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Biomedical subjects

M Giordano

Publications and source records attributed to M Giordano.

At least 19 recordsLinked to original sources

Deep dyspareunia and sex life after laparoscopic excision of endometriosis.

BACKGROUND: Among subjects with endometriosis and deep dyspareunia (DD), those with endometriosis of the uterosacral ligament (USLE) have the most severe impairment of sexual function. This study examines the effect of laparoscopic excision of endometriosis on DD and quality of sex life. METHODS: This observational cohort prospective study included 68 women with endometriosis suffering DD (intensity of pain >or= 6 on a 10-cm visual analogue scale). Patients underwent laparoscopic full excision of endometriosis. Following surgery, they were asked to use nonhormonal contraception devices. Before surgery, at 6- and at 12-month follow-up, patients answered a self-administered questionnaire based on the Sexual Satisfaction Subscale of the Derogatis Sexual Functioning Inventory. RESULTS: At 6- and 12-month follow-up, women with and without USLE had significant improvement in DD. Subjects with USLE reported increased variety in sex life, increased frequency of intercourse, more satisfying orgasms with sex, relaxing more easily during sex and being more relaxed and fulfilled after sex. Similar improvements were observed among women without USLE; however, for some variables statistical significance was not reached. CONCLUSIONS: Surgical excision of endometriosis improves not only DD but also the quality of sex life.

Adult↗

A family-based study does not confirm the association of MYO9B with celiac disease in the Italian population.

Association between Myosin IXB (MYO9B) gene polymorphisms and celiac disease (CD) was recently detected by a case-control association study in the Dutch, but not confirmed in the British and Swedish/Norwegian populations. We tested the association between CD and the three most associated single nucleotide polymorphisms (SNPs) in the Dutch study by the transmission disequilibrium test in the Italian population. A total of 252 pediatric patients and 504 parents were genotyped. No transmission distortion was detected either for the single SNPs or for their haplotypic combinations. Control allele frequencies, calculated from untransmitted alleles, were significantly different from those of the Dutch control population. Conversely, allele frequencies were very similar in Italian, British, Swedish/Norwegian and Dutch patients. In conclusion, MYO9B is not involved in CD susceptibility in the Italian population. The difference with the Dutch result might be explained by an imperfect selection of the Dutch controls.

Adult↗

Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma in a general population study.

Differences in response to carcinogenic agents are due to the allelic variants of the genes that control it. Key genes are those involved in the repair of the DNA damage caused by such agents. This paper describes the results of a case-control epidemiological study designed to determine the genotypes of four of these genes in persons exposed to a single genotoxic factor, i.e. asbestos, who had or had not developed malignant mesothelioma (MM). Our working hypothesis was that an imperfect DNA repair, as revealed by subtle polymorphic variants, could reduce protection against the chronic DNA insult provoked by asbestos and eventually result in mutagenesis and cancer. Seven variants (i.e. XRCC1-R399Q-NCBI SNP, XRCC1-R194W, XRCC3-T241M, XRCC3-IVS6-14, XPD-K751Q, XPD-D312N, OGG1-S326C) were investigated in 81 patients and 110 age and sex-matched controls, all residents at Casale Monferrato, a Piedmontese town highly exposed to asbestos pollution. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When considered as a categorical variable, XRCC1-399Q showed an increased OR both in heterozygotes (OR=2.08; 95% CI=1.00-4.33) and homozygotes (2.38; 95% CI=0.82-6.94), although individual ORs were not significant. When it was considered as a continuous variable OR was significant (OR=1.68; 95% CI: 1.02-2.75). When genotypes were divided into "non-risk" and "risk" genotypes, i.e. those thought to be associated with increased risk in the light of the functional significance of the variants, XRCC1-399Q (Q homozygotes+Q/R heterozygotes versus R homozygotes) had an OR=2.147 (95% CI: 1.08-4.28), whereas that of XRCC3-241T (T homozygotes+M/T heterozygotes versus M homozygotes) was 4.09 (95% CI: 1.26-13.21) and that of OGG1-326C was increased, though not significantly. None of the haplotypes showed a significantly different frequency between patients and controls. This is the first report of an association between polymorphisms in DNA repair genes and asbestos-associated MM. Our data indicate that genetic factors are involved in MM development.

