pain despite angiographically normal coronary arteries may have abnormal cardiac sensitivity to a variety of stimuli. This increased sensitivity may be of causal importance to their chest pain syndrome or may contribute to their perception of ischemia-induced pain. The same phenomenon was also commonly seen in symptomatic patients with hypertrophic cardiomyopathy. Whether this phenomenon represents abnormal activation of pain receptors within the heart or abnormal processing of visceral afferent neural impulses in the peripheral or central nervous system is unknown.
Surgical management of pulmonary metastatic leiomyosarcoma with gross endobronchial extension. Metastatic leiomyosarcoma occasionally is seen with gross endobronchial extension without invasion of the bronchial wall. These patients have major airway obstruction and partial or total atelectasis of the lung. Precise bronchoscopic assessment coupled with intraoperative bronchotomy allows the surgeon to determine the origin of the tumor and to save uninvolved pulmonary parenchyma. Our experience with 4 such patients illustrates the possibility of saving lung tissue despite total bronchial obstruction.
Fatigue in postpolio syndrome. A survey was conducted to better understand complaints of fatigue in patients previously diagnosed as having polio. Eighty-six individuals with postpolio syndrome and 20 healthy controls completed a questionnaire about their fatigue, the Beck Depression Inventory, and the CAGE questionnaire. The results showed that fatigue in postpolio syndrome usually occurred on a daily basis and increased in severity as the day progressed. Both the study group and controls described their fatigue as tiredness and a lack of energy. However, physical weakness was reported only in the postpolio group. Minimal physical exercise exacerbated fatigue in 48% of the postpolio group, whereas it diminished fatigue in 70% of the controls and in 15% of the postpolio group. Twenty-seven percent of the postpolio group and none of the controls reported mild to moderate depressive symptoms. However, depression, age, alcohol abuse, and employment status did not significantly affect the differences between groups in reported prevalence or description of chronic fatigue. Criteria to separate psychologic from organic causes of fatigue and treatment interventions are discussed.