tbuckley/cabot-search huggingface dataset:
Toll-like receptor 4 activity protects against hepatocellular tumorigenesis and progression by regulating expression of DNA repair protein Ku70 in mice
Authors: Ziyan Wang, Jun Yan, Heng Lin, Fang Hua, Xiaoxing Wang, Hanzhi Liu, Xiaoxi Lv, Jiaojiao Yu, Su Mi, Jiaping Wang, Zhuo-Wei Hu
Journal: Hepatology (2013)

Hepatocellular carcinoma (HCC) is a devastating consequence of chronic inflammatory liver diseases. The goal of this study was to investigate whether Toll-like receptor 4 (TLR4) activity contributes to HCC initiation and progression in mice. A mouse model of diethylnitrosamine (DEN)-induced HCC was generated with wild-type and TLR4 mutant mice, and the development and progression of HCC and senescent responses were assessed using morphologic, immunological, and biochemical criteria. We found that genetic or pharmacologic blocking of TLR4 increased susceptibility to DEN-induced HCC carcinogenesis and progression, which was indicated by increases in number of tumor nodules, tumor volume, and animal death. The enhanced HCC was associated with a broad-spectrum reduction of immune response to DEN liver injury, as indicated by decreases in the liver-infiltrating F4/80+ macrophages, the apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase/NF-κB and IRF3 signaling activities, and the expression of inflammatory cytokines. Suppressed immune networks resulted in a halt of cellular senescence induction in TLR4 mutant liver tissue, which promoted proliferation and suppressed programmed cell death. Moreover, TLR4 mutation resulted in a suppressed capacity of DNA repair due to a decrease in TLR4-medicated expression of DNA repair proteins Ku70/80 in liver tissue and cells. Isotopic expression of Ku70 in TLR4 mutant mice restored senescence and interrupted the positive feedback loop of DNA damage and oxidative stress, which reversed TLR4 mutation-deteriorated HCC carcinogenesis and progression.TLR4 plays an integrated defense role against HCC carcinogenesis by enhancing the expression and function of DNA repair protein Ku70. Our studies provide novel insight into TLR4 activity in the regulation of HCC tumorigenesis, which may be useful for the prevention of HCC development.
Effect of Case-Based Training for Medical Residents on Inpatient Glycemia
Authors: Ronald Tamler, Dina E. Green, Maria Skamagas, Tracy L. Breen, Helen C. Looker, Mark Babyatsky, Derek LeRoith
Journal: Diabetes Care (2011)

To determine whether an educational intervention for medical house staff improves blood glucose (BG) in hospitalized patients.All 116 medicine residents at an academic medical center were assigned to online or classroom training on inpatient dysglycemia in fall 2008. Both groups were offered an online refresher course in spring 2009 addressing gaps in clinical practice identified on chart review. We assessed event BG, the first BG of any 3-h period, on two teaching wards.A total of 108 residents (93.1%) completed the initial training. The primary outcome, median event BG, decreased from 152 mg/dL in August 2008 to 139 mg/dL in December 2008 (P < 0.0001). Prevalence of event BG >200 mg/dL decreased from 25.5 to 22.7% (P = 0.0207), at the expense of more event BGs <70 mg/dL (2.0-3.9%, P = 0.0124).A curriculum for medicine residents on inpatient glycemia led to lower inpatient BG.
Extradural Spinal-Cord Hematoma
Authors: Donald B. Alderman
Journal: New England Journal of Medicine (1956)

DICUMAROL (3,3′-methylenebis-4-hydroxycoumarin) is a well established agent in the prevention and treatment of embolism and intravascular thrombosis by virtue of its ability to depress prothrombin formation. It was early found that the clinical use of this anticoagulant might be accompanied by hemorrhage, which has been reported as commonly occurring in the genitourinary tract, brain and cerebral meninges, postoperative wounds, pleural cavity, skin and gastrointestinal tract. Other sites of hemorrhage include the retroperitoneal tissues (sometimes after lumbar sympathetic block), the pericardial cavity and joints. The case presented below is unusual in that an extradural spinal-cord hematoma developed secondary to Dicumarol therapy. . . .
Application of molecular biomarkers in epidemiology.
Authors: M T Smith, W A Suk
Journal: Environmental Health Perspectives (1994)

