tbuckley/cabot-search huggingface dataset:
Pulmonary Artery Remodeling Differs in Hypoxia- and Monocrotaline-induced Pulmonary Hypertension
Authors: ROBERT J. van SUYLEN, JOS F. M. SMITS, MAT J. A. P. DAEMEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

In the present study we analyzed structural characteristics of muscular pulmonary arteries and arterioles in two classic models of pulmonary hypertension, the rat hypoxia and monocrotaline models. We hypothesized that an increase in medial cross-sectional area would result in reduction of the lumen area and that these parameters would correlate with the increase in pulmonary artery pressure (PAP). Four weeks after a single injection of monocrotaline (MCT) or after 4 wk of hypoxic exposure the rats were killed. Both MCT and chronic hypoxia induced right ventricular hypertrophy. In separate groups of rats both MCT and chronic hypoxia increased PAP. MCT increased the media cross-sectional area of pulmonary arteries with an external diameter between 30-100 microm and 101-200 microm and reduced the lumen area of pulmonary arteries with an external diameter between 101-200 microm. Chronic hypoxia only slightly increased the media cross-sectional area without a change of the lumen area. Both MCT and hypoxia increased the percentage of partly muscularized and muscularized arterioles. The angiotensin-converting enzyme (ACE) inhibitor captopril (0.5 mg/kg/h) had no effect on MCT-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary artery remodeling. In chronic hypoxic rats it prevented an increase in medial cross-sectional area of pulmonary arteries with an external diameter between 30-100 microm and attenuated the increase in the percentage of muscularized arterioles, without any effect on the PAP. We conclude that MCT, in contrast to chronic hypoxia, induces structural changes of muscular pulmonary arteries with an external diameter between 101-200 microm which may contribute to an increased PAP and right ventricular hypertrophy. These data also suggest that angiotensin II plays a pivotal role in remodeling of pulmonary arteries in hypoxia but not in MCT-induced pulmonary hypertension.
SCHILDER'S DISEASE IN ERGOTAMINE INTOXICATION
Authors: GEORGE A. JERVIS, J. A. KINDWALL
Journal: American Journal of Psychiatry (1942)

The case is reported of an adult male patient, who, in the course of prolonged use of excessive doses of ergotamine given by the intravenous route, developed a severe condition characterized by profound mental confusion and tonic and clonic spasms, and terminating rapidly in death. Post mortem, there was the characteristic picture of acute Schilder's disease. The possible relation of the ergotamine intoxication to the demyelinating process is taken into consideration and briefly discussed.
A2: Rapid and Sustained Response in Patients Suffering From Severe Cryopyrin‐Associated Periodic Syndromes Treated With Anakinra (Kineret®)
Authors: Mika Leinonen, Bengt Hallén, Hans Olivecrona
Journal: Arthritis & Rheumatology (2014)

