tbuckley/cabot-search huggingface dataset:
Soundings: Cunegonde's ears, or multiple medical errors
Authors: George Dunea
Journal: BMJ (2000)

When Miss Cunegonde first arrived from the 18th century, riding on her broomstick, she had hoped to set up her own web page, appear on the Larry King show, and meet Miss Monica Lewinsky. Instead she developed a urinary infection unrelieved by Chinese herbs, megavitamins, acupuncture, and high doses of ibuprofen.

In the emergency room at the hospital the clerk misspells her name with a K, records her date of birth as 1980, loses her broomstick, but eventually enrols her in this benevolent healthcare system in which countless other “undocumented”—that is, illegal— immigrants receive chronic dialysis or cardiology or oncology treatment, indefinitely and at no cost to themselves.

That night on the medical floor the intern prescribes meetofloxacin, but the nurse, her mind on a late in life passionate love affair, forgets to administer the prescribed dose.

The next day Cunegonde is worse. The intern prescribes ampicillin, but forgets to ask about allergies. Now she looks like a bad case of measles.

The infectious diseases fellow now recommends putrimicin, a powerful new antibiotic with a wide spectrum of activity against diseases acquired before the French revolution. Five minutes later Cunegonde's right ear drops off, an unexpected reaction that premarketing testing had failed to detect and that should be reported in a letter to the BMJ.

Eventually Cunegonde recovers. Her pelvis and kidneys are fine, but the other end looks strangely asymmetrical with only one ear. She has surgery to stitch it back, but is mixed up in the operating room with the also earless Miss Cunningham and receives an ear two sizes too large—an error that experts now hope to avoid by adopting the systems that prevent most (but not all) aeroplanes from plunging into the sea.

An immunologist now suggests a heterotransplant—like the one that had worked so well on King Midas. But Cunegonde decides to call it quits. She lets her hair grow long and looks for her broomstick. Blissfully unaware of the local malpractice racket, she returns to between the covers of M. de Voltaire—or rather of his book. She plans to add a chapter on preventing medical errors by throwing all doctors and their medicines to the bottom of the sea.
Cholinergic inhibition of Na-K-ATPase via activation of protein kinase C in Madin-Darby canine kidney cells.
Authors: L C Garg, P K Saha, D Mohuczy-Dominiak
Journal: Journal of the American Society of Nephrology (1993)

Recently, it was reported that muscarinic-type cholinergic receptors coupled to the phosphoinositide messenger system are present in the rabbit inner medullary collecting duct and Madin-Darby canine kidney (MDCK) cells. The receptor density in MDCK cells is 50 times more than that in inner medullary collecting duct cells. To examine if muscarinic receptor activation influences Na-K-ATPase, the effects of a cholinergic agonist, carbachol, on Na-K-ATPase activity in MDCK cells were measured. Carbachol inhibited Na-K-ATPase activity in a time- and concentration-dependent manner. A maximum of approximately 80% of the enzyme activity was inhibited in 160 min with an EC50 of 5 microM carbachol. The inhibition of Na-K-ATPase activity was reversible; up to 80% of the enzyme activity was recovered within 4 h after carbachol was removed. The inhibitory effect of carbachol was blocked by a muscarinic antagonist atropine and by inhibitors of protein kinase C (PKC), 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine HCl, and N-(2-(methylamino)ethyl)-5-isoquinoline sulfonamide HCl. Direct activators of PKC, phorbol 12-myristate 13-acetate, N(n-heptyl)-5-chloro-1-naphthalene sulfonamide, and phosphatidyl serine, also inhibited Na-K-ATPase activity in MDCK cells, and their effect was also blocked by PKC inhibitors. These results indicate that cholinergic agonists inhibit Na-K-ATPase activity in MDCK cells by the activation of PKC. It is concluded that the inhibition of Na-K-ATPase by PKC may, in part, be responsible for the natriuretic action of cholinergic agonists, which have been shown to stimulate phosphoinositide hydrolysis in renal collecting duct cells.
Dismantling the NHS
Authors: John W Myles
Journal: Journal of the Royal Society of Medicine (2016)