Aged↗

A study on glucose metabolism in a small cohort of children and adolescents with kidney transplant.

Post-transplant diabetes mellitus (PTDM) and impaired glucose tolerance are now considered among the major adverse events following organ transplantation. The present study was aimed at investigating the regulation of glucose metabolism in pediatric recipients of a kidney transplant (KT), receiving tacrolimus or cyclosporine A-based immunosuppression. Twelve subjects, eight males and four females, aged 12.1+/-3.8 yr, and with a mean time from KT of 45.6 months were enrolled in the study. All patients had a basal evaluation of fasting glucose (GF), fasting insulin (IF), C-peptide and glycated hemoglobin (HbA1c) levels. They then underwent oral glucose tolerance test (OGTT), with measurement of blood glucose and insulin concentration. Two children had impaired GF, associated with supernormal HbA1c levels, one patient showed impaired glucose tolerance, none had PTDM. Peripheral insulin resistance, as measured by quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment estimate of insulin sensitivity (HOMA-IR) index, was enhanced in 3 patients. Subsequently, GF significantly increased with time from transplant (p=0.01), while fasting C-peptide and the area under the curve of insulin correlated with creatinine clearance. In conclusion, our results, although generated in a small sample size, would suggest that long-term follow-up of children receiving a KT should extend to explore the response to oral glucose load and at least the basal measure of insulin response.

Adolescent↗

[Nearly total thyroidectomy: versus total thyroidectomy: our experience].

AIM: Generally, the classification of thyroidectomy as benign pathology is: multinodular toxic goitre, simple goitre, toxic adenoma, Base-dow disease, Hashimoto's tyroiditis Subtotal thyroidectomy provides for the removal of the gland except for a bilateral residue of about 6-10 g, near total thyroidectomy provides for the near total removal of the gland except for a residue inferior to 5 grams. Near total thyroidectomy has taken the place of the subtotal thyroidectomy. METHODS: In two years, in our institute, there have been exeuted: 96 near total thyrodectomies, 96 total thyroidetomies, 8 lobectomies ad two revues for recurrencies. RESULTS: In 2 cases there have been haemorrhagies after nearly total thyroidetomy. Only in 1 case we practiced tracheotomy for follicular carcinoma infiltering thiroidic cartilage. In 2 cases treated with nearly total thyroidetomy and in 4 cases treated with total thyroidetomy, there has been temporary hypoparathyroidism. In no case treared wih nearly total thyroidetomy and in 2 cases treated with total thyroidetomy, there has been permanent hypo-parathyroidism. In 5 cases treated with total thyroidetomy and in no case treated with nearly total thyroidetomy, there has been, monolateral, temporary paralysis of the inferior laryngeal nerve that solved in 6 months for 3 patients and in 2 months for 2 patients. CONCLUSIONS: There has not been permanent paralysis of the mono or bilateral inferior laryngeal nerve. Even if the surgical approach to the benign disease is now orientated to the total thyroidectomy, a more conservative surgery is, in our opinion, justified when a malignant pathology is excluded and considering also the low effect of recurrencies and hypothyroidism.

Adolescent↗

Carcinoid of the vermiform appendix. Description of three clinical cases and review of the literature.

Carcinoids of the appendix represent a separate class of tumours with characteristics that vary between benign (adenomas) and malignant (carcinomas) neoplasias. A recent nomenclature identifies them as diffuse neuroendocrine system (DNS) and/or, parallely, as neuroendocrine tumours (NET): the gastroenteric tract is the site of about 64.3% of carcinoids, followed by the respiratory tract with 25.3%. Among the gastrointestinals, tumour of the small intestine is the one with the highest incidence with 28.5%, followed by the appendix with 4.77%, the rectum with 13.6% and the stomach with 4.6%. Carcinoid of the colon has an incidence of 8.62%, with the caecum which alone represents 34.5% of colic localisations. The 3 cases described are an example of the behavioural unpredictability of intestinal carcinoids. The first case is that of a female patient in whom the primary tumour was only discovered after liver metastasis was documented. The second case regards a girl who, at admission, presented a picture of acute abdomen with the symptomatological characteristics of acute appendicitis. She was submitted to an appendicectomy. Subsequent investigations carried out in the postoperative period documented the presence of liver metastasis at the V and VI liver segments. The last case, similar to the second from certain points of view, shows the need to carry out a right hemicolectomy with removal of locoregional lymphnodes in the event of an appendicular carcinoid >2 cm. Both laboratory and instrumental examinations contribute to the diagnosis of intestinal carcinoid. The main laboratory examinations are based on the measurement of serotonin and urinary 5-hydroxy-indolacetic acid. First level instrumental examinations for the diagnosis of intestinal carcinoid are represented by CT with and without contrast medium, diagnostic endoscopy and, to better highlight the presence of locoregional metastases, scintigraphy with octreotide and PET. An alternative treatment of liver metastases other than surgery is most certainly chemoembolisation. This latter treatment has also proved very effective as a neoadjuvant treatment for liver metastases before subjecting the patient to liver resection. Treatment with somatostatin, on the other hand, proved effective in controlling tumour secretion, so attenuating the inconveniences of carcinoid syndrome.

