tbuckley/cabot-search huggingface dataset:
Medical Mystery — The Answer
Authors: Leslie A. Kory
Journal: New England Journal of Medicine (2002)

To the Editor: Nuckton and associates (April 25 issue) 1 report an abnormally high dead-space fraction (the ratio of dead-space ventilation to tidal volume, or V D /V T ) early in the clinical course of the acute respiratory distress syndrome.Their inference of a heretofore unrecognized functional abnormality is unwarranted, because V D /V T was assessed on the basis of carbon dioxide excretion with the usual Bohr-Enghoff equation.By definition, the patients had refractory hypoxemia, which reflects a severe imbalance between alveolar ventilation (V A ) and perfusion (Q), leading to a reduction in the efficiency of intrapulmonary gas transfer for both oxygen and carbon dioxide. 2 Thus, assessment of V D /V T on the basis of carbon dioxide excretion is sensitive to any imbalance in V A /Q -notably, in the midrange of values for V A /Q -and even shunt, although to a lesser extent. 3,4 This fact depends on the carbon dioxide bloodair partition coefficient's being relatively close to the normal range of V A /Q. 4 Specific assessment of high V A /Q areas and "true" dead space is possible, although practical only in small numbers of subjects, with the multiple inert gas elimination technique.We found that in eight patients with the acute respiratory distress syndrome, the mean (±SD) value for V D /V T as measured on the basis of carbon dioxide excretion was considerably higher (0.64±0.03) than the value as measured with the multiple inert gas elimination technique (0.37±0.04). 5 In only one of these subjects did we detect areas with high values for V A /Q (range, 10 to 100).That V D /V T was more closely correlated with the outcome than was the ratio of the partial pressure of oxygen (PaO 2 ) to the fraction of inspired oxygen (FiO 2 ) remains a novel and highly relevant finding of the study by Nuckton et al. that may be due to the greater influence on the latter index of factors not intrinsic to the lung -notably, FiO 2 and mixed venous oxygen content.
Medical Advice to Travelers
Authors: B. H. Kean
Journal: New England Journal of Medicine (1957)

THE wanderlust of Americans is probably a fundamental "disease" that is incurable and must be accepted as characteristic of them. The exposure of millions of servicemen to foreign lands, the availability and relative economy of commercial air transport, the elimination of certain visa formalities and the current economic prosperity of the nation have combined to produce a progressive increase in foreign travel during the past several years. Statistics released by the State and Commerce departments indicate that almost 1,500,000 residents of the United States will travel to foreign countries in 1957, with approximately 700,000 going to Western Europe, and 500,000 . . .
Study the past to divine the future. Confucius' wisdom doesn't work for idiopathic pulmonary fibrosis
Authors: Martin Kolb, Gisli Jenkins, Luca Richeldi
Journal: Thorax (2016)

Predicting the future is one of the greatest challenges and for many people one of the greatest hopes of humanity. This applies to any aspect of human life and medicine included. In respiratory medicine, predicting the future is particularly difficult for chronic remodelling disorders, such as pulmonary hypertension or fibrosis.1 The course and recovery from an acute illness are usually easier to foresee than the progression and rate of decline for chronic diseases. In particular, one of the major current challenges is actually predicting the effect of the available pharmacological treatments on the course of idiopathic pulmonary fibrosis (IPF), which is of paramount importance but is still rarely possible. Nonetheless, the more we enter the era of the so-called personalised medicine , anticipating the response to a specific drug is becoming part of realistic expectations.2

Safety and efficacy of drugs are assessed in the context of placebo-controlled randomised clinical trials (RCTs). Although a well-established and worldwide accepted methodology, RCTs still have limitations: one of these is the fact that necessarily trials last for a definite period of time, for IPF typically 12 months, during which time all participants are blinded to the active treatment or to a placebo. This limitation is intrinsic and unavoidable, given the need to balance between harm and benefit when new drugs with unknown effects are tested in patients. However, once approved, all new drugs undergo a mandatory postapproval surveillance of several years. While this type of postmarketing surveillance provides valid information about long-term safety of new drugs, there is no formal way of assessing long-term efficacy, and even if these studies report on efficacy, they are never controlled and therefore the evidence base is less rigorous than for prospective trials. For this reason, other forms of clinical research may be used to inform clinical …
Case 32-2014
Authors: Marlene L. Durand, Derrick T. Lin, Amy F. Juliano, Peter M. Sadow
Journal: New England Journal of Medicine (2014)

