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Biomedical subjects

G Silvestri

Publications and source records attributed to G Silvestri.

At least 19 recordsLinked to original sources
PubMed2005

Retinal changes associated with type 2 glomerulonephritis.

AIMS: The aims of this study were to: Investigate retinal changes associated with type 2 membranoproliferative glomerulonephritis (type 2 MPGN). Assess whether there was a relationship between the severity of the kidney disease and ophthalmoscopically visible fundal changes. Find out if renal transplantation was linked with visual deterioration. Decide if patients with type 2 MPGN need to be referred for ophthalmological assessment. METHODS: The patients were identified from pathology department records as having renal biopsy proven type 2 MPGN from January 1981 to October 2003. Patients were invited to attend for ophthalmic assessment. RESULTS: A total of 26 biopsy proven cases of type 2 MPGN were identified. One patient lost vision from a possible occult choroidal neovascular membrane. The extent of ocular involvement did not consistently appear to be related to the severity of the renal involvement, although there was a relationship between the presence of ocular lesions and the duration of the disease. The longer the disease was present the more likely the patients were to have ophthalmoscopically visible fundal changes. Renal transplantation did not appear to have a detrimental effect on vision with the possible exception of one patient. CONCLUSION: Referral of type 2 MPGN patients by the renal physician for an initial ophthalmological assessment may be beneficial so that symptoms of choroidal neovascularization can be explained and patients advised to seek urgent help if distortion of central vision occurs. Renal transplantation does not appear to be a risk factor for the development of choroidal neovascular membranes.

Adolescent↗
PubMed2004

Gender-, age-, body composition- and training workload-dependent differences of GH response to a discipline-specific training session in elite athletes: a study on the field.

Ninety-nine Italian elite athletes (61 M, 38 F, mean age +/- SE: 24.1 +/- 0.6 yr, age range: 17-47 yr) of different disciplines volunteered to participate in this investigation. Basal GH concentrations were significantly higher (p<0.0001) in females (6.2 +/- 1.1 ng/ml) vs males (1.9 +/- 0.5 ng/ml). Basal GH values were negatively correlated with age and body mass index (BMI); no significant correlation was found between GH and IGF-I levels. Among female athletes, 8/38 had basal GH values higher than 10 ng/ml [2/8 athletes were taking oral contraceptives (OC)], while among males 6/61 had values higher than 5 ng/ml. In females, training sessions significantly increased (p<0.0001) basal GH concentrations (peak GH: 18.5 +/- 1.9 ng/ml), while in males GH responses were lower than in females (11.8 +/- 1.4 ng/ml, vs F: p<0.005). Six out of 38 female and 6/61 male athletes were considered GH hypo-responders (i.e. negative difference between peak GH and basal GH values), the large majority of them being subjects with elevated basal GH concentrations. In responsive athletes, peak GH values occurred immediately at the end of the training session both in males and in females; GH concentrations rapidly declined during recovery. No significant correlations were found between peak GH and age, body weight and BMI in either gender. GH responses were directly related (p<0.001) to the intensity of the workload during the sessions. In conclusion, the present study demonstrates that: 1) some elite athletes had increased GH concentrations before training, which were however associated with normal IGF-I levels; 2) GH peaks after a discipline-specific training session were significantly higher in females than in males performing the same discipline, gender-related differences disappearing when post-exercise total GH outputs (area under the curve) were compared; 3) peak GH values were directly correlated with training workload; 4) GH concentrations rapidly declined during recovery, values at the end of the post-training GH sampling being generally lower than those found in basal condition.

Adolescent↗
PubMed2004

Surveillance of endophthalmitis following cataract surgery in the UK.

