The cardiovascular world is definitely not flat.
Explore the source record for details and available documents.
Cardiology↗
Biomedical subjects
P Kaul
Publications and source records attributed to P Kaul.
Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1.
Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.
Administration, Oral↗
Relation between baseline risk and treatment decisions in non-ST elevation acute coronary syndromes: an examination of international practice patterns.
OBJECTIVES: To examine the interaction between ST segment depression on the baseline ECG and subsequent in-hospital revascularisation on six month mortality among patients with non-ST elevation acute coronary syndromes. To examine whether ST segment depression influenced clinical decision making and whether there was international variation in the use of cardiac procedures across ST segment depression categories. METHODS: 11 453 patients enrolled in GUSTO-IIB (global use of strategies to open occluded coronary arteries), PARAGON (platelet IIb/IIIa antagonism for the reduction of acute coronary syndrome events in a global organisation network) -A, and PARAGON-B were studied. Patients were categorised as having no ST segment depression, 1 mm ST segment depression in two contiguous leads, and ST segment depression > or = 2 mm in two contiguous leads. International practice across four geographic regions was examined: USA, Canada, Europe, and Australia/New Zealand. RESULTS: Revascularisation appeared to have no impact on survival among patients with no ST segment depression; however, revascularisation was associated with a significant survival benefit among patients with ST segment depression > or = 1 mm. There was an inverse relation between the extent of ST segment depression and the use of angiography as well as angioplasty (p < 0.01). However, patients with ST segment depression > or = 2 mm were more likely to undergo bypass surgery. The only significant trend of increasing use of revascularisation procedures with increasing ST segment depression was observed in the USA. CONCLUSIONS: International practice patterns in procedure use appear to be insensitive to the extent of ST segment depression. Major opportunities for more efficient delivery of care exist in all regions.
Acute Disease↗
Cardiac resynchronization therapy for congestive heart failure.
Explore the source record for details and available documents.
Adult↗
Effect of metal ions on structure and activity of papain from Carica papaya.
Papain, a powerful proteolytic enzyme, is an endoprotease belonging to cysteine endopeptidase family. It is used extensively in food processing especially in tenderization of meat. In this study, we have made an attempt to show the structure activity relationship of this enzyme and the role of calcium and magnesium ions in the activity and stability of the enzyme. Results of activation and stabilization of the enzyme by these cations showed concentration dependent effect. The enzymatic activity of papain increases to a maximum of 18% and 24% in presence of calcium and magnesium ions at 1 x 10(-3) M concentration, respectively. Thermal denaturation studies showed that the binding of calcium and magnesium ions bring about change in the thermal stability of papain at various concentrations of these metal ions. Far ultraviolet circular dichroic studies showed no significant change in the alpha-helix and beta-sheet structure of the papain upon binding of these metal ions. The mechanism underlying the structure activity relationship of papain in presence of these metal ions have been discussed here with reference to the ionic radii, ligand binding preference, coordination numbers and the electrostatic forces between the protein molecule and cations present in the microenvironment of the enzyme.
Binding Sites↗
Prognostic value of ST segment depression in acute coronary syndromes: insights from PARAGON-A applied to GUSTO-IIb. PARAGON-A and GUSTO IIb Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute Global Organization Network.
OBJECTIVES: Our objectives were to develop a risk-stratification model addressing the importance of the magnitude and distribution of ST segment depression in predicting long-term outcomes and to validate the model in an analogous patient population. BACKGROUND: Although patients without ST segment elevation presenting with acute coronary syndromes represent an increasingly frequent population admitted to coronary care units, little attention has been paid to quantifying their ST segment abnormalities. METHODS: ST segment depression was categorized into three groups: 1) no ST segment depression; 2) 1-mm ST segment depression in two contiguous leads; and 3) ST segment depression > or =2 mm in two contiguous leads. A logistic regression model was developed using Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A) data to assess the prognostic value of the extent and distribution of ST segment depression in predicting one-year mortality. The model was validated using the non-ST segment elevation population in Global Use of Strategies To Open occluded arteries in acute coronary syndromes (GUSTO-IIb). RESULTS: ST segment depression was the strongest predictor of one-year mortality, accounting for 35% of the model's predictive power. Patients with ST segment depression > or =2 mm were approximately 6 times (odds ratio [OR] 5.73, 95% confidence interval [CI] 2.8 to 11.6) more likely to die within one year than patients with no ST segment depression. On validation, the model showed good discriminatory power (c-index = 0.75). Patients with ST segment depression > or =2 mm in more than one region were almost 10 times more likely to die within one year than patients with no ST segment depression. CONCLUSIONS: These data provide new evidence supporting the powerful prognostic value of the baseline electrocardiogram and, in particular, the magnitude and distribution of ST segment depression in predicting unfavorable events.
