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Biomedical subjects

A Corsi

Publications and source records attributed to A Corsi.

At least 19 recordsLinked to original sources

Evaluation of hygiene and safety controls for on-line paired hemodiafiltration (PHF).

BACKGROUND: On-line hemodiafiltration is gaining popularity due to increasing evidence of clinical benefits however it also requires strict attention to hygiene and safety as notable quantities of liquid are reinfused into the patient. Although most centers are improving their attention to water quality, a frequent concern is the inadvertent or accidental contamination of water and whether the redundant safety controls are sufficient to protect the patient. In the present study, in order to simulate a worst-case safety condition, we tested in vitro the reliability of paired hemodiafiltration - (PHF), under low, moderate and high bacterial contamination of the water supply. Tests were performed using various bacterial concentrations (range 85-2000 cfu/mL) of Pseudomonas Aeruginosa. Samples were analyzed from different sites throughout the entire on-line hemodiafiltration circuit for bacteria endotoxin, fungus and ability to stimulate whole blood production of TNFalfa. RESULTS: In the in vitro contamination study, with the three bacterial concentrations tested at various points of the circuit, bacteria were below the level of detection and endotoxins were < 0.01 UE/mL. Addition of dialysate samples taken after the first stage of microfiltration, as well as after the first and second stage of ultrafiltration and incubated with whole blood were not associated with stimulated production of TNFalfa . CONCLUSIONS: PHF appeared to be a safe and feasible method for on-line hemodiafiltration even in the unforeseen presence of bacterial contamination of the feed water or water distribution system.

Endotoxins↗

Pheochromocytoma associated with adrenocortical tumor in the same gland. Two case reports and literature review.

Pheochromocytomas are catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglionic system that show 2 distinctive features, rarity and clinical variability. Pheochromocytoma occasionally is associated with pathological lesions of the adrenal cortex. We present 2 cases of patients referred to our hospital with a finding of clinical suspected pheochromocytoma. Both of them were hypertensive; the first patient with typical symptoms of pheochromocytoma and the second patient with chest pain and hypertension resistant to pharmacological treatment. The diagnosis of pheochromocytoma was confirmed in both cases with laboratory analysis and the lesion was achieved by employing 3 imaging techniques: computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy with (123)I-metaiodobenzilguanidine (MIBG). The patients underwent adrenalectomy and in the same adrenal gland we found a pheochromocytoma associated with a nonfunctioning cortical adenoma. As far as we know few cases with this association are available in the literature.

3-Iodobenzylguanidine↗

Incidence of visual loss in the Ponza Eye Study, Italy.

AIM: To study the incidence of visual loss over a 12-year period in the survivors of an original cohort aged 40 years or older at baseline. METHODS: Visual acuity (VA) was measured by means of a standardized logMAR chart. World Health Organization definition of blindness and low vision was adopted (respectively, best-corrected VA >1.3 logMAR or a visual field <10 degrees around central fixation, and best-corrected VA >0.5-1.3 logMAR or a visual field <20 degrees around central fixation). Moreover, binocular visual loss incidence (VA>0.5 logMAR) was calculated in a 'healthy' group who had uncorrected VA of 0.0 logMAR or better in both eyes at baseline and absence of eye diseases. RESULTS: Of the 584 eligible survivors, 411 (70.7%) had a 12-year follow-up visit. The overall incidence figures were as follows: best-corrected binocular blindness (0.7%), binocular low vision (3.9%), monocular blindness (2.7%), and monocular low vision (5.0%), respectively. The results for presenting VAs were 1.2, 9.5, 4.2, and 15.3%. Figures for uncorrected, best-corrected, and presenting binocular visual loss incidence in the 'healthy' group were respectively 12.7, 0.9, and 3.7%. CONCLUSION: The discrepancy between the ideal and real situations that emerges from this study has important implications for health-care planning. Over a period of 12 years, a substantial percentage of 'healthy' subjects will have to seek medical care. Incident visual loss was caused mainly by untreated cataract, glaucoma, myopia, and age-related macular degeneration.

Adult↗

Validation of the Italian version of the WHO-Well-Being Questionnaire (WHO-WBQ) and the WHO-Diabetes Treatment Satisfaction Questionnaire (WHO-DTSQ).

