tbuckley/cabot-search huggingface dataset:
Distribution and fate of 54Mn in the monkey: studies of different parts of the central nervous system and other organs
Authors: Darab K. Dastur, Daya K. Manghani, K. V. Raghavendran
Journal: Journal of Clinical Investigation (1971)

The fate and distribution of isotopic manganese administered as a single carrier-free dose of 200 muCi of maleate-(54)Mn to 12 rhesus monkeys was studied at different time periods from the 6th hr to the 278th day. Whole-body activity was measured, and all body organs and tissues and different parts of the central nervous system (CNS) were evaluated for specific activity, exponential analysis, and relative retention. Exponential analysis revealed a pattern of discharge with a fast and a slow component for the whole body and for many of the viscera. All parts of the CNS and, to a lesser degree, the thyroid and muscle showed an almost steady state of activity after the initial uptake. While the whole body and most organs and tissues appeared to discharge their radioactivity with the passage of time, first rapidly and then gradually, the CNS, endocrine glands, and muscle tissues showed persistent levels of specific activity. All components of the brain exhibited increasing relative retention, the lentiform nucleus and the cerebellum showing this more. It is suggested that the selective vulnerability of the brain in manganese miners might result from this inability on the part of the CNS to discharge the (54)Mn with time. This investigation confirms and amplifies our earlier similar study on the rat.
Sarcolemma, sarcoplasmic reticulum, and sarcomeres as limiting factors in force production in rat heart.
Authors: V J Schouten, J J Bucx, P P de Tombe, H E ter Keurs
Journal: Circulation Research (1990)

Inotropic interventions were compared with respect to their maximum effect on force of contraction in rat myocardium to identify limiting steps in calcium handling. Peak force, sarcomere length, and action potentials were measured in thin ventricular trabeculae. Relevant control conditions were stimulation frequency, 0.2 Hz; [Ca2+]o, 1 mM; [K+]o, 5 mM; [Na+]o, 150 mM. The inotropic interventions and results were as follows. 1) The interventions of high [Ca2+]o, low [Na+]o, high [K+]o, addition of tetraethylammonium chloride, or postextrasystolic potentiation resulted in approximately the same (within 5%) maximum force (Fmax). Above the respective optimum doses, force declined and aftercontractions were often observed. Combinations of the different interventions never enhanced force to above Fmax. This suggests that Fmax is determined by a maximum level of Ca2+ in the sarcoplasmic reticulum, above which spontaneous release occurs. 2) Sr2+ (10 mM) caused an increase of force to 1.3 X Fmax and lengthening of contraction and action potentials. The force-sarcomere length relation was, then, similar to that in skinned fibers at maximum activation. Hence, 1.3 X Fmax reflects saturation of the sarcomeres. We postulate that a large influx of Sr2+ during the long action potential can circumvent the reticulum and activate the sarcomeres directly. When the reticulum was blocked with ryanodine, maximum force of tetanic contractions was about 1.1 X Fmax. This result supports the above conclusions. 3) Isoproterenol increased force to a maximum that was 20% below Fmax and shortened the contraction. This may be due to a decreased sensitivity of the sarcomeres to Ca2+ or to stimulation of the Ca2+ pump in the reticulum, that is, an increasing fraction of the released Ca2+ is sequestered before it can activate the sarcomeres. Thus, three factors that limit force production were identified, depending on the inotropic stimulus.
Cultural group selection plays an essential role in explaining human cooperation: A sketch of the evidence
Authors: Peter Richerson, Ryan Baldini, Adrian V. Bell, Kathryn Demps, Karl Frost, Vicken Hillis, Sarah Mathew, Emily K. Newton, Nicole Naar, Lesley Newson, Cody Ross, Paul E. Smaldino, Timothy M. Waring, Matthew Zefferman
Journal: Behavioral and Brain Sciences (2014)

