tbuckley/cabot-search huggingface dataset:
A 47-Year-Old Woman With Fertility Problems Who Desires a Multiple Pregnancy
Authors: Robert J. Stillman
Journal: JAMA (2007)

Mrs Z is a 47-year-old woman with long-standing infertility who is about to undergo in vitro fertilization (IVF) using donor oocytes from an anonymous donor. She has already undergone an IVF cycle with her own oocytes and an IVF cycle using donor oocytes from a known donor without a successful pregnancy. Mrs Z has been advised by her infertility physician to consider the transfer of a single embryo, but she does not wish to decrease her likelihood of conception, and, after her long and expensive infertility saga, wishes to conceive twins. The science of IVF has evolved significantly in the last several years, increasing the likelihood of successful pregnancy and reducing the need to transfer more than 1 embryo with its inherent risks of multiple pregnancy. The state of the science and why patients may continue to want multiple embryos transferred, including costs and lack of insurance coverage for infertility treatments, are discussed.
Increase of Lung Neutrophils in Hypersensitivity Pneumonitis Is Associated with Lung Fibrosis
Authors: ANNIE PARDO, ROBERTO BARRIOS, MIGUEL GAXIOLA, LOURDES SEGURA-VALDEZ, GUILLERMO CARRILLO, ANDREA ESTRADA, MAYRA MEJÍA, MOISÉS SELMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Hypersensitivity pneumonitis (HP) is characterized by a T-cell-mediated alveolitis, and the putative role of other inflammatory cells in its pathogenesis remains unclear. In this study we determined whether increased quantities of neutrophils were present in HP lungs, and if they were positive for gelatinase B and collagenase-2. Fifteen nonsmoking patients with subacute/chronic active HP were included. Lung samples were analyzed using myeloperoxidase antibody, and neutrophil/total cell ratio was evaluated by digital processing. All HP tissue samples exhibited variable quantities of neutrophils located inside vessels, and in the interstitial and alveolar spaces. Lung neutrophil percentage ranged from 0.7% to 4.8% (2.1 +/- 1.4%). There was a positive correlation between the percentage of lung neutrophils and the percentage of lung fibrosis (r = 0.6, p < 0.02). Tissue neutrophils showed intense immunoreactive collagenase-2 and gelatinase B staining. Additionally, gelatinolytic activities corresponding to progelatinases A and B and their activated forms, were several-fold increased in the bronchoalveolar lavage fluid (BALF) from patients with HP as compared with control subjects. These findings suggest that in HP lungs there is a persistent traffic of neutrophils loaded with gelatinase B and collagenase-2 that may play a role in the lung damage and in the fibrotic response.
538 G-CSF is safe and improves adherence and SVR in HCV patients with genotype-1 who develop PEG-IFNa-2b related severe neutropenia. A multicenter study
Authors: J. Koskinas, G.H. Zacharakis, J. Sidiropoulos, J. Elefsiniotis, S. Savvas, D. Kountouras, M. Schina, F. Kostopoulos, A.J. Archimandritis
Journal: Journal of Hepatology (2006)
Heterosexual Transmission of HIV
Authors: James R. Allen
Journal: JAMA (1991)

The worldwide epidemic of the acquired immunodeficiency syndrome (AIDS) was recognized more than a decade ago. Quickly thereafter, the most common risk factors signifying probable means of infection were identified and used to describe the epidemic patterns in different areas and countries. These broad brush strokes of the epidemic, however, have made it difficult to appreciate the subtle complexities of human immunodeficiency virus (HIV) transmission that occur in different geographic areas and population subgroups. Each national epidemic is composed of multiple epidemics, each with its own rate, pattern, and trends. Some epidemics, such as new infections from contaminated blood transfusions in the United States or from clotting factor concentrates for people with hemophilia, are essentially finished. Others, such as new infections in homosexual men in New York, NY, and San Francisco, Calif, appear to be stabilizing. And some, such as heterosexual transmission in the United States, are in their early
Tool use as situated cognition
Authors: Andy Blitzer, Bryce Huebner
Journal: Behavioral and Brain Sciences (2012)

