tbuckley/cabot-search huggingface dataset:
Novel techniques for the estimation of intracorneal cohesion in vivo*
Authors: S. NICHOLLS, R. MARKS
Journal: British Journal of Dermatology (1977)

Desquamation is the result of loss of cohesion between horny squames. This study is concerned with the in vivo measurement of intracorneal cohesion using three new techniques. A new instrument, the cohesograph, directly measures the force (g) required to distract a known area of partial thickness of stratum corneum in vivo. Sex and site differences were detected with this method. A surfometer was employed to measure the surface contours of the internal face of skin surface biopsies and when this measurement of the surface irregularity was compared to the 'cohesograph' reading for the same sites in 16 normal individuals a significant positive correlation of r=0-79 was found between the two sets of results. It is therefore suggested that the surfometer provides indirect measure of horny layer cohesion. Desquamation has also been estimated by using a modified 'scrub technique'. The scrub apparatus used is able to deliver a controlled stimulus to the skin surface to release horny cells. The light absorbance at 400 nm of corneocyte suspensions was measured and found to correlate well (r=0-96) with the numbers of squames released. It is suggested that the three techniques used in conjunction provide a profile of stratum corneum cohesion in vivo.
Immunotherapy for Glioblastoma: The Devil Is in the Details
Authors: Maciej S. Lesniak
Journal: Journal of Clinical Oncology (2011)

Sampson et al 1 report encouraging progression-free survival and survival data using a vaccine that targets the tumor-specific epidermal growth factor receptor mutation, EGFRvIII.While selectively targeting a tumor-specific mutation with active immunotherapy has been the holy grail of this field for some time, the data presented by these authors also raises some concerns with regard to the value of singlearm phase II trials which have become perennial in neuro-oncology.While the authors' survival statistics are impressive, recent articles 2,3 demonstrate that such data in the context of single-arm phase II trials can be misleading.In the Sampson et al 1 article, however, additional data is provided which further supports the potential efficacy of the vaccine -that is, the nearly universal elimination of the target antigen in patients whose tumors recur.Radiation, by its very nature, and temozolomide, as more recently shown, 4 are mutagenic.In the context of this trial, we must remember that these patients also received both of these standard-ofcare therapies.Thus, it is possible that these potent mutagens cause either random or systematic mutations in EGFRvIII, resulting in its apparent absence.This finding might reduce the importance of this article.In contrast, if patients treated with standard-of-care radiation and temozolomide maintain expression of EGFRvIII, then these authors have strong support for the activity of their vaccine, and the apparent increase in survival that they demonstrate has greater importance.I think it is important for the authors to comment on this issue and perhaps reply within the context of the Journal.
Penalties for Sexual Offences
Authors: W. W. Horton
Journal: BMJ (1951)

G<i>α</i><sub>q</sub><i>βγ</i> heterotrimer (G<sub>q</sub>), an important mediator in the pathology of airway disease, plays a central role in bronchoconstriction and airway remodeling, including airway smooth muscle growth and inflammation. Current therapeutic strategies to treat airway disease include the use of muscarinic and leukotriene receptor antagonists; however, these pharmaceuticals demonstrate a limited clinical efficacy as multiple G<sub>q</sub>-coupled receptor subtypes contribute to these pathologies. Thus, broadly inhibiting the activation of G<sub>q</sub> may be an advantageous therapeutic approach. Here, we investigated the effects of broadly inhibiting G<sub>q</sub> activation in vitro and ex vivo using receptor-dependent and receptor-independent strategies. P4pal-10 is a protease activated receptor 4–derived pepducin that exhibits efficacy toward multiple G<sub>q</sub>-coupled receptors. Mechanistic studies demonstrated that P4pal-10 selectively inhibits all G protein coupling to several G<sub>q</sub>-coupled receptors, including protease activated receptor 1, muscarinic acetylcholine M3, and histamine H1 receptors, while demonstrating no direct effect on G<sub>q</sub>. We also evaluated the ability of FR900359, also known as UBO-QIC, to directly inhibit G<sub>q</sub> activation. FR900359 inhibited spontaneous G<i>α</i><sub>q</sub> nucleotide exchange, while having little effect on G<i>α</i><sub>s</sub><i>βγ</i>, G<i>α</i><sub>i</sub><i>βγ</i>, or G<i>α</i><sub>12/13</sub><i>βγ</i> heterotrimer activity. Both P4pal-10 and FR900359 inhibited G<sub>q</sub>-mediated intracellular signaling and primary human airway smooth muscle growth, whereas only FR900359 effectively interdicted agonist-promoted airway contraction in human precision cut lung slices. These studies serve as a proof of concept that the broad-based inhibition of G<sub>q</sub> activation may be a useful therapeutic approach to treat multiple common pathologies of airway disease.
Screening for Alcoholism
Authors: Thomas A. Cable
Journal: JAMA (1988)

