Showing papers by "Mayo Clinic published in 1991"

Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure

Abstract: Background. Milrinone, a phosphodiesterase inhibitor, enhances cardiac contractility by increasing intracellular levels of cyclic AMP, but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined. Methods. We randomly assigned 1088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with 40 mg of oral milrinone daily (561 patients) or placebo (527 patients). In addition, all patients received conventional therapy with digoxin, diuretics, and a converting-enzyme inhibitor throughout the trial. The median period of follow-up was 6.1 months (range, 1 day to 20 months). Results. As compared with placebo, milrinone therapy was associated with a 28 percent increase in mortality from all causes (95 percent confidence interval, 1 to 61 percent; P = 0.038) and a 34 percent increase in cardiovascular mortality (95 percent...

Effective surgical adjuvant therapy for high-risk rectal carcinoma.

Abstract: Background Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone. Methods Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU). Results After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0...

Risk for Serious Gastrointestinal Complications Related to Use of Nonsteroidal Anti-inflammatory Drugs: A Meta-analysis

Abstract: Objective To describe the relative risk for serious gastrointestinal complications due to non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure among NSAID users as well as in selected subgroups. Design Overview and meta-analysis. Data identification A literature search of English-language studies examining the association between NSAIDs and adverse gastrointestinal events for the period 1975 to 1990 identified using MEDLINE and communicating with three internationally recognized experts. Data analysis A qualitative summary of study characteristics and a critical appraisal of study quality were done. The results of 16 primary studies were selected and combined statistically. Summary estimates were weighted by sample size and quality score. Main results The overall odds ratio of the risk for adverse gastrointestinal events related to NSAID use, summarized from 16 studies (9 case-control and 7 cohort) was 2.74 (95% Cl, 2.54 to 2.97). The summary odds ratios were as follows: elderly patients, (aged greater than or equal to 60 years), 5.52 (Cl, 4.63 to 6.60); patients under 65 years of age, 1.65 (Cl, 1.08 to 2.53); women, 2.32 (Cl, 1.91 to 2.82); and men, 2.40 (Cl, 1.85 to 3.11). The summary odds ratio for NSAID users receiving concomitant corticosteroids compared with NSAID users not receiving corticosteroids was 1.83 (Cl, 1.20 to 2.78). The summary odds ratio for the first gastrointestinal event was 2.39 (Cl, 2.16 to 2.65). The relative risk for a subsequent or unspecified gastrointestinal event was 4.76 (Cl, 4.05 to 5.59). The summary odds ratio for less than 1 month of NSAID exposure was 8.00 (Cl, 6.37 to 10.06); for more than 1 month but less than 3 months of exposure, the summary odds ratio was 3.31 (Cl, 2.27 to 4.82); and for more than 3 months of exposure, the summary odds ratio was 1.92 (Cl, 1.19 to 3.13). Conclusions Users of NSAIDs are at approximately three times greater relative risk for developing serious adverse gastrointestinal events than are nonusers. Additional risk factors include age greater than 60 years, previous history of gastrointestinal events, and concomitant corticosteroid use. Another possible risk factor is the first 3 months of NSAID therapy. The risk for serious gastrointestinal events appears to be equal among men and women. These data represent summary statistics from 16 studies and cannot be considered generalizable to all NSAID users.

Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis.

Abstract: Background. Atherosclerosis is characterized by endothelial injury and the proliferation of arterial smooth-muscle cells. The latter may be a result of the release of growth factors from the vessel wall; such growth factors may include an endothelium-derived vasoconstrictor peptide with mitogenic properties. We tested the hypothesis that plasma endothelin concentrations are elevated in persons with symptomatic atherosclerosis, independently of age. Methods. We measured plasma endothelin levels in 100 normal subjects and in 40 patients with atherosclerosis predominantly of the following types: aortic and peripheral vascular disease (14 patients), renovascular disease (9 patients), coronary artery disease (9 patients), and carotid disease (8 patients). We also performed immunohistochemical staining for endothelin in the walls of atherosclerotic vessels. Results. In the normal subjects, the mean (±SD) plasma endothelin concentration was 1.4±0.2 pmol per liter, with no correlation between age and pla...

