tbuckley/cabot-search huggingface dataset:
Pressor Effect of Increased Cerebrospinal Fluid Pressure and Vertebral Artery Occlusion With and Without Anesthesia
Authors: C. J. DICKINSON, J. W. MCCUBBIN
Journal: Circulation Research (1963)

The intracranial pressures of conscious, lightly anesthetized and fully anesthetized dogs were altered by means of previously implanted intraventricular cannulas, while systemic arterial pressures were simultaneously measured. One vertebral artery was occluded in all these experiments by the catheter used to record aortic pressure. Increased intracranial pressure, which probably acts by reducing cerebral blood flow, caused a rise in systemic arterial pressure whose magnitude depended on the presence and depth of anesthesia. When anesthesia was not used, but when the animals were resting quietly, a significant pressor response occurred within the physiological range of CSF pressure. The response was typically of slow onset, developing over a period of one half to two minutes. It was reproducible, but tended to diminish gradually in the course of several hours if the experiment was continued, although it could be restored if CSF pressure was further increased. The pulse rate tended to increase slightly, or remain the same, providing CSF pressure was not increased too greatly or too rapidly. Respiratory effects were variable, but most commonly a slightly increased rate and depth of respiration occurred at first, with a return towards normal as the systemic arterial pressure rose. Similar responses were seen during bilateral artery occlusion, by means of previously implanted inflatable cuffs, in dogs whose carotid sinuses had been excised. These effects were also slow in onset, and were accompanied by comparable respiratory changes. In anesthetized animals with intact carotid arteries, bilateral vertebral artery occlusion produced negligible pressor effects, but was found to augment the response to increased intracranial pressure. Observations in four dogs with chronic experimental renal hypertension did not reveal notable differences, except that these animals may be less sensitive than normal to increases in intracranial pressure. The results of these experiments are compatible with the hypothesis that basal systemic arterial pressure during sleep in some degree depends on the cerebrovascular resistance, although it will be important to determine the nature of the slow adaptation seen in these experiments. If this adaptation is brought about by compensatory cerebral vasodilation, this investigation is in accord with the concept of Dickinson and Thomson that some forms of chronic high blood pressure in man might be initiated by cerebral artery occlusion or narrowing of sufficient severity and extent to prevent adequate compensatory vasodilation.
Air pollution, pollens, and daily admissions for asthma in London 1987-92
Authors: H R Anderson, A P. de Leon, J M Bland, J S Bower, J Emberlin, D P Strachan
Journal: Thorax (1998)

<h3>BACKGROUND</h3> A study was undertaken to investigate the relationship between daily hospital admissions for asthma and air pollution in London in 1987–92 and the possible confounding and modifying effects of airborne pollen. <h3>METHODS</h3> For all ages together and the age groups 0–14, 15–64 and 65+ years, Poisson regression was used to estimate the relative risk of daily asthma admissions associated with changes in ozone, sulphur dioxide, nitrogen dioxide and particles (black smoke), controlling for time trends, seasonal factors, calendar effects, influenza epidemics, temperature, humidity, and autocorrelation. Independent effects of individual pollutants and interactions with aeroallergens were explored using two pollutant models and models including pollen counts (grass, oak and birch). <h3>RESULTS</h3> In all-year analyses ozone was significantly associated with admissions in the 15–64 age group (10 ppb eight hour ozone, 3.93% increase), nitrogen dioxide in the 0–14 and 65+ age groups (10 ppb 24 hour nitrogen dioxide, 1.25% and 2.96%, respectively), sulphur dioxide in the 0–14 age group (10 μg/m<sup>3</sup> 24 hour sulphur dioxide, 1.64%), and black smoke in the 65+ age group (10 μg/m<sup>3</sup> black smoke, 5.60%). Significant seasonal differences were observed for ozone in the 0–14 and 15–64 age groups, and in the 0–14 age group there were negative associations with ozone in the cool season. In general, cumulative lags of up to three days tended to show stronger and more significant effects than single day lags. In two-pollutant models these associations were most robust for ozone and least for nitrogen dioxide. There was no evidence that the associations with air pollutants were due to confounding by any of the pollens, and little evidence of an interaction between pollens and pollution except for synergism of sulphur dioxide and grass pollen in children (p&lt;0.01). <h3>CONCLUSIONS</h3> Ozone, sulphur dioxide, nitrogen dioxide, and particles were all found to have significant associations with daily hospital admissions for asthma, but there was a lack of consistency across the age groups in the specific pollutant. These associations were not explained by confounding by airborne pollens nor was there convincing evidence that the effects of air pollutants and airborne pollens interact in causing hospital admissions for asthma.
A risky business
Authors: Glenn McGee, Sean Philpott, Emily Carroll
Journal: The Lancet (2006)

