tbuckley/cabot-search huggingface dataset:
Spermicides and Birth Defects
Authors: Godfrey P. Oakley
Journal: JAMA (1982)

Jick and collagues reported last year a cohort study of 4665 patients from the Group Health Cooperative (CHC) in Seattle, suggesting that presumed spermicide users had infants with a higher rate of malformations than presumed nonusers. They reported a 2-fold increase in major malformations and specific increases for Down's syndrome, limb reduction deformities, and hypospadias. They also noted an increase for neoplasms. The authors regarded the data as tentative because no well-defined syndrome was found among the infants of users. The diversity of the increased malformations was another strong reason to consider the findings tentative. There are other reasons for considering the findings tentative or preliminary. One must have reservations regarding the accuracy with which infants were classified as exposed or unexposed. The authors argue that the vast majority of GHC members who used spermicides obtained them from the GHC pharmacy. Their argument is not based on direct data but on a study that showed that 98% of GHC women who took hormones, available only by prescription, obtained them from the pharmacy. The argument is weak, since spermicides are relatively inexpensive and widely available without prescription. It is likely that GHC members did purchase spermicides "on the outside." Insufficient information is given to know to what extent such purchases occurred and whether such purchases were biased. Without such information, it is necessary to ask whether misclassification played a role in the reported positive associations. The reported incidence of major malformations in hospital-based studies is about 2%. The fact that the 2-fold increase in the study is based on the apparent 50% decrease in reporting of defects in the "unexposed" group rather than on an increase above the 2% level for the "exposed" group argues for the tentative nature of these findings. In this issue of the JAMA, Shapiro et al. report from the Collaborative Perinatal Study data that they can find no increase of overall malformations among 476 infants with a history of 1st trimester exposure to nonmercurial spermicides when compared with 49,820 unexposed infants. Polendak et al. reports on spermicide exposure of 715 women who had infants with major malformations. On the basis of the 3 studies it seems clear that no causal association has been shown between spermicide use and birth defects.
Emergency naloxone for heroin overdose: Naloxone is not the only opioid antagonist
Authors: Colin Brewer
Journal: BMJ (2006)

<h3>BACKGROUND/AIMS</h3> Regulation of plasmin mediated extracellular matrix degradation by vascular endothelial cells is important in the development of angiogenesis. The aim was to determine whether transforming growth factor β (TGF-β) affected the regulation of components of the plasminogen system by human retinal endothelial cells, in order to define more clearly the role of TGF-β in retinal angiogenesis in the context of diabetes mellitus. <h3>METHODS</h3> Human retinal endothelial cells (HREC) were isolated from donor eyes and used between passages 4–8. The cells were cultured in medium supplemented with 2, 5, 15, or 25 mM glucose, plus or minus TGF-β (1 ng/ml). The concentrations of tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and plasminogen activator inhibitor type 1 (PAI-1) in cell conditioned medium were determined by ELISA and the level of PAI-1 mRNA was determined using northern hybridisation. Cell associated plasminogen activity was determined using a clot lysis assay and a chromogenic assay. <h3>RESULTS</h3> Under basal conditions (5 mM glucose), HREC produced PAI-1, t-PA, and trace amounts of u-PA. Cell surface plasminogen activation observed by lysis of fibrin or by cleavage of chromogenic substrate, was mediated by t-PA. Glucose at varying concentrations (2–25 mM) had no significant effect on t-PA mediated clot lysis. In contrast, treatment with TGF-β resulted in increased synthesis of PAI-1 protein and mRNA. The increased expression of the PAI-1 mRNAs by TGF-β did not occur uniformly, the 2.3 kb mRNA transcript was preferentially increased in comparison with the 3.2 kb mRNA (p&lt;0.05). <h3>CONCLUSIONS</h3> These data demonstrate that TGF-β increases PAI-1 and decreases cell associated lysis. This is sufficient to decrease the normal lytic potential of HREC.
Responsibility of Gynecology and Obstetrics
Authors: Frank Shubeck
Journal: JAMA (1966)

