tbuckley/cabot-search huggingface dataset:
Paget's disease of bone in early adult life
Authors: S Holgado
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To determine the range and activity of the clinical and biological features of patients aged &lt;40 with Paget's disease of bone. <b>Methods:</b> A retrospective two centre study of 314 patients with Paget's disease of bone from two university hospitals. The disease was diagnosed by radiological, serum alkaline phosphatase (AP) levels, or clinical features, and bone scintigraphy in most patients. Demographic data, reason for diagnosis, bones affected, disease extent using Coutris' index, complications during progression, and disease activity using Renier's index were assessed. Patients over and under 40 were compared. <b>Results:</b> 18/314 (5.7%) patients were diagnosed before the age of 40; median (SD) age was 35.4 (5.5) (range 18–40) and AP 555.6 (566.3) IU/l (range 70–1949). Coutris' extension index was 12.8 (10.5) and Renier's activity index 35.9 (31.9). Younger patients had more affected bones (p&lt;0.05) than those aged &gt;40, higher level of extension (p&lt;0.05), higher AP value (p = 0.05), and greater incidence of thoracolumbar spine disease. Disease activity did not differ significantly between the groups. <b>Conclusions:</b> Paget's disease diagnosed before the age of 40 is more extensive but not more active, with higher AP values than in those diagnosed after age 40.
Association of Prehospital Advanced Airway Management With Neurologic Outcome and Survival in Patients With Out-of-Hospital Cardiac Arrest
Authors: Kohei Hasegawa, Atsushi Hiraide, Yuchiao Chang, David F. M. Brown
Journal: JAMA (2013)

<h3>Importance</h3>It is unclear whether advanced airway management such as endotracheal intubation or use of supraglottic airway devices in the prehospital setting improves outcomes following out-of-hospital cardiac arrest (OHCA) compared with conventional bag-valve-mask ventilation.<h3>Objective</h3>To test the hypothesis that prehospital advanced airway management is associated with favorable outcome after adult OHCA.<h3>Design, Setting, and Participants</h3>Prospective, nationwide, population-based study (All-Japan Utstein Registry) involving 649 654 consecutive adult patients in Japan who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions from January 2005 through December 2010.<h3>Main Outcome Measures</h3>Favorable neurological outcome 1 month after an OHCA, defined as cerebral performance category 1 or 2.<h3>Results</h3>Of the eligible 649 359 patients with OHCA, 367 837 (57%) underwent bag-valve-mask ventilation and 281 522 (43%) advanced airway management, including 41 972 (6%) with endotracheal intubation and 239 550 (37%) with use of supraglottic airways. In the full cohort, the advanced airway group incurred a lower rate of favorable neurological outcome compared with the bag-valve-mask group (1.1% vs 2.9%; odds ratio [OR], 0.38; 95% CI, 0.36-0.39). In multivariable logistic regression, advanced airway management had an OR for favorable neurological outcome of 0.38 (95% CI, 0.37-0.40) after adjusting for age, sex, etiology of arrest, first documented rhythm, witnessed status, type of bystander cardiopulmonary resuscitation, use of public access automated external defibrillator, epinephrine administration, and time intervals. Similarly, the odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.41; 95% CI, 0.37-0.45) and for supraglottic airways (adjusted OR, 0.38; 95% CI, 0.36-0.40). In a propensity score–matched cohort (357 228 patients), the adjusted odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.45; 95% CI, 0.37-0.55) and for use of supraglottic airways (adjusted OR, 0.36; 95% CI, 0.33-0.39). Both endotracheal intubation and use of supraglottic airways were similarly associated with decreased odds of neurologically favorable survival.<h3>Conclusion and Relevance</h3>Among adult patients with OHCA, any type of advanced airway management was independently associated with decreased odds of neurologically favorable survival compared with conventional bag-valve-mask ventilation.
Propentofylline decreases tumor growth in a rodent model of glioblastoma multiforme by a direct mechanism on microglia
Authors: V. L. Jacobs, R. P. Landry, Y. Liu, E. A. Romero-Sandoval, J. A. De Leo
Journal: Neuro-Oncology (2011)