Lesser Harms: the Morality of Risk in Medical Research comes on the heels of a bevy of books about the history of bioethics, most notably Jennifer Walter and Eran Klein's The Story of Bioethics and Albert Jonsen's Birth of Bioethics. But sociologist Sydney Halpern offers a dark and ironic account of the antecedent to contemporary research ethics that is essential reading for those who want to understand the history of clinical research.
Induction of metallothionein gene expression by epidermal growth factor and its inhibition by transforming growth factor-? and dexamethasone in rat hepatocytes*1
Authors: Pierre Moffatt, Gabriel L. Plaa, Francine Denizeau
Journal: Hepatology (1995)

Metallothionein (MT) is a small cysteine-rich protein thought to be mainly involved in metal regulation and detoxification. The implication of MT in cell growth and differentiation has also been suggested. This latter hypothesis was further investigated in adult rat hepatocytes induced to proliferate by epidermal growth factor (EGF). Exposure of hepatocytes to EGF resulted in significant increases (≈twofold) in MT protein and MT-1 messenger RNA (mRNA) levels, which were maximal after 48 hours. As revealed by nuclear run-on analysis, these changes were the result of transcriptional activation. Increases of MT occurred concomitantly with stimulation of DNA synthesis (48 hours). Addition of ZnSO4 or dexamethasone (Dex) was also effective at inducing MT protein (≈3.6 to 3.3 times) and mRNA. Combined addition of Zn and EGF produced an additive increase in MT protein and MT-1 mRNA levels. When both Dex and EGF were present together, the EGF-induced MT protein and mRNA expression was lost, whereas it had only minor inhibitory effects on DNA synthesis. Transforming growth factor beta (TGF-β), a known antagonist of EGF on hepatocytes, blocked the EGF-induced MT accumulation and stimulation of DNA synthesis. In addition, under the same conditions, the EGF-induced c-fos mRNA accumulation was blocked by Dex whereas TGF β had no effect. These results show that growth factors believed to play a role in liver regeneration can also modulate MT gene expression in vitro. This modulation does not strictly parallel that of DNA synthesis. The possibility that c-fos stimulation may play a role in MT induction by EGF cannot be ruled out.
To be or not to be B7
Authors: X. Zang, J. P. Allison
Journal: Journal of Clinical Investigation (2006)

The activation of lymphocytes and development of adaptive immune responses is initiated by the engagement of TCRs by antigenic peptide–MHC complexes and shaped at the clonal level by both positive and negative costimulatory signals. The B7 family members are involved at several stages in this process. In this issue of the JCI, Vogt et al. show that the B7 family–related protein V-set and Ig domain–containing 4 (VSIG4) can act as an inhibitor of T cell activation (see the related article beginning on page 2817). Intriguingly, the same molecule was recently independently identified as a complement receptor of the Ig superfamily (CRIg) and was convincingly demonstrated to be a receptor for complement component 3 fragments. These findings raise interesting questions regarding the physiological roles and mechanisms of action of this molecule. Identification of dual functions of this molecule provides an additional level of complexity in T cell costimulation.
Defect in the sodium-modulated tissue responsiveness to angiotensin II in essential hypertension.
Authors: D M Shoback, G H Williams, T J Moore, R G Dluhy, S Podolsky, N K Hollenberg
Journal: Journal of Clinical Investigation (1983)

