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Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Regional differences in coeliac disease prevalence in Scandinavia?

BACKGROUND: According to investigations from the central region of Sweden (Linköping), Norway, and Finland based on antibody screening, the prevalence of coeliac disease (CD) is around 1:300 (0.33%). In Denmark surveys in paediatric departments have shown a prevalence of only 1:10,000. The aim of the present study was to study the prevalence of CD in southern Sweden. METHODS: From October 1996 to February 1997, 1970 healthy blood donors were screened for CD in a serial procedure: first IgA and IgG gliadin antibodies (GA) and then endomysial antibodies in those positive for GA. RESULTS: One patient had previously known CD. Two patients had gastrointestinal symptoms and an increased number of intraepithelial lymphocytes, with improvement on a gluten-free diet. Three of 185 GA-positive blood donors had endomysial antibodies and biopsy-verified CD. Thus, 4 of 1970 blood donors had classic CD, resulting in a prevalence of 1:492 (0.20%)--that is, rather similar to that found in Linköping, Sweden, and in Finland and Norway. If the two persons with gluten-sensitive diarrhoea were also included, the prevalence was 6:1970 = 1:328, or 0.30%. CONCLUSIONS: The prevalence of classic CD (1:492) in southern Sweden is comparable to that found in the rest of Scandinavia, except for Denmark.

Adolescent↗
PubMed1999

Substrate/inhibitor properties of human deoxycytidine kinase (dCK) and thymidine kinases (TK1 and TK2) towards the sugar moiety of nucleosides, including O'-alkyl analogues.

Nucleoside analogues with modified sugar moieties have been examined for their substrate/inhibitor specificities towards highly purified deoxycytidine kinase (dCK) and thymidine kinases (tetrameric high-affinity form of TK1, and TK2) from human leukemic spleen. In particular, the analogues included the mono- and di-O'-methyl derivatives of dC, dU and dA, syntheses of which are described. In general, purine nucleosides with modified sugar rings were feebler substrates than the corresponding cytosine analogues. Sugar-modified analogues of dU were also relatively poor substrates of TK1 and TK2, but were reasonably good inhibitors, with generally lower Ki values vs TK2 than TK1. An excellent discriminator between TK1 and TK2 was 3'-hexanoylamino-2',3'-dideoxythymidine, with a Ki of approximately 600 microM for TK1 and approximately 0.1 microM for TK2. 3'-OMe-dC was a superior inhibitor of dCK to its 5'-O-methyl congener, consistent with possible participation of the oxygen of the (3')-OH or (3')-OMe as proton acceptor in hydrogen bonding with the enzyme. Surprisingly alpha-dT was a good substrate of both TK1 and TK2, with Ki values of 120 and 30 microM for TK1 and TK2, respectively; and a 3'-branched alpha-L-deoxycytidine analogue proved to be as good a substrate as its alpha-D-counterpart. Several 5'-substituted analogues of dC were good non-substrate inhibitors of dCK and, to a lesser extent, of TK2. Finally, some ribonucleosides are substrates of the foregoing enzymes; in particular C is a good substrate of dCK, and 2'-OMe-C is an even better substrate than dC.

Antimetabolites, Antineoplastic↗
PubMed1999

The prevalence and clinical significance of alpha 1-antitrypsin deficiency (PiZ) and ANCA specificities (proteinase 3, BPI) in patients with ulcerative colitis.

Our aim was to determine the prevalence of the PiZ allele for alpha 1-antitrypsin (AAT) deficiency and some relevant antineutrophil cytoplasmic antibody (ANCA) specificities in patients with ulcerative colitis (UC), and explore a possible association between these markers. In addition, we studied the relation to disease extension and activity. Sera from 141 patients with UC (72 women) were analyzed while 50 blood donors and 54 patients with acute myocardial infarction served as controls. Serum samples were screened for PiZ with ELISA and phenotyped by isoelectric focusing. BPI-ANCA and PR3-ANCA were detected by ELISA. Results were that 8.5% (12/141) of the patients with UC were PiZ carriers, higher than expected in the general Swedish population (4.7%) (p = 0.03). There was a significant difference between PiZ-carriers and non-PiZ-carriers in the extension and severity of colitis (odds ratio = 4.1, confidence interval = 1.1, 14.9; p = 0.028, and odds ratio = 9.0, confidence interval = 1.1, 73.3; p = 0.015; respectively). BPI-ANCA and PR3-ANCA were detected in 20.5% (29/141) and 12% (17/141) (p < 0.05 compared with controls for all parameters). Occurrence of BPI-ANCA and PR3-ANCA was not related to extension or severity of colitis (p > 0.05 for both variables). We observed no association between PiZ-carrier status and occurrence of BPI-ANCA or PR3-ANCA. The increased frequency of heterozygosity for the PiZ variant of AAT deficiency among patients with UC might imply a role played by protease inhibitors for regulation of inflammation and immunologic response in UC.

