tbuckley/cabot-search huggingface dataset:
Long-Term Hyperglycemia Is Related to Peripheral Nerve Changes at a Diabetes Duration of 4 years
Authors: Catherine Allen, Guanghong Shen, Mari Palta, Barend Lotz, Richard Jacobson, Donn D'Alessio
Journal: Diabetes Care (1997)

OBJECTIVE To examine longitudinal hyperglycemia and peripheral nerve responses in a population-based incident cohort. RESEARCH DESIGN AND METHODS A sample from an incident cohort of young people was comprehensively followed from diagnosis of IDDM. Participants were invited to submit blood samples three times per year for central testing of GHb. During their 4th year of diabetes, nerve conduction studies were performed on the median sensory and motor, peroneal motor, and sural sensory nerves. Relationships between mean GHb and nerve latencies, velocities, and amplitudes were explored. RESULTS GHb was positively related to all nerve latencies and negatively related to all nerve velocities. The relationships between mean GHb and nerve conduction latencies and velocities differed by sex for the peroneal nerve latency (β = 0.17 male subjects, β = −0.01 female subjects; P &amp;lt; 0.001). Pubertal participants had lower velocities and longer latencies than prepubertal participants (β = 0.37; P = 0.05 peroneal latency), after adjustment for GHb, height, and extremity temperature. Sensory and motor nerve amplitudes were related to GHb, and these relationships did not differ by sex. CONCLUSIONS Our study indicates that sustained hyperglycemia is related to functional changes, at the minimum, in peripheral sensory and motor nerve conduction at a diabetes duration of 4 years. Our findings are consistent with a dying-back neuropathy, and there is some suggestion that chronic hyperglycemia may be more detrimental to nerves in male subjects than in female subjects.
Novel Molecular Mechanism of Increased Myocardial Endothelin-1 Expression in the Failing Heart Involving the Transcriptional Factor Hypoxia-Inducible Factor-1α Induced for Impaired Myocardial Energy Metabolism
Authors: Yoshihiko Kakinuma, Takashi Miyauchi, Koichi Yuki, Nobuyuki Murakoshi, Katsutoshi Goto, Iwao Yamaguchi
Journal: Circulation (2001)

Background —Hypoxia-inducible factor (HIF)-1α is an important transcriptional factor that activates the gene expression of glycolytic enzymes, which are activated as compensation for impaired β-oxidation of fatty acid in the failing heart. We reported that cardiac endothelin (ET)-1 expression is markedly increased in heart failure. The mechanism, however, is unknown. Because we found an HIF-1α binding site in the 5′-promoter region of the ET-1 gene, we hypothesized that HIF-1α is involved in this mechanism. Methods and Results —In rat cardiomyocytes, luciferase assay and electrophoretic mobility shift assay showed that HIF-1α transcriptionally activates ET-1 gene expression by direct interaction with the predicted DNA binding site in the 5′-promoter region. HIF-1α mRNA and ET-1 mRNA in the failing heart increased during the aggravation of heart failure in vivo in animal models, ie, rats with myocardial infarction and hamsters with cardiomyopathy. In cultured cardiomyocytes treated with a mitochondrial inhibitor, HIF-1α mRNA and ET-1 mRNA were markedly increased with activated glycolysis, and antisense oligonucleotide for HIF-1α largely inhibited the increased gene expression of ET-1. Conclusions —The present study revealed a novel molecular mechanism of upregulation of myocardial ET-1 in heart failure, indicating that induction of HIF-1α to stimulate glycolysis as an adaptation in heart failure against impaired energy metabolism alternatively causes an elevation of cardiac ET-1 gene expression as a maladaptation.
Cancer Neurology in Clinical Practice
Authors: Muhyi Al-Sarraf
Journal: Annals of Internal Medicine (2003)

