tbuckley/cabot-search huggingface dataset:
Frequency of germline hereditary non-polyposis colorectal cancer gene mutations in patients with multiple or early onset colorectal adenomas
Authors: N E Beck, I P M Tomlinson, T F R Homfray, I M Frayling, S V Hodgson, W F Bodmer
Journal: Gut (1997)

The hereditary non-polyposis colorectal cancer (HNPCC) syndrome is caused by germline mutations in mismatch repair genes and predisposes individuals to cancers of the colon and other specific sites. On theoretical grounds, it is expected that patients with HNPCC also develop more colorectal adenomas than the general population. In essence, if the mutation rate is raised owing to mutations at a mismatch repair locus, more mutations are expected at loci such as APC (adenomatous polyposis coli) and more adenomas will start to grow. Not all data support this expectation, however.To search for germline mutations at HNPCC loci in patients with multiple adenomas.Twenty five patients (without known APC mutations) who have developed colorectal adenomas in unusually large numbers and, in some cases, at an early age.Germline APC mutations were excluded using the protein truction test for exon 15 and mismatch chemical cleavage analysis for remaining exons. Germline HNPCC mutations were detected by using PCR and single strand conformation polymorphism analysis.Just one germline HNPCC mutation was found (4% of cases) and this was of uncertain functional effect.In general, germline HNPCC mutations are not responsible for the phenotype of patients with multiple colonic adenomas. It is possible that patients with HNPCC tend to develop adenomas more frequently and earlier than the general population, but that this effect is relatively subtle. These results suggest that individuals with colorectal adenomas only should not strictly be classified as "affected" in HNPCC families (although they should certainly not be classified as "unaffected" either and may warrant intensive screening). In the absence of a personal or strong family history of colorectal cancer, it is probably not worthwhile performing diagnostic or predictive genetic testing for HNPCC mutations in subjects with colorectal adenomas. Although undetected APC mutations may be responsible for some of the phenotypes in this sample, as yet uncharacterised adenoma predisposing genes probably exist.
Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer
Authors: J. Aparicio, J.M. Vicent, I. Maestu, S. Garcerá, I. Busquier, C. Bosch, C. Llorca, R. Díaz, C. Fernández-Martos, A. Galán
Journal: Annals of Oncology (2003)
Generative grammar with a human face?
Authors: Shimon Edelman
Journal: Behavioral and Brain Sciences (2003)

The theoretical debate in linguistics during the past half-century bears an uncanny parallel to the politics of the (now defunct) Communist Bloc. The parallels are not so much in the revolutionary nature of Chomsky's ideas as in the Bolshevik manner of his takeover of linguistics (Koerner 1994) and in the Trotskyist (“permanent revolution”) flavor of the subsequent development of the doctrine of Transformational Generative Grammar (TGG) (Townsend &amp; Bever 2001, pp. 37–40). By those standards, Jackendoff is quite a party faithful (a Khrushchev or a Dubcek, rather than a Solzhenitsyn or a Sakharov) who questions some of the components of the dogma, yet stops far short of repudiating it.
Abstract 18452: Outcome of Pregnancy in Women with Aortic Disease: Data from ROPAC
Authors: Iris M van Hagen, Mark R Johnson, Roger Hall, Jolien W Roos-Hesselink
Journal: Circulation (2014)

Objectives: Cardiovascular disease is one of the major causes of maternal mortality. Pregnancy induces marked hemodynamic changes and may weaken the structure of the vessel wall. The aim of the present study is to describe the outcome of pregnancy in patients with aortic disease. Methods and Results: In the Registry Of Pregnancy And Cardiac disease (ROPAC), 2966 patients were enrolled from 39 countries. One hundred and one patients had aortic disease: 56 patients with Marfan syndrome (55.4%), 12 associated with bicuspid aortic valve (11.9%), 2 with Turner Syndrome (2.0%), 2 with familial thoracic aortic aneurysm disease (2.0%) and 29 with other aortic diseases (28.7%) e.g. Takayasu arteritis or previous aortic dissection without specified diagnosis. During pregnancy, aortic dissection occurred in 3 patients: a type B dissection in a Marfan patient at 25 weeks with a prior aortic diameter of 42 mm; a type A dissection in a Marfan patient at 37 weeks (pre-pregnancy aortic diameter not reported) and at 26 we...
Use of an anti-ALK antibody in the characterization of anaplastic large-cell lymphoma of childhood
Authors: R.E. Hutchison, K. Banki, J.J. Shuster, D. Barrett, C. Dieck, C.W. Berard, S.B. Murphy, M.P. Link, T.E. Pick, J. Laver, M. Schwenn, P. Mathew, S.W. Morris
Journal: Annals of Oncology (1997)
Medical error: the second victim
Authors: A. W Wu
Journal: BMJ (2000)

