tbuckley/cabot-search huggingface dataset:
Cholic acid mediates negative feedback regulation of bile acid synthesis in mice
Authors: Jia Li-Hawkins, Mats Gåfvels, Maria Olin, Erik G. Lund, Ulla Andersson, Gertrud Schuster, Ingemar Björkhem, David W. Russell, Gosta Eggertsen
Journal: Journal of Clinical Investigation (2002)

Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12α-hydroxylase gene (Cyp8b1) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7α-hydroxylase (CYP7A1) is lost in Cyp8b1–/– mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor.
Acute Poisoning with Ethinamate and with Carbromal
Authors: S. C. Siang
Journal: BMJ (1960)

MEDICAL MEMORANDA BRrr=excised nine months later was an anaplastic squamous-cell carcinoma, similar to that in the cervix, situated in the subcutaneous tissues and ulcerating through the skin.The clumps of tumour cells were surrounded by an abundant cellular stroma, and in this, and mingling with the tumour cells, were large numbers of histiocytes containing iron (Fig. 2), while in other areas the iron appeared to be lying free in the tissues.The amount of residual iron was greater than that reported at similar injection sites by Golberg (1960).The fibrous reaction around the carcinoma was unusually exuberant, and a similar reaction was present in the subcutaneous fat, which also contained iron, but there was no evidence that this reaction was neoplastic.COMMENT In the experimental animal the injection of large doses of iron-dextran have produced sarcomata at the injection site, but there is no evidence that this occurs in humans, nor is there any indication that the substance was directly carcinogenic in this case.It seems likely that the lesion in the buttock was a metastasis from the carcinoma in the cervix, but it does seem probable that the intense reactive hyperplasia induced in the subcutaneous tissues by the injection of iron-dextran localized this bizarre secondary tumour.
Exacerbations in 1-antitrypsin deficiency
Authors: M. Needham
Journal: European Respiratory Journal (2005)

This study aimed to investigate the nature and effect of exacerbations in patients with α<sub>1</sub>-antitrypsin deficiency and to assess the impact of exacerbations on health status. Furthermore, the relationship of exacerbations to changes in lung function and health status was investigated. In total, 265 patients with severe deficiency (PiZ phenotype) were assessed over 12 months and a subgroup of 87 patients was studied for 3 yrs. Exacerbations were recorded and patients underwent full lung function testing and health status measurement. Exacerbations occurred in 142 patients (54%) over 12 months, with a median duration of 14 days (interquartile range 7–21). Health status was significantly worse in patients with exacerbations, especially those with frequent exacerbations. Neither the presence nor the frequency of exacerbations showed a relationship to decline in forced expiratory volume in one second, but the number of exacerbations was weakly associated with decline in gas transfer of the lung for carbon monoxide. Despite lung function decline, health status did not change significantly over 3 yrs. In conclusion, exacerbations occur commonly in patients with α<sub>1</sub>-antitrypsin deficiency and are associated with worse health status. Exacerbations were associated with a decline in the gas transfer of the lung for carbon monoxide over time, but show no relationship to changes in forced expiratory volume in one second. Despite lung function decline, patients do not show a progressive loss in health status.
The Press of Iatric Articulation
Authors: H. Paul Johnson
Journal: JAMA (1964)

<h3>To the Editor:—</h3> One of the great derelictions in a democracy is the failure of citizens to realize they have a duty to respond, in writing, on subjects of public concern as they are treated in the public information media. If physicians have a poor press, it is because they do not express themselves sufficiently or frequently. It is not essential that the physician be prominent. He need only be factual, temperate, brief, and able to avoid bias and prejudicial language. The effectiveness of any such communication is not to be measured in terms of its being published, for if one letter is published it indicates that several more expressing the same convictions have been received. I am afraid we physicians are inclined to assume that our state and national organizations can carry the total responsiblity, and this is, in a sense, the reason why there is such a widespread
Vicarious Excretion of Technetium-99m MAG3 in a Patient with Polycystic Renal Disease
Authors: DENNIS W. WULFECK, NOLAN K. SAKOW, SEYHAN O. SENLER
Journal: Clinical Nuclear Medicine (1993)