AIM: To validate the Italian version of the World Health Organization (WHO)-Well-Being Questionnaire (WBQ) and the WHO-Diabetes Treatment Satisfaction Questionnaire (DTSQ) in Type 1 and Type 2 diabetic patients. METHODS: The cultural adaptation of the questionnaires was performed by using standard forward/backward techniques. Internal consistency reliability was estimated by Cronbach's alpha coefficient. Construct validity was evaluated using the Short Form-36 (SF-36) Health Status Questionnaire. Finally, the discriminative properties of the questionnaires were evaluated relative to the patients' characteristics. The questionnaires were administered to a random sample of patients identified in twelve outpatient diabetes clinics. RESULTS: Overall, 412 subjects were recruited, of whom 96 (23%) with Type 1 diabetes. Item-scale correlations were >0.40 for all the items. Cronbach's alpha coefficient was 0.86 for the WHO-DTSQ and ranged between 0.79 and 0.91 for the WHO-WBQ. High correlations were found between WHO-WBQ scales and the mental dimensions of the Short Form-36 (SF-36) questionnaire, but not between WHO-DTSQ and SF-36 scores. Women, obese subjects, those with longer diabetes duration and multiple complications showed a worse quality of life in all of the four areas of the WHO-WBQ. In Type 2 diabetic subjects, SF-36 scores, but not WHO-WBQ scores, were able to discriminate the population according to the treatment modalities. Lower levels of treatment satisfaction were related to female gender, longer diabetes duration, insulin treatment, presence of diabetes complications and HbA1c levels >7.0%. The flexibility of the treatement was perceived as a major problem even among patients treated with oral agents. CONCLUSIONS: The WHO-DTSQ can be considered as a valuable instrument to be used internationally for the description of diabetes treatment satisfaction. The WHO-WBQ also shows adequate psychometric properties, but additional data are needed to clarify whether it is more sensitive than SF-36, the most widely used generic instrument.

Adult↗

Coexpression of bone sialoprotein (BSP) and the pivotal transcriptional regulator of osteogenesis, Cbfa1/Runx2, in malignant melanoma.

Bone sialoprotein (BSP) is a member of the SIBLINGS family, normally restricted to the skeleton, but it has been shown to be ectopically expressed in some human invasive carcinomas. BSP expression in human cancer was initially associated with the ability of BSP-expressing tumors to metastasize to bone, although the mechanism whereby BSP expression should facilitate homing of cancer cells to the bone marrow environment has remained unexplained. More recently, clinical and experimental data have converged in highlighting a potential link between BSP expression and tumor invasiveness in general. We show here that human malignant melanoma cells express BSP in vivo as a function of extent of local invasion, and that expression of BSP mRNA and protein in melanoma cells is associated with the expression of the transcriptional regulator of osteogenic cell differentiation, Cbfa1/Runx2. It has been well established that expression of Cbfa1/Runx2 in the mouse is normally restricted to bone-forming cells. In the mouse, Cbfa1/Runx2 dictates osteogenic differentiation of mesodermal cells by regulating bone-specific genes. Since it also regulates expression of at least two matrix metalloproteases implicated in tumor invasion and metastasis (collagenase 3, membrane type 1 matrix metalloproteinase), we propose that the relationship between BSP expression and an invasive behavior in human epithelial cancer cells may be rooted in a common transcriptional control exerted by Cbfa1.

Cell Line, Tumor↗

Osteoclastogenesis in fibrous dysplasia of bone: in situ and in vitro analysis of IL-6 expression.

Fibrous dysplasia of bone (FD) is caused by somatic mutations of the GNAS1 gene, which lead to constitutive activation of adenylyl cyclase and overproduction of cAMP in osteogenic cells. Previous in vitro studies using nonclonal, heterogeneous strains of FD-derived cells suggested that IL-6 might play a critical role in promoting excess osteoclastogenesis in FD. In this study, we investigated IL-6 expression in FD in situ and its relationship to the actual patterns of osteoclastogenesis within the abnormal tissue. We found that osteoclastogenesis is not spatially restricted to bone surfaces in FD but occurs to a large extent ectopicly in the fibrous tissue, where stromal cells diffusely express IL-6 mRNA and exhibit a characteristic cell morphology. We also observed specific expression of IL-6 mRNA in a proportion of osteoclasts, suggesting that an autocrine/paracrine loop may contribute to osteoclastogenesis in vivo in FD, as in some other bone diseases, including Paget's disease. We also generated homogeneous, clonally derived strains of wild-type and GNAS1-mutated stromal cells from the same individual, parent FD lesions. In this way, we could show that mutated stromal cells produce IL-6 at a basal magnitude and rate that are significantly higher than in the cognate wild-type cells. Conversely, wild-type cells respond to db-cAMP with a severalfold increase in magnitude and rate of IL-6 production, whereas mutant strains remain essentially unresponsive. Our data establish a direct link between GNAS1 mutations in stromal cells and IL-6 production but also define the complexity of the role of IL-6 in regulating osteoclastogenesis in FD in vivo. Here, patterns of osteoclastogenesis and bone resorption reflect not only the cell-autonomous effects of GNAS1 mutations in osteogenic cells (including IL-6 production) but also the local and systemic context to which non-osteogenic cells, local proportions of wild-type vs mutated cells, and systemic hormones contribute.

