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Biomedical subjects

J Puolakka

Publications and source records attributed to J Puolakka.

At least 19 recordsLinked to original sources
PubMed1997

Responses of HDL subclasses, Lp(A-I) and Lp(A-I:A-II) levels and lipolytic enzyme activities to continuous oral estrogen-progestin and transdermal estrogen with cyclic progestin regimens in postmenopausal women.

Seventy postmenopausal women took part in the study. Subjects received either continuous oral 17 beta-estradiol 2 mg/day combined with norethisterone acetate 1 mg/day (E2/NETA, Kliogest) or transdermal treatment consisting of 28 day cycles with patches delivering 17 beta-estradiol 50 micrograms/day (Estraderm) combined with cyclic medroxyprogesterone acetate 10 mg/day (E2/MPA, Provera), on days 17-28. At baseline the serum lipid and lipoprotein concentrations, composition and concentrations of high density lipoprotein (HDL) subclasses, lipoprotein (Lp)(AI) and Lp(A-I:A-II) levels were comparable in the two groups. In the E2/NETA group, after 12 months hormone replacement therapy (HRT), the HDL2 cholesterol concentration decreased by 17% (P < 0.01) and the HDL3 cholesterol remained unchanged. The concentrations of HDL2b, HDL2a and HDL3a were reduced by 30, 26 and 15%, respectively, P < 0.001, and the cholesterol:triglyceride ratio decreased significantly in all HDL subclasses. Apolipoprotein (apo) A-I concentration decreased by 5% (P < 0.05), but apo A-II, Lp(A-I) and Lp(A-I:A-II) concentrations remained unchanged. In the E2/MPA group the HDL2 and HDL3 cholesterol levels were both reduced by 6% (P < 0.05) and the HDL3a, HDL3b and HDL3c concentrations decreased by 14, 12 and 17% during the E2/MPA phase compared with baseline (P < 0.01). No major changes in the composition of HDL subclasses occurred in the E2 MPA group during treatment. The apo A-I and Lp(A-I) levels were not changed, but apo A-II and Lp(A-I:A-II) concentrations decreased by 8 and 5%, P < 0.001 and P < 0.05, respectively. At 12 months the postheparin plasma hepatic lipase (HL) activity decreased only in the E2/NETA group (by 12%, P < 0.05). The cholesteryl ester transfer protein (CETP) activity was not affected by either HRT regimen. The results of our study show that the 2 HRT regimens have multiple effects on HDL particles and HRT induced changes in HDL are not associated with changes in activities of lipolytic enzymes or CETP.

Administration, Cutaneous↗
PubMed1997

Different effects of oral and transdermal hormonal replacement on prostacyclin and thromboxane A2.

OBJECTIVE: To elucidate the mechanism of cardiovascular protection of hormone replacement therapy (HRT) by comparing the effect of oral and transdermal HRTs on the production of antiaggregatory, vasodilatory prostacyclin, and its endogenous antagonist, thromboxane A2. METHODS: Oral estradiol (2.0 mg/d) plus norethisterone acetate (1.0 mg/d) (n = 13) or transdermal estradiol (50 micrograms/d) plus medroxyprogesterone acetate (10 mg/d) as 12-day courses at 4-week intervals (n = 13) were given to postmenopausal women. Urinary excretion of the metabolites of prostacyclin, ie, 6-ketoprostaglandinF1 alpha and 2,3-dinor-6-ketoprostaglandinF1 alpha, as well as those of thromboxane A2, ie, thromboxane B2 and 2,3-dinor-thromboxane B2, were measured by radioimmunoassays, after purification by extraction and high performance liquid chromatography, before and during the sixth and the 12th treatment cycles. RESULTS: Oral HRT stimulated excretion of thromboxane B2 from 3.4 +/- 0.7 ng/mmol creatinine to 4.5 +/- 1.5 (mean +/- standard deviation, P < .05) and that of 2,3-dinor-thromboxane B2 from 16.6 +/- 8.0 ng/mmol creatinine to 26.2 +/- 10.7 (P < .01), and thus led to the dominance of thromboxane A2. No changes in prostanoids occurred during transdermal HRT. CONCLUSIONS: The effects of various HRTs on prostanoids may significantly differ.

Administration, Cutaneous↗
PubMed1997

Effective obstetric paracervical block with reduced dose of bupivacaine. A prospective randomized double-blind study comparing 25 mg (0.25%) and 12.5 mg (0.125%) of bupivacaine.