Angina, Unstable↗
Distribution of cells bearing B-cell alloantigen(s) in North Indian rheumatic fever/rheumatic heart disease patients.
Numerous investigators have developed monoclonal antibodies against B-cell alloantigen(s) of rheumatic fever. However, the developed monoclonals do not have the same significance in all the populations. We have developed a battery of monoclonals against B-cell alloantigens of North Indian rheumatic fever patients. In the present study, we have used these monoclonals to examine the frequency of rheumatic antigens in 30 patients with recurrence of rheumatic activity (RRA), 30 of rheumatic heart disease (RHD) patients and 50 controls using alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. These patients were examined at the time of registry and after three months follow up. RRA patients showed higher percentage of lymphocyte positive as compare to RHD and controls. Interestingly, on follow-up RRA patients showed significant decline in positive lymphocyte as compare to first visit whereas no such change was observed in RHD patients. There were 90-93% of RRA and RHD patients positive with these monoclonals. A significant age variation of rheumatic cells was also noticed in all groups of rheumatic patients. We conclude that monoclonals raised from the same ethnic population are highly specific and cost effective to use them to develop an easy field test system such as APAAP, to identify the individual at risk, to develop rheumatic fever. It is also suggested that the alloantigen marker may persist through out life and gets activated after recurrence of the disease.
Adolescent↗
Evaluating the benefits of increasing measles immunization rates.
OBJECTIVE: To calculate the cost-effectiveness, expressed in dollars per quality-adjusted life years (QALY), of increasing measles immunization rates. DATA SOURCES/STUDY DESIGN: Published data were supplemented by expert opinion. We determined the cost savings and value of the health benefits from averting a single case of measles. Next we examined the U. S. data regarding the relationship between pre-school measles immunization and incidence rates. Finally, we calculated the cost-effectiveness of a program that would increase a locality's immunization rate to the point of disease elimination. PRINCIPAL FINDINGS: Averting a single case of measles, using "base case" assumptions, yields societal cost savings of $2,089 and an increase of 0.086 QALYs. Using a very low discount rate increases the total benefits to $2,251 in societal cost savings and 0.150 QALYs in health benefits. In general, programs to raise measles immunization rates are not cost-effective, except possibly during an outbreak of the disease or in areas with very low immunization rates. The extremely low measles incidence rates in the mid-1990s result in such programs having extremely high costs per QALY gained. CONCLUSIONS: Programs that are narrowly designed to increase immunization rates alone are not likely to be cost-effective. Yet these programs do have the potential to be cost-effective if the program design and evaluation also recognize the benefits associated with the primary and preventive care that can accompany immunizations. Such programs may also be cost-effective if they are components of a global eradication of measles.
Cost Savings↗
Rhinovirus-induced oxidative stress and interleukin-8 elaboration involves p47-phox but is independent of attachment to intercellular adhesion molecule-1 and viral replication.
Virus-induced elaboration of proinflammatory cytokines is mediated by virus-induced oxidative stress. The purpose of these studies was to determine the source of the virus-induced oxidative stress. Inhibition of viral replication with antibody to intercellular adhesion molecule-1 had no effect on virus-induced oxidative stress or interleukin-8 (IL-8) response (597+/-88 vs. 668+/-78 pg/mL in control cells). Treatment of cells with diphenylene iodonium inhibited virus-induced oxidative stress and IL-8 elaboration, but allopurinol, ibuprofen, and rotenone had no effect. Studies in cell lines produced from a patient with gp91-phox deficiency revealed normal responses. In contrast, the oxidative response was decreased and the IL-8 concentration was 227+/-36 pg/mL in cells from a patient with p47-phox deficiency, compared with 664+/-48 pg/mL in control cells. These studies suggest that the stimulation of reactive oxygen species by viral challenge occurs at the cell surface even in the absence of viral replication and involves a flavoprotein that may act in concert with p47-phox.
