tbuckley/cabot-search huggingface dataset:
Enhancement of regional myocardial efficiency and persistence of perfusion, oxidative, and functional reserve with paired pacing of stunned myocardium.
Authors: S R Bergmann, C J Weinheimer, M A Brown, J E Perez
Journal: Circulation (1994)

BACKGROUND Stunned myocardium reflects postreperfusion dysfunction in myocardium that is destined to ultimately fully recover. Most investigators attribute postreperfusion stunning to a primary defect in excitation-contraction coupling or to an altered sensitivity of the myofilaments to calcium. The aim of the present study was to evaluate the interrelation between myocardial perfusion, oxidative metabolism, and function in an effort to better characterize the phenomenon of myocardial stunning, to define the regional efficiency of stunned myocardium, and to characterize its reserve capacity. METHODS AND RESULTS Regional myocardial perfusion (measured with radiolabeled microspheres), myocardial oxygen consumption (MVO2) (quantified with positron emission tomography using 1-11C-acetate), and myocardial function (assessed with two-dimensional echocardiography) were evaluated in 12 anesthetized, closed-chest dogs subjected to 15 minutes of left anterior descending coronary artery occlusion followed by reperfusion. To evaluate flow, oxidative, and functional reserve after measurements were obtained 1 hour after reperfusion, dogs were subjected to paired pacing (an inotropic stimulus that does not alter systemic hemodynamics), and measurements were repeated. One hour after reperfusion, stunned myocardium was characterized by near-normal levels of myocardial perfusion (0.57 +/- 0.13 mL/g per minute, 81 +/- 13% of that in remote, normal regions) but severe dyskinesis (echo score, 2.6 +/- 0.7; percent wall thickening, 14 +/- 20%). Despite the low level of contractile function, MVO2 averaged 1.72 +/- 0.7 mumol/g per minute, 71 +/- 27% of that observed in remote myocardium. Regional myocardial efficiency (systolic wall thickening divided by MVO2) was markedly diminished. With paired pacing, myocardial perfusion increased proportional to that in remote myocardium, systolic function improved (echo score, 1.4 +/- 0.7; percent wall thickening, 30 +/- 15%), and regional MVO2 nearly doubled (to 3.41 +/- 1.82 mumol/g per minute, P &lt; .05 for each paired measurement). Importantly, with paired pacing, regional myocardial efficiency nearly normalized in reperfused myocardium. CONCLUSIONS Stunned myocardium is characterized by near-normal levels of perfusion and oxygen consumption despite marked dyskinesis. Myocardial efficiency is poor. With inotropic stimulation (in the present study, paired pacing), reperfused myocardium demonstrated considerable perfusion, oxidative, and functional reserve and a dramatic improvement in myocardial efficiency. These results may have implications for the treatment of postreperfusion pump failure.
Study of Completed Archaeal Genomes and Proteomes: Hypothesis of Strong Mutational AT Pressure Existed in Their Common Predecessor
Authors: Vladislav V. Khrustalev, Eugene V. Barkovsky
Journal: Genomics Proteomics & Bioinformatics (2010)

Abstract The number of completely sequenced archaeal genomes has been sufficient for a large-scale bioinformatic study. We have conducted analyses for each coding region from 36 archaeal genomes using the original CGS algorithm by calculating the total GC content (G+C), GC content in first, second and third codon positions as well as in fourfold and twofold degenerated sites from third codon positions, levels of arginine codon usage (Arg2: AGA/G; Arg4: CGX), levels of amino acid usage and the entropy of amino acid content distribution. In archaeal genomes with strong GC pressure, arginine is coded preferably by GC-rich Arg4 codons, whereas in most of archaeal genomes with G+C&amp;lt;0.6, arginine is coded preferably by AT-rich Arg2 codons. In the genome of Haloquadratum walsbyi, which is closely related to GC-rich archaea, GC content has decreased mostly in third codon positions, while Arg4&amp;gt;&amp;gt;Arg2 bias still persists. Proteomes of archaeal species carry characteristic amino acid biases: levels of isoleucine and lysine are elevated, while levels of alanine, histidine, glutamine and cytosine are relatively decreased. Numerous genomic and proteomic biases observed can be explained by the hypothesis of previously existed strong mutational AT pressure in the common predecessor of all archaea.
Prediction of severity of coronary artery disease using slope of submaximal ST segment/heart rate relationship
Authors: M S ELAMIN, D A S G MARY, D R SMITH, R J LINDEN
Journal: Cardiovascular Research (1980)

