tbuckley/cabot-search huggingface dataset:
Surgery as an Effective Early Intervention for Diabesity
Authors: John B. Dixon, Walter J. Pories, Paul E. O’Brien, Phillip R. Schauer, Paul Zimmet
Journal: Diabetes Care (2005)

We are currently in the midst of two closely linked epidemics: type 2 diabetes and obesity (1,2). At the present time, it is estimated that 190 million people worldwide have diabetes and that this will increase to 324 million by 2025 (3). This epidemic is taking place in both developed and developing nations. In the U.S. alone, at least 16 million people have type 2 diabetes, with 1 million more diagnosed annually (4). Obesity is also increasing at alarming rates. In the U.S., the majority diagnosed with type 2 diabetes are overweight, with 50% obese (i.e., BMI >30 kg/m2) and 9% morbidly obese (BMI >40 kg/m2) (5).

There is a strong relationship between obesity and type 2 diabetes, and the term “diabesity” has been coined to suggest a single problem (6,7). A substantial portion of the health costs attributed to obesity is related to type 2 diabetes (8). The socioeconomic impact of type 2 diabetes and its complications are substantial to individuals and their families and to society (9). In particular, it is an inexorably progressive disease, leading to deterioration in multiple organs and systems, and is the most common cause of adult blindness, limb amputations, and renal failure in western communities, as well as the leading independent risk factor for coronary artery disease (10).

Prevention of this diabesity epidemic through effective public health lifestyle and environmental initiatives to change the population’s dietary and movement behaviors should be of highest priority (2). For those already suffering from diabesity, effective treatment is important. A therapy that provides remission of both diabetes and obesity should attract enormous interest and activity.

Theoretically, weight loss is such a therapy (11,12). However, although intentional weight loss through diet and exercise is associated with better control, …
The Clamp-Like Index
Authors: Christian Anderwald, Marietta Anderwald-Stadler, Miriam Promintzer, Gerhard Prager, Martina Mandl, Peter Nowotny, Martin G. Bischof, Michael Wolzt, Bernhard Ludvik, Thomas Kästenbauer, Giovanni Pacini, Anton Luger, Michael Krebs
Journal: Diabetes Care (2007)

OBJECTIVE—Insulin resistance, the underlying pathophysiological mechanism of the metabolic syndrome, can not only predict type 2 diabetes development but also cardiovascular disease. Thus, precise insulin resistance measurement in individuals at risk for metabolic diseases would support clinical risk stratification. However, the gold standard for measuring insulin resistance, the hyperinsulinemic clamp test, is too labor intensive to be performed in large clinical studies/settings. RESEARCH DESIGN AND METHODS—Using plasma glucose and C-peptide concentrations from oral glucose tolerance tests (OGTTs), we developed the novel “clamp-like index” (CLIX) for insulin sensitivity calculation and compared CLIX to clamp glucose infusion rates (GIR) (100–120 min). We evaluated CLIX in 89 nondiabetic subjects (58 female and 31 male, aged 45 ± 1 years, BMI 27.5 ± 0.8 kg/m2) who underwent frequently sampled 3-h 75-g OGTTs and 2-h hyperinsulinemic-isoglycemic clamp (40 mU/min per m2) tests. RESULTS—CLIX, calculated as serum creatinine (×0.85 if male)/(mean AUCglucose × mean AUCC-peptide) × 6,600, was highly correlated (r = 0.670, P &amp;lt; 10−12) with and comparable to clamp GIRs100–120 min. In subgroup analyses, GIRs100–120 min were lower (P &amp;lt; 0.005) in type 2 diabetic offspring (6.2 ± 0.7 mg · min−1 · kg−1) than in sex-, age-, and BMI-matched subjects without a family history of type 2 diabetes (8.6 ± 0.5 mg · min−1 · kg−1), which was also reflected by CLIX (insulin-resistant offspring 6.4 ± 0.6 vs. those without a family history of type 2 diabetes 9.0 ± 0.5; P &amp;lt; 0.002). When compared with normal-weight subjects (GIR 8.8 ± 0.4 mg · min−1 · kg−1; CLIX 9.0 ± 0.5), both GIRs100–120 min and CLIX of obese (5.2 ± 0.9 mg · min −1 · kg−1; 5.7 ± 0.9) and morbidly obese (2.4 ± 0.4 mg · min −1 · kg−1; 3.3 ± 0.5) humans were lower (each P &amp;lt; 0.02). CONCLUSIONS—CLIX, a novel index obtained from plasma OGTT glucose and C-peptide levels and serum creatinine, without inclusion of anthropometrical measures to calculate insulin sensitivity in nondiabetic humans, highly correlates with clamp GIRs and reveals even slight insulin sensitivity alterations over a broad BMI range and is as sensitive as the hyperinsulinemic clamp test.
Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose
Authors: V Strand, M Svartengren, S Rak, C Barck, G Bylin
Journal: European Respiratory Journal (1998)

