tbuckley/cabot-search huggingface dataset:
Failure of Extinction of Fear Responses in Posttraumatic Stress Disorder: Evidence From Second-Order Conditioning
Authors: Michèle Wessa, Herta Flor
Journal: American Journal of Psychiatry (2007)

Objectives: Posttraumatic stress disorder (PTSD) is characterized by the re-experiencing of a traumatic event, although the trauma itself occurred in the past. The extinction of the traumatic response might be impeded if trauma reminders maintain fear responses by their association with the original trauma through second-order conditioning. Method: A differential conditioning paradigm with a trauma-specific picture, used as an acquired unconditioned stimulus, and graphic representations, used as conditioned stimuli, were employed in 14 PTSD patients, 15 trauma-exposed subjects without PTSD, and 15 healthy comparison subjects. The authors used event-related potentials of electroencephalogram (EEG), self-report measures, skin conductance responses, heart rate, and startle modulation to assess the differential conditioned response among subjects. Results: Trauma-exposed subjects with and without PTSD but not healthy comparison subjects showed successful differential conditioning to the trauma-relevant cue indicative of second-order conditioning. Only PTSD patients exhibited enhanced conditioned responses to the trauma reminder during acquisition and impaired extinction as evident in more negative evaluations of the conditioned stimuli associated with a trauma reminder as well as enhanced peripheral and brain responses. Conclusions: These findings suggest that PTSD may be maintained by second-order conditioning where trauma-relevant cues come to serve as unconditioned stimuli, thus generalizing enhanced emotional responses to many previously neutral cues and impeding extinction. The extinction deficit in PTSD patients observed in this study underlines the need for therapies focusing on the extinction of learned responses, such as behavioral treatment, with or without the addition of pharmacological substances that enhance the extinction of a learned response.
Urinary kallikrein and plasma renin activity as determinants of renal blood flow. The influence of race and dietary sodium intake.
Authors: S B Levy, J J Lilley, R P Frigon, R A Stone
Journal: Journal of Clinical Investigation (1977)

We investigated the relationship of the kallikrein-kinin system and the renin-angiotensin system in the regulation of blood pressure, salt and water excretion, and renal blood flow. Normotensive and hypertensive black and white men were studied during unresticted sodium intake as well as on a 10-meq/day sodium intake; potassium intake was held constant throughout the study (80 meq/day). During unrestricted sodium intake, urinary kallikrein activity was greater in white normotensives than white hypertensives or black normotensives. There was no difference (P greater than 0.05) between white and black hypertensives or between black normotensives and black hypertensives. All groups had greater urinary kallikrein activity on low sodium vs. unrestricted sodium intake, but the increase in black hypertensives was small, and they excreted significantly less kallikrein than the ogher groups on the low sodium diet. Plasma renin activity showed similar increments after sodium restriction in all groups. Urinary kallikrein activity correlated with renal blood flow in all groups except the black normotensives on low sodium intake. Renal blood flow could be correlated uniformly with log (urinary kallikrein activity/supine plasma renin activity) in all groups on either diet. Urinary sodium and potassium excretion and urine volume were not different among the groups. We conclude: (a) important racial differences exist in urinary kallikrein activity that are unrelated to sodium or potassium excretion or urine volume; (b) dietary sodium restriction further delineates racial differences and suggests alternative pathophysiologic mechanisms for huma hypertension; (c) urinary kallikrein activity correlates with renal blood flow; and (d) our data support the concept that the kallikrein-kinin system and the renin-angiotensin system contribute to the regulation of renal blood flow and may account for racial differences in renal vascular resistance.
Drinking nation: have we had enough?
Authors: J. Appleby
Journal: BMJ (2012)

For economists, alcohol is a normal good; a put-the-price-up-and-demand-goes-down type of good.1 But for many people (too many?) alcohol is “normal” and “good” in the more colloquial sense. In his introduction to the UK government’s latest alcohol strategy, Prime Minister David Cameron focused on erratic and excessive imbibing: “Binge drinking isn’t some fringe issue, it accounts for half of all alcohol consumed in this country. The crime and violence it causes drains resources in our hospitals, generates mayhem on our streets, and spreads fear in our communities.”2 So, have we had enough, and is the government’s adoption of the economist’s solution—raising the (minimum) price of alcohol1—the answer?

