tbuckley/cabot-search huggingface dataset:
Cytochrome P450 CYP3A4/5 Expression as a Biomarker of Outcome in Osteosarcoma
Authors: Hassan R. Dhaini, Dafydd G. Thomas, Thomas J. Giordano, Timothy D. Johnson, J. Sybil Biermann, Kirsten Leu, Paul F. Hollenberg, Laurence H. Baker
Journal: Journal of Clinical Oncology (2003)

Osteosarcoma, the most common pediatric primary bone tumor, is an aggressive malignancy with a tendency for early pulmonary metastasis. A reliable biomarker to predict clinical outcome at diagnosis has not yet been identified. To date, pathological review of neoadjuvant chemotherapy-induced necrosis is the most useful determinant of which patients are likely to develop metastatic disease. There is a clinical need to identify patients who will benefit from more aggressive preoperative therapy or perhaps require less aggressive chemotherapy. More than 30 human P450 isoenzymes have been characterized, with at least nine possessing some clinical relevance. One of these, CYP3A4/5 is involved in metabolic activation and detoxification of a wide number of carcinogens and chemotherapeutic agents, including many drugs that are useful in the treatment of osteosarcomas.Osteosarcoma tissue microarray blocks containing biopsies from 18 primary tumors were used to analyze the expression of P450s 1A1/2, 1B1, 2B6, 2D6, and 3A4/5 by enzyme-linked avidin-biotin complexed immunohistochemistry. The frequencies of expression were 83%, 67%, and 83% for P450s 1A1/2, 1B1, and 3A4/5, respectively. P450s 2B6 and 2D6 were not detectable.These results were extended by developing a fluorescent-based quantitative immunocytochemistry technique to assess the levels of CYP3A4/5 in 18 paraffin-embedded primary biopsy sections. Expression of CYP3A4/5 was found to be significantly higher in primary biopsies of patients who developed distant metastatic disease compared with biopsies from patients with nonmetastatic disease (P = 0.0004).High cytochrome P450 CYP3A4/5 expression may predict metastasis and poor prognosis in osteosarcomas. Its use as a biomarker of therapeutic response will have implications for the treatment of these tumors.
New public health Research is part of the political process
Authors: N Bruce, P Flynn, J Hotchkiss, J Springett, A S Samuel, N Mays, J Connelly
Journal: BMJ (1994)

J B Sharma and colleagues raise the question of whether smoking could account for the lower bone density in women using depot medroxyprogesterone.4We agree that smoking is a potential confounder and discussed this in our earlier publication.3We are puzzled by Sharma and colleagues' reference to the two groups in our recent study.There were three groups.The control subjects certainly smoked less than the women who used depot medroxyprogesterone, but the proportion of women smoking was the same in those who continued to use depot medroxyprogesterone and those who stopped using it.Bone density increased only in those who stopped using the contraceptive.Finally, we note Sharma and colleagues' (unrefer- enced) assertion that measurements of the bone density of the femoral neck and wrist by dual energy x ray absorptiometry might be more accurate and reliable than measurements of the bone density of the spine.This is contrary to our experience and to most published data.We believe that the reason we saw greater changes in the spine than the hip is that the spine contains a larger proportion of trabecular bone and is more sensitive to oestrogen.
Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression
Authors: M Bilban, D Heintel, T Scharl, T Woelfel, M M Auer, E Porpaczy, B Kainz, A Kröber, V J Carey, M Shehata, C Zielinski, W Pickl, S Stilgenbauer, A Gaiger, O Wagner, U Jäger
Journal: Leukemia (2006)
Treatment of Acne Vulgaris with Tetracyline Hydrochloride: a Double-blind Trial with 51 Patients
Authors: P. Lane, D. M. Williamson
Journal: BMJ (1969)

Fifty-one patients with acne vulgaris were included in a double-blind trial to assess the therapeutic effect of 250 mg. tetracycline hydrochloride twice daily for three months. The results, assessed clinically and photographically, showed that tetracycline hydrochloride had a statistically significant beneficial effect. Hence, since it is cheap and rarely has side-effects in healthy young adults, its use is suggested, as well as local therapy, in the more severe forms of acne.
Prospective Randomized Comparison of Irrigated-Tip Versus Conventional-Tip Catheters for Ablation of Common Flutter
Authors: Pierre Jaïs, Dipen C. Shah, Michel Haïssaguerre, Mélèze Hocini, Stéphane Garrigue, Philippe Le Metayer, Jacques Clémenty
Journal: Circulation (2000)

