tbuckley/cabot-search huggingface dataset:
Anatomy of a complaint
Authors: G F Davies
Journal: BMJ (1994)

It may seem a long time ago but the events of 26 December 1992 will remain etched in my memory for a long time. On Boxing Day evening I received a request for telephone advice from a husband worried about his wife. I decided to visit, took a history, performed a physical examination, and gave treatment and advice.

When I returned to work I was shocked to hear that Mrs X had died on 28 December 1992 following admission to hospital by my partner the day before. My emotions were mixed and multiple: shock, sympathy, fear - fear of a mistake, fear of a complaint.

I mentally tortured myself that evening reliving the events of that day. Did I make the right decision? Could I have done more? Why didn't I admit her to hospital? Racked with guilt I began to expect rumblings of discontent from the family, questioning from the family, or even a complaint.

Over the next two weeks I tried, with little success, to put the matter out of my mind until my partner called me to her surgery. Three uncompromising family members reeled off a battery of questions. I was ill prepared and failed to satisfy the family by justifying my actions. Notes were taken and a declaration made that they were dissatisfied and that they would take the matter further.

I pondered, trembling. What does this mean? What will happen next? Logic overtook me, there was nothing more I could do except await events.

The months passed ... February, March, April ... My confidence began …
Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia
Authors: Manju A. Kurian, Juan Zhen, Shu-Yuan Cheng, Yan Li, Santosh R. Mordekar, Philip Jardine, Neil V. Morgan, Esther Meyer, Louise Tee, Shanaz Pasha, Evangeline Wassmer, Simon J.R. Heales, Paul Gissen, Maarten E.A. Reith, Eamonn R. Maher
Journal: Journal of Clinical Investigation (2009)

Genetic variants of the SLC6A3 gene that encodes the human dopamine transporter (DAT) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder. In addition, the homozygous Slc6a3 knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile parkinsonism-dystonia (IPD) syndrome and identified homozygous missense SLC6A3 mutations (p.L368Q and p.P395L) in both families. Functional studies demonstrated that both mutations were loss-of-function mutations that severely reduced levels of mature (85-kDa) DAT while having a differential effect on the apparent binding affinity of dopamine. Thus, in humans, loss-of-function SLC6A3 mutations that impair DAT-mediated dopamine transport activity are associated with an early-onset complex movement disorder. Identification of the molecular basis of IPD suggests SLC6A3 as a candidate susceptibility gene for other movement disorders associated with parkinsonism and/or dystonic features.
Sanctity of life law has gone too far
Authors: R. Gillon
Journal: BMJ (2012)

Recent court ruling distorts healthcare provision and values and should be challenged 

Last year an English judge ruled, with the explicit approval of the president of the Court of Protection, that under the rules of that court all patients in a minimally conscious state must be referred to the Court of Protection if life prolonging treatment by artificial nutrition and hydration is to be withheld or withdrawn.1 2 3 Moreover, the judge emphasised that in deciding whether such withdrawal would be in these patients’ best interests it would “be wrong to attach significant weight” to their previously expressed values, wishes, and views unless these had been expressed in a legally valid and applicable advance decision. What should be given great “though not absolute” weight was the sanctity of life. The judge said (paragraph 230), “[given] the importance of the sanctity of life, and the fatal consequences of withdrawing treatment, and the absence of an advance decision that complied with the requirements previously specified …
Cut off values of bone mineral density defining postmenopausal women with bone fractures.
Authors: G G Riario-Sforza, C Incorvaia, A Scazzoso, T Travisi, F Nitti, M Fumagalli
Journal: Annals of the Rheumatic Diseases (1995)

To define cut off values of bone mineral density (BMD), measured at different forearm sites by single photon absorptiometry, that discriminated postmenopausal women who have had fractures from those who have not, in order to provide an index of fracture risk for screening purposes.BMD values were measured at distal third radius (DTR) and ultradistal radius (UDR) sites in two groups of postmenopausal women. Group 1 (n = 398) had not suffered fractures, and group 2 (n = 354) had appendicular fractures. Results were evaluated using receiver operating characteristic (ROC) curves.BMD values were significantly greater (p < 0.001) at both sites in group 1. Weight was lower in group 2 than in group 1 (p < 0.001). The BMD cut off value was 0.596 g/cm2 at DTR (sensitivity 63%, specificity 72%), and 0.310 g/cm2 at UDR (sensitivity 80%, specificity 80%). Values of area under ROC curves estimated for UDR were greater than for those DTR (p < 0.001).For screening purposes the BMD cut off value of 0.310 g/cm2 at the UDR may be useful in identifying women at high risk of fracture in an unselected postmenopausal population. BMD measured at UDR appeared to have a better predictive value than that at DTR.
Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example: Table 1
Authors: Robert B M Landewé, Josef S Smolen, Michael E Weinblatt, Paul Emery, Maxime Dougados, Roy Fleischmann, Daniel Aletaha, Arthur Kavanaugh, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2014)

