tbuckley/cabot-search huggingface dataset:
Foetal and Neonatal Pathology
Authors: Gordon F. Vawter
Journal: JAMA (1964)

The second edition of Foetal and Neonatal Pathology will interest all who are concerned with wastage of the fetus and newborn—principally pediatricians, obstetricians, workers in child health clinics, and pathologists. The material of the classic first edition, which has not been available in this country for some years, has now been updated by Dr. J. Edgar Morison of Belfast, with selected references as recent as 1963. To some it will seem that the strength of the scholarly work will lie as much in the attitudes and judgments presented as in the factual data brought together, for these judgments far transcend a static description of pathological anatomy.  While there are 128 figures (many diagrammatic), the text (embodied in over 500 pages) is the heart of the work. The guide lines marked out here will preserve the usefulness of the volume, despite the rapidly expanding advances of biology and medicine. Considerable emphasis
Placebo pills for children
Authors: Douglas Kamerow
Journal: BMJ (2008)

A deeply bad idea 

And so another trend begins in America. This time it is placebo pills for kids.

On 1 June a company called Efficacy Brands (I’m not making this up) put cherry flavoured sugar tablets on sale on the web. The company was started by a mother with three young children, who has appeared on the morning television shows in the US to publicise her inspiration. For just under $6.00 you can order a bottle of these pills to “treat” children when real medicine isn’t appropriate and a hug and a kiss aren’t enough. The pill is called Obecalp—placebo spelt backwards. How clever is that?

I first became aware of the power of placebos 30 years ago when I was an intern in a large US urban hospital. Our pharmacy stocked two “special” painkilling drugs, available by a doctor’s prescription only. One came in a brilliant red capsule and the other was deep purple. The interns were instructed that these pills were for people who abused pain medications and …
Prospective controlled trial comparing colostomy irrigation with "spontaneous-action" method.
Authors: N S Williams, D Johnston
Journal: BMJ (1980)

Thirty randomly selected patients with permanent colostomies entered a prospective controlled trial comparing colostomy irrigation with spontaneous action. Each patient was interviewed and examined before irrigation was begun and again after the technique had been used for three months. Each then reverted to spontaneous action for a further three months and was then reassessed. Eight patients abandoned irrigation and 22 (73%) adhered to the protocol. Irrigation caused no mishaps or complications. The mean time spent managing the stoma was 45 +/- SEM 9 min/24 hours during spontaneous action and 53 +/- 9 min/24 hours during irrigation. This difference was not significant. The numbers of bowel actions weekly were 13 +/ SEM 2 during spontaneous action and 6 +/- 1 during irrigation (p &lt; 0.01). Irrigation reduced odour and flatus in 20 patients and enabled 12 out of 18 to stop using drugs and seven to discard their appliance. Irrigation also improved the social life of 18 patients and the working conditions of eight out of 14. These finding show that some patients may not be suitable for irrigation but that for many it is better than the conventional British method of colostomy management. With modern apparatus the technique is safe.
ABC of the upper gastrointestinal tract: Dysphagia
Authors: W. Owen
Journal: BMJ (2001)

Dysphagia is a distressing symptom and indicates a delay in the passage of solids or liquids from the mouth to the stomach. It is sometimes difficult to understand why patients may take so long to consult their doctor for advice, but whenever patients present a diagnosis should be urgently sought. Dysphagia should be distinguished from odynophagia, which is discomfort or pain on swallowing hot or cold liquids and, occasionally, alcohol. 

