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PubMed1997

Patient dropout in an assisted reproductive technology program: implications for pregnancy rates.

OBJECTIVE: To study patient dropout and its impact on crude and cumulative pregnancy rates (PRs) after assisted reproductive technology (ART). DESIGN: Retrospective cohort study. SETTING: University hospital-based tertiary care fertility clinic. PATIENT(S): Two hundred two couples applying for their first ART treatment cycle. MAIN OUTCOME MEASURE(S): Drop-out rate and PR per cycle, cumulative drop-out rate and cumulative PR. RESULT(S): After three treatment cycles, the cumulative drop-out rate was 126 of 202 (62.4%); 13.9% (n = 28) was due to active censoring. Active censoring was shown to flatter cumulative PRs by life-table analysis. CONCLUSION: Dropout from ART is high, even when ART costs are covered by health cost insurance. Life-table analysis overestimates cumulative PRs in ART.

Cohort Studies↗
PubMed1998

The performance of subcutaneously injected Fertinex when used as the sole gonadotropin for in vitro fertilization stimulation.

OBJECTIVE: To assess the performance of Fertinex (urofollitropin; Serono Laboratories, Norwell, MA) in stimulating the development of multiple follicles and initiating subsequent pregnancy in patients undergoing controlled ovarian hyperstimulation (COH) for IVF. DESIGN: Prospective observational study. SETTING: Private assisted reproductive technology (ART) center. PATIENT(S): Ninety-three women who underwent an IVF cycle of COH in which Fertinex was used as the sole gonadotropin. INTERVENTION(S): The COH protocol included Fertinex with leuprolide acetate down-regulation in the late luteal phase or the early follicular phase. Embryo transfer was performed after 3 days of culture. MAIN OUTCOME MEASURE(S): Stimulation parameters, embryologic data, and pregnancy rates (PRs). RESULT(S): Ninety-three patients underwent 97 cycles of COH, with a cancellation rate of 13.4%. The clinical PR was 42% per initiation, 49% per retrieval, and 51% per transfer. Shorter stimulation periods, lower estradiol levels either per follicle punctured or per oocyte retrieved, and slower embryo development were observed. Patients responded to Fertinex in three distinct stimulation patterns: escalating response with a peak estradiol level of < or =3,000 pg/mL, escalating response with a peak estradiol level of >3,000 pg/mL, or escalating response characterized by a drop in the estradiol level or a plateau before hCG administration. All three responses had similar PRs. CONCLUSION(S): Fertinex can be used successfully as the sole gonadotropin for COH in ART without compromising high PRs. Traditional estradiol response curves or cancellation criteria may not apply when Fertinex is used as the sole gonadotropin for COH in ART.

Adult↗
PubMed1999

Oocyte morphology correlates with embryo quality and pregnancy rate after intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the relation of oocyte morphology with embryo quality and pregnancy rates (PRs) after intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective study of patients undergoing ICSI. SETTING: University Hospital IVF Center. PATIENT(S): Sixty-eight patients who underwent ICSI and had transfer of good-quality embryos (grade 3), 60 patients with transfer of both good- and poor-quality embryos (grade 3 and grade 2), and 18 patients with transfer of poor-quality embryos (grade 2). INTERVENTION(S): Comparison of the outcome of ICSI in the three groups of patients and the relation of oocyte morphology to embryo quality. MAIN OUTCOME MEASURE(S): Oocyte morphology and embryo quality (grade). Fertilization, cleavage, and pregnancy rates. Serum E2 on the day of hCG administration. RESULT(S): Oocytes with poor morphology (dark cytoplasm; many vacuoles or fragments in cytoplasm) led to poor-quality embryos and consequently to lower PRs (5.5% versus 29.4%). Serum E2 on the day of hCG administration was significantly higher in the group with good-quality embryos compared with that with poor-quality embryos (2,047 +/- 135.7 versus 1,651 +/- 164.8 pg/mL, respectively). CONCLUSION(S): Serum E2 on the day of hCG administration is a marker of embryo quality. Oocyte morphology correlates well with embryo quality and PRs after ICSI.

Adult↗
PubMed2000

Minimal stimulation IVF using clomiphene citrate and oral contraceptive pill pretreatment for LH suppression.