Sex Differences in the Management of Coronary Artery Disease

Abstract: Background. Despite the fact that coronary artery disease is the leading cause of death among women, previous studies have suggested that physicians are less likely to pursue an aggressive approach to coronary artery disease in women than in men. To define this issue further, we compared the care previously received by men and women who were enrolled in a large postinfarction intervention trial. Methods. We assessed the nature and severity of anginal symptoms and the use of antianginal and anti-ischemic interventions before enrollment in the 1842 men and 389 women with left ventricular ejection fractions ≤40 percent after an acute myocardial infarction who were randomized in the Survival and Ventricular Enlargement trial. Results. Before their index infarction, women were as likely as men to have had angina and to have been treated with antianginal drugs. However, despite reports by women of symptoms consistent with greater functional disability from angina, fewer women had undergone cardiac catheterizati...

Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms

Abstract: Forty-five patients with metastatic neuroendocrine tumors were treated with a regimen of etoposide 130 mg/m2/d for 3 days plus cisplatin 45 mg/m2/d on days 2 and 3. Both drugs were given by continuous intravenous infusion. Among 27 patients with well-differentiated carcinoid tumors or islet cell carcinomas, only two partial objective tumor regressions were observed (7%). Among 18 patients prospectively classified as having anaplastic neuroendocrine carcinomas, however, there were nine partial regressions and three complete regressions, an overall regression rate of 67%. For anaplastic disease, the median duration of regression was 8 months (range to 21 months). Tumor response was unrelated to primary site, endocrine hyperfunction, or prior therapy experience. The median survival of all patients with anaplastic tumors was 19 months; this seemed favorable when considering the small experiences with these rare tumors reported in the literature. Toxicity, which was severe for most patients, consisted primarily of vomiting, leukopenia, thrombocytopenia, anemia, alopecia, and neuropathy. The anaplastic neuroendocrine tumor is strongly responsive to therapy with combined etoposide and cisplatin. Patients with undifferentiated carcinomas, originating in typical neuroendocrine tumor sites (small and large bowel, pancreas, and stomach) or of unknown origin, who have consistent histologic findings by light microscopy should be evaluated for this possibility with appropriate immune staining or electron microscopy.

Prevalence of epilepsy in Rochester, Minnesota: 1940-1980.

