tbuckley/cabot-search huggingface dataset:
Nonneoplastic changes in the olfactory epithelium--experimental studies.
Authors: B A Gaskell
Journal: Environmental Health Perspectives (1990)

Interest in the olfactory mucosa has increased in recent years, since it has been shown to possess a considerable amount of cytochrome P-450-dependent monooxygenase activity and a wide variety of chemicals have been identified as olfactory toxins. Many chemicals induce lesions of a general nature in the olfactory mucosa, i.e., inflammation, degeneration, regeneration, and proliferation, whereas others cause more specific effects. Changes in the olfactory mucosa with reference to chemicals that initiate them are reviewed in this paper. Studies with 3-trifluoromethyl pyridine (3FMP) illustrate some of these general changes and show the importance of examining the olfactory mucosa at early time periods. The earliest damage seen by light microscopy was 6 hr after a single inhalation exposure to 3FMP, and by day 3, early regenerative changes were observed. Changes were seen by electron microscopy 30 min after an oral dose, and the primary site of toxicity appeared to be the Bowman's glands. Although atrophy of nerve bundles in the lamina propria would be the expected consequence of severe necrosis of the sensory cells, this is not always the case. Exposure to irritants such as acetaldehyde, formaldehyde, and dimethylamine results in nerve bundle atrophy, but with chemicals such as 3FMP, 3-methylindole, and 3-methylfuran--which are activated by mixed-function oxidases--the nerve bundles remain intact. Future work, including metabolism studies, will provide information on the mode of action of these chemicals.
The suprascientific in clinical medicine: a challenge for Professor Know-All
Authors: F I D Konotey-Ahulu
Journal: BMJ (2001)

I first heard of him half a century ago. He is one of those people who become more articulate, more cocksure, and more formidable in debate the older they get. Continental Europeans call him Erik the Genius. Although he is highly esteemed in the United Kingdom, he impresses Americans less. I call him Professor Know-All because every time a new fact emerges in science or medicine, he has expected it. Nothing puzzles him. So I decided to see what he would make of these four case histories.

A 58 year old Indian merchant working in an African country was admitted to hospital with severe retrosternal pain radiating upwards and down the right arm. His wife and 35 year old son were with him when electrocardiography confirmed posterior myocardial infarction. He believed he was about to die. Before treatment was started, he said: “Doctor, you know I am 58. My elder brother died three years ago, aged 58 years. My father died at 58 years. His younger sister, my auntie, also died in India at 58, and…” I interrupted him, thinking it amazing how superstition creeps into scientific medicine: “You are not going to die, sir. You need a good night's sleep. Just say good night to your wife and son.” “And my grandfather,” he continued from where I had interrupted him, “father's father, collapsed and died of a heart problem, I am told aged 58 years.”

After I sent his wife and son out of the private room, she asked me to let her stay with him overnight. But the received wisdom in those days did not allow relatives to sleep in. In Britain, even mothers were sent away from their babies. Britain was the gold standard; why should anyone prescribe less for an African country? The son pleaded with …
Salmeterol compared with slow‐release terbutaline in nocturnal asthma A multicenter, randomized, double‐blind, double‐dummy, sequential clinical trial
Authors: C. Brambilla, C. Chastang, D. Georges, L. Bertin, Dr Jean‐Luc Desfougeres
Journal: Allergy (1994)

