The additional use of buserelin in HMG-HCG ovulation induction in PCO: a double blind controlled study.
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Biomedical subjects
Publications and source records attributed to C W Burger.
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To characterize the oscillations of plasma LH in normally cycling and amenorrheic women, three groups of women were studied: I, normal women during the follicular phase of the cycle (n = 9); II, women with polycystic ovarian disease (PCOD; n = 11); and III, women with non-PCOD secondary amenorrhea (n = 12). Blood samples were obtained at 10-min intervals for 6 h on 2 separate days. A pulse was defined as an increase in LH at least 20% over the preceding lowest value (nadir). Since LHRH release immediately follows the nadir of the LH levels, the nadir interval (NI) was used for analysis. For analysis, the results from 1 day were selected at random from each subject, and from each day, the same number of NIs also were randomly selected. When two NIs from each patient were selected, the median NI was 75 min in group I, 45 min in group II, and 45 min in group III. When three or four NIs were chosen, the median NI was 60 min in group I, 50 min in group II, and 40 min in group III. The differences between the groups were statistically significant. When three NIs were selected, the mean of the corresponding LH amplitudes was 2.8 U/liter in group I, 6.0 U/liter in group II, and 1.5 U/liter in group III. The differences between these groups were statistically significant. Thus, the NI in PCOD patients was shorter than that during the follicular phase of the cycle, but this short NI is not unique for PCOD, since the NI in non-PCOD secondary amenorrhea patients was even smaller. The LH amplitude was higher in PCOD and lower in non-PCOD secondary amenorrhea compared to that during the follicular phase of the cycle. The decrease in NI in PCOD and/or non-PCOD secondary amenorrhea vs. the NI of the follicular phase could be explained by either a higher frequency of LHRH pulses from the hypothalamus or an increased sensitivity of the pituitary leading to a greater response of the pituitary to LHRH pulses.
Induction of ovulation with pulsatile administration of LRH by automatic portable infusion pump for 74 and 147 consecutive days in 2 patients with clomiphene resistant PCO-like disease is described. The patients exhibited 6 ovulatory cycles. One patient conceived during the fourth cycle. During the treatment a unilocular cyst, probably a lutein cyst, developed in one patient, but subsequently disappeared spontaneously under uninterrupted therapy. No chemical hyperstimulation was observed. Follicular phases lasted for 32 and 13 days in patient I and for 19, 25, 14 and 22 days in patient II. Luteal phases lasted for 16 and 15 days in patient I and for 17, 18 and 15 days, respectively in patient II. Total urinary oestrogen and pregnanediol excretion did not differ from that seen in normal cycles. LH baseline and peak values and LH responses declined to normal levels accompanied by a normalization of the LH/FSH ratio during pulsatile LRH treatment in both patients. The first pre-ovulatory episode occurred already after partial normalization of the LH/FSH ratio. The endocrinology of the second LRH induced cycles of patients I and II was not different from cycles similarly induced in hypogonadotrophic patients. We conclude that ovulation induction with pulsatile LRH administration in patients with clomiphene resistant PCO-like disease is possible. Our findings give hope that this mode of treatment may not only be effective, but may prove to be safer than ovulation induction with menopausal gonadotrophins in patients with clomiphene resistant PCO-like disease.
Randomized trials have shown that results of radiotherapy in patients with cervical cancer can be improved by combining the treatment with either cisplatin based chemotherapy, or hyperthermia. The studies on both the combination of radiotherapy with chemotherapy, and the combination on radiotherapy with hyperthermia, leave several important questions unanswered. At present, no definite conclusions can be drawn with regard to which combination results in the best therapeutic ratio. Therefore, on both ethical and scientific grounds, the next logical step would be to compare the two types of combined treatment to each other, and each combination with a treatment including all three modalities, in a randomized fashion.