Background —Radiofrequency (RF) ablation of common flutter requires the creation of a complete ablation line to produce bidirectional conduction block in the cavotricuspid isthmus. An irrigated-tip ablation catheter has been shown to be effective in patients in whom conventional ablation has failed. This randomized study compares the efficacy and safety of this catheter with those of a conventional catheter for de novo flutter ablation. Methods and Results —Cavotricuspid ablation was performed with a conventional (n=26) or an irrigated-tip catheter (n=24). RF was applied for 60 minutes with a temperature-controlled mode: 65°C to 70°C up to 70 W with a conventional catheter or 50°C up to 50 W (with a 17-mL/min saline flow rate) with the irrigated-tip catheter. The end point was the achievement of bidirectional isthmus block, and a crossover was performed after 21 unsuccessful applications. Procedural ablation parameters as well as number of applications, x-ray exposure, procedure duration, impedance rise, and clot formation were compared for each group. A coronary angiogram was performed before and after each ablation for the first 30 patients. Complete bidirectional isthmus block was achieved for all patients. Four patients crossed over from conventional to irrigated-tip catheters. The number of applications, procedure duration, and x-ray exposure were significantly higher with the conventional than with the irrigated-tip catheter: 13±10 versus 5±3 pulses, 53±41 versus 27±16 minutes, and 18±14 versus 9±6 minutes, respectively. No significant side effects occurred, and the coronary angiograms of the first 30 patients after ablation were unchanged. Conclusions —Irrigated-tip catheters were found to be more effective than and as safe as conventional catheters for flutter ablation, facilitating the rapid achievement of bidirectional isthmus block.
Physical Activity and Employment Status of Patients on Maintenance Dialysis
Authors: Robert A. Gutman, William W. Stead, Roscoe R. Robinson
Journal: New England Journal of Medicine (1981)

Existing data on the clinical outcome of maintenance dialysis for end-stage kidney disease focus mainly on the duration of life. We surveyed 18 dialysis centers to gain a broader overview of the current status of 2481 patients on dialysis, irrespective of the type or location of dialysis. The results suggest that 12 per cent of dialysis patients are diabetics and that 53 per cent are 50 years of age or older. There was considerable variation among centers in the degree of rehabilitation; nevertheless, only 60 per cent of the nondiabetic patients and 23 per cent of the diabetic patients were capable of a level of physical activity beyond that of caring for themselves. Only one quarter of the patients worked outside the home, whereas one third worked at home. These results suggest that a larger proportion of dialysis patients than previously suspected are severely debilitated. There is a need for improved data on the quality and length of life of patients on maintenance dialysis. (N Engl J Med. 1981; 304:309–13.)
FDA proposes changes in access and charges for experimental drugs
Authors: Bob Roehr
Journal: BMJ (2007)

The US Food and Drug Administration (FDA) has proposed new rules that would make experimental drugs for serious or life threatening diseases more widely available to patients who lack other therapeutic options. The draft regulations were issued on 11 December and public comments will be accepted for 90 days. 

Currently, access to experimental drugs has varied, depending on the disease and the section of the FDA with oversight of that pharmaceutical product. The proposed rules would clarify and standardise that process, explained Richard Klein of the FDA's office of special …
ON INTRACRANIAL THROMBOSIS AS THE CAUSE OF DOUBLE OPTIC NEURITIS IN CASES OF CHLOROSIS
Authors: C. O. Hawthorne
Journal: BMJ (1902)

MuMLJ1ALI INTRACRANIAL THROMBOSIS AND OPTIC NEURITIS.[FB. 8, 1 the peritoneum was present; but in the second case, a few hours before Ioperation, the patient's pulse was only ioo, there was no rise of temperature, and the tenderness and rigidity of the ahdomen were confined to the region of the appendix, and there was no distension at all.Yet the lower abdomen was full of pus.Severe nain and frequent vomiting were the prominent symptoms, but they are often very marked in well localized forms of appendicitis.When I operated there certainly was general rigidity of the belly wall, but at the time when I decided to advise operation as the safest course to adopt, e2ix hours earlier, there was not.The following is a description of my two last cases.They were both seen with Mr. F. E. Peake, and their successful termination is due to his recognition of the need for early iiuraicnal trpntmpnt.CASE I.
Case 12-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Daniel C. Shannon, Robert E. Scully, Herbert H. Schaumburg
Journal: New England Journal of Medicine (1971)

