tbuckley/cabot-search huggingface dataset:
Raynaud's phenomenon and thermal entrainment: an objective test.
Authors: K Lafferty, J C de Trafford, V C Roberts, L T Cotton
Journal: BMJ (1983)

A new objective test for diagnosing Raynaud9s phenomenon was assessed in practice. The test is based on entrainment of the thermal vasomotor control system and entails non-invasive measurement of blood-flow responses in one hand while alternating thermal stimuli are applied to the contralateral hand. A significant (p less than 0.001) abnormality of vasomotor control was found in patients with Raynaud9s phenomenon compared with normal subjects. When applied clinically this test is diagnostic and indicates the severity of the disease and the effect of treatment.
THOUGHTS ON VITAL RESISTANCE TO DISEASE—IMMUNITY, NATURAL AND ACQUIRED.
Authors: G. W. FINLEY
Journal: JAMA (1896)

We occasionally observe individuals whose state of health, physically and mentally, seems so thoroughly perfect that they can and do pass through epidemics of virulently infectious disease unscathed. We observe a far larger number who prove themselves, for the time being at least, impregnable to exposure or even inoculation with germs of certain contagious diseases, and who yet fall easy prey to other diseases on slight exposure. The latter class are protected only as to certain germs, either by the fact of having previously experienced an attack of the given malady, or by some inherent quality in their own organization. In this consideration, the possible protection afforded by some extraneous circumstance, such as approximately perfect sanitary surroundings or the influence of chemic disinfectants, is supposed to be excluded. This difference in susceptibility to infection, shown by different races of people, by different individual subjects under what is apparently the same
Evaluation of a decision support system for initiation and control of oral anticoagulation in a randomised trial
Authors: B Vadher, D L H Patterson, M Leaning
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether a computerised decision support system for initiation and control of oral anticoagulant treatment improves quality of anticoagulant control achieved by trainee doctors. <b>Design:</b> Randomised controlled trial. <b>Setting:</b> District general hospital in North London. <b>Subjects:</b> 148 inpatients requiring start of warfarin treatment. <b>Interventions:</b> Management by trainee doctors (to achieve therapeutic range of international normalised ratio of 2 to 3) with indirect assistance from computerised decision support system (intervention group) or without such assistance (control group). <b>Main outcome measures:</b> Median time to therapeutic range, stable dose, and first pseudoevent (excessive international normalised ratio after therapeutic range has been reached) and person time spent in the therapeutic range. <b>Results:</b> 72 patients were randomised to the intervention group and 76 to control group. Median time to reach international normalised ratio of ≥2 was not significantly different in the two groups (3 days). Median time to achieve a stable dose was significantly lower in intervention group than in controls (7 days <i>v</i> 9 days, P=0.01) without excessive overtreatment or undertreatment with anticoagulant. Patients in intervention group spent greater proportion of time in therapeutic range, both as inpatients (59% <i>v</i> 52%) and outpatients (64% <i>v</i> 51%). <b>Conclusion:</b> The computerised decision support system was safe and effective and improved the quality of initiation and control of warfarin treatment by trainee doctors. <h3>Key messages</h3> The quality of control of warfarin doses during initiation and maintenance of oral anticoagulation is generally poor We investigated whether a computerised decision support system for initiation and control of oral anticoagulation improved quality of anticoagulant control achieved by trainee doctors The median time to achieve a stable dose was significantly lower in the group assisted by the decision support system than in controls, without excessive overtreatment or undertreatment with anticoagulant Patients in the group with the decision aid spent more time within the therapeutic range both as inpatients and outpatients The computerised decision support system was safe and effective and improved quality of initiation and control of warfarin treatment by trainee doctors
Two distinct abnormalities in patients with C8 alpha-gamma deficiency. Low level of C8 beta chain and presence of dysfunctional C8 alpha-gamma subunit.
Authors: F Tedesco, L Roncelli, B H Petersen, V Agnello, J M Sodetz
Journal: Journal of Clinical Investigation (1990)

