tbuckley/cabot-search huggingface dataset:
Severe Combined Immunodeficiency and Adenosine Deaminase Deficiency
Authors: Robertson Parkman, Erwin W. Gelfand, Fred S. Rosen, Arnold Sanderson, Rochelle Hirschhorn
Journal: New England Journal of Medicine (1975)

Because others had described a lack of the enzyme adenosine deaminase as associated with severe combined immunodeficiency, we surveyed kindreds with infants affected with such an immunodeficiency. Three infants in two families with severe combined immunodeficiency were found to have no detectable erythrocyte adenosine deaminase. Eleven family members heterozygous for adenosine deaminase deficiency were encountered among the first-degree relatives; adenosine deaminase deficiency and severe combined immunodeficiency were associated and inherited as autosomal recessive traits in both kindreds. Successful bone-marrow transplantation was carried out in two of these infants. Normal immunologic function was established in both children, but the deficiency of adenosine deaminase persisted in their erythrocytes. The enzyme deficiency did not impair the successful establishment of normal humoral and cellular immunity by transplants of bone-marrow cells from siblings who were either normal or heterozygous for adenosine deaminase deficiency.
Return to work after coronary artery surgery for angina.
Authors: J Wallwork, B Potter, P K Caves
Journal: BMJ (1978)

The working habits of 115 consecutive patients who underwent coronary artery vein bypass grafting for angina were assessed. Only 25 patients worked up to the operation. Seven patients were housewives and seven retired. Sixty-eight patients had had to give up work because of their angina pectoris, and most of these had been off work for between six months and two years. After the operation 75 patients returned to full-time work, 59 within two to six months. These 75 patients included 23 of the 25 at work preoperatively and 47 of the 68 unable to work preoperatively. Most patients returned to their original occupation. We conclude that coronary artery surgery, as well as bringing symptomatic relief, increases the patient's ability to return to and maintain gainful employment.
Can we have a culture of patient safety without one of staff safety?
Authors: M. Sinnott, R. Z. Shaban
Journal: BMJ (2011)

The history of patient safetyThe patient safety movement reached its tipping point in 2000 after the publication, in the 1999 US Institute of Medicine Report, To Err is Human, of the extraordinary finding that there were up to 100 000 preventable deaths in US hospitals every year. 1 The patient safety movement used James Reason's paradigm of accident causation, the so called "Swiss Cheese Model", to explain why systems failures cause most adverse events among patients, and identified the "no blame" culture as a way to improve outcomes among patients. 2Removing the fear of reporting errors means that systems failures can be identified and remedied before bad patient outcomes occur.Can we have a culture of patient safety without one of staff safety?| BMJ
Bioinformatic Comparison of Bacterial Secretomes
Authors: Catharine Song, Aseem Kumar, Mazen Saleh
Journal: Genomics Proteomics & Bioinformatics (2009)

Abstract The rapid increasing number of completed bacterial genomes provides a good opportunity to compare their proteomes. This study was undertaken to specifically compare and contrast their secretomes—the fraction of the proteome with predicted N-terminal signal sequences, both type I and type II. A total of 176 theoretical bacterial proteomes were examined using the ExProt program. Compared with the Gram-positives, the Gram-negative bacteria were found, on average, to contain a larger number of potential Sec-dependent sequences. In the Gram-negative bacteria but not in the others, there was a positive correlation between proteome size and secretome size, while there was no correlation between secretome size and pathogenicity. Within the Gram-negative bacteria, intracellular pathogens were found to have the smallest secretomes. However, the secretomes of certain bacteria did not fit into the observed pattern. Specifically, the secretome of Borrelia burgdoferi has an unusually large number of putative lipoproteins, and the signal peptides of mycoplasmas show closer sequence similarity to those of the Gram-negative bacteria. Our analysis also suggests that even for a theoretical minimal genome of 300 open reading frames, a fraction of this gene pool (up to a maximum of 20%) may code for proteins with Sec-dependent signal sequences.
Diabetes does not add to the increased six-month mortality associated with increase in CK-MB after percutaneous coronary intervention
Authors: Sanjeev Puri, Bernard R. Chaitman, Jeffrey A. Gavard, Shunta Sakai, Karen Stocke, Leif Erhardt, Eric Chi, Andreas Jessel, Richard Gallo, Pierre Theroux
Journal: Journal of the American College of Cardiology (2003)
Toxicity of oral adjuvant chemotherapy in breast cancer.
Authors: J G Murray, J MacIntyre, D P Leiberman, D J Leaper
Journal: BMJ (1978)

