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Biomedical subjects

A Neri

Publications and source records attributed to A Neri.

At least 91 records · Page 5Linked to original sources

Conservative management of postmenopausal pelvic echo-free findings--preliminary results.

OBJECTIVES: To develop a conservative protocol for the treatment of echo-free findings in the pelvis, diagnosed by sonography in post-menopausal women, in order to avoid unnecessary surgical intervention. METHODS: A prospective study where each post-menopausal-patient underwent sonographic evaluation of the pelvic mass, serum Ca-125 levels, ambulatory aspiration of the cyst, and operative laparoscopy if necessary. RESULTS: One hundred and eighty-two women were included in the 3 years of the study. Only two cases of malignancy were diagnosed. There were no false-negative results. CONCLUSION: Although the results of our protocol of conservative management look promising, we cannot draw final conclusions because of the small sample size. Perhaps as our knowledge increases, physicians will feel more confident in handling adnexal findings conservatively.

Adnexa Uteri↗

p53 tumour suppressor gene and RAS oncogenes: molecular analysis in the chronic and leukaemic phases of essential thrombocythaemia.

A panel of 51 cases of essential thrombocythaemia (ET), in chronic or leukaemic phase, was investigated for p53 gene and RAS oncogenes mutations by PCR-SSCP-direct sequencing. No RAS oncogenes mutations were detected, but p53 mutations were identified in three cases: 1/27 cases (approximately 4%) in chronic phase not undergoing chemotherapy, 1/19 cases (approximately 5%) in chronic phase undergoing chemotherapy, and 1/5 cases (20%) which had progressed to leukaemia. Our results suggest that: (1) p53 gene mutations occur sporadically in the chronic phase of ET, independent of chemotherapy, and may contribute to the progression to the leukaemic phase in a limited number of ET patients; (2) the RAS genes family does not seem to be involved in the pathogenesis of ET, unlike other bcr/abl negative chronic myeloproliferative diseases (CMPDs).

Adult↗

p53 protein expression in laryngeal squamous cell carcinomas bearing wild-type and mutated p53 gene.

We performed an immunohistochemical analysis to investigate the expression of p53 protein in a panel of 18 laryngeal squamous cell carcinomas, 15 primary tumours and three in relapse, previously analysed by us for the presence of p53 gene mutations. Dysplastic and/or normal surrounding mucosa was evaluated in 15 different tumours. The results of our study are the following: (1) expression of p53 protein was observed in one out of five tumours positive for p53 gene mutations (20%) and in 10 out of 13 (80%) negative cases; (2), p53 protein over-expression was frequently observed in normal and/or dysplastic mucosa surrounding either wild-type (7/11) or mutated p53 tumours (2/4); (3), p53 immunoreactive cells showed a pattern of distribution in normal and mildly/ moderately dysplastic mucosa (basal layers), different from that in severely dysplastic mucosa (whole thickness). These data further support the hypothesis that p53 protein over-expression may be a marker of the earliest phases of multistep tumorigenesis in laryngeal squamous cell carcinoma.

Aged↗

Future fertility following conservative management of complete abortion.

Dilatation and curettage is the usual procedure implemented in cases of incomplete or missed abortion in the first trimester of pregnancy. The management of complete abortion depends on pregnancy age. We examined the possibility that conservative management of complete abortion can be effective and does not affect future fertility. A total of 172 women who presented with complete abortion to our Ambulatory Gynecological Clinics of the Dan Region, Israel, were managed conservatively. Of 161 who desired to become pregnant, 118 (73%) conceived within 18 months. We conclude that it is possible to avoid curettage in the management of complete abortion of<8 weeks' gestational age with little or no effect on future fertility.

Abortion, Incomplete↗

Ovarian angiotensin-converting enzyme activity in humans: relationship to estradiol, age, and uterine pathology.

The present study was designed to measure angiotensin-converting enzyme (ACE) activity in the human ovary and in serum and to relate this activity to age, serum estradiol levels, and uterine and endometrial pathology. ACE activity was determined in 56 females by a radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. Ovarian ACE activity, but not serum ACE, was found to increase with age (P < 0.01) and was significantly greater in postmenopausal subjects (n = 31; 1.35 +/- 0.05 nmol/mg.min) than in subjects with active ovaries (n = 21; 0.65 +/- 0.2 nmol/mg.min; P = 0.0033). Ovarian ACE activities in fertile women in the preovulatory phase (n = 14) and the postovulatory phase (n = 7) were not statistically different (0.66 +/- 0.23 and 0.63 +/- 0.17 nmol/mg.min, respectively). Serum ACE activities were similar in females with active and nonactive ovaries (87.6 +/- 5.0 vs. 81.7 +/- 5.3 nmol/mL-min, respectively). Serum estradiol levels in fertile women were significantly higher than those in postmenopausal women (P = 0.0023). Serum estradiol levels were negatively correlated with age (r = -0.46; P = 0.0041) and were not correlated with either serum ACE activity (r = 0.080; P = NS) or ovarian ACE activity. In summary, human ovarian ACE activity, but not serum ACE, is positively correlated with age. Serum estradiol levels decrease with age, but are not correlated with either ovarian or serum ACE activity. Endogenous serum estradiol levels had no apparent effect on ovarian or serum ACE activity. The presence of uterine pathology affects ovarian ACE activity. The cause of the increased ovarian ACE activity is not clear, but may be related to the aging process.

