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Biomedical subjects

S Saarikoski

Publications and source records attributed to S Saarikoski.

At least 91 records · Page 5Linked to original sources

Carrier diagnosis of the fragile X syndrome--a challenge in antenatal clinics.

OBJECTIVE: The fragile X syndrome, a common cause of mental retardation, is poorly recognized even in families at risk. The aims of our study were to evaluate the possibility of finding previously unidentified carriers of the genetic defect in fragile X families, to use this information in antenatal diagnosis, and to study the attitudes of these families to genetic screening. STUDY DESIGN: We identified 59 fragile X families living in a population of 900,000 inhabitants. A deoxyribonucleic acid test on the FMR1 gene was offered to 1071 persons in these families who had a risk of at least 12.5% of having the fragile X premutation or full mutation. RESULTS: A total of 48.1% of the persons who were offered the test accepted it. A diagnosis was made in 20 male and 66 female subjects with the full mutation and in 30 male and 133 female subjects with a premutation. All 21 pregnant carriers of this mutation accepted chorionic villus biopsy. CONCLUSION: Pregnant relatives should be informed of the availability of screening for fragile X carrier status in families with a member having clinical fragile X syndrome. Antenatal clinics offer a good gateway for approaching families with this inherited developmental defect.

DNA Mutational Analysis↗

Intraumbilical oxytocin for management of retained placenta.

OBJECTIVE: The purpose of the study was to investigate the removal of a retained placenta. METHOD: Oxytocin was injected into the vein of the umbilical cord. A total of 109 patients with retention of the placenta were randomized into two groups. Active management of the third stage of labor was carried out by giving oxytocin 5 IU intravenously and ergometrine maleate 0.2 mg intramuscularly after delivery of the fetus. Group 1, which comprised 68 patients, was allocated to receive 50 IU oxytocin diluted in 10 ml 0.9% sodium chloride solution, and the 41 patients in group 2 were given 20 ml plasma expander (dextran 70) into the umbilical vein. RESULTS: Forty-nine cases (72%) in the oxytocin group and 22 cases (54%) in the dextran 70 group required manual removal of the retained placenta. No significant differences were found between group 1 (oxytocin) and group 2 (dextran 70). CONCLUSION: Our results indicate that intraumbilical vein injection of oxytocin is not effective for removal of a retained placenta.

Adult↗

Myocardial infarction during pregnancy.

Myocardial infarction during pregnancy is rare. This report presents the case of a 38-year-old gravida whose only risk factors for coronary artery disease included habitual cigarette smoking and a history of pre-eclampsia during her earlier pregnancy, in whom an acute anterior myocardial infarction occurred in the 18th week of gestation. Coronary angiography during the 28th gestational week revealed significant coronary artery stenosis. Normal labour was at term without complications.

Adult↗

Two cases of placenta accreta managed conservatively.

Placenta accreta is a rare complication of pregnancy. Traditionally treatment has been operative, commonly total abdominal hysterectomy, in order to prevent serious haemorrhage or infection. Reproductive function can, however, be preserved by conservative management which is possible in carefully selected cases without risking maternal welfare. We report two cases of placenta accreta managed conservatively--both women delivered after this treatment.

Adult↗

The effect of gynecological risk factors on lumbar and femoral bone mineral density in peri- and postmenopausal women.

The relationship between gynecological history and bone mineral density (BMD) of the lumbar spine and femoral neck was studied in 3126 perimenopausal women. The study population was a random, stratified sample of participants, selected from the Kuopio Osteoporosis Study, which consisted primarily of all 14,220 women aged 47-56 years in Kuopio Province in 1989. After exclusion of 1521 women reporting past or present hormonal replacement therapy (HRT), 1605 women formed the final study population. Present HRT users had significantly higher lumbar BMD but not femoral BMD, than non-hormone users. Postmenopausal status, late menarche, and bilateral oophorectomy were risk factors for low BMD. Protective factors against low BMD were increased body weight, increased number of pregnancies, as well as hysterectomy without bilateral oophorectomy. The majority (43.8%) of these operations had been performed due to the presence of leiomyomas. No significant correlation was found between nulliparity, breast-feeding or amenorrhea before the age of 30 and BMD. In the multiple regression analysis, gynecological variables could account for only 18.4-26.8% of the variance in BMD, while time since last periods, age, age at menarche, weight and hysterectomy were the most significant variables. We conclude that reproductive history gives rise to some special risk groups, to whom BMD measurements and osteoporosis prevention efforts should be directed. However, it is impossible to predict BMD by gynecological characteristics.