The sera from three C8 alpha-gamma deficient patients previously reported to have a selective C8 alpha-gamma defect were analyzed by SDS-PAGE and Western blot using two polyclonal antisera to C8 alpha-gamma and a monoclonal antibody to C8 alpha. All three sera exhibited C8 alpha-gamma bands that dissociated into alpha and gamma chains under reducing conditions. Quantitation of the alpha-gamma subunit in these sera by a sensitive ELISA revealed an amount approximately 1% of that found in normal human serum. A similar assay performed with a specific antiserum to C8 beta showed unexpectedly low levels of C8 beta in these sera, which were confirmed by hemolytic titration of C8 beta. The remarkable differences between C8 alpha-gamma and C8 beta in the C8 alpha-gamma deficient sera was that in spite of their comparable immunochemical levels, C8 beta still exhibited functional activity whereas C8 alpha-gamma was totally inactive. That the residual C8 alpha-gamma was inactive was also proved by its inability to show lytic bands in an overlay system after SDS-PAGE and subsequent removal of SDS. The implications of these findings for a novel concept of C8 deficiency are discussed.
Abstract 526: Overexpression of chromosome 3q26-29 miRNAs in squamous cell carcinoma of the lung
Authors: Jun Qian, Xiangming Ji, Yong Zou, Megan Hoeksema, Heidi Chen, Pierre P. Massion
Journal: Cancer Research (2014)

Abstract The amplification of the distal portion of chromosome 3q in lung cancer is a major signature of neoplastic transformation, particularly in the squamous cell carcinoma (SCC) of the lung. A number of potential drivers in the 3q amplicon have been identified and are proposed to contribute to the development of lung SCC. miRNAs have emerged as a new class of small, non-coding RNAs that regulate gene expression and might act as integral parts of the molecular architecture of oncogene and tumor suppressor networks in human cancer, including non-small cell lung cancer (NSCLC). miR 1224-5p, 1248 and 944 are located at 3q amplicon and overexpressed in 50%, 26% and 53% of 30 primary SCCs when compared to normal tissues. The overexpression of these miRNAs was further validated in 237 TCGA lung SCC samples compared with 35 normal tissues (p=0.007, 1.18E-16 and 7.71E-20, respectively). The expression of the three miRNAs was higher in lung SCC compared to lung adenocarcinomas (p=8.19E-05, 1.04E-33 and 3.37E-95, respectively), suggesting unique roles of these miRNAs in the lung SCC development. Using miRNA mRNA target prediction tools (miRANDA and TargetScan) and in the combination with a literature search, we found RUNX1T1 and SMAD4 were candidate tumor suppressor gene target for miRNA-1224-5p and miRNA-1248. Downregulation of RUNX1T1 and SMAD4 were confirmed in TCGA lung SCC dataset. Using real-time RT-PCR, we found that the same three miRNAs 1224-5p, 1248 and 944 are overexpressed in 3q amplified lung SCC cell lines H520 and HCC95. When miRNA inhibitors were used to repress the expression of miR-1224-5p or miR-1248 in H520, we found that RUNX1T1 and SMAD4 protein expression levels were increased, suggesting that these tumor suppressor genes are regulated by miR-1224-5p or miR-1248. Lastly, knockdown of miR-1224-5p or miR-1248 using miRNA inhibitors led to 35-60% growth inhibition in H520 and HCC95 cells. Together, these results indicate potential roles for miR-1245-5p and 1248 in regulating cell proliferation by directly targeting tumor suppressor genes RUNX1T1 or SMAD4 in lung SCC. This work provides, for the first time, evidence for overexpression of miRNAs at the 3q26-29 amplicon that might be implicated in the oncogenesis of lung SCC. The work is supported by the NIH Grant R01 CA102353 to PPM and Lung Cancer Research Foundation grant (2011) to JQ. Note: This abstract was not presented at the meeting. Citation Format: Jun Qian, Xiangming Ji, Yong Zou, Megan Hoeksema, Heidi Chen, Pierre P. Massion. Overexpression of chromosome 3q26-29 miRNAs in squamous cell carcinoma of the lung. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 526. doi:10.1158/1538-7445.AM2014-526
Local anaesthetics in the management of duodenal ulceration: A clinical trial of oxethazaine hydrochloride (Mucaine)
Authors: A. H. Grabham
Journal: Gut (1964)

SYNOPSIS A double-blind clinical trial of a potent local anaesthetic used in the treatment of duodenal ulceration is described.No significant difference could be observed in the relief of epigastric pain, back pain or vomiting.The symptom of heartburn was, however, relieved in five out of six cases by the local anaesthetic.
What Works in Market-Oriented Health Policy?
Authors: Meredith B. Rosenthal
Journal: New England Journal of Medicine (2009)