Investigator-initiated trials, some of which have been referred to as comparative effectiveness trials, pragmatic trials, or strategy trials, are sometimes considered to be of greater clinical importance than industry-driven trials, because they address important but unresolved clinical questions that differ from the questions asked in industry-driven trials. Regulatory authorities have provided methodological guidance for industry-driven trials for the approval of new treatments, but such guidance is less clear for investigator-initiated trials. The European League Against Rheumatism (EULAR) task force for the update of the recommendations for the management of rheumatoid arthritis has critically looked at the methodological quality and conduct of many investigator-initiated trials, and has identified a number of concerns. In this Viewpoint paper, we highlight commonly encountered issues that are discussed using examples of well-known investigator-initiated trials. These issues cover three themes: (1) design choice (superiority vs non-inferiority designs); (2) statistical power and (3) convenience reporting. Since we acknowledge the importance of investigator-initiated research, we also propose a shortlist of points-to-consider when designing, performing and reporting investigator-initiated trials.
Prosthetic Valvular Endocarditis: A Twelve-Year Review.
Authors: Laura Slaughter
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Prosthetic Valvular Endocarditis: A Twelve-Year Review.Laura Slaughter, M.D., James F. Morris, M.D., Albert Starr, M.D.Laura Slaughter, M.D.Search for more papers by this author, James F. Morris, M.D.Search for more papers by this author, Albert Starr, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-826_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWe reviewed the case records of 48 patients with infected prosthetic cardiac valves (out of 1236 patients who had valves implanted during 1960 to 1972). Survival rate with valvular infections was 40%. Our purpose of the study was to identify the factors that aided or decreased patient survival and to develop a program of treatment with antimicrobial agents. Several antimicrobics and various dosage schedules were used. Of 19 surviving patients, medical treatment alone was effective in 14, despite the continued presence of a valvular prosthesis. Reoperation was successful in five of nine patients. Continued chemoprophylactic or chemo-suppressive therapy was unnecessary... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Portland, Oregon. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 826-826KeywordsAntimicrobialsEndocarditisPatientsProsthetic device infections Issue Published: 1 May 1973 PDF downloadLoading ...
709-1 Coronary Angioplasty in 20,006 Patients Over Age 80 in the United States
Authors: James G. Jollis, Eric D. Peterson, Judith D. Bebchuk, Elizabeth R. DeLong, J. O’Neal Humphries, Lawrence H. Muhlbaier, David B. Pryor, Daniel B. Mark
Journal: Journal of the American College of Cardiology (1995)
<i>N</i> -Methyl-1-Deoxynojirimycin (MOR-14), an α-Glucosidase Inhibitor, Markedly Reduced Infarct Size in Rabbit Hearts
Authors: Masazumi Arai, Shinya Minatoguchi, Genzou Takemura, Yoshihiro Uno, Tatsuya Kariya, Hisato Takatsu, Takako Fujiwara, Masaya Higashioka, Yoshiaki Yoshikuni, Hisayoshi Fujiwara
Journal: Circulation (1998)