We investigated the effects of NO2 and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 microg x m(-3) NO2 for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO2 and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO2 was at EP -25% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO2 exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO2 plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO2 enhances the airway response to a nonsymptomatic allergen dose.
Association between Pulmonary Function and Sputum Biomarkers in Cystic Fibrosis
Authors: Nicole Mayer-Hamblett, Moira L. Aitken, Frank J. Accurso, Richard A. Kronmal, Michael W. Konstan, Jane L. Burns, Scott D. Sagel, Bonnie W. Ramsey
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Sputum biomarkers of infection and inflammation are noninvasive measures that enable quantification of the complex pathophysiology of cystic fibrosis (CF) lung disease. Validation of these biomarkers as correlates of disease severity is a key step for their application.Objectives: We constructed a large database from four multicenter studies to quantify the strength of association between expectorated sputum biomarkers and FEV1.Methods: FEV1 (range, 25–120% predicted) and quantitative data on expectorated sputum biomarkers including free neutrophil elastase, IL-8, neutrophils, Pseudomonas aeruginosa, and Staphylococcus aureus were obtained from 269 participants (ages, 9–54 years) from 33 centers. Cross-sectional and longitudinal statistical analyses were performed to estimate associations between the markers and FEV1, including the use of multivariable analyses.Results: Elastase was negatively correlated with FEV1 (correlation [r] = −0.35; 95% confidence interval [CI]: −0.46, −0.22). On average, patients with CF who differed in their elastase measurements by 0.5 log differed in their FEV1 values by −7.3% (95% CI: −9.7, −4.6). Neutrophil counts and IL-8 were also each negatively correlated. In a multivariable regression, elastase and neutrophil counts were able to explain the majority of variation in FEV1. Elastase was further shown to have a significant longitudinal association with FEV1, specifically a −2.9% decline in FEV1 (95% CI: −5.0, −0.9) per 1-log increase in elastase. Although correlated with FEV1, bacterial densities were unable to explain clinically meaningful differences in FEV1 within and across patients.Conclusions: These data support the role of sputum biomarkers as correlates of disease severity in a diverse CF population.
New Pathogenic Candidates for Diabetic Macular Edema Detected By Proteomic Analysis
Authors: Cristina Hernández, Marta García-Ramírez, Nuria Colomé, Marta Villarroel, Lidia Corraliza, Luis García-Pacual, Joan Casado, Francesc Canals, Rafael Simó
Journal: Diabetes Care (2010)

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients. The aim of the present study was to explore the differential proteomic pattern of the vitreous fluid from DME patients by means of proteomic analysis. For this purpose, we used fluorescence-based difference gel electrophoresis (DIGE). This technique provides accurate quantitative comparisons, and we further optimized it in order to avoid potential confounding factors (1).

Samples of vitreous from eight type 2 diabetic patients (four with DME without proliferative diabetic retinopathy [PDR] and four with PDR without DME), and eight from nondiabetic subjects with idiopathic macular hole (control group) were selected from our vitreous bank for proteomic analysis. …
A stress fracture of the lumbar spine in a professional rugby player
Authors: Bernard H Castinel, Philippe Adam, Christophe Prat
Journal: British Journal of Sports Medicine (2006)

In modern rugby, the spine is subjected to great physical pressure, with an increased number of impacts, on both the cervical and the lumbar spine. This case report illustrates overuse injuries of the lumbar spine in international professional rugby players. A 32-year-old sportsman had been practising rugby for 24 years and was playing for a championship level French team when he started suffering from a right lateral pain in the lumbosacral spine. A CT scan showed a unilateral isthmolysis and a coronal irregular fracture of the right pars interarticularis of L5. This led to discussion of (1) the importance of the decision on the date of return to playing rugby and (2) the future of professional rugby players with chronic spinal injuries.
Cross-elicitation responses to 2-methoxymethyl-<i>p</i>-phenylenediamine under hair dye use conditions in<i>p</i>-phenylenediamine-allergic individuals
Authors: B. Blömeke, L.M. Pot, P.-J. Coenraads, J. Hennen, M. Kock, C. Goebel
Journal: British Journal of Dermatology (2014)

