Search PubMed⌕ Search

Biomedical subjects

A Kauppila

Publications and source records attributed to A Kauppila.

At least 73 records · Page 4Linked to original sources

Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen.

OBJECTIVE: To assess the estrogenic effect of tamoxifen and associated pathologic changes of the endometrium in postmenopausal breast cancer patients. METHODS: The endometrium of 103 gynecologically asymptomatic postmenopausal breast cancer patients was examined. Fifty-one had been treated with tamoxifen and 52 had not received any hormonal treatment. The two groups were similar in age, parity, age at menopause, and body mass index. RESULTS: Compared with the control subjects, the tamoxifen patients had a thicker endometrium (mean +/- standard deviation 10.4 +/- 5.0 versus 4.2 +/- 2.7 mm; P = .0001) and larger uterine volume (45 +/- 27 versus 25 +/- 11 cm3; P = .001), as determined by transvaginal sonography. Hysteroscopy showed an atrophic endometrium in 28% of the patients in the tamoxifen group, as compared with 87% of the control patients (P = .0001). Endometrial polyps were more frequent in the tamoxifen group (36 versus 10%; P = .004), which included one patient with atypical hyperplasia, one with adenomatous hyperplasia, and one with endometrial adenocarcinoma; two controls had endometrial adenocarcinoma. CONCLUSION: The results provide evidence for an estrogenic effect of long-term tamoxifen treatment on the postmenopausal uterus and show it to be associated with an increased occurrence of polyps.

Aged↗

Tumor markers of epithelial and stromal cell origin at second-look laparotomy in ovarian carcinoma.

The accuracy of CA 125, amino-terminal propeptide of type III procollagen (PIIINP), and clinical examination were evaluated in association with 48 second-look laparotomies of ovarian carcinoma patients treated with cytotoxic chemotherapy. At laparotomy, there were 23 macroscopical and 6 microscopical tumors. Nineteen patients were disease-free. Clinical examination, CA 125, and PIIINP were correctly positive in 93, 92, and 82% of cases, respectively. When CA 125 and PIIINP were used simultaneously this value increased to 100%. The sensitivity of CA 125 (43%) and PIIINP (56%) was unsatisfactory, but with their combination it increased to 62%. The use of CA 125, PIIINP, or both increased the sensitivity of clinical examination by 14, 24, and 27%, respectively. Of all the occult tumors, CA 125 detected 33%, PIIINP 57%, and both 66%. The detection rate of macroscopical tumors missed at clinical examination by both was 71%. Hence, PIIINP may be a clinically valuable complement to CA 125 and clinical examination before second-look laparotomy.

Adult↗

Laminin in the human embryo implantation: analogy to the invasion by malignant cells.

OBJECTIVE: To explore the possible similarities between the biochemical processes of embryo implantation and malignant invasion. DESIGN: The expression of a basement membrane (BM) glycoprotein laminin, a matrix binding cell surface receptor protein beta 1-integrin, and a BM collagen degrading metalloproteinase type IV collagenase, was studied in cultured human in vitro fertilized embryos. PATIENTS: Eight healthy women suffering from tubal infertility were participating in the IVF program in the Department of Obstetrics and Gynecology in University Hospital of Oulu. Twenty oocytes and 110 pre-embryos that were not transferred for the fertilizations were used in this study. MAIN OUTCOME MEASURES: Fibronectin, laminin, beta 1-integrin, and type IV collagenase immunoreactive proteins were studied in embryos by immunoperoxidase staining, and type IV collagen degrading activity was measured from the culture media of the embryos. RESULTS: Laminin and beta 1-integrin were expressed in the early human embryos before the time of implantation. Type IV collagen degrading activity and the 72 kd-type IV collagenase immunoreactive protein were expressed at the time of implantation. Laminin supported the expression of type IV collagenase. CONCLUSIONS: The expression of laminin, beta 1-integrin, and type IV collagenase in vitro are temporally in good correlation with the time of the implantation in vivo. Laminin and beta 1-integrin can relate to the attachment of the embryos to the uterine BM and type IV collagenase to the degradation of the BM collagen during the implantation. Laminin can augment the process locally.

