123rc/medical_text huggingface dataset:
Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.
Different plasma ionized calcium correlations with blood pressure in high and low renin normotensive adults in Utah. Plasma ionized calcium levels have been shown to be lower than normotensive control levels in hypertensive patients with low plasma renin activity and higher than control levels in hypertensive patients with high renin activity; they did not differ between high and low plasma renin activity groups of normotensive controls. To see if ionized calcium may have different relationships with blood pressure across renin categories in normotensive individuals, plasma ionized calcium was measured on 875 healthy individuals, ages 3 to 83, who had never been diagnosed as having hypertension. Blood pressures were measured in the sitting, standing, and supine positions, along with pressures measured during two stress maneuvers: isometric handgrip and a 50 degrees tilt from a supine position. There was no linear correlation of blood pressure with plasma ionized calcium in the entire sample of youths or adults. However, after dividing the adults into tertiles based on plasma renin activity, there were significant inverse correlations between ionized calcium and systolic and diastolic blood pressure in the low renin group (r = -0.16 to -0.25, P less than or equal to .05), while the systolic blood pressure correlations were significantly positive in the high renin group (r = 0.14 to 0.22, P less than or equal to .05). Adults with normal renin levels did not have any significant correlations of plasma ionized calcium with blood pressure. These confounding effects of renin were greater for systolic than for diastolic blood pressure. These correlations within renin tertiles occurred even though there were no differences in mean blood pressure, plasma ionized calcium, total plasma protein and plasma sodium across renin categories.
Coronary artery disease in Chinese males without hypercholesterolaemia The aim of this study was to determine the frequency of various metabolic risk factors for coronary artery disease (CAD) in 246 male patients studied over a 2-year period. CAD was diagnosed on the basis of a history indicative of angina pectoris, an electrocardiogram diagnostic of myocardial ischaemia, and a positive coronary angiogram. Thirty-eight per cent of this population had diabetes, hypertension or both. Of the remaining individuals, 39% had a plasma cholesterol concentration greater than 5.2 mmol l-1, whereas 23% had a cholesterol concentration less than 5.2 mmol l-1. Plasma lipid and lipoprotein levels of a non-smoking subset of those subjects with a total cholesterol concentration less than 5.2 mmol l-1 were compared with values of a matched group of individuals who did not have significant vessel disease as revealed by angiography. The results of these investigations indicated that patients with CAD and a plasma cholesterol concentration less than 5.2 mmol l-1 exhibited an increase in plasma triglyceride concentration and a decrease in plasma HDL-cholesterol concentration. Since these subjects were not diabetic, hypertensive or hypercholesterolaemic, it is suggested that the observed changes in triglyceride and HDL metabolism made a major contribution to the CAD in these individuals.
Isolated systolic hypertension in the elderly: an epidemiologic review. Isolated systolic hypertension (ISH) is usually defined as a systolic blood pressure greater than or equal to 160 mm Hg and diastolic blood pressure less than 90 or 95 mm Hg. Systolic blood pressure has been found to increase with age in most populations studied and thus the prevalence of ISH can be expected to increase with age. ISH is more prevalent in elderly women than in elderly men. Estimates of the prevalence of ISH vary according to its definition and the number of blood pressure measurements. There is evidence that the prevalence of ISH is decreasing. Results of a survey of the prevalence of ISH in 11 countries are presented; the estimates among men aged 60 to 69 years ranged from 1% in Israel to 24% in Norway. Only a prospective standardized survey conducted in several countries will reveal the true prevalence of ISH.
A randomized controlled trial of allopurinol in coronary bypass surgery. A plethora of experimental evidence indicates that allopurinol reduces the formation of cytotoxic free radicals during myocardial ischemia and reperfusion. The purpose of this study was to evaluate the effect of allopurinol on cardiac performance and early mortality after coronary bypass surgery. Allopurinol (n = 89) or placebo (n = 80) was administered to 169 patients before surgery. Randomization produced groups evenly matched for surgical risk factors. Hospital mortality rate in the placebo group was 14 of 80 (18%) in the allopurinol group 4 of 89 (4%), p = 0.014. Cardiac performance, scored by cardiac index and the need for ionotropic or mechanical support, was significantly better in the allopurinol group. More nonfatal complications occurred in the allopurinol group. When either a complication or death is termed an event, the proportion of events was equal in the two groups. No side effects were identified. We now administer allopurinol to all patients who are undergoing bypass surgery unless specifically contraindicated.