OBJECTIVE: To determine if oral contraceptive pill (OC) pre-treatment prior to minimal stimulation IVF using clomiphene citrate (CC) would make the procedure easier to perform by preventing the LH surge and result in pregnancy rates (PRs) comparable to stimulated IVF. DESIGN: Prospective cohort study. SETTING: Private tertiary infertility center. PATIENT(S): Thirty-two women with tubal or pelvic adhesive disease as the cause of their infertility, ovulatory cycles, under the age of 40, and no male factor. INTERVENTION(S): Two-month ovarian-hypothalamic-pituitary axis suppression with OC followed by CC 100 mg on day 3 of the cycle for 8 days, hCG administration midcycle, follicle aspiration, IVF, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocytes retrieved, serum LH and estradiol levels, maturity of oocytes, fertilization rates, embryo number and quality, and PRs. RESULT(S): Thirty-six patients completed 71 stimulation cycles and 64 follicle aspirations. No LH surges occurred with a mean mature oocytes retrieved of 3.2, 90% fertilization rate, and mean 2.5 embryos transferred. Twenty-one of the 64 cycles resulted in a clinical pregnancy (32.8% PR per retrieval) with 2 other biochemical pregnancies and 3 twin gestations. This was not significantly different from the matched cohort stimulated IVF. CONCLUSION(S): Minimal stimulation IVF is a simple, low-cost, and low-risk alternative to stimulated IVF with comparable PRs.

Adult↗
PubMed2003

Abnormal sharp transients on electroencephalograms in preterm infants with periventricular leukomalacia.

OBJECTIVE: To determine the clinical significance of abnormal sharp transients other than positive rolandic sharp waves (PRS), electroencephalograms were used for the diagnosis of periventricular leukomalacia (PVL). STUDY DESIGN: We evaluated 126 electroencephalograms from 93 preterm infants; 31 infants had PVL, and 62 were control infants. Frontal sharp waves (FS) were defined as sharp transients of positive polarity with an amplitude >100 microV. Occipital sharp waves (OS) were defined as those of negative polarity with an amplitude >150 microV. FS, OS, or PRS were considered to be present when there were >0.1 per minute. RESULTS: The number of FS per minute was significantly higher in the PVL group than in the control group during days 0 to 4 and 5 to 7. The number of OS per minute was also significantly higher in the PVL group than in the control group during days 0 to 4, 5 to 7, and 8 to 14. The sensitivity of FS or OS was relatively high but that of PRS was low. The presence of two or more types of abnormal sharp transients was correlated with a poor outcome. CONCLUSIONS: FS or OS may be useful for predicting which infant will have PVL.

Cerebral Palsy↗
PubMedDate not supplied

Progesterone action and responses in the alphaERKO mouse.

Ovarian steroids have important inter-related roles in many systems and processes required for mammalian reproduction. The female reproductive tract, ovaries, and mammary glands are all targets for both estrogen and progesterone. In addition, the actions of these hormones are intertwined in that, for example, progesterone attenuates the proliferative effect of estrogen in the uterus, whereas estrogen also induces the progesterone receptor (PR) mRNA and protein, thus enhancing progesterone actions. The generation of mice that lacks the progesterone receptor (PRKO) or the estrogen receptoralpha (alphaERKO) has provided numerous insights into the interacting roles of these hormones. The mammary glands of the PRKO mice develop with full epithelial ducts that lack side branching and lobular alveolar structures, whereas the alphaERKO mice develop only an epithelial rudiment. This indicates that estrogen is important for ductal morphogenesis, whereas progesterone is required for ductal branching and alveolar development. Both the alphaERKO and PRKO mice are also anovulatory, but exhibit different causal pathologies. The alphaERKO ovary seems to possess follicles up to the preantral stage and shows a polycystic phenotype as a result of chronic hyperstimulation by LH. The PRKO follicles seem to develop to an ovulatory stage, but are unable to rupture, indicating a role for progesterone in ovulation. The uteri of these two strains seem to develop normally; however, the function and hormone responses are abnormal in each. Because estrogen is known to induce PRs in the uterus, the progesterone responsiveness of the alphaERKO uterus was characterized. PR mRNA was detected but was not up-regulated by estrogen in the alphaERKO tissue. PRs are present in the alphaERKO tissue at 60% of the level in wild-type tissue and show a similar amount of A and B isoforms when measured by R5020 binding and detected by Western blotting. The PRs were able to mediate induction of two progesterone-responsive uterine genes: calcitonin and amphiregulin. The alphaERKO uterine tissue was also able to undergo a decidual reaction in response to hormonal and intraluminal treatments to mimic implantation; however, unlike normal wild-type uteri, this response was estrogen independent in the alphaERKO uterine tissue.