In normal subjects, dietary sodium intake modulates renovascular, adrenal, and pressor responses to infused angiotensin II (AII). To examine the hypothesis that this modulation is abnormal in some patients with essential hypertension, we studied 18 hypertensives and 9 normal subjects twice--during dietary sodium restriction and during loading. Paraaminohippurate (PAH) clearance was used to assess renal plasma flow. AII was infused in graded doses (0.3-3.0 ng/kg per min). Plasma aldosterone, cortisol, renin activity, AII, sodium, potassium, and PAH clearance were measured at the onset and end of each AII dose. During dietary sodium repletion, eight of the subjects with essential hypertension showed a normal renovascular response (greater than 125 ml/min per 1.73 m2) to AII infusion (3 ng/kg per min). The decrement in renal blood flow in these normal responders (NR) was 168 +/- 10, which was comparable to the range in normotensive subjects (206 +/- 25 ml/min per 1.73 m2). All of the remaining hypertensive patients, designated abnormal responders (AbR), had lower (less than 125) renal blood flow responses to the same dose of infused AII (mean decrement: 84 +/- 11 ml/min per 1.73 m2) compared with the NR and normotensive subjects. Renal blood flow responses to all AII doses were statistically greater on a high-vs.-low salt diet in the NR (P less than 0.001, chi-square) and normotensives (P = 0.004, chi-square) but sodium intake had no effect on this response in the AbR. Basal renal blood flow in NR increased significantly (P less than 0.001, paired t test) with dietary sodium repletion, from 491 +/- 36 (low salt) to 602 +/- 40 ml/min per 1.73 m2 (high salt), but was almost identical in the AbR on differing dietary sodium intakes (429 +/- 24 vs. 425 +/- 26 ml/min per 1.73 m2). The adrenal responses to sodium intake and infused AII also differed in the two subgroups. In the NR, the adrenal response to AII was significantly greater (P = 0.011, Wilcoxon signed rank test) after sodium restriction. In contrast, there was no significant difference in the aldosterone response to AII infusion between the low and high sodium diets in the AbR. Thus, a substantial subgroup of essential hypertensives has an abnormality in responsiveness to AII in two systems central to volume homeostasis: the kidney and adrenal. They fail to modulate their renal blood flow and aldosterone responses to AII with changes in dietary sodium intake. Moreover, basal renal blood flow does not increase appropriately with increased sodium intake. These abnormalities, which may be due to an increased local production of AII or a defect in the AII receptors in these three target tissues, could contribute to the elevated blood pressure.
ESCMID guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases
Authors: A.J. Ullmann, O.A. Cornely, J.P. DonneNy, M. Akova, M.C. Arendrup, S. Arikan-Akdagli, M. Bassetti, J. Bille, T. Calandra, E. Castagnola, J. Garbino, A.H. Groll, R. Herbrecht, W.W. Hope, H.E. Jensen, B.J. Kullberg, C. Lass-Flörl, O. Lortholary, W. Meersseman, G. Petrikkos, M.D. Richardson, E. Roilides, P.E. Verweij, C. Viscoli, M. Cuenca-Estrella
Journal: Clinical Microbiology and Infection (2012)
Fighting cancer with oncolytic viruses
Authors: Yuti Chernajovsky, Lorna Layward, Nicholas Lemoine
Journal: BMJ (2006)

5-Hydroxytryptamine (5HT)1C and 5HT2 receptors display paradoxical down-regulation when exposed to receptor antagonists in vivo, a property that is unique to these two subtypes of serotonin (5HT) receptors. Because of the absence of cell culture model systems, the mechanisms involved in this paradoxical down-regulation have been difficult to explore. The present study focuses on the regulation of 5HT1C receptors in primary cultures of rat choroid plexus epithelial cells. Exposure of the epithelial cell cultures to 100 nM mianserin, a receptor antagonist, or (-)-1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane, an agonist, for 72 hr caused a loss of 5HT1C receptor binding sites, as determined by [3H]mesulergine binding to crude membrane preparations. No significant changes in Kd values were observed. Neither the agonist nor antagonist caused a significant change in binding sites after 24 hr. A solution hybridization assay was used to determine whether the down-regulation by mianserin or (-)-1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane was accompanied by a decrease in the steady state level of 5HT1C receptor mRNA. These studies showed that neither treatment caused an alteration in the levels of 5HT1C receptor mRNA. Thus, it is possible to reproduce the in vivo regulatory effects of drugs on 5HT1C receptors in choroid plexus epithelial cells in culture, including the atypical down-regulation by receptor antagonists. Using this cell culture model system, indirect transynaptic effects and decreases in receptor mRNA levels have been ruled out as mechanisms accounting for the down-regulation.
SENSITIVITY TO CODEINE
Authors: Charles W. Haden
Journal: JAMA (1935)