I read the review of NICE by Professor Rawlins and was surprised that it does not mention at any point how much this bureaucratic process costs. I suspect it employs hordes of people and spends millions of pounds to produce guidance that usually seems to just tell us what we already know with a bit of stuff on quality-adjusted life years thrown in. In oncology we also have the bizarre situation where NICE produces guidance that is then bypassed by another bureaucratic system namely the Cancer Drugs Fund. Maybe it would be cheaper to allow clinician groups to make decisions on what constitutes good practice.
Abstract P5-03-14: MLN0128 regulates survival signaling by AKT and its downstream effectors in HER2+ breast cancer model
Authors: PK De, JH Carlson, Y Sun, X Lin, C Williams, N Dey, BR Leyland-Jones
Journal: Cancer Research (2016)

Abstract Evading apoptosis is considered to be a hallmark of cancers including breast cancer, since mutations in apoptotic regulators invariably accompany tumorigenesis. Chemotherapeutic agents induce apoptosis, and hence disruption of apoptosis during tumor progression may promote drug resistance. AKT is an apoptotic regulator that is activated in HER2+ breast tumor cells and promotes anti-HER2 therapy resistance in vitro. Nevertheless, how mTORC1/C2-AKT signaling disables apoptosis and its contribution to clinical drug resistance are not clear yet. Using HER2 amplified breast cancer cells [BT474 (HER2+/Trastuzumab-sensitive), BT474HerR (HER2+/Trastuzumab-resistant), HCC1954 and MDA-MB453 (both are HER2+/PIK3CA kinase domain mutated)], we show that mTORC1/C2 inhibitor; MLN0128 abrogates AKT (Ser473), Survivin and controls its downstream effectors of apoptotic signaling molecules (e.g. cleaved Caspase 3/9, cleaved PARP, MCL and BIM). MLN0128 also induces annexinV positive cells and regulates cellular proliferation (ON-TOP 3D colony formation and real-time proliferation assay). Additionally, increased cleaved Caspase 3 and decreased MCL1 expression were also observed following MLN0128 treatment in HER2+ xenograft model along with tumor growth inhibition. Our studies provide strong experimental evidence that high apoptotic signaling –specifically reduced MCL1 and increased cleaved-CASPASE3 expression expedite the response of targeted therapy that directly inhibits mTORC1/C2-AKT signaling. Citation Format: De PK, Carlson JH, Sun Y, Lin X, Williams C, Dey N, Leyland-Jones BR. MLN0128 regulates survival signaling by AKT and its downstream effectors in HER2+ breast cancer model. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-03-14.
A stratified phase II trial investigating sorafenib (SORA) in patients (pts) with metastatic or locally advanced angiosarcoma (AS).
Authors: N. Penel, I. Ray-Coquard, A. Cioffi, E. Bompas, C. Chevreau, A. Italiano, J. Bay, N. Isambert, S. Clisant, J. Blay
Journal: Journal of Clinical Oncology (2010)

10026 Background: AS represent an aggressive subtype of sarcoma. Preclinical data and limited clinical experience suggest that SORA has some antitumor activity against AS. Methods: We had conducted a stratified phase II trial. The primary endpoint was progression- free rate (PFR) at 9 months according to RECIST. A 2-stage design (Optimal Simon Design) was used. Patients received for 9 months SORA 400 mg b.i.d until unacceptable toxicity or tumor progression. Central pathological review was performed. Data of strata A (superficial AS) and strata B (visceral AS) are currently available. Results: [Strata A] From 06/2008 to 07/2009, 23 pts with superficial AS (8 scalp and skin/10 breast/6 soft tissue) have been enrolled (16 women/median age: 63 [31-82]). Twelve (52%) cases arose in irradiated fields. Sixteen tumors were metastatic (74%) and 7 locally advanced (26%). Eighteen patients (78%) have previously received chemotherapy (anthracyclines in 15 cases and taxanes in 8 cases). Grade-3 toxicities occurred in 5 pts (21%, mainly skin toxicities). Transient discontinuation and dose reduction were necessary in 9 (39%) and 10 (43%) cases, respectively. The best responses were: 2 CR (8%), 2 PR (8%), 4 SD (17%) and 15 PD (67%). The 4-month and 6-month PFR were 6/23 (26%) and 4/23 (17%). All pts experiencing SD at 6 month had had breast radio-induced AS. [Strata B] From 06/2008 to 11/2009, 15 pts with visceral AS have been enrolled (7 women/ median age: 49 [19-67]). One case arose in irradiated field. Metastases were present in 8 cases. Eight pts have received previous chemotherapy (anthracyclines in 7 cases and taxanes in 3 cases). Nine pts experienced at least one episode of grade-3 toxicity. Transient discontinuation and dose reduction were necessary in 3 and 4 cases. 7 pts are currently assessable for response. Best responses were: 4 SD and 3 PD. The 4-month and 6-month PFR were both 2/7. Conclusions: SORA provides a 6-month PFR of about 20% of pts with AS. Exploration of biological predictive factors is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer
Ten Years of Alendronate Treatment for Osteoporosis in Postmenopausal Women
Authors: Salvatore L Ruggiero, Bhoomi Mehrotra
Journal: New England Journal of Medicine (2004)

