tbuckley/cabot-search huggingface dataset:
Wegener's Granulomatosis of Lung: Diagnosis and Treatment
Authors: HAROLD L. ISRAEL
Journal: Annals of Internal Medicine (1971)

Twelve patients with pulmonary Wegener's granulomatosis are reported. In seven patients the disease appeared to be limited to the lungs; four patients had upper respiratory tract involvement, and one had cutaneous and subcutaneous lesions. A link between pulmonary and disseminated forms of this syndrome was provided by a patient who had a solitary pulmonary lesion for 4 years, after which involvement of the upper respiratory tract and the other lung developed. The course of the disease was extremely variable, rapid progression occurring in three patients, whereas one patient has had the disease for 12 years with little deterioration of health. Corticoid treatment resulted in transitory improvement in three patients and progression in four. Eight patients received cytotoxic therapy. One death occurred as the result of drug toxicity; at necropsy no evidence of Wegener's granulomatosis remained. Excellent responses have been obtained in three patients treated with chlorambucil and four treated with azathioprine. Surgical resection of pulmonary lesions was apparently curative in two cases but was unsuccessful in three. Recognition of this not uncommon disorder is important since cytotoxic therapy appears to be uniformly effective.
Calreticulin gene exon 9 frameshift mutations in patients with thrombocytosis
Authors: J Chi, K A Nicolaou, V Nicolaidou, L Koumas, A Mitsidou, C Pierides, M Manoloukos, K Barbouti, F Melanthiou, C Prokopiou, G S Vassiliou, P Costeas
Journal: Leukemia (2013)

Somatic frameshift mutations in exon 9 of the calreticulin (CALR) gene were recently identified in patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs), particularly essential thrombocythemia and myelofibrosis.1, 2 Calreticulin is a highly conserved endoplasmic reticulum (ER) luminal Ca2+-binding chaperone protein with a critical role in the process of glycoprotein folding and a number of other cellular functions both inside and outside the ER,3, 4 and has three domains with different structural and functional properties; a globular N domain, a proline-rich P domain and an acidic C domain.3, 4 The disrupted C-terminal region contains a KDEL ER-retention sequence multiple sites with high capacity for Ca2+ binding and sites for binding to the cell surface and to blood clotting factors.5, 6
Reply from Authors re: Alexander Kutikov, Marc C. Smaldone, Brian L. Egleston, Robert G. Uzzo. Should Partial Nephrectomy Be Offered to All Patients Whenever Technically Feasible? Eur Urol 2012;61:732–4
Authors: Maxine Sun, Quoc-Dien Trinh, Pierre I. Karakiewicz
Journal: European Urology (2012)
MULTIPLE LOOSE BODIES IN THE KNEE JOINT.
Authors: JOHN PRENTISS LORD
Journal: JAMA (1904)

W. C. S., a barber, aged 33 years, admitted to St. Joseph's Hospital Aug. 4, 1903. Family history negative. No history of injury nor other exciting cause. Left knee began to trouble him fourteen years ago. Had attacks of inflammation every two to four years, but later years the attacks were as often as three or four times yearly. He had knowledge of loose bodies within the joint for the greater portion of the time. They produced locking of the joint and inflammation followed. Recently these attacks have been much worse and great swelling and pain resulted. On presentation many loose bodies were easily distinguishable. <h3>Operation.</h3> —August 5, 1903, an incision was made as for a Volkmann resection of the knee. The patella was sawn transversely, the lateral and crucial ligaments divided, which exposed the whole articulation. Four bodies were removed from above the patella. One of these was the large
Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid
Authors: Tatjana Stojakovic, Csilla Putz-Bankuti, Günter Fauler, Hubert Scharnagl, Martin Wagner, Vanessa Stadlbauer, Gerald Gurakuqi, Rudolf E. Stauber, Winfried März, Michael Trauner
Journal: Hepatology (2007)