Background/Purpose: Cryopyrin‐Associated Periodic Syndromes (CAPS) are a group of rare inherited autoinflammatory diseases consisting of a spectrum of three conditions: FCAS, Muckle‐Wells Syndrome and the most severe form, NOMID. Anakinra was recently approved in the US for treatment of NOMID and in the European Union for treatment of CAPS. The objective of the present analysis is to assess the response rate to anakinra treatment and time to changes in symptom severity after initiation, withdrawal and re‐institution of the treatment in patients with severe CAPS. Methods: A prospective, open‐label withdrawal design study of anakinra treatment with long‐term extension including 43 patients was conducted at the National Institutes of Health (Goldbach‐Mansky et al 2006, Sibley et al 2012). The primary efficacy endpoint, the Diary Symptom Sum Score (DSSS) collected daily up to 60 months included 5 symptoms (fever, rash, joint pain, vomiting, headache); each scored from 0 (no symptoms) to 4 (severe symptoms). Earlier data demonstrated that rash and conjunctivitis disappeared in 3 days in all patients, the DSSS was decreased at 3 months and all patients except one met the criteria of a flare during the 7‐day withdrawal phase (Goldbach‐Mansky et al 2006). In the present analysis, we defined the response as at least 50% improvement from baseline in the weekly average DSSS. The mean changes in DSSS were estimated with Mixed Model for Repeated Measures (MMRM). Results: Twenty nine out of the 43 enrolled patients provided valid DSSS data for the analysis. A majority of the patients were children (17% &lt;2 years, 55% 2–11 years, 7% 12–17 years, 21% 18 years or more). All 29 patients responded to the treatment during the first 10 days based on DSSS. The average DSSS decreased from 4.5 to 0.8 in 2 days. This response was maintained throughout the study up to 60 months and at each post‐baseline visit &gt;80% of the patients met the response criteria. Eleven consecutive patients participated in the withdrawal phase at 3 months of treatment. After treatment withdrawal the average DSSS increased from 0.6 to 5.2 (p&lt;0.0001 compared to continuously treated patients). After re‐institution of treatment the DSSS returned to pre‐withdrawal levels within 3 days. Conclusion: All patients experienced a rapid response to the anakinra treatment, both initially and after a flare caused by the withdrawal phase. The response was maintained up to 60 months.
Short-term Effects of Coping Skills Training as Adjunct to Intensive Therapy in Adolescents
Authors: Margaret Grey, Elizabeth A Boland, Maryanne Davidson, Chang Yu, Susan Sullivan-Bolyai, William V Tamborlane
Journal: Diabetes Care (1998)

OBJECTIVE Given the urgent need to develop effective programs that improve the ability for adolescents to achieve metabolic control equivalent to programs studied in the Diabetes. Control and Complications Trial, we have undertaken a clinical trial to determine if a behavioral intervention (coping skills training [CST]) combined with intensive diabetes management can improve metabolic control and quality of life in adolescents implementing intensive therapy regimens. RESEARCH DESIGN AND METHODS A total of 65 youths between the ages of 13 and 20 years, who elected to initiate intensive insulin therapy, were randomly assigned to one of two groups: the intensive management with CST group and the intensive management without CST group. CST consists of a series of small group efforts designed to teach adolescents the coping skills of social problem-solving, social skills training, cognitive behavior modification, and conflict resolution. Data were collected at pre-intervention and at 3 months following the use of the Self-Efficacy for Diabetes scale, Children's Depression Inventory, Issues in Coping with IDDM scale, and the Diabetes Quality of Life: Youth scale. Clinical data (HbA1c, adverse effects) were collected monthly. RESULTS The experimental and control groups were comparable on all measures at baseline. Results show that adolescents who received CST had lower HbA1c and better diabetes self-efficacy and were less upset about coping with diabetes than adolescents receiving intensive management alone. In addition, adolescents who received the CST found it easier to cope with diabetes and experienced less of a negative impact of diabetes on quality of life than those who did not receive CST. CONCLUSIONS CST is useful in improving not only an adolescent's metabolic control, but also their quality of life. As more pediatric providers aim for improved control, in adolescents with diabetes, the addition of this behavioral intervention may be helpful in achieving metabolic and life goals.
HLA B27 related 'unclassifiable' seronegative spondyloarthropathies.
Authors: S Prakash, N K Mehra, S Bhargava, A N Malaviya
Journal: Annals of the Rheumatic Diseases (1983)

Twenty-five patients (22 males and 3 females) are described who had 'unclassifiable' seronegative peripheral arthritis affecting mainly the large joints of the lower limbs with other typical features of spondyloarthropathies such as heel pain, low back pain, and mucosal ulcers. But their disorders could not be diagnosed as any specific spondyloarthropathy such as ankylosing spondylitis, Reiter's disease, etc. The mean age of onset of disease was 21.4 years and 60% of them had mono- or oligoarthritis; 60% had arthritis of only lower limb joints. Knee, ankle, and hip joints were most commonly involved, often asymmetrically (mean degree of asymmetry = 0.28). Minimal radiographic sacroiliitis was present in 4 patients, though 13 had low back pain. HLA B27 antigen was detected in 21 (84%) of these patients and only 5.9% of 118 controls (relative risk 83). In addition to these 25 patients there were 4 others whose only symptom was severe bilateral heel pain: 3 of them were positive for HLA B27.
The Lung Macrophage: A Jack of All Trades
Authors: Alexander V. Misharin, G. R. Scott Budinger, Harris Perlman
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

