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PubMed1983

Peripheral metabolism of thyroid hormones in man. I. Direct measurement of the conversion rate of thyroxine to 3,5,3'-triiodothyronine (T3) and determination of the peripheral and thyroidal production of T3.

We describe here a new method for the direct measurement of the conversion rate of T4 to T3 in man. The metabolic study was performed in 23 subjects: 13 healthy controls, 7 T4-treated hypothyroids, and 3 sick euthyroid patients. The experimental protocol involved the simultaneous iv bolus injection of [125I]T4 and [131I]T3, and the use of Sephadex G-25 column chromatography to determine the plasma concentrations of [125I]T4, [131I]T3, and [125I]T3 newly formed through 5'-monodeiodination of labeled T4 in the peripheral tissues. The T4 and T3 kinetic parameters were determined by noncompartmental analysis. The conversion rate of T4 to T3 was computed by a method based on the precursor-product relationship, using the [131I]T3 disappearance curve for correcting the concentrations of newly formed [125I]T3 (convolution method). The conversion rate of T4 to T3 was 0.2541 +/- 0.0125 (mean +/- SEM) in the control group and was significantly reduced (0.1283 +/- 0.0204; P less than 0.001) in the sick euthyroid patients, while it was slightly, though not significantly, increased in the T4-treated patients (0.2932 +/- 0.0220). A close agreement was found between the values for the conversion rate obtained by the convolution approach and those derived from the ratio between the serum concentrations of [125I]T3 and [125I]T4 at equilibrium. The conversion rates obtained by the convolution approach were also in good agreement with the values estimated from the molar ratio between the turnover rates of T3 and T4. In the control group, 72.0 +/- 3.6% of the circulating T3 was produced by 5'-monodeiodination of T4 in the peripheral tissues, and 28.0 +/- 3.6% of the circulating T3 derived from direct thyroidal secretion. The sick euthyroid patients showed a significantly smaller proportion of circulating T3 deriving from peripheral conversion of T4 (52.5 +/- 3.9%; P less than 0.025).

Adult↗
PubMed1991

Postinsertional processing of sucrase-alpha-dextrinase precursor to authentic subunits: multiple step cleavage by trypsin.

Sucrase-alpha-dextrinase, a hybrid digestive carbohydrase of the intestinal brush border, is initially synthesized and transported to the surface membrane as a single-chain glycoprotein, P, which is then cleaved to alpha- and beta-subunits, presumably by one or more pancreatic proteases. However, efforts to convert P under controlled conditions to authentic alpha and beta have been unsuccessful. Sucrase-dextrinase immunoprecipitates from rats intraintestinally labeled with [3H]leucine or [35S]methionine without presence of biliary-pancreatic secretions revealed only the 230-kDa P precursor. Restoration of intestinal flow converted the brush border P to the alpha- (140 kDa) and beta- (125 kDa) subunits. Biliary plus pancreatic secretions facilitated this postinsertional cleavage, but bile alone played no role in conversion. When isolated brush borders, prelabeled in vivo, were exposed to a mixture of pancreatic proteases at physiological concentrations, P was converted to authentic alpha and beta, but only trypsin was responsible for the conversion. Kinetic analysis in prelabeled isolated brush-border vesicles revealed the appearance of several intermediate species (205-145 kDa) produced either by endogenous membrane proteases or by trypsin itself. Reconstituted duodenal luminal contents yielded a fragmentation pattern identical to that produced by trypsin alone. Trypsin was necessary and sufficient for processing of the intermediate precursors to the final authentic alpha- and beta-subunits. Based on the alpha- to beta radioactivity ratio and the known amino acid composition of the subunits, differential cleavage occurred with relatively greater production of the beta-subunit (alpha-to-beta molar ratio = 0.77). The conversion of P to the alpha- and beta-units, rather than occurring in a single step after membrane insertion, is differentially catalyzed by trypsin trimming to unequal amounts of the subunits involving a complex series of cleavage steps.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Bioconversion of isopropanol by a solvent tolerant Sphingobacterium mizutae strain.

