tbuckley/cabot-search huggingface dataset:
Hepatic stellate cells as a target for TZD: Can we treat liver fibrosis and type II diabetes at the same time?
Authors: Hide Tsukamoto
Journal: Hepatology (2002)

Background & Aims: The ligand-dependent transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in hepatic stellate cells (HSC), and its transcriptional activity is reduced during cell transdifferentiation in culture.PPARgamma transcriptional activation decreases platelet-derived growth factor-induced proliferation and inhibits alpha-smooth muscle actin expression in cultured HSC.The aim of our study was to evaluate whether oral administration of synthetic PPARgamma ligands, thiazolidinediones (TZD), might affect collagen deposition in animal models of liver fibrosis.Methods: The effect of 2 TZD (pioglitazone or rosiglitazone) was tested on liver fibrosis induced in rats by either toxin administration (dimethylnitrosamine or carbon tetrachloride) or bile duct ligation.In vivo PPARgamma activation was evaluated by gel shift assay using nuclear extracts from HSC isolated from control and treated rats.Results: Oral administration of TZD reduced extracellular matrix deposition and HSC activation in both toxic and cholestatic models of liver fibrosis.PPARgamma-specific DNA binding was significantly impaired in nuclear extracts of HSC isolated from fibrotic rats compared with HSC from control rats.TZD administration restored PPARgamma DNA binding in HSC nuclei.In vitro, TZD-induced PPARgamma activation inhibited collagen and fibronectin synthesis induced by transforming growth factor (TGF)-beta1 in human HSC, as measured by enzyme-linked immunosorbent assay and Northen blotting.TZD also reduced the TGF-beta1-induced activity of a 3.5-kilobase procollagen type I promoter transfected in human HSC.Conclusions: These findings indicate that PPARgamma activation in HSC retards fibrosis in vivo and suggest the use of TZD for the treatment of liver fibrosis.
The changing classification and diagnosis of diabetes
Authors: N. J Wareham, S. O'Rahilly
Journal: BMJ (1998)

Papers p 371 General practice p 390

At its annual meeting in June 1997 the American Diabetes Association announced the conclusions of an expert committee, which recommended changes to the way that diabetes is classified and to the choice of diagnostic method and cut off value that should be used to define the disease.1 A provisional report from a World Health Organisation consultation group, with some overlap in members with the American committee, has recently been published.2 These recommendations could have important epidemiological implications, but they will also affect individual patients. 

The previous classification of diabetes was based on the extent to which a patient was dependent on insulin.3Although this was a logical distinction that separated the two main forms of diabetes, it gave rise to clumsy and sometimes confusing subcategories. Both the reports of the American Diabetes Association and the WHO recommend altering the classification to define four main subtypes of diabetes. Type 1 includes immune mediated and idiopathic forms of β cell dysfunction which lead to absolute insulin deficiency. Type 2 diabetes is disease of adult onset, which may originate from insulin resistance and relative insulin deficiency or from a …
Virus-Like Structures in Lupus Erythematosus
Authors: Kinya Kawano, Leonard Miller, Paul Kimmelstiel
Journal: New England Journal of Medicine (1969)

IN five patients with lupus erythematosus and renal involvement virus-like cytoplasmic structures were reported by Györkey.1 Subsequently, he and his colleagues presented a series of 20 such cases with myxovirus-like particles, adding that they did not find them in 70 renal biopsies from patients without lupus erythematosus.2 , 3 In our laboratory a thorough examination of adequate electron micrographs of 260 percutaneous renal biopsies revealed 28 in which myxovirus-like structures could be demonstrated. In most cases (Figs 1 2 3) such structures were spotted at magnifications between 8000 and 11,000 times and clearly identified by subsequent sections with higher magnification.Twenty-five of these 28 . . .
Increased Tc-99m MDP Accumulation in Soft Tissue Caused by Bicycle Riding
Authors: Justin W. Kung, Jian Q. Yu, Bruce Lee, Abass Alavi, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2004)

Tc-99m MDP bone scintigraphy has long been used to evaluate bone pathology. However, a variety of etiologies can result in increased Tc-99m MDP accumulation in the nonosseous tissues. We present a case of a 61-year-old man with a history of daily prolonged bicycle use who had increased MDP uptake in the soft tissues of the gluteal region, corresponding to the contour of the saddle of the bicycle.
SURGICAL TREATMENT OF CHRONIC OTORRHEA.Read in the Section on Laryngology and Otology, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco. June 5-8, 1894.
Authors: CHARLES HENRY BURNETT
Journal: JAMA (1894)

