tbuckley/cabot-search huggingface dataset:
Synthetic peptides corresponding to third hypervariable region of human monoclonal IgM rheumatoid factor heavy chains define an immunodominant idiotype.
Authors: R D Goldfien, P P Chen, S Fong, D A Carson
Journal: The Journal of Experimental Medicine (1985)

Synthetic peptides corresponding to eight individual heavy chain complementarity-determining regions (CDR) of three human monoclonal IgM anti-IgG (rheumatoid factor [RF]) paraproteins elicited rabbit antibodies with markedly different properties. All antisera recognized the immunizing peptide, and several reacted with the isolated IgM heavy chain on immunoblots. However, only the antisera against peptides representing the third CDR bound consistently and specifically to the intact IgM-RF molecule. These data indicate that the third CDR of human mu chains comprises an immunodominant idiotype, and suggest that the D gene segment may be especially important in creating idiotypic diversity. Synthetic peptides corresponding to the third heavy chain CDR of human paraproteins may be clinically useful for the specific induction of antiidiotypic antibodies.
Diabetic Ketoacidosis During the Influenza Epidemic
Authors: P. J. Watkins, N. G. Soler, M. G. Fitzgerald, J. M. Malins
Journal: BMJ (1970)

During eight weeks of a recent influenza epidemic 29 patients with ketoacidosis were admitted to the General Hospital, Birmingham. This was an exceptionally large number of cases. Of these, 14 had complained of a cough, nine had clinical evidence of respiratory infection, and four extensive bronchopneumonia. Hypokalaemia was present on admission in several instances and caused respiratory failure and death in three patients. Since the dangers of initial hypokalaemia are increased during the treatment of ketoacidosis, especially when sodium bicarbonate is used, serum potassium levels must be estimated initially and, if necessary, potassium chloride given intravenously at more frequent intervals than usual.
Incidence and characteristics of spirometry in primary care
Authors: Michal Bednarek, Dariusz Kaminski, Teresa Rayska, Witold Pobozy, Barbara Gebala-Jarocka, Marzena Zaluska, Mariola Kumanska, Grzegorz Augustyniak, Dorota Gorecka
Journal: European Respiratory Journal (2013)

Aim: To evaluate incidence and quality of spirometry in primary care.

Methods: In 6 primary care centers (PCC), mean coverage population of 8.000 subjects, spirometry was monitored during 12 months. Each spirometric test was coded by PCC technician/nurse and doctor in structured way and electronically sent to the reference respiratory clinic.

Results: Over 1 year 3.215 spirometries were received, however eligible data with descriptions is limited to 3.004 tests. Mean weekly number of performed tests was 10.3 per centre. Mean subject age 49.6 ±17 years (range 4-93), 58.2% females, 50.8% never smokers, 26.8% current smokers, 17.5% ex-smokers and 4.9% passive smokers. A number of 1.057 subjects (35.2%) performed spirometry for the first time, the remaining 64.8% had it done previously. Mean number of blows was 5.4±1.9 (range 3-10), 88.7% of tests had quick start, 78.1% had smooth outline of flow-volume loop, 81.3% had correct end-of-test criteria. Reproducible (within 200ml) FVC was observed in 78.2%, reproducible FEV1 in 82.5%. ATS criteria of technical quality were met in 67.5% in the evaluation of technician/nurse and 62.1% in the evaluation of doctor. In 1.510 (50.3%) tests the result was normal, in 290 (9.6%) obstructive, in 48 (1.6%) suspected restrictive. The remaining tests were not evaluated due to poor quality.

Conclusions: Spirometry is an indispensable examination in primary care. Its quality is satisfactory and through staff awareness there is hope for improvement over time.

