Biomedical subjects

R M Reis

Publications and source records attributed to R M Reis.

13 recordsLinked to original sources

PubMed2006

Comparison of fundamental voice frequency between menopausal women and women at menacme.

OBJECTIVE: To analyze comparatively the speaking fundamental frequency (F0) between women at menacme and women in the climacterium taking or not hormonal replacement therapy. METHODS: A controlled transverse study was conducted on 45 women divided into three groups of 15 women each: Group A (women aged 20-40 years with regular menstrual cycles taking no hormonal contraceptives), Group B (women aged 45-60 years with a duration of menopause of at least 2 years taking 1mg estradiol valerate +90 microg norgestimate per day in a continuous treatment scheme lasting at least 6 months), and Group C (women aged 45-60 years with a duration of menopause of at least 2 years taking no HRT for at least 6 months). The mean age for Groups A, B and C was 30.3, 54.5 and 56.5 years, respectively. The groups were analyzed comparatively regarding F0 values for the sustained vowels /e/ and /i/. RESULTS: Mean F0 for the sustained vowels /e/ and /i/ were 215.97 and 229.89 Hz, 206.21 and 221.79 Hz, 200.71 and 212.79 Hz for Groups A, B and C, respectively, with no significant differences between groups. CONCLUSIONS: Although there is evidence of a probable modulating effect of sex steroids on the larynx, in the present study no significant differences in speaking voice were observed regarding menopause or the use of HRT. The absence of such differences observed in F0 does not necessarily mean that there is no difference in vocal quality between these groups since F0 represents only a vocal parameter.

Adult↗

PubMed2006

EGFR amplification and lack of activating mutations in metaplastic breast carcinomas.

Metaplastic breast carcinomas are reported to harbour epidermal growth factor receptor (EGFR) overexpression in up to 80% of the cases, but EGFR gene amplification is the underlying genetic mechanism in around one-third of these. In this study, EGFR gene amplification as defined by chromogenic in situ hybridization and protein overexpression was examined in a cohort of 47 metaplastic breast carcinomas. Furthermore, the presence of activating EGFR mutations in exons 18, 19, 20, and 21 was investigated. Thirty-two cases showed EGFR overexpression and of these, 11 (34%) harboured EGFR gene amplification. In addition, EGFR amplification showed a statistically significant association with EGFR overexpression (p < 0.0094) and was restricted to carcinomas with homologous metaplasia. Ten cases, five with and five without EGFR amplification, were subjected to microarray-based CGH, which demonstrated that EGFR copy number gain may occur by amplification of a discrete genomic region or by gains of the short arm of chromosome 7 with a breakpoint near the EGFR gene locus, the minimal region of amplification mapping to EGFR, LANCL2, and SEC61G. No activating EGFR mutations were identified, suggesting that this is unlikely to be a common alternative underlying genetic mechanism for EGFR expression in metaplastic breast carcinomas. Given that metaplastic breast carcinomas are resistant to conventional chemotherapy or hormone therapy regimens and that tumours with EGFR amplification are reported to be sensitive to EGFR tyrosine kinase inhibitors, these findings indicate that further studies are warranted to explore EGFR tyrosine kinase inhibitors as potential therapeutic agents for metaplastic breast carcinomas harbouring amplification of 7p11.2.

Breast Neoplasms↗

PubMed2005

Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study.

BACKGROUND: The present study assessed the effects of low-dose acarbose on obese patients with polycystic ovarian syndrome (PCOS). METHODS: A double-blind placebo-controlled study was conducted on 30 obese hyperinsulinaemic women with PCOS treated with 150 mg/day acarbose or placebo for 6 months. The women were evaluated for hirsutism, menstrual regularity, body mass index (BMI), insulin resistance and glucose tolerance, sex hormone-binding globulin (SHBG), LH, FSH, testosterone and androstenedione, and side-effects. RESULTS: The patients in the acarbose group showed a reduction in BMI (35.87 +/- 2.60 versus 33.10 +/- 2.94 kg/m(2)) and in the Ferriman-Gallwey index (8.85 +/- 2.31 versus 8 +/- 1.82), and an increased chance of menstrual regularity (rate = 2.67). SHBG concentration increased (21.01 +/- 7.9 versus 23.85 +/- 7.77 nmol/l) and the free androgen index was reduced (14.81 +/- 9.06 versus 11.48 +/- 6.18). None of these parameters were modified in the placebo group. Mild side-effects occurred in 84% of the patients in the acarbose group and disappeared after the first 3 months. CONCLUSION: A low dose of acarbose administered to obese patients with PCOS promotes a reduction in free androgen index and BMI and an increase in SHBG, with improvement of hirsutism and of the menstrual pattern, and is well tolerated by patients.