There is a widespread belief, embraced by President Barack Obama as well as congressional and industry leaders, that the next round of health care reform should leverage market forces to lower the cost of care and improve its quality. The use of market forces in health policy typically involves altering out-of-pocket prices and information for consumers (the demand side) and incentives for providers (the supply side). Such market-oriented reforms — policies that alter the economic environment in which consumers and providers make health care choices in pursuit of their individual interests — can be implemented even in highly regulated settings. . . .
The Relationship of Coffee Consumption with Mortality
Authors: Esther Lopez-Garcia
Journal: Annals of Internal Medicine (2008)

Background: Coffee consumption has been linked to various beneficial and detrimental health effects, but data on its relation with mortality are sparse. Objective: To assess the association between coffee consumption and mortality from cardiovascular disease (CVD), cancer, and all causes during 18 years of follow-up in men and 24 years of follow-up in women. Design: Sex-specific Cox proportional hazard models were used to investigate the association between coffee consumption and incidence of all-cause and disease-specific mortality in a prospective cohort study. Setting: Health Professionals Follow-up Study and Nurses' Health Study. Participants: 41 736 men and 86 214 women with no history of CVD or cancer at baseline. Measurements: Coffee consumption was assessed first in 1986 for men and in 1980 for women and then every 2 to 4 years through 2004. Investigators documented 6888 deaths (2049 due to CVD and 2491 due to cancer) among men and 11 095 deaths (2368 due to CVD and 5011 due to cancer) among women. Results: After adjustment for age, smoking, and other CVD and cancer risk factors, the relative risks for all-cause mortality in men across categories of coffee consumption (<1 cup per month, 1 cup per month to 4 cups per week, 5 to 7 cups per week, 2 to 3 cups per day, 4 to 5 cups per day, and ≥6 cups per day) were 1.0, 1.07 (95% CI, 0.99 to 1.16), 1.02 (CI, 0.95 to 1.11), 0.97 (CI, 0.89 to 1.05), 0.93 (CI, 0.81 to 1.07), and 0.80 (CI, 0.62 to 1.04), respectively (P for trend = 0.008). For women, the relative risks were 1.0, 0.98 (CI, 0.91 to 1.05), 0.93 (CI, 0.87 to 0.98), 0.82 (CI, 0.77 to 0.87), 0.74 (CI, 0.68 to 0.81), and 0.83 (CI, 0.73 to 0.95), respectively (P for trend < 0.001). This inverse association was mainly due to a moderately reduced risk for CVD mortality and was independent of caffeine intake. By contrast, coffee consumption was not statistically significantly associated with risk for cancer death after adjustment for potential confounders. Decaffeinated coffee consumption was associated with a small reduction in all-cause and CVD mortality. Limitation: Coffee consumption was estimated from self-report; thus, some measurement error is inevitable. Conclusion: Regular coffee consumption was not associated with an increased mortality rate in either men or women. The possibility of a modest benefit of coffee consumption on all-cause and CVD mortality needs to be further investigated.
Alveolar Walls in Mitral Stenosis
Authors: ROBERT M. O'NEAL, WILBUR A. THOMAS, KYU TAIK LEE, ERWIN R. RABIN
Journal: Circulation (1957)

Pathologic alterations of alveolar walls in 95 autopsied patients with mitral stenosis were not frequent. The most frequently encountered change was capillary dilatation, and in 83 per cent of the patients, even this change was slight or absent. Other alterations were focal and involved only small proportions of the area of tissue examined. A generalized increase in the thickness of basement membranes could not be demonstrated.
18FDG PET/CT Findings in the Unusual Urachal Adenocarcinoma
Authors: Marcos Duarte Guimarães, Almir Galvão Vieira Bitencourt, Eduardo Nóbrega Pereira Lima, Edson Marchiori
Journal: Clinical Nuclear Medicine (2014)

