tbuckley/cabot-search huggingface dataset:
Relief of Uremic Pruritus with Ultraviolet Phototherapy
Authors: Barbara A. Gilchrest, John W. Rowe, Robert S. Brown, Theodore I. Steinman, Kenneth A. Arndt
Journal: New England Journal of Medicine (1977)

We studied the effect of ultraviolet-light phototherapy on severe persistent pruritus in 18 adult patients on hemodialysis. Patients were randomly assigned to one of two light sources. The experimental group received conventional sunburn-spectrum light in gradually increasing doses. The control group received time-matched exposures to long-wave ultraviolet light. All patients received eight exposures to the entire skin surface over a four-week treatment period. Nine of 10 patients in the sunburn-spectrum group reported marked decrease in pruritus as opposed to two of eight in the placebo group (P less than 0.01). of those responding to sunburn-spectrum light, improvement usually occurred two to three weeks into treatment. Mild sunburn, noted by some patients in this group, was the only side effect. The response to phototherapy was unaffected by the presence of secondary hyperparathyroidism. Ultraviolet phototherapy is a safe, convenient, inexpensive and effective treatment for uremic pruritus.
A Prospective Study of Past Use of Oral Contraceptive Agents and Risk of Cardiovascular Diseases
Authors: Meir J. Stampfer, Walter C. Willett, Graham A. Colditz, Frank E. Speizer, Charles H. Hennekens
Journal: New England Journal of Medicine (1988)

We evaluated the effects of past use of oral contraceptive agents on the risk of various cardiovascular diseases among women in the Nurses' Health Study cohort. We studied 119,061 women who were 30 to 55 years of age in 1976, who provided information on their use of oral contraceptives, and who at entry had had no previous coronary disease or stroke. End points were documented by medical records. During eight years of follow-up (484,096 person-years among those who had never used oral contraceptives, 415,488 among past users, and 22,376 among current users), there were 485 new cases of major coronary disease (380 nonfatal myocardial infarctions and 105 deaths from coronary disease), 282 strokes (205 nonfatal and 77 fatal), and 48 other deaths from cardiovascular causes. We found no evidence to suggest an increase in the risk of cardiovascular diseases among past users of oral contraceptives, even with prolonged previous use. After adjustment for a variety of risk factors, the relative risk of major coronary disease for women who had used oral contraceptives in the past, as compared with those who had never used such agents, was 0.8 (95 percent confidence interval, 0.6 to 1.0); of stroke, 1.0 (95 percent confidence interval, 0.7 to 1.3); and of death from all cardiovascular causes, 0.9 (95 percent confidence interval, 0.7 to 1.2). We found neither evidence of increased risk with longer use nor any trend with the amount of time since the last use. According to these prospective data, the use of oral contraceptive agents in the past does not materially raise a woman's risk of subsequent cardiovascular disease. (N Engl J Med 1988; 319:1313–7.)
Prophylaxis of<i>Rhus toxicodendron</i>Dermatitis
Authors: Robert J. Hoagland
Journal: New England Journal of Medicine (1950)

EVALUATION of the results obtained by prophylactic inoculations of poison-ivy extract is made extremely difficult by factors that cannot be controlled. Some of the variables that impair the validity of conclusions are the following: fluctuation of a person's degree of sensitivity; inconstant environment; avoidance of poison ivy, whenever possible, by sensitive persons, minimizing and making unpredictable the incidence of contact; and spontaneous seasonal (and, lately, chemically induced) changes in vegetation. In addition, some studies depend on the results of patch tests or patients' statements that they have had poison-ivy dermatitis — neither entirely reliable bases for controlled work.1 A review . . .
A Mutation in the Human Lipoprotein Lipase Gene as the Most Common Cause of Familial Chylomicronemia in French Canadians
Authors: Yuanhong Ma, Howard E. Henderson, M.R. Ven Murthy, Ghislaine Roederer, Maria V. Monsalve, Lorne A. Clarke, Thierry Normand, Pierre Julien, Claude Gagné, Marie Lambert, Jean Davignon, Paul J. Lupien, John Brunzell, Michael R. Hayden
Journal: New England Journal of Medicine (1991)

