tbuckley/cabot-search huggingface dataset:
Prefrontal Cortical Dendritic Spine Pathology in Schizophrenia and Bipolar Disorder
Authors: Glenn T. Konopaske, Nicholas Lange, Joseph T. Coyle, Francine M. Benes
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Prior studies have demonstrated reduced dendritic spine density in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. However, it remains unclear how generalizable this finding is in schizophrenia and if it is seen in bipolar disorder, a historically distinct psychiatric condition. <h3>Objective</h3> To assess whether spine loss is present in the DLPFC of individuals with schizophrenia and individuals with bipolar disorder. <h3>Design, Setting, and Participants</h3> This study used postmortem human brain tissue from individuals with schizophrenia (n = 14), individuals with bipolar disorder (n = 9), and unaffected control participants (n = 19). Tissue samples containing the DLPFC (Brodmann area 46) were Golgi-stained, and basilar dendrites of pyramidal cells in the deep half of layer III were reconstructed. <h3>Main Outcomes and Measures</h3> The number of spines per dendrite, spine density, and dendrite length were compared across groups. We also assessed for the potential effects of clinical and demographic variables on dendritic parameters. <h3>Results</h3> The mean (SD) spine density was significantly reduced (ie, by 10.5%) in individuals with bipolar disorder (0.28 [0.04] spines/μm) compared with control participants (0.31 [0.05] spines/μm) (<i>P</i> = .02). In individuals with schizophrenia, the mean (SD) spine density was also reduced (by 6.5%; 0.29 [0.03] spines/μm) but just missed significance when compared with control participants (<i>P</i> = .06). There was a significant reduction in the mean (SD) number of spines per dendrite in both individuals with schizophrenia (72.8 [24.9] spines per dendrite) and individuals with bipolar disorder (68.9 [12.9] spines per dendrite) compared with controls (92.8 [31.1] spines per dendrite) (individuals with schizophrenia vs controls: 21.6% reduction [<i>P</i> = .003]; individuals with bipolar disorder vs controls: 25.8% reduction [<i>P</i> = .005]). In addition, both individuals with schizophrenia and individuals with bipolar disorder had a reduced mean (SD) dendrite length (246.5 [67.4] and 245.6 [29.8] μm, respectively) compared with controls (301.8 [75.1] μm) (individuals with schizophrenia vs controls: 18.3% reduction [<i>P</i> = .005]; individuals with bipolar disorder vs controls: 18.6% reduction [<i>P</i> = .005]). <h3>Conclusions and Relevance</h3> Dendritic spine loss in the DLPFC was seen in both individuals with schizophrenia and individuals with bipolar disorder, suggesting that the 2 disorders may share some common pathophysiological features.
The Risk and Cost of Coronary Angiography
Authors: Charles E. Hansing
Journal: JAMA (1979)

The National Guidelines for Health Planning require 300 cardiac studies per year in cardiac catheterization laboratories for adequate economic use and safety. To study how these guidelines would affect existing laboratories, data were collected on the cost of coronary angiography and use of all cardiac catheterization laboratories in Washington. The average cost of coronary angiography was $1,363, with the total cost affected by the duration of hospital stay, cardiac laboratory charges, and professional fees. Total angiographic use ranged from 293 to 791 studies per room, but eight laboratories did not perform 300 cardiac studies during 1977. Health planners recommend high use rates based on the theory that there is an inverse correlation between the number of studies and cost. In this study, the regression equation showed no fall in charges with increased number of studies. Therefore, while it may be reasonable from an economic point of view to expect 300 angiographic cases per year in existing laboratories, there is no economic justification for requiring a certain number of cardiac studies per year. (<i>JAMA</i>242:731-734, 1979)
UK residents labelled as “health tourists” have problems accessing health care
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

Some people in the United Kingdom are struggling to access routine medical care, including consultations with GPs and antenatal care, because they are wrongly being labelled as “health tourists,” says a report.

The report, from the charity Medecins du Monde UK, analyses the first year's activity of the charity in London, where it set up a clinic in the east end to improve access to health care for vulnerable people in and around the capital.

The group says that regulations introduced in April 2004 to charge “overseas visitors” for NHS hospital treatment is making it difficult for some people who have legitimate rights to NHS treatment to get routine care.

