tbuckley/cabot-search huggingface dataset:
Transdermal Application of Myelin Peptides in Multiple Sclerosis Treatment
Authors: Agata Walczak, Malgorzata Siger, Agnieszka Ciach, Marian Szczepanik, Krzysztof Selmaj
Journal: JAMA Neurology (2013)

Demonstration of efficacious antigen-specific therapy in multiple sclerosis.To assess the safety and efficacy of transdermally applied myelin peptides in patients with relapsing-remitting multiple sclerosis.One-year double-blind, placebo-controlled cohort study.Referral center.Thirty outpatients aged 18 to 55 years with relapsing-remitting multiple sclerosis.Skin patch with a mixture of 3 myelin peptides, MBP85-99, MOG35-55, and PLP139-155. MAIN OUTCOMES AND MEASURES Cumulative number of active gadolinium-enhanced (Gd+) lesions per patient per scan, mean volume of Gd+ lesions, cumulative number of new T2 lesions, and T2 lesion and T1 lesion volume change from baseline to the end of the study. Total number of relapses during the year of the study per patient (annual relapse rate), proportion of relapse-free patients, and proportion of patients with 3 months of confirmed disability worsening on the Expanded Disability Status Scale at month 12.All patients completed the study. Compared with placebo, treatment with a myelin peptide skin patch (1 mg) showed a 66.5% reduction in the cumulative number of Gd+ lesions (P = .02) during the 12 months of the study. The annual relapse rate in patients treated with a mixture of myelin peptides (1 mg) was significantly lower compared with the placebo group (0.43 vs 1.4; P = .007). Treatment with a myelin peptide skin patch was well tolerated and no serious adverse events were reported.In patients with relapsing-remitting multiple sclerosis, treatment with a myelin peptide skin patch significantly reduced both magnetic resonance imaging and clinically defined measures of disease activity and was safe and well tolerated.
Maximum oxygen uptake and objectively measured physical activity in Danish children 6–7 years of age: the Copenhagen school child intervention study
Authors: S Eiberg, H Hasselstrom, V Grønfeldt, K Froberg, J Svensson, L B Andersen
Journal: British Journal of Sports Medicine (2005)

To provide normative data on maximum oxygen uptake (Vo(2)max) and physical activity in children 6-7 years of age and analyse the association between these variables.Vo(2)max was measured in 366 boys (mean (SD) 6.8 (0.4) years of age) and 332 girls (6.7 (0.4) years of age) from preschool classes in two suburban communities in Copenhagen, during a progressive treadmill exercise. Habitual physical activity was measured with accelerometers.Boys had higher Vo(2)max both in absolute values (1.19 (0.18) v 1.06 (0.16) litres/min (+11%), p<0.001) and relative to body weight (48.5 (6.0) v 44.8 (5.6) ml/kg/min (+8%); p<0.001) than girls. The difference in Vo(2)max between boys and girls decreased to +2% when expressed relative to lean body mass (LBM). Absolute Vo(2)max was related to LBM, body mass, and stature (all p<0.001). Boys were more physically active than girls (mean counts +9.4%, p<0.001), and even when boys and girls with the same Vo(2)max were compared, boys were more active. The difference in physical activity between the sexes was higher when sustained activity of higher intensity was compared.Vo(2)max is higher in boys than girls (+11%), even when related to body mass (+8%) and LBM (+2%). Most of the difference in Vo(2)max relative to body mass was explained by the larger percentage body fat in girls. When boys and girls with the same Vo(2)max were compared, boys engaged in more minutes of exercise of at least moderate intensity.
Constitutive Phosphodiesterase Activity Restricts Spontaneous Beating Rate of Cardiac Pacemaker Cells by Suppressing Local Ca <sup>2+</sup> Releases
Authors: Tatiana M. Vinogradova, Syevda Sirenko, Alexey E. Lyashkov, Antoine Younes, Yue Li, Weizhong Zhu, Dongmei Yang, Abdul M. Ruknudin, Harold Spurgeon, Edward G. Lakatta
Journal: Circulation Research (2008)

