tbuckley/cabot-search huggingface dataset:
Abstract IA22: miRNA and lung cancer: Early detection in high-risk subjects
Authors: Gabriella Sozzi, Mattia Boeri, Carla Verri, Luca Roz, Paola Suatoni, Carlo M. Croce, Ugo Pastorino
Journal: Clinical Cancer Research (2012)

Abstract Background: Lung cancer remains the major cause of cancer mortality in the world. In addition to primary prevention, earlier detection and more targeted treatments, tailored on the biological characteristics of the tumor and its microenvironment, could significantly reduce morbidity and mortality for this disease. The real efficacy of lung cancer screening by spiral-computed tomography (CT) in heavy smokers is still to be defined since, in spite of a proved capacity to detect small asymptomatic nodules, the frequency of false positive CTs as well as unnecessary treatments is very high if compared to the limited mortality reductions. The development of biomarkers able to identify tumors in a pre-clinical phase and to track the different aggressiveness of lung tumors is of paramount importance. microRNAs (miRNAs) represent a recently identified class of regulatory molecules and several studies showed that miRNA are involved in lung tumor development and progression and also circulate in plasma and serum of lung cancer patients. Materials and Methods: We analyzed miRNA profiles of lung tumors, normal lung tissues and plasma samples from cases with variable prognosis identified in two independent spiral-CT screening trials where multiple plasma samples, collected from one to four years before radiological detection of the disease were available. Results: We found miRNA expression profiles associated with aggressiveness of the disease and poor survival in tumors and also in normal lung tissues of the patients, thus proving the critical influence of a smoking-related lung microenvironment on tumor progression. Specific microRNA signatures were identified in plasma samples collected up to two years before spiral-CT detection of the disease, thus able to catch the earlier biological phases of disease development. We also defined a plasma signature that discriminates subjects according to aggressiveness of their future tumors, and in particular the occurrence of early metastatic but spiral-CT invisible lung tumors or small spiral-CT detected lesions with aggressive potential. Of interest plasma miRNas involved in the signatures of lung cancer risk and of aggressive disease more closely reflected miRNAs expressed in the normal lung rather than those characterizing the tumor samples of patients, supporting the concept that normal lung microenvironment has a critical influence on tumor development and aggressiveness. Conclusion: These results open up the prospective of using plasma miRNAs as non invasive lung cancer biomarkers.
The Family Planning Attitudes, Practices, and Motivations of Mental Patients
Authors: HENRY U. GRUNEBAUM, VIRGINIA D. ABERNETHY, E. SAMUEL ROFMAN, JUSTIN L. WEISS
Journal: American Journal of Psychiatry (1971)

The family planning attitudes, practices and motivations were studied by interview in 21 patients of the Massachusetts Mental Health Center, 18-45 years of age, with varying racial, religious and socioeconomic backgrounds and a broad range of mental illness. Without investigating the relationships of mental illness to marital discord, an impressive frequency of divorce, unhappy marriages and lack of communication between the spouses was noted. Frequency patterns of sexual intercourse and orgasm in these patients reflected normal patterns as determined by sexual research. The patients also closely resembled normal women in responses on desired family size and the right of women to control the number of children they have. Behavior was found to differ strongly from attitudes in that contraceptive knowledge and approval, though low, was comparable to normal women, but actual contraceptive use was infrequent with a total of 26 unwanted pregnancies reported in 13 of the women. 9 of the unwanted pregnancies were aborted and 8 of the 13 women felt that raising the unwanted child contributed to their mental illness. Though all the patients thought hospitals should provide the postnatal family planning counseling, contraceptive motivation was determined to be poor in these women due to excessive dependency needs, passive-aggressive ambivalence towards men, and excessive use of the mechanism of denial. Greater communication between doctor and patient is needed on sexual attitudes and practices.
Electrical Remodeling of the Atrium in an Anatomic Model of Atrial Flutter
Authors: Joseph B. Morton, Melissa J. Byrne, John M. Power, Jai Raman, Jonathan M. Kalman
Journal: Circulation (2002)

Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist, yet the specific relationship between these arrhythmias, and particularly whether sustained AFL leads to AF, is unknown.We investigated the electrophysiological consequences of chronic AFL using an ovine anatomic right atrial Y-lesion model. AFL was induced in 7 animals, and 4 remained in sinus rhythm (controls). Sheep were monitored for spontaneous conversion of AFL to AF. Six of 7 sheep sustained AFL for 28 days. In 1 of 7 sheep, spontaneous conversion of AFL to AF occurred on day 5. AFL produced a highly significant fall in right and left atrial refractoriness (AERP, P<0.001), with 74+/-10% of the reduction occurring by day 3. Right atrial conduction velocity also fell significantly (baseline 89+/-9 cm/s versus day 28 64+/-14 cm/s, P<0.001) but over a slower time course. AERP and conduction velocity changes coincided with a characteristic biphasic decrease and increase in the AFL cycle length. The excitable gap (percent of AFL cycle length) increased from 13+/-3% at baseline to 46+/-8% by day 28 (P<0.001). Sustained AF (>30 seconds) was not inducible at baseline but after 28 days of AFL could be induced in 6 of 6 sheep by critically timed single or multiple extrastimuli delivered either in sinus rhythm or AFL. There was no significant change in any parameter in control sheep.In this model, AFL produced electrical remodeling and the substrate for sustained AF. However, spontaneous conversion to AF was uncommon, and the development of AF was dependent on specific triggers.
Summary Measures of the Insulin Resistance Syndrome Are Adverse Among Mexican-American Versus Non-Hispanic White Children
Authors: Lyn Steffen Batey, None RD, David C. Goff, Susan R. Tortolero, Milton Z. Nichaman, Wenyaw Chan, Frances A. Chan, JoAnne Grunbaum, None EdD, Craig L. Hanis, Darwin R. Labarthe
Journal: Circulation (1997)

Mexican-American (MA) adults are known to have a greater burden of diabetes and insulin resistance than non-Hispanic white (NHW) people. In this report, we examined data obtained from MA and NHW third-grade children for evidence of a pattern consistent with the insulin resistance syndrome. In addition, we developed two summary measures characterizing insulin resistance syndrome to compare measures of this syndrome among our population.Data regarding fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and body mass index (BMI) were available for 403 third-grade children. Median levels of insulin and glucose were significantly higher in MA boys and girls than in NHW boys and girls. Risk factors characterizing insulin resistance, including levels of insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI were categorized as above or below the total population median. MA children were more likely than NHW children to have three or more adverse risk factors (55% versus 37%). When risk factors were converted to Z scores, and the five Z scores were summed for each individual, MA boys and girls had higher mean scores than NHW boys and girls (means for boys, 0.65 versus -0.97, P<.0001; girls, 0.52 versus -0.30, P<.04). Principal components analysis was used to create a summary score or index representing the insulin resistance syndrome. This summary score was significantly higher among MA boys and girls than NHW boys and girls (means for boys, 0.34 versus -0.72, P<.0001; girls, 0.35 versus -0.04, P=.056).Our results support the hypothesis that MA children exhibit a greater degree of the insulin resistance syndrome than NHW children, especially among boys. We conclude that some of the factors responsible for the increased risk of NIDDM seen among MA adults are demonstrable in childhood.
Hypoxia Increases Tumor Cell Shedding of MHC Class I Chain-Related Molecule: Role of Nitric Oxide
Authors: D. Robert Siemens, Nianping Hu, Abdol Karim Sheikhi, Eugene Chung, Lisa J. Frederiksen, Hugh Pross, Charles H. Graham
Journal: Cancer Research (2008)

