tbuckley/cabot-search huggingface dataset:
Permanent Encephalopathy from Toluene Inhalation
Authors: J. William Knox, James R. Nelson
Journal: New England Journal of Medicine (1966)

INHALATION of glue vapors in an attempt to induce euphoria has recently become quite popular, particularly among teen-agers. The desired effects are probably produced by toluene, the major component of the vapors.1 The acute Central-nervous-system symptoms after toluene inhalation are transient euphoria, exhilaration and excitement, but in high doses confusion, headache, nausea, tinnitus, ataxia, tremors and fasciculations often occur. Acute, reversible hepatic decompensation and bone-marrow suppression are also prominent effects of exposure to high concentrations of toluene.2 3 4 The severity of the acute symptoms correlates well with the concentration of toluene vapor, and specific safeguards have been established for industrial workers . . .
Most OECD countries could save money by improving clinical guidelines and negotiating better drug prices
Authors: S. Arie
Journal: BMJ (2010)

A new report for the Organisation for European Cooperation and Development (OECD) says that most countries struggling to reduce public spending could make major savings in health care without sacrificing the quality or availability of care.

The report comes as health ministers from OECD countries meet in Paris to discuss the risks and options they face because of huge pressure on them to make cuts.

It warns that short term “command and control” policies can hold expenditures down in the short term but often have negative consequences in the long term.

The OECD points out that with health spending at an average of 9% of …
Some factors affecting bacterial colony counts in urinary infection.
Authors: A. P. Roberts, R. E. Robinson, R. W. Beard
Journal: BMJ (1967)

then be taken to cross-match blood, empty the uterus, give further oxytocics, and repair genital trauma.The report by the Ministry of Health (1963) on maternal deaths in England and Wales for the years 1958-60 emphasized the frequency with which attendants failed to realize the serious state of patients who had bled.Considerable underestimation of the cxtent of blood loss often contributed to this failure.Of the 742 deaths studied 130 were believed to have haemorrhage as the primary factor leading to death.In 61 of these (31 with avoidable factors) the bleeding was postpartum.This investigation has shown that in routine hospital prac- Zice there is considerable underestimation of blood loss, and yet this hospital is representative of those with a high standard of antenatal and intranatal care.The present finding of virtually invariable underestimation, especially when the recorded loss exceeds 300 ml., suggests most strongly that unappreciated and underestimated blood loss is a much more important factor in many maternal deaths than available statistics show.Reports have appeared in which the criterion for assessing the effect of anaesthetic and oxytocic preparations on the third stage of labour has been the incidence of postpartum haemor- rhage (Embrey et al., 1963 ; Friedman, 1957 ; McBride, 1954).The findings in this survey suggest that this criterion is of little value unless clinical estimation of blood loss is replaced by accurate measurement.It is hoped that the present investigation will emphasize to those attending vaginal deliveries how often considerable haemorrhages occur, so that by early action disastrous exsanguinations will be avoided. SummaryA method of accurately measuring blood loss is outlined.Blood is extracted in a washing-machine and measured spectro- metrically as oxyhaemoglobin.The bleeding that occurred after 57 vaginal deliveries was measured.When this measured amount was compared with the estimate recorded at the time of delivery the estimate was reasonably correct for small losses.However, when the recorded loss exceeded 300 ml.underestimation was invariable, anJ as the loss became greater so did the amount of undercstimation.On the basis of these measurements it is calculated that in over 20%/ of vaginal deliveries the blood loss exceeds 500 ml.A systolic blood pressure below 100 mmn.Hg and a pulse rate above 100 beats per minute are late signs of depleted blood volume and indicate commencing failure of the compensatory mechanisms.I wish to thank Mr. H.G. Dixon and Mr. W. G.
β-Adrenergic Receptor Stimulation Transactivates Protease-Activated Receptor 1 via Matrix Metalloproteinase 13 in Cardiac Cells
Authors: Fabrice Jaffré, Alan E. Friedman, Zhaoyang Hu, Nigel Mackman, Burns C. Blaxall
Journal: Circulation (2012)

