tbuckley/cabot-search huggingface dataset:
Prospective Study of Serum Cholesterol Levels and Large-Bowel Cancer
Authors: A. M. Y. Nomura, G. N. Stemmermann, P.-H. Chyou
Journal: JNCI Journal of the National Cancer Institute (1991)

Based on previous reports, it is uncerthin whether serum cholesterol levels are inversely related to colon cancer risk. In this study, serum cholesterol levels were measured in 7926 Japanese-American men who were followed for over 20 years. Two hundred thirty-one incident cases of colon cancer and 97 cases of rectal cancer were identified. An increase in serum cholesterol levels was associated with a decrease in risk for colon cancer ( P value for trend =.01) but not for rectal cancer. This association appeared stronger as the site of cancer moved from the sigmoid colon to the cecum. The data were further analyzed by interval from examination to diagnosis. The inverse association was present for colon cancer cases diagnosed within 10 years of examination ( P value for trend <.01), especially for cecum-ascending colon cancer cases ( P <.01). A similar inverse pattern was found for cecum-ascending colon cancer cases diagnosed after 10 years, but the association was not statistically significant. The results suggest that the preclinical effects of undiagnosed colon cancer contributed to the inverse association, but these effects do not entirely explain why the relationship with hypocholesterolemia was stronger in men who were subsequently diagnosed with right-sided colon cancer. [J Natl Cancer Inst 83:1403–1407, 1991]
Mentally abnormal prisoners on remand: I--Rejected or accepted by the NHS?
Authors: J. W Coid
Journal: BMJ (1988)

Increasing numbers of mentally abnormal offenders are sentenced to prison. The decision to treat or imprison them is influenced by the attitudes of consultant psychiatrists and their staff. The process whereby those decisions were made and the willingness of consultants to offer treatment were investigated. A retrospective survey of all (362) mentally abnormal men remanded to Winchester prison for psychiatric reports over the five years 1979-83 showed that one in five were rejected for treatment by the NHS consultant psychiatrist responsible for their care. Those with mental handicaps, organic brain damage, or a chronic psychotic illness rendering them unable to cope independently in the community were the most likely to be rejected. They posed the least threat to the community in terms of their criminal behaviour yet were more likely to be sentenced to imprisonment. Such subjects were commonly described by consultants as too disturbed or potentially dangerous to be admitted to hospital or as criminals and unsuitable for treatment. Consultants in mental hospitals were most likely and those in district general hospitals and academic units least likely to accept prisoners. The fact that many mentally ill and mentally handicapped patients can receive adequate care and treatment only on reception into prison raises serious questions about the adequacy of current management policies and the range of facilities provided by regional health authorities.
A13: The Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh Out) Cohort: Prospective Determination of the Incidence of New Onset Uveitis in Juvenile Idiopathic Arthritis
Authors: Karen N Watanabe Duffy, Jennifer Lee, Jaime Guzman, Nick Barrowman, Kimberly Morishita, Lynn R. Spiegel, Elizabeth Stringer, Michele Gibbon, Rae SM Yeung, Lori B. Tucker, Kiem Oen, Ciarán M. Duffy
Journal: Arthritis & Rheumatology (2014)

