Showing papers by "Mayo Clinic published in 1989"
TL;DR: In this paper, complementary oligodeoxyribonucleotide (oligo) primers and the polymerase chain reaction are used to generate two DNA fragments having overlapping ends, and these fragments are combined in a subsequent 'fusion' reaction in which the overlapping ends anneal, allowing the 3' overlap of each strand to serve as a primer for the three' extension of the complementary strand.
7,528 citations
TL;DR: Gene splicing by overlap extension is a new approach for recombining DNA molecules at precise junctions irrespective of nucleotide sequences at the recombination site and without the use of restriction endonucleases or ligase.
3,339 citations
TL;DR: Endothelium-dependent relaxation of blood vessels is produced by a large number of agents (e.g., acetylcholine, ATP and ADP, substance P, bradykinin, histamine, thrombin, serotonin). With some agents, relaxation may be limited to certain species and/or blood vessels as mentioned in this paper.
Abstract: Endothelium-dependent relaxation of blood vessels is produced by a large number of agents (e.g., acetylcholine, ATP and ADP, substance P, bradykinin, histamine, thrombin, serotonin). With some agents, relaxation may be limited to certain species and/or blood vessels. Relaxation results from release of a very labile non-prostanoid endothelium-derived relaxing factor (EDRF) or factors. EDRF stimulates guanylate cyclase of the vascular smooth muscle, with the resulting increase in cyclic GMP activating relaxation. EDRF is rapidly inactivated by hemoglobin and superoxide. There is strong evidence that EDRF from many blood vessels and from cultured endothelial cells is nitric oxide (NO) and that its precursor is L-arginine. There is evidence for other relaxing factors, including an endothelium-derived hyperpolarizing factor in some vessels. Flow-induced shear stress also stimulates EDRF release. Endothelium-dependent relaxation occurs in resistance vessels as well as in larger arteries, and is generally more pronounced in arteries than veins. EDRF also inhibits platelet aggregation and adhesion to the blood vessel wall. Endothelium-derived contracting factors appear to be responsible for endothelium-dependent contractions produced by arachidonic acid and hypoxia in isolated systemic vessels and by certain agents and by rapid stretch in isolated cerebral vessels. In all such experiments, the endothelium-derived contracting factor appears to be some product or by-product of cyclooxygenase activity. Recently, endothelial cells in culture have been found to synthesize a peptide, endothelin, which is an extremely potent vasoconstrictor. The possible physiological roles and pathophysiological significance of endothelium-derived relaxing and contracting factors are briefly discussed.
1,868 citations
TL;DR: Treatment with le uprolide and flutamide is superior to treatment with leuprolide alone in patients with advanced prostate cancer, and Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade.
Abstract: To test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer, we conducted a randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2). All 603 men received leuprolide, an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins, in combination with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. As compared with the 300 patients receiving leuprolide and placebo, the 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival (16.5 vs. 13.9 months; P = 0.039) and an increase in the median length of survival (35.6 vs. 28.3 months; P = 0.035). The differences between the treatments were particularly evident for men with minimal disease and good performance status; however, further studies should be conducted in this subgroup. Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade, when leuprolide alone often produces a painful flare in the disease. We conclude that in patients with advanced prostate cancer, treatment with leuprolide and flutamide is superior to treatment with leuprolide alone.
1,433 citations
TL;DR: Evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents, and the information may be useful in designing or altering chemotherapeutic protocols in these patients.
Abstract: Chemotherapy has proven to be an effective treatment for the cure and palliation of some human cancers (Chabner, 1982). Some tumors, however, appear to be intrinsically resistant to chemotherapy. For cancers that can be treated with chemotherapy, based on the hypothesis that resistance to single agents occurs with high frequency, protocols involving multiple drugs with different intracellular targets have been designed. In many cases, such as acute lymphocytic leukemia and neuroblastoma (Simone et al., 1982), Hodgkin’s disease (De-Vita and Hellman, 1982), and germ cell cancers (Paulson et al., 1982), dramatic results have been achieved with such protocols. However, all too frequently relapse occurs after such therapy and the recurrent tumors are resistant to further chemotherapy. In effect, such tumors develop a multidrug resistance (MDR) phenotype that is very similar to the intrinsic resistance of some primary cancers.