Cutaneous necrotising vasculitis induced by levamisoleThe anthelmintic agent levamisole has immunostimulant properties in patients with defective cell-mediated immune responses.We are assessing the drug in patients with breast cancer to see whether it can maintain surgically induced remission.One such patient developed a severe cutaneous necrotising vasculitis, which disappeared once the drug was withdrawn. Case reportA 59-year-old woman had been receiving thrice-weekly levamisole 150
Increased intragraft rejection–associated gene transcripts in patients with donor-specific antibodies and normal biopsies
Authors: Nicole Hayde, Pilib Ó. Broin, Yi Bao, Graciela de Boccardo, Michelle Lubetzky, Maria Ajaimy, James Pullman, Adriana Colovai, Aaron Golden, Enver Akalin
Journal: Kidney International (2014)
IMMUNIZATION WITH BACILLUS PERTUSSIS VACCINE
Authors: LOUIS W. SAUER
Journal: JAMA (1933)

That untreated whooping cough may run a mild course has long been known. Before the days of pertussis vaccine Neurath, in the first edition of Pfaundler and Schlossmann's "Handbuch," says: "bed-rest in a fresh, warm, dust-free atmosphere without drafts, not infrequently aborts the disease." And Pospischill, in his book "Pertussis," written after he had seen over 25,000 cases, says: "Most whooping cough patients need no physician, but those who do, need him badly." The outstanding pertussis vaccine study is that of the Danish physicians who injected, in the Faroe Islands, 2,094 patients and 364 children as a prophylactic measure. In the Cutter Lecture, Madsen<sup>1</sup>says: "Vaccination has no effect, once the disease has broken out.... It should be used to the widest possible extent as soon as an epidemic threatens.... Vaccination is most effective if completed a week before the disease breaks out.... The effect is greatest in patients
Attitudes of Mothers to Infant and Child Health and Welfare Clinics
Authors: R. M. Acheson
Journal: BMJ (1962)

The infant and child health and welfare services in Britain were conceived and grew in an era when poverty and ignorance were commonplace; when most women thought it natural that a considerable proportion of the babies they brought into the world should die before they were old enough to know that they were alive. Now in terms of individual experience the loss of a baby is a rarity, and the hard core of infant mortality rests with small or deformed children whose chances have been slim from the outset. It is therefore natural that searching inquiries should be made on whether expensive facilities concerned with routine medical care of babies and small children are still necessary and, if so, what shape they should take. Such inquiries could be directed towards the most efficient method of dispensing prophy lactic vaccinations and inoculations, to the problems of advising on infant management, to the most efficient methods of pre-symptomatic diagnosis, and so on. The present paper, however, confines itself to a study of the attitudes of some mothers to the existing services. Mothers, after all, are not only the customers but in the last resort the people in whose hands the health of the baby lies. Methods
Wrong conclusions drawn, again
Authors: J. Brind
Journal: BMJ (2010)

