tbuckley/cabot-search huggingface dataset:
Mutation of the Mg2+ Transporter SLC41A1 Results in a Nephronophthisis-Like Phenotype
Authors: Toby W. Hurd, Edgar A. Otto, Eikan Mishima, Heon Yung Gee, Hana Inoue, Masato Inazu, Hideomi Yamada, Jan Halbritter, George Seki, Masato Konishi, Weibin Zhou, Tsutomo Yamane, Satoshi Murakami, Gianluca Caridi, Gianmarco Ghiggeri, Takaaki Abe, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2013)

Nephronophthisis (NPHP)-related ciliopathies are recessive, single-gene disorders that collectively make up the most common genetic cause of CKD in the first three decades of life. Mutations in 1 of the 15 known NPHP genes explain less than half of all cases with this phenotype, however, and the recently identified genetic causes are exceedingly rare. As a result, a strategy to identify single-gene causes of NPHP-related ciliopathies in single affected families is needed. Although whole-exome resequencing facilitates the identification of disease genes, the large number of detected genetic variants hampers its use. Here, we overcome this limitation by combining homozygosity mapping with whole-exome resequencing in a sibling pair with an NPHP-related ciliopathy. Whole-exome capture revealed a homozygous splice acceptor site mutation (c.698G>T) in the renal Mg2+ transporter SLC41A1. This mutation resulted in skipping of exon 6 of SLC41A1, resulting in an in-frame deletion of a transmembrane helix. Transfection of cells with wild-type or mutant SLC41A1 revealed that deletion of exon 6 completely blocks the Mg2+ transport function of SLC41A1. Furthermore, in normal human kidney tissue, endogenous SLC41A1 specifically localized to renal tubules situated at the corticomedullary boundary, consistent with the region of cystogenesis observed in NPHP and related ciliopathies. Last, morpholino-mediated knockdown of slc41a1 expression in zebrafish resulted in ventral body curvature, hydrocephalus, and cystic kidneys, similar to the effects of knocking down other NPHP genes. Taken together, these data suggest that defects in the maintenance of renal Mg2+ homeostasis may lead to tubular defects that result in a phenotype similar to NPHP.
Chemical communication threatened by endocrine-disrupting chemicals.
Authors: Jennifer E Fox
Journal: Environmental Health Perspectives (2004)

Communication on a cellular level--defined as chemical signaling, sensing, and response--is an essential and universal component of all living organisms and the framework that unites all ecosystems. Evolutionarily conserved signaling "webs," existing both within an organism and between organisms, rely on efficient and accurate interpretation of chemical signals by receptors. Therefore, endocrine-disrupting chemicals (EDCs), which have been shown to disrupt hormone signaling in laboratory animals and exposed wildlife, may have broader implications for disrupting signaling webs that have yet to be identified as possible targets. In this article, I explore common evolutionary themes of chemical signaling (e.g., estrogen signaling in vertebrates and phytoestrogen signaling from plants to symbiotic soil bacteria) and show that such signaling systems are targets of disruption by EDCs. Recent evolutionary phylogenetic data have shown that the estrogen receptor (ER) is the ancestral receptor from which all other steroid receptors have evolved. In addition to binding endogenous estrogens, ERs also bind phytoestrogens, an ability shared in common with nodulation D protein (NodD) receptors found in Rhizobium soil bacteria. Recent data have shown that many of the same synthetic and natural environmental chemicals that disrupt endocrine signaling in vertebrates also disrupt phytoestrogen-NodD receptor signaling in soil bacteria, which is necessary for nitrogen-fixing symbiosis. Bacteria-plant symbiosis is an unexpected target of EDCs, and other unexpected nontarget species may also be vulnerable to EDCs found in the environment.
The advantages of VATS: a systematic review
Authors: R V Reddy
Journal: Thorax (2005)

▴ Sedrakyan A, van der Meulen J, Lewsey J, et al . Video assisted thoracic surgery for treatment of pneumothorax and lung resections: systematic review of randomised clinical trials. BMJ2004;329:1008–10. [OpenUrl][1][Abstract/FREE Full Text][2] The authors carried out a systematic review of 12 randomised clinical trials to determine if video assisted thoracic surgery (VATS) is associated with better clinical outcomes than thoracotomy for three common thoracic procedures: surgery for pneumothorax, minor resections (wedge and segmental resections), and lobectomy. Six trials compared … [1]: {openurl}?query=rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.38243.440486.55%26rft_id%253Dinfo%253Apmid%252F15385408%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=329/7473/1008&atom=%2Fthoraxjnl%2F60%2F3%2F238.atom
Building a framework for trust: critical event analysis of deaths in surgical care
Authors: A M Thompson, P A Stonebridge
Journal: BMJ (2005)

