tbuckley/cabot-search huggingface dataset:
Developmental Pharmacology — Drug Disposition, Action, and Therapy in Infants and Children
Authors: Gregory L. Kearns, Susan M. Abdel-Rahman, Sarah W. Alander, Douglas L. Blowey, J. Steven Leeder, Ralph E. Kauffman
Journal: New England Journal of Medicine (2003)

For those using drugs to treat infants and children, the integration of developmental pharmacology is crucial to appropriate clinical practice. Changes in metabolic capacity, distribution sites, and organ function all affect the way in which medications are handled in the very young. This review examines the developmental changes that profoundly affect the responses of children to medications and related therapies.
Planning and Managing New and Complex Medical and Surgical Procedures
Authors: John M. Long
Journal: JAMA (1966)

Traditionally, the only problems involved with medical and surgical procedures have been those more or less directly related to medicine. With the recent development of rather complex procedures such as organ transplants, another type of problem has arisen, namely, the planning and management of the procedure. We believe that the planning and management problem will increase and become a limiting factor in the development of more complex procedures. Computerized planning and management techniques are available to assist in the problem. Among these techniques is a procedure known originally as the critical path method (CPM).<sup>1</sup>Another, similar technique was later devised which is somewhat more elaborate known as the program evaluation and review technique (PERT).<sup>2</sup>The authors have attempted to evaluate these programs to see if they would be useful in the planning and managing of new and complex surgical procedures. In order to do this, we have applied
Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
Authors: Jörg Ederle, Joanna Dobson, Roland L Featherstone, Leo H Bonati, H Bart van der Worp, Gert J de Borst, T Hauw Lo, Peter Gaines, Paul J Dorman, Sumaira Macdonald, Philippe A Lyrer, Johanna M Hendriks, Charles McCollum, Paul J Nederkoorn, Martin M Brown
Journal: The Lancet (2010)
Effect of Very Small Tumor Size on Cancer-Specific Mortality in Node-Positive Breast Cancer
Authors: Jennifer Y. Wo, Kun Chen, Bridget A. Neville, Nancy U. Lin, Rinaa S. Punglia
Journal: Journal of Clinical Oncology (2011)

Traditionally, larger tumor size and increasing lymph node (LN) involvement have been considered independent predictors of increased breast cancer-specific mortality (BCSM). We sought to characterize the interaction between tumor size and LN involvement in determination of BCSM. In particular, we evaluated whether very small tumor size may predict for increased BCSM relative to larger tumors in patients with extensive LN involvement.Using Surveillance, Epidemiology and End Results registry data, we identified 50,949 female patients diagnosed between 1990 and 2002 with nonmetastatic T1/T2 invasive breast cancer treated with surgery and axillary LN dissection. Primary study variables were tumor size, degree of LN involvement, and their corresponding interaction term. Kaplan-Meier methods, adjusted Cox proportional hazards models with interaction terms, and a linear trend test across nodal categories were performed.Median follow-up was 99 months. In multivariable analysis, there was significant interaction between tumor size and LN involvement (P < .001). Using T1aN0 as reference, T1aN2+ conferred significantly higher BCSM compared with T1bN2+ (hazard ratio [HR], 20.66 v 12.53; P = .02). A similar pattern was seen among estrogen receptor (ER) -negative patients with T1aN2+ compared with T1bN2+ (HR, 24.16 v 12.67; P = .03), but not ER-positive patients (P = .52). The effect of very small tumor size on BCSM was intermediate among N1 cancers, between that of N0 and N2+ cancers.Very small tumors with four positive LNs may predict for higher BCSM compared with larger tumors. In extensive node-positive disease, very small tumor size may be a surrogate for biologically aggressive disease. These results should be validated in future database studies.
Assessment of the reproducibility of the lactulose H2 breath test as a measure of mouth to caecum transit time.
Authors: S J La Brooy, P J Male, A K Beavis, J J Misiewicz
Journal: Gut (1983)

