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Biomedical subjects

M Guida

Publications and source records attributed to M Guida.

At least 37 records · Page 2Linked to original sources

A full scale application in the control of the filamentous bulking generated by Type 021 N F. thiothrix sp.

The presence of industrial effluent in the wastewater incoming to municipal activated sludge treatment plants sometimes causes bulking events. In order to control one of these events a strategy of bacterial selection was applied with an anoxic selector before the main oxidation basin utilising the screw pumps basin. The result of this work confirms what is reported in the literature about the possibility to utilize a metabolic control of some filamentous forms (particularly Type 021 N) with high organic load. The remedial action could be realized using already existing facilities, without any additional costs.

Bacteria↗

[Options for uterine distension during hysteroscopy].

BACKGROUND: This comparative study evaluated effectiveness, complications and patient satisfaction following the use of carbon dioxide (CO2) compared with physiological solution for uterine distension during hysteroscopy. The study was motivated by doubts concerning the choice of distension methods and the implications of their use. METHODS: The study population included 189 patients attending the outpatient services of the Obstetrics/Gynecological Clinic of the University of Naples for sterility/infertility disorders. Patients were randomly assigned by computer to either of two treatment groups. Both groups underwent hysteroscopy. In Group A (92 patients), uterine distension was performed using carbon dioxide (CO2), while in Group B (97 patients) physiological solution was used. Treatment was assessed for effectiveness, causes of discomfort, patient compliance and satisfaction rate. RESULTS: Compared with carbon dioxide (CO2), the use of physiological solution as a means of uterine distension was demonstrated certain advantages that were statistically significantly for the parameters of operating time, onset of vagal reactions, causes of discomfort, compliance and satisfaction rate, and cost-effectiveness of equipment. CONCLUSIONS: The use of physiological solution for uterine distension was observed to enhance patient compliance with hysteroscopy, because the method was better tolerated, more rapid and involved fewer failures.

Female↗

Use of leuprolide acetate plus tibolone in the treatment of severe premenstrual syndrome.

OBJECTIVE: To evaluate the effectiveness of GnRH agonist (GnRH-a) plus tibolone in the treatment of severe premenstrual syndrome (PMS). DESIGN: Prospective, double-blind, placebo-controlled clinical trial. SETTING: Department of Obstetrics and Gynecology, University of Naples Federico II, Naples, Italy. PATIENT(S); Thirty patients affected by severe PMS, aged 23-29 years (mean age +/- SD, 25.3 +/- 2.9 years). INTERVENTION(S): Treatment for two cycles with leuprolide acetate depot (3.75 mg IM for 28 days) in association with tibolone (2.5 mg/d orally) or placebo (1 tablet per day orally). MAIN OUTCOME MEASURE(S): The mean severity of each symptom and sign of PMS was evaluated using a visual analog scale during the last 7 days of each treatment cycle in comparison with the last 7 days of the cycle before treatment. RESULT(S): Mean scores for each of the adverse psychological/physical and positive psychological symptoms were significantly improved during treatment. No statistically significant difference was detected between patients treated with tibolone and placebo. A significantly lower number of hot flushes per day was observed in groups treated with GnRH-a and tibolone in comparison with GnRH-a and placebo. CONCLUSION(S): Tibolone administered in association with GnRH-a does not reduce the therapeutic effect of GnRH-a in women affected by PMS. Tibolone used in association with GnRH-a may provide long-term medical treatment for women with PMS.

Adult↗

Paclitaxel, cisplatin and lonidamine in advanced ovarian cancer. A phase II study.

A potential way to improve the results obtained with the standard carboplatin/cisplatin (CDDP)-paclitaxel treatment regimen in advanced ovarian cancer is to incorporate a modulating agent such as lonidamine (LND). In fact, LND has been shown to revert the resistance to cisplatin and to potentiate cisplatin activity experimental models and in clinical studies. 35 consecutive patients with advanced ovarian cancer, not previously treated with chemotherapy were treated with paclitaxel at a dose of 135 mg/m(2) intravenously (i.v.) on day 1 (in a 3 h infusion) and cisplatin at a dose of 75 mg/m(2) iv on day 2 plus LND orally (p.o.) at a dose of 450 mg/die for 6 consecutive days starting two days before chemotherapy, every 3 weeks for six cycles. Complete plus partial responses were observed in 8 (80%) out of the 10 women with measurable disease. In the 25 patients with evaluable disease, only four clinical progressions were observed (16%). Median progression-free survival (PFS) and overall survival (OS) were 28.5 (95% confidence interval (CI) 22.2-34.8) and 46.5 (95% CI 32.4-60.00) months respectively. Grade 3-4 neutropenia was observed in 9 (26%) patients. Alopecia, nausea and vomiting (Grade 3) were observed in 33 (94%) and 5 (14%) patients, respectively. In conclusion, the combination of CDDP/paclitaxel plus LND is active and tolerable in the treatment of advanced ovarian cancer.