Allopurinol↗
Influence of metal ions on structure and catalytic activity of papain.
Papain is an endoprotease belonging to cysteine protease family. The catalytic activity of papain in presence of two different metal ions namely zinc and cadmium has been investigated. Both the metal ions are potent inhibitors of the enzyme activity in a concentration dependent manner. The enzyme loses 50% of its activity at 2 x 10(-4) M of CdCl2 and 4 x 10(-4) M of ZnCl2. It is completely inactivated above 1 x 10(-3) M concentration of either ZnCl2 or CdCl2. Of the two metal ions zinc with a ki value of 5 x 10(-5) M is a more potent inhibitor than cadmium which has a ki value of 8 x 10(-5) M. Both the metal ions have higher affinity for active site than the substrate. At concentrations above 1 x 10(-2) M of metal ions the inhibition is not reversible. Calorimetric studies showed decreased thermal stability of papain upon binding of these metal ions. Far UV circular dichroic spectral data showed only small changes in the beta-structure content upon binding of these metal ions. These data are also supported by decrease in the apparent thermal transition temperature of papain by 5 degrees C upon binding of metal ions indicating destabilization of the papain molecule. The mechanism of both partial and complete inactivation of papain in presence of these two metal ions both at lower and higher concentration has been explained.
Cadmium↗
The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells.
A direct correlation has been reported between the severity of symptoms associated with rhinovirus infection and the concentration of interleukin-8 in nasal secretions. The purpose of these studies was to examine the mechanism of rhinovirus-induced IL-8 elaboration. Rhinovirus infection induced oxidative stress in Beas-2b cells and the concentration of H2O2 in supernatant media from rhinovirus challenged cells was 12.5 +/- 6.1 microM 1 h after challenge compared to 0.7 +/- 0.3 microM in supernatant from control cells. N-acetyl cysteine inhibited RV-induced NF-kappaB activation and IL-8 elaboration. IL-8 concentrations were 36 +/- 2 pg/ml and 10 +/- 1 pg/ml 6 h after virus challenge in untreated and NAC-treated (30 mM NAC) cells, respectively. Despite the effects of NAC on IL-8 elaboration and NF-kappaB activation, RV stimulated increases in supernatant H2O2 were not altered by NAC. These data suggest that RV stimulation of IL-8 in respiratory epithelium is mediated through production of oxidative species and the subsequent activation of NF-kappaB.
Acetylcysteine↗
Health services research.
In the past year, several publications have reported on aspects of health services research in regard to musculoskeletal disorders. Utilization studies in the elderly have shown that an effective procedure such as hip arthroplasty may be underused in this population. As well, surgical complications in these patients appear to vary according to the number of procedures performed in a hospital, with high-volume hospitals showing better outcomes. Studies of practice patterns show variations among rheumatologists in the treatment of various rheumatic diseases. Practice variations between physician groups, in particular, rheumatologists versus primary care providers, have also been reported. Several studies show that primary care physicians may have some difficulties in diagnosing common rheumatic disorders. There is some evidence as well that rheumatologists may provide better care for some conditions, such as rheumatoid arthritis. These findings have major implications for restrictions to patient access to specialist care by health organizations. A variety of clinical practice guidelines have been developed and tested, most aimed at general practitioners. Physician compliance with guidelines continues to be low for most implementation strategies. Multidisciplinary programs for the treatment of rheumatoid arthritis appear to have a somewhat beneficial effect. Programs based only on patient education appear to have short-term gains, and longer-term effects are diluted because of noncompliant behaviors.
Health Services Research↗
Effect of nitric oxide on rhinovirus replication and virus-induced interleukin-8 elaboration.