to the editor: In their report on 10 years of alendronate therapy for osteoporosis in postmenopausal women, Bone et al. (March 18 issue) 1 mention the long retention time of alendronate in bone as an advantage. This view is based on the fact that the large reduction in bone turnover is present five years after the discontinuation of treatment. The authors claim that histomorphometric analysis confirmed long-term bone safety, 2,3 but the study they cite followed treatment for only two to three years in a small group of patients receiving 20 mg of alendronate. 2 What the present study actually shows is that two years of therapy with 20 mg of alendronate followed by three years’ treatment with 5 mg suppresses bone turnover to a degree from which it may not recover. This result is consistent with data from a study in Danish women, which showed that two years of treatment with 20 mg of alendronate led to a reduction in bone turnover that did not return to baseline five years after the discontinuation of therapy. 4 In contrast, with two years of therapy with 2.5 mg or 5 mg of alendronate, 5 bone turnover returned to placebo levels two years after discontinuation. Thus, the long-term safety with 20 mg of alendronate has not been established.
Report on the NCCN Third Annual Patient Safety Summit
Authors: Jennifer M Hinkel
Journal: Journal of the National Comprehensive Cancer Network (2008)

The issues of patient safety and preventing medical errors routinely make headlines, with reports of thousands of preventable deaths and costs in the billions of dollars per year. Far less noticeable, but potentially more important, is the work taking place on a daily basis to develop new systems and processes of safety and use of technology in the effort to reduce preventable adverse events. The NCCN Third Annual Patient Safety Summit examined 3 processes central to maintaining patient safety in the oncology setting: medication reconciliation, communication during patient hand-offs, and reporting of events, including “near-miss” events that do not reach a patient or result in harm. The NCCN Patient Safety Summit included a multidisciplinary audience of safety experts, clinicians, and hospital administrators from NCCN member institutions, with speakers from member institutions sharing clinical and practical experiences in implementing safety improvements. Common themes included transitions from paper to electronic systems, education and training for individuals and teams as new methods are put into place, and the need for all members of the multidisciplinary care team to recognize their impact on patient safety.
Abstract B22: Screening and validation of combination therapy in T cell leukemia
Authors: Marsilius Mues, Marthe F. Lindenbergh, Michael T. McManus, Jeroen P. Roose
Journal: Cancer Research (2016)

Abstract Oncogenic Ras mutations occur in more than 30% of metastatic cancers. There are no effective inhibitors to block oncogenic K- or N-RAS, however, blockade of Ras’ downstream RAF-MEK-ERK and PI3K-Akt-mTOR-S6 signaling cascades is currently being explored as therapy in clinical trials through the use of potent kinase inhibitors. Nonetheless, many cancers have a complex make-up of cooperating oncogenic lesions and it is therefore questionable if inhibition of single molecules in pathways will provide sufficient, long-term efficacy. To explore effective combination therapies to treat Ras-driven cancers we chose synthetic lethal screens (SLS), focusing on PI3K due to its frequent involvement in oncogenic signaling. We performed a set of SLS on T cell leukemia (T-ALL) cell lines combining specific PI3K inhibitors with high coverage shRNA libraries, initially aiming at kinases. We employed the UCSF EXPANDed RNAi library resource, which dramatically improves RNAi screening compared to commercial resources. This ultra-complex shRNA library targets each gene with &amp;gt;25 independent shRNAs, thus drastically minimizing experimental noise and allowing us to overcome both the common problems of high false-negative rates and high false-positive rates. Using deep sequencing of shRNAs recovered from our screening samples, we identified shRNAs that synergize with inhibitors in these drop-out SLS conditions and which represent key molecules for the survival of T-ALL lines. In addition, we also identified enriched shRNAs that confer inhibitor resistance or enhanced proliferation. To verify our screening results we used combinations of chemical inhibitors, targeting PI3K and molecules identified by our screens. To date, all inhibitor combinations tested caused strong synthetic lethality in T-ALL cells, confirming the robustness of the ultra-complex shRNA libraries used for SLS. The most promising results will be further verified in vivo, and we will expand our efforts to different leukemia and also solid cancer lines. Altogether, our high-troughput platform is a promising approach to identify effective partners for already established inhibitors, leading to novel combination therapies for the treatment of cancer. Citation Format: Marsilius Mues, Marthe F. Lindenbergh, Michael T. McManus, Jeroen P. Roose. Screening and validation of combination therapy in T cell leukemia. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B22.
Case 20-1965
Authors: Charles F. Barlow, Edward P. Richardson, Benjamin Castleman
Journal: New England Journal of Medicine (1965)