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer, with a median survival of less than 2 years after diagnosis. The tumor microenvironment plays a critical role in tumor invasion and progression. Microglia and infiltrating macrophages are the most abundant immune cells in the tumor. In the present study, we demonstrate that systemic propentofylline (PPF), an atypical methylxanthine with central nervous system (CNS) glial modulating and anti-inflammatory actions, significantly decreased tumor growth in a CNS-1 rat model of GBM by targeting microglia and not tumor cells. Rats received tumor injections of 1 × 10(5) CNS-1 cells in the right striatum with daily intraperitonial injections of PPF (50 mg/kg) or saline beginning the day of tumor injection. PPF did not cause apoptosis or decrease proliferation of CNS-1 tumor cells. Furthermore, we demonstrate, using in vitro methods, that PPF decreased microglial migration toward CNS-1 tumor cells and decreased MMP-9 expression. The effects of PPF were shown to be specific to microglia and not peripheral macrophages. These results support a differential functional role of resident microglia and infiltrating macrophages in the brain tumor environment. Our data highlight microglia as a crucial target for future therapeutic development and present PPF as a possible drug for treatment of human GBM.
Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease. Studies in nondiabetic and diabetic subjects.
Authors: R Meyer-Schwickerath, A Pfeiffer, W F Blum, H Freyberger, M Klein, C Lösche, R Röllmann, H Schatz
Journal: Journal of Clinical Investigation (1993)

Retinal capillary nonperfusion results in neovascularization of the eye, which is restricted to the retina in less severe cases and progresses to the anterior chamber and the iris angle in the most advanced case, called rubeosis. This angioneogenesis may be induced by the release of retinal growth factors into the vitreous. This study compared levels of the IGF-I and IGF-II, and of the IGF binding protein-2 (IGFBP-2) and IGFBP-3 in vitreous from three groups with different degrees of retinal ischemia, as judged by the extent of neovascularization: a control group without new vessel formation, retinal neovascularization in patients with proliferative diabetic retinopathy, and massive ischemia of various causes resulting in rubeosis. IGF-I and IGFBP-3 were increased 10- and 13-fold in rubeosis (P << 0.01) compared with no ischemia (n = 10), while IGF-II and IGFBP-2 were elevated 2.7- and 4.3-fold (P < 0.01). Within the rubeosis group similar changes were observed independently of the cause of ischemia, which was central vein occlusion, ischemic ophthalmopathy, or intraocular tumor in seven cases and diabetic retinopathy in three samples from two patients. Vitreous from patients with proliferative diabetic retinopathy but without rubeosis (n = 16) contained 2.5- and 2.2-fold elevated levels of IGF-I and of IGFBP-2 (P < 0.05), while IGF-II and IGFBP-3 were increased 1.4- and 1.6-fold, which was not significant. We conclude that: (a) ischemia appears to be a strong stimulus for the local production of IGF-I and -II and of IGFBP-2 and -3 in the eye. (b) Changes in IGF-I and IGFBP-2 in proliferative diabetic retinopathy may be secondary to local ischemia rather than being specific for diabetic retinopathy. (c) IGF-I and IGFBP-3 may play a role in mediating angioneogenesis in the eye.
Increased risk of end-stage renal disease in individuals with coeliac disease
Authors: Adina Welander, Karl-Göran Prütz, Michael Fored, Jonas F Ludvigsson
Journal: Gut (2011)

<h3>Objective</h3> The prevalence of end-stage renal disease (ESRD) is increasing worldwide. Although increased levels of coeliac disease (CD) autoantibodies are often seen in renal disease, the importance of biopsy-verified CD for the risk of future ESRD is unclear. The aim of this study was therefore to investigate the risk of future ESRD in individuals with CD. <h3>Methods</h3> This was a population-based prospective cohort study. 29 050 individuals with CD (Marsh III) were identified through small-intestinal biopsy reports obtained between July 1969 and February 2008 in Sweden9s 28 pathology departments. ESRD was defined as the need for renal dialysis or renal transplant in accordance with the international classification of disease and procedure codes in Swedish patient registers. Using Cox regression, the risk of ESRD in individuals with CD compared with age- and sex-matched reference individuals was estimated. <h3>Results</h3> During follow-up, 90 individuals with CD developed ESRD (expected count 31). This corresponded to a HR for ESRD of 2.87 (95% CI 2.22 to 3.71, p&lt;0.001). Adjusting for diabetes mellitus had only a marginal effect on the risk estimate (HR 2.52, 95% CI 1.92 to 3.31). Excluding individuals with any urinary/renal disorder before study entry, the HR for ESRD in CD was 2.47 (95% CI 1.80 to 3.40). When restricting the outcome measure to ESRD confirmed by independent data from the Swedish Renal Registry (SRR), the risk estimate increased to 3.20 (95% CI 2.39 to 4.28). <h3>Conclusion</h3> This study indicates that individuals with biopsy-verified CD suffer increased risk of subsequent ESRD.
Pericardial rupture from blunt chest trauma
Authors: J. Borrie, I. Lichter
Journal: Thorax (1974)