Statin therapy may target both hypercholesterolemia and cholestasis in primary biliary cirrhosis (PBC). However, little is known about the efficacy and safety of statins in PBC. The aim of this single-center study was therefore to prospectively examine the effects of atorvastatin on serum markers of cholestasis, aminotransferases, and lipid and bile acid metabolism as well as inflammatory and immunological markers in patients with PBC. Fifteen patients with early-stage PBC and an incomplete biochemical response to ursodeoxycholic acid (UDCA) therapy (defined as alkaline phosphatase 1.5-fold above the upper limit of normal after 1 year) were treated with atorvastatin 10 mg/day, 20 mg/day, and 40 mg/day for 4 weeks, respectively. Serum levels of alkaline phosphatase increased during atorvastatin 20 mg and 40 mg (P < 0.05), whereas leucine aminopeptidase and gamma-glutamyltransferase remained unchanged. No statistical differences in overall serum ALT, AST, bilirubin, and IgM levels were observed. However, atorvastatin was discontinued in 1 out of 15 patients because of ALT 2-fold above baseline, and 2 patients showed ALT elevations 3-fold above the upper limit of normal at the end of the atorvastatin treatment period. Serum total cholesterol and low-density lipoprotein cholesterol levels decreased by 35% and 49%, respectively (P < 0.001). Precursors of cholesterol biosynthesis (lanosterol, desmosterol, lathosterol) showed a similar pattern. No changes in serum bile acid levels and composition were observed during treatment.Atorvastatin does not improve cholestasis in PBC patients with an incomplete biochemical response to UDCA but effectively reduces serum cholesterol levels.
Extra- and intracellular factors regulating cardiomyocyte proliferation in postnatal life
Authors: S. Zacchigna, M. Giacca
Journal: Cardiovascular Research (2014)

One of the striking differences that distinguish the adult from the embryonic heart in mammals and set it apart from the heart in urodeles and teleosts is the incapacity of cardiomyocytes to respond to damage by proliferation. While the molecular reasons underlying these characteristics still await elucidation, mounting evidence collected over the last several years indicates that cardiomyocyte proliferation can be modulated by different extracellular molecules. The exogenous administration of selected growth factors is capable of inducing neonatal and, in some instances, also adult cardiomyocyte proliferation. Other diffusible factors can regulate the proliferation and cardiac commitment of endogenous or implanted stem cells. While the individual role of these factors in the paracrine control of normal heart homeostasis still needs to be defined, this information is relevant for the development of novel therapeutic strategies for cardiac regeneration. In addition, recent evidence indicates that postnatal cardiomyocyte proliferation is controlled by genetically defined pathways, such as the Hippo pathway, and can be modulated by perturbing the endogenous cardiomyocyte microRNA network; the identification of the cytokines that activate these molecular circuits holds great potential for clinical translation.
Pheochromocytoma
Authors: Shannon Brunjes, Varner J. Johns, Milton G. Crane
Journal: New England Journal of Medicine (1960)

IN the majority of the reported cases of operated pheochromocytomas, prolonged postoperative shock has been a major problem,1 particularly in patients with sustained rather than intermittent hypertension.2 Shock after removal of a pheochromocytoma has been regarded as being due to a vasopressor deficiency. It seems logical to treat shock that follows the removal of an endogenous source of vasopressors by providing exogenous vasopressors, and this has been the routine procedure.However, little attention has been paid to the actual mechanism of this shock or the pathologic physiology of this dependence on vasopressors. It has even been postulated3 that the hypotensive . . .
Donald William Gau
Authors: M. Hilary
Journal: BMJ (2003)

Former general practitioner Beaconsfield (b 1936; q Cambridge/St Bartholomew's Hospital, London, 1961; MRCP, FRCGP), died on 2 December 2002 following a fall.​fall.