BACKGROUND: To study whether paracervical block (PCB) with 12.5 mg (0.125%) of bupivacaine is as effective as with 25 mg (0.25%) and if there are differences in fetal heart rate (FHR) patterns between the doses. METHODS: A prospective, randomized double-blind study. Fifty-two patients received PCB with 25 mg and 45 patients with 12.5 mg of bupivacaine. Pain intensity was assessed by the patients on a horizontal visual analog scale (VAS). Fetal heart rates of the fetuses were analyzed visually concerning basal rate, variability, accelerations, bradycardia, silent pattern and decelerations. RESULTS: The pain relief was statistically significant in both groups up to 120 min after PCB. The VAS-values were similar in both groups both before and after PCB. Fetal heart rate changes appeared in both groups more frequently after than prior to PCB. In patients receiving 25 mg of bupivacaine there appeared to be more FHR changes than in those receiving 12.5 mg. CONCLUSIONS: Paracervical block with 12.5 mg of bupivacaine is an effective method to relieve pain during labor. Fetal heart rate changes seemed to appear less frequently with this reduced dose. It seems that by lowering the dose of bupivacaine it is possible to reduce fetal side-effects without losing analgesic effect.

Adolescent↗
PubMed1996

Effects of postmenopausal estrogen/progestin replacement therapy on LDL particles; comparison of transdermal and oral treatment regimens.

The aim of the study was to compare the effects of continuous oral estrogen/progestin therapy to the effects of transdermal estrogen therapy combined with cyclic oral progestin on the properties of LDL particles. Eighty postmenopausal women were randomly allocated to receive either oral (continuous 17-beta-estradiol 2 mg and norethisterone acetate 1 mg per day, E2/NETA) or transdermal therapy (patches delivering continuous 17-beta-estradiol, E2, 0.05 mg/day with sequential oral medroxyprogesterone acetate, MPA, 10 mg/day for 12 days/cycle). The groups had similar mean values and ranges of age, BMI and postmenopausal status. The blood samples were taken at baseline, and twice at 1 year before and after MPA administration. LDL particle size distribution was determined by gradient gel electrophoresis and LDL was isolated by sequential ultracentrifugation for compositional analyses. Concentrations of total LDL mass, LDL cholesterol and LDL protein decreased in the oral treatment group (p < 0.01, p < 0.001 and p < 0.01, respectively), whereas they remained unchanged during the transdermal therapy. Particle size of the major LDL peak remained unchanged during both transdermal and oral therapies. HDL cholesterol concentration decreased significantly in both treatment groups (p < 0.001 for both). Serum triglyceride and HDL cholesterol concentrations were the strongest determinants of LDL particle size ( r = -0.50 and r = 0.54, respectively, p < 0.001 for both). The cholesteryl esters and free cholesterol content of the LDL particles decreased in the oral treatment group (p < 0.05). Phospholipid content of LDL increased in both groups receiving either oral or transdermal therapy (p < 0.01 for both). In conclusion, oral administration of 17-beta-estradiol and norethisterone acetate caused a decrease in LDL mass by decreasing the number and cholesterol content of LDL particles. The concomitant decrease of HDL cholesterol by progestins may partly negate this beneficial effect of LDL lowering.

Administration, Cutaneous↗
PubMed1996

Different effects of continuous oestrogen-progestin and transdermal oestrogen with cyclic progestin regimens on low-density lipoprotein subclasses.

Seventy-five postmenopausal women were randomly allocated to receive either continuous oral 17 beta-oestradiol 2 mg day-1 and norethisterone acetate 1 mg day-1 (E2/NETA) or transdermal treatment consisting of 28-day cycles with patches delivering 17 beta-oestradiol 50 micrograms day-1 combined with oral cyclic medroxyprogesterone acetate 10 mg day-1, on days 17-28 (E2/MPA). At baseline, the plasma lipid and lipoprotein concentrations, composition and concentrations of low-density lipoprotein (LDL) subclasses (LDL1, LDL2 and LDL3) isolated by density-gradient ultracentrifugation were similar in the two groups. The post-heparin plasma hepatic lipase activity (HL) correlated inversely with the percentage of total LDL found in LDL1 (buoyant LDL) and directly with the percentage of LDL found in LDL3 (dense LDL). After 12 months of hormone replacement therapy (HRT), the total and LDL-cholesterol concentration of the E2/ NETA group decreased by 14% and 17% respectively (P < 0.001), while in the E2/MPA group these parameters remained unchanged. The lowering of LDL-cholesterol in the E2/NETA group was a consequence of a significant reduction of the large, buoyant LDL particles (LDL1) from 103 mg dL-1 to 60 mg dl-1 (P < 0.001) and of a decrease of cholesterol content of LDL particles in the major LDL subclass, LDL2. In the E2/MPA group, the concentration of LDL1 decreased, but less than in the oral group. In both groups, a significant increase in the concentration of the LDL3 subclass was observed, indicating an overall shift to denser LDL particles. After 12 months, the post-heparin plasma HL activity decreased only in the E2/NETA group (by 12%). The inverse correlation between post-heparin plasma HL activity and LDL1 persisted in both groups, but the direct correlation between HL and LDL3 vanished in the E2/NETA group and subsided in the E2/MPA group. Our results indicate that HRT has multiple effects on LDL subclasses and suggest that these changes cannot be explained by changes in HL activity.