Human cooperation is highly unusual. We live in large groups composed mostly of non-relatives. Evolutionists have proposed a number of explanations for this pattern, including cultural group selection and extensions of more general processes such as reciprocity, kin selection, and multi-level selection acting on genes. Evolutionary processes are consilient; they affect several different empirical domains, such as patterns of behavior and the proximal drivers of that behavior. In this target article, we sketch the evidence from five domains that bear on the explanatory adequacy of cultural group selection and competing hypotheses to explain human cooperation. Does cultural transmission constitute an inheritance system that can evolve in a Darwinian fashion? Are the norms that underpin institutions among the cultural traits so transmitted? Do we observe sufficient variation at the level of groups of considerable size for group selection to be a plausible process? Do human groups compete, and do success and failure in competition depend upon cultural variation? Do we observe adaptations for cooperation in humans that most plausibly arose by cultural group selection? If the answer to one of these questions is "no," then we must look to other hypotheses. We present evidence, including quantitative evidence, that the answer to all of the questions is "yes" and argue that we must take the cultural group selection hypothesis seriously. If culturally transmitted systems of rules (institutions) that limit individual deviance organize cooperation in human societies, then it is not clear that any extant alternative to cultural group selection can be a complete explanation.
US doctors and public disagree over mandatory reporting of errors
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

The US public is much more concerned about the quality and safety of health care than doctors are, says a new study.

Three years ago a report from the Institute of Medicine estimated that medical errors killed 44000 to 98000 Americans every year ( BMJ 1999;319:1519). A new study by Dr Andrew Robinson and colleagues at the University …
The role of angiotensin receptor-1 blockade on electromechanical changes induced by left ventricular hypertrophy and its regression
Authors: R GRAY, M TURNER, D SHERIDAN, C FRY
Journal: Cardiovascular Research (2006)

The aims of this study were to: i) investigate the role of angiotensin in mediating changes to myocardial electromechanical properties during the development and regression of left ventricular hypertrophy (LVH) generated by constriction of the thoracic aorta; ii) identify any role of angiotensin-1 receptor blockade on ameliorating changes to these electromechanical properties.LVH was induced in guinea-pigs by constricting the ascending aorta (AC groups). After 42+/-3 days, the constriction was either removed or left in place. Following the second operation animals were fed losartan (10 mg x kg(-1) x day(-1)) or saline for 42+/-3 days. Sham-operated animals served as controls. In other groups, LVH was generated by subcutaneous angiotensin II (200 ng x kg(-1) x min(-1)) infusion for 42+/-3 days with or without losartan administration (AT groups), and compared to animals undergoing aortic constriction for a similar period. Electromechanical changes were recorded in isolated left ventricular myocardial preparations.Wet and dry heart-to-body weight ratios (HBR) increased significantly in the AC and AT models compared to control. Losartan prevented the increase of HBR in the AT group. Removal of the constriction allowed LVH to regress to control. The force-frequency relationship was reduced in both models and recovered fully on regression. However, the two models generated different electrophysiological changes: in the AC group, longitudinal conduction velocity was reduced and transverse conduction increased, with a consequent reduction of the anisotropic conduction ratio. On regression recovery was only partial; action potential duration was prolonged and did not recover. In the AT group, electrophysiological changes were limited: only an increase of transverse conduction and a reduction of the anisotropic conduction ratio were observed. Losartan had no effect on HBR or electromechanical variables in the aortic constricted animals, nor did it affect the extent of recovery in animals with regression of LVH.The electromechanical changes to hypertrophied myocardium are different in these two models of LVH. Moreover, losartan was ineffective in modulating the consequences of hypertrophy induced by constriction of the thoracic aorta.
Acute interstitial pneumonia: report of a series
Authors: A. Bonaccorsi, A. Cancellieri, M. Chilosi, R. Trisolini, M. Boaron, N. Crimi, V. Poletti
Journal: European Respiratory Journal (2002)