Abstract: Summary: : The prevalence of epilepsy in Rochester, Minnesota has been determined for a specific date in each of 5 decennial census years. Individuals with a diagnosis of epilepsy (recurrent unprovoked seizures) who were known to have experienced a seizure or who had received antiepileptic medication in the preceding 5 years were considered active prevalence cases. By this definition, the age-adjusted prevalence per 1,000 population, increased steadily from 2.7 in 1940 to 6.8 in 1980. At each of five prevalence dates, for all prevalence cases, 60% had epilepsy manifest by partial seizures, and 75% had no known etiology. Prevalence was higher for males than females for all except the last prevalence day. After 1950, prevalence tended to increase with advancing age and was highest in the oldest age groups. On the average, the 1980 prevalence cases had epilepsy 50% had their first diagnosis in the first 20 years of life. RESUME La prevalence de ľ epilepsie dans le Comtede Rochester, dans le Minnesota, a eteevaluee pour une date precise de chacune des 5 annees du recensement decennal. Les individus pour lesquels le diagnostic ďepilepsie avait ete pose (crises spontanees recurrentes) et qui avaient presente une crise ou recevaient un traitement antiepileptiques dans les 5 annees precedentes, ont ete consideres comme des cas de prevalence active. Selon cette definition, la prevalence ajustee pour Page pour 1000 habitants a agumente constamment de 2.7 en 1940 a 6.8 en 1980. A chacune des 5 dates de prevalence, pour tous les cas, 60% ont presente une epilepsie se manifestant par des crises partielles, et 75% n'avaient pas ďetiologie connue. La prevalence teAait plus elevee chez les hommes que chez les femmes, sauf lors du dernier jour de prevalence. Apres 1950, la prevalence tendait a augmenter avec ľâge, elle etait la plus forte dans les groupes ďâge eleve En moyenne, les cas de 1980 avaient une epilepsie evoluant depuis moins de 10 ans et plus de 50% avaient une epilepsie diagnos-tiquee au cours des 20 premieres annees de vie. RESUMEN Se ha determinado la prevalencia de epilepsyia en Rochester, Minnesota, para una fecha especifica en cada uno de los 5 dece-nios del censo. Individuos con diagnostico de epilepsia “ataques recurrentes sin provocacion” que habian tenido un ataque o recibido medicateon antiepileptica en los 5 anos precedentes, fueron considerados como casos activos de prevalencia. Segun esta definition la prevalencia ajustada a la edad por 1.000 habitantes se incremento continuadamente de 2.7 en 1940 a 6.8 en 1980. En cada una de las 5 fechas de prevalencia para todos los casos prevalentes, el 60% tenia epilepsyia manifestada por ataques parciales y el 75% de etiologia desconocida. La prevalencia fue mas elevada en varones que en hembras en todos los dias de prevalencia excepto el ultimo. Despues de 1950 la prevalencia mostro una tendencia al aumento con incremento de la edad y fue mas elevada en los grupos de mayor edad. Como promedio, los casos de prevalencia en 1980 habian padecido epilepsyia durante menos de 10 anos y mas del 50% tuvieron el primer diagnostico en los primeros 20 anos de su vida. ZUSAMMENFASSUNG Die Praevalenz der Epilepsie in Rochester, Minnesota wurde an einem bestimmten Datum in funf aufeinanderfolgenden Cen-sus-Decenien bestimmt. Personen mit der Diagnose Epilepsie (wiederholte nicht provozierte Anfalle), die einene Anfall erlitten hatten oder Antiepileptika eingenommen hatten wurden als ak-tive Praevalenz-Falle betrachtet. Demnach stieg die altersberei-nigte Praevalenz fur 1000 Einwohner kontinuierlich von 2,7 1940 auf 6,8 1980 an. Zu jedem der funf Praevalenz-Daten aller Praevalenz-Falle manifestierte sich die Epilepsie in 60% durch Partialanfalle, davon 75% ohne bekannte Atiologie. Die Praevalenz war fur Manner hoher als fur Frauen wahrend aller Stichtage, ausgenommen des letzten. Nach 1950 stieg die Praevalenz mit zunehmendem Alter leicht an und erreichte ihren hochsten Wert in der altesten Altersgruppe. Im Durchschnitt hatten 1980 die Praevalen-Falle eine Epilepsie fur weniger als 10 Jahre. Bei mehr als 50% wurde die Erstdiagnose Epilepsie in den ersten 20 Le-bensjahren gestellt.

Valgus stability of the elbow. A definition of primary and secondary constraints.

Abstract: The stabilizing structures of the elbow that resist valgus stress were studied with a tracking device in a model simulating active motion and muscle activity. By varying the order of serial release of the medial collateral ligament complex and removal of the radial head, each structure's contribution to valgus stability against the effect of gravity was determined. In the otherwise intact elbow, absence of the radial head does not significantly alter the three-dimensional characteristics of motion in the elbow joint. Isolated medial collateral release, on the other hand, causes increases in abduction rotation of about 6 degrees-8 degrees in magnitude. Releasing both structures results in gross abduction laxity and elbow subluxation. This study defines the medial collateral ligament (MCL) as the primary constraint of the elbow joint to valgus stress and the radial head as a secondary constraint. This definition facilitates the proper management of patients with radial head fractures and MCL disruption. The comminuted radial head fracture uncomplicated by MCL insufficiency should be treated by excision without the need for an implant and without concern of altering the normal kinematics of the elbow.