To the Editor.—  We congratulate Drs Cyr and Wartman1for defining a more effective clinical approach to screen for alcoholism in ambulatory care settings. We do, however, question their premise that early detection and treatment of alcoholism may substantially reduce alcohol-related morbidity and  and thus their recommendation that all patients should be screened for alcoholism regardless of their reason for seeking care.  Readily accepted screening criteria for any disease require (1) the disease to be common, to be detectable in the presymptomatic stage, and to have important morbidity; (2) the screening test to be both sensitive and specific, safe, inexpensive, and available; and (3) the therapy in the presymptomatic state to be effective in reducing morbidity and mortality compared with treatment after symptoms develop. Screening for alcoholism passes the first two criteria but fails the third.  Unfortunately, there is no uniformly effective therapy for presymptomatic or symptomatic alcoholism.
Wound models for periodontal and bone regeneration: the role of biologic research
Authors: Anton Sculean, Iain L. C. Chapple, William V. Giannobile
Journal: Periodontology 2000 (2015)

Abstract The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory‐immune response, or to trauma, with tissues that possess the same structure and function, and the re‐establishment of a sustainable health‐promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof‐of‐concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal‐regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase.
Closer Look at Spinal Lesions
Authors: Donald A. Nagel
Journal: JAMA (1965)

In an attempt to gain some new insight into spinal lesions that produce back pain, clinical records of 254 patients admitted to the University Orthopaedic Surgery Service of Yale Medical Center from 1959 through 1963 were reviewed. Twenty of these patients had osteomyelitis and six had tumors of various types. Of the 254 patients, 159 underwent surgery. The third most common surgical procedure was biopsy which was carried out in 22 patients. From our study we are convinced that open surgical biopsy is of value in the diagnosis of obscure lesions of the vertebral bodies and may indeed provide a form of treatment as well as diagnosis. The posterior laminectomy approach may destroy the only remaining supporting structures of the spine; therefore, this "closer look" should be made by the anterior, anterolateral, or lateral approach.
Grand Challenges: Integrating Maternal Mental Health into Maternal and Child Health Programmes
Authors: Atif Rahman, Pamela J. Surkan, Claudina E. Cayetano, Patrick Rwagatare, Kim E. Dickson
Journal: PLoS Medicine (2013)

In the second article of a five-part series providing a global perspective on integrating mental health, Atif Rahman and colleagues argue that integrating maternal mental health care will help advance maternal and child health. Please see later in the article for the Editors' Summary
An Account of 2,500 Infant B.C.G. Vaccinations
Authors: H. M. Purser
Journal: BMJ (1954)