Abstract The MHC class I chain-related (MIC) molecules play important roles in tumor immune surveillance through their interaction with the NKG2D receptor on natural killer and cytotoxic T cells. Thus, shedding of the MIC molecules from the tumor cell membrane represents a potential mechanism of escape from NKG2D-mediated immune surveillance. Tumor hypoxia is associated with a poor clinical outcome for cancer patients. We show that hypoxia contributes to tumor cell shedding of MIC through a mechanism involving impaired nitric oxide (NO) signaling. Whereas hypoxia increased MIC shedding in human prostate cancer cells, activation of NO signaling inhibited hypoxia-mediated MIC shedding. Similar to incubation in hypoxia, pharmacologic inhibition of endogenous NO signaling increased MIC shedding. Parallel studies showed hypoxia-mediated tumor cell resistance to lysis by interleukin 2–activated peripheral blood lymphocytes (PBL) and NO-mediated attenuation of this resistance to lysis. Inhibition of NO production also led to resistance to PBL-mediated lysis. Interference of MIC-NKG2D interaction with a blocking anti-MIC antibody abrogated the effect of hypoxia and NO signaling on tumor cell sensitivity to PBL-mediated lysis. Finally, continuous transdermal delivery of the NO mimetic glyceryl trinitrate (7.3 μg/h) attenuated the growth of xenografted MIC-expressing human prostate tumors. These findings suggest that the hypoxic tumor microenvironment contributes to resistance to immune surveillance and that activation of NO signaling is of potential use in cancer immunotherapy. [Cancer Res 2008;68(12):4746–53]
Molecular defect in siblings with prolidase deficiency and absence or presence of clinical symptoms. A 0.8-kb deletion with breakpoints at the short, direct repeat in the PEPD gene and synthesis of abnormal messenger RNA and inactive polypeptide.
Authors: A Tanoue, F Endo, I Akaboshi, T Oono, J Arata, I Matsuda
Journal: Journal of Clinical Investigation (1991)

Prolidase deficiency is an autosomal recessive disorder with highly variable symptoms, including mental retardation, skin lesions, and abnormalities of collagenous tissues. In Japanese female siblings with polypeptide negative prolidase deficiency, and with different degrees of severity of skin lesions, we noted an abnormal mRNA with skipping of 192 bp sequence corresponding to exon 14 in lymphoblastoid cells taken from these patients. Transfection and expression analyses using the mutant prolidase cDNA revealed that a mutant protein translated from the abnormal mRNA had an Mr of 49,000 and was enzymatically inactive. A 774-bp deletion, including exon 14 was noted in the prolidase gene. The deletion had termini within short, direct repeats ranging in size of 7 bp (CCACCCT). The "slipped mispairing" mechanism may predominate in the generation of the deletion at this locus. This mutation caused a 192-bp in-frame deletion of prolidase mRNA and was inherited from the consanguineous parents. The same mutation caused a different degree of clinical phenotype of prolidase deficiency in this family, therefore factor(s) not related to the PEPD gene product also contribute to development of the clinical symptoms. Identification of mutations in the PEPD gene from subjects with prolidase deficiency provides further insight into the physiological role and structure-function relationship of this biologically important enzyme.
BMA gives evidence to review body New groups will advise on medical manpower Universities are losing clinical staff Isolated areas need help to provide out of hours care GPs are concerned about checks on medical records
Authors: L. Beecham
Journal: BMJ (1996)

# BMA gives evidence to review body {#article-title-2}

The BMA has given evidence to the Doctors' and Dentists' Review Body for the 1997 pay round, estimating that doctors need a pay increase of 53% to restore their comparative position to that of 1980 (p 769).

The BMA has expressed concern at the problem of translating the NHS pay award for clinical academic staff—they have not yet received the 1996 award—and the review body has been asked formally to recommend to the government increases for clinical academics in line with NHS doctors.

Junior hospital doctors are concerned about the discretionary nature of the top two points on the specialist registrar scale and want the review body to base the scale on the full range of registrar and senior registrar pay, but with seven incremental points. They have called for full shift additional duty hour rates to be paid to those doctors working full shift intensity on on call rotas or partial shifts.

