tbuckley/cabot-search huggingface dataset:
Attention deficit hyperactivity disorder: diagnosis and management in the USA
Authors: Michael Gordon
Journal: Journal of the Royal Society of Medicine (1999)

Perpetually enveloped in a haze of elusive criteria, hastily drawn conclusions, academic nit-picking and media-inspired sensationalism, attention deficit hyperactivity disorder (ADHD) never lacks for its share of controversy. Indeed, clinicians and patients on both sides of the Atlantic have good reason to be bewildered by what must often seem like constantly shifting diagnostic sands. Treatment strategies also fade in and out of professional and public acceptance. Yet, despite the many well-publicized debates about the management of ADHD, it would be inaccurate to portray this arena as wholly chaotic. After all, clinical researchers can point to a vast body of published work that offers ample information about genetic and family factors, the life history of the disorder, predictors of outcome, and the relative benefits of medical, educational, and parent-oriented treatments1'2. And while no one could fairly claim a monolithic American perspective on ADHD, a rough consensus has emerged within the professional community about some of the central issues associated with clinical management. Rather than review already-published diagnostic criteria, rehash oft-described symptom clusters, or develop an argument that the US approach to ADHD is somehow superior, I would instead like to consider some of the essential assumptions that, for most of us, drive the identification and treatment of this disorder. Perhaps by revisiting several of these fundamental principles, it is easier to cut through at least some of the hyperbole and clutter (for a more complete review, see refs 3 and 4).
Abstract 11802: Clinical Implementation Of CYP2C19-genotype Guided Antiplatelet Therapy Reduces Cardiovascular Events After PCI
Authors: Larisa H Cavallari, Oyunbileg Magvanjav, R.David Anderson, Yan Gong, Aniwaa Owusu-Obeng, Ben Kong, Teresa Vo, Jennifer N Ashton, Benjamin J Staley, Amanda R Elsey, Robert W Allan, Petr Starostik, Rhonda M Cooper-DeHoff, Kristin W Weitzel, Michael J Clare-Salzler, David R Nelson, Julie A Johnson
Journal: Circulation (2015)

Introduction: Clopidogrel is bioactivated by CYP2C19, and the CYP2C19 loss-of-function (LOF) genotype leads to reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). We examined whether clinical implementation of CYP2C19 genotype-guided antiplatelet therapy (APT) reduces the risk for cardiovascular events after PCI. Methods: CYP2C19 genotyping post-PCI was implemented at UF Health Shands Hospital in July 2012, with alternative APT recommended for LOF allele carriers. Major adverse cardiovascular events (MACE, comprised of cardiovascular death, MI, stroke and stent thrombosis) over the 6 months after PCI were determined via medical record review. MACE was compared between LOF allele carriers switched to alternative APT (LOF-alternative) and both LOF allele carriers who remained on clopidogrel (LOF-clopidogrel) and non-LOF carriers (non-LOF) using Kaplan-Meier method with additional multivariable Cox regression analysis and propensity score adjustment in LOF groups. Results: Of 412 patients (80% with ACS) who underwent PCI and genotyping, 126 (31%) had a LOF allele and 68 (54%) of these received alternative APT (prasugrel n=57, ticagrelor n=8, triple dose clopidogrel n=3). On Kaplan-Meier analysis (Figure), there was a lower incidence of MACE in LOF-alternative vs. LOF-clopidogrel groups and no significant difference between the LOF-alternative and non-LOF groups. On multivariable Cox regression analysis with propensity score adjustment, there was reduced risk of MACE in LOF-alternative vs. LOF-clopidogrel patients (HR 0.09, 95% CI 0.01-0.84, p=0.035). In the LOF-clopidogrel group, the majority of events (83%) occurred within 30 days; all were in patients who presented with an ACS. Conclusion: Changing from clopidogrel to alternative APT after PCI in patients with the CYP2C19 LOF genotype reduces the risk for MACE. These data support CYP2C19 genotyping in patients undergoing PCI, especially in those with ACS.
Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study
Authors: Amanda Mocroft, Jens D Lundgren, Michael Ross, Christoph A Fux, Peter Reiss, Olivier Moranne, Philippe Morlat, Antonella d'Arminio Monforte, Ole Kirk, Lene Ryom
Journal: The Lancet HIV (2015)
Anthony John Chetwynd Balfour
Authors: Mary Lindsay
Journal: BMJ (2015)

