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Biomedical subjects

S Alvarez

Publications and source records attributed to S Alvarez.

At least 55 records · Page 3Linked to original sources
PubMed1998

The use of a GnRH antagonist (Cetrorelix) in a single dose protocol in IVF-embryo transfer: a dose finding study of 3 versus 2 mg.

New gonadotrophin-releasing hormone (GnRH) antagonists, which allow suppression of luteinizing hormone (LH) surges, have recently become available. We compared in this study the results of a single administration of 3 versus 2 mg Cetrorelix in 65 patients undergoing ovarian stimulation and in-vitro fertilization (IVF). The GnRH antagonist (Cetrorelix) was non-randomly administered at a dose of 3 mg (34 patients) or 2 mg (32 patients) on day 8 of the stimulation cycle. In the case of slow follicular development, the injection was delayed until oestradiol reached 400 pg/ml. No difference was observed in the decrease in LH and in oestradiol secretion between the 3 and the 2 mg groups, but the LH secretion was suppressed for a shorter time in the 2 mg group. No LH surge was observed in the 3 mg group, while one surge (3%) and one significant rise in LH were observed in the 2 mg group. No significant difference was observed in IVF results in the two groups of patients. This study demonstrates that a single injection of 3 or 2 mg successfully prevents LH surges for at least 3 days in all the patients treated. The LH rises in the 2 mg group led us to choose the 3 mg dose as a safer dose in our single administration protocol.

Adult↗
PubMed1998

Cryopreservation in human assisted reproduction is now routine for embryos but remains a research procedure for oocytes.

Human embryo cryopreservation represents an indispensable extension of in-vitro fertilization (IVF) programmes as long as they are based upon the recovery of a large number of oocytes. The most widely used procedures include the cryopreservation of human zygotes or embryos in early cleavage, using 1,2-propanediol and sucrose as cryoprotectants. Our results over a 10 year period (1986-1995) on 5032 thawed cycles involving 14 222 stored embryos make it possible to appraise the results and the contribution of embryo freezing to assisted reproduction. Embryos survived the freeze-thaw process in 73% of cases leading to 4590 transfers of 2.2 embryos (91% of thawed cycles). The clinical pregnancy rate per transfer was 16%, the live birth rate 12%, and the rate of babies born alive per transferred embryo was 6%. Embryo freezing monitored 10 years later produced an average of 8% of additional births. By then, 86% of stored embryos had been thawed for transfer to patients. Destruction or donation were required for only 8% of all frozen embryos and there was no news from the parental couple in relation to almost 6% of embryos. The fate of the vast majority of embryos was decided during the first 5 years of storage. Blastocyst cryopreservation is making new strides, thanks to co-culture systems and embryo selection. Micromanipulation procedures seem to have little impact on the outcome of embryo freezing. Human oocyte freezing is again clinically applied. Indeed, much of the concern about injuries to the oocyte structures through the freeze-thaw process do not seem to be justified, and the problems with frozen-thawed oocyte fertilization has been overcome using intracytoplasmic sperm injection (ICSI). As long as oocyte in-vitro maturation is not well controlled, better results will probably be obtained with mature oocyte cryopreservation. Emerging methods include the freezing of immature oocytes, follicles and ovarian tissue.

Cryopreservation↗
PubMed1997

Growth inhibition of human breast cancer cells by 1,25-dihydroxyvitamin D3 is accompanied by induction of apolipoprotein D expression.

