tbuckley/cabot-search huggingface dataset:
Subclinical vasculitis in polymyalgia rheumatica
Authors: H Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2001)

Polymyalgia rheumatica (PMR) is an inflammatory condition of the aging population characterised by pain, stiffness, and symmetrical involvement of shoulder and pelvic girdles. It has been proposed that the primary site of disease may reside outside the synovial joint,1 2 but its aetiopathogenesis remains ill understood. There is good indirect evidence that vasculitis is important in the pathogenesis of PMR, based on observations from the closely related disease, giant cell arteritis (GCA).3 Many patients with GCA have PMR-like symptoms and the converse is also true. One of the characteristics of PMR is its dramatic response to moderate doses of corticosteroid treatment. However, a subset of patients responds inadequately to treatment or has difficulty with dose reduction, the basis for which is not well defined. We report here the case of a patient with PMR which was difficult to treat who was found to have underlying vasculitis on magnetic resonance imaging (MRI), a finding which explains the requirement for the …
Milia occurring in lichen sclerosus et atrophicus
Authors: BARBARA LEPPARD, I.B. SNEDDON
Journal: British Journal of Dermatology (1975)

Large numbers of milia were seen in areas of skin affected with bullae in a 68-year-old woman who had extensive lichen sclerosus et atrophicus. Although milia are frequently seen in other sub-epidermal bullous disorders, they have not previously been reported in lichen sclerosus et atrophicus.
UNRECOGNIZED CASES OF CONGENITAL SYPHILIS
Authors: STUART V. GOLDHURST
Journal: British Journal of Dermatology (1927)

Journal Article UNRECOGNIZED CASES OF CONGENITAL SYPHILIS Get access STUART V. GOLDHURST, M.R.C.S., L.R.C.P. STUART V. GOLDHURST, M.R.C.S., L.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 39, Issue 2, 1 February 1927, Pages 66–69, https://doi.org/10.1111/j.1365-2133.1927.tb10049.x Published: 01 February 1927
Thoracoscopy: general overview and place in the diagnosis and management of pleural effusion
Authors: F. Rodriguez-Panadero, J. P. Janssen, P. Astoul
Journal: European Respiratory Journal (2006)

