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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 163 records · Page 9Linked to original sources
PubMed1996

Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study.

BACKGROUND: Long-term safety is an important consideration in the selection and use of drugs, such as lipid-lowering agents, that are prescribed to reduce the risk of clinical events during long periods. METHODS: The Scandinavian Simvastatin Survival Study was designed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previous myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily, or placebo. In addition to previously reported end-point events, detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years (range in survivors, 4.9-6.2 years). RESULTS: The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different. Examination of the lens showed no between-group differences, and no previously unrecognized adverse effects of the drug were observed. There were no significant between-group differences in adverse events in any body system. In particular, the frequency of adverse events related to the central nervous system was similar in both groups. CONCLUSION: The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent.

Adult↗
PubMed1996

Effects of the inhibitors of energy metabolism, lonidamine and levamisole, on 5-aminolevulinic-acid-induced photochemotherapy.

The ability of endogenously synthesized protoporphyrin IX (PpIX) to damage Chinese hamster lung fibroblasts of the line V79 by exposure to light was examined. This treatment induced reduction of cellular ATP, GTP, of the NADH/NAD+ ratio and of oxygen consumption. The present results indicate a close relationship between inhibition of respiration of irradiated cells and their ability to survive, e.g. 1 min of light exposure induced 90% inhibition of oxygen consumption and inactivation of approximately 95% of the cells, while the cellular content of ATP was reduced by only 15%. This indicates that the mitochondria are one of the primary targets of 5-aminolevulinic acid (ALA)-mediated photochemotherapy (PCT). In the present study, ALA-PCT was combined with the modulators of the glycolysis and the respiration chain, levamisole (LEV) and lonidamine (LND). A synergistic effect of combining ALA-PCT with non-toxic concentrations of LND was observed when LND was given prior to light exposure. This synergism was observed despite a substantial LND-induced inhibition of PpIX formation. At increasing doses of LND (>0.15 mM) the combination treatment becomes less efficient. This is due to the inhibition of PpIX synthesis induced by LND. A synergistic effect of ALA-PDT and LEV was found when LEV was given prior to light exposure. This was at least partly due to an LEV-stimulated effect on ALA-induced PpIX formation. However, it is not clear from the present results whether LEV may perturb energy metabolism in V79 cells since LEV alone did not reduce the energy charge or the NADH/NAD+ ratio. When LEV or LND were given after ALA-PCT, these 2 treatment modalities acted in an additive or slightly synergistic manner.

Aminolevulinic Acid↗
PubMed1996

Cholesterol lowering and the use of healthcare resources. Results of the Scandinavian Simvastatin Survival Study.

BACKGROUND: Advances in the treatment of cardiovascular disease have increased costs; annual cardiovascular healthcare expenditure in the United States currently exceeds $100 billion. Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study is a randomized, double-blind, placebo-controlled trial in which simvastatin reduced the risk of death by 30% (P=.0003) over the median follow-up period of 5.4 years in patients with previous myocardial infarction or stable angina pectoris as a result of a 42% reduction in the risk of coronary deaths (P=.00001). In the present report, data prospectively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare resource use and perform a cost-minimization analysis. In the placebo group (n=2223), there were 1905 hospitalizations (average duration, 7.9 days) for acute cardiovascular events or coronary revascularization procedures among 937 patients, whereas in the simvastatin group (n=2221), there were 1403 such hospitalizations (average duration, 7.1 days) among 720 patients (all differences, P<.0001). The corresponding number of hospital days was 15089 and 9951 in the two groups, respectively (34% reduction,P<.0001). In the United States, the resulting reduction in hospitalization costs over the 5.4 years of the trial would be $3872 per patient, reducing the effective cost of simvastatin by 88% to $0.28 per day. CONCLUSIONS: In addition to reducing mortality and morbidity in coronary heart disease patients, simvastatin markedly reduces use of hospital services, thus offsetting most of its cost.

Adult↗
PubMed1996

Bilateral suppression of the sympathetic nervous system in hemispheric brain infarction.

