tbuckley/cabot-search huggingface dataset:
Overuse of Albumin
Authors: A. Gerson Hollander
Journal: JAMA (1980)

To the Editor.—  The article, Therapeutic Use of Albumin, by Alexander et al (241:2527, 1979), emphasizes the need to control cost by physician education. The authors are to be complimented for the thoroughly detailed method they used. However, their study required a considerable investment of time and personnel before effecting a saving.  I would like to share the method I used as chief of staff at the Boston Veterans Administration Hospital many years ago when faced with a similar situation.  The wards were requesting serum albumin on a pharmacy order form. These ampules were then dispensed by physician order. The drug bill for the hospital was increasing by $25,000 a month before it was brought to my attention. A program was initiated immediately whereby the physician wrote a prescription for the individual patient, stating the diagnosis and the number of ampules required. This prescription had to be countersigned by the
Effects of the molecular weight of hyaluronic acid and its action mechanisms on experimental joint pain in rats.
Authors: S Gotoh, J Onaya, M Abe, K Miyazaki, A Hamai, K Horie, K Tokuyasu
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--It has been shown previously that hyaluronic acid (HA) has an analgesic action on bradykinin induced pain in the knee joints of rats. This study further clarifies the effects of the molecular weight of HA and its mechanism of action in the same model using HA of molecular weight 800 to 2.3 x 10(6) daltons and a bradykinin antagonist. METHODS--Bradykinin and the test HA preparations were given to rats by intra-articular injection, and the severity of pain was evaluated by a change in the walking behaviour. RESULTS--HA with a molecular weight greater than 40 kilodaltons produces analgesic effects with a simultaneous or earlier injection. The ID50 values of HA with molecular weight 40, 310, 860, and 2300 kilodaltons were greater than 2.5, 0.6, 0.07, and 0.06 mg/joint respectively. The duration of the analgesic effect of 860 and 2300 kilodalton HA was 72 hours at 10 mg/ml, whereas that of 310 kilodalton HA was short, being undetectable after 24 hours. The analgesic action of HA of 860 kilodaltons was not changed by pretreatment with four saccharide HA and inhibited by pretreatment with HA larger than six to eight saccharides, capable of binding to HA receptors. Further, HA did not interfere with the analgesic action of the bradykinin antagonist, indicating that HA does not directly bind with bradykinin receptors. CONCLUSIONS--HA with a molecular weight of greater than 40 kilodaltons produced an analgesic effect, and HA of 860 and 2300 kilodaltons produced high and long-lasting analgesia. These effects of HA appear to be caused by the interaction between HA and HA receptors.
Precipitating antibodies against pigeon bloom antigens as a specific and sensitive measure of pigeon exposure
Authors: H. C. Siersted, N‐C. G. Hansen
Journal: Allergy (1990)

Precipitating antibodies against pigeon bloom antigen and pigeon serum were evaluated as a measure of pigeon exposure in 62 male pigeon breeders compared with 40 unexposed control subjects. We found a combination of highly antigenic bloom extract and a sensitive counter current immunoelectrophoresis suitable for clinical estimation of pigeon exposure. The sensitivity of the test was 86% in never‐smokers and 73% in smokers at the 98% specificity level. Smoking significantly reduced the humoral immune response to both antigens.
Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma
Authors: Chung-Che Chang, Xiaobo Zhou, Jesalyn J Taylor, Wan-Ting Huang, Xianwen Ren, Federico Monzon, Yongdong Feng, Pulivarthi H Rao, Xin-Yan Lu, Facchetti Fabio, Susan Hilsenbeck, Chad J Creighton, Elaine S Jaffe, Ching-Ching Lau
Journal: Journal of Hematology & Oncology (2009)

Plasmablastic lymphoma (PL) is a subtype of diffuse large B-cell lymphoma (DLBCL). Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM). The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related) and PCM using array-based comparative genomic hybridization. Examination of genomic data in PL revealed that the most frequent segmental gain (> 40%) include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related) cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation. To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related) than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.
PMO-138 The molecular mechanisms of B cell and B cell lymphoma recruitment to the human liver
Authors: S Shetty, T Bruns, C Weston, Z Stamataki, Y Oo, S Hubscher, S Jalkanen, P Lalor, D H Adams
Journal: Gut (2012)