Lipoprotein lipase hydrolyzes the triglyceride core of chylomicrons and very-low-density lipoproteins and has a crucial role in regulating plasma lipoprotein levels. Deficiencies of lipoprotein lipase activity lead to aberrations in lipoprotein levels. Worldwide, the frequency of lipoprotein lipase deficiency is highest among French Canadians. We sought to determine the molecular basis of the disorder in this population.
S69 Development of an<i>in vitro</i>assay to detect chemically-induced changes in ciliary beat frequency
Authors: A Turnbull, A Shoemark, H Lund-Palau, A Bush, E Alton, J Davies
Journal: Thorax (2015)

<h3></h3> Techniques are well-established to quantify ciliary beat frequency (CBF), which is often reduced in patients with primary ciliary dyskinesia. This project aims to determine the impact of genetic polymorphisms in the T2R38 (bitter taste) receptor in response to chemical ligands, which is predicted to lead to changes in CBF, which are transient and small in magnitude. These receptors are of interest as they have been shown to ‘sense’ quorum sensing molecules produced by <i>Pseudomonas aeruginosa</i> (Pa) and may thus be disease modifiers in patients with cystic fibrosis. This work describes the development of a rapid CBF assay with sufficient sensitivity to provide a read-out of airway epithelial cell responses to stimulation <i>in vitro</i>. Air-liquid interface (ALI) cultures were obtained from surplus clinical diagnostic samples. Cells in ALI were exposed to phosphate buffered saline (PBS; negative control) and adenosine 5’-triphosphate (ATP; positive control). Experiments were conducted in temperature-controlled wells under a 40× light microscope. Cilia were imaged by high-speed video camera and CBF expressed as a ratio of stimulated/basal frequencies. CBF increased in ALI cultures exposed to ATP (n = 4) but not PBS (n = 3), in experiments at 24–25˚C; this effect was not seen at 37 ˚C. Mean ±SEM stimulated/basal CBF ratio was 1.00 ± 0.05 in the PBS-exposed cells, and 1.31 ± 0.08 in the ATP-exposed cells (p = 0.029). Inter-observer variability (n = 2) was lower than within-sample CBF variability (95% limits of agreement from -0.66 to 1.62 Hz). Intra-observer variability was good with 95% limits of agreement between -0.31 to 0.52 Hz. An assay has been developed to detect rapid changes in CBF in ALI cultures using ATP as a positive control. Further work is being undertaken to a) optimise this assay in epithelial cells in suspension, thus increasing throughput, and b) assess more relevant chemicals and culture media. Once optimised, this assay will be used to study the effects of Pa quorum sensing molecules on ciliated epithelial cells <i>in vitro</i>, from patients of varying TAS2R38 genotypes.
Soundings: Assets for the meritocracy
Authors: Trisha Greenhalgh
Journal: BMJ (1999)

In Monty Python’s transplant sketch, a man is sitting nonchalantly minding his own business when there is a loud knock at the door. Enter an officious, clipboard-carrying administrator, closely followed by several white coated technicians who are vigorously sharpening their scalpels.

“Mr B?”

“Yes, that’s me.”

“We’re from the Transplant Agency. You signed a donor card, I believe.”

“I did.”

“Well, we’ve come for your liver.”

“But I’m not dead yet.”

“It doesn’t say anything here about needing to be dead. Now if you wouldn’t mind lying down immediately on that table, sir. You see, the patient is very ill and you’re a perfect tissue match.”

And so it continues. I was reminded of this peculiarly British genre of black humour the other day, when a friend recounted a telephone call he had had from his old medical school.

“Congratulations on your recent retirement, sir. Now, may I ask you if you have made a will?”

“No I haven’t. I’ve only just turned 60.”

“Well, sir, you can never be too careful. You might like to leave a legacy to support the college’s hardship fund. May I remind you, sir, that you yourself were fortunate enough not to have to pay fees for your education? I can send you the forms today, and someone can visit you to help you fill them out.”

My friend, like most of us, owes a great deal to his old medical school. He was an inarticulate boy from a poor family whose life would have been very different without a scholarship to grammar school and a genuinely free university place. But there is surely something questionable about a fundraising strategy that targets retired doctors and asks them to choose between underwriting the education of their own grandchildren and sponsoring an unknown youngster from the rough end of town.

