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Biomedical subjects

A Kauppila

Publications and source records attributed to A Kauppila.

At least 163 records · Page 9Linked to original sources

Treatment of inadequate lactation with oral sulpiride and buccal oxytocin.

Thirty-six puerperal women with inadequate lactation were treated with 50 mg sulpiride (N = 24) or placebo (N = 12) three times a day for two weeks. These treatments were supplemented with buccal oxytocin (100 IU, 300 IU, or 400 IU) or placebo preceding each breast-feeding on the sixth and 14th and on the seventh and 13th days of oral treatment, respectively. One woman treated with sulpiride and three women treated with placebo discontinued the trial because of the lack of the effect of treatment. The concentration of prolactin in maternal serum was higher (P less than .001) during sulpiride than placebo treatment at one week (380 +/- 43 ng/ml vs 23 +/- 7 ng/ml, mean +/- SE) and two weeks of treatment (381 +/- 38 ng/ml vs 34 +/- 10 ng/ml). Also, the daily breast milk yield, as measured objectively, was greater (P less than .05) during sulpiride than placebo treatment both at one week (628 +/- 51 ml vs 440 +/- 68 ml) and two weeks of treatment (684 +/- 67 ml vs 423 +/- 60 ml). Various doses of oxytocin failed to stimulate the milk secretion in the presence or absence of sulpiride-induced hyperprolactinemia. Thus, sulpiride improved inadequate lactation, whereas exogenous oxytocin alone or together with sulpiride had no effect on lactation in these mothers whose infants were able to suckle normally.

Adult↗

Selenium concentration in maternal and umbilical cord blood, placenta and amniotic membranes.

The selenium concentration of maternal and umbilical cord whole blood was determined by atomic absorption spectrophotometry in 21 parturients at term. Six placental and amniotic membrane tissue specimens were also investigated. The mean selenium concentrations in the maternal (0.73 +/- 0.15 mumol/l) and umbilical cord blood (0.77 +/- 0.18 mumol/l) were similar and without significant correlation. Placental (2.24 +/- 0.20 mumol/kg wet weight) and amniotic membrane tissue specimens (2.32 +/- 0.54 mumol/kg wet weight) also contained similar concentrations of selenium which were about 3 times higher than those in the maternal and umbilical cord blood. Low whole blood selenium concentration in Finnish parturients may be a sign of deficient nutritional intake of selenium during pregnancy. The relatively high concentration of selenium in the placenta and amniotic membranes on the other hand suggest that metabolically active organs are being provided primarily with this essential trace element.

Adolescent↗

Cytosol and nuclear estrogen and progestin receptors and 17 beta-hydroxysteroid dehydrogenase activity in non-diseased tissue and in benign and malignant tumors of the human ovary.

Significant but low concentrations (mean 8 fmol/mg cytosol protein) of cytosol estrogen receptors were found in 57% of non-diseased ovarian tissues, and higher concentrations (mean 211) of cytosol progestin receptors in all these tissues. An approximately similar distribution was found for the presence of nuclear female sex steroid receptors; the mean concentrations were 159 and 1149 sites/cell, for estrogen and progestin receptors, respectively. There were no major differences in these parameters between pre- and postmenopausal non-diseased ovaries. The activities of ovarian 17 beta-hydroxysteroid dehydrogenase (17-HSD) did not display correlations between circulating progesterone concentrations in pre- or postmenopausal women with non-diseased ovaries. The majority of benign epithelial tumors contained significant concentrations of cytosol estrogen receptors, and all showed cytosol progestin receptors. The concentration of estrogen receptors was identical to that seen in non-diseased ovaries (mean 9 fmol/mg cytosol protein), whereas that of progestin receptor was significantly lower (mean 95). Nuclear female sex steroid receptors were measured in all benign tumors, and their concentrations were significantly higher than in normal ovaries (440 and 3218 sites/cell for estrogen and progestin receptors, respectively). No difference in 17-HSD activities were detected between normal ovaries and benign tumors. In malignant ovarian tumors, the picture was different from that found in normal ovarian tissues and benign tumors. Cytosol estrogen receptor was found in 89% of malignant epithelial tumors, and its concentration was significantly higher (mean 64 fmol/mg cytosol protein). Cytosol progestin receptor was found in 91%, and its concentration (mean 75) was significantly lower than in normal ovarian tissue or benign ovarian tumors. Nuclear female sex steroid receptor concentrations were intermediate between those seen in non-diseased ovaries an in benign tumors. 17-HSD activity was significantly lower than in other tissue categories studied. In the small group (16) of non-epithelial ovarian carcinomas cytosol estrogen receptors were not found, whereas the results of other measurements did not display any coherent picture. Breast and endometrial carcinoma metastatic to the ovary showed receptor patterns which were typical of the primary tumors. When the different clinical stages (I-IV) of malignant epithelial ovarian tumors were compared, 17-HSD activity was significantly higher in the least advanced clinical stage (I), whereas no significant differences were found in the other parameters measured.(ABSTRACT TRUNCATED AT 400 WORDS)

