tbuckley/cabot-search huggingface dataset:
Itraconazole treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis
Authors: M Skov, N Høiby, C Koch
Journal: Allergy (2002)

Background: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is a potentially fatal inflammatory disease due to the dual‐type immune response provoked by the fungal antigens. Despite serious side effects long‐term treatment with corticosteroids is often required. Itraconazole has been reported to be a useful steroid‐sparing agent. Methods: In a retrospective follow‐up of 21 CF patients from a total of 250 treated once or twice within a five‐year study period (1994–98), 9 patients were treated with systemic glucocorticosteroids in combination with itraconazole and 12 patients were treated with itraconazole (200–600 mg/day) as monotherapy. Results: During treatment the percentage of Aspergillus fumigatus (AF)‐positive sputum cultures significantly reduced ( P &lt; 0.05); precipitating antibodies to AF decreased significantly in all patients ( P &lt; 0.05); forced expiratory volume (FEV 1) increased to pre‐exacerbation level; total IgE levels decreased in 42% of patients on monotherapy and in 56% on combination therapy. Specific IgE (radioallergosorbant; RAST) level decreased in 6 of 21 patients. Eleven patients had transient increased levels of alanine transaminase (ALAT). One patient had isolated increase in alkaline phosphatase and another in aspartate transaminase (ASAT). Conclusions: High dose itraconazole as monotherapy or in combination with systemic glucocorticosteroids seems effective in CF patients with ABPA. No hepatotoxicity was observed during long‐term therapy.
Growth hormone: uses and abuses
Authors: Raymond L Hintz
Journal: BMJ (2004)

It has anabolic effects, but its use in ageing and other conditions is not established 

The therapeutic use of human growth hormone was first shown 45 years ago.1 In these years the number of approved and proposed uses of human growth hormone has grown from one to more than a dozen, and the number of patients being treated with it has increased from a handful to tens of thousands worldwide. The officially approved uses of human growth hormone vary from country to country, but it is commonly used for children with growth hormone deficiency or insufficiency, poor growth due to renal failure, Turner syndrome (girls with a missing or defective X chromosome), Prader-Willi syndrome (usually due to uniparental disomy in chromosome 15), and children born small for gestational age with poor growth past 2 years of age (table). Recently the Food and Drug Administration in the United States has also approved the use of human growth hormone …
Radiofrequency ablation in patients with hepatocellular carcinoma
Authors: Florence Aslinia, Ayse L. Mindikoglu
Journal: Hepatology (2009)

We read with interest the article by N'Kontchou et al.1 The authors concluded that radiofrequency ablation (RFA) appeared to be a safe and effective treatment in patients with early-stage hepatocellular carcinoma (HCC) up to 5 cm in diameter.1 We write regarding several concerns. First, start dates that allow measurement of intervals between treatment and death or the last or most recent follow-up visits were not defined.1 Second, the authors reported that 50% of patients had cirrhosis secondary to chronic hepatitis C (HCV) infection.1 Previous reports indicate that more than 30% of patients with alcoholic liver disease are infected with HCV.2, 3 The authors commented on the good outcome of patients with HCV who underwent HCV eradication in addition to RFA for treatment of HCC.1 Given the overlap between alcoholic liver disease and chronic HCV, it is important to report the proportion of patients who had both HCV and alcohol-associated cirrhosis as well as the proportion of patients who achieved sustained virologic response among the overlap cases. Third, over the course of the study, RFA was performed using three types of electrodes (Cool Tip, HIIT, and Prosurge).1 Inclusion of the electrode type as a predictor of overall, recurrence-free, and tumor-free survival in multivariate analysis would be informative. Finally, although data on survival after RFA were informative, the study lacked a control group that were undergoing alternative treatment (e.g., chemoembolization).1 There is need for case-control studies to evaluate further the use of RFA as a down-staging intervention in similar patients. Florence Aslinia M.D.*, Ayse L. Mindikoglu M.D., M.P.H.*, * Department of Medicine, Division of Gastroenterology, and Hepatology, University of Maryland School of Medicine, Baltimore, MD.
The phosphorylation targets of p47phox, a subunit of the respiratory burst oxidase. Functions of the individual target serines as evaluated by site-directed mutagenesis.
Authors: L R Faust, J el Benna, B M Babior, S J Chanock
Journal: Journal of Clinical Investigation (1995)