Background/Purpose: Previous studies of uveitis in Juvenile Idiopathic Arthritis (JIA) patients have reported prevalence and not incidence. The ReACCh Out cohort, a large inception cohort of newly diagnosed JIA patients provided the opportunity to prospectively ascertain the true incidence of new onset uveitis. The objectives of this study were to determine the overall incidence rate and its trajectory over time. Methods: ReACCh Out recruited newly diagnosed JIA patients between January 2005 and December 2010, from 16 Canadian centres across the country. Prospective data was collected every 6 months for the first 2 years, then yearly. Data was collected on numerous clinical and laboratory measures including the diagnosis of uveitis and its complications, determined by an ophthalmologist. A Poisson model was used to estimate the overall incidence rate. A Kaplan‐Meier plot was used to evaluate the time from diagnosis of JIA to the time of diagnosis of new onset uveitis. Results: 1104 patients with newly diagnosed (≤6 months) JIA with ≥1 follow‐up visit were reviewed. Patients were predominantly female (63%), age at diagnosis was 9.3 (3.9, 13.0) years. Time from diagnosis to enrollment was 0.3 (0, 1.6) months. Follow‐up to last visit or study end was 34.2 (21.5, 48) months. 23 patients whose uveitis status was not available, were excluded. 77 patients with new onset uveitis were identified during the study period. The overall incidence rate of new cases of uveitis following the diagnosis of JIA was 2.9% per year (95% confidence interval 2.3–3.6). Following the trajectory of new cases of uveitis over time, the incidence of new cases showed a slow decline over time (Figure ). Importantly, new cases of uveitis occurred as far out from diagnosis as the end of the study period. Kaplan‐Meier plots were also used to evaluate age at diagnosis of new onset uveitis and gender. Results support previously identified risk factors for uveitis including younger age (&lt;5 years) and female gender. The frequency of uveitis occurred in the JIA patients in the following distribution according to subtype: oligoarthritis (43, 56%), polyarthritis RF negative (18, 23%), polyarthritis RF positive (1, 1%), psoriatic (4, 5%), ERA (1, 1%), systemic (1, 1%) and undifferentiated (9, 12%). Time (confidence intervals) from diagnosis of JIA to diagnosis of new onset uveitis image Conclusion: In a large inception cohort of newly diagnosed JIA patients followed prospectively, the overall incidence rate of new cases of uveitis was 2.9% per year. The slow decrease in incidence over time and the development of new cases of uveitis years later, highlight the importance of ongoing and long term surveillance.
Research Proposals: A Guide to Success
Authors: Frank L. Iber
Journal: JAMA (1996)

Dr Ogden in this second edition has added the experiences of Dr Goldberg, a longtime senior National Institutes of Health (NIH) administrator, to his own. The book emphasizes applications to the NIH, with a detailed presentation of the RO1 application (the traditional research grant application), its methods of review, and many of the avoidable reasons for rejection. It also contains much practical advice on how to proceed with the preparation of each section of the submission, which will save much time. Specific suggestions of essential inclusions and strong recommendations of things to avoid are presented for each section. Examples of pink sheets describing reasons for rejection and methods of resubmission to strengthen the application are well covered. Another section covers special types of NIH grants and site visits. Appendixes comprise almost one third of the volume. This book is a helpful guide to gransts-manship, rather than writing or conducting research,
Protecting reproductive health and the environment: toxics use reduction.
Authors: K Geiser
Journal: Environmental Health Perspectives (1993)

Toxics use reduction is a new chemical hazard management approach that has emerged in several state laws over the past years. While toxics use reduction has been promoted as a means of preventing environmental pollution, little thought has been given to its adoption as a means of managing reproductive hazards. This paper provides illustrations of use reduction approaches to conventionally recognized reproductive and developmental toxicants. These approaches will require the opening of a new dialogue between industrial designers and process managers and those most concerned about reproductive health. Several different strategies are proposed that might be adopted into state programs for promoting reduction in the use of reproductive and developmental toxicants.
Increased IL-6-production by cells isolated from the fibrous bone dysplasia tissues in patients with McCune-Albright syndrome.
Authors: T Yamamoto, K Ozono, S Kasayama, K Yoh, K Hiroshima, M Takagi, S Matsumoto, T Michigami, K Yamaoka, T Kishimoto, S Okada
Journal: Journal of Clinical Investigation (1996)

