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Biomedical subjects

A Ruiz

Publications and source records attributed to A Ruiz.

At least 163 records · Page 9Linked to original sources
PubMed1997

Prognostic significance of c-erbB-2/neu amplification and epidermal growth factor receptor (EGFR) in primary breast cancer and their relation to estradiol receptor (ER) status.

The aim of this study is to evaluate the prognostic significance of c-erbB-2/neu amplification and epidermal growth factor receptor (EGFR) expression in primary breast cancer (BC) and their prognostic implications when combined with estradiol receptor (ER) status. In this work, 825 BCs were studied. Neu amplification was evaluated by dot-blot and EGFR expression was evaluated by ligand binding assay using I125-EGF. Neu, EGFR, estradiol and progesterone receptors (ER and PR) had a marked influence on disease free survival (DFS) in univariate analysis. In node-negative (NO) cases only neu was associated with short DFS (p = 0.005). However, in node-positive (N+) cases both EGFR (p = 0.005) and neu (p = 0.002) influenced DFS. None of the biological markers were significant predictors for overall survival (OS) in NO/BC. On the contrary, in N+/BC, EGFR + (p = 0.003) was associated with short OS. The EGFR + /neu/phenotype represented a sub-group with an even worse prognosis with respect to DFS (p = 0.0034) as well as EGFR + /ER-tumors (p = 0.005). Moreover, neu + /ER-patients also had a high probability of relapse (p = 0.0000) and death (p = 0.006). C-erbB-2/neu, EGFR, histological grade, pN, pT and ER were subjected to a Cox multivariate regression analysis: neu was the most important parameter in predicting recurrence, and EGFR was a significant predictor for OS.

Adult↗
PubMed1997

Concentrations of estrone, estradiol and their sulfates, and evaluation of sulfatase and aromatase activities in patients with breast fibroadenoma.

In the present studies, the concentrations (mammary tissue and plasma) of estrone (E1), estradiol (E2) and their sulfates (E1S and E2S), as well as the sulfatase and aromatase activities, were evaluated in patients with breast fibroadenomas. Comparative studies of the evaluation of these parameters were carried out in: (A) tumor tissue, (B) areas surrounding the tumor and (C) areas distant from the tumor (glandular tissue) considered as normal tissue. The concentrations in the tumor tissue (in pmol/g tissue) of E1, E2 and E1S were significantly higher (2-3 times) than in the area of the breast considered as normal. Sulfatase and aromatase activities were found in the breast fibroadenoma tissue. Sulfatase activity was much higher than aromatase (30-150 times) and sulfatase levels were significantly higher in the fibroadenoma tissue than in the area considered as normal. Plasma evaluation of E1, E2, E1S and E2S concentrations showed no significant differences in relation to those of healthy control women. In conclusion, the high levels of estrogens and their sulfates, as well as the enzymes involved in estrogen formation--sulfatase and aromatase in breast fibroadenoma--contribute to the hypothesis that this disease may be hormone-dependent.

Adolescent↗
PubMed1997

E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles.

A single base substitution of a glutamic acid to an alanine codon 280 was found in the presenilin-1 (PS-1) gene on chromosome 14 in affected individuals in each of seven Colombian early-onset Alzheimer's disease (AD) kindreds. The mutation segregated with disease in kindreds tested. In the largest kindred (C2), the maximum two-point lod score between the mutation and AD was Z = 8.14 at theta = 0. The presence of a single mutation and the common geographic origin, with all families from the state of Antioquia, suggest a founder effect in this population. This finding is supported by the observation of a rare haplotype inherited with AD in all kindreds. These kindreds form the largest collection of AD cases with the same PS-1 mutation and the same educational, environmental, and ethnic background in which to study the phenotypic effect of putative risk factors, such as the epsilon4 allele of apolipoprotein E (ApoE) or head trauma. Of the few AD cases having a history of head trauma, the age of onset was not lowered. No effect of ApoE genotype on the age of onset was detected. Previous investigations of the effect of ApoE genotype on the age of onset were confounded by small patient numbers, familial clustering of ApoE genotypes, and combining data from unrelated families with different mutations.

Adult↗
PubMed1997

Serum levels of GH, IGF-I, LH and ovarian steroids in cyclic and RU486-treated rats.

