PubMed Health⌕ Search

Biomedical subjects

K Beckman

Publications and source records attributed to K Beckman.

At least 19 recordsLinked to original sources
PubMed2001

Follow-up of patients with unexplained syncope and inducible ventricular tachyarrhythmias: analysis of the AVID registry and an AVID substudy. Antiarrhythmics Versus Implantable Defibrillators.

INTRODUCTION: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND RESULTS: Included in the AVID registry were patients from all participating sites who had "out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms." In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.

Anti-Arrhythmia Agents↗
PubMed2001

Digital radiography of scoliosis with a scanning method: initial evaluation.

PURPOSE: To evaluate the radiation dose, image quality, and Cobb angle measurements obtained with a digital scanning method of scoliosis radiography. MATERIALS AND METHODS: Multiple images were reconstructed into one image at a workstation. A low-dose alternative was to use digital pulsed fluoroscopy. Dose measurements were performed with thermoluminescent dosimeters in an Alderson phantom. At the same time, kerma area-product values were recorded. A Monte Carlo dose calculation also was performed. Image quality was evaluated with a contrast-detail phantom and visual grading system. Angle measurements were evaluated with an angle phantom and measurements obtained on patient images. RESULTS: The effective radiation dose was 0.087 mSv for screen-film imaging, 0.16 mSv for digital exposure imaging, and 0.017 mSv for digital fluoroscopy; the corresponding kerma area-product values were 0.43, 0.87, and 0.097 Gy. cm(2), respectively. The image quality of the digital exposure and screen-film images was about equal at visual grading, whereas fluoroscopy had lower image quality. The angle phantom had lower angle values with digital fluoroscopy, although the difference in measured angles was less than 0.5 degrees. The patient images showed no difference in angles. CONCLUSION: The described digital scanning method has acceptable image quality and adequate accuracy in angle measurements. The radiation dose required for digital exposure imaging is higher than that required for screen-film imaging, but that required for digital fluoroscopy is much lower.

Fluoroscopy↗
PubMed2000

Implantable cardioverter defibrillator discharge rates in patients with unexplained syncope, structural heart disease, and inducible ventricular tachycardia at electrophysiologic study.

BACKGROUND AND HYPOTHESIS: The implantable cardioverter defibrillator (ICD) is the best available strategy to protect patients from life-threatening ventricular arrhythmia. Although unproven, it is commonly utilized to treat subjects with syncope, a negative clinical workup, structural heart disease, and inducible sustained monomorphic ventricular tachycardia (VT) on programmed electrophysiologic stimulation (EPS). The purpose of this paper was to validate this approach. METHODS: We retrospectively identified 36 subjects who received primary ICD therapy for syncope in the setting of structural heart disease with inducible sustained monomorphic VT on EPS. The cohort was predominantly male (32/36) with underlying coronary artery disease (29/36). The mean left ventricular ejection fraction was 31 +/- 12%, and a third of the patients (12/36) had undergone bypass surgery. RESULTS: The study group was followed for a mean of 23 +/- 15 months (range 3-81 months) and experienced an ICD event rate of 22% at 3 months, which increased to 55% at 36 months. This event rate was comparable with the 66% event rate seen in a group of patients with primary ICD therapy for spontaneous life-threatening VT treated during the same time period. No future predictors of ICD events in the study group could be identified. CONCLUSION: Syncope patients with negative workup, structural heart disease, and sustained monomorphic VT at EPS are at high risk for future tachyarrhythmic events. Based on present evidence, primary ICD therapy in this group appears warranted and justified.

Aged↗
PubMed1999

Metabolism of trideuterated iso-lignoceric acid in rats in vivo and in human fibroblasts in culture.

Saturated very long chain fatty acids (fatty acids with greater than 22 carbon atoms; VLCFA) accumulate in peroxisomal disorders, but there is little information on their turnover in patients. To determine the suitability of using stable isotope-labeled VLCFA in patients with these disorders, the metabolism of 22-methyl[23,23,23-2H3]tricosanoic (iso-lignoceric) acid was studied in rats in vivo and in human skin fibroblasts in culture. The deuterated iso-VLCFA was degraded to the corresponding 16- and 18-carbon iso-fatty acids by rats in vivo and by normal human skin fibroblasts in culture, but there was little or no degradation in peroxisome-deficient (Zellweger's syndrome) fibroblasts, indicating that its oxidation was peroxisomal. Neither the 14-, 20-, and 22-carbon iso-fatty acids nor the corresponding odd-chain metabolites could be detected. In the rat, the organ containing most of the iso-lignoceric acid, and its breakdown products, was the liver, whereas negligible amounts were detected in the brain, suggesting that little of the fatty acid crossed the blood-brain barrier. Our data indicate that VLCFA labeled with deuterium at the omega-position of the carbon chain are suitable derivatives for the in vivo investigation of patients with defects in peroxisomal beta-oxidation because they are metabolized by the same pathways as the corresponding n-VLCFA. Moreover, as iso-VLCFA and their beta-oxidation products are readily separated from the corresponding n-fatty acids by normal chromatographic procedures, the turnover of VLCFA can be more precisely measured.