Journal Article↗

Concordance, disease progression, and heritability of coeliac disease in Italian twins.

BACKGROUND AND AIMS: We adopted the twin method to disentangle the genetic and environmental components of susceptibility to coeliac disease (CD). We estimated disease concordance rate by zygosity and HLA genotypes, discordance times, progression rates to disease, and heritability. METHODS: We crosslinked the Italian Twin Registry with the membership lists of the Italian Coeliac Disease Association and recruited 23 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs with at least one affected member. Zygosity was assigned by DNA fingerprinting, and HLA-DQ and DR alleles were genotyped. Disease status was ascertained by antiendomysial, anti-human tissue transglutaminase antibodies, and bowel biopsy. RESULTS: Concordance was significantly higher in MZ (83.3% probandwise, 71.4% pairwise) than in DZ (16.7% probandwise, 9.1% pairwise) pairs. Concordance was not affected by sex or HLA genotype of the co-twin and being MZ was significantly associated with the occurrence of CD (Cox adjusted hazard ratio 14.3 (95% confidence interval 4.0-50.3)). In 90% of concordant pairs the discordance time was <or=2 years. MZ and DZ co-twins had 70% and 9% cumulative probability of having symptomatic or silent forms of CD, respectively, within five years. Under ACE (additive genetic, common, and unshared environmental factors) models, with CD population prevalences of 1/91 and 1/1000, heritability estimates were 87% and 57%, respectively. CONCLUSION: MZ pairs have a high probability of being concordant, regardless of sex or HLA genotype. Most of the affected co-twins receive a diagnosis within two years. A remarkable proportion of phenotypic variance is due to genetic factors.

Adolescent↗

Estimating the demand for municipal waste compost via farmers' willingness-to-pay in Ghana.

This paper has its primary focus on the analysis of perceptions and willingness-to-pay (WTP) for composted municipal solid and faecal waste among urban and peri-urban farmers and other potential compost users in Ghana. Participatory rural appraisal and contingent valuation methods (CVM) were used for the demand analysis. Most respondents were clear and firm in their responses to the principal question about WTP for compost, as well as in giving their views and perceptions about issues involved in demand for compost. The probit analysis proved valuable in highlighting variables, which explain variations in the WTP. The WTP analysis allowed the quantification of the compost demand under different scenarios of subsidized and non-subsidized compost production, with due allowance for a local reference price to cover compost station operating costs. The analysis revealed that the effective demand for compost for agricultural purposes is marginal and limited by farmers' transport costs. Only through the additional consideration of the demand of the construction sector can about 25% of the organic waste produced in Ghana's capital, Accra, be transformed and utilized. Public subsidies appear necessary and could be generated through savings in transport and disposal. Without subsidies, the challenge for an increased agricultural use is how to produce a low-cost but nutrient-rich compost, which can compete with abundant and cheap poultry manure and still achieve the price to maintain a compost station. The experience in Ghana shows that this is hardly possible except through private-public partnerships.

Agriculture↗

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.

Disease Susceptibility↗

Predictors of high level of burden and distress in caregivers of demented patients: results of an Italian multicenter study.