In 2006 a total of 349 people came to the Medecins du Monde clinic for 435 consultations. The …
Safe health care: are we up to it?
Authors: L. L Leape
Journal: BMJ (2000)

In the eight months since we put out the call for papers for this special issue of the BMJ devoted to medical errors, the landscape has changed considerably. In Britain the Bristol Inquiry has continued to focus professional and public attention on patient safety in a manner unprecedented both for its depth and for the extent of professional involvement.1 In the United States the recent publication of the report To Err is Human by the Institute of Medicine of the National Academy of Sciences2 received extraordinary media coverage as well as prompt responses to its recommendations from the President and Congress.3

The error prevention “movement” has clearly accelerated. As the papers in this issue bear witness, major changes are occurring in the way we think about and carry out our daily work. For practising physicians, some of the ideas and practices described here may be mind bending, or at least mind stretching. But most of the insights and solutions will, we think, have resonance for all those who strive to provide safe care for patients. All physicians, after all, have had the unwelcome experience of becoming what Wu calls “the second victim,” being involved in an error or patient injury and feeling the attendant sense of guilt or remorse as responsible professionals. Lucian Leape and Donald Berwick are the guest editors of this theme issue. 4 Familiar, too, are Helmreich's findings that doctors, like pilots, tend to overestimate …
Future Shock in Academic Medicine
Authors: Eugene Braunwald
Journal: New England Journal of Medicine (1972)

Abstract The current social revolution clearly influences patterns of academic medicine. The increasingly rapid turnover of academic physicians results largely from rapidly changing government-sponsored programs in goal-oriented research, in education and in clinical services carried out by medical schools. This increased transience of faculty inhibits personal pride in and loyalty to institutions, diminishes opportunities for professional identification and reduces the importance of academie tenure. The reorganization of clinical departments into divisions of primary and of specialty care is likely. The impact of an increased fraction of women in academic medicine is yet to be felt. The viability of monthly scientific journals as the backbone of communication among bio-medical investigations is questionable. A variety of steps may, however, be designed to maximize the potential benefits and to minimize the deleterious consequences resulting from these changes.
P78 Physical Inactivity is Associated with Mid-Thigh Intramuscular Fat in Patients with COPD
Authors: M Maddocks, D Shrikrishna, S Vitoriano, RJ Tanner, SA Natanek, N Hart, PR Kemp, J Moxham, MI Polkey, NS Hopkinson
Journal: Thorax (2012)

<h3>Introduction</h3> Quadriceps muscle impairment is an important complication of COPD occurring in mild as well as more advanced disease<sup>1</sup>. This is driven by physical inactivity and can include muscle atrophy and/or a shift towards a less aerobic phenotype with reduced Type I fibre proportions and a reduction in capillarity and oxidative enzymes.<sup>2</sup> We hypothesised that physical inactivity in COPD patients would be associated with intramuscular fat and that this could potentially be a non-invasive and non-volitional marker of muscle quality. <h3>Methods</h3> Mid-thigh cross-sectional area (MTCSA), percentage intramuscular fat and skeletal muscle attenuation (Hounsfield units [HU]) were assessed using computed tomography (CT) image analysis. Tissues were differentiated using standard attenuation ranges; fat: –190 to –30HU and skeletal muscle: –29 to 150HU Quadriceps isometric maximal voluntary contraction (QMVC) was measured using a strain gauge. Fat-free mass index (FFMI) and the impedance ratio (Z200/Z5) were determined by bioelectrical impedance analysis. Daily step count and physical activity level (PAL) were recorded over 6 days using a multisensory biaxial armband accelerometer (SenseWear, Bodymedia; Pittsburgh, US). <h3>Results</h3> 69 patients (mean (SD), 65(8) years, FEV1 44(21)% predicted, 54% male) participated in the study. Mean (SD) daily step count was 4502 (3274) steps; physical activity level 1.4 (0.2); QMVC 25.2 (5.9) kg; FFMI 17.3 (2.3)kg/m2, MTCSA 178 (43)cm2. Using a stepwise regression model incorporating MTCSA, intramuscular fat, skeletal muscle attenuation, QMVC, and FFMI as independent variables, only skeletal muscle attenuation (HU) was retained as an independent correlate of daily step count (r=0.34, p=0.006). In a similar model, percentage intramuscular fat was the only independent predictor of physical activity level (r=0.37, p=0.002). The bioelectrical impedance ratio (Z200/Z5) was also associated with skeletal muscle attenuation (r=0.40, p&lt;0.001) in this cohort. <h3>Conclusion</h3> These data suggest that muscle “quality” assessed using CT is independently associated with daily physical activity and may therefore have potential as a biomarker in this area. Shrikrishna D <i>et al.</i> Quadriceps wasting and physical inactivity in patients with COPD. <i>Eur Resp J</i> 2012; doi: 10.1183/09031936.00170111. Shrikrishna D, Hopkinson NS. Chronic obstructive pulmonary disease: consequences beyond the lung. <i>Clin Med</i> 2012; 12:71–4.
Toward a broadly protective influenza vaccine
Authors: Peter C. Doherty, Anne Kelso
Journal: Journal of Clinical Investigation (2008)