1,290 citations
TL;DR: Vertebral fracture prevalence was assessed in an age-stratified random sample of Rochester, Minnesota women aged 50 years and over, finding that vertebral fractures were common and increased with age.
Abstract: Vertebral fracture prevalence was assessed in an age-stratified random sample of Rochester, Minnesota women aged 50 years and over. Vertebral fractures, including wedge and concavity as well as compression fractures, were common and increased with age. The estimated incidence of new vertebral fractures also rose with age, reaching 29.6 per 1,000 person-years in women aged greater than or equal to 85 years. The prevalence of one or more vertebral fractures also increased with declining bone mass, reaching 42% in women with spinal bone mineral density less than 0.6 g/cm2 by dual photon absorptiometry. Bone mass and age contributed independently to the risk of vertebral fracture, but "age" may reflect other manifestations of osteoporosis.
904 citations
TL;DR: An adaptive technique for measuring and correcting the effects of patient motion during magnetic resonance image acquisition was developed and tested and shows promise for addressing the problem of respiratory motion in thoracoabdominal imaging.
Abstract: An adaptive technique for measuring and correcting the effects of patient motion during magnetic resonance image acquisition was developed and tested. A set of algorithms that can reverse the effects of object displacements and phase shifts was used. These algorithms essentially transfer the frame of reference of the image reconstruction from the static frame of the imager couch to the moving "visceral frame." An accurate record of tissue motion during image acquisition is required. To achieve this, the authors used specially encoded "navigator" echoes that are interleaved with the imaging sequence. Postprocessing of the navigator echo data provides a highly detailed record of the displacements and phase shifts that occur during imaging. Phantom studies demonstrated that the technique can directly correct image degradation caused by motion. In contrast to conventional artifact reduction techniques, such as ordered phase encoding and gradient moment nulling, this new method has a unique capacity to reduce motion unsharpness. Preliminary in vivo studies have demonstrated that the technique can markedly improve images degraded by voluntary motion and shows promise for addressing the problem of respiratory motion in thoracoabdominal imaging.
839 citations
TL;DR: The importance of the tibialis posterior tendon in normal hindfoot function and its treatment when injured are now being properly appreciated.
Abstract: Dysfunction of the tibialis posterior tendon evolves through a series of stages The pain symptoms, clinical signs, and roentgenographic changes for each of these stages are characteristic This staging system permits clarification and individualization of dysfunction, expected pathologic changes, and surgical treatment The importance of the tibialis posterior tendon in normal hindfoot function and its treatment when injured are now being properly appreciated
802 citations
TL;DR: The Cox regression method and comprehensive data from 312 Mayo Clinic patients with primary biliary cirrhosis were used to derive a model based on patient's age, total serum bilirubin and serum albumin concentrations, prothrombin time and severity of edema, which predicted survival accurately.
777 citations
TL;DR: The response of isolated blood vessels to a variety of vasoactive agonists is modulated by the presence of endothelial cells, and endothelium-derived relaxing factors may contribute to the regulation of the release of atrial natriuretic factor and renin.
Abstract: The response of isolated blood vessels to a variety of vasoactive agonists is modulated by the presence of endothelial cells. Indeed, these cells can release both dilator and constrictor substances. The major endothelium-derived relaxing factor may be nitric oxide, which activates soluble guanylate cyclase in the smooth muscle, although the endothelial cells also secrete an unidentified hyperpolarizing factor. Among the natural stimuli for the release of endothelium-derived relaxing factors are circulating hormones, platelet products, thrombin, shear stress, and certain autacoids. Endothelium-derived relaxing factors may contribute to the regulation of the release of atrial natriuretic factor and renin. The endothelial cells can also release constricting factors; among the likely candidates are superoxide anions or the peptide endothelin. In hypertensive blood vessels, the ability to release endothelium-derived relaxing factors but not endothelium-derived contracting factors is blunted.
692 citations
TL;DR: The lack of effect of agents having a powerful effect on somatic pain stimuli and the converse effects of glutamate receptor antagonists on the strychnine hyperesthesia at doses which do not affect the somaticPain response indicate discriminable processing systems, which resemble the clinical phenomenon observed in patients suffering from sensory dysesthesia following central and peripheral horn injury.