Adult↗

Alternative site blood glucose testing: a multicenter study.

The aim of this study was to compare glucose measurements between fingertip and forearm using the blood glucose (BG) monitoring system One Touch Ultra (LifeScan), an electrochemical sensor that requires only a very small drop of blood (1 microL). Patients with type 1 or type 2 diabetes were identified in five outpatient diabetes clinics. Participants were requested to use the One Touch Ultra at home for 1 week for the measurement of BG levels from both sites. Patients filled in a questionnaire about their experience with testing blood samples from fingertip and forearm. The agreement between the measurements from the two sites was assessed using linear regression analysis, mean absolute relative error (MARE), the Bland-Altman method, and Error Grid Analysis (EGA). Overall, 112 patients were recruited, of whom 58% had type 1 diabetes. Linear regression analysis showed an intercept of 17.7, statistically different from 0 (p<0.0001). The slope was 0.956, and the Pearson correlation coefficient was 0.95. A MARE of 12.1% (SD=11.8%) was obtained, with a greater deviation of the forearm values from the fingertip ones in the hypoglycemic range (MARE=22.3%; SD=21.7%). The Bland-Altman bias plot showed a mean bias of 10.2 mg/dL (SD=23.1), with no correlation between mean difference and average BG levels (r=0.02). The EGA showed that 89.2% of the values fell in zone A, 10.4% in zone B, and 0.4% in zone C. The vast majority of patients (71%) declared that the collection of blood from the forearm caused no pain or less pain than the traditional site. Only 17% of the patients declared that it was impossible to obtain any blood from the forearm, while 63% reported with satisfaction that the quantity requested was small. At the end of the study period, 32% of the participants indicated the forearm as the preferred test site. Alternative site testing on the arm, with a BG meter that requires only a very small drop of blood, is feasible and reliable under routine clinical conditions. When testing with the express purpose of detecting hypoglycemia, the finger still remains the recommended test site.

Adolescent↗

Competitive transport of cadmium and lead through a natural porous medium: influence of the solid/liquid interface processes.

Contaminated groundwater typically contains different metal contaminants which may compete with each other for the same adsorption sites. Understanding the fate of these micro-pollutants is of primary importance for the assessment of the risk associated with their dispersion in the environment and for the evaluation of the most appropriate remediation technology. In this regard, column techniques can be considered as useful tools both to perform transport experiments and to obtain equilibrium adsorption data without any perturbation of the actual solid/liquid interface. Cd and Pb monocomponent step column experiments were used to obtain adsorption isotherms on a natural aquifer material. A General Composite approach was used to define the equilibrium adsorption model characterized by two types of sites (ion-exchange and surface complexation sites). Coupling the adsorption model with the Advection-Dispersion equation (by IMPACT code) allowed us to well represent the monocomponent step experiments. The model was successfully used to predict the competitive Cd and Pb transport behaviour. Cd peaks of concentration due to Pb competition were experimentally observed and simulated by the model. This behaviour can be described only by an accurate modelling of the interaction and cannot be predicted by simple isotherms (such as Langmuir or Freundlich type).

Adsorption↗

An R201H activating mutation of the GNAS1 (Gsalpha) gene in a corticotroph pituitary adenoma.