Norepinephrine (NE) was released from perfused spleens either by nerve stimulation or injection of potassium in phenoxybenzamine-treated and normal cats. Krebs-bicarbonate solution was perfused at a rate of about 7 ml/min at 35°C. Perfusion of the phenoxybenzamine-treated spleens with 2.5 mM Mn<sup>++</sup> Krebs9 solution reduced the NE outputs to low levels. Perfusion of the normal spleens, pre-exposed to H<sup>3</sup>-NE infusion, with 0.8, 2.5 or 5 mM Mn<sup>++</sup> Krebs9 solution also significantly reduced the net increases in radioactivity, H<sup>3</sup>-NE and NE by nerve stimulation. Increasing the Ca<sup>++</sup> concentration to 10 mM did not significantly alter the inhibitory effect of Mn<sup>++</sup>. Mn<sup>++</sup> also blocked the spontaneous release of radioactivity from spleen. It is concluded that Mn<sup>++</sup> acts as a potent inhibitor of NE release and blocks both the nerve-induced and spontaneous release of NE.
Gender Differences in Incidence and Age at Onset of Mania and Bipolar Disorder Over a 35-Year Period in Camberwell, England
Authors: Noel Kennedy, Jane Boydell, Sri Kalidindi, Paul Fearon, Peter B. Jones, Jim van Os, Robin M. Murray
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Despite clear gender differences in the symptoms and course of bipolar affective disorder, studies investigating age at onset by gender have yielded inconsistent results. The authors investigated gender differences in age at onset and incidence of first-episode mania and bipolar disorder in an epidemiological catchment area in southeast London over a 35-year period. METHOD: All adult cases of first-episode psychosis, mania, or hypomania presenting to services in Camberwell, southeast London (1965–1999), were identified. Computerized diagnoses for these cases were generated by using the Operational Checklist for Psychotic Disorders program. Incidence rates and rate ratios of DSM-IV bipolar I disorder, first manic episode, by gender and age (10-year age-at-onset categories) were calculated. Differences in age at onset of first-episode mania and bipolar disorder by gender were examined by using univariate and multivariate analyses. RESULTS: Men had a significantly earlier onset of first-episode mania and bipolar disorder, with childhood antisocial behavior also being significantly associated, after multivariate analysis. Women had higher incidence rates of bipolar I disorder throughout adult life, except for early life (ages 16–25 years), although gender differences in individual age bands did not reach statistical significance. CONCLUSIONS: Men appear to have an earlier onset of mania and bipolar disorder than women. The association of male gender and childhood antisocial behavior with early-onset bipolar disorder raised the possibility of the existence of an early-onset subgroup.
Changes In PSA Kinetics After DNA Vaccine Therapy–Not So Fast!
Authors: Matthew R. Smith, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: In the September 1, 2009, issue of Journal of Clinical Oncology, McNeel et al reported the results of a phase I clinical trial of a DNA vaccine encoding prostatic acid phosphatase in men with nonmetastatic prostate cancer. They reported that nine of 22 (41%) participants developed prostatic acid phosphatase–specific T cell proliferation and seven of 22 (32%) had a post-treatment prostatespecific antigen doubling time (PSA DT) of greater than 200% of the baseline PSA DT. They offer the observed T cell responses and increased PSA DT as evidence of biologic activity and recommend a multi-institutional phase II trial to evaluate clinical efficacy. Although the observed T cell responses are compelling, the changes in PSA DT after vaccine treatment are similar to outcomes previously reported in placebo-treated participants. In two randomized controlled trials of men with rising PSA after prior surgery or radiation therapy for prostate cancer, post-treatment PSA DT of greater than 200% of the baseline PSA DT was observed in 20% to 31% of the participants assigned to placebo. The observed rates of positive PSA outcomes after placebo treatment appear to be explained primarily by variation in serial assessment of PSA DT. We conclude that the post-treatment changes in PSA DT after vaccine treatment do not provide evidence of biologic activity. Additional studies are necessary to assess the relationship between PSA kinetics and clinical outcomes and to evaluate the utility of post-treatment PSA DT or PSA velocity in the development of new drugs.
Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide.
Authors: K Donaldson, R E Bolton, A Jones, G M Brown, M D Robertson, J Slight, H Cowie, J M Davis
Journal: Thorax (1988)

The kinetics of the bronchoalveolar response was assessed in rats exposed, at equal airborne mass concentration (10 mg/m3), to titanium dioxide--a non-pathogenic dust--and the two pathogenic mineral dusts quartz and chrysotile asbestos. Rats were killed at intervals over a 75 day exposure period and groups of rats exposed for 32 and 75 days after recovery for two months. Bronchoalveolar lavage was carried out and the lavage fluid characterised for cellular content, macrophage activation, and concentrations of free total protein, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase. Inhalation exposure to the two pathogenic dusts resulted in an increased number of leucocytes, macrophage activation, and increased levels of free enzymes and total protein. The pattern and magnitude of the responses to quartz and chrysotile differed. Chrysotile caused less inflammation than quartz, and the main cellular response peaked around the middle of the period of dust exposure whereas the highest levels of enzymes occurred towards the end. The difference in timing suggests that macrophages were not available for lavage towards the end of the exposure, owing to their playing a part possibly in deposition of granulation tissue. Quartz caused a greater cellular and enzyme response than chrysotile, particularly towards the end of the dust exposure phase. There was a noticeable progression of inflammation in the quartz exposed groups left to recover for two months, but not in the chrysotile recovery groups.
Human eosinophil major basic protein induces airway constriction and airway hyperresponsiveness in primates.
Authors: R H Gundel, L G Letts, G J Gleich
Journal: Journal of Clinical Investigation (1991)

We have examined the effects of direct intratracheal instillation of purified eosinophil granule proteins on pulmonary function and airway responsiveness in primates. The results of this study show for the first time that installation of major basic protein (MBP) directly into the trachea of primates results in a significant and dose-related increase in airway responsiveness to inhaled methacholine. Furthermore, MBP and eosinophil peroxidase (EPO) induce a transient bronchoconstriction immediately after instillation that resolves by 1 h postinstillation. In contrast, instillation of other eosinophil granule proteins had no effect on airway responsiveness or pulmonary function. These data indicate a direct role of the eosinophil in the pathogenesis of airway hyperresponsiveness. We suggest that the MBP of human eosinophils has an effector role in the pathogenesis of airway hyperresponsiveness which may involve active interaction with resident airway tissue cells. MBP may also mediate altered lung function in various inflammatory lung diseases associated with pulmonary eosinophilia.
Myocardial transport of hexakis(2-methoxyisobutylisonitrile) and thallium before and after coronary reperfusion.
Authors: D J Meerdink, J A Leppo
Journal: Circulation Research (1990)