In clinical practice it is useful to separate those causes that predominantly affect the pharynx and proximal oesophagus (high dysphagia) and those mostly affecting the oesophageal body and oesophagogastric junction (low dysphagia).
PHAGOCYTOSIS OF IMMUNE COMPLEXES BY MACROPHAGES
Authors: B. Mantovani, M. Rabinovitch, V. Nussenzweig
Journal: The Journal of Experimental Medicine (1972)

Sheep red cells (E) sensitized with IgG antibody (EA) or with antibody and complement (EAC) interact in vitro with mouse peritoneal macrophage monolayers. The role of IgG and of C3 in the attachment and ingestion of the erythrocytes was examined by means of quantitative technique utilizing 51Cr-labeled E. Controlled osmotic lysis permitted the separate measurement of the radioactivity associated with bound or with ingested E. IgG-125I was used to estimate the number of IgG molecules bound per E as a function of the IgG concentration. Control experiments showed that iodination did not influence the extent of binding of IgG to E and that the binding of IgG prepared from immune serum could be essentially ascribed to its anti-E antibody content. Only between 103 and 104 rabbit anti-E IgG molecules per erythrocyte were needed for detectable attachment and ingestion of EA (a maximum number of 6 x 105 IgG antibody molecules could be accomodated on one erythrocyte). Evidence was obtained that C3 is primarily involved in particle attachment, whereas only IgG is able to markedly promote the ingestion of particles attached to macrophages: (a) Addition of complement to the EA substantially increased the binding to the macrophages, whereas ingestion was increased to a smaller extent. Both binding and ingestion of EAC were markedly inhibited by papain fragments of IgG obtained from a rabbit antiserum to mouse C3. (b) Low doses (2 µg/ml) of papain fragments of IgG from a rabbit antiserum to mouse IgG markedly reduced the ingestion of EAC, whereas attachment of EAC to macrophages was inhibited to a much smaller degree. The possible relevance of these findings for the in vivo fate of particulate immune complexes as they interact with macrophages is discussed. It is suggested that in the primary immune response, when the complexes are predominantly in the form of EA (IgM) or EA (IgM) C3, they would tend to remain on the surface of the macrophages and thus be in a position to stimulate immunocompetent cells. In the secondary response, when EA (IgG) or EA (IgG) C3 predominate, the complexes would tend to be more rapidly interiorized and degraded by the mononuclear phagocytes,
Modulation of the alternative complement pathways by beta 1 H globulin.
Authors: K Whaley, S Ruddy
Journal: The Journal of Experimental Medicine (1976)

C3b inactivator accelerator (A-C3bINA) was isolated from human plasma. An antiserum produced against the purified protein gave a reaction of identity with beta 1 H, a well-documented contaminant of C3 preparations. Beta 1 H appears to be composed of a single polypeptide chain containing a significant quantity of carbohydrate, and having a sedimentation coefficient of 5.6 on analytical, and 6.4 on sucrose density gradient ultracentrifugation. Its mol wt based on SDS polyacrylamide gel electrophoresis and equilibrium sedimentation is approximately 150,000, whereas it elutes from Sephadex G200 with an apparent mol wt of 300,000, suggesting that beta 1 H is an asymmetric molecule. Beta 1 H potentiates the inactivation of C3b by C3b inactivator, binds to EAC43 to limit the formation of EAC43bB and EAC43bBP, and in contrast to C3b inactivator, it increases the rate of loss of hemolytic sites from EAC43bB and EAC43bBP. For the C3b inactivator-potentiating effect, beta 1 H and C3b inactivator must necessarily be simultaneously present. The kinetics of inactivation of C3b by C3b inactivator and beta 1 H are first order, suggesting that potentiation is not a multistep process. The mechanisms of binding to C3b and inhibition of the alternative pathway convertases C3bB and C3bBP are currently unknown.
Processing and proliferative effects of human progastrin in transgenic mice.
Authors: T C Wang, T J Koh, A Varro, R J Cahill, C A Dangler, J G Fox, G J Dockray
Journal: Journal of Clinical Investigation (1996)