Animals↗
PubMed1999

GABA(A), D1, and D5, but not progestin receptor, antagonist and anti-sense oligonucleotide infusions to the ventral tegmental area of cycling rats and hamsters attenuate lordosis.

In hamsters, progesterone (P) in the hypothalamus and ventral tegmental area (VTA) is necessary for receptivity; in rats, hypothalamic P induces receptivity and midbrain P further enhances it. How P exerts its effects in the VTA on lordosis is of interest because few estrogen-induced P receptors (PRs) have been identified there. Sexual receptivity of rats and hamsters is enhanced when P's actions in the VTA are restricted to the membrane and when the gamma-aminobutyric acid (GABA)A agonist, muscimol, is infused into the VTA, but attenuated with infusions of the GABA(A) antagonist, bicuculline. The dopamine (DA) agonist. SKF38393, rapidly enhances receptivity when infused intravenously; this effect can be blocked by both DA receptor (DR) and PR antagonists. This study investigated the importance of PRs, glutamic acid decarboxylase (GAD), the enzyme responsible for GABA production, GABA(A) receptors (GBRs), and DRs in the VTA of cycling rats and hamsters for the expression of lordosis. Proestrous and diestrous animals implanted with bilateral VTA cannulae were pre-tested for receptivity, infused with either an antagonist (RU38486 (20 microg), bicuculline (100 ng), SCH23390 (100 ng)), anti-sense oligonucleotide (against PR (250 ng), GAD (500 ng), D1 (500 ng), D5 (250 ng)), or control infusions to each cannulae and re-tested. Vehicle and scrambled oligonucleotides were infused as controls and elicited similar effects. Antagonists of GBRs and DRs significantly reduced lordosis on post-tests compared to the PR antagonist and control conditions in rats and hamsters. Lordosis was significantly reduced, compared to controls, only by anti-sense oligonucleotides for GAD and D1- and D5-DR subtypes. These data suggest that in the VTA GABAergic and dopaminergic neurons may be more important in the mediation of sexual receptivity than neurons containing intracellular PRs.

Animals↗
PubMed2002

Glycosylphosphatidylinositol-anchored surface molecules of Trypanosoma congolense insect forms are developmentally regulated in the tsetse fly.

Procyclic culture forms of Trypanosoma congolense have been shown to express a glutamic acid/alanine-rich protein (GARP) on their surface. By labelling T. congolense procyclic culture forms with glycosylphosphatidylinositol (GPI) precursors, we show that GARP is bound to the membrane by a GPI anchor and demonstrate the presence of two additional GPI-anchored surface molecules of 24-34 and 58 kDa that are abundantly expressed. The 24-34 kDa molecule, which is recognised by monoclonal antibodies that bind to the surface of living trypanosomes, is resistant to proteolysis, suggesting that it consists (predominantly) of non-proteinaceous material. We have therefore named it protease-resistant surface molecule (PRS). In common with the EP and GPEET procyclins of Trypanosoma brucei, the relative expression of the T. congolense GPI-anchored molecules changes during parasite development in the tsetse fly. PRS is abundantly expressed by procyclic trypanosomes in the midgut shortly after infection, but is downregulated in established midgut forms and completely absent from the epimastigote form in the proboscis. In contrast, GARP is downregulated in parasites in the tsetse fly midgut, but upregulated in the epimastigote form. Unexpectedly, 14 days post-infection, procyclic forms frequently are negative for both PRS and GARP, suggesting that they might be expressing another stage-specific surface antigen at this point in the life cycle.