We have analyzed the effect of 1,25-dihydroxyvitamin D3 on the expression of the gene encoding apolipoprotein D (apoD), a protein component of the human plasma lipid transport system that is overproduced by a specific subset of breast carcinomas. Northern blot analysis revealed that 1,25-dihydroxyvitamin D3 strongly up-regulated apoD mRNA levels in T-47D human breast cancer cells in a time- and dose-dependent manner. The potency of this vitamin as an inducer of apoD expression was stronger than the effect observed for such steroid hormones as androgens and progesterone, described previously as hormonal up-regulators of apoD expression in these cells. A time course study demonstrated that the induction of apoD mRNA reached a level of 5-fold over the untreated cells after 48 h of incubation in the presence of 10(-7) M 1,25-dihydroxyvitamin D3. A dose-response analysis showed that a 10(-6) M concentration of this vitamin consistently induced a maximal accumulation of 7-fold over the control cells. Similar up-regulatory effects on the apoD gene expression were obtained by treatment of T-47D cells with 1,25-dihydroxyvitamin D3 analogues, including MC 903, which is relatively devoid of hypercalcemic side effects in clinical applications. Western blot analysis revealed that the inductive effect of 1,25-dihydroxyvitamin D3 was also reflected at the protein level as an increase of immunoreactive protein in the conditioned media of vitamin-treated cells. This increased expression of apoD was accompanied by an inhibition of cell growth and morphological changes in T-47D cells. By contrast, we did not detect any inductive effect of 1,25-dihydroxyvitamin D3 on apoD gene expression in MDA-MB-231 cells, which are refractory to the growth-inhibitory effects of this compound. On the basis of these results, we propose 1,25-dihydroxyvitamin D3 as an important regulator of the expression of the apoD gene in breast carcinomas. We also suggest that apoD may be of interest as a biochemical marker of the action of 1,25-dihydroxyvitamin D3 derivatives in current studies using these compounds as inhibitors of breast cancer cell growth or as chemotherapeutic agents in the prevention of breast cancer.

Antineoplastic Agents↗
PubMed1997

Copper deficiency with pancytopenia due to enteral nutrition through jejunostomy.

Copper deficiency is a rare complication of enteral nutrition. Haematologic abnormalities such as neutropenia and anaemia, but not pancytopenia, have been described associated to copper deficiency. We report the case of a patient requiring long term enteral nutrition through jejunostomy who developed copper deficiency and pancytopenia. In 1991, a 47-year-old woman was admitted with severe gastroesophageal mucositis after an attempted suicide with caustic intake. Enteral nutrition with a commercial, polymeric, fiber-containing formula was started. Twenty-eight months later, the patient developed anemia and neutropenia that did not respond to combined iron and parenteral vitamin B(12) supplementation. In 1996 the patient showed pancytopenia and low serum levels of copper and ceruloplasmin. Pancytopenia improved after copper supplementation. Possible mechanism causing copper deficiency and pancytopenia are discussed. We conclude that assessment of copper status is advisable in patients receiving long-term enteral nutrition by jejunostomy.

Journal Article↗
PubMed1997

p53 expression is of independent predictive value in lymph node-negative breast carcinoma.

The aim of this study was to evaluate p53 expression, determined by immunohistochemistry, in 151 infiltrating ductal breast carcinomas with negative axillary lymph nodes, and to determine whether p53 can be considered as an independent prognostic value for overall and disease-free survival. A monoclonal antibody (DO-7) that reacts with an epitope on the N terminal portion of the human protein p53 was used to detect p53 in paraffin-embedded sections, utilising a standard avidin-biotin-peroxidase complex (ABC) technique with a microwave oven antigen retrieval. Overexpression of p53 (more than 50% of stained cells) was found in 45 cases (30%). Forty-five cases were negative and occasionally or moderately stained cells were present in 61 cases. p53 protein overexpression was significantly associated with high histological grade and tumour necrosis, high MIB-1 value (MIB-1 > 30%) and negative oestrogen receptor status. Univariate analysis (log-rank) showed a shorter overall survival (P = 0.003) in patients with high tumour p53 positivity. This statistical significance was also seen on multivariate analysis (Cox's logistic regression, P = 0.004). p53 protein overexpression is an independent prognostic marker in node-negative breast carcinoma for overall survival and should be used with other prognostic factors.

Adult↗
PubMed1997

Antioxidant adaptive response in human blood mononuclear cells exposed to UVB.

