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N Gasparini

Publications and source records attributed to N Gasparini.

At least 19 recordsLinked to original sources
PubMed2005

The -308G/A polymorphism of TNF-alpha influences immunological parameters in old subjects affected by infectious diseases.

Abnormal increments of pro-inflammatory cytokines (IL-6 and TNF-alpha) characterize the outbreak of infectious diseases, which are the major cause of death in the elderly. A counterbalance to the inflammation is exerted by IL-10 with an inhibitory role on TNF-alpha production. As is well known, some cytokine gene polymorphisms influence the cytokine production, playing a role as susceptibility or resistance factors against immune-mediated and infectious disease. Genetic variations in the -308A/G locus for TNF-alpha seems to affect the clinical outcome of some infectious diseases. In fact, the -308A allele is associated with severe septic shock and death. On this basis, we have screened healthy old subjects, nonagenarians and old patients affected by the acute phase of chronic obstructive bronchitis and bronchopneumonia of bacteria origin for the -308G/A locus (PCR-RFLP). Subjects are grouped in A+ (AG, AA genotypes) and A- (GG genotype) and data on IL-6, TNF-alpha, IL-10, NK cell cytotoxicity, zinc and metallothioneins (MTs) gene expression (RT-PCR) were stratified according to different TNF-alpha genotypes. The frequency of the A allele was increased in infected patients in comparison with healthy old controls. No differences existed between A+ and A- young adult, old and nonagenarian controls in tested parameters. Conversely, A+-infected patients displayed elevated IL-6, TNF-alpha and MTmRNA, low IL-10 coupled with impaired NK cell cytotoxicity and lower zinc ion than A- patients. However, the data reported are gender independent. Therefore, the -308A polymorphism at the locus of TNF-alpha may be one of the susceptibility factor for infectious diseases in old persons, particularly considering its association to the increased release of pro-inflammatory cytokines and to the reduction of zinc release and MTs synthesis involved in the control of the inflammatory response. These data strongly suggest that the genetic screening of the -308G/A polymorphism may be a valid tool for identification of subjects needing a more appropriate therapy when affected by acute and/or recurrent infectious diseases.

Adult↗
PubMed2000

Different age-related effects of thymectomy in myasthenia gravis: role of thymoma, zinc, thymulin, IL-2 and IL-6.

Different age-related immune pathogenetic mechanisms in myasthenia gravis (MG) have been suggested because of restoration after thymectomy (Tx) of altered zinc, thymulin (TH) and T-cell subsets exclusively in early-onset patients (younger <50 years), not in late-onset patients (older >50 years). In this context interleukin-2 (IL-2), interleukin-6 (IL-6) and thymoma are crucial because both involved in MG pathogenesis and correlated with acetylcholine receptors (AchRs) Ab production. Moreover, IL-2 and IL-6 are zinc-dependent, are altered in aging and related with zinc and TH age-dependent declines. Moreover, zinc is relevant for immune efficiency. In order to confirm these different age-related pathogenetic mechanisms further, the role of thymoma, zinc, TH, IL-2 and IL-6 is studied in MG patients with generalized MG with and without thymoma before and 1 month and 1 year after Tx. The high IL-2, IL-6, zinc, and AChR Ab levels observed before Tx are significantly correlated each other in younger MG patients (<50 years) independently by thymoma and in older MG patients (>50 years) with thymoma. No correlations exist in older MG patients without thymoma. Thymulin is not correlated with other parameters considered to be both in younger and older MG patients independently by the thymoma. Thymectomy restores zinc; immune parameters and AChR Ab are exclusively in the younger group, not in the older one. These findings suggest that IL-2 and IL-6, via zinc, rather than TH, may be involved in different age-related pathogenetic mechanisms mainly in early-onset MG. By contrast, thymoma may be involved in MG etiology in late-onset representing, as such, a useful discriminant tool for MG etiology between early and late-onset MG patients. Because autoimmune phenomena may rise in aging, a parallelism with altered immune functions during aging is discussed.

Adolescent↗
PubMed2000

Enterotoxicity and cytotoxicity of Vibrio parahaemolyticus thermostable direct hemolysin in in vitro systems.