<h3>Background</h3> In high-risk children (due to underlying illness or immunosuppressive therapy), fever is often the only sign of serious bacterial infection (SBI). Biomarkers commonly used in emergency departments (EDs) do not predict SBI well, therefore most high-risk children are admitted and treated with IV antibiotics, awaiting final microbiological results. We describe current management and aetiology across Europe. <h3>Objectives</h3> 1. To describe the characteristics of high-risk paediatric patients presenting to A/E with febrile illness 2. To assess the current aetiology of febrile illness in the high-risk population 3. To assess current management and outcome of febrile illness in the high-risk paediatric population <h3>Methods</h3> High-risk children, presenting with fever/suspected infection and requiring blood investigations, were prospectively recruited, upon informed consent, in the Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union (PERFORM) study across 16 European centres between June 2016 and June 2019. Demographic, presenting features, microbiological, treatment, and outcome data were collected. Patients were assigned final phenotype diagnoses as per PERFORM protocol. <h3>Results</h3> 529 children were recruited of whom 56% had malignancies. 92.5% (n=490) had blood cultures taken with a positive yield of 16.1% (n=79), including 14 contaminants. 27.8% (n=146) had bacterial phenotypes, 22.4% (n=116) viral, and 31.7% (n=161) were unknown viral/bacterial. Only 12.4% (n=65) were definite bacterial and 9.70% (n=51) definite viral infections. In ED, only ill appearance was associated with bacterial infection (p&lt;0.001); vital signs and neutropenia were not. 82% (n=432) had antimicrobials started on admission, and were treated for median 7 days (IQR 3–10 days). Mortality was 1.7%, and 85.7% made full recovery, without difference between bacterial or viral phenotypes. Bacterial phenotype was associated with PICU admission (p=0.014). <h3>Conclusions</h3> Fever remains a major challenge in high-risk children. Ill appearance was the only feature in ED associated with bacterial phenotypes. The low yield of microbiological diagnostics supports the urgent need for new biomarkers. <h3>Acknowledgements</h3> This project received funding from the European Union’s Horizon2020 programme under grant agreement 668303.
Phylogeny of Nuclear-Encoded Plastid-Targeted Proteins Supports an Early Divergence of Glaucophytes within Plantae
Authors: A. Reyes-Prieto, D. Bhattacharya
Journal: Molecular Biology and Evolution (2007)

The phylogenetic position of the glaucophyte algae within the eukaryotic supergroup Plantae remains to be unambiguously established. Here, we assembled a multigene data set of conserved nuclear-encoded plastid-targeted proteins of cyanobacterial origin (i.e., through primary endosymbiotic gene transfer) from glaucophyte, red, and green (including land plants) algae to infer the branching order within this supergroup. We find strong support for the early divergence of glaucophytes within the Plantae, corroborating 2 important putatively ancestral characters shared by glaucophyte plastids and the cyanobacterial endosymbiont that gave rise to this organelle: the presence of a peptidoglycan deposition between the 2 organelle membranes and carboxysomes. Both these traits were apparently lost in the common ancestor of red and green algae after the divergence of glaucophytes.
Suppression of Familial Adenomatous Polyposis by CP-31398, a TP53 Modulator, in <i>APCmin/+</i> Mice
Authors: Chinthalapally V. Rao, Malisetty V. Swamy, Jagan M.R. Patlolla, Levy Kopelovich
Journal: Cancer Research (2008)

Abstract p53 mutations occur in a large number of human malignancies. Mutant p53 is unable to affect downstream genes necessary for DNA repair, cell cycle regulation, and apoptosis. The styrylquinazoline CP-31398 can rescue destabilized mutant p53 expression and promote activity of wild-type p53. The present study examines chemopreventive effects of CP-31398 on intestinal adenoma development in an animal model of familial adenomatous polyposis. Effects were examined at both early and late stages of adenoma formation. Effects of CP-31398 on early-stage adenomas were determined by feeding 7-week-old female C57BL/6J-APCmin (heterozygous) and wild-type C57BL/6J mice with American Institute of Nutrition-76A diets containing 0, 100, or 200 ppm of CP-31398 for 75 days. To examine activity toward late-stage adenomas, CP-31398 administration was delayed until 15 weeks of age and continued for 50 days. During early-stage intervention, dietary CP-31398 suppressed development of intestinal tumors by 36% (P &amp;lt; 0.001) and 75% (P &amp;lt; 0.0001), at low and high dose, respectively. During late-stage intervention, CP-31398 also significantly suppressed intestinal polyp formation, albeit to a lesser extent than observed with early intervention. Adenomas in treated mice showed increased apoptotic cell death and decreased proliferation in conjunction with increased expression of p53, p21WAF1/CIP, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase. These observations show for the first time that the p53-modulating agent CP-31398 possesses significant chemopreventive activity in vivo against intestinal neoplastic lesions in genetically predisposed APCmin/+ mice. Chemopreventive activity of other agents that restore tumor suppressor functions of mutant p53 in tumor cells is currently under investigation. [Cancer Res 2008;68(18):7670–5]
NICE was explicit in constructing guideline
Authors: Philip R Alderson, Mercia Page, Peter Littlejohns
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which
Transfusion-transmitted hepatitis B virus infection
Authors: Daniel Candotti, Jean-Pierre Allain
Journal: Journal of Hepatology (2009)