Surgical treatment of chronic purulent otitis media consists in the excision of necrotic tissue from the tympanic cavity. Instillation, insufflation or mopping of medicaments upon the diseased parts in the drum cavity in many cases result in a cure, but there are many instances in which all these forms signally fail after a long and fair trial. In these unyielding cases it will be found that one or more of the auditory bonelets are necrosed, and in some instances that the tympanic wall in apposition to the necrosed bonelets is itself carious. Manifestly in such cases the plain surgical indication is to excise the diseased bonelets or their remnants, in order to remove septic material from the drum cavity. This improves the drainage of this space, promotes a free application of antiseptics to the tympanum and favors the healing of its muco-periosteal lining. Under such treatment, in most cases,<i>after</i>
Cough mixture abuse in pregnancy, folate deficiency, and neural tube defects?
Authors: S.K. Tsang, W.Y. Au
Journal: American Journal of Hematology (2005)

of thalassemics due to the development of better chelating drugs will surely make HCC a major problem for thalassemics in future.Nowadays the outcome of HCC can be improved by various treatments, and when HCC develops in absence of cirrhosis, liver surgery can be curative [1,2].However, early detection of HCC is mandatory.Our experience suggests that US screening should be performed strictly in thalassemia syndromes, particularly when there is either HCV or HBV infection or sustained iron overload.
Knock-knee in Children
Authors: A. J. M. Morley
Journal: BMJ (1957)

ANAEMIA AFTER ANTICONVULSANT THERAPY BED:The serum vitamin-Bl2 concentrations of both patients were very low, but neither suffered from Addisonian pernicious anaemia.Both had been taking a very in- adequate diet, and one had recently suffered from scurvy.Vitamin-B12 deficiency was not the sole cause of the megaloblastic anaemia in the one patient in whom serial observations were made.We wish to thank
916. Genetically Modified Mesenchymal Stem Cells Expressing Transforming Growth Factor-β1 Develop a Cartilage Phenotype
Authors: Alan J. Nixon, Christina W. Cheng, Lisa Strassheim, Paul D. Robbins
Journal: Molecular Therapy (2006)

INTRODUCTIONAcute cartilage injury and subsequent osteoarthritis are a debilitating and common syndrome in the aging population. Transplantation of MSCs to joints has been successfully used in small animal models. However, in extensive defects the application of MSCs improved defect filling with only fibrous tissue. Enhancing chondrogenesis of the MSCs by TGF-β1 gene transduction before transplantation may provide the impetus for better quality cartilaginous repair.MATERIALS AND METHODSAadenovirus vector encoding equine TGF-β1 (AdTGF-β1) was used to transfect MSCs. Monolayer cultures were transduced with AdTGF-β1, AdGFP, or no virus. Monolayers were pelleted after 24 hours, and 15 pellets harvested at 2, 7, 14, and 21 days. Chondrogenesis was determined by qPCR assessment of TGF-β1, aggrecan, coll IIA, and coll IIB gene expression. Medium was assayed for PG and TGF-β1. Confirmation of pellet chondrogenesis was made by HandE architecture, collagen II elaboration on immunohistochemistry, and toluidine blue PG staining.RESULTSPCR indicated AdTGFβ1 transfected MSCs expressed TGF-β1 RNA (Fig1Fig1), which induced markers of chondrogenic differentiationincluding aggrecan, and collagen types IIA and IIB (Figs 2Figs 2). Aggrecan expression was significantly enhanced on day 2. Immuno analysis detected collagen type II as early as 2 days after beginning aggregate cultures. This phenomenon continued through day 21, with intense collagen type II as the predominant collagen on day 21 (Fig 2Fig 2).Fig. 1View Large Image | View Hi-Res Image | Download PowerPoint SlideFig. 2View Large Image | View Hi-Res Image | Download PowerPoint SlideCollagen type I immuno analysis showed collagen type I deposition throughout all time periods, with increases under the influence of TGF-β1.DISCUSSIONSignificant increases in TGF-β1 expression were induced in AdTGF-β1 transduced MSC cells. Chondrogenic response was reflected in collagen type IIA and IIB expression which were significantly increased on day 7, 14 and 21. Longer term cultures showed a preponderance of collagen type IIB expression. Combined with morphologic evidence of strong chondrogenic condensation, these data provide molecular, histological and immunohistochemical evidence for substantial in vitro chondrogenic differentiation of equinebone-marrow derived MSCs. Based on these results AdTGF-β1 treated MSCs may be a robust source of chondrocytes for use in cartilage repair.
Miss, Mister, Doctor: How we are titled is of little consequence
Authors: G. Feaver
Journal: Journal of the Royal Society of Medicine (2006)

