PubMed Health⌕ Search

Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Relationship between cladribine (CdA) plasma, intracellular CdA-5'-triphosphate (CdATP) concentration, deoxycytidine kinase (dCK), and chemotherapeutic activity in chronic lymphocytic leukemia (CLL).

Seventeen patients with CLL were treated with oral 2-chloro-2'-deoxyadenosine (cladribine, CdA, 10 mg/m2) on 3 consecutive days and the pharmacokinetic parameters of CdA in patient plasma and its intracellular nucleotides (CdAMP, CdATP) in circulating leukemic cells were studied after the last dose intake and up to 72 h thereafter. The median terminal half life (t1/2) of CdA in plasma was 21.1 h and the area under the curve (AUC) was median 1.2 microMh. The median t1/2 was 14.6 h for CdAMP and 9.7 h for CdATP. The AUC of CdATP in leukemic cells is lower than the AUC of CdAMP (median ratio 0.60). There was no correlation between cellular CdATP and plasma CdA concentrations or dCK activity. The clinical response was related to higher Cmax values for plasma CdA (p = 0.05) and higher products of dCK activity and CdA Cmax of plasma (p = 0.02). The activity of dCK alone was not related to the clinical outcome in this patient group. The results suggest that further steps in the mechanism of action of CdA beyond its bioactivation may be more important, e.g. the extent of DNA fragmentation or the ability of the leukemic cell to go into apoptosis, than the concentration of CdA nucleotides alone.

Adenine Nucleotides↗
PubMed1998

Personal resources, motives and patient education leading to changes in cardiovascular risk factors.

The purpose of this study was to assess the importance of patients' abilities and motivation to reduce their excess morbidity by benefiting from patient education designed to effect such change. The course consisted of a 4 week full-time program and 4 day refresher course 1 year later. The 295 consecutive patients (60%) who returned for the refresher had substantially reduced their overrisk for stroke or coronary heart disease. Personal ability to accomplish the desired change, such as standard of education, was found to be unimportant, whereas motives like having other people dependent on one were deemed important. One reason why resources such as education were found not to be important could be that the course was lengthy, requiring nearly 5 weeks, and practically oriented.

Adult↗
PubMed1998

Alpha 1-antitrypsin deficiency.

Alpha 1-Antitrypsin deficiency (PiZ) is frequent in Caucasian populations. The predominant clinical correlates of this inborn error, i.e. chronic liver disease, emphysema, and vasculitic syndromes including their pathogenetic background are discussed in the present review.

Adult↗
PubMed1998

Erythrocytic protein kinase C activity in primary hypertension.

OBJECTIVES: Increased protein kinase C activity has been reported in erythrocytes from patients with primary hypertension and also from hypertensive rats. In this phenomenological study, we investigated whether a possible increased activity was the result of an augmented amount of enzyme molecules or a more active enzyme. DESIGN: Collect blood samples, separate erythrocytes from other blood cells. After partial purification of protein kinase C in the erythrocyte lysate, assay the enzyme activity under optimal conditions using a specific peptide substrate. SETTING: Central Hospital in Eskilstuna and University Hospital in Uppsala, Sweden. SUBJECTS: Healthy individuals: 47 persons (20 women and 27 men). Ten patients with untreated primary hypertension. MAIN OUTCOME MEASURES: Erythrocytes were separated from leucocytes and platelets by passing through a cellulose column followed by repeated washings. Some proteins in the erythrocyte lysate interfering with protein kinase C assay were removed by chromatography on DEAE-cellulose. RESULTS: The mean protein kinase C activity in erythrocytes from healthy individuals was 0.18 +/- 0.02 pmol [32P]phosphate min(-1) x 10(6) cells, regardless of sex and age. The corresponding value for patients with primary hypertension was 0.16 +/- 0.04 pmol [32P]phosphate min(-1) x 10(6) cells. CONCLUSIONS: The amount of protein kinase C, measured as the activity at optimal assay conditions, in erythrocytes from patients with primary hypertension is not critical for the development of moderate hypertension.