<h3>Introduction</h3> There is gathering interest in the presence of B cells within liver tissue and their contribution to chronic inflammation and fibrosis but the recruitment signals for B cells into peripheral tissue is poorly understood. In addition a large proportion of lymphomas which infiltrate the liver are of B cell origin but again little is understood of the mechanism that underlies this process. Lymphocyte recruitment to the liver occurs within the hepatic sinusoidal channels. These low shear vascular beds are lined by specialised hepatic sinusoidal endothelial cells (HSEC). Our aim was to understand the molecular mechanisms of B cell and B cell lymphoma recruitment to the liver. <h3>Methods</h3> We used isolated human HSEC in flow assays with purified peripheral blood B cells to elucidate the molecular mechanisms of B cell recruitment via HSEC. The contribution of conventional adhesion molecules, ICAM-1 and VCAM-1 and unconventional molecules VAP-1 and CLEVER-1/stabilin-1 was assessed by using function blocking antibodies. We repeated our experiments with two B cell lymphoma cell lines, CRL-2261 and Karpas B cell line. We assessed the contribution of chemokines by performing transwell assays and adding chemokines to our flow assays. We also tracked the motility of B cells and lymphoma cell lines on HSEC using tracking software. <h3>Results</h3> B cells were captured from flow and firmly adhered to HSEC, the primary adhesion receptor on HSEC was VCAM-1. B cells also underwent transendothelial migration which was mediated by a combination of ICAM-1, VAP-1 and CLEVER-1/stabilin-1. Lymphoma cell line recruitment shared several features of primary lymphocyte homing, firm adhesion was mediated by ICAM-1 and VCAM-1 and they demonstrated shape-change and crawling behaviour which was ICAM-1 dependent. The lymphoma cell lines did not undergo transendothelial migration and this could not be initiated with the addition of SDF-1α. <h3>Conclusion</h3> There is increasing evidence that B cells play an important role in chronic inflammatory liver diseases. The recruitment signals we have identified for B cells in this study may provide potential therapeutic targets for liver disease. Furthermore we have demonstrated preserved lymphocyte homing mechanisms in malignantly transformed B cells. These properties could be therapeutic targets to prevent lymphoma dissemination to the liver. <h3>Competing interests</h3> None declared.
LOXL2-Mediated Matrix Remodeling in Metastasis and Mammary Gland Involution
Authors: Holly E. Barker, Joan Chang, Thomas R. Cox, Georgina Lang, Demelza Bird, Monica Nicolau, Holly R. Evans, Alison Gartland, Janine T. Erler
Journal: Cancer Research (2011)

Abstract More than 90% of cancer patient mortality is attributed to metastasis. In this study, we investigated a role for the lysyl oxidase-related enzyme lysyl oxidase-like 2 (LOXL2) in breast cancer metastasis, in both patient samples and in vivo models. Analysis of a published microarray data set revealed that LOXL2 expression is correlated with metastasis and decreased survival in patients with aggressive breast cancer. In immunocompetent or immunocompromised orthotopic and transgenic breast cancer models we showed that genetic, chemical or antibody-mediated inhibition of LOXL2 resulted in decreased metastasis. Mechanistic investigations revealed that LOXL2 promotes invasion by regulating the expression and activity of the extracellular proteins tissue inhibitor of metalloproteinase-1 (TIMP1) and matrix metalloproteinase-9 (MMP9). We found that LOXL2, TIMP1, and MMP9 are coexpressed during mammary gland involution, suggesting they function together in glandular remodeling after weaning. Finally, we found that LOXL2 is highly expressed in the basal/myoepithelial mammary cell lineage, like many other genes that are upregulated in basal-like breast cancers. Our findings highlight the importance of LOXL2 in breast cancer progression and support the development of anti-LOXL2 therapeutics for the treatment of metastatic breast cancer. Cancer Res; 71(5); 1561–72. ©2011 AACR.
Summative assessment for general practitioner registrars
Authors: T S. Murray
Journal: BMJ (1995)

EDITOR,--Linda Beecham's report that general practitioner registrars may withdraw from summative assessments--because of their uncertainty about the validity of the assessment package, the lack of a unified national assessment, poor communication within English regions, and inadequate testing of the assessment package1--suggests to me that these registrars are ill …
Expression, regulation and role of the MAGUK protein SAP-97 in human atrial myocardium
Authors: D Godreau
Journal: Cardiovascular Research (2002)