Medical Writings: Book Notes1 April 2003Cancer Neurology in Clinical PracticeMuhyi Al-SarrafMuhyi Al-SarrafSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-138-7-200304010-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Schiff D, Wen PY, eds. 464 pages. Totawa, NJ: Humana Pr; 2003. $175.00. ISBN 0896039226. Order at www.humanapress.com.Field of medicine: Clinical medicine.Format: Hardcover book.Audience: Neurologists, neurosurgeons, radiologists, medical oncologists, and general internists.Purpose: To analyze how cancer affects the nervous system. The book encompasses the experience of senior physicians actively engaged in the field of neurooncology.Content: The book explains the impact of neurologic diseases on cancer and on the field of neurooncology. It covers the diagnosis, mechanisms, and treatments of neurologic symptomsseizures, headaches, confusion, delirium, and painin patients with cancer and the use of corticosteroids in ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 2003Volume 138, Issue 7Page: 612KeywordsCancer treatmentMelanomaNervous systemNeurologyNeuromuscular diseasesNeurosurgeryRadiologistsSarcomaSkullSoftware tools ePublished: 1 April 2003 Issue Published: 1 April 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Infantile Paralysis: A Clinical Study
Authors: J. M. Gill
Journal: BMJ (1926)

TKsan have been many epidemics of infantile paralysis in Australia and New Zealand during the present century.The fir-st occurred in Sydney in 19032 during November and December, when about forty cases were treated at the Childreni's Hospital.From Sydney it spread durinig the couI-se of the following year over the greater palrt of Kew South WVales and Queensland.From 1903 to 199 there was ani interval, but from 1909 to 1916 there were annual epidemics, always reaching their height in the later ka.lf of the suimmer and in the autumn.There was again anl interval till 1921.There were mild epidemics in Sydney il 1921, 1923, and 1924, but none this year (1925).In 1923 I collected the notes of about ten or twelve cases altogether, some being doubtful.In 193 there were forty cases in the hospital, seventeen being under my care; one doubtful ealse was fatal, but no post-mortenm examination was allowed.In 1924 there were forty-five cases in the hos- pital, one fatal; no post-mortem examination was allow-ed.The last two epidemics were very similar.They both reached their maxium later than usual.In 1923 most -ases were admitted in May, a cool month; in 1924 in March.Both epidemics were mild, with a hiigh recover y and a low mortality rate.A very extensive epidemic visited New Zealand, but not Australia, in 1925.Age.-Of forty cases in the Children's H-ospital in 1923, eighteen were between 1 and 2 years of age, and twelve between 2 and 3 years; that is thirty out of forty were in the second and third' years of life.There was only one under 12 months (7 months); the oldest was 8 years of age.The age incidence in the 1924 epidemic was very similar.These figures agree with those published by other writers.In Sydney cases in adults lhave been very rare, anid the disease is ver y seldom seen even in adolescent boys and girls.Most authors follow Wickman and describe eight cliniical tyj)es.These are usually given as follows:1. Spinal or common type.2. Landry's paralysis type.3. Bulbar or pontine. 4. Encephalitic type, which is responsible for many of the fatal cases in infants. Neuritic type.There is some doubt about this forming a separate group, as neuritic symptoms are vely common in the spinal form.Speaking for myself, I have never seen a case in which the central nervous system was not involved.6. Meningitic form.7. Transverseniyelitis type.A. Abortive form.The classification into types is conveniient, as the sym- ptoms vary a good deal in differeiit cases.CAsE I.-Rigidity of Spine wcith Paralysis of Legs.T shall begin by describing a typical case in the Clhildren's Hospital last year (1924).She had been treated at the ouitdoor
Expression of Phosphodiesterase-5 in Lymphatic Malformation Tissue
Authors: Julie S. Green, Lori Prok, Anna L. Bruckner
Journal: JAMA Dermatology (2014)

Lymphatic malformations (LMs) are uncommon and sometimes debilitating congenital vascular anomalies that presumably arise because of developmental dysplasia of the lymphatic network in utero.They comprise primitive lymphatic sacs surrounded by a thickened layer of connective tissue and interspersed muscle fibers. 1 Current treatments for LM are palliative and only partially successful and include compression, surgical resection, laser ablation, and sclerotherapy.A recent report by Swetman and colleagues 2 noted marked reductions in LM size in 3 children after starting treatment with oral sildenafil citrate, an inhibitor of phosphodiesterase isoform 5 (PDE5).The localization of PDE5 in LM tissue and the mechanism of the effect of sildenafil on LM is unknown.To further investigate PDE5 localization within LM tissue, we performed immunohistochemical studies to identify the presence and relative location of PDE5 expression in vascular smooth muscle, vascular endothelium, and lymphatic endothelium.
A4-01: Intrapulmonary metastasis in resected pathological stage IIIB non-small cell lung cancer: possible contribution of aerogenous metastasis to the favorable outcome
Authors: Keiju Aokage, Genichiro Ishii, Kanji Nagai, Osamu Kawai, Yoichi Naito, Takahiro Hasebe, Mitsuyo Nishimura, Junji Yoshida, Atsushi Ochiai
Journal: Journal of Thoracic Oncology (2007)
Abstract 729: Norleual a hepatocyte growth factor/c-Met inhibitor blocks malignant phenotypes in cancerous cells
Authors: Leen H. Kawas, Kevin J. Church, Malte Lange, Michelle Mcmicheal, Brent Yamamoto, Joseph W. Harding
Journal: Cancer Research (2014)