Figure 1




Donald went up to Cambridge determined to become a test pilot, but his tutor, Robert Runcie—later archbishop of Canterbury— guided him towards medicine. He settled in Beaconsfield in 1969, where he pioneered the many major changes in general practice. He trained many of the current general practitioners in South Bucks and was also GP adviser to the surgical unit at Wycombe Hospital. His local legacy includes a thriving Good Neighbour Scheme, a patient participation group, and a home care cancer service. He leaves a wife, Gillian; two sons; and a grandson.
Suppression of human IL-1β, IL-2, IFN-γ, and TNF-α production by cigarette smoke extracts
Authors: Yanli Ouyang, Nisha Virasch, Ping Hao, Michael T. Aubrey, Neeta Mukerjee, Barbara E. Bierer, Brian M. Freed
Journal: Journal of Allergy and Clinical Immunology (2000)
The Ambiguity of Clinical Intentions
Authors: T E Quill
Journal: New England Journal of Medicine (1993)

Medical ethicists place great weight on the intentions of clinical actions. The religious principle of “double effect,” based on a distinction between intentions and consequences, is an ethical cornerstone in the medical treatment of the terminally ill1,2. Giving high doses of narcotic analgesics to a dying patient to relieve pain and suffering is considered ethical even if it inadvertently hastens death, provided the clinician did not intend to help the patient die. Death may even be foreseen as a side effect of the intervention as long as it is not intended. On the other hand, should a clinician . . .
Agency reports cases of rape on mental health wards
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

A review has been launched into allegations that mental health patients in England and Wales have been subjected to sexual abuse, including rape, while being cared for on hospital wards.

Altogether 122 incidents of sexual abuse were reported to the National Patient Safety Agency by mental health staff between November 2003 and the end of September 2005. These included 19 rapes and 20 cases of consensual sex as well as incidents of sexual advances, touching, and exposure. In 11 cases of rape the perpetrator is alleged to have been a member of staff.

The incidents are highlighted in a report from the safety watchdog, which has analysed almost …
Multimodality Imaging of Integrin α<sub>v</sub>β<sub>3</sub> Expression
Authors: Yin Zhang, Yunan Yang, Weibo Cai
Journal: Theranostics (2011)

Over the last decade, integrin α v β 3 has been studied with every single molecular imaging modality.Since no single modality is perfect and sufficient to obtain all the necessary information for a particular question, combination of certain molecular imaging modalities can offer synergistic advantages over any modality alone.This review will focus on multimodality imaging of integrin α v β 3 expression, where the contrast agent used can be detected by two or more imaging modalities, such as combinations of PET and optical, SPECT and fluorescence, PET and MRI, SPECT and MRI, and lastly, MRI and fluorescence.Most of these agents are based on certain type(s) of nanoparticles.Contrast agents that can be detected by more than two imaging modalities are expected to emerge in the future and a PET/MRI/fluorescence agent will likely find the most future biomedical/clinical applications.Big strides have been made over the last decade for imaging integrin α v β 3 expression and several PET/SPECT probes have been tested in human studies.For dualmodality and multimodality imaging applications, a number of proof-of-principle studies have been reported which opened up many new avenues for future research.The next decade will likely witness further growth and continued prosperity of molecular imaging studies focusing on integrin α v β 3 , which can eventually impact patient management.
Hormonal Control of Adrenocortical Cell Proliferation
Authors: Peter J. Hornsby, Gordon N. Gill
Journal: Journal of Clinical Investigation (1977)

A primary bovine adrenocortical cell culture system responsive to physiological concentrations of ACTH has been established. When added to cultures, ACTH inhibited DNA synthesis and cell division over the same concentration range required for stimulation of fluorogenic steroid production (0.01-10 nM). With chronic exposure to ACTH, cells became desensitized to the growth inhibitory effects of ACTH. Though cell growth was initially completely inhibited by ACTH, cells ultimately began to grow in its continued presence. The lag time to initiation of cell growth, the rate of growth, and the final density achieved depended on the ACTH concentration. Desensitization to ACTH1-39 was not induced by monobutyryl cyclic AMP nor by ACTH11-24. Specificity of desensitization was apparent because cells which had become desensitized to ACTH1-39 remained fully responsive to monobutyryl cyclic AMP, prostaglandin E1, and cholera toxin. Though the effects of ACTH on cell growth were readily reversible upon hormone removal, the desensitized response to readdition of ACTH persisted for at least 8 h.
Multiple plaque ruptures in patients with acute myocardial infarction: an angioscopic evidence of systemic cause of plaque instability
Authors: Yoshiharu Fujimori, Hiroshi Morio, Kuniko Terasawa, Takashi Shiga, Masaru Hatano, Masaaki Osegawa, Yasumi Uchida, Toshihiro Morita
Journal: Journal of the American College of Cardiology (2002)
284Cardiometabolic risk of visceral fat: Regulation of stem cells multipotency in visceral and subcutaneous adipose tissue
Authors: R Ferrer-Lorente, MT Bejar, L Badimon
Journal: Cardiovascular Research (2014)

