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Biomedical subjects

S Sacco

Publications and source records attributed to S Sacco.

At least 19 recordsLinked to original sources

B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection.

OBJECTIVES: To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation. METHODS: BLyS serum levels were analysed by enzyme-linked immunosorbent assay (positive when >0.85 ng/ml) in 66 patients with MCsn, 54 (81.8%) of whom were positive for hepatitis-C virus (HCV) infection. Thirty-three HCV-positive patients without MCsn were also studied. Patients were compared with 48 healthy blood donors (HBDs). BLyS modifications after antiviral therapy were also studied. RESULTS: A significantly higher frequency of BLyS serum positivity was detected both in MCsn patients and in HCV-positive patients without MCsn (37.9 and 30.3%, respectively) when compared with HBDs (4.2%) (P < 0.0001 vs MCsn and P = 0.0026 vs HCV-positive patients without MCsn, respectively). BLyS appeared significantly higher in MCsn (3.70 +/- 2.97 ng/ml) than in HCV-positive patients without MCsn (1.56 +/- 0.63 ng/ml; P = 0.0044). BLyS expression did not correlate with rheumatoid factor levels, cryoglobulin levels or definite MCsn-related systemic features. High BLyS levels were significantly associated only with MCsn-related overt lymphoproliferative disorder. Finally, antiviral treatment significantly increased BLyS levels, independently from HCV-RNA negativization. However, BLyS normalization was noticed after both HCV-RNA negativization and suspension of antiviral therapy by preliminary data. CONCLUSIONS: BLyS is up-regulated and may play a pathogenetic role in a fraction of patients with MCsn, similarly to other autoimmune diseases. HCV infection likely represents the early event leading to BLyS up-regulation in this setting. BLyS is up-regulated during antiviral treatment. Overall, these data provide new insights for BLyS and virus-related autoimmunity, lymphoproliferation and possible treatment strategies.

Adult↗

A population-based study of the incidence and prognosis of lacunar stroke.

OBJECTIVE: To evaluate incidence and prognosis of lacunar stroke in a prospective, population-based patient registry. METHODS: The authors included first-ever strokes occurring between 1994 and 1998. They assessed incidence, risk factors, mortality, and recurrence in patients with lacunar stroke. RESULTS: The authors identified 491 patients (15.3%) with lacunar stroke (252 men and 239 women) and 2,153 patients (67.3%) with nonlacunar stroke (998 men and 1,155 women). Crude annual incidence rate for a first-ever lacunar stroke was 33.0/100,000 (95% CI 30.2 to 36.0). At the univariate logistic regression analysis among patients with lacunar stroke there was a higher proportion of cigarette smoking and hypercholesterolemia and a lower proportion of chronic atrial fibrillation than in patients with nonlacunar stroke. For lacunar stroke, the 30-day case-fatality rate was 4.3% (95% CI 2.5 to 6.1) and the 1-year case-fatality rate was 13.0% (95% CI 10.0 to 16.0). During the first year of follow-up the average annual stroke recurrence rate was lower in patients with lacunar (2.83%; 95% CI 1.36 to 4.30) than in those with nonlacunar stroke (5.10%; 95% CI 4.17 to 6.03) while from the second year onward, rates were similar in both groups. CONCLUSION: In the short term, patients with nonlacunar stroke had more vascular events, but in the long term, the risk of death and of stroke recurrence was similar.

Adult↗

Efficacy of cyclosporin-A in the long-term management of thrombocytopenia associated with systemic lupus erythematosus.