Hepatitis B virus (HBV) remains a major risk of transfusion-transmitted infection due to the pre-seroconversion window period (WP), infection with immunovariant viruses, and with occult carriage of HBV infection (OBI). Reduction of HBV residual risk depends upon developing more sensitive HBV surface antigen (HBsAg) tests, adopting anti-HBc screening when appropriate, and implementing HBV nucleic acid testing (NAT), either in minipools or more efficiently in individual samples. HBV NAT combines the ability to significantly reduce the window period and to detect occult HBV carriage substantiating decades of clinical observation that HBsAg-negative/anti-HBc-positive blood could transmit HBV. Clinical observations suggest limited transmission rate of occult HBV compared to WP. Low transmission rate might be related to low viral load observed in OBIs or to the presence of mutants associated with occult carriage. OBIs carrying detectable anti-HBs ( approximately 50%) are essentially not infectious by transfusion. However, recent data suggest that the neutralizing capacity of low anti-HBs may be inefficient when overcome by exposure to high viral load. Anti-HBc blood units without detectable anti-HBs appear moderately infectious except in immunocompromised recipients. Immunodeficient elderly and patients receiving immunosuppressive treatments may be susceptible to infection with lower infectious dose even in the presence of anti-HBs. The immune status of blood recipients should be taken into consideration when investigating "post-transfusion" HBV infection. Pre-transfusion testing and post-transfusion long-term follow-up of recipients, and molecular analysis of the virus infecting both donor and recipient are critical to definitively incriminate transfusion in the transmission of HBV.
Adjuvant therapy decisions in breast cancer: comparison of a multi disciplinary team's decisions with the recommendations of web-based computer programme “Adjuvant Online”.
Authors: VA Nowak, D Ravichandran, A Austin, M Ah-See
Journal: Cancer Research (2009)

Abstract Abstract #2117 Introduction: Adjuvant therapy decisions in breast cancer impact on survival, recurrence and quality of life. We compared the hormonal and chemotherapy recommendations of a multi-disciplinary team (MDT) with the “best treatment” recommended by an evidence-based online computer programme “Adjuvant Online” (AO).&amp;#x2028; Materials and Methods: We prospectively monitored a breast cancer MDT for a period of one year. Among 218 breast cancer patients discussed, patients who had DCIS, neoadjuvant therapy, primary hormonal therapy, multifocal disease and micrometastases only in the axillary lymph nodes and recurrent disease were excluded leaving 122 suitable for input into AO. The MDT recommendation and actual treatment received were recorded. Ten-year cancer-related death and relapse rates were calculated using AO and estimates of proportional risk reduction with MDT recommended therapy and AO “best treatment” were made.&amp;#x2028; Results: Median age was 61 years (range 28-86). MDT recommended endocrine therapy (ET) to all patients with ER/PR positive cancers (n=103). Among 30 women aged 55 years or less with ER/PR positive cancers, 25 had tamoxifen, 4 had an aromatase inhibitor (AI) and one switched from tamoxifen to an AI. AO suggested AI or tamoxifen-AI switch as the best treatment for post-menopausal women. Among 73 women aged over 55 years with ER/PR positive cancers, 46% (n=34) received tamoxifen as per local cancer-network guidelines, which recommended tamoxifen for low-risk (T1 N0 M0) post-menopausal breast cancer. Others received an AI (n=38) except one patient who declined ET. There were 54 patients with &amp;gt;10% risk of cancer-related death in 10 years. Among these 36 were offered and 29 received chemotherapy. Chemotherapy was not offered to 17 patients due to age and/or comorbidity. Only 1 suitable patient with &amp;gt;10% risk was not offered chemotherapy by the MDT. Among those who had chemotherapy, only 31% had 3rd generation chemotherapy as recommended by AO, the main reason being national guidelines in the United Kingdom limiting the use of this regimen.&amp;#x2028; Discussion: There are differences between the adjuvant therapy decisions by the MDT and the “best treatment” recommended by Adjuvant Online. This study shows that in the majority of these cases the differences are due to either local or national guidelines that are in force in the United Kingdom. Cancer MDTs in the UK National Health Service are expected to adhere to these guidelines. However, calculation of the risk of death and recurrence rates using AO may be useful to facilitate decision making of the MDT by giving quantitative prognostic estimates and this could be a useful adjunct to help patients make informed decisions. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2117.
Anoxia-induced activation of ATP-sensitive K+ channels in guinea pig ventricular cells and its modulation by glycolysis
Authors: Sakuji Shigematsu, Makoto Arita
Journal: Cardiovascular Research (1997)