To assess sympathetic system function after hemispheric brain infarction rostral to the hypothalamus we investigated 24 patients with infarction in the territory of the middle cerebral artery. Anisocoria and basal lacrimal gland secretion were determined. The ninhydrin test was performed and the sympathetic skin response recorded in both hands and feet. The functions assessed by these tests were found to be reduced bilaterally. No significant lateralisation of the sympathetic nervous system could be demonstrated.

Adult↗
PubMed1996

[Accuracy of measurement and overestimation of CO2 of two capnometers intended for potential use in emergency medicine].

UNLABELLED: Capnometry, the noninvasive measurement of end-expiratory CO2 concentration (cCO2, vol%) or calculation of its respective partial pressure (pCO2; mmHg) is an established method. However, for prehospital settings, capnometry is still used very restrictively, mainly owing to the respective devices used. The prerequisite for their use is sufficient accuracy (+/-2 mmHg) and easy handling. Two special capnometers (STAT CAP. Nellcor: mainstream, semiquantitative estimation; Capnocheck 8200, BCI: sidestream, quantitative measurement, numeric display), developed recently for potential use in emergency medicine, are said to fit these criteria. Therefore, the objective of the present investigation was to assess the accuracy and precision of both devices, comparing methods under standardized in vitro (reference gases) and in vivo (intubated and ventilated patients) conditions. METHODS: Both devices ("STAT CAP": pCO2 range, light bars; "Capnocheck 8200") were evaluated regarding the accuracy of pCO2 (Capnocheck) and the precision of the CO2 range (STAT CAP). Tests were performed with four dry gas mixtures (STPD) of defined composition and during ventilation of 20 intubated patients (BTPS). All measurements were compared with the alveolar gas monitor "AGM 1304" (Brüel & Kjaer, Denmark) as a reference method with a proven +/- 1 mmHg accuracy of pCO2 measurement. RESULTS: The "Capnocheck" (BCI) presented an accuracy of the pregiven pCO2 of 0.7-1.4 mmHg (dry gas mixtures, STPD) and an overestimation of 0.2 +/- 4.1 mmHg (BTPS) during ventilation with pure oxygen; inaccuracy during ventilation with 70% N2O in O2 proved to be + 1.2 +/- 1.7 mmHg (BTPS). Nellcor's "STAT CAP" failed to reach the target value in 10% of analyses, as shown by the respective segment bar of the display. CONCLUSION: Evaluation of the accuracy of capnometers must focus on the necessary pH2O correction and the possible effects exercised by O2 (and N2O) as well as the possible dependence on barometric pressure (if pCO2, mmHg, is the desired value). The "Capnocheck" showed an accuracy of more than 2 mmHg in dry gas mixtures as well as in humidified air. Concerning the practical use during constant artificial ventilation, the digital display and accuracy of the sidestream capnometer allow for reliable conclusions on patients' ventilation and circulation (CO2 elimination). The 90% accuracy of the segment bar display of Nellcor's "STAT CAP", per se covering only a rather broad range of 20 mmHg, obviously does not provide more than a rough overview. Therefore, the STAT CAP cannot be recommended for prehospital capnometry in the field. However, both the accuracy of the BCI capnometer (Capnocheck) and its numeric display and easy handling strongly recommend this device also for clinical use.

Blood Gas Analysis↗
PubMed1996

Protection induced by a brief ischemic episode in the Langendorff perfused rat heart.

RATIONALE AND OBJECTIVES: Ischemic episodes lasting approximately 1 min may be associated with coronary angioplasty. We explored whether such episodes could induce myocardial protection against prolonged ischemic episodes in an ex vivo model. METHODS: Protection afforded by pretreatment with a 1-min ischemic episode (ischemic preconditioning) against prolonged ischemia was investigated in the isolated rat heart. Left ventricular developed pressure (LVDP; LV systolic pressure-LV end-diastolic pressure), heart rate (HR), and enzyme leakage (lactate dehydrogenase) were indexes of protection. RESULTS: An increased recovery of LVDP x HR after 16 and 19 min of ischemia of 37% and 28%, respectively, paralleled by reduced enzyme leakage, was observed in preconditioned hearts after 10 min of reperfusion. However, the difference between preconditioned and control hearts was lost after 30 min of reperfusion. CONCLUSION: Ischemic episodes lasting approximately 1 min are not sufficient to initiate stable protection even if initial functional and metabolic indexes suggest a protective effect.