The bioconversion of high concentration isopropanol (2-propanol, IPA) was investigated by a solvent tolerant strain of bacteria, which was identified as Sphingobacterium mizutae ST2 by partial 16S rDNA gene sequencing. This strain of bacteria exhibited the ability to utilise high concentration isopropanol as the sole carbon source, with mineralization occurring via an acetone intermediate into central metabolism. The biodegradative performance of this strain for IPA was examined over a 2-38 g l(-1) concentration range, using specific growth rate (mu) and conversion rate analysis. Maximum specific growth rates (mu(max)) of 0.0045 h(-1 )were routinely obtainable on IPA. In addition, the highest specific IPA degradation rate was obtained at a concentration of 7.5 g l(-1) with a corresponding value of 0.045 g IPA g cells(-1) h(-1). While the highest acetone yield reached its maximum value of 0.940 g acetone g IPA(-1) at 7.5 g IPA l(-1). This is the first report on bioconversion of isopropanol at such high concentration by this solvent tolerant strain of S. mizutae and may allow its application in novel biocatalytic processes for effective biological conversion in two-phase solvent systems.

2-Propanol↗
PubMed2005

[Application of Excel Visual Basic for efficiently complete statistic analysis].

OBJECTIVE: In order to analyze multiple statistic tables more efficiently Excel Visual Basic for Application (VBA) was introduced through the use of an example of calculating standardized mortality rates (SMRs). METHODS: Mortality data of cancer and cardiovascular diseases, by sex and age, have been collected from 1991 to 2003 by the Center for Disease Control and Prevention of Shanghai Huangpu District. Standard population composition was defined as Chinese census statistics in 2000. The male's SMRs were calculated, using Excel VBA for each year and classification of cancers. RESULTS: The male's SMRs were obtained by year and different cancers. At the same time, the results were listed in the cancer's SMRs table for male. CONCLUSIONS: Excel is more flexible than general database on the combination of data and annotation. Excel VBA is better than the basic Excel in operating multiple tables simultaneously and man-machine conversation. Statistic analysis can be efficiently completed by using Excel VBA.

Age Factors↗
PubMed1997

Spectral analysis of a thalamus-to-cortex seizure pathway.

Physiological evidence has shown that the anterior thalamus (AN) and its associated efferents/afferents constitute an important propagation pathway for one animal model of generalized tonic-clonic epileptic seizures. In this study we extend and confirm the support for AN's role by examining neuroelectric signal indicators during seizure episodes. We show that the electroencephalogram (EEG) recorded from AN is highly coherent with the EEG derived from the cortex (CTX). By removing the effects of another thalamic nucleus, posterior thalamus (PT)-unaffiliated with the tract linking AN to cortex-partial coherence analysis leaves the CTX/AN coherence undiminished. The most robust band of strong CTX-AN coherence is centered around the spike-wave pacing frequency of 1-3 Hz. Partial-multiple coherence analysis techniques are used to remove the possible signal contribution from hippocampus in addition to PT. The CTX-AN coherence still remains undiminished in the low-frequency bands. Conclusive evidence from coherence studies and other spectral measures reaffirm the special role of the AN in the propagation of seizure activity from subcortex to cortex.

Analog-Digital Conversion↗
PubMed1975

Studies on the induction of mitotic gene conversion by ultraviolet irradiation. I. Analysis of dose-frequency relationship.