Acarbose↗

PubMed2004

Estradiol and testosterone concentrations in follicular fluid as criteria to discriminate between mature and immature oocytes.

The objective of the present study was to examine the association between follicular fluid (FF) steroid concentration and oocyte maturity and fertilization rates. Seventeen infertile patients were submitted to ovulation induction with urinary human follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (hCG). A total of 107 follicles were aspirated after hCG administration, the oocytes were analyzed for maturity and 81 of them were incubated and inseminated in vitro. Progesterone, estradiol (E2), estrone, androstenedione, and testosterone were measured in the FF. E2 and testosterone levels were significantly higher in FF containing immature oocytes (median = 618.2 and 16 ng/ml, respectively) than in FF containing mature oocytes (median = 368 and 5.7 ng/ml, respectively; P < 0.05). Progesterone, androstenedione and estrone levels were not significantly different between mature and immature oocytes. The application of the receiver-operating characteristic curve statistical approach to determine the best cut-off point for the discrimination between mature and immature oocytes indicated levels of 505.8 ng/ml for E2 (81.0% sensitivity and 81.8% specificity) and of 10.4 ng/ml for testosterone (90.9% sensitivity and 82.4% specificity). Follicular diameter was associated negatively with E2 and testosterone levels in FF. There was a significant increase in progesterone/testosterone, progesterone/E2 and E2/testosterone ratios in FF containing mature oocytes, suggesting a reduction in conversion of C21 to C19, but not in aromatase activity. The overall fertility rate was 61% but there was no correlation between the steroid levels or their ratios and the fertilization rates. E2 and testosterone levels in FF may be used as a predictive parameter of oocyte maturity, but not for the in vitro fertilization rate.

Adult↗

PubMed2001

Mutation analysis of hBUB1, hBUBR1 and hBUB3 genes in glioblastomas.

Glioblastomas, the most malignant human brain tumors, are characterized by marked aneuploidy, suggesting chromosomal instability which may be caused by a defective mitotic spindle checkpoint. We screened 22 glioblastomas for mutations in the mitotic spindle check-point genes hBUB1, hBUBR1 and hBUB3. DNA sequencing revealed a silent mutation at codon 144 of hBUB1 (CAG-->CAA, Gln-->Gln) in one glioblastoma, a silent mutation at codon 952 of hBUBR1 (GAC-->GAT, Asp-->Asp) in another glioblastoma, and a silent mutation at codon 388 of the hBUBR1 gene (GCG-->GCA, Ala-->Ala) in 8 glioblastomas. We also observed a known polymorphism at hBUBR1 codon 349 (CAA/CGA, Gln/Arg), with an allelic frequency of 0.75 for Gln and 0.25 for Arg, which is similar to that among healthy Caucasian individuals (0.73 vs 0.27). The coding sequence of the hBUB3 gene did not contain any mutation, but in 4 glioblastomas (18%), a C-->T point mutation was detected at position -6 (6 nucleotides upstream of the ATG initiator codon). Analysis of blood DNA of these patients showed identical sequence alterations, indicating that this is a polymorphism. Again, the frequency in glioblastomas was similar to that in healthy Caucasians (15%). We further screened hBUB1 in 18 cases of giant cell glioblastoma, a variant characterized by a predominance of bizarre, multinucleated giant cells. There were no changes, except for a silent mutation at codon 144 in two cases. These results suggest that mutations in these mitotic spindle checkpoint genes do not play a significant role in the causation of chromosomal instability in glioblastomas.

Adult↗

PubMed2001

Genetic evidence of the neoplastic nature of gemistocytes in astrocytomas.

Gemistocytic astrocytoma is characterized by a predominance of large astrocytes with plump processes and massive accumulation of glial fibrillary acidic protein (gemistocytes). This histological variant of low-grade diffuse astrocytoma (WHO grade II) is prone to more rapid progression to anaplastic astrocytoma and glioblastoma than the ordinary fibrillary astrocytoma. The biological basis of this unfavorable prognosis is unclear, since gemistocytes themselves have low proliferative activity, even if present in anaplastic astrocytomas or glioblastomas. This has raised the question of whether gemistocytes are neoplastic cells or dysplastic reactive astrocytes. In this study, gemistocytes and non-gemistocytic neoplastic cells were separated by laser-assisted microdissection from six gemistocytic astrocytomas carrying TP53 mutations. In all cases, identical TP53 mutations were identified in both cell types, indicating that gemistocytes are indeed neoplastic cells. Their lack of proliferative activity may indicate terminal differentiation.