Spontaneous beating of rabbit sinoatrial node cells (SANCs) is controlled by cAMP-mediated, protein kinase A-dependent local subsarcolemmal ryanodine receptor Ca(2+) releases (LCRs). LCRs activated an inward Na(+)/Ca(2+) exchange current that increases the terminal diastolic depolarization rate and, therefore, the spontaneous SANC beating rate. Basal cAMP in SANCs is elevated, suggesting that cAMP degradation by phosphodiesterases (PDEs) may be low. Surprisingly, total suppression of PDE activity with a broad-spectrum PDE inhibitor, 3'-isobutylmethylxanthine (IBMX), produced a 9-fold increase in the cAMP level, doubled cAMP-mediated, protein kinase A-dependent phospholamban phosphorylation, and increased SANC firing rate by approximately 55%, indicating a high basal activity of PDEs in SANCs. A comparison of specific PDE1 to -5 inhibitors revealed that the specific PDE3 inhibitor, milrinone, accelerated spontaneous firing by approximately 47% (effects of others were minor) and increased amplitude of L-type Ca(2+) current (I(Ca,L)) by approximately 46%, indicating that PDE3 was the major constitutively active PDE in the basal state. PDE-dependent control of the spontaneous SANC firing was critically dependent on subsarcolemmal LCRs, ie, PDE inhibition increased LCR amplitude and size and decreased LCR period, leading to earlier and augmented LCR Ca(2+) release, Na(+)/Ca(2+) exchange current, and an increase in the firing rate. When ryanodine receptors were disabled by ryanodine, neither IBMX nor milrinone was able to amplify LCRs, accelerate diastolic depolarization rate, or increase the SANC firing rate, despite preserved PDE inhibition-induced augmentation of I(Ca,L) amplitude. Thus, basal constitutive PDE activation provides a novel and powerful mechanism to decrease cAMP, limit cAMP-mediated, protein kinase A-dependent increase of diastolic ryanodine receptor Ca(2+) release, and restrict the spontaneous SANC beating rate.
BIOCHEMICAL CHANGES ACCOMPANYING THE INGESTION OF A CARBOXYLIC CATION EXCHANGER IN THE HYDROGEN, AMMONIUM, SODIUM, POTASSIUM, OR CALCIUM FORM
Authors: L. Greenman, J. H. Peters, F. M. Mateer, F. A. Weigand, D. Wilkins, R. Tarail, G. Rhodes, T. S. Danowski
Journal: Journal of Clinical Investigation (1951)
EXPERIMENTALLY INDUCED CHANGES IN NASAL MUCOUS SECRETORY SYSTEMS AND THEIR EFFECT ON VIRUS INFECTION IN CHICKENS
Authors: Frederik B. Bang, Marie A. Foard
Journal: The Journal of Experimental Medicine (1969)

Chickens 3 wk old, inoculated intranasally with a mesogenic (moderately virulent) strain of Newcastle disease virus, developed necrotic lesions of the mucous acini, predominantly of the middle turbinates. The infection subsequently spread to involve much of the rest of the mucosa, including mucous and ciliated epithelial cells, and other acini. The early phase of adsorption of a virulent strain of the virus to the middle turbinates of chicks 5-21 days of age was studied by giving a standard inoculum intranasally to unanesthetized animals. Variation in amounts adsorbed by individual chickens was large, but was minimized by making measurements on pools of turbinates from three chicks at intervals of 1, 3, and 5 hr after exposure of the excised turbinates to antibody, by washing, and by trypsinization. The virus released from the cells into the trypsin was designated as adherent virus, and the infectious virus in the cells after destruction of the cells by water grinding, as cell virus. Paralysis of ciliary action by cocaine increased the number of infected cells in the turbinates about 10-fold at all three time intervals. Pilocarpine injection before virus inoculation caused a large increase in the amount of infected cells 1 hr after virus administration, but was followed by a sharp drop in infected cells by 3 or 5 hr. Pilocarpine given after the virus decreased the number of infected cells and changed the relationship of infected cells to adherent virus. Exposure of chicks to sustained or severe cold caused a similar but less marked effect. The drop in infected cells was restored to control values if chicks were returned to brooder temperatures. The marked drop of infected cells produced by pilocarpine and cold in living chicks, and in cultures of chicken trachea (previous study), is consonant with the idea that virus has been adsorbed on mucus granules in the mucous cells of the turbinates and then has been reexcreted, as unincorporated virus, into the moving mucous sheet. A series of accessory data support this interpretation.
"Nil by mouth" feeding should be last resort for all patients, experts say
Authors: A. O'Dowd
Journal: BMJ (2010)

Patients are too often put on artificial feeding systems in hospitals to save time or because of an overly cautious approach, concludes a report published this week.

Experts are recommending that tube feeding of patients should be adopted only as a last resort. More specialist nutrition teams are needed to advise on the most appropriate way to meet patients’ nutrition needs, they say.