Purpose: The precise mechanisms underlying the differential function and cardiometabolic risk of white adipose tissue (WAT) remain unclear. Visceral (VWAT) and subcutaneous (SCWAT) adipose tissue have different metabolic functions that seem related to their different intrinsic expansion capacities. Here we have hypothesized that WAT characteristics are determined by their resident adipose stem cells (ASCs) and understanding the differential regulation of adipocyte biogenesis may be critical to prevent the metabolic co-morbidities of visceral obesity. Methods: ASCs from 3 different VWAT depots (epididymal, mesenteric and retroperitoneal) and SCWAT were characterized by flow cytometry and real time PCR, in both healthy lean (ZLC) and diabetic obese (ZDF) rats, to identify their stemness and their adipogenic differentiation commitment. Notch signalling pathway, that plays a critical role in adipocyte differentiation, was analyzed in depth. Results: ASCs from different WAT showed significant differences in expression of main molecules governing the stemness and the earlier adipogenic differentiation steps in both ZLC and ZDF. The SCWAT and VWAT transcriptome differed greatly, showing a greater maintenance of the pluripotency and undifferentiated state in ASCs derived from VWAT compared with ASCs derived from SCWAT. The analysis performed on Notch system revealed that Notch target genes (Hes and Hey families) were up-regulated in ASCs derived from visceral depots. Upon adipogenic differentiation, adipocyte cell markers were down-regulated in ASCs from VWAT in comparison to ASCs from SCWAT, revealing a lower adipogenic capacity in ASCs of visceral origin than in those of SCWAT in accordance with the differential activation of Notch signalling. Notch up-regulation by its activator phenethylisothiocyanate (PEITC) attenuated the adipogenic differentiation of ASCs from SCWAT whereas Notch inhibition by N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-Butyl Ester (DAPT) increased the adipogenic differentiation of ASCs from visceral origin. We observed the same behaviour in healthy as well as diabetic conditions. In an adipogenic environment, ZDF rats, the inability of VWAT to form new adipocytes would lead to the adipocyte hypertrophy and limited storage capacity, leading to ectopic fat deposition and, ultimately, to the cardiometabolic alterations. Conclusions: The differential activation of Notch in ASCs is at the origin of the different intrinsic WAT expansion capacities that contribute to the regional variations in WAT-homeostasis and to its associated cardiometabolic risk.
Characterization of Fam20C expression in odontogenesis and osteogenesis using transgenic mice
Authors: Er-Xia Du, Xiao-Fang Wang, Wu-Chen Yang, Deborah Kaback, Siu-Pok Yee, Chun-Lin Qin, Anne George, Jian-Jun Hao
Journal: International Journal of Oral Science (2014)

Our previous studies have demonstrated that Fam20C promotes differentiation and mineralization of odontoblasts, ameloblasts, osteoblasts and osteocytes during tooth and bone development. Ablation of the Fam20C gene inhibits bone and tooth growth by increasing fibroblast growth factor 23 in serum and causing hypophosphatemia in conditional knockout mice. However, control and regulation of the expression of Fam20C are still unknown. In this study, we generated a transgenic reporter model which expresses green fluorescence protein (GFP) driven by the Fam20C promoter. Recombineering was used to insert a 16 kb fragment of the mouse Fam20C gene (containing the 15 kb promoter and 1.1 kb of exon 1) into a pBluescript SK vector with the topaz variant of GFP and a bovine growth hormone polyadenylation sequence. GFP expression was subsequently evaluated by histomorphometry on cryosections from E14 to adult mice. Fluorescence was evident in the bone and teeth as early as E17.5. The GFP signal was maintained stably in odontoblasts and osteoblasts until 4 weeks after birth. The expression of GFP was significantly reduced in teeth, alveolar bone and muscle by 8 weeks of age. We also observed colocalization of the GFP signal with the Fam20C antibody in postnatal 1- and 7-day-old animals. Successful generation of Fam20C-GFP transgenic mice will provide a unique model for studying Fam20C gene expression and the biological function of this gene during odontogenesis and osteogenesis. Expression of a regulator of tooth mineralization starts late during embryonic development in mice, continuing until four weeks after birth. Jian-Jun Hao and his colleagues at the University of Connecticut Health Center in the USA created a mouse model for tracking when and where the protein Fam20C is expressed in the body. The researchers engineered mice to make green fluorescence protein, a visible marker, in any tissues where Fam20C would normally be found. They saw the green glow in the dentin-forming cells of the teeth and in bone-forming cells of the craniofacial and alveolar bones starting at day 17.5 of embryonic development. The green signal decreased after the mice reached four weeks of age. The findings — and the mouse model itself — could lead to therapies for dentin and bone defects.
The Morals of Private Practice — Congress in Cyprus
Authors: John Lister
Journal: New England Journal of Medicine (1972)