Adult↗

PubMed2001

Second primary glioblastoma.

Although characterized by a highly variable phenotype and multiple genetic alterations, glioblastomas are considered monoclonal in origin. We here report on a 64-yr-old patient who developed a second glioblastoma in the left frontal lobe 10 yr after surgical resection of a glioblastoma of right frontal lobe. The first tumor contained 2 p53 mutations, in codon 213 (CGA-->TGA, Arg-->stop) and codon 306 (CGA-->TGA, Arg-->stop), further, 1 missense PTEN mutation (codon 257, TTC-->TTA, Phe-->Leu) and a silent PTEN mutation (codon 154, TTC-->TTT, Phe-->Phe). The second glioblastoma also contained multiple, but different mutations: p53 mutations in codons 158 (CGC-->CAC, Arg-->His) and 273 (CGT-->TGT, Arg-->Cys), and a PTEN mutation in codon 233 (CGA-->TGA, Arg-->Stop). Both neoplasms had a homozygous p16 deletion. The discordant pattern of mutations indicates that the second glioblastoma was not a recurrence but an independent second glioblastoma. The presence in these neoplasms of multiple mutations in tumor suppressor genes suggests the involvement of a novel disease mechanism but there was no indication of a DNA mismatch repair deficiency or of an inherited tumor syndrome.

Chromosomes, Human, Pair 10↗

PubMed2001

Doppler study of the uterine arteries and ovarian stroma in patients with polycystic ovary syndrome.

Doppler analysis of the uterine arteries and ovarian stroma was performed by transvaginal ultrasound in 24 patients with polycystic ovary syndrome (PCOS) and 22 ovulatory women. Vascularization of the ovarian stroma was more abundant in patients with PCOS than in control women, but no significant difference in the mean pulsatility index (PI) was observed between groups (1.14 +/- 0.28 for the PCOS group and 1.05 +/- 0.19 for the control group). The mean PI of the uterine arteries was significantly higher in the PCOS group (PI = 3.7 +/- 0.8) than in the control group (PI = 2.9 +/- 0.4). In the patients with PCOS, no correlation was observed between PI and luteinizing hormone, testosterone or androstenedione levels. Obesity had no effect on uterine artery PI, with no significant differences in this index when the 3 groups were subdivided into obese and non-obese groups.

Adolescent↗

PubMed2000

Genetic profile of gliosarcomas.

There are distinct genetic pathways leading to the glioblastoma, the most malignant astrocytic brain tumor. Primary (de novo) glioblastomas develop in older patients and are characterized by epidermal growth factor (EGF) receptor amplification/overexpression, p16 deletion, and PTEN mutations, whereas secondary glioblastomas that progressed from low-grade or anaplastic astrocytoma develop in younger patients and frequently contain p53 mutations. In this study, we assessed the genetic profile of gliosarcoma, a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. Single-strand conformation polymorphism followed by direct DNA sequencing revealed p53 mutations in five of 19 gliosarcomas (26%) and PTEN mutations in seven cases (37%). Homozygous p16 deletion was detected by differential polymerase chain reaction in seven (37%) gliosarcomas. The overall incidence of alterations in the Rb pathway (p16 deletion, CDK4 amplification, or loss of pRb immunoreactivity) was 53%, and these changes were mutually exclusive. Coamplification of CDK4 and MDM2 was detected in one gliosarcoma. None of the gliosarcomas showed amplification or overexpression of the EGF receptor. Thus gliosarcomas exhibit a genetic profile similar to that of primary (de novo) glioblastomas, except for the absence of EGFR amplification/overexpression. Identical PTEN mutations in the gliomatous and sarcomatous tumor components were found in two cases. Other biopsies contained p16 deletions, an identical p53 mutation, or coamplification of MDM2 and CDK4 in both tumor areas. This strongly supports the concept of a monoclonal origin of gliosarcomas and an evolution of the sarcomatous component due to aberrant mesenchymal differentiation in a highly malignant astrocytic neoplasm.

Adult↗

PubMed2000

Hypogonadotropic hypogonadism: retrospective analysis of 19 cases.