Animals↗
PubMed1996

Evidence of two catalytically active carnitine medium/long chain acyltransferases in rat liver peroxisomes.

Peroxisomal matrix proteins were extracted from the highly purified peroxisomes with sodium pyrophosphate, and the membranes were sedimented by high speed centrifugation. Biochemical marker enzyme analyses revealed a quantitative release of a number of well-known peroxisomal matrix proteins from the purified peroxisomes. In contrast, carnitine medium/long chain acyltransferase activity, assayed with decanoyl-CoA and palmitoyl-CoA as substrates, was equally distributed in the membrane and the matrix fractions. The matrix and the membrane enzyme activities were differentially affected by a number of detergents. The enzyme in the membrane fraction showed higher malonyl-CoA sensitivity compared to the enzyme in the matrix fraction. The enzyme(s) from the purified peroxisomes or the peroxisomal membranes was quantitatively solubilized by sodium cholate, and the cholate-solubilized enzyme retained malonyl-CoA sensitivity. The membrane enzyme was separated from the matrix enzyme by hydroxylapatite column chromatography. The separation of the membrane enzyme or the matrix enzyme by hydroxylapatite column chromatography resulted in loss of malonyl-CoA sensitivity. The partially purified membrane and the matrix enzymes showed broad substrate specificity, and the highest enzyme activities for both were observed with decanoyl-CoA. In contrast to the matrix enzyme, the membrane enzyme was strongly inhibited by high concentrations (> or = 50 microM) of acyl-CoAs (> 10 carbons in length). The matrix enzyme showed a 2.5-fold lower Km for carnitine compared to the membrane enzyme. The catalytic properties of the partially purified matrix enzyme appear to be similar to the well-characterized peroxisomal carnitine octanoyltransferase, though we find highest activity with decanoyl-CoA rather than octanoyl-CoA as a substrate. The data presented clearly indicate that the membrane and the matrix enzyme activities are due to different proteins.

Acyl Coenzyme A↗
PubMed1994

Peroxisomal beta-oxidation of branched chain fatty acids in rat liver. Evidence that carnitine palmitoyltransferase I prevents transport of branched chain fatty acids into mitochondria.

Fatty acid beta-oxidation was investigated in highly purified mitochondrial and peroxisomal preparations from rat liver. Under isotonic conditions, pristanic and homophytanic acid beta-oxidation in purified peroxisomes was severalfold greater compared to the oxidation in purified mitochondria. Branched chain fatty acid beta-oxidation in purified mitochondria was very low, and the oxidation was not stimulated by exogenous L-carnitine or L-malate. In contrast, stearic acid beta-oxidation by purified mitochondria depended upon exogenous L-carnitine, and the oxidation was stimulated by L-malate. Both mitochondrial and peroxisomal beta-oxidation of branched chain fatty acids was strongly inhibited by fatty acid-free bovine serum albumin, whereas stearic acid oxidation was either unaffected or slightly inhibited by bovine serum albumin. The results presented clearly indicate that branched chain fatty acids are mainly degraded in peroxisomes in rat liver. Branched chain fatty acids were efficiently converted to coenzyme A thioesters by purified mitochondria, peroxisomes, and microsomes. Although pristanic and phytanic acids were rapidly converted to pristanoyl-CoA and phytanoyl-CoA, respectively, they were not converted to carnitine esters by mitochondrial outer membranes. The results indicate that acyl-CoA synthetase and carnitine acyltransferase located at the mitochondrial outer membranes regulate entry of branched chain fatty acids into mitochondria. Mitochondrial carnitine acyltransferase I appears to be highly specific for straight chain fatty acids and restricts entry of branched chain fatty acids into mitochondria. Thus, branched chain fatty acids which cannot be transported across the mitochondrial membranes via the carnitine acyltransferase system are directed to peroxisomes for beta-oxidation. The results reported indicate that phytanic acid, the fatty acid which can be initially degraded by alpha-oxidation due to the presence of a beta-methyl group in the molecule, cannot be transported across the mitochondrial membranes. The data presented strongly suggest that phytanic acid alpha-oxidation occurs in organelles other than mitochondria and possibly in peroxisomes.