Human blood mononuclear cells exposed to UVB radiation develop increased antioxidant enzyme activities. Catalase (5.50 +/- 0.65 pmol (mg protein)-1), CuZn-superoxide dismutase (16.7 +/- 2.1 pmol (mg protein)-1), Mn-superoxide dismutase (11.3 +/- 1.7 pmol (mg protein)-1), Se-dependent glutathione peroxidase (13.2 +/- 1.5 mU (mg protein)-1) and Se-independent glutathione peroxidase (3.30 +/- 0.52 mU (mg protein)-1) activities increase by 1.3-1.5-fold from the control activities after exposure to 0.3 W m-2 of 280-315 nm light for 15 min and a 3 h dark incubation period. DT-diaphorase activity (2.86 +/- 0.21 mumol DCPIP min-1 (mg protein)-1) increases threefold from the indicated control values. In contrast, cytochrome oxidase (0.36 +/- 0.04 min-1 (k') (mg protein)-1) and succinate dehydrogenase (3.06 +/- 0.25 mumol DCPIP min-1 (mg protein)-1) activities remain unchanged during the same irradiation and incubation period. The treatment of cells with cycloheximide prevents the response triggered by UVB exposure. These findings suggest that an inducible antioxidant defence mechanism operates on photo-oxidative stress and that both superoxide dismutase and DT-diaphorase may display a concerted antioxidant role.

Adaptation, Physiological↗
PubMed1997

Assisted reproductive technology and complex chromosomal rearrangements: the limits of ICSI.

Complex chromosomal rearrangements are very rare events in the human population. According to our knowledge on the consequences of simple reciprocal translocations for male fertility, translocations involving three or more chromosomes are thought to lead to severe reproductive impairments in terms of meiotic disturbance or chromosomal imbalance of gametes. We report the case of a 48 year old man whose sperm count revealed either oligozoospermia (<10(3) spermatozoa/ml) or azoospermia. He was referred to the laboratory for in-vitro fertilization after intracytoplasmic sperm injection. Cytogenetic investigations showed a complex chromosomal rearrangement involving firstly a translocation between the short arm of chromosome 7 and the long arm of chromosome 13 and secondly a translocation between the short arm of the same chromosome 13 and the short arm of chromosome 9. Diagnosis was ascertained by fluorescence in-situ hybridization and staining of the nucleolar organizer regions. Theoretical study of the translocated chromosomes predicted a 'chain' configuration of the hexavalent at the pachytene stage of meiosis. In all, 32 modes of segregation were considered and only one resulted either in a normal or a balanced gamete karyotype. Genetic counselling and choice of appropriate artificial reproduction technique are discussed.

Chromosomes, Human, Pair 13↗
PubMed1997

[Clinical use of recombinant gonadotropins (FSH, LH, hCG)].

The production of recombinant gonadotropins is independent of urine collection. They have a high specific activity and a better batch to batch consistency than urinary gonadotropins. In our IVF programme 62 normo-ovulatory patients less than 38 years old, with tubal or idiopathic infertility and normal sperm, were treated by r-FSH and randomized into four groups : with or without LHRH agonist, step-up or step-down stimulation. The overall results were higher in the agonist groups, but did not reveal any significant difference between step-up and step-down stimulation.

Adult↗
PubMed1997

Monoethylglycinexylidide formation measurement as a hepatic function test to assess severity of chronic liver disease.

OBJECTIVES: Monoethylglycinexylidide (MEGX) is the main lidocaine metabolite and its formation depends on liver microsomal activity. MEGX formation was studied in comparison with the histological score of chronic hepatitis and with the clinical score (Child-Pugh) of cirrhosis. Furthermore, we evaluated its ability to distinguish between the two liver diseases. METHODS: We studied 284 patients: 130 with chronic hepatitis (on the basis of the histological activity index, 45 had mild chronic hepatitis, 54 had moderate chronic hepatitis, and 31 had chronic hepatitis with cirrhosis) and 154 with cirrhosis (49 Child-Pugh's class A, 78 class B, and 27 class C). MEGX formation was evaluated 15, 30, and 60 min after lidocaine administration. RESULTS: MEGX formation showed a stepwise decline corresponding to worsened liver disease. MEGX values were related both to the histological score in chronic hepatitis and to the clinical score in cirrhosis. Significantly lower values were found in females < 50 yr of age than in males of the same age. The MEGX test showed great efficacy in discriminating between chronic hepatitis and cirrhosis compared with standard liver tests. CONCLUSIONS: Measurement of MEGX formation proved to be a safe test, allowing us to show that functional subgroups can be identified both in chronic hepatitis and in cirrhosis. Thus, this test could integrate both the histological grading of chronic hepatitis and the clinical staging of cirrhosis.