The factors influencing elicitation responses in individuals allergic to p-phenylenediamine (PPD) in hair dyes are not well understood.Investigation of the elicitation response to the new, less-sensitizing PPD alternative 2-methoxymethyl-p-phenylenediamine (ME-PPD) under simulated hair dye use conditions.The cross-elicitation response to ME-PPD (2% in a hair dye test product for 30 min on forearm then rinsing) was analysed at days 2 and 3 in 30 PPD-allergic individuals with diagnostic patch test grades +, ++ or +++ according to the classification of the International Contact Dermatitis Research Group.Cross-reactivity to the ME-PPD-containing hair dye test product was elicited in nine of 30 subjects (30%), while 70% were negative. Cross-reactivity was elicited in two of four cases with grade +++, three of 10 with grade ++ and four of 16 with grade +. Under identical conditions, PPD was previously found to elicit a response in 21 of 27 PPD-allergic individuals. In 18 of these 21 individuals, either the strength of the cross-elicitation response to ME-PPD was decreased or no response occurred.Under simulated hair dye use conditions, a significantly lower degree of cross-elicitation to ME-PPD (30%) was observed than previously reported for PPD (32 of 38, 84%). Additionally, a decreased cross-elicitation strength was observed across all three patch test grades, likely reflecting the reduced skin-sensitization properties of ME-PPD. Consequently, careful dermatological evaluation is required to assess cross-reactivity to ME-PPD in patients allergic to hair dyes.
The endothelial glycocalyx affords compatibility of Starling's principle and high cardiac interstitial albumin levels
Authors: M JACOB, D BRUEGGER, M REHM, M STOECKELHUBER, U WELSCH, P CONZEN, B BECKER
Journal: Cardiovascular Research (2006)

Objective: To test the role of an oncotic pressure gradient across the endothelial glycocalyx with respect to extravasation of fluid and colloids and development of tissue edema in a whole organ setting.
Immunoglobulin G–mediated Inflammatory Responses Develop Normally in Complement-deficient Mice
Authors: Diana Sylvestre, Raphael Clynes, Minga Ma, Henry Warren, Michael C. Carroll, Jeffrey V. Ravetch
Journal: The Journal of Experimental Medicine (1996)

The role of complement in immunoglobulin G–triggered inflammation was studied in mice genetically deficient in complement components C3 and C4. Using the reverse passive Arthus reaction and experimental models of immune hemolytic anemia and immune thrombocytopenia, we show that these mice have types II and III inflammatory responses that are indistinguishable from those of wild-type animals. Complement-deficient and wild-type animals exhibit comparable levels of erythrophagocytosis and platelet clearance in response to cytotoxic anti–red blood cell and antiplatelet antibodies. Furthermore, in the reverse passive Arthus reaction, soluble immune complexes induce equivalent levels of hemmorhage, edema, and neutrophillic infiltration in complement-deficient and wild-type animals. In contrast, mice that are genetically deficient in the expression of Fc receptors exhibit grossly diminished reactions by both cytotoxic antibodies and soluble immune complexes. These studies provide strong evidence that the activation of cell-based FcγR receptors, but not complement, are required for antibody-triggered murine inflammatory responses.
Joint effusions in sickle cell-beta-thalassemia disease
Authors: E. J. Van Slyck
Journal: JAMA (1976)