A 48-year-old woman presented with a hard, painless mass in the left lower quadrant and no other significant complaint. Laboratory tests, including those for tumor markers, showed no significant abnormal value. CT showed an extraperitoneal mixed solid and cystic mass in the anterior abdominal wall, located anterocranial to and in close contact with the bladder. Percutaneous biopsy findings were compatible with adenocarcinoma of unknown origin. PET/CT showed increased 18FDG uptake on the mass and no evidence of disease at other sites. The patient underwent tumor resection, and the pathological diagnosis was moderately differentiated urachal adenocarcinoma.
2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update)
Authors: Hani Jneid, Jeffrey L. Anderson, R. Scott Wright, Cynthia D. Adams, Charles R. Bridges, Donald E. Casey, Steven M. Ettinger, Francis M. Fesmire, Theodore G. Ganiats, A. Michael Lincoff, Eric D. Peterson, George J. Philippides, Pierre Theroux, Nanette K. Wenger, James Patrick Zidar
Journal: Circulation (2012)
The biological function of β-secretase
Authors: Christian Haass
Journal: Molecular Neurodegeneration (2013)

Proteolytic shedding of cell surface proteins generates paracrine signals involved in numerous signaling pathways. Neuregulin 1 (NRG1) type III is involved in myelination of the peripheral nervous system, for which it requires proteolytic activation by proteases of the ADAM family and BACE1. These proteases are major therapeutic targets for the prevention of Alzheimer’s disease because they are also involved in the proteolytic generation of the neurotoxic amyloid β-peptide. Identification and functional investigation of their physiological substrates is therefore of greatest importance in preventing unwanted side effects. Here we investigated proteolytic processing of NRG1 type III and demonstrate that the ectodomain can be cleaved by three different sheddases, namely ADAM10, ADAM17, and BACE1. Surprisingly, we not only found cleavage by ADAM10, ADAM17, and BACE1 C-terminal to the epidermal growth factor (EGF)-like domain, which is believed to play a pivotal role in signaling, but also additional cleavage sites for ADAM17 and BACE1 N-terminal to that domain. Proteolytic processing at N- and C-terminal sites of the EGF-like domain results in the secretion of this domain from NRG1 type III. The soluble EGF-like domain is functionally active and stimulates ErbB3 signaling in tissue culture assays. Moreover, the soluble EGF-like domain is capable of rescuing hypomyelination in a zebrafish mutant lacking BACE1. Our data suggest that NRG1 type III independent myelination is not only controlled by membrane-retained NRG1 type III, but also in a paracrine manner via proteolytic liberation of the EGF-like domain.
Progression of coronary atherosclerosis: Is coronary spasm related to progression?
Authors: Masakiyo Nobuyoshi, Makoto Tanaka, Hideyuki Nosaka, Takeshi Kimura, Hiroatsu Yokoi, Naoya Hamasaki, Kotaku Kim, Takashi Shindo, Kazuo Kimura
Journal: Journal of the American College of Cardiology (1991)
Hepatitis B virus carriers without precore mutations in hepatitis B e antigen-negative stage show more severe liver damage
Authors: M Lindh, P Horal, A P Dhillon, Y Furuta, G Norkrans
Journal: Hepatology (1996)

Hepatitis B e antigen (HBeAg) is considered to be a major target for the immune response in chronic hepatitis B. The G → A mutation at nucleotide 1896 may mediate viral escape by creating a TAG stop codon in the precore region, thus preventing HBeAg production. This mutation frequently evolves during HBe seroconversion if thymine, but rarely if cytosine, is present in position 1858. Applying a combination of polymerase chain reaction (PCR) and restriction enzyme action, we have studied the relation of the TAG mutation and the nucleotide (nt) 1858 variants to liver damage assessed by histology activity index (HAI) scoring in 175 chronic hepatitis B virus (HBV) carriers. A TAG mutation was found in 68 of 71 (96%) of HBeAg–negative carriers infected with a T–1858 strain, but not in any of 33 carriers infected exclusively with a C–1858 strain. Four patients showed a mutation of the precore start codon, and 2 had a TAA stop mutation at codon 2. HBeAg–positive infection with a mixture of wild–type and TAG mutant virus indicated active liver damage, because 8 of 9 (89%) of such patients had a Knodell HAI greater than or equal to 8. In HBeAg–negative stage, both inflammation and fibrosis were more pronounced in carriers infected with wild–type HBV compared with precore mutants. C–1858 strains were associated with more inflammation and fibrosis compared with T–1858 strains. C–1858 strains were found in 71% of northern European, 17% of southern European, 31% of African, 2% of Middle Eastern, and 10% of Far Eastern carriers. Analysis of these variants and mutants may prove useful for clinical evaluation and choice of therapy, and may be facilitated by the methods described.
Timing and Duration of Obesity in Relation to Diabetes
Authors: Natalie S. The, Andrea S. Richardson, Penny Gordon-Larsen
Journal: Diabetes Care (2012)