The British public's confidence in doctors and hospitals has been dented in recent years. Use of an independent review of deaths before, during, or after surgery reflects an attempt to improve care in this area and may also help to restore the public's trust in their health service

Events over recent years have undermined patients' and society's trust in clinicians and healthcare institutions. For clinicians to restore and retain public confidence, they need to show that effective mechanisms exist for assessing events such as death and to justify patients' faith in the delivery of care.1

In the high profile world of cardiac surgery, the audited results of key elective procedures may be sufficient to restore confidence.2 In wider surgical practice, simple death rates are unlikely to be sufficient; case-mix (particularly for emergency admissions), institutional, and national issues can jeopardise the interests of high risk patients.3

Any critical incident review by peers working in the same speciality or subspecialty of patients who die under surgical care should take into account the nature of the patient and the circumstances of admission. In Scotland, the Scottish Audit of Surgical Mortality (SASM) is a national system of peer review of deaths that occur under surgical care that has been in place since 1994.4 Full details of how SASM works, and the annual reports, are on its website (http://www.sasm.org.uk/).

SASM uses the consultant surgeon responsible for the care of the deceased patient as a proxy for the secondary care system and includes all deaths under surgical care in Scotland (including the private sector) except for cardiac surgery and obstetric deaths, which are currently audited separately. SASM assesses the patient's last journey of care, not simply the role of a single clinician or clinical team.

The method of case assessment and …
Positional Effects on Distribution of Ventilation in Chronic Obstructive Pulmonary Disease
Authors: CHANG SHIM
Journal: Annals of Internal Medicine (1986)

Ventilation is distributed predominantly to the dependent lung in normal persons in the decubitus position. We evaluated the distribution of ventilation in four patients with mild-to-moderate chronic obstructive pulmonary disease using 81mKr gas. Patients were tested in the sitting and right and left decubitus positions with and without the application of positive end expiratory pressure (PEEP). In contrast to findings in controls, ventilation was predominantly distributed to the nondependent lung in patients in the decubitus position. Mean ventilation in the right lung decreased from 51% of the total in the sitting position to 31% in the right decubitus position; it increased with the application of 10 cm PEEP. Reduced ventilation in the dependent lung most likely is caused by closure of the airways after a decrease in volume. Application of PEEP resulted in increased lung volume and preferential distribution of ventilation to the dependent lung.
Pirfenidone reduced disease progression in idiopathic pulmonary fibrosis
Authors: Fiona Lake
Journal: Annals of Internal Medicine (2014)

Source Citation King TE Jr, Bradford WZ, Castro-Bernardini S, et al; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083-92. 24836312
Henoch-Schönlein Syndrome Associated With Quinidine
Authors: A. Aviram
Journal: JAMA (1980)

<h3>To the Editor.—</h3> We have seen a case of Henoch-Schönlein syndrome with severe irreversible renal involvement we believe was due to quinidine. <h3>Report of a Case.—</h3> A 63-year-old man was admitted because of uremia of recent onset. He had had a single attack of gouty arthritis 15 years previously, for which he continuously received allopurinol, 200 mg daily. One year ago he had an acute myocardial infarction. There was no history of allergies or drug reactions. Six weeks before the admission, he was hospitalized because of paroxysmal atrial fibrillation. Following DC-cardioversion he was given quinidine (0.8 grains/day). His BUN level was 35 mg/dL; the level of uric acid was 5.8 mg/dL; and the results from urinalysis were normal. After two uncomplicated days, he was discharged with instructions to continue the quinidine and allopurinol treatment. Two weeks later he was admitted to a department of dermatology because of a purpuric eruption
Ang1 and Tie2 Are Predictive Biomarkers for Bevacizumab—Letter
Authors: Joseph Ciccolini, Cindy Serdjebi, Dominique Barbolosi, Bruno Lacarelle, Fabrice Barlesi
Journal: Clinical Cancer Research (2015)