Incompletely processed gastrins have been postulated to play a role in growth of the gastrointestinal tract, but few studies have examined the effects of progastrin on mucosal proliferation in vivo. Human gastrin gene expression and progastrin processing were therefore studied in transgenic mice containing a human gastrin (hGAS) minigene, and compared to processing in mice bearing an insulin gastrin (INS-GAS) transgene that overexpresses amidated gastrin. Progastrin processing was studied using region-specific antisera and radioimmunoassays, biosynthetic labeling, immunoprecipitation, and HPLC. Proliferative effects due to overexpression of processed and unprocessed gastrin in INS-GAS and hGAS mice, respectively, were determined using routine histology and BrdU incorporation. The pancreatic islets of INS-GAS mice were able to produce carboxyamidated G-17, resulting in a twofold elevation of serum amidated gastrin, marked thickening of the oxyntic mucosa, and an increased BrdU labeling index (LI) of the gastric body. In contrast, livers of adult hGAS mice expressed abundant human gastrin mRNA and human progastrin but were unable to process this peptide to the mature amidated form, resulting in markedly elevated serum progastrin levels and normal amidated gastrin levels. Nevertheless, there was a marked increase in the BrdU labeling index of the colon in hGAS mice (LI 7.46+/-1.90%), as well as in INS-GAS mice (LI 6.16+/-1.17%), compared to age-matched, wild type control mice (LI 4.01+/-0.98%, P < 0.05). These studies suggest that incompletely processed gastrin precursors may contribute to colonic mucosal proliferation in vivo.
EVALUATION OF IMMEDIATE AND MAXIMAL EXERCISE ON LEFT VENTRICULAR FUNCTION USING GOLD-195m
Authors: K. A. Narahara, I. Mena, M. Brizendine, J. Fain, K. Wasserman
Journal: Clinical Nuclear Medicine (1982)

Division of Nuclear Medicine, Cardiology, and Respiratory Physiology, Harbor-UCLA Medical Center, Torrance, CA.
Abstract S3-8: Identification of Novel Synthetic-Lethal Targets for MYC-Driven Triple-Negative Breast Cancer
Authors: A Goga, S Samson, D Horiuchi
Journal: Cancer Research (2012)

Abstract Currently, the greatest clinical challenge in treating breast cancer occurs in those patients whose tumors lack expression of the estrogen and progesterone receptors and the HER2 oncoprotein. No targeted agents currently exist against this aggressive type of receptor ‘triple negative’ breast cancer that disproportionately affects young African American women and also a substantial number of white American women. We have discovered that triple-negative tumors frequently express high levels of the MYC proto-oncogene. We sought to identify new “synthetic-lethal” strategies to selectively kill triple-negative breast tumors with MYC overexpression. Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death, whereas a mutation in only one of these genes has little effect. Using this strategy, we can take advantage of the elevated MYC signaling in triple-negative tumors to selectively kill them, while sparing normal tissues in which MYC is expressed at much lower levels. RESULTS: We performed a shRNA synthetic-lethal screen to identify new molecules, such as cell cycle kinases, which when inhibited can preferentially kill triple-negative breast tumor cells. The unbiased shRNA-based screening approach was performed in human mammary epithelial cells (HMECs) that have inducible MYC over-expression. A high-throughput screen of ∼2000 shRNAs, that target the human kinome (∼ 600 kinases) was performed, and identified 13 kinases whose inhibition by &amp;gt;1 shRNAs gave rise to &amp;gt;50% inhibition of cell growth. Two of the kinases identified in our screen, ARK5 and GSK3A, were also recently identified by other studies and shown to have a synthetic-lethal interaction with MYC. These results validated our ability to identify synthetic-lethal targets. We are currently characterizing and validating the 11 novel targets identified in this screen, using human cancer cell lines as well as mouse cancer models to determine the impact of inhibiting these targets on triple-negative breast cancer development and proliferation. Additional synthetic-lethal interactions with MYC over-expression in triple-negative breast cancers will be presented. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S3-8.
Direct measurement of changes in intracellular calcium transients during hypoxia, ischemia, and reperfusion of the intact mammalian heart.
Authors: Y Kihara, W Grossman, J P Morgan
Journal: Circulation Research (1989)