Adult↗

Using complete breastfeeding and lactational amenorrhoea as birth spacing methods.

The aim of this study was to evaluate the effectiveness of lactational amenorrhoea and to determine the relationship between extended breastfeeding and the return of fertility. Breastfeeding pattern, basal body temperature, cervical mucus, salivary ferning, vaginal blood discharge, frequency of sexual intercourse, and the presence of ovulation in the first cycle after the resumption of menses with ultrasonography were evaluated in 40 women. All subjects completed the study with only one case of incomplete breastfeeding. No pregnancies were observed. The mean number of feeding sessions and mean interval between sessions decreased significantly (p <0.01) during the first six months postpartum (7.5 +/- 1.3 after 60 days postpartum vs. 5.7 +/- 2.1 after 180 days, and 3.6 +/- 0.8 vs. 5.1 +/- 0.9, respectively). Eight women (20%) menstruated before weaning, but none had an adequate thermal shift, while 32 (80%) had their first vaginal bleeding after weaning with 12 (37.5%) registering an adequate thermal shift. Both basal body temperature and salivary ferning proved to be suggestive of ovarian activity, while mucus characteristics were not reliable in identifying fertile periods. Our study showed that breastfeeding associated with lactational amenorrhoea proved to be a good method of postpartum fertility control. Since the importance of supplementation is still debated, it is recommended that a "complete" breastfeeding program be used.

Adult↗

Minilaparoscopic ovarian drilling under local anesthesia in patients with polycystic ovary syndrome.

OBJECTIVE: To assess pain control in patients with polycystic ovary syndrome (PCOS) who are undergoing ovarian drilling during minilaparoscopy under local anesthesia and conscious sedation and to evaluate the efficacy of this protocol compared with the traditional approach in terms of operative and discharge times, subsequent ovulation, and pregnancy. DESIGN: Prospective randomized study. SETTING: University hospitals and private day-surgery unit. PATIENT(S): Sixty-two infertile women with PCOS. INTERVENTION(S): Group A underwent minilaparoscopic ovarian drilling under local anesthesia and conscious sedation. Group B (control group) was treated with traditional ovarian drilling by laparoscopy under general anesthesia. MAIN OUTCOME MEASURE(S): Intraoperative pain score in group A. Hormonal profile before and after surgery, operative and discharge times, postoperative analgesic requirements, and reproductive follow-up in both groups. RESULT(S): Group A showed a good intraoperative pain score. The hormonal profile after surgery did not differ between groups A and B. Operative times were also similar for both groups. The number of patients discharged within 2 hours after surgery was significantly higher in group A. The need for postoperative analgesics was significantly higher in group B. No statistically significant differences were noted between the groups in terms of pregnancy and ovulation rates. CONCLUSION(S): Intraoperative and postoperative local anesthesia plus conscious sedation allows outpatient bilateral ovarian drilling by minilaparoscopy to be performed without general anesthesia. The high pregnancy rates, the simplicity of the method, and the faster discharge time offer a new option for patients with PCOS who are resistant to clomiphene citrate. Moreover, ovarian cauterization can be performed simultaneously with a diagnostic minilaparoscopy and integrated into the infertility workup of these patients.

Adult↗

Genomic organization of the UGT2b gene cluster on human chromosome 4q13.

