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31.
Increased risk of leukaemia in patients with juvenile chronic arthritis treated with chlorambucil 总被引:2,自引:0,他引:2
MJ Kauppi HA Savolainen V-J Anttila HA Isomäki 《Acta paediatrica (Oslo, Norway : 1992)》1996,85(2):248-250
Two cases of acute leukaemia have developed in a group of 77 patients treated with chlorambucil (Chl) because of severe juvenile chronic arthritis. The total follow-up from the beginning of Chl treatment in these patients was 560 years, indicating a highly increased risk of leukaemia. Despite favourable results, especially in patients with secondary amyloidosis, Chl should only be used in selected cases. 相似文献
32.
Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure 总被引:9,自引:0,他引:9
Sioris T Husgafvel-Pursiainen K Karjalainen A Anttila S Kannio A Salo JA Perhoniemi V Heikkilä L Vainio H 《International journal of cancer. Journal international du cancer》2000,86(4):590-594
Validated markers are needed to identify operable lung cancer patients with poor prognosis. About one-half of non-small-cell lung cancers (NSCLCs) carry a mutation in the p53 tumor-suppressor gene. We examined 101 NSCLC patients for surgical stage, completeness of resection, tobacco smoking, asbestos exposure, age, gender and p53 gene mutations as prognostic factors after a follow-up period of 4 years. Cox's multivariate regression model was applied to quantify the associations with overall and cancer-related survival. Patients with a wild-type p53 gene had an overall 4-year survival of 43% and those with a mutated p53 gene, 35%. In squamous-cell carcinoma, stage and heavy smoking, defined as the median of pack-years smoked, had prognostic significance for overall survival. Only stage was associated with poor cancer-related survival. Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma. In adenocarcinoma, p53 mutation, in addition to stage, emerged as a significant predictor of poor cancer-related survival. 相似文献
33.
An uncommon phenotype of poor inducibility of CYP1A1 in human lung is not ascribable to polymorphisms in the AHR, ARNT, or CYP1A1 genes 总被引:2,自引:0,他引:2
Anttila S Lei XD Elovaara E Karjalainen A Sun W Vainio H Hankinson O 《Pharmacogenetics》2000,10(8):741-751
Cigarette smoking can induce CYP1A1 in the lung. Induction requires the aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins. Lung samples from seven of 75 Finnish patients who smoked until the time of surgery exhibited absent or low levels of CYP1A1 protein, mRNA and enzymatic activity, suggesting that these individuals might be genetically non or poorly inducible for CYP1A1. All seven lung samples expressed normal levels of AHR mRNA and ARNT mRNA, indicating that they did not carry inactivating polymorphisms in the 5' upstream regulatory regions of these genes. Sequencing of cDNAs encompassing the complete coding regions of AHR and ARNT identified a previously known codon 554 polymorphism in AHR, which was present in the homozygous state in one individual. This polymorphism, which leads to an amino acid substitution, has previously been reported either to have no effect or to enhance CYP1A1 induction. Previously unreported silent single nucleotide polymorphisms were identified in codon 44 of AHR and codon 189 of ARNT. 1500 bp of genomic sequence from the 5' upstream regulatory sequence of the CYP1A1 gene was also sequenced in the non-inducible individuals. A nucleotide substitution polymorphism at position -459 was detected in the heterozygous state in two individuals. This polymorphic site does not reside in any known regulatory sequence. The complete CYP1A1 coding sequence and intron/exon boundaries were then sequenced. None of the non or poorly inducible individuals exhibited any polymorphisms, either homozygous or heterozygous compared to representative inducible individuals or the previously published CYP1A1 sequence. Thus, no polymorphisms in the AHR, ARNT or CYP1A1 genes were identified that could be responsible for the non/low inducibility phenotype observed. 相似文献
34.