Personal view p 812 

When I was a house officer another resident failed to identify the electrocardiographic signs of the pericardial tamponade that would rush the patient to the operating room late that night. The news spread rapidly, the case tried repeatedly before an incredulous jury of peers, who returned a summary judgment of incompetence. I was dismayed by the lack of sympathy and wondered secretly if I could have made the same mistake—and, like the hapless resident, become the second victim of the error.

Strangely, there is no place for mistakes in modern medicine. Society has entrusted physicians with the burden of understanding and dealing with illness. Although it is often said that “doctors are only human,” technological wonders, the apparent precision of laboratory tests, and innovations that present tangible images of illness have in fact created an expectation of perfection. Patients, who have an understandable need to consider their doctors infallible, have colluded with doctors to deny the existence of error. Hospitals react to every error as an anomaly, for which the solution is to ferret out and blame an individual, with a promise that “it will never happen again.” Paradoxically, this approach has diverted attention …
Phase I Trial of a New Schedule of Romidepsin in Patients with Advanced Cancers
Authors: Laleh Amiri-Kordestani, Victoria Luchenko, Cody J. Peer, Kambiz Ghafourian, James Reynolds, Deb Draper, Robin Frye, Sue Woo, David Venzon, John Wright, Monica Skarulis, William D. Figg, Tito Fojo, Susan E. Bates, Richard L. Piekarz
Journal: Clinical Cancer Research (2013)

Romidepsin is a potent histone deacetylase inhibitor (HDI) with activity in T-cell lymphoma. Given preclinical data showing greater induction of gene expression with longer exposures to HDIs, a phase I study of a day 1, 3, and 5 romidepsin schedule was evaluated. A secondary objective was to assess the effect of romidepsin on radioactive iodine (RAI) uptake in thyroid cancers.Open-label, single-arm, phase I, 3 + 3 dose escalation study. Romidepsin was administered as a 4-hour infusion on days 1, 3, and 5 of a 21-day cycle. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed, including histone acetylation in peripheral blood mononuclear cells (PBMC), RAI uptake in refractory thyroid cancer, and HDI-related ECG changes.Twenty-eight patients with solid tumors, including 11 patients with thyroid cancer were enrolled. Six dose levels were explored, and 7 mg/m(2) on days 1, 3, and 5 was identified as tolerable. No Response Evaluation Criteria In Solid Tumors-defined objective responses were recorded although 9 patients had stable disease a median 30 weeks (range, 21-112) including 6 with thyroid cancer a median of 33 weeks. PD studies detected acetylated histones in PBMCs and ECG changes beginning at low dose levels. Follow-up RAI scans in patients with RAI refractory thyroid cancer did not detect meaningful increases.A romidepsin dose of 7 mg/m(2) administered on days 1, 3, and 5 was found tolerable and resulted in histone acetylation in PBMCs. Although there were no objective responses with romidepsin alone, this schedule may be useful for developing combination studies in solid tumors.
Syringotropic cutaneous T-cell lymphoma: an immunophenotypic and genotypic study of five cases
Authors: M. Thein, F. Ravat, G. Orchard, E. Calonje, R. Russell-Jones
Journal: British Journal of Dermatology (2004)