<h3>Introduction</h3> Early recognition and effective treatment of internal bleeding impose a cardinal challenge for trauma teams. The reduction of the superior mesenteric artery (SMA) blood flow is among the first compensatory responses to blood loss, thus being a promising candidate as a diagnostic tool for occult haemorrhage. Unfortunately, methods for monitoring the SMA flow have not been elaborated to date. Nevertheless, animal experiments suggest that exhaled methane (CH<sub>4</sub>) levels correspond to the SMA perfusion. We hypothesise that real-time detection of CH<sub>4</sub> concentrations in the exhaled air is an applicable technique for the early recognition of haemorrhage in severely injured patients. We also hypothesise that exhaled CH<sub>4</sub> levels reflect the volume of blood loss more accurately than conventional markers of blood loss and shock such as shock index, haemoglobin, base deficit, lactate, end-tidal carbon dioxide and sublingual microcirculatory indices. <h3>Methods and analysis</h3> One hundred and eleven severely injured (Injury Severity Score ≥16), intubated, bleeding patients sustaining blunt trauma will be included in this prospective observational study. Blood loss will be detected with CT and estimated with CT-linked radiologic software. Exhaled CH<sub>4</sub> concentrations will be monitored by attaching a near-infrared laser technique-based photoacoustic spectroscopy apparatus to the exhalation outlet of the ventilator on patient arrival. The primary outcome is the volume of blood loss. Need for massive transfusion and 24-hour mortality will constitute secondary outcomes. The relation of exhaled CH<sub>4</sub> to study outcomes and its performance in predicting blood loss in comparison with conventional shock markers and microcirculatory indices will be tested. <h3>Ethics and dissemination</h3> Our protocol (ID: 5400/2021-SZTE) has been registered on ClinicalTrials.gov (NCT04987411) and complies with the Declaration of Helsinki and has been approved by the medical ethics committee at the University of Szeged (Ref.nr.:121/2021-SZTE RKEB). It is in data collection phase, theresults will be shared with the scientific community through publication in a peer-reviewed journal. <h3>Trial registration number</h3> NCT04987411; ClinicalTrials.gov, registered on 27 July 2021.
Hepatic steatosis in Wilson disease – Role of copper and PNPLA3 mutations
Authors: Albert Friedrich Stättermayer, Stefan Traussnigg, Hans-Peter Dienes, Elmar Aigner, Rudolf Stauber, Karoline Lackner, Harald Hofer, Judith Stift, Friedrich Wrba, Andreas Stadlmayr, Christian Datz, Michael Strasser, Andreas Maieron, Michael Trauner, Peter Ferenci
Journal: Journal of Hepatology (2015)
Leprosy type 1 reaction as the first manifestation of borderline lepromatous leprosy in a young native German
Authors: T. BIEDERMANN, K. DEGITZ, C.G. SCHIRREN, W. BURGDORF, G. PLEWIG, T. BIEBER
Journal: British Journal of Dermatology (1997)

While leprosy is usually a chronic disease, leprosy reactions may lead to acute problems. These reactions most often occur after initiation of therapy, but can also develop before treatment. Leprosy rarely presents with a reaction. We describe a German patient who presented in this unusual way in order to demonstrate the various tools used to confirm the diagnosis. A young German woman suddenly developed progressive functional loss of the left hand and within a few weeks an increasing number of erythematous macules and nodules appeared. Histological examination of a skin biopsy revealed tuberculoid granulomas, some located around small nerves; acid-fast bacilli were detected microscopically and DNA from Mycobacterium leprae was identified by polymerase chain reaction in the biopsy and a nasal swab; serological tests were positive. The disease was classified as borderline lepromatous leprosy. The acute neuritis followed by skin lesions represented a leprosy type 1 reaction in which the immune system reacts to bacilli previously unrecognized in nerve tissue, both in nerve and skin.
Gulf War Symptoms Remain Puzzling
Authors: Paul Cotton
Journal: JAMA (1992)