Oral cholecystography in contemporary gallstone imaging: a review. The introduction of nonoperative alternatives to elective cholecystectomy in the management of gallstones has resurrected use of oral cholecystography (OCG). This article reviews basic principles involved in the proper performance of OCG and interpretation of the resulting images. The role of OCG in the current management of gallstones is discussed.
4-Hydroperoxycyclophosphamide purging of breast cancer from the mononuclear cell fraction of bone marrow in patients receiving high-dose chemotherapy and autologous marrow support: a phase I trial. We designed an ex vivo bone marrow treatment for breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support (ABMS), using 4-hydroperoxycyclophosphamide (4-HC), an active derivative of cyclophosphamide with known activity against breast cancer. This phase I bone marrow purging trial used ficoll-separated mononuclear cells (MNC) (devoid of granulocytes and RBCs), as opposed to the buffy coat. Twenty-five patients with metastatic breast cancer were studied. Patients received three cycles of the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), fluorouracil, and methotrexate (Duke AFM) regimen, followed by marrow harvest. An MNC fraction of marrow was prepared and treated with 4-HC in concentrations of 20 micrograms/mL (four patients), 40 micrograms/mL (four patients), 60 micrograms/mL (nine patients), or 80 micrograms/mL (eight patients) and cryopreserved. Patients then received high-dose systemic cyclophosphamide, cisplatin, and carmustine, followed by infusion of the purged marrow. The study end point was marrow engraftment, defined as WBC count greater than 1,000 cells per microliter. At the first three dose levels (20, 40, and 60 micrograms/mL 4-HC), there was no significant delay in time to engraftment (19, 20, and 23 days, respectively) compared with the unpurged historical controls (17 days). At 80 micrograms/mL, engraftment was significantly delayed compared with the lower concentrations (P = .027), and further escalation of 4-HC was not attempted. A significant correlation was observed between the time of leukocyte engraftment and the 4-HC concentration (P = .017). With a methylcellulose-based tissue culture assay, we demonstrated a statistically significant correlation between the colony-forming unit-granulocyte-macrophage (CFU-GM) content in the purged marrow and the days to engraftment. Ninety-five percent of patients responded clinically to the entire program, 55% of them completely. Longer follow-up is required to assess the ultimate benefit of intensive therapy on long-term survival.
Occupational distribution of inflammatory bowel disease among German employees. Previous reports have shown that both Crohn's disease and ulcerative colitis affect people in white collar occupations associated with higher income and higher social class more frequently than other groups in the population. This study sought to carry these analyses one step further and investigate the distribution of inflammatory bowel disease by individual occupations. The German social security statistics for 'rehabilitation' were used to assess the occupational distribution of Crohn's disease and ulcerative colitis. From 1982 to 1988, a total of 12,014 people were granted rehabilitation as a result of inflammatory bowel disease. Low male prevalence of inflammatory bowel disease was found among bricklayers, road construction workers, unskilled workers in brick and stone, unskilled labourers, and security personnel. Low rates were found among women employed in cleaning and maintenance, and in those without occupation. In contrast, a high male prevalence was found among instrument makers, electricians, bakers, and technical assistants. Among female employees, inflammatory bowel disease was significantly associated with sales representatives, office workers, health occupations, and hairdressers. These associations were found in the complete data for 1982-8 as well as in the separate data for the two half periods 1982-5 and 1986-8. Highly significant correlations between the occupational distribution of Crohn's disease and ulcerative colitis were found among both male and female employees. It seems that occupations involving work in the open air and physical exercise are protective, while being exposed to air conditioned artificial working conditions or extended and irregular shift working confer a risk of contracting inflammatory bowel disease.
Pneumonia complicating abdominal sepsis. An independent risk factor for mortality. Nosocomial pneumonia (NP) is associated with a significant mortality, 66% in a previous retrospective study of NP complicating intra-abdominal sepsis (IAS). We prospectively compared the outcome of NP complicating IAS with that of recurrent IAS (R-IAS) in the absence of NP. Data were collected prospectively on 300 patients with IAS; 34 patients who presented with pneumonia were excluded from the analysis (44% mortality). One hundred seventy-one patients with no NP and no R-IAS (group 1) had a hospital mortality of 20% (34 patients); 36 without NP in whom R-IAS developed (group 2) had a 17% mortality (six patients); and 47 with NP but no R-IAS (group 3) had a 53% mortality (25 patients). Finally, 12 patients who had both NP and R-IAS suffered a 75% mortality (nine patients). We examined the relationships among the following putative risk factors and mortality: APACHE (acute physiology and chronic health evaluation) II score (at initial presentation with IAS), the need for mechanical ventilatory assistance following initial treatment for peritonitis, steroid requirement, generalized peritonitis vs abscess, and the need for surgical as opposed to percutaneous treatment. Using mortality as the dependent variable, group 2 vs 3 as the explanatory variable, and the risk factors as confounders, logistic regression analysis indicated that the group difference was significant after controlling for confounders. We conclude that NP complicating IAS is an independent risk factor associated with a significant mortality compared with R-IAS. These data challenge the notion that death in IAS is usually due to recurrent or persistent intra-abdominal infection.