There is uncertainty about the exact nosological relationship between mycosis fungoides, follicular mucinosis, syringolymphoid hyperplasia with alopecia (SLHA) and syringotropic cutaneous T-cell lymphoma (CTCL). We report the clinical, histological, immunophenotypic and genotypic characteristics of a series of five patients (three men and two women) with syringotropic CTCL. We also review the 15 cases of SLHA previously reported in the literature. We conclude that syringotropic CTCL is a distinct clinicopathological variant of mycosis fungoides which may present on its own with characteristic punctate erythema or more commonly in association with folliculotropic lesions. Syringotropic CTCL is characterized histologically by infiltration of sweat glands by atypical lymphocytes in association with syringolymphoid hyperplasia. Cases of SLHA represent a syringotropic form of CTCL in association with follicular involvement, and such cases need to be investigated using T-cell receptor gene analysis of both skin and blood. Only limited conclusions on prognosis can be derived from our preliminary data. However, a review of the literature suggests that the prognosis does not differ significantly from other types of mycosis fungoides of equivalent stage.
Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial
Authors: Amar Gajjar, Murali Chintagumpala, David Ashley, Stewart Kellie, Larry E Kun, Thomas E Merchant, Shaio Woo, Greg Wheeler, Valerie Ahern, Matthew J Krasin, Maryam Fouladi, Alberto Broniscer, Robert Krance, Gregory A Hale, Clinton F Stewart, Robert Dauser, Robert A Sanford, Christine Fuller, Ching Lau, James M Boyett, Dana Wallace, Richard J Gilbertson
Journal: The Lancet Oncology (2006)
Parallel Array and Mixture-Based Synthetic Combinatorial Chemistry: Tools for the Next Millennium
Authors: Richard A. Houghten
Journal: The Annual Review of Pharmacology and Toxicology (2000)

Technological advances continue to be a central driving force in the acceleration of the drug discovery process. Combinatorial chemistry methods, developed over the past 15 years, represent a paradigm shift in drug discovery. Initially viewed as a curiosity by the pharmaceutical industry, combinatorial chemistry is now recognized as an essential tool that decreases the time of discovery and increases the throughput of chemical screening by as much as 1000-fold. The use of parallel array synthesis approaches and mixture-based combinatorial libraries for drug discovery is reviewed.
Racial Differences in the Impact of Elevated Systolic Blood Pressure on Stroke Risk
Authors: George Howard, Daniel T. Lackland, Dawn O. Kleindorfer, Brett M. Kissela, Claudia S. Moy, Suzanne E. Judd, Monika M. Safford, Mary Cushman, Stephen P. Glasser, Virginia J. Howard
Journal: JAMA Internal Medicine (2012)

Between the ages 45 and 65 years, incident stroke is 2 to 3 times more common in blacks than in whites, a difference not explained by traditional stroke risk factors.
Hypoglycemic Coma in a Diabetic Patient on Peritoneal Dialysis due to Interference of Icodextrin Metabolites With Capillary Blood Glucose Measurements
Authors: Emmanuel Disse, Charles Thivolet
Journal: Diabetes Care (2004)

Continuous ambulatory peritoneal dialysis is used in about one-third of the diabetic population as an alternative to hemodialysis for end-stage renal disease (ESRD). Several case reports and articles (1–3) have alerted health professionals on the potential interference of dialysis fluid containing 7.5% icodextrin, a cornstarch-derived glucose polymer (Extraneal; Baxter Healthcare, Castlebar, Ireland), with some glucose reagent systems using a glucose dehydrogenase enzyme …
Serial studies of 100 patients with chronic airway obstruction in London and Chicago
Authors: N. L. Jones, B. Burrows, C. M. Fletcher
Journal: Thorax (1967)

One hundred patients with chronic airway obstruction, 50 in Chicago and 50 in London, were studied by standardized techniques in 1961. The results of the initial studies, previously reported, showed that the patients in the two cities were similar; using clinical and physiological criteria based on pathological studies, the patients were divided into three types—emphysematous type A, bronchial type B, and an indeterminate type X. The patients were studied again in succeeding years, 1962-65. During this time 26 died, 19 due to their respiratory disease; these 19 patients were initially more breathless, had a higher incidence of cor pulmonale, and had more severe airway obstruction and higher carbon dioxide pressures than the remainder. Type B patients (mortality 36%) had a worse prognosis than either type A (15%) or type X (12%). Of the measurements made, high carbon dioxide pressures were most closely related (p&lt;0·001) to mortality. During the period of follow-up about one-third of the patients who did not die became more short of breath and developed more severe airway obstruction and carbon dioxide retention: about 10% showed definite improvement in symptoms and pulmonary function. The F.E.V.<sub>1·0</sub> declined on average by 46 ml./year, 4·8% of the initial value; V.C. declined by 120 ml./year, 4·0% of the initial value; mixed venous Pco<sub>2</sub> increased 1 mm. Hg/year. The changes that occurred during this time confirmed the previously reported similarity between the patients attending the two clinics. Although the incidence of bronchitic exacerbations was similar in the two cities, such illnesses in the London patients led to more frequent and more prolonged incapacity.
Familiality of Postpartum Depression in Unipolar Disorder: Results of a Family Study
Authors: Liz Forty
Journal: American Journal of Psychiatry (2006)