The UV (270-nm) dose-frequency relationship for the induction of intragenic mitotic recombination at trp 5 locus in Saccharomyces cerevisiae was non-linear. Two parameters, alpha and a, in the proposed equation for the non-linear relationship f = (at)alpha were determined so as to fit the experimental data by the method of least squares. The analysis was extended over 5 cell stages during synchronous growth. It was found that (1) parameter alpha changed from 2.02 for unbudded small cells to 1.09 for the stage where the cell had finished the division of the nucleus, and (2) parameter a changed correspondingly from 7.25-10(-4) to 0.180-10(-4) sec-1 during the same period. One interesting outcome in this analysis was the deduction of a dose-dependent nature of relative sensitivity with respect to the stage. The determination of these two parameters enabled us to calculate dose-effect relationships beyond the limits of experimental restrictions. Such an "imaginary" relationship, calculated at an extremely low dose, revealed the existence of maximal sensitivity around the DNA synthesis period. It was further shown that this maximum would easily be masked even in the moderate dose range. Thus, we conclude that the validity of single dose comparisons is diminished unless alpha is constant regardless of the cell stage. Some considerations on the proposed parameters have been made in relation to the mechanisms of the induction of gene conversion by UV.

DNA↗
PubMed1996

Safety and risk/benefit analysis of ibutilide for acute conversion of atrial fibrillation/flutter.

Safety data were reviewed from several controlled clinical trials of ibutilide, a new class III antiarrhythmic drug recently approved for the acute interruption of atrial fibrillation and flutter. Noncardiovascular adverse effects of ibutilide were similar in frequency to those with placebo. Cardiovascular adverse effects occurred in 24.9% of 586 ibutilide-treated patients as compared with 22.2% of 108 sotalol-treated patients, and 7.1% of 127 patients who received placebo. Polymorphous ventricular tachycardia, diagnosed as torsades de pointes, was more common with ibutilide than with placebo or sotalol treatment. It occurred in 4.3% of patients, including 1.7% whose torsades de pointes was sustained and required cardioversion. In the ibutilide group, 4.9% of patients had nonsustained monomorphic ventricular tachycardia compared with 3.7% of patients who received sotalol and 0.8% of patients who received placebo. All of the sustained arrhythmias except 1 occurred within 1 hour of the end of ibutilide infusion, and all were successfully terminated without sequelae. In a multiple logistic regression analysis, bradycardia, low body weight, and history of congestive heart failure were predictive of the occurrence of torsades de pointes. Hypotension, conduction block, bradycardia, and all other cardiovascular adverse effects all occurred at similar rates in the ibutilide- and placebo-treated groups. For patients who failed to convert while receiving ibutilide, there was no decrease in the efficiency of cardioversion, nor was there an increase in the mean energy requirements for subsequent electrical cardioversion. Analysis of a 3-month follow-up study showed that patients receiving ibutilide had similar outcomes compared with patients receiving placebo. One placebo-treated patient died. Other than torsades de pointes, ibutilide has a very good safety profile. Under the proper clinical conditions, this complication of ibutilide therapy can be rapidly diagnosed and effectively treated.

Anti-Arrhythmia Agents↗
PubMed2006

Improved renal function after conversion from tacrolimus/sirolimus to tacrolimus/mycophenolate mofetil in kidney transplant recipients.

BACKGROUND: There is limited data on the potential nephrotoxicity of sirolimus (SRL) and tacrolimus (TAC) in combination. METHODS: We reviewed the course of 97 kidney transplant patients treated with SRL and reduced-dose TAC. Conversion from SRL to mycophenolate mofetil (MMF) was prescribed in a minority (n = 19) for various nonrenal side effects. We compared outcomes of converted patients to those remaining on TAC/SRL (n = 78). RESULTS: TAC levels were increased in converters (P = 0.009). Rejection rates were similar between groups over 18 months (21% vs. 16%, p = ns). Serum creatinine (Cr) and MDRD glomerular filtration rate (GFR) were similar between groups at nadir and six-months, but at 18 months the percent change from six-month Cr was +17% in non-converters vs. -10% in converters (P = 0.004 for the difference). The difference in GFR between groups at 18 months was also significant (P = 0.01). By multivariate analysis, only conversion to MMF was associated with a greater percent change in Cr from 6 to 18 months (P = 0.015). Conversion to MMF also correlated with higher GFR at 18 months independent of rejection, delayed graft function, and ethnicity. CONCLUSIONS: Conversion from TAC/SRL to TAC/MMF led to improved renal function despite increased TAC exposure after conversion.