<h3>To the Editor:—</h3> InThe Journal, March 24, 1934, page 908, was an article by Drs. Scheer and Keil reporting a case of hypersensitiveness to codeine and stating that there were only seven proved cases on record. Since then I have seen no new reports, so I am reporting a case of mine which I think is a proved case. It made no impression on me at that time as I did not know that the condition was so rare, but the circumstances leading up to it did make a lasting impression. About eighteen years ago my brother-in-law, about 30 years old, was assisting with preparations for a wedding and was taken with a severe pain in his abdomen and applied to me for temporary relief. I gave him one-fourth grain (0.016 Gm.) of codeine, which relieved the pain but within a short time caused pruritus and a generalized eruption
Efficacy of permanent pacing in the management of high-risk patients with long QT syndrome.
Authors: A J Moss, J E Liu, S Gottlieb, E H Locati, P J Schwartz, J L Robinson
Journal: Circulation (1991)

From the international long QT syndrome (LQTS) study, 30 patients with corrected QT interval (QTc) of more than 0.44 second 1/2 were identified who had permanent pacemakers implanted for management of recurrent syncope or aborted cardiac arrest.Pacemakers were implanted on average 7 years after the onset of the first syncopal episode. Most of the patients were female (87%), the average age at implantation was 19 +/- 13 years, the mean QTc was 0.55 +/- 0.08 second, and 57% were receiving antiadrenergic treatment for LQTS when the pacemaker was placed. Using birth as the time origin, the median cardiac event rate was significantly (p less than 0.001) reduced by pacing from 0.5 to 0 events per patient per year, with 21 patients experiencing no cardiac events during an average pacemaker follow-up of 49 months per patient. In 10 patients in whom the demand atrial pacing rate was faster than the intrinsic sinus rate, the average heart rate was increased 23 beats/min (from 58 to 81 beats/min) with pacing with reduction in the QT interval from 0.59 seconds to 0.46 seconds.The beneficial effects of pacing in high-risk LQTS patients probably relate to the prevention of bradycardia, pauses, and the shortening of long QT intervals--factors that are known to be arrhythmogenic in this syndrome. Permanent cardiac pacing reduces the rate of recurrent syncopal events in high-risk LQTS patients, but it does not provide complete protection.
Osteoplastic Re-amputation of Thigh
Authors: A. Kotov
Journal: BMJ (1945)

The bone, in re-amputation, is dealt with by the Bunge method.The bone canal is tamponed with a section of muscle, bleeding vessels are carefully tied, the nerve is cut at a fairly high level with a razor blade, and drainage tubes are inserted for one day.The use of the osteoplastic operations of Pirogov, Bier, Gritti-Stokes, and Kirschner is widely recommended.
Downregulation of Monocyte Chemoattractant Protein-1 Involving Short Interfering RNA Attenuates Hapten-induced Contact Hypersensitivity
Authors: Takuji Ishimoto, Yoshifumi Takei, Yukio Yuzawa, Koji Hanai, Shunji Nagahara, Yuzo Tarumi, Seiichi Matsuo, Kenji Kadomatsu
Journal: Molecular Therapy (2007)