Body Mass Index↗
PubMed1996

Hormone replacement therapy lowers plasma Lp(a) concentrations. Comparison of cyclic transdermal and continuous estrogen-progestin regimens.

To study the responses of serum lipoproteins, apoproteins (apo's), and lipoprotein(a) (Lp[a]) to two frequently used hormone replacement therapies (HRTs), 120 postmenopausal women were randomly allocated to receive either transdermal therapy consisting of 28-day cycles with patches that delivered 17 beta-estradiol (50 micrograms/d) combined with cyclic oral medroxyprogesterone acetate (10 mg/d for 12 days per cycle) or continuous oral 17 beta-estradiol (2 mg/d) together with norethisterone acetate (1 mg/d) for 12 months. Blood samples were taken before and at 6 and 12 months of HRT. Concentrations of serum total, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol decreased by 14% (P < .001), 17% (P < .001), and 9% (P < .001) in the oral HRT group. Respective changes were 5.7% (P < .001), 4.8% (P < .05), and 4.7% (NS) in the transdermal group. Serum triglycerides remained unchanged in the oral group but decreased by 15.7% (P < .001) in the transdermal group. We observed only trivial changes in serum apo B levels. The changes in apo A-I levels paralleled those of HDL cholesterol in the oral HRT group. The concentration of serum Lp(a) decreased by 31% (P < .001) and 16% (P < .001) in the two groups. The combination of progestin and transdermal estrogen was not associated with any further change of Lp(a). The decrement in Lp(a) during therapy was positively associated with baseline Lp(a) levels in both groups (r = .96, P < .001 and r = .88, P < .001). Thus, both HRT regimens were highly effective in lowering elevated Lp(a) levels in postmenopausal women. The divergent responses of LDL and HDL cholesterol in the two HRT groups may influence the potential cardioprotective effects of the two HRT regimens. Prospective trials are needed to define the long-term effects with respect to coronary heart disease risk.

Administration, Cutaneous↗
PubMed1995

Can progestin be limited to every third month only in postmenopausal women taking estrogen?

We evaluated whether a progestin, added for 14 days every 3 months to estrogen replacement therapy, is capable of preventing the development of endometrial hyperplasia in postmenopausal women during a treatment period of 2 years. Postmenopausal women (263) in 10 hospitals and medical centers in Finland participated in this non-randomized prospective multicenter trial. The women received estradiol valerate 2 mg daily for 84 days and 20 mg of medroxyprogesterone acetate daily for days 71-84 followed by seven drug-free tablets. This regimen was repeated four times per year. The first year of treatment was completed by 227 (86%) women and the second year by 143 out of 146 women. The incidence of unscheduled and heavy bleedings was higher in women who were postmenopausal for less than 3 years. Endometrial biopsies demonstrated progestational response in 64% at 12 and 24 months, respectively. The 3 month regimen prevented development of endometrial hyperplasia but was not able to restore a hyperplastic endometrium to normal.

Adult↗
PubMed1995

Postmenopausal hormonal replacement decreases plasma levels of endothelin-1.

Hormone replacement therapy (HRT) protects against cardiovascular disorders, but the mechanisms of this action are poorly understood. We assessed the plasma levels of vasoconstrictive endothelin-1 (ET-1) in 26 healthy postmenopausal women before and during HRT. The women were randomized to receive either continuous transdermal (estradiol 50 ug/24 hrs) complemented with periodic 12 days' courses with medroxyprogesterone (10.0 mg/day)(n = 13) or continuous oral estradiol (2.0 mg/day) and continuous norethisterone acetate (1.0 mg/day)(n = 13). ET-1 was measured with specific radioimmunoassay after concentrating the sample with solid phase extraction. Pretreatment plasma ET-1 (1.28 +/- 0.36 pmol/ml, mean +/- SD) in the whole study group decreased (p < 0.01) to 1.05 +/- 0.26 pmol/ml at 6 months and to 1.10 +/- 0.32 pmol/ml at 12 months of treatment. A subgroup analysis between the two HRT regimens revealed no significant differences in the response of plasma ET-1 to HRT. These first data on HRT-induced reduction in plasma ET-1 may provide a new explanation for the cardiovascular protection by HRT.