After postings at home and abroad as a general pathologist, Anthony John Chetwynd Balfour (Tony) was appointed to Halton in 1976. This meant that he became involved with all air accidents in the UK and military planes overseas. Often on site as an aviation pathologist in the RAF (for example, in Lockerbie …
Pim1 kinase promotes angiogenesis through phosphorylation of endothelial nitric oxide synthase at Ser-633
Authors: Ming Chen, Bing Yi, Ni Zhu, Xin Wei, Guan-Xin Zhang, Shengdong Huang, Jianxin Sun
Journal: Cardiovascular Research (2015)

AimsPosttranslational modification, such as phosphorylation, plays an essential role in regulating activation of endothelial NO synthase (eNOS). In the present study, we aim to determine whether eNOS could be phosphorylated and regulated by a novel serine/threonine–protein kinase Pim1 in vascular endothelial cells (ECs).
Soundings: Chekhov's bottle
Authors: Colin Douglas
Journal: BMJ (2000)

A hundred years ago there was a fine tradition in German and Russian medicine: a piece of professional etiquette of which I knew nothing until I came across it in Donald Rayfield's excellent Anton Chekhov: a Life.

In July 1904 at a spa town in Germany, Chekhov, in the last stages of tuberculosis, was wasted, weak, and breathless. Evicted from the best hotel because his desperate coughing distressed other guests, he was dying in a modest boarding house.

He received oxygen treatment and was forbidden coffee. There were injections of camphor and of morphine. Chloral hydrate did not control his ravings. Crushed ice was placed over his heart, evoking from him a bleak joke.

Chekhov, who had qualified in medicine 20 years before but practised little, then briefly enjoyed professional privilege. At the deathbed of a medical colleague, when hope was gone, it was the duty of the attending doctor to offer his patient a glass of champagne. Dr Schworer duly sent for a bottle. Very soon afterwards Chekhov died peacefully. His last words? “I haven't had champagne for a long time.”

I read the scene, remembered it, and have thought of it quite often since. The sheer futility of treatment for tuberculosis until the 1950s is an aching horror, and the death of a literary giant in his early 40s—what might he have done had he lived as long as Tolstoy?—an enigma of Mozartian proportions.

But there is something else, too. In a couple of decades as a consultant I have looked after perhaps a few dozen doctors, not all of whom have done well. The care of the latter is complex: resonant with overtones admissible and less admissible, with challenge, interest, and threat.

Professional courtesy imposes a convention that we discuss things differently—in effect consult together—and also that more time is taken to talk. From dying doctors I have learnt much: of medicine long ago; of stocism and detachment; of peace and closure; and of our common mortality.

There is comfort in the fact that symptomatic treatment of the dying is simply far better than it was, though still some seem surprised by that. There is sheer gratitude expressed for good nursing care, again much improved in recent decades. But I sense that there's room for something more: a last gesture from one colleague to another, a stirrup cup to eternity—a glass, perhaps, from Chekhov's bottle?
The Neural Basis of Language
Authors: Antonio R. Damasio, Norman Geschwind
Journal: Annual Review of Neuroscience (1984)

Until the middle of the 1960s, the understanding of the anatomical basis of language in humans had grown on the strength of a handful of methods. The oldest and admittedly the most fruitful of them was the neuropathological study of focal cerebral lesions in patients with aphasia. A closely related method was the behavioral study of patients who had undergone surgical interventions, such as the ablation of a cerebral lobe or even an entire hemisphere. Other approaches were provided by (a) the electrical stimulation of the human cerebral cortex, in awake patients, during surgical interventions, aimed at studying the effect of stimulation on language behaviors; (b) the use of estab­ lished neuroradiological techniques, such as cerebral angiography and pneumoencephalography, for indirect localization of lesions related to lan­ guage disturbance; and (c) the study of language behavior after transient hemispheric inactivation caused by a barbiturate injected into the carotid artery of one side (the Wada Test). Unquestionably, the advances brought about by the combination of those methods were remarkable. For instance, from about the middle of the nineteenth century and for a period of nearly 100 years, neurologists collected a large number of single case studies in which distinctive disturbances of the use of language were correlated with specifically located
Sulfonylureas and the Heart
Authors: G S Levey, K C Lasseter, R F Palmer
Journal: Annual Review of Medicine (1974)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis: results from the Norfolk Arthritis Register
Authors: Jennifer H Humphreys, Marije K Verheul, Anne Barton, Alexander J MacGregor, Mark Lunt, Rene EM Toes, Deborah PM Symmons, Leendert A Trouw, Suzanne MM Verstappen
Journal: Annals of the Rheumatic Diseases (2015)

Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years' follow-up in a cohort of patients with inflammatory polyarthritis (IP).Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA.
A phase I clinical trial of recombinant DNA gamma interferon.
Authors: T D Brown, J Koeller, K Beougher, J Golando, E M Bonnem, R J Spiegel, D D Von Hoff
Journal: Journal of Clinical Oncology (1987)

Recombinant gamma interferon (r-GIFN) demonstrates in vitro and in vivo characteristics that contrast with those of alpha and beta interferons. It has relatively weak antiviral properties, yet relatively potent immunomodulatory effects. A phase I trial was performed with r-GIFN (specific activity 2.6 X 10(6) IU/mg protein), administered as a continuous intravenous (IV) infusion over 24 hours for five days (Cl X 5) and repeated every 28 days. This schedule was chosen based on the short half-life of r-GIFN in animal systems and the in vitro augmentation of biologic effects with continuous exposure to interferons. Twenty-one patients with refractory solid tumors received 46 evaluable courses of therapy. The dose-limiting toxicities included fever, flu-like symptoms, cardiovascular toxicity, and neurotoxicity. The cardiovascular toxicity included hypotension and one episode of cardiac ischemia with chest pain. Neurotoxicity consisted of lethargy and confusion. These toxicities were reversible, and although dose-limiting, occurred sporadically throughout all dosage levels. Mild to moderately severe non-dose-limiting toxicities included nausea and vomiting, leukopenia, and liver function abnormalities. Other infrequent toxicities included hypocalcemia, diarrhea, constipation, and alopecia. The maximally tolerated dose of r-GIFN on this schedule is 0.5 X 10(6) IU/m2/d. Partial responses were seen in one patient with metastatic melanoma and in one patient with renal cell carcinoma. Toxicity and antitumor activity were seen at doses where interferon serum levels could not be detected by radioimmunoassay. In addition, the toxicity and antitumor activity seen were at much lower doses than previously described for shorter infusion schedules of other recombinant gamma interferon preparations. Differences in biologic activity of interferon preparations and/or differences in scheduling may account for this variability. Although this study defines a recommended phase II dose of r-GIFN based on the maximally tolerated dose, the optimal therapeutic index may exist at a lower dosage level.
Linkage Between Axonal Ensheathment and Basal Lamina Production by Schwann Cells
Authors: R P Bunge, M B Bunge, C F Eldridge
Journal: Annual Review of Neuroscience (1986)

The availability of several methods for the preparation of SCs free of other cell types has allowed recent experimentation providing new insights into the capacity of SCs to synthesize, release, and organize extracellular matrix materials, particularly those of the basal lamina. When these SC populations are combined in tissue culture with pure populations of neurons capable of directing SC function (without fibroblasts), new aspects of interrelationships between these cell types have come to light. In this brief chapter we review the results from this experimental approach during the last decade, and suggest the implications these observations have for interpreting known differences in SC functional expression in various body regions as well as for understanding certain disease processes. Of particular note is the discovery of an apparently essential linkage between the function of the SCs in organizing and relating to basal lamina and their ability to ensheathe and myelinate axons. It now appears that SC functional expression requires an alliance not only with the nerve fiber but also with the ECM through the production and organization of a basal lamina.
US Supreme Court to hear challenge to restrictive Texas abortion law
Authors: M. McCarthy
Journal: BMJ (2015)

The US Supreme Court announced on 13 November that it will hear a challenge to a Texas law that has imposed regulations on abortion clinics and abortion providers that opponents say effectively deny women access to abortion.

The 2013 law requires that clinics providing abortions meet facility standards similar to those required of ambulatory surgery centers and that physicians providing abortion services have admitting privileges to a hospital within 30 miles (48 km) of the clinic.

The law’s supporters say that the requirements are necessary to protect patients’ health. “The abortion industry doesn’t like these laws, because abortion clinics would be forced to spend money to meet basic health and safety standards,” said Carol Tobias, president of National Right to Life, an anti-abortion group. “For them, [the …
The T Cell Response to the Malaria Circumsporozoite Protein: An Immunological Approach to Vaccine Development
Authors: M F Good, J A Berzofsky, L H Miller
Journal: Annual Review of Immunology (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Cell-Mediated Immunity in Glomerular Disease
Authors: B H Rovin, G F Schreiner
Journal: Annual Review of Medicine (1991)