Rats lacking progesterone action due to RU486 treatment have been reported to show numerous endocrine and morphological similarities with respect to human polycystic ovary syndrome (PCO). Nevertheless, abnormalities on insulin or insulin-like growth factor I (IGF-I) production, a frequent finding in the polycystic disease, have not been studied in such rats yet. The aim of these experiments was to evaluate the serum concentrations of IGF-I in rats treated with 4 mg of the antiprogestagen RU486 over 4 or 8 consecutive days starting on estrus (day 1) and decapitated on the morning of day 5 and 9. Serum levels of growth hormone (GH), luteinizing hormone (LH), testosterone (T) and 17 beta estradiol (E2) were determined and correlated with those of IGF-I. Controls were rats injected with oil and killed in the morning of metestrus, diestrus, proestrus and estrus. Rats treated with RU486 had increased serum concentrations of IGF-I, LH, T and E2 with respect to control rats on estrus, while no differences were found in the serum concentrations of GH. Parallel estrous cycle related changes were observed in the serum concentrations of IGF-I, T and E2 with the highest values at proestrus. However, changes on serum concentrations of GH were not associated with those of IGF-I in control rats through the estrous cycle. The present results are consistent with the idea that beside on GH, serum concentrations of IGF-I in the rat depend also on LH or LH-dependent ovarian steroid production. Moreover, the results indicate that IGF-I production increased in RU486-treated rats, which may have a role in the ovarian abnormalities induced by RU486 treatment in the rat.

Animals↗
PubMed1997

Inherited susceptibility to several cancers but absence of linkage between dysplastic nevus syndrome and CDKN2A in a melanoma family with a mutation in the CDKN2A (P16INK4A) gene.

Genetic predisposition plays an important role in the development of nearly 10% of cases of cutaneous malignant melanoma (CMM). The CDKN2A gene has been described as responsible for melanoma susceptibility in a proportion of families with CMM linked to 9p. CDKN2A encodes a cyclin-dependent kinase inhibitor also implicated in the carcinogenesis of several sporadic tumors. Even though the incidence of other cancers is higher in CMM families, pancreatic adenocarcinoma is the only other well demonstrated cancer associated with CDKN2A mutations in some CMM pedigrees. We describe a family with four cases of CMM, eight patients affected by other cancers, and nine patients affected by dysplastic nevus (DN) syndrome. A CDKN2A frameshift mutation (358delG) was present in all the CMM patients, in at least three of the patients with other cancers (CDKN2A status is unknown in four patients), and in only two of the DN patients (CDKN2A status is unknown in one patient). An absence of linkage between chromosome 9p markers and the 358delG CDKN2A mutation and DN was detected, indicating genetic heterogeneity for DN and CMM in this family. The study strongly suggests that CDKN2A mutations are involved not only in the predisposition to CMM but also to several other types of cancer.

Adult↗
PubMed1997

The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination.

OBJECTIVE: To determine an optimal insemination technique in patients undergoing IVF after failed IUI and the role of intracytoplasmic sperm injection (ICSI) in such cases. DESIGN: Prospective, randomized study in couples with unexplained infertility (n = 63) and mild endometriosis (n = 7) undergoing IVF after four IUI cycles. Sibling oocytes were randomized into standard IVF or ICSI insemination according to the order of retrieval. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Italy. PATIENT(S): Seventy couples with unexplained infertility undergoing IVF after failing to conceive with controlled ovarian stimulation and IUI. INTERVENTION(S): In vitro fertilization and ICSI. MAIN OUTCOME MEASURE(S): Fertilization, cleavage, and embryo quality were compared in IVF- and ICSI-inseminated oocytes. RESULT(S): There was no significant difference in fertilization rates between ICSI (60.4%) and conventional IVF (54.0%). Similarly, there was no difference in embryo quality between both groups. There was no total fertilization failure in ICSI-inseminated oocytes, whereas 8 (11.4%) of 70 cases showed absence of fertilization when conventional IVF was used. CONCLUSION(S): Couples with unexplained infertility and mild endometriosis failing to conceive with IUI and undergoing IVF have an 11.4% chance of fertilization failure that can be overcome easily by using ICSI in at least some oocytes. ICSI, however, is not superior to IVF as an insemination technique in most cases. These data should be used in counseling patients.

Adult↗
PubMed1997

Mediastinal non-seminomatous germ cell tumours (MNSGCT) treated with cisplatin-based combination chemotherapy.

