tbuckley/cabot-search huggingface dataset:
Determinants of glomerular hypofiltration in nephrotic patients with minimal change nephropathy.
Authors: A Guasch, B D Myers
Journal: Journal of the American Society of Nephrology (1994)

Physiologic and morphologic techniques were used to elucidate the determinants of the GFR in 25 nephrotic patients with minimal change nephropathy. They were divided into two groups according to the finding of either a normal (Group 1, N = 13) or a depressed (Group 2, N = 12) inulin clearance. RPF, afferent oncotic pressure, and dextran sieving coefficients were determined. Mathematical models of glomerular ultrafiltration were then used to compute likely upper bounds for the ultrafiltration coefficient and pore area/length ratio (a measure of pore density). The upper bounds for each measure of intrinsic ultrafiltration capacity were depressed below estimated normal values in healthy controls by 55 and 47% in Group 1 patients and by 86 and 83% in Group 2 patients with minimal change nephropathy. A corresponding excess of ultrafiltration pressure (versus control), attributable solely to reduced intracapillary oncotic pressure, was by 10.8 and 11.5 mm Hg, respectively. Glomerular morphometry revealed peripheral capillary filtration surface area to be preserved in both minimal change nephropathy groups. However, a significant reduction in filtration slit frequency due to epithelial podocyte broadening correlated with the computed ultrafiltration coefficient across the two minimal change nephropathy groups (r = 0.65; P < 0.001). It was concluded that podocyte deformation invariably lowers the ultrafiltration coefficient and pore area/length ratio in minimal change nephropathy but that an offsetting reduction in intracapillary oncotic pressure prevents the GFR from declining in many cases. However, the models presented here predict that the depression of capillary oncotic pressure is insufficient to compensate when the ultrafiltration coefficient is lowered by substantially more than half and that it is in this circumstance that minimal change nephropathy is most likely to be accompanied by glomerular hypofiltration.
Prognostic value of coronary blood flow velocity and myocardial perfusion in intermediate coronary narrowings and multivessel disease
Authors: Steven A.J. Chamuleau, Rene A. Tio, Carel C. de Cock, Ebo D. de Muinck, Nico H.J. Pijls, Berthe L.F. van Eck-Smit, Karel T. Koch, Martijn Meuwissen, Marcel G.W. Dijkgraaf, Angelina de Jong, Hein J. Verberne, Rob A.M. van Liebergen, Gert Jan Laarman, Jan G.P. Tijssen, Jan J. Piek
Journal: Journal of the American College of Cardiology (2002)
Psychiatric Malpractice: A Regional Incidence Study
Authors: PAUL FREDRIC SLAWSON
Journal: American Journal of Psychiatry (1970)

Systematic studies of psychiatric malpractice are scarce. Defendant psychiatrists try to avoid publicity, and many cases escape notice. A survey of psychiatric malpractice claims in southern California between 1958 and 1967 showed no increase in claims rate and an average of 1.5 claims per 100 psychiatrists per year. Most claims were settled for a modest fee before trial. The author describes some malpractice cases and analyzes different types of risks.
Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy
Authors: P H Dixon, S W C van Mil, J Chambers, S Strautnieks, R J Thompson, F Lammert, R Kubitz, V Keitel, A Glantz, L-A Mattsson, H-U Marschall, M Molokhia, G E Moore, K J Linton, C Williamson
Journal: Gut (2008)

<h3>Background:</h3> Intrahepatic cholestasis of pregnancy (ICP) has a complex aetiology with a significant genetic component. <i>ABCB11</i> encodes the bile salt export pump (BSEP); mutations cause a spectrum of cholestatic disease, and are implicated in the aetiology of ICP. <h3>Methods:</h3> <i>ABCB11</i> variation in ICP was investigated by screening for five mutant alleles (E297G, D482G, N591S, D676Y and G855R) and the V444A polymorphism (c.1331T&gt;C, rs2287622) in two ICP cohorts (n = 333 UK, n = 158 continental Europe), and controls (n = 261) for V444A. PCR primers were used to amplify and sequence patient and control DNA. The molecular basis for the observed phenotypes was investigated in silico by analysing the equivalent residues in the structure of the homologous bacterial transporter Sav1866. <h3>Results:</h3> E297G was observed four times and D482G once. N591S was present in two patients; D676Y and G855R were not observed. The V444A polymorphism was associated with ICP (allelic analysis for C vs T: OR 1.7 (95% CI 1.4 to 2.1, p&lt;0.001)). In addition, CC homozygotes were more likely to have ICP than TT homozygotes: OR 2.8 (95% CI 1.7 to 4.4 p&lt;0.0001). Structural analyses suggest that E297G and D482G destabilise the protein fold of BSEP. The molecular basis of V444A and N591S was not apparent from the Sav1866 structure. <h3>Conclusions:</h3> Heterozygosity for the common <i>ABCB11</i> mutations accounts for 1% of European ICP cases; these two mutants probably reduce the folding efficiency of BSEP. N591S is a recurrent mutation; however, the mechanism may be independent of protein stability or function. The V444A polymorphism is a significant risk factor for ICP in this population.
Analysis of Glucose Responses to Automated Insulin Suspension With Sensor-Augmented Pump Therapy
Authors: Trang T. Ly, Jennifer A. Nicholas, Adam Retterath, Elizabeth A. Davis, Timothy W. Jones
Journal: Diabetes Care (2012)