Explosions in recent years—atomic bombs, knowledge, and population—have produced changes affecting each of us in our daily lives. Much has been written about the social impact of the atomic explosions. The knowledge explosion has produced feelings of inadequacy and frustration from the rapidity of obsolescence. The population explosion has made it imperative that man learn to live with his fellow man.  Many physicians have a tendency to shun social responsibility, and an attitude of sociology for the sociologists often prevails. That physicians neither can nor should avoid  responsibility has been aptly pointed out by Allan C. Barnes, the editor of Social Responsibility of Gynecology and Obstetrics . He writes, this is not to say that the gynecologist-obstetrician can solve these problems alone, but neither can he hide from them.  The book compiles the information presented at a conference in Baltimore. Facts about population explosions and means for its control are
The laws of attraction: chemokines, neutrophils and eosinophils in severe exacerbations of asthma
Authors: G. Turato, S. Baraldo, R. Zuin, M. Saetta
Journal: Thorax (2007)

A possible new therapeutic strategy for preventing exacerbations

Asthma is an extremely common illness which affects an estimated 300 million people of all ages and ethnic backgrounds worldwide with significant costs for healthcare systems.1 The clinical course of the disease is characterised by acute episodes of worsening of symptoms and decrease in lung function known as exacerbations. Prevention of exacerbations has been the goal of most therapeutic interventions developed so far because exacerbations seriously affect the quality of life of patients and their families.2 The clinical presentation of asthma exacerbations may be extremely heterogeneous; they can be rapid in onset or occur more gradually. The severity of asthma exacerbations is also extremely variable, ranging from mild episodes to severe attacks which result in respiratory failure and may ultimately lead to death.

Airway inflammation is a characteristic feature consistently present in patients with asthma from the early stages in children3 to elderly people.4 The inflammatory process has been extensively investigated in stable conditions, showing an increased infiltration of eosinophils, mast cells and CD4 T lymphocytes characterised by a Th2 profile, with release of cytokines such as interleukin (IL)-4, IL-5, IL-13, eotaxin and RANTES.5 Conversely, little is known about the cellular mechanisms activated during exacerbations and, in particular, in severe exacerbations.

In this issue of Thorax …
Experimentally Induced Benignancy of Neoplasm. V. The Influence of Hormones on the Host's Resistance to Implanted Neoplasm
Authors: William T. Salter, Ira T. Nathanson, Hildegarde Wilson
Journal: Cancer Research (1941)

Several authors have reported the experimental production of neoplasms with estrogenic substances administered parenterally. These observations include not only the production of new growths in primary and secondary sex organs, but also of subcutaneous sarcoma by the implantation of crystalline estrone, as demonstrated by Gardner, Smith, Strong, and Allen ( 9 ) . Regarding the first group of observations, it is still debatable whether the hormone actually stimulates to malignancy, or merely hastens the development of tissue to the point where an independent predisposition to cancer may become effective. In the case of mammary tumor this point has been discussed by Lacassagne (15), by Geschickter ( I i ) , and by Nathanson and Andervont ( i8 ) . In the case of the uterus, Gardner and Allen ( Io) classified seriatim the pathological stages which precede recognizable malignant tissue; i.e., hyperplasia, secretory epithelial activity, stromal fibrosis, and pyometra. In this first group it is not clear that the action of the hormone is that of a true carcinogen. In the second group, however, the female sex hormone appears to produce the same reaction as methylcholanthrene and other carcinogens, and these interesting demonstrations of carcinogenic effect might suggest at first sight that an excess of estrogenic hormone in the body always favors malignant growth. It is possible, however, to demonstrate another effect of the hormone, as reported from this laboratory in another publication ( i9 ) . This effect is not concerned with carcinogenesis, but rather with the fitness of the animal host as an animated culture medium for supporting the continued growth of a small island of tumor consisting of cells
Abstract 905: Mirk/Dyrk1B mediates cell survival and G0/G1 phase of cell cycle via interacting with MAPK/ERK pathway in human cancer cells
Authors: Jingchun Gao
Journal: Cancer Research (2012)