Adult↗
PubMed1998

Screening for coeliac disease in adult insulin-dependent diabetes mellitus.

OBJECTIVES: To study, by sequential screening for gliadin antibodies (GA) and endomysial antibodies (EMA), the prevalence and clinical characteristics of coeliac disease (CD) in adult IDDM patients. SUBJECTS AND MEASUREMENTS: A series comprising 1664 diabetes patients [848 with IDDM, 745 with non-insulin-dependent diabetes (NIDDM) and 71 with secondary diabetes] were screened for GA. IgA- or IgG-GA positive sera were analysed for EMA. RESULTS: IgA-GA were more frequent in all the diabetes subgroups (13.7% in IDDM,12.3% in NIDDM and 23.9% in secondary diabetes, P < 0.001 in all three cases) than among healthy blood donors (4.7%). Two patients with NIDDM had CD. Of the IDDM group (n = 848), 8 had previously diagnosed CD and 14 more (of whom 7 could be biopsied) were EMA positive. All had villous atrophy. The minimum prevalence of CD (including probable cases) in IDDM was 2.6% (22/848). Patients with previously known CD had more symptoms (P < 0.001), more deficiency states (P < 0.001) and more autoimmune diseases (P < 0.04) than those identified by screening. IDDM patients with a diabetes duration of 31-40 years were characterised by a higher prevalence of CD than patients with a duration of less than 30 years (6.7% vs. 1.7%; P < 0.02). CONCLUSIONS: Serial analysis of GA and EMA confirmed a high prevalence of CD in adult IDDM (2.6%). False-positive IgA-GA test results are frequent in patients with diabetes, irrespective of type. EMA analysis is the preferable screening tool for CD in diabetes.

Adult↗
PubMed1998

Factors associated with cirrhosis development in chronic hepatitis C patients from an area of low prevalence.

The aim of this study was to evaluate the importance of different endogenous and exogenous factors associated with cirrhosis development among hepatitis C virus (HCV)-positive individuals from an area of low prevalence. We studied 106 consecutive HCV RNA positive patients who had undergone liver biopsy. Each patient was assessed with special attention to risk factors for hepatitis C infection, average daily alcohol consumption and analysis of plasma levels of alpha1-antitrypsin (alpha1AT) and alpha1-antichymotrypsin (alpha1ACT). Viral RNA, amplified from serum with the polymerase chain reaction (PCR) technique, was used for genotyping. Liver biopsies were assessed according to conventional histopathological criteria, and for necroinflammatory activity (grade) and fibrosis (stage) according to a numerical scoring system. The presence of cirrhosis (stage 4) was used as the dependent variable in multivariate logistic regression analysis. Alcohol abuse (P = 0.007), age at entry (P < 0.001), immigrant status (P = 0.017) and a low alpha1ACT level (P = 0.008) were all independent determinants of progression to cirrhosis whereas HCV genotype 1, estimated duration of HCV infection and positivity for antibodies to hepatitis B core antigen (HBcAb) were not. Cirrhosis occurred at a significantly younger age (P = 0.00(5) among alcohol abusers. Hence, both endogenous and exogenous factors such as subnormal alpha1ACT levels and alcohol appear to contribute to the rate of progression to cirrhosis among HCV-positive patients.

Adult↗
PubMed1998

Long-term outcome of chronic hepatitis C infection in a low-prevalence area.