17-Hydroxysteroid Dehydrogenases↗

Metoclopramide and breast feeding: transfer into milk and the newborn.

The pharmacokinetics and endocrinological effects of metoclopramide were investigated in 5 mothers with deficient lactation and in their children soon after delivery. In addition, the transfer of metoclopramide into breast milk was evaluated in 18 mothers during the 8th to 12th puerperal weeks. Metoclopramide was detected in all the milk samples studied, generally at a higher concentration than in maternal plasma. Metoclopramide was found in plasma from only 1 of the 5 neonates studied. Exposure of the child to metoclopramide, estimated by multiplying the daily breast milk volume by the concentration of metoclopramide in the milk, ranged from 6 to 24 micrograms/kg/day for the 5 children in the early puerperium to 1 to 13 micrograms/kg/day for the 18 children during the late puerperium. These quantities are considerably less than the therapeutic dose of 500 micrograms/kg/day recommended for children. However, the plasma concentration of prolactin in 4 out of 7 neonates sampled taken during administration of metoclopramide to the mother were higher than the highest plasma prolactin level in children of same age of untreated mothers. The plasma concentration of thyrotrophin in the newborns remained within the normal range.

Female↗

Placental transfer and hormonal effects of metoclopramide.

In order to study the transplacental transfer of metoclopramide, and its endocrine effects, measurements were made of its concentration in maternal and fetal blood, and in the amniotic fluid, together with maternal and fetal plasma concentrations of prolactin, TSH and oestradiol, during delivery by selective Caesarean section. The drug, 10 mg, was injected i.m. 12 and 2 h and just before the onset of anaesthesia. Metoclopramide was detectable in all the umbilical arterial and venous and amniotic fluid samples, in mean concentrations of 50, 63 and 75 ng/ml, respectively. The mean ratio between the umbilical venous and maternal plasma concentrations was 0.63. Accurate maternal plasma half-lives could not be established but they must have averaged 2 to 4 h. The high amniotic fluid concentrations and relatively high umbilical venous and arterial concentrations soon after administration suggest that metoclopramide equilibrates relatively rapidly between the mother and fetus. Metoclopramide raised the maternal plasma prolactin levels from 315 +/- 128 ng/ml (SD) before therapy to 357 +/- 112 ng/ml at the time birth. No statistically significant difference in cord arterial or venous plasma prolactin levels was seen between the control and metoclopramide-treated groups. Metoclopramide did not affect maternal plasma TSH or oestradiol levels. The only change was a slight but significant increase in TSH level in cord blood taken from the umbilical artery after metoclopramide treatment.

Anesthesia, Obstetrical↗

Comparison of megestrol acetate and clomiphene citrate as supplemental medication in postmenopausal oestrogen replacement therapy.

In a prospective clinical trial lasting one year, 35 postmenopausal women with severe climacteric symptoms were cyclically treated with conjugated oestrogens (1.25 mg daily). This oestrogen replacement therapy was randomly supplemented with 10 mg of megestrol acetate daily (18 women) or 50 mg of clomiphene citrate (17 women) for 10 days four times a year. Both treatment regimens significantly alleviated climacteric symptoms. At the end of the oestrogen-megestrol acetate treatment no endometrial proliferation or hyperplasia was seen, while at the end of the oestrogen-clomiphene citrate treatment the endometrium was proliferative or hyperplastic in two women and atrophic in the other 15. Regular uterine bleeding occurred in each woman after megestrol acetate but never after clomiphene citrate administration. Break-through bleeding during the oestrogen treatment periods appeared in the megestrol and clomiphene groups in five and eight women, respectively. There were no clinically adverse hormonal or metabolic changes during megestrol acetate or clomiphene citrate treatment periods. Our results provide further evidence that in addition to progestins postmenopausal oestrogen replacement therapy can safely be supplemented with antioestrogen and thereby avoid the bleeding which occurs regularly after progestin withdrawal.