A 78-year-old woman with rheumatoid arthritis was admitted to the Massachusetts Eye and Ear Infirmary because of pain in the right side of the throat, odynophagia, and a tonsillar mass. A diagnostic procedure was performed.
Phosphatidylinositol 3-Kinase Is Involved in the Protection of Primary Cultured Human Erythroid Precursor Cells From Apoptosis
Authors: Yoshihito Haseyama, Ken-ichi Sawada, Atsushi Oda, Kazuki Koizumi, Hina Takano, Takashi Tarumi, Mitsufumi Nishio, Makoto Handa, Yasuo Ikeda, Takao Koike
Journal: Blood (1999)
Homogeneously Staining Region in a Retinoblastom Cell Line: Relevance to Tumor Initiation and Progression&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Fred Gilbert
 6, Gloria Balaban, W. Roy Breg, Brenda Gallle, Ted Reid, Warren Nichols
Journal: JNCI Journal of the National Cancer Institute (1981)

A human retinoblastoma cell line was found to contain a homogeneously staining region (HSR) on chromosome 1 (at 1p34). An HSR had previously been Identified at the same site In a human neuroblastoma cell line. Of the original retinoblastoma line. a subpopulation was found which did not contain the 1pHSR but did contain a 3p+ chromosome In which the additional segment resembled a small HSR. The 3p+ was most likely the result of a translocation between the 1pHSR and the short arm of a chromosome 3. Preliminary results also indicate that the retinoblastoma cells with the 1pHSR produced tumors in athymlc nu/nu mice In an average of 28 days, while identical numbers of the retinoblastoma cells with the 3p+ (probable HSR) produced tumors In an average of 75 days.
Variation in Biologic Availability of Digoxin from Four Preparations
Authors: John Lindenbaum, Mark H. Mellow, Michael O. Blackstone, Vincent P. Butler
Journal: New England Journal of Medicine (1971)

The unexplained association of unusually large maintenance doses of digoxin and low serum digoxin concentrations in several patients prompted a study of the biologic availability of various digoxin products recently available for use on the wards of a New York City municipal hospital. In crossover studies in which 0.5 mg of digoxin was administered orally to normal volunteers, marked differences in serum digoxin levels achieved over a five-hour period were demonstrated. With one product peak serum levels were seven times those obtained with another. Significant variation between different lots prepared by a single manufacturer was also observed. Evidence of biologic as well as chemical equivalency of digoxin products for use in man should be required.
P87 Repeat survey of vitamin K prescribing patterns and bone health surveillance in UK paediatric CF centres
Authors: MR Nortier, DS Urquhart
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> CF bone disease is multi-factorial; UK guidelines for screening and treatment of CF bone disease are published.<sup>1</sup> Despite evidence of a key role for Vitamin K in bone formation, there is limited agreement on supplementation in CF. A previous 2005/06 survey<sup>2</sup> of bone health surveillance and Vitamin K use in CF reported wide variation in practice. The current survey aimed to ascertain practice 10 years on. <h3>Methods</h3> Questionnaires were sent via email to all 25 UK paediatric CF centres. Data were collected on use of vitamins A, D, E and K including preparation, dose and criteria for Vitamin K supplementation. In addition, information was obtained on bone health surveillance including use of dual-energy X-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD). <h3>Results</h3> A 60% questionnaire response representing 2805 CF children was collected. All centres reported that &gt;90% pancreatic insufficient patients receive multivitamin supplements and 12/15 centres reported &gt;90% patients receive additional Vitamin E. Only 3 centres routinely supplement Vitamin K, with only 1 reporting that &gt;90% patients receive Vitamin K. Criteria for prescribing Vitamin K were deranged liver function (10/15), clotting (5/15), low Vitamin K levels (2/15), and low BMD (3/15). Vitamin K dosage varied from 0.3–10 mg/day, with most (12/15) prescribing 10 mg/day. Menadiol was mainly (10/15) used with some using Phytomenadione for younger patients. Four centres used AquaDEKs, whilst three reported limitations in prescribing AquaDEKs due to formulary constraints. All centres measured vitamin D levels and 14/15 (94%) routinely perform DXA scans. Dietary calcium intake was assessed in 11/15 centres. <h3>Conclusion</h3> Bone health surveillance is routinely undertaken in all paediatric CF centres, with Vitamin D levels and BMD (by DXA) measurement universal. Vitamin K prescribing (criteria and dose) is still heterogeneous. A Cochrane review<b><sup>3</sup></b> of routine vitamin K supplementation in CF concluded that evidence is currently limited to two small trials, with further evidence needed to establish optimal dose and long-term benefit. <h3>References</h3> 1 UK Cystic Fibrosis Trust Bone Mineralisation Working Group. <i>Bone mineralisation in Cystic Fibrosis</i>. London: UK Cystic Fibrosis Trust, 2007 2 Urquhart DS, Fitzpatrick M, Cope J. <i>et al.</i> Vitamin K prescribing patterns and bone health surveillance in UK children with cystic fibrosis.<i> J Hum Nutr Diet</i>. 2007;<b>20</b>:605–10 3 Jagannath VA, Fedorowicz Z, Thaker V. <i>et al.</i> Vitamin K supplementation for cystic fibrosis.<i> Cochrane Database Syst Rev</i>. 2015;<b>1</b>:CD008482
RARE-02FOURTH VENTRICLE GERMINOMA: A CASE REPORT WITH LITERATURE REVIEW
Authors: Kyuha Chong, Seungjoo Lee, Eun Jung Lee, Young Hyun Cho, Seok Ho Hong, Chang Jin Kim, Jeong Hoon Kim
Journal: Neuro-Oncology (2015)