Spiral calcium wave propagation and annihilation in Xenopus laevis oocytes

Abstract: Intracellular calcium (Ca2+) is a ubiquitous second messenger. Information is encoded in the magnitude, frequency, and spatial organization of changes in the concentration of cytosolic free Ca2+. Regenerative spiral waves of release of free Ca2+ were observed by confocal microscopy in Xenopus laevis oocytes expressing muscarinic acetylcholine receptor subtypes. This pattern of Ca2+ activity is characteristic of an intracellular milieu that behaves as a regenerative excitable medium. The minimal critical radius for propagation of focal Ca2+ waves (10.4 micrometers) and the effective diffusion constant for the excitation signal (2.3 x 10(-6) square centimeters per second) were estimated from measurements of velocity and curvature of circular wavefronts expanding from foci. By modeling Ca2+ release with cellular automata, the absolute refractory period for Ca2+ stores (4.7 seconds) was determined. Other phenomena expected of an excitable medium, such as wave propagation of undiminished amplitude and annihilation of colliding wavefronts, were observed.

Exposure to an Aeroallergen as a Possible Precipitating Factor in Respiratory Arrest in Young Patients with Asthma

Abstract: Background. Exposure to airborne spores of the common mold Alternaria alternata has been implicated in asthma attacks. Such exposure is particularly frequent in the Midwest during the summer and fall months. To determine the role of A. alternata in triggering severe asthma attacks, we investigated the cases of 11 patients with asthma who had sudden respiratory arrest and determined the frequency of sensitivity to this allergen in these patients. Methods. The 11 patients (age range, 11 to 25 years) with initial episodes of respiratory arrest, which was fatal in 2 patients, were identified in the course of their care in our pediatric and adult clinical allergy practice and by a retrospective review of all Mayo Clinic records of patients with severe asthma cared for between 1980 and 1989. Skin-test reactivity to A. alternata and levels of IgE antibody against this mold in the 11 patients were compared with those in 99 matched controls with asthma who had no history of respiratory arrest. Results. All the pat...

50-year trends in the incidence of anorexia nervosa in Rochester, Minn.: a population-based study.

Abstract: Objective The aim of the study was to determine incidence and prevalence rates and long-term trends in incidence of anorexia nervosa by identifying all persons residing in the community of Rochester, Minn., during the 50-year period 1935 through 1984 who had the disorder. Method From a community-based epidemiologic resource, 13,559 medical records with diagnoses of amenorrhea, starvation, weight loss, anorexia nervosa, or other conditions were screened to identify true cases of anorexia nervosa determined by using standard diagnostic criteria. Results One hundred eighty-one residents (166 female and 15 male) fulfilled the diagnostic criteria for anorexia nervosa; these were the incidence cases. Due to a quadratic trend in the rates for girls 10-19 years old, the incidence rate among female residents fell from 16.6 per 100,000 person-years in the 1935-1939 period to a low of 7.0 in 1950-1954 and increased to 26.3 in 1980-1984. The incidence rates for women 20 years old and older and for males remained constant. For females 15-24 years old, there was a linear increase. The overall age-adjusted incidence rate per 100,000 person-years was 14.6 for females and 1.8 for males. The prevalence rate per 100,000 population was 269.9 for females and 22.5 for males. Conclusions Anorexia nervosa is more common than previously recognized. Among girls 15-19 years old it is a very common chronic illness. Its incidence has increased among females 15-24 years old but not among older women or among males.

Reliability of measurements of cervical spine range of motion--comparison of three methods.

Abstract: To determine reliabilities within and between persons measuring cervical active range of motion (AROM) three methods were examined: use of a cervical-range-of-motion (CROM) instrument, use of a universal goniometer (UG), and visual estimation (VE). Measurements were made on 60 patients with orthopedic disorders of the cervical spine who were divided into three groups of 20 subjects each. All subjects were tested in a standardized seated position using operationally defined goniometric placements and nongoniometric estimation techniques. Cervical flexion and extension, lateral flexion, and rotation were measured. Intraclass correlation coefficients (ICCs) were used to quantify within-tester and between-tester reliability. We found that goniometric measurements of AROM of the cervical spine made by the same physical therapist had ICCs greater than .80 when made with the CROM device or the UG. When different physical therapist measured the same patient's cervical AROM, the CROM device had ICCs greater than .80, whereas the UG and VE generally had ICCs less than .80.