Adolescent↗
PubMed1999

Surgical treatment of epilepsy--clinical, radiological and histopathological findings in 139 children and adults.

The present study relates clinical and radiological data to histopathological diagnoses in the first 139 patients (children and adults) in the Göteborg Epilepsy Surgery series. Temporal lobe resections were most common (54.0%) followed by frontal lobe (18.0%) and multilobar resections (11.5%). All histopathological specimens were re-evaluated in connection with this study. Parenchymal malformations and atrophic-gliotic lesions were the most common histopathological findings. Microdysgenesis was more common than major malformations (24.5% versus 11.5%). When the MRI scans were blindly re-evaluated the MRI findings correlated with histopathological diagnosis in all of the vascular malformations, in 77.8% of the tumours, in 76.5% of the cases with hippocampal sclerosis but only in 28.6% of the major cortical development malformations. Hemispherectomies carried the best seizure outcome prognosis followed by temporal lobe resections (75.0% versus 57.3% seizure free 2 years after surgery). Vascular malformations carried the best, and microdysgenesis the worst prognosis (76.9% versus 39.4% seizure free).

Adolescent↗
PubMed1999

Microdysgenesis in surgical specimens from patients with epilepsy: occurrence and clinical correlations.

Malformations of cortical development are commonly associated with epilepsy. In the first 139 consecutive patients in the Göteborg epilepsy surgery series, parenchymal malformations were found in 56. 1% of the children and in 23.1% of the adults. Microdysgenesis (MDG), which was the most common parenchymal malformation, was found in 35. 1% of the children and in 16.7% of the adults. The aim of this study was to identify clinical characteristics of patients with MDG. Mental retardation was found to be significantly more common in patients with major parenchymal malformations and in patients with MDG compared with patients without parenchymal malformations. Patients with major parenchymal malformations as well as patients with MDG also had a significantly earlier onset of seizures than patients without parenchymal malformations, also when adjusting for mental retardation. Patients with MDG were in these clinical aspects shown to closely resemble patients with major malformations. These findings suggest that MDG is a pathoanatomical entity of clinical relevance, with implications both in mental retardation and in epileptogenesis.

Adolescent↗
PubMed1999

Omeprazole and ranitidine in the prevention of relapse in patients with duodenal ulcer disease.

BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse. PATIENTS AND METHODS: In a double-blind, parallel-group clinical trial of 928 patients (from 70 centres in 16 countries) with duodenal ulcers who after a short term study had relief of symptoms and healed ulcers proved endoscopically, 308 were randomly assigned to receive omeprazole 10 mg in the morning, 308 to receive omeprazole 20 mg in the morning and 312 to receive ranitidine 150 mg at bedtime for up to 12 months. Symptoms were assessed every three months and endoscopy repeated at three, six and 12 months, or more often if indicated by recurrence of symptoms. The safety screening included basal serum gastrin concentrations and gastric mucosal histopathology. RESULTS: The remission rates up to 12 months were 87% for the omeprazole 20 mg group, 71% for the omeprazole 10 mg group and 63% for the ranitidine group. Omeprazole 20 mg differed significantly from both omeprazole 10 mg (P=0.0001, 95% CI 9 to 23) and ranitidine (P=0.0001, 95% CI 17 to 31). There was no statistically significant difference between omeprazole 10 mg and ranitidine over the 12-month period, but the 95% confidence interval allowed differences between 0% and 16% in favour of omeprazole at 12 months. A Cox regression analysis revealed that longer treatment courses to heal, smoking, a long ulcer history and young age negatively contributed to the odds of staying in remission. The treatments were well tolerated. There was a slight increase in basal serum gastrin concentrations, reflecting the different degrees of acid inhibition induced by the three treatments. No dysplastic or neoplastic lesions were found in any biopsies. CONCLUSIONS: More duodenal ulcer patients are maintained in remission with omeprazole 20 mg daily than with omeprazole 10 mg daily or with ranitidine 150 mg at bedtime.

Adolescent↗
PubMed1999

Diagnostic accuracy in 2,351 patients undergoing appendicectomy for suspected acute appendicitis: A retrospective study 1986-1993.