Objective: In various cell types, membrane-associated guanylate kinases proteins called MAGUK play a major role in the spatial localization and clustering of ion channels. Here, we studied the expression and role of these anchoring proteins in human right atrial myocardium by means of various molecular, biochemical and physiological methods. Methods and results: SAP-97, PSD-95, Chapsyn and SAP-102 messengers were detected by reverse transcriptase–polymerase chain reaction (RT-PCR) on mRNA extracted from both whole myocardium and isolated myocytes. Western blot revealed that the MAGUK protein SAP-97 and, to a lesser extent, PSD-95, is abundantly expressed in human atrial myocardium, while Chapsyn are almost undetectable. Confocal microscopic visualization of cryosection of atrial myocardium stained with the anti-PSD-95 family antibody showed positive staining at the plasma membrane level and cell extremity. Calpain-I cleaved both SAP-97 and PSD-95 proteins, resulting in an accumulation of short bands, including an 80-kDa band that was also detected in the cytosolic protein fraction. Immunoprecipitation of SAP-97 co-precipitated hKv1.5 channels, and vice versa. Co-expression of cloned SAP-97 and hKv1.5 channels in Chinese hamster ovarian (CHO) cells increased the K+ current (157.00±19.45 pA/pF vs. 344.50±58.58 pA/pF at +50 mV). Conclusions: The protein SAP-97 is abundantly expressed in human atrial myocardium in association with hKv1.5 channels, and probably contributes to regulating the functional expression of the latter.
Cerebrospinal fluid M staging for medulloblastoma: Reappraisal of Chang's M staging based on the CSF flow
Authors: J. H. Phi, J. Lee, K.-C. Wang, B.-K. Cho, I.-O. Kim, C.-K. Park, C.-Y. Kim, H. S. Ahn, I. H. Kim, S.-K. Kim
Journal: Neuro-Oncology (2010)

Tumor seeding is a strong negative prognostic factor for patients with medulloblastoma. Because Chang's M staging is based primarily on CT and myelographic findings and might be contradictory to the direction of normal cerebrospinal fluid (CSF) flow, seeding patterns and appropriate staging of medulloblastoma need to be revisited in patients diagnosed in the MRI era. We retrospectively reviewed the clinical and radiological data of 86 patients with a diagnosis of medulloblastoma who were treated in the MRI era. The presence of seeding in each subarachnoid space compartment and the patterns of seeding were analyzed in correlation with patient survival data. Thirty-four patients had gross seeding on perioperative MRI. Thirty-two patients had seeding in the spinal compartment. Sixteen and 12 patients had seeding in the infratentorial and supratentorial compartments, respectively. There was an apparent hierarchy of seeding (ie, from seeding in the spinal compartment up to the supratentorial compartment). Patients with seeding in the spinal compartment had longer progression-free survival (P = .038) and a tendency toward better overall survival (P = .053) compared with patients with seeding in intracranial compartments. We modified Chang's M staging based on the CSF flow and termed this approach "CSF M staging." CSF M staging for medulloblastoma, in which intracranial seeding occupies a higher rank than spinal seeding, was a better predictor of patient prognosis. This modified staging method may be applied to metastatic staging of brain tumors located in the fourth ventricle.
Hypercholesterolemia Stimulates Angiotensin Peptide Synthesis and Contributes to Atherosclerosis Through the AT <sub>1A</sub> Receptor
Authors: Alan Daugherty, Debra L. Rateri, Hong Lu, Tadashi Inagami, Lisa A. Cassis
Journal: Circulation (2004)

