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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 127 records · Page 7Linked to original sources
PubMed1997

The pH dependency of protoporphyrin IX formation in cells incubated with 5-aminolevulinic acid.

Chinese hamster cells (V79) and human adenocarcinoma cells (WiDr) were incubated with 5-aminolevulinic acid (ALA) at different pH values and the rate of production of protoporphyrin IX (PpIX) was measured. The rate of production increased with pH in the range 6.0-7.5. Above pH 7.5 the rate decreased, possibly due to a reduced metabolic activity of the cells. The observations may be explained by the known pH-dependency of the activity of porphobilinogen deaminase (PBGD) and are in agreement with the assumption that PBGD constitutes a rate-limiting step in the synthesis of PpIX from ALA.

Adenocarcinoma↗
PubMed1997

[Application of gene technology in the diagnosis of familial hypercholesterolemia].

Familial hypercholesterolaemia is an autosomal dominant disorder characterized by hypercholesterolaemia, xanthomas and premature coronary heart disease. Treatment of hypercholesterolemia is effective and consists of dietary changes and lipid lowering drugs. Only a minor proportion of familial hypercholesterolaemia patients are adequately treated, however. One explanation for this is assumed to be the relatively vague clinical diagnostic criteria applied. Because familial hypercholesterolaemia is caused by a mutation in the gene encoding the low density lipoprotein (LDL) receptor, mutation analysis of this gene could form the basis for specific diagnosis. 29 different mutations in the LDL receptor gene have been found to cause familial hypercholesterolaemia among Norwegian patients, and a total of 681 patients from 322 unrelated families have been provided with a molecular genetic diagnosis. We conclude that the use of molecular genetic analysis is feasible, and should be used clinically.

DNA Mutational Analysis↗
PubMed1997

Photobleaching of protoporphyrin IX in cells incubated with 5-aminolevulinic acid.

Protoporphyrin IX (Pp IX) is the main photosensitizer in photochemotherapy with 5-aminolevulinic acid (ALA). Pp IX is photolabile and the present work shows that 70-95% of Pp IX in cells is degraded by clinically relevant light exposures (40-200 J cm(-2) at 630 nm). During light exposure a small yield of photoprotoporphyrin, which is also photolabile, is formed. A substantial fraction of Pp IX in cells incubated with ALA is bound to proteins. During light exposure these binding sites are destroyed, those close to tryptophan residues being the most sensitive. The rate of photodegradation of Pp IX in the cells is dependent on the initial concentration of Pp IX. The degradation mechanisms are therefore not only first order processes. Different degradation rates appear to be related to different types of binding sites. During light exposure, Pp IX molecules appear to move to different binding sites, evidently sites that are more vital for cell survival. Thus, the yield of photoinactivation of the cells, as measured per emitted photon of Pp IX fluorescence, increased during light exposure.

Aminolevulinic Acid↗
PubMed1997

A novel method for the study of autophagy: destruction of hepatocytic lysosomes, but not autophagosomes, by the photosensitizing porphyrin tetra(4-sulphonatophenyl)porphine.

A photoactivatable porphyrin, tetra(4-sulphonatophenyl)porphine (TPPS4), was shown to accumulate in rat hepatocytes as a linear function of dose after intravenous injection, and to localize predominantly in hepatocytic lysosomes. A major fraction of the lysosomal enzymes acid phosphatase and N-acetyl-beta-D-glucosaminidase was inactivated by TPPS4 after 20 h of contact with the drug in vivo in the absence of photoactivation. On exposure of isolated hepatocytes to light, photoactivated TPPS4 caused additional inactivation of the lysosomal enzymes as well as inactivation of intralysosomal lactate dehydrogenase (LDH), a cytosolic enzyme that accumulated in lysosomes as a result of autophagy during a 2 h incubation of hepatocytes at 37 degrees C in the dark (in the presence of the proteinase inhibitor leupeptin to prevent degradation of intralysosomal LDH). Photoactivation of TPPS4 also induced lysosomal rupture, with a loss of lysosomal enzymes, autophagocytosed LDH, endocytosed 125I-tyramine-cellobiose-asialo-orosomucoid and TPPS4 from the lysosomes. However, LDH-containing autophagosomes, accumulated in the presence of vinblastine (a microtubule inhibitor used to prevent the fusion of lysosomes with autophagosomes or endosomes), were not affected by TPPS4. TPPS4 may thus be useful as a selective lysosomal (or endosomal) perturbant in the study of autophagic-endocytic-lysosomal interactions.