The respiratory burst oxidase of phagocytes and B lymphocytes catalyzes the reduction of oxygen to O2- at the expense of NADPH. Dormant in resting cells, the oxidase is activated by exposing the cells to appropriate stimuli. During activation, p47phox, a cytosolic oxidase subunit, becomes extensively phosphorylated on a number of serines located between S303 and S379. To determine whether this phosphorylation is necessary for oxidase activation, we examined phorbol-elicited oxidase activity in EBV-transformed B lymphoblasts deficient in p47phox after transfection with plasmids expressing various S-->A mutants of p47phox. The mutant containing S-->A mutations involving all serines between S303 and S379 [S(303-379)A] was not phosphorylated, did not translocate to plasma membrane during activation and was almost devoid of function. As to individual serines, S379 was of special interest because (a) p47 phox S379 was phosphorylated in phorbol-activated lymphoblasts expressing wild-type p47phox, and (b) p47phox S379A failed to translocate to the membrane, and was as functionless as p47phox S(303-379)A; other single S-->A mutations had little effect on oxidase activity. These findings suggest that the phosphorylation of S379 may be important for oxidase activation in whole cells.
A BRIEF NOTE ON THE PATHOLOGY, DIAGNOSIS AND TREATMENT OF NASAL ACCESSORY-SINUS AFFECTIONS.
Authors: E. LARUE VANSANT
Journal: JAMA (1901)

It is now generally recognized that affections of the nasal accessory sinuses are more common than they were formerly supposed to be. Many physicians still hold the opinion, however, that neither their frequency nor import are as yet fully appreciated. By careful examination many a case of supposed rhinitis will be found to be associated with, and dependent upon, a chronic, or acute, sinusitis. This is particularly the case in the condition known as purulent rhinitis in children, where the sinusitis is the rule rather than the exception. Moreover, the proper treatment of the sinus disease will result in great amelioration, if not complete cure, of the so-called purulent rhinitis. If it be true that a chronic purulent rhinitis is due to, and maintained by, a chronic sinusitis, and if we accept the view that atrophic rhinitis is a sequel of chronic purulent rhinitis, then it is evident that we
French health minister announces reform of drug regulation
Authors: P. Benkimoun
Journal: BMJ (2011)

The 88 year old founder of France’s second largest drug company, Laboratoires Servier, has been subpoenaed by lawyers acting for six patients who experienced serious cardiovascular side effects after being treated with the diabetes drug benfluorex (Mediator).

The drug, which was mainly prescribed as an appetite suppressant in patients with type 2 diabetes, has been linked to around 500 deaths (BMJ 2010;341:c6882; doi: 10.1136/bmj.c6882). The delay in banning the drug in France is set to be one of the biggest medical scandals of recent years.

French health minister Xavier Bertrand has announced that he will radically reform the way that drugs are regulated in France.

He said he favoured granting a marketing authorisation only to drugs which showed they are “at least equivalent to …
Dysregulation of Airway Cytokine Expression in Chronic Obstructive Pulmonary Disease and Asthma
Authors: Jeffrey D. Hasday, Kimberly A. McCrea, Susan S. Meltzer, Eugene R. Bleeker
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Cigarette smoking is the major factor responsible for chronic obstructive pulmonary disease (COPD). COPD occurs in a minority of smokers, but the host factors that modify risk of disease have not been clearly elucidated. There is significant clinical and histopathologic overlap between COPD and asthma, including the accumulation and activation of airway inflammatory cells. These two disorders are compared and contrasted. Abnormal airway inflammatory cytokine expression in these disorders is discussed.
Psychotherapy of Childhood Anxiety Disorders: A Meta-Analysis
Authors: Tina In-Albon, Silvia Schneider
Journal: Psychotherapy and Psychosomatics (2006)

