tbuckley/cabot-search huggingface dataset:
VACCINE TREATMENT IN THE PREVENTION OF DYSENTERY IN INFANTS
Authors: W. P. Lucas, Harold L. Amoss
Journal: The Journal of Experimental Medicine (1911)

This investigation is very limited and the number of patients treated is few, yet the following conclusions may not be amiss:- 1. The vaccine in no instance did harm, and the reactions in the majority were very mild and of short duration. 2. Cases in which bacteriologically B. dysenteriae were proved to be present, but in a clinically unrecognizable form, were not affected differently from those which were culturally negative. This may in part be due to the fact that this mode of vaccination produces an immediate passive immunity, while the bacterial vaccine is producing an active immunity. 3. The work is of interest and holds out a possible means of preventing the great mortality from infantile dysentery during the summer months.
Rare diseases, orphan drugs, and orphan diseases
Authors: Jeff Aronson
Journal: BMJ (2006)

Rare comes from the Latin rarus (loosely spaced or sparse) and eventually from the putative Indo-European root ERE, denoting separation, as in hermits and eremites and the net-like structures rete, retinaculum, and retina.

Orphan comes from the Greek orphanos (a child deprived of one parent or both, or an adult deprived of a child). Metaphorically it denoted poverty and unspiced food. Its Indo-European root was ORBH (bereft) giving the Latin orbus and the obsolete English words orbation and orbity (orphanhood or childlessness). One bereft of freedom is a slave, forced into hard work, as in the German Arbeit and the Czech robota. Karel Eapek coined the word robot (female robotka) in his play R.U.R. ( Rossum's Universal Robots , 1920) to denote an imagined race of mechanical people. And the etymology reflects the link between orphans and the workhouse.

Modern …
Plus ça Change, Plus C'est les Mêmes HMOs
Authors: F. Peter Rescigno
Journal: JAMA (1986)

To the Editor.—   Plus ca change, plus c'est la meme chose , 1 or is it? The author 2 states that, In spite of all its great advances, what medicine is still all about is the patient, the physician, and the quality of the relationship that exists between them.  How is the quality of the relationship affected when patients see a doctor not of their choosing but the one selected or available from the roster of a health maintenance organization (HMO) or preferred provider organization? How is that relationship affected by the physician's knowledge that the patient did not necessarily choose that physician? How is the nature of the relationship affected by the physician's sense of his relatively diminished role as another employee in a corporation of many employees whose management may consider the bottom line on the financial balance sheet as the prime consideration of that corporation and may direct its
Child and adolescent mental health referrals jump as cases get more extreme and complex, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2014)

The number of mental health referrals in children and adolescents is rising sharply, and the referrals are becoming more complex and more acute, psychiatrists have told MPs. One expert witness also claimed that health professionals were seeing an unprecedented degree of “social disintegration” and a remarkable level of insecurity among young people.

MPs on the parliamentary health select committee questioned several psychiatrist witnesses on 10 June as part of their inquiry into child and adolescent mental health services (CAMHS). When asked by MPs how demand on these services had changed in recent years, all of the witnesses said that it had risen sharply.

Liz Myers, a consultant child and adolescent psychiatrist for CAMHS at Cornwall Partnership NHS Foundation Trust, …
The FDA Critical Path Initiative and Its Influence on New Drug Development
Authors: Janet Woodcock, Raymond Woosley
Journal: Annual Review of Medicine (2008)

Societal expectations about drug safety and efficacy are rising while productivity in the pharmaceutical industry is falling. In 2004, the US Food and Drug Administration introduced the Critical Path Initiative with the intent of modernizing drug development by incorporating recent scientific advances, such as genomics and advanced imaging technologies, into the process. An important part of the initiative is the use of public-private partnerships and consortia to accomplish the needed research. This article explicates the reasoning behind the Critical Path Initiative and discusses examples of successful consortia.
Enhanced Metastatic Potential of Tumor Cells Harvested From Spontaneous Metastases of Heterogeneous Murine Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: James E. Talmadge, Isaiah J. Fidler
Journal: JNCI Journal of the National Cancer Institute (1982)