MMP-9) activity and thereby limit aberrant elastin degradation, and/or by limiting excessive TGF-b signaling, perhaps by preventing TGF-b activation, or TGF-b release from the extracellular matrix, and/or by limiting pulmonary inflammation.However, none of these possibilities have been experimentally confirmed.In addition, the authors have not considered any direct effects of elafin on the innate and adaptive immune system, recently reviewed by Sallenave (13).A mechanistic explanation for their observations will go a long way to deepen our understanding of the mechanistic basis of BPD, and should be addressed in future studies.
SOME EYE INJURIES AND THEIR LESSONS.
Authors: F. C. HEATH
Journal: JAMA (1905)

Eye injuries present such an infinite number of possibilities, so many differences in course, extent, symptoms and complications, that while we may derive some valuable points from experience and may lay down rules and principles applicable to many conditions, still each serious eye injury is largely a rule to itself and offers an interesting field for study. I desire to present, briefly, three groups of three cases each, representing three serious forms of injury worthy of our attention. The first group comprises cases of foreign bodies in the lens; the second, foreign bodies in the iris; the third, wounds in or near the ciliary region. <h3>GROUP 1: FOREIGN BODIES IN THE CRYSTALLINE LENS.</h3><h3>Case 1.</h3> —W. B. consulted me Octotber 13, 1894, with history of injury to right eye by a guncap nine years before. <h3>Examination.</h3> —This showed traumatic cataract with piece of cap in the lens. R. V. = Light
Scientific Misconduct in Environmental Science and Toxicology
Authors: Herbert N. Nigg
Journal: JAMA (1994)

Scientific misconduct easily occurs in environmental science and toxicology; we encountered four such cases. Only one case was discovered by editors; three were reported by other authors. All guilty authors were eventually banned from future publication in the<i>Bulletin of Environmental Contamination and Toxicology</i>. Cases in the<i>Bulletin</i>indicate that scientific misconduct may occur undetected across phyla, genera, and species; that distance from the publishing source makes detection more difficult; that editors and reviewers are not organized to take action against scientific misconduct; that plagiarized authors are likely to report plagiarism; and that there is only a small risk of censure from any source for authors engaging in scientific misconduct. (<i>JAMA</i>. 1994;272:168-170)
Pentoxifylline inhibits growth and collagen synthesis of cultured human hepatic myofibroblast-like cells
Authors: A Preaux, A Mallat, J Rosenbaum, E Zafrani, P Mavier
Journal: Hepatology (1997)

During the course of liver fibrogenesis, myofibroblast-like cells (MFLC), mostly derived from hepatic stellate cells, proliferate and synthesize excessive amounts of extracellular matrix components. Pentoxifylline (PTX) elicits antiproliferative and antifibrogenic effects in human dermal fibroblasts. The aim of this study was to test the effects of PTX on the proliferation and the synthesis of collagen and gelatinase A in cultured human hepatic MFLC. MFLC were obtained by outgrowth from human liver explants. PTX markedly reduced serum-driven cell proliferation, as assessed by nuclear autoradiography experiments and measurement of actual cell growth. Growth inhibition was totally reversed after removal of the drug. PTX also affected collagen synthesis, as measured by [3H]hydroxyproline incorporation into proteins. Synthesis of secreted collagen was reduced by 24% and 67% at concentrations of 100 microg/mL and 500 microg/mL, respectively. This was associated with a decrease in type I and III procollagen messenger RNA (mRNA), indicating an effect at a pretranslational level. In contrast, PTX did not affect either gelatinase A activity released in culture medium or the expression of its specific mRNA. In conclusion, PTX exhibits potent antiproliferative and antifibrogenic effects toward hepatic MFLC. These results suggest that PTX might have therapeutic implications in chronic liver disease.
Benzene toxicity and risk assessment, 1972-1992: implications for future regulation.
Authors: D J Paustenbach, R D Bass, P Price
Journal: Environmental Health Perspectives (1993)