In their interesting article published in the September 2014 issue of Clinical Cancer Research , Backen and colleagues ([1][1]) analyzed angiogenesis-related factors as predictive biomarkers in patients with ovarian cancer treated with bevacizumab. Combined Ang1 and Tie2 concentrations in plasma
Factors Influencing Primary Cesarean Rates-Reply
Authors: Kiyoko M. Parrish
Journal: JAMA (1994)

<h3>In Reply.</h3> —We are pleased that Ms Taffel and colleagues, using a national data set, have confirmed our statewide findings concerning the impact of demographic changes on cesarean rates. Birth weight and plurality were not important components of the change in cesarean rates in their analysis because these distributions have not changed dramatically during the past two decades in the United States. However, birth weight may be an important confounder in international comparisons, if countries vary widely in low-birth-weight rates. We found that primiparous women delivering lowbirth-weight infants had twice the risk of cesarean delivery of those delivering infants weighing 2500 to 3499 g, while among multiparous women the risk was more than fivefold. We appreciate the utility of the approach by Taffel et al, using nationally compiled vital records data. However, we believe that one strength of our study lay in the accuracy with which we were able to
Combined Test for Assessment of Anterior Pituitary Function
Authors: P. Harsoulis, J. C. Marshall, S. F. Kuku, C. W. Burke, D. R. London, T. R. Fraser
Journal: BMJ (1973)

A combined test consisting of the simultaneous administration of insulin, thyrotrophin-releasing hormone (TRH), and luteinizing hormone and follicle stimulating hormone-releasing hormone (LH/FSH-RH) was performed in 24 people. Eleven of these also had the three individual tests performed separately, and the remaining 13 had a separate test of either LH/FSH-RH and TRH together or singly at a later date. In both normal people and patients, whether the tests were performed alone or in combination, no difference was found between the hormone responses (growth hormone, cortisol, LH, FSH, thyroid-stimulating hormone) seen to these stimuli. It is proposed that combined administration of insulin and the hypothalamic releasing hormones may be used as a single test for the assessment of anterior pituitary function. The test is convenient and time saving, and with care can be performed in outpatients.
Troglitazone: antihyperglycemic activity and potential role in the treatment of type 2 diabetes.
Authors: A J Scheen, P J Lefèbvre
Journal: Diabetes Care (1999)

Insulin resistance is a major component of type 2 diabetes; therefore, an insulin sensitizer agent like the thiazolidinedione compound troglitazone is considered a very promising drug. Troglitazone exerts an antihyperglycemic activity in a dose-dependent manner between 200 and 600 mg/day in type 2 diabetic patients treated with diet alone, sulfonylureas, or insulin. Additive antihyperglycemic effect may also be obtained by combining troglitazone and metformin. The antihyperglycemic effect of troglitazone as monotherapy is rather modest (reduction of HbA1c by 0.5-1.0%), but it appears to be somewhat greater when it is combined with other antidiabetic drugs. No double-blind studies have directly compared the activity of troglitazone with that of sulfonylureas or metformin. Troglitazone has been shown to exert additional beneficial effects on serum lipid profile and arterial blood pressure. It may be considered as a valuable alternative in insulin-resistant (obese and hyperinsulinemic) diabetic patients who appear to be the best responders to the drug. However, the efficacy of troglitazone is challenged by its safety profile, and the risk of hepatotoxicity still remains a major concern in clinical practice.
Letter: Medicine in the open university.
Authors: W I Shipley
Journal: BMJ (1973)

Lung Cancer and Smoking SIR,-It seems that cigarette smokers adjust the number of cigarettes smokzd to obtain a predetermined dose of nicotine (Dr.M. A. H. Russell and others, 1 December, p. 512).Would it not be much safer (no tar), and much cleaner for non-smokers in the vicinity, to market nicotine inhalers, similar to those used by asthmatics?The price of these could be adjusted so that the Govern- ment need not lose revenue.The nicotine addicts would presumably not be at risk from bronchogenic carcinoma and chronic bronchitis, and there would be no carbon monoxide to contribute to atheroma forma- tion.-Iam, etc.,
Limited role of intravenous propafenone hydrochloride in the treatment of sustained ventricular tachycardia: Electrophysiologic effects and results of programmed ventricular stimulation
Authors: John U. Doherty, Harvey L. Waxman, Michael G. Kienzle, Dennis M. Cassidy, Francis E. Marchlinski, Alfred E. Buxton, Mark E. Josephson
Journal: Journal of the American College of Cardiology (1984)
Gastroscopy
Authors: Emmanuel Deutsch
Journal: New England Journal of Medicine (1954)