Adult↗

Aminoterminal propeptide of type III procollagen in ovarian cancer. A review.

The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a measure of the activity of the metabolism of type III collagen, which is a major constituent of soft connective tissues and of the connective tissue stroma of solid tumours. In advanced ovarian carcinoma, serum PIIINP serves as a tumour-associated antigen, its changes reflecting and preceding changes in the clinical behaviour of the malignancy. Elevated values of serum PIIINP are also observed in endometrial and cervical malignancies, though less frequently than in ovarian tumours. Very high concentrations of PIIINP are found in ovarian carcinoma ascites, suggesting an ongoing fibro-proliferative reaction in the peritoneal cavity as a response to the tumour.

Antigens, Tumor-Associated, Carbohydrate↗

GnRH agonist analog therapy in advanced/recurrent granulosa cell tumors: further evidence of a role of inhibin in monitoring response to treatment.

Five patients with advanced ovarian granulosa cell malignancies resistant to cytotoxic chemotherapy were treated with monthly subcutaneous injections of long-acting gonadotropin releasing hormone (GnRH) agonist analog. One partial response and one stabilization of the disease were observed. In three patients, the tumor continued to progress. Treatment response was monitored with serum inhibin assay. Four patients had high serum inhibin concentrations at the beginning of GnRH analog treatment, while one patient had an inhibin-negative tumor. In three of four patients, serum inhibin remained relatively constant, or decreased during the first 3 months of therapy. It subsequently increased, in parallel with clinical deterioration. Further clinical trials with GnRH analogs are warranted in this malignancy in which serum inhibin appeared to be a clinically valuable tumor marker.

Adult↗

Gonadotropin pulsatility in a stimulated cycle: clomiphene citrate increases pulse amplitudes of both luteinizing hormone and follicle-stimulating hormone.

OBJECTIVE: To elucidate gonadotropin secretory patterns during ovarian hyperstimulation for in vitro fertilization. DESIGN: All volunteers who attended the unit during a period of 3 months were prospectively investigated. SETTING: Infertility unit of the University Central Hospital of Oulu. PARTICIPANTS: Normally menstruating tubal infertility patients (n = 8) and healthy women with ovulatory cycles (hospital personnel, n = 11). All patients finished the study. INTERVENTIONS: Clomiphene citrate (CC), 50 mg, was administered on cycle days 5 to 9 and 300 IU of pure follicle-stimulating hormone (FSH) on cycle day 7 and 150 IU on cycle day 8. MAIN OUTCOME MEASURES: Serum samples for luteinizing hormone (LH) and FSH measurements were collected at 10-minute intervals for 6 hours on cycle day 7 (effect of CC) and day 9 (effect of CC/FSH), and the data were analyzed with the Munro computer program. RESULTS: The number of LH peaks was identical in the controls and study subjects on cycle days 7 and 9, whereas the pulse amplitude (P less than 0.025) and the pulse area (P less than 0.01) were higher in the CC/FSH-treated patients. The increase in overall mean LH level during the hormone therapy was not significant. In the CC/FSH-treated women, a decreased number of FSH pulses (P less than 0.01) with increased amplitude (P less than 0.001) and pulse area (P less than 0.01) was found. Clomiphene citrate treatment increased the mean FSH level (control versus cycle day 7, P less than 0.05) which was further increased (cycle day 7 versus cycle day 9, P less than 0.05) by FSH administration on cycle days 7 to 8. Otherwise pure FSH was found to be unable to modify endogenous LH or FSH secretory patterns under these conditions. CONCLUSIONS: Clomiphene citrate increases the amplitudes of both LH and FSH pulses in the midfollicular phase of a stimulated cycle, an effect which is not influenced by pure FSH administration.

Adult↗

Insulin-like growth factor binding protein-1 and ovarian stimulation.

Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) were measured in 42 patients with tubal infertility undergoing two different regimens of ovarian stimulation for in-vitro fertilization. The first group comprised 24 women given a luteinizing hormone-releasing hormone agonist analogue (buserelin, LHRHa) on cycle days 1-4 followed by follicle-stimulating hormone and human menopausal gonadotrophin (LHRHa group). The second group of 18 women received clomiphene citrate and gonadotrophins (CC group). On the day of human chorionic gonadotrophin administration, the sum of follicular diameters (P less than 0.05) and the number of follicles punctured in the LHRHa group (P less than 0.01) were significantly higher than in the CC group. In spite of the greater number of follicles, the oestrogen levels were similar in both groups, but women in the LHRHa group had significantly higher serum IGFBP-1 concentrations during the last 5 days of stimulation. These results suggest that the stimulated preovulatory follicles may contribute to the elevation of serum IGFBP-1.

Adult↗

Use of various epithelial tumor markers and a stromal marker in the assessment of cervical carcinoma.

The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15-3, and TAG 72, and the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, were evaluated in 111 cervical carcinoma patients. Squamous cell carcinoma antigen was pathologic in 47%, aminoterminal propeptide of type III procollagen in 40%, CA 125 in 13%, CA 15-3 in 30%, and TAG 72 in 9% of the 91 patients with squamous cell carcinoma. The squamous cell carcinoma antigen, aminoterminal propeptide of type III procollagen, and CA 125 correlated with the clinical stage. The predictive value of a pathologic squamous cell carcinoma antigen was 78% and that of a negative result 68%. Squamous cell carcinoma antigen and aminoterminal propeptide of type III procollagen further increased the detection rate by approximately 20% from that obtained by squamous cell carcinoma antigen alone. In 16 patients with advanced disease, squamous cell carcinoma antigen correlated with the behavior of the disease in eight, aminoterminal propeptide of type III procollagen in nine, and CA 125 in six patients. Pathologic squamous cell carcinoma antigen, CA 125, CA 15-3, TAG 72, and aminoterminal propeptide of type III procollagen appeared in 11, 32, 31, 31, and 47% of 19 patients with adenocarcinoma, respectively. Squamous cell carcinoma antigen is clinically useful in squamous cell carcinoma but poor in adenocarcinoma, for which the other markers are better. Squamous cell carcinoma antigen, CA 125, and aminoterminal propeptide of type III procollagen may be used for monitoring the behavior of advanced squamous cell carcinoma.

Adenocarcinoma↗

Serum concentrations of CA 125 and aminoterminal propeptide of type III procollagen (PIIINP) in patients with endometrial carcinoma.

Serum CA 125 (a marker of coelomic epithelial cells) and aminoterminal propeptide of type III procollagen (PIIINP; an indicator of collagen metabolism) concentrations were measured in 148 patients with endometrial carcinoma. An initial serum concentration of CA 125 was pathologic in 17% of the patients, the frequency of abnormal values being higher (P = 0.0001) in advanced (63%) than in early disease (10%). The serum PIIINP concentration was increased in 35% of the patients and more often (P less than 0.05) so in advanced (63%) than in early disease (31%). Among all the patients, at least one of the tumor markers was increased in 43% of the cases. In early disease 12 of 108 patients contracted recurrent cancer. The accuracy of the pathologic CA 125 (9%) and PIIINP (18%) concentrations in their prediction was poor. In the total material, pathologic CA 125 and PIIINP concentrations appeared simultaneously in 11 patients, of whom eight had poor prognoses. In monitoring of treatment response of 24 patients, regression was accompanied by normal or decreasing CA 125 and PIIINP values. The persistence of pathologic CA 125 and/or PIIINP concentration predicted relapse of the malignancy. In progressive disease, CA 125 and PIIINP concentrations together or separately remained at a pathologic level or increased continuously. In clinically stable endometrial carcinoma, CA 125 gave false-negative results in 71% of the determinations and PIIINP only in 12%. The current results suggest the use of CA 125 and PIIINP, simultaneously, in monitoring the clinical course of advanced endometrial carcinoma.