Background— Chronic β-adrenergic receptor (β-AR) overstimulation, a hallmark of heart failure, is associated with increased cardiac expression of matrix metalloproteinases (MMPs). MMP-1 has been shown to cleave and activate the protease-activated receptor 1 (PAR1) in noncardiac cells. In the present study, we hypothesized that β-AR stimulation would result in MMP-dependent PAR1 transactivation in cardiac cells. Methods and Results— β-AR stimulation of neonatal rat ventricular myocytes (NRVMs) or cardiac fibroblasts with isoproterenol transduced with an alkaline phosphatase–tagged PAR1 elicited a significant increase in alkaline phosphatase–PAR1 cleavage. This isoproterenol-dependent cleavage was significantly reduced by the broad-spectrum MMP inhibitor GM6001. Importantly, specific MMP-13 inhibitors also decreased alkaline phosphatase–PAR1 cleavage in isoproterenol-stimulated NRVMs, as well as in NRVMs stimulated with conditioned medium from isoproterenol-stimulated cardiac fibroblasts. Moreover, we found that recombinant MMP-13 stimulation cleaved alkaline phosphatase–PAR1 in NRVMs at DPRS 42 ↓ 43 FLLRN. This also led to the activation of the ERK1/2 pathway through Gαq in NRVMs and via the Gαq/ErbB receptor pathways in cardiac fibroblasts. MMP-13 elicited similar levels of ERK1/2 activation but lower levels of generation of inositol phosphates in comparison to thrombin. Finally, we demonstrated that either PAR1 genetic ablation or pharmacological inhibition of MMP-13 prevented isoproterenol-dependent cardiac dysfunction in mice. Conclusions— In this study, we demonstrate that β-AR stimulation leads to MMP-13 transactivation of PAR1 in both cardiac fibroblasts and cardiomyocytes and that this likely contributes to pathological activation of Gαq and ErbB receptor–dependent pathways in the heart. We propose that this mechanism may underlie the development of β-AR overstimulation–dependent cardiac dysfunction.
The survival pathways phosphatidylinositol-3 kinase (PI3-K)/phosphoinositide-dependent protein kinase 1 (PDK1)/Akt modulate liver regeneration through hepatocyte size rather than proliferation
Authors: Sanae Haga, Michitaka Ozaki, Hiroshi Inoue, Yasuo Okamoto, Wataru Ogawa, Kiyoshi Takeda, Shizuo Akira, Satoru Todo
Journal: Hepatology (2008)

Liver regeneration comprises a series of complicated processes. The current study was designed to investigate the roles of phosphoinositide-dependent protein kinase 1 (PDK1)-associated pathways in liver regeneration after partial hepatectomy (PH) using liver-specific Pdk1-knockout (L-Pdk1KO) and Pdk1/STAT3 double KO (L-DKO) mice. There was no liver regeneration, and 70% PH was lethal in L-Pdk1KO mice. Liver regeneration was severely impaired equally in L-Pdk1KO and L-DKO mice, even after nonlethal 30% PH. There was no cell growth (measured as increase of cell size) after hepatectomy in L-Pdk1KO mice, although the post-PH mitotic response was the same as in controls. As expected, hepatectomy did not induce hepatic Akt-phosphorylation (Thr308) in L-Pdk1KO mice, and post-PH phosphorylation of Akt, mammalian target of rapamycin (mTOR), p70 ribosomal S6 kinase (p70S6K), and S6 were also reduced. To examine the specific role of PDK1-associated signals, a "pif-pocket" mutant of PDK1, which allows PDK1 only to phosphorylate Akt, was used. Liver regeneration was recovered in L-Pdk1KO mice with a "pif-pocket" mutant of PDK1. This re-activated Akt in L-Pdk1KO mice liver and induced post-PH cell growth, without affecting cell proliferation. Further deletion of STAT3 (L-DKO mice) did not further deteriorate liver regeneration, although this certainly reduced post-PH mitotic response. These findings indicate that PDK1/Akt contribute to liver regeneration by regulating cell size. Regarding phosphatidylinositol-3 kinase (PI3-K), immediate upstream signal of PDK1, activation of PI3-K induced cell proliferation via STAT3 activation in the liver of L-Pdk1KO mice but did not improve impaired liver regeneration. This confirmed the pivotal role of PDK1 in liver regeneration and cell growth. Conclusion: PDK1/Akt-mediated responsive cell growth is essential for normal liver regeneration after PH, especially when cell proliferation is impaired. (HEPATOLOGY 2009;49:204-214.)
Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia
Authors: Eduardo Olavarria, Shamyla Siddique, Michael J. Griffiths, Sharon Avery, Jenny L. Byrne, Karen P. Piper, Anne L. Lennard, Lalit Pallan, Julie M. Arrazi, Jolanta B. Perz, Derville O'Shea, John M. Goldman, Jane F. Apperley, Charles F. Craddock
Journal: Blood (2007)
Neutrophils give us a shock
Authors: Clifford A. Lowell
Journal: Journal of Clinical Investigation (2011)