The current inactivated influenza virus vaccines induce antibodies that protect against closely related virus strains. They do not, however, protect against antibody-escape variants of seasonal influenza A viruses or new pandemic influenza A viruses emerging from non-human reservoirs. Might boosting influenza A virus–specific CD8+ T cell memory diminish the danger posed by these variant viruses? Pre-existing CD8+ T cell–mediated immunity directed at peptides from conserved internal proteins of the influenza A virus does not prevent infection, but it can promote early virus clearance and decrease morbidity in mice. In this issue of the JCI, Lee et al. show that people who have not been exposed to avian influenza A (H5N1) viruses have cross-reactive CD8+ T cell memory to a wide range of H5N1 peptides (see the related article beginning on page 3478). These peptides could be used to add a CD8+ T cell component to current antibody-focused vaccine strategies with a view to reducing the impact of infection with novel influenza A viruses.
Treatment of postoperative nausea and vomiting
Authors: M. R Tramer
Journal: BMJ (2003)

Better data, improved control have been achieved during recent years 

Postoperative nausea and vomiting is a nuisance. The anaesthetist is usually blamed, despite evidence that postoperative nausea and vomiting results from several factors, some related to anaesthesia, others to surgery, and some to the patients themselves. The importance of postoperative nausea and vomiting is generally underestimated because it is self limiting, never becomes chronic, and almost never kills. However, its impact on the cost of health care is not negligible. Ten per cent of the population undergo general anaesthesia every year,1 and about 30% of them are affected by postoperative nausea and vomiting.2 This amounts to about two million people in the United Kingdom every year. About 1% of patients undergoing ambulatory surgery are admitted overnight because of uncontrolled postoperative nausea and vomiting.2

Surgical patients prefer to suffer pain rather than postoperative nausea and vomiting3 and would be willing to pay considerable amounts of money for an effective antiemetic.4 However, successful control of postoperative nausea and vomiting has proved elusive. A major obstacle to the development of an effective treatment has been the lack of a valid animal model for postoperative nausea and vomiting. New insights into pathways for emesis and efficacy of antiemetics have come from animal research with highly emetogenic chemotherapy. Extrapolation of these data to postoperative nausea and vomiting has been of …
Physicians’ View of Their Work Environment and Organisation
Authors: Bengt B. Arnetz
Journal: Psychotherapy and Psychosomatics (1997)

The objective of this study was to assess physicians' perception of their work, organisation and professional development.All major disciplines at a major regional hospital were studied. Participants responded to a structured questionnaire concerning broad aspects of physicians' work. The response rate was approximately 78%, with 356 respondents.The results show that even though physicians are overall very satisfied with their work, they list high workload, lack of influence on daily work and work processes as dissatisfactory. Skills utilisation and development are some major areas for improvement. Physicians that were aware of the overall mission statement for their hospital were more satisfied with and informed about departmental goals. Perceived organisational efficiency and leadership qualities were important determinants of perceived workload and work climate.Stress among physicians is a growing occupational health concern, impacting negatively on patient care. In this article important individual and organisational factors related to physician stress are identified and suggestions to assess stress and intervene are provided.
Formation and persistence of 8-oxoguanine in rat lung cells as an important determinant for tumor formation following particle exposure.
Authors: P Nehls, F Seiler, B Rehn, R Greferath, J Bruch
Journal: Environmental Health Perspectives (1997)