GASTROSCOPY is a valuable procedure in differentiating benign from malignant lesions of the stomach but is nevertheless only an adjunct to detailed history taking and physical, laboratory and x-ray examinations. It can sometimes establish a diagnosis, particularly in the gastritides, when other diagnostic methods have failed. Much of the uncertainty and speculation concerning enlarged gastric rugae demonstrated by x-ray examination has been eliminated since its introduction; when a lesion can be seen at gastroscopy, a precise anatomic diagnosis can be made.From October, 1950, to September, 1953, I performed gastroscopic examination in more than 300 patients, some more than once, . . .
Incoherent policies and excessive change undermine health strategy
Authors: Caroline White
Journal: BMJ (2004)

Incoherent policies and constant structural change are undermining the UK government's blueprint for health service improvements and fostering a culture of distrust, concludes a swingeing critique published this week.

Lost in Translation , from the NHS Plan Working Group, is the third in a series of reports on the government's progress in achieving its stated aims for modernising health services, set out in the NHS Plan in July 2000.

The report, which covers health inequalities and …
Blood pressure in chronic kidney disease stage 5D—report from a Kidney Disease: Improving Global Outcomes controversies conference
Authors: Nathan W. Levin, Peter Kotanko, Kai-Uwe Eckardt, Bertram L. Kasiske, Charles Chazot, Alfred K. Cheung, Josep Redon, David C. Wheeler, Carmine Zoccali, Gérard M. London
Journal: Kidney International (2009)
Sodium Salicylate and Aspirin Disease
Authors: Ronald Dahl
Journal: Allergy (1980)

Patients with “aspirin disease” are often offered a diet devoid not only of food colorants and food preservatives but also of salicylic acid. In patient reacting with bronchial asthma after aspirin ingestion administration of large amounts of sodium salicylate did not elicit any reaction. It is therefore concluded that a less strict diet without exclusion of salicylate‐containing food can be recommended.
The Physician and the Hypochondriacal Patient
Authors: Gerald Adler
Journal: New England Journal of Medicine (1981)

THE hypochondriacal patient is one who insistently complains about physical symptoms for which there are no demonstrable organic findings, or who has symptoms that are notably out of proportion to the (usually minor) physical signs. For such patients, the relationship with the physician is especially important; concerns about physical symptoms become a major way of interacting, often making it difficult for the physician to help the patient. The patient's behavior is frequently insistent and demanding, with overt or barely submerged anger. Current or past physicians may be devalued and blamed for inadequacies in diagnosis and care. The feelings and responses . . .
Blood Exchange and Hepatic Coma
Authors: Ralph F. Wells
Journal: JAMA (1968)

ABSTRACT To the Editor:— The paper, Blood Exchange in the Treatment of Hepatic Coma, by Berger et al which appeared in The Journal recently (202:267,1967) presents a novel approach to a grave and frustrating problem. Having observed the enthusiasm with which his earlier report (New Eng J Med274:497, 1966) was seized upon by members of my house staff, I feel it necessary to sound a note of caution. When such a paper is presented in a widely read journal it is incumbent on the author to stress that this is a therapeutic innovation or more specifically an area for further clinical investigation. Meticulous attention must be given to assessment of fluid and electrolyte balance and the full utilization of other more readily available therapeutic measures. The proposed approach places an enormous burden on area blood banking facilities, the hospital laboratory, and nursing personnel. At the present time it
Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity
Authors: Wei-Tien Tai, Chung-Wai Shiau, Yong-Shi Li, Chun-Wei Chang, Jui-Wen Huang, Ting-Ting Hsueh, Hui-Chuan Yu, Kuen-Feng Chen
Journal: Journal of Hepatology (2014)
Role of automatic staplers in the aetiology of bronchopleural fistula.
Authors: W S Hennig
Journal: Thorax (1985)