As we prepare to welcome a new intake of medical students, we know that those without rich parents will struggle to make ends meet with a late night bar job, a colossal bank loan, and a pathological level of mental stress. Perhaps a more reasonable contribution for a school to ask of its alumni would be to keep reminding the public and the politicians of this unacceptable and worsening reality.
Inhibition of Mediator Release in Allergic Rhinitis by Pretreatment with Topical Glucocorticosteroids
Authors: Ulf Pipkorn, David Proud, Lawrence M. Lichtenstein, Anne Kagey-Sobotka, Philip S. Norman, Robert M. Naclerio
Journal: New England Journal of Medicine (1987)

Patients with allergic rhinitis often have immediate symptoms after antigen challenge (the early-phase response), followed several hours later by a recurrence of symptoms (the late-phase response). Systemic glucocorticosteroids are known to inhibit the late-phase but not the early-phase response. We studied the effect of one week of pretreatment with topical (rather than systemic) glucocorticosteroids on the response to nasal challenge with antigen in a double-blind, randomized, placebo-controlled crossover study of 13 allergic patients who had previously had a dual response to nasal challenge. The patients were challenged with three 10-fold increments of allergen, producing an early response, and were then followed for 11 hours, encompassing the late response, before they were rechallenged with the lowest dose of allergen. We monitored their responses by means of symptom scores and measurements of the levels of histamine, tosyl-L-arginine methyl ester (TAME)-esterase activity, and kinins in nasal lavages. Topical glucocorticosteroids significantly reduced both the symptoms and the levels of histamine, TAME-esterase activity, and kinins in the early, late, and rechallenge allergic reactions. The fact that, in contrast to treatment with systemic glucocorticosteroids, prolonged pretreatment with topical glucocorticosteroids inhibited the early-phase response to antigen suggests that the route and duration of administration affect the mechanisms of action of the steroids. We conclude that inhibition of the early-phase as well as the late-phase response by topical glucocorticosteroids may provide an advantage over treatment with systemic glucocorticosteroids in patients with allergic rhinitis.
Polypoid Epithelial Tumors of the Bile Ducts
Authors: Richard B. Cattell, John W. Braasch, Fred Kahn
Journal: New England Journal of Medicine (1962)

LITTLE attention has been paid to polypoid epithelial tumors of the bile ducts in spite of their favorable prognosis, often disabling symptoms, difficulty of clinical recognition and relation to invasive carcinoma.1 Reports in the literature2 , 3 hinder their accurate appraisal because they have been included with other benign tumors of the bile duct and subdivided without clinical implication into papillomas, polyps and adenomas. Furthermore, some confusion exists about the differentiation of true papillomas in the region of the ampulla from hyperplasia of the normal papillary folds of the lining membranes.4 We consider the true polypoid tumors as a single group, and . . .
A Cohort Study of the Risk of Cervical Intraepithelial Neoplasia Grade 2 or 3 in Relation to Papillomavirus Infection
Authors: Laura A. Koutsky, King K. Holmes, Cathy W. Critchlow, Claire E. Stevens, Jorma Paavonen, Anna Marie Beckmann, Timothy A. DeRouen, Denise A. Galloway, Debra Vernon, Nancy B. Kiviat
Journal: New England Journal of Medicine (1992)

Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors.
Evaluating the Health Risks of Breast Implants: The Interplay of Medical Science, the Law, and Public Opinion
Authors: Marcia Angell
Journal: New England Journal of Medicine (1996)

This is the story of the controversy over the safety of silicone-gel–filled breast implants — a controversy that has raged in this country for nearly a decade and is still not resolved. It is a story fascinating in itself, but one particularly worth telling here because of the insights it affords into how contemporary American society deals with the problems of evaluating health risks. The breast-implant story illustrates better than almost any other event in recent times how litigation, fear, bias, and greed can interfere with scientific efforts to answer an important public health question. Perhaps most troubling of all, . . .
Miliary Calcification of the Lungs after Treated Miliary Tuberculosis
Authors: Sol Katz, James Stanton, Georges McCormick
Journal: New England Journal of Medicine (1955)

