tbuckley/cabot-search huggingface dataset:
A memorable patient: Diphtheria
Authors: Caleb Tucker
Journal: BMJ (2006)

In the 1940s we were still seeing occasional cases of diphtheria in our provincial hospital in New Zealand's North Island. Two I clearly remember died from overwhelming toxaemia; they had come from isolated country districts and presumably had not been immunised.

In April 1946, a 16 year old schoolgirl, also from an isolated country district, was admitted with severe respiratory obstruction due to diphtheria. She had widespread membrane formation in the mouth and throat, and, when I performed an urgent tracheotomy, we were alarmed to find a similar membrane lining the trachea. This feature of the case explained the utter frustration we experienced in the after care. We just could not obtain a satisfactory airway. In addition to the usual nursing care of a tracheotomy, I judiciously removed the outer tube periodically to endeavour to clear the trachea, but to no avail.

Three days after the operation, I was due to go off duty for the weekend. I discussed the care of my patient with the duty house surgeon and asked to be rung if there was any change in her condition.

Early on the Saturday evening while I was visiting friends the house surgeon rang and said rather sadly, “I think we are going to lose our patient; her breathing is much worse.” I was back at the hospital within 10 minutes and proceeded to remove the tracheotomy tube. I discovered immediately what had happened; the diphtheritic membrane was lying, apparently free, in the trachea. With some trepidation, I proceeded to gently ease it out with a pair of Desjardins forceps. The membrane kept coming and did not seem to be attached at the lower end. We became quite excited and relieved to find we were holding a complete cast of the trachea and its commencing bifurcation.

We were so busy looking at this that we nearly forgot the patient. The staff nurse pointed out to us that the patient was trying to say something: she was mouthing, “I feel much better.” From that moment she made a steady recovery and was able to go home some days later.

I can only leave the reader to imagine what I learnt from this case. Sixty years later I am still pleased and relieved that I went back to the hospital that Saturday evening.
Impaired monocyte function in liver cirrhosis.
Authors: A Hassner, Y Kletter, D Shlag, M Yedvab, M Aronson, S Shibolet
Journal: BMJ (1981)

Monocyte function in patients with cirrhosis of the liver was measured by phagocytosis and killing of Candida pseudotropicalis and C albicans. Both variables were significantly decreased in the patients compared with controls. Control monocytes exposed for two hours to patients9 serum showed a significant decrease in intracellular killing compared with control monocytes incubated in autologous serum. This suggests the presence of an inhibiting factor in the patients9 serum. This inhibitory factor passed through a dialysis membrane that permitted the passage of molecules of less than 12 000 daltons. Treating monocytes from patients with trypsin significantly increased phagocytosis, indicating that the possible inhibitory factor was attached to the monocyte surface. Metabolism of monocytes during phagocytosis as determined by chemoluminescence was significantly lower in monocytes from patients compared with controls, indicating metabolic impairment. Monocytes are a component of the monocyte-macrophage system, which includes Kupffer9s cells. Impairment of the function of these cells, which have a pivotal role in clearing portal blood, might well be extremely important in the development of chronic liver disease.
Struma Ovarii in Pregnancy
Authors: Zayd Merza, Duncan White, Noor Khanem
Journal: Clinical Nuclear Medicine (2015)

A 28-year-old woman presented with weight loss and tiredness. Investigations revealed hyperthyroidism. She was commenced on treatment and later became pregnant. Her thyroid levels remained raised, and she later underwent an elective cesarean delivery and ovarian cystectomy. Only a partial cystectomy was achieved, and histopathology examination revealed struma ovarii. An isotope uptake scan (123I) including her pelvis revealed low uptake in the thyroid gland and an area of high uptake in her pelvis. The cyst was subsequently removed, and within days, her thyroid hormone levels dropped. This case illustrates the importance of considering uncommon causes of hyperthyroidism.
Thrombopoietin in Patients With Congenital Thrombocytopenia and Absent Radii: Elevated Serum Levels, Normal Receptor Expression, But Defective Reactivity to Thrombopoietin
Authors: Matthias Ballmaier, Harald Schulze, Gabriele Strauβ, Klara Cherkaoui, Nicole Wittner, Stefanie Lynen, Susanne Wolters, Jakob Bogenberger, Karl Welte
Journal: Blood (1997)
A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer.
Authors: Aaron James Scott, Bert H. O'Neil, Christina Gomes, Joaquina Celebre Baranda, Steven J. Cohen, Mohamedtaki Abdulaziz Tejani, Robert T. Maguire, Francois Wilhelm, Manoj Maniar, Deirdre Jill Cohen, Wen Wee Ma, Dara Aisner, Jonathan K. Cho, Olugbenga Olanrele Olowokure, Andrew L. Coveler, Alex R. Menter, Peter Rubin, Mike Cusnir, Wells A. Messersmith
Journal: Journal of Clinical Oncology (2015)