Animals↗
PubMed1998

Molecular cloning of a human cDNA for the 41-kDa phosphoribosylpyrophosphate synthetase-associated protein.

A human cDNA encoding 41-kDa phosphoribosylpyrophosphate (PRPP) synthetase (PRS)-associated protein (PAP41) was cloned from two expressed sequence tag (EST) clones having the nucleotide similarity of 61.5 and 70.0% to human PAP39 cDNA. The predicted open reading frame of 1107 base pairs (bp) has the nucleotide identity of 91.8% to rat PAP41 and encodes a protein of 369 amino acids with a calculated molecular weight (MW) of 40,925. The deduced amino acid sequence exhibits the 98.9% identity to rat PAP41 and 72.2, 50.6, and 50.0% identity with human PAP39, PRS I, and PRS II, respectively, but lacks the PRPP binding site. Southern blot analysis suggested that the PAP41 gene exists as a single copy in the human genome. The single PAP41 mRNA of about 2.1 kb was shown to be present in five human cell lines by Northern blot analysis.

Adenocarcinoma↗
PubMed2003

Are poor readers semantically challenged? An event-related brain potential assessment.

This study explores visual event-related potentials components in a group of poor readers (PRs) and control children who carried out figure and word categorization tasks. In both tasks, every child had to categorize between animal and non-animal stimuli in an odd-ball GO-GO paradigm. During the word categorization task, PRs presented longer reaction times, a poorer performance, longer and larger P2 amplitudes, and smaller amplitudes and longer P300 latencies than controls. There were no differences in the N400 component between groups. These results suggest that semantic processing underachievement in PRs may not be a semantic deficit per se, but the late reflection of an early word codification problem, deficient use of attentional resources and lack of target identification during reading.

Analysis of Variance↗
PubMed2002

Comparison of the ICSI outcome of ejaculated sperm with normal, abnormal parameters and testicular sperm.

OBJECTIVE(S): To compare fertilization rates, quality of embryos, pregnancy rates (PRs) and outcome of pregnancies in intracytoplasmic sperm injection (ICSI) using sperm from ejaculates of normal and abnormal semen and testicular sperm of non-obstructive azoospermia. STUDY DESIGN: Four hundred fifty-four patients who underwent 454 ICSI cycles were evaluated retrospectively. Patients were divided into three groups according to the quality and source of sperm. Patients in group 1 underwent 133 cycles of ICSI using ejaculated normal semen, group 2 underwent 235 cycles using ejaculated abnormal semen, and group 3 underwent 86 cycles using testicular sperm. RESULTS: The parameters were compared among the groups with respect to cycles induced by long (n = 160) and short (n = 294) protocol. In group 3, the fertilization and PRs were significantly lower than in all other groups (51.3 and 10.6% in the long protocol cycles, 53.3 and 5.1% in the short protocol cycles, respectively). There was no significant difference in the outcome of pregnancies in respect to abortion rates between different groups. CONCLUSION(S): The fertilizing ability of sperm in ICSI is highest with ejaculated sperm and lowest with sperm extracted by testicular biopsy. Also, the clinical PRs are significantly lower in ICSI with sperm from testicular biopsy. However, the outcomes of pregnancies are not affected by using surgically retrieved sperm from ejaculated semen.

Adult↗
PubMed1999

Cyclophosphamide or ifosfamide in patients with advanced and/or recurrent endometrial carcinoma: a randomized phase II study of the EORTC Gynecological Cancer Cooperative Group.