The lactulose H2 breath test is in use as a simple non-invasive measurement of mouth to caecum transit time, but its reproducibility has never been assessed. We have examined the reproducibility of mouth to caecum transit time in 21 normal subjects using lactulose 10, 15, and 20 g; seven subjects being studied with 10 g and 12 each with 15 and 20 g doses. Transit time decreased with increasing doses of lactulose although the differences were not significant between or within (n = 5) individuals. Variation in transit times between individuals was considerable with all doses of lactulose (mean coefficient of variation of 18.5, 29.7 and 28.3% with 10, 15, and 20 g respectively). The addition of lactulose to a liquid meal containing carbohydrate, fat, and protein decreased the coefficient of variation to less than 10% in four subjects studied. The lactulose H2 breath test could be made more reproducible by including a liquid meal.
Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells.
Authors: M Pinzani, L Gesualdo, G M Sabbah, H E Abboud
Journal: Journal of Clinical Investigation (1989)

In vitro and in vivo studies suggest that liver fat-storing cells (FSC) may play an important role in the development of liver fibrosis. We explored the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and TGF-beta, and basic fibroblast growth factor (bFGF) on DNA synthesis and growth of rat liver FSC. PDGF, EGF, TGF-alpha, and bFGF induced a dose-dependent increase in DNA synthesis with a peak effect at 24 h. PDGF produced the most striking effect with a maximum 18-fold increase over control. EGF, TGF-alpha, and bFGF elicited a maximum three- to fourfold increase in DNA synthesis. Analysis of growth curves revealed a similar pattern of potency of the growth factors. TGF-beta did not affect DNA synthesis of FSC; however, TGF-beta markedly potentiated the stimulatory effects of both EGF and PDGF. FSC showed high specific binding of 125I-PDGF and Scatchard analysis revealed high affinity receptors with an apparent Kd of 2.3 x 10(-10) M. Our data suggest that PDGF is a key mitogen for FSC and that the coordinate release of other growth factors together with PDGF by inflammatory cells represents a potent potential stimulus for FSC proliferation in conditions of chronic self-perpetuating liver inflammation.
New Epidemiologic Evidence Confirming That Bias Does Not Explain the Aspirin/Reye's Syndrome Association
Authors: Brian W. Forsyth
Journal: JAMA (1989)

To determine the validity of the aspirin/Reye's syndrome association, we developed an epidemiologic investigation to assess the effects of five potential sources of bias. A case-control study incorporated procedures to avoid temporal precedence and susceptibility bias. These included classifying cases as having monophasic or biphasic patterns of illness and matching for severity of symptoms at zero-time. To evaluate the effect of a potential recall bias, an "alternate-condition" control group was enrolled. A medical record review study was conducted to assess the potential for diagnostic bias, and a blanket surveillance of all hospitals in a region was conducted to evaluate reporting bias. Twenty-four case subjects and 48 matched controls were enrolled. Eight-eight percent of case subjects and only 17% of controls had received aspirin prior to the onset of Reye's syndrome (matched odds ratio, 35; 95% confidence interval, 4.2 to 288). Further analyses demonstrated that the association could not be attributed to the five potential sources of bias.
Chloride conductance and genetic background modulate the cystic fibrosis phenotype of ΔF508 homozygous twins and siblings
Authors: Inez Bronsveld, Frauke Mekus, Jan Bijman, Manfred Ballmann, Hugo R. de Jonge, Ulrike Laabs, Dicky J. Halley, Helmut Ellemunter, Gianni Mastella, Stephen Thomas, Henk J. Veeze, Burkhard Tümmler
Journal: Journal of Clinical Investigation (2001)