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The introduction of paclitaxel/platinum combination chemotherapy and (interval) debulking surgery has significantly improved the prognosis of patients with ovarian cancer. Yet, many patients die of drug-resistant disease. Second-line chemotherapy may result in prolonged secondary remissions with alleviation of symptoms and improvement of quality of life. The response to second-line chemotherapy is strongly related to platinum sensitivity. More than 60% of platinum-sensitive patients respond to a re-challenge with platinum-containing chemotherapy. In platinum-resistant patients, on the contrary, the response rate to a re-challenge with 3-weekly platinum or any nonplatinum chemotherapy is less than 20%. The response to dose-dense weekly platinum-based regimens ranged from 48% to 64% in platinum-resistant patients. Moreover, the majority of the patients responded within 8 weeks after the start of the treatment. The progression-free survival ranged from a median of 5 months in a study using cisplatin/etoposide, to 11 months in a study with paclitaxel/carboplatin. The median survival was 11-15 months. The outpatient weekly paclitaxel/carboplatin regimen, with paclitaxel at a dose of 90 mg/m(2) and carboplatin at area under the curve 4, seems similarly effective and is better tolerated. Dose-dense weekly paclitaxel/carboplatin is an effective and well-tolerated therapy for platinum-sensitive, as well as platinum-resistant tumors. Responses to therapy are observed within 8 weeks in the majority of the patients. Whether a weekly regimen indeed is more effective than 3-weekly paclitaxel/carboplatin needs to be answered in a randomized study.
Estrogen-stimulated growth of the malignant human endometrium can be balanced by the differentiating properties of progesterone. To study the molecular basis behind this, gene expression profiling was performed using complementary DNA microarray analysis. In this study, the human endometrial cancer cell lines ECC-1 and PRAB-36 were used as models. The ECC-1 cell line, which expresses high levels of estrogen receptor alpha and is stimulated in growth by estrogens, was used to study estrogen regulation of gene expression. The Ishikawa sub-cell line PRAB-36, expressing both PRA and PRB, progesterone receptor isoforms, and inhibited in growth by progestagens, was used to study progesterone regulation of gene expression. Using these two well-differentiated human endometrial cancer cell lines, 148 estrogen- and 148 progesterone-regulated genes were identified. After functional classification, the estrogen- and progesterone-regulated genes could be categorized in different biologically relevant groups. Within the group of "cell growth and/or maintenance," 81 genes were clustered, from which a number of genes could be involved in arranging the cross talk that exists between estrogen and progesterone signaling. On the basis of analysis of the current findings, it is hypothesized that cross talk between estrogen and progestagen signaling does not occur by counterregulation of single genes, but rather at the level of differential regulation of different genes within the same functional families.
The pleomorphic adenoma of the vulva is an extremely scarce diagnosis. This form of neoplasm is more frequently observed in other topographic sites of the human body. Treatment modalities largely derive from experiences with the pleomorphic adenoma located in these other sites. As a result of similarity with other tumors and scarcity of the neoplasm, the diagnosis of pleomorphic adenoma of the vulva is easily missed in daily routine practice. Recurrences of this neoplasm are frequently observed with an estimated incidence of malignant transformation of 25%. Addressing this previously mentioned issue, an extensive surgical excision and long-term follow-up is advocated. This report is illustrated by the case of a 66-year-old woman who was admitted to our hospital with a pleomorphic adenoma of the vulva, diagnosed by pathologic assessments following surgical excision. As a result of the rarity of this diagnosis, characteristics and treatment of extravulvar in addition to vulvar localizations of the pleomorphic adenoma are reviewed.
In advanced endometrial cancer, the importance of peritoneal cytology and optimal surgical cytoreduction remain subjects of discussion. We evaluated our clinical experience of 67 patients with FIGO stage III and IV endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis on stage IIIA disease based on positive cytology only and optimal cytoreduction. Lymphadenectomy was not routinely performed and peritoneal cytology was examined in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom had positive cytology only. Analysis showed that incidence of recurrence and survival rates of patients with stage IIIA disease based on positive cytology only were comparable with stage IIIA disease based on other factors. In 50 patients, it was possible to remove all macroscopic tumor, whereas in 17 patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer patients, positive peritoneal cytology seems an important prognostic factor in stage IIIA disease if lymph node status is unknown. Survival is improved if optimal surgical cytoreduction is achievable.