tbuckley/cabot-search huggingface dataset:
BASAL CEREBRAL HEMORRHAGES
Authors: MAURICE PACKARD
Journal: JAMA (1925)

During the last century, it was not uncommon to find in medical literature references and reports in regard to cases of basal cerebral hemorrhage. However, recent literature on the subject in the United States is remarkably limited. In most of the few cases cited, attention is paid to the fact that the lesion was discovered accidentally, a condition that leads us to conclude that this type of hemorrhage is much more frequent than is realized, more frequent at any rate than is recognized in diagnostic statistics. Because of the history of a fall or other form of trauma, these cases often find their way into the surgical ward of a hospital, or because of a nuchal rigidity and occipital headache they are treated as frank cases of meningitis. Sydney Smith<sup>1</sup>cites an instance of a patient brought in and treated for opium poisoning, a diagnosis in which all attending
Abstract SY27-04: Engineering improved cancer vaccines.
Authors: Glenn Dranoff
Journal: Cancer Research (2013)

Abstract Efficacious cancer immunotherapies will likely require combinations of strategies that enhance tumor antigen presentation and antagonize negative immune regulatory circuits. We demonstrated that vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF followed by antibody blockade of CTLA-4 accomplishes clinically significant tumor destruction with minimal toxicity in a majority of stage IV metastatic melanoma and some advanced ovarian carcinoma patients. The extent of tumor necrosis in post-treatment biopsies was linearly related to the natural logarithm of the ratio of infiltrating CD8+ effector T cells to FoxP3+ Tregs, suggesting that further Treg inhibition might increase the frequency of clinical responses. Through an analysis of cytokine deficient mice, we delineated a critical role for GM-CSF in Treg homeostasis. GM-CSF is required for the expression of the phosphatidylserine binding protein MFG-E8 in antigen presenting cells, whereas the uptake of apoptotic cells by phagocyte-derived MFG-E8 maintains peripheral Treg activity. The pharmacologic inhibition of MFG-E8 function through genetic or engineering-based approaches blocks Treg induction, which intensifies vaccine-induced responses, leading to the regression of established tumors in mice. The clinical translation of these therapeutic strategies to Phase I testing in humans is underway. The detailed analysis of patients achieving sustained clinical benefits from irradiated, autologous GM-CSF secreting tumor cell vaccines and CTLA-4 antibody blockade also affords a rich opportunity to identify antigens associated with immune-mediated tumor destruction and to delineate mechanisms of therapeutic immunity. We elucidated several of the molecular pathways that underlie these anti-tumor effects, including the NKG2D system and multiple secreted/or cell surface proteins that contribute to tumor promoting inflammation. The therapy-induced antibodies manifest functional activity in vitro, antagonizing tumor cell survival, invasive potential, and angiogenesis. These findings support a key role for humoral immunity in tumor destruction, and highlight interest in more detailed characterization of the anti-tumor B cell repertoire in vaccinated patients. Citation Format: Glenn Dranoff. Engineering improved cancer vaccines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY27-04. doi:10.1158/1538-7445.AM2013-SY27-04
The Renal Transport of Nitrofurantoin
Authors: Marvin W. Woodruff
Journal: JAMA (1961)

The mechanism of excretion of nitrofurantoin in the kidney was studied in anesthetized dogs by direct collection of urine from ureteral catheters. The method of stop flow analysis, involving a period of occlusion of the ureter, was applied in order to determine in which part of the nephron nitrofurantoin is excreted; in addition, simultaneous nitrofurantoin and creatinine clearance determinations were performed on four dogs at varying levels of urinary pH and plasma CO2combining power. The results showed that nitrofurantoin is handled by glomerular filtration and tubular reabsorption. Tubular reabsorption was greater when the urine was acid. Alkalinizing the urine resulted in higher nitrofurantoin concentrations in the urine and less tubular reabsorption.
The Ret Receptor Tyrosine Kinase Pathway Functionally Interacts with the ERα Pathway in Breast Cancer
Authors: Anne Boulay, Madlaina Breuleux, Christine Stephan, Caroline Fux, Cathrin Brisken, Maryse Fiche, Markus Wartmann, Michael Stumm, Heidi A. Lane, Nancy E. Hynes
Journal: Cancer Research (2008)