Drug Therapy, Combination↗
PubMed2002

Identification of phosphoserine and phosphothreonine as cysteic acid and beta-methylcysteic acid residues in peptides by tandem mass spectrometric sequencing.

Tandem mass spectrometry has long been an intrinsic tool to determine phosphorylation sites in proteins. However, loss of the phosphate moiety from both phosphoserine and phosphothreonine residues in low-energy collision-induced dissociation is a common phenomenon, which makes identification of P-Ser and P-Thr residues complicated. A method for direct sequencing of the Ser and Thr phosphorylation sites by ESI tandem mass spectrometry following beta-elimination/sulfite addition to convert -HPO4 to -SO3 has been studied. Five model phosphopeptides, including three synthetic P-Ser-, P-Thr-, or P-Ser- and P-Thr-containing peptides; a protein kinases C-phosphorylated peptide; and a phosphopeptide derived from beta-casein trypsin digests were modified and then sequenced using an ESI-quadrupole ion trap mass spectrometer. Following incubation of P-Ser- or P-Thr-containing peptides with Na2SO3/NaOH, 90% P-Ser and 80% P-Thr was converted to cysteic acid and beta-methylcysteic acid, respectively, as revealed by amino acid analysis. The conversion can be carried out at 1 microM concentration of the peptide. Both cysteic acid and beta-methylcysteic acid residues in the sequence were shown to be stable and easily identifiable under general conditions for tandem mass spectrometric sequencing applicable to common peptides.

Amino Acid Sequence↗
PubMed1990

A study of variance in densitometry of retinal nerve fiber layer photographs in normals and glaucoma suspects.

The main object of this research was to develop a reliable method of screening glaucoma suspects and patients for early loss of or changes in the retinal nerve fiber layer (RNFL). This study quantifies the variances due to photography, digitizing, and analysis of red-free photographs of the RNFL. The influence of pupil size, optic disc position and eye movements, film processing, digitizing, and intra- and interphotographic-session and intra- and interoperator variances were established. It was found that pupils needed to be dilated to at least 6 mm, that the optic disc had to be positioned in a standardized area in the negative, that the head of the subject had to remain still during photography, and that film processing and digitizing of the negative needed to be strictly controlled to minimize the variance in collection of densitometry data from RNFL red-free photographs. It was established that focusing of the negatives during digitization was not crucial. Criteria were defined for acceptable negatives. Interphotographic-session and intraoperator variances were not significant in most cases when negatives were digitized to these criteria. Analysis of interphotographic-session variance showed that there were still some factors in photography, film processing, and/or image digitizing that were not sufficiently controlled for long-term follow-up without normalization of the data. Densitometry data gathered using the established protocol, from negatives of 71 subjects were analyzed; best sensitivity and specificity rates of 80% and 100%, respectively, were achieved for the diagnosis of glaucoma.

Adult↗
PubMed1998

Leaching of zinc sulfide by thiobacillus ferrooxidans: experiments with a controlled redox potential indicate No direct bacterial mechanism

The role of Thiobacillus ferrooxidans in bacterial leaching of mineral sulfides is controversial. Much of the controversy is due to the fact that the solution conditions, especially the concentrations of ferric and ferrous ions, change during experiments. The role of the bacteria would be more easily discernible if the concentrations of ferric and ferrous ions were maintained at set values throughout the experimental period. In this paper we report results obtained by using the constant redox potential apparatus described previously (P. I. Harvey and F. K. Crundwell, Appl. Environ. Microbiol. 63:2586-2592, 1997). This apparatus is designed to control the redox potential in the leaching compartment of an electrolytic cell by reduction or oxidation of dissolved iron. By controlling the redox potential the apparatus maintains the concentrations of ferrous and ferric ions at their initial values. Experiments were conducted in the presence of T. ferrooxidans and under sterile conditions. Analysis of the conversion of zinc sulfide in the absence of the bacteria and analysis of the conversion of zinc sulfate in the presence of the bacteria produced the same results. This indicates that the only role of the bacteria under the conditions used is regeneration of ferric ions in solution. In this work we found no evidence that there is a direct mechanism for bacterial leaching.

Journal Article↗
PubMed1987

Analysis of the in vivo phosphorylation state of protein phosphatase inhibitor-2 from rabbit skeletal muscle by fast-atom bombardment mass spectrometry.

A new procedure has been developed for identifying phosphoserine residues in proteins, and is used to analyse the in vivo phosphorylation state of inhibitor-2. The method employs reverse-phase liquid chromatography to resolve phosphorylated and dephosphorylated forms of peptides and fast-atom bombardment mass spectrometry (FABMS) to identify phosphorylated derivatives. The positions of phosphorylation sites within peptides are located by gas-phase sequencer analysis after conversion of phosphoserine residues to S-ethylcysteine. The phosphorylation sites on inhibitor-2 were identified as serines-86, -120 and -121, the three residues phosphorylated in vitro by casein kinase-II. Serine-86 was phosphorylated to 0.7 mol/mol and serines-120 and -121 each to 0.3 mol/mol. These values were not altered significantly by intravenous injection of adrenalin or insulin. No phosphate was present in the region comprising residues 1-49, even after injection of adrenalin, demonstrating that inhibitor-2 is not a substrate for cyclic AMP-dependent protein kinase in vivo. The absence of phosphotyrosine also indicated that inhibitor-2 is not a physiological substrate for the insulin receptor. Surprisingly, no phosphate was present at threonine-72, the residue phosphorylated in vitro by glycogen synthase kinase-3, after injection of either propranolol, adrenalin or insulin. The implications of this finding for the in vivo activation of protein phosphatase 1I (the 1:1 complex between inhibitor-2 and the catalytic subunit of protein phosphatase-1) are discussed. FABMS analysis of inhibitor-2 confirmed the accuracy of the primary structure reported previously, and showed that the only post-translational modifications were an N-acetyl moiety and the three phosphoserine residues. FABMS also demonstrated the presence of an additional serine residue at the C-terminus, and showed that 50% of isolated inhibitor-2 molecules lack the C-terminal Ser-Ser dipeptide.

Animals↗
PubMedDate not supplied

Cusp reinforcement by bonding of amalgam restorations.

The purpose of the present study was to assess the effectivenes of several adhesives in bonding amalgam in order to recover tooth stiffness. A non-destructive experimental methodology was adopted, using strain gauges bonded to the midbuccal surfaces of 40 teeth, with sequential evaluation of loaded intact, prepared and restored stages of the same tooth. Continuous strain measurement as a function of the applied load was acquired by A/D equipment and a data acquisition programme. The strain-force behaviour of the sound teeth under non-axial force up to 97.5 N served as the baseline. The five experimental groups (8 x 5) consisted of control (no adhesive) and four different adhesives. One-way analysis of variance with repeated measures was calculated for the deformation ratio, relative stiffness and recovery values. Reductions in tooth structure by cutting a mesio-occlusal-distal preparation, width one-third intercuspal distance, resulted in 39-52% loss of buccal cusp stiffness. Non-bonded amalgam produced negligible increase (5%) in the stiffness recovery values of the buccal cusps. The adhesives splinted the cusps together, thereby decreasing cuspal flexure and increasing relative stiffness values. Recovery values obtained ranged from 39% to 61%. Assuming that cusp fracture occurs as a result of brittle tooth structure fatigue, amalgam adhesives may contribute to the strengthening of weakened cusps.

Adhesives↗
PubMed1995

Comparison of three methods of critical evaluation of microleakage along restorative interfaces.