Abstract Minibrain-related kinase (Mirk) known as the dual specificity tyrosine-phosphorylation-regulated kinase (Dyrk) 1B is a serine/threonine kinase. Our recent studies have also demonstrated that knockdown of Mirk by small interfering RNA (siRNA) resulted in reduction of viable cells and cell apoptosis in both ovarian cancer and non-small cell lung cancer (NSCLC) cell lines. Furthermore, it has been reported that Mirk/Dyrk1B can be negatively regulated by mitogenic-activated protein (MAP) / extracellular signal-regulated kinase (ERK) kinase signaling. In this study, we demonstrated the widely overexpressed Mirk protein in variant cell lines of both human ovarian cancer and NSCLC was correlated with the levels of activated ERK examined by western blot analysis. Interestingly, knockdown of Mirk by siRNA in those ovarian cancer cells (OVCAR3, OVCAR10, OVCAR1063, MDAH2774), and NSCLC cells (H292, H441, H1299, PC9) led to increased cell number and cells from G0/G1 into S phase of cell cycle accompanied by up-regulated activation of ERK and its upstream signals, increased cyclin D1, reduced p27, and no evidence of cleaved PARP which are not consistent with our previous findings in the other cell lines. We hypothesized that the increased activation of ERK after Mirk siRNA treatment may block the anti-proliferative effects of Mirk siRNA in some lines or may counterbalance cell loss through apoptosis in human cancer. To examine this further in both OVCAR3 and H292 cells, the increase in cell proliferation induced by Mirk siRNA could be blocked by the MEK inhibitor U0126 in a dose-dependent manner. MEK inhibition abrogated the activation of ERK and subsequent changes in cell cycle proteins (cyclin D1, p27) induced by Mirk knockdown. Combined Mirk siRNA and U0126 induced cell apoptosis in both OVCAR3 and H292 cells. In summary, Mirk may mediate cell survival and G0/G1 phase of cell cycle via interacting with MAPK/ERK pathway in human cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 905. doi:1538-7445.AM2012-905
Influenza Vaccine Pilot Study in Acute Coronary Syndromes and Planned Percutaneous Coronary Interventions
Authors: Enrique P. Gurfinkel, Ricardo Leon de la Fuente, Oscar Mendiz, Branco Mautner
Journal: Circulation (2002)

Background — Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season. In addition, the World Health Organization recommended vaccination against influenza infection for the Southern hemisphere in the winter of 2001.We evaluated the preventive impact of vaccination on subsequent ischemic events in myocardial infarction patients and in subjects undergoing planned percutaneous coronary angioplasty. Methods and Results — We included 200 myocardial infarction patients admitted in the first 72 hours and 101 planned angioplasty/stent (PCI) patients without unstable coronary artery disease, prior bypass surgery, angioplasty, or tissue necrosis, in a prospective, multicenter log during the winter season. Infarct patients received a standard therapy and were then randomly allocated in a single-blind manner to either a unique intramuscular influenza vaccination or a control group. Similarly, PCI patients were allocated to either vaccination or control groups. Combined end points (death, reinfarction, and rehospitalization for ischemia) were assessed at 6 months’ follow-up. The first primary outcome, cardiovascular death, occurred in 2% of the patients in the vaccine group compared with 8% in the control group (relative risk with vaccine as compared with controls, 0.25; 95% CI 0.07 to 0.86; P =0.01). The triple composite end point occurred in 11% of the patients in the vaccine group compared with 23% in controls ( P =0.009). Conclusions — Influenza vaccination may reduce the risk of death and ischemic events in patients suffering from infarction and those recovering from angioplasty during flu season. This response could be related to a humoral immune response with positive consequences during flu seasons.
Dynamic Gene Expression Analysis Links Melanocyte Growth Arrest with Nevogenesis
Authors: Guang Yang, Khanh Thieu, Kenneth Y. Tsai, Adriano Piris, Durga Udayakumar, Ching-Ni Jenny Njauw, Marco F. Ramoni, Hensin Tsao
Journal: Cancer Research (2009)