Four cases of acute interstitial pneumonia (AIP) are described with special emphasis on clinical background, lung imaging and bronchoalveolar lavage findings. A retrospective chart review of four patients with histologically-proven AIP, diagnosed between 1998 and 2000, was carried out. Clinical data, bronchoalveolar lavage (BAL) findings, high-resolution computed tomography (HRCT) and histological features were analysed. Three patients died and only one is in follow-up. HRCT showed areas of ground glass attenuation and alveolar consolidation in all patients. Histology, documented by open lung biopsy or autopsy specimens, was consistent with the organising form of diffuse alveolar damage pattern. BAL findings were characteristic, with a huge neutrophilia associated with scattered atypical type II pneumocytes collected in clusters with extracellular amorphous material (fragments of hyaline membranes) observed in two out of three cases. In this paper, four cases of acute interstitial pneumonia are reported in detail. The poor prognosis associated with this entity has been confirmed and the possible diagnostic role of the bronchoalveolar lavage is emphasised.
What is evaluative normativity, that we (maybe) should avoid it?
Authors: Jonathan M. Weinberg
Journal: Behavioral and Brain Sciences (2011)

Abstract Elqayam &amp; Evans (E&amp;E) argue that we should avoid evaluative normativity in our psychological theorizing. But there are two crucial issues lacking clarity in their presentation of evaluative normativity. One of them can be resolved through disambiguation, but the other points to a deeper problem: Evaluative normativity is too tightly-woven in our theorizing to be easily disentangled and discarded.
A Lecture on Miners' Nystagmus
Authors: T. L. Llewellyn
Journal: BMJ (1913)

MINERS' NYSTAGMUS.r LJoumiA '359 wrong, and you need waste no further time in treating it as such.Moreover, the powerful effect of emetine on amoebic cases, compared with its uselessness in bacillary cases, may, I think, be taken as strong proof that amoebic dysentery is really a separate entity.That is why, in the earlier part of this address, I said that we might reject the view that intestinal amoebae play no part in the causation of this disease.
Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion
Authors: Masahiro Abe, Kenji Hiura, Javier Wilde, Atsushi Shioyasono, Keiji Moriyama, Toshihiro Hashimoto, Shinsuke Kido, Takashi Oshima, Hironobu Shibata, Shuji Ozaki, Daisuke Inoue, Toshio Matsumoto
Journal: Blood (2004)
A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice
Authors: Stefano Biressi, Elen H. Miyabara, Suchitra D. Gopinath, Poppy M. M. Carlig, Thomas A. Rando
Journal: Science Translational Medicine (2014)

A Wnt-TGFβ2 signaling pathway modulates stem cell dysfunction in muscles of dystrophic mice.
Gene expression in human embryonic stem cell lines: unique molecular signature
Authors: Bhaskar Bhattacharya, Takumi Miura, Ralph Brandenberger, Josef Mejido, Yongquan Luo, Amy X. Yang, Bharat H. Joshi, Irene Ginis, R. Scott Thies, Michal Amit, Ian Lyons, Brian G. Condie, Joseph Itskovitz-Eldor, Mahendra S. Rao, Raj K. Puri
Journal: Blood (2004)
Unravelling the cardioprotective mechanism of action of estrogens
Authors: J MOOLMAN
Journal: Cardiovascular Research (2006)

See article by Xu et al.  [1]  (pages 836–844) in this issue. 

Cardiovascular diseases are the major cause of morbidity and mortality in the developed world, and are increasing in significance in the developing world. Elucidation of the mechanisms involved in preventing the development of coronary artery disease and protecting the myocardium against the deleterious consequences of myocardial ischaemia therefore stays an important research goal. The sex hormone estrogen has received increased attention for its ability to exert cardioprotective effects against atherosclerosis, but it has become clear that estrogen also exerts a direct protective effect against ischaemia/reperfusion injury on the myocardium. In this edition of Cardiovascular Research Xu et al. [1] provide evidence for decreased TNFα production during ischaemia/reperfusion in the mechanism of estrogen-mediated cardiac protection.