Adult↗

Perinatal complications following gestational diabetes mellitus how 'sweet' is ill?

OBJECTIVE: We tested the effect of patient compliance, fasting plasma glucose on oral glucose tolerance test, maternal body constitution, and the method of treatment (diet versus insulin) on the perinatal outcome of patients with gestational diabetes mellitus. STUDY DESIGN: A prospective population-based study compared the perinatal outcome of patients with gestational diabetes mellitus (n = 470) (diabetic with regard to the parameters specified above) and a contemporaneous control group (nondiabetic, n = 250). RESULTS: The diabetic and control groups were matched in demographic characteristics. Patient compliance reduced the rate of macrosomia (14.4%) and neonatal hypoglycemia (3.4%) but not to the levels of the control group (5.2% and 1.2% respectively, p < 0.05). The level of fasting plasma glucose on the oral glucose tolerance test had no effect on perinatal outcome. Intensified (insulin) treatment reduced the rate of macrosomia and large-for-gestational age infants in the subgroups with intermediate and high levels of fasting plasma glucose on the oral glucose tolerance test (9.5%/14.2% and 12.2%/24.2% respectively), again not to levels of the control group (5.2%/10.8%). Obese patients were found to have more perinatal complications than lean patients. Intensified (insulin) treatment has proved to be beneficial in terms of reducing the rate of perinatal complications in the obese patients, but not to the corresponding levels of the control group. Such treatment had no effect on the lean patients. CONCLUSIONS: Strict control of maternal hyperglycemia and high patient compliance are imperative for an effective reduction of perinatal complication in patients with gestational diabetes mellitus. The desired plasma glucose level in the glycemic control of these patients should be further reduced, thus bringing the rate of perinatal complications to that of the normal population.

Adult↗

Intranasal nafarelin versus buserelin (short protocol) for controlled ovarian hyperstimulation before in vitro fertilization: a prospective clinical trial.

The aim of this study was to compare the effect of nafarelin acetate with that of buserelin acetate nasal spray, when administered in a 'short' protocol, as an adjunct to human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation before in vitro fertilization (IVF). Twenty-two IVF subjects were randomly recruited. Each underwent two consecutive treatment cycles; one with buserelin (900 micrograms/day) and another with nafarelin (400 micrograms/day). The treatment protocol included transnasal gonadotropin-releasing hormone (GnRH) analog from the second cycle day and hMG from the fourth day of the cycle. The buserelin and nafarelin cycles did not differ significantly in the following parameters: baseline hormone profile, duration of GnRH analog treatment, mean hMG dose required, peak estradiol levels, number of preovulatory follicles, number of aspirated oocytes, fertilization rate and number of transferred or frozen embryos. No side-effects or cancellations of treatment were recorded. The average dose required was lower for nafarelin and, because this analog was given only twice a day, it was more convenient to administer. These findings suggest that nafarelin is as effective as buserelin (when administered in a "short' protocol) in achieving controlled ovarian hyperstimulation. It even offers advantages over buserelin with respect to the total dose required (which probably reflects its relatively high potency) and the subjects' compliance.

Administration, Intranasal↗

The involvement of the candidate proto-oncogene NFKB2/lyt-10 in lymphoid malignancies.