BACKGROUND: Primary mediastinal non-seminomatous germ cell tumours (MNSGCT) constitute a rare malignancy. This study was performed to review our experience with cisplatin-based chemotherapy in patients with MNSGCT. PATIENTS AND METHODS: Patients with MNSGCT treated with cisplatin-based combination chemotherapy between 1978-1995 in three university hospitals in Spain were retrospectively studied. RESULTS: There were 25 males and two females with a median age of 26 years (range 4-71). Fifteen patients had disease confined to the mediastinum and 12 had metastatic disease. All patients were treated with cisplatin chemotherapy regimens (PVB: 7, BEP: 6, and other regimens 12) and considered for residual mass surgery (RMS) when indicated. Eleven patients (40.7%) were rendered disease-free with initial treatment: four with chemotherapy alone, one with surgery plus adjuvant chemotherapy and six with chemotherapy plus RMS. Three of these patients relapsed at two, six and seven months. The remaining 16 had unfavourable responses (five partial response, three no change, seven progressive disease and one toxic death). Eleven patients received salvage treatment but none of them achieved a durable response. After a median follow-up of 77 months (range 1-168), 10 patients remain alive. Actuarial survival at five years is 31.7%. No patients in this series developed a haematological malignancy. Chromosomal analysis showed that 2 out of 10 patients (20%) had a 47XXY karyotype. CONCLUSIONS: Only patients who achieved disease-free status are likely to be cured. Therefore, new up-front strategies are needed for the treatment of MNSGCT.

Adolescent↗
PubMed1997

Chromosomal homology and molecular organization of Muller's elements D and E in the Drosophila repleta species group.

Thirty-three DNA clones containing protein-coding genes have been used for in situ hybridization to the polytene chromosomes of two Drosophila repleta group species, D. repleta and D. buzzatii. Twenty-six clones gave positive results allowing the precise localization of 26 genes and the tentative identification of another nine. The results were fully consistent with the currently accepted chromosomal homologies and in no case was evidence for reciprocal translocations or pericentric inversions found. Most of the genes mapped to chromosomes 2 and 4 that are homologous, respectively, to chromosome arms 3R and 3L of D. melanogaster (Muller's elements E and D). The comparison of the molecular organization of-these two elements between D. melanogaster and D. repleta (two species that belong to different subgenera and diverged some 62 million years ago) showed an extensive reorganization via paracentric inversions. Using a maximum likelihood procedure, we estimated that 130 paracentric inversions have become fixed in element E after the divergence of the two lineages. Therefore, the evolution rate for element E is approximately one inversion per million years. This value is comparable to previous estimates of the rate of evolution of chromosome X and yields an estimate of 4.5 inversions per million years for the whole Drosophila genome.

Animals↗
PubMed1997

Recombination and gene flux caused by gene conversion and crossing over in inversion heterokaryotypes.

A theoretical analysis of the effects of inversions on recombination and gene flux between arrangements caused by gene conversion and crossing over was carried out. Two different mathematical models of recombination were used: the Poisson model (without interference) and the Counting model (with interference). The main results are as follows. (1) Recombination and gene flux are highly site-dependent both inside and outside the inverted regions. (2) Crossing over overwhelms gene conversion as a cause of gene flux in large inversions, while conversion becomes relatively significant in short inversions and in regions around the breakpoints. (3) Under the Counting model the recombination rate between two markers depends strongly on the position of the markers along the inverted segment. Two equally spaced markers in the central part of the inverted segment have less recombination than if they are in a more extreme position. (4) Inversions affect recombination rates in the univerted regions of the chromosome. Recombination increases in the distal segment and decreases in the proximal segment. These results provide an explanation for a number of observations reported in the literature. Because inversions are ubiquitous in the evolutionary history of many Drosophila species, the effects of inversions on recombination are expected to influence DNA variation patterns.

Animals↗
PubMed1997

Effects of progesterone on the secondary surge of follicle-stimulating hormone in the rat.