There is an abundance of scientific evidence for the protective effect of estrogen against atherosclerosis, such as short-term vasodilating effects as well as long-term vascular protective and anti-atherosclerotic effects [2]. Epidemiological evidence shows that pre-menopausal women have a reduced risk for mortality from cardiovascular diseases [3] and that women are at a lower risk for the development of heart failure [4] and have enhanced cognitive function and reduced neurodegeneration associated with Alzheimer's disease and stroke [5]. Further proof for the protective effect of female gender is the fact that post-menopausal women have a similar or even increased risk for cardiovascular disease compared to men [3] and have an increased risk for adverse outcome after myocardial infarction and acute coronary syndromes, despite similar treatment with thrombolysis and percutaneous interventions [6]. It was therefore postulated that estrogen replacement would be beneficial in preventing cardiovascular diseases in post-menopausal females. However, clinical trials designed to investigate the effects of estrogen replacement therapy in secondary prevention were surprising–in the Heart and Estrogen/Progestin Replacement Study (HERS) no … 

*Tel.: +27 21 9389392. Email address: jamool{at}sun.ac.za
CHEMORADIOTHERAPY FOR COLORECTAL CANCER
Authors: N Andre
Journal: Gut (2005)

Recent estimates for cancer incidence and mortality in Europe continue to rank colorectal cancer as the second most common cause for cancer related death. Every year more than 376 000 patients are newly diagnosed with colorectal cancer and approximately 200 000 people die from the disease.1 Even though these numbers show a slight decrease,2,3 partially due to more effective screening programmes, they still represent a major medical and economic challenge. During the past 10 years, intensive clinical studies helped to establish the value of adjuvant therapy for colorectal cancer. The introduction of new chemotherapeutic agents such as irinotecan and oxaliplatin has led to a significant increase in tumour response and median survival. In advanced colorectal cancer, impressive prolongation of overall survival can be achieved through sequential application of combined systemic chemotherapy. In addition, targeted manipulation of molecular tumour mechanisms with new substances such as monoclonal antibodies against the epidermal growth factor receptor or vascular endothelial growth factor shows promising effects. Apart from the encouraging improvement in treatment results, introduction of new drugs and strategies has multiplied the available treatment options, which are much more complex and sometimes confusing in their variety.

This review aims to summarise the current systemic treatment options of colorectal cancer with an additional focus on new classes of targeted compounds recently introduced into clinical management.

The only curative strategy in the treatment of colorectal cancer is, and so far remains, complete surgical resection. Despite the fact that approximately 70–80% of patients are eligible for curative surgical resection at the time of diagnosis,4,5 five year overall survival is only 50–60%.6–8 Two out of three patients who undergo curative resection will experience local recurrence or distant metastases. In 85%, relapse is diagnosed within the first 2.5 years after surgery.9 This …
STUDIES ON THE VELOCITY OF BLOOD FLOW
Authors: Herrmann L. Blumgart, Soma Weiss
Journal: Journal of Clinical Investigation (1927)

This paper presents the first measurements of the velocity of blood flow through the lungs of man.Thorough understanding of the blood flow through the lungs is of great significance in understanding adapta- tions of the circulation in health and disease.The study of the pulmonary circulation has, therefore, always at- tracted the interest of investigators.The literature is voluminous and was reviewed in 1903 by Tigerstedt (1) and in 1921 by Wiggers (2).In animals the study of the pulmonary circulation necessitates such distortion of the normal physiological conditions that interpre- tation of the results is diflicult.The chest has usually been opened, the negative intrathoracic pressure abolished, and normal inspiration has been replaced by forcible distention of the lungs with positive blasts of air.By such methods Plunier (3) in 1904 first studied the
Peripheral deposition of 1-protease inhibitor using commercial inhalation devices
Authors: P. Brand, H. Beckmann, M. Maas Enriquez, T. Meyer, B. Müllinger, K. Sommerer, N. Weber, T. Weuthen, G. Scheuch
Journal: European Respiratory Journal (2003)

