tbuckley/cabot-search huggingface dataset:
Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus
Authors: Noriyoshi Kuzushita, Norio Hayashi, Toyoki Moribe, Kazuhiro Katayama, Tatsuya Kanto, Sayaka Nakatani, Toshihiko Kaneshige, Tomohide Tatsumi, Akihiko Ito, Kiyoshi Mochizuki, Yutaka Sasaki, Akinori Kasahara, Masatsugu Hori
Journal: Hepatology (1998)

The human leukocyte antigen is a crucial genetic factor that initiates or regulates immune response by presenting foreign or self antigens to T lymphocytes. The aim of this study was to investigate whether HLA polymorphism is associated with the onset or progression of liver injury in chronic hepatitis C virus (HCV) infection. We determined HLA class I antigens and class II alleles in 130 hepatitis C virus (HCV)-infected patients (33 carriers with persistently normal alanine transaminase [ALT] values and 97 patients with chronic liver disease [CLD]). HLA class I (A, B) was typed serologically, and class II (DRB1, DQB1) was typed by means of polymerase chain reaction-restriction fragment length polymorphism methods. The frequencies of DRB1*0405 and DQB1*0401 were higher in HCV-infected patients than in uninfected subjects. Among HCV-infected patients, the frequencies of B54, DRB1*0405, and DQB1*0401 were significantly higher in patients with CLD than in those carriers with persistently normal ALT values, whereas DRB1*1302, DRB1*1101, and DQB1*0604 were more frequently found in carriers with persistently normal ALT values than in patients with CLD. From extended haplotype analyses, in carriers with B54-DRB1*0405-DQB1*0401 haplotype, the risk of having liver injury was 13.2 times greater than in carriers with DRB1*0405-DQB1*0401 but without B54 [ P = 0.0015, Haldane odds ratio = 13.2 (95% confidence interval, 1.7-103.8)]. In contrast, carriers with B44-DRB1*1302-DQB1*0604 had a 12.7-fold lower relative risk of developing liver injury compared to those with the haplotype containing B44 but not DRB1*1302-DQB1*0604 [ P = 0.0076, Haldane odds ratio = 0.079 (0.009-0.695)]. Our findings show that extended haplotypes including class I B54 are closely associated with the progression of liver injury, whereas extended haplotypes including class II DRB1*1302-DQB1*0604 are associated with low hepatitis activity in chronic HCV infection.
Pharmacodynamic and pharmacokinetic studies with azelastine in the guinea pig: evidence for preferential distribution into the lung
Authors: N. Chand, V. E. Adusumalli, K. Nolan, W. Diamantis, J. K. Wichmann, J. Pivonka, C. N. Langevin, K. K. Wong, N. Kucharczyk, R. D. Sofia
Journal: Allergy (1993)

The correlation between the antiasthma activity of azelastine and the concentrations of azelastine and its major metabolite, desmethylazelastine, in the blood and lung were investigated in guinea pigs. Blood and lung tissue samples collected at 15 min after aeroallergen (ovalbumin, 0.5 mg/ml, 30 s, 15 psi) challenge, i.e., 2-1/4 h after oral administration of the drug, were analyzed for azelastine and its desmethyl metabolite by specific HPLC assay. Azelastine afforded protection against immediate allergic responses (IAR, characterized by gasping and bronchospasmic convulsions). Based on the reduction of the severity of IAR, the ID50 was 0.04 mg/kg. It also delayed the onset of IAR and prevented mortalities. A positive correlation (r2 = 0.944) between the antiallergic activity and the sum concentrations of azelastine and desmethylazelastine in the lung was observed. Preferential uptake of azelastine and desmethylazelastine by the lung was demonstrated by the mean lung/blood ratio of about 22 and 146, respectively. The selective uptake of azelastine and its active metabolite by the lungs could contribute to its antiasthmatic/antiallergic activity in guinea pigs.
Nature withdraws papers describing easy way to generate stem cells
Authors: N. Hawkes
Journal: BMJ (2014)

Two papers describing a quick and easy way of generating stem cells have been retracted by Nature six months after they were hailed as groundbreaking. It turned out that what was broken were the rules of scientific evidence, Nature has conceded in an editorial,1 while arguing that outright falsification was extremely hard for editors and reviewers to detect.

The papers, from the Riken research centre in Japan, claimed that immersing mature mouse cells in a bath of weak acid shocked them back into a quasi-embryonic state with the power …
NICE and its value judgments: Option of safe “understudy” treatments should be available
Authors: Woody Caan
Journal: BMJ (2004)

EDITOR—The National Institute for Clinical Excellence (NICE) aims for the highest attainable standards of care.1 The bedrock of its advice is published evidence of benefits from treatment (mainly pharmaceuticals).