NF-kappa B transcription factors regulate the expression of a variety of genes involved in immune responses and cell growth. In higher vertebrates, the NF-kappa B family encompasses five distinct members. Three NF-kappa B proteins, p65/RelA, RelB, and c-rel/Rel, have high transactivating potential in addition to their DNA binding activity. Two subunits, NF-kappa B1p50 and NF-kappa B2p52, coded respectively by the NFKB1 and NFKB2 genes, may only have DNA binding activity. Moreover, p50 and p52 subunits are translated as precursors, respectively p105 and p100, which can be processed into the mature active forms by the removal of their carboxy-terminal ankyrin domain. The five proteins share a homologous amino-terminal domain (rel domain) involved in DNA binding, dimerization, nuclear transport, and binding of regulatory subunits. All members form homo- and heterodimeric complexes with different DNA binding specificity and transactivating potential. Structural alterations of some members of the NF-kappa B gene family have been observed in lymphoid malignancies. In particular, the NFKB2 gene, localized on chromosome 10q24, represents a candidate proto-oncogene, since it has been found rearranged in certain types of lymphoma and more commonly in cutaneous lymphoma. Molecular analysis indicated that these rearrangements may occur as a consequence of chromosomal translocations or small internal chromosomal deletions. Rearrangements cluster within the carboxy-terminal ankyrin domain of the NFKB2 gene leading to the production of carboxy-terminally truncated proteins which, in some cases, are fused to heterologous protein domains. Experimental data showed that these abnormal proteins are constitutively localized in the nucleus, have lost the transcriptional repressor functions typical of normal NF-kappa B2p52 and may be capable of transactivation activity. These findings suggest that abnormal NFKB2 proteins may contribute to lymphomagenesis by altering the NF-kappa B system, both quantitatively and qualitatively, and leading to the activation of specific subsets of kappa B-controlled genes.

Chromosome Mapping↗

Selective second trimester fetal reduction due to 46XY, 10q+ fetus.

Second-trimester amniocentesis of a twin gestation revealed one normal karyotype, whereas the other had a 46XY, 10q+, indicating an excess of genetic material on chromosome number 10. A selective reduction of the affected twin was carried out on the 20th week of gestation; the outcome of pregnancy and delivery at term of the normal twin were both uneventful.

Adult↗

Once-daily fluocinonide-bifonazole combination for the treatment of vulvar itching and vulvovaginal candidiasis. Preliminary study.

Vulvovaginitis presents a therapeutic challenge. Treatment of vulvovaginal candidiasis with topical imidazole preparations is well accepted. In our work we tested a new cream combining antifungal Bifonazole with a corticosteroid agent (Fluocinonide). The results suggest that most of the patients with vulvovaginitis can benefit from treatment with this new combination cream.

Adolescent↗

The biology of ovarian cancer of epithelial origin.

Ovarian cancer of epithelial origin is associated with the highest mortality rate of all gynecologic malignancies. Since no symptoms or signs are manifested at the early stages of the disease, it is no surprise that in 75% of patients peritoneal metastases are found during primary surgery. Despite advances in conservative treatment methods (invasive and noninvasive), screening for early detection of the disease is not yet available, and the overall survival rate is as low as 5-15%. Recent studies in molecular biology have drawn attention to different research directions in ovarian cancer and have contributed much to our understanding of this disease and its underlying pathologic mechanisms. This review is intended to highlight some of the new aspects of this research, specifically: hereditary ovarian cancer, genetic background in terms of chromosomal changes, DNA anomalies, oncogenes, tumor-suppressor genes, peptide growth factors and cytokines, invasiveness and metastasis, and finally, drug resistance. No breakthrough has as yet occurred in any of the subjects screened in this review, but results are promising. The clinical application of the steadily increasing knowledge in the biology of ovarian cancer may assist in the development of new treatment modalities that will improve survival.

Cell Transformation, Neoplastic↗

Molecular analysis of cutaneous B- and T-cell lymphomas.

Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs) represent a consistent group of B- and T-cell malignancies. We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor-suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6, and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were assayed using PCR, single-strand conformation polymorphism analysis, and direct DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or oncogenes were found in 25 of the 52 CBCLs. In particular, we detected rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of these cases showed a germline arrangement of the Ig genes. Clonal rearrangements of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt-10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53 gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1) clonal rearrangement of Ig genes is frequently undetectable by means of Southern blot in CBCLs (60%); (2) genetic lesions are involved in a limited but significant fraction of primary CLs showing a molecular marker of clonality (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci, associated with specific subsets of nodal lymphoid neoplasias, are rarely observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may play a pathogenetic role in non-acute T-cell malignancies and that, in the context of lymphoid malignancies, CLs may represent a favorable target for the possible oncogenic potential of the NFKB2/lyt-10 gene.

Adult↗

Microinjection of monoclonal antibody PAb421 into human SW480 colorectal carcinoma cells restores the transcription activation function to mutant p53.

The p53 tumor suppressor is a transcription factor frequently mutated in human malignancies. Tumor-derived p53 missense mutants are defective in sequence-specific DNA binding and fail to activate p53 target genes. mAb PAb421 was shown previously to restore DNA binding to selected p53 mutants in vitro. Here we show that mAb PAb421 when microinjected into human SW480 colorectal carcinoma cells restores the transcription activation function to the resident mutant p53 (arg to his 273, pro to ser 309). Codon 273 is the second most frequent p53 missense mutant found in human tumors. Our results lend support to the concept of restoring wild-type function to mutant p53 as a strategy for cancer therapy.

Antibodies, Monoclonal↗