These studies demonstrated that cells populating spontaneous metastases are, in general, more metastatic than the cells populating the parent neoplasm, thereby providing direct evidence that the process of metastasis is selective and not random. The tumors used in these studies were the UV-2237 fibrosarcoma, an in vitro cloned line (C-40) from the UV-2237 tumor, and the K-1735 melanoma, all of which are syngeneic to the C3H/HeN (mammary tumor virus-negative) mouse strain; the M5076 reticulum cell sarcoma and the Lewis lung carcinoma 3LL, which are syngeneic to the C57BL/6 mouse strain, were also used. All tumors were implanted sc into the footpads of syngeneic mice, and several resulting spontaneous metastases were isolated and established in culture as individual cell lines. For each tumor system, comparison was made of the ability of parent tumor cells and cells isolated from several spontaneous metastases to produce either experimental or spontaneous metastases. Cells populating spontaneous metastases produced by heterogeneous and poorly metastatic tumors were significantly more metastatic than the cells of their respective parent tumors. In contrast, cells populating metastases produced by previously selected tumors did not differ significantly in metastatic potential from cells populating their parent tumors. In such systems, metastasis appeared to be random.
Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study
Authors: CJ Hawkey, Z Tulassay, L Szczepanski, CJ van Rensburg, A Filipowicz-Sosnowska, A Lanas, CM Wason, RA Peacock, KRW Gillon
Journal: The Lancet (1998)
Observations on Lithotrity, with a Series of Forty Consecutive Cases
Authors: F. S. Edwards
Journal: BMJ (1891)

c mpanying table varied very much onI admissioln.Some were tlhe plumlp offspring of well-to-do parents, but tbe greater number were underfed and emaciated chlildren of poor villagers from remote and nmalarious districts.Some of the chiildreni were, sufferincr from fever on arrival, and, in suchI cases, operationl lhad of course to be deferred.Nine times out of tell, however, it was of necessity performed on the imlorniing following the arrival of the patient.TIlle variation in the calibre of the uretlhral passages was remarkable.The fact of this variation has already beeni pointed out by Surgeon-MNajor Keeganl.Tlhus, the uretlhra of hle boy aged a, Case 20, admitted a No. 7 lithotrite, wlhile in Case 19, that of a boy aged 10, onily a No. 6 could with diffi- (ulty be passed.fI thle very great majority of the cases tlle operation was followed by immIiediate relief, witlhout ainythlinig more than a trifling rise of temperature.The boy, if allowed, would be IIp and(1 playing about in twvo or tlhree days.In1 a few+ soine fever ensuecl---always of ani initermittent type, never high, and yiCldinf,l readily to quinline.append DOteS of the fev cases occurring dtring the samiie period in vcitich I' foiiid 1 itliolopaxy imlpracticable.CASE i.-At bov-, aged 3. Tlhe smallest litlhotrite at lhanid (No. fi) could t to be l)assed inl this case; lateral litlhotomy was tlherefore performed, anild twvo stoines, wveighing togetlher 153 grains, were extracted.The patieilt did wvell.CASE ms--A box-, aced :1I.In tlhis case also time smallest litlhotrite could not I)e passed.Sulrapubic litlhotomy was performiied, and two stonies, weighinig togetlher ')5s; grraiis, vere extracted.Tlle patient did well.Uriine comumenced to pass p)er rct/iream on time sixtth day, but the fistula was not entir-ely closed tuntil time tlhirty-eiglhtli day.CASE mii.-A l)oy, a-ed 4I'.Nothing larger than a No. 2 cathieter could be passed iinto this t]lild's bladder; suprapubic litlhotomiiy was thlcrefore per'for-miied.Failiim a proper india-rubber bag asheep's bladder was used to disteind tme ric tuiii.le wvas a fat elhild, and tlle dissection down to time bladder took sosaie little timiie.wllhile it was going oma some of time water leaked from tlle sheep's bladder, whicla was suiddenly expelled froint the rectumiii by tll child's straining.As the bladder had beeil reaclied whei i iss halppened, it was tlhought better to proceed with the operation ivitlmoist delayiinto reinitroduce the bag.Shortly afterwards the per itoneuimi appeai ed in the upper anigle of the wounid; it was kept out of the wvay by a forefinger, anid tIme operation completed, a stone weigling 109 grains bein-extracted.The patienat did well, and vas dis- chtarged on lie twenty-third day after the operation.Tlhe case afforcd a striikin(r illustratioil of the valuc of distensioni of the sectum in silpra- pubic litlhotoimiy.CASFE mv.-Tlmis paticnt, a boy, aged 12, lad suffered from stone for 1013
Hepatitis C Virus Testing of Persons Born During 1945–1965: Recommendations From the Centers for Disease Control and Prevention
Authors: Bryce D. Smith, Rebecca L. Morgan, Geoff A. Beckett, Yngve Falck-Ytter, Deborah Holtzman, John W. Ward
Journal: Annals of Internal Medicine (2012)