<b>Borrie, J. and Lichter, I. (1974).</b><i>Thorax</i>, <b>29</b>, 329-337. <b>Pericardial rupture from blunt chest trauma.</b> Pericardial rupture may occur in two distinct anatomical sites, namely the diaphragmatic pericardium and the pleuropericardium. They may be combined. The problems in each type are different. In <i>ruptured diaphragmatic pericardium</i> the rent may involve the pericardial cavity alone, or may extend into one or both adjoining pleural cavities. Upward herniation of abdominal viscera can occur, with or without strangulation. The presence of a pericardial rent may be suggested by diagnostic pneumoperitoneum, and chest films showing displaced abdominal viscera; its extent may be fully revealed only by thoracotomy. If the rent involves only the diaphragmatic pericardium without lateral spread into a pleural cavity, the presence of a rent may be revealed only by exploratory thoracotomy with pericardiotomy. In <i>ruptured pleuropericardium</i> the rent is usually vertical and may occur on either side, more usually on the left. It may be recognized on chest films in its early stages by the presence of intrapericardial air arising from associated lung trauma. There is serious risk of heart dislocation with or without strangulation. The defect must be surgically repaired and, because of pericardial retraction, it may require a fabric patch. Teflon fabric has proved to be a long-term satisfactory pericardial substitute. Two cases of each type of pericardial rupture are described and illustrate these points.
Effect of fish oil on neutrophil chemiluminescence induced by different stimuli in patients with rheumatoid arthritis.
Authors: M Magaro, A Zoli, L Altomonte, L Mirone, P De Sole, G Di Mario, E De Leo
Journal: Annals of the Rheumatic Diseases (1992)

Lipid composition plays an important part in the structural and metabolic functions of cell membranes. In particular the production of inflammatory mediators such as prostaglandins and leukotrienes is dependent on polyunsaturated fatty acid precursors. Neutrophil leucocytes participate in inflammatory processes by their phagocytic and killing activities which can be monitored by measuring the photon emission (chemiluminescence). Chemiluminescence was measured in a luminol dependent system after stimulation by either particulate (zymosan) or soluble (phorbol myristate acetate) stimulus in a group of 10 patients with rheumatoid arthritis before and 21 and 45 days after treatment with a diet supplemented with eicosapentaenoic and docosahexaenoic acids. Ten patients with rheumatoid arthritis continuing their usual diet were used as control subjects. A progressive reduction of chemiluminescence stimulated by zymosan and phorbol myristate acetate was found in the patients treated with fish oil supplementation. This result correlated well with the reduction in erythrocyte sedimentation rate and an improvement of clinical parameters. The effects of fish oil derived lipids on neutrophil chemiluminescence are probably due to a change of the lipid composition of the cell membrane which is dependent on the esterification of eicosapentaenoic acid and docosahexaenoic acid in cellular membrane phospholipids. The modification of membrane lipid composition seems to interact in a non-specific way with the metabolic activation of neutrophils during phagocytosis.
Adenoma detection with cap-assisted colonoscopy versus regular colonoscopy: a randomised controlled trial
Authors: Thomas R de Wijkerslooth, Esther M Stoop, Patrick M Bossuyt, Elisabeth M H Mathus-Vliegen, Jan Dees, Kristien M A J Tytgat, Monique E van Leerdam, Paul Fockens, Ernst J Kuipers, Evelien Dekker
Journal: Gut (2011)

<h3>Objective</h3> Conventional colonoscopy (CC) is considered the reference standard for detection of colorectal neoplasia, but it can still miss a substantial number of adenomas. The use of a transparent plastic cap may improve colonic visualisation. Cap-assisted colonoscopy (CAC) was compared with CC for adenoma detection. Secondary outcomes were caecal intubation time, caecal intubation rate and the degree of discomfort of colonoscopy. <h3>Design</h3> This is a parallel, randomised, controlled trial at two centres. Asymptomatic participants (aged 50–75 years) in a primary colonoscopy screening programme were consecutively invited. Consenting subjects were 1:1 randomised to either CAC or CC. All colonoscopies were performed by experienced endoscopists (≥1000 colonoscopies) who were trained in CAC. Colonoscopy quality indicators were prospectively recorded. <h3>Results</h3> A total of 1380 participants were randomly allocated to CC (N=694) or CAC (N=686). Caecal intubation rate was comparable in the two groups (98% vs 99%; p=0.29). Caecal intubation time was significantly lower in the CAC group: 7.7±5.0 min with CAC vs 8.9±6.2 min with CC (p&lt;0.001) (values mean±SD). Adenoma detection rates of all endoscopists were ≥20%. The proportion of subjects with at least one adenoma was similar in the two groups (28% vs 28%; RR 0.98; 95% CI 0.82 to 1.16), as well as the mean number of adenomas per subject (0.49±1.05 vs 0.50±1.03; p=0.91). Detection of small size, flat and proximally located adenomas was comparable. CAC participants had lower Gloucester Comfort Scores during colonoscopy (2.2±1.0 vs 2.0±1.0; p=0.03). <h3>Conclusion</h3> CAC does not improve adenoma detection, but does reduce caecal intubation time by more than 1 min and does lessen the degree of discomfort during colonoscopy.
OC-113 Prevention of post-ERCP acute pancreatitis: complete systematic review
Authors: K Altaf, M A Javed, D Lythgoe, F Wright, R Sutton
Journal: Gut (2012)