The group of experts has recommended good practice guidelines for doctors in response to concerns about the lack of consensus, particularly among clinicians, about when artificial nutrition and hydration is appropriate.

The guidance has been produced by a working party for the Royal College of Physicians and the British …
Excess of Nonsynonymous Polymorphism at Acph-1 in Different Gene Arrangements of Drosophila subobscura
Authors: A. Navarro-Sabate
Journal: Molecular Biology and Evolution (2003)

Nucleotide variation in the Acph-1 gene region was analyzed in a natural population of Drosophila subobscura from Bizerte (Tunisia). The lines studied differed in their gene arrangement for segment I of the O chromosome: 21 lines were O3+4+8, 21 were O3+4+23, and 3 were O3+4. According to chromosomal phylogenies, O3+4 is a central arrangement from which O3+4+8 and O3+4+23 originated. Strong genetic differentiation at Acph-1 was detected among the different arrangements, which is reflected in strong linkage disequilibrium between the variants at informative polymorphic sites and the type of arrangement. Estimates of silent nucleotide diversity are slightly lower within O3+4+23 (πsilent = 0.0166) than within O3+4+8 (πsilent = 0.0228) or O3+4 (πsilent = 0.0234). In contrast, nonsynonymous nucleotide diversity estimates (around 0.1%) are similar in the three arrangements. Most nonsynonymous rare variants are singletons, which results in highly significant Tajima's neutrality tests within the young O3+4+8 and O3+4+23 arrangements. This test is not significant for nonsynonymous mutations within a large Spanish O3+4 sample. In addition, a significant and marginally significant excess of nonsynonymous polymorphism was detected by the McDonald and Kreitman test within O3+4+23 and O3+4+8, respectively. This excess results in a rather high neutrality index (NI = 5.25) when both arrangements are jointly analyzed, in contrast to its value within the old O3+4 arrangement (NI = 1.74). The pattern of variation at Acph-1 within the young arrangements is unusual for nuclear genes and has the same characteristics previously detected in most genes of the mitochondrial genome. Assuming that most nonsynonymous mutations at Acph-1 are under weak negative selection, a smaller effective size of the young arrangements relative to O3+4 might explain the observed results. The relatively low frequency of O3+4+8 and O3+4+23 in the distribution area of D. subobscura, the more recent origin of these arrangements relative to O3+4 and the suppression of recombination in heterokaryotypes might contribute to the relatively small effective size of the young arrangements. Therefore, present results indicate that the differences in effective size and recombination caused by chromosomal arrangements are modulating nonsynonymous variation at Acph-1.
American Psychiatric Association says no to industry funding for symposiums
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

The board of trustees of the American Psychiatric Association (APA) decided last month to phase out symposiums sponsored by industry and meals at annual meetings.

The board did not say when it would end events funded by industry, and the association’s president, Nada Stotland, said that industry sponsorship might continue through 2010 (www.medpagetoday.com, 26 Mar, “Psychiatry group plans phase-out of industry-sponsored symposia”).

Dr Stotland said, “Although we took great care to avoid biased reporting at all our symposia, we came to the conclusion …
The Role of Innate Immunity in Acute Allograft Rejection after Lung Transplantation
Authors: Scott M. Palmer, Lauranell H. Burch, R. Duane Davis, Walter F. Herczyk, David N. Howell, Nancy L. Reinsmoen, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of innate immunity in the development of allograft rejection, we assessed the impact of two functional polymorphisms in the toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness on the development of acute rejection after human lung transplantation. Patients and donors were screened for the TLR4 Asp299Gly and Thr399Ile polymorphisms by polymerase chain reaction using sequence-specific primers. The rate of acute rejection at 6 months was significantly reduced in recipients, but not in donors, with the Asp299Gly or Thr399Ile alleles as compared with wild type (29 vs. 56%, respectively, p = 0.05). This association was confirmed in Cox proportional hazards and multivariate logistic regression models. Our results suggest activation of innate immunity in lung transplant recipients through TLR4 contributes to the development acute rejection after lung transplantation. Therapies directed at inhibition of innate immune responses mediated by TLR4 may represent a novel and effective means to prevent acute rejection after lung transplantation.
Interference With Immune Response at the Level of Generating Effector Cells by Tumor-Associated Haptoglobin
Authors: S.-K. Oh, S.-H. Kim, J. E. Walker
Journal: JNCI Journal of the National Cancer Institute (1990)