This in vitro study compared microleakage along the dentin-restorative interface by use of a conventional single-surface and two stereoscopical protocols. The extent of microleakage in class V cylindric cavities that were restored with Scotchbond 2/P-50 was assessed after thermocycling and silver staining were performed. Specimens were randomized into three groups of 10 teeth for the three different protocols to be investigated. The categories were group 1, a single longitudinal section through the midline of the restoration, group 2, a multiple-surface protocol based on computer reconstruction of digitized images from multiple serial abrasions, and group 3, a clearing protocol based on immersion of demineralized specimens in methyl salicylate. The severity of microleakage for all groups was recorded on an ordinal scale and based on linear leakage length. The median leakage score for groups 1 through 3 was 2, 4, and 4, respectively. When comparisons were performed with nonparametric statistical analysis, both the clearing and the multiple-surface protocols recorded significantly more severe leakage than those detected from a conventional, single longitudinal, midline sectioning technique, (x2 = 8.595, p < 0.02). Furthermore microleakage patterns generated from the two stereoscopical protocols revealed extensive microleakage that advanced unilaterally or bilaterally through the dentin-restorative interface along the embrasure regions into the axial wall of the restorations. No significant difference was noted between the two stereoscopical protocols (Q = 0.260, p > 0.05), which suggested that the clearing protocol, which is less labor-intensive than the multiple-surface protocol, may be recommended for future comparative microleakage studies that involve the dentin-restorative interface.

Analog-Digital Conversion↗
PubMed1998

Quantitative analysis of spiral computed tomography for craniofacial clinical applications.

OBJECTIVE: To determine the relative accuracy of craniofacial measurements obtained from volumetric spiral computed tomography (CT) in two-dimensional (2D) and three-dimensional (3D) reconstructions. MATERIALS AND METHODS: Nine cadaver heads were examined with spiral CT at 3 mm collimation with 2 mm/s table feed. The CT data, stored on optical disks to allow full retrospective review of any image, were transferred to a networked computer workstation for off-line visualization, measurement and analysis. Three-dimensional surface images (3DCT) were generated from spiral CT scans (2DCT). Measurements (n = 28) were made from (both unique and conventional craniometric anatomical) landmarks (n = 23) identified in 2DCT and 3DCT images by two observers twice. The soft tissues were then removed from the cadavers and the measurements performed with an electromagnetic digitizer. RESULTS: The accuracy for 3DCT was higher than 2DCT images for seven of 28 measurements. Twenty five per cent of the 2DCT measurements were found to be significantly different from the physical measurements. All measurements with 3DCT were found to have satisfactory accuracy in comparison with physical measurements. CONCLUSIONS: Three-dimensional spiral CT can distinguish craniofacial anatomy more accurately with some measurements.

Analog-Digital Conversion↗
PubMed2007

Long-term results of endovascular abdominal aortic aneurysm treatment with the first generation of commercially available stent grafts.

HYPOTHESIS: Little information about the long-term results of endovascular abdominal aortic aneurysm repair is available. This study was performed to evaluate the long-term data of patients treated with the first generation of commercially available stent grafts. DESIGN: Multicenter registry. SETTING: Sixty-two European centers that participated in the EUROSTAR (EUROpean collaborators on Stent-graft Techniques for abdominal aortic Aneurysm Repair) registry. PATIENTS: A total of 1190 patients with a follow-up of up to 8 years, who underwent endovascular abdominal aortic aneurysm repair with a stent graft (Stentor or Vanguard). INTERVENTION: Elective endovascular abdominal aortic aneurysm repair. MAIN OUTCOME MEASURES: The morbidity and mortality data of patients treated with the first-generation stent graft who enrolled in the EUROSTAR registry were analyzed. Incidence rates of complications were calculated to quantify annual risks. Life-table analyses and multivariate Cox proportional hazards models were used for the survival analysis. RESULTS: Conversion to open repair, aneurysm rupture, all-cause death, and aneurysm-related death occurred in 7.1%, 2.4%, 19.9%, and 3.0% of the patients, respectively. The cumulative percentage of the combined outcome event, conversion-free and rupture-free survival, after 8 years was 48.0%. Procedure-related complications that frequently occurred were endoleak (13.0 cases per 100 patient-years), stenosis/thrombosis (4.6 cases per 100 patient-years), and stent migration (4.3 cases per 100 patient-years). CONCLUSIONS: Patients treated with the first generation of stent grafts will need lifelong surveillance because of a considerable risk of late complications. How these findings translate to the outcome of newer-generation stent grafts is unknown. For this reason, vigilant surveillance remains indicated in all patients who undergo endovascular abdominal aortic aneurysm repair.