In studies of ischemia and reperfusion, a major experimental problem has been the inability to measure intracellular ionized calcium ([Ca2+]i) in the intact heart. We have developed a new approach in which the bioluminescent calcium indicator aequorin is used to measure [Ca2+]i in the isolated, coronary-perfused ferret heart. Aequorin is loaded into subepicardial myocytes of the left ventricle, and the signals are recorded simultaneously along with isovolumic left ventricular (LV) pressure at a constant pacing rate. This system shows 1) no attenuation or change of time course of LV pressure development or coronary perfusion pressure after aequorin loading; 2) consistent responses to physiological interventions and drugs; 3) individual aequorin and pressure signals that do not require signal averaging for analysis; and 4) [Ca2+]i levels comparable with those reported in tissue or isolated myocyte cell preparations. During 5 minutes of hypoxia, diastolic [Ca2+]i and LV diastolic pressure increased while the systolic values of both [Ca2+]i and pressure decreased. The peak-to-peak systolic [Ca2+]i versus LV isovolumic pressure relation remained close to the control curve. In contrast, during 3 minutes of global ischemia, LV systolic and diastolic pressures fell rapidly, while [Ca2+]i increased substantially. The [Ca2+]i versus pressure relations for both systole and diastole shifted to the right, indicating desensitization of the contractile apparatus to [Ca2+]i. These results provide evidence that different primary mechanisms determine the systolic and diastolic responses to acute hypoxia versus ischemia. During hypoxia, changes in [Ca2+]i handling probably play a major role, while during ischemia, changes in the Ca2+ sensitivity of the myofilaments appear to be of primary importance in the modulation of contractile dysfunction.
A New Mode of Affording Permanent Relief to Intractable Chronic Cytstitis, and to Confirmed Prostatic Retention of Urine
Authors: W. F. Teevan
Journal: BMJ (1883)

<h3>Background</h3> Primary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype. <h3>Methods</h3> We prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV). <h3>Results</h3> Sixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of <i>DNAI1</i> mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of <i>CCDC39</i> mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of <i>RSPH1</i> mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF. <h3>Conclusion</h3> Quantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.
A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement.
Authors: S Matsuoka, Y Asano, K Sano, H Kishimoto, I Yamashita, H Yorifuji, M Utsuyama, K Hirokawa, T Tada
Journal: The Journal of Experimental Medicine (1995)

A monoclonal antibody, RE2, raised by immunizing a rat with cell lysate of a mouse T cell clone, was found to directly kill interleukin 2-dependent T cell clones without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments with anti-rat immunoglobulin reconstituted the cytotoxicity. The cytotoxicity was temperature dependent: the antibody could kill target cells at 37 degrees C but not at 0 degrees C. Sodium azide, ethylenediaminetetraacetic acid, and forskolin did not affect the cytolytic activity of RE2, while the treatment of target cells with cytochalasin B and D completely blocked the activity. This suggested that the cell death involves a cytoskeleton-dependent active process. Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. The antibody also killed T cell lymphomas and T and B cell hybridomas only when these cells were preactivated with concanavalin A, lipopolysaccharide, or phorbol myristate acetate. Preactivated peripheral T and B cells were sensitive to the cytotoxicity of RE2, while resting T and B cells were insensitive. These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation.
The Hypocholesterolemic Effects of β-Glucan
Authors: Frank M. Sacks
Journal: JAMA (1991)

<h3>To the Editor.</h3> —There are several troubling aspects to the recent article by Davidson et al<sup>1</sup>on oat products. In their study, the authors purport to show a dose-response effect of 28, 56, and 84 g (1,2, and 3 oz, respectively) of oat products per day on serum cholesterol levels. Unfortunately, proper control was lacking in the authors' design, which renders their conclusion untenable. To show an independent action of oats, it is critical to use for a control the identical amount of a low-fiber cereal product, such as refined wheat. The authors actually compared 28, 56, and 84 g of oat products (28 g is equivalent to one serving of oatmeal or oat bran) with 28 g of wheat. The only well-controlled comparison in this study, 28 g of oats vs 28 g of wheat, showed no statistically significant effect of the oats. Incredibly, the conclusion of the
Clofibrate and Eosinophilic Pneumonia
Authors: Roman M. Hendrickson
Journal: JAMA (1982)