AIMS: To investigate the pre-operative findings, accuracy, perforation rate and complication rate in 2,351 patients who underwent appendicectomy during 1986-1993. METHOD: The 2,351 records from patients who underwent surgery were analysed to determine whether the pre-operative investigations introduced can improve the diagnostic accuracy when analysed in total. RESULTS: The total diagnostic accuracy which was 70.9% in 1986 increased to a statistically significant figure of 87.1% in 1993. In female patients, the figure increased from 61.7 to 82.4% and in males from 82.0 to 91.2% during the studied period. The complication rate was in total 10.4% including a mortality of 0.21% (5 patients). CONCLUSION: We believe that with a combination of increased interest in patients with acute appendicitis, a wider use of active in-hospital observation, a more standardised pre-operative laboratory investigation and the use of ultrasonography, a high diagnostic accuracy could be reached without an increased rate of complications and perforations.

Acute Disease↗
PubMed1999

Decline in FEV1 related to smoking status in individuals with severe alpha1-antitrypsin deficiency (PiZZ).

Severe alpha1-antitrypsin (AAT) deficiency predisposes to emphysema development. Highly variable rates of decline in lung function are reported in PiZZ individuals. The annual decline in forced expiratory volume in one second (FEV1; delta FEV1) was analysed in relation to smoking status in a cohort of 608 adult PiZZ individuals included in the Swedish national AAT deficiency register. Delta FEV1 was analysed in 211 never-smokers, in 351 exsmokers, and in 46 current smokers after performing at least two spirometries during a follow-up time of 1 yr or longer (median 5.5 yrs, range 1-31). The adjusted mean delta FEV1 in never-smokers was 47 mL x yr(-1) (95% confidence interval (CI) 41-53 mL x yr(-1)), 41 mL x yr(-1) (95% CI 36-48 mL x yr(-1)) in exsmokers, and 70 mL x yr(-1) (95% CI 58-82 mL x yr(-1)) in current smokers. A dose-response relationship was found between cigarette consumption and delta FEV1 in current smokers and exsmokers. In never-smokers, a greater delta FEV1 was found after 50 yrs of age than before. No sex differences were found in delta FEV1. In conclusion, among PiZZ individuals, the change in forced expiratory volume in one second is essentially the same in never-smokers and exsmokers. Smoking is associated with a dose-dependent increase in the change in forced expiratory volume in one second.

Adult↗
PubMed1999

Male reduction mammaplasty after vertical banded gastroplasty.

BACKGROUND: Breast reduction surgery is common in females; however, in males it is mainly due to gynecomastia. After weight reduction following obesity surgery, it is a problem in women, but also in some men. METHOD: One patient is described in whom the weight reduction declined from BMI 52 to BMI 36 after vertical banded gastroplasty, giving the patient ptotic breasts. RESULTS: The patient underwent reduction mammaplasty with lateral single-based cutaneous flaps, and a total of 1,000 g was removed. CONCLUSION: Reduction mammoplasty can be performed in males with the methods used today, after successful weight loss following obesity surgery.

Adult↗
PubMed1999

Effects of high resistance training in patients with myotonic dystrophy.

Nine ambulatory subjects with myotonic dystrophy participated in a supervised 12-week progressive high-resistance training program. Knee extensor muscles were trained 3 times a week with free weights, 3 x 10 repetitions at 80% of 1RM. One leg was randomly chosen for training and the other served as control. Six patients completed the training program. In the trained leg, 1RM increased from 16.4 +/- 3.4 kg to 21.8 +/- 2.6 kg (p = 0.0002). There was no difference between pre- and post-training concentric or eccentric isokinetic values at 30 degrees/second in either leg. Muscle biopsy from m. vastus lateralis in the trained leg revealed no systematic difference in the degree of histopathological abnormalities before and after training. After training, there was a tendency toward increase in cross-sectional area of type I muscle fibres. However, the number of subjects was too small to draw conclusions regarding the effects of training on the histopathological changes. Magnetic resonance imaging revealed no difference in the m. quadriceps area after training. In conclusion, patients with myotonic dystrophy improved their muscle strength without any observed negative side effects after a 12-week high-resistance training program.

Adult↗
PubMed1999

Biochemical pharmacology and resistance to 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine, a novel analogue of cladribine in human leukemic cells.