This case demonstrates vicarious excretion of Tc-99m mercaptoacetyltriglycine (MAG 3 ) establishing cystic and common bile duct patency in a patient with polycystic kidney disease
Hepatitis C virus in a hemodialysis unit: Molecular evidence for nosocomial transmission
Authors: Lieven Stuyver, Hendrik Claeys, Ann Wyseur, Wouter Van Arnhem, Hans De Beenhouwer, Stijn Uytendaele, Jan Beckers, Dirk Matthijs, Geert Leroux-Roels, Geert Maertens, Marc De Paepe
Journal: Kidney International (1996)
Exploring the Substitution of Exenatide for Insulin in Patients With Type 2 Diabetes Treated With Insulin in Combination With Oral Antidiabetes Agents
Authors: Stephen N. Davis, Don Johns, David Maggs, Hangtao Xu, Justin H. Northrup, Robert G. Brodows
Journal: Diabetes Care (2007)

OBJECTIVE— This 16-week study explored the safety of substituting exenatide for insulin in patients with type 2 diabetes using insulin in combination with oral antidiabetes agents. RESEARCH DESIGN AND METHODS— Successful maintenance of glycemic control was predefined as an A1C increase of &amp;lt;0.5%. A total of 49 patients (aged 53 ± 8 years, with BMI 34 ± 4 kg/m2, A1C 8.1 ± 1.1%, and duration of diabetes 11 ± 7 years) were randomized to either substitute exenatide for insulin or remain on their current insulin regimen. Patients who either completed ≥8 weeks of study or discontinued because of loss of glycemic control were included in primary efficacy analysis. RESULTS— A total of 62% (18 of 29) of the exenatide-treated patients maintained glycemic control compared with 81% (13 of 16) of the insulin-treated patients. Of the 11 exenatide-treated patients who did not maintain control, 5 discontinued before week 16 because of loss of glucose control. The overall safety profile was generally consistent with previous exenatide trials. The mean overall hypoglycemia rates were 1.72 and 0.97 events/patient-year for the exenatide and insulin reference groups, respectively. CONCLUSIONS— This pilot study suggests that it is feasible to sustain glycemic control when substituting exenatide for insulin. Although it is not possible to characterize clear predictors of outcome given the size and exploratory nature of the study, the data suggest that patients with longer disease duration, who are taking higher doses of insulin and have less endogenous β-cell function, may experience deterioration in glucose control if exenatide is substituted for insulin therapy.
CINACIGUAT, A SOLUBLE GUANYLATE CYCLASE ACTIVATOR, UNLOADS THE HEART IN ACUTE DECOMPENSATED HEART FAILURE
Authors: Erland Erdmann, Marc J. Semigran, Markku S. Nieminen, Rahul Agrawal, Veselin Mitrovic, Alexandre Mebazaa
Journal: Journal of the American College of Cardiology (2010)
Commentary: The value of complexity
Authors: E. Peile
Journal: BMJ (2009)

This case is complex.1 For undergraduate learning “complex and elaborate examples are likely to be suboptimal as effective teaching tools,”2 but is the same true for postgraduate learners? What do we learn in the midst of complexity? Initially we are caught up in the urgency of lifesaving measures as the desperately ill patient fails to respond to primary interventions, and then when she does respond to steroids we have to ask ourselves why. The authors reflect the frustration of clinicians and patient alike as potential diagnostic clues are followed down blind alleys.

There is rich learning here about our clinical reasoning processes. Now that we know the denouement …
Ovarian hyperstimulation: actual and theoretical risks.
Authors: B H Smith, I D Cooke
Journal: BMJ (1991)

themselves in the month after childbirth and did so by violent means suggests that many of them were psychotic.Suicide is always a tragic event, particularly if the victim is-like Shakespeare's Lucretia or Ibsen's Hedda Gabler-a young woman with an unborn or newborn child.We can be thankful that suicides ofthis kind are now so rare.We can also derive some satisfaction from our ability to make sense of the trends and relations we observe.
Doxycycline Therapy for Leptospirosis
Authors: J. BRUCE L. McCLAIN
Journal: Annals of Internal Medicine (1984)

To study antibiotic efficacy, 29 patients with leptospirosis were treated in a randomized, double-blinded fashion with doxycycline, 100 mg orally twice a day, or placebo. Therapy was given for 7 days in a hospital, and patients were followed for 3 weeks afterwards. Duration of illness before therapy and severity of illness were the same in both groups. Doxycycline reduced the duration of illness by 2 days and favorably affected fever, malaise, headache, and myalgias. Treatment prevented leptospiruria and had no adverse effects. Doxycycline is effective in therapy for patients with leptospirosis.
British surgeon faces compensation claims for patient deaths
Authors: C. Dyer
Journal: BMJ (1998)

A British surgeon whose conviction in New Zealand for the manslaughter of a patient was overturned by the Privy Council in London now faces compensation claims from families of patients who died during surgery.