Like all primary cells in vitro, normal human melanocytes exhibit a physiologic decay in proliferative potential as it transitions to a growth-arrested state. The underlying transcriptional program(s) that regulate this phenotypic change is largely unknown. To identify molecular determinants of this process, we performed a Bayesian-based dynamic gene expression analysis on primary melanocytes undergoing proliferative arrest. This analysis revealed several related clusters whose expression behavior correlated with the melanocyte growth kinetics; we designated these clusters the melanocyte growth arrest program (MGAP). These MGAP genes were preferentially represented in benign melanocytic nevi over melanomas and selectively mapped to the hepatocyte fibrosis pathway. This transcriptional relationship between melanocyte growth stasis, nevus biology, and fibrogenic signaling was further validated in vivo by the demonstration of strong pericellular collagen deposition within benign nevi but not melanomas. Taken together, our study provides a novel view of fibroplasia in both melanocyte biology and nevogenesis.
Aggression and the general practitioner.
Authors: P. D'Urso, R. Hobbs
Journal: BMJ (1989)

The growing concern over violence against health service staff is reflected in an increasing number of anecdotal reports in both the medical and the lay press describing violent incidents.`6Family practitioner committees have recently started to gather information on the subject.The Health and Safety Commission has described some of the common factors in assaults against em- ployees.4These include difficulties patients experience in gaining access to medical help and disturbed person- alities.Drugs and alcohol, job location, prolonged waiting, and working alone also contributed to the risk.The Department of Health and Social Services advisory committee on violence to staff emphasised the vulnerability of doctors when performing home visits.'It noted that general practitioners have no formal system for reporting violence and must personally identify and fund any initiatives to reduce risk.The only published study of violence towards general practitioners concerned doctors in five health authorities.6In the year preceding the survey 0 5% of general practitioners had suffered major injuries and 0-5% minor injuries, 5% had been threatened with a weapon, and 24 9% had received verbal abuse.In this study we attempted to assess the extent of violence in a sample of urban practices. MethodA postal questionnaire was sent to all general practitioners with a surgery address in the Sparkhill, Sparkbrook, Harborne, Quinton, and Hall Green wards of Birmingham during July 1987 (n=83).Sparkhill and Sparkbrook are inner city wards, with high rates ofunemployment and much accommodation of poor quality.7 Sparkbrook is among the 50 most underprivileged wards as regards health in England and Wales."Harborne, Quinton, and Hall Green are more suburban and less socially deprived.The questionnaire divided aggressive behaviour into verbal abuse, attempted physical injury, and actual physical injury.Additional information was requested on the number of aggressive attacks, the role of drugs or alcohol, the location and timing, the person respons- ible, and the times when the general practitioner felt that he or she was under threat.
Abnormal Mitral Valve Motion in Patients with Elevated Left Ventricular Diastolic Pressures
Authors: LEE L. KONECKE, HARVEY FEIGENBAUM, SONIA CHANG, BETTY C. CORYA, JOHN C. FISCHER
Journal: Circulation (1973)

In order to see whether or not the echocardiographically recorded mitral valve could reflect alterations in left ventricular pressure, simultaneous mitral valve echograms and left ventricular pressures were obtained on patients undergoing diagnostic cardiac catheterization. Attention was given to the left ventricular initial diastolic pressure (LVIDP), left ventricular end-diastolic pressure (LVEDP), and the atrial component of the left ventricular pressure (LV a ). The echocardiographic measurements included the opening velocity of the mitral valve in early diastole (D-E slope) and the interval between the A point, which is the onset of closure of the mitral valve following atrial systole, and the C point, which represents closure of the mitral valve as indicated by the meeting of the anterior and posterior mitral leaflets. In order to compensate for variations in atrioventricular conduction, the A-C interval was subtracted from the electrocardiographic P-R interval. In 19 patients, the LVIDP was less than 14 mm Hg, the LVEDP was less than 20 mm Hg, and the LV a was less than 8 mm Hg. In these patients, the D-E slope was greater than 25 cm/sec and the PR-AC interval was greater than 0.06 sec. Six patients who had an LVIDP of 14 mm Hg or greater had a D-E slope of less than 25 cm/sec. There were 14 patients with an LVEDP greater than 20 mm Hg and an LV a of 8 mm Hg or greater. All of these patients had a PR-AC interval of less than 0.06 sec. There were an additional three patients who had an LVEDP above 20 mm Hg, but whose LV a was less than 8 mm Hg. In these three patients, the PR-AC interval was greater than 0.06 sec. Thus, the shortened PR-AC interval correlated primarily with an elevated LV a . This study indicates that the echocardiographic pattern of mitral valve motion is altered in patients who have markedly elevated left ventricular diastolic pressures.
Effects of atrial natriuretic peptide and vasopressin on chloride transport in long- and short-looped medullary thick ascending limbs.
Authors: H Nonoguchi, K Tomita, F Marumo
Journal: Journal of Clinical Investigation (1992)