Background — N -methyl-1-deoxynojirimycin (MOR-14), an α-glucosidase inhibitor, reduces the glycogenolytic rate by inhibiting the α-1,6-glucosidase of glycogen-debranching enzyme in the liver, in addition to possessing an antihyperglycemic action by blocking α-1,4-glucosidase in the intestine. Because the reduction of the glycogenolytic rate may be one of the mechanisms of myocardial protection in ischemic preconditioning, the compounds inhibiting myocardial α-1,6-glucosidase may be protective against ischemic damage. Thus, we investigated whether MOR-14 could inhibit α-1,6-glucosidase and reduce the infarct size in rabbit hearts without collateral circulation. Methods and Results —MOR-14 dose-dependently decreased the α-1,6-glucosidase activity in rabbit heart extract. A tracer study demonstrated the myocardial uptake of a considerable amount of MOR-14 sufficient to fully inhibit α-1,6-glucosidase. To assess the infarct size–reducing effect of MOR-14, 54 rabbits were subjected to 30-minute coronary occlusion followed by 48-hour reperfusion. Preischemic treatment with 25, 50, and 100 mg/kg of MOR-14 dose-dependently reduced the infarct size (to 26±4%, 19±3%, and 14±2% of the area at risk, respectively), compared with the saline control (45±5%) without altering the blood pressure or heart rate. Another 40 rabbits given 100 mg of MOR-14 or saline 10 minutes before ischemia were euthanized at 10 or 30 minutes of ischemia for biochemical analysis. MOR-14 decreased the α-1,6-glucosidase activity to ≈20% in vivo, reduced the glycogen breakdown, and attenuated the lactate accumulation at both 10 and 30 minutes of ischemia. Conclusions —Preischemic treatment with MOR-14 preserved glycogen, attenuated the accumulation of lactate, and reduced the myocardial infarct size by 69%. This cardioprotective effect was independent of changes of blood pressure and heart rate or regional blood flow. It may be associated with α-1,6-glucosidase inhibition, because MOR-14 markedly decreased the α-1,6-glucosidase activity in the heart.
One New Humanity: the Challenge of AIDS
Authors: K. M Boyd
Journal: BMJ (1996)

Anne Bayley SPCK, £9.99, pp 330 ISBN 0 281 04923 8

“How does a society with a history of violence, buckling under the pressure of poverty and land scarcity, react to the news that an unknown third of its members carry the virus?” In Rwanda, with a population prevalence of HIV among the highest in the world, a survey in 1992 in a military camp found that 70% of the soldiers were more afraid of HIV and AIDS than of being at war. The cumulative incidence of HIV infections in Africa (over 11 million) and increasingly in Asia (over 3 million) is far …
Endothelin and increased contractility in adult rat ventricular myocytes. Role of intracellular alkalosis induced by activation of the protein kinase C-dependent Na(+)-H+ exchanger.
Authors: B K Krämer, T W Smith, R A Kelly
Journal: Circulation Research (1991)

Endothelin, a 21-amino acid vasoactive peptide, is among the most potent positively inotropic agents yet described in mammalian heart. Having demonstrated that endothelin's inotropic effect is due, in part, to an apparent sensitization of cardiac myofilaments to intracellular calcium, we determined whether this could be due to a rise in intracellular pH (pHi). In isolated adult rat ventricular cells loaded with the H(+)-selective fluorescent probe BCECF, 100 pM endothelin increased contractile amplitude to 190 +/- 26% of baseline and pHi by 0.08 +/- 0.02 (n = 8), whereas 1 nM endothelin increased pHi by 0.13 +/- 0.03 with little further increase in contractility. Amiloride (10(-4)M) prevented the increase in pHi in response to endothelin and reduced the inotropic response by 45%, although the inotropic effect could be readily restored by subsequent NH4Cl-induced alkalinization. Similarly, inhibitors of protein kinase C (H-7 and sphingosine) diminished or abolished the rise in pHi after endothelin superfusion while causing a decline in its inotropic effect comparable with that observed with amiloride. Pretreatment with pertussis toxin, which we have demonstrated results in complete ADP-ribosylation of the alpha-subunits of Go and Gi GTP-binding proteins and abolition of endothelin's positive inotropic effect, only partially reduced the intracellular alkalinization induced by the peptide, suggesting a complex signal transduction mechanism. Thus, the positive inotropic action of endothelin is due in part to stimulation of the sarcolemmal Na(+)-H+ exchanger by a protein kinase C-mediated pathway, resulting in a rise in pHi and sensitization of cardiac myofilaments to intracellular Ca2+.
Early Improvement Predicts Reduced Risk of Incident Diabetes and Improved Cardiovascular Risk in Prediabetic Asian Indian Men Participating in a 2-Year Lifestyle Intervention Program
Authors: Arun Nanditha, Jagannathan Ram, Chamukuttan Snehalatha, Sundaram Selvam, Susairaj Priscilla, Ananth Samith Shetty, Raghavan Arun, Ian F. Godsland, Desmond G. Johnston, Ambady Ramachandran
Journal: Diabetes Care (2014)