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In the report accepted in May consideration of safety issues focused on invasive surgical and diagnostic procedures, and the “judgment” on risk assumed that such risks are small and …

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TRENDS IN THE MANAGEMENT AND OUTCOMES OF CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
Authors: Sen Matsumoto, Yasuhiko Sakata, Masahiko Shimizu, Shinichirou Suna, Masaya Usami, Tatsuya Sasaki, Masami Nishino, Issei Komuro, Hiroshi Sato
Journal: Journal of the American College of Cardiology (2010)
Continuing Education in Opioid Prescribing—Reply
Authors: Lewis S. Nelson, Jeanmarie Perrone
Journal: JAMA (2012)

In Reply: We concur that the ACCME has made great strides in reducing commercial bias in medical education. The concern that we raised for independence is related to the unique CME mechanism proposed in the REMS for extended-release and long-acting (ER/LA) opioid analgesics.
Type 2 diabetes is a major drain on resources
Authors: P. Moore
Journal: BMJ (2000)

Type 2 diabetes costs Britain's NHS £2bn ($3.2bn) a year—4.7 of total NHS expenditure—and an additional £36m is spent on related social services and private health costs, claims a new report published this week.

This high cost is caused largely by the treatment of complications of the disease, as they increase the overall NHS spending for an affected patient more than fivefold.

The study, published in the TARDIS report, was conducted jointly by the British Diabetic Association, the King's Fund, the Economists Advisory Group, and SmithKline Beecham Pharmaceuticals UK. …
Effects of neural stimuli on blood flow through vasa vasorum in dogs.
Authors: D D Heistad, M L Marcus, J B Martins
Journal: Circulation Research (1979)

The purpose of this study was to determine whether neural stimuli alter blood flow through vasa vasorum in the thoracic aorta. We measured flow with microspheres in anesthetized dogs and observed responses to sympathetic stimulation and baroreceptor stimulation. During these interventions, changes in arterial pressure were prevented with propranolol or an arterial reservoir, to minimize indirect effects on vasa vasorum mediated through changes in aortic wall tension. Electrical stimulation of the stellate ganglion at 10 Hz reduced blood flow to vasa vasorum in the thoracic aorta from 11 +/- 1.6 (mean +/- SE to 6.8 +/- 1.1 ml/min per 100 g (p less than 0.05). Aortic diameter, measured with a sonomicrometer technique, did not change during sympathetic stimulation. Thus, the reduction in blood flow through vasa vasorum during sympathetic stimulation appears to be a direct effect, and not the result of constriction of the aorta and compression of vasa. To determine effects of physiological alterations in neurogenic vasoconstrictor activity, we examined responses to stimulation of carotid baroreceptors. When pressure in isolated, perfused carotid sinus baroreceptors was raised from 81 +/- 3 to 198 +/- 2 mm Hg, blood flow to vasa vasorum of the thoracic aorta increased from 3.7 +/- 0.6 to 10 +/- 2.2 ml/min per 100 g (P less than 0.05). We conclude that vasa vasorum are responsive to neural stimuli, since they constrict during sympathetic stimulation and dilate in response to baroreceptor stimulation.
Variations of ferritin levels over a period of 15 years as a compliance chelation index in thalassemic patients
Authors: Antonios Kattamis, Argyris Dinopoulos, Vassilios Ladis, Helen Berdousi, Christos Kattamis
Journal: American Journal of Hematology (2001)

Abstract We studied the changing pattern of the distribution of ferritin levels in 430 regularly‐transfused patients with thalassemia in an attempt to evaluate compliance of chelation with deferoxamine. The study covered 15 years and was divided in three periods: 1981 – 1985, 1986 – 1990, and 1991 – 1995. The patients were stratified in age‐groups. The mean ferritin levels of each period were calculated for each patient individually. The study showed that: (i) When all the patients were compared as a group, there was a significant decrease in mean ferritin between 1981 – 1985 and 1991 – 1995, despite a significant change in the patients’ mean age; (ii) When patients of same age were compared between periods, there was a decrease in mean ferritin between 1981 – 1985 and 1991 – 1995, as well as a decrease in the proportion of patients with ferritin &gt;4000 μg/L, with a parallel increase in the proportion of patients who had ferritin &lt;2000 μg/L; (iii) When the same patients were followed longitudinally, they showed a decrease in their ferritin levels in all age groups with the exception of the late adolescence period. The decrease in iron overload observed in patients on close follow up implies that compliance with chelation therapy has improved with time and therefore, a favourable influence in survival could be expected. Am. J. Hematol. 68:221–224, 2001. © 2001 Wiley‐Liss, Inc.
Psychosomatic Factors in the Process of Cancerogenesis Theoretical Models and Empirical Results
Authors: Ronald Grossarth-Maticek, Dusan T. Kanazir, Peter Schmidt, Hermann Vetter
Journal: Psychotherapy and Psychosomatics (1982)