In the pituitary gland, activating mutations of the GNAS1 (Gsalpha) gene at Gln227 have been identified in adrenocorticotrophin secreting, growth hormone secreting, and prolactin secreting adenomas. To date, mutations at the codon encoding R201, typically underlying the McCune-Albright syndrome and isolated fibrous dysplasia of bone, have been demonstrated only in growth hormone secreting pituitary adenomas. In this study, a polymerase chain reaction amplified target sequence in exon 8 of the GNAS1 gene was sequenced, identifying the first R201 mutation seen in an isolated basophilic adenoma which generated Cushing's disease in a child. This case adds Cushing's disease to the range of human diseases caused by R201 mutations of the GNAS1 gene.

Adenoma, Basophil↗

Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues.

Decorin (dcn) and biglycan (bgn), two members of the family of small leucine-rich proteoglycans (SLRPs), are the predominant proteoglycans expressed in skin and bone, respectively. Targeted disruption of the dcn gene results in skin laxity and fragility, whereas disruption of the bgn gene results in reduced skeletal growth and bone mass leading to generalized osteopenia, particularly in older animals. Here, we report that bgn deficiency leads to structural abnormality in collagen fibrils in bone, dermis, and tendon, and to a "subclinical" cutaneous phenotype with thinning of the dermis but without overt skin fragility. A comparative ultrastructural study of different tissues from bgn- and dcn-deficient mice revealed that bgn and dcn deficiency have similar effects on collagen fibril structure in the dermis but not in bone. Ultrastructural and phenotypic analysis of newly generated bgn/dcn double-knockout (KO) mice revealed that the effects of dcn and bgn deficiency are additive in the dermis and synergistic in bone. Severe skin fragility and marked osteopenia characterize the phenotype of double-KO animals in which progeroid changes are observed also in the skin. Ultrastructural analysis of bone collagen fibrils in bone of double-KO mice reveals a complete loss of the basic fibril geometry with the emergence of marked "serrated fibril" morphology. The phenotype of the double-KO animal mimics directly the rare progeroid variant of human Ehlers-Danlos syndrome (EDS), in which skin fragility, progeroid changes in the skin (reduced hypodermis), and osteopenia concur as a result of impaired glycosaminoglycan (GAG) linking to bgn and dcn core proteins. Our data show that changes in collagen fibril morphology reminiscent of those occurring in the varied spectrum of human EDS are induced by both bgn deficiency and den deficiency in mice. The effects of an individual SLRP deficiency are tissue specific, and the expression of a gross phenotype depends on multiple variables including level of expression of individual SLRPs in different tissues and synergisms between different SLRPs (and likely other macromolecules) in determining matrix structure and functional properties.

Animals↗

Biomarkers of frailty in older persons.

Trajectories of health and functioning with age show extreme variability among different individuals. Normal aging implies a progressive decline of physiological reserve and ability to compensate, but it is compatible with autonomy over the entire life span. In frail, older persons the decline in functional reserve is accelerated and compensatory mechanisms start failing, with high risk of homeostasis disruption and consequent negative health outcomes. Frailty is currently conceptualized as an age-related alteration in physiology and pathology that results into a typical constellation of signs and symptoms. Although current attempts to identify frail, older individuals for clinical purposes are based on measures of mobility and motor performance, candidate biological markers that may characterize the frailty syndrome start to emerge in the literature. These potential markers include, but are not limited to, soluble mediators of the inflammatory response, hormones, free radicals, antioxidants and macro- and micro-nutrients. This is a research area undergoing a rapid, dynamic development that may profit from new ways of defining disability outcomes in epidemiological studies of the elderly.

Aged↗

In vitro release of activin A from human normal and pathological thyroid tissues.

Activin A is a dimeric glycoprotein belonging to the transforming growth factor beta (TGF-beta) superfamily characterized by the ability to affect FSH secretion. Activin A was originally indicated as a gonadal product but the expression of activin A has been successively identified in several different tissues, including the thyroid gland. The aim of this study was to evaluate the release of activin A from human normal and pathological thyroid tissues in culture. Activin A concentration was evaluated in media obtained from primary culture of perinodular normal tissues (no.=2), hyperplastic hyperfunctioning thyroid tissues due to Graves' disease (no.=3) and autonomous thyroid adenomas (no.=3). Detectable levels of activin A were found in the incubation media from all tissues, without significant differences between normal and pathological samples. We conclude that activin A is secreted by follicle thyroid cells in normal and pathological conditions.

Activins↗

New aspects of the insulin resistance syndrome: impact on haematological parameters.