Keith Ramstead was convicted of the manslaughter of Nancie Muncie, 72, but acquitted of similar charges over the deaths of two other patients. Last month, the Privy Council quashed his conviction because of a “material irregularity” in the 1996 trial. The deaths happened between 1991 and 1993 while Mr Ramstead, …
Psychoanalysis. Alive and well at 80
Authors: G. L. Engel
Journal: JAMA (1975)

ON THE occasion of Freud's death in 1939,The Journaleditorialized that "Psychoanalysis has become firmly established in psychology, education, and medicine."<sup>1</sup>Thirty-five years later,The Journalpublished a COMMENTARY by Jacob Conn entitled, "The Decline of Psychoanalysis."<sup>2</sup>Both express the wishes of their respective authors, for neither very accurately reflects the true state of affairs, not in 1939, not in 1974. By 1939 psychoanalysis had had considerable impact on psychology, relatively little on education other than in a popularized form, and virtually none at all on the mainstream of medicine, psychiatry included. It was not part of the educational experience of medical students, few analysts being members of medical school faculties in 1939. Nor did psychiatrists have any significant exposure to psychoanalysis as part of their formal education. In 1939 there were six psychoanalytic training institutes and the total membership of the American Psychoanalytic Association was less
Effects of ghrelin, growth hormone–releasing peptide–6, and growth hormone–releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus
Authors: Larissa Bianca Paiva Cunha de Sá, Sergio Oliva Nascif, Silvia Regina Correa-Silva, Patricia Molica, José Gilberto Henriques Vieira, Sergio Atala Dib, Ana-Maria Judith Lengyel
Journal: Metabolism (2010)
OUTCOMES OF THE SECOND-GENERATION DRUG ELUTING STENTS IN TREATING SMALL VESSEL: ABLUMINAL BIOLIMUS-ELUTING BIODEGRADABLE POLYMER STENT AND ZOTAROLIMUS-ELUTING PERMANENT POLYMER STENT
Authors: Young Won Yoon, Hyuck Moon Kwon, Byung Kwon Lee, Bum-Kee Hong, Hye Moon Chung, Ji Hyun Yoon, Se Joong Rim
Journal: Journal of the American College of Cardiology (2014)
Strangulated Femoral Hernia: Reduction by Inversion
Authors: T. T. Griffith
Journal: BMJ (1863)

<b>Background:</b> Previous studies show that sickness absence predicts health, but it is unclear whether this association is persistent over time and whether specific diseases underlie long-term associations. The aim of this study was to investigate overall and diagnosis-specific sickness absences as predictors of sustained sub-optimal health. <b>Methods:</b> Prospective occupational cohort study of 15,320 employees (73% men) aged 37 to 51. Sickness absence records in 1990-1992, including 13 diagnostic categories, were examined in relation to self-rated health measured annually for the years 1993-2006. <b>Results:</b> 3,385 employees (22%) had &gt;30 days of sickness absence and 5,564 (36%) 1-30 days during the 3-year exposure window. Repeated-measures logistic regression analysis adjusted for age, sex, occupational status and chronic diseases show employees with &gt;30 absence days, compared to those with no absences, had 2.14 (95% CI 2.00-2.29) times higher odds for suboptimal health over the 14 years of follow-up. Retirement did not dilute this association. 9 sickness absence diagnostic categories, such as diseases of the nervous, circulatory, metabolic, musculoskeletal, sensory and gastro-intestinal systems, cancer, mental disorders and external causes, independently predicted increased risk of sustained sub-optimal health. <b>Conclusions:</b> There is a remarkably persistent association between sickness absence and future long-term self-rated health status for the majority of diagnostic categories for sickness absence. This suggests that the association between sickness absence and health is ubiquitous and not driven by a limited number of rare and severe diseases.
Comprehensive analysis for viral elements and interleukin-28B polymorphisms in response to pegylated interferon plus ribavirin therapy in hepatitis C virus 1B infection
Authors: Shinya Maekawa, Minoru Sakamoto, Mika Miura, Makoto Kadokura, Ryota Sueki, Kazuki Komase, Hiroko Shindo, Nobutoshi Komatsu, Kuniaki Shindo, Asuka Kanayama, Takako Ohmori, Fumitake Amemiya, Shinichi Takano, Tatsuya Yamaguchi, Yasuhiro Nakayama, Takatoshi Kitamura, Taisuke Inoue, Shunichi Okada, Nobuyuki Enomoto
Journal: Hepatology (2012)