The core of the authors' research program consists in the assumption that complex statistical interactions of sociological and psychological factors with pathophysiological and standard risk factors are more important for the early detection, prediction and prevention of cancer than one or just a few medical risk factors, e.g. the relationship between smoking and lung cancer. As the analysis of these relationships can only be done in interdisciplinary research, interpretation and discussion of social scientific, molecular biological and epidemiological aspects was attempted. In the first part we explicate a model of relevant propositions from the psychosomatic literature to explain the relationship between psychosocial factors of carcinogenesis. A discussion of the authors' research program contains additional variables and propositions. It appears to the authors that among the psychosocial and sociological factors of carcinogenesis, the molecular biological variables are especially relevant, as they form the intervening link between the social science variables and cancer. Discussion of the methodology and the sampling of the authors' empirical studies follows. Two prospective studies, carried out in Yugoslavia and West Germany, are described in detail. The data of these studies are used in the empirical analysis. In the next part the empirical results of different multivariate analyses are presented: The effects of the sociological and psychological variables on carcinogenesis are described; standard risk factors and biochemical-molecular biological factors are brought together, special attention being given to the interaction between these two groups of variables.
Effects of Cardiac Surgery with Extracorporeal Circulation on Intellectual Function in Children
Authors: VICTOR WHITMAN, DENNIS DROTAR, SALLY LAMBERT, DANIEL W. VANHEECKEREN, GORDON BORKAT, JAY ANKENEY, JEROME LIEBMAN
Journal: Circulation (1973)

The effect of extracorporeal circulation during open heart surgery on changes in intellectual function was studied in 18 children. A group of patients undergoing such surgery was compared to a control group undergoing cardiac surgery without extracorporeal circulation. The Wechsler Intelligence Scale for Children was used to evaluate the patients. No significant differences were found in either the performance IQs, verbal IQs, or full scale IQs by comparing the postoperative scores to the preoperative scores either within each group or between the groups. Extracorporeal circulation during open heart surgery does not appear to alter intellectual functioning in the pediatric age group.
Associations of Extracranial Carotid Atherosclerosis Progression With Coronary Status and Risk Factors in Patients With and Without Coronary Artery Disease
Authors: John R. Crouse, Rong Tang, Mark A. Espeland, James G. Terry, Timothy Morgan, Michele Mercuri
Journal: Circulation (2002)

Intimal medial thickness of the extracranial carotid arteries (IMT) is related to coronary artery disease (CAD) and CAD risk factors. Few studies have explored the association of risk factors with progression of IMT, and none have evaluated their associations with IMT progression specifically in patients with and without CAD.We used coronary angiography to identify 280 patients equally divided between men and women and those with either > or =50% coronary artery stenosis or no CAD. Risk factors were measured at baseline and IMT was measured at baseline and yearly for 3 years in 241 of these individuals. Baseline risk factors and CAD status were related to IMT progression. IMT of patients with CAD progressed 3 times faster than that of patients with no CAD (mean+/-SEM, 33.7+/-7.4 versus 8.9+/-7.1 microm/year; P=0.02), and CAD status and high-density lipoprotein (HDL) cholesterol were independently associated with IMT progression. Male sex, increased waist to hip ratio, cigarette smoking, increased triglycerides, and decreased HDL cholesterol were associated with increased progression in CAD patients.Patients with CAD have more rapid progression of IMT than CAD-free controls, and risk factors are related to progression in them.
Tiotropium respimat: Comparison of bronchodilator efficacy of 5 and 2.5 µg doses
Authors: Peter Calverley, Michael Könen-Bergmann, Norbert Metzdorf, Susan Bell, Jens Hohlfeld
Journal: European Respiratory Journal (2014)

Background: Safety and efficacy of tiotropium Respimat 5 µg (R5) and 2.5 µg (R2.5) doses were compared with tiotropium HandiHaler 18 μg (HH) in two recent chronic obstructive pulmonary disease (COPD) trials.