Fracture-dislocation of the base of the fifth metacarpal with an ulnar motor nerve lesion: case report. We report a case of delayed diagnosis of a fracture dislocation of the base of the fifth metacarpal with a resultant ulnar motor nerve lesion. The patient achieved marked improvement after fracture reduction and ulnar neurolysis.
Onset phase of spinal bupivacaine analgesia assessed quantitatively by laser stimulation. Analgesia was assessed quantitatively at various dermatomes (C7, T8, T10, T12, L1, L3, S1) for the first 30 min after subarachnoid administration of 0.5% bupivacaine 3.5 ml. Stimulation with 10 needles and laser stimulation could evoke pain in dermatomes with adequate analgesia to single needle stimulation. Analgesia was assessed by thresholds (sensory and pain) and by pain-related brain potentials (amplitude and latency) to laser stimulation. Little analgesia was found at T10, but it increased gradually towards caudal segments. The dermatome related to the site of the injection (L3) was not blocked to a greater extent than the surrounding dermatomes. Conduction time (the latency of the evoked brain potential) was increased relatively more from the S1 dermatome compared with L1.
Possible mechanisms limiting N-methyl-D-aspartate receptor overactivation and the therapeutic efficacy of N-methyl-D-aspartate antagonists. Cytotoxic overactivation of neuronal N-methyl-D-aspartate receptors is postulated to contribute to the pathogenesis of neuronal loss in hypoxia-ischemia. However, several events associated with hypoxia-ischemia may limit N-methyl-D-aspartate receptor-mediated injury. Perhaps the most important of these events is the development of extracellular acidosis. These limiting events may help explain why N-methyl-D-aspartate receptors contribute to injury more in focal ischemia or hypoxia in vitro than in global ischemia.
Correction of metabolic acidosis in experimental CPR: a comparative study of sodium bicarbonate, carbicarb, and dextrose. STUDY OBJECTIVE: Carbicarb, sodium bicarbonate, and 5% dextrose were compared for effects on resuscitability in a canine model of electromechanical dissociation after ventricular fibrillation. DESIGN/INTERVENTIONS: 21 healthy mongrel dogs were anesthetized with pentobarbital, intubated, and mechanically supported. They were instrumented to measure heart rate, arterial pressure, pulmonary artery pressure, right atrial pressure, cardiac output, and arterial and mixed venous blood gases. The dogs were then subjected to a protocol that consisted of three successive CPR episodes. During each episode they were treated with repeated injections of one of the three substances, randomly chosen. After two minutes of ventricular fibrillation and four minutes of electromechanical dissociation, CPR was started with a thumper (rate, 60; duty cycle, 50%). If recovery was not obtained after five minutes of CPR, 1 mEq/kg carbicarb or sodium bicarbonate or 5 mL D5W was injected in the right atrium. Half the dose of the same substance was injected every five minutes thereafter; 1 mg epinephrine was also injected every five minutes until recovery. Hemodynamic and gasometric evaluations were performed five and 20 minutes after recovery. This later evaluation served as baseline for the next CPR episode. MEASUREMENTS AND MAIN RESULTS: The duration and success rates of CPR are similar in the three CPR groups. Hemodynamic parameters were also similar during recovery. Bicarbicarb and sodium bicarbonate increased bicarbonate levels and corrected pH in the arterial and mixed venous blood. There was no difference in the blood gas values after carbicarb and sodium bicarbonate. CONCLUSION: In this model of cardiac arrest, carbicarb was not superior to sodium bicarbonate in the correction of metabolic acidosis during CPR.
