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J Heiskanen

Publications and source records attributed to J Heiskanen.

6 recordsLinked to original sources

Maternal susceptibility locus for obstetric cholestasis maps to chromosome region 2p13 in Finnish patients.

BACKGROUND: Obstetric cholestasis, attributed to maternal hypersensitivity to estrogens, is a pregnancy-specific disorder characterized by pruritus and biochemical cholestasis in the second or third trimester of pregnancy. The pathophysiology of the disorder is incompletely understood, but the familial nature of the disease has long been recognized. Carriership of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency has been reported to be associated with an increased risk of obstetric cholestasis and the gene is located in the p23 region of chromosome 2. METHODS: On the basis of this information, we conducted population-based linkage disequilibrium (LD) screening to find potential cholestasis-associated loci on chromosome 2. The study was carried out in 47 unrelated control women and in 45 cholestatic women, eight of whom had a positive family history. RESULTS: During initial screening with chromosome 2-specific microsatellite markers, the tetranucleotide marker D2S1394 was found to be in LD in the 2p13 region. Screening this region with additional microsatellite markers revealed that the adjacent marker D2S1374 was also significantly associated with obstetric cholestasis, whereas no association was found with the markers located in the vicinity of the hydroxyacyl-CoA dehyrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit (HADHA) gene. CONCLUSIONS: Collectively, these data suggest that there may be a novel obstetric cholestasis-associated gene located in the vicinity of the 2p13 LD region.

3-Hydroxyacyl CoA Dehydrogenases↗

Apolipoprotein E alleles in women with intrahepatic cholestasis of pregnancy.

OBJECTIVE: To investigate the frequency of apolipoprotein E (apoE) alleles among women with intrahepatic cholestasis of pregnancy. METHODS: The presence of the three most common apoE alleles (epsilon2, epsilon3, epsilon4) was determined by polymerase chain reaction-restriction fragment length polymorphism in two groups of women: healthy pregnant women (n = 47) and pregnant women with a diagnosis of intrahepatic cholestasis of pregnancy (n = 44). In addition, the frequencies of the alleles in the general population in our area are presented for comparison. RESULTS: The frequency of the apo epsilon4 allele was 21.6% among women with intrahepatic cholestasis and it was 16.0% among healthy pregnant women (Fisher exact test; P= 0.216), which is close to the rate in the general population in our area (19%). None of the apoE genotypes was significantly over-represented, and homozygous genotype epsilon4 was not associated with more severe clinical disease than other genotypes. CONCLUSION: The observed profiles of allele and genotype frequencies confirm the equilibrium state between apoE polymorphism and obstetric cholestasis and suggest that apoE does not play a major role in the development of intrahepatic cholestasis of pregnancy.

Adult↗

Linking patient medication data with laboratory information system.

Dozens of new drugs are taken into clinical use each year. Even if the clinicians were able to learn the most important therapeutic effects of the drugs they prescribe, they would still be unable to remember all of their minor effects. After storing patient related medication data on computerized patient records it is possible to build decision support modules which automatically remind of possible drug influences on laboratory tests and cause alarms or alerts of drug interactions. Medication profiles coded using the Anatomical Therapeutic Chemical-code (ATC-code) constitutes a valuable part of an Electronic Patient Record (EPR). In this paper, we describe the benefits of our system. By building links to commercially available drug and laboratory databases we can automatically inform clinicians on clinically relevant drug influences on laboratory test results.

Clinical Laboratory Information Systems↗

Using computerized individual medication data to detect drug effects on clinical laboratory tests.

In clinical practice, thousands of drugs are used daily. Clinicians know the therapeutic effects of drugs but other minor drug effects are often ignored either because of inadequate knowledge of these effects or simply because of the limited memory capacity of a human being. This problem can be solved by using a computerized information system, which includes medication data of individual patients as well as information about non-therapeutic drug-effects. One of these non-therapeutic confusing drug effects is the influence of drugs on laboratory tests; a problem that should be taken into account in clinical practice and diagnostics. Other complicating drug effects include drug interactions and patient related adverse drug reactions. In a computerized information system, it is possible to build decision support modules that automatically give alarms or alerts of important drug effects other than therapeutic effects. If these warnings concern laboratory tests they are checked by a laboratory physician and only those with clinical significance are sent to clinicians. Warnings of drug interactions and adverse drug reactions are immediately evaluated by the physician responsible for the treatment. By means of the computerized information system, it is also possible to get better information of current medication practice which in turn gives better chances to agree on common guidelines and enables better quality assurance.

Adverse Drug Reaction Reporting Systems↗

Taxane sensitivity of ovarian carcinoma in vitro.

Paclitaxel, the first clinically available taxane, has proven to be effective in the treatment of ovarian carcinoma. Docetaxel is the second taxoid derivative which has also shown activity in ovarian carcinoma. These two compounds have clear differences in pharmacokinetics and side-effects. In the present study we have tested the cytotoxic effect of docetaxel in seven ovarian carcinoma cell lines using the 96-well plate clonogenic assay. These results have been compared with data obtained from our recent study on cisplatin and paclitaxel sensitivities of the same cell lines. Chemosensitivity has been expressed as IC50 value, the drug concentration causing 50% inhibition of clonogenic survival. The IC50 values for docetaxel were 0.23-2.30 nM showing a 10-fold difference between individual cell lines. On a molar basis, docetaxel was 1.2 to 2.6 times more active than paclitaxel in six out of seven cell lines. This may be explained by differences in the mechanism of action or by differences in other pharmacological properties.

Adenocarcinoma↗