Supported by: National Science Centre grant #N N404 0818343.
Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients With cholesteryl ester storage disease
Authors: Manisha Balwani, Catherine Breen, Gregory M. Enns, Patrick B. Deegan, Tomas Honzík, Simon Jones, John P. Kane, Vera Malinova, Reena Sharma, Eveline O. Stock, Vassili Valayannopoulos, Edmond J. Wraith, Jennifer Burg, Stephen Eckert, Eugene Schneider, Anthony G. Quinn
Journal: Hepatology (2013)

Cholesteryl ester storage disease (CESD), an inherited deficiency of lysosomal acid lipase (LAL), is an underappreciated cause of progressive liver disease with no approved therapy. Presenting features include dyslipidemia, elevated transaminases, and hepatomegaly. To assess the clinical effects and safety of the recombinant human LAL, sebelipase alfa, nine patients received four once-weekly infusions (0.35, 1, or 3 mg·kg(-1) ) in LAL-CL01, which is the first human study of this investigational agent. Patients completing LAL-CL01 were eligible to enroll in the extension study (LAL-CL04) in which they again received four once-weekly infusions of sebelipase alfa (0.35, 1, or 3 mg·kg(-1) ) before transitioning to long-term every-other-week infusions (1 or 3 mg·kg(-1) ). Sebelipase alfa was well tolerated, with mostly mild adverse events unrelated to sebelipase alfa. No antidrug antibodies were detected. Transaminases decreased in patients in LAL-CL01 and increased between studies. In seven patients receiving ongoing sebelipase alfa treatment in LAL-CL04, the mean ± standard deviation (SD) decreases for alanine transaminase and aspartate aminotransferase at week 12 compared to the baseline values in LAL-CL01 were 46 ± 21 U/L (-52%) and 21 ± 14 U/L (-36%), respectively (P ≤ 0.05). Through week 12 of LAL-CL04, these seven patients also showed mean decreases from baseline in total cholesterol of 44 ± 41 mg/dL (-22%; P = 0.047), low density lipoprotein-cholesterol of 29 ± 31 mg/dL (-27%; P = 0.078), and triglycerides of 50 ± 38 mg/dL (-28%, P = 0.016) and increases in high density lipoprotein-cholesterol of 5 mg/dL (15%; P = 0.016).These data establish that sebelipase alfa, an investigational enzyme replacement, in patients with CESD is well tolerated, rapidly decreases serum transaminases, and that these improvements are sustained with long-term dosing and are accompanied by improvements in serum lipid profile.
Primary Prevention of Cardiovascular Disease in Nursing Practice: Focus on Children and Youth
Authors: Laura L. Hayman, Janet C. Meininger, Stephen R. Daniels, Brian W. McCrindle, Liz Helden, Joyce Ross, Barbara A. Dennison, Julia Steinberger, Christine L. Williams
Journal: Circulation (2007)

C ardiovascular disease (CVD) is a leading cause of morbidity and premature mortality in women and men in the United States, most of the industrialized world, and many developing countries. 1Data accumulated over the past 3 decades indicate that atherosclerotic-CVD processes begin early in childhood and are influenced over the life course by genetic and potentially modifiable risk factors and environmental exposures.Taken together, these data provide compelling evidence for primary prevention of CVD beginning early in childhood.Within the pediatric healthcare community, this evidence has prompted and informed the development of science-based guidelines with recommendations for individual/high-risk and population-based approaches to primary prevention of CVD in children and youth.The purpose of this statement is to provide an overview of the evidence and current science-based recommendations and to emphasize the role of advanced practice nurses in the implementation of strategies consistent with population-based and individual/high-risk approaches to CVD prevention in children and youth.The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel.Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
The three attentional networks and the two hemispheric mechanisms
Authors: Uri Fidelman
Journal: Behavioral and Brain Sciences (1995)

Abstract A methodological problem may distort the implications derived from the metabolism scans of the brain, but Posner &amp; Raichle may have found neural networks which underlie the analytical and synthetical hemispheric data processing mechanism. This methodological problem is that a large regional consumption of energy, detected by the PET technique, is not necessarily related to more data processing. It may be related to the inefficiency of the neural system at this region.
Modification by prostaglandins E1 and E2, indomethacin, and arachidonic acid of the vasoconstrictor responses of the isolated perfused rabbit and rat mesenteric arteries to adrenergic stimuli.
Authors: K U Malik, P Ryan, J C McGiff
Journal: Circulation Research (1976)