Adult↗

Collagen metabolism in gynecologic patients: changes in the concentration of the aminoterminal propeptide of type III procollagen in serum.

We have previously found the serum concentration of the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, to be increased in advanced ovarian cancer. In this study we measured the serum aminoterminal propeptide of type III procollagen concentration in healthy women during the menstrual cycle and in patients with salpingo-oophoritis, leiomyomas, endometriosis, and benign ovarian tumors. The concentration was higher in the luteal phase than that in the follicular phase, suggesting an association of collagen metabolism with ovarian steroid hormones. Severe salpingo-oophoritis increased the serum level of the aminoterminal propeptide of type III procollagen with a decrease to normal during recovery. Elevated values were occasionally seen in endometriosis and leiomyomas. These findings indicate that the aminoterminal propeptide of type III procollagen is a relatively unspecific indicator of ovarian carcinoma.

Adult↗

Placebo-controlled study on the efficacy of the pyrimido-pyrimidine derivative RA 233 in ovarian cancer.

This prospective double-blind, multicenter study was aimed at evaluating the clinical efficacy of RA 233 (a derivative of dipyridamole) in ovarian cancer. Following primary surgery, 497 patients with ovarian cancer were treated with combination cytotoxic chemotherapy; those in clinical stage II were also treated with pelvic irradiation. The patients were randomly allocated to receive RA 233 (N = 251) or placebo (N = 246) for 2 years. The groups did not significantly differ from each other in any of the clinical, therapeutic, or histopathological variables evaluated. There were no significant differences between RA 233-treated patients and placebo-treated patients with respect to appearance of new metastases, progressive growth of malignancy, or survival of all patients, in any of the clinical stages of the disease, in radically operated patients or in nonradically operated patients, in different histopathological groups, or in different age groups. Hence, supplementation of carcinoma therapy with long-term administration of the antiplatelet drug RA 233 has no clinical benefit in this malignancy. Using Cox's multifactorial stepwise analysis, this study revealed that the clinical stage of the disease, the extent of surgery, and the histopathology of the tumor, but not the age of the patient or the use of RA 233, were significant and independent predictors of survival. With respect to the histopathology, the poor prognosis of serous and mesonephric carcinomas appeared to be independent of the other prognosis indicators.

Combined Modality Therapy↗

Endocrine responses to gonadotrophins after LHRH agonist administration on cycle days 1-4: prevention of premature luteinization.

A treatment regime comprising an intranasally administered luteinizing hormone-releasing hormone (LHRH) agonist analogue (buserelin) on cycle days 1-4, followed by gonadotrophin administration [follicle stimulating hormone (FSH)/human menopausal gonadotrophin (HMG)] resulted in identical oestradiol (E2) responses compared with the reference method using clomiphene citrate (CC) and gonadotrophins. Immediately after analogue administration (day 4), buserelin-treated women showed short-lived elevations in serum LH and progesterone concentrations, but in the later follicular phase, the serum LH concentration was lowered compared with the controls. None of the women treated with analogue displayed elevated serum LH or progesterone concentrations at the time of injection of human chorionic gonadotrophin. In the early luteal phase, these women had higher serum levels of progesterone and higher progesterone to E2 ratios than the controls, but the length of the luteal phase was slightly shortened. Hence, in hyperstimulated cycles, 4-day treatment with buserelin caused profound endocrinological changes: namely, short-term rescue of the corpus luteum, prevention of an endogenous LH rise and premature luteinization and increased progesterone production in the early luteal phase.

Adult↗

Melatonin in infants and mothers at delivery and in infants during the first week of life.