Effects of no-flow ischemia (NFI) and reperfusion (RPF) on myocardial extraction and retention of technetium-99m hexakis(2-methoxyisobutylisonitrile) (sestamibi) and thallium-201 were investigated in 12 isolated, blood-perfused rabbit hearts with isotope dilution studies at constant coronary perfusion. After a control injection of tracers, NFI was induced for 30-60 minutes. After coronary reflow, repeat tracer injections were given at early RPF (5-15 minutes of RPF) and late RPF (40-60 minutes of RPF). After NFI-RPF, maximal fractional extraction and capillary permeability-surface area product increased for sestamibi (from +39% to 69%) and decreased for thallium (from -14% to -68%). Net extraction was 33% lower for sestamibi than for thallium at control, 13% lower at early RPF, and 90% higher than thallium at late RPF. Interstitial-myocyte exchange estimates were always higher for sestamibi than for thallium and increased for both with NFI-RPF (sestamibi, from 57.4 to 122.4 ml/min/g; thallium, from 3.1 to 22.3 ml/min/g). Intramyocyte volumes of distribution were higher for sestamibi than for thallium (greater than 200% at control, 800-1,000% with RPF), and NFI-RPF had opposite effects on the two tracers (late RPF vs. control: +28% for sestamibi, -50% for thallium). Our results suggest that sestamibi and thallium have different transport or sequestering mechanisms and that NFI-RPF had opposite effects on myocardial capillary-tissue exchange and tissue retention of sestamibi and thallium. Therefore, myocardial perfusion might be overestimated with sestamibi and underestimated with thallium during early RPF.
High response rate to additive-free diet in chronic urticaria
Authors: T. Zuberbier, B. M. Czarnetzki
Journal: British Journal of Dermatology (1996)

Journal Article High response rate to additive‐free diet in chronic urticaria Get access T. Zuberbier, T. Zuberbier Hautklinik, Hautpoliklinik und Asthmapoliklinik Virdww‐Klinikum, Augustenhurger Platz 1, 13353 Berlin Germany Search for other works by this author on: Oxford Academic Google Scholar B. M. Czarnetzki B. M. Czarnetzki Hautklinik, Hautpoliklinik und Asthmapoliklinik Virdww‐Klinikum, Augustenhurger Platz 1, 13353 Berlin Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 6, 1 June 1996, Page 1159, https://doi.org/10.1111/j.1365-2133.1996.tb07971.x Published: 01 June 1996
INCOMPLETE SIMIAN PAPOVAVIRUS SV40
Authors: Joseph L. Melnick, Sara E. Stinebaugh, Fred Rapp
Journal: The Journal of Experimental Medicine (1964)

A study was made of the effects of 5-fluorouracil (FU) and 5-fluorodeoxyuridine (FUDR) on the replication of the simian papovavirus SV40 in cercopithecus monkey kidney cells and on the production of virus antigen by these cells. Both drugs markedly suppressed the production of new infectious virus by SV40-infected cells. Synthesis of viral protein was also markedly suppressed by FUDR, but not by FU. In the presence of FU, infected cells produced large amounts of viral protein which were detected by the fluorescent antibody technique. The antigen was not distributed in a particulate fashion as in untreated cells. Diffuse virus antigen was observed in the nuclei of FU-treated cells, resembling the distribution of antigen near the end of the eclipse period in untreated, infected cultures. This stage of antigen production presumably preceded viral assembly. Virus particles with or without cores were rarely seen with the electron microscope in infected FU-treated cells, although large numbers of SV40 particles were readily visualized in untreated, infected cells. It appears that at least one antigenic protein of this papovavirus is synthesized abundantly in FU-treated cells, but is not assembled into virus shells in the presence of the inhibitor.
Phase I Study of Oxaliplatin, Full-Dose Gemcitabine, and Concurrent Radiation Therapy in Pancreatic Cancer
Authors: Sameer P. Desai, Edgar Ben-Josef, Daniel P. Normolle, Isaac R. Francis, Joel K. Greenson, Diane M. Simeone, Alfred E. Chang, Lisa M. Colletti, Theodore S. Lawrence, Mark M. Zalupski
Journal: Journal of Clinical Oncology (2007)