How we are titled is of little consequence I found the editorial (April 2006 JRSM 1 ) on how we are titled most interesting.This is a continuation of the debate that the dental profession has been having for many years, fuelled by both an influx of overseas graduates styling themselves as 'Doctor', and by the development of the role of dentists from 'toothwrights' to practitioners with a more holistic approach encompassing the oral health and wellbeing of those in their care.However all of us, physicians, surgeons, general practitioners and dentists have one thing in commonpatients.But that may be about to change.The same week as the editorial appeared, the chief executive of the Sussex Partnership NHS Trust ordered staff not to refer to people receiving medical care as patients but as clients.This not only demonstrates a misunderstanding of our roles but also devalues both practitioners and those that we care for.Patients are not simply clients or users of health services.Patients are those receiving care, who are given time, are listened to and treated with sympathy, understanding and expertise.There is something special about the term patient, and although to give a precise dictionary definition is difficult, it is well understood by those who deliver the care.How we are titled may well, as the editorial states, be of little consequence; far more important is how we refer to, and perceive, those in our care.
Is that it? How online articles have changed over the past five years
Authors: T. Delamothe
Journal: BMJ (2002)

OBJECTIVE--To compare the efficacy and safety of a single dose of 1 mg of cabergoline with that of bromocriptine 2.5 mg twice daily for 14 days in the inhibition of puerperal lactation. DESIGN--Prospective, randomised, double blind, parallel group, multicentre study. SETTING--University of hospital departments of obstetrics and gynaecology in different European countries. SUBJECTS--272 puerperal women not wishing to lactate (136 randomised to each drug). INTERVENTIONS--Women randomised to cabergoline received two 0.5 mg tablets of cabergoline and one placebo tablet within 27 hours after delivery and then placebo twice daily for 14 days. Those randomised to bromocriptine received 2.5 mg of bromocriptine and two placebo tablets within 27 hours and then 2.5 mg of bromocriptine twice daily for 14 days. MAIN OUTCOME MEASURES--Success of treatment (complete or partial) according to milk secretion, breast engorgement, and breast pain; rebound symptomatology; serum prolactin concentrations; and number of adverse events. RESULTS--Complete success was achieved in 106 of 136 women randomised to cabergoline and in 94 of 136 randomised to bromocriptine and partial success in 21 and 33 women respectively. Rebound breast symptomatology occurred respectively in five and 23 women with complete success up to day 15 (p less than 0.0001). Serum prolactin concentrations dropped considerably with both drugs from day 2 to day 15; a prolactin secretion rebound effect was observed in women treated with bromocriptine. cabergoline and 36 receiving bromocriptine (p = 0.054), occurring most during the first treatment day. CONCLUSION--A single 1 mg dose of cabergoline is at least as effective as bromocriptine 2.5 mg twice daily for 14 days in preventing puerperal lactation. Because of the considerably lower rate of rebound breast activity and adverse events and the simpler administration schedule cabergoline should be the drug of choice for lactation inhibition.
Characteristics of Pulmonary Artery Pressure Waveform for Differential Diagnosis of Chronic Pulmonary Thromboembolism and Primary Pulmonary Hypertension
Authors: Yasunori Nakayama, Norifumi Nakanishi, Masaru Sugimachi, Hiroshi Takaki, Shingo Kyotani, Toru Satoh, Yoshiaki Okano, Takeyoshi Kunieda, Kenji Sunagawa
Journal: Journal of the American College of Cardiology (1997)
The Use and Diagnostic Significance of Thallium-201 SPECT Imaging in a Case of Anomalous Left Coronary Artery
Authors: PAUL J. PETROZZO, MARK L. WOODARD, DOLORES A. VITULLO, CARLOS BEKERMAN, MICHAEL J. BLEND, STEVEN M. PINSKY
Journal: Clinical Nuclear Medicine (1988)

A 6-year-old female with an anomalous left coronary artery (ALCA) originating from the main pulmonary artery underwent a resting TI-201 SPECT examination before and after surgical reimplantation. Preoperative TI- 201 SPECT images demonstrated decreased perfusion to the anterior wall and a dilated left ventricle. Post operative TI-201 SPECT images showed marked improvement of perfusion to the anterior wall as well as a decreased left ventricular size. This is one of the few documented demonstrations of a perfusion defect due to an ALCA in a young child using TI-201 SPECT imaging methods in conjunction with other tests.
Inhibition of smooth muscle cell proliferation by visible light-activated psoralen.
Authors: B E Sumpio, G Li, L I Deckelbaum, F P Gasparro
Journal: Circulation Research (1994)