In isolated perfused rabbit mesenteric arteries, prostaglandin (PG) E1 and E2, 1-5NG/ML, did not alter the basal perfusion pressure, but reduced the vasoconstrictor responses to sympathetic nerve stimulation; the responses to injected norepinephrine were reduced by PGE1 and variably affected by PGE2. In contrast, in rat mesenteric arteries PGE1 and PGE2, 1-5 ng/ml, potentiated the vasoconstrictor responses to nerve stimulation and to injected norepinephrine. In rabbit mesenteric arteries, the inhibitor of PG synthesis, indomethacin, augmented the responses to sympathetic nerve stimulation and to injected norepinephrine, whereas in rat mesenteric arteries indomethacin inhibited the responses to both adrenergic stimuli. Arachidonic acid, a PG precursor, reduced the vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine in rabbit, whereas in rat, potentiation of the responses to adrenergic stimuli occurred. Since these effects of arachidonic acid were abolished by the simultaneous infusion of indomethacin, they appear to be mediated through conversion of arachidonic acid to PG. We conclude that prostaglandins modulate adrenergic transmission in mesenteric arteries and this effect is species dependent.
Randomized Trial of Endobronchial Ultrasound–guided Transbronchial Needle Aspiration under General Anesthesia versus Moderate Sedation
Authors: Roberto F. Casal, Donald R. Lazarus, Kristine Kuhl, Graciela Nogueras-González, Sarah Perusich, Linda K. Green, David E. Ost, Mona Sarkiss, Carlos A. Jimenez, Georgie A. Eapen, Rodolfo C. Morice, Lorraine Cornwell, Sheila Austria, Amir Sharafkanneh, Rolando E. Rumbaut, Horiana Grosu, Farrah Kheradmand
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Data about the influence of the type of sedation on yield, complications, and tolerance of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) are based mostly on retrospective studies and are largely inconsistent.Objectives: To determine whether the type of sedation influences the diagnostic yield of EBUS-TBNA, its complication rates, and patient tolerance.Methods: Patients referred for EBUS-TBNA were randomized (1:1) to undergo this procedure under general anesthesia (GA) or moderate sedation (MS). Pathologists were blinded to group allocation.Measurements and Main Results: The main outcome was "diagnostic yield," defined as the percentage of patients for whom EBUS-TBNA rendered a specific diagnosis. One hundred and forty-nine patients underwent EBUS-TBNA, 75 under GA and 74 under MS. Demographic and baseline clinical characteristics were well balanced. Two hundred and thirty-six lymph nodes (LNs) and six masses were sampled in the GA group (average, 3.2 ± 1.9 sites/patient), and 200 LNs and six masses in the MS group (average, 2.8 ± 1.5 sites/patient) (P = 0.199). The diagnostic yield was 70.7% (53 of 75) and 68.9% (51 of 74) for the GA group and MS group, respectively (P = 0.816). The sensitivity was 98.2% in the GA group (confidence interval, 97–100%) and 98.1% in the MS group (confidence interval, 97–100%) (P = 0.979). EBUS was completed in all patients in the GA group, and in 69 patients (93.3%) in the MS group (P = 0.028). There were no major complications or escalation of care in either group. Minor complications were more common in the MS group (29.6 vs. 5.3%) (P < 0.001). Most patients stated they "definitely would" undergo this procedure again in both groups (P = 0.355).Conclusions: EBUS-TBNA performed under MS results in comparable diagnostic yield, rate of major complications, and patient tolerance as under GA. Future prospective multicenter studies are required to corroborate our findings.Clinical trial registered with www.clinicaltrials.gov (NCT 01430962).
THE IMMUNE RESPONSE TO A HYBRID PROTEIN MOLECULE
Authors: K. Rajewsky, Elke Rottländer, G. Peltre, Brigitte Müller
Journal: The Journal of Experimental Medicine (1967)