Vibrio parahaemolyticus is a marine bacterium known to be a common cause of seafood gastroenteritis worldwide. The thermostable direct hemolysin (TDH) has been proposed to be a major virulence factor of V. parahaemolyticus. TDH causes intestinal fluid secretion as well as cytotoxicity in a variety of cell types. In this study, we investigated the interplay between the hemolysin's enterotoxic and cytotoxic effects by using both human and rat cell monolayers. As revealed by microspectrofluorimetry, the toxin causes a dose-dependent increase in intracellular free calcium in both Caco-2 and IEC-6 cells. This effect was reversible only when low toxin concentrations were tested. The TDH-activated ion influx pathway is not selective for calcium but admits ions such sodium and manganese as well. Furthermore, in the same range of concentration, the hemolysin triggers a calcium-dependent chloride secretion. At high concentrations, TDH induces a dose-dependent but calcium-independent cell death as assessed by functional, biochemical, and morphological assays.

Animals↗
PubMed2000

Near final height after GnRH agonist treatment in central precocious puberty.

The impact of treatment of central precocious puberty (CPP) with gonadotropin-releasing hormone agonists (GnRHa) on final height remains controversial. We analyzed the long term results of 23 girls with CPP treated with triptorelin or leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14 years and expressed as SDS, was compared either with predicted height before treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after 8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS). Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our patients, treated either earlier or later, reached a near final height comparable to predicted height and familial target; however, these results might still improve further because the girls have not yet reached their final adult height.

Body Height↗
PubMed1999

Liver abnormalities in Turner syndrome.

UNLABELLED: We evaluated whether hepatic abnormalities represent a specific feature in girls with Turner syndrome (TS) or whether they are related to an increased susceptibility to hormonal therapies and/or other factors. Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase were monitored in 70 patients with TS for a mean period of 7.6+/-4.2 years. An increase in serum liver enzymes was observed in 14 out of 70 girls (20%) at a mean age of 12.7 years; it was present at entry before hormonal therapy in 3 girls and developed thereafter during the follow up in the other 11. The increase in serum liver enzymes was never observed before the age of 7 years. In the majority of cases (10/14) it was drug related: in 50% the liver abnormalities were transient and self-limiting, in the remaining cases they required interruption of hormonal therapy. Hepatotoxicity was more frequently observed in girls treated with oestrogens or oxandrolone than in those treated with growth hormone. In a small number of cases, liver disease was either auto-immunity-related (2/14), or cryptogenic (1/14) with a benign and self-limiting course. Obesity was a frequent finding, but it played a likely pivotal role only in one patient. CONCLUSION: Hepatic abnormalities are relatively frequent in Turner syndrome and surveillance of liver function should be included in the management of these patients independent of initiation of hormonal treatment.

Alanine Transaminase↗
PubMed1999

Intellectual outcome at 12 years of age in congenital hypothyroidism.

BACKGROUND: The intellectual outcome in children with congenital hypothyroidism detected by neonatal screening is generally good; however, subtle neurological dysfunctions, subnormal IQ, or both, have been reported. OBJECTIVE: To evaluate the intellectual outcome in 12-year-old patients with congenital hypothyroidism, detected by neonatal screening, in an attempt to identify factors that may affect intellectual development. METHODS: The intelligence quotient (IQ) of 40 children with congenital hypothyroidism was evaluated at 12 years of age, using the Wechsler Intelligence Scale for Children -- Revised, and compared with the IQ of 40 healthy siblings (control group). RESULTS: The mean IQ score (88.4+/-13.1) was not significantly different from that of the control group (93.4+/-10.7). Thirteen patients showed subnormal IQ score (72.4+/-4.9) compared with their siblings (86.7+/-9.6; P<0.0001) and with the other patients (96.1+/-9.6; P<0.0001). The low IQ score was associated with lower serum concentrations of thyroxine at diagnosis, poor treatment compliance during follow-up and lower familial IQ. Interviews with parents of children with congenital hypothyroidism revealed that a refusal to acknowledge the disease was linked to poor attention to the child's emotional life and to poor treatment compliance in some cases (11%). CONCLUSION: Even though the mean IQ score in patients with congenital hypothyroidism falls within normal for the control population, low IQ scores may be present in patients with severe hypothyroidism, inadequate compliance to replacement therapy during follow-up and poor parental pedagogic attitude.

Adaptation, Psychological↗
PubMed1999

Treatment of hypopituitarism in infancy. Effect on head circumference growth.