To investigate the impact of chloride (Cl–) permeability, mediated by residual activity of the cystic fibrosis transmembrane conductance regulator (CFTR) or by other Cl– channels, on the manifestations of cystic fibrosis (CF), we determined Cl– transport properties of the respiratory and intestinal tracts in ΔF508 homozygous twins and siblings. In the majority of patients, cAMP and/or Ca2+-regulated Cl– conductance was detected in the airways and intestine. Our finding of cAMP-mediated Cl– conductance suggests that, in vivo, at least some ΔF508 CFTR can reach the plasma membrane and affect Cl– permeability. In respiratory tissue, the expression of basal CFTR-mediated Cl– conductance, demonstrated by 30% of ΔF508 homozygotes, was identified as a positive predictor of milder CF disease. In intestinal tissue, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid–insensitive (DIDS-insensitive) Cl– secretion, which is indicative of functional CFTR channels, correlated with a milder phenotype, whereas DIDS-sensitive Cl– secretion was observed mainly in more severely affected patients. The more concordant Cl– secretory patterns within monozygous twins compared with dizygous pairs imply that genes other than CFTR significantly influence the manifestation of the basic defect.
Diabetic Patients’ Medication Underuse, Illness Outcomes, and Beliefs About Antihyperglycemic and Antihypertensive Treatments
Authors: James E. Aikens, John D. Piette
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to determine how patients’ beliefs about antihyperglycemic and antihypertensive medications relate to medication underuse and health status. RESEARCH DESIGN AND METHODS—In diabetic patients from an economically distressed region, we assessed perceived necessity and harmfulness for antihyperglycemic (n = 803) and antihypertensive (n = 573) medications, past year's medication underuse, A1C, systolic blood pressure (SBP), and diastolic blood pressure (DBP). RESULTS—After correction for multiple analyses, multivariate models indicated that perceived need for antihyperglycemic medication was associated with being younger, being prescribed insulin, and being prescribed multiple medications. Concern about antihyperglycemic medications was associated with being younger, African American, dissatisfied with information received about medication, and of low health literacy. For antihypertensives, perceived necessity was associated with having numerous medical comorbidities and being dissatisfied with medication information; concern was associated with being younger, dissatisfied with information received about medication, and of low health literacy. Up to one-half of patients underused at least one of the types of medication; many of these patients attributed this underuse to cost. For both types of medications, concern was significantly associated with both cost-related and non–cost-related underuse, and antihypertensive concern was associated with higher SBP and DBP. CONCLUSIONS—Even after adjustment for economic factors, patients who are younger, African American, or of low health literacy are especially concerned about medication harmfulness, which is in turn associated with medication underuse and higher blood pressure. To enhance adherence and outcomes, interventions should address patients’ underlying concerns about potential adverse treatment effects and focus on both cultural factors and health literacy.
Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial
Authors: Jamie R Barwell, Colin E Davies, Jane Deacon, Kate Harvey, Julia Minor, Antonio Sassano, Maxine Taylor, Jenny Usher, Clare Wakely, Jonathan J Earnshaw, Brian P Heather, David C Mitchell, Mark R Whyman, Keith R Poskitt
Journal: The Lancet (2004)
The doctor as human being
Authors: A. Yawar
Journal: Journal of the Royal Society of Medicine (2005)

There are times when I am not sure whether I am a doctor, a quack or a bit of both. As a psychiatrist, I see patients in the raw. They come believing that they are being pursued by racist thugs; that state secrets are being held in a vault in the Science Museum; that the world is sad and lonely, and that there is no point in living. They bring themselves, haunted by their girlfriends and their pasts, enmeshed in tangled, torn relationships, with all their longings and their fears. The more we get to know our patients, the more we recognize that ‘diagnosis’ is inadequate; what we have is a human being shaped by time, circumstance, and unseen matters beyond measurement and comprehension.
ULTRASTRUCTURAL LOCALIZATION OF ANTIBODY IN DIFFERENTIATING PLASMA CELLS
Authors: Elizabeth H. Leduc, Stratis Avrameas, Michel Bouteille
Journal: The Journal of Experimental Medicine (1968)