Animals↗
PubMed1997

[Successful thrombolysis of a fulminant lung embolism during cardiopulmonary resuscitation].

A healthy 38-year-old woman suffered a sudden cardiac arrest 2 days after a vaginal hysterectomy. Although standard cardiac life support (CPR) was instituted immediately after the event, it was not possible to re-establish a spontaneous circulation for about 40 min. Systemic intravenous thrombolytic therapy with slow injection of 1.5 million IU urokinase was performed as a final life-maintaining measure because of the high probability that the underlying cause was a pulmonary embolus; 10 min later (after 60 min of ongoing CPR) the patient regained a stable circulation. She survived without neurological deficit in spite of the long duration of CPR.

Adult↗
PubMed1997

Energy metabolism in human melanoma cells under hypoxic and acidic conditions in vitro.

The response to treatment and the malignant progression of tumours are influenced by the ability of the tumour cells to withstand severe energy deprivation during prolonged exposure to hypoxia at normal or low extracellular pH (pHe). The objective of the present work was to demonstrate intertumour heterogeneity under conditions of microenvironment-induced energy deprivation and to investigate whether the heterogeneity can be attributed to differences in the capacity of the tumour cells to generate energy in an oxygen-deficient microenvironment. Cultures of four human melanoma cell lines (BEX-c, COX-c, SAX-c, WIX-c) were exposed to hypoxia in vitro at pHe 7.4, 7.0 or 6.6 for times up to 31 h by using the steel-chamber method. High-performance liquid chromatography was used to assess adenylate energy charge as a function of exposure time. Cellular rates of glucose uptake and lactate release were determined by using standard enzymatic test kits. The adenylate energy charge decreased with time under hypoxia in all cell lines. The decrease was most pronounced shortly after the treatment had been initiated and then tapered off. BEX-c and SAX-c showed a significantly higher adenylate energy charge under hypoxic conditions than did COX-c and WIX-c whether the pHe was 7.4, 7.0 or 6.6, showing that tumours can differ in the ability to avoid energy deprivation during microenvironmental stress. There was no correlation between the adenylate energy charge and the rates of glucose uptake and lactate release. Intertumour heterogeneity in the ability to withstand energy deprivation in an oxygen-deficient microenvironment cannot therefore be attributed mainly to differences in the capacity of the tumour cells to generate energy by anaerobic metabolism. The data presented here suggest that the heterogeneity is rather caused by differences in the capacity of the tumour cells to reduce the rate of energy consumption when exposed to hypoxia.

Cell Hypoxia↗
PubMed1997

Manganese and the heart: acute cardiodepression and myocardial accumulation of manganese.

The aim of study was to assess acute effects of the divalent manganese ion (Mn2+) in an intact but isolated heart preparation. Rat hearts were perfused in the Langendorff mode at constant flow rate. Left ventricular (LV) developed pressure (LVDP). LV pressure first derivatives (LVdp/dt max and min), heart rate (HR) and aortic pressure (AoP) were recorded. Ventricular contents of high energy phosphate compounds (HEP) and Mn metal were measured at the end of experiment. Infusion of MnCl2 for 5 min with perfusate concentrations 1-3000 microM induced an immediate depression of contractile function at and above 30 microM and negative chronotropy at and above 300 microM. These IC50 values were found (microM): LVDP 250; LVdp/dt max 160; LVdp/dp min 120; HR 1000; and increase in AoP 80. Recovery of function during a 14 min washout period was rapid and extensive except for Mn2+ 3000 microM. Somewhat unexpected, Mr2+ 30-1000 microM raised coronary vascular resistance up to about twice the control level, whereas the vasoconstrictory response was overcome at 3000 microM. Mn2+ 3000 microM reduced tissue HEP Ventricular Mn content rose stepwise for perfusate Mn2+ above 1 microM up to about 55 times the control level for perfusate Mn2+ 3000 microM. It is concluded that: acute effects of Mn2+ like depression of contractility and rate is rapidly reversible; and rat hearts accumulate and buffer large amounts of Mn2+ without affecting cardiac function or energy metabolism in the acute stage.

Animals↗
PubMed1997

Molecular genetics of familial hypercholesterolaemia in Norway.