OBJECTIVE Objectives of this ancillary analysis of a prospective, prevention study among Asian Indians with impaired glucose tolerance (IGT) were a) to quantify the reduction in incident diabetes at 24 months in participants who achieved normal glucose tolerance (NGT) at 6 months (NGT-6 m) compared with the other participants, b) the factors influencing the reversal to NGT at the end of the study at 24 months (NGT-24 m), and c) to assess changes in cardiometabolic risk factors in different categories of dysglycemia at 24 months. RESEARCH DESIGN AND METHODS Data from a 2-year primary prevention trial were used. Effect of reversion to NGT-6 m on incidence of type 2 diabetes mellitus (T2DM) was analyzed using the Cox proportional hazards model. Predictive variables for reversal to NGT were identified using multiple logistic regression analysis. Changes in cardiometabolic risk factors were estimated according to the final glycemic status using fixed-effect, mixed-linear regression modeling. RESULTS The risk of T2DM in 2 years was lower by 75% in NGT-6 m group (hazard ratio 0.25 [95% CI 0.12–0.52]). Predictive variables for reversal to NGT-24 m were good baseline β-cell function (odds ratio [OR] 2.79 [95% CI 2.30–3.40]) and its further improvement (OR 5.70 [95% CI 4.58–7.08]), and NGT-6 m (OR 2.10 [95% CI 1.14–3.83]). BMI decreased in those who reverted to NGT. Deterioration to T2DM was associated with an increase in the levels of cardiometabolic risk factors. CONCLUSIONS Early reversion to NGT by lifestyle intervention in prediabetic men was associated with a significant reduction in subsequent incidence of diabetes. Good baseline β-cell function and its further improvement and NGT-6 m were associated with reversion to NGT-24 months. Reversion to NGT was associated with modest improvements, whereas conversion to T2DM was associated with significant worsening of the cardiometabolic risk profile.
Vitamin-B12 Deficiency in Pregnancy and the Puerperium
Authors: S. J. Baker, E. Jacob, K. T. Rajan, S. P. Swaminathan
Journal: BMJ (1962)

Among the non-pregnant population of South India megaloblastic anaemia due to vitamin-B12 deficiency occurs frequently, and is often associated with tropical sprue or tropical malabsorption syndrome (Baker, 1957,
Comparative Evaluation of Hemodialysis in the Home, Community Hospital, and Regional Center.
Authors: William J. Johnson
Journal: Annals of Internal Medicine (1968)

Abstracts1 May 1968Comparative Evaluation of Hemodialysis in the Home, Community Hospital, and Regional Center.Authors: William J. Johnson, M.D., F.A.C.P., David S. Hathaway, M.D., and Roger A. Carlson, B.B.A.Author, Article, & Disclosure InformationPublication: Annals of Internal MedicineVolume 68, Number 5https://doi.org/10.7326/0003-4819-68-5-1181_2 Get AccessSubmit a CommentContributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.Name (if multiple authors, separate names by comma)Name field is requiredComment TitleTitle field is requiredAffiliation & Institution (max characters: 200)Affiliations field is requiredCommentComment field is requiredPlease disclose any conflicts of interest or leave the box unchecked if you have noneDisclosure of Any Conflicts of InterestCancelSubmit
Differential Thymidylate Synthase Expression in Different Variants of Large-Cell Carcinoma of the Lung
Authors: Valentina Monica, Giorgio V. Scagliotti, Paolo Ceppi, Luisella Righi, Alberto Cambieri, Marco Lo Iacono, Silvia Saviozzi, Marco Volante, Silvia Novello, Mauro Papotti
Journal: Clinical Cancer Research (2009)

PURPOSE: In non-small cell lung cancer, higher thymidylate synthase (TS) levels have been reported in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC). Data on TS expression in large-cell carcinoma (LCC) are scanty. EXPERIMENTAL DESIGN: TS mRNA and protein levels were analyzed in 42 surgical cases of pulmonary LCC, including 8 large-cell neuroendocrine carcinomas, and were compared with controls represented by ADC (n = 41), SCC (n = 30), and small-cell lung carcinoma (SCLC; n = 33). TS levels were also correlated with the expression of Ki67 and E2F1. Moreover, the reliability of TS expression analysis was assessed in 22 matched cytologic and surgical specimens of non-small cell lung cancer. RESULTS: TS mRNA levels of LCC were comparable with those of control SCC, but significantly higher than those of ADC (P < 0.001) and lower than SCLC (P < 0.001). A correlation between TS mRNA and protein levels was observed in control ADC and SCC, but not in LCC. Large-cell neuroendocrine carcinomas had the highest TS expression, whereas in non-neuroendocrine LCCs, TS protein levels were significantly higher (P = 0.02) in LCC immunoreactive for p63 and desmocollin3 (markers of squamous differentiation) than those expressing TTF-1 (a marker of ADC). Both E2F1 and Ki67 levels were not correlated with TS in LCCs. Finally, a linear correlation in TS protein levels was observed between matched cytologic and surgical specimens. CONCLUSION: The pulmonary LCC immunoprofile may resemble that of SCCs or ADCs. This immunoprofile is associated with differential TS expression levels, which may support a more appropriate therapeutic strategy decision. (Clin Cancer Res 2009;15(24):7547-52).
Stress-Induced Endocrine and Immunological Changes in Psoriasis Patients and Healthy Controls
Authors: Gerhard Schmid-Ott, Roland Jacobs, Burkard Jäger, Sabine Klages, Joana Wolf, Thomas Werfel, Alexander Kapp, Thomas Schürmeyer, Friedhelm Lamprecht, Reinhold E. Schmidt, Manfred Schedlowski
Journal: Psychotherapy and Psychosomatics (1998)