Upon immunization with LDH-III (subunit composition AABB) rabbits produce anti-A and anti-B antibodies in comparable amounts. These antibodies fit equally well to the hybrid enzyme and to LDH-V (AAAA) or LDH-I (BBBB) respectively, as tested by passive hemagglutination inhibition. No antibodies reacting with both LDH-I and LDH-V were detected. A minority of hybrid-specific antibodies was, however, present in the sera. Animals primed with LDH-III respond regularly to a boosting injection of LDH-V with the production of large amounts of anti-A (but not anti-B) antibodies. A similar injection of LDH-I stimulates (if it has any effect at all) the production of anti-B antibodies only. Stimulation with one of the pure types does not impair a subsequent response to the other. The majority of the animals primed with LDH-III responded not at all or weakly to a boosting injection of LDH-I, though antibodies to LDH-I were present in the sera at the time of stimulation. This effect can hardly be explained on the basis of serological sepcificity. Hyporesponsiveness to LDH-III can be induced by injection of LDH-V into the newborn. Both anti-A and anti-B titers are equally depressed. Within the dose range tested, LDH-I does not exert any tolerogenic action with respect to LDH-III. The carrier property of subunit A is evident in the induction of both immunity and tolerance to LDH-III. The early phase of the immune response to the hybrid enzyme may be carrier-specific, and receptors for the haptenic subunit B may not exist at that stage.
Homeostasis Model Assessment Is a Reliable Indicator of Insulin Resistance During Follow-up of Patients With Type 2 Diabetes
Authors: Akira Katsuki, Yasuhiro Sumida, Esteban C. Gabazza, Shuichi Murashima, Masahiko Furuta, Rika Araki-Sasaki, Yasuko Hori, Yutaka Yano, Yukihiko Adachi
Journal: Diabetes Care (2001)

OBJECTIVE— To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS— The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (∼1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization. RESULTS— Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P &amp;lt; 0.0001) and after(r = -0.734, P &amp;lt; 0.0001) treatment. Neither the slopes(-0.71 ± 0.12 vs. -0.79 ± 0.09, F = 0.25, P =0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P &amp;lt; 0.0001). CONCLUSIONS— HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes.
Head-up Tilt Test
Authors: Anders Englund, Mia Fredrikson, Ma˚rten Rosenqvist
Journal: Circulation (1997)

Background Patients with bifascicular block have an increased risk of syncopal attacks, but the underlying mechanism often remains unclear despite an extensive diagnostic workup. The head-up tilt test has been established as an important diagnostic tool in the unmasking of vasovagal syncope in patients with unexplained syncope. Its role in the evaluation of patients with bifascicular block has not been studied. Methods and Results A head-up tilt test, using a 60° angle of tilt for 45 minutes without pharmacological provocation, was performed in 25 patients with bifascicular block and syncope that remained unexplained after an extensive invasive and noninvasive electrophysiological investigation. As a control group, 25 subjects with bifascicular block without syncope, matched for age, sex, left ventricular function, and underlying heart disease, were included. A positive head-up tilt test was found in 7 (28%) of the syncope patients and in 8 (32%) of the control subjects ( P =NS). Six patients, of whom 3 had a positive tilt test, had recurrent syncopal attacks during 32 months of follow-up. None of the control subjects had syncope during follow-up. Conclusions This study gives rise to serious concern regarding the specificity of the head-up tilt test in patients with bifascicular block. A head-up tilt test should therefore be interpreted with caution, and its role as a diagnostic tool in this patient category remains to be established.
Using absolute risks to assess the risks and benefits of treatment
Authors: Mitchell H Gail
Journal: Thorax (2014)