Abstract Vaesen disregards a plausible alternative to his position, and so fails to offer a compelling argument for unique cognitive mechanisms. We suggest an ecological alternative, according to which divergent relationships between organism and environment, not exotic neuroanatomy, are responsible for unique cognitive capacities. This approach is pertinent to claims about primate cognition; and on this basis, we argue that Vaesen's inference from unique skills to unique mechanisms is unwarranted.
Adamantane Resistance Among Influenza A Viruses Isolated Early During the 2005-2006 Influenza Season in the United States
Authors: Rick A. Bright
Journal: JAMA (2006)

The adamantanes, amantadine and rimantadine, have been used as first-choice antiviral drugs against community outbreaks of influenza A viruses for many years. Rates of viruses resistant to these drugs have been increasing globally. Rapid surveillance for the emergence and spread of resistant viruses has become critical for appropriate treatment of patients.To investigate the frequency of adamantane-resistant influenza A viruses circulating in the United States during the initial months of the 2005-2006 influenza season.Influenza isolates collected from 26 states from October 1 through December 31, 2005, and submitted to the US Centers for Disease Control and Prevention were tested for drug resistance as part of ongoing surveillance. Isolates were submitted from World Health Organization collaborating laboratories and National Respiratory and Enteric Virus Surveillance System laboratories.Using pyrosequencing and confirmatory assays, we identified viruses containing mutations within the M2 gene that are known to confer resistance to both amantadine and rimantadine.A total of 209 influenza A(H3N2) viruses isolated from patients in 26 states were screened, of which 193 (92.3%) contained a change at amino acid 31 (serine to asparagine [S31N]) in the M2 gene known to be correlated with adamantane resistance. Two of 8 influenza A(H1N1) viruses contained the same mutation. Drug-resistant viruses were distributed across the United States.The high proportion of influenza A viruses currently circulating in the United States demonstrating adamantane resistance highlights the clinical importance of rapid surveillance for antiviral resistance. Our results indicate that these drugs should not be used for the treatment or prophylaxis of influenza in the United States until susceptibility to adamantanes has been reestablished among circulating influenza A isolates.
Further Experience with Oral Therapy in Diabetes
Authors: K. L. Granville-Grossman, S. Crawfurd, M. F. Crowley, A. Bloom
Journal: BMJ (1959)

Tolbutamide has proved to be a successful hypoglycaemic agent in many diabetic patients.It is well tolerated and safe, and it does not lead to severe hypoglycaemic symptoms.Nevertheless, it suffers from two disadvantages.First, its effective action is short-lived (Stowers et al., 1958), and so it has to be given twice daily.Second, it is successful mainly in patients with mild diabetes with onset at maturity (Marble, 1958).Hence there is a need for compounds which are effective in a wider range of diabetics and with a more prolonged action.Short-term trials of a new oral hypoglycaemic agent can determine in what type of diabetic the agent is successful, its length of action, and whether it is well tolerated.Long-term trials are necessary before the possibility of toxic effects can be eliminated with confidence.Carbutamide proved to be a well-tolerated and effective oral hypoglycaemic agent, but it had been in use for over a year in Germany I. Carbutamide I -butyl-3-sulphonylurea H2N-SO2-NH-CO0-NH-4H9 II.Tolbutamide 1-butyl-3-p-tolylsulphonylurea CH8-0 02-NH-C0NH-C,H, III.Chlorpropamide I -propyl-3-p-chlorbenzenesulphonylurea Cl-o< 02-NH CO-NH-C3H7 IV.Metahexamide 1-cyclohexyl-3-m-amino-p-tolylsulphonylurea CH5
Abstract 4482: Novel and selective small molecule inhibitors of 3-phosphoinositide-dependent kinase-1 inhibit the PDK-1/AKT signaling pathway and cell proliferation
Authors: Sangita M. Baxi, Lars Engstrom, Marlena Walls, Matthew A. Marx, Sean Murphy, Jacques Ermolieff, Laura Lingardo, Hieu Lam, Aihua Zou, Gordon Alton, Tod Smeal, Min-Jean Yin
Journal: Cancer Research (2010)