342 Background: Rigosertib (ON 01910.Na), a dual non-ATP inhibitor of polo-like kinase 1 (Plk1) and phosphoinositide 3-kinase (PI3K) pathways, was assessed in patients with treatment-naïve metastatic pancreatic adenocarcinoma. Methods: Patients with metastatic adenocarcinoma of the pancreas were randomized in a 2:1 fashion to gemcitabine 1000 mg/m 2 weekly for 3 weeks of a 4-week cycle plus rigosertib 1800mg/m 2 via 2-hr CIV infusions given twice weekly for 3 weeks of a 4-week cycle versus gemcitabine 1000mg/m 2 weekly for 3 weeks in a 4-week cycle. Results: A total of 160 patients were enrolled globally and randomly assigned to rigosertib plus gemcitabine (106 patients) or gemcitabine (54). The most common grade 3 or higher adverse events were neutropenia (8% in the rigosertib plus gemcitabine group vs. 6% in the gemcitabine group), hyponatremia (17% vs. 4%), and anemia (8% vs. 4%). The primary outcome of the study, median OS, was 6.1 months in the gemcitabine plus rigosertib arm versus 6.4 months with gemcitabine alone (hazard ratio (HR), 1.24; 95% confidence interval [CI], 0.85-1.81). The median PFS was 3.4 months for both groups (HR, 0.96; 95% CI, 0.68-1.36). The overall best response between arms were partial response rates of 19% versus 13% and stable disease in 50% versus 56% in the gemcitabine plus rigosertib versus gemcitabine alone, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40/47, 85%), which included c.35G&gt;T, p.G12V (12 cases), c.35G&gt;A, p.G12D (21 cases), c.34G&gt;C, p.G12R (4 cases), c.34G&gt;T, p.G12C (1 case) and c.183C&gt;A, p.Q61H (2 cases). Other mutations detected included TP53 (13 cases) and PIK3CA(1 case). No correlation between mutational status and efficacy was detected. Conclusions: The combination of rigosertib plus gemcitabine failed to demonstrate an improvement in survival or response compared to gemcitabine alone in metastatic pancreatic adenocarcinoma. Clinical trial information: NCT01360853.
Health insurer extinguishes tobacco investment
Authors: Anne Gulland
Journal: BMJ (2016)

Health insurer Axa has announced that it is to become the first global insurer to divest its tobacco investments, worth around €1.7bn ($1.91bn; £1.3bn).

Thomas Buberl, deputy chief executive of Axa, said that as one of the world’s leading health insurers the company had to “lead by example.”

He said that, while doctors, healthcare organisations, and governments call for tighter tobacco controls, investors were putting their money into the tobacco industry.

“That is inconsistent and has to …
Abstract IA04: Targeting DNA repair in ovarian cancer therapy.
Authors: Alan D. D'Andrea.
Journal: Clinical Cancer Research (2016)