Background— Hypercholesterolemia-induced atherosclerosis is attenuated by either pharmacological antagonism of AT 1 receptors or AT 1A receptor deficiency. However, the mechanism underlying the pronounced responses to angiotensin II (Ang II) antagonism has not been determined. We hypothesized that hypercholesterolemia stimulates the production of angiotensin peptides to provide a rationale for the profound effect of AT 1A receptor deficiency on atherogenesis. Methods and Results— Atherosclerotic lesions were analyzed in LDL receptor–deficient mice. Immunocytochemical analysis demonstrated that atherosclerotic lesions contained all the components of the conventional pathway for Ang II synthesis. AT 1A receptor deficiency caused a marked decrease in atherosclerotic lesion size in both the aortic root and arch of male and female mice, without a discernible effect on composition. AT 1A receptor deficiency–induced reductions in atherosclerosis were independent of systolic blood pressure and measurements of oxidation and chemoattractants. Aortic AT 2 receptor mRNA expression was not altered in AT 1A receptor–deficient mice, and AT 2 receptor deficiency had no effect on lesion area or cellular composition. Hypercholesterolemia greatly augmented the systemic renin-angiotensin system, as demonstrated by large increases in plasma concentrations of angiotensinogen and angiotensin peptides (Ang II, III, IV, and 4–8). These increases were ablated in hypercholesterolemic AT 1A receptor–deficient mice. Conclusions— AT 1A receptor deficiency had a striking effect in reducing hypercholesterolemia-induced atherosclerosis in LDL receptor–negative mice. Hypercholesterolemia was associated with increased systemic angiotensinogen and angiotensin peptides, which were reduced in AT 1A receptor–deficient mice. These results demonstrate that hypercholesterolemia-induced stimulation of angiotensin peptide production provides a basis for the marked effect of AT 1A receptor deficiency in reducing atherosclerosis.
Pakistan's doctors protest at killing of 13 colleagues this year
Authors: Z. Khan
Journal: BMJ (2002)

More than 50 prominent Karachi physicians staged a six hour hunger strike last Saturday in protest at the targeted killing of fellow physicians in Karachi and elsewhere in Pakistan. Also, the Pakistan Medical Association, angered by the government's apparently uncaring attitude towards the killings, has now called for a countrywide strike on 8 April.

Doctors here have been calling for adequate security for some time now. This year alone, 13 doctors, most of them belonging to the Shiite sect of Islam, were killed in Karachi, while 270 have been killed …
Monilethrix: a clinicopathological illustration of a cortical defect
Authors: D.A.R. BERKER, D.J.P. FERGUSON, R.P.R. DAWBER
Journal: British Journal of Dermatology (1993)

We describe two sisters aged 2 and 7 years, with monilethrix. The older sister was clinically less severely affected but, microscopically, the features of weathering and alternating nodes and internodes were more obvious. The younger girl had more severe alopecia, with shorter hair, but the microscopic features were less marked. Scanning-electron microscopy demonstrated only slight cuticular weathering in both cases, and evidence of breakage in the cuticle at points of no obvious cuticular pathology. Transmission-electron microscopy showed normal cuticle cells in cross-section, but an abnormal cortex. The abnormalities included areas of homogeneous non-fibrillar material, and a deviated axis of some microfibrils. We consider that these findings support the possibility that a cortical defect contributes significantly to the fragility of hair in moniiethrix. This might explain why hair with marked beading can be stronger than hair from an affected sibling with less apparent abnormality.
The Spectrum of Ocular Alterations in Patients with β-Thalassemia Syndromes Suggests a Pathology Similar to Pseudoxanthoma Elasticum
Authors: Giulio Barteselli, Laura Dell'Arti, Robert P. Finger, Peter Charbel Issa, Alessia Marcon, Diego Vezzola, Chiara Mapelli, Elena Cassinerio, Maria D. Cappellini, Roberto Ratiglia, Francesco Viola
Journal: Ophthalmology (2013)
Splenic Rupture after Vomiting
Authors: M Lemon, M Dorsch, K Street, R Cohen, P Hale
Journal: Journal of the Royal Society of Medicine (2001)

Splenic rupture is usually secondary to trauma. Most non-traumatic ruptures are consequent on underlying disease affecting the spleen such as infection (Epstein-Barr virus, hepatitis, salmonella, malaria), neoplasia (lymphoma, leukaemia) and connective-tissue disease.
Differential activation of alpha 1- and alpha 2-adrenoceptors on microvascular smooth muscle during sympathetic nerve stimulation.
Authors: M Ohyanagi, J E Faber, K Nishigaki
Journal: Circulation Research (1991)