To comprehensively characterize the contribution of virological factors as well as interleukin-28B (IL28B) single-nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated-interferon plus ribavirin (Peg-IFN/RBV) therapy for chronic hepatitis C virus (HCV)-1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino-acid (aa) sequence study in 103 consecutive HCV-1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding-window comparison analysis to characterize response-specific viral sequences, along with IL28B SNP analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), nonearly viral response (nEVR), sustained virological response (SVR), or relapse, the following regions were extracted as most significantly associated with the different responses respectively: nonstructural protein 5A (NS5A) aa.2224-2248 (P = 1.2E-07); core aa.70 (P = 4E-04); NS5A aa.2340-2382 (P = 7.0E-08); and NS5A aa.2360-2377 (P = 1.1E-05). Those NS5A regions nearly coincided with the interferon (IFN) sensitivity-determining region (NS5A aa.2209-2248) and the IFN/RBV resistance-determining region (NS5A aa.2339-2379). In a multivariate analysis, the IL28B SNP (odds ratio [OR] = 16.8; P = 0.009) and NS5A aa.2340-2382 (OR = 13.8; P = 0.0003) were extracted as the two most-significant independent variables contributing to the final outcome.In Peg-IFN/RBV therapy, polymorphisms in IL28B, NS5A aa.2224-2248, core aa.70, and, most important, NS5A aa.2340-2382 have a tremendous influence on treatment response in association with viral kinetics, resulting in significantly different outcomes in chronic HCV-1b infection.
'Tuning' of type I interferon–induced Jak-STAT1 signaling by calcium-dependent kinases in macrophages
Authors: Lu Wang, Ioannis Tassiulas, Kyung-Hyun Park-Min, Alicia C Reid, Hava Gil-Henn, Joseph Schlessinger, Roland Baron, J Jillian Zhang, Lionel B Ivashkiv
Journal: Nature Immunology (2007)
A 66 year old woman with breathlessness: case presentation
Authors: Douglas Lowdon, Marion McMurdo
Journal: BMJ (2004)

Mrs Dempsey is a 66 year old woman who until recently had led a fit and active life. She was referred to the acute medical assessment clinic with a two month history of breathlessness and swollen ankles. She complained, “I get out of breath when I do the housework and I can't even walk to the corner shop.” Her general practitioner had thought she had heart failure and prescribed diuretics. Further questioning revealed the onset to be insidious and that her dyspnoea had not improved despite diuretics. She described four pillow orthopnoea and denied chest pain, palpitations, wheeze, or cough.

On …
Prevention of Warts
Authors: C. E. Hollman
Journal: BMJ (1961)

the discrepancy between the diagnosis of thyroid carcinoma in surgical specimens (4.1 %) and the incidence of thyroid carcinoma at post-mortem (0.6%).The present position is unsatisfactory, and the reasons advanced for the difference are unconvincing.The matter is not merely academic.To justify modern teaching that all thyroid adenomata should be removed to prevent cancer, patients should know whether the chance of cancer is 25 to 1 or 1,000 to 6.In North America, where a fee for each operation colours the picture, the matter is still more important.In 1960 I investigated the subject in London, Paris, Basle, Vienna, and Fribourg, and consulted authorities from Edinburgh and Rotterdam.No one I saw was satisfied with the present position.
Fortnightly review: Update on male erectile dysfunction
Authors: G Wagner, I Saenz de Tejada
Journal: BMJ (1998)