To determine a biweekly dose of oxaliplatin for combination with full-dose gemcitabine and concurrent radiation therapy (RT) in pancreatic cancer.Patients with previously untreated pancreatic cancer received gemcitabine days 1, 8, and 15, and oxaliplatin days 1 and 15, repeated at 28-day intervals. RT (27 Gy in 1.8-Gy fractions) was administered during cycle 1. Dose escalation was guided using the time-to-event continuous reassessment method. Dose levels 1 to 4 included gemcitabine 1 g/m2 intravenously (IV) during 30 minutes and oxaliplatin 40, 55, 70, or 85 mg/m2 IV during 90 minutes, respectively; for dose levels 5 and 6, oxaliplatin dose remained 85 mg/m2 but infusion time for gemcitabine 1 g/m2 was increased to 65 or 100 minutes, respectively. The trial objective was to determine the dose level associated with dose-limiting toxicity (DLT) through cycle 2 in < or = 20% of patients.Forty-four patients were enrolled (median age, 64 years; 27 men, 17 women) with resectable (n = 12), unresectable (n = 29), and metastatic (n = 3) pancreatic cancer. Ten DLTs occurred in nine patients, including grade 4 platelets (n = 4), decline in performance status (n = 2), GI bleeding (n = 2), and GI toxicity (n = 2). The estimated probability of DLT for dose level 3 was .21 (90% posterior probability interval [PI], .12 to .33); for dose level 4, the estimated probability was .24 (90% PI, .14 to .36).The addition of oxaliplatin 85 mg/m2 days 1 and 15 to full-dose gemcitabine and radiation therapy was well tolerated. On the basis of these results, a multi-institutional neoadjuvant phase II study in resectable pancreatic cancer is planned.
Methodological Challenges in Injury Epidemiology and Injury Prevention Research
Authors: P Cummings, T D Koepsell, B A Mueller
Journal: Annual Review of Public Health (1995)

In the past decade there has been increasing attention to the public health importance of injuries. Public health agencies seeking to reduce injuries need methods for counting injuries, calculating injury rates, identifying the causes of injuries, and measuring outcomes of interventions. All of these areas present problems for injury epidemiologists and injury prevention programs. This paper provides a framework for classifying these problems into five categories: (a) numerator problems; (b) denominator problems; (c) causation; (d) exposure measurement problems; and (e) multiplicity. For most problems, we identify proven or potential solutions, using examples from the literature of injury epidemiology.
Ultrasound Measurement of Arm and Leg Blood Pressures
Authors: W. Robert Felix
Journal: JAMA (1973)

Arm and leg systolic and diastolic blood pressures were measured using a Doppler ultrasound technique in fifty-seven healthy male patients. The average upper limb supine blood pressure was 130/80 mm Hg. The average leg systolic pressure was 6.8 mm Hg higher than the average arm systolic pressure. The average diastolic pressure in the leg was 2.1 mm Hg higher than the average arm diastolic pressure. Agreement between pressures in opposite limbs was better than that obtained with the Korotkoff sound method. The only important difference was between supine and erect arm diastolic pressures. Electrocardiographic abnormalities were noted in six subjects; all had mild to moderate hypertension, but no overt cardiovascular disease.
How do mutations in lamins A and C cause disease?
Authors: Howard J. Worman, Jean-Claude Courvalin
Journal: Journal of Clinical Investigation (2004)

Mutations in lamins A and C, nuclear intermediate-filament proteins in nearly all somatic cells, cause a variety of diseases that primarily affect striated muscle, adipocytes, or peripheral nerves or cause features of premature aging. Two new studies use lamin A/C–deficient mice, which develop striated muscle disease, as a model to investigate pathogenic mechanisms. These reports provide evidence for a stepwise process in which mechanically stressed cells first develop chromatin and nuclear envelope damage and then develop secondary alterations in the transcriptional activation of genes in adaptive and protective pathways.
Charities demand urgent steps to prevent another Mid Staffordshire scandal
Authors: A. O'Dowd
Journal: BMJ (2012)

A coalition of 150 health and social care charities has called for urgent action to prevent another scandal like that at Mid Staffordshire NHS Foundation Trust from happening.