Most of the immune response regulators identified to date proved to be products of tumor, of an immune system or of combinations of such systems or to be tumor-induced host products. We have described how the haptoglobin isolated from cancer patients can impose serious hindrance to cell-mediated immune functions in vivo and in vitro under the pathophysiologic concentrations seen in these patients. Because the tumor-associated haptoglobin interferes with the innate and adaptive immune functions, elimination of the haptoglobin by passive removal or by active therapy could be an important adjunct for immunotherapy in cancer patients.
Detection of an outbreak of methicillin-resistant Staphylococcus aureus with reduced susceptibility to glycopeptides in a French hospital
Authors: F.-O. Mallaval, A. Carricajo, F. Delavenna, C. Recule, N. Fonsale, G. Manquat, D. Raffenot, O. Rogeaux, G. Aubert, J. Tous
Journal: Clinical Microbiology and Infection (2004)
Immunoglobulin E—mediated asthma and hypersensitivity pneumonitis with precipitating anti-hapten antibodies due to diphenylmethane diisocyanate (MDI) exposure
Authors: C.Raymond Zeiss, Theodore M. Kanellakes, Jack D. Bellone, Doris Levitz, J.J. Pruzansky, Roy Patterson
Journal: Journal of Allergy and Clinical Immunology (1980)
Role of Insulin Resistance in Predicting Progression to Type 1 Diabetes
Authors: Ping Xu, David Cuthbertson, Carla Greenbaum, Jerry P. Palmer, Jeffrey P. Krischer
Journal: Diabetes Care (2007)

The purpose of this study was to determine whether insulin resistance is a risk factor for the development of type 1 diabetes in autoantibody-positive first-degree relatives of diabetic family members.Subjects (n = 186) who had a projected 25-50% risk for diabetes and subjects (n = 170) who had a projected >50% risk for type 1 diabetes in 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial-Type 1. We assessed insulin secretion with the first-phase insulin response (FPIR) and insulin resistance with homeostasis model assessment of insulin resistance (HOMA-IR) from an intravenous glucose tolerance test. The median follow-up was 4.3 years for moderate-risk subjects and 3.7 years for high-risk subjects.During the follow-up period, 53 subjects in the moderate-risk group and 70 subjects in the high-risk group developed type 1 diabetes. After adjustments for confounders using multivariate analysis, HOMA-IR and the FPIR-to-HOMA-IR ratio were significantly associated with type 1 diabetes in both risk groups. In the moderate-risk population, the hazard ratio (HR) of HOMA-IR was 2.70 (95% CI 1.45-5.06) and the HR of FPIR-to-HOMA-IR was 0.32 (95% CI 0.18-0.57). In the high-risk population, the HR of HOMA-IR was 1.83 (95% CI 1.19-2.82) and the HR of FPIR-to-HOMA-IR was 0.56 (95% CI 0.40-0.78).There is clear evidence of the association between insulin resistance and progression to type 1 diabetes. The combination of FPIR and HOMA-IR could be used as a better metabolic indicator for type 1 diabetes risk for prediction and suggests possible intervention strategies for diabetes prevention.
Controversies in primary care Setting prescribing budgets in general practice Capitation based prescribing budgets will not work
Authors: A. Majeed, S. Head
Journal: BMJ (1998)

Controversies in primary care Setting prescribing budgets in general practiceGeneral practice prescribing costs have risen rapidly in recent years, and there are wide variations between practices in rates and costs of prescribing.Setting general practice prescribing budgets with a capitation based formula seems to offer a solution to these problems.However, capitation based formulas may unfairly penalise legitimate variations and increases in prescribing costs.We therefore asked Azeem Majeed and Trisha Greenhalgh to give their views on the subject.
Self-Monitoring of Blood Glucose in Noninsulin-Using Type 2 Diabetic Patients
Authors: William H. Polonsky, Lawrence Fisher
Journal: Diabetes Care (2012)

Given the importance of glycemic control in the development of diabetes complications, the plethora of tools now available to monitor the day-to-day trends in glycemia is remarkable. In this regard, self-monitoring of blood glucose (SMBG) has been considered a key component of patient management. Arguably, there remains almost universal agreement that SMBG should be available to all diabetic patients regardless of current treatment strategy. However, recently there have been reports that have challenged the current paradigm that all patients should use SMBG and concluded that SMBG for type 2 diabetic patients not on insulin may not be beneficial on glycemic control and must be weighed against the expense and inconvenience. In the counterpoint narrative following the contribution by Malanda et al., Drs. Polonsky and Fisher provide a compelling argument suggesting that while it is evident that implementing SMBG in unstructured ways without training patients and clinicians is likely to be a waste of resources, there are effective and powerful ways to use structured SMBG in insulin-naïve type 2 diabetic patients. -William T. Cefalu, MD Editor in Chief, Diabetes Care.
Experimental mitral valve replacement with a heterograft aortic valve in a rigid metal ring
Authors: E. Proctor
Journal: Thorax (1968)

