tbuckley/cabot-search huggingface dataset:
Telaprevir-Related Dermatitis
Authors: Jean-Claude Roujeau, Maja Mockenhaupt, Steven R. Tahan, Joshua Henshaw, Emily C. Martin, Matt Harding, Ben van Baelen, Leif Bengtsson, Priya Singhal, Robert S. Kauffman, Robert S. Stern
Journal: JAMA Dermatology (2012)

To evaluate the incidence, type, and severity of telaprevir-associated skin reactions.Three dermatologists assessed available information including photographs, biopsy results, and clinical summaries of all cases with skin eruptions reported as moderate or severe during the telaprevir clinical development program. For cases from placebo-controlled trials, they were masked to exposure.Phase 1 to 3 studies of telaprevir combination therapy for hepatitis C.All patients with skin eruptions enrolled in telaprevir clinical trials prior to 2011 MAIN OUTCOME MEASURES: Incidence, diagnosis, morphologic features, extent, and severity of skin eruption.Skin eruptions were more frequent in patients who received telaprevir as part of hepatitis C treatment compared with pegylated interferon (peginterferon) and ribavirin alone (56% vs 34% overall; 3.7% vs 0.4% severe). Occurring at any time during the 12 weeks of telaprevir combination regimen, in more than 90% of cases, this eruption is pruritic eczematous dermatitis. None of the clinical or genetic factors examined were substantial risk factors for dermatitis. Three cases of Stevens-Johnson Syndrome (SJS), and 11 cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) were suspected, with 2 SJS and 3 DRESS cases considered likely.Telaprevir-related dermatitis occurs in a majority of telaprevir-treated patients. It is an eczematous dermatitis that differs in timing and appearance from the eruptions usually associated with drug reactions. The strong signal for an increased risk of DRESS or SJS requires particular vigilance in telaprevir-treated patients.
Changes of Serum Growth Hormone in Psychosomatic Disorders
Authors: Hiroyuki Suematsu, Nobuo Kurokawa, Hajime Tamai, Yujiro Ikemi
Journal: Psychotherapy and Psychosomatics (1974)

The authors have measured serum growth hormone (GH) in various psychosomatic disorders by a radioimmunoassay technique, and have obtained the following results. (1)The resting levels of serum GH in anorexia nervosa were high in 14 of 20 cases. The response of GH secretion to induced hypoglycemia was abnormal in some cases of anorexia nervosa. (2) Serum GH in depressive patients was found to be high in 20 % of all cases. (3) Although serum GH showed an increase during stress interviews and asthmatic attacks in a few cases, it did not increase in most. (4) Serum GH was found to be high in only 2 of 8 cases during the time when patients were undergoing a 10-day fasting treatment. (5) Minor tranquilizers have no effect on GH secretion. Chlorpromazine reduced GH secretion, while L-dopa increased it. The study of individual variations in the degree of change in the level of GH seems to be one of the most important themes which needs to be pursued in the future.
Mechanism of cGMP-mediated protection in a cellular model of myocardial reperfusion injury
Authors: Y ABDALLAH, A GKATZOFLIA, H PIEPER, E ZOGA, S WALTHER, S KASSECKERT, M SCHAFER, K SCHLUTER, H PIPER, C SCHAFER
Journal: Cardiovascular Research (2005)