<h3>Introduction</h3> Post-ERCP acute pancreatitis (post-ERCP-AP) occurs in ∼5% of patients undergoing ERCP, severe in ∼1%. Despite multiple trials, optimal prophylaxis remains undetermined. We sought to clarify the effectiveness of prophylactic interventions for post-ERCP AP through multiple meta-analyses of randomised controlled trials (RCTs). <h3>Methods</h3> MEDLINE, EMBASE and the Cochrane Library were searched by two independent reviewers to identify all RCTs that tested treatments to reduce post-ERCP AP. Data were extracted to permit Jadad scoring, grouping of RCTs by therapeutic mechanism and separate meta-analysis of each group. The main outcome measure was post-ERCP AP, defined as amylase elevated to &gt;3× upper limit of normal with &gt;24 h abdominal pain. <h3>Results</h3> 71 RCTs of the highest quality (Jadad score 5 for pharmacological and three for interventional trials) were identified. Pancreatic stents (trials (T)—5; patients (P)—377; RR 0.20; 95% CI 0.09 to 0.42) were most effective; significant reductions in post-ERCP AP resulted from secretion inhibitors (T—12; P—4851; RR 0.54; CI 0.36 to 0.83), protease inhibitors (T—9; P—3752; RR 0.54; CI 0.38 to 0.78) and smooth muscle relaxants (T—9; P—2110; RR 0.67; CI 0.52 to 0.87). Non-steroidal anti-inflammatory drugs (NSAIDs; T—4; P—733; RR 0.68; CI 0.46 to 1.00), interleukin-10 (IL-10; T—3; P—642; RR 0.79; CI 0.55 to 1.14), anti-oxidants (T—5; P—2100; RR 0.90; CI 0.54 to 1.50), anti-coagulants (T—2; P—533; RR 0.85; CI 0.48 to 1.53), non-ionic (vs ionic) contrast agents (T—8; P—3095; RR 1.32; CI 0.92 to 1.88), wire guided cannulation, (T—7; P—2103; RR 0.63; CI 0.34 to 1.17) pre cut papillotomy (T—4; P—558; RR 0.57; CI 0.20 to 1.59) and steroids (T—3; P—924; RR 1.09; CI 0.70 to 1.70) did not reduce post-ERCP AP. <h3>Conclusion</h3> This is the most comprehensive systematic review on the subject to date which shows that pancreatic stents, secretion and protease inhibitors and smooth muscle relaxants reduce the risk of post-ERCP AP. Large well-designed RCTs of combination vs single agent prophylaxis are required. <h3>Competing interests</h3> None declared.
Chronic immunosuppression of the renal transplant patient.
Authors: J H Helderman, D H Van Buren, W J Amend, J D Pirsch
Journal: Journal of the American Society of Nephrology (1994)