Objective: The authors previously reported strong evidence for familial aggregation of postpartum (puerperal) psychotic episodes in women with bipolar disorder. The authors here examine whether vulnerability to postpartum triggering of depressive episodes aggregates in families and assess how this aggregation varies with the definition of postpartum onset. Method: Postpartum depression occurrence was studied in the female members of 120 sibling pairs recruited at a site within an international multicenter study of sibling pairs with recurrent unipolar depression. Employing a range of definitions of postpartum onset, the authors examined concordance for postpartum episode status between sisters. Results: Episodes of depression with onset within 4 weeks of delivery clustered in families, but there was no significant evidence of familial clustering of broadly defined postpartum depression (onset within 6 months). Among women with a family history of narrowly defined postpartum episodes, 42% experienced depression following their first delivery, whereas only 15% of women with no such family history experienced depression following first delivery. The evidence for familiality maximized with a postpartum onset definition of 6–8 weeks. Conclusions: These results implicate familial factors in susceptibility to the triggering of narrowly defined postpartum depressive episodes in women with recurrent major depression. They suggest that a postnatal onset definition of within 6–8 weeks of delivery may be optimal in studies of the triggering of depressive illness by childbirth.
Basal Vertebrates Clarify the Evolutionary History of Ciliopathy-Associated Genes Tmem138 and Tmem216
Authors: Byrappa Venkatesh, Vydianathan Ravi, Alison P. Lee, Wesley C. Warren, Sydney Brenner
Journal: Molecular Biology and Evolution (2012)

Recently, Lee et al. (Lee JH, Silhavy JL, Lee JE, et al. (30 co-authors). 2012. Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science (335:966-969.) demonstrated that mutation in either of the transmembrane protein encoding genes, TMEM138 or TMEM216, causes phenotypically indistinguishable ciliopathy. Furthermore, on the basis of the observation that their orthologs are linked in a head-to-tail configuration in other mammals and Anolis, but present on different scaffolds or chromosomes in Xenopus tropicalis and zebrafish, the authors concluded that the two genes were joined by chromosomal rearrangement at the evolutionary amphibian-to-reptile transition to form a functional module. We have sequenced these gene loci in a cartilaginous fish, the elephant shark, and found that the two genes together with a related gene (Tmem80) constitute a tandem cluster. This suggests that the two genes were already linked in the vertebrate ancestor and then rearranged independently in Xenopus and zebrafish. Analyses of the coelacanth and lamprey genomes support this hypothesis. Our study highlights the importance of basal vertebrates as critical reference genomes.
Moderate- to low-risk variant alleles of cutaneous malignancies and nevi: lessons from genome-wide association studies
Authors: Durga Udayakumar, Hensin Tsao
Journal: Genome Medicine (2009)

Cutaneous malignancies, especially malignant melanoma, exhibit great genetic heterogeneity. As a result, some individuals and families have particularly increased risk due to genetic predisposition to the disease. The susceptibility alleles range from rarely occurring, heritable, high-risk variants to ubiquitously occurring low-risk variants. Although until now the focus has been mostly towards the familial high-risk genes, the development of genome-wide association studies has uncovered a number of moderate- to low-risk predisposition alleles. The ability to specifically identify genetic variation associated with visible pigmentation traits and disease risk has provided a much richer view of the genetics of cutaneous malignancies. In this review, we provide an update on the recently identified risk loci. Existing clinical data, combined with vast genome information, will provide a better understanding of the biology of disease, and increased accuracy in risk prediction.
Distribution and Functional Role of Inositol 1,4,5- <i>tris</i> phosphate Receptors in Mouse Sinoatrial Node
Authors: Yue-Kun Ju, Jie Liu, Bon Hyang Lee, Donna Lai, Elizabeth A. Woodcock, Ming Lei, Mark B. Cannell, David G. Allen
Journal: Circulation Research (2011)