Presentation of Case*A three-day-old white male infant was referred to the hospital because of tachypnea.The patient was the product of a full-term, normal delivery and weighed 3.5 kg. (7 pounds, 11 1/2 ounces) at birth. He cried spontaneously and had a good color. Feedings were taken well, and the vital signs were normal until the day of admission, when the temperature rose to 101°F., the respirations increased to 120, and irritability and crying were observed. A lumbar puncture revealed 700 red cells and 4 mononuclear cells per cubic millimeter in the cerebrospinal fluid; the glucose content was 66 . . .
Feline Malignant Mammary Tumors. II. Immunologic and Electron Microscopic Investigations Into a Possible Viral Etiology
Authors: K. Weijer, Jero Calafat, J. H. Daams, Philomena C. Hageman, W. Misdorp
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Feline Malignant Mammary Tumors. II. Immunologic and Electron Microscopic Investigations Into a Possible Viral Etiology Get access K. Weijer, K. Weijer 2The Netherlands Cancer Institute, 121 Plesmanlaan, Amsterdam, The Netherlands.3Department of Pathology. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jero Calafat, Jero Calafat 2The Netherlands Cancer Institute, 121 Plesmanlaan, Amsterdam, The Netherlands.4Department of Electron Microscopy. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. H. Daams, J. H. Daams 2The Netherlands Cancer Institute, 121 Plesmanlaan, Amsterdam, The Netherlands.5Department of Immunology. Search for other works by this author on: Oxford Academic PubMed Google Scholar Philomena C. Hageman, Philomena C. Hageman 2The Netherlands Cancer Institute, 121 Plesmanlaan, Amsterdam, The Netherlands.6Department of Biology. Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Misdorp W. Misdorp 2The Netherlands Cancer Institute, 121 Plesmanlaan, Amsterdam, The Netherlands.3Department of Pathology. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 673–679, https://doi.org/10.1093/jnci/52.3.673 Published: 01 March 1974 Article history Received: 19 March 1973 Accepted: 23 October 1973 Published: 01 March 1974
Alan Wilfrid Gough Goolden
Authors: Alastair J Munro
Journal: BMJ (2016)

Alan Wilfrid Gough Goolden, who died in 2015 at the age of 95, was a member of that great generation of doctors who came back from the war and helped to found the NHS and, by so doing, changed utterly, and for the better, the lives of the British people.

Alan’s background was conventional, his approach to life less so. He was born in Maidenhead in 1919. His father, Francis Goolden, was a naval officer, and his mother, Dorothy French, was from Ireland. As a boy, Alan had always assumed that he would follow his father into the navy, but a minor problem with his eyesight meant that he was turned down for naval service. Forced to change his plans, he applied to study medicine and entered St Bartholomew’s Medical School just before the second world war. In preparation for war, and the anticipated bombing of central London, preclinical students were taught in Cambridge, and many of the hospital’s services had been evacuated to hospitals around St Albans and Friern Barnet. After qualifying and doing house jobs at the Metropolitan Hospital in the East End of London, Alan’s original wish was granted and in 1944 he joined the Royal Naval Volunteer Reserve as a surgeon lieutenant. He served for two years and, on his discharge from the navy, worked first as registrar and then senior registrar in the radiotherapy department at the Royal South Hants Hospital. He then went to work with Constance Wood at the Hammersmith Hospital. He was surprised to be offered the position. Later on, he found out that his ticket of admission had been a paper that he had published in The BMJ in 1951, entitled “Radiation Cancer of the Pharynx.” He spent the rest of his career based at the Hammersmith but, through some quirk …
Are psychiatric educators "losing the mind"?
Authors: M F Reiser
Journal: American Journal of Psychiatry (1988)