Magnetic resonance imaging–based volume studies in temporal lobe epilepsy: Pathological correlations

Abstract: We performed a prospective study correlating magnetic resonance imaging volume measurements of the hippocampal formation with histopathology in 24 patients with intractable partial epilepsy who subsequently underwent an anterior temporal lobectomy for their seizure disorder. Patients with mass lesions verified pathologically were excluded from this study. In 71% of patients, quantitative hippocampal formation atrophy correctly lateralized the temporal lobe of seizure origin; in 29%, the volume study was indeterminant. The severity of the pathological alterations in the hippocampus correlated with the hippocampal formation volume determination. Mesial temporal sclerosis was identified in the surgically excised temporal lobe in 15 patients. The magnetic resonance imaging volume studies indicated hippocampal atrophy in the temporal lobe resected in 14 of the 15 patients. Magnetic resonance imaging-based volume measurements of the hippocampal formation increase the diagnostic yield of magnetic resonance imaging scanning in patients with intractable partial epilepsy related to mesial temporal sclerosis.

Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial.

Abstract: Objectives To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. Design A multicenter, randomized, controlled trial. Setting Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). Interventions Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. Measurements Patients were monitored for hemorrhagic events during hospitalization. Main results In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. Conclusions Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy.

Biomechanical study of ligaments around the elbow joint.

Abstract: The ligamentous contribution to elbow joint stability is a product of morphology and biologic parameters of each of the collateral ligaments. Better understanding of these characteristics is of paramount importance for successful ligament reconstruction in the surgery for joint replacement and traumatic injury. Two experiments were performed. In the first, the arc of elbow flexion where the individual ligament was either taut or slack was measured; in the second, the structural properties of each collateral ligament were determined by using bone-ligament-bone preparations. The anterior medial collateral ligament (AMCL) and radial collateral ligament (RCL) were taut throughout most of the entire arc of flexion. The posterior medial collateral ligament (PMCL) was taut only when the elbow was in a flexed position. Among the collateral ligaments, the AMCL was the strongest and stiffest with an average failure load of 260 N. The palmaris longus tendon, the most frequently used graft for elbow ligament reconstruction, was similar in strength (357 N).

Survivorship analysis of total knee arthroplasty. Cumulative rates of survival of 9200 total knee arthroplasties.

Abstract: From 1971 through 1987, 9200 total knee arthroplasties were performed at the Mayo Clinic. Actuarial analysis was used to estimate cumulative rates of survival. Use of a proportional-hazard, general linear model led to the identification of four independent variables that were associated with a significantly lower risk of failure: primary total knee arthroplasty, a diagnosis of rheumatoid arthritis, an age of sixty years or more, and use of a condylar prosthesis with a metal-backed tibial component. When all four of these favorable variables were present (without regard for radiographic changes and non-disabling symptoms), the probability of an implant being in situ was 97 per cent at both five and ten years.

Functional ranges of motion of the wrist joint

Abstract: We have examined 40 normal subjects (20 men and 20 women) to determine the ideal range of motion required to perform activities of daily living. The amount of wrist flexion and extension, as well as radial and ulnar deviation, was measured simultaneously by means of a biaxial wrist electrogoniometer. The entire battery of evaluated tasks could be achieved with 60 degrees of extension, 54 degrees of flexion, 40 degrees of ulnar deviation, and 17 degrees of radial deviation, which reflects the maximum wrist motion required for daily activities. The majority of the hand placement and range of motion tasks that were studied in this project could be accomplished with 70 percent of the maximal range of wrist motion. This converts to 40 degrees each of wrist flexion and extension, and 40 degrees of combined radial-ulnar deviation. This study provides normal standards for the functional range of motion of the wrist.