McCune-Albright syndrome (MAS) is characterized by café-au-lait spot, multiple endocrine hyperfunction, and polyostotic fibrous dysplasia. A somatic point mutation of Gsalpha protein was reported to decrease GTPase activity, leading to increase in the GSalpha-associated hormone actions via cAMP. IL-6 is known to stimulate osteoclast formation and in the IL-6 promoter, a cAMP responsive element has been identified. In this paper, we investigated the role of IL-6 in the bone lesions of MAS, using the isolated fibrous cells from the polyostotic fibrous dysplasia tissues in bones of the two patients with MAS. Bone biopsy specimen revealed the increased osteoclast in number. In both patients, a GSalpha mutation (Arg201 -> His) was identified in the cultured fibrous cells. Intracellular cAMP content and IL-6 secretion by the patient cells were increased. Rp-8Br-cAMP significantly inhibited IL-6 production in the patient cells, while it had no effect on normal control. The addition of dibutyryl cAMP significantly increased the synthesis of IL-6 in normal control cells. In contrast, no effect of dibutyryl cAMP on IL-6 synthesis was observed in the cells from one of the MAS patients. These data suggest that IL-6 is, at least, one of the downstream effectors of cAMP and that the increased IL-6 synthesis has a pathogenic role in the bone lesions of MAS patients via increasing the number of osteoclasts. These results may provide a new strategy for the therapy of MAS patients.
Efficacy and safety of systemic treatments for moderate‐to‐severe psoriasis: meta‐analysis of randomized controlled trials
Authors: J. Schmitt, S. Rosumeck, G. Thomaschewski, B. Sporbeck, E. Haufe, A. Nast
Journal: British Journal of Dermatology (2013)

Dermatologists may choose from various conventional and biological systemic agents to treat patients with moderate-to-severe psoriasis. We set out to analyse systematically the efficacy and tolerability of approved treatments for moderate-to-severe psoriasis. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the efficacy of systemic treatment approved for moderate-to-severe psoriasis. Efficacy was assessed as the proportion of participants with 75% improvement in Psoriasis Area and Severity Index at primary efficacy measurement (week 8-16). Safety was summarized as rates of adverse events and withdrawals. Direct and indirect comparative efficacy was assessed by random effects meta-analysis of risk differences (RDs). In total, 48 eligible RCTs totalling 16 696 patients (11 178 randomized to biologics, 1888 to conventional treatments) were identified. In placebo-controlled trials, infliximab was the most efficacious [RD 76%, 95% confidence interval (CI) 73-79%]. Adalimumab (RD 61%, 95% CI 56-67%), and ustekinumab 45 mg (RD 63%, 95% CI 59-66%) and 90 mg (RD 67%, 95% CI 60-74%) each had similar efficacy. These biologics are more effective than etanercept and all conventional treatments. Head-to-head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept, the nonsignificant superiority of ciclosporin over MTX, and the dose-dependent efficacy of etanercept and ustekinumab. Fumaric acid is as efficacious as MTX. Safety of treatments could not be pooled due to a lack of standardization in reporting across trials. In conclusion, the qualitative and quantitative evidence is much stronger for biological interventions than for conventional treatments.
Accuracy of Coalescent Likelihood Estimates: Do We Need More Sites, More Sequences, or More Loci?
Authors: Joseph Felsenstein
Journal: Molecular Biology and Evolution (2005)

A computer simulation study has been made of the accuracy of estimates of Θ = 4Neμ from a sample from a single isolated population of finite size. The accuracies turn out to be well predicted by a formula developed by Fu and Li, who used optimistic assumptions. Their formulas are restated in terms of accuracy, defined here as the reciprocal of the squared coefficient of variation. This should be proportional to sample size when the entities sampled provide independent information. Using these formulas for accuracy, the sampling strategy for estimation of Θ can be investigated. Two models for cost have been used, a cost-per-base model and a cost-per-read model. The former would lead us to prefer to have a very large number of loci, each one base long. The latter, which is more realistic, causes us to prefer to have one read per locus and an optimum sample size which declines as costs of sampling organisms increase. For realistic values, the optimum sample size is 8 or fewer individuals. This is quite close to the results obtained by Pluzhnikov and Donnelly for a cost-per-base model, evaluating other estimators of Θ. It can be understood by considering that the resources spent collecting larger samples prevent us from considering more loci. An examination of the efficiency of Watterson's estimator of Θ was also made, and it was found to be reasonably efficient when the number of mutants per generation in the sequence in the whole population is less than 2.5.
Evaluation of human herpesvirus type 8 infection in childhood Langerhans cell histiocytosis
Authors: Hal B. Jenson, Kenneth L. McClain, Charles T. Leach, Jian-Hong Deng, Shou-Jiang Gao
Journal: American Journal of Hematology (2000)