The advent of sensor-augmented pump therapy with a low-glucose suspend (LGS) function (Medtronic Paradigm Veo System), allowing insulin to be automatically suspended for up to 2 h when sensor glucose falls below a preset threshold, has the potential to reduce the duration of hypoglycemia. In this article, we analyzed blood glucose profiles following a full 2-h insulin suspension activated by the LGS function, as well as examined different patterns of use among patients.Data from a cohort of participants using the Veo System for up to 6 months were analyzed to determine the time and duration of insulin suspension activated by the LGS function. We further evaluated overnight suspend events with no patient response occurring prior to 3:00 a.m., which allowed us to determine the pattern of sensor glucose values with no patient intervention during and after the period of insulin suspension.There were 3,128 LGS events during the 2,493 days evaluated. The median duration was 11.2 min, and 36% of events occurred overnight. There were 126 full 2-h suspend events that occurred overnight with no patient response, occurring before 3:00 a.m. For these events, the mean sensor glucose at the end of the 2-h suspend period was 99 ± 6 mg/dL ([means ± SE] 5.5 ± 0.3 mmol/L). The mean sensor glucose 2 h after insulin delivery resumed was 155 ± 10 mg/dL (8.6 ± 0.6 mmol/L). There were no episodes of severe hypoglycemia or diabetic ketoacidosis.Analyses of sensor glucose patterns following insulin suspension activated by LGS suggest that this technology is safe and unlikely to be associated with adverse outcomes.
Expansion of Voltage-dependent Na+ Channel Gene Family in Early Tetrapods Coincided with the Emergence of Terrestriality and Increased Brain Complexity
Authors: Harold H. Zakon, Manda C. Jost, Ying Lu
Journal: Molecular Biology and Evolution (2010)

Mammals have ten voltage-dependent sodium (Nav) channel genes. Nav channels are expressed in different cell types with different subcellular distributions and are critical for many aspects of neuronal processing. The last common ancestor of teleosts and tetrapods had four Nav channel genes, presumably on four different chromosomes. In the lineage leading to mammals, a series of tandem duplications on two of these chromosomes more than doubled the number of Nav channel genes. It is unknown when these duplications occurred and whether they occurred against a backdrop of duplication of flanking genes on their chromosomes or as an expansion of ion channel genes in general. We estimated key dates of the Nav channel gene family expansion by phylogenetic analysis using teleost, elasmobranch, lungfish, amphibian, avian, lizard, and mammalian Nav channel sequences, as well as chromosomal synteny for tetrapod genes. We tested, and exclude, the null hypothesis that Nav channel genes reside in regions of chromosomes prone to duplication by demonstrating the lack of duplication or duplicate retention of surrounding genes. We also find no comparable expansion in other voltage-dependent ion channel gene families of tetrapods following the teleost-tetrapod divergence. We posit a specific expansion of the Nav channel gene family in the Devonian and Carboniferous periods when tetrapods evolved, diversified, and invaded the terrestrial habitat. During this time, the amniote forebrain evolved greater anatomical complexity and novel tactile sensory receptors appeared. The duplication of Nav channel genes allowed for greater regional specialization in Nav channel expression, variation in subcellular localization, and enhanced processing of somatosensory input.
It Is Time to Include Patients With Brain Tumors in Phase I Trials in Oncology
Authors: Patrick Y. Wen, David Schiff, Timothy F. Cloughesy, David A. Reardon, Tracy T. Batchelor, Bruce A. Chabner, Keith Flaherty, John F. de Groot, Mark R. Gilbert, Evanthia Galanis, Susan M. Chang, Gary K. Schwartz, David Peereboom, Minesh P. Mehta, W.K. Alfred Yung, Stuart A. Grossman, Michael D. Prados, Lisa M. DeAngelis
Journal: Journal of Clinical Oncology (2011)