Gastric Adenocarcinoma and Helicobacter pylori Infection

Abstract: Helicobacter pylori infection, thought to be causally related to chronic gastritis, may also be associated with an increased risk of gastric cancer. To determine whether an association with gastric cancer does exist, we retrospectively evaluated serum samples from 69 patients with histologically confirmed gastric adenocarcinoma (32 with cancer at the cardia and 37 with cancer at other sites) and from 218 patients with one of three categories of nongastric cancers, with other gastric cancers, or with benign gastric neoplasms. These samples were compared with samples from 252 cancer-free control subjects, a group comprising 76 asymptomatic volunteers and 176 persons with nonmalignant disorders. Serum samples collected from cancer patients prior to surgery and from cancer-free controls were tested for antibodies to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The risk of H. pylori infection in the case patients relative to the control subjects was estimated with the use of multivariate logistic regression analysis to adjust for potential confounding variables. Antibodies to H. pylori were detected in 65% of the patients with noncardia gastric cancer but in only 38% of the patients with gastric cancer located at the cardia. A significant association was found between H. pylori infection and noncardia gastric cancer (odds ratio = 2.67; 99% confidence interval = 1.01-7.06). Within the subset of patients with noncardia gastric cancer, a statistically nonsignificant tendency existed for those with the intestinal versus the diffuse histologic type of noncardia gastric cancer to have a higher risk of H. pylori infection. Our results support the hypothesis of a relationship between H. pylori infection and the development of noncardia gastric adenocarcinoma.

Avian osteoclasts as estrogen target cells.

Abstract: Although in vivo effects of 17 beta-estradiol (estrogen) on bone turnover have been shown to occur mainly through influences on osteoclast-mediated bone resorption, the mechanism by which estrogen reduces bone resorption is unclear. To approach this question, we have examined authentic osteoclasts for evidence of a direct osteoclast response to estrogen in vitro. Highly purified (greater than (90%) viable avian osteoclasts from birds maintained on a low calcium diet were obtained using an osteoclast-specific monoclonal antibody coupled to magnetic beads. Isolated cells were either analyzed directly for estrogen receptor (ER) levels or cultured to assess the biological effects of estrogen. Northern blot analysis revealed a 5.2-kilobase mRNA that hybridized with a cDNA to human ER mRNA in the osteoclasts. An anti-human ER antibody recognized proteins of 66 kDa and 140 kDa in osteoclast extracts by Western blot analysis. The 66-kDa size is in close agreement with the reported size of the human ER. Nuclear binding of estrogen to intact viable osteoclasts was steroid-specific and saturable, with 5662 +/- 1420 molecules bound per nucleus (mean +/- SEM). In vitro estrogen responses in osteoclasts included a dose-dependent decrease in resorption as well as an increase in nuclear protooncogene mRNA levels. These observations indicate that osteoclasts are capable of directly responding to estrogen in vivo.

Cholangiocarcinoma complicating primary sclerosing cholangitis.

Abstract: Cholangiocarcinoma is more likely to develop in patients with primary sclerosing cholangitis. Our aims were to describe the clinical presentation, course, and management of patients afflicted with both cholangiocarcinoma and primary sclerosing cholangitis and to estimate the prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis. A retrospective analysis was conducted of 30 patients with both primary sclerosing cholangitis and cholangiocarcinoma managed at our institution during an 8-year period. Development of cholangiocarcinoma was heralded by rapid clinical deterioration with jaundice, weight loss, and abdominal discomfort. Cholangiocarcinoma complicating primary sclerosing cholangitis often was detected at an advanced tumor stage, which precluded effective therapy, and overall median survival was 5 months. Earlier recognition and treatment of cholangiocarcinoma in such patients will be necessary to increase survival rates. Seventy patients with primary sclerosing cholangitis were followed prospectively in a clinical trial of medical therapy for an average of 30 months. Twelve patients died and five were found at autopsy to have cholangiocarcinoma. The potential for cholangiocarcinoma to develop in patients with primary sclerosing cholangitis may indicate that liver transplantation should be considered earlier in the course of the disease.

Emboli in Infective Endocarditis: The Prognostic Value of Echocardiography

Abstract: Objective: To determine whether vegetations visualized on two-dimensional echocardiography are an independent risk factor for the development of subsequent emboli in patients with infective endocar...

Screening for lung cancer. A critique of the Mayo Lung Project.

Abstract: The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.

Flow of aqueous humor in humans [The Friedenwald Lecture].