In 2010, UK households spent around £42.1bn (€50.9bn, $66.6bn) on alcohol through off-sales (£15.2bn) and in restaurants and hotels (£26.9bn). This is equivalent to around 3% of the gross domestic …
Changes in blood gas transport of altitude native soccer players near sea-level and sea-level native soccer players at altitude (ISA3600)
Authors: Nadine Wachsmuth, Marlen Kley, Hilde Spielvogel, Robert J Aughey, Christopher J Gore, Pitre C Bourdon, Kristal Hammond, Charli Sargent, Gregory D Roach, Rudy Soria Sanchez, Jesus C Jimenez Claros, Walter F Schmidt, Laura A Garvican-Lewis
Journal: British Journal of Sports Medicine (2013)

The optimal strategy for soccer teams playing at altitude is not known, that is, 'fly-in, fly-out' versus short-term acclimatisation. Here, we document changes in blood gas and vascular volumes of sea-level (Australian, n=20) and altitude (Bolivian, n=19) native soccer players at 3600 m.Haemoglobin-oxygen saturation (Hb-sO₂), arterial oxygen content (CaO₂), haemoglobin mass (Hbmass), blood volume (BV) and blood gas concentrations were measured before descent (Bolivians only), together with aerobic fitness (via Yo-YoIR1), near sea-level, after ascent and during 13 days at 3600 m.At baseline, haemoglobin concentration [Hb] and Hbmass were higher in Bolivians (mean ± SD; 18.2 ± 1.0 g/dL, 12.8 ± 0.8 g/kg) than Australians (15.0 ± 0.9 g/dL, 11.6 ± 0.7 g/kg; both p ≤ 0.001). Near sea-level, [Hb] of Bolivians decreased to 16.6 ± 0.9 g/dL, but normalised upon return to 3600 m; Hbmass was constant regardless of altitude. In Australians, [Hb] increased after 12 days at 3600 m to 17.3 ± 1.0 g/dL; Hbmass increased by 3.0 ± 2.7% (p ≤ 0.01). BV decreased in both teams at altitude by ∼400 mL. Arterial partial pressure for oxygen (PaO₂), Hb-sO₂ and CaO₂ of both teams decreased within 2 h of arrival at 3600 m (p ≤ 0.001) but increased over the following days, with CaO₂ overcompensated in Australians (+1.7 ± 1.2 mL/100 mL; p ≤ 0.001). Yo-YoIR1 was lower on the 3rd versus 10th day at altitude and was significantly related to CaO₂.The marked drop in PaO₂ and CaO₂ observed after ascent does not support the 'fly-in, fly-out' approach for soccer teams to play immediately after arrival at altitude. Although short-term acclimatisation was sufficient for Australians to stabilise their CaO₂ (mostly due to loss of plasma volume), 12 days appears insufficient to reach chronic levels of adaption.
Liposomal Alendronate Inhibits Systemic Innate Immunity and Reduces In-Stent Neointimal Hyperplasia in Rabbits
Authors: Haim D. Danenberg, Gershon Golomb, Adam Groothuis, Jianchuan Gao, Hila Epstein, Rajesh V. Swaminathan, Philip Seifert, Elazer R. Edelman
Journal: Circulation (2003)