Health providers and their patients are accustomed to taking risks and benefits into account when deciding whether or not to use a particular treatment. In some instances the choice is clear cut, as when the treatment has few side effects or the patient has a strong aversion to a particular health outcome. When an intervention has favourable effects on some health outcomes and unfavourable effects on others and patient preferences regarding particular outcomes are unclear, the decision becomes more difficult. Part of the difficulty is simply gathering relevant information for the decision. Most healthcare providers do not have the time to compile information on the effects of an intervention on each health outcome as well as on the absolute risk (or probability) of that outcome in the absence of intervention, which are necessary ingredients for a formal approach to decision making. Yu et al 1 have provided such information to help inform the decision of whether or not to use roflumilast to suppress exacerbations of COPD. They also address whether that decision should be ‘yes’ for some patients and ‘no’ for others.

Yu et al 1 used summary data from the US Food and Drug Administration to evaluate the risks and benefits of roflumilast to prevent exacerbations of COPD. They distinguished between moderate exacerbations and severe exacerbations, defined by hospitalisation or death. They concluded that roflumilast provided a net benefit only to patients at high risk of severe exacerbations. Here I review their methods and assumptions and indicate some opportunities for using additional data for treatment decisions.

The essential ingredients for a treatment decision are: (1) A list of the adverse health outcomes affected by the treatment. We denote the number of such health outcomes by K. For example, Yu et al studied K=11 outcomes, including COPD exacerbation and various …
Premotor biomarkers for Parkinson's disease - a promising direction of research
Authors: Brian R Haas, Tessandra H Stewart, Jing Zhang
Journal: Translational Neurodegeneration (2012)

The second most serious neurodegenerative disease is Parkinson's disease (PD). Over the past several decades, a strong body of evidence suggests that PD can begin years before the hallmark clinical motor symptoms appear. Biomarkers for PD are urgently needed to differentiate between neurodegenerative disorders, screen novel therapeutics, and predict eventual clinical PD before the onset of symptoms. Some clinical evaluations and neuroimaging techniques have been developed in the last several years with some success in this area. Moreover, other strategies have been utilized to identify biochemical and genetic markers associated with PD leading to the examination of PD progression and pathogenesis in cerebrospinal fluid, blood, or saliva. Finally, interesting results are surfacing from preliminary studies using known PD-associated genetic mutations to assess potential premotor PD biomarkers. The current review highlights recent advances and underscores areas of potential advancement.
An Indistinct Balance
Authors: ANATOLE BESARAB, STANLEY FRINAK, JERRY YEE
Journal: Journal of the American Society of Nephrology (1999)

Recombinant epoetin therapy and correction of the chronic anemia of renal failure have greatly reduced the number of red cell transfusions and hence the propensity to iron overload. The majority of HD patients require intravenous iron therapy to achieve the hematocrit levels that correspond to improved outcome measures. Although the short-term benefits of intravenous iron have been clearly defined, the long-term risks of intravenous iron are less well-defined. Iron overload before the availability of epoetin constituted a serious problem; our review of the literature does not decisively conclude that these patients had more serious bacterial infections or increased mortality when compared with their non-iron overloaded counterparts, unless chronic transfusion-related hepatic disease was superimposed. Specifically, no data unequivocally confirm that iron overload from parenteral iron contributes to all-cause patient morbidity or mortality. Furthermore, therapy that maintains intravenous iron optimal iron stores and replaces iron losses associated with the dialytic procedure does not engender iron overload in the carefully monitored patient. Optimized anemia therapy in ESRD requires individualized and specific application of epoetin and iron for each patient, and significant cost savings can result from such a strategy. Prospective studies are clearly necessary to define those parameters that reflect adequacy of iron storage in renal failure patients. We should develop alternative means of iron delivery and develop monitors that accurately discriminate between patients who will respond to additional iron therapy and those who will not. Whether ferritin should be supplanted by another parameter and whether iron itself poses an increased risk to those patients it has so beneficially served are issues that must be resolved. Until these answers are known, the importance of carefully crafted iron therapy cannot be overstated.