Acute and chronic exposure to benzene vapors poses a number of health hazards to humans. To evaluate the probability that a specific degree of exposure will produce an adverse effect, risk assessment methods must be used. This paper reviews much of the published information and evaluates the various risk assessments for benzene that have been conducted over the past 20 years. There is sufficient evidence that chronic exposure to relatively high concentrations of benzene can produce an increased incidence of acute myelogenous leukemia (AML). Some studies have indicated that benzene may cause other leukemias, but due to the inconsistency of results, the evidence is not conclusive. To predict the leukemogenic risk for humans exposed to much lower doses of benzene than those observed in most epidemiology studies, a model must be used. Although several models could yield plausible results, to date most risk assessments have used the linear-quadratic or conditional logistic models. These appear to be the most appropriate ones for providing the cancer risk for airborne concentrations of 1 ppb to 10 ppm, the range most often observed in the community and workplace. Of the seven major epidemiology studies that have been conducted, there is a consensus that the Pliofilm cohort (rubber workers) is the best one for estimating the cancer potency because it is the only one with good exposure and incidence of disease data. The current EPA, OSHA, and ACGIH cancer potency estimates for benzene are based largely on this cohort. A retrospective exposure assessment and an analysis of the incidence of disease in these workers were completed in 1991. All of these issues are discussed and the implications evaluated in this paper. The range of benzene exposures to which Americans are commonly exposed and the current regulatory criteria are also presented.
PTFE-covered stents improve TIPS patency in Budd-Chiari syndrome
Authors: Manuel Hernández-Guerra, Juan Turnes, Pablo Rubinstein, Simon Olliff, Elwyn Elias, Jaime Bosch, Juan Carlos García-Pagán
Journal: Hepatology (2004)

Transjugular intrahepatic portosystemic shunt (TIPS) have been shown to be an efficient portal-systemic derivative treatment for Budd-Chiari syndrome (BCS) patients uncontrolled by medical therapy. However, the main drawback of TIPS for this condition is a very high rate of shunt dysfunction. Recently, polytetrafluoroethylene (PTFE)-covered stents have been shown to reduce the incidence of TIPS dysfunction in patients with cirrhosis. The aim of the study was to assess the incidence of TIPS dysfunction in 2 cohorts of BCS patients treated with bare or PTFE-covered stents. The study included 25 TIPS procedures (16 bare stents and 9 covered stents) with a median follow-up period of 20.4 months (range, 3.9-124.8). Fourteen of 16 patients (87%) receiving bare stents had TIPS dysfunction compared to 3 of the 9 patients (33%) receiving PTFE-covered stents ( P = .005). The actuarial rates of primary patency in the bare-stent group were 19% at 1 year compared with 67% in the PTFE-covered stent group ( P = .02; log-rank test). The number of additional interventional procedures to maintain TIPS patency was significantly greater in the bare-stent than in the PTFE-covered stent group (1.9 ± 1.2 vs. 0.6 ± 0.9; P = .007). The number of patients with clinical relapses was greater in the bare-stent group compared to the PTFE-covered stent group (13 vs. 5 episodes in 9 and 3 patients, respectively). In conclusion , PTFE-covered stents have a considerable advantage over bare stents for the TIPS treatment of BCS patients, with a lower dysfunction rate, a lower number of reinterventions, and fewer prosthesis requirements. PTFE-covered stents are preferable in patients with Budd-Chiari Syndrome. (Hepatology 2004;40:1197-1202.)
Public Attitudes About Abortion-Reply
Authors: Robert J. Blendon
Journal: JAMA (1994)