In the cyclic rat, the secondary surge of FSH on estrus appears to depend on the LH surge-induced fall in serum concentrations of inhibin. To investigate the involvement of progesterone in the regulation of the secondary surge of FSH, 4-day cyclic rats were treated on proestrus with an antagonist of LHRH (LHRHant) and with an ovulatory dose of ovine (o) LH, progesterone, the antiprogestin RU486, or the combination of RU486 and oLH. Serum concentrations of gonadotropins and inhibin at 1830 h on proestrus and at 0030 h on estrus were determined, and the expression of inhibin/activin subunit mRNAs in the ovary at 0030 h on estrus was analyzed by in situ hybridization. Rats receiving saline showed low expression of alpha-, beta(A)-, and beta(B)-subunit mRNAs in the ovary and low serum levels of inhibin in conjunction with the elevated serum concentrations of FSH on estrus. Administration of LHRHant blocked the decrease in the synthesis and secretion of inhibin and abolished the FSH secondary surge, whereas the injection of oLH prevented these effects. Exogenous progesterone, compared with LHRHant injection, increased alpha-, beta(A)-, and beta(B)-subunit mRNA hybridization intensity in the ovary and serum inhibin immunoreactivity, and also restored, in part, the surge of FSH on estrus. The antiprogestin RU486 did not modify the effect of oLH on either inhibin/ activin subunit mRNAs in the ovary or serum levels of inhibin, but blocked the FSH surge. These results indicate that, in the cyclic rat, 1) the secretion of progesterone on proestrous afternoon, induced by the LH surge, is not involved in the fall of ovarian inhibin synthesis and secretion; and 2) in combination with a drop in serum inhibin, a stimulatory action of progesterone on another factor, possibly pituitary activin, could be necessary to elicit a complete secondary surge of FSH.

Animals↗
PubMed1997

Lack of ability of ciprofloxacin-rifampin prophylaxis to decrease infection-related morbidity in neutropenic patients given cytotoxic therapy and peripheral blood stem cell transplants.

We compared ciprofloxacin alone with ciprofloxacin plus rifampin (C + R) as a prophylactic antibacterial regimen for 40 patients with solid tumors treated with high-dose chemotherapy and autologous stem cell transplantation support. No differences were found between groups in the time elapsed to the onset of fever, incidence of febrile episodes, amphotericin B use, and length of hospital stay. However, C + R combination prophylaxis significantly reduced the incidence of gram-positive bacteremia (five versus zero episodes) but was associated with a higher incidence of drug-related side effects.

Adult↗
PubMed1997

Experience of Oncopaz Cooperative Group with oral fluoropyrimidines in tumors of the stomach, lung, head and neck, and breast.

The Oncopaz Cooperative Group designed a chemotherapy regimen to modulate UFT (Tegafur and Uracil) with leucovorin. The regimen consisted of a high intravenous dose of leucovorin, followed by oral UFT and oral leucovorin twice daily for 14 days. Based on the promising results obtained with this regimen in patients with advanced colorectal cancer, the Oncopaz group performed several phase II trials using this combination with other drugs to treat advanced gastric, lung, head and neck, and breast cancers. When combined with etoposide in gastric cancer, the regimen was shown to be active and well tolerated. However, when used with cisplatin to treat non-small cell lung cancer, a low response rate and high toxicity precluded its recommendation for further study. The addition of carboplatin in the treatment of head and neck cancer demonstrated moderate activity with low toxicity. In an ongoing trial of advanced breast cancer, preliminary results indicate that the combination of idarubicin, UFT, and leucovorin is active, with moderate, primarily hematologic toxicity. Trials of new combinations are warranted to take advantage of the pharmacokinetic properties and oral bioavailability of UFT and leucovorin.

Adenocarcinoma↗
PubMed1997

The steroid antagonist RU486 given at pro-oestrus induces hypersecretion of follicle-stimulating hormone from oestrus afternoon to early metoestrus in the rat.