WITH OIL FIRES exonerated and a special registry and referral centers set up, the mystery continues over unexplained signs and symptoms ( JAMA . 1992;267:2579) reported by some 300 Persian Gulf war veterans.  Hair loss, bleeding gums, myalgias, arthralgias, rashes, liver problems, and especially debilitating fatigue have both the veterans who say they are afflicted and military health officials stressing the importance of preventing another Agent Orange—like ordeal. In the latter situation, Vietnam veterans' complaints of health problems and birth defects were registered so long after exposure to the dioxin-based defoliant that scientific proof or disproof of cause and effect was virtually impossible.  In the post—Persian Gulf situation, a panel of experts in toxicology, occupational medicine, and epidemiology from the armed forces, Centers for Disease Control and Prevention (CDC, Atlanta, Ga), and the private petroleum industry has concluded that there is no objective evidence that a single soldier, sailor, airman, or Marine
Effects of Schizophrenia Risk Variation in the NRG1 Gene on NRG1-IV Splicing During Fetal and Early Postnatal Human Neocortical Development
Authors: Clare Paterson, Yanhong Wang, Joel E. Kleinman, Amanda J. Law
Journal: American Journal of Psychiatry (2014)

Neuregulin 1 (NRG1) is a multifunctional neurotrophin that mediates neurodevelopment and schizophrenia risk. The NRG1 gene undergoes extensive alternative splicing, and association of brain NRG1 type IV isoform expression with the schizophrenia-risk polymorphism rs6994992 is a potential mechanism of risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique signaling capabilities, have been cloned in fetal brain tissue. The authors investigated the temporal dynamics of transcription of NRG1-IVNV, compared with the major NRG1 isoforms, across human prenatal and postnatal prefrontal cortical development, and they examined the association of rs6994992 with NRG1-IVNV expression.NRG1 type I-IV and NRG1-IVNV isoforms were evaluated with quantitative real-time polymerase chain reaction in human postmortem prefrontal cortex tissue samples at 14 to 39 weeks gestation and postnatal ages 0-83 years. The association of rs6994992 genotype with NRG1-IVNV expression and the subcellular distribution and proteolytic processing of NRG1-IVNV isoforms were also determined.Expression of NRG1 types I, II, and III was temporally regulated during prenatal and postnatal neocortical development. NRG1-IVNV was expressed from 16 weeks gestation until age 3. Homozygosity for the schizophrenia risk allele (T) of rs6994992 conferred lower cortical NRG1-IVNV levels. Assays showed that NRG1-IVNV is a novel nuclear-enriched, truncated NRG1 protein resistant to proteolytic processing.To the authors' knowledge, this study provides the first quantitative map of NRG1 isoform expression during human neocortical development and aging. It identifies a potential mechanism of early developmental risk for schizophrenia at the NRG1 locus, involving a novel class of NRG1 proteins.
Knowledge to Action? Evidence-Based Health Care in Context
Authors: Matt Williams
Journal: BMJ (2006)

M ost of us are familiar with the idea of evidence based medicine (EBM), and the resulting slew of guidelines and care pathways that has become its unavoidable spouse. The unhappy marriage of the high minded ambitions of EBM and the bloated, lifeless prose of protocols does more than offend our literary sensibilities; it points to a harder problem in trying to implement the evidence in EBM. At root, this is a failure to grasp that just as there is evidence in EBM, there must also be evidence about EBM and its applications.
All UK doctors to be required to prove competence
Authors: Z. Kmietowicz
Journal: BMJ (1999)

All doctors in the United Kingdom will be required to prove that they are competent, that theirskills are up to date, and that they are willing to undergo continued monitoring of their skills if they wish to continue practising medicine, doctors' leaders agreed last week.

In what Sir Donald Irvine, president of the General Medical Council (GMC), described as a “defining moment,” the council endorsed proposals to overhaul the current regulation of doctors as …
Response to Comment on Dalmas et al. Intima-Media Thickness in Severe Obesity: Links With BMI and Metabolic Status but Not With Systemic or Adipose Tissue Inflammation. Diabetes Care 2013;36:3793–3802
Authors: Michèle Guerre-Millo, Christine Poitou
Journal: Diabetes Care (2014)

We appreciate that our study has been read with such interest by Dogru et al. (1). The main objective of our study (2) was to evaluate the relationships between inflammation, especially in adipose tissue, and subclinical atherosclerosis. Here, we would like provide some clarification.