&lt;i&gt;Background:&lt;/i&gt; The present study compared the efficacy of psychotherapy for childhood anxiety disorders (excluding trials solely treating post-traumatic stress disorder or obsessive-compulsive disorder). &lt;i&gt;Methods:&lt;/i&gt; The meta-analysis included studies that met the basic CONSORT (consolidated standards of reporting trials) criteria. Several outcome variables (e.g. effect sizes, percentage of recovery) were analyzed using completer and intent-to-treat analyses during post-treatment and follow-up assessment. Twenty-four studies published by March 2005 were included in this meta-analysis. &lt;i&gt;Results:&lt;/i&gt; In all the included studies, the active treatment condition was cognitive-behavioral. The overall mean effect of treatment was 0.86. No differences in outcome were found between individual and group treatments or child- and family-focused treatments. Follow-up data demonstrated that treatment gains were maintained up to several years after treatment. &lt;i&gt;Conclusions&lt;/i&gt;: These findings provide evidence that anxiety disorders in children can be treated efficaciously. The gathered data support the clinical utility of cognitive-behavioral therapy in this regard. Randomized controlled trial studies investigating treatments other than cognitive-behavioral therapy are missing.
Comments on the psychosocial aspects of the International Conference on Radiation and Health.
Authors: J Cwikel
Journal: Environmental Health Perspectives (1997)

Summary comments on the psychosocial aspects of the International Conference on Radiation and Health highlighted the issues that were salient in the conference. There was a broad consensus that long-term psychosocial effects may turn out to be the most significant source of morbidity. In addressing health concerns there is a need to consider psychological responses, as they may be the source of the high rate of morbidity and use of health services. The public's response to radiation is one of anxiety, fear, and concerns about lack of control over modern technology. Aside from stress there may be alternative mechanisms that explain the high rates of morbidity, such as direct biological effects of radiation on the cardiovascular system. The issue of social stigma is not addressed in most studies of affected populations but may be a potent social force. There is a need for concerned scientists to reach a better consensus about the health effects of radiation and to communicate effectively with the lay public. We need more cross-cultural research on psychosocial aspects and how to more effectively help affected populations. There are auspicious beginnings in this direction.
Nocturnal ambulatory blood pressure measurement
Authors: A Shennan, M De Swiet, A Halligan
Journal: BMJ (1994)

EDITOR, - We disagree that the findings of R J O Davies and colleagues should be taken into account as part of clinical and epidemiological interpretation.1

The authors assume that the “aroused” ambulatory blood pressure is less accurate than the true physiological pressure. This is self evident but has no clinical relevance, as physiological pressure can never …
Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer: A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study
Authors: Aimée R. Kreimer, Paul Brennan, Krystle A. Lang Kuhs, Tim Waterboer, Gary Clifford, Silvia Franceschi, Angelika Michel, Martina Willhauck-Fleckenstein, Elio Riboli, Xavier Castellsagué, Allan Hildesheim, Renée Turzanski Fortner, Rudolf Kaaks, Domenico Palli, Ingrid Ljuslinder, Salvatore Panico, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Sylvie Mesrine, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Petra H. Peeters, Amanda J. Cross, H. Bas Bueno-de-Mesquita, Paolo Vineis, Nerea Larrañaga, Valeria Pala, María-José Sánchez, Carmen Navarro, Aurelio Barricarte, Rosario Tumino, Kay-Tee Khaw, Nicholas Wareham, Heiner Boeing, Annika Steffen, Ruth C. Travis, J. Ramón Quirós, Elisabete Weiderpass, Michael Pawlita, Mattias Johansson
Journal: Journal of Clinical Oncology (2015)

Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non–type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.
Abstract 575: Cdk1 prevents DNA rereplication in G2/M by phosphorylating and facilitating the removal of Cdc7 from chromatin at the end of S phase.
Authors: James Knockleby, Byung Ju Kim, Hoyun Lee
Journal: Cancer Research (2013)