The advent of potent immunosuppressive drugs to prevent rejection has led to a phenomenal improvement in renal transplant results increasing spectacularly the number of transplant recipients to arrive in the transplant clinic who remain for many years. This has engendered a series of questions about the most appropriate cyclosporine dosing for these patients that prevents rejection while avoiding toxicity. Three separate issues were analyzed: the most appropriate combination strategy with cyclosporine as a base "double" or "triple" therapy; the possibility of conversion from regimens containing cyclosporine to those devoid of it; and the optimal cyclosporine dose for a maintenance regimen. A meta-analysis of seven individual prospective and randomized trials of double versus triple therapy encompassing 1,080 patients revealed no statistical difference between the two regimens in terms of graft survival at 1 or 5 yr, patient survival, the rejection rate per patient, or the infection rate. In an analysis of 17 separate studies in which conversion away from cyclosporine was attempted, in 629 individuals with 702 individuals left on cyclosporine as controls, a significant risk of acute rejection (P < 0.001) was found in the withdrawn group without evidence of improved graft survival. Certain factors such as previous rejection, race, and degree of reactivity predicted even more rejection in the withdrawn group. Analyzing six separate studies of renal transplant recipients maintained on cyclosporine for up to 5 yr with renal functional stability, one can conclude that a dose of approximately 4.0 mg/kg per day is optimal. Because of variant pharmacokinetics or concomitant medicines, blood levels can confirm a therapeutic concentration with this target dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Unsteadiness of breathing in patients with hyperventilation syndrome and anxiety disorders
Authors: JN Han, K Stegen, K Simkens, M Cauberghs, R Schepers, O Van den Bergh, J Clement, KP Van de Woestijne
Journal: European Respiratory Journal (1997)

The breathing pattern of 399 patients with hyperventilation syndrome (HVS) and/or with anxiety disorders and that of 347 normal controls was investigated during a 5 min period of quiet breathing and after a 3 min period of voluntary hyperventilation. The diagnosis of HVS was based on the presence of several suggestive complaints occurring in the context of stress, and reproduced by voluntary hyperventilation. Organic diseases as a cause of the symptoms were excluded. The anxiety disorders were diagnosed by means of an abbreviated version of the Anxiety Disorders Interview Schedule (ADIS). There was a large overlap between the two diagnoses. Simply breathing via a mouthpiece and pneumotachograph made end-tidal CO2 fractional concentration (FET,CO2) decrease progressively both in hyperventilators and in patients with anxiety disorders, but not in normals. At the start of the measurement the FET,CO2 was not different between patients and healthy subjects. In patients &lt; or = 28 yrs, the decrease of FET,CO2 resulted from a higher tidal volume, and in patients &gt; or = 29 years from an increase in frequency. After voluntary hyperventilation, the recovery of FET,CO2, was delayed in patients, due to a slower normalization of respiratory frequency in females and in older males, and of tidal volume in younger males, and also due to less frequent end-expiratory pauses. When breathing was recorded first by means of inductive plethysmography (Respitrace), the progressive decline of FET,CO2 seen in patients was not observed: from the onset of the recording, FET,CO2 was reduced in patients. It did not change further when, immediately afterwards, the subject switched to mouthpiece breathing. The finding that breathing through a mouthpiece induces hyperventilation in patients and that recovery of FET,CO2 is delayed after voluntary hyperventilation, suggests that the respiratory control system is less resistant to challenges (mouthpiece or voluntary hyperventilation) in those patients. On the other hand, the lower values of FET,CO2 measured during recording by means of a Respitrace probably result from a challenge, prior to the recordings, induced by the fitting of the measuring device to the patient. This unsteadiness of breathing characterizes patients with hyperventilation syndrome and those with anxiety disorders, but is not sufficiently sensitive to be used for individual diagnosis.
Controlling Off-Label Medication Use
Authors: Muriel R. Gillick
Journal: Annals of Internal Medicine (2009)

Off-label prescribing may lead to innovative new uses of old medications, is essential in such fields as pediatrics, and avoids the lengthy and expensive process of modifying U.S. Food and Drug Administration (FDA) drug labeling. Using medications for unapproved indications, however, raises concerns about patient safety when the drugs have a high potential for toxicity and generates economic concerns when their cost is high. A possible means of controlling the use of off-label drugs is to focus on medications used off-label that are both expensive and potentially risky. These are principally biotechnology drugs, such as recombinant enzymes, cytokines, and monoclonal antibodies. This article suggests a 2-step process for controlling use of such drugs, analogous to that used for devices. Once a drug is FDA approved, it would undergo scrutiny using the Centers for Medicare & Medicaid Services (CMS) National Coverage Determination method if its cost exceeds a specified benchmark-for example, $12 000, which is the average cost of a pacemaker. The CMS would pay only for off-label uses for which there is adequate evidence in its National Coverage Determination process. Other insurance companies would probably adopt the recommendations of CMS.
Report of the European Task Force on Lymphomas: Workshop on peripheral T-cell lymphomas
Authors: E. Campo, P. Gaulard, E. Zucca, E.S. Jaffe, N.L. Harris, J. Diebold, B. Schlegelberger, A.C. Feller, G. Delsol, C. Gisselbrecht, E. Montserrat
Journal: Annals of Oncology (1998)