Recent studies have suggested a selective effect of atrial natriuretic peptide (ANP) in regulating NaCl reabsorption in juxtamedullary nephrons. We examined (a) functional differences between medullary thick ascending limbs from long and short loops of Henle (lMAL and sMAL, respectively) and (b) the interaction of ANP and arginine vasopressin (AVP) on Cl- transport (JCl) in these two segments. AVP-, glucagon-, and calcitonin-stimulated cAMP accumulation was higher in lMAL than in sMAL. 10(-10) M AVP increased JCl in lMAL but not in sMAL. ANP-stimulated cGMP production was higher in lMAL than in sMAL. 10(-10) and 10(-8) M ANP inhibited AVP-stimulated JCl in lMAL by 26-30% (from 70.3 +/- 11.4 to 51.7 +/- 13.6 pmol/mm per min and from 88.1 +/- 10.1 to 61.8 +/- 11.7 pmol/mm per min, respectively), and this effect was mimicked by 10(-5) to 10(-4) M cGMP. This effect of ANP in lMAL could account for a large part of the ANP-induced natriuresis and diuresis in vivo, in that the rate of NaCl reabsorption in MAL is the largest among distal nephron segments, providing the chemical potential energy for the renal countercurrent multiplication system.
Reduced Cytosolic Ca <sup>2+</sup> Loading and Improved Cardiac Function After Cardioplegic Cold Storage of Guinea Pig Isolated Hearts
Authors: David F. Stowe, Srinivasan G. Varadarajan, Jianzhong An, Steven C. Smart
Journal: Circulation (2000)

Background —Hypothermia is cardioprotective, but it causes Ca 2+ loading and reduced function on rewarming. The aim was to associate changes in cytosolic Ca 2+ with function in intact hearts before, during, and after cold storage with or without cardioplegia (CP). Methods and Results —Guinea pig hearts were initially perfused at 37°C with Krebs-Ringer’s (KR) solution (in mmol/L: Ca 2+ 2.5, K + 5, Mg 2+ 2.4). One group was perfused with CP solution (Ca 2+ 2.5, K + 18, Mg 2+ 7.2) during cooling and storage at 3°C for 4 hours; another was perfused with KR. LV pressure (LVP), dP/dt, O 2 consumption, and cardiac efficiency were monitored. Cytosolic phasic [Ca 2+ ] was calculated from indo 1 fluorescence signals obtained at the LV free wall. Cooling with KR increased diastolic and phasic [Ca 2+ ], whereas cooling with CP suppressed phasic [Ca 2+ ] and reduced the rise in diastolic [Ca 2+ ]. Reperfusion with warm KR increased phasic [Ca 2+ ] 86% more after CP at 20 minutes and did not increase diastolic [Ca 2+ ] at 60 minutes, compared with a 20% increase in phasic [Ca 2+ ] after KR. During early and later reperfusion after CP, there was a 126% and 50% better return of LVP than after KR; during later reperfusion, O 2 consumption was 23% higher and cardiac efficiency was 38% higher after CP than after KR. Conclusions —CP decreases the rise in cardiac diastolic [Ca 2+ ] observed during cold storage in KR. Decreased diastolic [Ca 2+ ] and increased systolic [Ca 2+ ] after CP improves function on reperfusion because of reduced Ca 2+ loading during and immediately after cold CP storage.
How connectionist simulations fail to account for developmental disorders in children
Authors: Christine Temple, Harald Clahsen
Journal: Behavioral and Brain Sciences (2002)

Using connectionist modelling, Thomas &amp; Karmiloff-Smith (T&amp;K-S) claim that developmental disorders in children are characterised by atypical trajectories and an ultimate functional architecture that is fundamentally different from normal. We argue that there is no empirical evidence for these claims in any developmental disorder and that the available evidence provides support for Residual Normality in both developmental and acquired disorders. We also refute the claim that modular accounts cannot encompass developmental trajectories in children with developmental disorders.