Thrombocytopenia frequently complicates systemic lupus erythematosus (SLE), and its long-term management may be problematic. Intravenous immunoglobulins and high doses of steroids are often effective as induction therapy, but thrombocytopenia frequently relapses during steroid tapering. Several immunosuppressive agents have been evaluated as induction or maintenance therapy in small series or in case reports. We describe six consecutive unselected SLE patients where cyclosporin-A (CyA) was effective and safe in the long-term management of thrombocytopenia and allowed steroid tapering. One relapse occurred during CyA reduction and responded to CyA dose adjustment. Steroids could be stopped in three out of six patients, and were maintained at very low doses in the remaining patients. CyA was stopped in one patient after one year of treatment, without relapse at month 11+ from discontinuation. No severe side effects were documented. Overall, these data suggest that CyA may prove to be an effective and safe therapeutic option for SLE-related thrombocytopenia.

Adrenal Cortex Hormones↗

Capsule endoscopy for the detection of bleeding Meckel's diverticulum. A case report.

The case of a 59-year-old man with a history of recurrent severe gastrointestinal bleeding due to Meckel's diverticulum is described. The diagnosis was achieved by means of capsule endoscopy. The histological examination revealed the presence of Meckel's diverticulum with ectopic gastric mucosa. The use of capsule endoscopy for the detection of Meckel's diverticulum is discussed.

Capsule Endoscopes↗

Prevalence of Parkinson's disease in the L'Aquila district, central Italy.

OBJECTIVE: We estimated the prevalence of Parkinson's disease (PD) in the L'Aquila district. METHODS: Cases of PD were identified screening all available case sources including general practitioners and antiparkinsonian drug-users by means of pharmacy records. Prevalence of PD was computed considering the prevalence day of December 31, 2001. RESULTS: On the prevalence day, 682 patients with PD were alive and residing in the L'Aquila district. A total of 354 patients were women and 328 men. The overall crude prevalence rate was 229.3/100,000 (95% CI 212.7-247.1), without any difference between men (227.4/100,000; 95% CI 200.0-257.5) and women (231.1/100,000; 95% CI 202.2-263.1). Prevalence rates increased with age in both sexes and were higher in urban (244.5/100,000; 95% CI 213.7-278.5) than in rural residents (214.7/100,000; 95% CI 189.0-242.9) (SRR = 1.7; 95% CI 1.3-2.1). CONCLUSIONS: The prevalence of PD in the L'Aquila district was within the range of prevalence rates found in our country and steeply increased with advancing age in both sexes.

Age of Onset↗

Burden of first-ever ischemic stroke in the oldest old: evidence from a population-based study.

OBJECTIVE: To evaluate the contribution of subjects 80 years old or older to the burden of ischemic stroke as compared with subjects younger than 80 years. METHODS: All first-ever ischemic strokes occurring in a 5-year period (1994 to 1998) in the population-based L'Aquila registry were traced. Incidence, total health care utilization, disability, and mortality were assessed in patients 80 years old or older, and differences with those younger than 80 years were assessed by univariate and survival analyses. RESULTS: One thousand three hundred sixteen of 3,594 first-ever ischemic strokes (36.6%) occurred in patients 80 years old or older, accounting on average for one-third of health care utilization. The crude annual incidence rate was 21.54 per 1,000 (95% CI 20.42 to 22.72). At the 1-year follow-up, 27.7% of patients had mild or no disability, 20.7% had severe disability, and 51.6% had died. With respect to patients under 80 years of age, older patients showed a higher proportion of women (61.3 vs 47.7%), atrial fibrillation (30.2 vs 20.7%), coronary heart disease (31.0 vs 23.4%), and peripheral arterial disease (14.6 vs 10.8%) and a lower proportion of cigarette smoking (15.3 vs 29.2%) and hypercholesterolemia (20.4 vs 29.4%). Thirty-day (34.6 vs 13.4%) and 1-year (51.6 vs 22.3%) mortality were higher in patients 80 years old or older than in those younger than 80, mostly in the presence of atrial fibrillation (hazard ratio [HR] was 1.39 for 30-day mortality and 1.37 for 1-year mortality) and diabetes mellitus (HR was 1.39 for 30-day mortality and 1.31 for 1-year mortality). CONCLUSION: The burden of ischemic stroke is high in subjects 80 years old or older, contributing about one-third of health care utilization and 59.8% of deaths within 30 days.