Administration, Cutaneous↗
PubMed1989

Circulating lipid and lipoprotein concentrations during danazol and high-dose medroxyprogesterone acetate therapy of endometriosis.

In a study on endometriosis, ten patients were treated with danazol (200 mg three times a day) and ten patients with high-dose medroxyprogesterone acetate (MPA) (100 mg a day) for 6 months. The circulating high-density lipoprotein-cholesterol concentration decreased significantly in the danazol (53%) and in the MPA groups (26%); the change in the danazol group was significantly higher than that in the MPA group. Danazol also significantly increased the low-density lipoprotein-cholesterol levels (37%), whereas MPA had no significant effect. Danazol (29%) and MPA (12%) decreased the apolipoprotein A-1 levels significantly. The decrease caused by danazol was significantly greater. Danazol also significantly decreased the apolipoprotein A-2 levels (12%) and significantly increased the apolipoprotein B levels (17%), whereas MPA had no significant effects on them. Three months after the end of medication, all values were at the pretreatment levels. The circulating cholesterol, triglyceride, and very low-density lipoprotein concentrations remained unchanged during both treatments. Danazol and high-dose MPA induced a similar significant regression of peritoneal endometriotic implants in relation to placebo. Our present results, showing that danazol, to a greater extent than high-dose MPA, is associated with changes in lipoprotein metabolism that expose the individual to an increased risk of cardiovascular diseases, suggest that high-dose MPA is preferable to danazol in the long-term treatment of endometriosis.

Adult↗
PubMed1988

The effect of bupivacaine paracervical block on the neurobehavioural responses of newborn infants.

The effects of maternal bupivacaine paracervical block on neonatal neurobehavioural responses were studied at the ages of 3 h, 1 day, 2 days and 4-5 days. Subjects were healthy, term neonates born vaginally to 10 mothers with paracervical block and to 12 mothers without analgesia. No statistically significant differences were found in the responses between the groups. It is concluded that paracervical block with a small dose of bupivacaine, applied by experienced obstetricians to non-risk parturients with healthy foetuses, has no detrimental effects on newborn behaviour or neurological recovery.

Adult↗
PubMed1987

Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis.

A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis.

Adult↗
PubMed1986

Ectopic pregnancy--an analysis of the etiology, diagnosis and treatment in 552 cases.

An analysis of the clinical data of 552 patients treated for ectopic pregnancy during 1973-82 in our hospital showed that the prevalence of this complication rose twofold (P less than 0.01) from an annual rate of 10.9 per thousand in 1973 to 20.9 per thousand in 1982. As regards parity distribution, the proportion of the 2-paras increased significantly (P less than 0.05) and this increase was significantly greater (P less than 0.001) than in the total population of parturients during this period. The increasing incidence of ectopic pregnancies had a significant positive correlation (P less than 0.05) with the use of an intrauterine device (IUD), but not with previous or present pelvic inflammatory disease or gynaecological or abdominal surgery. Because the 158 patients with an IUD in situ (34%) had a significantly less frequent past history of salpingitis, pelvic operation, infertility, ectopic pregnancy or spontaneous abortion and had less actual pelvic inflammatory changes than the 259 patients without contraception (57%), the IUD seemed to be directly involved with the increased risk of ectopic pregnancy. In the present study lower abdominal pain occurred in 97% of the patients and menstrual disorders in 93%; pelvic examination revealed adnexal mass in 63% and adnexal tenderness in 90% of the patients. Laparoscopy, a sensitive urinary pregnancy test (detection limit 75 IU/1) and culdocentesis were the most important factors in the diagnosis of ectopic pregnancy as evidenced by positive results in 97, 90 and 83% of the cases, respectively. Due to improved diagnostic procedures the annual rate of an unruptured tube at operation increased from 49% to 73% during the study period.

Adolescent↗
PubMed1986

Tiaprofenic acid in the treatment of primary dysmenorrhoea.