The coalition, National Voices, published a report on 15 October to coincide with the planned publication date of Robert Francis QC’s second report into failures at the trust.1 That report has now been delayed until January next year.

The whole process of investigation and inquiry into the trust had taken too long, and NHS planners were continuing to “wait for further instructions” when they should have been taking steps to improve the safety and care of patients, said the charities. These …
A Novel Chromogranin-A Promoter-Driven Oncolytic Adenovirus for Midgut Carcinoid Therapy
Authors: Justyna Leja, Helena Dzojic, Elisabet Gustafson, Kjell Öberg, Valeria Giandomenico, Magnus Essand
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The use of replication-selective oncolytic adenoviruses is an emerging therapeutic approach for cancer, which thus far has not been employed for carcinoids. We therefore constructed Ad[CgA-E1A], a novel replication-selective oncolytic adenovirus, where the chromogranin A (CgA) promoter controls expression of the adenoviral E1A gene. Experimental Design: The Ad[CgA-E1A] virus was evaluated for E1A protein expression, replication ability, and cytolytic activity in various cell lines. It was also evaluated for treatment of xenografted human carcinoid tumors in nude mice. To use Ad[CgA-E1A] for the treatment of carcinoid liver metastases, it is important that normal hepatocytes do not support virus replication to minimize hepatotoxicity. We therefore evaluated CgA protein expression in normal hepatocytes. We also evaluated CgA gene expression in normal hepatocytes and microdissected tumor cells from carcinoid metastases. Results: We found that Ad[CgA-E1A] replicates similarly to wild-type virus in tumor cells with neuroendocrine features, including the BON carcinoid cell line and the SH-SY-5Y neuroblastoma cell lines, whereas it is attenuated in other cell types. Thus, cells where the CgA promoter is active are selectively killed. We also found that Ad[CgA-E1A] is able to suppress fast-growing human BON carcinoid tumors in nude mice. Furthermore, CgA is highly expressed in microdissected cells from carcinoid metastases, whereas it is not expressed in normal hepatocytes. Conclusion: Ad[CgA-E1A] is an interesting agent for the treatment of carcinoid liver metastases in conjunction with standard therapy for these malignancies.
Observer variation in the diagnosis of superficial oesophageal adenocarcinoma
Authors: A H Ormsby
Journal: Gut (2002)

<b>Background and aims:</b> When to perform oesophagectomy for neoplastic progression in Barrett’s oesophagus is controversial. Some resect for high grade dysplasia whereas others defer treatment until intramucosal adenocarcinoma is diagnosed. Interobserver agreement for a diagnosis of high grade dysplasia or intramucosal adenocarcinoma remains unknown and may have therapeutic implications. <b>Methods:</b> Histological slides from 75 oesophagectomy specimens with high grade dysplasia or T<sub>1</sub> adenocarcinoma were blindly reviewed by two gastrointestinal pathologists and one general surgical pathologist, and classified as high grade dysplasia, intramucosal adenocarcinoma, or submucosal adenocarcinoma. A subsequent re-review of all 75 cases by the same observers following establishment of uniform histological criteria was undertaken. Interobserver agreement was determined by kappa statistics. Coefficients &lt;0.21, 0.21–0.40, 0.41–0.60, 0.61–0.80, and &gt;0.80 were considered poor, fair, moderate, good, and very good agreement, respectively. <b>Results:</b> Interobserver agreement among all pathologists and between gastrointestinal pathologists when comparing high grade dysplasia with intramucosal adenocarcinoma was only fair (k=0.42; 0.56, respectively) and did not substantially improve on subsequent re-evaluation following establishment of uniform histological criteria (K=0.50; 0.61, respectively). <b>Conclusions:</b> When evaluating resection specimens and after implementation of uniform histological criteria, even experienced gastrointestinal pathologists frequently disagree on a diagnosis of high grade dysplasia versus intramucosal adenocarcinoma. Treatment strategies based on the histological distinction of high grade dysplasia from intramucosal adenocarcinoma using limited biopsy specimens should be re-evaluated.