OBJECTIVE The influence on diabetes of the timing and duration of obesity across the high-risk period of adolescence to young adulthood has not been investigated in a population-based, ethnically diverse sample. RESEARCH DESIGN AND METHODS A cohort of 10,481 individuals aged 12–21 years enrolled in the U.S. National Longitudinal Study of Adolescent Health (1996) was followed over two visits during young adulthood (18–27 years, 2001–2002; 24–33 years, 2007–2009). Separate logistic regression models were used to examine the associations of diabetes (A1C ≥6.5% or diagnosis by a health care provider) in young adulthood with 1) obesity timing (never obese, onset &amp;lt;16 years, onset 16 to &amp;lt;18 years, onset ≥18 years) and 2) obesity duration over time (never obese, incident obesity, fluctuating obesity, and persistent obesity), testing differences by sex and race/ethnicity. RESULTS Among 24- to 33-year-old participants, 4.4% had diabetes (approximately half were undiagnosed), with a higher prevalence in blacks and Hispanics than whites. In multivariable analyses, women who became obese before age 16 were more likely to have diabetes than women who became obese at or after age 18 (odds ratio 2.77 [95% CI 1.39–5.52]), even after accounting for current BMI, waist circumference, and age at menarche. Persistent (vs. adult onset) obesity was associated with increased likelihood of diabetes in men (2.27 [1.41–3.64]) and women (2.08 [1.34–3.24]). CONCLUSIONS Diabetes risk is particularly high in individuals who were obese as adolescents relative to those with adult-onset obesity, thus highlighting the need for diabetes prevention efforts to address pediatric obesity.
The Crystal Ball
Authors: Leroy D. Vandam
Journal: New England Journal of Medicine (1970)

Resembling certain members of the animal species, more than a few new drugs, while demonstrating admirable familial traits, also indulge in streaks of abnormal behavior. The volatile inhalation anesthetics provide no exception to this rule although early in the history of use, their deviations are apt to be concealed in the complications of surgery. Over the last 15 years chemists have concentrated on the synthesis of new halogen-substituted hydrocarbons in an effort to eliminate undesirable features of the primordial anesthetics. The result has been the introduction into clinical anesthesia of several compounds incorporating the most wanted characteristic — inertness, therefore . . .
Can the standard gamble and rating scale be used to measure quality of life in rhinoconjunctivitis? Comparison with the RQLQ and SF‐36
Authors: E. F. Juniper, A. K. Thompson, J. N. Roberts
Journal: Allergy (2002)

Background: With interest in health economics growing, it is important to know whether utilities may be used to measure health‐related quality of life in patients with rhinoconjunctivitis. The objective was to compare the validity and measurement properties of disease‐specific versions of the standard gamble and rating scale with those of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the Short‐Form 36 (SF‐36). Methods: One hundred adults with symptomatic rhinoconjunctivitis participated in a 5 week observational study, completing the standard gamble, rating scale, RQLQ and SF‐36 at baseline and after 1 and 5 weeks. Symptom diaries were completed for 1 week before each follow‐up visit. Results: Reliability was highest for the RQLQ (intraclass correlation coefficient = 0.97), followed by the rating scale (0.75), the SF‐36 physical (0.75), the SF‐36 mental (0.74) and the standard gamble (0.12). The responsiveness index was highest for the RQLQ (0.76), followed by the rating scale (0.56) and the SF‐36 mental (0.28). Both cross‐sectional and longitudinal validity were strongest for the RQLQ and the rating scale. Conclusions Both the rating scale and the RQLQ have strong evaluative and discriminative properties. The SF‐36 has acceptable discriminative properties but its evaluative properties are poor. All measurement properties for the standard gamble are inadequate. Poor correlation between the standard gamble and the rating scale indicates that utilities cannot be derived from rating scale data.
Treatment of Varicella Pneumonia
Authors: Ira M. Cimons
Journal: JAMA (1968)

Varicella pneumonia, especially in adults, can have a fatal outcome. Impairment of pulmonary function can become so severe that usual methods of treatment are inadequate. Prolonged mechanical ventilation, with the use of respiratory depressants and muscle relaxants, may be necessary to keep the patient alive. The patient should be treated in an institution where necessary teamwork and technology are available.