OBJECTIVES: To characterize mutations in the low density lipoprotein (LDL) receptor gene causing familial hypercholesterolaemia (FH) amongst Norwegian patients. DESIGN: Molecular genetic analyses of the LDL receptor gene have been performed in patients with a clinical diagnosis of FH. SUBJECTS: A total of 742 probands have been studied. Of these, 476 had a diagnosis of definite FH. The rest had a diagnosis of possible FH. RESULTS: Twenty-three different mutations in the LDL receptor gene as well as the apolipoprotein B-3500 mutation have been found. Six of the mutations in the LDL receptor gene are novel mutations. A molecular genetic diagnosis was achieved in 295 of the probands with definite FH (62%) and in 317 probands total. Of the 317 probands, 3% carried the apolipoprotein B-3500 mutation. When family members were included, a total of 624 persons carried a mutation in the LDL receptor gene and 20 carried the apolipoprotein B-3500 mutation. CONCLUSIONS: Approximately 5% of Norwegian FH patients have been provided with a molecular genetic diagnosis. Our data suggest that molecular diagnosis of FH in Norway is feasible and should be implemented in clinical medicine.

Adult↗
PubMed1997

[Comparative study of pethidine and clonidine for prevention of postoperative shivering. A prospective, randomized, placebo-controlled double-blind study].

OBJECTIVE: Patients with ischaemic heart disease and cardiac failure are endangered by an increase in oxygen consumption caused by postoperative shivering. The purpose of this study was to evaluate if pethidine and clonidine, which are well known for their effectiveness in the treatment of this undesirable side effect, can also prevent postoperative shivering if administered at the end of surgery. In addition it was investigated whether their intraoperative application influences the time of extubation and analgesics demand in the early postoperative period. METHODS: 60 patients (ASA I-II) scheduled for elective microsurgical vertebral disc resection were included in the study. After standardised induction of anaesthesia (5 mg x kg-1 thiopental, 2 micrograms x kg-1 fentanyl, 0.1 mg x kg-1 vecuronium) lungs were ventilated with isoflurane vaporized in 66% N2O and 33% O2. The concentration of the inhalation anaesthetic was adjusted to maintain a surgical plane of anaesthesia without supplementary doses of opioids. Patients were randomly allocated in a double-blind fashion to one of three groups (each n = 20) to receive either pethidine (0.3 mg x kg-1) or clonidine (2 micrograms x kg-1) or 0.9% saline (control) 5 minutes prior to the end of surgery. Heart rate, arterial blood pressure and rectal temperature were measured at defined times, as well as the recovery time between the end of anaesthesia and extubation, incidence of postoperative shivering, and the pain level of the patients with a visual analog scale. The frequency and total demand of analgesics were determined using patient controlled analgesia and recorded for two hours postoperatively. RESULTS: The incidence of postoperative shivering in the clonidine group (5%) was less than in the pethidine group (25%) and significantly less than in the saline group (55%). Heart rate and blood pressure values after the administration of clonidine were lower than after pethidine and significantly lower than after saline. The time between end of surgery and extubation was similar in all groups with an average of 18 minutes. No significant differences among the pain scores and the analgesics demand were noted among any of the groups, including the saline control-group. CONCLUSION: Intraoperative administration of clonidine (2 micrograms x kg-1) is suitable for prevention of postoperative shivering. Despite its sedative effects the recovery time until extubation was not prolonged. 0.3 mg x kg-1 pethidine proved to be less beneficial.

Adjuvants, Anesthesia↗
PubMed1997

[Craniosynostosis operations in childhood].

Premature osteosynthesis of one or more cranial bones, either intrauterine or within the first postnatal months, is defined as craniosynostosis. The resulting limitation of intracranial space can cause retardation of cranial growth which, in turn, leads to craniostenosis with increasing intracerebral pressure. Complex forms of craniosynostosis with concomitant malformations (i.e. Apert-, Crouzon-, and Pfeiffer syndromes) must be principally distinguished from simple craniosynostosis. This complex cranio-facial dysostosis is a premature osteosynthesis of cranial and facial bones. In general, as far as Germany is concerned, the incidence of cranio-synostosis amounts to 1/1000 births. If they remain untreated, many of these children will suffer from cortex-associated retardation of intelligence. Surgical management, therefore, is initiated at a very early stage, and should be performed in specialised centres. Recommendations for operation vary from an age of 4 to 36 months. However, an age of 6 months or more is the most frequently preferred age for surgical intervention. Severe respiratory disorders, as well as impossibility of enteral intake of nourishment, are considered absolute indications for surgery, independent of the age; elimination of the stigmatisation regarding environmental contacts of the child is another mandatory indication for operation. The goal of early surgery is reconstruction of physiological, cranial, and facial bone structures ("fronto-orbital" or "fronto-facial advancement"). Correction of craniofacial malformation may be associated with--in part--severe complications for the child. From the anaesthesiologist's point of view, this disease demands highly qualified perioperative management, since a variety of idiosyncrasies and risks must be taken into account: These are, for example, venous air embolism, hypothermia, disorders of water and electrolyte equilibrium, and, extremely vital, difficult intubation and substantial blood loss.