EVER since the National Health Service began there has been controversy about the place that private practice should occupy in a country where a comprehensive health service is available. The late Aneurin Bevan, who was minister of health when the Service was introduced in 1948, realized that he had to obtain the co-operation of the medical profession if it was to be workable. General practitioners were determined to retain their status as independent contractors and only agreed to enter the Service when they had been persuaded that their independence would be preserved by the capitation fee system whereby they would . . .
THE DIFFERENTIAL DIAGNOSIS AND PROGNOSIS OF TUMORS OF THE UVEAL TRACT.
Authors: H. V. WÜRDEMANN
Journal: JAMA (1906)

The literature of tumors of the eye covers many hun- dreds of cases and thousands on thousands of printed pages.The delegation of this subject to me by the offi- cers of the Section on Ophthalmology of the American Medical Association appalled me by its vastness, and I, therefore, selected only one portion, which is, perhaps, its most important phase, that of the differential diag- nosis and prognosis of tumors of the uveal tract, dealing with this subject mostly from the clinical standpoint.A companion essay on "The Microscopic Findings of the So-called Leucosarcoma" is offered to the Section by Dr. E. V. L. Brown, of Chicago.The most important monograph on this subject is by Felix LaGrange,1 which comprises two massive volumes, 1,739 pages in all, and to this work I am indebted for much of the information which follows:From the richness of its circulation, its complex structure, its superficial situation and its embryology, the eye is greatly exposed to new growths.It is com- posed of both ectodermic and mesodermic elements, the proliferation or implantation of which gives rise to diverse forms of tumors.I follow LaGrange and clas- sify the tumors developing in the iris, the ciliary body and the choroid under the following heads :1. Cysts. 2. Angioma.-3. Myoma. 4. Sarcoma.5. Metastatic Tumors (Sarcoma and Carcinoma). I. CYSTS.From their situation we may designate all tumors of the uveal tract malignant as regards the integrity of vision and of the eye itself.Therefore, even the so- called benign tumors, such as cysts, which in other local- ities would give rise but to deformity or more or less disturbance of function, are dangerous growths to the eye.These forms of tumors are practically limited to the iris.Alt2 says: "No doubt epithelial new forma- tions occur primarily in the eyeball, springing from the two epithelial layers of the ciliary body or iris, and seem to be benign."Differential Diagnosis.-Thediagnosis is generally easy.In the beginning they may be confused with sarcoma, syphilis and tuberculosis of the iris.Sarcoma develops rapidly; it is plainly seen and pre- sents a dark aspect, very different from the color of the cysts which are, as a rule, gray, yellow, blue, or rarely green.Leucosareoma of the iris, which is extremely rare, is white, presents a surface rich in blood vessels and somewhat mammillated.Cysts of the iris usually arise after traumatism, whereas sarcoma does not.Gummata of the iris are generally to be seen in both eyes, preferably selecting the internal or superior seg- ment of the iris.They are yellowish and under specific treatment are absorbed, leaving an atrophie area.They generally arise in the so-called tertiary form of syphilis.Tubercles of the iris are of a clear yellowish color, occasionally white.They are vascular, round, multiple,