Abstract: Intrathecal administration of glycine (strychnine) or GABA (bicuculline) but not opioid (naloxone), adrenergic (phentolamine) or serotonin (methysergide) receptor antagonists resulted in a dose-dependent organized agitation response to light tactile stimulation. This effect was maximally evoked by oscillating but not continuous stimulation applied to a dermatome corresponding to the levels of spinal cord acted upon by the intrathecal antagonist. Similar results were observed in chloralose-urethane anesthetized rats in which tactile stimulation evoked hypertensive responses following local tactile stimuli. The effects were only mildly depressed by even high doses of spinal morphine or DADL and not at all by ST-91 or baclofen. In contrast, intrathecal injections of glutamate receptor antagonists resulted in a dose-dependent depression of the strychnine evoked hyperesthesia with the ordering of activity being MK-801, AP-5, kynurenic acid, SKF10047 and ketamine. At doses below those which produced motor dysfunction, however, these agents had no effects on the hot-plate response latency. These data emphasize that low threshold afferent input is likely subject to an ongoing modulation, the loss of which results in a miscoding of the afferent stimulus yielding a pain relevant message. The lack of effect of agents having a powerful effect on somatic pain stimuli and the converse effects of glutamate receptor antagonists on the strychnine hyperesthesia at doses which do not affect the somatic pain response indicate discriminable processing systems, the characteristics of which resemble the clinical phenomenon observed in patients suffering from sensory dysesthesia following central and peripheral horn injury.
TL;DR: Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03).
Abstract: A total of 401 eligible patients with resected stages B and C colorectal carcinoma were randomly assigned to no-further therapy or to adjuvant treatment with either levamisole alone, 150 mg/d for 3 days every 2 weeks for 1 year, or levamisole plus fluorouracil (5-FU), 450 mg/m2/d intravenously (IV) for 5 days and beginning at 28 days, 450 mg/m2 weekly for 1 year. Levamisole plus 5-FU, and to a lesser extent levamisole alone, reduced cancer recurrence in comparison with no adjuvant therapy. These differences, after correction for imbalances in prognostic variables, were only suggestive for levamisole alone (P = .05) but quite significant for levamisole plus 5-FU (P = .003). Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03). Therapy was clinically tolerable with either regimen and severe toxicity was uncommon. These promising results have led to a larg...
TL;DR: Both types of obesity were associated with impaired suppression of FFA turnover in response to euglycemic hyperinsulinemia compared to nonobese women, suggesting specific differences in FFA metabolism may reflect adipocyte heterogeneity, which may in turn affect the metabolic aberrations associated with different types of Obesity.
Abstract: In order to determine whether differences in body fat distribution result in specific abnormalities of free fatty acid (FFA) metabolism, palmitate turnover, a measure of systemic adipose tissue lipolysis, was measured in 10 women with upper body obesity, 9 women with lower body obesity, and 8 nonobese women under overnight postabsorptive (basal), epinephrine stimulated and insulin suppressed conditions. Results: Upper body obese women had greater (P less than 0.005) basal palmitate turnover than lower body obese or nonobese women (2.8 +/- 0.2 vs. 2.1 +/- 0.2 vs. 1.8 +/- 0.2 mumol.kg lean body mass (LBM)-1.min-1, respectively), but a reduced (P less than 0.05) net lipolytic response to epinephrine (59 +/- 7 vs. 79 +/- 5 vs. 81 +/- 7 mumol palmitate/kg LBM, respectively). Both types of obesity were associated with impaired suppression of FFA turnover in response to euglycemic hyperinsulinemia compared to nonobese women (P less than 0.005). These specific differences in FFA metabolism may reflect adipocyte heterogeneity, which may in turn affect the metabolic aberrations associated with different types of obesity. These findings emphasize the need to characterize obese subjects before studies.
TL;DR: The Third National Wilms' Tumor Study as discussed by the authors sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse by randomized treatment regimens.