Abstract: Based on clinical experiments with fluorophotometry, several observations can be made about aqueous flow through the chambers of the human eye. 1. The rate of flow is 2.75 +/- 0.63 microliters/min in normal subjects, as derived from measurements averaged during normal office hours. The normal range (95%) is 1.8 to 4.3 microliters/min. 2. There is a circadian rhythm of flow, with the highest rates during morning hours, slightly lower rates during afternoon hours, and rates during sleep that are approximately one half of those during the morning. The hormonal basis for this rhythm is unknown, but it is known to be present in both eyes of persons with unilateral Horner's syndrome. 3. A slight decline of the rate occurs after age 10 yr--3.2% per decade. There is no significant difference in aqueous flow between men and women. 4. Of the hundreds of drugs that are used clinically, most are unlikely to have a significant effect on aqueous flow. Exceptions are the beta-adrenergic agonists that, under certain circumstances, are able to increase flow, the corticosteroids that may have a stimulating effect on flow, and three classes of drugs that have therapeutically useful suppressing effects on flow: carbonic-anhydrase inhibitors, beta-adrenergic antagonists, and alpha 2-selective adrenergic agonists. 5. Timolol, which has a remarkably consistent suppressing effect on flow during the day, has no effect on the flow of sleeping subjects. By contrast, acetazolamide and apraclonidine are able to reduce the flow of sleeping subjects. 6. Acute doses of beta-adrenergic antagonists and alpha 2-agonists are not additive, but beta-adrenergic antagonists and carbonic-anhydrase inhibitors are partly additive. 7. The eye adapts partly to the chronic use of timolol and recovers from its effects when it is discontinued. 8. The rate of disappearance of the effect of beta-adrenergic antagonists is longer for the noncardioselective agents, such as timolol and levobunolol, but is relatively short for the cardioselective agent, betaxolol. 9. The rate of aqueous flow is insensitive to moderate changes of intraocular pressure. Clinical studies can provide suggestive leads for more basic investigations or test specific hypotheses. Biochemical, biologic, and pharmacologic approaches in simpler, more controlled experimental conditions are necessary to determine the fundamental processes that bring about aqueous formation in the living eye. The combination of many disciplines (eg, studying molecules, cells, tissues, organs, and the intact living system) has the best chance of furthering our understanding of the aqueous circulation.

Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice.

Abstract: Borrelia burgdorferi dissemination to selected target organs was examined on days 1, 2, 3, 4, 7, 10, 15, 21, and 30 after intradermal inoculation of 4-week-old C3H mice. Infection was determined by culture (blood, spleen, kidney, ear punch); polymerase chain reaction (PCR) for outer surface protein A (OSP A) DNA (ear punch); histology and spirochete histochemistry (spleen, kidney, skin, heart, joints); and OSP A DNA in situ hybridization (joints, heart). Blood or spleen of most mice were culture positive by day 3 and ear punch by day 10. Polymerase chain reaction performed on ear punches was also positive by day 10. Inflammation of joints and tendons began on days 4 through 7 and heart on days 7 through 10, which coincided with colonization of tissues with spirochetes. Spirochetes were multifocal in distribution, with a predilection for collagenous connective tissue of joints, heart, arteries, nerves, muscle, skin, and other tissues. Relative numbers of spirochetes peaked at 15 days, then decreased by 21 days. Gamma M immunoglobulin (IgM) antibody was detectable on immunoblots as early as day 4, with subsequent declining reactivity, and IgG antibody was detectable by day 7, with expanding reactivity to multiple antigens through day 30.

Granulocyte/macrophage colony-stimulating factor and interleukin 3 release from human peripheral blood eosinophils and neutrophils.

Abstract: Human peripheral blood eosinophils released eosinophil survival-enhancing activity when stimulated with the calcium ionophore, ionomycin. The release of activity was detected as early as 3 h after stimulation and was inhibited by an immunomodulating agent, cyclosporin A. The survival-enhancing activity was completely abolished by treatment with anti-interleukin 3 (IL-3) and anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) monoclonal antibodies. Moreover, IL-3 and GM-CSF were measurable in ionomycin-stimulated eosinophil supernatants by immunoassay. Eosinophils produced approximately one-half as much IL-3 and one-fifth as much GM-CSF as ionomycin-stimulated mononuclear cells. Neutrophils also produced IL-3 and GM-CSF, but the amounts were less than those produced by eosinophils. These observations suggest a novel role for eosinophils in pathophysiology of allergic inflammation and host defense mechanisms.