The UDP-glucuronosyltransferases (UGTs) comprise a large family of proteins capable of detoxifying a wide variety of both endogenous and exogenous substrates. The primary function of this gene superfamily is to catalyze the glycosylation of substrates such as biogenic amines, steroids, bile acids, phenolic compounds and various other pharmacologically relevant compounds, including numerous carcinogens, toxic environmental pollutants and prescription drugs. This conjugation increases the solubility of these compounds, allowing them to be excreted more readily through hepatic or renal mechanisms. This paper describes the genomic characterization and chromosomal localization of three UGT2B genes which together comprise part of a large cluster of related sequences, including pseudogenes found on human chromosome 4q13. A genomic map spanning approximately 500-1000 kb of this region reveals the presence of three previously described UGT2B genes, at least two previously uncharacterized pseudogenes and a significant number of remnant gene fragments and places UGT2B4 between UGT2B7 and UGT2B15. Additionally, access to a large reference DNA bank allowed us to calculate allele frequencies for two UGT2B SNPs: D85R in UGT2B15 and Q458D in UGT2B4 amongst 803 unrelated individuals representing five ethnic populations. The data presented here suggest a recent evolutionary history of gene duplication, mutation and rearrangement. Furthermore, they suggest that a re-evaluation of the current description of the UGT2B gene family with respect to the number of specific genes, degree of allelic diversity and molecular evolution may be necessary.

Biological Evolution↗

Characterization of two highly polymorphic human tryptase loci and comparison with a newly discovered monkey tryptase ortholog.

Tryptases are serine proteases involved in mast cell-mediated inflammatory responses which represent potential targets of drugs against diseases such as asthma, arthritis and inflammatory bowel disease. In order to interpret pharmacodynamic data on the tryptase inhibitors undergoing clinical trials, we defined the genetic variability of the tryptase 1 (TPS1) and tryptase 2 (TPS2) loci by screening a reference population of 32 individuals representing three major ethnic groups (Caucasian, African American, Asian). Using overlapping PCR products, we resequenced the entire tryptase genes with the only exclusion of TPS2 intron 1 and 20 bp of TPS2 5' untranslated region included in exon 1 and we identified 21 novel single nucleotide polymorphisms in TPS1 and 17 single nucleotide polymorphisms plus a large polymorphic deletion in the TPS2 gene. We also compared the type, frequency and distribution of single nucleotide polymorphisms in TPS1 and TPS2 and we observed that the polymorphism frequency within these two loci is unexpectedly high (approximately 1 SNP every 90 bp) and that some of the allele frequencies differ significantly among the three ethnic groups. Based on differences observed in preclinical studies using a cynomolgus monkey (Macaca fascicularis) asthma model system, we investigated the difference between monkey and human tryptase genes in order to better understand the mechanism of action of our tryptase inhibitors.

Amino Acid Sequence↗

The importance of user compliance on the effectiveness of natural family planning programs.

Nowadays, there is an increasing interest in natural family planning methods. The biological basis for the application of natural family planning methods is the recognition of ovulation and, more extensively, of the fertile period. Several studies in the past decade have shown the efficacy of these methods and that the main cause of failure was either a conscious departure from the rules of the method or erroneous application of the method. Another problem affecting natural family planning that has been highlighted is the relatively high discontinuation rate. These features are probably due to low compliance in applying the natural family planning rules, which may be too demanding for a number of couples. In this review, there are comments on the application of natural family planning methods, the discontinuation rates and the failure of the method due to mistakes in the studies carried out in the past 15 years. Steps that can be taken to limit mistakes and discontinuity are also addressed.

Family Planning Services↗

Population distribution and effects on drug metabolism of a genetic variant in the 5' promoter region of CYP3A4.

BACKGROUND: There are large interindividual differences in CYP3A4 expression and in the metabolism of drug substrates for this enzyme. We and others have identified a polymorphism in the 5' promotor region of the CYP3A4 gene; however, its functional significance is not currently known. This study was conducted to determine whether this polymorphism plays a clinically important role in determining CYP3A4 phenotype. METHODS: An adenine (A) to guanine (G) transition was identified in the 5' promotor region of the CYP3A4 gene at position -292 (from the start codon), in a sequence motif known as the nifedipine-specific element. The frequency of this polymorphism was assessed in 802 healthy volunteers from five broadly defined racial groups. The population distribution of the G allele in these groups was as follows: white Americans (3.6%; n = 273), black Americans (54.6%, n = 186), Hispanic Americans (9.3%; n = 188), Japanese Americans (0.0%; n = 77), and Chinese Americans (0.0%; n = 78). In a subsequent study, 90 additional black Americans were genotyped, and a subset of the homozygous subjects (AA, n = 8; GG, n = 23) were given the CYP3A4 probe substrates erythromycin and nifedipine to allow genotype-phenotype comparisons to be made. RESULTS: There was no difference in the rate of CYP3A4-dependent demethylation of erythromycin (erythromycin breath test) or the pharmacokinetics of nifedipine or its CYP3A4-dependent metabolite dehydronifedipine between the two genotype groups (AA or GG). CONCLUSIONS: This promotor region polymorphism does not appear to play a major role in determining constitutive CYP3A4 expression.