BACKGROUND: Considerable suffering is experienced by carers of patients with dementia. Most existing studies do not consider the coexistence of subjective and objective aspects that cause, interacting to each other, this suffering. OBJECTIVES: In this study we: (1) define the high-risk group of caregivers on the bases of the scores obtained on the four scales evaluating burden, distress, depression and anxiety (BDDA) taken into account simultaneously and (2) evaluate risk factors related to the high level of BDDA. SUBJECTS AND METHODS: 419 elderly outpatients with dementia and their caregivers were enrolled. Patients were evaluated for their cognitive, neuropsychological and functional impairment and for comorbidity. Caregivers were evaluated with four scales for the assessment of burden, distress related to neuropsychological disturbances, depression and anxiety. Cluster analysis was used to identify the group with the High level of BDDA (HBDDA). RESULTS: By multiple logistic analysis, disability, specific behavioural disturbances of the patients as well as caregiver's age, type of relationship and living in the south of Italy were observed to be a major risk factor for HBDDA. CONCLUSION: The targeted use of scales specifically assessing BDDA of the caregiver and the identification of particular patient and caregiver characteristics are able to allow a precise and early definition of caregivers at high risk of burden and distress. This might be helpful in planning the correct social/clinical/rehabilitative approach.

Adolescent↗

Glutathione reductase inhibition and methylated arsenic distribution in Cd1 mice brain and liver.

Inorganic arsenic exposure via drinking water has been associated with cancer and serious injury in various internal organs, as well as with peripheral neuropathy and diverse effects in the nervous system. Alterations in memory and attention processes have been reported in exposed children, whereas adults acutely exposed to high amounts of inorganic arsenic showed impairments in learning, memory, and concentration. Glutathione (GSH) is extensively involved in the metabolism of inorganic arsenic, and both arsenite and its methylated metabolites have been shown to be potent inhibitors of glutathione reductase (GR) in vitro. Brain would be more susceptible to GR inhibition because of the decreased activities of superoxide dismutase (SOD) and catalase reported in this tissue. To investigate whether GR inhibition could be documented in vivo, we determined the activity and levels of GR in brain as well as in liver, the main organ of arsenic metabolism in mice exposed to 2.5, 5, or 10 mg/kg/day of sodium arsenite over a period of 9 days. In contrast to what has been observed in vitro, significant inhibition of the expression and activity of GR was observed only at the highest concentration used (10 mg/kg/day) in both organs. Although the disposition of arsenicals was higher in liver, significant amounts of inorganic and methylated arsenic forms were determined in the brain of exposed animals. The formation of monomethylarsenic (MMA) and dimethylarsenic (DMA) metabolites in the brain was confirmed by incubating brain slices for 24, 48, and 72 h with sodium arsenite.

Animals↗

Second line therapy with weekly low-dose docetaxel for pretreated non-small-cell lung carcinoma patients: a multicenter Italian phase II study.

Docetaxel is one of the most active drugs in second-line therapy for non-small-cell-lung-carcinoma (NSCLC). The aim of this multicenter study was to evaluate the safety and efficacy of weekly low-dose docetaxel. Forty-two patients with advanced NSCLC pretreated with cisplatinum-based chemotherapy were enrolled. Docetaxel was administered at a dose of 25 mg/m(2) weekly for 12 consecutive weeks. A total of 386 doses were given with a median number of 10 doses per patient (range: 3-12). Treatment showed low incidence of hematologic toxicity and modest non-hematologic toxicity. An episode of grade 4 thrombocytopenia was reported but no episodes of grade 3 or 4 neutropenia. Most frequent non-hematologic toxicities were asthenia and alopecia. Response rate was 10.5% and median survival time (MST) was 12.8 weeks. Weekly treatment with 25 mg/m(2) docetaxel for 12 consecutive weeks appears to be a feasible and active regimen with mild toxicity in heavily pretreated NSCLC patients.

Adult↗

Genetic defects in GH synthesis and secretion.

Growth hormone (GH) is a multifunctional hormone produced in the anterior pituitary that promotes postnatal growth of skeletal and soft tissues. GH secretion and release are complex phenomena depending on several intrinsic and extrinsic factors modulating the release of two hypothalamic hormones, GH releasing hormone and somatostatin. Any genetic or acquired disorder that impairs GH secretion or action causes a pathological phenotype characterized by harmonic short stature with isolated GH deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). In this article we report current knowledge about the genetic basis of IGHD and CPHD.