Although most common loci of intracranial primary germinoma (IPG) are pineal and suprasellar regions, there are some reports of unusually located IPG which makes confusion of differential diagnosis of the tumor. Especially within posterior fossa area, IPG is hardly considered because of its extreme rareness and unmatched clinical characteristics comparing with supratentorial IPGs. Most usual areas within posterior fossa are known as fourth ventricle and medullar oblongata. With the best of our knowledge, there are only less than twenty reported cases of fourth ventricle IPG, yet. Herein, we presents a case of 24 years old female patient who had a large fourth ventricle tumor which turned out to be germinoma. The tumor had been suspected as an ependymoma with consideration of age of patient and features of imaging findings. But, intraoperative and pathologic findings were differ from ependymoma, and finally defined as a germinoma. After chemotherapy with consecutive radiation therapy, complete remission of the tumor without neurological complications was acquired.
Inhibitory Effect of Disulfiram on Rat Mammary Tumor Induction By N-2-Fluorenylacetamide and on its Metabolic Conversion To N-Hydroxy-N-2-fluorenylacetamide2
Authors: D. Malejka Giganti, R. C. McIver, R. E. Rydell
Journal: JNCI Journal of the National Cancer Institute (1980)

The effect of an antioxidant, disulfiram (DSF), on the carcinogenicities of N-2-fluorenylacetamide (2-FAA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) was examined. DSF given in a diet at a concentration of 0.9% for 1 week before and throughout the carcinogen treatment (0.1 mmol/kg 3 times a week for 4 weeks) reduced the incidence of mammary tumors induced with 2-FAA by 50% and extended the mean latency period of malignant tumors from 5 to 10 months. By contrast, DSF had no effect on mammary carcinogenesis by N-OH-2-FAA. Consistent with these results was the demonstration of the inhibitory effect of DSF on the first step of metabolic activation of 2-FAA, i.e., N-hydroxylation. N-hydroxylation of 2-FAA was significantly inhibited in hepatic microsomes of untreated and 2-FAA-treated male and female rats by DSF given orally. A similar inhibition was shown in vitro after preincubation of hepatic microsomes with DSF. Measurements of cytochrome P450 after pretreatment of rats or microsomes with the inhibition showed no appreciable changes in the hemoprotein content. It was concluded, therefore, that the inhibitory effect of DSF on N-hydroxylation of 2-FAA is accomplished through mechanism(s) other than depression of the cytochrome P450 level. Because both 2-FAA and DSF bind to cytochrome P450 producing a type I spectrum, DSF may interfere with the binding of 2-FAA and thus alter its metabolism.
Some physiologic antecedents of adult mental health
Authors: K A Phillips, G E Vaillant, P Schnurr
Journal: American Journal of Psychiatry (1987)