Aims and objectives: To compare bronchodilator efficacy of once-daily R5 and R2.5 and HH in TIOtropium Safety and Performance In Respimat (TIOSPIR; [NCT01126437][1])1 and the 205.458 ([NCT01222533][2])2 trials.

Methods: TIOSPIR: Randomized, double-blind (n=17,135; mean 2.3 years' follow up) trial assessing mortality and exacerbations. Included a spirometry substudy (n=1370), predefined test of noninferiority of R5 and R2.5 vs HH for trough forced expiratory volume in 1 second (FEV1), average 24-120 weeks (noninferiority margin 50 mL). 205.458: Multicentre, placebo-controlled, randomized within Respimat (1.25, 2.5, 5 µg), five-way crossover trial with 4-week treatment periods (n=154).

Results: TIOSPIR: Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285L for R5 and 1.295 L for HH (difference vs HH, -10 mL; 95% confidence interval [CI], -38 to 18 mL), and 1.258 L for R2.5 (difference vs HH, -37 mL; 95% CI, -65 to -9 mL).

205.458: R2.5, R5 and HH showed significant improvements in trough FEV1 versus placebo. Mean trough FEV1 for R5 was comparable to HH but was 27 and 41 mL lower than HH for R2.5 and R1.25, respectively.

Conclusion: In TIOSPIR, R5 was noninferior to HH for FEV1, but R2.5 was inferior to HH. Similar results were seen in the 205.458 trial and support the use of tiotropium Respimat 5μg once daily for the maintenance treatment of COPD.

TIOSPIR and 205.458 trials were funded by Boehringer Ingelheim.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01126437&atom=%2Ferj%2F44%2FSuppl_58%2FP924.atom
 [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01222533&atom=%2Ferj%2F44%2FSuppl_58%2FP924.atom
William Shakespeare: A Biography
Authors: Lester S. King
Journal: JAMA (1964)

Although Shakespeare was only incidentally concerned with medicine, nevertheless, since 1964 marks the 400th anniversary of his birth, even a medical journal might appropriately notice a new biography. A. L. Rowse, an outstanding historian of the Elizabethan era, has written a full-length biography of Shakespeare. Historical scholarship, however, does not necessarily confer the ability to write graceful prose. While sometimes Professor Rowse can hold the reader enthralled, at other times he repels with a sprawling, rambling (albeit scholarly) presentation that seems to lack discipline. The text in large part distills the biographical and historical data from the poetry itself, a process facilitated by Rowse's profound knowledge of things Elizabethan. Yet in the writing the scholar pursuing his point often overshadows the biographer, and all too often the pages smell of the lamp. Furthermore, on much of the presentation only the deeply versed Shakespearean scholar is competent to give an opinion.
CLINICAL MANAGEMENT OF URINARY RETENTION IN CHILDREN
Authors: Tracy O. Powell
Journal: JAMA (1953)

Pronounced urinary retention (megalobladder) in children is related in most cases to congenital lesions of the urogenital tract. The majority of these lesions are neuromuscular in origin. Effective treatment depends on accurate evaluation of the cause. Unless prompt and adequate urologie treatment is instituted, however, profound damage to the kidneys, with resultant shortening of the child's life, can ensue. This problem is encountered frequently in large pediatrie clinics. The present study reviews the mechanics of urinary retention, describes a plan of examination that has proved useful in determin ing the type of retention in the particular case and its cause, and discusses treatment. Although in many cases of pronounced urinary retention neurologic lesions may not be demonstrable, I am convinced the majority are of neurogenic origin. Etiological factors in neuromuscular dysfunction of the bladder in children include the following lesions. <h3>Neuromuscular Lesions.—</h3> Neuromuscular lesions may be extrinsic to the musculature of bladder (including both upper and/or lower motor neuron lesions). Such lesions may be associated with cerebral palsy, cord bladder, spina bifida with meningocele, anomalies of the spine and sacrum, poliomyelitis, arachnoiditis, and tumors.
Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers
Authors: Y Adachi, H Yamamoto, F Itoh, Y Hinoda, Y Okada, K Imai
Journal: Gut (1999)

