Chronic autoimmune autonomic neuropathy responsive to immunosuppressive therapy.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Silvestri.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Fibrodysplasia Ossificans Progressiva (FOP) is a rare inherited disease in which progressive ossification of striated muscles leads to severe disability and respiratory impairment early in life and there are associated characteristic congenital skeletal malformations. Although this condition may prove demanding for the anaesthetist, few reports are available regarding anaesthesia in paediatric patients. We review the clinical features of the disease relevant to anaesthesia and describe the perioperative care of an 18-month-old boy with FOP who underwent endoscopic third-ventriculostomy for hydrocephalus associated with a brainstem mass. We emphasize the importance of an appropriate anaesthetic management of these patients, as inadequate care may lead to exacerbation of the disease with permanent sequelae.
BACKGROUND AND AIM: The effects of combined physical exercise and a hypocaloric diet on left ventricular function in obese subjects without heart disease are not well defined and have never been studied with the tissue Doppler technique. The purpose of our study was to describe the modification of left ventricular systolic and diastolic functions after a short period of physical exercise and a hypocaloric diet in obese patients. METHODS AND RESULTS: Fifteen patients (10 females and 5 males) aged 29.7+/-6.1 years with uncomplicated obesity (mean body mass index=41.4+/-5.5 kg/m(2)) were subjected to a low calorie diet and physical exercise. Systolic and diastolic functions were evaluated by Doppler and tissue Doppler echocardiography. After 3 weeks echocardiographic and conventional Doppler measurements were unchanged, while Sa increased (0.109+/-0.019 vs 0.118+/-0.016 m/s) and Ea decreased (0.162+/-0.029 vs 0.147+/-0.022 m/s, P=0.044) resulting in a decrease in Ea/Aa (1.66+/-0.53 vs 1.40+/-0.28, P=0.033) and an increase in E/Ea (5.65+/-1.00 vs 6.35+/-1.21, P=0.038). CONCLUSION: Physical exercise and a hypocaloric diet in obese healthy subjects result in an improvement of a TDI index of systolic function and a slight reduction in early diastolic velocity of mitral annulus.
AIMS: To study risk factors for presumed infectious endophthalmitis complicating cataract surgery in the United Kingdom. METHODS: Two hundred and fourteen clinically diagnosed patients with presumed infectious endophthalmitis were compared with 445 control patients throughout the United Kingdom in a prospective case-control study. The cases were identified through the British Ophthalmological Surveillance Unit reporting card system. Control patients undergoing cataract surgery from 13 'control centres' throughout the United Kingdom were selected randomly. Risk factors were identified by univariate and multivariate logistic regression analyses. Pertinent variables relating to the cataract extraction procedure, antimicrobial prophylaxis, ophthalmic and medical history were analysed with regard to postoperative infection. RESULTS: Statistically significant risk factors in the multivariate model included inpatient cataract surgery (P=0.001), surgery in dedicated eye theatres (P<0.001), consultant grade surgeon (compared to registrar) (P=0.001), posterior capsule tear during cataract surgery (P=0.001). The use of face masks by the scrub nurse and surgeon during cataract surgery (P<0.001) and the administration of subconjunctival antibiotics at the end of surgery (P<0.001) were protective against postoperative infection. CONCLUSIONS: In order to minimise the risk of postoperative endophthalmitis we would recommend the wearing of face masks by the surgeon and scrub nurse during cataract surgery and subconjunctival antibiotics at the end of surgery.
Vascular Endothelial Growth Factor (VEGF) and its receptor KDR are involved in the regulation of angiogenesis and are up-regulated in a number of tumours in humans and in particular, breast cancer. We therefore evaluated the prognostic potential of the angiogenetic process in feline and canine mammary carcinomas by the immunohistochemical assessment of VEGF expression and micro vessel density (MVD) quantification and examined the interplay between VEGF and KDR. These variables were related to some relevant clinicopathological parameters and to overall survival (OS). VEGF and KDR expression were evaluated in epithelial, stromal and endothelial compartments in order to identify autocrine and/or paracrine loops. In dogs an increased VEGF expression did not show any statistical correlation with the clinicopathological parameters examined and was not correlated to a poorer prognosis. MVD was found to be significantly correlated to the histologic type (P=0.04), tumour grading (P=0.02), and to the OS (P=0.01). In cats VEGF expression was significantly correlated to tumor grading (P=0.01) and OS (P=0.03), while no significant associations were found between MVD and the other parameters. VEGF and KDR were found to be detected on the epithelial, and/or endothelial and/or stromal cells of the carcinomas in both species, suggesting indications for some possible autocrine and paracrine loops. Our results encourage further studies on the possible prognostic role of VEGF and MVD in canine and feline mammary tumours and on the role of growth factors and their receptors in promoting tumour proliferation and an "angiogenetic shift". The VEGF/KDR system may play a role in malignant transformation and tumor progression.