Antibody was localized by electron microscopy within differentiating and mature plasma cells of the spleens of hyperimmunized rabbits. Horseradish peroxidase was used as antigen. Intracellular antibody to peroxidase was revealed in glutaraldehyde-fixed tissue by coupling it with its antigen and then revealing the sites of peroxidase activity cytochemically. Antibody first appears in the perinuclear space of hemocytoblasts where it persists through differentiation into immature plasma cells, but it disappears from this site in mature plasma cells. Concomitant with the development of the ergastoplasm, antibody accumulates in many but not all of its cisternae. Antibody is present in the lamellar portion of the Golgi apparatus in all phases of plasmacytic differentiation. Mature plasma cells exhibit two types of antibody distribution, a concentration into large spherical intracisternal granules or an overflowing into all parts of the cytoplasm.
Managing symptoms of irritable bowel syndrome in patients with inflammatory bowel disease
Authors: M. Camilleri
Journal: Gut (2011)

In many patients with inflammatory bowel disease (IBD), the symptoms of abdominal pain, bloating and diarrhoea are out of proportion with the demonstrated degree of inflammation; some symptomatic patients may have complete mucosal healing. Such patients often may undergo invasive, costly and potentially dangerous tests in search of residual inflammation. What are the diagnostic considerations in such patients? How should they be managed?

Irritable bowel syndrome (IBS) is a commonly encountered disorder, with point prevalence of ∼10%1; symptom-based criteria facilitate its diagnosis.2 Although IBD affects ∼0.4% of the population in the United States and Europe,3 4 IBD and IBS may concur in a patient, purely by chance. How often do patients with IBD and inflammation in remission manifest symptoms that suggest IBS, usually IBS with diarrhoea (IBS-D)?

From a database of over 1500 patients with IBD, Zaman et al 5 identified 30 with ileal Crohn's disease and 25 with ulcerative colitis involving only the rectosigmoid, and stable symptoms, no changes in medications or use of chronic steroids for 3 months, and no prior bowel surgery. Rome II IBS criteria were met by 67% of patients with Crohn's disease and 60% of ulcerative colitis, with similar symptoms in the two diseases. Thus, symptoms of IBS are common in IBD patients whose inflammation appears to be stable or in remission.

In patients who do not suffer IBD, the symptoms of IBS are not sufficiently specific to differentiate, in the absence of objective tests, other conditions such as pelvic floor dyssynergia or coeliac disease that respectively mimic constipation-predominant IBS (IBS-C) and IBS-D.6 Similarly, in patients with IBD, the presence of diarrhoea, urgency and pain in the absence of significant inflammation typically occur without constitutional symptoms or rectal bleeding, and may result from specific diseases that require specific treatment (figure …
Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction.
Authors: E P Reaven, G M Reaven
Journal: Journal of Clinical Investigation (1981)