On behalf of doctors working in public health medicine and community health the BMA has asked the review body to maintain the link between the salary scales of clinical consultants and consultants in public health medicine; revise the supplements payable to directors of public health to take account of the major changes in the number and size of health authorities; recognise the increased workload resulting from the drastic shortfall in consultant posts in public health medicine; recommend an increase in the out of hours supplement for trainees in public health medicine; and maintain existing relativities between the salary scales of community health doctors and …
Referral from primary to secondary care
Authors: M. Jiwa
Journal: BMJ (2010)

Older and more deprived patients remain at a disadvantage

Only a minority of people require hospital services, most people treat themselves or consult a generalist.1 General practitioners, who are usually the first point of contact for patients, must decide which patients to refer to secondary care.2 We do not know the extent to which people who are denied access to specialist services by the gatekeeper are disadvantaged. Some may be denied timely access to experts who are best placed to help. Alternatively, others may be harmed by unnecessary diagnostic tests and interventions. Therefore, the appropriate referral of cases to secondary care has economic, quality, and safety ramifications that resonate across the health sector and the globe. In light of this, the linked study by McBride and colleagues (doi:10.1136/bmj.c6267), presenting referral data for 130 000 British patients, is useful⇓.3



St Bartholomew’s Hospital, London/Science Photo Library

A conceptual framework that could be used to analyse this study was published by Glasziou and Haynes.4 It proposes that, for patients to receive …
P5-21-01: A Renewable Tissue Resource of Phenotypically Stable Human Breast Cancer Xenografts for Preclinical Studies.
Authors: X Zhang, LE Dobrolecki, Q Lai, MD Landis, H Wong, A Tsimelzon, S Claerhout, A Contreras, C Gutierrez, J Huang, M-F Wu, AC Pavlick, AM Froehlich, SG Hilsenbeck, GB Mills, L Wiechmann, I Petrovic, MF Rimawi, R Schiff, JC Chang, MT Lewis
Journal: Cancer Research (2011)

Abstract Introduction Translational breast cancer research is hampered severely by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that accurately reflect patient tumor biology. These limitations are due, in part, to the fact that traditional immunocompromised mouse models are not generally permissive for growth. We sought to circumvent some of these limitations by transplanting and growing human mammary tumors in the mammary fat pad of SCID/Beige immunocompromised mice in the absence of exogenous human fibroblasts. Aims and Methods To establish a set of stable human breast cancer xenografts for preclinical studies. Human breast cancer biopsies were received, minced into small fragments and then transplanted directly into “cleared” fat pads of recipient SCID/Beige immunocompromised mice. Transplanted fat pads were checked weekly. After initial tumor was palpated and harvested, tumor fragments were transplanted into new SCID/Beige hosts for subsequent transplant generations. Serial immunohistochemical evaluations were performed to confirm human origin and biomarker status. Analytical flow cytometry for evaluating expression of proposed “cancer stem cell” markers, and gene and protein expression analysis were carried out on all stable lines. Results and Conclusions Xenograft lines were established directly from breast cancer patient samples, without intervening culture in vitro, using the epithelium-free mammary fat pad as the transplantation site. Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet without exogenous human fibroblasts. Thirty six stably transplantable xenograft lines representing 27 patients were established, using pre-treatment, mid-treatment, and/or post-treatment samples. Most patients yielding xenografts were “triple-negative” (ER-PR-HER2−) (n=21), we were able to establish lines from three ER-PR-HER2+ patients, one ER+PR+HER2−, one ER+PR-HER2−and one “triple-positive” (ER+PR+HER2+) patients. Serially passaged xenografts show phenotypic consistency with the tumor of origin at the histopathology level, and remarkable stability across multiple transplant generations at both the genomic, transcriptomic, and proteomic levels. Of 27 lines evaluated fully, thirteen xenografts showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource, and should prove useful for preclinical evaluation of experimental therapeutics. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-21-01.
THE PHYSICIAN AND THE CANCER PATIENT
Authors: Samuel G. Taylor
Journal: JAMA (1952)