BACKGROUND: Although hepatitis C virus (HCV) infection is recognized as an important causative factor in the development of liver cirrhosis and hepatocellular cancer (HCC), the strength of this correlation has been difficult to confirm in low-prevalence areas. METHODS: Stored serum samples from 987 consecutive (1978-88) patients with chronic liver disease were tested with an enzyme-linked immunosorbent assay for anti-HCV and further confirmed by immunoblot. To evaluate the long-term outcome, the cohort was followed up until 1995, for a median observation time of 10 years. RESULTS: Anti-HCV, confirmed by immunoblot, was found in 9.5% (94 of 987) of the patients, and at inclusion most patients were asymptomatic irrespective of anti-HCV status. Of the 445 patients who died during the study period, 44 were HCV-positive. A liver-related cause of death was far commoner and the age-adjusted survival shorter among HCV-positive patients than among HCV-negative ones. At death 68% (30 of 44) of the HCV-positive subgroup had developed cirrhosis, and 30% (13 of 44) had concurrent HCC, as compared with 36% (142 of 393) (P = 0.001) and 8% (31 of 393) (P = 0.001), respectively, of the HCV-negative subgroup. HCV infection (P < 0.001), alcohol abuse (P < 0.001), and immigrant status (P = 0.045) were independent factors with regard to the development of cirrhosis, whereas HCV infection (P = 0.040) and immigrant status (P = 0.012) were independent factors with regard to HCC. CONCLUSIONS: HCV infection is common among patients with chronic liver disease, even when clinical evidence of viral infection is sparse, and constitutes a significant cause of death even in a low-prevalence area.

Carcinoma, Hepatocellular↗
PubMed1998

Interval appendicectomy: a retrospective study.

OBJECTIVE: To investigate the complication rate after open interval appendicectomy and compare it with the complication rate after acute appendicectomy. DESIGN: Retrospective study. SETTING: Teaching hospital, Sweden. SUBJECTS: 38 patients with appendiceal abscess or chronic appendicitis who underwent interval appendicectomy. MAIN OUTCOME MEASURES: Operative and histological findings, and postoperative complications after interval appendicectomy. RESULTS: The reasons for interval appendicectomy were appendiceal abscess (n = 32, verified by ultrasonography in 25 cases), chronic appendicitis (n = 4), and previous acute appendicitis (n = 2). Five patients underwent drainage of the abscess during the acute episode. The median interval between first symptoms of appendicitis and interval appendicectomy was 3.5 months (range 1.5-15). In two patients (5%) there were no macroscopic or microscopic signs of previous appendicitis and in one patient (61 years old) an adenocarcinoma was found in the base of the appendix. The complication rate was 13% (5/38), which is similar to our morbidity after acute appendicectomy (244/2352, 10%). CONCLUSIONS: Interval appendicectomy has the same complication rate as acute appendicectomy, and is hardly ever done. We no longer recommend it as a routine and it should be done only for special indications such as persisting complaints that suggest appendicitis.

Abscess↗
PubMed1998

Short and long term course of elderly patients with peptic ulcer bleeding--analysis of factors influencing fatal outcome.

OBJECTIVE: To study long and short term survival in patients aged 60 years or over admitted with a peptic ulcer bleeding and find out which factors influence outcome. DESIGN: Cohort study with matched controls. SETTING: Two emergency hospitals, Sweden PATIENTS: 676 of the 687 patients aged 60 years or over admitted to the two emergency hospitals serving Gothenburg, Sweden during 1989-1993 who fulfilled the diagnostic criteria and whose case notes were available for study. MAIN OUTCOME MEASURES: Seven year survival rates and odds ratios for risk factors based on multiple logistic regression analyses. RESULTS: 37 patients died and the timing was evenly distributed within the first 30 days of admission with a cumulated case-fatality rate of 5.5% at day 30. Mortality was increased among the patients compared with the control group during the subsequent years. Factors that influenced day 30 mortality were age and Forrest class. CONCLUSION: Mortality is increased among patients with peptic ulcer bleeding even long after the event. Old age and signs of recent haemorrhage increase the risk.

Age Factors↗
PubMed1998

Substrate specificity of human recombinant mitochondrial deoxyguanosine kinase with cytostatic and antiviral purine and pyrimidine analogs.