Abstract Cancer is inextricably linked with aneuploidy. Aneuploidy can arise for a number of reasons, including the deregulation of DNA and centrosome replication. Mechanisms have evolved that are designed to ensure that DNA is replicated only once per cell cycle. The initiation of DNA replication is a key target of these mechanisms, which includes regulating Cdc6, Cdt1 and Cyclin dependent kinases (Cdks). Although the regulatory mechanisms of Cdc6 and Cdt1 are known, the role of Cdk1 in particular is less clear. One potential target for Cdk1 regulation is the Dbf4-Cdc7 kinase (DDK), which acts as a licensing factor for DNA replication. DDK performs an essential and critical step in initiating DNA replication. As such, it is a target for novel cancer therapeutic drugs currently in clinical trials. Even so, the regulatory mechanisms dictating DDK function in human cells remains poorly understood. A site-directed mutagenesis approach was undertaken to determine the in vivo function of Cdk-dependent phosphorylation sites on the primary Cdc7 sequence. Using over-expressed Cdc7 in human cells (HEK293T), the functional significance of Cdc7 phosphorylation was determined; both the lack of phosphorylation and constitutive phosphorylation of Cdc7 was analyzed. We found that Cdc7, the catalytic subunit of the DDK, is a target of Cdk1. Cdc7 is phosphorylated in G2/M phase by Cdk1. Phosphorylation of Cdc7 removes the catalytic subunit of DDK from origins of replication and chromatin with the assistance of the nuclear export factor CRM1, which relocates Cdc7 to the microtubule cytoskeleton. Finally, the Cdk1-dependent removal of Cdc7 from chromatin prevents the cell from initiating DNA replication, indicating that Cdc7 is a target of Cdk1-dependent inhibition of DNA re-replication. We conclude that (1) Cdk1 phosphorylates Cdc7 in vivo. (2) Cdk1 dependent phosphorylation of Cdc7 regulates chromatin binding and DNA replication and (3) pCdc7 is associated with the nuclear export factor CRM1 in G2/M phase, suggesting a mechanism that couples the down-regulation of Cdc7 function at the end of S phase through nuclear localization and chromatin association. Taken together, our data provides key insight into the functional understanding of DDK. Citation Format: James Knockleby, Byung Ju Kim, Hoyun Lee. Cdk1 prevents DNA rereplication in G2/M by phosphorylating and facilitating the removal of Cdc7 from chromatin at the end of S phase. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 575. doi:10.1158/1538-7445.AM2013-575
Psychiatric Evaluations and Mitigating Circumstances in Capital-Punishment Sentencing
Authors: William J. Curran
Journal: New England Journal of Medicine (1982)

The Supreme Court of the United States has instructed the state courts and legislatures that they must not be "arbitrary and capricious" in applying the death penalty in capital cases. This instruction was part of the background when in 1972 the Court struck down existing statutes permitting the death penalty, as cruel and unusual punishment, in the landmark decision of Furman vs. Georgia.1 In response, some states have enacted mandatory death penalties for specified crimes, allowing little or no discretion in the application of the law. The Supreme Court did not agree with this solution. In Lockett vs. Ohio . . .
Pharmacologic treatment of portal hypertension contributes to preventcommunity-acquired spontaneous bacterial peritonitis (SBP)
Authors: B. González Suárez, C. Guarner, J. Miñana, J. Sola-Vera, A. Gallego, C. Gómez, J.M. Dedéu, M. Sàbat, C. Villanueva, G. Soriano, J. Balanzó
Journal: Journal of Hepatology (2000)
BRITISH LIBRARIES SUFFER LOSSES
Authors: Florence A. Cooksley
Journal: JAMA (1941)

To the Editor:—  A new Aid to Britain has been established by the Medical Library Association. Letters were sent a few months ago to the medical libraries of England and Scotland asking how much damage had been suffered to their books. The Medical Library Association has offered to restore these losses as far as possible from duplicate books and journals in the American medical libraries.  The British librarians are responding enthusiastically, saying that such an understanding of their difficulties and the desire to cooperate in rehabilitating libraries that have suffered damage through enemy action make the burden easier to bear. Most of the libraries succeeded in moving their books to safer areas before the bombing reached their buildings. However, they have suffered considerable loss of recent journals through sinking of vessels enroute to England. Shipments of November issues of American journals seem to have been particularly unfortunate.  The medical library
Anticytoskeletal autoantibody to microfilament anchorage sites recognizes novel focal contact proteins.
Authors: J L Senécal, S Fortin, A Roussin, F Joyal
Journal: Journal of Clinical Investigation (1987)