Age Distribution↗

Medical treatment of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) occurs as a result of bleeding into the brain parenchyma and formation of a focal hematoma. Treatment for ICH is primarily supportive, and outcome remains poor. Initial management is directed toward stabilizing breathing and circulation. Increased intracranial pressure is currently managed with osmotic agents (mannitol and glycerol); steroids, hypovolemia, controlled hyperventilation, and barbiturate coma can also be employed. Arterial blood pressure control is useful and requires adequate compliance to specific guidelines. Ultra-early hemostatic therapy may represent a promising tool to reduce early hematoma enlargement and to improve outcome.

Brain↗

Relationship between the tumor necrosis factor receptor II (TNF-RII) gene polymorphism and sTNF-RII plasma levels in healthy controls and in rheumatoid arthritis.

OBJECTIVE: To assess the relationship between tumor necrosis factor receptor II (TNF-RII) gene polymorphisms and sTNFRII plasma levels in healthy blood donors (HBDs) and in rheumatoid arthritis (RA) patients. 113 HBDs and 49 RA patients were genotyped for the T/G polymorphism in exon 6 of the TNF-RII gene. In the same cases, sTNF-RII plasma levels were determined by an enzyme-linked immunosorbent assay (ELISA) procedure. sTNF-RII levels were higher in RA patients than in HBDs (p < 0.0001). No difference in sTNF-RII levels arose between RA patients on low oral doses of glucocorticoids versus those not taking glucocorticoids. In healthy controls, we observed lower levels of the sTNF-RII in carriers of the TT genotype compared to TG/GG genotype (p = 0.04). In RA there was the same behaviour between TT and TG/GG carriers, even though the difference was not statistically significant. When analyzing the correlation between sTNF-RII plasma levels and disease activity parameters, significant correlations were seen with disease activity score (r = 0.40, p = 0.01), swollen joint count (r = 0.38, p = 0.01), and tender joint count (r = 0.42, p = 0.01), but not with erythrocyte sedimentation rate (r = 0.22, p = ns) nor with C-reactive protein (r = 0.14, p = NS). The correlation remained significant only in the RA subgroup carrying the TT genotype. Healthy donors carrying the TT genotype showed lower sTNF-RII plasma levels than carriers of the TG/GG genotypes, while in RA patients we observed only a trend.

Adolescent↗

Central nervous system vasculitis.

Vasculitis is an inflammation of the vessel wall. It may be either primary or secondary. Primary vasculitis includes systemic vasculitis (large, medium, and small-vessel vasculitis) and localized vasculitis (isolated angiitis of the central nervous system and non-systemic vasculitic neuropathy). Secondary vasculitis may be present in connective tissue disorders or may be caused by infections, neoplasms, and substance abuse. Patients presenting with symptoms suggestive of vasculitis require brain neuroimaging, lumbar puncture, and angiography, but only biopsy allows a definite diagnosis.

Cerebral Angiography↗

[TNF- alpha gene polymorphisms in rheumatoid arthritis patients treated with anti-TNF-alpha agents: preliminary results].

OBJECTIVES: To study -238 and +489 TNF-alpha polymorphisms in severe-unresponsive (more than 6 swollen joints and still active disease despite at least 6 months of DMARDs combination therapy) and mild-responsive (less than 3 swollen joints and good response to MTX or other conventional DMARDs) rheumatoid arthritis (RA). METHODS: We investigated 100 RA patients (56 with severe and 44 with mild disease activity) and 45 healthy blood donors (HBDs). Genotyping was performed by PCR-restriction fragment length polymorphism procedure. Several clinical and serological parameters were also examined. RESULTS: Severe RA patients disclosed the -238 GG genotype in 100% of the cases versus 95.5% in the mild-responsive patients and 91.2% in the HBDs. The +489 GG genotype disclosed only a trend towards a prevalence in severe RA patients. However the +489 A allele seems to associates with early onset, longer disease duration and longer responsiveness to conventional therapy. CONCLUSION: The -238 AG genotype is absent in severe-unresponsive RA, but present in mild-responsive RA subjects. Thus -238 GG homozygosity associates with severity and unresponsiveness. In contrast the +489 polymorphism does not segregate differently between responsive and unresponsive RA patients.