Traditionally,themajorityofphaseIstudiesofnovelagentsin oncology have excluded patients with primary brain tumors. Although phase I studies are designed to determine optimal dosing, efficacy data are increasingly used to look for a signal in particular tumors. Excluding patients with primary brain tumors from phase I studies results in a significant handicap in the identification of drugs that may be particularly active in these tumor types. In this era of targeted therapies, we suggest that the reasons for excluding these patients are largely obsolete. It is time to reconsider this practice and include patients with brain tumors in phase I trials in oncology. Several reasons are given for the exclusion of patients with brain tumors from phase I trials. First, patients with brain tumors were historically treated with cytochrome P450 enzyme-inducing antiepileptic drugs (EIAEDs), such as phenytoin and carbamazepine, which potentially accelerated hepatic metabolism of the agent under study. Asaresult,aseparatephaseIstudywasoftenrequiredforpatientswith
Intestinal Permeability as Assessed with Polyethyleneglycols in Birch Pollen Allergic Children Undergoing Oral Immunotherapy
Authors: C. Möller, K.‐E. Magnusson, T. Sundqvist, R. Stenling, B. Björkstén
Journal: Allergy (1986)

Twenty‐four children with rhinoconjunctivitis due to birch pollinosis were treated in a double‐blind manner with enteric‐coated capsules containing either a high dose of a birch pollen preparation ( n = 11) or placebo ( n = 13). The permeability of the small intestine was analysed at three different occasions with a mixture of differently sized poly‐ethyleneglycols (PEG 400 and PEG 1000), before the start of oral immunotherapy (OIT), at the moment of maximum allergen dose, and after 3 months of therapy which was at the beginning of the pollen season. The actively treated children did not significantly change their permeability characteristics as determined from PEG recovery in the urine. By contrast, in the control group of patients the recovery of larger PEG molecules was decreased after 3 months of therapy, possibly due to the commencing pollen season. In addition, small bowel biopsies were taken at the time of maximum allergen dose from two children openly treated with OIT. Both specimens were normal.
Epidemiological link between wheat allergy and exposure to hydrolyzed wheat protein in facial soap
Authors: Y. Fukutomi, M. Taniguchi, H. Nakamura, K. Akiyama
Journal: Allergy (2014)

Recent studies have highlighted the importance of extra-intestinal routes of sensitization to food-related allergens as the cause of epidemics of food allergy. Instances of Japanese women developing food allergy to wheat after exposure to hydrolyzed wheat protein (HWP) present in facial soap have been reported. However, the epidemiologic impact of these ingredients as a cause of food allergy has not been well studied.To clarify the epidemiological relationship between food allergy to wheat and contact exposure to HWP, a case-control study of Japanese women aged 20-54 years with self-reported wheat allergy (WA) (cases, n = 157) and age-matched control subjects without WA (controls, n = 449) was performed using a large-scale Web-based research panel. Subjects answered a Web-based questionnaire regarding the use of skin and hair care products, as well as other possible risk factors.Current use of an HWP-containing facial soap (Cha no Shizuku; Yuka) was significantly associated with an increased risk of WA (adjusted odds ratio, 2.6; 95% confidence interval, 1.2-5.7; frequencies of current use in cases and controls; 11% and 6%, respectively). Use of Cha no Shizuku was more common in subjects with more recent-onset WA, implying that this soap may have contributed to the recent epidemic of WA.An epidemiological relationship between WA and contact exposure to HWP has been documented. This study implicates a possible role of contact exposure to food-derived protein hydrolysates as a risk factor for the development of food allergy manifesting itself as anaphylaxis.
Intrathoracic neural tumours.
Authors: K G Davidson, P R Walbaum, R J McCormack
Journal: Thorax (1978)