BACKGROUND: Head circumference of children with multiple pituitary-hormone deficiency (MPHD) may be subnormal for age. Moreover it is known that linear growth in infancy is growth-hormone (GH) dependent. Therefore, aim of the study has been to compare head circumference measurements in children with hypopituitarism after L-thyroxine (L-T4) therapy alone, before therapy with GH, and after GH was added to the therapy. METHODS: Five infants (2 girls, 3 boys) with MPHD, diagnosed and treated before the age of 2 years and whose auxological parameters records during L-T4 therapy alone were available, were retrospectively studied. Head circumference and length measurements were expressed as standard deviation score (SDS). Weight measurements were expressed as weight for length ratio percentage. RESULTS: Initially treated with L-T4 alone for a mean period of 4, 5 months, there were neither positive effects on head circumference nor on linear growth. A significant catch-up growth was observed only employing GH therapy in addition to L-T4: mean head circumference SDS and length SDS increased respectively from -2.20 to -0.89 SDS and from -4.16 to -0.87 SDS after a mean period of 18 months of combined GH and L-T4 therapy. CONCLUSIONS: Therefore, head circumference growth, in infancy, is growth hormone dependent as well as linear growth, and during GH treatment, monitoring head circumference growth is important as much as monitoring linear growth.

Adolescent↗
PubMed1998

Central precocious puberty: a single blood sample after gonadotropin-releasing hormone agonist administration in monitoring treatment.

This study was designed to evaluate whether a single blood sample drawn after the home injection of a long-acting gonadotropin-releasing hormone (GnRH) agonist (GnRHa) in patients treated for central precocious puberty (CPP) could be a more simple and inexpensive test with respect to the conventional GnRH stimulating test in assessing adequate suppression of the pituitary-gonadal axis. The response to the first therapeutic injection of the GnRHa triptorelin was studied in 14 newly diagnosed untreated females with CPP. The results were compared with the response that the same patients had to the conventional GnRH stimulation test performed at the time of diagnosis. A significant increase in LH, FSH and E2 levels was observed 12 h after the triptorelin intramuscular injection; serum peak values of LH (70.3 +/- 58.5 IU/l), FSH (44.2 +/- 21.7 IU/l) and E2 (489.7 +/- 263.9 pmol/l) were significantly greater than those obtained with the conventional GnRH test (LH 31.4 +/- 21.7, p = 0.002; FSH 19.8 +/- 10. 7, p = 0.001; E2 83.3 +/- 25, p < 0.001). In particular, the E2 response, 12 h after triptorelin injection, was clearly consistent with gonadal activation compared to the modest E2 increase in response to the GnRH test. Thereafter 22 girls who were already being treated with triptorelin for CPP were evaluated to see whether a single blood sample drawn 12 h after the therapeutic home injection of GnRHa could be informative in assessing adequate suppression of the pituitary-gonadal axis. This response was also compared to the conventional GnRH stimulation test performed 2 days before the therapeutic triptorelin injection. In 7 girls with evidence of pubertal progression, the E2 response following the GnRHa injection (136.3 +/- 44.4 pmol/l) was significantly higher with respect to the response after the GnRH stimulation test (73.0 +/- 0.0; p < 0.02) indicating an inadequate suppression of the pituitary-gonadal axis. The present data suggest that a single blood sample drawn 12 h after the therapeutic home administration of triptorelin provides a simple, comfortable and inexpensive means of monitoring pituitary as well as gonadal function in girls treated for CPP.

Child↗
PubMed1997

Growth pattern during the first 36 months of life in congenital adrenal hyperplasia (21-hydroxylase deficiency).

The longitudinal growth pattern during the first 36 months of life was studied in 24 patients (17 females) with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency by analyzing the mean required daily dose of cortisone with respect to steroid suppression, height and weight growth velocities and bone age maturation. All patients were treated with cortisone acetate and 9-fluorohydrocortisone. The standard deviation score for length (SDS-L), the percentage of ideal body weight (% IBW) and biochemical parameters, 17-hydroxy-progesterone (17-OHP) and androstenedione (A) were evaluated every 3 months; bone age (BA) was evaluated annually. At diagnosis, the female population of patients with respect to the males were younger (chronological age (CA): 15 +/- 14 vs. 45 +/- 16 days, p < 0.005) and had a higher % IBW (91.7 +/- 8.0 vs. 76.3 +/- 16.7%, p < 0.05). At 3 months of age (45 days after initiating treatment) the % IBW in males normalized (97 +/- 19%) and was similar to that found in females (101 +/- 12.8%). No differences were noted in SDS-L at the moment of diagnosis (females-1.1 +/- 1.1 vs. males -0.5 +/- 0.7); however, at 3 months of age the SDS-L in females increased (0.41 +/- 0.88, p < 0.005 vs. diagnosis SDS-L) whereas that of males progressively decreased to reach the nadir at 6 months (-1.41 +/- 0.96). No differences between males and females were noted throughout this time with regard to: (a) A or 17-OHP levels (neither of which were suppressed to 'control values'); (b) the dosage of cortisone received (13.5-17.8 mg/m2/day), and (c) change in BA/CA ratio. In all patients the SDS-target height (TH) correlated with the SDS-L at 2 years (r = 0.74, p < 0.0005) and at 3 years (r = 0.60, p < 0.02) of age. In 12 patients who reached 7 years of age the SDS-L correlated with both SDS-predicted adult height (PAH) (r = 0.75, p < 0.001) and SDS-TH (r = 0.80, p < 0.005). Although the commonly accepted definition of "good control' for patients with CAH has generally included, in addition to adequate suppression of hormone markers, normal growth and skeletal maturation, the present data suggest that normal growth and BA maturation are the most useful parameters to follow and not necessarily strive for hormone suppression. Early diagnosis and replacement therapy using cortisone doses less than those currently recommended allow normal growth within the genetic potential at least for the first 7 years of life.