Role of automatic staplers in the aetiology of broncho- pleural fistula SIR,-In their article in January 1985 (40:27-31) Mr M Hakim and Mr BB Milstein reported on the incidence of bronchopleural fistula following pneumonectomy.They suggest that the use of the TA-55 Premium instrument contributes to a significantly higher rate of bronchopleural fistula following pneumonectomy than the original style and indicate that the differences are related to differences in design and function of the two staplers.
Identification of Autoantibody-Negative Autoimmune Type 2 Diabetic Patients
Authors: Barbara M. Brooks-Worrell, Jessica L. Reichow, Amit Goel, Heba Ismail, Jerry P. Palmer
Journal: Diabetes Care (2010)

OBJECTIVE Islet autoimmunity has long been recognized in the pathogenesis of type 1 diabetes and is becoming increasingly acknowledged as a component in the pathogenesis of type 2 diabetes. Islet reactive T cells and autoantibodies have been demonstrated in type 1 diabetes, whereas islet autoimmunity in type 2 diabetes has been limited to islet autoantibodies. In this study, we investigated whether islet reactive T cells might also be present in type 2 diabetic patients and how islet reactive T cells correlate with β-cell function. RESEARCH DESIGN AND METHODS Adult phenotypic type 2 diabetic patients (n = 36) were screened for islet reactive T-cell responses using cellular immunoblotting and five islet autoantibodies (islet cell antibody, GADA, insulin autoantibody, insulinoma-associated protein-2 autoantibody, and zinc transporter autoantibody). RESULTS We identified four subgroups of adult phenotypic type 2 diabetic patients based on their immunological status (Ab−T−, Ab+T−, Ab−T+, and Ab+T+). The Ab−T+ type 2 diabetic patients demonstrated T-cell responses similar to those of the Ab+T+ type 2 diabetic patients. Data were adjusted for BMI, insulin resistance, and duration of diabetes. Significant differences (P &amp;lt; 0.02) were observed among groups for fasting and glucagon-stimulated C-peptide responses. T-cell responses to islet proteins were also demonstrated to fluctuate less than autoantibody responses. CONCLUSIONS We have identified a group of adult autoimmune phenotypic type 2 diabetic patients who are Ab−T+ and thus would not be detected using autoantibody testing alone. We conclude that islet autoimmunity may be more prevalent in adult phenotypic type 2 diabetic patients than previously estimated.
Directed Biopsy Using a Small Endoscope
Authors: Stephen R. Ash, Felice Manfredi
Journal: New England Journal of Medicine (1974)

THE diagnosis of diseases of the pleura and peritoneum often requires histologic examination of material from the serosa or from related organs. For this reason, blind biopsy of the lung, liver, pleura or peritoneum is often performed. However, serious sampling errors are involved in blind biopsy, which is positive in only 48 to 67 per cent of cases of pleural carcinomatosis1 , 2 and in only 58 to 65 per cent of cases of tuberculous pleuritis.1 , 2 Blind biopsy of the liver is positive in only 20 to 31 per cent of cases of metastatic disease.3 , 4 Visually directed biopsy can greatly reduce such . . .
Symptoms and immunologic markers induced by exposure to methyltetrahydrophthalic anhydride
Authors: J. Nielsen, H. Welinder, I. Bensryd, P. Andersson, S. Skerfving
Journal: Allergy (1994)

A study was performed in 43 workers exposed to methyltetrahydrophthalic anhydride (MTHPA) used as a hardener in an epoxy resin system. Ten workers sensitized to MTHPA (group SS; presence of serum IgE antibodies against a conjugate of MTHPA and human serum albumin (HSA) detected by RAST) had significantly higher levels of tryptase in nasal lavage fluid than 19 nonsensitized workers with work‐related nasal symptoms (group NS) and 14 nonsensitized workers without nasal symptoms (group NN). This suggests an ongoing mast‐cell‐mediated reaction in the sensitized group. No statistically significant differences were found in the three groups concerning eosinophil cationic protein (ECP) and TAME‐activity in lavage fluid. However, there was a significant increase in serum ECP in the SS group, as compared with a group of unexposed controls. Nasal challenge with MTHPA‐HSA, performed in a subsequent study in seven workers from the SS group, six from the NS group, and seven from the NN, caused a larger increase of symptom score and a more pronounced decrease in nasal inspiratory peak flow in the SS group than in the other two groups. No significant rise was recorded for tryptase and ECP in lavage fluid in any of the three groups after challenge. The combined results of the two studies indicate that specific IgE antibodies play a pathogenetic role in at least some of the cases of work‐related nasal symptoms associated with MTHPA exposure.