Description: The Centers for Disease Control and Prevention (CDC) and a group of governmental and private sector partners developed these evidence-based recommendations to increase the proportion of hepatitis C virus (HCV)–infected persons who know their status and are linked to appropriate care and treatment. The recommendations also address brief alcohol screening, as alcohol accelerates progression of liver disease among HCV-infected individuals. These recommendations augment CDC's 1998 and 1999 recommendations based on risk and medical indications and are not meant to replace those recommendations. Methods: These recommendations are based on systematic reviews of evidence published from 1995 through February 2012 in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Database of Abstracts of Reviews of Effects. Selected studies included cross-sectional and cohort studies that addressed either prevalence of hepatitis C in the United States or clinical outcomes (for example, hepatocellular carcinoma and serious adverse events) among treated patients and systematic reviews of trials that assessed effectiveness of brief screening interventions for alcohol consumption. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess quality of the evidence. Recommendation 1: Adults born during 1945–1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk. (Grade: strong recommendation; moderate-quality evidence). Recommendation 2: All persons with identified HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions (Grade: strong recommendation; moderate-quality evidence).
Comparison of Bare Metal Stenting and Percutaneous Pulmonary Valve Implantation for Treatment of Right Ventricular Outflow Tract Obstruction
Authors: Philipp Lurz, Johannes Nordmeyer, Vivek Muthurangu, Sachin Khambadkone, Graham Derrick, Robert Yates, Michael Sury, Philipp Bonhoeffer, Andrew M. Taylor
Journal: Circulation (2009)

Treatment of right ventricular outflow tract obstruction is possible with a bare metal stent (BMS), although this treatment causes pulmonary regurgitation. In this study, we assessed the acute physiological effects of BMS versus percutaneous pulmonary valve implantation (PPVI) using an x-ray/magnetic resonance hybrid laboratory.Fourteen consecutive children (median age, 12.9 years) with significant right ventricular outflow tract obstruction underwent BMS followed by PPVI. Magnetic resonance imaging (ventricular volumes and function and great vessel blood flow) and hemodynamic assessment (invasive pressure measurements) were performed before BMS, after BMS, and after PPVI; all were performed under general anesthesia in an x-ray/magnetic resonance hybrid laboratory. BMS significantly reduced the ratio of right ventricular to systemic pressure (0.75+/-0.17% versus 0.41+/-0.14%; P<0.001) with no further change after PPVI (0.42+/-0.11; P=1.0). However, BMS resulted in free pulmonary regurgitation (21.3+/-10.7% versus 41.4+/-7.5%; P<0.001), which was nearly abolished after PPVI (3.6+/-5.6%; P<0.001). Effective right ventricular stroke volume (right ventricular stroke volume minus pulmonary regurgitant volume) after BMS remained unchanged (33.8+/-7.3 versus 32.6+/-8.7 mL/m2; P=1.0) but was significantly increased after revalvulation with PPVI (41.0+/-8.0 mL/m2; P=0.004). These improvements after PPVI were accompanied by a significant heart rate reduction (75.5+/-17.7 bpm after BMS versus 69.0+/-16.9 bpm after PPVI; P=0.006) at maintained cardiac output (2.5+/-0.5 versus 2.4+/-0.5 versus 2.7+/-0.5 mL x min(-1) x m(-2); P=0.14).Using an x-ray/magnetic resonance hybrid laboratory, we have demonstrated the superior acute hemodynamic effects of PPVI over BMS in patients with right ventricular outflow tract obstruction.
Treatment-emergent hypertension and outcomes in patients with advanced non-small-cell lung cancer receiving chemotherapy with or without the vascular endothelial growth factor receptor inhibitor cediranib: NCIC Clinical Trials Group Study BR24
Authors: R. Goodwin, K. Ding, L. Seymour, A. LeMaître, A. Arnold, F.A. Shepherd, M. Dediu, T. Ciuleanu, D. Fenton, M. Zukin, D. Walde, F. Laberge, M. Vincent, P.M. Ellis, S.A. Laurie
Journal: Annals of Oncology (2010)
Functional Characterization of Connexin43 Mutations Found in Patients With Oculodentodigital Dysplasia
Authors: Junko Shibayama, William Paznekas, Akiko Seki, Steven Taffet, Ethylin Wang Jabs, Mario Delmar, Hassan Musa
Journal: Circulation Research (2005)