Animals↗
PubMed1996

Diagnostic accuracy and confusability analyses: an application to the Diagnostic Interview for Genetic Studies.

The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder-especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other.

Bipolar Disorder↗
PubMed1996

Apoptosis and necrosis induced with light and 5-aminolaevulinic acid-derived protoporphyrin IX.

The mode of cell death induced by photodynamic treatment (PDT) was studied in two cell lines cultured in monolayer, V79 Chinese hamster fibroblasts and WiDr human colon adenocarcinoma cells. The cells were incubated with 5-aminolaevulinic acid (5-ALA) as a precursor for the endogenously synthesised protoporphyrin IX, which was activated by light. Free DNA ends, owing to internucleosomal DNA cleavage in apoptotic cells, were stained specifically with a fluorescent dye in the terminal deoxynucleotidyl transferase (TdT) assay. The free DNA ends were measured by flow cytometry and the fractions of apoptotic cells determined. Total cell death was measured in a cell survival assay to determine the necrotic fraction after subtraction of the apoptotic fraction. V79 cells did undergo apoptosis while WiDr cells were killed only through necrosis. With time, the apoptotic fraction of V79 cells increased until a maximum was reached about 3-4 h after ALA-PDT treatment. For increasing ALA-PDT doses, a maximal apoptotic fraction 75-85% of the cells was measured at about 85% of total cell death. The flow cytometric assay of apoptosis was confirmed by the typical ladder of oligonucleosomal DNA fragments obtained from agarose gel electrophoresis, by fluorescence micrographs visualising the induced free DNA ends and by electron micrographs showing the typical morphology of apoptotic cells.

Adenocarcinoma↗
PubMed1996

The influence of iron chelators on the accumulation of protoporphyrin IX in 5-aminolaevulinic acid-treated cells.

Human adenocarcinoma cells of the line WiDr and Chinese hamster lung fibroblasts of the line V79 were treated with 5-aminolaevulinic acid (5-ALA) and exposed to light. The effects of the iron chelators ethylenediaminetetraacetic acid (EDTA) and desferrioxamine (DEF) were assessed. Both cell lines were treated with various concentrations of 5-ALA in the presence or absence of the iron chelators for 4 h in serum-free medium. The accumulation of protoporphyrin IX (PpIX) reached a maximum level at 1 mM 5-ALA in WiDr cells [280 ng PpIX (mg protein x 4 h-1] and at 0.1 mM 5-ALA in V79 cells [55 ng PpIX (mg protein x 4 h)-1]. PpIX was the only fluorescing porphyrin in these cells after 5-ALA treatment alone or in combination with the chelators. The iron chelators did not influence the intracellular localisation pattern of PpIX in 5-ALA-treated cells. While both chelators enhanced the accumulation of PpIX in 5-ALA-treated cells, DEF was found to be superior at equal concentrations. A linear relationship between the applied concentration of DEF and the DEF-induced increase in PpIX accumulation was observed in double-reciprocal plots. The intercepts of the regression lines with the ordinate indicate that the ferrochelatase is saturated with PpIX when the 5-ALA concentration exceeds 0.3 mM and 0.05 mM in WiDr and V79 cells respectively. The DEF-induced enhancement of PpIX accumulation in 5-ALA-treated cells was cell line and 5-ALA concentration dependent. At a 5-ALA concentration inducing a maximum level of PpIX accumulation, inhibition of ferrochelatase activity enhanced the PpIX accumulation 3- and 1.4-fold in V79 and WiDr cells respectively. The relative gain in PpIX accumulation increased with decreasing concentration of 5-ALA. In cells treated with the lowest concentrations of 5-ALA used in this study, DEF enhanced PpIX accumulation 44- and 3.5-fold in V79 and WiDr cells respectively. The iron chelator-induced increase in cellular PpIX accumulation was followed by a similar increase in sensitivity to photoinactivation. The ferrochelatase inhibitor dihydropyridine 3,5-diethoxycarbonyl-1,4-dihydrocollidine reduced the accumulation of PpIX in both cell lines.