Systemic anaphylaxis is generally recognized as a severe allergic reaction caused by IgE-mediated activation of mast cells, leading to massive release of vasoactive mediators that induce acute hypotension and shock. However, experimental evidence in mice suggests that this view is too simple. Using a variety of techniques to manipulate immune cell makeup, Jönsson et al. come to the conclusion in this issue of the JCI that recognition of IgG1 and IgG2 antibodies by FcγRIII and FcγRIV receptors on neutrophils is a major pathway for induction of anaphylaxis. These exciting results suggest that we have to reevaluate our models for anaphylaxis in humans, which will have a direct impact on our therapeutic approaches for prevention of this potential deadly hypersensitivity reaction.
Skin infection caused by <i>Mycobacterium avium</i>
Authors: Y. ICHIKI, M. HIROSE, T. AKIYAMA, C. ESAKI, Y. KITAJIMA
Journal: British Journal of Dermatology (1997)

A patient with skin infection due to Mycobacterium avium is reported. A 9-year-old female had 10 subcutaneous nodules and two ulcers on the abdomen and legs. She had no medical history of systemic disease, skin disease or immunosuppressive therapy. Cultures of a biopsy specimen and of aspirated seropurulent fluid in nodules showed acid-fast bacteria, identified as M. avium by the DNA-DNA hybridization method. We treated her with a combination of surgery and the antibiotics, cycloserine, isoniazid and clarithromycin.
GrpL, a Grb2-related Adaptor Protein, Interacts with SLP-76 to Regulate Nuclear Factor of Activated T Cell Activation
Authors: Che-Leung Law, Maria K. Ewings, Preet M. Chaudhary, Sasha A. Solow, Theodore J. Yun, Aaron J. Marshall, Leroy Hood, Edward A. Clark
Journal: The Journal of Experimental Medicine (1999)

Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain–containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL–SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells.
Does the cerebellum learn strategies for the optimal time-varying control of joint stiffness?
Authors: Allan M. Smith
Journal: Behavioral and Brain Sciences (1996)

Although there is increasing agreement that the cerebellum plays an important role in motor learning, the basic substance of what constitutes motor learning has been difficult to define. Unless motor learning is somehow radically different from other forms of learning, it must involve relatively simple stimulus-stimulus and stimulus-response associations. All forms of learning, including purely sensory associations and cognitive learning as well as motor learning, effect changes in behavior. However, a singular characteristic of motor learning is that it adjusts joint and limb mechanics by altering the neural input to muscles through practice and mental rehearsal. The hypothesis proposed here is that the cerebellum plays an important role in motor learning by forming and storing associated muscle activation patterns for the time-varying control of limb mechanics. By modulating the cocontraction of agonist-antagonist muscles through adjustments in the timing and amplitude of muscle activity, the viscoelastic properties of joints can be appropriately regulated throughout Movement and adapted for transitions between postures and movements. Optimal control of joint viscoelastic properties cannot be achieved by online corrections initiated by reflex feedback because of the delays and consequent instabilities incurred. Instead, strategies for optimizing muscle activation patterns or synergies must be learned from the temporal association of proprioceptive stimuli signaling muscle lengths and forces and the rates of changes in these parameters, with reinforcement occurring when the movement achieves its objective. Such strategies would involve varying degrees of cocontraction or reciprocal inhibition of agonist-antagonist muscles that ultimately contribute to joint and limb stiffness. Evidence from neural recordings and clinical and experimental lesion studies are presented, suggesting that the cerebellum uses teleceptive and proprioceptive feedback as feedforward conditioned stimuli for specific muscle activation patterns contributing to joint stiffness (i.e., agonist-antagonist muscle synergies) for particular tasks and postures. A wide variety of observations are thought to be consistent with such a role for the cerebellum, but ultimately additional experiments could confirm or disconfirm this hypothesis.
ANGIOTENSIN CONVERTING ENZYME INHIBITOR USE IS ASSOCIATED WITH REDUCED MORTALITY IN PATIENTS WITH AORTIC REGURGITATION
Authors: Douglas Elder, Benjamin R. Szwejkowski, Adnan M. Nadir, Maheshwar Pauriah, Sushma Rekraj, Tiong Lim, Jacob George, Alexander Doney, Stuart D. Pringle, Anna-Maria Choy, Allan D. Struthers, Chim C. Lang
Journal: Journal of the American College of Cardiology (2011)
A CASE OF PSEUDOHERMAPHRODITISM
Authors: PAUL OLIVER
Journal: JAMA (1913)