UNLABELLED: Currently, available chemotherapy regimens for patients with advanced or recurrent endometrial cancer are generally not curative. Thus, there is a need to identify more active single agents in this disease. In this study patients pre-treated and not pre-treated with first line combination chemotherapy were entered into a randomized phase II study of either cyclophosphamide (CYCLO) or Ifosfamide (IFOS). PATIENTS AND METHOD: Sixty one eligible patients with recurrent or metastatic histologically proven, adenocarcinoma of the uterine corpus entered the study. The median age at entry was 62 (range 40-74) years. Twenty patients (33%) had prior hormonal treatment and 31 (51%) prior chemotherapy. CYCLO was given at a dose of 1200 mg/m2 and IFOS at a dose of 5 g/m2. Both drugs were administered i.v. over 24 hours on day one every three weeks. Adequate pre- and post hydration as well as use of Mesna in the Ifosfamide arm were mandatory. RESULTS: A median of two treatment cycles (range 1-12) per patient were given. In the chemotherapy-naive patients, in the CYCLO arm two PRs (RR 14%, C.I. 2-43%) were seen and in the IFOS arm two CRs, two PRs, (RR 25%, C.I. 7-52%) were observed. No responses were seen in pre-treated patients. The duration of responses were: 15+, 7+ months for the CRs, 15+ and 5 months for PRs in IFOS arm and 67+, 4 months in CYCLO arm. The hematological toxicity was dose-limiting and similar in both treatment arms. No serious non hematological toxicities were reported, but a transient increase of the creatinine blood level was seen in two IFOS patients (6%). CONCLUSION: Ifosfamide is an active drug in the treatment of chemotherapy-naive patients with advanced endometrial cancer and its application in currently used (combination) regimens should be considered.

Adenocarcinoma↗
PubMed1999

Postradiation sarcomas: 20 cases and a literature review.

PURPOSE: To analyze 20 cases of postradiation sarcoma (PRS) to determine dose levels at which this condition developed, the pathology of the initial and postradiation tumors, latency period, and outcome; and to review the literature and propose modified criteria for diagnosis. METHODS AND MATERIALS: Patient records were reviewed. Previous radiation fields and isodose charts were reconstructed to determine the dose received in the tissue in which the PRS subsequently developed. RESULTS: There were 16 female patients and 4 male patients. Mean age at the time of initial radiotherapy was 28 years. Mean latency was 14 years, with no difference in latency between the adult and pediatric group (t = 0.45, p = 0.37), but shorter latency in the retinoblastoma than in the nonretinoblastoma patients (t = 3.18, p = 0.003). The outcome was poor; 2 patients were alive and disease-free at 2 and 5 years. The 18 patients who died as a result of PRS had a median survival of 1 year. CONCLUSION: PRSs are rare. Unnecessary radiation must be avoided. Cases should be reported with full details so that risk factors can be ascertained. PRSs usually arise in moderate to higher dose areas. Diagnostic criteria should allow soft tissue tumors and short latency.

Adult↗
PubMed2001

Neural correlates of auditory stream segregation in primary auditory cortex of the awake monkey.

An important feature of auditory scene analysis is the perceptual organization of sequential sound components, or 'auditory stream segregation'. Auditory stream segregation can be demonstrated by presenting a sequence of high and low frequency tones in an alternating pattern, ABAB. When the tone presentation rate (PR) is slow or the frequency separation (DeltaF) between the tones is small (<10%), a connected alternating sequence ABAB is perceived. When the PR is fast or the DeltaF is large, however, the alternating sequence perceptually splits into two parallel auditory streams, one composed of interrupted 'A' tones, and the other of interrupted 'B' tones. The neurophysiological basis of this perceptual phenomenon is unknown. Neural correlates of auditory stream segregation were examined in A1 of the awake monkey using neuronal ensemble techniques (multiunit activity and current source density). Responses evoked by alternating frequency sequences of tones, ABAB, were studied as a function of PR (5, 10, 20 and 40 Hz). 'A' tones corresponded to the best frequency (BF) of the cortical site, while 'B' tones were situated away from the BF by an amount DeltaF. At slow PRs, 'A' and 'B' tones evoked responses that generated an overall pattern of activity at the stimulus PR. In contrast, at fast PRs, 'B' tone responses were differentially suppressed, resulting in a pattern of activity consisting predominantly of 'A' tone responses at half the PR. The magnitude of 'B' tone response suppression increased with DeltaF. Differential suppression of BF and non-BF tone responses at high PRs can be explained by physiological principles of forward masking. The effect of DeltaF is explained by the hypothesis that responses to tones distant from the BF are more susceptible to suppression by BF tones than responses to tones near the BF. These results parallel human psychoacoustics of auditory stream segregation and suggest a cortical basis for the perceptual phenomenon.