Adenocarcinoma↗
PubMed1996

Patterns of recovery among Norwegian heart surgery patients.

Utilizing a prospective longitudinal design, the recovery pattern of 91 heart patients was followed for the first 8 weeks following coronary artery by-pass graft surgery. The patients' perceived and actual performance of walking, their resumption of roles, and social support and family functioning were measured pre-operatively and at 4 and 8 weeks postoperatively. Findings indicate that recovery is swift in terms of health and physical functioning, somewhat more time-consuming in terms of role functioning, and delayed with regard to work-related role activities. Contrary to American findings, the heart surgery recovery process did not significantly affect family functioning in this Norwegian sample. Social support was experienced as high throughout the recovery period, with spouses and children being the main providers.

Activities of Daily Living↗
PubMed1996

High levels of Lp(a) lipoprotein in a family with cases of severe pre-eclampsia.

We report a family with two cases of severe pre-eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre-eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre-eclampsia that is genetically determined.

Adult↗
PubMed1996

Recombination between the postulated CCD/MHE/MHS locus and RYR1 gene markers.

Malignant hyperthermia (MH) susceptibility is considered a subclinical myopathy or a pharmacogenetic trait, and is believed to be closely associated with central core disease (CCD). Data support the notion that MH susceptibility is heterogeneous, with the ryanodine receptor I (RYR1) locus on chromosome 19 being one locus harboring a gene that can cause MH susceptibility. The gene for CCD is believed to reside in the locus on chromosome 19. In the family presented here, a girl has CCD, and several close relatives are MH susceptible (MHS). DNA studies conducted on available family members uncovered recombination between the MH susceptibility locus and RYR1 markers. Consequently, if one postulates that the CCD gene in this family resides in the same locus as the MH susceptibility gene, an additional CCD locus different from the RYR1 locus must also be postulated.

Alleles↗
PubMed1996

RYR mutation G1021A (Gly341Arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility.

Malignant hyperthermia (MH) is a pharmacogenetic disorder. Susceptibility to MH (MHS) is presumed to be inherited in an autosomal dominant way. MH crises are triggered by halogenated inhalational anaesthetics and suxamethonium, and may be lethal if not treated early and adequately. Until now, eight mutations in the RYR1 gene have been described as causes of MHS phenotype in various MH families. The mutation RYR1 G1021A (Gly341Arg) has been reported to account for approximately 10% of Caucasian MHS cases. However, in our study this mutation was discovered in only 1 out of 89 Scandinavian families, indicating that this mutation may be the cause of MHS in only about 1% of MHS families in those populations. The mutation may have been brought to Scandinavia by an immigrant.

Calcium Channels↗
PubMed1996

Two novel missense mutations in the LDL receptor gene causing familial hypercholesterolemia.

We have employed analysis of single-strand conformation polymorphisms to identify mutations in the low density lipoprotein receptor gene causing familial hypercholesterolemia. Two familial hypercholesterolemia heterozygotes had abnormal single-strand conformation polymorphism patterns of exons 4 and 8. DNA sequencing revealed that the abnormal pattern of exon 4 was due to heterozygosity (G/T) at nucleotide 502. Nucleotide 502 is the first base of codon 147, and the G->T mutation (D147Y) changes this codon from AspGAC to TyrUAC. The abnormal pattern of exon 8 was due to heterozygosity (A/G) at nucleotide 1097. Nucleotide 1097 is the second base of codon 345, and the A->G mutation (Q345R) changes this codon from GlnCAG to ArgCGG. Based upon screening of 437 unrelated familial hypercholesterolemia heterozygotes, both D147Y and Q345R account for about 0.5% of the mutations causing familial hypercholesterolemia in Norway.