ABSTRACT To the Editor.— The report of Crout and colleagues (235:1878, 1976) describes joint effusions in a patient in whom they claim a diagnosis of sickle cell-β-thalassemia. The purpose of my letter is not to question the coexistence of this clinical manifestation with the disease ascribed to it, since I have made this observation in my own practice; but I do question their interpretation of the data on which they relied for a diagnosis of sickle cell-β-thalassemia.The hemoglobin values were as follows: hemoglobin S, 86.2%; hemoglobin A2,2.5%; and hemoglobin F, 11.3% (the last heterogenously distributed); this pattern can be seen in homozygous sickle cell disease, and is the more likely diagnosis in their case. Although the combination of the β-thal0 and the sickle gene can produce no demonstrable hemoglobin A1, the hemoglobin A2 value should exceed 3.5%. It is remotely possible that their patient had
Altered Expression of Type II Sodium/Phosphate Contransporter in Polycystic Kidney Disease
Authors: MORITZ VOGEL, BETTINA KRA[Combining Diaeresis]NZLIN, JO[Combining Diaeresis]RG BIBER, HEINI MURER, NORBERT GRETZ, SEBASTIAN BACHMANN
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Renal phosphate (Pi) absorption is mediated via the type II sodium/Pi cotransporter (NaPi-2) in the brush border membrane (BBM) of proximal tubules. Simultaneous detection of NaPi-2 mRNA by in situ hybridization and of NaPi-2 immunoreactivity by immunohistochemistry was performed to investigate the distribution of the cotransporter in healthy control rats and during progression of autosomal dominant polycystic kidney disease (ADPKD). The purpose of the study was to disclose a relation between proximal tubular cell differentiation and NaPi-2 expression. In controls, NaPi-2 expression was present in the entire proximal tubule. In the Han:SPRD (cy/+) model for ADPKD, the proximal nephron is primarily affected by the cystic changes. Epithelial proliferation and impaired epithelial-matrix interaction result in a loss of cell differentiation that eventually leads to cystic enlargement of the nephron. Normal expression of NaPi-2 in this model was found only in tubules with intact BBM. Loss of BBM and cellular interdigitation were paralleled by the loss of NaPi-2 in situ hybridization and immunoreactive signals. These changes were moderate and focal in 2-mo-old rats and generalized all over the cortex after 8 mo. Advanced renal damage in the older PKD group was associated with mild phosphaturia, which suggests functional insufficiency of tubular NaPi-2 reabsorption. These data show how proliferative changes and loss of tubular epithelial differentiation in ADPKD may prevent functional expression of the NaPi-2 system in the proximal tubule in a rapidly progressive manner. NaPi-2 in proximal tubule BBM is suggested to play an important role in impaired tubular absorption of Pi in renal disease.
Development of the Gastrointestinal Tract
Authors: L Weaver
Journal: Gut (2000)

Development of the Gastrointestinal Tract . Edited by I R Sanderson, W A Walker (Pp 324; illustrated). Canada: BC Decker Inc, 2000. ISBN 1 55009 081 X.

When I was a fellow with Allan Walker 15 years ago, gut development was a topic of interest to a handful of researchers worldwide. A classic review by Grand, Watkins, and Torti published in Gastroenterology in 1976, and Koldovsky's monograph Development of the Functions of the Small Intestine in Mammals and Man in 1969 brought together much of what was then known about the ontogeny of the human gut. Developmental biologists were beginning to recognise the opportunities offered by this rapidly differentiating organ to understand the interactions of genetic endowment and environmental influences in early life. The focus of much research was on the process of adaptation to milk feeding. With the survival of …
Does Biology and Location Predict Chemotherapy Benefit? Patients with Distal Gastric Cancer Have Superior Outcome with Addition of Taxanes Into Combination Chemotherapy While Proximal and Diffuse Gastric Cancers Don'T
Authors: Sedef Ali Murat, Besen Ayberk, Kose Fatih, Tatlı Ali Murat, Dogan Ozlem, Mertsoylu Huseyin, Muallaoglu Sadık, Sezer Ahmet, Ozyilkan Ozgur, Abali Huseyin
Journal: Annals of Oncology (2014)
Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect
Authors: S. Stacchiotti, T. Negri, N. Zaffaroni, E. Palassini, C. Morosi, S. Brich, E. Conca, F. Bozzi, G. Cassinelli, A. Gronchi, P.G. Casali, S. Pilotti
Journal: Annals of Oncology (2011)
The effect of phenolic glycolipid-1 from Mycobacterium leprae on the antimicrobial activity of human macrophages.
Authors: M A Neill, S J Klebanoff
Journal: The Journal of Experimental Medicine (1988)