Background— Innate immunity is of major importance in vascular repair. The present study evaluated whether systemic and transient depletion of monocytes and macrophages with liposome-encapsulated bisphosphonates inhibits experimental in-stent neointimal formation. Methods and Results— Rabbits fed on a hypercholesterolemic diet underwent bilateral iliac artery balloon denudation and stent deployment. Liposomal alendronate (3 or 6 mg/kg) was given concurrently with stenting. Monocyte counts were reduced by &gt;90% 24 to 48 hours after a single injection of liposomal alendronate, returning to basal levels at 6 days. This treatment significantly reduced intimal area at 28 days, from 3.88±0.93 to 2.08±0.58 and 2.16±0.62 mm 2 . Lumen area was increased from 2.87±0.44 to 3.57±0.65 and 3.45±0.58 mm 2 , and arterial stenosis was reduced from 58±11% to 37±8% and 38±7% in controls, rabbits treated with 3 mg/kg, and rabbits treated with 6 mg/kg, respectively (mean±SD, n=8 rabbits/group, P &lt;0.01 for all 3 parameters). No drug-related adverse effects were observed. Reduction in neointimal formation was associated with reduced arterial macrophage infiltration and proliferation at 6 days and with an equal reduction in intimal macrophage and smooth muscle cell content at 28 days after injury. Conversely, drug regimens ineffective in reducing monocyte levels did not inhibit neointimal formation. Conclusions— Systemic transient depletion of monocytes and macrophages, by a single liposomal bisphosphonates injection concurrent with injury, reduces in-stent neointimal formation and arterial stenosis in hypercholesterolemic rabbits.
Individual Variation in the Effects of Dietary Cholesterol on Plasma Lipoproteins and Cellular Cholesterol Homeostasis in Man
Authors: P. Mistry, N. E. Miller, M. Laker, W. R. Hazzard, B. Lewis
Journal: Journal of Clinical Investigation (1981)

The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from -6 to +75 mg/dl; mean change, +29 mg/dl; P < 0.001). Increases in plasma cholesterol reflected increased cholesterol concentrations in intermediate density lipoprotein (IDL; 1.006-1.019 g/ml), low density lipoprotein (LDL; 1.019-1.063 g/ml), and the HDL(2) subclass (1.063-1.125 g/ml) of high density lipoprotein, which on average accounted for 20, 58, and 22%, respectively, of the total increment. Similar responses occurred in 14 other subjects given 750 mg cholesterol per day for 28 d. Plasma apolipoprotein B concentrations in IDL and LDL also increased. THESE EFFECTS ON PLASMA LIPOPROTEINS WERE ACCOMPANIED BY THREE CHANGES IN FRESHLY ISOLATED BLOOD MONONUCLEAR CELLS: (a) an increase in cell cholesterol content (mean change, +17%; P < 0.01); (b) suppression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity (-32%; P < 0.001); and (c) reduction of LDL receptor activity (-74%; P < 0.01), quantified as the rate of degradation of (125)I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism.The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = -0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade (125)I-LDL after derepression by preincubation for 72 h in lipoprotein-deficient medium (r = -0.74, P < 0.001). Thus, differences between individuals in the responses of the plasma lipoproteins to dietary cholesterol appear to be related in part to differences in the capacity of peripheral cells to catabolize LDL and to down-regulate cholesterol synthesis.
Increased frequencies of pulmonary regulatory T-cells in latent<i>Mycobacterium tuberculosis</i>infection
Authors: Christian Herzmann, Martin Ernst, Stefan Ehlers, Steffen Stenger, Jeroen Maertzdorf, Giovanni Sotgiu, Christoph Lange
Journal: European Respiratory Journal (2012)

Regulation of specific immune responses following exposure to Mycobacterium tuberculosis in humans and the role of regulatory T (Treg) cells in the immune control of latent infection with M. tuberculosis are incompletely understood. Latent infection was assayed by an interferon-γ release assay (IGRA) in healthcare workers regularly exposed to tuberculosis (TB) patients and in household TB contacts in Germany. Immunophenotypes of bronchoalveolar lavage (BAL) mononuclear cells and peripheral blood mononuclear cells (PBMCs) were analysed by fluorescence-activated cell sorting. All TB contacts with latent infection (n=15) had increased (p&lt;0.0001) frequencies of CD4+ CD25+ CD127- Treg cells (median 2.12%, interquartile range (IQR) 1.63–3.01%) among BAL mononuclear cells compared with contacts (n=25) with negative IGRA results (median 0.68%, IQR 0.32–0.96%) No differences were seen when PBMC immunophenotypes of IGRA+ and IGRA- TB contacts were compared (IGRA+ median 9.6%, IQR 5.9–10.1%; IGRA- median 7.7%, IQR 4.6–11.3%; p=0.47). Five out of 25 contacts with negative blood IGRAs showed a positive IGRA from BAL cells, possibly indicating a limited local immune response. In Germany, latent infection with M. tuberculosis , as defined by a positive M. tuberculosis -specific IGRA response on cells from the peripheral blood, is characterised by an increased frequency of Treg cells in the BAL.
Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know
Authors: E Suresh
Journal: Journal of the Royal Society of Medicine (2004)