Brambilla C, Chastang C, Georges D, Bertin L. Salmeterol compared with slow‐release terbutaline in nocturnal asthma. A multicenter, randomized, double‐blind, double‐dummy, sequential clinical trial. The aim of the multicenter, randomized, double‐blind, double‐dummy, parallel‐group clinical trial with a 2‐week treatment period was to compare the efficacy and safety of salmeterol (50 ug twice daily) with slow‐release (SR) terbutaline (5 μg orally, twice daily) in nocturnal asthma. A total of 159 asthmatic adults (FEV, 50‐90% of predicted value; sex ratio: 0.87) with at least two nocturnal awakenings during a 7‐d run‐in period was included in the study. Patients were centrally randomized with a national computer network (Minitel®). The main variable (number of awakening‐free nights during the last week of treatment) was analyzed according to a sequential method with the one‐sided triangular test. The number of awakening‐free nights (± SD) was significantly higher in the salmeterol group: 5.3 ± 2.4 vs 4.6 ± 2.3 (P = 0.006). Salmeterol was significantly more effective than SR‐terbutaline in the following factors: number of patients without any awakening during the last week of treatment (50% vs 27%, P = 0.003), mean morning PEF (351 ± 1091/min ‐1 vs 332 + 105 I/min ‐1 , P = 0.04), PEF diurnal variation 6 ± 10% vs 11 ± 12%, P = 0.01), overall assessment of efficacy by the patient and the investigator (P = 0.001 and 0.005, respectively), and daily rescue salbutamol intakes ( P =0.004). In the salmeterol group, significantly fewer patients reported adverse events (16% vs 29%, P = 0.04). This study confirms that salmeterol, 50 μg twice daily, is particularly useful in controlling nocturnal symptoms of asthma: as compared with the control group, twice as many salmeterol‐treated patients were totally free of nocturnal symptoms after 2 weeks of treatment.
Detection of Cardiac Abnormalities in Elite Black and White Athletes
Authors: Antonio B. Fernandez, Paul D. Thompson
Journal: Circulation (2014)

S ports are "hot."The average cost of a 30-second adver- tisement at the 2014 Super Bowl was $4 000 000, 1 and millions of fans worldwide spent much of their February 2014 watching the Sochi Winter Olympics and its advertising.Sports cardiology is also hot.The American College of Cardiology in 2011 established a section dedicated to sports and exercise cardiology, and now there are several sports cardiology sessions during its annual meeting.Additional heat in sports cardiology comes from for the controversy regarding whether the screening of young athletes for sports participation requires an ECG.European colleagues favor ECG screening primarily because of a 2006 observational study demonstrating reduced cardiovascular deaths among screened athletes and no decrease in a nonathletic comparison population. 2 At least 2 subsequent articles 3,4 failed to corroborate a reduction in events with ECG screening.
Fifth person dies from anthrax
Authors: D. Josefson
Journal: BMJ (2001)

A 94 year old woman has become the fifth person in the United States to die of inhalational anthrax in recent weeks. The case has deepened the mystery about the bacteria's source and raised troubling questions about whether more cases are looming.

The woman, Ottilie Lundgren, was a resident of Oxford, Connecticut, a rural farming community of 9000, 30 miles from Hartford, the state capital. For the past year, she was increasingly home bound, only occasionally going to church, the public library, or the beauty salon. She had no connection with the media or politics, and why she should have been targeted or infected with anthrax has baffled both investigators and members of the normally quiet Oxford community. Moreover, preliminary tests …
THYROID TISSUE IN THE LARYNX AND TRACHEA.
Authors: OTTO T. FREER
Journal: JAMA (1900)

Up to the present time nine cases of thyroid tissue growing within the larynx and trachea have been reported. The histories of these have been collected by Baurowicz, who reports one of his own together with these, in Fränkel's Archives of Laryngology and Rhinology, volume viii, 1898. I have been unable to find a description of the affection since the publication of Baurowicz's article, so think that I can claim that the case of my own that I shall describe is the tenth recorded of this rare affection. Up to the present time the cases reported are 3 by Paul Bruns, 2 by Heise from Bruns' clinic, and 1 each by Ziemssen, Paltauf, Baurowicz and Roth. The principal symptom caused by thyroid tissue in the larynx and trachea is dyspnea. This may have lasted for years, months or weeks before the patient is seen, and generally there is a history
Tubular Mechanism for the Spontaneous Hypercalciuria in Laboratory Rat
Authors: Kai Lau, Bonnie K. Eby
Journal: Journal of Clinical Investigation (1982)

Recently it has been observed that Ca excretion in laboratory rats does not follow a Gaussian distribution, with ∼10% of them excreting Ca at a rate of 2 SD above the group mean. This phenomenon has been described as spontaneous hypercalciuria (SH). Our studies were designed to define its mechanism. 48 Wistar rats were subjected to metabolic studies to identify SH, prospectively defined as Ca excretion 2 SD above the group mean during 7 d of dietary Ca deprivation (≤0.03% by analysis), in the absence of hypercalcemia, PO4 depletion, or exaggerated natriuresis.
Treatment of Impetigo
Authors: George Heller
Journal: JAMA (1971)