Adolescent↗

Role of cytokines in cancer cachexia in a murine model of intracerebral injection of human tumours.

To study the role of cytokines that are relevant in cancer cachexia syndrome due to intracerebral tumours, mice were injected with human A431 epidermoid carcinoma, OVCAR3 ovarian carcinoma and GBLF glioma cells comparing intracerebral (i.c.) and systemic (i.p. or s.c.) routes of implantation. Anorexia and weight loss developed within 7-10 days in mice injected i.c. with A431 or OVCAR3 cells well before a large tumour developed, while i.c.-injected GBLF cells did not induce cachexia until day 20, when the tumour was large. By contrast, mice injected i.p. or s.c. developed tumours without evidence of anorexia. Thus, intracerebrally-growing A431 and OVCAR3 resulted in cancer cachexia independent of tumour mass, and we investigated their cytokine pattern. Serum levels of murine and human cytokines are not predictive of cancer cachexia development. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis revealed in the brain of i.c.-injected A431 tumour-bearing mice expression of human interleukin-(IL-)1alpha, IL-1beta and LIF in all samples and IL-6 in two of four samples while in i.c.-injected OVCAR3 tumour-bearing animals IL-6, and LIF were detected in all samples and tumour necrosis factor-alpha (TNFalpha) in two of four samples. Only LIF was expressed in brains of mice injected with GBLF cells. Murine IL-6 was increased only in the brains of A431-bearing mice. Only mice injected i.c. simultaneously with a monoclonal antibody (mAb) directed against the murine IL-6 receptor and OVCAR3 cells, but not those with mAb and A431 cells, showed a significant increase in survival time with a partial and temporary attenuation of cachexia symptoms. These results suggest that IL-6 in OVCAR3 model may be important cachectogenic factor when centrally released by even a limited number of tumour cells.

Animals↗

Gastric motor effects of triptans: open questions and future perspectives.

Sumatriptan is a 5-HT1B/D receptor agonist of documented efficacy in relieving migraine and associated symptoms such as nausea and vomiting. In the past decade, several studies reported an important delay of gastric emptying induced by sumatriptan in healthy humans. The impact of this gastric motor effect of sumatriptan in migraineurs is difficult to predict: a further delay in gastric emptying could be detrimental (i.e. increased nausea and epigastric symptoms) in patients already having delayed gastric emptying. However, in patients with functional dyspepsia, sumatriptan is also reported to improve gastric accommodation to a meal and reduce perception of gastric distention, hence relieving epigastric symptoms. Thus, reduced visceral perception could be a mechanism involved in reducing nausea during a migraine attack. Paradoxically, sumatriptan is reported both to relieve the nausea of a migraine attack and to have nausea as a side effect. Although careful analysis of the time of onset of nausea may offer a clue as to the origin of this symptom, available data do not support definite conclusions, all the more so because the gastric motor effect of second-generation triptans are still unexplored. Taken together, the available evidence warrants further studies to clarify the following issues: first, the mechanism responsible for the gastric motor effect of sumatriptan [receptor subtype(s) involved; central vs peripheral mechanism]; secondly, the effects on gastric motility/visceral sensitivity of second-generation triptans (which are 5-HT1B/D receptor agonists) and more recent selective 5-HT1D receptor agonists (proposed as investigational antimigraine agents with less potential to induce coronary vasoconstriction through 5-HT1B receptors); finally, the possible use of drugs improving gastric accommodation to a meal in the management of those dyspeptic patients with impaired fundic relaxation/altered visceral sensitivity.