Abstract: The Third National Wilms' Tumor Study sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse. Eligible patients (1439) were randomized according to stage (I-IV) and histology (favorable [FH] or unfavorable [UH]), and contributed data to survival and relapse-free survival (RFS) analyses. Four-year (postnephrectomy) survival percentages and randomized treatment regimens for low-risk patients were 96.5% for 607 Stage I/FH patients who received dactinomycin (Actinomycin D [AMD], Merck Sharp & Dohme, West Point, PA) and vincristine (VCR) for 10 weeks versus 6 months; 92.2% for 278 Stage II/FH patients; and 86.9% for 275 Stage III/FH patients who received AMD + VCR +/- Adriamycin (ADR, Adria Laboratories, Columbus, OH) for 15 months. Stage II/FH patients also had either zero or 2000 cGy irradiation (RT) postoperatively and Stage III/FH patients either 1000 or 2000 cGy. Four-year survival was 73.0% for 279 high-risk patients (any Stage IV, all UH) who received postoperative radiation therapy (RT) and AMD + VCR + ADR +/- cyclophosphamide (CPM). Statistical analysis of survival and RFS experience shows that the less intensive therapy does not worsen results for low-risk patients and CPM does not benefit those at high risk.
TL;DR: Reduction and fixation, followed by early motion when possible, may be the preferred treatment for patients who have a Type-III fracture, which correlated well with the type of fracture.
Abstract: A review of thirty-five patients who had a fracture of the coronoid process of the ulna revealed three types of fracture: Type I--avulsion of the tip of the process; Type II--a fragment involving 50 per cent of the process, or less; and Type III--a fragment involving more than 50 per cent of the process. A concurrent dislocation or associated fracture was present in 14, 56, and 80 per cent of these patients, respectively. The outcome correlated well with the type of fracture. According to an objective elbow-performance index used to assess the results for the thirty-two patients who had at least one year of follow-up (mean, fifty months), 92 per cent of the patients who had a Type-I fracture, 73 per cent who had a Type-II fracture, and 20 per cent who had a Type-III fracture had a satisfactory result. Residual stiffness of the joint was most often present in patients who had a Type-III fracture. We recommend early motion within three weeks after injury for patients who have a Type-I or Type-II fracture. Reduction and fixation, followed by early motion when possible, may be the preferred treatment for patients who have a Type-III fracture.
TL;DR: Multivariate analysis (Cox proportional hazards regression modeling) revealed that age, serum bilirubin concentration, blood hemoglobin concentration, presence or absence of inflammatory bowel disease and histologic stage on liver biopsy were independent predictors of high risk of dying.
TL;DR: Right-left asymmetry in the volumes of the anterior temporal lobes and hippocampal formations was a normal finding and no effect of age, sex, or handedness was seen in normalized hippocampal formation volumes.
Abstract: Volumes of the right and left anterior temporal lobes and hippocampal formations were measured from magnetic resonance images in 52 healthy volunteers, aged 20-40 years. Subjects were selected by age, sex, and handedness to evaluate possible effect of these variables. Data were normalized for variation in total intracranial volume between individuals. Right-left asymmetry in the volumes of the anterior temporal lobes and hippocampal formations was a normal finding. The anterior temporal lobe of the non-dominant (right) hemisphere was larger than the left by a small (mean right-left difference, 2.3 cm3) but statistically significant amount (P less than .005) in right-handed subjects. No significant effect of age or sex was seen in normalized right or left anterior temporal lobe volume. The right hippocampal formation was larger than the left for all subjects by a small (mean right-left difference, 0.3 cm3) but statistically significant amount (P less than .001). No effect of age, sex, or handedness was see...
TL;DR: Using the records linkage system of the Mayo Clinic and of the Rochester Epidemiology Project, which accesses diagnostic data on the entire population of Olmsted County, Minnesota, it is found that 45 new cases of idiopathic dilated cardiomyopathy (DCM) and 19new cases of hypertrophic cardiopathy (HCM) among county residents for the years 1975-1984 are identified.