Psychiatry is part of medicine, and developing competence to deal with the mental life of patients is an essential part of general medical as well as psychiatric subspecialty education. As psychiatry's neurobiological data base, therapeutic armamentarium, scope of interest, and philosophical views expand and competitive pressures for time in residency training are intensified, teaching in the mental sciences and opportunities for residents to develop solid psychodynamic diagnostic and therapeutic skills are rapidly disappearing. However, brain science does not yet, and probably never will, fully explain the mind. The author urges psychiatric educators not to give up the mind or, worse yet, lose it by default.
Second malignancies after testicular cancer.
Authors: L B Travis, R E Curtis, B F Hankey
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.2.533 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7844617 Second malignancies after testicular cancer. L B TravisxL B TravisSearch for articles by this author , R E CurtisxR E CurtisSearch for articles by this author , B F HankeyxB F HankeySearch for articles by this author https://doi.org/10.1200/JCO.1995.13.2.533 PDF "Second malignancies after testicular cancer.." Journal of Clinical Oncology, 13(2), pp. 533–534© 1995 by American Society of Clinical Oncology
S49 Ventilatory irregularity quantified by approximate entropy identifies disordered breathing in patients with unexplained dyspnoea: Abstract S49 Table 1
Authors: T Bansal, GS Haji, HB Rossiter, MI Polkey, JH Hull
Journal: Thorax (2015)

<h3>Introduction</h3> Patients with idiopathic persistent exertional dyspnoea are often labelled as having a breathing pattern disorder (BPD). There are no agreed objective diagnostic measures for BPD, which complicates its characterisation and response to therapy. Approximate entropy (ApEn) is a measure of unpredictability, based on chaos theorem, which quantifies the degree of irregularity in time-series data. <h3>Objectives</h3> To measure ApEn of ventilatory variables during a cardiopulmonary exercise test (CPET) in patients referred with unexplained dyspnoea. We hypothesised that ApEn of tidal volume and breathing frequency would be greater (i.e. more irregular) in patients with BPD than healthy controls. <h3>Methods</h3> We studied 20 adults (14 female) with unexplained dyspnoea referred for CPET and diagnosed with BPD (by a senior respiratory physiotherapist blinded to ApEn data) and 15 age- gender- and BMI-matched healthy controls. Underlying cardiorespiratory disease was excluded using various investigations (e.g. imaging and echocardiography) prior to referral, in addition to tests performed on the day of CPET; namely pulmonary function and blood gas analysis. ApEn of various ventilatory parameters including tidal volume, breathing frequency and minute ventilation was calculated at rest and during a cycle-ergometer CPET. <h3>Results</h3> BPD patients had greater dyspnoea (modified BORG) at rest (1.4 ± 1.2 vs 0.2 ± 0.6; P &lt; 0.01) and lower peak oxygen uptake (VO<sub>2</sub>) (P &lt; 0.01; Table 1). Peak exercise respiratory exchange ratio was similar between groups (1.14 ± 0.17 vs 1.13 ± 0.08, P = 0.84) as were nadir values for ventilatory equivalent for CO<sub>2</sub> (28.5 ± 5.2 vs 25.5 ± 3.6, P = 0.07) and end-exercise arterial PCO<sub>2</sub> (4.21 ± 0.68 vs 4.1 ± 0.67, P = 0.68). ApEn was significantly greater in the BPD cohort for the duration of the test (Table 1); however differences were not apparent at rest. There was no relationship between ApEn and baseline symptom scores. <h3>Conclusion</h3> Measurement of ventilatory ApEn in patients referred with unexplained dyspnoea quantified irregularity of breathing pattern and was significantly greater (more irregular) in BPD than controls. These differences were not apparent from resting phase analysis. Quantifying increased dys-regulation in exercise hyperpnoea using ApEn can be applied to ventilatory variables collected during standard CPET, and thus could aid in diagnosis and evaluating treatment response in BPD. Further work should explore how ventilatiory ApEn relates to perception of symptoms.