Bone Density↗

Does vitamin D3 have negative effects on serum levels of lipids? A follow-up study with a sequential combination of estradiol valerate and cyproterone acetate and/or vitamin D3.

The effects of four different treatment schedules on serum lipid concentrations were studied for 1 year in 402 postmenopausal women in the Kuopio Osteoporosis Study. The women were randomized to four treatment groups: A, Sequential combination of estradiol valerate and cyproterone acetate (Climen); B, Vitamin D3, 300 IU/day; C, Climen+Vitamin D3, D, placebo. In group A, serum concentrations of total cholesterol (Chol) decreased by 4.8% in 6 months and by 6.2% in 12 months (P < 0.001), but in group C the decrease was only 2.9% in 6 months (P < 0.05) and 3.4% in 12 months (P < 0.01). The decline of total-Chol in group A was accounted for by the 6.8% to 7.5% decrease in LDL-Chol levels (P < 0.001). The decrease of LDL-Chol in group C was statistically non-significant. Use of vitamin D3 (group B), increased serum Chol by 2.7% (6 months), P < 0.05 and by 2.1% (12 months) and the increases were the result of the 6.0% to 6.2% increase in LDL-Chol levels in 6 and 12 months, respectively (P < 0.001). Serum concentrations of HDL-Chol and TG remained relatively stable in all groups. No correlations were found between LDL-Chol, 25-OH-D3 and 1,25(OH)2-D3 levels in group B. Our results confirm the beneficial effect of estradiol valerate and cyproterone acetate on the lipid profile. In contrast, vitamin D3 had a negative influence on this profile by increasing serum concentrations of LDL-Chol.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecalciferol↗

Fractures and low axial bone density in perimenopausal women.

The relationship between past fractures and current bone density (BMD) was analyzed in a population sample of 3222 women aged 48-58. BMD was determined with dual X-ray absorptiometry (DXA) at the spine and femoral neck. 702 women reported fractures. Wrist and ankle were the most common fracture sites. Fracture history increased the risk [OR (95% CI)] of low spinal BMD (of more than 1 SD below the study population mean) by 1.75 (1.41; 2.18). The sensitivity and specificity of fracture history to detect a low spinal BMD were 31 and 80%, respectively. One SD decreases of spinal and femoral BMD equalled to respective overall fracture risks (adjusted ORs) of 1.36 (1.24; 1.50) and 1.38 (1.25; 1.51). Both BMDs related more strongly to wrist fracture [1.73 (1.47; 2.05)/1.69 (1.43; 1.99)] than to all nonwrist fractures combined [1.24 (1.11; 1.37)/1.27 (1.14; 1.42)]. Ankle and rib fractures related only to spinal [1.21 (1.00; 1.46)/1.45 (1.12; 1.87)] but tibia and foot bone fractures only to femoral [2.04 (1.37; 3.04)/2.20 (1.42; 3.41)] BMD. Spinal BMD related more strongly to fractures due to falls on same level than to fractures due to all other trauma combined. Fracture history poorly screens out low perimenopausal BMD. The results suggest that pre- and perimenopausal fractures relate to low axial bone density and that the magnitude of this relation depends on the sites of fracture and densitometry as well as on the type of trauma.

Absorptiometry, Photon↗

Risks of perimenopausal fractures--a prospective population-based study.