Reperfusion injury of the myocardium is characterised by development of cardiomyocyte hypercontracture. Previous studies have shown that cGMP-mediated stimuli protect against reperfusion injury, but the cellular mechanism is still unknown.To simulate ischemia/reperfusion, adult rat cardiomyocytes were incubated anoxically (pH(o) 6.4) and then reoxygenated (pH(o) 7.4). Cytosolic calcium [Ca(2+)](i) (fura-2 ratio), pH(i) (BCECF ratio), cell length, and phospholamban phosphorylation were analysed. Under simulated ischemia cardiomyocytes develop [Ca(2+)](i) overload. When reoxygenated they rapidly undergo hypercontracture, triggered by oscillations of [Ca(2+)](i). We investigated whether cGMP-mediated stimuli can modulate [Ca(2+)](i) or pH(i) recovery and whether this contributes to their protective effect. Membrane-permeable cGMP analogues, 8-bromo-cGMP (1 mmol/L) or 8-pCPT-cGMP (10 micrommol/L), or a receptor-mediated activator of particulate guanylyl cyclase, urodilatin (1 micromol/L), were applied.The investigated stimuli protect against reoxygenation-induced hypercontracture (cell length as percent of end-ischemic length; control: 68+/-1.6; 8-bromo-cGMP: 88+/-1.5*; 8-pCPT-cGMP: 84+/-2.9*; urodilatin: 87+/-1.1*; n=24; *p<0.05). Recovery from [Ca(2+)](i) overload after 2 min reoxygenation [fura-2 ratio (a.u.); control: 1.43+/-0.15; 8-bromo-cGMP: 1.86+/-0.15*; 8-pCPT-cGMP: 1.92+/-0.19*; urodilatin: 1.93+/-0.24*; n=25; *p<0.05] was accelerated, and the frequency of [Ca(2+)](i) oscillations (min(-1)) was significantly reduced (control: 49+/-5.0 min(-1); 8-bromo-cGMP: 18+/-3.5* min(-1); 8-pCPT-cGMP: 18+/-4.5* min(-1); urodilatin: 16+/-4.1* min(-1); n=24; *p<0.05). cGMP-mediated stimuli increased sarcoplasmic Ca(2+) sequestration (caffeine-releasable Ca(2+) pool: 2-3 fold increase vs. control). Inhibition of sarcoplasmic Ca(2+)-ATPase (SERCA) by thapsigargin (150 nmol/L) or of protein kinase G with KT-5823 (1 micromol/L) abolished the effect of these stimuli on [Ca(2+)](i) recovery. The investigated stimuli significantly enhanced phospholamban phosphorylation.We conclude that cGMP-dependent signals activate SERCA via a protein kinase G-dependent phosphorylation of phospholamban. The increase in SERCA activity seems to reduce peak [Ca(2+)](i) and [Ca(2+)](i) oscillation during reoxygenation and to attenuate the excessive activation of the contractile machinery that otherwise leads to the development of hypercontracture.
S33 Suppression of constitutive and stimulated secretion of histamine from human lung mast cells by a secreted factor from lung epithelial cells
Authors: N. Martin, G. K. Arthur, W. Y. H. Wan, L. Woodman, C. E. Brightling, I. D. Pavord, P. Bradding
Journal: Thorax (2010)

<h3>Introduction</h3> Constitutive and IgE-dependent secretion of histamine from human lung mast cells (HLMC) is suppressed by direct contact with the BEAS-2B bronchial epithelial cell line, but not conditioned epithelial cell media. This suggests that direct contact or a low concentration/labile secreted factor is involved. We explored this relationship further using a Transwell co-culture system of HLMC with BEAS-2B monolayers or air liquid interface primary bronchial epithelial cultures (ALI) derived from asthmatic and healthy subjects. <h3>Methods</h3> ALI and BEAS-2B were grown on Transwell membranes. IgE-sensitised HLMC were then cultured i) on the luminal surface of a BEAS-2B monolayer, ii) separated from the BEAS-2B basal surface by a Transwell membrane, or iii) on the well bottom with BEAS-2B and ALI sitting on the Transwell insert. Cells were co-cultured for 16 h, media removed, and HLMC stimulated with anti-IgE for 30 min. Parallel controls without epithelial cells were performed. Histamine concentrations were determined by radioenzymic assay. <h3>Results</h3> <i>BEAS-2B (n=3)</i>: Compared to no epithelium control, constitutive histamine secretion from HLMC in direct contact with BEAS-2B was suppressed by a mean (±SEM) 57±15% (p=0.04), and by 55±9% when separated by Transwells (p=0.02). IgE-dependent secretion was suppressed by 79±8% (p=0.04) from HLMC in direct contact with BEAS-2B and by 88±7% (p=0.03) when separated by Transwells, compared to control. <i>ALI-culture (n=6 healthy, 6 asthmatic)</i>: Compared to control, healthy ALI suppressed constitutive HLMC histamine release by 39±5% (p=0.01), but asthmatic ALI did not (mean 19±11% suppression, p=0.07). There was a significant difference between healthy compared to asthmatic ALI (p=0.01). Healthy and asthmatic ALI suppressed IgE-dependent histamine release by 55±4%, p=0.001 and 48±1%, p=0.001, respectively. <h3>Conclusions</h3> BEAS-2B and healthy airway epithelial cells suppress constitutive and IgE-dependent HLMC histamine secretion when separated by Transwell membranes. Asthmatic ALI cultures do not suppress constitutive HLMC histamine secretion, but do suppress IgE-dependent secretion. These results suggest that the normal regulation of this process is by a secreted, probably labile factor(s), which may be partially deficient in asthma. Isolation and manipulation of this factor may have interesting therapeutic potential.
Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation
Authors: Janine Beale, Annabelle Jayaraman, David J. Jackson, Jonathan D. R. Macintyre, Michael R. Edwards, Ross P. Walton, Jie Zhu, Yee Man Ching, Betty Shamji, Matt Edwards, John Westwick, David J. Cousins, You Yi Hwang, Andrew McKenzie, Sebastian L. Johnston, Nathan W. Bartlett
Journal: Science Translational Medicine (2014)