In Reply.  —The Data and Methods section of our article noted five criteria for inclusion of data in our review, including (of importance here) relevance to key policy choices, consistency with other survey findings, and avoidance of biased or confusing questions. We specifically noted the problems with the wording of Roe v Wade questions because, while we thought any discussion of abortion and its legality must include available data about the public's views of Roe v Wade , such a discussion should also acknowledge a potential problem in relying solely on these questions to understand the public's views of the legality of abortion. In keeping with our other criteria, we looked at other surveys for confirmation of what we saw as a general trend in favor of legality that persisted despite the public's apparent misgivings about the circumstances under which legal abortion services are utilized. Indeed, as we presented, several general
Spectrum and Prevalence of <i>FP/TMEM127</i> Gene Mutations in Pheochromocytomas and Paragangliomas
Authors: Li Yao, Francesca Schiavi, Alberto Cascon, Yuejuan Qin, Lucia Inglada-Pérez, Elizabeth E. King, Rodrigo A. Toledo, Tonino Ercolino, Elena Rapizzi, Christopher J. Ricketts, Luigi Mori, Mara Giacchè, Antonella Mendola, Elisa Taschin, Francesca Boaretto, Paola Loli, Maurizio Iacobone, Gian-Paolo Rossi, Bernadette Biondi, José Viana Lima-Junior, Claudio E. Kater, Marie Bex, Miikka Vikkula, Ashley B. Grossman, Stephen B. Gruber, Marta Barontini, Alexandre Persu, Maurizio Castellano, Sergio P. A. Toledo, Eamonn R. Maher, Massimo Mannelli, Giuseppe Opocher, Mercedes Robledo, Patricia L. M. Dahia
Journal: JAMA (2010)

<h3>Context</h3> Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest–derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene<i>FP/TMEM127</i>in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. <h3>Objectives</h3> To examine the prevalence and spectrum of<i>FP/TMEM127</i>mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. <h3>Design, Setting, and Participants</h3> We sequenced the<i>FP/TMEM127</i>gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction–based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. <h3>Main Outcome Measures</h3> The frequency and type of<i>FP/TMEM127</i>mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. <h3>Results</h3> We identified 19 potentially pathogenic<i>FP/TMEM127</i>germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (<i>P</i> = 2.7 × 10<sup>−4</sup>) and/or with familial disease (5 of 20 samples;<i>P</i> = .005). The median age at disease onset in the<i>FP/TMEM127</i>mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively;<i>P</i> = .54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel<i>FP/TMEM127</i>mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. <h3>Conclusions</h3> Germline mutations of<i>FP/TMEM127</i>were associated with pheochromocytoma but not paraganglioma and occured in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein.
The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells
Authors: Xiao-Xing Wang, Yang-Bing Li, Hong-Juan Yao, Rui-Jun Ju, Yan Zhang, Ruo-Jing Li, Yang Yu, Liang Zhang, Wan-Liang Lu
Journal: Biomaterials (2011)
Divergency of leptin response in intestinal inflammation
Authors: A BALLINGER
Journal: Gut (1999)

The identification of the obesity ( ob ) gene in 1994 signalled a new era of appetite research and for many brought hope for a quick and simple cure for obesity.1 The biotechnology company Amgen, who have paid $20 million for the rights to the gene product, must also hope that the ob protein will fulfil its promise as an effective appetite suppressant and treatment for obesity. At the other end of the weight spectrum, investigators have also examined the role of this protein in the metabolic response to starvation, and its potential role in the anorexia and weight loss that frequently accompany chronic inflammatory and infectious diseases.

The protein product of the ob gene, ob protein or leptin (from the Greek leptos meaning thin), is secreted into the circulation by adipose cells. A rising concentration of circulating leptin with increasing adiposity is proposed to serve as a negative feedback signal to the hypothalamus of the brain, resulting in decreased food intake, increased energy expenditure and return of body weight towards a predetermined set point. The key physiological role of leptin in the control of energy balance has been demonstrated in mice which have a mutation in the ob gene and lack functioning leptin ( ob/ob mice), or have a mutation in the leptin receptor and are resistant to the action of circulating leptin2 ( db/db mice). These mice develop extreme obesity from an early age as a result of hyperphagia and a reduction in energy expenditure. Administration of recombinant leptin leads to decreased food consumption and weight loss in both normal and ob/ob mice, but not db/db mice.3 4 Leptin deficiency or resistance has also been identified as a cause, albeit extremely rarely, of extreme obesity in humans.5 6 

In healthy individuals, starvation results in a reduction in fat …