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects about 1% of the population. It leads to irreversible joint damage and systemic complications, and the age-adjusted mortality of those affected exceeds that of the general population.1–3 When joint damage was seen to be an early feature of the disease,4–12 rheumatologists put forward the point at which they prescribed disease-modifying antirheumatic drugs (DMARD), in the hope of slowing or even arresting disease progression. Patients in whom DMARD therapy is introduced early have better function and radiological outcome in the long-term than those in whom it is delayed.13–19 It was for these reasons that a SIGN (Scottish Intercollegiate Guideline Network) guideline20 in 2000 indicated that a patient with inflammatory arthritis lasting >6–8 weeks should be referred for a specialist (rheumatology) opinion. However, a recent audit in our unit showed that such patients were referred after a mean of 16 weeks (interquartile range 6–34) from onset of symptoms.21 Other studies suggest that the long lag between symptom onset and the diagnosis of RA is mainly due to late referral rather than patient delay in reporting symptoms or long waits for outpatient appointments.22 Moreover, in most referral letters from general practitioners, a tentative rheumatological diagnosis is either not stated or stated wrongly.23,24 The reason is clear: RA has no disease-specific diagnostic features25 and patients can present with a wide range of manifestations. In this article I discuss the difficulties of early diagnosis, taking an illustrative case of polyarthritis (inflammation of more than four joints), the commonest presentation.
Child Public Health
Authors: Helen Roberts
Journal: BMJ (2004)

Just as the HIV and AIDS epidemic turned the curiously unsexy specialty of genitourinary medicine into prime-time television and ratcheted sexually transmitted infections up the scientific agenda, current policy interest in child public health means that this book is coming out at just the right time to persuade students that what used to be thought of as a backwater of baby clinics, bad kids, and nits is not just important but fun. They can make a difference to children's and adult health, make friends and allies outside medicine, and have a role in social and public policy.

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Mitch Blair, Sarah Stewart-Brown, Tony Waterston, Rachel Crowther

Oxford University Press, £29.50, pp 250 ISBN 0 19 263192 6

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Child …

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Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail
Authors: L Drake, D Babel, D M Stewart, P Rich, M R Ling, D Breneman, R K Scher, A G Martin, D M Pariser, R J Pariser, C N Ellis, S Kang, H I Katz, C J McDonald, J Muglia, R C Savin, G Webster, B E Elewski, J J Leyden, A D Bucko, E H Tschen, J M Hanifin, M R Morman, J L Shupack, D L Greer
Journal: Journal of the American Academy of Dermatology (1998)
Patients with Sjögren-Larsson Syndrome Lack Macular Pigment
Authors: Rob L.P. van der Veen, Joris Fuijkschot, Michèl A.A.P. Willemsen, Johannes R.M. Cruysberg, Tos T.J.M. Berendschot, Thomas Theelen
Journal: Ophthalmology (2010)
P199 Discrepancy between symptom severity and self-reported palliative care needs in Interstitial Lung Disease patients
Authors: S Tsim, G Chalmers
Journal: Thorax (2013)