To the Editor.—  Clofibrate (Atromid-S) is a widely used agent for the treatment of hypercholesterolemia. Adverse effects are numerous, including weight gain, polyphagia, fatigue, malaise, headache, blood disorders, skin disorders, myalgia, arthralgia, gastrointestinal abnormalities (including nausea, diarrhea, abdominal upset, gallstones), hepatic abnormalities, and cardiovascular abnormalities.  This case illustrates another adverse side effect of the drug—eosinophilic pneumonia.  Report of a Case.—  A man aged 73 years had an 18-month history of hypercholesterolemia treated with clofibrate.  In October 1976 the patient was seen with an eight-week history of gradually increasing dyspnea on exertion, a cough that was usually nonproductive though sometimes productive of a mucoid sputum, and loss of energy. At the time of initial examination the patient was found to be mildly dyspneic and tachycardic, with moist inspiratory rales present at both lung bases. A chest roentgenogram showed extensive pulmonary fibrosis. Pulmonary functions subsequent to hospitalization for evaluation of this patient's
Role of the Diabetes Educator for Older Adults
Authors: Martha Mitchell Funnell
Journal: Diabetes Care (1990)

Patient education is an essential component in the care of patients with diabetes. Older adults often have particular educational needs due to the effects of aging, concomitant illnesses, and the complications of diabetes. Because of the necessity for appropriately trained patients, the role of health-care professionals as diabetes educators is of paramount importance to the health-care team. The diabetes educator is able to assume responsibility for all aspects of the education process, including assessment, teaching, and follow-up, and take into account the individual needs presented by the older adult patient with diabetes.
P748Vascular smooth muscle cell proteome changes in a high fat diet animal model of atherogenesis.
Authors: S Rocchiccioli, N Ucciferri, F Viglione, L Citti, O Parodi, G Pelosi, MG Trivella, A Cecchettini
Journal: Cardiovascular Research (2014)

Purpose: De-differentiation and phenotype changes in vascular smooth muscle cells (VSMCs) are hallmarks of vascular disorders such as atherosclerosis (ATS). High fat diet pigs were exploited as model of accelerated coronary ATS. In the present study, a gel-free proteomics approach was proposed to highlight protein markers modulated during atherogenesis and plaque growth in cultured VSMCs obtained from coronary and femoral arteries.
New Paramedical Personnel — To License or Not to License?
Authors: William J. Curran
Journal: New England Journal of Medicine (1970)

DANIEL Patrick Moynihan, currently a Presidential advisor at the White House, has received wide publicity for his suggestion of a period of "benign neglect" of race relations in the United States. Some medicolegal experts seem to be giving similar advice regarding the legal problems surrounding the use of paramedical personnel. The American Medical Association legal staff, among others, seems prone to this point of view. Basically, this position is that we should not rash to the state legislatures with new licensure laws for the legitimization of the ill defined and still very few new classes of physician's assistants. Such efforts . . .
Smoking, Alcohol, and Neuromuscular Function in Older Women-Reply
Authors: Heidi D. Nelson, Michael C. Nevitt, Katie L. Stone, Steven R. Cummings, Jean C. Scott
Journal: JAMA (1995)

<h3>In Reply.</h3> —Dr Slade suggests that nicotine may impair neuromuscular performance and increase the risk of subsequent injury. A relaxing effect of nicotine on the neuromuscular system has been described.<sup>1</sup>It may be one of several mechanisms acting together in a cumulative fashion to impair function. Dr Spilich suggests that one more such mechanism may be a direct effect of nicotine on the central nervous system. Nicotine and brain neurotransmitter systems have been studied, although their relationships to performance have been limited to animal investigations.<sup>2</sup>Others have documented lower cerebral blood perfusion levels in elderly chronic smokers compared with nonsmokers with improvement in perfusion within 1 year after smoking cessation.<sup>3</sup>Both of these central nervous system mechanisms could contribute to impaired performance. We hope our observations stimulate physiologic studies of the mechanism for this important adverse effect of smoking on the quality of smokers' lives.