Deoxyguanosine kinase (dGK) is an enzyme responsible for the phosphorylation of purine deoxynucleosides in mitochondria of mammalian cells. Its role in activation of pharmacologically used nucleoside analogs is not well understood, because of the low levels of dGK found in tissue extracts and its inactivation during purification. The cDNA for dGK was recently cloned and expressed in Escherichia coli. Here we present an improved procedure for expression and purification of a highly active form of human recombinant dGK. The enzyme showed a broad substrate specificity toward natural purine and pyrimidine deoxynucleosides as well as toward important nucleoside analogs. The Km and Vmax values for deoxyguanosine, deoxyinosine, deoxyadenosine, and deoxycytidine were 4, 13, 460, 330 microM and 43, 330, 430 and 60 nmol/min/mg of protein, respectively. Antileukemic purine analogs such as arabinosyl guanine, 2-chloro-2'-deoxyadenosine, 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine, and 2-fluoro-arabinosyl-adenine were phosphorylated as efficiently by dGK as the natural nucleoside substrates. This is the first report in which 2-fluoro-arabinosyl-adenine and 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine were shown to be good substrates for dGK. The antiviral analogs dideoxyinosine and arabinosyl adenine also showed significant activity with dGK, as did several pyrimidine analogs (e.g., the cytostatic drugs 5-fluoro-2'-deoxycytidine and difluorodeoxycytidine). The broad specificity of dGK described here may change our understanding of the mechanisms responsible for the efficacy and mitochondrial toxicity of several nucleoside analogs.

Humans↗
PubMed1998

An Escherichia coli system expressing human deoxyribonucleoside salvage enzymes for evaluation of potential antiproliferative nucleoside analogs.

Deoxyribonucleoside salvage in animal cells is mainly dependent on two cytosolic enzymes, thymidine kinase (TK1) and deoxycytidine kinase (dCK), while Escherichia coli expresses only one type of deoxynucleoside kinase, i.e., TK. A bacterial whole-cell system based on genetically modified E. coli was developed in which the relevant bacterial deoxypyrimidine metabolic enzymes were mutated, and the cDNA for human dCK or TK1 under the control of the lac promoter was introduced. The TK level in extract from induced bacteria with cDNA for human TK1 was found to be 20,000-fold higher than that in the parental strain, and for the strain with human dCK, the enzyme activity was 160-fold higher. The in vivo incorporation of deoxythymidine (Thd) and deoxycytidine (dCyd) into bacterial DNA by the two recombinant strains was 20 and 40 times higher, respectively, than that of the parental cells. A number of nucleoside analogs, including cytosine arabinoside, 5-fluoro-dCyd, difluoro-dCyd, and several 5-halogenated deoxyuridine analogs, were tested with the bacterial system, as well as with human T-lymphoblast CEM cells. The results showed a close correlation between the inhibitory effects of several important cytostatic and antiviral analogs on the recombinant bacteria and the cellular system. Thus, E. coli expressing human salvage kinases is a rapid and convenient model system which may complement other screening methods in drug discovery projects.

Antineoplastic Agents↗
PubMed1998

Environmental correlates of impaired lung function in non-smokers with severe alpha 1-antitrypsin deficiency (PiZZ).

BACKGROUND: Active smoking is the most important risk factor for pulmonary emphysema in subjects with severe alpha 1-antitrypsin (AAT) deficiency. The aim of this study was to analyse the effects of environmental risk factors other than active smoking on lung function and on respiratory symptoms in non-smoking PiZZ individuals. METHODS: Lifetime exposure to passive smoking, domiciliary use of a kerosene (paraffin) heater or gas cooker, and all occupations since leaving school were reported by 205 non-smoking PiZZ individuals (95 men and 110 women) included in the Swedish AAT deficiency register. Lung function test results and histories of respiratory symptoms (chronic bronchitis, recurrent wheezing, and exertional dyspnoea) were elicited from the AAT register records. RESULTS: After adjustment for age, agricultural employment and domiciliary kerosene heater usage, but not gas cooker usage or passive smoking, were both associated with significantly decreased lung function. Multiple linear regression analysis showed age, sex, kerosene heater usage, and agricultural employment to be independent determinants of lung function impairment. Age and passive smoking for 10 years or more, both at home and at the work place, were associated with the presence of chronic bronchitis. Age and agricultural employment for > or = 10 years were associated with recurrent wheezing and exertional dyspnoea. CONCLUSIONS: Domiciliary kerosene heater usage and an agricultural occupation therefore appear to be environmental factors associated with decreased lung function in non-smoking PiZZ individuals, and passive smoking is associated with an increased frequency of chronic bronchitis, but not with impaired lung function.