To evaluate the possible effect of the extreme and permanent changes in the hormonal milieu and in the lighting conditions at birth on the pineal hormone, melatonin (MT), we measured maternal vein and umbilical artery concentrations of MT in 19 parturients, post-partum urinary concentrations of MT in 14 mothers and their infants, and daytime (0800-2000 h) and night-time (2000-0800 h) urinary concentrations of MT and 6-sulphatoxymelatonin in 22 infants during the first 8 days of life. The mean MT concentrations in maternal venous blood and umbilical arterial blood did not differ significantly from each other and there was a positive correlation between them. The same was true for postpartum urinary MT of the mothers and their infants. There was no diurnal rhythm of MT during the first week of life. MT excretion in neonates was 2-5 pmol/12 h (only 1-5% in comparison with adults) and that of 6-sulphatoxymelatonin 150-300 pmol/12 h. In reverse phase high pressure liquid chromatography (HPLC) studies, 84-100% of total MT immunoreactivity was eluted at the same position as synthetic MT, and a small amount of hydrophobic MT-like immunoreactive material was also detected in five of the 10 urine extracts studied. This material (perhaps a novel neonatal metabolite of MT) may be indicative of immaturity of neonatal metabolism of MT although 6-hydroxylation is also functional in neonates. Although infant MT immediately after delivery at least partly reflects maternal MT secretion, our results show that the pineal gland is capable of producing MT at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Circadian and seasonal variation in human preovulatory follicular fluid melatonin concentration.

The concentrations of melatonin in 112 preovulatory follicular fluid (FF) samples obtained from 60 women undergoing in vitro fertilization and 27 patients at laparotomy during a spontaneous cycle were measured by RIA and compared with those in peripheral serum. The circadian and seasonal variations in FF melatonin were also analyzed. The FF melatonin concentrations in stimulated (mean +/- SEM, 61.9 +/- 6.4 pmol/L) and spontaneous cycles (98.1 +/- 8.9 pmol/L) were significantly higher (P less than 0.005) than those in peripheral serum (25.4 +/- 1.2 and 38.6 +/- 1.8 pmol/L, respectively), and in the stimulated cycles there was a positive correlation between them. The FF melatonin concentration in the morning (58.9 +/- 3.8 pmol/L) was significantly higher (P less than 0.005) than that in the daytime (23.2 +/- 0.8 pmol/L), but the morning concentrations did not differ between the light and the dark seasons of the year, whereas the daytime values were higher (P less than 0.005) during the dark season (27.1 +/- 2.1 pmol/L) than during the light season (21.1 +/- 2.1 pmol/L). The FF melatonin concentration did not correlate with follicular volume, and FF and serum melatonin concentrations showed no significant correlation with the serum concentrations of estradiol, progesterone, testosterone, or PRL. There were also no differences between FF melatonin concentrations in aspirates with or without an ovum. In summary, significant circadian and circannual variations in high FF melatonin concentrations were found, which suggest that melatonin could potentially interfere with the regulation of reproduction in humans at the follicular level.

Chromatography, High Pressure Liquid↗

Simultaneous evaluation of epithelial cell function by CA 125 and stromal cell activity by aminoterminal propeptide of type III procollagen (PIIINP) in ovarian carcinoma.

Serum concentrations of CA 125 and the aminoterminal propeptide of type III procollagen (PIIINP) were measured in 50 patients with clinical stage I or II (N = 16) and stage III or IV (N = 34) ovarian carcinoma before and during cytotoxic chemotherapy. Initially pathological concentrations of CA 125 were found in 92% of all patients and 100% of those in clinical stages II, III and IV. The concentration of PIIINP was at pathological levels in 71% of patients. Serum concentrations of CA 125 (P = 0.04) and PIIINP (P = 0.005) were higher in stages III and IV than in stages I and II. Initial concentration of PIIINP, but not of CA 125, was significantly (P less than or equal to 0.001) higher in the 19 patients who died of the malignancy than in the 31 patients alive at the end of the follow-up period. There was a significant inverse correlation (P = 0.01) between the initial PIIINP values and the survival time among patients with a poor prognosis. Initial concentration of CA 125 was of no prognostic value. During the follow-up, the serum concentrations of CA 125 and PIIINP correlated closely with clinical changes in the disease. Either or both of the tumour markers increased or remained at pathological levels before clinical relapse in patients who had initially responded. PIIINP was a more accurate marker (84%) than CA 125 (63%) in this respect. The information obtained from CA 125 and PIIINP concentrations was identical in 65% and complementary in 33% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Amino-terminal propeptide of type III procollagen: a new prognosis indicator in human ovarian cancer.