The principal conclusions and opportunities that can be drawn from this conference are as follows. The meeting demonstrated the large communication gap that still exists between most epidemiologists and laboratory scientists. This problem could be overcome if epidemiologists worked closely with laboratory scientists at the outset of any project so that a better understanding could be built between them. Epidemiologists need simple, well-characterized, reproducible assays that can be applied to hundreds or thousands of people. Most laboratory scientists have little interest in running large numbers of assays, but wish to continually refine their methods so that they stay on the "cutting edge" of basic research. This problem could be overcome if the new laboratory technology could be transferred to contract laboratories or small companies. Problems of technology transfer therefore need to be addressed. Current and new biomarkers need to be better validated in the field and by studying animal models. More information on the background expression of biomarkers in the general population is needed (i.e. what is the normal range?). Ethical issues, such as the possibility that biomarkers of susceptibility could be used to exclude people from the workplace, need to be addressed.
UK government signals its support for telemedicine
Authors: J. Wise
Journal: BMJ (2011)

The UK government is backing wider use of telehealth and telecare to help people live independently and monitor their health, delegates attending a telemedicine conference heard this week.

Stephen Johnson, head of long term conditions at the Department of Health for England, told the eHealth and Telemed 2011 conference that commissioning groups had been given a very clear message about telemedicine in the NHS operating framework for 2012-13, published last week ( BMJ 2011;343:d7712, doi:10.1136/bmj.d7712).

The framework says, “PCTs [primary care trusts] working with local authorities and the emerging CCGs [clinical commissioning groups] should spread the benefits of innovations such as telehealth and telecare as part of their ongoing transformation of NHS services. They should also take full consideration of the use of telehealth and telecare as part of any local reconfiguration plans.”

It continues: “Telehealth and telecare offer opportunities for delivering care differently but also more efficiently. Use of both of these technologies in a transformed service can lead to significant reductions in hospital admissions and lead to better outcomes for patients.”

Telecare uses a combination of alarms, sensors, and …
A piece of my mind. Social Darwinism
Authors: M. A. LaCombe
Journal: JAMA (1988)

... Look, you came to me and you've got a complaint and I'll handle it, OK? But you let me be the lawyer and do this my way or you can look for somebody else. OK, OK, I just don't like somebody telling me my business, that's all. Look, we both know he's responsible for this. But you've got to sue everybody in a case like this. That's just the way it's done. That's the way the court system runs. You sue everybody to make it a big deal and very complicated and that increases your chances of winning the suit. No, it's not a question of hurting the other doctors at all. That never enters their minds, believe me. They know this is just the cost of doing business. They've got coverage, understand? It's their insurance that gets burned. Trust me. ... I don't understand why he left town, Emily. He
Increased Renal Clearance of Amylase in Pancreatitis
Authors: Michael D. Levitt, Sidney R. Cooperband
Journal: New England Journal of Medicine (1975)

To evaluate the specificity of any new method for diagnosing a disease, the correct diagnosis must first be definitively established by means independent of the test being evaluated. When the test under consideration is for the diagnosis of acute pancreatitis, a problem arises in that an operation is contraindicated, and even when surgery is performed, pathological specimens of the pancreas are seldom obtained. For lack of a better technic, the diagnosis of acute pancreatitis usually depends on demonstration of an elevated serum or urinary amylase level although such elevations are occasionally observed in a variety of other conditions such as . . .
On the cheap
Authors: Ike Iheanacho
Journal: BMJ (2007)

Like much else in health care in Britain, attempts to prescribe drugs by generic rather than brand names can be frustrating. This crucial contribution to containing the national drugs bill is sometimes disrupted by the tactics of the drug industry. And it must be rare to find patients who actively welcome being switched from a product with a familiar name and look. 

Despite these negative aspects, the prescribing of generic drugs is a success story in the UK and should be cause for celebration. That it isn't celebrated (at least, …
Is it time for an evidence based uniform for doctors?
Authors: R. Clement
Journal: BMJ (2012)

Read on to find out about Rhys Clement ’s super idea for a uniform for doctors

Hippocrates advised that doctors should “be clean in person, well dressed, and anointed with sweet smelling unguents.”1 Although this remains sound advice, the concept of acceptable attire for doctors is constantly evolving. Two hundred years ago doctors wore formal attire for all clinical activity, including surgery, because they had no idea that their clothing could transmit infection. The demonstration of micro-organisms by Pasteur revolutionised the way people thought about infection and paved the way for Lister’s concept of antisepsis that has shaped our modern approach towards infection control. 