Male erectile dysfunction—defined as “the inability to achieve or maintain an erection sufficient for sexual intercourse”—is one of the most common sexual dysfunctions in men.1 Although erectile dysfunction can be primarily psychogenic in origin, most patients have an organic disorder, commonly with some psychogenic overlay.1 Some men assume that erectile failure is a natural part of the aging process and tolerate it; for others it is devastating. Withdrawal from sexual intimacy because of fear of failure can damage relationships and have a profound effect on overall wellbeing for the couple.2 Since erectile dysfunction often accompanies chronic illnesses, such as diabetes mellitus, heart disease, hypertension, and a variety of neurological diseases, physicians from many medical disciplines will see patients with this disorder.3

#### Summary points

Although around 10% of men aged 40 to 70 years have complete erectile dysfunction, only a few seek medical help

As erectile dysfunction is frequently associated with a number of systemic illnesses and surgical treatments, a wide range of doctors must be aware of the condition in their patients

Current effective treatments include psychosexual counselling, vacuum erection devices, intracavernosal and transurethral drug delivery, and penile prostheses

Promising oral treatments are currently being investigated

Both doctors and the public need to be better informed about erectile dysfunction and its treatment

The publications comprising this review were selected from a formal search of the full Medline database (using the terms erectile dysfunction, impotence, and penile erection). Articles from the authors' personal collections are also included.

The Massachusetts male aging study measured several health related variables in 1290 men aged 40 to 70 years.3 Erectile dysfunction was very common. Fifty two per cent of the men reported some degree of impotence—mild in 17.1%, moderate in 25.2%, and complete in 9.6%.3 Complete impotence was reported by 5% …
Increased endothelin in experimental heart failure.
Authors: K B Margulies, F L Hildebrand, A Lerman, M A Perrella, J C Burnett
Journal: Circulation (1990)

Recent studies demonstrate that endothelin, a potent endogenous vasoconstrictor peptide, circulates in plasma of normal animals and humans. However, the role of this peptide in pathophysiological states remains unclear. The present study was designed to test the hypothesis that circulating endothelin concentrations are increased in experimental congestive heart failure (CHF), a pathophysiological state characterized by activation of vasoconstrictor mechanisms. In anesthetized dogs with CHF produced by 8 days of rapid ventricular pacing (n = 28), circulating plasma endothelin was increased compared with values for normal controls (n = 28; 20.4 +/- 1.4 versus 9.7 +/- 0.9 pg/ml, respectively; p less than 0.0001). A plasma endothelin level of more than 14.0 was a sensitive and specific indicator of significant CHF. Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels. Based on recent studies demonstrating the physiological actions of twofold increases in circulating endothelin, as observed in the present study, a possible role for endothelin in the pathophysiology of CHF is advanced.
Abstract 4733: Function of cytoplasmic histone deacetylase 5 is required for HIF-1α stability
Authors: Shuyang Chen, Chengqian Ying, Dongming Liang, Niti Jethava, Nianli Sang
Journal: Cancer Research (2012)

Abstract Hypoxia is frequently associated with solid tumors and ischemic disorders, which are the top two leading causes of mortality in the world. Hypoxia-inducible factor 1 is a major regulator of angiogenesis and cellular adaptation to hypoxia. Accordingly HIF function has been considered a therapeutic target for multiple diseases. Histone deacetylase (HDAC) activity has been involved in regulating HIF function and HDAC inhibitors (HDACIs) have been documented to repress HIF function. However, histone deacetylases encompass multiple members, each has different cellular functions. HDACIs in clinical application or under development generally inhibit more than one HDAC. It is unclear which specific member of the HDAC family is involved in the regulation of HIF function. We present data here to show that histone deacetylase 5 (HDAC5) is required for HIF-1α protein stability. Knock-down of HDAC5 impaired hypoxic accumulation of HIF-1α and its function. In contrast, knock-down of HDAC1, HDAC3 or HDAC6 showed little or no effect. On the other hand, overexpression of HDAC5 enhanced HIF-1α stability. Specifically, cytosol localized HDAC5 mutant shows stronger effects on stabilizing HIF-1α compared to wild-type HDAC5. Mutation demolishing the deacetylase activity abolished the ability of HDAC5 to stabilize HIF-1α. Taken together, our data suggest that a cytosolic deacetylase activity of HDAC5 is required to stabilize HIF-1α. These findings also suggest that HDAC5 could be biological target for therapies based on modulating HIF function. This work is supported in part by grant R01-CA129494 (N.S.) from NCI, NIH. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4733. doi:1538-7445.AM2012-4733