Abstract Large-scale genomic studies have shown that half of epithelial ovarian cancers (EOCs) have alterations in genes regulating homologous recombination (HR) repair. Loss of HR accounts for the genomic instability and replicative stress of EOCs and for their cellular hyperdependence on alternative poly-ADP ribose polymerase (PARP)-mediated DNA repair mechanisms. On the basis of this hyperdependence, in 2014, the FA approved the PARP inhibitor, olaparib, for patients with advanced ovarian cancer associated with BRCA1 and BRCA2 germline mutations, whose tumors are HR deficient. Previous studies have implicated the DNA polymerase POLQ in an error-prone pathway required for the repair of DNA double-strand breaks, referred to as alternative endjoining (alt-EJ). In Drosophila melanogaster and Caenorhabditis elegans, POLQ functions in alt-EJ and in the maintenance of genome stability at sites of G-quadruplex structures. Whether POLQ interacts with canonical DNA repair pathways to prevent genomic instability at stalled replication forks has remained unknown. We have recently demonstrated an inverse correlation between HR activity and POLQ expression in EOCs (Ceccaldi R. et al, Nature, 518: 258-262, 2015). While knockdown of POLQ in HR-proficient cells upregulates HR activity and RAD51 nucleofilament assembly, knockdown of POLQ in HR-deficient EOCs results in enhanced cell death. Consistent with these results, genetic inactivation of an HR gene (Fancd2) and Polq in mice results in embryonic lethality. Moreover, POLQ contains a repeat of RAD51 binding motifs, and it blocks D-loop formation and recombination. Importantly, PARP1 activity is required for the recruitment of POLQ to sites of DNA repair, accounting, in part, for the PARP1 hyperdependence of HR-deficient ovarian tumor cells. Taken together, these results reveal a synthetic lethal relationship between the HR pathway and PARP1/POLQ-mediated alternative end-joining in EOCs, and identify POLQ as a novel druggable target for ovarian cancer therapy. Such inhibitors may be useful in the treatment of PARP inhibitor-resistant ovarian cancers. Citation Format: Alan D. D'Andrea. Targeting DNA repair in ovarian cancer therapy. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA04.
Successful Repair of High Ventricular Septal Defect with Aorto-pulmonary Septal Defect Associated with Aortic Insufficiency : What we Call "Bulbar Septal Defect"
Authors: Togo Horiuchi, Kei Koyamada, Ichiro Matano, Hitoshi Mohri, Takeshi Ishitoya
Journal: Circulation (1963)
Update on the epidemiology of anorexia nervosa in a defined region of Switzerland
Authors: J Willi, G Giacometti, B Limacher
Journal: American Journal of Psychiatry (1990)

In this follow-up investigation, the authors studied all Swiss women in the canton of Zurich who developed anorexia nervosa between ages 12 and 25 years and who were hospitalized for the first time with this diagnosis between 1983 and 1985. Data were compared with those from an earlier study, which focused on the periods 1956-1958, 1963-1965, and 1973-1975. The incidence of anorexia nervosa did not increase significantly during 1983-1985 compared to 1973-1975, in contrast to the constant increase found between 1956 and 1975. However, the more frequent use of vomiting and abuse of laxatives in 1983-1985 may indicate an increase in cases with mixed features of anorexia nervosa and bulimia.
BCG vaccination in the newborn.
Journal: BMJ (1980)

claimed success with resection of the roof of the diverticulum endoscopically in six cases of recurrent diverticulum, but others have not found this technique so uniformly successful.Diverticula of the urethra are unexpectedly common: one American paper') quoted an incidence of between 2% and 400, suggesting that most must be symptomless.Andersen7 found a diverticulum in nine patients without symptoms among 300 women undergoing injection urethrography.None of these lesions were palpable.Diverticula have been reported only very occasionally in children, and symptoms most often occur in women between the ages of 20 and 50.2 7 Whether they are congenital or acquired (usually secondary to infection of paraurethral glands) is uncertain but of little practical im- portance.A high index of suspicion is the key to the diagnosis.
Daclizumab to Prevent Acute Rejection in Renal Transplantation
Authors: D Abramowicz
Journal: New England Journal of Medicine (1998)