Adolescent↗
PubMed1996

Effects of ethanol and temperature on NMDA receptor function in different mouse genotypes.

The present study investigated whether temperature-related changes in NMDA receptor sensitivity to ethanol might play a role in mediating the effects of body temperature on behavioral sensitivity to ethanol or in determining genotypic differences in sensitivity to ethanol. We accomplished this by determining the effects of ethanol on three different mouse genotypes (C57, LS, and SS) on two types of NMDA receptor-mediated responses at 30 degrees and 35 degrees C: (i) extracellularly recorded synaptic potentials elicited in the CA1 region of the in vitro hippocampal slice preparation by stimulation of the Schaffer-commisural pathway in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor blocker, 6,7-dinitroquinoxaline-2,3-dione, and low magnesium concentration; and (ii) increase in [3H]MK-801 binding elicited by glutamate in telencephalic membrane preparations. Ethanol significantly decreased NMDA receptor-mediated excitatory postsynaptic potential (EPSP) amplitude and area in the three genotypes. In C57, the effect of ethanol on NMDA receptor-mediated EPSP amplitude and area was more pronounced at 30 degrees C, compared with that at 35 degrees C. In most cases, there was a good correlation between the effects of ethanol on EPSP amplitude and area. The order of sensitivity between the three genotypes was C57 = LS > SS at 35 degrees C and C57 > LS = SS at 30 degrees C. Similarly, ethanol significantly decreased glutamate-stimulated [3H]MK-801 binding in membrane fractions. The effect of ethanol was temperature-dependent, because ethanol produced more inhibition at 30 degrees C than at 35 degrees C in all genotypes. The effect of ethanol on MK-801 binding was concentration-dependent, and the sensitivity to 100 mM ethanol of the genotypes at 35 degrees C was LS > SS = C57, whereas it was SS > LS = C57 at 30 degrees C. Collectively, the results demonstrate that temperature is an important variable that can influence NMDA receptor sensitivity to ethanol measured via electrophysiological and binding techniques, and that temperature can influence relative sensitivity of NMDA receptors to ethanol between mouse genotypes. Furthermore, the findings indicate that temperature-induced changes in sensitivity of NMDA receptors to ethanol may play a role in mediating the effects of body temperature on behavioral sensitivity to ethanol in LS, but not C57 and SS mice.

Alcoholism↗
PubMed1996

Assessment of routine use of an anaerobic bottle in a three-component, high-volume blood culture system.