OBJECTIVE: To examine the associations between potential risk factors and fractures in perimenopausal women. SUBJECTS: A total of 3,140 women (mean age 53.4 +/- 2.8 (s.d.) years) were followed-up for 2.4 years after axial bone densitometry (lumbar spine and femoral neck) with regard to the occurrence of fractures. RESULTS: In all, 5.6% of the women sustained a fracture. There were 169 low energy fractures (falling on a level surface) in 157 women after the exclusion of 18 fractures caused by a high energy trauma. The wrist was the most frequent site of fracture (n = 46). Lumbar bone mineral density was 5.8% lower and femoral bone mineral density 4.6% lower among fracture cases compared with non-fracture cases (p < 0.0001). History of a fracture during 1980-1989 elevated the risk of all fractures 2.83-fold (95% confidence interval (CI) 1.95-4.10) and the risk of a first wrist fracture 2.25-fold (95% CI 1.10-4.62). The amount of weekly alcohol intake was higher among fracture cases than among non-fracture cases yielding an age-adjusted odds ratio (OR) of 1.45 (95% CI 1.05-2.02). Past or present use of hormone replacement therapy was protective against fractures (age-adjusted OR 0.70, 95% CI 0.50-0.96). If bilateral oophorectomy had been carried out under the age of 45 years, the risk of fracture was 3.64-fold (95% CI 1.01-13.04) compared with women operated upon after the age of 45 years. Age at menarche, parity, lactation and smoking history did not differ between the fracture and non-fracture groups. CONCLUSIONS: A former history of fractures, low baseline bone mineral density (BMD) and use of alcohol are predisposing factors associated with perimenopausal fractures, while hormone replacement therapy is protective in this respect.

Alcohol Drinking↗

Inverse relation of physical activity and apolipoprotein AI to blood pressure in elderly women.

To study the relation of habitual physical activity, diet, and serum lipoproteins to blood pressure, a cross-sectional study was carried out in a cohort of 202 women, age 60-69 yr. Sitting, supine, and standing blood pressure was measured with a standard sphygmomanometer. Physical activity was assessed by questionnaire, diet by food records, serum lipoprotein cholesterol enzymatically, and apolipoprotein AI turbidimetrically. Among the women not taking antihypertensive medication (N = 127), the physically most active (physical activity 5 times per week or more) had sitting diastolic blood pressure of 86 mm Hg (adjusted for high-density-lipoprotein cholesterol, body mass index, and cardiovascular health status), which was 8 mm Hg lower (P = 0.007) than in the least active (physical activity twice per week or less) women. Subjects in the highest tertile of apolipoprotein AI (> 1.46 g.l-1) had a mean sitting systolic blood pressure of 147 mm Hg (adjusted for age, body mass index, and cardiovascular health status), which was 16 and 13 mm Hg lower (P = 0.001) than in women in the middle and lowest tertiles (< 1.32 g.l-1), respectively. The present data suggest that, in elderly women, regular physical activity is associated with a clinically significant lowering of diastolic blood pressure. Moreover, a higher level of serum apolipoprotein AI, the major protein component of high-density lipoprotein particles, is inversely associated with systolic blood pressure.

Aged↗

Pretranslational induction of cytochrome P4501A enzymes by beta-naphthoflavone and 3-methylcholanthrene occurs in different liver zones.

Most of the cytochrome P450 (CYP) genes are expressed in an uneven, zonated pattern in the liver. Factors regulating this regionally restricted expression are not well known. In this study we have analysed cell lysates obtained from opposite zones of rat liver by infusing digitonin to the perfused liver to study the zonation of CYP1A1 and CYP1A2 induction. 3-Methylcholanthrene induced CYP1A1 protein in perivenous cells, while a low dose of beta-naphthoflavone caused periportal induction. Analysis of CYP1A1 mRNA from cell lysates by reverse transcriptase-coupled polymerase chain reaction (RT-PCR) and in situ hybridization experiments both demonstrated that this inducer-specific differently localized effect occurred at the pretranslational level. A corresponding difference in the regional pattern of CYP1A2 induction was seen: induction by beta-naphthoflavone reversed the constitutive perivenous pattern into a periportal CYP1A2 mRNA pattern while induction after 3-methylcholanthrene treatment was more panacinar. Attempts to identify the regiospecific factors involved were made by comparing the in vitro induction of CYP1A1 by beta-naphthoflavone and 3-methylcholanthrene in hepatocytes isolated from the periportal and perivenous region. However, after isolation, induction seemed to be independent of the source of the cells. Our results demonstrate the existence in the liver of regionally acting factors that mediate the induction of CYP1A1 and 1A2 in a local and inducer-specific fashion. These factors could be Ah receptor associated binding proteins operating in vivo, but no longer in isolated cells.

Animals↗

Fragile-X syndrome in east Finland: molecular approach to genetic and prenatal diagnosis.