<h3>History</h3> — The patient, Lillian K., aged 4, was the fourth of five girls and weighed 8½ pounds at birth. She was breast-fed, walked at eight months, and suffered from marked bow-legs. The mother noticed that she was exceptionally active and rough in play with the other children. "She loved to run and jump like a boy." The mother first noticed a swelling in the right groin when the child was 2 years old. This caused no discomfort and completely disappeared in the recumbent position. There was a gradual increase in size and extension downward as the child grew older, until it finally reached to the right labium majus. At the age of 3 years the child contracted whooping-cough and a swelling appeared in the left groin, similarly located but smaller than that on the right. The family physician at this time made a diagnosis of double inguinal hernia and advised
Expression and regulation of leukotriene-synthesis enzymes in rat liver cells
Authors: Kazuo Shimada, Javier Navarro, Douglas E. Goeger, Shamimunisa B. Mustafa, Paul H. Weigel, Steven A. Weinman
Journal: Hepatology (1998)

The liver plays a major role in metabolism and elimination of leukotrienes (LT). It produces cysteinyl leukotrienes (cLT), and cLT have been implicated in hepatocellular toxicity in several models of lipopolysaccharide (LPS)–associated liver injury. However, the liver cell types responsible for cLT production are poorly defined, and the expression of the LT–synthesis enzymes, 5–lipoxygenase (5–LO) and LTC 4 synthase (LTC 4 –S), in liver cells has never been demonstrated. The aim of the present study was to examine the ability of rat liver cells to produce cLT by determining whether hepatocytes, Kupffer cells, and sinusoidal endothelial cells express mRNA and enzyme activities of the LT–synthesis enzymes and whether expression is altered by LPS. 5–LO mRNA was expressed in whole liver, and expression was enhanced by LPS. Cell fractionation studies demonstrated that expression was present in Kupffer cells and sinusoidal endothelial cells, but not in hepatocytes. LTC 4 –S mRNA was detected in whole liver, hepatocytes, and sinusoidal endothelial cells, but not in Kupffer cells. Semiquantitative reverse–transcriptase polymerase chain reaction (RT–PCR) showed that LPS increased LTC 4 –S expression in hepatocytes by a factor of 3 (n = 3; P &lt; .03). LTC 4 –S enzyme activity in the microsomal fraction of hepatocytes was also increased from 0.52 ± 0.13 to 1.90 ± 0.66 nmol · mg protein -1 · 5 min -1 (n = 6; P &lt; .015) after LPS treatment. These results indicate that hepatocytes do not possess the ability for de novo synthesis of cLT from arachidonic acid, but they may actively participate in cLT production by conjugation of LTA 4 with glutathione to produce LTC 4 . LPS enhances LTC 4 –S expression in hepatocytes. This intrinsic cLT production may contribute to hepatocellular injury during inflammation.
Immunization Policies and Vaccine Coverage Among Adults
Authors: WALTER W. WILLIAMS
Journal: Annals of Internal Medicine (1988)

A substantial proportion of vaccine-preventable diseases occur among adults. Each year, there are more than 20 000 influenza-associated deaths during epidemics, approximately 40 000 deaths related to pneumococcal disease, and one to five cases of diphtheria. More than 300 000 hepatitis B infections occur annually, mostly in patients 15 to 29 years old. From 1982 to 1986, 96% of patients with tetanus were age 20 and older. Among young adults, 5% to 20% are susceptible to rubella and measles, and outbreaks occur where these persons congregate. Most adults are not immunized, despite recommendations for vaccines against these diseases. Vigorous efforts are needed to implement strategies to reduce disease incidence, morbidity, and death among adults.
Characteristics of the Unipolar Precordial Electrocardiogram in Normal Infants
Authors: ROBERT F. ZIEGLER
Journal: Circulation (1951)