17-alpha-Hydroxyprogesterone↗
PubMed1997

Pubertal growth, sexual maturation, and final height in children with IDDM. Effects of age at onset and metabolic control.

OBJECTIVE: To evaluate growth and pubertal development in children with IDDM and the influence of the age at onset of IDDM and the degree of metabolic control on final height. RESEARCH DESIGN AND METHODS: We conducted a retrospective evaluation of 62 subjects followed longitudinally both clinically and metabolically from the onset of IDDM until final height was reached. RESULTS: Height at diagnosis was within the normal percentiles in boys (0.5 +/- 1.0 standard deviation score [SDS]) and girls (0.4 +/- 1.0 SDS), but above the genetic target height (-1.0 +/- 0.9 SDS in boys and -1.1 +/- 0.6 SDS in girls; P = 0.0001 for both comparisons). Although a lesser height gain was observed during the ensuing years, the final height reached by boys (-0.4 +/- 1.1 SDS) and girls (-0.4 +/- 0.9 SDS) was higher than the genetic target height. Blunted total pubertal growth was observed both in boys (24.5 +/- 3.6 cm) and girls (20.1 +/- 4.2 cm). The decrease in height gain was independent of the duration of IDDM, the degree of metabolic control, or the insulin requirement. The greater the height at diagnosis, with respect to the genetic target height, the lesser was the subsequent height gain to reach final adult height (r = 0.34, p < 0.01). BMI increased with age as normally occurs in healthy children, independent of the duration of disease and the degree of metabolic control. Pubertal development began and progressed normally both in boys and girls. In boys, a testicular volume of 4 ml was reached at a mean age of 12.1 +/- 0.9 years. In girls, breast enlargement occurred at a mean age of 10.4 +/- 1.2 years and the mean age of menarche was 12.8 +/- 1.4 years. Pubertal development and progression occurred independent of the age at onset of IDDM, the glycemic control, or the insulin requirement during the pubertal period. CONCLUSIONS: Children with IDDM have normal onset of puberty and normal sexual maturation. Even though final height falls within the normal percentiles, the diminished height gain after diagnosis requires further investigation.

Adult↗
PubMed1996

Thyroxine effect on intestinal Cl-/HCO3- exchange in hypo- and hyperthyroid rats.

Changes in transepithelial water and electrolyte transport as causative or contributing factors of the diarrhoea and constipation found associated with changes in thyroid physiology were studied. Albino Wistar rats were pharmacologically made either hypothyroid or hyperthyroid. After sacrifice, the small intestine was mounted in Ussing chambers in order to measure in vitro ion net fluxes under short-circuit conditions. Hypothyroid animals showed an increase in intestinal transit time, Cl- absorption (mainly due to an increment in its mucosal to serosal component) and residual ion flux (which is believed to represent HCO3- secretion) when compared with euthyroid animals. The hyperthyroid animals showed a decrease in Cl- mucosal to serosal transport. Furthermore, a significant correlation was found between serum L-thyroxine (T4) levels and both net Cl- transport (r = -0.74, P < 0.00001) and residual ion flux (r = -0.55, P < 0.005). These results indicate that the effect of T4 is firstly to inhibit Cl-/HCO3- anion exchange thereby influencing transepithelial flux transport and secondly to affect intestinal motility. Such inhibition was not found when T4 was acutely added to rat ileum, suggesting that the effect on electrolyte transport probably requires protein synthesis. In conclusion, the phenomenon observed in vitro could explain the clinical manifestations of constipation and diarrhoea in hypo- and hyper-thyroidism respectively.