Exposure of rats to quartz (or various other particles) can lead to the development of lung tumors. At the moment, the mechanisms involved in particle-induced tumor formation are not clarified. However, it is suggested that inflammation, in conjunction with the production of reactive oxygen species (ROS) and an enhancement of epithelial cell proliferation, may play a key role in the development of lung tumors. ROS induces 8-oxoguanine (8-oxoGua) and other mutagenic DNA oxidation products, which can be converted to mutations in proliferating cells. Mutation formation in cancer-related genes is a critical event with respect to tumor formation. In this study we investigated the effects of quartz (DQ12) and of the nontumorigenic dust corundum on the induction of 8-oxoGua in the DNA of rat lung cells, as well as on cell proliferation and pulmonary inflammation. Wistar rats were exposed by intratracheal instillation to quartz (2.5 mg/rat) or corundum (2.5 mg/rat) suspended in physiological saline; control animals exposed to physiological saline or left untreated. Measurements were carried out 7, 21, and 90 days after the exposures. 8-oxoGua levels were determined in lung tissue sections at the single cell level by immunocytological assay using a rabbit anti-8-oxoGua antibody. After exposure to quartz, 8-oxoGua levels were significantly increased at all time points of investigation. Additionally, we observed inflammation and an enhanced cell proliferation. Exposure to corundum had no adverse effects on the lung; neither increased 8-oxoGua levels nor enhanced cell proliferation or inflammation were detected. These observations support the suggestion that inflammation associated with increased 8-oxoGua levels in lung cells and increased cell proliferation is an important determinant for particle-induced development of lung tumors in the rat.
Case of Rupture of the Left Ventricle of the Heart
Authors: M. Bodington
Journal: BMJ (1843)

the bones of the face, destroyed the orbit, bled pro.fusely, and the poor fellow died.I savw another case where the fungus occupied a Jarge part of the nostril, and projected into the pharynx; Sir Astley Cooper and I agreed to remove a part of it by ligature.The ligature came away, but there was so small a piece of fungus included in it, that it could scarcely be seen.It was composed entirely of vessels similar to the cauliflower excre- scence of the uterus.The tumor grew again, and I have not heard the result, but I have no doubt the patient died.As for these maligriant tumors, let them alone; from tny own experience, I consider, from their having so broad a base, that any operation for them would do no good.In the next lecture, Gentlepieii, I shall mention
Intraperitoneal Insulin for Control of Blood Sugar in Diabetic Patients during Peritoneal Dialysis
Authors: K. Crossley, C. M. Kjellstrand
Journal: BMJ (1971)

We have added insulin to peritoneal dialysis fluid in three uraemic diabetic patients. The hyperglycaemia and pronounced fluctuations in blood glucose which complicate peritoneal dialysis in diabetic subjects have not occurred with this technique. Studies with <sup>131</sup>I-labelled insulin showed that less than 5% of the intraperitoneally administered insulin was absorbed during a one-hour exchange. While the physiology of the procedure needs further evaluation, this procedure has reduced the morbidity of peritoneal dialysis in diabetic patients and made its management easier.
5q- syndrome presenting chronic myeloproliferative disorders-like manifestation: A case report
Authors: Hidenobu Takahashi, Tatsuo Furukawa, Shigeo Hashimoto, Naoko Kanazawa, Naoaki Satoh, Noriatsu Suzuki, Jun Takizawa, Yumiko Uesugi, Masuhiro Takahashi, Yoshifusa Aizawa, Tadashi Koike
Journal: American Journal of Hematology (2000)

A 28-year-old Japanese woman with suspected essential thrombocythemia (ET) had marked thrombocytosis, mild leukocytosis with normal neutrophil alkaline phosphatase activity, and no anemia. She was monitored without being given any medication. Eleven years later, complete blood counts showed no remarkable changes but some non-lobulated mononuclear megakaryocytes were found in the bone marrow. Cytogenetic analysis revealed deletion of the long arm of chromosome 5 (5q-). Subsequently, hemoglobin and platelet counts decreased gradually, splenomegaly appeared and progressed, after which myelofibrosis developed. Acute leukemia developed 16 years after the first documentation of thrombocytosis. 5q- syndrome is known to be a myelodysplastic syndrome (MDS) with unique clinical features and cases with this syndrome presenting with thrombocytosis of more than 1,000 × 109/L but without anemia are rare. Furthermore, it is noteworthy that in this patient transition to acute leukemia occurred following development of myelofibrosis and marked splenomegaly, which are generally observed in blastic crises resulting from chronic myeloproliferative disorders (CMPD). The patient showed features indicative of CMPD rather than of MDS in spite of presenting with 5q- chromosomal abnormality. This case supports the concept of “mixed myelodysplastic and myeloproliferative syndromes” and suggests the possibility of the appearance of CMPD-like manifestations in 5q- syndrome. Am. J. Hematol. 64:120–123, 2000. © 2000 Wiley-Liss, Inc.
Activation of alpha1-adrenergic receptors stimulate the growth of small mouse cholangiocytes Via calcium-dependent activation of nuclear factor of activated T cells 2 and specificity protein 1
Authors: Gianfranco Alpini, Antonio Franchitto, Sharon DeMorrow, Paolo Onori, Eugenio Gaudio, Candace Wise, Heather Francis, Julie Venter, Shelley Kopriva, Romina Mancinelli, Guido Carpino, Franco Stagnitti, Yoshiyuki Ueno, Yuyan Han, Fanyin Meng, Shannon Glaser
Journal: Hepatology (2010)