The experience of one regional thoracic surgical unit in managing intrathoracic neural tumours over a 25-year period is presented. Neural tumour was diagnosed in 55 patients, of whom 41 were asymptomatic. In 11 patients complete resection was not achieved--the reasons for this and its effect on the outcome of the patient are discussed. There were 52 posterior mediastinal and three lateral chest wall tumours. The pathological distribution was as follows--benign nerve sheath tumours (neurofibroma, neurilemoma) 39, ganglioneuroma 13, and neuroblastoma 3. One neurofibroma recurred as a neurosarcoma six years after its apparently complete resection and was removed by an extensive resection at reoperation. One neuroblastoma recurred within the spinal canal four years after incomplete excision at thoracotomy--this patient died subsequently of widespread metastatic neuroblastoma. No other tumour is known to have recurred.
Variability in knee radiographing: implication for definition of radiological progression in medial knee osteoarthritis
Authors: P. Ravaud, B. Giraudeau, G.-R. Auleley, J.-L. Drape, B. Rousselin, L. Paolozzi, C. Chastang, M. Dougados
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVES</h3> (1) To assess reproducibility of medial knee joint space width (JSW) measurement in healthy subjects and osteoarthritic (OA) patients. (2) To define minimal relevant radiological change in knee JSW based on the reproducibility of its measurement. <h3>PATIENTS AND METHODS</h3> (1) Healthy volunteers: in the first part of the study, 20 knees of healthy adult volunteers were radiographed in the weightbearing, anteroposterior extended view, twice, two weeks apart, using three different radiographic procedures: (a) without guidelines, (b) with guidelines and without fluoroscopy, (c) with guidelines and fluroroscopy. (2) Knee OA patients: in the second part of the study, 36 knees of OA patients were radiographed twice with guidelines and without fluoroscopy. JSW was measured blindly using a graduated magnifying glass. Based on the Bland and Altman graphic approach, cut off points defining minimal relevant radiological change are proposed. <h3>RESULTS</h3> Standard deviation (SD) of differences in JSW measurement between two sets of knee radiographs in healthy subjects were 0.66 mm for radiography performed without guidelines, 0.37 mm for radiography performed with guidelines and without fluoroscopy, and 0.31 mm for radiography with guidelines and fluoroscopy. SD of differences in JSW measurement in OA patients were 0.32 mm for radiography performed with guidelines and without fluoroscopy. A minimal relevant change in JSW between two radiographs performed in healthy subjects can be defined by a change of at least 1.29 or 0.59 mm when radiographs are taken without guidelines, and with guidelines and fluoroscopy, respectively. When radiographs are taken with guidelines and without fluoroscopy, the change must be at least 0.73 mm. A similar figure, 0.64 mm was observed in knee OA patients. <h3>CONCLUSION</h3> Definition of radiological progression varies greatly according to the radiographic procedure chosen. Use of guidelines reduces the threshold of progression required to consider that change between two measures is relevant.
Cardiovascular role of angiotensin type1A receptors in the nucleus of the solitary tract of mice
Authors: B. Abegaz, P. J. Davern, K. L. Jackson, T.-P. Nguyen-Huu, J. K. Bassi, A. Connelly, Y.-T. Choong, A. M. Allen, G. A. Head
Journal: Cardiovascular Research (2013)

AimsThe nucleus of the solitary tract (NTS) is important for cardiovascular regulation and contains angiotensin type 1A (AT1A) receptors. To assess its function, we examined the effect of expressing in AT1A receptors in the NTS of mice lacking these receptors.
Long-term Outcome after Pulmonary Endarterectomy
Authors: Angelo G. Corsico, Andrea M. D'Armini, Isa Cerveri, Catherine Klersy, Elena Ansaldo, Rosanna Niniano, Elena Gatto, Cristian Monterosso, Marco Morsolini, Salvatore Nicolardi, Corrado Tramontin, Ernesto Pozzi, Mario Viganò
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

There are few follow-up studies on long-term cardiopulmonary function after pulmonary endarterectomy (PEA), the operation of choice for chronic thromboembolic pulmonary hypertension (CTEPH).To prospectively evaluate long-term outcome of patients with CTEPH treated with PEA.Between 1994 and 2006, 157 patients (mean age 55 yr) were treated with PEA at Pavia University Hospital. The patients were evaluated before PEA and at 3 months (n = 132), 1 year (n = 110), 2 years (n = 86), 3 years (n = 69), and 4 years (n = 49) afterward by NYHA class, right heart hemodynamic, spirometry, carbon monoxide transfer factor (Tl(CO)), arterial blood gas, and treadmill incremental exercise test.Cumulative survival was 84%. Within 3 months, 18 patients died in-hospital and 2 had lung transplantation; during long-term follow-up, 6 died, 1 had lung transplantation, and 3 had a second PEA (2.5 events per 100 person-years). NYHA class III-IV was the most important predictor of late death, lung transplant, or PEA redo (hazard ratio, 3.94). Extraordinary improvement in NYHA class, hemodynamic, and Pa(O(2)) were achieved in the first 3 months (P < 0.001) and persisted during follow-up; exercise tolerance progressively increased over time (P < 0.001). At 4 years, although 74% of the patients were in NYHA class I and none was in class IV, 24% had pulmonary vascular resistance greater than 500 dyne.s/cm(5) or Pa(O(2)) less than 60 mm Hg; they were significantly older and were more frequently in NYHA class III-IV 3 months after surgery than the others.After PEA, long-term survival and cardiopulmonary function recovery is excellent in most patients.
Epithelium Smooth Muscle Regulation and Interactions
Authors: D. SPINA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Section:ChooseTop of pageAbstract <<AIRWAY EPITHELIUM: A SOUR...EPITHELIUM-DERIVED INHIBI...OTHER EPITHELIAL-DERIVED ...DIFFUSION BARRIERMETABOLIC SINKCONCLUSIONReferencesCITING ARTICLES
Cognitive Approaches to Schizophrenia: Theory and Therapy
Authors: Aaron T. Beck, Neil A. Rector
Journal: Annual Review of Clinical Psychology (2004)