AIMS: To estimate the incidence of acute-onset presumed infectious endophthalmitis (PIE) following cataract surgery in the UK and provide epidemiological data on the presentation, management, microbiology, and outcome of cases of endophthalmitis. METHODS: Cases were identified prospectively by active surveillance through the British Ophthalmological Surveillance Unit reporting card system, for the 12-month period October 1999 to September 2000 inclusive. Questionnaire data were obtained from ophthalmologists throughout the UK at baseline and 6 months after diagnosis. Under-reporting was estimated by independently contacting units with infection databases. RESULTS: Data were available on 213 patients at baseline and 201 patients at follow-up. The minimum estimated incidence of PIE was 0.086 per 100 cataract extractions and the corrected incidence was 0.14 per 100 cataract extractions. For the management of PIE, 96% of patients received intravitreal, 30% subconjunctival, 65% oral, and 17% intravenous antibiotics. In all, 17% of patients received intravitreal steroid. From the intraocular samples taken for microbiological analysis, 56% were culture positive. At follow-up, 48% of patients achieved visual acuity of 6/12 or better and 66% achieved better than 6/60. 13% of patients were unable to perceive light or had evisceration of the globe. CONCLUSIONS: The incidence of PIE after cataract surgery in the UK is comparable to that of other studies. Approximately 50% of patients achieved a visual acuity close to the driving standard.

Acute Disease↗
PubMed2004

Cell-cycle dysregulation in the immunopathogenesis of AIDS.

For a number of years the pathogenesis of AIDS was thought to be essentially related to direct human immunodeficiency virus (HIV)-mediated killing of CD4+ T cells. More recently, attention has shifted to pathogenic models that emphasize the role of generalized immune system activation and the excess apoptosis of uninfected T cells in inducing HIV-associated CD4+ T-cell depletion. The main focus of our research is to better define the determinants and the consequences of these "indirect" mechanisms of immunodeficiency by studying both HIV-infected patients and nonhuman primates infected with simian immunodeficiency virus (SIV). We have discovered that pathogenic models of retroviral infections of primates (i.e., HIV infection in humans and SIV infection in rhesus macaques) are associated with the presence of a set of perturbations of normal cell-cycle control in T lymphocytes. These perturbations, to which we collectively refer to as cell-cycle dysregulation, or CCD, may represent an important biological link between chronic immune activation and excess apoptosis and therefore may play a significant role in the pathogenesis of AIDS. A better understanding of the determinants and consequences of CCD may pave the way for the introduction of new therapeutic strategies to be used in addition to standard antiretroviral therapy in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Changes of autonomic cardiac profile after a 3-week integrated body weight reduction program in severely obese patients.

The autonomic control of the heart is abnormal in obese subjects due to a prevalence of sympathetic over parasympathetic limb of the autonomic balance. We evaluated the effects of a short-term (3 weeks) integrated body weight reduction program (consisting of energy restricted diet and high-intensity exercise training) on heart rate variability (HRV) in severely obese, normotensive patients. The HRV was evaluated both in the time and frequency domain over a 18-hour Holter recording period obtained before and at the end of the third week. Three-week body weight reduction program reduced BMI (from 41.4 +/- 4.6 to 39.5 +/- 4.3 kg/m2, -4.6%, p<0.0001) and heart rate (from 77.8 +/- 8.6 to 73.6 +/- 8.7 b/min, p=0.0003). Significant changes in the autonomic profile were observed both in the time and frequency domain (SD of RR interval, SDRR: +16.1%; mean squared successive difference: (MSSD) +16.7%; percentage of RR intervals differing more than 50 msec from the preceding one, pNN50: +31.8%; low frequency oscillation, LF: +17.1%; high frequency oscillation, HF: +/- 18.2%). In conclusion, this study demonstrates that a short-term, integrated body weight reduction program is able to favorably modify the autonomic profile in a population of normotensive, severely obese subjects. The reduction of heart rate and the increase in parasympathetic activity may consistently contribute to a reduction of the risk of cardiovascular morbidity and of sudden cardiac death, still high in this patients' group.

Adult↗
PubMed2003

Effects of cryopreservation on lymphocyte immunophenotype and function.

Cryopreservation of isolated peripheral blood mononuclear cells (PBMCs) for phenotypic and functional analyses is considered a standard procedure in order to minimize operator-dependent inter-assay variability and to optimize the use of available resources. However, only few and somewhat conflicting data are presently available on the effects of cryopreservation on PBMCs, especially in samples from HIV-infected patients in which assessment of lymphocyte phenotype and function is of the outmost importance. In this study, we compared fresh versus frozen/thawed (F/T) samples isolated from 19 healthy individuals and 21 HIV-infected patients, showing that cryopreservation induces: (i) a profound decrease of CD62L expression, with a consequent significant decline of the calculated proportions of "naïve" (CD45RA+CD62L+) and "central memory" (CD45RO+CD62L+) T cells; (ii) an increase of the calculated proportions of "effector" CD8+ T cells (CD45RA+CD62L- and CD45RO+CD62L-) in the healthy subjects, while no changes were observed in the HIV-infected group; (iii) a significant decline of CC chemokine receptor 5 (CCR5) expression; (iv) a loss of proliferative responses to some HIV antigens (i.e. p24) and recall antigens [cytomegalovirus (CMV) and Influenza] in HIV-infected patients. We thus conclude that cryopreservation induces a consistent set of changes in PBMCs from both healthy and HIV-infected individuals, and that certain immunological studies of HIV-infected patients (i.e. studies of immune reconstitution following antiretroviral therapy in HIV-infected patients or studies of HIV-infectivity in vitro using CCR5-tropic strains) should be performed on fresh samples.