AIM/HYPOTHESIS: Previous studies have shown that insulin has an important in vitro role in the regulation of human erythropoiesis. We investigated whether in vivo hyperinsulinaemia/insulin resistance affects haematological parameters. METHODS: A total of 608 subjects between 22 and 99 years of age were enrolled in the Chianti study, an epidemiological study of factors affecting mobility in old age. The degree of insulin resistance was assessed using the homeostasis model. RESULTS: We found a correlation between insulin resistance and red blood cell count, (r = 0.14 p < 0.001), plasma haemoglobin (r = 0.16 p < 0.001), haematocrit (r = 0.15 p < 0.001) and plasma iron (r = 0.1 p < 0.05) concentrations. Red blood cell count was also associated with the other biological markers of insulin resistance syndrome. Subjects with higher insulin resistance (4 degrees quartile) had higher red blood cell count, plasma triglycerides and low density lipoproteins (LDL) cholesterol concentrations and lower high density lipoproteins (HDL) cholesterol concentrations then subjects at the lowest quartiles of insulin resistance. Insulin resistance and BMI were significant and independent predictors of red blood cell count even when the analysis was adjusted for age, sex, waist-to-hip ratio, plasma iron and drug intake. CONCLUSION/HYPOTHESIS: Our findings provide in vivo evidence of a relation between hyperinsulinaemia/insulin resistance, the main variables of insulin resistance syndrome and erythropoiesis. Increased red blood cell count could be considered as a new aspect of the insulin resistance syndrome that could contribute to the increased risk of developing cardiovascular problems.

Adult↗

Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects.

Aim of the study was to investigate activin A serum concentration in healthy adult males and post-menopausal females over a wide age-range and its correlation to gonadotropins, inhibin B and testosterone concentrations. The study included 73 males (aged 30-101 years) and 42 postmenopausal females (aged 50-104 years). Blood samples were collected after an overnight fast to measure serum activin A, inhibin B, LH, FSH, and gonadal steroid levels. A significant increase in serum activin A levels over age in both genders, especially in the oldest age-groups, was observed. Serum inhibin B and testosterone concentrations showed a sharp decrease in male subjects, reflecting the age-related decrease of testicular function and by consequence serum FSH and LH significantly increased. In female subjects LH and FSH levels were very high in subjects in their 50s and showed a continuous decline due to pituitary aging. Simple and multivariable regression analyses demonstrated the lack of correlation between activin A and FSH in both males and females. In conclusion, a steep increase in activin A levels is present during aging in both genders, especially in the last decades of life. The physiologic role and site of production of activin A in old subjects remain to be clarified.

Activins↗

Reversible binding of glycolytic enzymes and size change in the actin-containing filaments of the frog skeletal muscle.

Electron microscopy was used in order to study the change of the actin-containing filaments when the bound glycolytic enzymes were removed by a high ionic strength solution. The effectiveness of the extraction medium was checked by estimating the aldolase activity released. Evidence was provided that the larger diameter of the actin filaments in the I-bands in comparison with the A-bands can be accounted for by the bound glycolytic enzymes.

Actin Cytoskeleton↗

Reduced growth and skeletal changes in zinc-deficient growing rats are due to impaired growth plate activity and inanition.

We investigated the effects of dietary zinc deficiency on skeletal metabolism in an animal model. Thirty 21-d-old male Sprague-Dawley rats were fed for 28 d either a zinc-deficient (ZD) diet (1 mg zinc/kg) or a normal diet ad libitum (AL, 50 mg zinc/kg) or in the same quantity as the ZD (pair-fed, PF). Only in the ZD group were general physical signs of zinc deficiency observed. Compared with the AL and PF rats, ZD rats showed significantly lower mean values in ponderal growth rate, femur weight and length, circulating levels of insulin-like growth factor-I, bone mechanical properties and concentration of zinc and, on histomorphometry, a decrease in the thicknesses of the overall growth plate and hypertrophic cartilage. In contrast, although bone volume was significantly lower in the ZD and PF rats than in the AL rats, no difference was observed between the ZD and PF rats. Osteoclast surface/bone surface and osteoclast number/bone surface ratios were significantly greater in PF rats than in the other two groups and not different in ZD and AL rats. Collectively, these data indicate that zinc deficiency has profound effects on the skeletal system of growing rats. In particular, the effects of zinc deficiency on bone growth and mass are the result of the reduced activity of the growth plate, likely mediated by impairment in the insulin-like growth factor-I system. We did not demonstrate an effect on bone mass via increased bone resorption.

Animals↗