Abstract The primary purpose of this study was to demonstrate that the hepatocyte growth factor (HGF) antagonist norleual is capable of attenuating the cellular responses of cancer cells to HGF. The angiotensin IV analog norleual [Nle-Tyr-Ile-ψ-(CH2-NH2)3-4-His-Pro-Phe] exhibits structural homology with the hinge (linker) region of HGF and acts to block HGF dimerization, a process required for its activation. Norleual competitively inhibited the binding of a H3-Hinge peptide sequence to the HGF, and binds directly to HGF with a Ki = 3.6x10-12M. Predictably, norleulal is able to block the cellular responses due to HGF activation in multiple cell types at concentrations in the picomolar range including HGF/c-Met sensitive pancreatic cancer cells. Norleual's ability to inhibit the growth and survival of several cell lines including pancreatic cancer cells was evaluated using viability testing and cell sorting tags to identify living, dead and apoptotic cells. HGF/c-Met activation increases the invasive potential of the pancreatic cancer cells, which provides a mechanistic basis for the ability of c-Met to support pancreatic tumor metastasis. In this regard norleual as an HGF antagonist was able to block the migration and invasion of cancer cells through collagen gels in a transwell chamber. Over-activation of the growth factor system HGF/c-Met is a critical contributor to cancer's ability to disseminate rapidly and its refractoriness to standard chemotherapy. Norleual, which is a representative of a “first-in-class” group of molecules that blocks the activation step of HGF, represent a novel therapeutic approach to the treatment of HGF/Met sensitive cancers including pancreatic cancer. Citation Format: Leen H. Kawas, Kevin J. Church, Malte Lange, Michelle Mcmicheal, Brent Yamamoto, Joseph W. Harding. Norleual a hepatocyte growth factor/c-Met inhibitor blocks malignant phenotypes in cancerous cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 729. doi:10.1158/1538-7445.AM2014-729
The Changing Face of Asthma
Authors: Roland B. Christian
Journal: JAMA (1991)

To the Editor.—  The observations that the increased mortality and hospitalization for asthma occur in urban areas, and particularly with geographical localization in the Northeast and North Central1,2areas, bring to mind possible correlation with air pollutants. Urban localities tend to have a higher concentration of smog, particularly in the Northeast and North Central areas, which have been plagued by nitrous oxide and sulfur dioxide emissions as well as ozone problems. Neither article mentions an association to possible ozone or nitrous oxide levels in these areas as a cause for the changing patterns of hospitalization and mortality in asthma.  It is known that ozone decreases pulmonary function in younger and older nonsmoking volunteer patients.3Concentrations of ozone and other air pollutants are regularly determined in metropolitan areas and, generally, at several locations in large metropolitan areas. This information thus should allow correlation with the asthma hospitalization and mortality
Unemployment and mortality among Finnish men, 1981-5.
Authors: P T Martikainen
Journal: BMJ (1990)

OBJECTIVE--To ascertain whether, after controlling for several relevant background variables simultaneously, unemployment is related to mortality and to assess whether this relation is causal or whether unhealthy people are more likely to become unemployed. DESIGN--Prospective study of mortality in Finland during 1981-5 based on 1980 census data on 30-54 year old wage earner men and with particular attention to unemployment in the year before the census. SETTING--Research project at the University of Helsinki. SUBJECTS--All wage earner men in Finland aged 30-54 at the 1980 census. MAIN OUTCOME MEASURES--Causes of death during 1981-5 and duration of unemployment in the year before the census. Background variables controlled for were age, socioeconomic state, marital state, and health. The data were analysed by log linear regression models. RESULTS--During the study period 1981-5, which covered almost 2.7 million person years, there were 9810 deaths. After controlling for all background variables relative total mortality among unemployed versus employed men was 1.93 (95% confidence interval 1.82 to 2.05). The excess mortality was highest in accidental and violent causes of death (relative mortality 2.51; 95% confidence interval 2.28 to 2.76). For circulatory diseases the relative death rate was 1.54 (95% confidence interval 1.40 to 1.70), but among neoplasms only lung cancer was associated with excess mortality. Selection for unemployment based on age, socioeconomic state, and marital state was evident but no such selection was detected based on health. Effects of unemployment on mortality were more pronounced with increasing duration of unemployment. CONCLUSIONS--The relative excess mortality of unemployed men in Finland cannot fully be explained by demographic, social, and health variables preceding unemployment. Unemployment therefore seems to have an independent causal effect on male mortality. Further studies are needed to elucidate the mechanisms between unemployment and mortality.
Geriatric Accommodation in Acute Illness
Authors: R. Tepper
Journal: BMJ (1972)