Forecasting↗

Effect of Mentha x piperita essential oil and monoterpenes on cucumber root membrane potential.

Peppermint (Mentha piperita L.) essential oil and its main components were assessed for their ability to interfere with plant plasma membrane potentials. Tests were conducted on root segments isolated from etiolated seedlings of cucumber (Cucumis sativus L.). Increasing the concentration of peppermint essential oil from 5 to 50 ppm caused a decrease in membrane potential (Vm) hyperpolarization of 10-3 mV, whereas concentrations from 100 up to 900 ppm caused an increasing depolarization of Vm (from 5 to 110 mV). When tested at 300 ppm, (+)-menthyl acetate, (-)-limonene and 1,8-cineole did not exert any significant effect on V(m), whereas (+)-menthofuran (73 mV), (+)-pulegone (85 mV), (+)-neomenthol (96 mV), (-)-menthol (105 mV) and (-)-menthone (111 mV) showed increased ability to depolarize V(m). A plot of log of octanol-water partition coefficient (K(ow)) against their depolarizing effect showed a significant negative correlation, suggesting that among all monoterpenoids increased membrane depolarization depends on lower K(ow). However, among monoterpene ketones, alcohols and furans, increased membrane depolarization is associated with a decline in water solubility. The possible effect of monoterpenoids on membrane ion fluxes is also discussed, since changes in the bioelectric potential of cells imply changes in the flux of ions across the plasma membrane

Cucumis sativus↗

Decreased T lymphocyte infiltration in bronchial biopsies of subjects with severe chronic obstructive pulmonary disease.

BACKGROUND: Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied. OBJECTIVE: The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa. METHODS: We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3+, CD4+, CD8+ cells and the number of CD3+ cells coexpressing the chemokine receptor CCR5 (CCR5+CD3+) in the subepithelium. RESULTS: Subjects with severe COPD had lower numbers of CD3+, CD8+ and CCR5+CD3+ cells than mild/moderate COPD (P < 0.012, P < 0.02 and P < 0.02, respectively) and control smokers (P < 0.015, P < 0.005 and P < 0.015, respectively). In subjects with airflow limitation the number of CD3+ and CD8+ cells was inversely correlated with the degree of airway obstruction (r = 0.59, P < 0.015 and r = 0.52, P < 0.032, respectively). CONCLUSIONS: Bronchial inflammation in severe COPD is characterized by lower numbers of CD3+ and CD8+ cells and decreased numbers of CD3+ cells coexpressing the chemokine receptor CCR5. T lymphocyte infiltration is inversely correlated with the degree of airflow limitation.

Aged↗

Average magnitude of heartbeat fluctuations in healthy subjects after exposure to 4 hours head down bed rest.

Orthostatic intolerance, induced by microgravity exposure, has been hypothesized to be related to a disorder of the autonomic control of the cardiovascular system. Non-invasive measurement of Heart Rate Variability (HRV) have been used as a valuable tool to characterize the ability of the autonomic system to modulate the cardiovascular function by analyzing the spontaneous fluctuations of arterial pressure and heart period on a beat-to-beat basis. Concerning this, conflicting results have been reported on the heart rate and blood pressure variability responses during exposure to microG. These differences seem to be due to different experimental designes used. Moreover, the different behavior of normal subjects in response to orthostatic stress after HD, i.e. Symptomatic (S) or Non Symptomatic (NS), could play some role in producing these discrepancies [correction of dicrepancies]. In this study we suggest the analysis of "magnitude" or "volatility" as a new method to study HRV variability. The volatility is a measure of the beat-to-beat excursion capability of the heart, regardless to its direction (positive or negative): the higher the volatility, the greater the excursion. The aim of the present study was to examine R-R volatility before and after 4 hours of HD -6 degrees in normal subjects.

Adult↗