The authors report on 188 healthy college men followed biennially from age 19 years to age 63. A relatively low standing heart rate and long treadmill running time in college predicted mental--but not physical--health during the next 40 years, whereas a relatively low blood pressure predicted future physical--but not mental--health. These relationships remained significant when the effects of physical fitness and body build were partialled out, suggesting that psychological components of physiologic phenomena accounted for their prediction of mental health outcome. The authors speculate that a high resting heart rate reflected social anxiety and prolonged running time reflected perseverance and stoicism.
Scientists Explore a Master Genetic Switch That Plays a Key Role in Energy Metabolism and Human Brain Evolution and Function
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2016)

Scientists have long used comparative animal studies to better understand the nuances of human evolution, from making diverse body plans to the emergence of entirely powerful and unique features structures, including the human brain. Now, in a new study appearing in the advanced online edition of Molecular Biology and Evolution, corresponding authors Perdomo-Sabogal et al. (2016) have explored the global gene regulator GABPa to better understand its influence as a master switch. Their work honed in on human-specific DNA regions potentially contributing to human evolution in key functions including cell energy, division and death, and diseases ranging from brain disorders to diabetes. Many of the GABPa gene regulatory sites were found to be significantly enriched at genes important for brain, central nervous system and spinal cord functions that are unique to humans, an area ripe for future research, and GABPa deficits linked to Alzheimer’s and Parkinson diseases, breast cancer, and autism. GABPa exerts its profound genomic influence by a tandem repeat of four highly conserved DNA letters. The GGAA consensus motif is found to control genes in all primates, mice, dogs, and cows, underscoring its importance in these animals. By performing ChIP-Seq experiments in a human cell line, the group found that GABPa exercises its influence across the genome at 11,619 putative GABPa binding sites representing nearly 4,000 genes. Through a tour de force sequence comparison of the human GABPa binding sites with similar sequences from 34 mammals, they identified 224 GABPa binding sites unique to humans. Comparing chimpanzee, macaque, and human cell lines and mutating the GGAA sequence to more ancestral states to determine how these changes affected GABPa function, they further narrowed down their function. For instance, when the human GABPa binding sites were introduced into primate cells, gene expression was increased up to five times in 17 out of 18 cases, indicating that a recent human mutation in GABPa resulted in higher gene expression and forces behind the evolution of novel, uniquely human functions. “Mutations that cause changes in the regulation of gene activities are one of the major factors in shaping species during evolution,” said corresponding author Robert Querfurth. “Our study demonstrates how, out of the millions of DNA regions, in which we differ from other apes, we can sift out those that, in response to a specific regulatory protein, cause gene activity changes in human cells. In this set, we find genes involved in brain and breast development and also in diseases like Alzheimer’s and Parkinson’s.” Reference
The Histone Deacetylase Inhibitor Trichostatin a (TSA) Suppresses Alternaria Extract-Induced Murine Innate Allergic Inflammation By Blocking Group 2 Innate Lymphoid Cell (ILC2) Activation
Authors: Shinji Toki, Kasia Goleniewska, Sara Reiss, Weisong Zhou, Dawn C. Newcomb, Melissa H. Bloodworth, Matthew T. Stier, Kelli L. Boyd, Vasiliy V. Polosukhin, Sriram Subramaniam, R. Stokes Peebles
Journal: Journal of Allergy and Clinical Immunology (2016)
NIMG-49RESPONSE ASSESSMENT OF BEVACIZUMAB FOR MALIGNANT GLIOMA BY USING<sup>11</sup>C-METHIONINE AND<sup>18</sup>F-FLUOROMISONIDAZOLE PET TRACERS
Authors: Keisuke Miyake, Masaaki Kouchi, Daisuke Ogawa, Masaki Okada, Tetsuhiro Hatakeyama, Aya Shinomiya, Takashi Tamiya
Journal: Neuro-Oncology (2015)