usually refers to the destruction of the fetus per se.But as Dr. Wilkinson points out, many doctors conscientiously consider the needs of the whole person, allowing for the possibility that these needs may conflict with the patient's immediate demands.In my view these two issues are not distinct from each other; the destruction of the fetus must rarely be compatible with the whole patient's needs.If a woman (in one way way or another) procures an abortion, this indicates that we, as doctors, relatives, or citizens, have been failing to help her.-Iam, etc.,
Improved L.E. Cell Test Using Finger-prick Blood
Authors: H. Lempert, G. M. Berlyne
Journal: BMJ (1957)

The L.E. cell is recognized as a neutrophil polymorphonuclear leucocyte whose nuclear lobes are compressed to the periphery of the cell by the inclusion of homo- genous material which stains a reddish purple with the usual blood stains.There is much evidence in favour of the inclusion material being nuclear in origin.Occasionally cells are found in which an ingested cell can still be recognized; these cells are " tart" cells and must not be confused with L.E. cells, in which the ingested material has lost all its nuclear structure.The production of L.E. cells from bone marrow or blood of patients suffering from systemic lupus erythematosus (S.L.E.) would appear to be essential for a complete diagnosis.Many methods have been devised for producing L.E. cells from venous blood, amongst
A Theory of Medical Ethics
Authors: Howard Brody
Journal: JAMA (1982)

Veatch's volume now takes its place in the third generation of works on medical ethics to appear since this field was revitalized in the 1960s. The first-generation books, mostly collections of essays, called attention to the importance of ethical issues in medicine and summarized current physician thinking. The second generation, to which Veatch made notable contributions (as associate for medical ethics at the Hastings Center, before assuming his current position as professor of medical ethics at the Kennedy Institute of Ethics at Georgetown), produced single-author texts or carefully edited anthologies, isolating central principles and subjecting first-generation views to critical scrutiny. We are now in need of treatises like this one that look beneath and beyond case- and issue-oriented analyses to discern the theoretical underpinnings of a true<i>system</i>of medical ethics. A Theory of Medical Ethics contrasts usefully with another distinguished third-generation work, Edmund Pellegrino and David Thomasma's A Philosophical
Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome
Authors: Jérôme Ruzzin, Rasmus Petersen, Emmanuelle Meugnier, Lise Madsen, Erik-Jan Lock, Haldis Lillefosse, Tao Ma, Sandra Pesenti, Si Brask Sonne, Troels Torben Marstrand, Marian Kjellevold Malde, Zhen-Yu Du, Carine Chavey, Lluis Fajas, Anne-Katrine Lundebye, Christian Lehn Brand, Hubert Vidal, Karsten Kristiansen, Livar Frøyland
Journal: Environmental Health Perspectives (2009)

The incidence of the insulin resistance syndrome has increased at an alarming rate worldwide, creating a serious challenge to public health care in the 21st century. Recently, epidemiological studies have associated the prevalence of type 2 diabetes with elevated body burdens of persistent organic pollutants (POPs). However, experimental evidence demonstrating a causal link between POPs and the development of insulin resistance is lacking.We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders.Sprague-Dawley rats were exposed for 28 days to lipophilic POPs through the consumption of a high-fat diet containing either refined or crude fish oil obtained from farmed Atlantic salmon. In addition, differentiated adipocytes were exposed to several POP mixtures that mimicked the relative abundance of organic pollutants present in crude salmon oil. We measured body weight, whole-body insulin sensitivity, POP accumulation, lipid and glucose homeostasis, and gene expression and we performed microarray analysis.Adult male rats exposed to crude, but not refined, salmon oil developed insulin resistance, abdominal obesity, and hepatosteatosis. The contribution of POPs to insulin resistance was confirmed in cultured adipocytes where POPs, especially organochlorine pesticides, led to robust inhibition of insulin action. Moreover, POPs induced down-regulation of insulin-induced gene-1 (Insig-1) and Lpin1, two master regulators of lipid homeostasis.Our findings provide evidence that exposure to POPs commonly present in food chains leads to insulin resistance and associated metabolic disorders.
Health bill will destroy NHS, says union
Authors: C. Dyer
Journal: BMJ (2011)