<h3>To the Editor.—</h3> In his article, "Therapy of Impetigo and Furunculosis" (<b>214</b>:1862-1866, 1970), Fritsch favors the use of antibiotics orally rather than topical treatment of impetigo as is sanctioned by most texts and is the custom of most physicians. The report by Dillon in whose "extensive study... there was a 13% incidence of glomerular nephritis" is at least partially the rationale for his preference.<sup>1</sup> This figure of a 13% incidence of glomerular nephritis following impetigo is hard to accept. At a recent staff meeting of pediatricians at the Englewood (NJ) Hospital, we discovered that 11 of us, with a total of 191 years of private practice, had<i>never</i>encountered a complication of this kind, nor in five years of private practice had a 12th member, who had previously cared for three such cases within a short time at an Air Force clinic, however. I have never had occasion
Hereditary aspects of decreased hypoxic response.
Authors: D D Collins, C H Scoggin, C W Zwillich, J V Weil
Journal: Journal of Clinical Investigation (1978)

Decreased ventilatory responses to hypoxia and hypercapnia have been demonstrated in a variety of disorders; however, the etiology of these decreased drives remains virtually unknown. Recent observations have suggested a familial influence on hypoxic and hypercapnic ventilatory response, but it is unclear whether this influence is the result of hereditary or environmental influences. Therefore we measured the ventilatory response to isocapnic hypoxia (HVR) and hyperoxic hypercapnia in 12 pairs of identical and 12 pairs of nonidentical twins. Significant correlation (P less than 0.01) was found for HVR within identical twin pairs but not within nonidentical twin pairs. Identical twins resembled each other more closely with respect to HVR than was the case for nonidentical twins (P less than 0.0125). This was independent of body size, blood PCO2, or pH. No such correlation could be found for ventilatory response to hyperoxic hypercapnia. It is concluded that hereditary influences affect HVR and it is speculated that such influences may play a role in clinical conditions characterized by decreased hypoxic ventilatory responses.
A Pilot Study: Trivalent Inactivated Influenza Vaccine (TIV) and Myopericarditis
Authors: M.I. Slingluff, M.M. Klote, B.A. Hemann, M.R. Nelson, M.A. Yacavone, J.E. Atwood, S. Black, R.J.M. Engler
Journal: Journal of Allergy and Clinical Immunology (2007)
Abstract 403: The role of HER2 in the brain metastatic cascade in breast cancer.
Authors: Yunxiang Liao, Matthias Osswald, Brunilde Gril, Patricia Steeg, Wolfgang Wick, Frank Winkler
Journal: Cancer Research (2013)

Abstract Approximately 20% of brain metastases originate from breast cancer, which is the most common invasive cancer of women worldwide. HER2 inhibitors have revolutionized the treatment of HER2 positive breast cancer patients, but have no or marginal activity against brain metastases yet - which is becoming increasingly problematic, since 40% of HER2 positive breast cancer patients will eventually develop this devastating complication of the disease. Therefore we aimed to understand which step of the brain metastatic cascade is actually affected by HER2 overexpression; which is crucial for successful growth to a macrometastasis; and which is most amenable to a prophylactic therapy. For this we used our novel animal model which allows to non-invasively follow single metastasizing cancer cells through a chronic cranial window over time, using in vivo multiphoton microscopy. Human MDA-MB-231 breast cancer brain-seeking subclones with high HER2 expression or with control vector have been injected into the circulation of female nude mice. As shown before for other cancer entities, only a very small proportion of cancer cells initially arrested in brain capillaries can successfully form brain metastases, which was similar for both groups (1.02% vs 1.67% - for HER2 overexpression and vector control, respectively). However, more of the injected HER2+ cells managed to initially arrest compared with HER2- cells (47.5 vs. 27.7 per 100,000 injected cells). Moreover, they extravasated earlier, and showed more early interaction with brain capillaries leading to intensive vascular remodeling, but no angiogenesis. We therefore focussed on factors of early breast cancer cell - blood vessel - interaction, and found integrins to be overexpressed in HER2+ cells. In ongoing experiments, we test an integrin αvβ3-5 inhibitor regarding its activity to prevent the early metastatic steps, and find that these steps are markedly inhibitied in treated animals. Our results provide a better understanding of the breast cancer brain metastatic cascade, and the role of HER2. Importantly, they suggest that inhibition of crucial early steps involving cancer cell - blood vessel interactions via integrin pathways can serve as a well tolerated long-term prophylactic treatment for HER2-positive breast cancer patients which are at risk to develop brain metastases. Citation Format: Yunxiang Liao, Matthias Osswald, Brunilde Gril, Patricia Steeg, Wolfgang Wick, Frank Winkler. The role of HER2 in the brain metastatic cascade in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 403. doi:10.1158/1538-7445.AM2013-403
The microbiota-gut-brain axis in functional gastrointestinal disorders
Authors: Giada De Palma, Stephen M Collins, Premysl Bercik
Journal: Gut Microbes (2014)

Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.
PML-RARA–targeted DNA vaccine induces protective immunity in a mouse model of leukemia
Authors: Rose Ann Padua, Jerome Larghero, Marie Robin, Carol le Pogam, Marie-Helene Schlageter, Sacha Muszlak, Jan Fric, Robert West, Philippe Rousselot, Thi Hai Phan, Liesbeth Mudde, Helene Teisserenc, Antoine F Carpentier, Scott Kogan, Laurent Degos, Marika Pla, J Michael Bishop, Freda Stevenson, Dominique Charron, Christine Chomienne
Journal: Nature Medicine (2003)
Sudden, Unexplained Nocturnal Death Syndrome and Night Terrors
Authors: Ronald B. Melles
Journal: JAMA (1987)

<h3>To the Editor.—</h3> We read with great interest the recent correspondence suggesting sleep apnea as a possible explanation for the sudden, unexplained nocturnal death syndrome (SUNDS).<sup>1,2</sup>We would like to offer a different pathophysiological mechanism that we suspect is behind many of these deaths. The SUNDS occurs largely in young, previously healthy Asian men and includes<i>Bangungut</i>in the Philippines,<i>Pokkuri</i>in Japan, and sudden, unexplained nocturnal deaths among Southeast Asians in the United States. Ventricular fibrillation is thought to be the common physiological mechanism of these deaths.<sup>3</sup>Special postmortem cardiac studies reported by Kirschner et al<sup>2</sup>and previously by others<sup>4,5</sup>have documented abnormalities of the cardiac conduction system and cardiomegaly in victims of SUNDS. These cardiac defects are not manifest during the victim's life, and the event that provokes the fatal arrhythmia has never been explained. Our review of the clinical descriptions of the victims
Inhibition of Urokinase Activity Reduces Primary Tumor Growth and Metastasis Formation in a Murine Lung Carcinoma Model
Authors: Ingrid Henneke, Susanne Greschus, Rajkumar Savai, Martina Korfei, Philipp Markart, Poornima Mahavadi, Ralph T. Schermuly, Malgorzata Wygrecka, Jörg Stürzebecher, Werner Seeger, Andreas Günther, Clemens Ruppert
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Lung cancer is the most common malignancy in humans. Urokinase (uPA) plays a crucial role in carcinogenesis by facilitating tumor cell invasion and metastasis.We investigated the effect of the highly specific urokinase inhibitor CJ-463 (benzylsulfonyl-D-Ser-Ser-4-amidinobenzylamide) on tumor growth, metastasis formation, and tumor vascularization in the murine Lewis lung carcinoma (LLC) and a human small lung cancer model.A quantity of 3 x 10(6) LLC cells were subcutaneously injected into the right flank of C57Bl6/N mice, uPA knock out, and uPA receptor knockout mice. Seven days later mice were randomized to receive intraperitoneally either saline (control group), CJ-463 (10 and 100 mg/kg, twice a day), or its ineffective stereoisomer (10 mg/kg, twice a day). Tumor volume was measured every second day and metastasis formation was monitored by volumetric-computed tomography. Twelve days after onset of treatment mice were killed and tumors were prepared for histologic examination.Treatment with CJ-463 resulted in a significant inhibition of primary tumor growth, with the highest efficacy seen in the 100 mg/kg group. In addition, histological analysis of the lung revealed a significant reduction in lung micrometastasis in the 100 mg/kg group. Similarly, a reduced seeding of tumor cells into the lung after intravenous injection of LLC cells was observed in inhibitor-treated mice. In these mice, treatment with CJ-463 appeared not to significantly alter the relative extent of tumor vascularization. In vitro, proliferation of LLC cells remained unchanged upon inhibitor treatment. CJ-463 was found to similarly reduce tumor growth in uPA receptor knockout mice, but was ineffective in uPA knockout mice.Our results suggest that synthetic low-molecular-weight uPA-inhibitors offer as novel agents for treatment of lung cancer.
Abstract 5352: A high percentage of Merkel cell carcinomas is biologically associated with Merkel cell polyomavirus
Authors: Ernst-Jan M. Speel, Andreia Schmidt, M Baumann, Annick Haesevoets, J Diebold, P Hofmann, Michael Kurrer, N Willi, F Offner, Guido Sauter, V Zsikla, Gieri Cathomas
Journal: Cancer Research (2010)