Acyl Coenzyme A↗
PubMed1994

Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil.

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.

Adolescent↗
PubMed1993

Model-based rhythm analysis of the ECG. Evaluation of a prototype implementation.

Current computer algorithms that interpret cardiac rhythms based solely on the surface electrocardiogram are limited, yet offer many benefits to health care. To address the limitations, novel computer algorithms for the automatic diagnosis of complex cardiac rhythms based solely on the surface electrocardiogram are presented. Using the hypothesize-and-test paradigm, a physiologic model of the cardiac conduction system and production rule-based knowledge are combined to reason about the time- and space-varying characteristics of complex heart rhythms. In addition, an evaluation of a prototype implementation of the algorithms is presented. A database of the time of onset, width, and shape classifications of each P wave, QRS complex, and T wave from 59 electrocardiographic strips was developed from an introductory textbook by hand-annotation using calipers. The database was not used in the development of the prototype. The prototype's diagnoses were reviewed by a clinical cardiac electrophysiologist who was not involved in the development process. Pair-wise comparisons among the prototype, textbook, and cardiac electrophysiologist, assuming either the textbook or electrophysiologist as the gold standard, were performed. The specific comparisons performed were prototype versus textbook, electrophysiologist versus textbook, prototype versus electrophysiologist, and textbook versus electrophysiologist. For all diagnostic categories, sensitivities of 88.0%, 97.2%, 78.6%, and 82.1%, respectively, and specificities of 99.2%, 98.5%, 99.7%, and 99.8%, respectively, were attained. When accounting for design and implementation limitations of the prototype, sensitivities of 93.0%, 98.5%, 89.1%, and 92.7%, respectively, and specificities of 99.4%, 99.2%, 99.6%, and 99.8%, respectively, were attained. The results indicate that these algorithms offer clinical advantages over currently available arrhythmia analysis systems.

Algorithms↗
PubMed1993

Exclusive localization in peroxisomes of dihydroxyacetone phosphate acyltransferase and alkyl-dihydroxyacetone phosphate synthase in rat liver.

Dihydroxyacetone phosphate acyl transferase (DHAP-AT), alkyl dihydroxyacetone phosphate synthase (alkyl-DHAP-synthase), and glycerol-3-phosphate acyltransferase (GPAT) activities were investigated under optimal assay conditions using highly purified organelle preparations. The data presented clearly indicate that GPAT activity was mainly localized in mitochondria and microsomes, whereas DHAP-AT and alkyl-DHAP-synthase activities were exclusively localized in peroxisomes. A small fraction of the total DHAP-AT and alkyl-DHAP-synthase activities observed in purified mitochondrial preparations was due to the presence of intact peroxisomes. DHAP-AT and alkyl-DHAP-synthase activities were very low in purified microsomes (< 1% compared to peroxisomes) and these activities are thought to be due to sedimentation of peroxisomal fragments (generated during homogenization of liver and processing of liver homogenate) with microsomes. The results indicate that the dihydroxyacetone phosphate pathway does not contribute to the synthesis of glycerolipids other than ether lipids in rat liver. The ether bond formation occurs exclusively in peroxisomes, and all the biosynthetic reactions for plasmalogen synthesis may also be operating within peroxisomes in rat liver.

Acyltransferases↗
PubMed1992

Very long-chain fatty acids in peroxisomal disease.