&lt;b&gt;Background:&lt;/b&gt; Clinical observations suggest that psychological stress can induce exacerbation of psoriasis. It is hypothesized that these stress effects on the course and outcome of psoriasis are caused by neuroendocrine modulation of immune functions. Therefore we investigated the cardiovascular, endocrine and immunological response to a laboratory stressor in psoriasis patients and healthy controls. &lt;b&gt;Methods:&lt;/b&gt; Untreated (n = 7) and PUVA-treated (n = 4) psoriatics and healthy controls (n = 7) were exposed to a brief laboratory stressor (public speaking and mental arithmetic). Heart rate and blood pressure, catecholamine, cortisol, and DHEA plasma concentration, as well as distribution of T and NK lymphocytes were analyzed before, immediately after and 1 h after stress exposure. &lt;b&gt;Results&lt;/b&gt;: Heart rate and blood pressure increased in all three groups during stress exposure with the most pronounced changes in PUVA-treated patients. Psoriasis patients displayed higher adrenaline values but diminished cortisol and DHEA plasma concentrations compared to controls. NK cell numbers (CD16&lt;sup&gt;+&lt;/sup&gt;, CD56&lt;sup&gt;+&lt;/sup&gt;), but not T lymphocyte subsets, increased immediately after stress exposure in untreated patients and controls. This effect was significantly diminished in PUVA-treated patients. &lt;b&gt;Conclusions:&lt;/b&gt; The data of this pilot study indicate an enhanced stress-induced autonomic response and diminished pituitary-adrenal activity in psoriasis patients. PUVA treatment seems to interfere with the cardiovascular and NK cell response to acute psychological stress. Future studies will analyze the stress-induced neuroimmunological mechanisms in psoriatics in more detail.
Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor ?B independently of I?B degradation
Authors: Ralf M. Zwacka, Yulong Zhang, Weihong Zhou, Jeff Halldorson, John F. Engelhardt
Journal: Hepatology (1998)

For many inherited and acquired hepatic diseases, liver transplantation is the only possible therapeutic strategy. Ischemia/reperfusion (I/R) damage to donor tissue is thought to be one component that may play a role in the decline of posttransplant tissue function and ultimately rejection. The transcription factors, AP-1 and nuclear factor kappaB (NF-kappaB), play important roles in the acute cellular responses to tissue damage, as well as the inflammatory phase following I/R. We have found that the DNA binding activity of AP-1 was dramatically increased following warm ischemia at 1 to 3 hours postreperfusion. Induced DNA binding activity was composed of predominately c-Jun and JunD hetero- and homodimers as determined by electrophoretic mobility supershift assays. This increase in AP-1 activity occurred in the absence of significant changes in the steady-state protein levels of c-Jun and JunB. Maximal activation of Jun amino-terminal kinase ( JNK) occurred within the 25 to 30 minutes postreperfusion, just before the peak in AP-1 DNA binding. These findings suggest that phosphorylation may play an important role in regulating AP-1 transcriptional complexes. Furthermore, JunD protein levels slightly increased at 3 hours postreperfusion, concordant with changes in AP-1 DNA binding activity. The activation of NF-kappaB at 1 hour postreperfusion was independent of proteolytic degradation of IkappaB- or IkappaB-beta. This activation of NF-kappaB DNA binding activity in the nucleus was preceded by an increase in tyrosine phosphorylation of IkappaB-. These studies suggest that JNK, IkappaB tyrosine kinase, and JunD are potential targets for therapeutic intervention during liver I/R injury.