<h3>Introduction</h3> Patients with interstitial lung disease (ILD) have a high symptom burden but their palliative care needs are not well reported. We hypothesised that there was an unmet need for social and palliative care input in ILD patients. <h3>Methods</h3> 131 consecutive ILD clinic patients (September 2013–January 2013) completed a questionnaire unsupervised. 6 ILD patients on home oxygen completed the same questionnaire during a home visit. The questionnaire consisted of the 15 questions included in the King’s Brief Interstitial Lung Disease (K-BILD) health status questionnaire, concerning experiences in the preceding two weeks, and an additional 9 questions aimed at assessing patients’ perceptions of their needs and concerns. <h3>Results</h3> Despite reporting significant physical symptoms in the questionnaire, including breathlessness in 69%, chest tightness in 52% and wheeze (60%), only 10% felt that their physical needs were not being met. Emotional and psychological symptom reporting was high, including worry about the seriousness of their lung condition (54%), feeling “down” in 52% and anxiety in 43%. Only 32% felt in control of their lung condition, with 43% expecting to get worse and 39% thinking about the end of their life. 49% of patients worried about how their spouse or carer was coping with their condition. However, only 7% and 9% felt they needed more emotional or spiritual support respectively. The majority of patients avoided doing things that made them breathless (64%) and felt that their lung condition interfered with their activities of daily living (60%) or limited them carrying things (43%) but only 13% felt they needed more practical help. Most patients wanted to be involved in care decisions should they become unwell (81%, n = 110). <h3>Conclusions</h3> ILD patients report significant physical and psychological symptoms, but there is a marked discrepancy between reported symptoms and the perceived need for additional support, including practical, emotional and spiritual support. The reason for this is unclear. It may relate to perceived lack of benefit of such services or to poor understanding of the questionnaire itself. Most patients wanted to be involved in care decisions if they become unwell, highlighting the importance of anticipatory care planning.
Randomized Trial of Preoperative Chemoradiation Versus Surgery Alone in Patients With Locoregional Esophageal Carcinoma
Authors: Susan G. Urba, Mark B. Orringer, Andrew Turrisi, Mark Iannettoni, Arlene Forastiere, Myla Strawderman
Journal: Journal of Clinical Oncology (2001)

PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m 2 /d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m 2 /d on days 1 through 21, and vinblastine 1 mg/m 2 /d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference.
Development of Lithium-Induced Nephrogenic Diabetes Insipidus Is Dissociated from Adenylyl Cyclase Activity
Authors: Yuedan Li, Stephen Shaw, Erik-Jan Kamsteeg, Alain Vandewalle, Peter M.T. Deen
Journal: Journal of the American Society of Nephrology (2006)

In antidiuresis, vasopressin (AVP) occupation of V2 receptors in renal collecting ducts activates adenylyl cyclase, resulting in increased intracellular cAMP levels, which activates protein kinase A (PKA). PKA phosphorylates both the cAMP responsive element binding protein, which induces aquaporin-2 (AQP2) transcription, and AQP2, which then is translocated to the apical membrane, allowing urine concentration. Lithium treatment often causes nephrogenic diabetes insipidus (NDI), which coincides with decreased AQP2 expression and which generally is ascribed to reduced adenylyl cyclase activity. However, the underlying mechanism by which lithium causes NDI is poorly understood. This study demonstrated that the mouse cortical collecting duct mpkCCD(c14) cells are a good model; the deamino-8 D-arginine vasopressin (dDAVP)-induced endogenous AQP2 expression and plasma membrane localization was time-dependently reduced by treatment with clinically relevant lithium concentrations. Lithium did not affect AQP2 stability but decreased its mRNA levels. Surprising, the effect of lithium was cAMP independent; it did not alter AVP-stimulated cAMP production or PKA-dependent phosphorylation of AQP2 or cAMP responsive element binding protein. In vivo, kidney tissue of rats with lithium-induced NDI indeed generated less dDAVP-induced cAMP than that of controls, but this could be due to elevated blood AVP levels in rats with lithium-induced NDI. Indeed, Brattleboro rats, which lack endogenous AVP, with clamped blood dDAVP levels, showed no difference in dDAVP-generated cAMP generation between kidneys of rats with lithium-induced NDI and control rats. In conclusion, the first proper cell model to study lithium-induced NDI was developed, and it was demonstrated that the lithium-induced downregulation of AQP2 and development of NDI occur independent of adenylyl cyclase activity in vitro and in vivo.
Functions of idh1 and its mutation in the regulation of developmental hematopoiesis in zebrafish
Authors: Xiangguo Shi, Bai-Liang He, Alvin C. H. Ma, Yuhan Guo, Yali Chi, Cheuk Him Man, Wenqing Zhang, Yiyue Zhang, Zilong Wen, Tao Cheng, Anskar Y. H. Leung
Journal: Blood (2015)