Thirty-one patients with primary dysmenorrhoea were treated in a double-blind, six-period, cross-over clinical trial with tiaprofenic acid, naproxen sodium and a placebo in randomized order, each for 2 consecutive cycles. Complete disappearance of the symptoms or pronounced therapeutic effects were obtained with tiaprofenic acid, naproxen sodium and the placebo in 74%, 65% and 35% of cases, respectively, while these treatments were ineffective in 3%, 6% and 38% of cases, respectively. Tiaprofenic acid was superior to the placebo for relieving pelvic pain and overall discomfort and for reducing the need for bed-rest. Naproxen sodium compared favourably with the placebo with respect to pelvic pain and overall discomfort. The effects of tiaprofenic acid and naproxen sodium were not significantly different. Tiaprofenic acid had no side-effects, whereas tiredness was experienced in 3 cases of naproxen sodium treatment. The results indicate that tiaprofenic acid is a useful alternative for the treatment of primary dysmenorrhoea.

Adolescent↗
PubMed1986

Dermal prostacyclin, thromboxane A2 and prostaglandin F2 alpha in climacteric women: effect of oestrogen replacement therapy.

The involvement of dermal prostanoids in menopausal flushing was studied in 8 women suffering from climacteric hot flushes and in 10 asymptomatic control subjects by inducing suction blisters on abdominal skin and assaying blister fluids for 6-keto-PGF1 alpha, a metabolite of the vasodilative prostacyclin (PGI2), thromboxane B2 (TxB2), a metabolite of the vasoconstrictive thromboxane A2 (TxA2), and 13,14-dihydro-15-keto-PGF2 alpha (M-PGF2 alpha), a metabolite of prostaglandin F2A (PGF2A). No marked differences were observed in the levels of these prostanoids in the two study groups. The women experiencing flushes then received conjugated oestrogens for 3 mth to abolish vascular instabilities. This decreased the blister fluid concentration of M-PGF2 alpha from 1720 +/- 476 pg/ml (mean +/- SE) to 1490 +/- pg/ml (P less than 0.05), but had no effect on the dermal levels of 6-keto-PGF1 alpha or TxB2. It was concluded that although certain dermal prostanoids may be affected by oestrogen treatment they are not of primary significance as regards menopausal flushing.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Biochemical and clinical effects of treating the premenstrual syndrome with prostaglandin synthesis precursors.

The clinical and biochemical effects of a prostaglandin synthesis precursor (Efamol) containing linoleic acid and its metabolite, gamma-linolenic acid, were studied in 30 women with severe, incapacitating premenstrual syndrome. Efamol treatment alleviated the premenstrual symptoms in general and depression especially better than did a placebo. The capacity of platelets to release thromboxane B2 during spontaneous clotting was decreased in patients undergoing Efamol treatment (141 +/- 59 ng/ml, mean +/- SD) as compared to those undergoing placebo treatment (186 +/- 44 ng/ml, p less than 0.01) and control subjects (176 +/- 40 ng/ml, n = 25, p less than 0.05). No changes were found in plasma 6-keto-prostaglandin F1alpha or in FSH, LH, prolactin, progesterone, estradiol and testosterone. The data suggest that prostaglandins might play a role in the pathophysiology of the premenstrual syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Vasoconstrictory thromboxane A2 and vasodilatory prostacyclin in climacteric women: effect of oestrogen-progestogen therapy.

The production of vasoconstrictory thromboxane A2 (TxA2) and vasodilatory prostacyclin ( PG2 ) was studied in women suffering from climacteric vascular instabilities before and during the oestrogen-progestogen therapy. The serum concentrations of TxB2, a metabolite of TxA2, in climacteric patients were similar (170.5 +/- 25.5 ng/ml, mean +/- SE, n = 14) to those in control subjects (196.0 +/- 27.5 ng/ml n = 17) before the start of treatment, but rose to 209.3 +/- 24.5 ng/ml after 3 wk of treatment (P less than 0.01 in comparison with the pre-treatment level), to 227.2 +/- 44.1 ng/ml after 3 mth (P less than 0.05) and to 237.4 +/- 30.3 ng/ml after 6 mth (P less than 0.05). The plasma concentrations of 6-keto-prostaglandin F1a , a stable breakdown product of PG2 , were normal in climacteric (43.5 +/- 7.3 pg/ml as against 46.1 +/- pg/ml) and did not change during replacement therapy. It was concluded, firstly, that climacteric symptoms are not accompanied by changes in TxA2/ PG2 which can be detected in peripheral blood and, secondly, that the increase in the concentration of vasoconstrictory TxA2 induced by oestrogen-progestogen therapy may contribute to the disappearance of climacteric vascular instabilities.

6-Ketoprostaglandin F1 alpha↗