Patients with hereditary α 1 ‐proteinase inhibitor (α 1 ‐PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, α 1 ‐PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug. In order to optimise this treatment approach, lung deposition of inhaled radiolabelled α 1 ‐PI (Prolastin®) was studied using four different commercial inhalation devices (PARI‐LC Star®, HaloLite®, and AKITA® system in combination with LC Star® and Sidestream®) in six patients with α 1 ‐PI deficiency and mild-to-severe chronic obstructive pulmonary disease. The time required to deposit 50 mg of the Prolastin® (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled α1‐PI. This time was shortest for the AKITA® system (18–24 min) and significantly higher for the PARI‐LC Star® (44 min) and the HaloLite® (100 min). The higher efficiency of drug delivery using the AKITA® system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.
Electronic Medical Records and Diabetes Care Improvement
Authors: Patrick J. O’Connor
Journal: Diabetes Care (2003)

We have been waiting for electronic medical records (EMRs) to improve chronic disease care for a long time (1). Availability of sophisticated EMR systems has enticed an increasing number of health plans and medical groups to invest resources in such systems. Many EMR systems are able to improve documentation of care, communication of clinical information across sites, and measurement of productivity and variation in care (2). Inpatient EMR systems have led to improvements in care in some clinical domains (3). However, the potential impact of outpatient EMR use on quality of chronic disease care has not been fully realized.

In this issue of Diabetes Care , Meigs et al. (4) report on a randomized trial designed to assess the impact of a web-based EMR system on quality of diabetes care at an outpatient teaching practice. Physicians using the EMR ordered significantly more A1C and LDL cholesterol tests in patients with diabetes. However, increased test frequency did not translate into better A1C or LDL levels in the patients of physicians with access to the EMRs compared with patients of physicians without access to the EMRs. The authors conclude that EMR use leads to better quality of diabetes care, because more A1C and LDL tests were ordered.

While it is encouraging that EMR use led to increased frequency of testing, it is disappointing that key care outcomes such as A1C …
Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement
Authors: K. M. Antoniou, G. Margaritopoulos, F. Economidou, N. M. Siafakas
Journal: European Respiratory Journal (2009)

The connective tissue disorders (CTDs), also called collagen vascular diseases (CVDs), represent a heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs. Individuals with a CTD (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren9s syndrome, polymyositis/dermatomyositis and mixed connective tissue disease) are susceptible to respiratory involvement. When the lungs are affected, an increasing mortality and morbidity in CVDs occurs. Interstitial lung disease (ILD) is established as a clinical corollary across the spectrum of CTDs, with an overall incidence estimated at 15%. Therefore, pivotal clinical dilemmas remain in the evaluation and management of ILD involvement in CVDs. Critical questions are the presence of fibrosis and whether the disease is clinically significant. Moreover, the clinician has to decide if treatment is warranted and which is the best therapeutic approach. The use of additional tests, such as pulmonary function tests, high-resolution computed tomography scan, bronchoalveolar lavage fluid and surgical lung biopsy, deserves better discussion. The present review focuses on establishing the diagnosis of ILD in CTD, and on evaluating disease activity and prognosis. This will provide the basis for therapeutic decisions that will be discussed, including an overview of recent advances.
Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis
Authors: F. Sjögren, C. Svensson, C. Anderson
Journal: British Journal of Dermatology (2002)

Cutaneous microdialysis in vivo in human skin is demonstrably of use in the study of skin metabolism, percutaneous absorption and skin inflammation. A promising area for cutaneous microdialysis is the measurement of cytokines. This requires catheters equipped with membranes permeable to molecules of high molecular weight.To address technical problems of poor sample volume retrieval and analysis sensitivity in the simplest model of provocation, namely the insertion of the catheter itself in vivo into human dermis.Use of a polyethylenesulphone membrane, with a cut-off value of 100,000 Da, allowed measurement of target molecules of large molecular weight. Using an adaptation of a commercially available high sensitivity enzyme-linked immunosorbent assay, the ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal skin of six healthy volunteers after insertion of the microdialysis catheter.Reliable sample volumes and high analyte recovery were achieved either by push-pull pumping or by standard pumping using a perfusate consisting of Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during the first 100 min after catheter insertion. The IL-6 concentration then increased and remained elevated for the duration of the experiments.Technical and analytical modifications in the microdialysis technique have allowed the measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine production is the result of the dermal trauma caused by catheter insertion, but the cellular source of the IL-6 is at present unknown.