BACKGROUND/AIM Matrilysin is one of the matrix metalloproteinases that has a critical role in tumour invasion, and is often expressed in gastrointestinal cancers. The aim of this study was to examine the role of matrilysin in metastasis of human colorectal cancers. PATIENTS (SUBJECTS)/METHODS The relation between matrilysin expression and Dukes’s type was investigated immunohistochemically in 83 surgically resected colorectal cancers, including five with liver metastasis. Moreover, the effects of matrilysin on the in vivo invasive and metastatic potential of colon cancer cells transfected with matrilysin cDNA were examined after subcutaneous injection into SCID mice. RESULTS In 46% of primary and all of metastatic liver tumours, over 10% of cancer cells were stained positively for matrilysin. The expression of matrilysin correlated significantly with the presence of nodal or distant metastases (p&lt;0.05). In addition, matrilysin transfectants formed invasive tumours and multiple liver metastases in SCID mice, without producing any significant difference in the subcutaneous tumour growth from mock transfectants. Casein zymography showed that the invading and metastasised tumours showed conspicuous matrilysin activity, which correlated with the number of metastatic lesions (p&lt;0.001). CONCLUSIONS Matrilysin showed a correlation with metastasis in a cohort of 83 colorectal cancer patients and marked metastatic potentiation in human colorectal cancer xenografts, indicating that it may play a critical role in the metastatic pathway of colorectal cancers.
Undertreatment of Medical Inpatients with Narcotic Analgesics
Authors: RICHARD M. MARKS
Journal: Annals of Internal Medicine (1973)

Structured interviews of 37 medical inpatients being treated with narcotic analgesics for pain showed that 32% of the patients were continuing to experience severe distress, despite the analgesic regimen, and another 41% were in moderate distress. Chart review suggested significant undertreatment with narcotics: meperidine in doses of 50 mg every 3 to 4 hours or less (if needed) was prescribed for 63% of the 37 patients; a dose of more than 75 mg was prescribed for only 1 patient. The average amount actually received per day by the patients was 90 mg. A questionnaire survey of 102 house staff physicians in two New York teaching hospitals showed considerable misinformation about meperidine. Many physicians underestimated the effective dose range, overestimated the duration of action, and exaggerated the dangers of addiction for medical inpatients receiving meperidine in a therapeutic dosage range. Physicians who exaggerated the dangers of addiction were more likely to prescribe lower doses of drugs, even for patients with terminal malignancy. The authors suggest that such misconceptions probably lead to undertreatment with narcotic analgesics, causing much needless suffering in medical inpatients.
New England journal endorses institute's proposals for FDA
Authors: Janice Tanne
Journal: BMJ (2006)

The United States faces a “mounting public health crisis in drug safety, and definitive action must be taken” to revitalise the Food and Drug Administration, said Jeffrey Drazen, editor of the New England Journal of Medicine in an editorial that was also signed by two of the journal's senior editors.

The FDA has been politicised, and “this trend must be stopped,” says the editorial, which was published online on 9 October (http://www.nejm.org/, doi:10.1056/NEJMe068237). The FDA's decisions about the nation's drug supply “should be based solely on scientific evidence.”

The FDA has “critical issues of …
Circulating Antinuclear and Rheumatoid Factors in Coal Miners
Authors: M. LIPPMANN
Journal: Annals of Internal Medicine (1973)

Serums from 207 coal miners were examined for the presence of rheumatoid factor and antinuclear antibodies. The population included miners with simple and complicated pneumoconiosis, miners without pneumoconiosis, and also a few subjects in whom Caplan's syndrome was suspected. Of the 156 miners with pneumoconiosis, serums from only 9 were positive for rheumatoid factor, although 34% of them had antinuclear antibodies. There was a regional variation in the prevalence of antinuclear antibodies; it was highest in the anthracite miners with complicated pneumoconiosis. A geographic association of antinuclear antibodies in coal workers' with pneumoconiosis was observed, that is, miners from those geographic regions in which the disease was most prevalent were most likely to have antinuclear antibodies. In contrast to other reports, serums from miners with complicated pneumoconiosis did not contain rheumatoid factor more often than those serums from subjects with the simple form of the disease.
Autonomic Disorders and Their Recognition
Authors: Christopher J. Mathias
Journal: New England Journal of Medicine (1997)

The autonomic nervous system, through the sympathetic and parasympathetic pathways, supplies and influences every organ in the body. It closely integrates vital processes, such as blood pressure and body temperature. Its immense capability and flexibility depend on intricate neurologic pathways, involving the action of numerous transmitters. As we approach the centennial of the use of the term “autonomic nervous system,” which was coined by Langley in 1898, we should ask whether autonomic disorders are being sufficiently considered, suitably investigated, and appropriately managed in clinical practice.Awareness is the first step in recognition. Autonomic disorders may be localized or generalized.1 The . . .