Growth Disorders↗

Descriptive and topographic anatomy of the accessory infraorbital foramen. Clinical implications in maxillary surgery.

AIM: Study of frequency and position of accessory infraorbital foramen in a large craniological sample. METHODS: A sample of 1 064 skulls from the craniological collection of the Department of Anatomy, Pharmacology and Forensic Medicine of the University of Turin (Italy) was investigated. RESULTS: Accessory infraorbital foramen was found in 4.7% of the skulls (5.4% in male and 4.26% in female skulls) with a higher frequency on the left side, both in male and in female skulls. CONCLUSION: These results increase our knowledge of the interindividual anatomic variability of the infraorbital region and can be of help for the maxillo-facial surgeon, especially in trunk block of the infraorbital nerve.

Adolescent↗

The effects of arsenic exposure on the nervous system.

Arsenic (As) is a common environmental contaminant widely distributed around the world. Human exposure to this metalloid comes from well water and contaminated soil, from fish and other sea organisms rich in methylated arsenic species, and from occupational exposure. It has been reported that human arsenic exposure causes several health problems such as cancer, liver damage, dermatosis, and nervous system disturbances such as polyneuropathy, EEG abnormalities and, in extreme cases, hallucinations, disorientation and agitation. Although there is evidence that arsenic exposure has a toxic effect on the nervous system there are few studies that address this issue. The purpose of this review is to describe what is presently known about the effects of arsenic compounds on the nervous system in humans and rodents and to discuss its possible mechanisms of action.

Animals↗

Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6-162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9-162 months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD) (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135 months)) (P<0.0001) in patients whose disease progressed while they were receiving first induction chemotherapy. Causes of death were more frequently (P=0.04) related to MM in patients who had progressive disease (PD) than in patients who had a CR or PR or SD. The main clinical and laboratory characteristics were similar in the four groups. These data indicate that patients who maintain SD during first-line chemotherapy have a prognosis similar to that of patients who attain a response. Only patients whose disease progresses have a distinctly worse outcome.

Analysis of Variance↗

Two new PROP1 gene mutations responsible for compound pituitary hormone deficiency.

Mutations in the Prophet of Pit-1 (Prop-1), a paired-like homeodomain transcription factor involved in the early embryonic pituitary development, have been reported as a cause of combined hormone deficiency (CPHD) involving growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), gonadotrophins and in some cases adrenocorticotrophic hormone (ACTH). We report two pre-pubertal siblings with short stature and deficiency of GH and TSH at presentation. Molecular analysis of the PROP1 gene revealed compound heterozygotes for two novel missense mutations of the PROP1 gene affecting the same amino acid (Arg71Cys and Arg71His) in the first alpha helix of the Prop-1 homeodomain.

Base Sequence↗

Downregulation of mac-1 expression in monocytes by surface-bound IgG.

Physical and functional association between the beta2-integrin Mac-1 (CD11b/CD18) and receptors of immunoglobulin G (IgG) (FcgammaRs) has been previously reported. In this study, we examined the modulation of Mac-1 expression by IgG in different leucocyte populations. Our data show that human monocytes, but not neutrophils, macrophages, dendritic or natural killer cells, downregulate the expression of Mac-1 after overnight exposure to surface-bound IgG. This effect, which requires at least 6 h of incubation, is not associated with a general downmodulation of membrane antigens, and is selectively induced by immobilized IgG (iIgG), as the stimulation of monocytes with N-formyl-methionyl-leucyl-phenylalanine, lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha) or soluble IgG did not modify the Mac-1 expression after 18 h in culture. The loss of Mac-1 was completely prevented by blocking antibodies (Abs) directed to FcgammaRII (CD32) or CD18. On the other hand, the serine protease inhibitor, phenyl methyl sulphonyl fluoride, but not inhibitors of cysteine proteases or neutral endopeptidases, partially prevented the downregulation of Mac-1 by iIgG. Monocytes cultured overnight on iIgG exhibited a dramatic decrease in their capacity to ingest zymosan particles that could be attributed to the reduced expression of Mac-1. However, there was no inhibition of TNF-alpha production induced by zymosan, suggesting that Mac-1-dependent responses require different levels of its expression to be fully activated.

Actin Cytoskeleton↗