Anesthesia, General↗
PubMed1997

Rehabilitation in nursing homes: a cross-national comparison of recipients.

OBJECTIVE: to examine the prevalence of therapy use in nursing homes in selected countries and to describe the characteristics of nursing home residents who receive therapy. DESIGN and SAMPLING: the design of the study is cross-sectional, using Minimum Data Set (MDS) assessments of nursing home residents. The sample includes all nursing home residents in six US states (n = 273491), in Copenhagen, Denmark (n = 3451), Reyjkavik, Iceland (n = 1254), and selected locations in Italy (n = 1089) and Japan (n = 1255). METHOD: we determined who had received physical or occupational therapy treatments in the last 7 days. Demographic and clinical characteristics of recipients were compared relative to other nursing home residents within each country. RESULTS: in the five countries, the prevalence of receiving therapy was 31% (Iceland), 30% Japan), 23% (Denmark), 14% (Italy) and 11% (USA). Substantial proportions of the recipients were over the age of 85, were clinically stable and had been in the nursing home for longer than 90 days. Across all countries, residents with poorer activities of daily living (ADL) scores but good cognitive scores were more likely to receive therapy than other residents. Rehabilitation nursing, an adjunct to therapy, was concentrated on residents with poor ADL scores. CONCLUSIONS: substantial numbers of long-stay residents receive therapy in nursing homes, including those over the age of 85 years and those with cognitive impairment. Hence, future rehabilitation outcome studies can involve these previously understudied patient populations.

Activities of Daily Living↗
PubMed1997

An international study of social engagement among nursing home residents.

METHOD: data using the Resident Assessment Instrument (RAI) from nursing home populations in five countries (Denmark, Iceland, Italy, Japan, USA) were assembled from 396277 residents. The distribution of a new quality of life measure, 'social engagement', embedded in the RAI and found to be reliable and valid in the USA, was examined and compared in the international samples. RESULTS: in all five countries' nursing home populations engagement was highest among residents with adequate functioning in activities of daily living (ADL) and cognition, but the level of social engagement differed considerably by country among residents with poor ADL functioning, who had adequate cognition. The lowest scores were in Italy and Japan. The amount of time residents spend in activities stratified by ADL and cognition reveal the same pattern cross-culturally--cognitively impaired residents are least actively involved. CONCLUSIONS: the Minimum Data Set measure of social engagement is stable across types of residents and across nations and can serve as a marker of nursing home quality.

Activities of Daily Living↗
PubMed1997

Transitions across various continuing care settings.

PURPOSE: to compare cross-nationally the sources and rates of admission and discharge in nursing homes. METHODS: data on admission were used from the Minimum Data Set of the Resident Assessment Instrument as collected in a multi-nation database at the University of Michigan. Additional data containing longitudinal episodes were used from databases in the Netherlands, Switzerland and the USA. RESULTS: the sources and rates of admission and discharge in nursing homes vary widely between countries. In Japan 47.5% of the sample was admitted from another long-term care setting, in Italy and the USA 36% and 42% respectively were admitted directly from hospital, while in Denmark and Iceland more than 60% came from home. The longitudinal data show that in the Netherlands, residents' return to home was much more likely than in Geneva or the USA (27% vs 5% vs 10%) and that in the USA a relatively large number of nursing home residents (>45%) was discharged (intermittently) to a hospital within 180 days after first admission as compared to the Netherlands (10%). CONCLUSIONS: there are large differences between countries in admission and discharge to and from nursing homes. Various policies, payment schemes, care patterns and routine referrals influence this and can be studied with cross-national data now available.

Aged↗
PubMed1997

Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia.