OBJECTIVE: To evaluate [1] the effects of levels of sex hormone-binding globulin (SHBG), albumin, and total testosterone on the distribution of testosterone between SHBG-bound and non-SHBG-bound fractions; [2] the independent effects of polycystic ovary syndrome (PCOS) and body mass index on serum levels of total testosterone, non-SHBG-bound testosterone, SHBG, and albumin; and [3] the usefulness of levels of total testosterone and non-SHBG-bound testosterone and of the free androgen index in the diagnosis of PCOS. DESIGN: Retrospective clinical study. SETTING: An academic research environment. PATIENT(S): Forty-three women with oligomenorrhea and PCOS. Twenty-five women with regular menstrual cycles and without hirsutism served as controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of non-SHBG-bound testosterone, total testosterone, SHBG, and albumin in serum. RESULT(S): Levels of total testosterone and non-SHBG-bound testosterone, and the free androgen index were higher in patients with PCOS than in healthy controls. PCOS did not have an effect on the levels of SHBG or albumin, or on the percentage of non-SHBG-bound testosterone. Levels of SHBG and albumin were inversely related to body mass index. The percentage and concentration of non-SHBG-bound testosterone and the free androgen index were directly related to body mass index. Hirsutism did not have an effect on any outcome measure. CONCLUSION(S): The distribution of total testosterone into SHBG-bound and non-SHBG-bound fractions is associated with body mass index, not with PCOS. The high levels of non-SHBG-bound testosterone and the high free androgen index in patients with PCOS reflect mainly high levels of total testosterone. Thus, the measurement of levels of non-SHBG-bound testosterone and the calculation of the free androgen index provide no further information in the diagnosis of PCOS beyond that provided by the measurement of levels of total testosterone. 相似文献
35.
Evaluation of toremifene for reversal of multidrug resistance in renal cell cancer patients treated with vinblastine 总被引:8,自引:0,他引:8
Braybrooke JP Vallis KA Houlbrook S Rockett H Ellmén J Anttila M Ganesan TS Harris AL Talbot DC 《Cancer chemotherapy and pharmacology》2000,46(1):27-34
Purpose: Expression of P-glycoprotein (Pgp), which confers the multidrug resistance (MDR) phenotype, is thought to contribute to
the insensitivity of renal cell cancer (RCC) to chemotherapy. The development of Pgp inhibitors for clinical application has
been hampered by unacceptable toxicity at doses required to achieve adequate cellular concentration. Toremifene is able to
reverse MDR and sensitise RCC to vinblastine in vitro. However, in vivo toremifene is tightly bound to serum proteins, in
particular the acute phase protein α1-acid glycoprotein (AAG), which may limit tissue availability. In this phase I–II study we assessed the tolerability of short
courses of high dose toremifene in combination with vinblastine and evaluated the key determinants of MDR reversal in vivo.
Methods: Twenty-seven patients with metastatic RCC received escalating doses of oral toremifene for 3 days every 2 weeks in combination
with vinblastine 6 mg/m2 i.v. on day 3 of each cycle. The serum concentration of toremifene, its metabolites and AAG were measured and the effect
of patients' serum on inhibition of Pgp in vitro was determined. Results: Twenty-six patients were evaluable for response. Eight patients (31%) had stable disease and 18 patients (69%) progressive
disease. The mean serum concentration of toremifene at 780 mg daily for 3 days was 7.82 μM [standard deviation (SD) 2.48, range 2.50 to 14.70], which exceeds that known to reverse MDR in vitro. The serum concentration
of the major metabolite of toremifene, N-demethyltoremifene, which also reverses MDR, was 5.13 μM (SD 1.78, range 1.80 to 9.00). In 60% of patients the pre-treatment AAG concentration was above that known to block the effects
of toremifene in vitro. However, addition of serum from patients on toremifene to MCF-7 adr cells in vitro inhibited Pgp-mediated
efflux of rhodamine 123. Conclusions: We have shown that short course, high-dose toremifene in combination with vinblastine is generally well tolerated and that
the concentration of toremifene required to reverse MDR in vitro is achievable in vivo.
Received: 7 July 1999 / Accepted: 15 November 1999 相似文献
36.
37.