Abstract: Using the records linkage system of the Mayo Clinic and of the Rochester Epidemiology Project, which accesses diagnostic data on the entire population of Olmsted County, Minnesota, we identified 45 new cases of idiopathic dilated cardiomyopathy (DCM) and 19 new cases of hypertrophic cardiomyopathy (HCM) among county residents for the years 1975-1984. Overall age- and sex-adjusted incidence rates were 6.0/100,000 and 2.5/100,000 person-years, respectively. The incidence of DCM doubled from 3.9/100,000 in the first 5 years to 7.9/100,000 person-years in the last 5 years of study. The corresponding change for HCM was from 1.4 to 3.6/100,000 person-years. Age- and sex-adjusted prevalence rates as of January 1, 1985, for DCM and HCM were 36.5/100,000 and 19.7/100,000 population, respectively. The prevalence of DCM in persons less than 55 years old was 17.9/100,000, over a third of whom were New York Heart Association functional Class III or IV at diagnosis. These estimates may be of value in determining the potential use of health care resources, particularly cardiac transplantation.
TL;DR: In Inherited low TPMT activity appears to be a major risk factor for acute azathioprine‐induced myelosuppression.
Abstract: Azathioprine therapy can cause acute myelosuppression. Toxicity is in part caused by the incorporation of azathioprine-derived 6-thioguanine nucleotides (6-TGN) into deoxyribonucleic acid (DNA). The enzyme thiopurine methyltransferase (TPMT) plays an important role in azathioprine catabolism. TPMT activity is controlled by a common genetic polymorphism, and one in 300 subjects has very low enzyme activity. Azathioprine was withdrawn in five study patients because of acute myelosuppression. The duration of azathioprine treatment was 21 to 70 days (median, 28), and the daily oral dose was 1.0 to 2.5 mg/kg. Sixteen control patients who had been taking oral azathioprine (1.1 to 2.0 mg/kg daily for more than 6 months) with no history of myelosuppression were studied. All subjects had normal liver and kidney function. When compared with the control group, the five patients with myelosuppression had very low TPMT activities and abnormally high 6-TGN concentrations. Inherited low TPMT activity appears to be a major risk factor for acute azathioprine-induced myelosuppression.
TL;DR: The findings support the notion that IBM is a distinct entity in which a set of pathological features is associated with a constellation of clinical findings, and Prednisone treatment at dose levels frequently effective in polymyositis failed to prevent disease progression in those patients observed for 2 or more years.
Abstract: Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic fibres, and an autoaggressive endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle specimens. All three of these features were present in 88% of the specimens. Electron microscopy confirmed the presence of filamentous inclusions in 40 of 43 patients. The inclusions are typically near vacuoles and a minimum of three vacuolated fibres must be scrutinized to detect them with confidence. There is no electromyographic pattern that can reliably distinguish IBM from other inflammatory myopathies. The typical clinical features in the patients diagnosed by histological criteria as IBM were: insidious onset after age 50 yrs with painless, proximal lower extremity weakness; slow but relentless progression with selectively severe involvement of quadriceps, iliopsoas, tibialis anterior, biceps and triceps muscles; relatively early depression of the knee reflexes; and a normal or mildly elevated serum creatine kinase level. The male: female ratio was 3:1. Distal weakness occurred in about 50%, but only in 35% was it as great or greater than proximal weakness. Significant associated illnesses include other autoimmune disorders (15%), diabetes mellitus (20%), and diffuse peripheral neuropathy (18%). Prednisone treatment at dose levels frequently effective in polymyositis failed to prevent disease progression in those patients observed for 2 or more years. Our findings support the notion that IBM is a distinct entity in which a set of pathological features is associated with a constellation of clinical findings.
TL;DR: Psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF-alpha) rather than deficient expression of an growth inhibitor (T GF-beta 1) in normal, uninvolved, and lesional psoriatic Epidermis.
Abstract: Transforming growth factor alpha (TGF-alpha) is produced by and required for the growth of epithelial cells and is angiogenic in vivo. Since epidermal hyperplasia and angiogenesis are hallmarks of psoriasis, TGF-alpha gene expression was analyzed in epidermal biopsies of normal and psoriatic skin. TGF-alpha messenger RNA and protein are much more abundant in lesional psoriatic epidermis than in normal-appearing skin of psoriatic patients or in normal epidermis. In contrast, messenger RNA levels of transforming growth factor beta 1 (TGF-beta 1), which inhibits epithelial cell growth, are not significantly different in normal, uninvolved, and lesional psoriatic epidermis. Thus, psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF-alpha) rather than deficient expression of a growth inhibitor (TGF-beta 1).