Rationale: Inositol 1,4,5- tris phosphate receptors (IP 3 Rs) have been implicated in the generation of arrhythmias and cardiac muscle nuclear signaling. However, in the mammalian sinoatrial node (SAN), where the heart beat originates, the expression and functional activity of IP 3 Rs have not been investigated. Objectives: To determine whether SAN express IP 3 Rs and which isoforms are present. To examine the response of the SAN to IP 3 R agonists and antagonist, and the potential role played by IP 3 Rs in cardiac pacemaking. Methods and Results: The expression and distribution of IP 3 Rs were studied by reverse-transcription polymerase chain reaction, Western blotting, and immunolabeling. Ca 2+ signaling and electric activity in intact mouse SAN were measured with Ca 2+ -sensitive fluorescent dyes. We found that although the entire SAN expressed three IP 3 R mRNA isoforms, the type II IP 3 R (IP 3 R2) was the predominant protein isoform detected by Western blot using protein extracts from the SAN, atrioventricular node, and atrial tissue. Immunohistochemistry studies also showed that IP 3 R2 was expressed in the central SAN region. Studies using isolated single pacemaker cells revealed that IP 3 R2 (but not IP 3 R1) was located with a similar distribution to the sarcoplasmic reticulum marker protein SERCA2a with some labeling adjacent to the surface membrane. The application of membrane-permeable IP 3 (IP 3 -butyryloxymethyl ester) increased Ca 2+ spark frequency and the pacemaker firing rate in single isolated pacemaker cells. In intact SAN preparations, IP 3 R agonists, endothelin-1 and IP 3 -butyryloxymethyl ester both increased intracellular Ca 2+ and the pacemaker firing rate, whereas the IP 3 R antagonist, 2-aminoethoxydiphenyl borate decreased Ca 2+ and the firing rate. Both of these effects were absent in the SAN from transgenic IP 3 R2 knockout mice. Conclusions: This study provides new evidence that functional IP 3 R2s are expressed in the mouse SAN and could serve as an additional Ca 2+ -dependent mechanism in modulating cardiac pacemaker activity as well as other Ca 2+ -dependent processes.
Bench testing of auto-adjusting positive airway pressure devices
Authors: F. Abdenbi
Journal: European Respiratory Journal (2004)

Continuous positive airway pressure devices are routinely used to treat sleep breathing disorders. Automated devices that adjust the therapeutic pressure have recently been proposed. The utility of such devices is still controversial, as rigorous clinical comparisons are difficult to perform as a result of patient and device differences. The current authors studied automated devices in a respiratory model that was able to mimic upper airway mechanics and to interact with pressure adjustment in a closed loop. Five auto-adjusted devices were submitted to this model, in order to determine their ability to detect respiratory events and adjust pressure accordingly. All apnoeas were suppressed, whilst the reaction to repetitive hypopnoeas was dependent on the airflow shape. In some devices, repetitive hypopnoeas were changed to flow limitation. Artificial snoring caused a pressure increase in four devices, and constant mask leak was not systematically compensated. Only one device did not raise pressure in response to central apnoeas with opened upper airways. These findings show that, in some devices, event classification failed and normal airflow was not fully restored, resulting in elevated residual event indices. In conclusion, this model is useful in order to reproducibly compare diagnostic and therapeutic capacities of commercial devices as a first step, before costly clinical studies.
Prostatic carcinoma presenting with respiratory symptoms: response to orchidectomy.
Authors: F G Simpson, H A King, P Whelan, N J Cooke
Journal: Thorax (1984)

Pulmonary lymphangitis carcinomatosa carries a poor prognosis.'We report a case of prostatic carcinoma in a patient who presented with respiratory symptoms only.The diagnosis of lymphangitis carcinomatosa was made by transbronchial lung biopsy.Symptoms, results of respirat- ory function tests, and radiological appearances all improved considerably after orchidectomy. Case reportA 68 year old man, a non-smoker, presented in May 1983 with a four week history of increasing dyspnoea on exer- tion and weight loss of 3 kg.He denied any urinary symp-