Area Under Curve↗

Efficacy of methods for determining ovulation in a natural family planning program.

OBJECTIVE: To evaluate the efficacy in ovulation detection of methods used in natural family planning in comparison with pelvic ultrasonography. DESIGN: Prospective analysis of ovulation detection by natural family planning methods and ultrasonography. SETTING: Natural family planning clinic, Department of Obstetrics and Gynecology, University of Naples "Federico II". PATIENT(S): Forty healthy women who were highly motivated to use natural family planning. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Transvaginal ultrasonographic findings, urinary LH levels, salivary beta-glucuronidase activity, salivary ferning levels and characteristics of cervical mucus, and BBT. RESULT(S): Urinary LH level determination yielded a 100% correlation with the simultaneous ultrasonographic diagnosis of ovulation. Mucus sensations and characteristics yielded a 48.3% correlation when simultaneously evaluated with ovulation. Beta-glucuronidase levels yielded a 27.7% correlation. The salivary ferning test had a 36.8% ovulation-detection rate the day of ovulation, but 58.7% of results were uninterpretable. Body temperature measurements yielded a 30.4% correlation with the simultaneous ultrasonographic diagnosis of ovulation. CONCLUSION(S): Measuring urinary LH levels is an excellent method for determining ovulation. Although variations in mucus characteristics and basal body temperature correlate somewhat with ovulation, the length of the fertile period is overestimated with these methods. The salivary ferning test and measurement of beta-glucuronidase levels are not good methods for home ovulation testing.

Adult↗

Scutumplasty: costal cartilage versus bone paté.

This study was carried out to evaluate the anatomical and hearing results of the reparation of attic defects in closed tympanoplasty. Reparation was carried out in 194 patients by using a costal cartilage allograft, and in 159 patients with a bone pate autograft. The follow-up was from 1 to 5 years. The study was not truly randomized owing to an occasional lack of allogenic costal cartilage. In the group 'costal cartilage' a partial resorption was observed in 5.7% and a complete resorption in 4.7% of the cases. In the group 'bone pate', partial resorption was observed in 5.5% and total resorption in 2.7% of the patients. Satisfactory hearing results were obtained in 86% of the patients of the group 'costal cartilage' and in 82% of the patients of the group 'bone paté'. Both graft materials may be recommended for repairing erosions caused by the cholesteatoma in the wall of the external auditory canal.

Adult↗

Revertant and potentiating activity of lonidamine in patients with ovarian cancer previously treated with platinum.

PURPOSE: Lonidamine (LND) is an energolytic derivative of indazol-carboxylic acid that has been shown to enhance cisplatin (CDDP) activity in both sensitive (A2780) and resistant (A2780/Cp8) ovarian cancer cell lines. The aim of this study was to confirm the potentiating or reverting activity of LND on CDDP activity obtained in experimental models in a phase II study of advanced ovarian cancer patients previously treated with platinum-based regimens. PATIENTS AND METHODS: Twenty-seven consecutive women with histologically proven and measurable ovarian cancer previously treated with platinum compounds were treated with CDDP plus LND. CDDP was administered at 1 mg/kg intravenously (IV) once weekly for 6 weeks and every 3 weeks thereafter until disease progression or toxicity. LND was administered at 450 mg daily (1 tablet every 8 hours) for the entire period of therapy starting 3 days before the first CDDP administration. In addition, a higher LND dosage was provided on the day of CDDP administration in an attempt to maximize the synergy of this drug with CDDP. RESULTS: Ten patients achieved a complete response (CR) or partial response (PR) for an overall response rate of 37% (95% confidence interval [CI], 19% to 55%). In particular, responses were observed in five of 18 (28%) refractory or early relapsed patients (one CR and four PRs) and in five of nine patients (55%) in the late-relapsed group (two CRs and three PRs). Grade 3 or 4 anemia, leukopenia, and thrombocytopenia were observed in 19%, 15%, and 11% of patients, respectively, whereas seven of 27 patients (26%) showed LND-related myalgia. Grade 3 renal toxicity was observed in two patients (8%). Neurotoxicity, often concealed by LND-related myalgia, was recorded as grade 1 or 2 in six patients (22%) and as grade 3 in one (4%). CONCLUSION: The 37% response rate observed in this study (28% in refractory or early-relapsed patients), suggests that the synergism between CDDP and LND observed in vitro against ovarian cancer cell lines can be clinically confirmed. However, larger series and randomized studies are needed to assess definitely the revertant activity of LND on CDDP-refractory patients.