Administration of the steroid antagonist RU486 to cyclic rats at pro-oestrus blunts the preovulatory surge of LH and suppresses the first and second surges of FSH. In addition, administration of oestradiol to RU486-treated rats reactivates the LH surge the following day. The present study explored the effects of RU486 (4 mg/0.2 ml oil), administered at 0800 h on the day of pro-oestrus, on serum FSH and LH concentrations through oestrus and early metoestrus. RU486 induced a hypersecretion of FSH, which started at 1400 h on the day of oestrus and was maintained until 0800 h on the day of metoestrus. Because the timing and magnitude of this secretion of FSH were similar to those of the periovulatory secretion of FSH during pro-oestrus and early oestrus in intact cyclic rats, we investigated the effects of: 1) LHRH antagonist (LHRHa) injected at either 0900 h or 2000 h on the day of oestrus, 2) oestradiol benzoate injected at 1600 h on the day of pro-oestrus and at 0900 h on the day of oestrus, 3) bovine follicular fluid (bFF) given either at 1100 h or at 2000 h on the day of oestrus, or 4) adrenalectomy (ADX) at 1100 h on the day of oestrus, on serum FSH and LH concentrations at 1800 h on the day of oestrus and at 0200 h on the day of metoestrus in rats injected with RU486 at pro-oestrus. The results showed that 1) both components (late oestrus and early metoestrus) of FSH hypersecretion in RU486-injected rats in pro-oestrus were inhibited by oestradiol benzoate and bFF, 2) the metoestrous component was not affected by LHRHa, whereas the oestrous component was partially reduced, and 3) ADX partially reduced serum FSH concentrations only on the day of metoestrus, possibly because, as the serum concentrations of corticosterone reflected, the antiglucocorticoid activity of 4 mg RU486 lasted only 24 h. The results support the hypothesis that blockade of progesterone actions at pro-oestrus results in the maintenance of the daily neural signal that activates the release of gonadotrophins. Whereas the expression of LH secretion requires high levels of oestradiol, FSH secretion is expressed against a background of low oestradiol levels. The results of this study also indicate that the release of FSH during oestrus and metoestrus in rats injected with RU486 at pro-oestrus is a consequence of the lack of ovarian negative feedback inhibition on the pituitary.

Adrenalectomy↗
PubMed1997

PCR mutagenesis-based method for generation of positive controls for SSCP analysis.

We have developed a primer-mediated PCR mutagenesis-based method for the generation of positive controls to test the sensitivity of single-strand conformation polymorphism (SSCP) or any other PCR-based mutation screening method. This technique is based on the incorporation of a third longer primer, containing a mismatched base, into the PCR along with the two wild-type primers normally used to amplify DNA fragments for SSCP analysis. The longer mismatch primer (LMP) shares the sequence of one of the wild-type primers and also contains 5 to 10 additional bases, which include the mismatched base. The resulting PCR product is identical in length and sequence to the wild-type template with the exception that the LMP base mismatch is incorporated into nearly 100% of the product. We have observed an altered SSCP mobility pattern in all cases where positive controls have been generated using this technique. We believe that the use of such in vitro-generated controls can contribute to the interpretation of band patterns and to the optimization of experimental conditions for SSCP to facilitate maximum detection of sequence variants.

Base Sequence↗
PubMed1997

Prevalence of infection, mean worm burden and degree of worm aggregation as determinants of prevalence of disease due to intestinal helminths.

Theoretical predictions of disease prevalence due to helminth infections based upon a simple probabilistic model which considers the infection prevalence, the mean worm burden and the degree of worm aggregation are presented. A numerical reappraisal of the likely estimates of the degree of aggregation based upon maximum likelihood estimates of the negative binomial distribution is presented. The prevalence of disease shows a positive relationship with the mean worm burden. This association is hyperbolic when helminth parasites are severely aggregated but is s-shaped when helminth parasites tend to be overdispersed. The prevalence of disease decreases with the degree of worm aggregation when the values of the mean intensity are low; as the mean intensity increases this association becomes positive. The relationship between prevalence of disease and prevalence of infection is hyperbolic for severe degrees of parasite aggregation and is s-shaped for intermediate degrees of aggregation. However, if the mean intensity is low and the degree of aggregation is high there could be a negative relationship between the prevalence of disease and the prevalence of infection. The presence of disease due to helminth parasites is feasible for determined ranges of values of the infection prevalence, mean intensity and the degree of worm clumping.

Animals↗
PubMed1997

Primary central nervous system lymphoma in patients with AIDS.

Primary central nervous system lymphoma (PCNSL), once considered a rare brain neoplasm, has been steadily increasing in incidence mainly due to an enlarging population of immunosuppressed patients. PCNSL has become the second most common brain space occupying lesion in patients with the acquired immunodeficiency syndrome. A rapid diagnosis of this entity may represent weeks to months of survival to immunosuppressed HIV-positive patients. The radiologist now plays an important role in the noninvasive diagnosis and management of this condition through the accurate interpretation of imaging findings provided by CT, MR, and brain SPECT studies. This article focuses on the pathogenesis, clinical manifestations, neuropathology, and imaging characteristics of this brain neoplasm. New accurate imaging algorithms combining the diagnostic information provided by CT, MR, and T1-201 brain SPECT are discussed.

Brain↗