MANY authors1 2 3 4 5 reporting on disseminated pulmonary calcification have suggested that this entity represented healed miliary tuberculosis even though a history suggestive of acute miliary tuberculosis was lacking. Geever6 studied 2 patients clinically, bacteriologically and pathologically and concluded, without bacteriologic proof, that tuberculosis was the cause. On the basis of negative tuberculin tests he assumed that tuberculoallergy was spontaneously extinguished because the tuberculous infection was completely healed or because the tests were done shortly before death from ulcerative ileitis in 1 patient and leukemia in the other.Sutherland7 believed that miliary calcification of the lungs was due to an oversaturation of . . .
Assessing mucosal healing in ulcerative colitis: the simpler, the better…
Authors: Vincenzo Villanacci, Elisabetta Antonelli, Marianna Salemme, Gabrio Bassotti
Journal: Endoscopy (2015)

We read with great interest the article by Iacucci et al. on endoscopic and histological mucosal healing in ulcerative colitis [1]. The authors are to be complimented for their thorough approach, which adopted state-of-the-art technology to confirm that even in apparently macroscopically healed mucosa (the parameter on which healing evaluation in inflammatory bowel diseases usually relies), histological abnormalities are still often present. As we are persuaded that complete histological healing should be the ultimate target for assessment of the effectiveness of a given therapeutic approach in this setting [2] [3], we also believe that, apart from scientific purposes as in the Iacucci study, the daily histological assessment should be kept as simple as possible, in order to ensure the widest possible common language between pathologists and to increase reproducibility [4]. In fact, although the specific literature displays several scoring systems [2], these are usually not utilized in real life because of their subjectivity and complexity [2] [3] [5]. These concepts also apply to the study of Iacucci et al. where another, relatively complex and subjective scoring system is proposed. Although we have no doubts concerning its validity in a research setting, we are quite skeptical about its widespread use in routine clinical practice.
Routine Fogarty Thrombectomy in Arterial Catheterization
Authors: Lawrence D. Baker, Stephen J. Leshin, Virendra S. Mathur, Joseph V. Messer
Journal: New England Journal of Medicine (1968)

Routine use of the Fogarty embolectomy catheter after cardiac catheterization through a brachial arteriotomy in 25 patients was associated with a decline in major and minor complications from 28 to 4 per cent, whereas the proportion of unchanged or improved peripheral pulses increased from 55 to 80 per cent. Thrombus was found in 56 per cent, suggesting that decreased or absent arterial pulsation after cardiac catheterization, frequently attributed to "vasospasm," may result from thrombus formation with subsequent lysis. The simplicity and efficacy of the Fogarty technic in preventing this complication recommend its use whenever arterial catheterization is performed through an arteriotomy.
Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003–2010
Authors: Ami R. Zota, Cassandra A. Phillips, Susanna D. Mitro
Journal: Environmental Health Perspectives (2016)

Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food.To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the U.S.We combined data on 8,877 participants from the National Health and Nutrition Examination Survey (NHANES 2003-2010). Using 24-hr dietary recall data, we quantified: a) fast food intake [percent of total energy intake (TEI) from fast food]; b) fast food-derived fat intake (percent of TEI from fat in fast food); and c) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression.We observed evidence of a positive, dose-response relationship between fast food intake and exposure to phthalates (p-trend < 0.0001) but not BPA; participants with high consumption (≥ 34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than nonconsumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend < 0.0001). After adjusting for other food groups, ΣDEHPm was associated with grain and other intake, and DiNPm was associated with meat and grain intake.Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure reduction strategies.Zota AR, Phillips CA, Mitro SD. 2016. Recent fast food consumption and bisphenol A and phthalates exposures among the U.S. population in NHANES, 2003-2010. Environ Health Perspect 124:1521-1528; http://dx.doi.org/10.1289/ehp.1510803.
Safety results of a phase III trial evaluating ADT+ docetaxel versus ADT alone in hormone-naïve metastatic prostate cancer patients (GETUG-AFU 15/0403).
Authors: I. Latorzeff, B. Esterni, M. Habibian, G. Delplanque, C. Theodore, M. Baciuchka, J. Dauba, B. Laguerre, I. Krakowski, G. Gravis
Journal: Journal of Clinical Oncology (2010)