A new exercise electrocardiography test has been examined in patients with angina pectoris; the rate of development of ST segment depression with respect to increases in heart rate during exercise on a bicycle ergometer was measured during exercise using 13 leads in 64 patients. The steepest slope of regression lines relating displacement of ST segment to increases in heart rate (maximal ST/HR slope) was used as an index of myocardial ischaemia and was compared with the results of coronary angiography which were determined by the radiologists and the cardiologist responsible for the management of these patients. The maximal ST/HR slope could be derived consistently from a linear ST/HR relationship (r≥0.95) only in 50 patients with significant coronary artery disease (≥75% luminal narrowing). The ranges of the maximal ST/HR slope in 17 patients with single-vessel disease, in 18 patients with double-vessel disease and in 15 patients with triple-vessel disease were different from each other and the differences between the means were statistically significant (P <0.0005). The maximal ST/HR slopes for the patients with single-vessel disease were also different from those in the 14 patients in whom significant coronary disease could not be demonstrated. In contrast, the criteria of heart rate at which ST segment depression began, maximum ST segment depression, rate-pressure product and heart rate attained at the end of the test showed an overlap between the groups of the patients studied; using the usual exercise test criteria in the same population, there were three false negative results, one false positive result and the results in eight of the patients were indeterminate. It is concluded that the maximal ST/HR slope, used as an index of myocardial ischaemia, reliably predicted the presence and severity of coronary artery disease, as determined by coronary arteriography in each of the patients with anginal pain.
Cervico-oculo-acoustic Dysplasia
Authors: W. I. Fraser, R. C. MacGillivray
Journal: BMJ (1970)

The 14-day Gemini and 18-day Soyuz missions dispel the dire prophecy that man's bones may fold up after three or four weeks in the weightless state.Artificial gravity may have an important part to play in the exploration of the solar system, particularly with regard to changes in cardiovascular function,7 but refrigeration is in the realm of science fiction rather than the logical development of aerospace physiology.-I
Pneumococcal Infections and Sickle Cell Disease-Reply
Authors: Maurice A. Mufson
Journal: JAMA (1982)

<h3>In Reply.—</h3> I agree with Dr Eustatia that children with sickle cell disease suffer high risk of bacteremic pneumococcal disease and fatal outcome. It is likely that their underlying functional hyposplenism or autosplenectomy accounts for this unique susceptibility to serious pneumococcal infections. The incidence of pneumococcal infection in persons with sickle cell anemia is 40/1,000/yr and of pneumococcal meningitis it is 5.8/ 1,000/yr. These important points were emphasized in my article. Additionally, some persons with sickle cell anemia have a defect in the alternate pathway of complement activation.<sup>1</sup>This is another reason to administer pneumococcal vaccine, since it induces antibody that can activate the classic pathway of complement. I am pleased to learn that pneumococcal vaccine is given to all children with sickle cell disease residing in Curaçao. Such a program can be expected to reduce the incidence of serious pneumococcal infection in these children. Immunization with pneumococcal vaccine
Brilliant Blue FCF as an Alternative Dye for Saphenous Vein Graft Marking
Authors: Igor V. Voskresensky, Eric S. Wise, Kyle M. Hocking, Fan Dong Li, Michael J. Osgood, Padmini Komalavilas, Colleen Brophy, Joyce Cheung-Flynn
Journal: JAMA Surgery (2014)