However, Lister did not recognise clothing as a source of infection and continued to operate in formal attire. MacEwan, a student under Lister who became professor of surgery in Glasgow, is credited with introducing the sterile surgical gown. White coats made their appearance on wards and in clinics during the 20th century and are an iconic symbol of the medical profession. They were cited as a defining factor in the emerging role of hospital based care and the acceptance of the sick role outside of the home.2

The white coat remained the status quo until 2007, when the Department of Health (DOH) released dress code guidelines that forced doctors to remove their white coats, jackets, ties, and watches and roll up their sleeves.3 These guidelines were based on the findings of two literature reviews known as TVU1 and TVU2,4 5 which were commissioned and funded by the DOH “to inform policy development.”

Critics argue that evidence to support the new dress code is lacking, and the conclusions of TVU1 and TVU2 suggest there may be some merit in their argument.6 7 8 TVU1 stated that “the hypothesis that uniforms/clothing could be …
Role of conventional ovarian screening is questioned
Authors: G. Narayansingh, K. Chew, D. Parkin
Journal: BMJ (1999)

EDITOR—It is heartening to read Roylance and Waxman's personal view of cancer screening.1 They say that current screening schedules are predominantly subjective and are heavily based on individuals' interpretation, and proposed that we should pursue the path of molecular screening technologies.

Three postmenopausal women recently presented to our service with advanced ovarian cancer; of note was the fact that they had been evaluated for vaginal bleeding within the past six months. All three had had examination under anaesthesia, hysteroscopy, …
In support of the early presence of functional categories in second language acquisition
Authors: Kazue Kanno
Journal: Behavioral and Brain Sciences (1996)

Abstract This commentary focuses on whether the full set of categories is available to beginning L2 learners. After critiquing Epstein et al.'s experimental evidence for the presence of functional categories, I outline the results of an experiment involving English speakers learning Japanese as a second language that does indeed point toward the early presence of fuuctional categories.
Resumption of Hormonal Therapy
Authors: W. W.S. Loui
Journal: CA A Cancer Journal for Clinicians (1986)

if we have no Mohs-trained surgeons?â€•We reply by recommending that the ophthalmic surgeon ask his or her patholo gist colleague to make horizontal rather than vertical sections to be certain of the removal of all malignancy.Fig. 6 shows (A)
Carcinogenic potential of phthalic acid esters and related compounds: structure-activity relationships.
Authors: W M Kluwe
Journal: Environmental Health Perspectives (1986)

Chronic toxicity and carcinogenicity studies of several phthalic acid esters (PAEs) and compounds containing a 2-ethylhexyl moiety were conducted in Fischer 344 rats and B6C3F1 (hybrid) mice. The compounds studied were phthalic anhydride, di(2-ethylhexyl) phthalate, butyl benzyl phthalate, diallyl phthalate, di(2-ethylhexyl) adipate, tris(2-ethylhexyl) phosphate, and 2-ethylhexyl sulfate (sodium salt). Estimated maximum tolerable doses and fractionally lower doses of each compound were administered to groups of 50 male and 50 female rats and mice for 2 years, followed by sacrifice, necropsy, and histopathological examination of major organs and tissues. The low toxic potencies of most of the compounds allowed for relatively high doses to be given during the chronic studies. In general, the toxic manifestations of the PAEs were closely correlated with their ester substituents. Although many of the PAEs possessed some carcinogenic activity, target sites for such effects were dissimilar, suggesting the absence of a common mode of action. In contrast, all of the 2-ethylhexyl-containing compounds studied possessed some hepatocarcinogenic activity, indicating that this moiety may have a propensity for causing hepatocarcinogenesis in mice, particularly those of the female sex. The 2-ethylhexyl compound that caused the greatest hepatocarcinogenic response in mice, di(2-ethylhexyl) phthalate, was also hepatocarcinogenic in rats. Similarly, those with a relatively greater effect in female mice were also active in male mice. Thus, sex and species differences in 2-ethylhexyl-induced hepatocarcinogenesis in rodents are probably quantitative rather than qualitative in nature.
Molecular analysis of T‐cell clonality with concomitant specific T‐cell proliferation <i>in vitro</i> in nickel‐allergic individuals
Authors: B. Summer, C. A. Sander, B. Przybilla, P. Thomas
Journal: Allergy (2001)