Hospitals will close, tens of thousands of staff will be made redundant, and healthcare will become more expensive if the UK government’s plans for controversial reforms to the NHS in England go ahead, the country’s biggest union claims.

In a briefing for MPs and media to coincide with the second reading debate on the Health and Social Care Bill, the union Unite said that the biggest shake up in the history of the NHS would herald the “slow-motion privatisation” of the service.

Gail Cartmail, assistant general secretary of the union, said, “This bill will destroy the NHS. It will allow NHS staff, skills, buildings, and resources to be snatched by profit hungry companies. It will shove NHS patients to the back of …
A microRNA-30e/mitochondrial uncoupling protein 2 axis mediates TGF-β1-induced tubular epithelial cell extracellular matrix production and kidney fibrosis
Authors: Lei Jiang, Wenjing Qiu, Yang Zhou, Ping Wen, Li Fang, Hongdi Cao, Ke Zen, Weichun He, Chenyu Zhang, Chunsun Dai, Junwei Yang
Journal: Kidney International (2013)

Mitochondria dysfunction has been reported in various kidney diseases but how it leads to kidney fibrosis and how this is regulated is unknown. Here we found that mitochondrial uncoupling protein 2 (UCP2) was induced in kidney tubular epithelial cells after unilateral ureteral obstruction in mice and that mice with ablated UCP2 resisted obstruction-induced kidney fibrosis. We tested this association further in cultured NRK-52E cells and found that TGF-β1 remarkably induced UCP2 expression. Knockdown of UCP2 largely abolished the effect of TGF-β1, whereas overexpression of UCP2 promoted tubular cell phenotype changes. Analysis using a UCP2 mRNA-3'-untranslated region luciferase construct showed that UCP2 mRNA is a direct target of miR-30e. MiR-30e was downregulated in tubular cells from fibrotic kidneys and TGF-β1-treated NRK-52E cells. A miR-30e mimic significantly inhibited TGF-β1-induced tubular-cell epithelial-mesenchymal transition, whereas a miR-30e inhibitor imitated TGF-β1 effects. Finally, genipin, an aglycone UCP2 inhibitor, significantly ameliorated kidney fibrosis in mice. Thus, the miR-30e/UCP2 axis has an important role in mediating TGF-β1-induced epithelial-mesenchymal transition and kidney fibrosis. Targeting this pathway may shed new light for the future of fibrotic kidney disease therapy.
Infant Botulism in Adults
Authors: John C. Bartlett
Journal: New England Journal of Medicine (1986)

Botulism is a severe paralytic disease caused by the most potent of all natural toxins, according to lethality assays in animals. The appellation "botulism" is derived from the Latin botulus, in reference to the improperly prepared blood sausages that were implicated in causing the disease in the late 18th century. The putative agent is Clostridium botulinum, first isolated during an investigation of food poisoning involving 23 members of a music club in Belgium who had consumed contaminated raw salted ham.1 The organism is phenotypically identical to C. sporogenes but is unique in its production of seven serologically distinct protein . . .
The Weight of an Ounce
Authors: David Satcher
Journal: JAMA (1995)

An ounce of prevention may seem a heavy load for the already overburdened, costly US health care system. But as health reformers somewhat wishfully argued during the 19th century, the road to wellness, although a lifelong journey, holds benefits along the way for those who seek prevention before they have to seek cure. The present generation has seen evidence of what those earlier reformers could only allege: that positive effects of prevention are sometimes just around the bend. The past two decades have witnessed dramatic declines in death rates for heart disease (51% reduction) and stroke (60% reduction).<sup>1,2</sup>These vast improvements in the nation's health are attributable to medical advances and nationwide changes in specific risk factors that were identified through epidemiologic research and addressed through population-based interventions.<sup>3-5</sup>. See also p 1123. Prevention works, then. But in this era of fiscal belt-tightening, the question arises, "At what cost?"