TL;DR: It is indicated that endothelin is a potent vasoconstrictor that elevates systemic blood pressure in association with marked decreases in cardiovascular and renal function and may function as a counterregulatory hormone to the effects of endothelial-derived vasodilator agent(s).
Abstract: Endothelin, a newly discovered endothelial-derived peptide, has been demonstrated in vitro to have potent vasocontractile properties and has been speculated to play a role in vivo in arterial pressure-volume homeostasis. The present studies in anesthetized dogs were designed to determine the action of endothelin on cardiovascular-renal and endocrine function in vivo as in acute arterial pressure-volume regulation. Intravenous infusion of endothelin (50 ng/kg per min) increases arterial pressure by increasing peripheral vascular resistance but in association with an increase in coronary vascular resistance and decreases in cardiac output. Renal blood flow and glomerular filtration rate were markedly reduced in association with a sustained reduction in sodium excretion and an increase in plasma renin activity. Atrial natriuretic factor, vasopressin, and aldosterone were also elevated. These results indicate that endothelin is a potent vasoconstrictor that elevates systemic blood pressure in association with marked decreases in cardiovascular and renal function. This peptide may function as a counterregulatory hormone to the effects of endothelial-derived vasodilator agent(s).
TL;DR: It is concluded that both androgens and estrogens act directly on human bone cells through their respective receptor-mediated mechanisms.
Abstract: The sex steroids, androgens and estrogens, are major regulators of bone metabolism. However, whether these hormones act on bone cells through direct or indirect mechanisms has remained unclear. A nuclear binding assay recently used to demonstrate estrogen receptors in bone [Eriksen, E.F., Colvard, D.S., Berg, N.J., Graham, M.L., Mann, K.G., Spelsberg, T.C. & Riggs, B.L. (1988) Science 241, 84-86] was used to identify specific nuclear binding of a tritiated synthetic androgen, [3H]R1881 (methyltrienolone), in 21 of 25 (84%) human osteoblast-like cell strains and a concentration of bound steroid receptors of 821 +/- 140 (mean +/- SEM) molecules per cell nucleus. Binding was saturable and steroid-specific. Androgen receptor gene expression in osteoblasts was confirmed by RNA blot analysis. Relative concentrations of androgen and estrogen receptors were compared by measuring specific nuclear estrogen binding. Nuclear binding of [3H]estradiol was observed in 27 of 30 (90%) cell strains; the concentration of bound estradiol receptor was 1537 +/- 221 molecules per cell nucleus. The concentrations of nuclear binding sites were similar in males and females for both [3H]R1881 and [3H]estradiol. We conclude that both androgens and estrogens act directly on human bone cells through their respective receptor-mediated mechanisms.
TL;DR: This questionnaire is believed to be an additional and useful diagnostic tool for identifying patients with functional gastrointestinal symptoms and elicited symptoms in a highly reliable manner and was shown to be a valid measure of functional bowel complaints.
Abstract: Although functional gastrointestinal symptoms are seen frequently by internists and are the commonest reason for patients to be referred to gastroenterologists, no validated self-report qu...
TL;DR: In this paper, the authors conducted a population-based study to investigate the rate of expansion of abdominal aortic aneurysms and the risk of rupture in relation to their size.
Abstract: Information is incomplete about the rate of expansion of abdominal aortic aneurysms and the risk of rupture in relation to their size. To address these questions, we conducted a population-based study. Of the 370 residents of Rochester, Minn., with an aneurysm initially diagnosed from 1951 through 1984, 181 had the aneurysm documented by ultrasound examination. Among the 103 patients who underwent more than one ultrasound study, the diameter of the aneurysm increased by a median of 0.21 cm per year. Only 24 percent had a rate of expansion of 0.4 cm or more per year. Among the 176 patients who had an unruptured aneurysm at the time of the initial ultrasound study, the cumulative incidence of rupture was 6 percent after 5 years and 8 percent after 10 years. However, the risk of rupture over five years was 0 percent for the 130 patients with an aneurysm less than 5 cm in diameter and 25 percent for the 46 patients with an aneurysm 5 cm or more in diameter. All 16 patients who had ruptures had aneurysms that were 5 cm or more in diameter at the time of the rupture. These population-based data challenge the clinical perception that aneurysms typically expand at a rate of 0.4 to 0.5 cm per year. Our data also suggest that for aneurysms less than 5 cm in diameter the risk of rupture is considerably lower than has been reported previously. However, the risk of rupture is substantial for aneurysms 5 cm or more in diameter.