OBJECTIVES: To survey the clinical data of patients with isolated gonadotropin deficiency. METHODS: We retrospectively surveyed the medical records of 19 patients with isolated gonadotropin deficiency aged 16-31 years (mean: 20 years). The major complaint was primary amenorrhea in 100% of the patients, with 42.1% of them also reporting absence of secondary sex traits, and 10% reporting anosmia or hyposmia. Seventy-four percent of the patients had been submitted to hormonal replacement therapy. RESULTS: Bone densitometry was determined in 5 patients and revealed lumbar spine osteopenia in 3 patients and femoral osteopenia in 1. An association with urologic malformations was detected in 10.5% of cases and an association with gynecologic malformations was detected in 31.6%. CONCLUSIONS: Isolated gonadotropin deficiency can be easily diagnosed but requires early estrogen replacement therapy because of a higher risk of osteopenia and consequently of osteoporosis. Concomitant urogenital malformations are frequent and should be investigated.

Adolescent↗

PubMed2000

Loss of heterozygosity on chromosome 10 is more extensive in primary (de novo) than in secondary glioblastomas.

Glioblastomas develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). There is increasing evidence that these glioblastoma subtypes develop through different genetic pathways. Primary glioblastomas are characterized by EGFR and MDM2 amplification/overexpression, PTEN mutations, and p16 deletions, whereas secondary glioblastomas frequently contain p53 mutations. Loss of heterozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas; the involvement of tumor suppressor genes, other than PTEN, has been suggested. We carried out deletion mappings on chromosome 10, using PCR-based microsatellite analysis. LOH#10 was detected at similar frequencies in primary (8/17; 47%) and secondary glioblastomas (7/13; 54%). The majority (88%) of primary glioblastomas with LOH#10 showed LOH at all informative markers, suggesting loss of the entire chromosome 10. In contrast, secondary glioblastomas with LOH#10 showed partial or complete loss of chromosome 10q but no loss of 10p. These results are in accordance with the view that LOH on 10q is a major factor in the evolution of glioblastoma multiform as the common phenotypic end point of both genetic pathways, whereas LOH on 10p is largely restricted to the primary (de novo) glioblastoma.

Adult↗

PubMed2000

Extended structural variation of a pentanucleotide repeat in the GSTP1 gene: characterisation in a normal population and in thyroid and gastric tumours.

The promoter region of the human GSTP1 gene contains a polymorphic short tandem repeat (STR) locus consisting of pentanucleotide repeat units (ATAAA). In this work we report the existence of a total of 26 alleles in a Caucasian population. While differences in size (ranging from one to five base pairs) were responsible for the major variation, in five size-defined classes, two alternative sequences were found. Automatic fragment sizing and sequencing analysis revealed that this polymorphism is of a highly complex nature in contrast with previous reports. A genetic population study was carried out on a random sample from Portugal showing no deviation from Hardy-Weinberg equilibrium. Somatic instability studies were also performed on gastric and thyroid tumours using this STR: no instability was detected in thyroid tumour tissues when compared with their normal counterpart but in gastric tumour tissues microsatellite instability (MSI) was detected in 9.6% of the cases and loss of heterozygosity (LOH) also in 9.6% of the cases studied. The results obtained with GSTP1 in gastric cancer were compared with previously reported data on MSI using BAT-26 and several dinucleotide repeat markers.

Alleles↗

PubMed1999

Acquisition of the glioblastoma phenotype during astrocytoma progression is associated with loss of heterozygosity on 10q25-qter.

Loss of heterozygosity on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas and occurs in more than 80% of cases. We recently reported that PTEN (MMAC1) on 10q23.3 is mutated in approximately 30% of primary (de novo) glioblastomas but rarely in secondary glioblastomas that progressed from low-grade or anaplastic astrocytomas. Because secondary glioblastomas also show LOH#10, tumor suppressor genes other than PTEN are likely to be involved. We analyzed LOH on chromosomes 10 and 19, using polymorphic microsatellite markers in microdissected foci showing histologically an abrupt transition from low-grade or anaplastic astrocytoma to glioblastoma, suggestive of the emergence of a new tumor clone. When compared to the respective low-grade or anaplastic astrocytoma of the same biopsy, deletions were detected in 7 of 8 glioblastoma foci on 10q25-qter distal to D10S597, covering the DMBT1 and FGFR2 loci. Six of 8 foci showed LOH at one or two flanking markers of PTEN but did not contain PTEN mutations. LOH on 10p and 19q was found in only one case each. These data indicate that acquisition of a highly anaplastic glioblastoma phenotype with marked proliferative activity and lack of glial fibrillary acidic protein expression is associated with loss of a putative tumor suppressor gene on 10q25-qter.

Adult↗