The objective of the present study was to investigate the biochemical pharmacology of 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA)--a fluorinated analogue of cladribine [2-chloro-2'-deoxyadenosine, Leustatin (CdA)] with improved acid and metabolic stability--in human leukemic cell lines and in mononuclear cells isolated from patients with chronic lymphocytic leukemia (CLL) and acute myelocytic leukemia (AML). We have also made and characterized two cell lines that are not sensitive to the growth inhibitory and cytotoxic effects of CAFdA. Incubation of cells isolated from the blood of CLL and AML patients with various concentrations of CdA or of CAFdA accumulated CdA and CAFdA nucleotides in a dose-dependent manner. A significantly higher rate of phosphorylation to monophosphates was observed for CAFdA than for CdA in cells from CLL patients (n = 14; P = 0.04). The differences in the phosphorylation were even more pronounced for the respective triphosphates in both CLL (n = 14; P = 0.001) and AML (n = 4; P = 0.04) cells. Retention of CAFdA 5'-triphosphate (CAFdATP) was also longer than that for CdA 5'-triphosphate (CdATP) in cells from leukemic patients. The relative efficacy of CAFdA as a substrate for purified recombinant deoxycytidine kinase (dCK), the key enzyme in the activation of nucleoside analogues, was very high and exceeded that of CdA as well as the natural substrate, deoxycytidine, by a factor of 2 and 8, respectively. The Km for CAFdA with dCK was also lower than that for CdA, as measured in crude extracts from the human acute lymphoblastic leukemia cell line CCRF-CEM and the promyelocytic leukemia cell line HL60. Acquired resistance to CAFdA in HL60 and in CCRF-CEM cell lines was directly correlated to the decreased activity of the nucleoside phosphorylating enzyme, dCK. Resistant cells also showed a considerable degree of cross-resistance to analogues that were activated by dCK. These observations demonstrated that dCK phosphorylates CAFdA more efficiently than CdA. Furthermore, CAFdATP is apparently more stable than CdATP and the mechanisms of resistance to CAFdA are similar to those leading to CdA resistance. These results encourage studies on the clinical effect of CAFdA in lymphoproliferative diseases.

Adenine Nucleotides↗
PubMed1999

Acute appendicitis in the elderly. An analysis of 47 patients over 80 years of age.

OBJECTIVE: To correlate the preoperative findings, perforation rate and the mortality rate after appendicectomy in the elderly age. DESIGN: Retrospective study. SETTING: Teaching hospital, Sweden. SUBJECTS: Forty-seven patients over 80 years of age who have undergone acute appendicectomy. MAIN OUTCOME MEASURES: Operative and postoperative outcome after acute appendicectomy in the elderly. RESULTS: The complication rate after appendicectomy was statistically significantly increased to 28% as well as the mortality increased to 8.5% in the elderly patients when compared to the other age group. The perforation rate was also statistically significantly increased to 64% when compared to the same group. CONCLUSIONS: Our study shows that at the time of clinical symptoms, inflammatory parameters in acute appendicitis in the elderly do not differ from the young patient, but patients older than 80 years of age have a high risk of perforation, morbidity and mortality.

Aged↗
PubMed1998

The intracellular localization of deoxycytidine kinase.

Deoxycytidine kinase (dCK) catalyzes the rate-limiting step of the deoxynucleoside salvage pathway in mammalian cells and plays a key role in the activation of several pharmacologically important nucleoside analogs. Using a highly specific polyclonal antibody raised against a C-terminal peptide of the human dCK, we analyzed its subcellular localization by Western blots of biochemically fractionated nuclear and cytoplasmic fractions as well as by in situ immunochemistry. Native dCK was found to be located mainly in the cytoplasm in several cell types, and the enzyme was more concentrated in the perinuclear and cellular membrane area. In contrast, when dCK was overexpressed in the cells, it was mainly located in the nucleus. The results demonstrate that native dCK is a cytoplasmic enzyme. However, it has the ability to enter the nucleus under certain conditions, suggesting the existence of a cytoplasmic retention mechanism that may have an important function in the regulation of the deoxynucleoside salvage pathway.

Amino Acid Sequence↗
PubMed1998

Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2'-deoxyadenosine (Cladribine) in human lymphocytes.

Deoxycytidine kinase (dCK, EC.2.7.1.74), a key enzyme in intracellular metabolism of many antileukemic drugs, was shown to be activated during treatment of lymphocytes by 2-chloro-2'-deoxyadenosine (Cl-dAdo, cladribine), a potent inhibitor of DNA synthesis. While 5-[3H]-thymidine (TdR) incorporation into DNA was decreased by 80-90%, dCK activity was doubled as a consequence of incubating the cells with 1 microM 2-chloro-2'-deoxyadenosine. Thymidine kinase (dTK, EC.2.7.1.21) activity was slightly decreased under the same conditions, similarly to 5-[3H]-thymidine incorporation. dCK activation could not be prevented by cycloheximide, and neither the amount of dCK protein nor its mRNA level was increased after 2-chloro-2'-deoxyadenosine treatment. These results suggest a post-translational activation of dCK protein during inhibition of DNA synthesis.