Abstract Receptor tyrosine kinases (RTKs), PTEN (phosphatase and tensin homolog deleted on chromosome 10), and PIK3CA (encodes the p110α subunit of phosphatidylinositol 3-kinase [PI3K]) frequently contribute to tumor progression through their ability to regulate the intracellular level of phosphatidylinositol-3,4,5-triphosphate (PIP3). 3-phosphoinositide-dependent kinase-1 (PDK-1), a serine/threonine kinase, activates the catalytic domain of numerous kinases by phosphorylating their T-loop sites. PDK-1 activity is required for activation of AKT, p70S6K, and RSK which lead to cell proliferation and transformation. The interaction of the pleckstrin homology (PH) domain of AKT with the membrane bound PIP3 confers a conformational change in AKT, allowing PDK-1 to phosphorylate AKT at the residue threonine-308 (T308). This T-loop activation at T308, along with the phosphorylation of the serine-473 residue by mTOR, fully activates the AKT pathway. Although the roles of many PDK-1 substrates have yet to be characterized, the oncogenic activity of aberrant PI3K pathway signaling through PDK-1 has been extensively validated. We have developed a series of 3-Carbonyl-4-Amino-Pyrrolopyrimidne (CAP) compounds that are potent inhibitors of human PDK-1 (full length and kinase domain) which demonstrate more than 100-fold selectivity against P70S6K, PI3K, AKT, and mTOR. In this study, representative compounds from the CAP series were used to perform a variety of anti-tumor assays. We demonstrate PDK-1 compounds inhibit the phosphorylation of T308 on AKT as well as downstream molecules of the PI3K pathway, such as S6 ribosomal protein (S6RP) in breast, lung and colon cancer cell lines harboring a PI3KCA mutation. Additionally, blockade of AKT and molecules in the PI3K pathway leads to the inhibition of cell proliferation and cell transformation in cancer cells. Our data suggest that the inhibition of PDK-1 activity is sufficient to induce anti-tumor activity in cancer cells through the PI3K-PDK1-AKT axis, and that a potent and specific PDK-1 inhibitor could potentially be developed as a therapeutic agent against several cancer types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4482.
Differences in Airway Closure between Normal and Asthmatic Subjects Measured with Single-Photon Emission Computed Tomography and Technegas
Authors: GREGORY G. KING, STEFAN EBERL, CHERYL M. SALOME, IVEN H. YOUNG, ANN J. WOOLCOCK
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The absence of a maximal dose–response plateau as well as gas trapping and increases in closing capacity (CC) suggest that increased airway closure is an important mechanical abnormality of asthmatic airways. We compared the extent and distribution of airway closure in 13 normal and in 23 asthmatic subjects. Airway closure (LVclosed) was measured with single-photon emission computed tomography (SPECT) and an inhaled Technegas bolus as the percentage of lung volume without Technegas (LVtrans), and with CC, using nitrogen washout. LVclosed was compared in the apical, middle and lower zones, each being of equal vertical height. Values of mean LVclosed ± 95% confidence interval (CI) were similar in normal (30 ± 6.0% LVtrans) and asthmatic subjects (30 ± 7.8% LVtrans). In normal subjects, LVclosed correlated with both age (r = 0.89, p < 0.01) and CC (r = 0.86, p < 0.01), was more extensive in the lower zone (58 ± 18.8% LVtrans, p < 0.01) than in the middle and upper zones (17 ± 8.7% and 26 ± 8.2 LVtrans, respectively), and increased with age in both the middle and lower zones (r = 0.94 and r = 0.90, respectively, p < 0.01). In asthmatic subjects, LVclosed did not correlate with age; was greatest in the lower zone, intermediate in the middle zone, and lowest in the apical zone (59 ± 13.2%, 22 ± 5.8%, and 12 ± 4.4% LVtrans, respectively, p < 0.01); and correlated weakly with age in the middle zone only (r = 0.46, p < 0.05). We conclude that there is a predictable pattern of airway closure in normal subjects and that it is primarily influenced by pulmonary elastic recoil. This pattern is lost in asthmatic subjects. This may be explained by an increased range of closing pressures and a patchy distribution of airway closure, probably secondary to allergic inflammation.
192 THE LB MODEL: A NEW PROGNOSTIC TOOL FOR PREDICTION OF SHORT TERM SURVIVAL IN PATIENTS WITH END STAGE LIVER DISEASE
Authors: D. Duller, J. Haas, V. Stadlbauer, D. Kniepeiss, S.T. Palma, G. Gurakuqi, H.R. Gallent, F. Iberer, R.E. Stauber
Journal: Journal of Hepatology (2008)
Let us avoid Pascal's two excesses in quest for secularism's medical voice
Authors: G. C. Young
Journal: BMJ (2011)