Purified PGL-1 and dPGL from M. leprae can prevent bacterial killing by intact phagocytes and cell-free antimicrobial systems. Both glycolipids completely abolished the antimicrobial effect of the acetaldehyde-XO-Fe2+ system. Because the cytotoxicity of this system is inhibited by catalase, SOD, mannitol, and ethanol, but not by heated SOD or catalase, these data suggest that toxicity is due to OH. generated by the Haber-Weiss reaction. That the antimicrobial killing in the XO system is completely blocked by the addition of PGL-1 or dPGL suggests that these glycolipids can act as OH. scavengers. A modest protective effect against the cytotoxicity of the MPO-H2O2-halide system by both PGL-1 and dPGL was also observed. The antimicrobial activity of the MPO system was abolished with chloride, but not iodide, as the halide. The effect of the M. leprae-derived glycolipid on bacterial killing by intact phagocytes was examined. Two linking antibodies were used to bind the dPGL to a rapidly growing test organism, S. aureus, a murine IgM mAb specific for the terminal glycoside of PGL-1, and a rabbit IgG anti-mouse IgM which bound the staphylococcal protein A via its Fc region. Examination by transmission EM of human monocyte-derived macrophages which had ingested staphylococci either coated with both antibodies and dPGL, or coated only with the IgG and IgM antibodies, demonstrated the presence of bacteria in phagosomes of control and IFN-gamma-activated macrophages. Activation of the macrophage monolayers by pretreatment with IFN-gamma markedly increased their staphylocidal activity. When dPGL coated staphylococci were ingested, killing by both control and IFN-gamma-activated macrophages was completely blocked. These results, suggesting that PGL-1 can scavenge reactive oxygen species and prevent microbial death within the phagosome, may in part explain the intracellular survival of M. leprae in certain cell types.
PERSISTENCE OF ANTIBIOTICS IN BLOOD OF PATIENTS WITH ACUTE RENAL FAILURE. I. TETRACYCLINE AND CHLORTETRACYCLINE*†
Authors: Calvin M. Kunin, Searle B. Rees, John P. Merrill, Maxwell Finland
Journal: Journal of Clinical Investigation (1959)

The management of patients with severe renal disease is frequently complicated by infections; these commonly involve the urinary tract, but in- fections elsewhere are not unusual.Overwhelm- ing infection, particularly with gram-negative bacteria, is often associated with shock and anuria (2) and antibiotic therapy is an integral part of the management in such cases.The persistence of a drug in the blood, once it is absorbed or after it is given systemically, depends on many factors which include: removal by the kidneys, binding to plasma proteins, sequestration in various organs and body compartments, excretion into the bile and feces, detoxification and degradation mecha- nisms and the inherent stability of the substance; most important for nearly all antibiotics, however, is their removal by the kidneys.Knowledge con- cerning the fate of antibiotics in patients with im- paired renal function is, therefore, necessary for planning therapy so that it will insure adequate blood and tissue levels without undue retention that may be harmful.A series of studies was, therefore, undertaken in patients with anuria or impaired renal function from various causes, who either were receiving antibiotics as part of their therapy, or were given test doses of some of the commonly used anti- biotics.The half-life of the antibiotics in the
Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors
Authors: Anneclaire J. De Roos, Nathaniel Rothman, Merideth Brown, Douglas A. Bell, Gary S. Pittman, William R. Shapiro, Robert G. Selker, Howard A. Fine, Peter M. Black, Peter D. Inskip
Journal: Neuro-Oncology (2006)

Genes involved in phase I and phase II regulation of aromatic hydrocarbon-induced effects exhibit sequence variability that may mediate the risk of adult brain tumors. We evaluated associations between gene variants in CYP1A1, CYP1B1, GSTM3, EPHX1, and NQO1 and adult brain tumor incidence. Cases were patients with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) diagnosed from 1994 to 1998 at three U.S. hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples collected from 1277 subjects, and genotyping was conducted for CYP1A1 I462V, CYP1B1 V432L, EPHX1 Y113H, GSTM3 *A/*B (intron 6 deletion), and NQO1 P187S. The CYP1B1 V432L homozygous variant was associated with decreased risk of meningioma (odds ratio [OR] = 0.6; 95% CI, 0.3-1.0) but not the other tumor types. The GSTM3 *B/*B genotype was associated with increased risk of glioma (OR = 2.3; 95% CI, 1.0-5.2) and meningioma (OR = 3.6; 95% CI, 1.3-9.8). Increased risks associated with GSTM3 *B/*B were observed in younger subjects (age < 50) and older subjects (age > or = 50), in men and women, and within each study site. The magnitude of association for GSTM3 with glioma and meningioma was greater among ever-smokers than among those who had never smoked. None of the other genotypes showed consistent associations with any tumor type. The association with the GSTM3 *B allele, while intriguing, requires replication, and additional research is needed to clarify the function of the GSTM3 alleles studied here.