Surgical skin markers are used off-label to mark human saphenous veins (HSVs) to maintain orientation before implantation as aortocoronary or peripheral arterial bypass grafts. These surgical skin markers impair functional responses of the HSV tissue.To investigate the effect of brilliant blue dye 1 (brilliant blue FCF [for food coloring]; hereinafter, FCF) as a nontoxic alternative marking dye and to determine whether FCF has pharmacological properties.Segments of HSVs were collected in university hospitals from patients undergoing coronary artery bypass grafting procedures immediately after harvest (unmanipulated) or after typical intraoperative surgical graft preparation (after manipulation). Rat inferior venae cavae were used to determine the pharmacological properties and cellular targets of FCF. Endothelial and smooth muscle functional responses were determined in a muscle bath, and intimal thickening in HSVs was determined after 14 days in organ culture.Contractile responses were measured in force and converted to stress. Smooth muscle function was expressed as maximal responses to potassium chloride depolarization contractions. Endothelial function was defined as the percentage of relaxation of maximal agonist-induced contraction. Neointimal thickness was measured by histomorphometric analysis.Human saphenous veins stored in the presence of FCF had no loss of endothelial or smooth muscle function. Unmanipulated HSVs preserved in the presence of FCF demonstrated a significant increase in endothelial-dependent relaxation (mean [SEM], 25.2% [6.4%] vs 30.2% [6.7%]; P = .02). Application of FCF to functionally nonviable tissue significantly enhanced the smooth muscle responses (mean [SEM], 0.018 [0.004] × 10⁵ N/m² vs 0.057 [0.016] × 10⁵ N/m²; P = .05). Treatment with FCF reduced intimal thickness in organ culture (mean [SEM], -17.5% [2.1%] for unmanipulated HSVs vs -27.9% [3.7%] for HSVs after manipulation; P < .001). In rat inferior venae cavae, FCF inhibited the contraction induced by the P2X7 receptor agonist 2'(3')-O-(4-benzoyl)benzoyl-adenosine-5'-triphosphate (mean [SEM], 14.8% [2.2%] vs 6.5% [1.8%]; P = .02) to an extent similar to the P2X7 receptor antagonist oxidized adenosine triphosphate (mean [SEM], 5.0% [0.9%]; P < .02 vs control) or the pannexin hemichannel inhibitor probenecid (mean [SEM], 7.3% [1.6%] and 4.7% [0.9%] for 0.5mM and 2mM, respectively; P < .05).Treatment with FCF did not impair endothelial or smooth muscle function in HSVs. Brilliant blue FCF enhanced endothelial-dependent relaxation, restored smooth muscle function, and prevented intimal hyperplasia in HSVs in organ culture. These pharmacological properties of FCF may be due to P2X7 receptor or pannexin channel inhibition. Brilliant blue FCF is an alternative, nontoxic marking dye that may improve HSV conduit function and decrease intimal hyperplasia.
Pharmacokinetics, Safety, and Efficacy of Trastuzumab Administered Every Three Weeks in Combination With Paclitaxel
Authors: Brian Leyland-Jones, Karen Gelmon, Jean-Pierre Ayoub, Andrew Arnold, Shail Verma, Reg Dias, Parviz Ghahramani
Journal: Journal of Clinical Oncology (2003)

Purpose: This phase II study evaluated the pharmacokinetics and safety of trastuzumab and paclitaxel given every 3 weeks to women with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer. Patients and Methods: Thirty-two patients received a loading dose of trastuzumab 8 mg/kg intravenously (day 1) and paclitaxel 175 mg/m 2 (day 0). Thereafter, trastuzumab 6 mg/kg was administered on the same day as paclitaxel 175 mg/m 2 every 3 weeks for seven cycles. In responding patients, trastuzumab monotherapy every 3 weeks was then continued until disease progression or patient withdrawal. Results: Trastuzumab trough levels were more than 20 μg/mL by the end of cycle 1. The half-life of trastuzumab was estimated to be 18 to 27 days, although this may be an underestimate. The combination of paclitaxel and trastuzumab was generally well tolerated, with no unexpected toxicities and no pharmacokinetic interaction. The most common adverse events were myalgia, paresthesias, alopecia, arthralgia, and fatigue. Events associated with trastuzumab included infusion-related reactions and cardiac dysfunction. Ten patients had a ≥ 15% decrease in ejection fraction, but only one had symptomatic heart failure. The investigator-assessed objective response rate was 59% (four complete and 15 partial responses) and seven patients (22%) had stable disease. The median duration of response was 10.5 months and median time to progression was 12.2 months. Conclusion: Additional investigation of trastuzumab administered every 3 weeks is warranted. In combination with paclitaxel, it is generally well tolerated. Plasma trastuzumab trough levels and clinical response rates compare favorably with those achieved with the standard weekly trastuzumab regimen plus chemotherapy. The presence of trastuzumab does not alter exposure to paclitaxel.
Autonomic Nerve Testing Predicts the Development of Complications
Authors: Ann M. Maguire, Maria E. Craig, Anne Craighead, Albert K.F. Chan, Janine M. Cusumano, Stephen J. Hing, Martin Silink, Neville J. Howard, Kim C. Donaghue
Journal: Diabetes Care (2006)

Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests.From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0-16.8], duration of diabetes 6.3 years [4.0-9.6], and A1C 8.3% [7.5-9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35).At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P = 0.016) and retinopathy (4.83 [1.3-17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later.In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.
Seasonal Changes in IgE Antibodies and Their Relationship to IgG Antibodies during Immunotherapy for Ragweed Hay Fever
Authors: John W. Yunginger, Gerald J. Gleich
Journal: Journal of Clinical Investigation (1973)

Seasonal changes in IgE antibodies and their relationship to IgG antibodies were studied in 52 patients with ragweed hay fever and 10 normal controls. Allergic patients received either no immunotherapy, preseasonal immunotherapy, or high dose perennial immunotherapy with aqueous-mixed ragweed extract. Serums were collected before, during, just after, and 4 mo after the ragweed pollination season. IgE antibodies to ragweed antigen E (AgE) were measured using the radioallergosorbent test, and IgG antibodies were measured by radioimmunoprecipitation.IgE antibodies to AgE were elevated in all allergic patients, and rose during the ragweed pollination season. The magnitude of the rise in IgE antibody was a function of the preseasonal IgE antibody level. IgE antibody production in the treated groups was the same as in the untreated group when patients were matched on the basis of their preseasonal IgE antibody levels. Thus, we were not able to confirm previous reports that immunotherapy suppresses the seasonal rise in IgE antibodies. Furthermore, there was a close relationship between the levels of IgE and IgG antibodies in the high dose group. This finding is contrary to what one would expect were IgG antibodies acting to suppress the formation of IgE antibodies. Rather, it suggests that in certain patients either humoral immunological reactivity to ragweed antigens in the IgG and IgE classes is low to begin with or that this reactivity may wane after treatment with high doses of ragweed extract.
North of England evidence based guidelines development project: methods of developing guidelines for efficient drug use in primary care
Authors: M. Eccles, N. Freemantle, J. Mason
Journal: BMJ (1998)

Practice guidelines are valid if “they lead to the health gains and costs predicted for them.”1 When implemented, valid guidelines lead to changes in clinical practice and improvements in outcomes for patients.2-5 Invalid guidelines, however, may lead to the use of ineffective interventions that waste resources, or even to harm.

Guidelines must offer recommendations for both effective and efficient care, and these have not previously been available in the United Kingdom. We have reported the development and content of guidelines for primary care in the United Kingdom based explicitly on evidence of effectiveness.6-9 Here, we present the methods used to develop evidence based guidelines on the use in primary care of four important groups of drugs—angiotensin converting enzyme inhibitors in patients with heart failure, choice of antidepressants, non-steroidal anti-inflammatory drugs in patients with osteoarthritis, and aspirin as an antithrombotic agent.10-13 Abridged versions of the guidelines on angiotensin converting enzyme inhibitors, aspirin, and non-steroidal anti-inflammatory drugs will be published in subsequent articles.14-16

#### Summary points

Guideline development groups defined important clinical questions, produced search criteria, and drew up protocols for systematic review and, where appropriate, meta-analysis

Medline and Embase were searched for systematic reviews and meta-analyses, randomised trials, quality of life studies, and economic studies

Meta-analysis was used extensively by the group to answer specific clinical questions

Statements on evidence were categorised in relation to study design, reflecting their susceptibility to bias

Strength of recommendations was graded according to the category of evidence and its applicability, economic issues, values of the guideline group and society, and the groups' awareness of practical issues

Recommendations cease to apply in December 1999, by which time relevant results that may affect recommendations may be known

Guideline development groups comprised three broad classes of members—relevant healthcare professionals (up to five general practitioners (all with …
Regulator of devices investigates complaints about multifocal lens
Authors: C. Dyer
Journal: BMJ (2015)

The UK regulator of healthcare products is investigating reports that patients who had the intraocular lens Mplus X implanted have experienced problems with distance vision.