Animals↗
PubMed1994

Impairment of T-cell growth-promoting lymphokines in human insulin-dependent diabetes mellitus.

T-cell growth factor (TCGF) activity was studied in phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 10 type-1 diabetic patients who had been diagnosed within the previous 12 months (group A), from 9 diabetic patients in whom the duration of disease was more than 1 year (group B) and from 12 healthy controls (group C). The effects of indomethacin on PHA-induced TCGF activity and the effects of adherent cells (macrophages) from group A and group C on TCGF production of normal group-matched non-adherent cells (lymphocytes) were also studied. TCGF activity was assayed on TCGF-dependent blast cells and calculated as a stimulation index (SI). TCGF activity in group A (SI 0.86 +/- 0.8) was significantly different from that in group B (SI 1.75 +/- 1.02; P = 0.037) and in group C (SI 1.91 +/- 1.29; P = 0.023). Following the addition of indomethacin, TCGF SI was 1.35 +/- 0.74 in group A, 1.85 +/- 0.73 in group B and 2.06 +/- 1.19 in group C. The responses to indomethacin were found to correlate with the basal TCGF activity in all subjects (r = -0.48; P = 0.006) independently of the disease process studied or its duration. No correlation was found between TCGF activity and parameters of metabolic control (HBA1c and fructosamine). Interestingly, a significant inverse correlation was found between TCGF activity and the required dose of insulin only in group A (r = -0.66; P < 0.05). Adherent cells from diabetic patients were found not to inhibit TCGF production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Measuring contrast sensitivity in aretinopathic patients with Insulin Dependent Diabetes Mellitus.

Contrast sensitivity measurements were obtained from 66 patients with Insulin Dependent Diabetes Mellitus (IDDM) and no visible diabetic retinopathy (Group A, n = 30 prepubescent and pubescent subjects; Group B, n = 36 postpubescent subjects). Contrast thresholds were determined for stationary and 6.87 Hz phase-alternating gratings at eight spatial frequencies from 0.18 to 15.7 c/deg. Data from each group of diabetic patients was compared with data from puberty-matched normal subjects. Mean value of the last four determinations of glycohemoglobin Alc (HbAlc) was used as a index of glycemic control. We found that patients with IDDM and no retinopathy had normal contrast sensitivity and that contrast thresholds were not significantly related to sexual maturity, duration of diabetes and glycemic control.

Adolescent↗
PubMedDate not supplied

Two interesting cases of transient neonatal diabetes mellitus.

Two cases of transient neonatal diabetes mellitus associated with anemia, macroglossia and umbilical hernia were studied in relation to the possible etiologies that have been postulated to be responsible for this syndrome. Both patients required insulin therapy for the control of their hyperglycemia but case number two needed to be treated for 14 months before glucose normalization occurred. This patient developed classical insulin dependent diabetes mellitus during our follow-up; the HLA typing showed DR4 allele.

Blood Glucose↗
PubMedDate not supplied

Treatment of hypopituitarism in infancy. Effect on head circumference growth.

BACKGROUND: Head circumference of children with multiple pituitary-hormone deficiency (MPHD) may be subnormal for age. Moreover it is known that linear growth in infancy is growth-hormone (GH) dependent. Therefore, aim of the study has been to compare head circumference measurements in children with hypopituitarism after L-thyroxine (L-T4) therapy alone, before therapy with GH, and after GH was added to the therapy. METHODS: Five infants (2 girls, 3 boys) with MPHD, diagnosed and treated before the age of 2 years and whose auxological parameters records during L-T4 therapy alone were available, were retrospectively studied. Head circumference and length measurements were expressed as standard deviation score (SDS). Weight measurements were expressed as weight for length ratio percentage. RESULTS: Initially treated with L-T4 alone for a mean period of 4, 5 months, there were neither positive effects on head circumference nor on linear growth. A significant catch-up growth was observed only employing GH therapy in addition to L-T4: mean head circumference SDS and length SDS increased respectively from -2.20 to -0.89 SDS and from -4.16 to -0.87 SDS after a mean period of 18 months of combined GH and L-T4 therapy. CONCLUSIONS: Therefore, head circumference growth, in infancy, is growth hormone dependent as well as linear growth, and during GH treatment, monitoring head circumference growth is important as much as monitoring linear growth.

Drug Therapy, Combination↗