Abstract A limited number of receptor tyrosine kinases (e.g., ErbB and fibroblast growth factor receptor families) have been genetically linked to breast cancer development. Here, we investigated the contribution of the Ret receptor tyrosine kinase to breast tumor biology. Ret was expressed in primary breast tumors and cell lines. In estrogen receptor (ER)α-positive MCF7 and T47D lines, the ligand (glial-derived neurotrophic factor) activated signaling pathways and increased anchorage-independent proliferation in a Ret-dependent manner, showing that Ret signaling is functional in breast tumor cells. Ret expression was induced by estrogens and Ret signaling enhanced estrogen-driven proliferation, highlighting the functional interaction of Ret and ER pathways. Furthermore, Ret was detected in primary cancers, and there were higher Ret levels in ERα-positive tumors. In summary, we showed that Ret is a novel proliferative pathway interacting with ER signaling in vitro. Expression of Ret in primary breast tumors suggests that Ret might be a novel therapeutic target in breast cancer. [Cancer Res 2008;68(10):3743–51]
HFEA investigates websites matching sperm donors to would be mothers
Authors: C. Dyer
Journal: BMJ (2010)

The UK Human Fertilisation and Embryology Authority (HFEA) is investigating websites that match up sperm donors with women who want to conceive, to see whether they may be breaking the law.

The move by the HFEA follows the conviction at Southwark Crown Court in London of Ricky Gage and Nigel Woodforth, who made £250 000 (€295 000; $400 000) from their company Fertility 1st, which couriered sperm from donors to women who were trying to conceive. The pair face a possible jail term when they are sentenced in October.

They fell foul …
Laboratory-Acquired Infection with<i>Pseudomonas pseudomallei</i>(Melioidosis)
Authors: Walter F. Schlech, James B. Turchik, Robert E. Westlake, George C. Klein, Jeffrey D. Band, Robert E. Weaver
Journal: New England Journal of Medicine (1981)

INFECTION with Pseudomonas pseudomallei acquired in the Western hemisphere is exceedingly rare. Careful questioning of patients with acute or chronic melioidosis will usually reveal a recent or remote history of travel to Asia or, infrequently, South America. Recently, a patient with acute melioidosis, who was a laboratory technician and had not traveled to these areas, was reported to the Centers for Disease Control (CDC). The circumstances made it likely that this was an example of laboratory-acquired infection.Case ReportA previously well 33-year-old man was hospitalized in June 1980 with fever, pleuritic chest pain, a slightly productive cough, and swelling . . .
REACTION OF RABBITS TO STREPTOCOCCI: COMPARATIVE SENSITIZING EFFECT OF INTRACUTANEOUS AND INTRAVENOUS INOCULA IN MINUTE DOSES
Authors: M. P. Schultz, Homer F. Swift
Journal: The Journal of Experimental Medicine (1932)

1. Rabbits were rendered very hypersensitive by relatively small doses of green streptococci given intracutaneously, and somewhat less hypersensitive by similar doses of heat-killed vaccine prepared from hemolytic streptococci. 2. Animals receiving the same doses intravenously gave, upon subsequent testing, lesions slightly more marked than normal controls; but these lesions were qualitatively hard and nodular compared with the large edematous lesions in the cutaneously sensitized group. 3. There was no parallelism between the degree of cutaneous or ophthalmic hypersensitivity and agglutinin titer in the blood serum. 4. Bacterial hypersensitivity to whole streptococci appears to depend more upon previously induced focal infection than upon circulating antibodies.
Added value of blue dye injection in sentinel node biopsy of breast cancer patients: Do all patients need blue dye?
Authors: Ramin Sadeghi, Ghazaleh Alesheikh, Seyed Rasoul Zakavi, Asiehsadat Fattahi, Abbas Abdollahi, Mehdi Assadi, Ali Jangjoo, Mohammed Keshtgar
Journal: International Journal of Surgery (2014)
Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells.
Authors: V Vetvicka, B P Thornton, G D Ross
Journal: Journal of Clinical Investigation (1996)