PRESENTATION OF CASEA three-day-old girl was admitted to the hospital because of tachypnea.The child was the product of a vaginal delivery after an uncomplicated, full-term gestation in a gravida-4 mother. During her first two days she fed poorly but displayed no neonatal distress, cyanosis or tachypnea. On the third day she vomited twice, and tachypnea developed. An x-ray film of the chest revealed cardiac enlargement and clear lungs, and the patient was transferred to this hospital.The parents, aged 32 and 31 years, were in good health, as were three siblings, who ranged in age from four to . . .
Self-Monitoring of Blood Glucose, Cutaneous Finger Injury, and Sensory Loss in Diabetic Patients
Authors: Jean-Pierre Le Floch, Bernard Bauduceau, Marc Lévy, Helen Mosnier-Pudar, Claude Sachon, Benedicte Kakou
Journal: Diabetes Care (2008)

To achieve glycemic targets and prevent complications of diabetes, self-monitoring of blood glucose (SMBG) is recommended three or more times daily, especially in patients treated with insulin (1). However, increasing the number of these tests may provoke unexpected adverse events (2).

The manner in which diabetic patients perform SMBG and its outcomes, including pain, finger injury, and sensory loss, were studied in 165 consecutive diabetic patients, from four French specialized centers, who were performing SMBG at least three times daily. The mean ± SD duration of diabetes was 17 ± 12 years and A1C was 8.1 ± 1.4%; 90% were …
Preventing Stroke in Sickle Cell Anemia
Authors: Orah S. Platt
Journal: New England Journal of Medicine (2005)

In the late 1930s, William Bosworth Castle and his colleague Thomas Hale Ham were studying blood samples obtained from patients with sickle cell anemia and found that the viscosity of the blood increased dramatically as its oxygen content decreased. As Castle later reflected, "It immediately occurred to us that this was because the elongated, sickled red cells had become tangled up `like haywire.'"1 Castle and Ham went on to hypothesize about the pathophysiology of organ damage in sickle cell anemia in a way that still drives much of our thinking today: "a vicious cycle of erythrostasis may be set up . . .
Beta-blockers in hypertension.
Authors: J. C. Wilkinson
Journal: BMJ (1970)

MEBURNSHenjoy.I agree with Dr. Wells that transfer- ring the patient from barbiturates to nitra- zepam is usually easily achieved.If the patient is taking much in excess of twice the hypnotic dose of barbiturates I would suggest that substitution be carried out in hospital, as the withdrawal illness can be so dangerous.I think we need to learn far more about the reasons for so many people being dependent on hypnotics.Finally, many of the barbiturate addicts need skilled followup often with long-term psychotherapy.-Iam, etc.,
Efficacy of thalidomide- or lenalidomide-based therapy in proliferative multiple myeloma
Authors: P Kapoor, S Kumar, S J Mandrekar, K M Laumann, A Dispenzieri, M Q Lacy, D Dingli, M A Gertz, R A Kyle, P R Greipp, S V Rajkumar, T E Witzig
Journal: Leukemia (2011)
Effect of an eccentric severe stenosis on fibrin(ogen) deposition on severely damaged vessel wall in arterial thrombosis. Relative contribution of fibrin(ogen) and platelets.
Authors: A Mailhac, J J Badimon, J T Fallon, A Fernández-Ortiz, B Meyer, J H Chesebro, V Fuster, L Badimon
Journal: Circulation (1994)