The present study was designed to evaluate the effect of 8-methoxypsoralen (8-MOP) activated with visible light (419 nm) on the suppression of smooth muscle cell (SMC) proliferation in vitro. We hypothesize that if visible light (VL) instead of UVA is used to photoactivate 8-MOP, cytotoxic 8-MOP-DNA cross-link formation can be minimized. Bovine aorta SMCs (2 x 10(4)/cm2) were incubated with 8-MOP (1 micrograms/mL) for 30 minutes (in the dark) and exposed to a range of VL (2 to 69 J/cm2) to determine the dose of VL that inhibits SMC proliferation with minimal toxicity. The results show that 8-MOP in combination with 2 to 12 J/cm2 VL reversibly inhibited SMC proliferation for up to 5 days after treatment. SMC viability was confirmed by trypan blue exclusion. 8-MOP in combination with 23- or 69-J/cm2 VL irreversibly inhibited SMC proliferation. In cell cycle studies, 12-J/cm2 VL was used to activate 8-MOP. A phase-specific G2 blockade that correlated temporally with recovery of SMC replication was observed. Photoadduct repair studies showed that cell proliferation rates recovered when 60% of the adducts had been removed. These results demonstrate for the first time the possibility of using VL to activate 8-MOP to inhibit cell proliferation and suggest that 8-MOP/VL photochemotherapy can be used to control SMC growth.
Fournier's Syndrome in a Ketoacidotic Diabetic Patient After Intrascrotal Insulin Injections Because of Impotence
Authors: Kevin O'Dell, Joseph Shipp
Journal: Diabetes Care (1983)

Fournier's syndrome is a necrotizing fasciitis most commonly confined to the male genitalia with high morbidity and mortality rates. The salient features are (1) sudden explosive illness in the midst of apparent health; (2) rapid necrosis and sloughing of tissues of the scrotum and penis; (3) absence of an obvious cause; (4) a mixed bacteriologic picture; and (5) gangrene affecting the whole thickness of the scrotal skin, but not the underlying testes. With the propensity toward life-threatening infections in patients with diabetes, it is surprising that Fournier's syndrome is not more common in suboptimally treated diabetic patients. This report is to illustrate the recognition and treatment of Fournier's syndrome in a patient with diabetes. Also, it must be emphasized that the explosive course of the disease process begins with a benign-appearing, epididymitis-like picture. Prompt recognition followed by prompt surgical debridement and appropriate antibiotic therapy along with surgical wound closure is necessary to reduce morbidity and mortality. The present case is unusual for the following reasons: (1) necrosis of the testicles requiring orchiectomy; (2) extensive spread of gangrene beyond the genitalia; and (3) the route of infection, which appeared to be intrascrotal injections of insulin in a vain attempt to cure impotence.
The Detection of Iron Overload
Authors: Clement A. Finch
Journal: New England Journal of Medicine (1982)

Human physiology is such that few people accumulate excess iron. Indeed, normal persons are able to control the accumulation of body iron despite ingestion of up to 5 to 10 times the normal amount.1 There are, however, two disorders in which large amounts of iron accumulate in the parenchymal cells. One category of parenchymal iron overload includes patients with extremely high rates of erythropoiesis — i.e., those with thalassemia and sideroblastic anemia, in which the hyperplastic erythroid marrow in some way directs the intestinal mucosa to take in excessive amounts of iron.2 A second category is the homozygous HLA-related disorder . . .
Hypothyroidism After Low-Dose ^131I Treatment of Hyperthyroidism
Authors: JOSEPH A. GLENNON
Journal: Annals of Internal Medicine (1972)

Sixty-four patients with hyperthyroidism were treated with a single dose of 3 mCi or less of 131I before 1951. Nine were lost to follow-up shortly after treatment. The other 55 were found, their thyroid status at last examination noted, and the incidence of hypothyroidism calculated, using the life-table method. Few were hypothyroid (3.7%) at the end of the first year, and the incidence remained low (7.5%) after 5 years. Thereafter, however, the incidence increased annually at a rate of 3.4% yearly from the fifth to the seventeenth year, reaching a total of 48% at the end of this time. The rate of increase was similar to that noted by others, using larger doses of radioiodine. Although the number of patients studied was small, the data suggest that low doses of radioiodine, compared with conventional doses, result in a lower incidence of hypothyroidism at 1 year and a delay in the appearance of hypothyroidism but no change in the later annual increment in the incidence of hypothyroidism and perhaps no effect on the ultimate incidence of hypothyroidism.
SOME MUTANT PHAGES PRODUCED DIRECTLY BY BACILLUS MEGATHERIUM 899A WITH THEIR RATE OF OCCURRENCE
Authors: James S. Murphy
Journal: The Journal of Experimental Medicine (1954)