When phagocyte CR3 binds to iC3b on bacteria or yeast, phagocytosis and degranulation are triggered because of simultaneous recognition of iC3b via a CD11b I-domain binding site and specific microbial polysaccharides via a lectin site located COOH-terminal to the I-domain. By contrast, when phagocyte or natural killer (NK) cell CR3 adheres to iC3b on erythrocytes or tumor cells that lack CR3-binding membrane polysaccharides, neither lysis nor cytotoxicity are stimulated. This investigation showed that soluble CR3-specific polysaccharides such as beta-glucan induced a primed state of CR3 that could trigger killing of iC3b-target cells that were otherwise resistant to cytotoxicity. Anti-CR3 added before sugars prevented priming, whereas anti-CR3 added after sugars blocked primed CR3 attachment to iC3b-targets. Polysaccharide priming required tyrosine kinase(s) and a magnesium-dependent conformational change of the I-domain that exposed the CBRM1/5 activation epitope. Unlike LPS or cytokines, polysaccharides did not up-regulate neutrophil CR3 expression nor expose the mAb 24 reporter epitope representing the high affinity ICAM-1-binding state. The current data apparently explain the mechanism of tumoricidal beta-glucans used for immunotherapy. These polysaccharides function through binding to phagocyte or NK cell CR3, priming the receptor for cytotoxicity of neoplastic tissues that are frequently targeted with iC3b and sparing normal tissues that lack iC3b.
Successful Surgical Correction of Traumatic Aortic Valve Regurgitation
Authors: Arthur C. Beall, Albert L. Shirkey
Journal: JAMA (1964)

Traumatic aortic valve regurgitation has been recognized for more than a century, but only recently has surgical correction been possible. Typical clinical features include trauma, followed by pain and often syncope, a musical aortic diastolic murmur, and progressive cardiac decompensation. Successful replacement of the aortic valve was performed in a 41-year-old woman whose aortic valve was torn in an automobile accident. This case is believed to be the first reported in which total correction was followed by survival, and illustrates the necessity for accurate diagnosis and surgical therapy in such patients.
Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells.
Authors: A Rambaldi, N Wakamiya, E Vellenga, J Horiguchi, M K Warren, D Kufe, J D Griffin
Journal: Journal of Clinical Investigation (1988)

Macrophage colony-stimulating factor (CSF-1; M-CSF) is a growth factor required for growth and differentiation of mononuclear phagocytes. The effects of CSF-1 are mediated through binding to specific, high-affinity surface receptors encoded by the c-fms gene. CSF-1 and c-fms gene expression was investigated in fresh human acute myeloblastic leukemic cells by Northern blot hybridization using cDNA probes. 4.0-kb CSF-1 transcripts were detected in 10 of 17 cases of acute myeloblastic leukemia (AML), while c-fms transcripts were detected in 7 of 15. Coexpression of CSF-1 and c-fms was observed in five cases, and in five other cases neither gene was expressed. In situ hybridization demonstrated that transcripts for CSF-1 were present in 70-90% of cells in each of three cases studied while c-fms mRNA was detected in 40-70% of cells. The constitutive expression of CSF-1 transcripts was associated with production of CSF-1 protein, although detectable amounts of CSF-1 were not secreted unless the cells were exposed to phorbol ester. These results demonstrate that leukemic myeloblasts from a subset of patients with AML express transcripts for both the CSF-1 and CSF-1 receptor genes, often in the same leukemic cells in vitro.
Clinical classification of cardiac deaths.
Authors: L E Hinkle, H T Thaler
Journal: Circulation (1982)