IL-25 critically links rhinovirus infection and allergic asthma exacerbations.
Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate.
Authors: I J Doull, N J Freezer, S T Holgate
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.
Neuropeptide-containing nerves in painful hypertrophic human scar tissue
Authors: R. CROWE, N. PARKHOUSE, D. MCGROUTHER, G. BURNSTOCK
Journal: British Journal of Dermatology (1994)

Specimens of hypertrophic scar tissue (n = 9), non-hypertrophic, flat scar tissue (n = 5) and control skin (n = 3) were obtained from eight adult females (aged 22-56) and three adult males (aged 22-59). The specimens were studied histologically and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, substance P, somatostatin, [Met]enkephalin, [Leu]enkephalin, and the enzyme dopamine beta-hydroxylase. The non-hypertrophic scar tissues were not dissimilar to the control tissue, but contained connective tissue in bundles with a greater number of collagen fibres. In the hypertrophic scar tissue of some patients, the dermis contained adipose tissue displaced upwards from the hypodermis. The connective tissue contained densely packed collagen fibres and fibroblasts; this region was devoid of hair follicles, sweat glands and blood vessels, although they were observed in the region of loosely packed connective tissue. The normal skin contained all the neuropeptides studied, except somatostatin-, and dopamine beta-hydroxylase-immunoreactive nerves, which were seen as single fibres or in nerve bundles, and were associated with blood vessels in the dermis. Neuropeptide Y-immunoreactive nerves were found in the arrector pili muscle, and neuropeptide Y-, vasoactive intestinal polypeptide-, calcitonin gene-related peptide-, [Met]enkephalin- and dopamine beta-hydroxylase-containing nerves were found within sweat glands. In patients with flat, non-hypertrophic scar tissue, neuropeptides and dopamine beta-hydroxylase-containing nerves were absent. In patients with hypertrophic scars, the density of neuropeptide Y-, vasoactive intestinal polypeptide-, substance P-, calcitonin gene-related peptide- and dopamine beta-hydroxylase-immunoreactive nerves was greater in the dermis when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Baroreflex Buffering Is Reduced With Age in Healthy Men
Authors: Pamela Parker Jones, Demetra D. Christou, Jens Jordan, Douglas R. Seals
Journal: Circulation (2003)