4681 Background: Androgen deprivation therapy (ADT) is the standard treatment of hormone naïve metastatic prostate cancer (HNMPC). We decided to initiate a phase III multicentre trial to evaluate the additional docetaxel (D) chemotherapy in these populations. Methods: Patients (pts) with HNMPC were randomly assigned to either arm A (ADT plus D: 75mg/m2 q3w, 9 cycles) or arm B (ADT alone). Primary endpoint was overall survival. Secondary endpoints included the toxicity profile of D. Results: From 10/2004 to 12/2008, 385 pts were accrued. Median age was 63 years (43-84), median PSA 26.6 ng/ml (0.1-11900), Gleason score >8: 57%. Median number of applied cycles was 9. Pts were classified according to Glass et al. risk groups as good (48%), intermediate (29%), and poor prognosis (22%). Among the 385 pts, neutropenia grade ≥ 3 was observed in 33%, febrile neutropenia: 7%. After accrual of 215 patients, 3 toxic deaths occurred in arm A, 2 due to neutropenia, 1 due to general impairment. After a safety interim analysis, the independent data monitoring committee recommended systematic use of G-CSF from day 5 to day 10 after each D administration. No subsequent toxic death was observed. Furthermore, in arm A rates of toxicity were observed: G ≧ 3 sexual dysfunction 15%, G ≧ 3 fatigue 7%, G ≧ 3 hot flushes 4%, G ≧ 3 nail changes 3%, G ≧ 3 anemia 2% and G ≧ 3 dyspnea 2%. Other toxicities with ≤1% grade ≥3 toxicity were: alopecia 54%, nausea/vomiting 35%, diarrhea 30%, sensory neuropathy 29%, mucositis 29% and peripheral oedema 29%.In arm B: hot flushes 62% (2% G≥ 3), sexual dysfunction 29% (8% G ≥ 3), anemia 22%, and fatigue 19%. Conclusions: Relative to ADT alone D chemotherapy is associated with a significant increase of toxicity. However, apart from a higher incidence of febrile neutropenia, overall toxicity was comparable to toxicity rates observed in previous studies in metastatic castration resistant prostate cancer patients. Systematic use of G-CSF is recommended in this setting. No significant financial relationships to disclose.
P235 Temocillin for Burkholderia Infection in Cystic Fibrosis – adding to Treatment Options?
Authors: S Ajab, J Marlow, K Delisle, M Walshaw, M Ledson
Journal: Thorax (2015)

<h3>Introduction</h3> Burkholderia spp infection in cystic fibrosis (CF) confers a worse prognosis, with increased morbidity and mortality. Treatment can be problematic because strains are often resistant to many of the commonly available intravenous antibiotics, leading to a search for new therapies. We have studied the use of Temocillin, a derivative of Ticarcillin with promising in-vitro activitiy against Burkholderia spp,<sup>1</sup> in the treatment of acute exacerbations in CF patients infected with Burkholderia spp. <h3>Methods</h3> We have used Temocillin in IV form, often in combination, in acute respiratory exacerbations in CF patients attending our large adult unit who are chronically infected with Burkholderia spp. We present our two year data, looking at the subspecies treated, length of treatment, improvement in clinical parameters, and co-antibiotic use. <h3>Results</h3> Nineteen courses of IV Temocillin were administered to 7 CF patients (mean age 29 years, [range 23–42 years], 2 males, 1 infected with B Cenocepacia, 6 with B Multivorans.) All patients completed their treatment without complication. Median length of Temocillin treatment was 9.7 days (range 3–16 days), and most patients finished their therapy as outpatients (mean inpatient stay 5.2 days). All patients had clinical improvement, with all gaining weight (mean 3 kg [range 6.5 to 0.9]) and most increased spirometry (mean change in FEV1% predicted 6 [17 to -3]). As regards the efficacy of co-antibiotic use, the 11 courses accompanied by Ceftazidime had a mean 3% improvement in FEV1, 8% with Meropenem (6 courses) and 9% with Colomycin (2 courses). <h3>Discussion</h3> This clinical study has shown that Temocillin is well tolerated by CF patients and is associated with clinical improvement in those infected with Burkholderia spp when given in combination with other antibiotics. Temocillin adds to the limited antibiotic armamentarium available to treat these difficult infections in CF patients and we recommend its use to other clinicians. <h3>Reference</h3> 1 Bonacorsi S, Fitoussi F, Lhopital S, Bingen E. Comparative <i>in vitro</i> activities of meropenem, imipenem, temocillin, piperacillin, and ceftazidime in combination with tobramycin, rifampin or ciprofloxacin against Burkholderia cepacia isolates from patients with cystic fibrosis.<i> Antimicrob Agents Chemother</i>. 1999;<b>43</b>:213–217