Fatty acids with from 24 to 28 carbon atoms (very long-chain fatty acids, VLCFA) are present in small amounts in all mammalian tissues. Even longer chain fatty acids with from 30 to 38 carbon atoms (ultra-long-chain fatty acids, ULCFA) are found in certain specialized tissues including retina, brain, and spermatozoa. In patients with inherited defects in peroxisomal structure and/or function, there is an accumulation of VLCFA in most tissues, while VLCFA and ULCFA levels are increased in brain. The most pronounced changes occur in those patients who have defects in peroxisomal assembly (Zellweger syndrome, infantile Refsum's disease, and neonatal adrenoleukodystrophy). In the brain of these individuals, ULCFA are distributed largely in molecular species of phosphatidylcholine with penta-, hexa-, and heptaenoic acids. In contrast, patients with X-linked adrenoleukodystrophy have increased levels of phosphatidylcholine with monoenoic rather than polyenoic ULCFA. A defect in a peroxisomal VLCFA CoA synthetase or ligase has been reported for these patients, but assembly of their peroxisomes is apparently normal. We speculate that ULCFA are normal products of carbon chain elongation. We have confirmed this by demonstrating the elongation of [1-14C]hexacosatetraenoic acid (26:4n-6) by rat brain in vivo to a series of longer chain tetraenoic acids with carbon chain lengths up to 34. Elongation to ULCFA can occur as well in non-neural tissues as shown by detection of labeled saturated and monoenoic fatty acids with up to 32 carbon atoms after incubation of normal and Zellweger syndrome fibroblasts with [2-14C] acetate. Increased labeling of VLCFA and ULCFA is observed in cells from patients with peroxisomal disorders. Our data suggest that ULCFA with up to at least 32 carbon atoms are formed normally, as a part of the elongation process in most mammalian tissues, and that control of carbon chain elongation is a major function of peroxisomes. Impairment of this function as occurs in peroxisomal disease results in the accumulation of VLCFA and ULCFA. The relative enrichment in normal tissues of ULCFA such as 32:6n-3 in ram and bull spermatozoa and 36:4n-6 in human and rat brain suggests a probable physiological role for this class of fatty acids in these tissues.

Adolescent↗
PubMed1992

Monoenoic fatty acids in human brain lipids: isomer identification and distribution.

The carbon chain length distribution and the double bond positional isomer composition of the monoenoic fatty acids of the lipids of total human brain tissue have been determined using gas chromatography and gas chromatography/mass spectrometry of the fatty acid methyl and picolinyl esters. The even chain length monoenoic C16 to C28 fatty acids contain predominantly two positional isomer series, the n-7 and n-9 cis homologues, whose relative proportion varies significantly with chain length. The odd chain length long-chain fatty acids consist of n-8 and n-10 isomers, whereas the odd chain length very long-chain (more than 22 carbon) fatty acids are n-7 and n-9 isomers.

Adolescent↗
PubMed1992

Comparison of the pharmacokinetics and electrocardiographic effects of sublingual and intravenous verapamil.

Using a dog model, a sublingual form of the free base of verapamil (SLV) was developed with the intent of avoiding stereoselective first-pass metabolism and the necessity of intravenous administration. Intravenous verapamil (IVV) 5 mg and SLV 40 mg or 60 mg were sequentially administered to seven healthy human volunteers. Electrocardiograms and serum concentrations were obtained before and periodically from 5 to 480 minutes after each dose. The time to peak serum concentration (mean +/- SD) was 77.6 +/- 38.1 minutes after SLV. Bioavailability of SLV was 58.2 +/- 36.9% compared to IVV. Verapamil half-lives after IVV and SLV were 2.83 +/- 0.93 and 2.28 +/- 0.45 hours (NS), respectively. In one subject, the time to peak effect was delayed and overall change in PR interval was minimum. In the remaining six subjects, the maximum percentage increases in PR interval after IVV and SLV were 20.6 +/- 6.4% and 14.8 +/- 5.5% (p less than 0.05), respectively. Times to peak increase in PR interval were 28.3 +/- 15.7 and 57.0 +/- 17.5 minutes after IVV and SLV (p less than 0.05), respectively. Analysis of plots of percentage change in PR interval versus serum concentration revealed a shift to the right and therefore, lesser effect of SLV than of IVV in six subjects. All seven subjects complained of oral numbness and bitter taste. In conclusion, SLV is inferior to IVV in terms of rate and extent of absorption and pharmacologic effect in delaying atrioventricular nodal conduction. Probably SLV has little clinical utility because of its slow onset and poor tolerance.

Administration, Oral↗
PubMed1991

Glyceryl ethers in peroxisomal disease.

1-O-Alkyl and 1-O-alk-1-enyl (plasmalogens) glyceryl ether lipid levels were measured in post-mortem brain and/or liver biopsies from 7 patients with ultrastructural and biochemical evidence of a defect in peroxisomal biogenesis and/or enzymological evidence of a disturbance in ether lipid synthesis. Near normal levels of both species of glyceryl ether lipids were found in neonatal adrenoleukodystrophy and infantile Refsum's disease but marked deficiencies were found in Zellweger's syndrome and rhizomelic chondrodysplasia punctata, the latter manifesting the most profound reduction in ether lipid levels. These observations suggest that little ether lipid biosynthesis occurs in vivo in rhizomelic chondrodysplasia punctata or Zellweger's syndrome. However, in some phenotypes with apparently gross reductions in peroxisomal numbers, e.g. neonatal adrenoleukodystrophy and infantile Refsom's disease, there is significant ether lipid synthesis in liver and brain.