Specific mutations in GJA1, the gene encoding the gap junction protein connexin43 (Cx43), cause an autosomal dominant disorder called oculodentodigital dysplasia (ODDD). Here, we characterize the effects of 8 of these mutations on Cx43 function. Immunochemical studies have shown that most of the mutant proteins formed gap junction plaques at the sites of cell-cell apposition. However, 2 of the mutations (a codon duplication in the first extracellular loop, F52dup, and a missense mutation in the second extracellular loop, R202H, produced full-length connexins that failed to properly form gap junction plaques. Cx43 proteins containing ODDD mutations found in the N-terminus (Y17S), first transmembrane domain (G21R, A40V), second transmembrane domain (L90V), and cytoplasmic loop (I130T, K134E) do form gap junction plaques but show compromised channel function. L90V, I130T, and K134E demonstrated a significant decrease in junctional conductance relative to Cx43WT. Mutations Y17S, G21R, and A40V demonstrated a complete lack of functional electrical coupling even in the presence of significant plaque formation between paired cells. Heterologous channels formed by coexpression of Cx43WT and mutation R202H resulted in electrically functional gap junctions that were not permeable to Lucifer yellow. Therefore, the mutations found in ODDD not only cause phenotypic variability, but also result in various functional consequences. Overall, our data show an extensive range of molecular phenotypes, consistent with the pleiotropic nature of the clinical syndrome as a whole.
Use of in situ detection of histone mRNA in the assessment of epidermal proliferation: comparison with the Ki67 antigen and BrdU incorporation
Authors: M.D SMITH, E. HEALY, V. THOMPSON, A. MORLEY, J.L REES
Journal: British Journal of Dermatology (1995)

The labelling index is commonly used as a measure of proliferation. However, the use of tritiated thyraidine or BrdU labelling of S-phase cells is limited to prospective samples. We have employed an oligonucleotide cocktail complementary to the mRNA species encoding the repiication-dependent histones H2B, H3 and H4 for non-isotopic in situ hybridization (NISH), and have compared the resultant proliferation indices in normal skin with those obtained by bromodeoxyuridine (BrdU) incorporation and by Kift 7 immunohistochemistry (MC) using the monoclonal antibody MIB1. In addition, we compared the staining characteristics of histone NISH and Kif>7 IHC in a further 25 samples from a variety of inflammatory dermatoses and neoplastic conditions, as well as from normal skin. In normal skin, S-phase (histone NISH and BrdU) and cycling (Ki67) cells were conflned to the basal and Jow suprabasal layers. The labetling indices determined by histone NISH and BrdU incorporation were similar, whereas that of Ki67 IHC was four times greater. In biopsies from hyperproliferative dermatoses and dysplastic or malignant lesions. the number of histone NISH- and Ki67 IHC-positive cells was generally elevated; in accordance with the differential expression of these two markers during the cell cycle, M1B1 consistently gave higher results. The advantage of histone NISH over Ki67 MC is that it is a marker of the same part of the cell cycle as BrdU incorporation. However, the combined use of both histone NISH and Ki67 MC to measure two cell cycle parameters, namely S-phase and the number of cycling cells, aliows more detailed retrospective study of epidermal proliferation than has been possible previously.
Mast Cell Targeting Hampers Prostate Adenocarcinoma Development but Promotes the Occurrence of Highly Malignant Neuroendocrine Cancers
Authors: Paola Pittoni, Claudio Tripodo, Silvia Piconese, Giorgio Mauri, Mariella Parenza, Alice Rigoni, Sabina Sangaletti, Mario P. Colombo
Journal: Cancer Research (2011)