Coronary thrombosis is a dynamic process dependent on the pathological substrate, the local shear forces, and blood factors.We investigated the effect of a severe (80%) eccentric stenosis on fibrin(ogen) interaction with a deeply damaged vessel wall, its relation to platelet deposition in thrombus formation, and the influence of time on thrombus growth. Porcine 125I-fibrinogen and autologous 111In-platelets were injected into pigs instrumented for extracorporeal circulation and treated with low-dose heparin (aPTT ratio < 1.5) that has been previously shown and herein confirmed not to affect platelet and/or fibrin(ogen) attachment. Tunica media, as a model of severely injured vessel wall, was mounted in a tubular perfusion chamber containing an eccentric axisymmetric sinusoidal stenosis obstructing the lumen and exposed for 1, 5, and 10 minutes to perfusing blood. A shear rate of 424 s-1 at the laminar, parallel parabolic local flow perfused segments one to two orders of magnitude greater at the apex of the stenosis. Fibrin(ogen) deposition, its axial distribution with respect to the apex, and its relation to platelet deposition were determined by an ex vivo analysis of the test substrates. Fibrin(ogen) and platelet deposition were both significantly higher at the apex of the stenosis than at either the prestenotic or poststenotic area at all the studied perfusion times (P < .02). However, fibrin(ogen) deposition demonstrated a significantly smaller degree of increase from the prestenotic area to the apex as well as a smaller degree of decrease from the latter to the poststenotic region, compared with platelet deposition (P < .05). Although both fibrin(ogen) and platelet deposition increased over time, the ratio of fibrin(ogen) to platelets showed a progressive decrease that became significant from 5 to 10 minutes (P < .03) at either low or high shear rate. The rate of platelet deposition was relatively constant; however, fibrin(ogen) deposition progressively decreased, especially at the apex.On severely damaged vessel wall, fibrin(ogen) and platelet deposition is maximal at the apex of the stenosis where shear rate is extremely high and parallel streamlines are deformed. Nevertheless, fibrin(ogen) deposition is significantly less dependent on high shear rate than is platelet deposition, and the pattern is not influenced by time. Finally, fibrin(ogen) deposition appears to be predominant in the thrombus layers adjacent to a severely damaged vessel wall regardless of the local shear stress levels and flow conditions.
Ga-67 and CT Fusion Imaging of an Infected Aortic Graft
Authors: Kevin London, Robert Howman-Giles
Journal: Clinical Nuclear Medicine (2008)

A 17-year-old girl with a background of aortic coarctation repaired with insertion of a prosthetic graft presented with persisting fever and nonspecific back pain. Whole body Ga-67 scintigraphy was performed to evaluate occult infection. Intense uptake was noted in the region of the superior mediastinum. Fusing Ga-67 tomographic reconstruction with CT images allowed accurate determination of the area of enhanced uptake to be at the site of the aortic graft.
Italy drops ban on infertile couples using donated eggs or sperm
Authors: Michael Day
Journal: BMJ (2014)

Italy’s ban on infertile couples using donated eggs or sperm has been overturned by the country’s Constitutional Court.

The prohibition, which was stated in article 4 of the controversial Law 40 on assisted reproduction, has prompted thousands of Italian couples to go overseas to pay for egg or sperm donation.

“It was an outdated ban that penalised and discriminated . . . against the right to procreate, as is sanctioned …
Induction of acetylcholine receptor-specific suppression. An in vitro model of antigen-specific immunosuppression in myasthenia gravis.
Authors: S Bogen, E Mozes, S Fuchs
Journal: The Journal of Experimental Medicine (1984)

This report describes the in vivo and in vitro induction of murine (AChR)-specific suppressor T cells (Ts) and T cell factors (TsF), and the development of an appropriate assay system for their measurement. The assay described is based on the in vitro Mishell-Dutton culture system. Using this assay, it was shown that the AChR-specific helper cell is an Lyt-2- radiosensitive T cell. Moreover, the proliferating cell measured in the lymphocyte transformation assay was shown to provide AChR-specific T cell help. In vivo induction of Ts cells is achieved by injection of soluble AChR; potent AChR-specific suppression is found in the spleen 1 wk later. In vitro induction of Ts cells involves the primary education of naive splenocytes by culturing them with high concentrations of AChR. Both the in vivo- and in vitro-induced Ts cells were shown to secrete AChR-specific factors that mediate their suppressive effects. The possibility of specifically suppressing the AChR-immune response may be of a particular clinical importance since the AChR is the target autoantigen in the neuromuscular autoimmune disease myasthenia gravis.
The Histiocytic Disorders: A Pathophysiologic Analysis
Authors: JEROME E. GROOPMAN
Journal: Annals of Internal Medicine (1981)