Abstract Merkel cell polyomavirus (MCPyV) DNA has been detected by PCR in 75-100% of Merkel cell carcinomas (MCC), an aggressive neuroendocrine skin cancer. MCPyV is a 5.4 kb DNA virus that expresses tumor (T) antigen in tumor tissues. The aim of this study was to analyze which subset of MCC is biologically associated with MCPyV using various viral detection methods. Genomic DNA isolated from paraffin-embedded tissue of 61 MCC was analyzed by MCPyV-specific PCR. Using a 5kb MCPyV DNA probe, the physical status of MCPyV was determined by fluorescence in situ hybridization (FISH) using tyramide signal amplification and ApoTome microscopy. Expression of large T antigen was assessed by immunohistochemistry (IHC) using monoclonal antibody CM2B4 (kindly provided by Y. Chang). A total of 44 of 61 (72%) MCC were positive for MCPyV by PCR. 34 of these 44 cases (77%) were also positive for MCPyV by FISH and 28 (64%) showed strong nuclear large T antigen expression by IHC. In contrast, none of the 17 PCR-negative tumors showed FISH signals and only 1 case showed a weak immunostaining for large T antigen. FISH analysis showed in 16 cases (47%) tumor nuclei with a single punctate signal indicating viral integration. In 8 of these tumors also areas were observed with a granular pattern with &amp;gt;1 nuclear signals varying significantly in size and intensity, indicating the presence of episomal viral DNA and/or RNA. In the remaining 18 cases (53%) an exclusive granular FISH pattern was observed. Our data indicate that a subset of MCC is caused by MCPyV as determined by PCR, FISH and IHC analysis (46% is positive with all 3 detection methods). FISH and IHC showed a strong positive and negative concordance. FISH signal evaluation furthermore suggests viral integration in half of the positive MCC and a non-clonal viral persistence in the remaining positive cases. Further studies have to validate these findings and elucidate the molecular mechanisms underlying MCV-positive and -negative MCC development. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5352.
Pituitary Gland: Do Anticancer Drugs Sit in the Turkish Saddle?
Authors: Astrid A.M. van der Veldt, Egbert F. Smit, Adriaan A. Lammertsma
Journal: Journal of Clinical Oncology (2013)

With interest we have read the study by Zeller et al 1 in Journal of Clinical Oncology.In their cross-sectional study, the authors compared regional brain volumes in 130 adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) with those in healthy controls.In this study, ALL survivors had been treated with chemotherapy consisting of vincristine, methotrexate, and antracyclines.To prevent CNS leukemia, most ALL survivors had received intrathecal injections of methotrexate, whereas only 13.8% of the survivors had received cranial irradiation.Structural magnetic resonance imaging showed smaller volumes of multiple brain structures in long-term survivors of childhood ALL compared with matched healthy controls.Although the study contained the largest number of
Fifth of e antigen negative carriers of hepatitis B virus should not perform exposure prone procedures
Authors: E H Boxall, A Ballard
Journal: BMJ (1997)

Martyn Halle has reported on a surgeon with hepatitis B who transmitted the infection to a patient who subsequently died.1 2 This case has put pressure on the Department of Health to review guidelines on the employment of healthcare workers with hepatitis B who carry out exposure prone procedures. The current guidelines exclude all carriers of hepatitis B virus who are also positive for hepatitis B e antigen (that is, those with high infectivity) from carrying out such procedures.

It has been recognised that carriers of hepatitis B …