Fragile X is the most common inherited form of mental retardation, having an incidence of one in 1,250 males. The fragile X syndrome results from amplification of the CGG repeat found in the fragile X mental retardation-1-gene (FMR-1). This CGG repeat shows length variation in normal individuals and is increased significantly in both carriers and patients. Non-retarded carriers of both sexes can be detected reliably only by direct DNA analysis of the fra(X) mutation. Here we investigate fragile X families using the intragenic probes St.B 12.3 and St.B 12.3 XX (J-L Mandel). Fragile X syndrome could be verified in 51 families of the population of 900,000 in East-Finland during 1989-92. The index cases of the syndrome were found by the help of health care personnel, 463 relatives of these families consented to be tested for the mutation of the FMR-1 gene. Ninety-three relatives with the full mutation and 127 healthy carriers with the premutation of the fragile X syndrome were diagnosed. In addition, 28 decreased males were obligate carriers. During the year 1992 prenatal diagnosis for fragile X was carried out in nine pregnancies. For understanding of the occurrence of fragile X syndrome and for better prevention of this syndrome in next generations, systematic genetic counseling and carrier screening in these families is essential.

Female↗

Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver.

Expression of human cytochrome P450 (CYP) genes in human adult and fetal liver were studied using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. In adult liver mRNA of CYPs 1A1, 1A2, 2A6/2A7, 2B6/2B7, 2C8-19, 2D6, 2E1, 3A3/3A4 and 3A7 were detected while CYPs 2F1 and 4B1 were absent. In fetal liver mRNA of CYPs 2C8, 2D6, 3A3/3A4 and 3A7 were found but all other forms studied were undetectable. The results provide a comprehensive qualitative picture of the expression of CYP genes in families CYP1 through CYP4 in human adult and fetal liver.

Adult↗

Bone mineral density and risk factors for osteoporosis--a population-based study of 1600 perimenopausal women.

Population-based epidemiological studies on osteoporosis are few. Our study evaluated the effects of menopause and certain putative behavioural risk factors on bone mineral density (BMD). Spinal and femoral neck BMD were measured with dual X-ray absorptiometry (DXA) from 1600 perimenopausal women aged 48-59 years (mean 53.2 years) with no diseases or medications known to affect bone metabolism. These women were a selected sample of the Kuopio Osteoporosis Risk Factor and Prevention Study population (n = 14,220). There was a wide variation of BMD among perimenopausal women. Menopause had a major effect on BMD. Postmenopausal women had significantly lower BMD in both spine (-6.2%) and femoral neck (-3.9%) as compared with premenopausal women. Multiple regression analysis showed that weight, menopausal status, age, and grip strength were significant independent predictors of both spinal and femoral BMD. Additionally, physical activity was found to be a significant predictor of femoral BMD, and alcohol consumption was a significant predictor of spinal BMD. However, current anthropometric and lifestyle factors explained only 18.7-25.4% of the variability of BMD. Therefore, the estimation of the risk factor status at menopause is not an adequate substitute for bone densitometry. However, our results may in part help clinicians to identify the risk groups at which to direct bone density measurements.

Absorptiometry, Photon↗

The effect of previous oral contraceptive use on bone mineral density in perimenopausal women.

The bone mineral density (BMD) of the lumbar vertebrae L2-4 and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) in 3222 perimenopausal women-a random stratified sample of the population-based Kuopio Osteoporosis Study (OSTPRE). The mean age of the women was 53.4 years (range 47.9-59.6 years). Twenty-nine percent of the women were past users of oral contraceptives (OC) containing 50 micrograms or less of ethinyl estradiol and 7.4% (n = 250) of the women reported OC use for more than 6 years. There was a slight but statistically significant difference between OC users (n = 939) and non-users (n = 2283) in lumbar BMD (1.134 +/- 0.155 g/cm2 v 1.123 +/- 0.161 g/cm2, p = 0.014). A statistically significant difference was recorded also after adjustment for years since menopause, duration of hormonal replacement therapy (HRT) and present weight (p = 0.044). When the analysis was performed among women who had never used oestrogen replacement therapy (n = 1427) and among premenopausal women (n = 387), no differences in BMD were found between OC users and non-users. Similarly, femoral neck BMD did not differ between the groups. This population-based study demonstrated a slightly higher lumbar BMD among past OC users. However, OC users and non-users differed from each other in many behavioral characteristics. Thus, the differences in BMD may be accounted for more by other factors than by past OC use itself. The low-dosage estrogen OCs used today would not be expected to have any positive bone effects among future perimenopausal women.