Adult↗

An overview on the effectiveness of natural family planning.

Recent years have witnessed important developments in natural family planning (NFP), which is based on the observation of fertile and infertile periods of the menstrual cycle, so that the couple is able to know when sexual intercourse may lead to a pregnancy. A review of the main studies regarding the effectiveness of NFP showed a decrease in the Pearl Index and life table values from the early 1980s to date, indicating that progress both in the teaching and in the application of these contraception, methods has been achieved. The main cause of lack of success seems to be the misapplication of NFP rules, whereas the errors due to the method itself are few. Furthermore, it seems that the symptothermal method might give better results than the ovulation method, even though no comparative study has been carried out, and that the first studies on the lactational amenorrhea method show encouraging results. Finally, it seems that NFP is best suited for 'spacers' of pregnancies, rather than for 'limiters'. Indeed, the former are more likely to show good compliance, since the sexual abstinence periods are limited and an unwanted pregnancy is not regarded as a completely negative event.

Clinical Trials as Topic↗

Mutational spectrum in the neurofibromatosis type 2 gene in sporadic and familial schwannomas.

Using a heteroduplex approach and direct sequencing, we have completed the screening of approximately 88% of the neurofibromatosis type 2 (NF2)-coding sequence of DNA extracted from 33 schwannomas from NF2 patients and from 29 patients with sporadic schwannomas. The extensive screening has resulted in the identification of 33 unique mutations. Similarly to other human genes, we have shown that the CpG sites are more highly mutable in the NF2 gene. The frequency, distribution, and types of mutations were shown to differ between the sporadic and familial tumors. The majority of the mutations resulted in protein truncation and were consistent with more severe phenotype, however three missense mutations were identified during this study and were all associated with milder manifestations of the disease.

Codon↗

Subcutaneous recombinant interleukin-2 plus chemotherapy with cisplatin and dacarbazine in metastatic melanoma.

The aim of our study was to verify the efficacy and tolerability of subcutaneous low doses of interleukin-2 with cisplatin and dacarbazine for malignant melanoma. 24 patients were included. The following schedule was used: cisplatin (CDDP) 100 mg/m2 day 1; darcarbazine (DTIC) 375 mg/m2 days 1-5; recombinant interleukin-2 (rIL-2) 4.5 million IU x 2/day days 13-17 and 20-24. The therapy was recycled every 28 days. 10 patients obtained clinical remission (42%), with 2 complete responses (8%) persisting for 12 and 15+ months, and 8 partial responses (35.5%) with a median duration of 5 months. Median survival of all 24 patients was 8 months, 13 months for responders and 6 months for non-responders. Responses were seen predominantly in lymph nodes (48%) and skin-soft tissue (38%), but were also seen in the liver (29%) and lung (14%). Treatment was relatively well tolerated and toxicity was mainly related to chemotherapy.

Adult↗

Strategies for Amplification of Trinucleotide Repeats: Optimization of Fragile X and Androgen Receptor PCR.

Background: Trinucleotide repeat regions are heritable unstable elements that change in copy number from generation to generation. Amplification of these triplet repeats is an important diagnostic tool for molecular medicine. However, these repeats are often difficult to amplify and may require the use of different cosolvents or amplification strategies. Methods and Results: We used the fragile X and androgen receptor triplet repeat regions to demonstrate a series of conditions that may be used to optimize the amplification of repeat sequences. Conclusions: For androgen receptor, we show that predigestion of the template DNA was sufficient to generate consistent amplification. In the case of fragile X we found that predigestion, when combined with use of betaine as a destabilizing additive, was superior to other methods and yielded consistent amplification of normal and premutation alleles in both isotopic and nonisotopic reactions.

Journal Article↗