Small cholangiocytes proliferate via activation of calcium (Ca(2+) )-dependent signaling in response to pathological conditions that trigger the damage of large cyclic adenosine monophosphate-dependent cholangiocytes. Although our previous studies suggest that small cholangiocyte proliferation is regulated by the activation of Ca(2+) -dependent signaling, the intracellular mechanisms regulating small cholangiocyte proliferation are undefined. Therefore, we sought to address the role and mechanisms of action by which phenylephrine, an α(1) -adrenergic agonist stimulating intracellular D-myo-inositol-1,4,5-triphosphate (IP(3) )/Ca(2+) levels, regulates small cholangiocyte proliferation. Small and large bile ducts and cholangiocytes expressed all AR receptor subtypes. Small (but not large) cholangiocytes respond to phenylephrine with increased proliferation via the activation of IP(3) /Ca(2+) -dependent signaling. Phenylephrine stimulated the production of intracellular IP(3) . The Ca(2+) -dependent transcription factors, nuclear factor of activated T cells 2 (NFAT2) and NFAT4, were predominantly expressed by small bile ducts and small cholangiocytes. Phenylephrine stimulated the Ca(2+) -dependent DNA-binding activities of NFAT2, NFAT4, and Sp1 (but not Sp3) and the nuclear translocation of NFAT2 and NFAT4 in small cholangiocytes. To determine the relative roles of NFAT2, NFAT4, or Sp1, we knocked down the expression of these transcription factors with small hairpin RNA. We observed an inhibition of phenylephrine-induced proliferation in small cholangiocytes lacking the expression of NFAT2 or Sp1. Phenylephrine stimulated small cholangiocyte proliferation is regulated by Ca(2+) -dependent activation of NFAT2 and Sp1.Selective stimulation of Ca(2+) -dependent small cholangiocyte proliferation may be key to promote the repopulation of the biliary epithelium when large bile ducts are damaged during cholestasis or by toxins.
Induction of Bone-Type Alkaline Phosphatase in Human Vascular Smooth Muscle Cells
Authors: Atsushi Shioi, Miwako Katagi, Yasuhisa Okuno, Katsuhito Mori, Shuichi Jono, Hidenori Koyama, Yoshiki Nishizawa
Journal: Circulation Research (2002)

Inflammatory cells such as macrophages and T lymphocytes play an important role in vascular calcification associated with atherosclerosis and cardiac valvular disease. In particular, macrophages activated with cytokines derived from T lymphocytes such as interferon-gamma (IFN-gamma) may contribute to the development of vascular calcification. Moreover, we have shown the stimulatory effect of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on in vitro calcification through increasing the expression of alkaline phosphatase (ALP), an ectoenzyme indispensable for bone mineralization, in vascular smooth muscle cells. Therefore, we hypothesized that macrophages may induce calcifying phenotype, especially the expression of ALP in human vascular smooth muscle cells (HVSMCs) in the presence of IFN-gamma and 1,25(OH)2D3. To test this hypothesis, we used cocultures of HVSMCs with human monocytic cell line (THP-1) or peripheral blood monocytes (PBMCs) in the presence of IFN-gamma and 1,25(OH)2D3. THP-1 cells or PBMCs induced ALP activity and its gene expression in HVSMCs and the cells with high expression of ALP calcified their extracellular matrix by the addition of beta-glycerophosphate. Thermostability and immunoassay showed that ALP induced in HVSMCs was bone-specific enzyme. We further identified tumor necrosis factor-alpha (TNF-alpha) and oncostatin M (OSM) as major factors inducing ALP in HVSMCs in the culture supernatants of THP-1 cells. TNF-alpha and OSM, only when applied together, increased ALP activities and in vitro calcification in HVSMCs in the presence of IFN-gamma and 1,25(OH)2D3. These results suggest that macrophages may contribute to the development of vascular calcification through producing various inflammatory mediators, especially TNF-alpha and OSM.