One hundred forty-two deaths among 743 men ages 50 - 65 years who had been examined and followed 5 - 10 years were investigated and classified on the basis of clinical information from medical and non-medical observers, ECGs and autopsies. A classification based on the condition of the circulation immediately before death appears to be most relevant to studies of sudden death. In 58% of the cases, the subjects collapsed abruptly and his pulse ceased without prior circulatory collapse (arrhythmic death); in 42%, the pulse ceased only after the peripheral circulation had collapsed (deaths in circulatory failure). Thirty-three percent of arrhythmic deaths and 10% of deaths in circulatory failure occurred in a setting of clinical evidence of acute ischemic heart disease (p less than 0.005). Forty-five percent of arrhythmic deaths were preceded by chronic congestive heart failure without circulatory collapse. Ninety-three percent of final illnesses that lasted less than 1 hour ended in arrhythmic deaths; 74% lasted more than 1 day ended in deaths in circulatory failure (p less than 0.001). Eighty-eight percent of deaths that occurred outside of the hospital were arrhythmic; 71% of deaths that occurred in the hospital were deaths in circulatory failure (p less than 0.001). Ninety percent of deaths in which the primary cause of the final illness was heart disease were arrhythmic; 86% of deaths in which the primary cause was other than heart disease were deaths in circulatory failure (p less than 0.001). Ninety-one percent of deaths precipitated by an acute cardiac event were arrhythmic; 98% precipitated by acute respiratory obstruction, hemorrhage, infection, stroke or other noncardiac events were deaths in circulatory failure (p less than 0.001).
Effect of corticotrophin therapy on pituitary-adrenal function.
Authors: M E Carter, V H James
Journal: Annals of the Rheumatic Diseases (1970)

There is now an extensive literature which describes the effects ofcorticosteroid therapy on hypothalamicpituitary-adrenal function.These investigations have shown a diminished adrenal responsiveness to corticotrophin and impaired responses to metyra- pone in patients receiving corticosteroids (see for example Landon, Wynn, James, and Wood, 1965;
US doctors call for simpler Medicare rules
Authors: F. Charatan
Journal: BMJ (2001)

The American Medical Association and doctors groups representing different specialties are seeking relief from burdensome regulations that have resulted in many doctors refusing to accept new patients under Medicare, the healthcare programme for Americans aged over 65.

The doctors' drive comes at a time when the Bush administration and Congress are reviewing the Health Care Financing Administration and its management of Medicare. An annual audit of Medicare payments to doctors, hospitals, and other healthcare providers showed an error rate of 6.8% in the financial year 2000, representing an estimated $11.9bn (£8bn) …
Percutaneous Polyethylene Tube Tracheostomy
Authors: Vincent J. Felitti
Journal: JAMA (1965)

To the Editor:—  The percutaneous transtracheally placed polyethylene catheter described by Myers, R.N., et al (JAMA192:960-972 [June 14] 1965) for postoperative cough induction is occasionally very helpful in obtaining diagnostic sputum specimens.  It is ideal for obtaining a good sputum from semicomatose, or uncooperative patients, or those in whom a sputum specimen collected via an intratracheal catheter passed through a crusted, dirty mouth has produced a confusing variety of organisms. A large catheter (Intracath or Deseret) is passed into the trachea percutaneously, 1 or 2 cc of sterile saline is injected into the trachea, and suction on the syringe is maintained during the resultant paroxysm of coughing. The resultant sputum specimen, though small, is not contaminated by passage through the pharynx and mouth. Several years ago this method was reported to have no complications in a large series from a New York tuberculosis sanatorium.
Targeting Transgene Expression to Airway Epithelia and Submucosal Glands, Prominent Sites of Human CFTR Expression
Authors: Yu-Hua Chow, Jonathan Plumb, Yanxia Wen, Brent M. Steer, Zhan Lu, Manuel Buchwald, Jim Hu
Journal: Molecular Therapy (2000)

Targeting therapeutic gene expression to disease-affected tissues is an essential component of effective and safe gene therapy. After birth, <i>CFTR</i> gene expression in human lungs is localized predominantly in the epithelial cells lining the upper airways, especially in the ducts and serous tubules of the submucosal glands. We have developed a K18 expression cassette, based on the DNA control elements of the human cytokeratin 18 gene. Temporal and spatial analyses of transgenic mice demonstrated that this expression cassette targets transgene expression to almost all cell types in which CFTR is expressed. Airway epithelium expression started as early as 11.5 days of gestational age and continued into the adulthood of the transgenic mice. In these adult mice, the pattern of the reporter expression strikingly matched that of the human cytokeratin 18 and human <i>CFTR</i> genes. The transgene expression was epithelium-specific and undetectable in connective tissue, muscle, bone, cartilage, blood, and endothelial cells. Significantly, high levels of expression were detected in tracheal submucosal glands. Together, these results suggest that our K18 expression cassette has a high potential for clinical application in gene therapy for patients with cystic fibrosis.
Human Epididymis Protein 4 (HE4) Is a Secreted Glycoprotein that Is Overexpressed by Serous and Endometrioid Ovarian Carcinomas
Authors: Ronny Drapkin, Hans Henning von Horsten, Yafang Lin, Samuel C. Mok, Christopher P. Crum, William R. Welch, Jonathan L. Hecht
Journal: Cancer Research (2005)