Antineoplastic Agents↗
PubMed1998

A comparison of the enantioselectivities of human deoxycytidine kinase and human cytidine deaminase.

The stereoselectivities of recombinant human deoxycytidine kinase (EC 2.7.1.74) (dCK) and of recombinant human cytidine deaminase (EC 3.5.4.5) (CDA) were investigated with respect to a series of cytidine analogs, most of them having the unnatural L-stereochemistry. The enantioselectivity of dCK was always low and generally favored the L-enantiomers in the case of beta-2',3'-dideoxycytidine (beta-ddC), 5-fluoro-beta-2',3'-dideoxycytidine (beta-FddC) and beta-cytidine (beta-riboC). Concerning beta-2'-deoxycytidine, dCK showed a preference for the D-enantiomer. All other examined beta-L-cytidine analogs, [1-beta-L-lyxofuranosyl cytosine (beta-L-lyxoC), l-beta-L-xylofuranosyl cytosine (beta-L-xyloC), and 5-fluoro-1-beta-L-xylofuranosyl cytosine (beta-L-Fxylo C)], were substrates of dCK regardless of the nature of the pentose. None of the studied alpha-L-anomers (alpha-L-riboC, alpha-L-araC, alpha-L-lyxoC, or alpha-L-xyloC) was a substrate of dCK. Contrasting with the relaxed enantioselectivity of dCK, CDA had a strict requirement for D-cytidine analogs since none of the already listed beta-L- or alpha-L analogs was a substrate or an inhibitor of the enzyme. The conjunction of the preceding stereochemical properties of dCK and CDA confers to L-cytidine analogs important potentialities in antiviral and anticancer therapies.

Antiviral Agents↗
PubMed1998

Decrease in thymidylate kinase activity in peripheral blood mononuclear cells from HIV-infected individuals.

Nucleosides and nucleoside analogs are anabolised to their triphosphates by intracellular kinases. The anti-HIV analogue zidovudine (AZT) is phosphorylated by cytosolic thymidine kinase 1 (TK1), thymidylate kinase (dTMPK), and nucleoside diphosphate kinase. It is known that dTMPK is one of the rate-limiting steps in the activation of zidovudine. The activities of TK1, dTMPK, and deoxycytidine kinase (dCK) were determined in extracts of in vitro activated peripheral blood mononuclear cells from HIV-infected patients and healthy noninfected individuals. dTMPK activity was 10-fold lower and TK1 activity was five-fold lower in extracts from infected as compared to uninfected persons. Deoxycytidine kinase activities in the extracts from both groups were very similar. Differences in in vitro activation, as determined by flow cytometry, of the peripheral lymphocytes were not responsible for the decreased TK1 and dTMPK activities. A reduced level of intracellular azido-dideoxythymidinetriphosphate in activated mononuclear cells from HIV-infected patients was also observed. The low levels of TK1 and dTMPK in lymphocytes from HIV-infected patients may be related to the anergy phenomenon observed as a result of HIV infection. This effect should also be considered in the development of new anti-HIV drugs.

Cell Cycle↗
PubMed1998

The in vitro effect of lithocholic acid on the polymerization properties of PiZ alpha-1-antitrypsin.

We describe here an in vitro effect of lithocholic acid (LA), a secondary, hydrophobic bile acid, on the rate of polymerization of mutant, Z and wild-type, M alpha-1-antitrypsin (AAT). Using thioflavine T fluorescence and turbidity assays we demonstrated that the rate of aggregation for the Z AAT in the presence of LA at a molar ratio of 1:5 AAT to LA, in Tris-buffered saline, pH 7.4, is at least twice that of the Z protein alone or the M variant with and without LA. Also, Z AAT incubated for 48 h at room temperature had more than 50% diminished antielastase activity, while M AAT had only a 25% reduction in activity. Analysis of the AAT and AAT-LA samples after cleavage with pancreatic elastase by SDS-PAGE 10% gels showed that interaction between Z or M AAT and LA abolishes their ability to form SDS stable complexes with an enzyme and both of these forms of AAT showed elastase substrate behavior. Furthermore, Z as well as M AAT incubated with LA at 41 degrees C and cleaved with elastase showed only 80 to 60% increased thermal stability compared to 100% stabilization for the cleaved AAT alone in the absence of LA. These observations suggest that a rearrangement of the AAT molecule as a result of interactions with LA increases aggregation of AAT and diminishes its inhibitory activity.

Benzothiazoles↗