A mitral valve replacement is described in which a heterograft (pig) aortic valve is supported in a rigid metal ring having three spurs to support the commissures. The ring frame is completely covered by the heterograft, and no artificial material is in contact with the blood stream. Completely fabricated and tested for competency beforehand, it requires only one row of interrupted sutures—after the manner of the Starr-Edwards prosthesis—for insertion, and can be used in either the mitral or the aortic position. Experimental results in the dog indicate that the valve may require only temporary anticoagulation to cover the immediate post-operative period.
Glucarpidase, Leucovorin, and Thymidine for High-Dose Methotrexate-Induced Renal Dysfunction: Clinical and Pharmacologic Factors Affecting Outcome
Authors: Brigitte C. Widemann, Frank M. Balis, AeRang Kim, Matthew Boron, Nalini Jayaprakash, Aiman Shalabi, Michelle O'Brien, Michelle Eby, Diane E. Cole, Robert F. Murphy, Elizabeth Fox, Percy Ivy, Peter C. Adamson
Journal: Journal of Clinical Oncology (2010)

To assess the role of the recombinant bacterial enzyme, glucarpidase (carboxypeptidase-G(2)), leucovorin, and thymidine in the management and outcome of patients with high-dose methotrexate (HDMTX) -induced nephrotoxicity.Patients with HDMTX-induced nephrotoxicity received one to three doses of intravenous (IV) glucarpidase and leucovorin rescue. The initial cohort (n = 35) also received thymidine by continuous IV infusion. Subsequently, thymidine was restricted to patients with prolonged exposure (> 96 hours) to methotrexate (MTX) or with substantial MTX toxicity at study entry. Plasma MTX, leucovorin, and 5-methyltetrahydrofolate (5-mTHF) concentrations were measured pre- and postglucarpidase. Toxicities were monitored, and logistic regression analysis was used to assess the relationship of baseline characteristics to the development of severe toxicity and death.Glucarpidase was administered at a median of 96 hours (receiving thymidine, n = 44) and 66 hours (not receiving thymidine, n = 56) after the start of the MTX infusion. Plasma MTX concentrations decreased within 15 minutes of glucarpidase by 98.7%. Plasma 5-mTHF concentrations also decreased more than 98% after administration of glucarpidase. Of 12 deaths, six were directly attributed to irreversible MTX toxicity. Presence of grade 4 toxicity before administration of glucarpidase, inadequate initial increase in leucovorin dosing, and administration of glucarpidase more than 96 hours after the start of the MTX infusion were associated with development of grade 4 and 5 toxicity.Early intervention with the combination of leucovorin and glucarpidase is highly effective in patients who develop HDMTX-induced renal dysfunction. Severe toxicity and mortality occurred in patients in whom glucarpidase rescue was delayed and occurred despite thymidine administration.
The aetiology of acne inversa: an evolving story
Authors: J.R. Ingram
Journal: British Journal of Dermatology (2011)

Conflicts of interest None declared. Research interest in acne inversa (AI; previously ‘hidradenitis suppurativa’ or HS) is gathering momentum. A PubMed search using the terms AI and HS demonstrates that about a third of the total publications have been produced in the past 5 years (265 of 739 papers). In particular, attention has been drawn to a potential genetic aetiology. Twenty‐five years ago Fitzsimmons et al.1 examined the family history of 26 consecutive patients with AI from Nottingham, U.K. and identified autosomal dominant inheritance in 11 families, with a total of 48 affected members. Only nine of the probands were confirmed to have no family history of AI. The story goes cold for the subsequent 15 years, until in 2000 von der Werth et al.2 replicated this finding in the same Nottingham patient group, using a consensus definition of AI. The advent of genome‐wide association studies (GWAS) permitted Gao et al.3 to perform linkage analysis of a large four‐generation Chinese family with 10 affected individuals to identify a chromosomal location for this potential single‐gene disorder. They found linkage to 1p21.1–1q25.3, a 73‐Mb region of chromosome 1 containing nearly 900 genes.