Decreased operative risk of surgical treatment of mitral regurgitation with or without coronary artery disease. The consecutive 2 year experience with patients undergoing first-time surgery for mitral regurgitation with and without coronary artery disease was reviewed. From January 1988 to January 1990, 127 patients with pure mitral regurgitation undergoing first-time operation were surgically treated. No other valve lesion, no reoperation and no congenital defects were included. The mean patient age was 62 years with 26% of the patients greater than 70 years. Twenty-six percent of the entire group was in functional class IV. Seventy-five patients received mitral valve repair and 52 underwent mitral valve replacement with a St. Jude or Hancock valve. In patients undergoing mitral valve repair, there was a higher incidence of those greater than 70 years old and of coronary artery disease and in patients undergoing mitral valve replacement there was a higher incidence of functional class IV. The operative mortality rate was 2.3% (3 of 127 patients). No patient failed to be discontinued from cardiopulmonary bypass and all three deaths occurred after mitral valve replacement, with one from complications of chronic renal failure and dialysis. There was no significant difference in patients who either did or did not have a concomitant coronary artery bypass graft and there was no difference related to age or functional class. Postoperative complications occurred in five patients in the valve repair group, including recurrent mitral regurgitation in two necessitating reoperation, and in three patients in the valve replacement group. With newer operative and postoperative management techniques, especially preservation of the papillary muscle annular continuity, the risk of mitral valve surgery, particularly of valve repair, is considerably lower than in previous years.
New directions in medical imaging of cancer. Magnetic resonance methods and single photon emission computed tomography. Magnetic resonance methods and single photon emission computed tomography (SPECT) are developing technologies that provide both functional and anatomic information. Their role in the diagnosis and monitoring of cancer is the subject of current clinical research. Magnetic resonance imaging (MRI) delineates organs and tissue heterogeneities using differences in the relaxation parameters of water and fat protons; both protons and other nuclei can be imaged or studied by magnetic resonance spectroscopy (MRS) to provide information on the state of naturally occurring or infused molecules. SPECT quantifies the distribution of radiolabeled agents in tissues and organs; labeled monoclonal antibodies provide highly specific imaging of tumors. Spatial resolution is the limiting technologic factor. Proton MRI provides the highest current resolution, better than 1 mm in vivo in deep tissues, whereas the resolution of MRS and SPECT is limited to several cubic centimeters. Recent advances in these technologies have significantly increased their specificity and ability to detect small, deep lesions.
Aortic dissection with a fistulous communication into the right atrium: a case report. A case of aortic dissection (type 1, De Bakey) with a rent into the right atrium (RA), diagnosed by echocardiography (echo) and confirmed by aortography, is reported. The patient presented with cardiac failure and a continuous murmur in the right second and third intercostal spaces. The patient has survived for two years with medial treatment.
Relationship between blood groups and behavior patterns in men who have had myocardial infarction. Consistent correlations have been found between physical dysfunctional states and blood factors. Some of these disorders have possible psychosomatic components (eg, duodenal ulcer, myocardial infarction). This study focused on the relationship between blood types and various indices of behavior patterns (eg, type A behavior scores, anger ratings) in young patients who had had an initial myocardial infarction. Patients with blood type O scored significantly higher on type A behavior scales and related indices than those having blood type A. Those with blood group B responded on several scales between those with types A and O. We discuss the utility of blood groupings in future research in the prediction of myocardial infarction, methodologic limitations, the relationship of these results to temperament studies, Jenkins Activity Survey subtest patterns, anti-H reactivity pattern, and hypotheses relating blood factors and behavioral traits in patients with psychosomatic disorders.
Antisecretory and antilesional effect of a new histamine H2-receptor antagonist, IT-066, in rats. The effects of a new histamine H2-receptor antagonist, IT-066 (3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-++ +butenylamino]- 3-cyclobutene-1,2-dione hydrochloride), were investigated on the secretagogue-induced acid secretion in vivo and in vitro, and on experimental gastric and duodenal lesion in rats. IT-066 (10-60 micrograms/kg) given i.v. inhibited histamine-stimulated acid secretion dose-dependently in gastric lumen-perfused rats, and the inhibitory effect was observed for about 12 hr. Famotidine (FMD) (10-60 micrograms/kg i.v.) also had an antisecretory effect, but the acid secretion recovered to the control level 4 hr after the administration. Cold stress plus indomethacin-induced lesion was significantly inhibited by IT-066 and FMD given i.v. 30 min before the cold stress plus indomethacin treatment. IT-066 given 7 hr before the cold stress plus indomethacin treatment also inhibited lesion formation significantly, but such antilesional effect was not observed with FMD. In the rat isolated gastric mucosal sheet, IT-066 inhibited histamine-stimulated acid secretion dose-dependently and noncompetitively; its action was produced via a unique mechanism. The inhibitory effect of IT-066 remained after washing of the mucosa, and became more potent time-dependently. The inhibitory effects of FMD and cimetidine were not observed after washing the mucosa. These data suggest that IT-066 has a potent and long lasting antisecretory effect in vivo and in vitro, and that these properties are responsible for the long lasting antilesional action.