TL;DR: Results confirm prior observations showing the toxicity of MBP to tracheal epithelium and indicate that ECP and EPO alone, as well as EPO + GO + halide, cause damage, indicating that several eosinophil granule proteins are able to damage respiratory epithelia.
Abstract: We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 µg/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 µg/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2-producing enzyme glucose oxidase (GO), Cl−, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3....
TL;DR: It is suggested that lung inflammation contributes substantially to respiratory impairment in patients with P. carinii pneumonia and increased lavage neutrophils (rather than parasite number) correlate with poorer oxygenation and poorer patient survival.
Abstract: Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS To determine differences in P carinii pneumonia in patients with and without AIDS, the P carinii parasite numbers, lung inflammatory cell populations, gas exchange, and survival were assessed in a series of 75 consecutive patients with P carinii pneumonia Bronchoalveolar lavage was used to quantify the parasite and inflammatory cell numbers in these patients The data from this study indicate: (1) patients with P carinii pneumonia and AIDS have significantly greater numbers of P carinii per ml of lavage compared to other immunocompromised patients with P carinii pneumonia (p < 00001); (2) patients with P carinii pneumonia and AIDS also have significantly fewer neutrophils recovered in the lavage compared to other immunocompromised patients with P carinii pneumonia (p = 00001); (3) patients with AIDS and P carinii pneumonia have higher arterial oxygen
TL;DR: The results in sixteen patients who had a displaced, comminuted intra-articular fracture of the distal end of the radius and who were treated by open reduction and internal fixation were retrospectively reviewed, and four patients in whom the fracture healed with this amount of incongruity all had post-traumatic arthritis at follow-up.
Abstract: The results in sixteen patients who had a displaced, comminuted intra-articular fracture of the distal end of the radius and who were treated by open reduction and internal fixation were retrospectively reviewed. At a mean follow-up of 4.8 years, 81 per cent of the patients had a rating of good or excellent by the scoring system of Gartland and Werley, but only 56 per cent had such a rating when the modified scoring system of Green and O'Brien was used. All of the fractures healed at an average of nine weeks. A step-off of two millimeters or more in the distal radial articular surface at the time of healing was important, because the four patients in whom the fracture healed with this amount of incongruity all had post-traumatic arthritis at follow-up, compared with only three of twelve in whom the incongruity was less than two millimeters.
TL;DR: Observations are consistent with the hypothesis that superoxide anion, rather than prostaglandins generated by hydroperoxidase activity of cyclooxygenase, is an endothelium-derived contracting factor in canine cerebral arteries.
Abstract: The calcium ionophore A23187 causes endothelium-dependent contractions in canine basilar arteries. Removal of the endothelium, or treatment with indomethacin or superoxide dismutase (SOD), prevented the endothelium-dependent excitatory effect of the calcium ionophore. Catalase and deferoxamine were without effect. Superoxide anion generated by xanthine plus xanthine oxidase in the presence of catalase caused contractions of the vascular smooth muscle, which were abolished by SOD or heat inactivation of xanthine oxidase. The A23187-induced production of prostaglandins F2 alpha and E2 and thromboxane B2 was abolished by the removal of endothelium and by treatment with indomethacin but was not affected by the presence of SOD plus catalase. These observations are consistent with the hypothesis that superoxide anion, rather than prostaglandins generated by hydroperoxidase activity of cyclooxygenase, is an endothelium-derived contracting factor in canine cerebral arteries.
TL;DR: The evidence for a relationship between radical formation and the biological activity of the antitumor quinones is evaluated and it is suggested that cardiotoxicity and skin toxicity may also be related to oxygen radical formation.