Abstract Among the genes most commonly identified in gene expression profiles of epithelial ovarian carcinomas (EOC) is the gene for human epididymis protein 4 (HE4). To ascertain its clinical utility, we did a comprehensive assessment of HE4 protein expression in benign and malignant ovarian and nonovarian tissues by immunohistochemistry. In comparison with normal surface epithelium, which does not express HE4, we found that cortical inclusion cysts lined by metaplastic Mullerian epithelium abundantly express the protein. Its expression in tumors was restricted to certain histologic subtype: 93% of serous and 100% of endometrioid EOCs expressed HE4, whereas only 50% and 0% of clear cell carcinomas and mucinous tumors, respectively, were positive. Tissue microarrays revealed that the majority of nonovarian carcinomas do not express HE4, consistent with our observation that HE4 protein expression is highly restricted in normal tissue to the reproductive tracts and respiratory epithelium. HE4 is predicted to encode a secreted protein. Using reverse transcription-PCR, we identified ovarian cancer cell lines that endogenously overexpress HE4. Cultured medium from these cells revealed a secreted form of HE4 that is N-glycosylated. This observation is consistent with the recent report that HE4 circulates in the bloodstream of patients with EOC. Therefore, HE4 is a secreted glycoprotein that is overexpressed by serous and endometrioid EOCs. Its expression in cortical inclusion cysts suggests that formation of Mullerian epithelium is a prerequisite step in the development of some types of EOCs.
TCT-202 Clinical Outcomes of Guidewire Induced Vessel Injury in Retrograde versus Antegrade Approach for Percutaneous Intervention of Coronary Chronic Total Occlusions: Insights from Intravascular Ultrasound
Authors: Mahmoud M. Sabbah, Takeshi Tada, Kazushige Kadota, Seiji Habara, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2014)
Internal Medicine and Family Practice
Authors: Robert G. Petersdorf
Journal: New England Journal of Medicine (1975)

Abstract Internal medicine and family practice have come into conflict because both specialties consider primary care to be part of their "turf." Moreover, in academic medical centers there is competition for scarce resources, including patients and support for residents. Analysis of the number of physicians in practice as well as in training shows clearly that both internists and family physicians, as well as pediatricians and obstetricians, must participate in rendering primary care if the needs for this type of physician are to be met. Internal medicine also has to achieve a better balance between generalists and subspecialists, and family practice must define its limitations, monitor its rapid growth and assure the quality of its training programs. Most of these problems are internal to each specialty rather than between two specialties, and, where there is conflict, compromise is clearly possible. (N Engl J Med 293:326–332, 1975)
Drug points: Pancreatitis associated with hydroxyurea in combination with didanosine
Authors: H J Longhurst
Journal: BMJ (2001)

Hydroxurea is a popular, but unlicensed, means of intensifying treatment in patients receiving didanosine, an inhibitor of nucleoside reverse transcriptase (a “nucleoside analogue”) used in combination with other retroviral drugs for the treatment of HIV infection. We report on a patient who developed pancreatitis after hydroxyurea was added to didanosine.

In January 1998 a 26 year old man who was HIV positive started taking stavudine 40 mg twice daily (Zerit, Bristol-Myers Squibb), didanosine 400 mg daily (Videx, Bristol-Myers Squibb), and nevirapine 200 mg twice …
Independent review of Worcester PFI is needed
Authors: S. Parkinson
Journal: BMJ (2002)

EDITOR—We at Worcestershire Local Medical Committee wish to refute McCloskey's assertions on the cost of the private finance initiative (PFI) hospital scheme in Worcester.1 We have had major anxieties about the strategic review of health care in Worcestershire and the Worcester PFI project. We have been unable to obtain the clarification we seek from the health authority and have welcomed expert independent assessment of the …