The article by Stelfox et al. (Jan.8 issue) 1 is ambiguous and undermined by a self-fulfilling prophecy.The authors concluded that there is no evidence of conflict of interest but not before compiling confusing information to the contrary.Supporters and critics of calcium-channel antagonists were questioned about five types of financial relationships as though they were independent variables.However, three of these relationships -"support to attend symposium," "honorarium to speak at symposium," and "support for educational program" -are often found together.Simply receiving such support is equated with financial conflict of interest without any attempt at quantitative or temporal analysis.Research funding from pharmaceutical companies had the highest positive correlation with papers favoring calcium-channel antagonists, and the reverse was also true.But those receiving the support were clinical researchers and would have been expected to require grants to perform these studies.When their research was criticized, they defended themselves in print.Is it fair simply to equate that with financial conflict of interest?Conversely, the authors of critical papers had few ties to research funding.This speaks for objectivity, but 15 of their 23 papers came from just three lead authors, all epidemiologists, not likely to be doing clinical drug research.Hence, their knowledge of the results is not based on firsthand information but rather on analysis of data produced by others.That they do not receive research funding from
Proliferation Signaling and Activation of Shc, p21Ras, and Myc Via Tyrosine 764 of Human Granulocyte Colony-Stimulating Factor Receptor
Authors: John P. de Koning, Amrita A. Soede-Bobok, Anita M. Schelen, Louise Smith, Daphne van Leeuwen, Valeria Santini, Boudewijn M.T. Burgering, Johannes L. Bos, Bob Löwenberg, Ivo P. Touw
Journal: Blood (1998)
PTU-255 Characterisation of drug transporter gene expression in colorectal tissue and cell lines: induction with anti-retrovirals for microbicide optimisation
Authors: I Mukhopadhya, S Berry, J Thomson, GI Murray, EM El-Omar, GL Hold, K Hijazi
Journal: Gut (2015)

<h3>Introduction</h3> Drug transporter expression in the colorectal epithelium is likely to play a role in the mucosal disposition of anti-retrovirals (ARVs) in rectal microbicidal preparations and impact their efficacy in prevention of HIV-1 infection. However, there is limited information on expression levels available. This study aims to assess expression of 84 drug transporter genes in human colorectal tissue and representative cell lines pre and post ARV exposure. <h3>Method</h3> Drug transporter mRNA expression was quantified from colorectal biopsies (n = 12) and 6 colorectal cell lines using real time PCR. Relative mRNA expression was quantified in Caco-2 cells after induction with tenofovir (TFV; 5 mM), dapivirine (DPV; 10 µM) and darunavir (DRV; 250 µM) for up to 3 days. Data were analysed using Pearson’s correlation (r), hierarchical clustering and principal component analysis. <h3>Results</h3> Fifty-eight of the 84 transporters were expressed in colorectal tissue. SLC28A2/CNT2 was the most expressed uptake transporter (&gt;25 fold increase) followed by efflux transporters ABCB1/P-gp and ABCC3/MRP3 (4–5 fold increase). No difference was noted between individual patients, either sexes or biopsy sites (rectum or sigmoid) (r = 0.95–0.99). Similarities between tissue and cell lines were low (r values 0.67–0.81). Principal component analysis showed distinct clustering of colorectal tissue and cell lines with Caco-2 cells showing least variance with tissues. Immunohistochemical staining of 7 colorectal biopsy sections confirmed high expression of Pgp and CNT2 drug transporters. TFV stimulation of Caco-2 cells resulted in &gt; 2 fold increase in expression of MRP5, LAT2, OATPE and GLUT1 mRNA. DPV stimulation resulted in &gt; 2 fold increase in expression of GLUT1, PEPT1 and ABCA1. DRV stimulation resulted in &gt; 2 fold increase in expression of SLC3A2, OATPE and MCT3 mRNA. <h3>Conclusion</h3> This study has enumerated drug transporter mRNA expression in colorectal tissue and cell lines. There was partial correlation between cell lines and tissue limiting cell line use as <i><i>in vivo</i></i>surrogate. TFV and DPV did not induce majority of efflux transporters in Caco-2 cells. This would entail increased retention of drug within the mucosa and as a result enhanced delivery to CD4 T cells. Further studies will elucidate whether combination of ARVs will be similarly effective. <h3>Disclosure of interest</h3> None Declared.
Fluvoxamine treatment of obsessive-compulsive disorder
Authors: T L Perse, J H Greist, J W Jefferson, R Rosenfeld, R Dar
Journal: American Journal of Psychiatry (1987)