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalation anaesthetics and depolarizing neuromuscular blocking agents. To date, eight mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in malignant hyperthermia susceptible (MHS) and central core disease (CCD) cases. We have screened the RYR1 gene in affected individuals for novel MHS mutations by single stranded conformational polymorphism (SSCP) analysis and have identified a G to T transition mutation which results in the replacement of a conserved arginine (Arg) at position 614 with a leucine (Leu). The Arg614Leu mutation was present in three unrelated MHS individuals of 151 investigated. The mutation was not detected in 148 normal chromosomes and segregated precisely with MHS in family members from one of the probands where DNA was available for analysis. This mutation occurs at the same position as the previously identified Arg to Cys mutation reported in all cases of porcine MH and in approximately 5% of human MH. A comparison of the phenotypes of the Arg614Leu and Arg614Cys probands is presented.

Amino Acid Sequence↗
PubMed1997

Effects of MnDPDP, DPDP--, and MnCl2 on cardiac energy metabolism and manganese accumulation. An experimental study in the isolated perfused rat heart.

RATIONALE AND OBJECTIVES: Recent studies indicate that manganese dipyridoxyl diphosphate (MnDPDP) may function as a slow release agent for manganese ions (Mn++) and that MnDPDP is approximately 10 times less potent than manganese chloride (MnCl2) in depressing cardiac function. The authors examined the possibility that MnDPDP and MnCl2 may influence cardiac metabolism and enzyme release and lead to a tissue accumulation of Mn. METHODS: Manganese DPDP, DPDP--, or MnCl2 (1000 microM) was infused in isolated rat hearts, which were freeze-clamped at various time intervals during infusion (5 minutes) and recovery (14-minute washout). Enzyme (lactate dehydrogenase) release, tissue high energy phosphates, Mn contents, and physiologic indices were measured at various time intervals. RESULTS: No significant differences were noted for: lactate dehydrogenase in the treated groups; tissue creatine phosphate (CrP) and adenosine triphosphate in MnDPDP, DPDP--, and control groups; and tissue Mn in DPDP-- and control groups. Manganese-chloride and MnDPDP-treated hearts accumulated and retained Mn in an 8:1 ratio. Manganese chloride depressed cardiac function more effectively than MnDPDP. CONCLUSIONS: The study has shown that: heart tissue uptake and retention of Mn++ is rapid and effective; MnCl2 is approximately eight times more potent than MnDPDP in promoting these effects; and a rise in tissue Mn content to eight to nine times (MnDPDP) or 60 to 70 times (MnCl2) the normal level does not lead to acute side effects on cardiac energy metabolism, function, and enzyme release. The study indicates that MnDPDP may act like a slow release compound for Mn++ ions.

Animals↗
PubMed1997

Impact of the Medicare Catastrophic Coverage Act on nursing homes.

The Medicare Catastrophic Coverage Act (MCCA) of 1988 altered eligibility and coverage for skilled nursing facility (SNF) care and changed Medicaid eligibility rules for nursing-home residents. Detailed data on the residents of a for-profit nursing-home chain and Medicare claims for a 1 percent sample of beneficiaries were used to examine the impact of the MCCA on nursing homes. The case mix of nursing-home admissions was scrutinized, specifically for length of stay, discharge disposition, rate of hospitalization, and changes in payer source. Findings revealed that, although the proportion of Medicare-financed nursing-home care increased, as did the case-mix severity of residents during the MCCA period, there was no corollary reduction in hospital use by nursing-home residents.

Diagnosis-Related Groups↗
PubMed1997

Malignant hyperthermia susceptibility, an autosomal dominant disorder?

A large series of Swedish nuclear families, in which malignant hyperthermia (MH) reactions had occurred during anaesthesia, have been examined with respect to malignant hyperthermia susceptibility. In vitro contracture tests (IVCT) of muscle strips were conducted to diagnose MH status. Included in this series were some families where only one of the parents was tested by IVCT, while in 79 of the families both parents were tested by IVCT. Six known mutations in the gene encoding the calcium release channel of sarcoplasmic reticulum in skeletal muscle (the RYR1 gene), believed to cause MHS in man, were searched for in 41 nuclear families. The present paper focuses on findings in eight families, where both parents were malignant hyperthemia negative (MHN), while at least one child was either malignant hyperthermia susceptible (MHS) or malignant hyperthermia equivocal (MHE). There was no suggestion of non-paternity. The RYR1 mutations investigated were Arg163Cys, Gly341Arg, Ile403Met, Arg614Cys, Gly2433Arg and Arg2434His. No family had any of the six RYR1 mutations searched for.

Adolescent↗