Background: The peripheral blood mononuclear cells (PBMC) of individuals with nickel contact allergy are reported to proliferate to a varying degree upon nickel stimulation in vitro . Different phenotypes of the T cells involved are described. With regard to preferential use of the T‐cell receptor (TCR), analysis of the several families of the TCR‐γ gene allows rearrangement evaluation of all T cells regardless of predominant surface expression of TCR α/β. Methods: The PBMC of 10 nickel‐allergic and five nonallergic individuals were cultured for 4 days in the presence of either medium, PHA, NiSO 4 , or tetanus toxoid (TT). Proliferation was measured by radioactive thymidine uptake and expressed as stimulation index (SI). T‐cell clonality was assessed by analysis of the TCR‐γ chain gene, including the use of PCR with a primer combination covering the four main groups (Vγ1‐8, Vγ9, Vγ10, and Vγ11) of the variable region of the TCR‐β chain gene. Results: In the allergic individuals, proliferation to NiSO 4 was significantly ( P &lt;0.05) higher than in nonallergics (mean SI: 18.05/17.87 vs 0.67/2.27). In unstimulated and PHA‐stimulated cultures, there was a random TCR spectrum in both groups. In contrast, in nickel‐allergic individuals or individuals with recent TT‐booster, oligoclonality could be observed in the correspondingly stimulated cultures. Conclusions: In addition to proliferation assay, analysis of T‐cell clonality may be a further means to characterize clinical hypersensitivity reactions on the basis of antigen‐dependent oligoclonal T‐cell expansion, as in the case of tissue‐infiltrating lymphocytes.
Research on Humans Published in JAMA-Reply
Authors: Courtenay Bartholomew
Journal: JAMA (1987)

<h3>In Reply.—</h3> The recognition of the first cases of atypical lymphocytes and AIDS in Trinidad prompted an inquiry into the prevalence of HIV and human T-cell lymphotropic virus (HTLV-I) antibodies among homosexual men and the general population. At that time, there were no commercial assays available, so we sought the collaboration of our colleagues at the National Cancer Institute. On this island, communitywide publicity in the local press and at scientific meetings of the medical fraternity has been given to all our research projects on hepatitis, HTLV-I, and HIV since 1983. Obviously, we considered it to be of urgent public health importance to ascertain the prevalence of HTLV infections in Trinidad, and the only available stored serum samples from adults at that time were those from the hepatitis survey of 1982. In fact, of the 4450 coded samples, only 1729 were found suitable for retesting. The hepatitis cohort was not
Dangerous antihypertensive treatment.
Authors: R Goodfellow
Journal: BMJ (1979)

of myocardial infarction,"' 12 together with the relationship between the incidence of PVF and early admission in the hospital series,7 suggests electrophysiological dis- turbance within the heart leading to ventricular fibrillation but clearing within 24 hours.Thus, although it is true that the heart at 17-18 hours after the onset of symptoms may not be especially vulnerable to serious arrhythmias and that they do not at this stage constitute an independent risk factor, the same conclusion cannot be drawn when these serious arrythmias occur within the first two hours.
Systemic lupus erythematosus, pulmonary hypertension, and left recurrent laryngeal nerve palsy.
Authors: O M Aszkenasy, T J Clarke, P Hickling, A J Marshall
Journal: Annals of the Rheumatic Diseases (1987)

Pulmonary hypertension in systemic lupus erythematosus (SLE) is rare in the absence of parenchymal lung disease. We report such a case, which was complicated by the subsequent development of a left recurrent laryngeal nerve palsy, and in which there was a strong family history of SLE.
Study authors respond to points in editorial
Authors: N. Cullum, M. Bland, J. Dumville, C. Iglesias, S. O'Meara, M. Soares, D. Torgerson, A. Nelson, G. Worthy
Journal: BMJ (2009)

In the editorial accompanying our three papers on leg ulcers, Grey and colleagues make several points that deserve reply.1 2 3 4

They do not like our selection of time to healing as the primary outcome in the larval therapy study, but debridement is practised precisely because it is thought to aid healing. They claim that debridement “is more valuable to clinicians,” but is …
Popliteal Cyst: Diagnostic Dilemmas
Authors: Hugh H. Hussey
Journal: JAMA (1974)