Radiofrequency ablation in the liver close to the bile ducts: can intraductal cooling offer protection? 总被引:1,自引:0,他引:1
Background One complication of radiofrequency ablation (RFA) of the liver is biliary duct damage. Intraductal cooling (IDC) has been proposed as a means of protection.Methods In the first experiment, designed to evaluate the influence of IDC on the RFA procedure per se and on lesion formation, lesions were created in vivo in pig liver with and without IDC. The RFA needle was placed with a 1.5-cm safety margin from the bile ducts. In the second experiment, designed to evaluate the potential protective effects of IDC, lesions were created close to a bile duct with and without IDC.Results With the safety margin, the RFA parameters and lesion size were not negatively affected by IDC. Microscopic examination revealed that IDC had a protective effect in most of the lesions created close to a bile duct.Conclusions The IDC procedure was feasible and had no negative effect on the RFA procedure or the lesions. However, the protective effect of IDC was not statistically significant (p = 0.12). 相似文献
38.
Venäläinen ER Anttila M Peltonen K 《Bulletin of environmental contamination and toxicology》2005,74(3):526-536
No abstract available. 相似文献
39.
Biomarkers of alcohol consumption in patients classified according to the degree of liver disease severity 总被引:2,自引:0,他引:2
Anttila P Järvi K Latvala J Romppanen J Punnonen K Niemelä O 《Scandinavian journal of clinical and laboratory investigation》2005,65(2):141-151
OBJECTIVE: In the search for optimal biomarkers of excessive drinking, only a few studies have been conducted to compare the relationships between ethanol consumption, liver status, and various laboratory markers of ethanol-induced diseases. MATERIAL AND METHODS: Concentrations of carbohydrate-deficient transferrin (%CDT and CDTect methods), serum sialic acid (SA), gamma-glutamyl transferase (gamma-GT), aspartate aminotransferase (ASAT), mean corpuscular volume (MCV), and a marker of fibrogenesis (PIIINP) were studied in 102 alcoholics with (n=59) or without (n=43) alcoholic liver disease. Controls were 34 healthy volunteers who were either social drinkers or abstainers. RESULTS: Although concentrations of all markers were significantly higher in the alcoholic patients than in the healthy controls, their diagnostic characteristics showed a considerable degree of variation. The %CDT, SA, and MCV showed the strongest correlations with the amount of recent alcohol intake. The presence of liver pathology notably influenced the results of CDTect, GT, ASAT, and PIIINP. In ROC analyses, the highest rates of diagnostic accuracy for detecting hazardous drinking were reached with GT (0.94), CDT (0.86), and SA (0.85), followed by MCV (0.79) and ASAT (0.77). Upon abstinence, the estimated times for normalization varied between 10 days (CDTect) and 25 days (GT). CONCLUSIONS: Our data suggest distinct differences in the clinical characteristics of biological markers of ethanol consumption. While the overall accuracy of CDT and GT appear to be highest in the detection of problem drinking, serum SA and PIIINP measurements are of further value when the effects of liver pathology and ethanol drinking need to be differentiated. 相似文献
40.
Huuhka M Anttila S Leinonen E Huuhka K Rontu R Mattila KM Huhtala H Lehtimäki T 《The journal of ECT》2005,21(1):7-11
The apolipoprotein E (APOE) polymorphism is associated with neurodegenerative diseases. Its role regarding psychiatric disorders is controversial. It has been suggested to affect antidepressant treatment response and response to electroconvulsive therapy (ECT). In the present study, the association between APOE polymorphism and response to ECT in 119 patients with major depressive disorder was investigated. Moreover, a relation between APOE polymorphism and the age of onset of depression as well as the cognitive outcome of ECT was studied. In the whole population, no association was found between APOE polymorphism and response to ECT. However, in nonpsychotic patients, the epsilon2 allele tended to be more frequent in responders than nonresponders. Earlier onset of depression was observed in the patients with epsilon4 allele in late-life depression. There was no association between the APOE genotype and the cognitive change caused by ECT in the population as a whole. In women, however, epsilon2 allele may play a protective and epsilon4 allele a deleterious role in cognition during ECT. 相似文献