A theoretical analysis of schizophrenia based on a cognitive model integrates the complex interaction of predisposing neurobiological, environmental, cognitive, and behavioral factors with the diverse symptomatology. The impaired integrative function of the brain, as well as the domain-specific cognitive deficits, increases the vulnerability to aversive life experiences, which lead to dysfunctional beliefs and behaviors. Symptoms of disorganization result not only from specific neurocognitive deficits but also from the relative paucity of resources available for maintaining a set, adhering to rules of communication, and inhibiting intrusion of inappropriate ideas. Delusions are analyzed in terms of the interplay between active cognitive biases, such as external attributions, and resource-sparing strategies such as jumping to conclusions. Similarly, the content of hallucinations and the delusions regarding their origin and characteristics may be understood in terms of biased information processing. The interaction of neurocognitive deficits, personality, and life events leads to the negative symptoms characterized by negative social and performance beliefs, low expectancies for pleasure and success, and a resource-sparing strategy to conserve limited psychological resources. The comprehensive conceptualization creates the context for targeted psychological treatments.
Therapeutic Targeting of Mitochondrial Superoxide in Hypertension
Authors: Anna E. Dikalova, Alfiya T. Bikineyeva, Klaudia Budzyn, Rafal R. Nazarewicz, Louise McCann, William Lewis, David G. Harrison, Sergey I. Dikalov
Journal: Circulation Research (2010)

Rationale : Superoxide ( ) has been implicated in the pathogenesis of many human diseases including hypertension; however, commonly used antioxidants have proven ineffective in clinical trials. It is possible that these agents are not adequately delivered to the subcellular sites of superoxide production. Objective : Because the mitochondria are important sources of reactive oxygen species, we postulated that mitochondrial targeting of superoxide scavenging would have therapeutic benefit. Methods and Results : In this study, we found that the hormone angiotensin (Ang II) increased endothelial mitochondrial superoxide production. Treatment with the mitochondria-targeted antioxidant mitoTEMPO decreased mitochondrial , inhibited the total cellular , reduced cellular NADPH oxidase activity, and restored the level of bioavailable NO. These effects were mimicked by overexpressing the mitochondrial MnSOD (SOD2), whereas SOD2 depletion with small interfering RNA increased both basal and Ang II–stimulated cellular . Treatment of mice in vivo with mitoTEMPO attenuated hypertension when given at the onset of Ang II infusion and decreased blood pressure by 30 mm Hg following establishment of both Ang II–induced and DOCA salt hypertension, whereas a similar dose of nontargeted TEMPOL was not effective. In vivo, mitoTEMPO decreased vascular , increased vascular NO production and improved endothelial-dependent relaxation. Interestingly, transgenic mice overexpressing mitochondrial SOD2 demonstrated attenuated Ang II–induced hypertension and vascular oxidative stress similar to mice treated with mitoTEMPO. Conclusions : These studies show that mitochondrial is important for the development of hypertension and that antioxidant strategies specifically targeting this organelle could have therapeutic benefit in this and possibly other diseases.
Correlation between lipid and glycogen contents in liver and insulin resistance in high-fat[ndash ]fed rats treated with the lipoprotein lipase activator NO-1886
Authors: Masataka Kusunoki, Kazuhiko Tsutsumi, Tsutomu Hara, Hitoshi Ogawa, Takao Nakamura, Tetsuro Miyata, Fumihiko Sakakibara, Yoshitaka Fukuzawa, Takashi Suga, Shinichi Kakumu, Yutaka Nakaya
Journal: Metabolism (2002)
Control of the establishment of aversive memory by calcineurin and Zif268
Authors: Karsten Baumgärtel, David Genoux, Hans Welzl, Ry Y Tweedie-Cullen, Kyoko Koshibu, Magdalena Livingstone-Zatchej, Céline Mamie, Isabelle M Mansuy
Journal: Nature Neuroscience (2008)