Bone Density↗

Comparison of flow cytometric measurement of seminal antisperm antibodies with the mixed antiglobulin reaction and the serum tray agglutination test.

OBJECTIVE: To compare the mixed antiglobulin reaction (MAR) and the serum tray agglutination test (TAT) with the flow cytometric (FCM) measurement of sperm antibodies. To evaluate by FCM the correlation in sperm antibody parameters between paired semen ejaculates obtained 2 to 4 weeks apart and the effect of washing on sperm antibody levels. SETTING: University-based infertility clinic. PATIENTS: The TAT and FCM were done on 81 patients with a positive immunoglobulin (Ig)G-MAR test. The correlation of sperm antibody parameters between paired semen samples was done in 16 men. A few samples were used to study the effect of washing on sperm antibody parameters. MAIN OUTCOME MEASURES: The proportion of spermatozoa positive for IgG and IgA antibodies as well as the number of antibody molecules per spermatozoa measured by FCM. RESULTS: In general, the degree of MAR positivity but not that of the TAT correlated with the sperm antibody load. With reference to FCM the MAR test had an 1% false positive rate, whereas the serum TAT had a 25% false negative rate. Correlation between FCM measurements of paired semen samples was good. Washing the spermatozoa once removed the loosely bound antibodies; further washes were not useful. CONCLUSION: Flow cytometry is a reliable technique that correlates with the MAR test. In patients with a strongly positive MAR, FCM is useful to identify patients with a low sperm antibody load. It is speculated that patients with a low sperm antibody load may respond better to IVF treatment.

Agglutination Tests↗

The effect of fluoridated drinking water on axial bone mineral density--a population-based study.

Bone mineral density (BMD) of the spine and femoral neck was measured in a random stratified sample of 3222 perimenopausal women aged 47-59 years. A total of 969 women had used fluoridated drinking water (1.0-1.2 mg/l) for over 10 years. These women were compared with 2253 women with low levels of fluoride in drinking water (< 0.3 mg/l). BMD of the spine was significantly higher in the fluoride group than in the non-fluoride group (1.138 +/- 0.165 vs. 1.123 +/- 0.156 g/cm2, P = 0.026). Femoral neck BMDs did not differ between the groups. When the BMD values were adjusted for confounding factors (age, weight, menopausal status, calcium intake, physical activity level, deliveries, alcohol consumption and estrogen use), the differences between the groups increased (P < 0.001 for the spine and P = 0.004 for the femoral neck, respectively). There was no significant difference between the groups in the prevalence of self-reported fractures sustained during 1980-1989. We propose that the fluoridation of drinking water has a slight increasing effect on axial BMD in women in low fluoride areas.

Absorptiometry, Photon↗

A flow cytometric study on the effect of low dose cyclic prednisolone treatment on sperm-bound antibody levels.

Using flow cytometry the changes in the proportion of spermatozoa positive for antisperm antibody, and for levels of sperm-bound immunoglobulin (Ig)G and IgA antibody and some other semen parameters were monitored during low dose cyclic prednisolone treatment to 11 male patients. Patients were given prednisolone 20 mg/day for the first 10 days of the partner's menstrual cycle and then 5 mg on days 11 and 12. The treatment was repeated for three cycles and the sperm parameters measured after the first cycle, third cycle and in four cases also 1 and 3 months after cessation of treatment. A clear reduction of sperm-bound IgG antibody levels was seen in 3/11 (27%) patients, while only IgA was reduced in 2/11 (18%) patients. Only minor changes in sperm-bound antibody levels were shown in 63% (7/11) of patients, and in one patient the levels of sperm antibody even increased. Thus, corticosteroid treatment did not reduce sperm-bound antibodies in the majority of cases. In those cases in which the levels of sperm antibody declined, the decrease in sperm-bound antibodies was noticeable even after one cycle of prednisolone treatment.

Autoantibodies↗