First, to avoid a confounding effect of type 2 diabetes on cytokine concentration or on adipose tissue inflammation, we have excluded diabetic subjects in the analysis of relationships between bioclinical phenotypes, inflammation, and arterial intima-media thickness (IMT).

Second, in the series of analyses showing that BMI …
Mechanism(s) of altered mitochondrial calcium transport in acutely ischemic canine hearts.
Authors: L A Sordahl, M L Stewart
Journal: Circulation Research (1980)

Studies were undertaken to determine the mechanisms leading to altered mitochondrial function in ischemic myocardium. A new procedure has been developed to routinely isolate 60-70% of the total mitochondrial protein from heart tissue. After 1 hour of ischemia, mitochondria exhibit decreases of more than 50% in phosphorylating respiration for both NADH- and succinate-linked substrates compared to controls. However, no significant decreases in the efficiency of mitochondrial ATP synthesis (ADP:0) or ATPase activity are observed. Rates of substrate-driven Ca2+ uptake exhibit decreases greater than that seen with phosphorylating respiration with incomplete uptake and premature release of Ca2+. Spectrophotometric measurements in ischemic heart reveal rapid oxidation or loss of mitochondrial NADH with marked "swelling" of the inner membrane compartment; both changes parallel the loss of Ca2+. Significant losses in intramitochondrial adenine nucleotides also are found. Mitochondrial retention of accumulated Ca2+ can be restored by addition of small amounts of exogenous adenine nucleotides (ATP or ADP) with concomitant attenuation of both NADH oxidation and "swelling." The data indicate that, following 1 hour of ischemia, the efficiency of mitochondrial ATP production is still relatively intact whereas both electron transport chain activity and calcium transport are severely compromised. These decreases appear to be related to selective membrane damage in the mitochondrial inner membrane.
SEGMENTAL ANALYSIS OF MITRAL VALVE LEAFLETS IN ISCHEMIC MITRAL REGURGITATION
Authors: Caroline Morbach, Diego Bellavia, Pramod Bonde, Abeel Mangi, David Yuh, Irena Vaitkeviciute, Lynn Weinert, Berthold Klas, Lissa Sugeng
Journal: Journal of the American College of Cardiology (2013)
Helicobacter pylori Infection: Genetic and Environmental Influences: A Study of Twins
Authors: Hoda M. Malaty
Journal: Annals of Internal Medicine (1994)

Objective: To investigate the importance of genetic effects for acquiring Helicobacter pylori infection. Design: Cross-sectional study on monozygotic and dizygotic twins, reared apart and reared together. Setting: Twins from a subregistry of the Swedish Twin Registry, which includes entries for about 25 000 twin pairs who were born in Sweden. Measurements: Helicobacter pylori status was assessed as the presence of anti-H. pylori IgG in 269 pairs of twins, including 36 monozygotic twin pairs reared apart, 64 monozygotic twin pairs reared together, 88 dizygotic twin pairs reared apart, and 81 dizygotic twin pairs reared together. Results: The probandwise concordance rate for H. pylori infection was higher in monozygotic twin pairs (81%) than in dizygotic twin pairs (63%) (P = 0.001). Probandwise concordance rates for H. pylori infection among 124 pairs of twins reared apart were 82% and 66% for monozygotic and dizygotic twins, respectively (P = 0.003). The correlation coefficient was 0.66 for monozygotic twins reared apart, and it provides the best single estimate of the relative importance of genetic effects (heritability) for variation in the acquisition of H. pylori infection. The heritability estimate from model-fitting analyses was 0.57, a similar result. The remaining variance was accounted for by shared rearing environmental (20%) and nonshared environmental factors (23%). The latter contribute to differences, not similarities, among family members. Conclusion: This twin study showed that genetic effects influence the acquisition of H. pylori infection because of greater similarities within the monozygotic twin pairs. Further, sharing the same rearing environment also contributes to the familial tendency for acquiring H. pylori infection.