Two opposing prevailing views both seem to be reductio ad absurdum type arguments: all religion is flawed and run by uneducated murderous lunatics who belong to the dark ages, or, to question the word of God is to commit blasphemy and you shall be condemned for it, especially if your God is different from mine.1 Neither of these premises …
Enhanced Regional Deformation at the Anterior Papillary Muscle Insertion Site After Chordal Transsection
Authors: Yasuo Takayama, Jeffrey W. Holmes, Ian LeGrice, James W. Covell
Journal: Circulation (1996)

Background Clinical and experimental studies of mitral valve replacement have shown a depression of ventricular function after chordal transsection; most recent studies have proposed that this is secondary to a depression of local function near the papillary muscle insertion site. However, there is no direct experimental evidence for changes in local fiber shortening in the wall of the left ventricle overlying the papillary muscle. Accordingly, we investigated the effect of chordal transsection on left ventricular shape and on three-dimensional regional deformation of the myocardium near the insertion of the anterior papillary muscle. Methods and Results In six open-chest dogs, two sets of three transmural columns of radiopaque markers were implanted in the anterior wall, one set at the tip of the papillary muscle (basal) and one at the site of papillary muscle fiber insertion (apical). A Björk-Shiley mitral valve was placed in the left atrium adjacent to the native valve. Markers were then tracked with biplane cineradiography, and deformation was quantified with the use of finite strain analysis. Chordal transsection resulted in reduced left ventricular end-systolic pressure and slowed relaxation. After chordal transsection, outward displacement of the ventricular wall and transverse shearing deformation were observed in the area of the papillary muscle during isovolumic contraction. Circumferential and radial strains during ejection were maintained at our basal site and enhanced on our apical site. Conclusions Chordal transsection led to enhanced local shortening and wall thickening and regional strain nonuniformity. These results indicate that chordal transsection induces an unloading of myocardium at the papillary muscle insertion site and that the resulting heterogeneity of regional function is the mechanism for the reduced global function and slowed ventricular relaxation.
TREATMENT AND ETIOLOGY OF PNEUMONIA.
Authors: W. J. GALBRAITH
Journal: JAMA (1904)

Including those cases mentioned in my article, published inThe Journal, July 9, 1904, I have had up to date, July 30, thirty-seven successive recoveries of uncomplicated cases of pneumonia which were treated according to that article. My experience during the season just passed covers over two hundred cases, and careful observations lead me to belieave there is a factor preceding the active physical signs of pneumonia which, by careful examination, can be detected in many cases prior to the stage of engorgement. Unfortunately, it is impossible to get a positive history as the anesthetic properties of alcohol are a mask for reliable record. However, in those cases that have come under my care at an early date I have frequently been able to detect tenderness, from a mild to a severe degree, in the region of the gall bladder, with a corresponding amount of pain in the same
OCCURRENCE OF POLIOMYELITIS VIRUS IN AUTOPSIES, PATIENTS, AND CONTACTS
Authors: John F. Kessel, Frederick J. Moore, Fred D. Stimpert, Roy T. Fisk
Journal: The Journal of Experimental Medicine (1941)

1. Poliomyelitis virus has been recovered in monkeys from 50 per cent of spinal cords, 10 per cent of olfactory bulbs, 50 per cent of tonsil-adenoid tissue, and from 26 per cent of the colon contents of autopsies; from the stools of 20 per cent of patients, and of 5 per cent of the contacts examined in this series. 2. Other materials as indicated in Table I were tested without success. 3. In autopsies with positive cords, tonsil-adenoid tissues, or colon contents were positive in 73 per cent. 4. 22 per cent of stools from patients with paralysis yielded virus and 19 per cent of the stools from patients without paralysis yielded virus. 5. 20 per cent of the stools from males and 22 per cent of the stools from females yielded virus. 6. 40 per cent of 35 stools from patients under 16 years yielded virus while 8 per cent of 38 stools from patients above the age of 15 yielded virus. 7. 71 per cent of the cords of 35 autopsies under 16 years yielded virus while 31 per cent 16 years and over yielded virus. 8. Repeat stools from 5 positive cases, 1 month after the first positive stool, were negative. The stool of one contact was positive the 2nd month after first recovery but was negative the 3rd month.
Poor growth in school entrants as an index of organic disease: the Wessex growth study.
Authors: L. D. Voss, J. Mulligan, P. R. Betts, T. J. Wilkin
Journal: BMJ (1992)