Explore the source record for details and available documents.
A major limitation of highly active antiretroviral therapy is that it fails to eradicate human immunodeficiency virus (HIV) infection due to its limited effects on viral reservoirs carrying replication-competent HIV, including monocytes/macrophages (M/M). Therefore, therapeutic approaches aimed at targeting HIV-infected M/M may prove useful in the clinical management of HIV-infected patients. In previous studies, we have shown that administration of fludarabine-loaded red blood cells (RBC) in vitro selectively induces cell death in HIV-infected M/M via a pSTAT1-dependent pathway. To determine the in vivo efficacy of this novel therapeutic strategy, we treated six naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) with either 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) only, fludarabine-loaded RBC only, or PMPA in association with fludarabine-loaded RBC. The rationale of this treatment was to target infected M/M with fludarabine-loaded RBC at a time when PMPA is suppressing viral replication taking place in activated CD4+ T cells. In vivo administration of fludarabine-loaded RBC was well tolerated and did not induce any discernible side effect. Importantly, addition of fludarabine-loaded RBC to PMPA delayed the rebound of viral replication after suspension of therapy, thus suggesting a reduction in the size of SIV reservoirs. While administrations of fludarabine-loaded RBC did not induce any change in the CD4+ or CD8+ T-cell compartments, we observed, in chronically SIV-infected SMs, a selective depletion of M/M expressing pSTAT1. This study suggests that therapeutic strategies based on the administration of fludarabine-loaded RBC may be further explored as interventions aimed at reducing the size of the M/M reservoirs during chronic HIV infection.
In contrast to human immunodeficiency virus (HIV) infection of humans and experimental simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs), SIV infection of sooty mangabeys (SMs), a natural host African monkey species, is typically nonpathogenic and associated with preservation of CD4+ T-cell counts despite chronic high levels of viral replication. In previous studies, we have shown that the lack of SIV disease progression in SMs is related to lower levels of immune activation and bystander T-cell apoptosis compared to those of pathogenic HIV/SIV infection (G. Silvestri, D. Sodora, R. Koup, M. Paiardini, S. O'Neil, H. M. McClure, S. I. Staprans, and M. B. Feinberg, Immunity 18:441-452, 2003; G. Silvestri, A. Fedanov, S. Germon, N. Kozyr, W. J. Kaiser, D. A. Garber, H. M. McClure, M. B. Feinberg, and S. I. Staprans, J. Virol. 79:4043-4054, 2005). In HIV-infected patients, increased T-cell susceptibility to apoptosis is associated with a complex cell cycle dysregulation (CCD) that involves increased activation of the cyclin B/p34-cdc2 complex and abnormal nucleolar structure with dysregulation of nucleolin turnover. Here we report that CCD is also present during pathogenic SIV infection of RMs, and its extent correlates with the level of immune activation and T-cell apoptosis. In marked contrast, naturally SIV-infected SMs show normal regulation of cell cycle control (i.e., normal intracellular levels of cyclin B and preserved nucleolin turnover) and a low propensity to apoptosis in both peripheral blood- and lymph node-derived T cells. The absence of significant CCD in the AIDS-free, non-immune-activated SMs despite high levels of viral replication indicates that CCD is a marker of disease progression during lentiviral infection and supports the hypothesis that the preservation of cell cycle control may help to confer the disease-resistant phenotype of SIV-infected SMs.
Explore the source record for details and available documents.
We describe the case of a 13-year-old boy, in good health, with transient occipital MRI abnormalities just after one generalized seizure and the appearance of macropsia. The EEG showed a 3-5 Hz sub-continuous left occipital activity, with sporadic sharp waves. Macropsia disappeared in 2 years. This case may suggest that the presence of transient MRI abnormalities does not exclude a favorable prognosis.