The rate at which cultures of B. megatherium 899a produce certain mutants of its phage T (wild type) has been investigated in two media; one (peptone) in which reinfection of sensitive cells, if present, is virtually certain, and one (asparagine) in which reinfection is extremely unlikely. Little difference either in the number or types of mutants produced has been detected. It is concluded that phage mutants are produced directly by B. megatherium 899a and that no intermediate passage through a sensitive cell is necessary for the mutation. 396 individual mutant plaques have been isolated and classified into at least 18 types of plaque-forming mutants of B. megatherium 899a. The over-all mutant ratio found was in the order of 1:2000 while individual mutants appeared with rates between 1:7000 and less than 1:100,000.
Spray-Adhesive Ban Lifted
Authors: Frank A. Ubel
Journal: JAMA (1974)

To the Editor.—  In the September 24, 1973, issue ofThe Journal(225:1581, 1973), you published the article, Possible Link to Chromosomal Gaps Leads to Ban on Spray Adhesives. Recently, the Consumer Product Safety Commission (CPSC) announced its intention to remove the ban on the spray adhesives, effective March 1, 1974. This was based on the review of considerable data submitted to the CPSC by government, industry, and independent investigators.  Unfortunately, the general public read the press releases at the onset of the ban and were greatly alarmed. Much anxiety was created in pregnant women and in others who were anticipating starting their families. Little medical information was given them or the medical profession since that time.  Now that the ban is to be lifted, I think that physicians and the American public should be informed. The information should include the medical facts and should be adequate to relieve their
Wayne County, Mich., Medical Society.
Authors: E. B. Smith
Journal: JAMA (1893)

Detroit, Mich., Oct. 10, 1893. <h3>To the Editor:</h3> —At the annual meeting of the Wayne County Medical Society the following officers were elected for the ensuing year: President, Hal. C. Wyman, M.D.; Vice-President, E. B. Smith, M.D.; Secretary, R. H. Horner, M.D.; Treasurer, C. Henri Leonard, M.D. Board of Directors: J. E. Clark, M.D.; E. W. Jenks, M.D.; James Newell, M.D.; J. E. Westgate, M.D.; K. Gunsolus, M.D. Yours truly,
Blockade of beta 1-integrins in skin causes edema through lowering of interstitial fluid pressure.
Authors: R K Reed, K Rubin, H Wiig, S A Rodt
Journal: Circulation Research (1992)

The increased capillary fluid filtration required to rapidly create edema in acute inflammation can be generated by increased negativity of the interstitial fluid pressure (Pif). This observation suggests that connective tissues can "actively" enhance capillary fluid filtration. We now show that in vivo blockade of beta 1-integrin adhesion receptors in rat skin causes local edema concomitant with increased negativity of Pif. Experiments were performed on the dorsal side of the hind paw, and Pif was measured with sharpened glass capillaries (tip diameter, 3-7 microns) connected to a servo-controlled counterpressure system. Measurements were made after circulatory arrest had been induced with intracardiac potassium chloride in pentobarbital anesthesia. This procedure prevents the vascular phenomena of increased fluid and protein flux leading to edema formation, which in turn can increase Pif and therefore potentially mask an increased negativity of Pif. Control Pif averaged -0.58 +/- 0.81 (mean +/- SD) mm Hg (n = 37). Subdermal injection of 5 microliters monospecific rabbit anti-rat integrin beta 1-subunit immunoglobulin G caused increased negativity of Pif to average values between -4 and -6 mm Hg within 10 minutes after injection. Subdermal injection of 0.9% NaCl, preimmune immunoglobulin G, rat anti-fibronectin, and peptides with Arg-Gly-Asp and Arg-Gly-Glu sequences did not change Pif significantly. In another series of experiments, 5 microliters anti-beta 1 integrin immunoglobulin G was injected subdermally in rats with intact circulation and resulted in an increase in total tissue water corresponding to a doubling of the interstitial fluid volume in 10 minutes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)