Popliteal cyst (sometimes called Baker cyst, for the man who first described it and not because it afflicts bakers especially) is a benign disorder that ordinarily does nothing more than cause mild discomfort and represent a cosmetic annoyance when present in a woman. Occasionally, however, a popliteal cyst engenders diagnostic dilemmas. This fact is exemplified in a report by Schmidt et al in the current issue of the Archives of Internal Medicine (134:694-698, 1974).  The authors describe ten patients in whom a popliteal cyst was part of the picture of rheumatoid or other arthritis of the knee joint. They noted that the gastrocnemiussemimembranosus bursa frequently communicates with the knee joint, wherein an effusion may thereby lead to a popliteal cyst. In the ten patients, rupture of the cysts caused extravasation of the cyst fluid into the compartments of the calf. There followed symptoms and signs that closely mimicked thrombophlebitis of
Transmission of Infectious Hepatitis by Transfusion of Whole Blood
Authors: A. Gardner Harden, Jeremiah A. Barondess, Brent Parker
Journal: New England Journal of Medicine (1955)

CLINICAL, epidemiologic and experimental studies in recent years have defined some of the features of infection with the viruses of infectious (epidemic) hepatitis and serum hepatitis. It has been noted that the former disease is usually transmitted by person-to-person contact, probably by the fecal-oral route; the virus of infectious hepatitis has been found in the stool in acute cases of the disease,1 , 2 and in the stools of 2 children, five and fifteen months respectively after the acute illness.3 Blood-stream invasion by this virus is probably common, and may be an integral part of the infection; it has been noted in . . .
Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C
Authors: Yasuji Arase, Mariko Kobayashi, Fumitaka Suzuki, Yoshiyuki Suzuki, Yusuke Kawamura, Norio Akuta, Masahiro Kobayashi, Hitomi Sezaki, Satoshi Saito, Tetsuya Hosaka, Kenji Ikeda, Hiromitsu Kumada, Tetsuro Kobayashi
Journal: Hepatology (2012)

The aim of this retrospective cohort study was to assess the cumulative development incidence and predictive factors for malignancies after the termination of interferon (IFN) therapy in Japanese patients for hepatitis C virus (HCV). A total of 4,302 HCV-positive patients treated with IFN were enrolled. The mean observation period was 8.1 years. The primary outcome was the first onset of malignancies. Evaluation was performed using the Kaplan-Meier method and Cox proportional hazard analysis. A total of 606 patients developed malignancies: 393 developed hepatocellular carcinoma (HCC) and 213 developed malignancies other than HCC. The cumulative development rate of HCC was 4.3% at 5 years, 10.5% at 10 years, and 19.7% at 15 years. HCC occurred significantly (P<0.05) when the following characteristics were present: advanced histological staging, sustained virological response not achieved, male sex, advanced age of ≥50 years, total alcohol intake of ≥200 kg, and presence of type 2 diabetes (T2DM). T2DM caused a 1.73-fold enhancement in HCC development. In patients with T2DM, HCC decreased when patients had a mean hemoglobin A1c (HbA1c) level of <7.0% during follow-up (hazard ratio, 0.56; 95% confidence interval, 0.33-0.89; P=0.015). The cumulative development rate of malignancy other than HCC was 2.4% at 5 years, 5.1% at 10 years, and 9.8% at 15 years. Malignancies other than HCC occurred significantly when patients were of advanced age of ≤50 years, smoking index (package per day×year) was ≥20, and T2DM was present. T2DM caused a 1.70-fold enhancement in the development of malignancies other than HCC.T2DM causes an approximately 1.7-fold enhancement in the development of HCC and malignancies other than HCC in HCV-positive patients treated with IFN. In T2DM patients, maintaining a mean HbA1c level of <7.0% reduces the development of HCC.
MALPRACTICE RISKS CONFRONTING THE PSYCHIATRIST: A NATIONWIDE FIFTEEN-YEAR STUDY OF APPELLATE COURT CASES, 1946 TO 1961
Authors: WILLIAM A. BELLAMY
Journal: American Journal of Psychiatry (1962)

It is remarkable that this small series of clinical-legal psychiatric cases reflects nearly all the legal trends relating to malpractice found within high risk groups in medical practice : eminence is no protection against being sued for negligence; the courts are expecting a higher duty of care from the psychiatrist as the specialty gains status in the eyes of medicine and law; awards are beginning to appear against psychiatrists, and in increasing amounts; claims on the basis of unenlightened consent and breach of warranty are beginning to appear; the law of warranty, generally, is being applied in more cases; and the relative immunity from negligence action formerly enjoyed by hospitals (including charitable organizations) is rapidly being lost, if recent court decisions continue to prevail.