To investigate the clinical usefulness of the amino-terminal propeptide of type III procollagen (PIIINP) as an indicator of ovarian cancer behavior, 30 patients with advanced epithelial malignancy were monitored with serial serum PIIINP and CA-125 determinations before and during treatment. Initially, PIIINP and CA-125 concentrations were each separately increased in 87% of the cases and, simultaneously, in 77% of the cases. In monitoring treatment responses, PIIINP and CA-125 were identical in 17 patients (57%), both being good predictors of the clinical behavior of the disease in 16 cases and poor predictors in one case. In 13 patients (43%) they were complementary to each other. In three cases PIIINP alone and in one case CA-125 alone were clinically useful prognosis indicators. During the period of complete clinical response to cytotoxic chemotherapy of 16 patients, the CA-125 concentrations decreased to normal before the clinical disappearance of the tumor in eight cases. PIIINP did so in only two cases, thus correlating more precisely with the presence of malignancy. In second-look laparotomies, PIIINP concentrations correlated with the presence of occult cancer better than those of CA-125. In predicting recurrent malignancy in patients with transient complete response, PIIINP and CA-125 were clinically equal. According to the present data, PIIINP concentrations often give information not obtainable by CA-125, thus being useful in monitoring the clinical behavior of ovarian cancer.

Adult↗

Successful colposuspension in stress urinary incontinence reduces bladder neck mobility and increases pressure transmission to the urethra.

Twenty-nine consecutive patients with stress urinary incontinence were investigated by bead chain urethrocystography (UCG) and single cough urethrocystometry before operation and 8-12 months after a Burch colposuspension producing clinical improvement. The operation significantly elevated the bladder neck and reduced its mobility during acute stress. The urethral inclination angle and the posterior urethrovesical angle also became smaller at rest and on straining. A significant negative correlation was found between the postoperative mobility of the bladder neck and the post-operative pressure transmission ratio (PTR), indicating that correction of the urethrovesical anatomical disorder eliminates the functional disorder in this disease and restores continence.

Adult↗

Elevated serum levels of endometrial secretory protein PP14 in patients with advanced endometriosis. Suppression by treatment with danazol and high-dose medroxyprogesterone acetate.

The circulating concentration of endometrial protein PP14 varied during the menstrual cycle in patients with endometriosis. The highest levels were found on days 1 to 4 of the cycle (176 +/- 123 micrograms/L; mean +/- SD), and the lowest on days 5 to 20 (44.1 +/- 29.7 micrograms/L). Rising levels were observed on days 21 to 30 (58.3 +/- 62.6 micrograms/L). On days 5 to 20 (i.e., during period of the lowest levels) patients with advanced endometriosis had higher PP14 levels (63.9 +/- 39.0 micrograms/L) than those with mild endometriosis (29.3 +/- 18.2 micrograms/L; p less than 0.01). Patients with mild endometriosis had slightly higher serum PP14 levels than apparently healthy control subjects (p less than 0.05), but overlapping of values between the two groups is remarkable. Conservative surgical elimination of endometriosis significantly decreased the serum PP14 levels. Treatment with danazol (600 mg/day), or with medroxyprogesterone acetate (100 mg/day) after laparoscopy also resulted in significant decreases in the serum PP14 concentration. After 6 months of treatment, conservative surgery in combination with danazol or with medroxyprogesterone acetate, yielded more pronounced declines in serum PP14 level than conservative surgery plus placebo. No significant difference was observed between the effects of danazol and medroxyprogesterone acetate. We conclude that endometriosis tissue contributes to the circulating PP14 level, and the decline in PP14 level during danazol and medroxyprogesterone acetate treatments reflects regression of intrauterine and ectopic endometrial tissues.

Adult↗