Abstract Mast cells (MC) are c-Kit–expressing cells, best known for their primary involvement in allergic reactions, but recently reappraised as important players in either cancer promotion or inhibition. Here, we assessed the role of MCs in prostate tumor development. In prostate tumors from both tumor-prone transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and human patients, MCs are specifically enriched and degranulated in areas of well-differentiated (WD) adenocarcinoma but not around poorly differentiated (PD) foci that coexist in the same tumors. We derived novel TRAMP tumor cell lines, representative of WD and PD variants, and through pharmacologic stabilization or genetic ablation of MCs in recipients mice, we showed that MCs promote WD adenocarcinoma growth but are dispensable for PD tumors. WD tumors rely on MCs for matrix metalloprotease 9 (MMP-9) provision, as reconstitution of MC-deficient mice with wild-type but not MMP-9−/− MCs was sufficient to promote their growth. In contrast, PD tumors are MMP-9 self-competent, consistently with epithelial-to-mesenchymal transition. Such a dual source of MMP-9 was confirmed in human tumors, suggesting that MCs could be a good target for early-stage prostate cancer. Interestingly, in testing whether MC targeting could block or delay tumorigenesis in tumor-prone TRAMP mice, we observed a high incidence of early and aggressive tumors, characterized by a neuroendocrine (NE) signature and c-Kit expression. Taken together, these data underscore the contribution of MCs in tumor progression and uncover a new, opposite role of MCs in protecting against the occurrence of aggressive NE variants in prostate cancer. Cancer Res; 71(18); 5987–97. ©2011 AACR.
Hepatocellular Carcinoma in Children: Results of the First Prospective Study of the International Society of Pediatric Oncology Group
Authors: P. Czauderna, G. Mackinlay, G. Perilongo, J. Brown, E. Shafford, D. Aronson, J. Pritchard, P. Chapchap, J. Keeling, J. Plaschkes, J.B. Otte
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To improve survival and reduce operative morbidity and mortality in children with primary epithelial liver tumors by using preoperative chemotherapy, as well as to collect information on the epidemiology, natural history, and prognostic factors. PATIENTS AND METHODS: Forty children with hepatocellular carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors International Society of Pediatric Oncology’s first study from January 1990 to February 1994. The outcome could be analyzed in 39 of those patients. Disease was often advanced at the time of diagnosis; metastases were identified in 31% of the children and extrahepatic tumor extension, vascular invasion, or both in 39%. Multifocal tumors were common (56%). Thirty-three percent of tumors were associated with hepatic cirrhosis. All but two patients received preoperative chemotherapy (cisplatin and doxorubicin). RESULTS: Partial response was observed in 18 (49%) of 37 patients; there was no response or progression in the remainder. Complete tumor resection was achieved in 14 patients (36%). Twenty patients (51%) never became operable. Overall survival at 5 years was 28%, and event-free survival was 17%. Most deaths resulted from tumor progression (26 of 28). Presence of metastases and pretreatment extent of disease system grouping at diagnosis had an adverse influence on overall survival in multivariate analysis. CONCLUSION: Survival for pediatric HCC patients is significantly inferior to that for children with hepatoblastoma. Complete tumor excision remains the only realistic chance of cure, although it is often prevented by advanced disease. The presence of metastases is the most potent predictor of poor prognosis. A prospective worldwide cooperation in the field of pediatric HCC should be encouraged to look for novel therapeutic concepts.
A Novel SNPs Detection Method Based on Gold Magnetic Nanoparticles Array and Single Base Extension
Authors: Song Li, Hongna Liu, Yingying Jia, Yan Deng, Liming Zhang, Zhuoxuan Lu, Nongyue He
Journal: Theranostics (2012)

To fulfill the increasing need for large-scale genetic research, a high-throughput and automated SNPs genotyping method based on gold magnetic nanoparticles (GMNPs) array and dual-color single base extension has been designed. After amplification of DNA templates, biotinylated extension primers were captured by streptavidin coated gold magnetic nanoparticle (SA-GMNPs). Next a solid-phase, dual-color single base extension (SBE) reaction with the specific biotinylated primer was performed directly on the surface of the GMNPs. Finally, a "bead array" was fabricated by spotting GMNPs with fluorophore on a clean glass slide, and the genotype of each sample was discriminated by scanning the "bead array". MTHFR gene C677T polymorphism of 320 individual samples were interrogated using this method, the signal/noise ratio for homozygous samples were over 12.33, while the signal/noise ratio for heterozygous samples was near 1. Compared with other dual-color hybridization based genotyping methods, the method described here gives a higher signal/noise ratio and SNP loci can be identified with a high level of confidence. This assay has the advantage of eliminating the need for background subtraction and direct analysis of the fluorescence values of the GMNPs to determine their genotypes without the necessary procedures for purification and complex reduction of PCR products. The application of this strategy to large-scale SNP studies simplifies the process, and reduces the labor required to produce highly sensitive results while improving the potential for automation.