The etiology of Langerhans cell histiocytosis (LCH) is unknown. Viral causes, including human herpesvirus type 6 (HHV6), have been suggested but remain unproved. The recently discovered human herpesvirus type 8 (HHV8), the cause of Kaposi's sarcoma, infects dendritic cells in the bone marrow associated with multiple myeloma. Evidence for an association of HHV8 infection with LCH in children was studied by two approaches: indirectly by HHV8-specific serologic assays and directly by detection of HHV8 sequences using polymerase chain reaction in affected bone marrow samples. Using three different assays specific for HHV8 antibodies, 3 of 10 (30%) children with LCH had detectable HHV8 antibodies, which was not different from the prevalence of 5 of 30 (17%) in healthy controls of similar age (P = 0.65). Of bone marrow samples from three additional children with LCH, all had amplifiable DNA but were negative for HHV8 sequences. These studies of a small number of patients do not demonstrate an increased prevalence of HHV8 infection in children with LCH, and they do not suggest a causal role for HHV8 in the etiology of LCH. Am. J. Hematol. 64:237–241, 2000. © 2000 Wiley-Liss, Inc.
Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study
Authors: G. Marazza, H.C. Pham, L. Schärer, P.P. Pedrazzetti, T. Hunziker, R.M. Trüeb, D. Hohl, P. Itin, S. Lautenschlager, L. Naldi, L. Borradori
Journal: British Journal of Dermatology (2009)

Bullous pemphigoid (BP), pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune bullous diseases characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Although rare, these diseases run a chronic course and are associated with significant morbidity and mortality. There are few prospective data on gender- and age-specific incidence of these disorders.Our aims were: (i) to evaluate the incidence of BP and PV/PF in Swiss patients, as the primary endpoint; and (ii) to assess the profile of the patients, particularly for comorbidities and medications, as the secondary endpoint.The protocol of the study was distributed to all dermatology clinics, immunopathology laboratories and practising dermatologists in Switzerland. All newly diagnosed cases of BP and pemphigus occurring between 1 January 2001 and 31 December 2002 were collected. In total, 168 patients (73 men and 95 women) with these autoimmune bullous diseases, with a diagnosis based on clinical, histological and immunopathological criteria, were finally included.BP showed a mean incidence of 12.1 new cases per million people per year. Its incidence increased significantly after the age of 70 years, with a maximal value after the age of 90 years. The female/male ratio was 1.3. The age-standardized incidence of BP using the European population as reference was, however, lower, with 6.8 new cases per million people per year, reflecting the ageing of the Swiss population. In contrast, both PV and PF were less frequent. Their combined mean incidence was 0.6 new cases per million people per year. CONCLUSIONS; This is the first comprehensive prospective study analysing the incidence of autoimmune bullous diseases in an entire country. Our patient cohort is large enough to establish BP as the most frequent autoimmune bullous disease. Its incidence rate appears higher compared with other previous studies, most likely because of the demographic characteristics of the Swiss population. Nevertheless, based on its potentially misleading presentations, it is possible that the real incidence rate of BP is still underestimated. Based on its significant incidence in the elderly population, BP should deserve more public health concern.
Number and proliferation of neuroendocrine cells in normal human airway epithelium.
Authors: J E Boers, J L den Brok, J Koudstaal, J W Arends, F B Thunnissen
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Pulmonary neuroendocrine cells (PNECs) are ubiquitous in human adult airway epithelium, and are implicated in pulmonary disease as PNEC hyperplasia has been described in a great number of different pulmonary lesions. The purpose of this study was to determine the baseline quantity and proliferative fraction of adult PNECs in the conducting airway epithelium of normal lungs. Autopsy was performed within 6 h of death on 250 subjects. In 9 of 250 cases without pulmonary disease, seven sequential samples were taken from trachea down to respiratory bronchioles, fixed in formalin, and embedded in paraffin. After microwave pretreatment in citrate buffer, sequential immunohistochemical staining was carried out, using MIB-1 (antibody directed against recombinant parts of the Ki-67 antigen) as marker for the proliferation fraction and chromogranin-A (CgA) for the identification of PNECs. Quantification of all epithelial cells of the conducting airways, MIB-1, and CgA immunoreactive cells, and length of basement membrane was interactively performed using image analysis. The results show that microwave treatment significantly enhances the sensitivity of CgA without loss of specificity. In total, 326,500 epithelial cells and 105 cm of basement membrane (BM) length were counted (3,101 cells/cm BM). The proliferation fraction of all epithelial cells was 0.76 +/- 0.53% (mean +/- SD). No mitosis was seen. The mean quantity of PNECs was 0.41 +/- 0.17% of all epithelial cells (12.5 cells/cm BM). Many dendritic PNEC processes parallel to the basement membrane could be appreciated between adjacent epithelial cells. No difference in the number of PNECs was found between large and small conducting airways. PNECs were not observed in the alveoli. Only 13 PNECs were immunoreactive for MIB-1; the proliferative fraction of PNECs was 1 to 2%. In histologically normal adult human conducting airway epithelium, the average overall proliferation fraction is 0.76%. The proliferation fraction of PNECs is equal to the overall proliferative fraction. The fraction of PNECs is 0.41%, using anti-CgA antiserum after microwave pretreatment of slides, 12 times more than previously reported. Many dendritic neuroendocrine cell processes were seen between non-neuroendocrine epithelial cells adjacent to the basement membrane. The widely held belief that neuroendocrine cells are of little importance in the adult lung is contradicted by the relative high density of PNECs and its cytoplasmic processers.
Diet in the Treatment of Acute Hepatitis
Authors: O. Gertzen
Journal: BMJ (1950)