Cryopreservation↗
PubMed2003

Measuring T cell-mediated cytotoxicity using fluorogenic caspase substrates.

Cytotoxic T lymphocytes (CTLs) play a major role in the immune response against viruses and other intracellular pathogens. In addition, CTLs are implicated in the control of tumor cells in certain settings. Accurate measures of CTL function are of critical importance to study the pathogenesis of infectious diseases and to evaluate the efficacy of new vaccines and immunotherapies. To this end, we have recently developed a flow cytometry-based CTL (FCC) assay that measures the CTL-induced caspase activation within target cells using cell permeable fluorogenic caspase substrates. This novel assay reliably detects, by flow cytometry or fluorescence/confocal microscopy, antigen-specific CTLs in a wide variety of human and murine systems, and is safer and more informative than the standard 51Cr-release assay. In addition, the flow cytometric CTL (FCC) assay provides an alternative method that is often more sensitive and physiologically informative when compared to previously described FCC assays, as it measures a biological indicator of apoptosis within the target cell. The FCC assay may thus represent a useful tool to further understand the molecular and cellular mechanisms that underlie CTL-mediated killing during tumorigenesis or following infection with viruses or other intracellular pathogens.

Animals↗
PubMed2003

Homozygosity mapping of Marinesco-Sjögren syndrome to 5q31.

Marinesco-Sjögren syndrome (MSS), first described in 1931, is an autosomal recessive condition characterised by somatic and mental retardation, congenital cataracts and cerebellar ataxia. Progressive myopathy was later reported to be also a cardinal sign of MSS, with myopathic changes on muscle biopsies. Hypergonadotrophic hypogonadism and skeletal deformities related to pronounced hypotonia were also reported. The major differential diagnosis of MSS is the syndrome defined by congenital cataracts, facial dysmorphism and peripheral neuropathy (CCFDN), which is localised to 18qter. Using homozygosity mapping strategy in two large consanguineous families of Turkish and Norwegian origin, respectively, we have identified the MSS locus on chromosome 5q31. LOD score calculation, including the consanguinity loops, gave a maximum value of 2.9 and 5.6 at theta=0 for the Turkish and the Norwegian families, respectively, indicating linkage between the disease and the D5S1995-D5S436 haplotype spanning a 9.3 cM interval. Patients of the two families presented with the strict clinical features of MSS. On the other hand, the study of two smaller French and Italian families, initially diagnosed as presenting an atypical MS syndrome, clearly excluded linkage from both the MSS locus on 5q31 and the CCFDN locus in 18qter. Patients of the two excluded families had all MSS features (but the myopathic changes) plus peripheral neuropathy and optic atrophy, and various combinations of microcornea, hearing impairment, seizures, Type I diabetes, cerebral atrophy and leucoencephalopathy, indicating that only the pure MSS syndrome is a homogeneous genetic entity.

Cataract↗
PubMed2003

Effects of short-term, integrated body mass reduction program on maximal oxygen consumption and anaerobic alactic performance in obese subjects.