OBJECTIVE: Use of the positron imaging agents, such as 11C-Methionine (MET) and 18F-Fluoromisonidazole (FMISO), is expected to lead the way for novel applications aimed at achieving efficient malignancy grading and treatment of gliomas. The aim of this study was to assess MET and FMISO PET studies to evaluate the biological effects induced by bevacizumab therapy in patients treated for high grade gliomas. METHODS: Twenty-two patients with high grade gliomas were treated biweekly with bevacizumab from July 2013 to May 2015. MR images, as well as MET and FMISO PET scans were obtained at baseline and at follow-up (4 weeks after treatment onset). MRI treatment response was evaluated by T1/T2 volumetry according to the response assessment in neuro-oncology (RANO) criteria. Based on the RANO criteria, we divided the patients into three groups (PR, SD, and PD), and compared changes of MET T/N ratio or FMISO T/B ratio between baseline and follow-up. These PET response assessments were compared in relation to PFS and OS. RESULTS: At the follow-up, MRI showed PR in 6 of 22 patients, SD in 11 of 22 patients, and PD in 5 of 22 patients. The median PFS were 13.1 months, 13.5 months and 2.4 months for PR, SD and PD, respectively. The median OS were 14.6 months, 14.5 months and 5.7 months for each group. MET and FMISO images in the PD group had a tendency to show the increase of changes. FMISO images in the SD group revealed 3 of 11 increased changes (15.1% up) and 8 of 11 decreased changes (11% down). The median PFS were 2.4 months and 16.3 months for each change, and the median OS were 9.8 months and 16.8 months. CONCLUSION: Decreased changes in FMISO-PET after bevacizumab therapy may be a useful biomarker for predicting PFS and OS in high-grade gliomas.
S37 The response of objectively-measured cough to treatment in tuberculosis: an exploratory study
Authors: RD Turner, SS Birring, GH Bothamley
Journal: Thorax (2015)

<h3>Introduction and objective</h3> Cough is predominant in pulmonary tuberculosis and transmits infection, yet it is unclear how rapidly it responds to treatment. We explored changes in objectively-measured cough frequency during TB therapy with respect to other markers of disease. <h3>Method</h3> Before or on commencing anti-tuberculous treatment, consecutive patients with pulmonary tuberculosis wore the Leicester Cough Monitor for 24 h, a device comprising a small digital audio recorder and microphone with software for cough detection. Those with a baseline cough frequency greater than the upper limit of normal (<i>c. </i>100 coughs/24 h [c/24h]) were asked to undergo repeat monitoring during initial hospitalisation (if applicable), and later to coincide with routine clinic attendance or directly observed therapy (DOT). <h3>Results</h3> Median baseline cough frequency was 203 (IQR 75–470) c/24 h in all participants (n = 44), and &gt;100 c/24 h in 32 (73%). 22 patients were willing and available to undergo serial cough monitoring (12 current smokers, 18 sputum smear positive disease [12 also with visible lung cavities], and one with HIV). Three had isoniazid-resistant disease; the remainder were fully drug-sensitive. All were eventually treated successfully. None had other respiratory diagnoses. Cough frequency in the majority declined consistently during therapy with substantial improvements by one week (Figure 1). At 2 and/or 8 weeks, five patients had a higher cough frequency than at baseline. Amongst these slow responders there was initial extensive radiographic change (n = 1), poor drug adherence with ongoing weight loss (n = 1), a paradoxical reaction to treatment with the development of a paraspinal abscess (n = 1), and, in the patient with HIV, persistent sputum smear positivity at 8 weeks with minimal radiographic improvement despite DOT and normal plasma rifampicin levels. One other patient had a highly variable cough frequency during the first 8 weeks of treatment. There was no evidence for an effect of isoniazid resistance, cavitary disease, smear status or smoking on early rates of cough resolution, although there was a trend towards relatively higher cough frequencies in smokers than non-smokers at the end of treatment (<i> p</i> = 0.100). <h3>Conclusions</h3> Objective cough frequency measurement is feasible in tuberculosis and could provide a novel biomarker of treatment response.
Brain–Gut–Bone Marrow Axis
Authors: Monica M. Santisteban, Seungbum Kim, Carl J. Pepine, Mohan K. Raizada
Journal: Circulation Research (2016)

Hypertension is the most prevalent modifiable risk factor for cardiovascular disease and disorders directly influencing cardiovascular disease morbidity and mortality, such as diabetes mellitus, chronic kidney disease, obstructive sleep apnea, etc. Despite aggressive attempts to influence lifestyle modifications and advances in pharmacotherapeutics, a large percentage of patients still do not achieve recommended blood pressure control worldwide. Thus, we think that mechanism-based novel strategies should be considered to significantly improve control and management of hypertension. The overall objective of this review is to summarize implications of peripheral- and neuroinflammation as well as the autonomic nervous system–bone marrow communication in hematopoietic cell homeostasis and their impact on hypertension pathophysiology. In addition, we discuss the novel and emerging field of intestinal microbiota and roles of gut permeability and dysbiosis in cardiovascular disease and hypertension. Finally, we propose a brain–gut–bone marrow triangular interaction hypothesis and discuss its potential in the development of novel therapies for hypertension.