Background— Baroreflex buffering is an important mechanism in arterial blood pressure control. The effect of healthy (physiological) aging on tonic baroreflex buffering in humans is unknown. Methods and Results— Baroreflex buffering was determined in 27 young (aged 25±1 years) and 16 older (aged 65±1 years) healthy normotensive men by measuring the potentiation of the systolic blood pressure (SBP) responses to a phenylephrine bolus (BRB bolus ) and incremental infusion (BRB slope ) during compared with before ganglionic blockade with trimethaphan. The SBP responses to phenylephrine either were not different or greater in the older men before ganglionic blockade, but smaller during ganglionic blockade. BRB bolus (2.1±0.4 versus 5.1±0.7, P &lt;0.001) and BRB slope (1.6±0.2 versus 3.5±0.4, P &lt;0.0001) were ≈115% smaller in the older men. Baroreflex buffering was not consistently related to mean levels or variability of blood pressure or heart rate, or to cardiovagal baroreflex sensitivity, but correlated with muscle sympathetic nerve activity (BRB bolus : r =−0.55, BRB slope : r =−0.69, P &lt;0.005) and the SBP responses to phenylephrine during ganglionic blockade (BRB bolus : r =0.53; BRB slope : r =0.98, P &lt;0.0001). BRB bolus was also inversely related to the SBP response to phenylephrine before ganglionic blockade ( r =−0.78, P &lt;0.0001). Conclusions— Physiological aging in men is associated with a marked reduction in baroreflex buffering. The decrease in baroreflex buffering with aging is related to increases in basal sympathetic nerve activity and reductions in systemic α 1 –adrenergic vascular responsiveness. These findings are helpful for interpreting changes in baroreflex buffering in older patients with cardiovascular disease, as well as changes in responsiveness to vasoactive drugs with aging.
Unilateral Papilledema in 'Benign' Intracranial Hypertension (Pseudotumor Cerebri)
Authors: Neal A. Sher
Journal: JAMA (1983)

Three patients with benign intracranial hypertension ([BIH], or pseudotumor cerebri) had verified increased CSF pressure and unilateral papilledema. One patient had slowly progressive loss of visual acuity until unilateral optic nerve sheathotomy was performed. One patient had spontaneous venous pulsation in the unaffected eye. The diagnosis of BIH must be considered even in the absence of bilateral papilledema. (<i>JAMA</i>1983;250:2346-2347)
SAT0468 The risk of cardiovascular events is increased in people with glucocorticoid-induced lipodystrophy
Authors: L. Fardet, I. Petersen, I. Nazareth
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Glucocorticoid exposure is associated with a two- to threefold increased risk of cardiovascular events [1, 2]. There are reasonable clinical and biological bases to hypothesize that this risk is higher in glucocorticoid-exposed people who develop lipodystrophy than in glucocorticoid-exposed patients without lipodystrophy. <h3>Objectives</h3> To assess the incidence rates of cardiovascular events in people prescribed systemic glucocorticoids and with a diagnosis of glucocorticoid-induced lipodystrophy (GCs+GIL+) by comparison to two comparison population, i.e., people prescribed systemic glucocorticoids with no diagnosis of glucocorticoid-induced lipodystrophy (GCs+GIL–) and people not prescribed systemic glucocorticoids (GCs–). To assess the association between lipodystrophy and the risk of cardiovascular events. <h3>Methods</h3> The Health Improvement Network primary care database was used to identify the three study populations. Cox proportional hazards models were used to estimate hazard ratios associated with lipodystrophy.Models were adjusted for sex, age, duration of glucocorticoid exposure, underlying disease, smoking status and past history of antidiabetic, antihypertensive or lipid lowering drug prescription. <h3>Results</h3> 547 GCs+GIL+ people were compared to 3231 GCs+GIL- people and to 3282 GCs- people. 417 cardiovascular events (coronary heart disease n=239, heart failure n=112, ischemic stroke n=66) occurred within a year after diagnosis of lipodystrophy or after a randomly selected date in 341 patients. Taking into account only the first event by patient, the incidence rates of cardiovascular event per 100 person-year at risk were 15.1 (95% confidence interval, 11.8 to 18.4), 6.4 (5.5 to 7.3) and 4.1 (3.4 to 4.8), respectively in GCs+GIL+, GCs+GIL– and GCs– groups. By comparison to GCs+GIL– people, those in the GCs+GIL+ group had a nearly three fold increased risk of cardiovascular events (adjusted hazard ratios: 2.27 (1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure and 2.23 (0.96 to 5.17) for ischemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the GCs+GIL+ group was compared to the GCs– group <h3>Conclusions</h3> In glucocorticoid-exposed patients, lipodystrophy should be aggressively targeted for early screening and management of atherosclerosis and other cardiovascular risk factors. <h3>References</h3> Souverein PC, Berard A, Van Staa TP, Cooper C, Egberts AC, Leufkens HG et al. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart. 2004;90:859-65 Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med. 2004;141:764-70 <h3>Disclosure of Interest</h3> None Declared
Parallel analysis of tissue-type plasminogen activator and type 1 plasminogen activator inhibitor in plasma and endothelial cells derived from patients with chronic pulmonary thromboemboli.
Authors: I M Lang, J J Marsh, M A Olman, K M Moser, R R Schleef
Journal: Circulation (1994)