Climacteric↗

Female sex steroid receptors in gynecological malignancies: clinical correlates.

Cytosol estrogen (ERc) and progestin (PRc) receptors were measured in 135 endometrial carcinoma specimens from 127 patients, and in 84 ovarian carcinoma specimens from 84 patients before any treatment. In endometrial carcinoma, early clinical stages (I and II) were more often receptor-rich (ERc and PRc greater than or equal to 30 fmol/mg cytosol protein) than stage III-IV tumors, or metastatic and recurrent lesions. Anaplastic lesions (grade 3) had lower receptor concentrations than moderately (grade 2) and well (grade 1) differentiated stage I lesions. PRc concentrations of the stage I malignancies clearly infiltrating into the myometrium were lower than those in superficial tumors. Our follow-up (24 months or more) data of 41 patients with clinical stage I disease, and of 21 patients with clinical stage III or IV disease show that the receptor-poor tumors tend to behave more aggressively than receptor-rich malignancies in relation to patient survival. In 59 primary epithelial ovarian carcinomas, there were no significant differences in ERc and PRc concentrations in the four clinical stages. In contrast to this, the concentrations of these receptors were significantly lower in recurrent than in primary epithelial carcinomas. In anaplastic serous carcinomas, PRc was significantly lower than in differentiated tumors, and in anaplastic endometrioid carcinomas, ERc and PRc were lower than in corresponding differentiated tumors. Follow-up (24 months or more) data of 22 patients show that patients with advanced ovarian malignancy characterized by low ERc and/or PRc concentrations survive for a shorter time than the other patients.

Cytosol↗

Prostacyclin and thromboxane in ovarian cancer: effect of cytostatics and prostaglandin synthesis inhibitors.

The production of the antiaggregatory prostacyclin (PG1(2) ) and proaggregatory thromboxane A2 (TxA2) were studied in 19 patients with residual ovarian cancer. The plasma 6-keto-PGF1 alpha (a metabolite of PG1(2) ) in cancer patients (146.7 +/- 14.7 pg/ml, mean +/- SE) was higher (P less than 0.02) than that in the controls (85.3 +/- 9.2 pg/ml, n = 17). Also the releases of TxB2 (a metabolite of TxA2) during spontaneous clotting of the blood samples were greater (P less than 0.05) in the patients (253.4 +/- 30.1 ng/ml) than controls (183.2 +/- 19.8 ng/ml). The combined administration of doxorubicin, cyclophosphamide and cis-platinum temporarily decreased the plasma 6-keto-PGF1 alpha levels but caused no changes in TxB2 generation. Prostaglandin synthesis inhibitors (acetylsalicyclic acid or indomethacin) during cytostatic infusion did not prevent the occurrence of the acute side effects of cytostatics, but they inhibited the TxB2 generation. Thus our data suggest that residual ovarian cancer is accompanied by increased production of PG1(2) and TxA2, and that prostaglandins have no role in the acute side effects of cancer chemotherapy.

6-Ketoprostaglandin F1 alpha↗

Cell-mediated immunocompetence of children exposed in utero to short- or long-term action of glucocorticoids.

In the present study the in vitro sensitivity to mitogens (phytohemagglutinin, PHA, concanavalin A, Con A) and purified protein derivative (PPD) antigen of lymphocytes of children exposed in utero to short-term (n = 7) or long-term (over the whole pregnancy, n = 9) action of synthetic glucocorticoids was evaluated. Blood samples from these children and their age- and sex-matched controls were collected 3-4 and 3-10 years after delivery in the short-term and long-term exposure groups, respectively. After short- and long-term exposure to glucocorticoids the counts of all lymphocytes and alpha-naphthyl-acetate-esterase-positive lymphocytes in the peripheral blood, and the responses of T lymphocytes to mitogens or PPD antigen were similar in the subjects and their controls. The present data thus provide additional evidence of the safety of prenatal glucocorticoid prophylaxis for respiratory distress syndrome. Fetal lymphocytes also seem to be resistant to the extended action of exogenous glucocorticoids.