Nitric oxide (NO) has been reported to have disparate effects in different viral infections. We conducted a study to determine whether rhinovirus (RV) infection is associated with production of NO, and to assess the effect of NO on RV-induced interleukin-8 (IL-8) elaboration both in vitro in monolayers of BEAS-2B cells, an immortalized respiratory epithelial cell line, and in MRC-5 cells, a diploid human embryonic lung fibroblast cell line, challenged with purified RV type 39, as well as in vivo, in experimental infections with RV type 23. Virus replication was not affected by pretreatment of cell monolayers with any of three different NO donors, and RV infection did not stimulate production of NO. Pretreatment of cell monolayers with either NO donors or inhibitors of NO synthase had no effect on RV-induced IL-8 elaboration measured either 6 or 24 h after virus challenge. Nasal wash specimens from RV-infected volunteers contained low concentrations of nitrite that were not different from the concentrations in specimens from sham-challenged subjects. The concentration of nitrite in these specimens did not change over the course of the subjects' rhinoviral illness. These results suggest that NO does not participate in the pathogenesis of RV infections.
Cell Line↗
The cost-effectiveness of magnetic resonance imaging for patients with internal derangement of the knee.
Magnetic resonance imaging (MRI) has excellent specificity and sensitivity for the diagnosis of internal derangement of the knee (IDK). The use of MRI to screen patients with suspected IDK could avoid unnecessary arthroscopies with a reduction in costs. The purpose of this study was to evaluate the use of arthroscopy among patients with IDK, and to estimate the potential cost-effectiveness of MRI in these patients to avoid unnecessary arthroscopies. The study was based on a retrospective cohort of all patients attending three orthopedic clinics between April and September 1993 with a new diagnosis of IDK. Charts were reviewed in 1994 to allow for a follow-up of more than 6 months. An economic evaluation was performed based on cost-effectiveness ratios (per averted arthroscopy), including direct and indirect costs. There were 241 patients with a new diagnosis of IDK (67% males, mean age 35 +/- 12 years), and 110 (46%) underwent arthroscopy. The remaining patients received conservative therapy and were not scheduled for arthroscopy within the period of observation. Using a priori established criteria, 10% of the arthroscopies could be considered diagnostic only (e.g., normal knee) and 27% were of doubtful efficacy from a therapeutic perspective (e.g., debridement alone). Many of these arthroscopies could have been avoided by performing a prior MRI. Using these findings, we conducted decision tree analyses of the use of MRI among patients requiring arthroscopy of the knee. A sensitivity analysis was performed to evaluate the various model assumptions. In general, MRI appeared to be a cost-effective diagnostic procedure for patients with IDK requiring arthroscopy of the knee, and there were cost savings associated with it in some of the models tested.
Adult↗
Serum S100beta release after coronary artery bypass grafting: roller versus centrifugal pump.
BACKGROUND: Microemboli generated during cardiopulmonary bypass (CPB) are implicated in the cerebral injury seen after coronary artery bypass grafting. Centrifugal pumps generate fewer microemboli than roller pumps. Increased S100beta levels have been reported after coronary artery bypass grafting, with levels greater than 1 ng/mL resulting in poorer neuropsychologic outcome. This study investigated the potential neurologic benefits of centrifugal pumps, by using S100beta as a marker for cerebral injury. METHODS: Thirty-two patients who had coronary artery bypass grafting were randomly assigned to two groups. Serial blood samples (preoperative, end of bypass, 30 minutes, and 2 and 24 hours after cardiopulmonary bypass) were taken and the serum analyzed for S100beta using a new immunoluminometric assay. RESULTS: Both groups were matched for age, number of grafts, and cardiopulmonary bypass and cross-clamp times. Postoperative serum S100beta levels were significantly higher in both groups than preoperative levels. Peak S100beta levels did not correlate with cardiopulmonary bypass time; however, 24-hour S100beta levels correlated with intubation time r = 0.40, p = 0.04). Th ere was no significant difference in S100beta levels between the groups at any of the time points. CONCLUSIONS: S100beta levels increased after coronary artery bypass grafting. Centrifugal pumps do not significantly decrease S100beta release. Persistently increased S100beta levels are associated with longer intubation times.
Calcium-Binding Proteins↗
Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin.