The electrocardiogram should have as much clinical value in infants and children as in adults. Such value, as in adults, must depend upon an accurate knowledge of normal standards which change progressively during infancy and early childhood. Some of the more important measurements in the precordial leads of normal infants are presented and discussed. These measurements, the amplitude and the time of inscription of the intrinsic deflection, are believed to indicate the changing relationship between the mass of the right and left ventricles, and on the basis of these data it is also believed that an earlier and more accurate diagnosis of ventricular hypertrophy can be made at any age.
THE TREATMENT OF INFECTED WAR WOUNDS BY MAGNESIUM SULPHATE
Authors: A. E. Morison
Journal: BMJ (1918)

JOURNAL_the empty stomach was found to be flattened out over the front of a greatly distended lesser sac.This exploratory wound was therefore closed, and an incision was made in the back of the left loin immediately below the twelfth rib.Oni opening the lesser sac by thiseroute four or five pints of clear fluid gusbed ouit, followed by a little pus.On digital exploration of the lesser sac a fragment of the copper band of a shell, 1 in. in lenigth, wvas found lying free in the cavity, and was easily removed.The loin wound was drained.Captain G. E. Loveday, R.A.M.C.(T.), examined a specimen of the fluid and reported that it contained both trypsin and amylopsin.After-History.The patient made a somewhat slow recovery, and vomited for some ten days after operation.He then improved more rapidly, and after a change to an auxiliary hospital was dis- clharged as fit for general service.
US government cuts penalty on tobacco firms as racketeering case closes
Authors: Anne Harding
Journal: BMJ (2005)

The US Justice Department has announced that it will seek $10bn (£5.5bn; €8.2bn) in penalties from the country's six largest tobacco companies to fund a five year smoking cessation programme. It had previously demanded $130bn for a 25 year effort designed to help all 45 million current US smokers kick the habit.

The sudden shift came on the closing day of the government's civil case against racketeering by “big tobacco.” Democratic politicians and public health activists immediately accused the government of caving in to the industry.

Judge Gladys Kessler, who is hearing the case …
Allergen‐reactive antibodies are found in nasal fluids from patients with birch pollen‐induced intermittent allergic rhinitis, but not in healthy controls
Authors: M. Benson, J. Reinholdt, L. O. Cardell
Journal: Allergy (2003)

Background: Increased levels of allergen‐reactive immunoglobulins (Igs) have been reported in nasal fluids from patients with intermittent allergic rhinitis (IAR) sensitive to ragweed and grass. The aims of this study were to make a detailed characterization of nasal fluid Igs in birch pollen‐induced IAR. Methods: Nasal fluids were obtained from 23 patients with birch pollen‐induced IAR during and after the birch pollen season, and from 20 healthy controls. Nasal fluid total and Bet v 1‐reactive (IgA), IgE and IgG as well as albumin were analyzed by immunoassays. The integrity of IgA and IgG, and the molecular form of IgA were assessed by Western blotting and column fractionation, respectively. Results: Nasal fluid total IgE and IgG, but not IgA, were higher in patients compared with controls. Western blotting indicated no significant degradation of IgA (including S‐IgA) and IgG. Most of the IgA, including Bet v 1‐reactive antibodies, was of the secretory form and of the IgA1 subclass. Bet v 1‐reactive IgA and IgG were present in all patients, but was mostly nondetectable in controls. No significant differences in the levels of Bet v 1‐reactive IgA and IgG were found in patients during the birch pollen season compared with off season. Both Bet v 1 and Bet v 2‐reactive IgE were nondetectable in most samples. Conclusions: Nasal fluid Bet v 1‐reactive IgA and IgG were found in all patients with birch pollen‐induced IAR, but not in controls. However, no significant differences were found between patients during and after the birch pollen season.
Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells
Authors: Giovanni Luca, Mario Calvitti, Francesca Mancuso, Giulia Falabella, Iva Arato, Catia Bellucci, Edward O. List, Enrico Bellezza, Giovanni Angeli, Cinzia Lilli, Maria Bodo, Ennio Becchetti, John J. Kopchick, Don F. Cameron, Tiziano Baroni, Riccardo Calafiore
Journal: Journal of Controlled Release (2012)
Natural History and Expansive Clinical Profile of Stress (Tako-Tsubo) Cardiomyopathy
Authors: Scott W. Sharkey, Denise C. Windenburg, John R. Lesser, Martin S. Maron, Robert G. Hauser, Jennifer N. Lesser, Tammy S. Haas, James S. Hodges, Barry J. Maron
Journal: Journal of the American College of Cardiology (2010)