The histiocytoses are a diverse group of disorders involving cells of the mononuclear phagocyte series. These diseases are usually characterized by proliferation and activation of macrophages caused either by external stimuli or by an intrinsic cellular abnormality. We propose that these conditions be classified as reactive histiocytosis (inciting agent known or unknown), lipid storage disorder, and mononuclear phagocyte neoplasia based on apparent cause and natural history. Recent knowledge of monocyte-macrophage development and function allows for construction of pathophysiologic models of diseases formerly approached in a descriptive fashion. Macrophage activation appears to mediate many clinical features of the histiocytic disorders, such as hemophagocytosis, fever, and osteolysis. Further understanding of the pathogenesis of the histiocytic disorders should lead to improved therapy.
Identification of the allergenic components of kiwi fruit and evaluation of their cross-reactivity with timothy and birch pollens☆, ☆☆, ★
Authors: E PASTORELLO, V PRAVETTONI, M ISPANO, L FARIOLI, R ANSALONI, F ROTONDO, C INCORVAIA, I ASMAN, A BENGTSSON, C ORTOLANI
Journal: Journal of Allergy and Clinical Immunology (1996)
HLA-Bw51 and Behçet's Disease
Authors: Shigeaki Ohno
Journal: JAMA (1978)

To the Editor.—  Regarding the association of HLA antigens with disease, we have demonstrated that Japanese patients with Behcet's disease have a significantly higher frequency of HLA-B5 than their controls. 1,2 This genetically determined association between HLA-B5 and Behcet's disease was also confirmed among the French, Jewish, Tunisian, and Turkish cases. 3 According to the epidemiologic survey, this disease is known to occur most frequently among the Japanese and Mediterranean populations, where the frequency of HLA-B5 is equally high.  Recently it has been shown that HLA-B5 antigen is of a heterogeneous nature and may be divided into at least two subcomponents, HLA-Bw51 and HLA-Bw52. Since HLA-Bw52 is frequent almost equally to the counterpart among the Japanese but rather rare among whites, we suspected that the close association of HLA-B5 and Behcet's disease may be due to that of HLA-Bw52 and this disease. Twelve male and 11 female patients with this
Strokes and the pill.
Authors: J. E. Cosnett
Journal: BMJ (1969)

MEDICBrOURNALThe Table shows two groups of patients:(1) Those with mesenteric adenitis who have evidence of recent appendicitis-that is, are iron-positive-in whom appendicectomy coin- cides with cure in 24 of 25 cases (96%).This approximates closely to the cure rate of 98 % which I have described for removal of acutely inflamed appendices.4 (2) Thcee who have no evidence of recent appendicitis-that is, are iron-negative-in whom appendicectomy co- incides with cure in only 9 of 15 cases (60%).This is well below the cure rate of 86% norm- ally associated with emergency removal of a normal appendix.'
A new era for blood pressure management
Authors: F. Godlee
Journal: BMJ (2009)

This week we publish two studies that, taken together, may herald a new era of blood pressure management. So say our editorialists Richard McManus and Jonathan Mant (doi:10.1136/bmj.b940). The studies challenge the current orthodoxy, which is still that antihypertensive treatment should be titrated against regular blood pressure measurements. If acted on, these studies will simplify how we manage cardiovascular risk, with antihypertensive treatment being offered regardless of blood pressure, with less frequent blood pressure monitoring, and with checking for adverse events as the main focus of medical care.

The first paper, by Malcolm Law and colleagues, represents an enormous amount of work (doi:10.1136/bmj.b1665 …
Prescribing of Tetracycline to Children Less Than 8 Years Old
Authors: Wayne A. Ray
Journal: JAMA (1977)

The committee on Drugs of the American Academy of Pediatrics finds virtually no indications for administering tetracyclines to children less than 8 years old. This study analyzes tetracycline prescribing to ambulatory children less than 8 years of age in the Tennessee Medicaid program during a two-year period. Of the nearly 59,000 children in the study, 4,026 (7%) received 7,046 tetracycline prescriptions. Twenty-seven percent (527) of 1,947 participating physicians prescribed tetracycline; 26 physicians (5%) wrote 54% of the prescriptions for 45% of the children. Physicians in family practice prescribed the greatest quantity of tetracycline. Surgeons and internists prescribed more tetracycline to young children than did pediatricians. Rural location of practice was independently associated with increased tetracycline prescribing for all specialties. Recent graduates from medical school were less apt to prescribe tetracycline than were earlier graduates.