Child↗

Factors related to an improved outcome for twins.

We observed that perinatal mortality among the 220 twins born at our hospital in 1977-78 (3.6%) was significantly lower than for the 210 twins born in 1975-76 (11.0%). At the same time the frequency of postpartum asphyxia had decreased significantly. An analysis of factors related to the diagnosis and therapy revealed that during the later period both the diagnosis of twins and bed rest in hospital had been initiated significantly earlier than during the former period. The duration of pregnancy, length of stay in hospital, use of beta-adrenergic drugs or glucocorticoids, duration and type of delivery and birthweight of the infants were similar in both groups. Early diagnosis permits the greatest degree of readiness for both the mothers and the obstetrical and pediatric personnel in order to meet the possible complications commonly associated with a twin pregnancy and birth.

Asphyxia Neonatorum↗

Endocrine and metabolic effects of low-dose estrogen-progestin treatment in climacteric women.

In a double-blind clinical trial with 31 premenopausal women suffering from climacteric symptoms, 16 (group A) were treated with an estrone (sodium estrone sulfate 1.5 mg)-norethisterone (5 mg) combination, and 15 (group B) were treated with an estrone-megestrol acetate (5 mg) combination. These treatments effectively alleviated climacteric symptoms without causing any bleeding disorders or pathological changes in the cytology of the uterine cervix or endometrium. In groups A and B, respectively, postovulatory progesterone concentrations above 5 nmoles/liter were found in six and five patients before, in five and seven patients during, and in two and four patients after the treatments. Serum levels of luteinizing and follicle-stimulating hormones decreased significantly and testosterone decreased slightly during both treatments. Serum cholesterol (P less than .01) and high-density lipoprotein cholesterol(P less than .001) in group A decreased during the treatment; only the high-density lipoprotein cholesterol values (P less than .05) decreased in group B. Because of the minor endocrine and metabolic changes without any significant difference between the progestins, both norethisterone acetate and megestrol acetate seem to be suitable for estrogen-progestin combinations aimed at alleviating climacteric symptoms.

Adult↗

Cytosol and nuclear estrogen and progestin receptors and 17 beta-hydroxysteroid dehydrogenase activity in normal and carcinomatous endometrium.

Endometrial estrogen and progestin receptors were quantitatively measured in the cytosol (ERc, PRc) and nuclear (ERn, PRn) fractions, the activity of 17 beta-hydroxysteroid dehydrogenase measured in 13 normal women in the late proliferative phase of the cycle (control group), in 33 patients with adenocarcinoma, and in 6 patients with other malignancies of the endometrium. The parameters measured had relatively small variations in the control group, whereas the opposite was true for the malignant endometrium. ERc and PRc were present in significantly higher concentrations in normal endometrial tissue (167 and 1697 fmol/mg cytosol protein, respectively) than in malignant endometrial tissue (45 and 116 fmol/mg cytosol protein, respectively), and the ratios of ERc/ERn and PRc/PRn were higher (P much less than .001 in both cases) in the normal group. The activities of 17 beta-hydroxysteroid dehydrogenase were identical in normal and adenocarcinoma tissue and correlated with PRc in carcinomatous endometrium. The present results support previous findings that the great majority of endometrial adenocarcinoma specimens have significant concentrations of ERc and PRc and that these concentrations are lower than in normal endometrium. In addition, they demonstrate that nuclear location of the female sex steroid receptors is favored in the malignant tissue. Despite these differences, the 17 beta-hydroxysteroid dehydrogenase activities were identical in proliferative endometrium and in endometrial adenocarcinoma.

17-Hydroxysteroid Dehydrogenases↗

Prevention of posthysterectomy infection with a combination of preoperative vaginal and perioperative intravenous administration of metronidazole.

In a prospective double-blind study 58 patients received 1000 mg of metronidazole vaginally 12--16 hours preoperatively and 500 mg intravenously during abdominal hysterectomy while 54 patients were treated with placebo. The lack of all operative site infections in the metronidazole group in comparison with 9 infections (17%) in the placebo group (P less than 0.01) proved the combined short-term vaginal and intravenous use of metronidazole to be efficacious in the prevention of posthysterectomy infections.