The relative contribution of postjunctional alpha 1- and alpha 2-adrenoceptors to constriction of microvessels was examined during sympathetic nerve stimulation and sympathetic escape (difference between peak and steady-state constriction). Large arterioles (120 +/- 4 microns control diameter) and venules (174 +/- 6 microns) and small arterioles (13 +/- 4 microns) were examined in rat cremaster skeletal muscle during stimulation of the cremaster efferent innervation (decentralized lumbar sympathetic chain, 0.5-16 Hz, 2-minute train). The muscle was suspended in a tissue bath, and diameter was measured with intravital microscopy. Frequency-response curves were obtained after vehicle (prazosin or rauwolscine) was added to the bath. In large arterioles, prazosin (10(-7) M) significantly attenuated constriction by 60-80%; a fivefold higher concentration had no additional effect. In contrast, rauwolscine (1 to 5 x 10(-7) M) had no effect. Venules evidenced minimal response to nerve stimulation. In small arterioles, rauwolscine (5 x 10(-7) M) significantly attenuated constriction by 50-60%, while prazosin (10(-7) M) had no effect. These data suggest that for large arterioles, which are known to possess both receptors, alpha 1-adrenoceptors are preferentially stimulated by nerve-released norepinephrine. In contrast, sympathetic constriction of small arterioles is mediated by alpha 2-adrenoceptors. Compared with large arterioles, small arterioles exhibited greater peak and steady-state constriction at all frequencies, with maximal responses achieved over the 0.5-4 Hz range. Large arterioles exhibit graded constriction over the entire frequency range. Sympathetic escape exhibited a small, negatively correlated frequency dependence for large arterioles, tended to be greater for small arterioles, and was more evident in large arterioles during alpha 2-adrenoceptor constriction at low-frequency stimulation. This distinct neural control of large resistance vessels by alpha 1-adrenoceptors and small terminal arterioles by alpha 2-adrenoceptors may allow neurogenic regulation of these vessel segments to be differentially susceptible to modulation by other extrinsic and intrinsic vasoactive controls that preferentially interact with alpha 1- and alpha 2-adrenergic contractile mechanisms.
Pharmacological modulation of neutrophil phagocytic function in a patient with recurrent sepsis, pyoderma gangrenosum and impaired phagocytosis
Authors: C. B. BENTLEY-PHILLIPS, R. C. COOPER, A. F. HALLETT
Journal: British Journal of Dermatology (1982)

A 50-year-old man with recurrent life-threatening sepsis and a cutaneous condition resembling pyoderma gangrenosum, was found to have a defect of neutrophil phagocytic function. Phagocytosis could be enhanced by corticosteroids, both in vitro in a dose-dependent manner, and in vivo, when it was accompanied by rapid clinical improvement. Studies with steroid hormones and immuno-stimulatory drugs are described.
Pneumococcal disease seasonality: incidence, severity and the role of influenza activity
Authors: Daniel M. Weinberger, Zitta B. Harboe, Cécile Viboud, Tyra G. Krause, Mark Miller, Kåre Mølbak, Helle B. Konradsen
Journal: European Respiratory Journal (2013)

We tested whether the effect of influenza activity on invasive pneumococcal disease incidence and severity varies between age and comorbidity groups. Weekly rates of invasive pneumococcal disease were obtained from the Danish National Laboratory Surveillance System (1977–2007). Influenza-like illness data were collected from a sentinel surveillance system at the Statens Serum Institut (Copenhagen, Denmark). We fitted Poisson regression models for invasive pneumococcal disease, with predictors of seasonality, trends and influenza activity, and allowed the influenza activity variable to vary by comorbidity level and clinical presentation. Influenza activity accounted for 8.4% (95% CI 4.8−11.9%) and 6.9% (95% CI 5.4–10.2%) of all invasive pneumococcal disease cases among those aged 15–39 and ≥40 years, respectively, but had no measurable impact among children aged &lt;15 years. Influenza activity was associated with significant increases in the incidence of invasive pneumococcal pneumonia in both children and adults. The association was more pronounced among younger adults without comorbidities. Case fatality also varied seasonally among the elderly, and this variation might be associated with influenza activity. Pneumococcal incidence and the severity of disease varied seasonally and between age groups. The effect of influenza activity on pneumococcal disease varied between children and adults, and this difference was largely due to differences in disease presentation.