Acoustic Stimulation↗
PubMed2000

The antiovulatory potential of progesterone antagonists correlates with a down-regulation of progesterone receptors in the hypothalamus, pituitary and ovaries.

These studies analyze the regulation of progesterone receptors (PRs) in central and peripheral tissues with the aim of further understanding mechanistically the inhibition of ovulation by progesterone antagonists (PA). Therefore, it was of interest to investigate the influence of the progesterone receptor antagonist, Onapristone (ON), on PRs in the ovary, pituitary (PT), and hypothalamus (HYP), since ON effectively inhibits ovulation in rats. For this study PMSG/hCG-primed immature and adult female rats were treated with ON. Immunohistochemistry was used for the detection of PRs. Progesterone (P4) and estradiol (E2) levels were determined by RIA. PR expression in the ovaries of immature rats was not detectable until after hCG administration. In these animals, ON caused a reduction in the staining intensity of PR in the tertiary follicles at the time when the preovulatory P4-surge was inhibited (6 h post hCG). Adult rats treated for 15 days with ON showed a decreased PR expression in PT and HYP. At this time (proestrus, 7 p.m.) the P4 and E2 levels are significantly lowered. These results suggest that after treatment with ON the expression of PR is reduced in the ovary, PT and HYP. The regulation of PR in the ovary seems to be less dependent on estrogens than on LH. Thus, it is conceivable that the reduced PR expression after ON treatment may be a result of decreased LH sensitivity in the ovary. In the pituitary and hypothalamus, PR expression is stimulated by estrogens and progesterone, and therefore the fall in the P4 and E2 levels in ON-treated animals may be responsible for the reduced PR expression in PT and HYP, and may contribute to the antiovulatory effect of ON. We therefore conclude that the mechanism of the antiovulatory potency of progesterone antagonists is based on a reduced preovulatory P4-production and PR expression in the ovary and also on the down-regulation of PR in the anterior pituitary and hypothalamus.

Animals↗
PubMed1992

Long-term results of prosthetic and non-prosthetic reconstruction for obstructive aorto-iliac disease.

In this retrospective study the results of 518 prosthetic aorto-iliac reconstructions (PRS) and of 229 thrombo-endarterectomies (TEA) were evaluated, with inclusion of follow-up results up to 20 years after surgery. Patients in the PRS group had presented with more severe ischaemic symptoms and more extensive arterio-sclerotic obstructions than the patients in the TEA group. Results in the TEA group were further analysed according to the extension of arterio-sclerotic disease: there were 93 patients with obstructions limited to the aorta or common iliac arteries and 136 patients with more extensive lesions. Patients with limited obstructions were younger, proportionally more often female, had fewer risk factors, and presented with less severe ischaemic symptoms than patients with more extensive obstructions. Operative mortality and early technical and functional results were similar in the PRS and TEA group, but long-term survival and patency rates were significantly better, and the need for late, additional operations was less in the TEA group. Late functional success rates were similar in both groups. The differences in outcome were explained by patient selection. Within the TEA group significantly superior results regarding survival, patency, need for late, additional surgery, and functional success were observed in the subset of patients with obstructions limited to the aorta or common iliac arteries. Considering these results and the risks inherent in a prosthetic reconstruction, such as prosthetic infection and the chance for false aneurysms, we advocate the use of an aorto-iliac TEA in properly selected patients.

Aorta, Abdominal↗
PubMed2000

Biweekly irinotecan or raltitrexed plus 6S-leucovorin and bolus 5-fluorouracil in advanced colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase II-III randomized trial.