INTRODUCTION: Membranoproliferative glomerulonephritis type II or dense deposit disease (MPGN II/DDD) causes chronic renal dysfunction that progresses to end stage renal disease in about half of patients within 10 years of diagnosis. Deficiency of and mutations in the complement factor H (CFH) gene are associated with the development of MPGN II/DDD, suggesting that dysregulation of the alternative pathway of the complement cascade is important in disease pathophysiology. SUBJECTS: Patients with MPGN II/DDD were studied to determine whether specific allele variants of CFH and CFHR5 segregate preferentially with the MPGN II/DDD disease phenotype. The control group was compromised of 131 people in whom age related macular degeneration had been excluded. RESULTS: Allele frequencies of four single nucleotide polymorphisms in CFH and three in CFHR5 were significantly different between MPGN II/DDD patients and controls. CONCLUSION: We have identified specific allele variants of CFH and CFHR5 associated with the MPGN II/DDD disease phenotype. While our data can be interpreted to further implicate complement in the pathogenesis of MPGN II/DDD, these associations could also be unrelated to disease pathophysiology. Functional studies are required to resolve this question.
Pathogenic human immunodeficiency virus (HIV)/Simian immunodeficiency virus (SIV) infection is associated with increased T-cell apoptosis. In marked contrast to HIV infection in humans and SIV infection in macaques, the SIV infection of natural host species is typically nonpathogenic despite high levels of viral replication. In these nonpathogenic primate models, no observation of T-cell apoptosis was observed, suggesting that either SIV is less capable of directly inducing apoptosis in natural hosts (likely as a result of coevolution/coadaptation with the host) or, alternatively, that the indirect T-cell apoptosis plays the key role in determining the HIV-associated T-cell depletion and progression to acquired immune deficiency syndrome (AIDS). Understanding the molecular and cellular mechanisms responsible for the disease-free equilibrium in natural hosts for SIV infection, including those determining the absence of high levels of T-cell apoptosis, is likely to provide important clues regarding the mechanisms of AIDS pathogenesis in humans.
OBJECTIVE: To investigate the short- and medium-term (ie, at 1-y follow-up) effects of a hospital-based body weight reduction (BWR) program lasting 3 weeks in severely obese individuals. DESIGN: Longitudinal, clinical intervention study entailing energy-restricted diet, tailored aerobic-strength exercise, psychological counselling and nutritional education during a 3-week period followed by 49 weeks of indirect supervision at home. SUBJECTS: In all, 45 women and 19 men aged 30.2 +/- 7.2 y (mean +/- s.d.) with severe obesity (BMI: 41.3 +/- 4.3 kg/m(2)), classified as weight losers (final < initial weight) and regainers (final> or =initial weight). INTERVENTIONS: Body composition, physical performance and cardiovascular risk factors before and after the BWR program and at follow-up. RESULTS: The large majority of the experimental subjects obtained a clinical success after the 1-y period, and the rate was higher in females (n = 37/45, ie, 82.2%) than in males (n = 11/19, ie, 57.9%). At follow-up, weight losers had higher percent fat-free mass, muscle strength, HDL-cholesterol and self-reported physical activity level and lower total cholesterol and glucose levels than weight regainers (P < 0.05-0.01). Males displayed significantly larger fat-free mass losses than females at post-BWR and at follow-up. CONCLUSIONS A 3-week hospital-based integrated BWR program resulted in a high rate of clinical success in severely obese individuals at 1-y follow-up (particularly in females), that was associated with increased levels of self-reported physical activity and improved muscle strength and lipid profile. Further research is needed to establish the long-term effects (ie, at 2-5 y) associated to this treatment.
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.
Successful HIV vaccine strategies will likely require the induction of robust cellular immune responses, in addition to strong humoral responses. Unfortunately, there is no clear molecular definition of an effective HIV-specific CD8 T cell response. In this review, we discuss the differentiation of CD8 T cells in response to acute and chronic viral infections. We then apply concepts derived from these studies to predict the desirable characteristics of HIV-specific CD8 T cell memory.
Explore the source record for details and available documents.
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.