Fortunately for the physician, the majority of human ills for which he is consulted are self-limited or are only matters of temporary discomfort that can be remedied with relative ease. Nevertheless, every human being must have one fatal disease or accident. From the philosophical standpoint it could be argued that life itself is the only inevitably fatal condition, yet it is obvious that there are many pathological states that result in inexorable death. These fatal diseases have been progressively eliminated by advances in medical science until there are only three main categories of causes of fatality, namely, cardiac failure and the degenerative diseases in the broad sense, accidents and war, and malignant neoplastic diseases.  Of death due to these three problems, death due to cancer is the most preventable from the standpoint of the individual physician. Therein lies the tragic irony of this disease. Death from cancer should be unnecessary,
The diastolic viscous properties of cat papillary muscle.
Authors: M I Noble
Journal: Circulation Research (1977)

The measurement of ventricular diastolic compliance is complicated by the presence of viscous properties. To approach this problem, cat papillary muscles contracting isometrically at 15/min at 26 degrees C were stretched at different velocities during diastole. At a given length there was no excess of force above that defined by the static force-length curve until velocity of stretch exceeded 1 muscle length/sec. At greater velocities of stretch there was an increase of force with increasing velocity of stretch denoting viscous resistance to stretch. The viscous characteristic was alinear and increased with muscle length. At a given muscle length potentiation of contractile state by paired pulse stimulation caused a change in the diastolic force-length curve but there was no apparent relationship between viscous resistance to stretch and contractile state or the length of the "series viscous element." These results lead one to expect viscous resistance to stretch during rapid filling of the intact left ventricle.
Intravenous Administration of Drugs for Obtaining Regional Adrenergic Block
Authors: B. L. Ardill, V. M. Bhatnagar, P. H. Fentem
Journal: Cardiovascular Research (1967)

A technique is described by which the sympathetic vasoconstrictor nerves of one region of a limb can be blocked without resort to an intra-arterial infusion or perineural injection. The drug is administered into a vein when the circulation to the limb is occluded and the limb contains as little blood as possible. Following the release of the circulation the block remains effective for at least 5 hr. Bethanidine and guanethidine have been used in this way in 8 subjects and the testing of the block produced is described.
Patient-triggered ventilation in neonates: comparison of a flow-and an impedance-triggered system.
Authors: H D Hummler, T Gerhardt, A Gonzalez, J Bolivar, N Claure, R Everett, E Bancalari
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We conducted a study with the objective of comparing the performance of two different systems for patient-triggered ventilation in neonates (impedance versus flow/volume-triggered) by measuring response time, autotrigger and trigger failure rates, ventilation, and gas exchange. The two ventilator systems were applied in random order in 10 preterm neonates (median gestational age: 30.5 wk; range: 27 to 34 wk; body weight: 1,266 g; range: 840 to 2,240 g) using identical ventilator settings. The median (range) response time was 169 (98 to 305) ms for the impedance system and 115 (79 to 184) ms for the flow/volume system (p < 0.01). The longer and more variable response time of the impedance system was secondary to a phase lag of the impedance signal caused by chest wall distortion. Although 13.1 (0.2 to 29.4)% of mechanical breaths were autotriggered with the impedance system, there were no autotriggered breaths using the flow/volume system (p < 0.01). The rate of trigger failures was not significantly different with the two systems, at 1.2 (0 to 4.4)% (impedance) versus 3.1 (0 to 6.4)% (flow/volume). Minute ventilation was smaller with the impedance system (p < 0.001), because of the larger number of breaths triggered late in inspiration or during expiration. We conclude that the flow/volume-triggered system is less prone to autotriggering and has a shorter and more consistent response time than the impedance-triggered system. The impedance-triggered system is more susceptible to artifacts and chest wall distortion.