Adult↗
PubMed2002

Dynamics of the heart rate response to sinusoidal work in humans: influence of physical activity and age.

The purpose of the present study was to define the influence of age and exercise training on the heart rate (HR) dynamic response (i.e. kinetics) to sinusoidal work. A total of 63 healthy subjects (31 men and 32 women; age range 19-69 years) underwent a three-step incremental work test, during which peak oxygen uptake (.V(O)(2peak)) was estimated by the YMCA method. Sinusoidal work varying between 20% and 60% of HR(reserve) was employed for periods of 1, 3, 6, 9 and 12 min. HR was monitored in a beat-by-beat manner with a cardiotachometer. The kinetics of the HR response were analysed by frequency analysis and estimated by a first-order transfer function with time constant (tau) and time delay (TD). Physical training status was estimated as stepping frequency, as measured with a pedometer during the daytime, and averaged over seven consecutive days. The mean response time of HR kinetics (HR(MRT): tau pulse TD) tended to increase gradually with age (0.36 s.year(-1)), and linear regression analysis revealed that the correlation between HR(MRT) and age was significant (r=0.31, P<0.05), although not as highly significant as that between HR(MRT) and physical activity (r=-0.48, P<0.0001). HR(MRT) was not related to the S.D. of HR variation (an indicator of parasympathetic mediation) at rest. In addition, .V(O)(2peak) showed a significantly greater correlation with age (r=-0.60, P<0.0001) than with physical activity (r=-0.14, not significant). In conclusion, these findings suggest that HR dynamics, which may depend on sympathetic nervous activity, are more sensitive to physical activity than to age, but that .V(O)(2peak), as estimated by the age-associated decline in maximum HR, is unrelated to physical training status.

Adult↗
PubMed2003

Adapting the Charlson Comorbidity Index for use in patients with ESRD.

BACKGROUND: Accurate prediction of survival for patients with end-stage renal disease (ESRD) and multiple comorbid conditions is difficult. In nondialysis patients, the Charlson Comorbidity Index has been used to adjust for comorbidity. The purpose of this study is to assess the validity of the Charlson index in incident dialysis patients and modify the index for use specifically in this patient population. METHODS: Subjects included all incident hemodialysis and peritoneal dialysis patients starting dialysis therapy between July 1, 1999, and November 30, 2000. These 237 patients formed a cohort from which new integer weights for Charlson comorbidities were derived using Cox proportional hazards modeling. Performance of the original Charlson index and the new ESRD comorbidity index were compared using Kaplan-Meier survival curves, change in likelihood ratio, and the c statistic. RESULTS: After multivariate analysis and conversion of hazard ratios to index weights, only 6 of the original 18 Charlson variables were assigned the same weight and 6 variables were assigned a weight higher than in the original Charlson index. Using Kaplan-Meier survival curves, we found that both the original Charlson index and the new ESRD comorbidity index were associated with and able to describe a wide range of survival. However, the new study-specific index had better validated performance, indicated by a greater change in the likelihood ratio test and higher c statistic. CONCLUSION: This study indicates that the original Charlson index is a valid tool to assess comorbidity and predict survival in patients with ESRD. However, our modified ESRD comorbidity index had slightly better performance characteristics in this population.

Aged↗