The study investigated the effect of a short-term (3-week) body mass reduction program, combining energy-restricted diet, nutritional education, psychological counselling and aerobic exercise training (DEP-AT) on maximal oxygen consumption (VO2max) and anaerobic alactic performance evaluated with different techniques in obese patients (grade II and III). Fifty-three (14 males, 39 females) obese subjects [average +/- SD body mass index (BMI): 41.6 +/- 4.2 kg/m2] were tested before and after the DEP-AT program characterised by a daily conditioning protocol of aerobic exercise on cycloergometer, treadmill and armergometer for a total duration of 35 min at an intensity corresponding to 50% of individual VO2max during the first week of the program and at 60% in the following 2 weeks. VO2max was determined with the cycloergometric indirect method. Short-term alactic anaerobic performance was evaluated with: a) jumping test (5 consecutive jumps with maximal effort, Bosco technique), b) short sprint running test (8m), and c) stair climbing test (modified Margaria test). The DEP-AT program induced a significant weight loss (-4.57 +/- 1.26%, p < 0.001) and a significant VO2max increase (14.1 +/- 20.5%, p < 0.001). After the DEP-AT program, lower limb alactic anaerobic power output, calculated on a per kg body mass basis, increased significantly both in jumping and in stair climbing (20.1 +/- 24.8%, p < 0.001 and 13.5 +/- 19.75%, p < 0.001, respectively), as well as average horizontal velocity during short sprinting (7.2 +/- 17.6%, p < 0.01). Power output was a major determinant of the motor performance, being significantly correlated with: a) vertical displacement of the centre of gravity (R2 = 0.884, p < 0.001) in jumping test, b) vertical velocity (R2 = 0.348, p < 0.001) in stair climbing test, and c) horizontal velocity (R2 = 0.394, p < 0.001) in short running test. In conclusion, short-term DEP-AT program induces significant improvements in both aerobic capabilities and anaerobic performance, possibly through the combination of a number of contributory mechanisms, such as exercise-mediated training, shift in the balance between parasympathetic and sympathetic activity, a weight-loss dependent shift toward a more favourable region of the muscle power-velocity curve, acquisition of a certain degree of motor skill during the conditioning program, improvement of self-esteem and motivation.

Adolescent↗
PubMed2001

Highly active antiretroviral therapy induces specific changes in effector and central memory T cell sub-populations.

Highly active antiretroviral therapy (HAART) improves the immunodeficiency of HIV-infected individuals. In this report we show that HAART increases both naive (CD45RA+CD62L+) and central memory (CD45RO+CD62L+) CD4 lymphocytes. On CD8 lymphocytes, HAART induces an increase of naive cells associated with a consistent decrease of effector cells (CD45 RO+CD62L-). No specific differences in phenotypic changes were observed with different HAART regimens, suggesting that, once viral suppression is achieved, the pharmacological class of antiretroviral drugs does not affect immune reconstitution.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency.

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

Adolescent↗
PubMed2001

Abnormal intracellular kinetics of cell-cycle-dependent proteins in lymphocytes from patients infected with human immunodeficiency virus: a novel biologic link between immune activation, accelerated T-cell turnover, and high levels of apoptosis.

Human immunodeficiency virus (HIV)-infection is characterized by loss of CD4+ T cells associated with high levels of immune activation, T-cell proliferation, and lymphocyte apoptosis. To investigate the role of intrinsic perturbations of cell-cycle control in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS), we studied the expression of cell-cycle-dependent proteins in lymphocytes from HIV-infected patients. Cyclin B1 expression, Nucleolar Organizer Regions (NORs) number, and NORs area of distribution were all consistently increased in HIV-infected patients, but returned to normal after effective antiretroviral therapy, suggesting that viral replication is directly implicated in the genesis of the observed changes. Analysis of cyclin B1 intracellular turnover showed that the increased cyclin B1 expression is (1) caused by defective degradation in the presence of normal rates of synthesis, and (2) is temporally associated with decreased levels of ubiquitination. After in vitro activation of lymphocytes from healthy individuals, cyclin B1 and cdc25 expression and ubiquitination, p34 cdc2 activity, NORs morphology, and C23/nucleolin localization showed a 72- to 96-hour cyclic pattern that led to a biologic state similar to baseline. On the contrary, complex but consistent changes of the same indices followed activation of T lymphocytes from HIV-infected patients, resulting in a 5-fold increase in apoptosis. Overall, our data indicate that a profound dysregulation of cell-cycle control is present in lymphocytes from HIV-infected patients. This finding may provide a novel biologic link between immune activation, accelerated lymphocyte turnover, and increased apoptosis during HIV infection.

Anti-HIV Agents↗
PubMed2001

Apoptosis and ROS detoxification enzymes correlate with cytochrome c oxidase deficiency in mitochondrial encephalomyopathies.