Contact hypersensitivity (CHS) is a common skin disease, presenting clinically as allergic contact dermatitis. At inflammatory sites in a typical CHS model in the mouse ear, elevated expression of monocyte chemoattractant protein-1 (MCP-1) has been reported. MCP-1 is a potent chemotactic factor for many types of leukocytes including monocytes/macrophages and T cells. In this study, we aimed at developing a therapy for CHS involving RNA interference targeting MCP-1. A short interfering RNA (siRNA) to mouse MCP-1 successfully inhibited the secretion of MCP-1 by a fibroblastic cell line, L929, and RAW 264.7 cells derived from macrophages, and strikingly suppressed ear swelling in a CHS model. The siRNA systemically administered inhibited the infiltration of both monocytes/macrophages and T cells in the CHS model. Atelocollagen was used in this therapy as a delivery reagent for siRNA into the animal body. Atelocollagen facilitated the incorporation of the siRNA into macrophages/monocytes and fibroblasts, which vigorously secrete MCP-1 protein at inflammatory sites in CHS. This therapy had no adverse effects such as induction of interferon, or liver or renal damage. Our data indicate that the systemic delivery of siRNA targeting MCP-1 is a potent therapeutic strategy for CHS treatment. Contact hypersensitivity (CHS) is a common skin disease, presenting clinically as allergic contact dermatitis. At inflammatory sites in a typical CHS model in the mouse ear, elevated expression of monocyte chemoattractant protein-1 (MCP-1) has been reported. MCP-1 is a potent chemotactic factor for many types of leukocytes including monocytes/macrophages and T cells. In this study, we aimed at developing a therapy for CHS involving RNA interference targeting MCP-1. A short interfering RNA (siRNA) to mouse MCP-1 successfully inhibited the secretion of MCP-1 by a fibroblastic cell line, L929, and RAW 264.7 cells derived from macrophages, and strikingly suppressed ear swelling in a CHS model. The siRNA systemically administered inhibited the infiltration of both monocytes/macrophages and T cells in the CHS model. Atelocollagen was used in this therapy as a delivery reagent for siRNA into the animal body. Atelocollagen facilitated the incorporation of the siRNA into macrophages/monocytes and fibroblasts, which vigorously secrete MCP-1 protein at inflammatory sites in CHS. This therapy had no adverse effects such as induction of interferon, or liver or renal damage. Our data indicate that the systemic delivery of siRNA targeting MCP-1 is a potent therapeutic strategy for CHS treatment.
Diabetes-Related Distress and Physical and Psychological Health in Chinese Type 2 Diabetic Patients
Authors: Rose Z.W. Ting, Hairong Nan, Mandy W.M. Yu, Alice P.S. Kong, Ronald C.W. Ma, Rebecca Y.M. Wong, Kitman Loo, Wing-Yee So, Chun-Chung Chow, Gary T.C. Ko, Yun-Kwok Wing, Juliana C.N. Chan
Journal: Diabetes Care (2011)

To validate a Chinese version of the Diabetes Distress Scale (CDDS).The CDDS was derived using forward-backward translation and administered in 189 Chinese type 2 diabetic patients with evaluation of its psychometric properties.On the basis of principal-component analysis, three factors of the 15-item version of the CDDS (CDDS-15) accounted for 63% of the variance. The correlation coefficient between the original 17-item and 15-item scales was 0.99. The Cronbach α for internal consistency was 0.90, and the test-retest reliability coefficient was 0.74. The CDDS-15 score was significantly associated with glycemic control, obesity, depressive symptoms, and quality of life.The CDDS-15 is a valid and reliable instrument to assess diabetes-related distress.
Endoscopic Ultrasonographic Diagnosis of Pancreatic Cancer Complicating Chronic Pancreatitis
Authors: M. Barthet, I. Portal, J. Boujaoude, J.-P. Bernard, J. Sahel
Journal: Endoscopy (1996)

Background and Study Aims: Pancreatic cancer is a rare complication of chronic pancreatitis (CP), and its diagnosis remains difficult. The present study attempted to evaluate the ability of endoscopic ultrasonography (EUS) to diagnose pancreatic masses associated with CP and provide evidence of malignancy in patients with a pancreatic mass on EUS.
Cutaneous Malassezia flora in atopic dermatitis differs between adults and children
Authors: Y. Takahata, T. Sugita, H. Kato, A. Nishikawa, M. Hiruma, M. Muto
Journal: British Journal of Dermatology (2007)

Malassezia species are suspected to be involved in the development of skin lesions in atopic dermatitis (AD) when the response of adult AD to anti-inflammatory treatments is poor. However, a comparative analysis of Malassezia flora between adults and children with AD has not been performed.To compare the cutaneous Malassezia flora between adults and children with AD.Scale samples were collected from skin lesions of 58 patients with AD in the head and neck regions (28 males and 30 females; 31 children and 27 adults), and fungal DNA was extracted from the samples directly. The number and identities of the Malassezia species were analysed with high accuracy using a polymerase chain reaction-based culture-independent method. The in vivo level of anti-Malassezia IgE antibody was also assayed.Malassezia restricta was the predominant species in the children with AD, while both M. restricta and M. globosa predominated in the adults. The adults showed increased sensitization in terms of anti-Malassezia-specific IgE responses in the sera to both M. globosa and M. restricta in comparison with the children.The cutaneous Malassezia flora differs significantly between the two age groups.