BACKGROUND Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries. METHODS AND RESULTS To determine if the failure to lyse pulmonary thromboemboli is caused by an abnormality in the endothelial cell (EC)-associated fibrinolytic system, conditions were established to culture ECs from patient main pulmonary arteries during surgical pulmonary thromboendarterectomies and to analyze the conditioned media for levels of tissue-type plasminogen activator (TPA) and type 1 plasminogen activator inhibitor (PAI-1). Our data indicate that the levels of TPA antigen and PAI-1 activity in media conditioned by primary ECs harvested from areas free of thrombus were not significantly different between patients with chronic thromboemboli and organ donors. In 13 consecutive patients, no correlation was obtained in either the TPA antigen or PAI-1 activity level in a patient's plasma and the respective levels in media conditioned by the patient's pulmonary ECs. Moreover, patient pulmonary arterial ECs were observed to increase the secretion of TPA and PAI-1 in response to thrombin in a fashion similar to donor pulmonary artery ECs. CONCLUSIONS The data suggest that an inherent EC-mediated fibrinolytic imbalance is not a generalized phenomenon observed in pulmonary arteries of patients with chronic pulmonary thromboemboli.
Antibiotics carried in general practitioners' emergency bags: four years on
Authors: M J Colbridge, G G Baily, E M Dunbar, E L C Ong
Journal: BMJ (1995)

decision making is influenced by a multitude of diverse factors.Black takes the view that in relation to the increase in testing in recent years the ease of access and the use of autoanalysers may be the most important factors in influencing practice.9The division into positive and negative defensive practices warrants further explanation.For example, in relation to "increased diagnostic testing" one doctor's defensive medicine may be another doctor's good practice.Diagnostic testing may reach a defen- sive level in different doctors at differing levels and thus, in this study, inquiring about specific tests was avoided.Avoiding certain procedures in practice was used to indicate negative defensive practice.However, though this accords with definitions used elsewhere, Black has suggested that if risk avoidance leads to a concentration of services in the hands of fewer specialised doctors it could enhance rather than lower the quality of care.9The response rate in the survey was 60%.This compares favourably with response rates in similar medicolegal surveys and accords with a recent review of general practice based research published in the British Journal of General Practice.10Some biases may have arisen both from the choice of the sampling frame and from response bias.For several reasons the Medical Defence Union might be more successful at recruiting from certain medical schools.Response bias was examined to some extent by comparing the general practitioners responding to the survey with known demographic variables among British general practitioners.The results indicate the generally representative nature of this study.11Some defensive practices such as increased patient explanations or more detailed note taking are clearly beneficial.However, the existence of negative defensive medical practice is perhaps best viewed as a symptom of the fundamental problems inherent within the present judicial and quasijudicial regulatory systems.The reforms proposed by the Wilson com- mittee will encourage complaints, and my results indicate that in the current climate there could be a Key messages * Implementing the findings of the Wilson committee will encourage complaints in general practice * Some defensive practices may be beneficial but others will have adverse effects on both patient care and resource allocation * Some 98% of general practitioners claim to be making practice changes in response to the possibility of a patient complaining * Defensive medical practices correlate with concerns about risks but not with a lack of understanding of the concept of negligence or the general practitioner's terms of service; such an association is particularly strong in the case of negative defensive practices significant rise in such negative defensive medical practices with adverse consequences for patient care.I acknowledge the help of Dr P Hoyte and the Medical Defence Union for help in distributing the questionnaire.