Exposure to anoxia has been reported to activate ATP-sensitive potassium (K+(ATP)) channels in isolated ventricular myocytes. We aimed to investigate the mechanisms underlying the anoxia-induced activation of K+(ATP) channels.Guinea pig ventricular myocytes were isolated using collagenase digestion. Action potentials and membrane currents were recorded in the whole-cell mode of patch clamp. Exposure to anoxia was performed in a semi-closed airtight chamber, which prevented the diffusion of atmospheric oxygen into anoxic perfusate.Exposure to glucose-free anoxia shortened the action potential duration (APD) to less than 20% of control in 13 +/- 3 min. Subsequent reoxygenation rapidly and completely restored the APD. The time-independent large outward current which developed during anoxia was completely suppressed by reoxygenation or by the application of glibenclamide, a K+(ATP) channel blocker. The presence of extracellular glucose did not prevent APD shortening during anoxia, although it significantly decreased the rate of shortening. Reoxygenation-induced restoration of the APD was inhibited after a long-lasting anoxia. In addition, repeated exposures to anoxia/reoxygenation progressively impaired the recovery of APD during reoxygenation.Activation of K+(ATP) channels occurs during anoxia. The primary source of ATP that regulates the channel activity seems to be oxidative phosphorylation. ATP derived from anaerobic glycolysis (attained by the increase of extracellular glucose) was observed to partially suppress the channel activity only when oxidative phosphorylation was severely impaired during anoxia.
SPECIAL LENS FOR HEAD MIRROR
Authors: Edward J. Bernstein
Journal: JAMA (1927)

To the Editor:  —To overcome the disadvantages of presbyopia, many otolaryngologists must change from their ordinary street glasses to their near vision ones, or use a device sold by the instrument makers consisting of a clip to hold a small lens, which clip is attached to the head mirror by three hooks, one in the sight hole and two on the periphery of the head mirror. This is a very handy device, but unfortunately it often slips at most inopportune moments. To overcome this I had a one centimeter lens plus 2 D. spheres made which I fastened by sealing wax, which is permanent but not neat. A few days ago I had the Uhleman Optical Company grind down my presbyopic correction lens to fit the sight hole and it is such a beautiful, neat and permanent job that I want to pass the information on to others like myself.
Bowel Infarction as a Cause of Death in Dialysis Patients
Authors: Susan M. Diamond
Journal: JAMA (1986)

Bowel infarction as a frequent occurrence in patients with end-stage renal disease has not been previously recognized. This report describes 12 dialysis patients with nonocclusive bowel infarction. All patients with bowel infarction had large weight losses secondary to vomiting, diarrhea, or ultrafiltration when undergoing dialysis, preceding the development of this disease. Of the potential risk factors analyzed, frequent and severe hypotension (systolic blood pressure, less than 100 mm Hg) when receiving dialysis occurred more commonly in patients developing bowel infarction. The weight loss was not often recognized initially as an important compromising problem. A fatal outcome was experienced in nine of the 12 patients. We conclude that bowel infarction may be a significant cause of morbidity and mortality in dialysis patients.
A role for the IgH intronic enhancer Eμ in enforcing allelic exclusion
Authors: Fubin Li, Laurel A. Eckhardt
Journal: The Journal of Experimental Medicine (2008)

The intronic enhancer (Eμ) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine Eμ's subsequent functions, we created an Igh allele with assembled VH gene but with Eμ removed. In mice homozygous for this Eμ-deficient allele, B cell development was normal and indistinguishable from that of mice with the same VH knockin and Eμ intact. In mice heterozygous for the Eμ-deficient allele, however, allelic exclusion was severely compromised. Surprisingly, this was not a result of reduced suppression of V-DJ assembly on the second allele. Rather, the striking breakdown in allelic exclusion took place at the pre-B to immature B cell transition. These findings reveal both an important role for Eμ in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion.