Biomedical subjects

A Ruiz

Publications and source records attributed to A Ruiz.

At least 145 records · Page 8Linked to original sources

PubMed1999

Specific polymorphisms in the RET proto-oncogene are over-represented in patients with Hirschsprung disease and may represent loci modifying phenotypic expression.

Hirschsprung disease (HSCR) is a common genetic disorder presenting with functional intestinal obstruction secondary to enteric aganglionosis. HSCR can be familial or sporadic. Although five putative susceptibility genes have been identified, only germline mutations in the RET proto-oncogene account for a significant minority (up to 50%) of familial HSCR; 3% of sporadic HSCR in a population based series carry RET mutations. From 1998 to February 1999, we prospectively ascertained 64 cases of sporadic HSCR from the western Andalusia region. To determine if polymorphic sequence variants within RET could act as low penetrance predisposing alleles, we examined allelic frequencies at seven polymorphic loci in this population based series. Whether allele frequencies differed from those in the control population were determined by either chi-squared analysis or Fisher's exact test. For two sequence variants, A45A (c 135G-->A) (exon 2) and L769L (c 2307T-->G) (exon 13), the rarer polymorphic allele was over-represented among HSCR cases versus controls (p<0.0006). In contrast, two other polymorphisms, G691S (c 2071C-->A) (exon 11) and S904S (c 2712C-->G) (exon 15), were under-represented in the HSCR patients compared to controls (p=0.02). Polymorphisms in the RET proto-oncogene appear to predispose to HSCR in a complex, low penetrance fashion and may also modify phenotypic expression.

Case-Control Studies↗

PubMed1999

The antiprogestin RU486 dissociates LH and FSH secretion in male rats: evidence for direct action at the pituitary level.

Administration of 4 mg of the antisteroid RU486 over 8 consecutive days to adult male rats dissociated in vivo and in vitro gonadotrophin secretion, increasing FSH and decreasing LH secretion. In subsequent experiments we evaluated the involvement of testicular or adrenal secretory products, as well as hypothalamic LHRH, in the effects of 4 consecutive days of RU486 treatment on the secretion of gonadotrophins. The first day of RU486 injection was designated day 1, subsequent days being numbered consecutively. Groups of rats injected with oil (0.2 ml) or RU486 (4 mg) were: (i) injected s.c. from day 1 to day 4 with the antiandrogen flutamide (10 mg/kg); (ii) bilateral orchidectomized (ORCH) on day 1; and (iii) bilateral adrenalectomized (ADX) on day 1. Controls were given flutamide vehicle or were sham operated. To ascertain whether the secretion of LHRH is involved in the effects of RU486 on gonadotrophin secretion, we measured the LHRH secretion into the pituitary stalk blood vessels at 1100 h on day 5 in oil- or RU486-treated rats. Additional oil- and RU486-treated rats were injected i.p. with 100 ng LHRH at 1000 h on day 5, or s.c. with 1 mg LHRH antagonist (LHRH-ANT) at 1000 h on days 2 and 4. Controls were given saline. All animals were decapitated at 1100 h on day 5, trunk blood collected and serum stored frozen until FSH, LH and testosterone assays.%While ADX had no effect on FSH and LH secretion in either oil- or RU486-treated rats, the removal of androgen negative feedback with flutamide treatment or by ORCH substantially increased serum levels of FSH and LH in both oil- and RU486-treated rats, and thus annulled the effects of RU486. No differences in pituitary stalk plasma LHRH concentrations were found between oil- and RU486-treated rats. Injection of LHRH increased serum FSH and LH concentrations in oil-treated rats but only, and to a lesser extent, LH concentrations in RU486-treated rats. Treatment with LHRH-ANT decreased serum concentrations of FSH and LH in both oil- and RU486-treated rats. These results suggest that RU486 inhibited LHRH-stimulated LH secretion at the pituitary level, and that FSH secretion increased in response to a reduction in the negative feedback of androgen.

Adrenalectomy↗

PubMed1999

[Multicenter study of the variability and adequacy of antimicrobial therapy for community-acquired pneumonia in adults].

We performed a study to evaluate the variability and adequacy of prescribing antibiotics in community-acquired pneumonia (CAP) in 10 Spanish hospitals. We studied 452 patients with CAP. Initial empirical administration of antibiotics was prescribed in 90.7% of the cases, 82.5% as monotherapy. Macrolides and third and second generation cephalosporins were the most widely used groups of antibiotics. Penicillin and amoxicillin were only prescribed in 1. 7% of the patients. A significant variability between hospitals was observed. Reference patterns for the use of antibiotics in CAP were devised by a panel of experts. According to the recommendations of this panel, 29% of the total prescriptions were not adequate, with this percentage reaching 65% in outpatients older than 65 years or with comorbidity. This was mainly due to the fact that monotherapy with erythromycin, which was considered inadequate, was the most widely prescribed treatment.

Adult↗

PubMed1999

CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia.

The CDKN2A gene has been implicated in cutaneous malignant melanoma (CMM) in about 40% of families with linkage to chromosome 9p21, while a small proportion of families have mutations in the CDK4 gene. In order to estimate the importance of these genes in the predisposition to CMM in Spanish families and patients we have analysed, by SSCA, a total of 56 subjects belonging to 34 CMM families, and nine patients with multiple CMM and other neoplasia. We have detected germline CDKN2A mutations in six out of the 34 families (17%). A frameshift mutation (358delG) and four missense mutations (G59V, G101W (two cases), D84Y, and R87W) were identified. Five CMM patients from different families (14%) carried the A148T variant, which is known not to affect p16 activity. No mutations were detected in the patients with multiple CMM or other neoplasms. We have not found mutations either in exon 1 beta of the CDKN2A gene or in exon 2A of CDK4. Linkage analysis of the 9p21 region showed exclusion for one of the families for CMM and for four families for CMM/dysplastic naevi. This study indicates a small role for CDKN2A in Spanish CMM families and suggests that other genes are also responsible for CMM predisposition.

Carrier Proteins↗

PubMed1999

[Multicenter study of the variability and adequacy of antimicrobial therapy for community-acquired pneumonia in adults]

We performed a study to evaluate the variability and adequacy of prescribing antibiotics in community-acquired pneumonia (CAP) in 10 Spanish hospitals. We studied 452 patients with CAP. Initial empirical administration of antibiotics was prescribed in 90.7% of the cases, 82.5% as monotherapy. Macrolides and third and second generation cephalosporins were the most widely used groups of antibiotics. Penicillin and amoxicillin were only prescribed in 1.7% of the patients. A significant variability between hospitals was observed. Reference patterns for the use of antibiotics in CAP were devised by a panel of experts. According to the recommendations of this panel, 29% of the total prescriptions were not adequate, with this percentage reaching 65% in outpatients older than 65 years or with comorbidity. This was mainly due to the fact that monotherapy with erythromycin, which was considered inadequate, was the most widely prescribed treatment.

Journal Article↗

PubMed1999

High prevalence of the C634Y mutation in the RET proto-oncogene in MEN 2A families in Spain.

The RET proto-oncogene encodes a receptor tyrosine kinase expressed in neural crest derived tissues. Germline mutations in the RET proto-oncogene are responsible for three different dominantly inherited cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). MTC can also occur sporadically. Molecular characterisation of the RET proto-oncogene has been performed by PCR-SSCP analysis, direct DNA sequencing, and restriction enzyme analysis in 49 unrelated, Spanish, MEN 2 families: 30 MEN 2A families, six FMTC families, and 13 families classified as "other". Germline missense mutations in one of six cysteine codons (609, 611, 618, and 620 in exon 10, and codons 630 and 634 in exon 11), which encode part of the extracellular cysteine rich domain of RET, have been detected in the majority of these families: 100% of MEN 2A families, 67% of FMTC families, and 54% of families classified as "other". No RET mutations in exons 10, 11, 13, 14, 15, or 16 were detected in the remaining families. The most frequent RET mutation in MEN 2A Spanish families is C634Y, occurring in 73% of cases. Haplotype analysis does not exclude the possibility of founder effects in Spanish MEN 2A families with the C634Y mutation.

Chromosomes, Human, Pair 1↗

PubMed1998

Retention of the CDKN2A locus and low frequency of point mutations in primary and metastatic cutaneous malignant melanoma.

CDKN2A has been found mutated in melanoma families which show linkage to chromosome 9p21. In contrast, a low mutation rate has been found in melanomas, suggesting that CDKN2A might not be the first target for mutation in the development of this type of tumour. To elucidate the role of the CDKN2A gene and its alternative transcript p19ARF in the development of cutaneous malignant melanoma (CMM) we have analyzed 48 primary and metastasic CMM tumours for mutations and for loss of heterozygosity (LOH). Only one point mutation was detected (2%), while hemizygous deletions were identified in 20% of these tumours. Retention of the CDKN2A locus was found in 10 (47%) tumours with deletions at one or both sides of CDKN2A, suggesting that loss of this gene is not involved in CMM-tumour initiation and that another tumour-suppressor gene involved in melanoma is located at 9p21.

Gene Deletion↗

PubMed1998

Prescription patterns of recently graduated physicians in Colombia: a survey during the mandatory social work period.

MAIN OBJECTIVE: To quantify prescribing patterns of physicians during their year of social work in health centers of Bogotá, Colombia, for three tracer conditions: acute respiratory infection (ARI), systemic hypertension (SH) and acute diarrhea (AD). DESIGN: Cross-sectional survey. SETTING: Primary Care Health Centers in the city of Bogotá. STRATEGY: The Health District Department of Bogotá (Secretaria Distrital de Salud) provided the sampling frame of SILOS (Local Health System) and UPAS (primary health service units) with a physician in the social work year. Samples of patient-physician encounters for the three tracer conditions within UPAS were examined, and detailed information collected on prescription indicators. RESULTS: Information was collected on a total of 1099 patient-physician encounters. Results show that 61% (95% CI: 58.6-63.1) of prescriptions in these settings are non-generic, and only 62% (95% CI: 59.5-64.0) are from the Colombian essential drug list. Number of medications prescribed per encounter were higher with ARI, as well as prescriptions for non-generic forms, antibiotics, and medications outside of the Colombian essential drug list. Inappropriate prescriptions were seen in 31% (95% CI: 28.1-33.7) of all encounters. DISCUSSION: Inadequacy of prescriptions (based on diagnosis) suggest that the teaching of rational prescribing patterns should be targeted with much more emphasis in schools of medicine. Interventions focused on the outstanding deficiencies should be designed and properly evaluated.

Journal Article↗

PubMed1998

The antiemetic efficacy of granisetron plus dexamethasone, haloperidol and loracepam in breast cancer patients treated with high-dose chemotherapy with peripheral blood stem-cell support.

There has recently been a marked trend to increasing dose intensity in cancer chemotherapy, with or without peripheral blood stem-cell support, which has been associated with a higher frequency of nausea and vomiting. Antiemetic treatment in this setting has not been extensively analysed. From October 1995 to January 1997, prevention of emesis with granisetron 3 mg/12 h i.v., dexamethasone 12 mg/24 h i.v., haloperidol 0.5 mg/12 h p.o., and loracepam I mg/24 h p.o. was instituted in 30 breast cancer patients treated with high-dose chemotherapy (a 4-day intravenous continuous infusion of cyclophosphamide 1500 mg/m2 per day, thio-TEPA 125 mg/m2 per day and carboplatin 200 mg/m2 per day).A total of 30% of the patients (9/30) obtained complete or major protection on the 4 days of chemotherapy treatment (96.7% (29/30) on day 1, 86.7% (26/30) on day 2, 70% (21/30) on day 3, and 50% (15/30) on day 4). On the days following chemotherapy, 46.7% (14/30) presented fewer than two emetic episodes on day 5, 70% (21/30) on day 6, 83.4% (25/30) on day 7 and, 93.3% (28/30) on day 8. This energic antiemetic combination treatment has hardly any effect in the prevention of emesis, providing complete or major protection of 30% for the 4 days of chemotherapy treatment. Further investigation aimed at improving antiemetic treatment results is necessary.

Adult↗

PubMed1998

Polymerase chain reaction procedure to detect Trypanosoma cruzi in blood samples from chronic chagasic patients.

The feasibility of DNA amplification by the polymerase chain reaction for specific detection of Trypanosoma cruzi in human blood was investigated. We have used primers flanking a 220-bp fragment of highly repetitive elements, the E13 element, in T. cruzi nuclear DNA. Only polymerase chain reaction products from blood samples of chronic chagasic patients showed several amplified fragments in 1.6% agarose gels stained with ethidium bromide. Southern blot analysis demonstrated that the 220-bp amplified fragment is specific for T. cruzi DNA and very useful to detect the presence of the parasite in blood from chronic chagasic patients.

Animals↗

PubMed1998

Malignant proliferating trichilemmal tumours: an histopathological and immunohistochemical study of three cases with DNA ploidy and morphometric evaluation.

AIMS: Malignant proliferating trichilemmal tumours (MPTT) are rare neoplasms capable of tissue invasion and metastasis, the diagnosis of which is based essentially on histological features. In difficult cases, however, evaluation of additional parameters may be needed to diagnose malignancy. METHODS AND RESULTS: We report three cases of MPTT in which, in addition to the histological features, we have determined the DNA ploidy, nuclear area and proliferative fraction. CD34 immunoreactivity has also been tested. Two cases were aneuploid, and one diploid with increased proliferating index. PCNA immunostaining labelled 40% and 80% of tumour cells in aneuploid tumours and 30% of the diploid neoplasm. In all cases, nuclear area was consistent with large pleomorphic tumour cells. No CD34 immunostaining was detected. CONCLUSIONS: Aneuploidy is common in MPTT, particularly in tumours with a high proliferative fraction. Loss of CD34 immunoreactivity is an additional feature of potential, though limited, value. Therefore, evaluation of the DNA content, proliferation markers and CD34 immunostaining may be helpful in the diagnosis of MPTT.

Aged↗

PubMed1998

A major locus for autosomal recessive retinitis pigmentosa on 6q, determined by homozygosity mapping of chromosomal regions that contain gamma-aminobutyric acid-receptor clusters.

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy, with extensive allelic and nonallelic genetic heterogeneity. Autosomal recessive RP (arRP) is the most common form of RP worldwide, with at least nine loci known and accountable for approximately 10%-15% of all cases. Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter in the CNS. Different GABA receptors are expressed in all retinal layers, and inhibition mediated by GABA receptors in the human retina could be related to RP. We have selected chromosomal regions containing genes that encode the different subunits of the GABA receptors, for homozygosity mapping in inbred families affected by arRP. We identify a new locus for arRP, on chromosome 6, between markers D6S257 and D6S1644. Our data suggest that 10%-20% of Spanish families affected by typical arRP could have linkage to this new locus. This region contains subunits GABRR1 and GABRR2 of the GABA-C receptor, which is the effector of lateral inhibition at the retina.

Chromosome Mapping↗

PubMed1998

The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation.

Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for pituitary desensitization may impair the outcome of IVF as compared to classical short-acting formulations. Whether the negative effects are directed against the corpus luteum, the endometrium, or both is unknown. However, the presence of high affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human endometrium suggests a possible role of these analogues on this target organ, affecting embryo implantation. In the present study, we tested direct effects of two different forms of GnRHa on implantation using the ovum donation model. Patients were prospectively allocated to one of the three study groups: the short-acting form of the analogue leuprolide acetate (group I; n=64), the long-acting form of the same analogue (group II; n=58), and the long-acting preparation of the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo transfer was carried out in group I, whereas 67 were performed in group II and 65 in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because of bleeding while being on the waiting list for anonymous oocyte donation. The number of oocytes donated, fertilization rates and embryos replaced in each group were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6% respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1 and 17.0%. These data suggest that the use of a long-acting form of GnRHa provides success rates similar to the short-acting preparations, resulting in more convenient medication for patients with ovarian function included in ovum donation programmes.

Adult↗

PubMed1998

Intracytoplasmic sperm injection as a routine indication in low responder patients.

The aim of this study was to determine if a low response to gonadotrophin stimulation could be considered as an indication for intracytoplasmic sperm injection (ICSI). This prospective study included a total of 96 non-male infertile couples with six or fewer retrieved oocytes, who underwent 104 in-vitro fertilization (IVF) cycles between January 1996 and April 1997. They were randomly divided into two groups for fertilization, one by IVF and the other by ICSI. Groups were compared in terms of fertilization rates, fertilization failure, embryo quality, embryos transferred and reproductive outcome. ICSI provided similar fertilization rates per inseminated oocyte (77.7 versus 70.2%) and per obtained oocyte (56.5 versus 58.8%) as IVF. Furthermore, equal numbers (2.2 versus 2.5) and quality of embryos were obtained and comparable pregnancy (21.1 versus 17.3%) and implantation (14.0 versus 11.1%) rates. Neither the number of retrieved oocytes, nor patient age was relevant for the fertilization rates obtained with both techniques. The number of cases with complete fertilization failure was similar in both procedures. We conclude that the technique of fertilization is not related to the reproductive outcome of low responders, and the routine use of ICSI is not indicated.

Adult↗

PubMed1998

Involvement of estrogen and follicle-stimulating hormone on basal and luteinizing hormone (LH)-releasing hormone-stimulated LH secretion in RU-486-induced 3-day estrous cycle in the rat.

Administration of 4 mg of the antiprogestogen RU-486 on proestrus (Day 1) to 4-day-cyclic rats advances the pituitary desensitization to negative estrogen feedback and enhances pituitary responsiveness to LHRH. These effects of RU-486 lead to a 1-day estrous cycle shortening. Moreover, administration of RU-486 in this study increased serum estradiol-17beta and decreased FSH concentrations during diestrus (experiment 1). The aim of the study was to examine the contribution of the excess of estrogen and the deficiency of FSH during diestrus to the 1-day estrous cycle-shortening effect of RU-486 when injected on Day 1 in 4-day-cyclic rats. The aim of the second and third experiments was to evaluate the effects of 3 mg/0.2 ml oil of the antiestrogen LY117018-HCl (LY) at 1800 h on Days 2 and 3, or 10 IU/0.2 ml saline of a recombinant human FSH (rhFSH) at 1700 h on Day 3 and at 0900 h on Day 4, with or without 100 ng/0.5 ml saline of LHRH at 1200 h on Day 4, on uterine weight and serum concentrations of LH and estradiol-17beta at 1300 h on Day 4 in rats given oil or RU-486 on Day 1 or 2. The aim of the fourth experiment was to evaluate the effect of combined LY and rhFSH treatments on uterine weight and serum levels of LH and estradiol-17beta in rats injected with RU-486 on Day 1. Administration of RU-486 on Day 1 significantly increased serum estradiol-17beta on Days 3 and 4, whereas administration on Day 2 slightly increased serum estradiol-17beta on Day 4 only. Injection of RU-486 on either Day 1 or 2 decreased FSH serum concentrations on Days 3 and 4 to a similar extent. Treatment with LY reduced both basal and LHRH-stimulated LH secretion only in rats injected with RU-486 on Day 1, while rhFSH treatment attenuated basal and stimulated LH secretion regardless of treatment. Treatment with LY and rhFSH combined completely reversed the effects of RU-486 on Day 1 on LH serum concentrations. These data suggest that both the increased estradiol-17beta and the decreased FSH serum concentrations during diestrus in rats given RU-486 on proestrus are involved in the changes of pituitary function leading to a 1-day estrous cycle shortening.

Animals↗

PubMed1998

[A chromatographic analysis of the Mycobacterium tuberculosis strains isolated from an outbreak in HIV patients in Cuba].

A group of strains of Mycobacterium tuberculosis isolated from an outbreak in HIV-infected patients was studied by chromatographic techniques. A group of strains of M. Tuberculosis from symptomatic respiratory patients (SR+ 14) and patterns strains from the laboratory collection were used as a reference aimed at making a qualitative comparison of the chromatographic patterns described by the strains isolated from patients. The chromatographic profiles of the strains isolated from patients (SR+) and fro HIV+ were obtained and compared by thin layer chromatography (TLC). Each of the present fatty acids was identified by using the gas chromatography technique (GC) coupled to mass spectrum analysis. All the studied strains were classified as Mycobacterium tuberculosis. According to the results attained, the usefulness of the chromatographic techniques as alternative techniques for the mycobacterial diagnosis is demonstrated.

AIDS-Related Opportunistic Infections↗

PubMed1998

Effect of RU486 injected on proestrous morning on LHRH, LH and 17beta-estradiol secretion during the estrous cycle in rat.

The antiprogesterone RU486 injected on proestrus to cyclic rats advances the preovulatory surge of LH, resulting in a 3-day estrous cycle. To ascertain whether proestrous progesterone secretion regulates ovulation by synchronizing the functions of the ovary, the pituitary and the hypothalamus, in this study the effects of RU486 (4 mg/0.2 ml oil/s.c.) at 09:00 h on proestrus (day 1), on LHRH secretion into the pituitary stalk blood vessels and on peripheral plasma concentrations of LH and 17beta-estradiol at 10:00 h and at 18:00 h on each day of the estrous cycle, have been investigated. Control rats present the expected surges of LHRH and LH at 18:00 h on day 1 and a second increase in LHRH but no LH secretion was found in the afternoon of day 2. RU486 decreases both LHRH and LH surges in the afternoon of day 1, while it increases plasma concentrations of LHRH and LH in the morning of day 2. During the rest of the estrous cycle RU486-injected rats show high basal secretion of LH in comparison to controls, and at 18:00 h of day 4 advanced preovulatory surges of both LHRH and LH are present in RU486-injected rats. In relation to 17beta-estradiol concentrations, RU486 injection increases those on day 3 and induces an advanced preovulatory surge of 17beta-estradiol in the morning of day 4. These results show that, in the 4-day cyclic rat, the 24 hours-shortening of the estrous cycle induced by the antiprogesterone RU486 is due to the enhanced secretion of estrogen during the days of metestrus and diestrus, which stimulates the release of a surge of LHRH in the afternoon of diestrus and this, in turn, induces the advanced preovulatory surge of LH.

Animals↗

PubMed1997

Complex segregation analysis of schizophrenia in Santiago, Chile.

Genetic epidemiologic studies have provided evidence that genetic factors contribute to familial aggregation of schizophrenia. However, the precise mode of inheritance has not been elucidated. The majority of such studies have been carried out in Caucasian populations. The present study was performed in Santiago, Chile, whose population stems from the admixture of Amerindians with Spaniards. The sample consisted of 44 randomly ascertained schizophrenic probands (22 males and 22 females) with ages ranging between 20 and 48 years. The diagnosis was made according to DSM-III-R criteria. Both probands and relatives were interviewed using a structured interview (CIDI) and the DSM-III-R checklist. Complex segregation analysis was carried out using the computer program POINTER. The non-transmission model (Q = H = 0) was rejected as well as the recessive single locus (H = 0, Z = 1). The multifactorial, the single codominant, the non-major locus component, the non-polygenic component transmission model and the non-transmission of a major effect could not be rejected. The model that best fits the data of the present study is that of a mixed model with a great environmental component (93.12%). The frequency of the major gene was estimated at 0.000155. Our results are similar to previous reports in ethnically different populations.

Adult↗