The aim of this work was to investigate in muscle the role of apoptosis and of oxidative stress in mitochondrial disorders with dysfunction of respiratory chain. In patients with cytochrome c oxidase deficiency (COX) we found a variable number of myofibers with apoptotic nuclei that matched with the level of enzymatic reduction and roughly correlated with muscle weakness. In parallel, a positive immunostaining for apoptosis-related proteins and Mn and Cu/Zn superoxide dismutase (SOD) were mostly localized in COX-negative fibers. Moreover, glutathione peroxidase activity was increased in muscles with high number of SOD-positive myofibers and prominent apoptotic features. No signs of apoptosis were observed in patients with deficiencies of complexes I and II and without muscle weakness. These data suggest that apoptosis along with increased ROS production, revealed by anti-oxidant enzymes overexpression, may play an important role in the pathophysiology of mitochondrial diseases associated with COX deficiency.

Adult↗
PubMed2001

Improvements in measures of vision and self-reported visual function after cataract extraction in patients with late-stage age-related maculopathy.

PURPOSE: A recent study indicated that patients with cataracts and early age-related maculopathy may benefit from cataract extraction. To ascertain whether cataract extraction in the presence of concurrent advanced age-related maculopathy was also associated with a clear benefit, we studied visual function and self-reported visual functioning in a cohort of 12 patients pre- and post-phakoemulsification. METHODS. All 12 patients had a diagnosis of advanced age-related maculopathy in the eye scheduled for cataract surgery. Preoperative assessment included refraction and recording of best corrected distance and near acuity and contrast sensitivity in both eyes. The Daily Living Tasks Dependent on Vision questionnaire was administered. After phakoemulsification and intraocular lens implantation, all patients were reviewed and assessed. RESULTS: After surgery, improvement in acuity was recorded in nine operated eyes, whereas acuity remained unchanged in three eyes. Improvement in contrast sensitivity in the operated eye occurred in 10 patients, but in two patients contrast was reduced postoperatively. In terms of self-reported visual functioning, improvement in the ability to undertake many daily living tasks dependent on vision was recorded after cataract surgery. CONCLUSIONS: Significant improvements in specific areas of self-reported visual functioning and measures of vision were recorded after cataract surgery. During the follow-up period, none of the operated eyes suffered a fall in visual acuity. There was also no evidence of worsening of the pre-existing macular lesion as judged by clinical examination and fundus photography.

Aged↗
PubMed2001

Exogenous interleukin-2 administration corrects the cell cycle perturbation of lymphocytes from human immunodeficiency virus-infected individuals.

Human immunodeficiency virus (HIV)-induced immunodeficiency is characterized by progressive loss of CD4(+) T cells associated with functional abnormalities of the surviving lymphocytes. Increased susceptibility to apoptosis and loss of proper cell cycle control can be observed in lymphocytes from HIV-infected individuals and may contribute to the lymphocyte dysfunction of AIDS patients. To better understand the relation between T-cell activation, apoptosis, and cell cycle perturbation, we studied the effect of exogenous interleukin-2 (IL-2) administration on the intracellular turnover of phase-dependent proteins. Circulating T cells from HIV-infected patients display a marked discrepancy between a metabolic profile typical of G(0) and a pattern of expression of phase-dependent proteins that indicates a more-advanced position within the cell cycle. This discrepancy is enhanced by in vitro activation with ConA and ultimately results in a marked increase of apoptotic events. Conversely, treatment of lymphocytes with IL-2 alone restores the phase-specific pattern of expression of cell cycle-dependent proteins and is associated with low levels of apoptosis. Interestingly, exogenous IL-2 administration normalizes the overall intracellular protein turnover, as measured by protein synthesis, half-life of newly synthesised proteins, and total protein ubiquitination, thus providing a possible explanation for the effect of IL-2 on the intracellular kinetics of cell cycle-dependent proteins. The beneficial effect of IL-2 administration is consistent with the possibility of defective IL-2 function in vivo, which is confirmed by the observation that lymphocytes from HIV-infected patients show abnormal endogenous IL-2 paracrine/autocrine function upon in vitro mitogen stimulation. Overall these results confirm that perturbation of cell cycle control contributes to HIV-related lymphocyte dysfunction and, by showing that IL-2 administration can revert this perturbation, suggest a new mechanism of action of IL-2 therapy in HIV-infected patients.

Antiretroviral Therapy, Highly Active↗