The relative value of routine anaerobic blood culture for recovery of organisms and identification of episodes of bloodstream infection was assessed in a three-component, high-volume blood culture system which employs aerobic and anaerobic bottles of BacT/Alert (Organon-Teknika, Durham, N.C.) and aerobic cultures of Isolator (Wampole Laboratories, Cranbury, N.J.). The results of 5,595 blood culture sets from patients with suspected bloodstream infection were analyzed. Compared with either the aerobic BacT/Alert bottle or aerobic culture of Isolator, the BacT/Alert anaerobic bottle recovered significantly fewer isolates (242 versus 294, P < 0.05; 242 versus 298, P < 0.05) but did not detect significantly fewer episodes of bloodstream infection (141 versus 157, P > 0.05; 141 versus 147, P > 0.05). The BacT/Alert anaerobic bottle recovered significantly more isolates of obligately anaerobic bacteria (16 versus 4, P < 0.05; 16 versus 0, P < 0.05) and detected significantly more episodes of bloodstream infection caused by obligately anaerobic bacteria (10 versus 3, P < 0.05; 10 versus 0, P < 0.05) than either the aerobic bottle of BacT/Alert or the aerobic culture of Isolator. The combination of the BacT/Alert anaerobic bottle and the aerobic culture of Isolator recovered as may isolates (374 versus 377) and detected as many episodes of bloodstream infection (194 versus 191) as the combination of the aerobic bottle of BacT/Alert and the aerobic culture of Isolator, and both of these combinations identified at least 8% more isolates and detected at least 3% more bloodstream infections than the combination of the BacT/Alert aerobic and anaerobic bottles. Further analysis of the data revealed that the utility of the BacT/Alert anaerobic bottle, especially when combined with the aerobic culture of Isolator, resulted from not only enhanced recovery of obligately anaerobic bacteria but also effective recovery of facultatively anaerobic bacteria. These results demonstrate the utility of the anaerobic BacT/Alert bottle for detecting bloodstream infection caused by either facultatively anaerobic bacteria or obligately anaerobic bacteria and support the routine inclusion of anaerobic blood culture in the three-component blood culture system used in our hospital.

Aerobiosis↗
PubMed1996

[Influence of infertility etiology and follicular stimulation protocols on pregnancy outcomes by in vitro fertilization].

During a retrospective study on 152 singles pregnancies obtained by in vitro fecondation at Tenon hospital, and followed in this department between January 1990 and December 1994, we have studied the influence of the IVF (tubal origin, masculine or idiopathic) and the type of stimulation (human menopausal gonadotrophin: hMG or follicle stimulating hormone: FSH) on the weight of the newborn and the pathologies that occurred during the pregnancy. No difference in the antecedents has been found in the different group of patients. This study shows a significative difference (p < 0.001) of the newborn's weight when the indication of IVF is tubal origin or masculine. Also, in all IVF indications, the weight is significantly (p < 0.01) higher after a follicular stimulation by FSH versus hMG. For the pregnancy pathologies, no significative difference has been noted, although arterial hypertension, fetal growth retardation and gestational diabetes appear to be more frequent in the group of women who had stimulation by hMG.

Adult↗
PubMed1996

[Cryopreservation of human embryos after in vitro fertilization: immediate and long-term results].

Between 1990 and 1994, a clinical retrospective study has been carried out at Tenon Hospital on 1200 patients: during this periods. 4845 embryos have been cryopreserved and 31% of the patients had this procedure for their supranumerary embryos. The rate of implantation by embryo was 8% per transfer, comparable to those fresh embryos. Less than 1% of the embryos were abandoned. The contribution of cryopreservation to the IVF program is substantial, increasing pregnancy rate by 10%. Moreover, the rate of multiples pregnancies is significantly lower when implanting frozen thawed embryos (9.6%) vs fresh embryos (p < 0.001). There was no difference between frozen-thawed and fresh embryos, in the implantation rate by embryo, the mean gestational age, and birth weight of singleton, twin and triplet births. From a biological point de vue, a series of 3693 embryos, carried on the same period, in our center has showed that for the success of this procedure, the quality of the embryos was more important, than the duration of the storage. The incidence of major and minor congenital malformations was not different in the two groups of babies (less than 3%). But a retrospective analysis carried out on 84 children, showed 4 major abnormalities, after a follow up of 1 to 9 years. However these anomalies do not seem to have some evident correlation with the cryopreservation procedure; a larger series and a prospective study are needed to get significant results concerning the health of the children born after the procedure of cryopreserved embryos.

Birth Weight↗
PubMed1996

[Oocyte fertilizability and embryo development in poor responders].

Oocyte quality (atresia, immaturity), fertilizability, the incidence of abnormal fertilization (parthenogenesis, triploidy) and embryo development (rate of division and morphology) are similar in poor and normal responders. Only, the small number of available embryos (0.9/patient vs 4.4) penalize these patients.

Adult↗