inflammation, in spite of suppression of the local tissue reaction, general improvement should not occur, except perhaps very fleetingly, but rather the reverse, since spread of the local infection would be facilitated.An inquiry into the mechanism of mitosis suppression by A.C.T.H. forms one part of current investigations into the mechanism of shock by the Sheffield team.Observa- tions on mitosis in cancer cells under similar conditions are also in progress.The changes in carbohydrate metabolism in shock and their bearing on aspects of A.C.T.H. activity, including that reported here, are being made by Stoner, Green, and Threlfall, and will, it is hoped, be published in the near future.
Socs3 Expression In Eosinophils And Cd4T Cells Regulates Inflammation In Th2 Respiratory Disorders
Authors: E. López, B. Sastre, C. Gámez, M. Fernandez Nieto, J. Sastre, C. Lahoz, S. Quirce, V. Del Pozo
Journal: Journal of Allergy and Clinical Immunology (2009)
γ-H2AX Foci Formation as a Pharmacodynamic Marker of DNA Damage Produced by DNA Cross-Linking Agents: Results from 2 Phase I Clinical Trials of SJG-136 (SG2000)
Authors: Jenny Wu, Peter H. Clingen, Victoria J. Spanswick, Maria Mellinas-Gomez, Tim Meyer, Igor Puzanov, Duncan Jodrell, Daniel Hochhauser, John A. Hartley
Journal: Clinical Cancer Research (2012)

To evaluate γ-H2AX foci as a pharmacodynamic marker for DNA damage induced by DNA interstrand cross-linking drugs.
Japanese Encephalitis — A Plague of the Orient
Authors: Thomas P. Monath
Journal: New England Journal of Medicine (1988)

Japanese encephalitis has attracted attention recently in the United States, Europe, and Australia because of a small number of cases among travelers, but the epidemic proportions of the disease in Asia have compelled immunization of entire regional or national populations. Japanese encephalitis, which is caused by a flavivirus transmitted by mosquitoes, often strikes in unpredictable form. It affects principally school-age children and is greatly feared because of its high lethality and frequency of permanent neurologic sequelae.The clinical disease was described as early as 1871 in Japan, but the causative agent (Japanese encephalitis virus) was not isolated until 1934. A . . .
Case 21-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Lester A. Klein, Karl H. Proppe
Journal: New England Journal of Medicine (1980)

Presentation of CaseA 36-year-old man was admitted to the hospital because of urinary retention.He was well until one year earlier, when he became impotent. Three months before admission intermittent difficulty in voiding developed, with hesitancy, decreased force of stream, incomplete voiding, urinary frequency, and nocturia, and he became constipated. Two months before admission he began to have pain in the left flank that usually occurred on bending forward and was relieved by sitting. Two days before entry dysuria recurred, and on the next day he was unable to void or to move his bowels. He was taken to . . .