Acidic conditions within the endosomal lumen induce the T domain of receptor-bound diphtheria toxin (DT) to insert into the endosomal membrane and mediate translocation of the toxin's catalytic domain to the cytosol. A conformational rearrangement in the toxin occurring near pH5 allows a buried apolar helical hairpin of the native T domain (helices TH8 and TH9) to undergo membrane insertion. If the inserted hairpin spans the bilayer, as hypothesized, then the two acidic residues within the TL5 interhelical loop, Glu 349 and Asp 352, should become exposed at the neutral cytosolic face of the membrane and reionize. To investigate the roles of these residues in toxin action, we characterized mutant toxins in which one or both acidic residues had been replaced with nonionizable ones. Each of two double mutants examined showed a several-fold reduction in cytotoxicity in 24-h Vero cell assays (sixfold for E349A + D352A and fourfold for E349Q + D352N), whereas the individual E349Q and D352N mutations caused smaller reductions in toxicity. The single and double mutations also attenuated the toxin's ability to permeabilize Vero cells to Rb+ at low pH and decreased channel formation by the toxin in artificial planar bilayers. Neither of the double mutations affected the pH-dependence profile of the toxin's conformational rearrangement in solution, as measured by binding of the hydrophobic fluorophore, 2-p-toluidinyl-naphthalene 6-sulfonate. The results demonstrate that, although there is no absolute requirement for an acidic residue within the TL5 loop for toxicity, Glu 349 and Asp 352 do significantly enhance the biological activity of the protein. The data are consistent with a model in which ionization of these residues at the cytosolic face of the endosomal membrane stabilizes the TH8/TH9 hairpin in a transmembrane configuration, thereby facilitating channel formation and translocation of the toxin's catalytic chain.
Animals↗
Calculogenic potential of galactose and fructose in relation to urinary excretion of lithogenic substances in vitamin B6 deficient and control rats.
OBJECTIVE: Calculogenic potential of refined sugars galactose and fructose was examined in vitamin B6 deficient and control rats in terms of their capacity to increase urinary excretion of lithogens. METHODS: Male albino rats were fed vitamin B6 deficient diet with 51.7% sucrose+ starch or galactose or fructose as the source of carbohydrate. Pair-fed controls were maintained for all the groups for a period of four weeks. Twenty-four hour urine samples obtained at weekly intervals were analyzed for creatinine, calcium, oxalate, phosphate and uric acid. Microscopic urinalysis was performed at the end of the study. RESULTS: Urinary calcium excretion increased with respect to baseline in all groups except vitamin B6 control group. On day 28, galactose and fructose-fed rats demonstrated significant hypercalciuria as compared to the sucrose + starch fed group. Vitamin B6 deficient rats (irrespective of the sugar fed) excreted significantly greater urinary calcium compared to pair-fed controls. Oxalate excretion was significantly increased in rats fed galactose compared to those fed fructose or sucrose + starch. Vitamin B6 deficiency further increased oxalate excretion by 1.5, 1.9 and 1.7 fold in sucrose + starch, fructose or galactose fed animals, respectively. Urinary uric acid excretion was enhanced only in fructose-fed rats. There was no change in urinary excretion of creatinine and phosphate in different experimental and control groups. Increased urinary saturation with lithogens caused pronounced crystalluria in all the vitamin B6 deficient groups as well as galactose control group. CONCLUSION: The results suggest galactose ingestion is associated with a greater propensity to form calcium oxalate kidney stones than fructose. Calculogenic potential of galactose and fructose is further enhanced in vitamin B6 deficiency.
Animals↗
Membrane-protein interaction and the molten globule state: interaction of alpha-lactalbumin with membranes.
The insertion of soluble proteins into membranes has been a topic of considerable interest. We have studied the insertion of bovine alpha-lactalbumin into single-bilayer vesicles prepared from egg phosphatidylcholine (PC). Fluorescence studies indicated rapid and tight binding of apo-alpha-lactalbumin (apo-alpha-LA) to PC vesicles as a function of pH. The binding was maximal at pH values which favor the formation of the molten globule state. As an increase of hydrophobic surface is observed in the molten globule state, this conformational state can provide a molecular basis for insertion of soluble proteins into membranes. The membrane-bound complex formed at low pH (3.0) could be isolated and was found to be stable at neutral pH. The structural characterization of the apo-alpha-LA-PC complex was studied by fluorescence quenching using iodide, acrylamide, and 9,10-dibromostearic acid. The results obtained indicated that some of the tryptophans of apo-alpha-LA were buried in the membrane interior and some were exposed on the outer side. Fluorescence quenching and CD studies indicated the membrane-bound conformation of apo-alpha-LA was some conformational state that is between the soluble, fully folded conformation and the molten globule state.
Acrylamides↗