Actin microfilaments are anchored to the plasma membrane at focal contacts. Using an indirect immunofluorescence method, we detected an autoantibody reactive with focal contacts in PtK2, HEp-2, and BHK-21 cells in serum from two patients with early systemic sclerosis. With double immunofluorescence, using the actin-binding drug phalloidin, we localized the plaques decorated by these sera specifically at the termini of microfilament bundles. The reactive antigens were identified by immunoblotting as proteins of 80,000- and 75,300-mol wt in PtK2, and of 53,500-mol wt in HEp-2 and BHK-21 cells. The 53,500-mol wt protein was also identified in rat skeletal, myocardial, and smooth muscle tissues. The detergent solubility of these proteins suggested that they may be linked to the plasma membrane. The autoantigens were immunologically distinct from vinculin and alpha-actinin, two major proteins also known to be concentrated at the ends of microfilament bundles. Our observations suggest that this novel anticytoskeletal autoantibody may identify a novel family of vertebrate cell proteins involved in the linkage of microfilaments to the plasma membrane at focal contacts.
Vaccines protect monkeys against Marburg and Ebola viruses
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Canadian and US scientists have developed safe and effective vaccines that completely protect non-human primates against the often lethal Marburg and Ebola haemorrhagic fever viruses. “They have high potential for use in humans,” said Steven Jones of the National Microbiology Laboratory of the Public Health Agency of Canada in Winnipeg. The study was published online in Nature Medicine on 5 June 2005 (www.nature.com/naturemedicine, doi: 10.1038/nm1258).
Surgeon Volume vs Hospital Volume: Which Matters More?-Reply
Authors: Edward L. Hannan
Journal: JAMA (1990)

<h3>In Reply.—</h3> The letters regarding our article cover five main points: (1) the potential dangers of directing patients toward higher-volume surgeons and hospitals, (2) the absence of board certification as an explanatory variable, (3) the fact that lower-volume providers operated on higher-risk patients on average, (4) the failure to take into account whether aneurysms were ruptured and whether patients with ruptured aneurysms were stabilized at a low-volume hospital prior to admission to a high-volume hospital, and (5) "picking one variable and assigning it a cause-and-effect relationship in... a cavalier way." These five points are addressed in order. There are certainly potential dangers in directing patients to assembly line clinics that emphasize the volume of patients treated rather than the quality of care. However, the cases in this study are all inpatients who were operated on in hospitals with fairly low volumes by surgeons with surprisingly low volumes of the procedures
Diet-heart disease hypothesis is wishful thinking
Authors: U. Ravnskov
Journal: BMJ (2002)

EDITOR—Mann et al and Hu et al list several shortcomings in the trials reviewed by Hooper et al that explain why dietary treatments for patients with coronary heart disease were ineffective.1–3 Inferior studies with negative results are prevalent, but where is the positive evidence that justifies the dietary recommendations?

Mann et al point to the improved outcome in the subgroup analysis of the five prolonged trials. But in that analysis Hooper et al excluded the Sydney diet-heart study, where total mortality was significantly increased, …
Immunotherapy with Transfer Factor
Authors: H. Sherwood Lawrence
Journal: New England Journal of Medicine (1972)

IT is one of life's little ironies that certain investigative findings are destined to appear initially somewhat exotic or obscure only to have the principle resurface after a variable eclipse and provide lucid insights into the cause of disease or a potent means of restoring health. This has been the recent fate of transfer factor in its successful application to the immunotherapy of a variety of infectious and immunodeficiency diseases.1 , 2 The report by Bullock, Fields and Brandriss on leprosy elsewhere in this issue of the Journal provides an example of this principle. Their carefully controlled evaluation of the potential use . . .