Adult↗
PubMed1998

Treatment of perforated appendicitis: an analysis of 362 patients treated during 8 years.

BACKGROUND AND METHOD: In a retrospective study 2,351 records from patients who underwent surgery for acute appendicitis during 1986-1993 were analysed. During this period, there were 362 patients with perforated appendicitis. The aim of this study was to analyse the complication rate, the period of antibiotic treatment and whether the complication rate decreased when intravenous treatment was followed by oral antibiotic treatment. RESULTS: The complication frequency was 18% which was significantly higher than that for non-perforated appendicitis of 10%. The complication rate was 15% in the group receiving additional oral antibiotics compared to 19% in the group receiving only intravenous antibiotics. This difference is not significant. CONCLUSION: Perforated appendicitis is however still associated with increased mortality and morbidity.

Administration, Oral↗
PubMed1998

Pharmacokinetics of cladribine in plasma and its 5'-monophosphate and 5'-triphosphate in leukemic cells of patients with chronic lymphocytic leukemia.

The pharmacokinetic parameters of cladribine (CdA) in patient plasma and its intracellular nucleotides CdA 5'-monophosphate (CdAMP) and CdA 5'-triphosphate (CdATP) were delineated in circulating leukemia cells in 17 patients with chronic lymphocytic leukemia, after the last dose intake and up to 72 h thereafter. Patients were treated with 10 mg/m2 CdA p.o. on 3 consecutive days. A novel and specific ion-pair liquid chromatographic method, which separates the intracellular CdA nucleotides, was used. The area under the concentration versus time curve (AUC) of CdAMP in leukemia cells was generally higher (median, 47 micromol/liter x h) than the AUC of CdATP (median, 22 micromol/liter x h); however, in some patients (3 of 17), the reverse relationship was seen. The median ratio between the AUC values for CdATP and CdAMP was 0.60 (95% confidence interval, 0.4-1.0). The median half-life (t(1/2)) of CdAMP was 15 h, and that of CdATP was 10 h. The median terminal t(1/2) of CdA in plasma was 21 h. A significant correlation was found between the maximum plasma CdA and cellular CdAMP concentrations (r = 0.56, P = 0.02). There was no correlation between the AUC values of cellular CdAMP and CdATP (r = 0.224, P = 0.55). No correlation was found between deoxycytidine kinase activity and intracellular pharmacokinetic parameters of CdAMP or CdATP. The response to treatment was not significantly related to intracellular concentration of CdAMP or active metabolite CdATP. There is great heterogeneity among patients in terms of AUC and t(1/2) of CdAMP and CdATP. Furthermore, the results emphasize the differences between the pharmacokinetics of plasma CdA and those of the metabolites in circulating leukemic cells.

Adenosine Monophosphate↗
PubMed1998

The view of caring among patients and personnel.

All patients in hospital care and primary health care in the country of Västerbotten, Sweden (n = 5158) were asked to express their level of satisfaction with the quality of care. The study was carried out on one specific day. All personnel on duty that day (n = 2824) were also included and asked to give their interpretations of their patients' experiences. A questionnaire containing positive and negative statements concerning both the relationship and the task aspects of care was used. The results showed that the youngest and oldest patients expressed the highest degree of satisfaction, while young and middle-aged patients expressed a more restrained view. The least satisfactory aspects concerned the opportunities to express criticism and the possibilities of receiving information about access to help outside the health care organization. The personnel's responses agreed with those of the patients, but fewer personnel thought that their patients were satisfied than was in fact the case.

Adolescent↗