Adrenoleukodystrophy↗
PubMed1988

Rhizomelic chondrodysplasia punctata: clinical, pathologic, and biochemical findings in two patients.

The clinical, pathologic, and biochemical features of rhizomelic chondrodysplasia punctata are described in two patients. Although both patients had clinical and radiologic similarities, one patient survived for only 13 days and the other is still alive at 8 years. The most prominent pathologic feature was the marked degenerative change in the chondrocytes from resting cartilage. Fibroblast alkyldihydroxyacetone phosphate synthase activity was markedly reduced in both patients (approximately 10% of control mean); in contrast, dihydroxyacetone phosphate acyltransferase activity was only moderately reduced (50% of control mean). Alkyl and alk-l-enyl ether (plasmalogens) levels were very low in brain and liver. The accumulation of phytanic acid observed in plasma or liver was paralleled by a reduced ability of the patients' fibroblasts to oxidize phytanic acid. Our data indicate that the genetic defect in rhizomelic chondrodysplasia punctata results in abnormalities in two apparently unrelated pathways (i.e., phytanic acid oxidation and ether lipid biosynthesis.

Brain↗
PubMed1987

Occurrence of unusual molecular species of sphingomyelin containing 28-34-carbon polyenoic fatty acids in ram spermatozoa.

The high levels of very long chain fatty acids found in ram spermatozoa are located almost exclusively in one of two separable species of sphingomyelin. Mass spectral analysis, including fast atom bombardment of the purified sphingomyelin, has shown the fatty acids to have a carbon chain length of between 28 and 34, with between four and six double bonds, and to belong predominantly to the n-3 series.

Animals↗
PubMed1986

Natural cytotoxic T cells (NCTC) that differ from natural killer (NK) and natural cytotoxic (NC) cells are present in Peyer's patches of mice.

We have examined noninduced cytotoxicity of mouse gut associated and peripheral lymphoid tissues for a wide variety of syngeneic as well as allogeneic cell lines and lymphoblasts. Lymphoid cells from Peyer's patches were found to lyse these targets in a 3-hr chromium release assay whereas lymphoid cells from intestinal mucosa, mesenteric or peripheral lymph nodes, spleen, and thymus did not. The variety of targets toward which Peyer's patch cells were cytotoxic established the latter as nonspecific and H-2 unrestricted. The cell responsible for the lytic event was identified as possessing Thy 1.2 and Ia surface antigens. This naturally cytotoxic T cell (NCTC) was found to be adherent to nylon-wool but not to plastic plates. Although both natural killer cell (NK) and non-NK targets served as targets for the NCTC, the latter were further differentiable from NK cells by lack of asialo GM1 surface marker, which is present on NK cells. In addition, NCTC remained fully functional in mice given either of the drugs cyclophosphamide or cortisone. Each of these drugs, in the doses used, markedly reduced poly(I:C)-induced NK activity. Thus, NCTC differs from NK on the basis of the spectrum of targets against which it is functional, phenotypic surface markers, insusceptibility to stimulation with poly(I:C), and insensitivity to diminution by the immunosuppressive drugs cyclophosphamide and hydrocortisone. Since NCTC is a Thy 1.2 antigen-bearing cell and is detectable in a 3-hr cytotoxic assay, it also differs from the natural cytotoxic (NC) cell. NC lacks the Thy 1.2 marker and becomes detectable only in an 18-hr cytotoxic assay. Thus, NCTC is neither an NK nor an NC cell. We have discussed the possibility that the three naturally occurring cells may be related by being dedifferentiated descendants of an antigen-specific cytotoxic T lymphocyte (CTL). Alternatively, since NCTC is confined to an anatomical site prone to ample antigenic exposure and is still identifiable as a T cell, it may be in linear transition from the CTL to the NK or NC stages.

Animals↗
PubMed1986

Classic and concealed entrainment of typical and atypical atrial flutter.

Classic and concealed entrainment was demonstrated in a patient with spontaneous typical atrial flutter and pacing-induced atypical atrial flutter. The form of entrainment manifested depended on the site of pacing and the direction of tachycardia as determined by endocardial mapping.

Atrial Flutter↗