OBJECTIVE--To establish whether poor height or height velocity, assessed during the year of school entry, might identify children with previously undiagnosed organic disease. DESIGN--Observation of a total population and their case controls. SETTING--Community base. SUBJECTS--All 14,346 children in two health districts entering school during two consecutive years were screened for height by school nurses, and those whose height lay below the 3rd centile according to Tanner and Whitehouse standards (n = 180) were identified. After excluding 32 with known organic disease, five from ethnic minorities, and three who refused to take part, the remaining 140 short normal children were matched with 140 age and sex matched controls of average height (10th-90th centile) and their height velocities over 12 months measured. MAIN OUTCOME MEASURES--Height, height velocity, previously diagnosed organic disease, and organic disease diagnosed as a result of blood tests and specialist examination. RESULTS--Twenty five of the 180 short children (14%) were already known to have chronic organic disease which could explain their poor growth. Blood tests and specialist examination revealed a further seven with organic disease, which was acquired rather than congenital in three, and a second cause of short stature in one with known organic disease. These eight conditions had been missed at the school entry medical examination. The shorter the child, the more likely an underlying organic disorder, with seven of the 12 children whose heights were more than 3 standard deviations below the mean having some organic disease. Height velocity measured over 12 months, however, did not distinguish short normal children from those with disease or from their matched controls. CONCLUSIONS--Height, but not height velocity, is a useful index for identifying unrecognised organic disease at school entry. The shorter the stature the greater the prevalence of organic disease. The frequency of newly diagnosed remediable disease in this study (1 in 3-4000) is similar to that of neonatal hypothyroidism, which is routinely screened for. Routine investigation of all very short school entrants is recommended.
Improving Transcriptional Termination of Self-inactivating Gamma-retroviral and Lentiviral Vectors
Authors: Axel Schambach, Melanie Galla, Tobias Maetzig, Rainer Loew, Christopher Baum
Journal: Molecular Therapy (2007)

Adverse events relating to insertional mutagenesis have reinforced the interest in self-inactivating (SIN) gamma-retroviral and lentiviral vectors without enhancer-promoter sequences in the U3 region of the long terminal repeats. However, SIN vectors suffer from leaky transcriptional termination, increasing the probability of read-through into cellular genes. To improve 3' end processing, we incorporated seven upstream polyadenylation enhancer elements (or upstream sequence elements, USEs) derived from viral or cellular genes into the 3' U3 region of gamma-retroviral and lentiviral SIN vectors. A 100-base-pair sequence representing a recombinant direct repeat of the USE derived from simian virus 40 (2xSV USE) gave the best results, improving both titer and gene expression. In both gamma-retroviral and lentiviral SIN vectors, the 2xSV USE partially substituted for effects provided by the much larger post-transcriptional regulatory element derived from woodchuck hepatitis virus (wPRE). By northern blot and reporter assays, we found that the 2xSV USE greatly improved proper messenger RNA (mRNA) processing at the retroviral termination signal. Importantly, the 2xSV USE was superior to the wPRE in suppressing transcriptional read-through, improving not only vector efficiency but potentially also biosafety.
Blockade of CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus-1 replication in human lymphoid tissue by CC chemokines.
Authors: L B Margolis, S Glushakova, J C Grivel, P M Murphy
Journal: Journal of Clinical Investigation (1998)

The CC chemokines MIP-1alpha, MIP-1beta, and RANTES suppress replication of certain HIV-1 strains in cultured PBMC and T cell lines by blocking interaction of gp120 with CC chemokine receptor 5 (CCR5). However, the same chemokines can enhance HIV-1 replication in cultured macrophages. The net effect of chemokines on HIV-1 infection in intact lymphoid tissue, the major reservoir of HIV-1 in vivo, is unknown and unpredictable since the tissue contains both T lymphocytes and macrophages. Here we show that exogenous MIP-1alpha, MIP-1beta, and RANTES markedly suppressed replication of CCR5-tropic HIV-1 strains in blocks of human lymphoid tissue infected ex vivo. Moreover, endogenous MIP-1alpha, MIP-1beta, and RANTES were upregulated in tissues infected ex vivo with CXC chemokine receptor 4-tropic but not CCR5-tropic HIV-1. Such an upregulation may contribute to the virus phenotype shift in the course of HIV disease in vivo.