Base Sequence↗
PubMed1996

Pretreatment with ischaemia attenuates acute epirubicin-induced cardiotoxicity in isolated rat hearts.

We investigated whether a brief ischaemic episode (ischaemic pretreatment) preconditioning might attenuate the acute cardiotoxicity of the anthracycline, epirubicin. Isolated rat hearts perfused at a constant flow rate of 10 ml/min, were preconditioned with 5 min. of global ischaemia and 10 min. of reperfusion (preconditioned hearts), or were perfused for 15 min. (control hearts). The hearts were then subjected to 20 min. of infusion with epirubicin (2 mg/ml) or vehicle by a side arm of the perfusion system at a rate of 0.1 ml/min. (0.2 mg epirubicin/min.). Attenuation of cardiotoxicity of a total dose of 4 mg of epirubicin was assessed by functional and metabolic parameters during infusion and during the following 30 min. recovery period. Cardiotoxic effects were reduced in preconditioned hearts compared to control hearts. Thus left ventricular developed pressure and heart rate product after 20 min. of epirubicin infusion was depressed to 27 +/- 7% (mean +/- S.D.) and 40 +/- 4% (mean +/- S.D.) of baseline values in the control group and the preconditioned group, respectively (P < 0.05). Furthermore, we observed less contracture during epirubicin infusion and more effective reversal of contracture during the recovery period in the preconditioned hearts. Improvement in cardiac function was associated with a significantly lower (P < 0.05) myocardial content of epirubicin in the preconditioned group at the end of the infusion period. We conclude that ischaemic preconditioning attenuates the acute cardiotoxicity of epirubicin, probably by reducing the myocardial accumulation of the anthracycline.

Adenosine Triphosphate↗
PubMed1996

Monoclonal antibodies against human immunodeficiency virus type 1 integrase: epitope mapping and differential effects on integrase activities in vitro.

Human immunodeficiency virus type 1 (HIV-1) integrase (IN) catalyzes the integration of viral DNA into the host chromosome, an essential step in retroviral replication. As a tool to study the structure and function of this enzyme, monoclonal antibodies (MAbs) against HIV-1 IN were produced. Epitope mapping demonstrated that the 17 MAbs obtained could be divided into seven different groups, and the selection of MAbs representing these groups were tested for their effect on in vitro activities of IN. Four groups of MAbs recognized epitopes within the region of amino acids (aa) 1 to 16, 17 to 38, or 42 to 55 in and around the conserved HHCC motif near the N terminus of IN. MAbs binding to these epitopes inhibited end processing and DNA joining and either stimulated or had little effect on disintegration and reintegration activities of IN. Two MAbs binding to epitopes within the region of aa 56 to 102 in the central core or aa 186 to 250 in the C-terminal half of the protein showed only minor effects on the in vitro activities of IN. Three Mabs which recognized on epitope within the region of aa262 to 271 of HIV-1 IN cross-reacted with HIV-2 IN. MAbs binding to this epitope clearly inhibited end processing and DNA joining and stimulated or had little effect on disintegration. In contrast to the N-terminal-specific MAbs, these C-terminal-specific MAbs abolished reintegration activity of IN.

Animals↗
PubMed1996

Functional assessment of balance and gait.

Individuals must be able to maintain an upright posture under a variety of conditions and to move independently. These constructs of balance and gait are fundamental components of physical functioning and should be incorporated into clinical assessment of older adults. The primary objective, therefore, is to review existing measures of functional balance and gait, concentrating on those which are quantitative, practical for use in clinical settings, and have demonstrated acceptable measurement properties. In addition, we discuss the rationale for the functional assessment of balance and gait, review essential measurement criteria, and discuss the utility of valid standardized measurement in clinical practice.

Activities of Daily Living↗