Adult↗

The effect of parturition on umbilical blood plasma levels of norepinephrine.

The norepinephrine concentration in 77 umbilical, arterial, and venous plasma samples, and in 31 simultaneous maternal plasma samples, was measured. The mean (+/- SEM) of 8.7 +/- 1.9 ng/ml in the umbilical artery was higher (P less than .001) than that of 3.6 +/- 0.9 ng/ml in the umbilical vein. In paired fetal-maternal venous samples the norepinephrine concentration of 3.8 +/- 1.7 ng/ml in the fetus was higher (P less than .05) than that of 0.3 +/- 0.1 ng/ml in the mother. Among the different types of vaginal deliveries the umbilical arterial norepinephrine concentrations were: 5.8 +/- 2.1 ng/ml in uncomplicated vaginal deliveries; 16.4 +/- 2.1 ng/ml in breech deliveries (P less than .05 as compared with uncomplicated vaginal deliveries); 8.8 +/- 2.5 ng/ml in vacuum extraction deliveries; and 0.8 +/- 0.3 ng/ml and 11.3 +/- 7.7 ng/ml in twin A and twin B deliveries, respectively. All these values were higher (P less than .001) than those after elective cesarean section, except that for twin A, which was lower (P less than .01) than that for twin B, indicating that labor and vaginal delivery induced activation of the fetal sympathoadrenal system.

Adult↗

Clinical significance of estrogen and progestin receptors in ovarian cancer.

Concentrations of cytosol estrogen and progestin receptors were determined in ovarian carcinoma samples from 84 patients with early (stages I to II; N = 17), advanced (III to IV; N = 39), recurrent epithelial (N = 9), and nonepithelial (N = 5) cancer and with ovarian metastases of other malignancies (N = 11). Seventy-one percent of all the specimens contained estrogen and progestin receptors (3 or more and 6 or more fmol/mg cytosol protein, respectively, receptor-positive group), whereas 10% of the tumors were receptor-negative. Primary epithelial ovarian carcinomas were more often receptor-positive (81% versus 44%), and they had higher receptor concentrations than recurrent epithelial ovarian tumors. Primary endometrioid and serous carcinomas had higher concentrations of cytosol estrogen receptors than did mucinous tumors. Anaplastic endometrioid malignancies had significantly lower concentrations of both receptors than the differentiated tumors, whereas in serous carcinomas only cytosol progestin receptor displayed this difference. Patients with advanced malignancy characterized by low estrogen and/or progestin receptor concentrations had nonremovable tumor more often, and they survived for a shorter time than the other patients.

Adult↗

Cytosol estrogen and progestin receptors in endometrial carcinoma of patients treated with surgery, radiotherapy, and progestin. Clinical correlates.

Cytosol progestin (PR) and estrogen receptor (ER) concentrations were measured in 114 endometrial carcinoma specimens from 109 patients; these levels were correlated with clinical and histopathologic characteristics, and with clinical outcome in 44 patients followed for at least two years after the primary therapy consisting of surgery, irradiation and adjuvant administration of progestin. Eighty percent of all specimens were simultaneously PR- and ER-positive (greater than or equal to 6 fmol and greater than or equal to 3 fmol/mg protein, respectively) whereas 10% were both PR- and ER-negative. Early clinical stages (I and II) were more often receptor-positive, and the receptor concentration in these tumors was higher than in advanced or recurrent disease. The same was the case for superficial as compared with deeply invasive lesions. Both PR and ER concentrations in well or moderately differentiated tumors were higher than in anaplastic carcinomas. PR and ER concentrations did not correlate with the age of menopausal status, body weight or carbohydrate metabolism of the patients. In the patient group followed up for two years or more, the receptor-poor tumors tended to behave more aggressively than did receptor-rich malignancies in relation to patient survival. The measurement of PR and ER concentrations in advanced endometrial carcinoma has been proved useful in the selection of hormonal or cytotoxic chemotherapy. The current results advocate their use of prognostic risk factors which might be useful in selection of the most efficient treatment modalities for individual patients.

Adult↗