Moorfields Eye Hospital in London has said that it has discontinued using the multifocal lens, which is used to treat nearsightedness, and has reported problems with “a very small number” of patients to the Medicines and Healthcare Products Regulatory Agency (MHRA). The agency later received reports about the lens from three other surgeons through its yellow card system.

A spokeswoman for the hospital said, “Two surgeons had used these lenses in a very small number of patients, but some of these cases …
Blastomycosis
Authors: Michael L. Furcolow
Journal: JAMA (1966)

With recent knowledge of blastomycosis, emphasis is placed on the frequency of the disease in the Midwest and South. Comparison of summarized clinical and epidemiologic information with the findings in 183 cases of blastomycosis from the state of Kentucky exemplifies this point: The frequency of this disease in Kentucky suggests that the disease is endemic throughout most of the state, with the exception of the mountainous eastern part. The data presented suggest that recognition is delayed in most cases and that many cases are unrecognized. This supposition is supported by the frequency of cutaneous lesions as opposed to the frequency of purely pulmonary lesions. The pulmonary forms appear to be the most frequently missed. It is hoped that these data will stimulate better recognition and a higher index of suspicion on the part of practicing physicians.
TOXIC SUBSTANCES PRODUCED BY PNEUMOCOCCUS
Authors: Rufus Cole
Journal: The Journal of Experimental Medicine (1912)

1. The filtered blood serum of rabbits infected with pneumococci is not toxic. 2. Extracts of pneumococci prepared by keeping emulsions of the bacteria in salt solution at 37 degrees C. for varying periods of time may be toxic, and when injected intravenously into guinea pigs, may produce a train of symptoms followed by acute death resembling that seen in acute anaphylaxis. Such extracts, however, are not uniformly toxic and it has been impossible to discover the exact conditions under which such extracts become toxic. 3. When the centrifugalized peritoneal washings of guinea pigs infected with pneumococci are injected into the circulation of normal guinea pigs, these animals very frequently exhibit symptoms like those seen in acute anaphylaxis, and a considerable proportion of the animals die acutely. 4. When pneumococci are dissolved in dilute solutions of bile salts and the solution resulting is injected intravenously into rabbits and guinea pigs, these animals show with great constancy the same symptoms that are seen in acute anaphylaxis. The solution of pneumococci in bile may occur in ten minutes at 37 degrees C. or in half an hour on ice. This is considered evidence that the toxicity of the solution does not result from digestion of the bacterial protein, but is due to substances preformed in the bacterial cells and set free on their solution. The toxicity of the solution is diminished or destroyed by heating to 55 degrees C. or over.
Raised plasma glutathione S-transferase values in hyperthyroidism and in hypothyroid patients receiving thyroxine replacement.
Authors: R J Mardell, T R Gamlen
Journal: BMJ (1985)

are inconclusive, but Chamberlain et al have shown that chronically hypertensive women who do not get pre-eclampsia can expect a normal perinatal outcome.3It therefore seems a pity that all the authors' patients have been grouped together and that there is no separate analysis according to the severity of the hypertension.Some of their patients seem to have been overtreated, and this would limit the validity of their conclusions on the benefit of oxprenolol in pregnancy.
Large-Bowel Obstruction Secondary to Localized Rectal Giant Pseudopolyposis Complicating Ulcerative Colitis: First Reported Case
Authors: D. P. Hurlstone
Journal: Endoscopy (2002)

Localized giant pseudopolyposis is a rare complication of ulcerative colitis and Crohn’s disease [1]. However, the formation of pseudopolyps in ulcerative colitis, is more common. Incidence rates reported vary from 12.5 % to 74 % [2] [3].