Sixteen outpatients who met DSM-III criteria for obsessive-compulsive disorder completed a 20-week double-blind, crossover trial with fluvoxamine and placebo. Thirteen (81%) improved with fluvoxamine, while three (19%) improved with placebo. Fluvoxamine treatment was associated with significant improvement on measures of obsessive-compulsive symptoms, anxiety, and depression. Depressed subjects' improvement on obsessive-compulsive measures correlated with improvement in symptoms of depression. Nondepressed subjects also showed improvement on measures of obsessive-compulsive symptoms. In this trial, fluvoxamine was an effective and safe treatment for obsessive-compulsive disorder.
Circulating tumor cells (CTCs) in patients with HER2-negative recurrent or metastatic breast cancer treated with eribulin as third-line therapy: ONSITE trial (OncoSur Analysis of the Treatment in Third Line of ABC with Eribulin).
Authors: Luis Manso, Fernando Moreno, Juan Ignacio Delgado Mingorance, Maria Jose Echarri, Ana Lopez-Gonzalez, Yann Izarzugaza, Pablo Borrega, Noelia Martínez, Clara Olier, Ana Isabel Ballesteros Garcia, Jose Ignacio Chacon, Eva Ciruelos, Tomas Pascual, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2015)

e22042 Background: CTCs in peripheral blood are an ideal source for the detection of tumor dissemination. Their poor prognosis significance (CTCs > 5) has been demonstrated in metastasic breast carcinoma (Cristofanilli, NEJM 2004). Eribulin (E) is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Onsite trial is a multicentre, single arm, study to evaluate the safety of Eribulin as third line of chemotherapy in advanced breast cancer (ABC) progressed to anthracycline and a taxane. Aims of this sub-study are the evaluation of the prevalence and kinetics of CTCs before and after treatment with E in pts with MBC in third line Methods: A total of 57 patients received E (1.23 mg/m2 on Days 1 and 8 of every 21-day cycle) as third-line therapy, until disease progression, unacceptable toxicity or withdrawal. CTCs were measured in 7.5ml of blood at baseline and after the first cycle of treatment and enumeration were performed by CellSearch System, Veridex LCC Results: CTCs data were available for 44 pts. The media value of CTCs at baseline determination was 17 cells (min 0- max 21) and 5 cells (min 0-max 8) in second determination, p = 0,002. Baseline value of CTCs > 5 was presented in 36% of the pts and in 22% after first cycle, p = 0,033. After 1st cycle of eribulin 84% of pts presented a CTCs value < 5. First follow-up was made in 26 pts after 3 months of treatment with CR 0%, PR 9% (n = 5), ED 21% (n = 11), PD 18% (n = 10). 55% (N = 10) of pts that had stable disease/partial response, decreased or maintained CTCs value < 5 post-treatment. Conclusions: Treatment with eribulin in third line ABC was related with a high reduction of poor prognosis value of CTCs > 5 and baseline CTCs counts. Clinical trial information: 2013-001416-30.
Production of Malignancy &lt;italic&gt;in vitro&lt;/italic&gt;. XI. Further Results from Reinjection of &lt;italic&gt;in vitro&lt;/italic&gt; Cell Strains into Strain C&lt;sub&gt;3&lt;/sub&gt;H Mice
Authors: Wilton R. Earle, Emma Shelton, Edward L. Schilling
Journal: JNCI Journal of the National Cancer Institute (1950)

Journal Article Production of Malignancy in vitro. XI. Further Results from Reinjection of in vitro Cell Strains into Strain C3H Mice Get access Wilton R. Earle, Wilton R. Earle Search for other works by this author on: Oxford Academic PubMed Google Scholar Emma Shelton, Emma Shelton Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward L. Schilling Edward L. Schilling National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 5, April 1950, Pages 1105–1113, https://doi.org/10.1093/jnci/10.5.1105 Published: 01 April 1950 Article history Received: 12 December 1949 Published: 01 April 1950
Leber's optic neuropathy.
Authors: C Orssaud, J L Dufier
Journal: BMJ (1980)

Leber hereditary optic neuropathy is associated to mutations of the mitochondrial DNA that seem to be pathogenic of this disease. However, other genetic or environmental factors must play a role in the development of this optic atrophy. Leber hereditary optic neuropathy is usually isolated. Its typical clinical feature includes in a young man a sudden and severe decrease of vision of one eye. The second eye is affected few weeks later. But, atypical feature can be observed. Thus, this diagnosis must be suspected as soon as there is no evident aetiology for an optic neuropathy, whatever the clinical feature, the age or the sex of the patient can be. There is no treatment. But visual recovery can spontaneously occurred even years after the disease appearance.