The current study was conducted to determine if physical activity and/or weight control could influence the age-related decrease in beta cell insulin response noted in earlier studies. As such, virgin, male Sprague-Dawley rats were maintained in our facility for 1 yr on three differential experimental programs; in the first group, control rats lived under standard laboratory conditions; the second group of rats ran several miles a day in exercise wheels, and the third group was given a calorie-restricted diet designed to keep the rats weight-matched with the exercising rats. The results showed that the 12-mo-old sedentary control rats weighed an average of 800g. From the time these rats were 4 mo old, they were significantly hyperinsulinemic, with mean (+/- SEM) serum insulin levels of 55 +/- 6 microU/ml. Morphological studies on the pancreas of these rats at the end of the year revealed enlarged, multilobulated, fibrotic islets. After collagenase digestion, the most normal-appearing islets from the 12-mo-old controls were used for insulin secretion studies, these islets showed significantly reduced glucose-induced insulin release (0.83 microU insulin/min per volume islet) compared with islets from young rats (1.80 microU insulin/min per volume islet). In contrast, 12-mo-old exercised or calorie-restricted rats weighed approximately 500 g and did not show the changes in serum insulin levels or pancreas pathology exhibited by the sedentary control animals. However, islets from the calorie-restricted group functioned in vitro no better than islets from he sedentary control group. Islets from the exercised rats were somewhat improved in this regard. In summary, we believe exercise and weight control diminishes the animals' need for insulin-resulting in youthful-appearing islets after a year's time. However, these regimes do not appear able to correct the beta cell decline in function previously described.
Hepatoma-Derived Growth Factor Is a Novel Prognostic Factor for Patients with Pancreatic Cancer
Authors: Hirokazu Uyama, Yasuhiko Tomita, Hideji Nakamura, Shoji Nakamori, Binglin Zhang, Yoshihiko Hoshida, Hirayuki Enomoto, Yorihide Okuda, Masato Sakon, Katsuyuki Aozasa, Ichiro Kawase, Norio Hayashi, Morito Monden
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Hepatoma-derived growth factor (HDGF) is a nucleus-targeted growth factor playing an important role in the development and progression of cancers. This study investigated the correlation of HDGF expression and prognosis in patients with pancreatic ductal carcinoma. Patients and Methods: HDGF expression in pancreatic cancer cell lines was analyzed by Western blotting. HDGF expression was analyzed by immunohistochemistry for 50 patients with primary ductal carcinoma of the pancreas (33 male and 17 female) ranging in age from 48 to 80 years (median, 65 years) receiving surgical treatment. Cancer cells showing stronger staining than the noncancerous ducts were regarded as positive. Cases showing positive staining in &amp;lt;90% and &amp;gt;90% of tumor cells were regarded as HDGF labeling index (LI) levels 1 and 2, respectively. HDGF LI was determined separately for the nucleus and the cytoplasm. Results: Western blotting showed HDGF expression in pancreatic cancer cells similar to that of hepatic cell lines. Twenty-three (46%) and 27 (54%) cases and 22 (44%) and 28 (56%) cases showed HDGF LI levels 1 and 2 for the nucleus and the cytoplasm, respectively. Patients with nuclear HDGF LI level 1 showed a significantly better 5-year survival rate (37.0%) than those with level 2 (6.8%; P = 0.023). No significant difference was observed in the cytoplasmic HDGF LI classification. Multivariate analysis revealed nuclear HDGF LI to be an independent prognosticator. Conclusions: These findings suggest that HDGF could be a novel prognostic factor for pancreatic ductal carcinoma.
Well-Defined Melanoma Antigens as Progression Markers for Melanoma: Insights into Differential Expression and Host Response Based on Stage
Authors: F. Stephen Hodi
Journal: Clinical Cancer Research (2006)

Decades of investigation have sought the identification of melanoma antigens associated with immune-mediated tumor destruction. These efforts arose from a need for effective therapies as limited options for patients with advanced disease exist. Compelling evidence showed that melanoma stimulates
Safety performance evaluation of taekwondo headgear
Authors: David M O'Sullivan, Gabriel P Fife, Willy Pieter, Insik Shin
Journal: British Journal of Sports Medicine (2013)

Background With over 20 years of taekwondo concussion research highlighting the high incidence of injury, previous studies recommend an investigation of headgear impact attenuation performance. Objective To examine impact attenuation differences between the anterior, posterior and sides of selected taekwondo headgear brands. Design Between-groups. Setting Biomechanics laboratory. Methods Five different commercially available taekwondo headgear were selected for impact testing. A 50th percentile Hybrid II Dummy Crash Test head and neck was fitted with the selected helmet and was bolted to a 25 kg steel torso-like structure. Each headgear model was impacted eight times to the anterior, posterior and sides by a 6.75 kg bowling ball at three heights to produce 52.25, 85 and 144 J strikes. Main outcome measurements Resultant head linear acceleration. Results Two-way (Helmet×Location) mixed analysis of variance with repeated measures on the second factor was performed to determine the differences between headgear by location of impact. There was a two-way (Helmet×Location) interaction for acceleration (η 2 =0.368). Conclusions Taekwondo headgear manufacturers and sport governing bodies must consider improving the design of especially anterior helmet properties.