PURPOSE: The aim of this randomised trial was to evaluate the activity and toxicity of a biweekly regimen including 6S-leucovorin-modulated 5-fluorouracil (LFA-5-FU), combined with either irinotecan (CPT-11 + LFA 5-FU) or raltitrexed (Tomudex) (TOM + LFA-5-FU), in advanced colorectal cancer patients, and to make a preliminary comparison of both these experimental regimens with a biweekly administration of LFA-5-FU modulated by methotrexate (MTX + LFA-5-FU). PATIENTS AND METHODS: One hundred fifty-nine patients with advanced colorectal carcinoma previously untreated for the metastatic disease (34 of them previously exposed to adjuvant 5-FU) were randomly allocated to receive: CPT-11, 200 mg/m2 i.v. on day 1, followed on day 2 by LFA, 250 mg/m2 i.v. infusion and 5-FU, 850 mg/m2 s i.v. bolus (arm A); TOM, 3 mg/m2 i.v. on day 1, followed on day 2 by LFA, 250 mg/m2 i.v. infusion and 5-FU, 1050 mg/m2 i.v. bolus (arm B); or MTX, 750 mg/m2 i.v. on day 1, followed on day 2 by LFA, 250 mg/m2 i.v. infusion and 5-FU, 800 mg/m2 i.v. bolus (arm C). Courses were repeated every two weeks in all arms of the trial. Response rate (RR) was evaluated after every four courses. The sample size was defined to have an 80% power to detect a 35% RR for each experimental treatment, and to show a difference of at least 4% in RR with the standard treatment if the true difference is 15% or more. RESULTS: The RRs were: 34% (95% confidence interval (95%, CI): 21%-48%) in arm A, including 3 complete responses (CRs) and 15 partial responses (PRs), 24% (95% CI: 14%-38%) in arm B, including 2 CRs and 11 PRs, and 24% (95% CI: 14%-38%), with 2 CRs and 11 PRs, in arm C. After a median follow-up time of 62 (range 18-108) weeks, the median time to progression was 38, 25, and 27 weeks for arm A, B, and C, respectively. With 94 patients still alive, the one-year probability of survival was 61%, 54%, and 59%, respectively. WHO grade 3 or 4 neutropenia and diarrhoea affected 46% and 16%, respectively, of patients treated with CPT-11 + LFA 5-FU. Median relative dose intensity over eight cycles (DI8) was 78% for CPT-11 and 82% for 5-FU. Severe toxicities of TOM + LFA-5-FU were neutropenia (16%) and diarrhoea (16%), but median relative DI8 was 93% for TOM, and 82% for 5-FU. CONCLUSIONS: CPT-11 + LFA-5-FU compares favorably in term of activity and toxicity with other combination regimens including CPT-11 and continuous infusional 5-FU. The hypothesis of a RR 15% higher than the MTX + LFA-5-FU treatment can not be ruled out after this interim analysis. The TOM + LFA 5-FU regimen showed a RR and a toxicity profile very close to the MTX + LFA 5-FU combination, and dose not deserve further evaluation in advanced colorectal cancer patients.

Adult↗
PubMed2000

The effects of E2 supplementation from the early proliferative phase to the late secretory phase of the endometrium in hMG-stimulated IVF-ET.

PURPOSE: Our purpose was to determine if pregnancy rates (PRs) for hMG (human menopausal gonadotropin)-stimulated IVF-ET (in vitro fertilization--embryo transfer) can be increased by estradiol (E2) supplementation from the early proliferative phase to the late secretory phase of the endometrium. METHOD: Eighty-one infertile women with pure tubal factor were randomized into two groups. One group received no E2 supplementation (control group) and the other received oral E2 supplementation (2 mg two times daily) from the early proliferative phase starting on the third day of the menstrual cycle to the late secretory phase of the endometrium, with hMG stimulation for ovulation induction starting on the sixth day of the menstrual cycle. RESULTS: In 85 cycles, at least one embryo was transferred. Compared with the control group (n = 27 cycles), the E2 supplementation group (n = 58 cycles) had a significantly higher PR (control, 25.9%, versus E2 supplementation, 48.3%) and IR per ET (control, 10%, versus E2 supplementation, 26%), but FRs per retrieved oocytes were not statistically different between the two groups (control, 74%, versus E2 supplementation group, 73%). Four spontaneous abortions occurred in the E2 supplementation group, and one case in the control group. Ectopic pregnancy occurred in one case in the control group. CONCLUSIONS: Clinical PRs and IRs in the E2 supplementation group were significantly higher than in the control group, while FRs in the control group did not differ statistically from the E2 supplementation group. This suggests that E2 supplementation from the early proliferative phase to the late secretory phase of the endometrium in hMG-stimulated IVF-ET increases the receptivity of the endometrium for transferred embryos and clinical PRs.

Adult↗