Our understanding of the role of the immune system in modulating glomerular injury continues to evolve. The participation of antibody, complement, and neutrophils alone cannot completely explain many aspects of the pathways of experimental and human glomerulonephritis. The elements of the immune system that mediate cellular immunity, T lymphocytes and monocytes, also appear to be important effectors of glomerulonephritis. An understanding of the role of cell-mediated immunity in renal disease is essential in designing therapies to interrupt immunologically sustained glomerular damage.
VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association.
Authors: D V Jackson, P J Zekan, R D Caldwell, M L Slatkoff, R W Harding, L D Case, J O Hopkins, H B Muss, F Richards, D R White
Journal: Journal of Clinical Oncology (1984)

The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.
British nurse makes "full recovery" from reactivated Ebola virus
Authors: H. Murphy
Journal: BMJ (2015)

Our objectives were to investigate the utility of the Hachinski Ischemic Score (HIS) in differentiating patients with pathologically verified Alzheimer9s disease (AD), multi-infarct dementia (MID), and "mixed" (AD plus cerebrovascular disease) dementia, and to identify the specific items of the HIS that best discriminate those dementia subtypes. Investigators from six sites participated in a meta-analysis by contributing original clinical data, HIS, and pathologic diagnoses on 312 patients with dementia (AD, 191; MID, 80; and mixed, 41). Sensitivity and specificity of the HIS were calculated based on varied cutoffs using receiver-operator characteristic curves. Logistic regression analyses were performed to compare each pair of diagnostic groups to obtain the odds ratio (OR) for each HIS item. The mean HIS (± SD) was 5.4 ± 4.5 and differed significantly among the groups (AD, 3.1 ± 2.5; MID, 10.5 ± 4.1; mixed, 7.7 ± 4.3). Receiver-operator characteristic curves showed that the best cutoff was ≤4 for AD and ≥7 for MID, as originally proposed, with a sensitivity of 89.0% and a specificity of 89.3%. For the comparison of MID versus mixed the sensitivity was 93.1% and the specificity was 17.2%, whereas for AD versus mixed the sensitivity was 83.8% and the specificity was 29.4%. HIS items distinguishing MID from AD were stepwise deterioration (OR, 6.06), fluctuating course (OR, 7.60), hypertension (OR, 4.30), history of stroke(OR, 4.30), and focal neurologic symptoms (OR, 4.40). Only stepwise deterioration (OR, 3.97) and emotional incontinence (OR, 3.39) distinguished MID from mixed, and only fluctuating course (OR, 0.20) and history of stroke(OR, 0.08) distinguished AD from mixed. Our findings suggest that the HIS performed well in the differentiation between AD and MID, the purpose for which it was originally designed, but that the clinical diagnosis of mixed dementia remains difficult. Further prospective studies of the HIS should include additional clinical and neuroimaging variables to permit objective refinement of the scale and improve its ability to identify patients with mixed dementia.
Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations
Authors: J.G. Timmerman, D. Heederik, T. Spee, F.G. van Rooy, E.J.M. Krop, G.H. Koppelman, T. Rustemeyer, L.A.M. Smit
Journal: British Journal of Dermatology (2015)

A high prevalence of contact dermatitis (CD) and respiratory symptoms has been observed in the construction industry, probably due to widespread exposure to irritants and allergens. It is unknown whether carriers of loss-of-function mutations in the gene encoding filaggrin (FLG), a known risk gene for eczema and asthma, are at increased risk.To investigate associations of FLG mutations with CD and respiratory symptoms in Dutch construction workers.A questionnaire including items on dermal and respiratory symptoms such as wheeze, shortness of breath and asthma was administered to construction workers. Total and specific serum IgE was analysed by enzyme immunoassays. Four FLG loss-of-function mutations were genotyped. CD was diagnosed by a team of a dermatologist and a clinical occupational medicine specialist using photographs of the subjects' hands and self-reported questionnaire data.Of the 506 participating workers, 6·3% carried at least one FLG mutation. Mild CD was diagnosed by the specialists in 34·0%, and severe CD in an additional 24·3%. CD was considered work related in 282 of 295 subjects (95·6%). Carriers of FLG variants had an increased risk of CD compared with subjects carrying wild-type alleles [mild CD: odds ratio (OR) 5·71, 95% confidence interval (CI) 1·63-20·06; severe CD: OR 8·26, 95% CI 2·32-29·39]. FLG variants and the presence of CD were not associated with respiratory symptoms and atopy.Contact dermatitis prevalence in construction workers is high. FLG loss-of-function mutations increase the risk of CD even further. FLG mutations were not associated with respiratory symptoms or atopy.