tbuckley/cabot-search huggingface dataset:
Transbronchial Lung Biopsy in the Compromised Host
Authors: Neil T. Feldman
Journal: JAMA (1977)

Thirty-eight immunocompromised patients underwent transbronchial lung biopsy via the fiberoptic bronchoscope as part of a diagnostic evaluation for fever and roentgenographic evidence of a new pulmonary infiltrate. Diagnostic information was obtained from lung biopsy in 29 patients (76%), with infection accounting for ten cases and a nonspecific interstitial pneumonitis in 13 patients. Concomitant bronchial brushings were diagnostic in only three patients (all with infections). Diffuse roentgenographic infiltrates were expecially amenable to bronchoscopic lung biopsy diagnosis (84%), while in localized infiltrates, there was only a 43% diagnostic yield. Although thrombocytopenia and hypoxemia were common in these patients, morbidty was low (four patients had pneumothoraces with no noteworthy bleeding) and there were no deaths resulting from this procedure. Prebiopsy platelet transfusions were used in five patients with severe thrombocytopenia (platelet cound, less than 50,000/cu mm). The diagnostic efficiency and low morbidity associated with transbronchial lung biopsy indicate that this procedure can safely play a role in the evaluation of pneumonia in the compromised host.
Identification of a His54Gln substitution in von Willebrand factor from a patient with defective binding of factor VIII
Authors: Margaret E. Rick, Dennis M. Krizek
Journal: American Journal of Hematology (1996)

A patient with type 2N (“Normandy” variant) von Willebrand's disease is described. Her von Willebrand factor level was borderline low, while her factor III was markedly decreased to 7%. Her plasma von Willebrand factor demonstrated a decreased ability to complex with factor VIII in vitro, binding less than 10% when compared to normal plasma von Willebrand factor. The factor VIII released into the circulation after the patient received DDAVP had a shortened survival in vivo. Nucleotide sequence analysis revealed a T-to-A transition at nucleotide 2451 on both alleles. This transition results in a substitution of Gln for His at amino acid 54 in the mature subunit of von Willebrand factor. © 1996 Wiley-Liss, Inc.
New global health fund
Authors: T. Richards
Journal: BMJ (2001)

> But then nothing came to us for free. Not even water. It had to be carried a mile and a half, and boiled. “Boiled,” a small word, meant twenty minutes over a roaring fire on a stove that resembled the rusted carcass of an Oldsmobile. “Fire” meant gathering up a pile of sticks in a village that had already been gathering firewood for all the years since God was child, picking its grounds clean of combustibles as efficiently as an animal combing itself for lice. So “fire” meant longer and longer forays into the forest, stealing fallen branches from under the blunt eyed gaze of snakes for just one single bucket of drinkable water.1

The gap between the rich and poor has widened steadily. Estimates based on World Bank data suggest that over 40% of the 614 million people in less developed countries live in absolute poverty and that average life expectancy is now 25 years less than it is in developed countries.2 Ten years ago the countries of the Organisation for Economic Cooperation and Development (OECD) promised to scale up their development assistance. Since then the flow of aid has actually decreased to its lowest level (in relation to members' combined gross national product) for 20 years.3 Oxfam describes the rich country record on aid as “derisory” and their trade policies akin to “highway robbery.”4 The …
Video Imaging of Atrial Defibrillation in the Sheep Heart
Authors: Richard A. Gray, Gregory Ayers, Jose´ Jalife
Journal: Circulation (1997)

Background The effects of defibrillatory shocks on the organization of atrial fibrillation (AF) have not been studied previously. In this study, we examined the events that precede, accompany, and follow the application of atrial defibrillatory shocks. Methods and Results We used video imaging to study the sequence of activation on the surface of the atria in the Langendorff-perfused sheep heart. We recorded transmembrane potentials simultaneously from &gt;20 000 sites on the epicardium during AF as well as during and after biphasic shocks applied by a programmable atrial defibrillator. Defibrillatory shocks (1.2±0.6 J; n=6) depolarized all epicardial regions of the atria, and asynchronous repolarization occurred. The shocks resulted in four types of responses: (1) immediate cessation of epicardial activity, (2) single postshock activation, (3) organized activation for 0.8 to 1.5 seconds followed by termination, and (4) organized activity followed by degeneration back into AF. Types 2 through 4 involved a quiescent period lasting 110±28 ms immediately after the shock, then an activation sequence similar to those observed during sinus rhythm. The first cycle length after the shock for types 3 and 4 (170±36 ms) was longer than during AF (144±33 ms). Repolarization time after a shock was significantly longer for successful compared with unsuccessful shocks. Conclusions These results indicate that the shock depolarized the entire atrial epicardial surface, followed by a quiescent period, after which organized activation emanated from the sinoatrial pacemaker region.
Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts
Authors: J.-L. Tang, J. K Morris, N. J Wald, D. Hole, M. Shipley, H. Tunstall-Pedoe
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To investigate relation between tar yield of manufactured cigarettes and mortality from smoking related diseases. <b>Design</b>: Prospective epidemiological study of four cohorts of men studied between 1967 and 1982. <b>Setting</b>: Combined data from British United Provident Association (BUPA) study (London), Whitehall study (London), Paisley-Renfrew study (Scotland), and United Kingdom heart disease prevention project (England and Wales). <b>Subjects</b>: Of the 56255 men aged over 35 who were included in the studies, 2742 deaths occurred among 12400 smokers. Average follow up was 13 years. <b>Main outcome measures</b>: Relative mortality from smoking related diseases according to tar yields of cigarettes smoked. <b>Results</b>: Age adjusted mortality from smoking related diseases in smokers of filter cigarettes was 9% lower (95% confidence interval 1% to 17%) than in smokers of plain cigarettes (P=0.047). Mortality from smoking related diseases consistently decreased with decreasing tar yield. Relative mortality in cigarette smokers for a 15 mg decrease in tar yield per cigarette was 0.75 (0.52 to 1.09) for lung cancer, 0.77 (0.61 to 0.97) for coronary heart disease, 0.86 (0.50 to 1.50) for stroke, 0.78 (0.40 to 1.48) for chronic obstructive lung disease, 0.78 (0.65 to 0.93) for these smoking related diseases combined, and 0.77 (0.65 to 0.90) for all smoking related diseases. <b>Conclusion</b>: About a quarter of deaths from lung cancer, coronary heart disease, and possibly other smoking related diseases would have been avoided by lowering tar yield from 30 mg per cigarette to 15 mg. Reducing cigarette tar yields in Britain has had a modest effect in reducing smoking related mortality.
The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis
Authors: P. C. Adams, Y. Deugnier, R. Moirand, P. Brissot
Journal: Hepatology (1997)

The aim of this study was to investigate the relationship between iron overload, age, and clinical symptoms in genetic hemochromatosis. The relationship was studied between clinical symptoms and liver iron concentration, serum ferritin, and iron removed in a retrospective study of 410 homozygotes diagnosed using strict criteria. No significant relationship was found between liver iron concentration, iron removed by venesection, and serum ferritin level with age. The prevalence of cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue increased as liver iron concentration increased. The most common presentations at diagnosis were fatigue or as an incidental finding in all age groups. Twenty–seven percent of patients (110 of 410) had no clinical symptoms of hemochromatosis. Iron accumulation is highly variable in patients with genetic hemochromatosis. The significant relationship between liver iron concentration and cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue confirms the importance of iron toxicity in the pathogenesis of hepatic and extrahepatic disease. The nonspecific nature of the presenting features in patients and the presence of significant clinical symptoms in patients discovered through family investigations underscore the importance of family and population screening for hemochromatosis.
Follicular helper T cells are required for systemic autoimmunity
Authors: Michelle A. Linterman, Robert J. Rigby, Raphael. K. Wong, Di Yu, Robert Brink, Jennifer L. Cannons, Pamela L. Schwartzberg, Matthew C. Cook, Giles D. Walters, Carola G. Vinuesa
Journal: The Journal of Experimental Medicine (2009)

Production of high-affinity pathogenic autoantibodies appears to be central to the pathogenesis of lupus. Because normal high-affinity antibodies arise from germinal centers (GCs), aberrant selection of GC B cells, caused by either failure of negative selection or enhanced positive selection by follicular helper T (T(FH)) cells, is a plausible explanation for these autoantibodies. Mice homozygous for the san allele of Roquin, which encodes a RING-type ubiquitin ligase, develop GCs in the absence of foreign antigen, excessive T(FH) cell numbers, and features of lupus. We postulated a positive selection defect in GCs to account for autoantibodies. We first demonstrate that autoimmunity in Roquin(san/san) (sanroque) mice is GC dependent: deletion of one allele of Bcl6 specifically reduces the number of GC cells, ameliorating pathology. We show that Roquin(san) acts autonomously to cause accumulation of T(FH) cells. Introduction of a null allele of the signaling lymphocyte activation molecule family adaptor Sap into the sanroque background resulted in a substantial and selective reduction in sanroque T(FH) cells, and abrogated formation of GCs, autoantibody formation, and renal pathology. In contrast, adoptive transfer of sanroque T(FH) cells led to spontaneous GC formation. These findings identify T(FH) dysfunction within GCs and aberrant positive selection as a pathway to systemic autoimmunity.
A Longitudinal Study of Urinary Phthalate Excretion in 58 Full-Term and 67 Preterm Infants from Birth through 14 Months
Authors: Hanne Frederiksen, Tanja Kuiri-Hänninen, Katharina M. Main, Leo Dunkel, Ulla Sankilampi
Journal: Environmental Health Perspectives (2014)

Background: Some phthalates have shown antiandrogenic effects in rat offspring. Premature infants may be exposed to high amounts of specific phthalates during hospitalization, and thus are potentially at risk.Objective: We evaluated longitudinal phthalate exposure and metabolism in full-term (FT) and preterm (PT) infants.Methods: Fifty-eight FT and 67 PT (gestational age, 24.7–36.6 weeks) infants were recruited at birth and followed until 14 months (nine times). Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl phthalate isomers (DiBP and DnBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and diisononyl phthalate (DiNP) were measured in 894 samples. Daily intake and a hazard index for antiandrogenic effects were estimated, and excretion patterns of DEHP and DiNP metabolites were analyzed.Results: Metabolites of BBzP, DiNP, and DEHP were 5–50 times higher at day 7 (D7) and month 1 (M1) in PT than in FT infants. Thereafter, metabolite concentrations were similar between the two groups. The estimated hazard index for combined DiBP, DnBP, BBzP, and DEHP exposures 7 days after birth exceeded the antiandrogenic threshold in &gt; 80% of PT and &gt; 30% of FT infants, and after M2, in 30% of all infants. The excretion pattern of DEHP and DiNP metabolites changed with age.Conclusion: Most PT infants and approximately one-third of healthy FT newborns were exposed to phthalates during early life at a potentially harmful level according to the European Food Safety Authority’s recommended limits of daily exposure. Changes in the relative proportions of secondary phthalate metabolites over time were consistent with maturation of infant metabolic pathways during the first year of life. Further research is needed on the health effects of phthalate exposures and the influence of changes in metabolic capacity in neonates and infants.Citation: Frederiksen H, Kuiri-Hänninen T, Main KM, Dunkel L, Sankilampi U. 2014. A longitudinal study of urinary phthalate excretion in 58 full-term and 67 preterm infants from birth through 14 months. Environ Health Perspect 122:998–1005; http://dx.doi.org/10.1289/ehp.1307569
A randomized, controlled, split-face clinical trial of 1320-nm Nd:YAG laser therapy in the treatment of acne vulgaris
Authors: Jeffrey S. Orringer, Sewon Kang, Lisa Maier, Timothy M. Johnson, Dana L. Sachs, Darius J. Karimipour, Yolanda R. Helfrich, Ted Hamilton, John J. Voorhees
Journal: Journal of the American Academy of Dermatology (2007)
Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome
Authors: Joanna F. Flatt, Hélène Guizouarn, Nicholas M. Burton, Franck Borgese, Richard J. Tomlinson, Robert J. Forsyth, Stephen A. Baldwin, Bari E. Levinson, Philippe Quittet, Patricia Aguilar-Martinez, Jean Delaunay, Gordon W. Stewart, Lesley J. Bruce
Journal: Blood (2011)
Time to focus on positive health indicators to reduce health inequalities
Authors: M. C. Watson, E. C. Watson
Journal: BMJ (2013)

This “shocking variation in early and unnecessary deaths” across England is not a surprise to those working in public health.1 Inequality in health is a well established problem, and a wealth of varied sources of information is readily available.2 3 More than 30 years ago the delegates of a World Health Organization global …
NHS to come under Race Relations Act
Authors: J. Warden
Journal: BMJ (1999)

Race relations laws in the United Kingdom are to be enforced more widely in the public sector, including the NHS, the UK government decided last week in the wake of a damning official report on “institutional racism” in the police service.

The Stephen Lawrence inquiry into the racist murder of a black teenager in South London in 1993 found that collective racism exists in both the Metropolitan Police-which failed to …
Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization
Authors: Laura E. McCoy, Anna Forsman Quigley, Nika M. Strokappe, Bianca Bulmer-Thomas, Michael S. Seaman, Daniella Mortier, Lucy Rutten, Nikita Chander, Carolyn J. Edwards, Robin Ketteler, David Davis, Theo Verrips, Robin A. Weiss
Journal: The Journal of Experimental Medicine (2012)

Llamas (Lama glama) naturally produce heavy chain–only antibodies (Abs) in addition to conventional Abs. The variable regions (VHH) in these heavy chain–only Abs demonstrate comparable affinity and specificity for antigens to conventional immunoglobulins despite their much smaller size. To date, immunizations in humans and animal models have yielded only Abs with limited ability to neutralize HIV-1. In this study, a VHH phagemid library generated from a llama that was multiply immunized with recombinant trimeric HIV-1 envelope proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian-HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent from previous anti–HIV-1 VHH and its own germline sequence. J3 achieves broad and potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1 Env. This study may represent a new benchmark for immunogens to be included in B cell–based vaccines and supports the development of VHH as anti–HIV-1 microbicides.
Two new mutations in the <i>HIF2A</i> gene associated with erythrocytosis
Authors: Melanie J. Percy, Yu Jin Chung, Claire Harrison, Jane Mercieca, A. Victor Hoffbrand, Carla L. Dinardo, Paulo C.J.L. Santos, Guilherme H.H. Fonseca, Sandra F.M. Gualandro, Alexandre C. Pereira, Terence R.J. Lappin, Mary Frances McMullin, Frank S. Lee
Journal: American Journal of Hematology (2012)

Abstract Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen‐sensing pathway that regulates the Erythropoietin ( EPO ) gene. More specifically, recent studies have identified erythrocytosis‐associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor‐2α (HIF‐2α), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met‐535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe‐540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF‐2α with both VHL and PHD2. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Bone Disease in Primary Biliary Cirrhosis: Increased Bone Resorption and Turnover in the Absence of Osteoporosis or Osteomalacia
Authors: Jennifer A. Cuthbert, Charles Y. C. Pak, Joseph E. Zerwekh, Kenneth D. Glass, Burton Combes
Journal: Hepatology (1984)

The role of vitamin D in hepatic osteodystrophy was examined. Eleven unselected patients with primary biliary cirrhosis (PBC) were assessed for disorders of mineral and vitamin D metabolism. Six were not receiving supplementary vitamin D, and five were being treated with oral vitamin D (50,000 IU daily). Serum levels of 25-hydroxyvitamin D were normal in all patients receiving oral therapy and in 4 of 6 untreated patients. Levels of serum 1,25-dihydroxy vitamin D and 24,25-dihydroxyvitamin D were normal or near normal in all patients. Studies were repeated after 6 months of therapy with parenteral vitamin D 2 (100,000 IU i.m. monthly) in 7 patients. Initial bone histomorphometry revealed no evidence of osteomalacia or osteoporosis. However, the bone resorption surface of trabecular bone was increased. This abnormality was no longer present on repeat bone biopsies obtained after parenteral vitamin D therapy, and bone formation had decreased. In addition, trabecular bone volume remained normal in the face of the lower rate of bone formation. Increased bone resorption surface in the absence of osteoporosis or osteomalacia has not been previously described in PBC. Improvement in this bone parameter, associated with the finding of a decrease in the formation of bone and in hydroxyproline excretion in urine after parenteral vitamin D, suggests that increased turnover may be an early feature of the bone disease which complicates PBC and that parenteral vitamin D may retard the rate at which hepatic osteodystrophy develops in chronic cholestatic liver disease.
Noxythiolin as a possible cause of peritoneal adhesions.
Authors: M A Morris
Journal: BMJ (1977)

toxaemia" were higher in every one of the six years.Deaths from these two causes in 1969 amounted to 6-8 per 1000 and in 1975 to 8-8 per 1000 births, an increase almost exactly equal to the reduction in the rate for the "mature, cause unknown" category.In- creases in both premature birth rates and maternal toxaemia have been reported in asso- ciation with high induction rates, so these changes may be more than coincidental.If this is the case it may explain the failure of high induction rates to reduce overall perinatal mortality rates, even if some unexplained deaths of mature infants are thereby pre- vented.
Production of 6-oxo-prostaglandin F1 alpha and prostaglandin E2 by isolated glomeruli from normal and diabetic rats.
Authors: S P Rogers, R G Larkins
Journal: BMJ (1982)

Production of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and prostaglandin E2 (PGE2) was measured by radioimmunoassay in supernatants of isolated glomeruli from rats with streptozocin-induced diabetes and non-diabetic rats. Production of 6-oxo-PGF1 alpha by discs of aortas from these rats was measured at the same time. As shown before, aortic discs from diabetic rats produced significantly less 6-oxo-PGF1 alpha than aortic discs from non-diabetic rats (diabetic 1.99 +/- SEM 0.27 ng v non-diabetic 2.92 +/- 0.46 ng/mg net weight aorta; p less than 0.05). In contrast production of 6-oxo-PGF1 alpha by isolated glomeruli was not reduced in the diabetic rats (diabetic 77 +/- 7 pg v non-diabetic 70 +/- 8 pg/micrograms glomerular DNA). Similarly production of PGE2 was not diminished in the diabetic glomeruli (diabetic 1.20 +/- 0.15 ng v non-diabetic 0.91 +/- 0.12 ng/microgram glomerular DNA). It is concluded that regional differences in production of prostacyclin and 6-oxo-PGF1 alpha occur in experimental diabetes. Diminished prostacyclin production may contribute to the increased susceptibility of diabetic patients to atherosclerosis but is less likely to have a role in the pathogenesis of microangiopathy.
A smile from the Chancellor?
Authors: P. Johnston
Journal: BMJ (1985)

Nigel Lawson once confided that he finds it difficult to smile. The shape of his mouth, which droops at the edges like Zapata moustaches, forms  permanent scowl. It remains even as he distributes his newly discovered largesse. Last week we could discern  Herculean effort from the Chancellor to produce at least  self satisfied grin. He was in  position, at last, to give money away, to invest in public utilities without stoking up inflation. The National Health Service is to be one of the beneficiaries of the melting of Nigel's heart. For next year there is an extra ?250 million over and above spending increases already planned to meet inflation. The following year  further ?300 million will be injected, bringing total spending to ?16*5 billion by 1988. Health authorities are also to be allowed to keep the benefits of their efficiency drives, estimated at ?150 million this year. In the cold light of dawn, however, the spending spree seemed to fall short of its billing. The cash increases will be more than that required by inflation, but only 1% more. The local health authori? ties still have to meet the recent pay rises and price increases from within these resources. This will consume half the extra money next year. More is needed, members of parliament pointed out, to allow some growth in the service, to allow room for some improvements, cover new technology, and cope with the increasing number of elderly patients. Mr Lawson may indeed be throwing money around in  fashion unusual by his standards, but not enough to remove the incentive from the health authorities to find extra necessary funding else? where. The government is expecting a very substantial increase in the receipts from the sales of surplus land and buildings, now running at ?50 million  year. Mr Lawson said that the extra cash he had released should enable health authorities to meet demographic pressures and to deliver improvements in services as well. And he was not smiling when he said it, either.