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Biomedical subjects

G Cavalli

Publications and source records attributed to G Cavalli.

At least 37 records · Page 2Linked to original sources

Early increase in blood nitric oxide, detected by electron paramagnetic resonance as nitrosylhaemoglobin, in haemodialysis.

The objective of this study was to determine intradialytic blood levels of nitric oxide (NO), in patients undergoing chronic haemodialysis. This was done by detection of nitrosylhaemoglobin by a sensitive technique of spin trap electron paramagnetic resonance at 0, 5, 15, 60, 180 and 240 min of a 4-h standard bicarbonate dialysis, using the same dose (6000 U) of heparin and different dialysis membranes. The study group included 12 patients treated with cellulose-derived dialysis membranes (nine with cuprophan and three with cellulose triacetate) and 10 patients treated with synthetic membranes (five with polysulfone and five with polymethylmethacrylate). Control groups included 11 normal subjects and six patients with end-stage renal failure who were receiving intermittent peritoneal dialysis. Basal blood levels of nitrosylhaemoglobin in haemodialysis patients were significantly higher than normals, but similar to peritoneal dialysis patients. A significant increase (P < 0.01) in nitrosylhaemoglobin level was detected at 15 min of haemodialysis irrespective of the membrane used. A decrease to basal levels at 180 min was observed in all but two cuprophan-treated patients who, in contrast to the others, had a symptomatic hypotension at the end of the session and a further increase in blood nitric oxide. Patients undergoing peritoneal dialysis did not show any change in blood levels of nitrosylhaemoglobin during the first 180 min of the procedure. Thus, a constant increase in nitrosylhaemoglobin levels was observed early in haemodialysis, but not in peritoneal dialysis patients. Very preliminary evidence was obtained for a role of nitric oxide in the vascular instability at the end of haemodialysis in a few patients who had hypotensive episodes.

Adult↗

Inactivation of topoisomerases affects transcription-dependent chromatin transitions in rDNA but not in a gene transcribed by RNA polymerase II.

Previous studies on a chromatin reporter gene (GAL-URARIB) in yeast showed that nucleosomes were maintained but rearranged during transcription in galactose, which was consistent with local dissociation of histones at the site of the RNA polymerase. Furthermore, repositioning of nucleosomes occurred rapidly after glucose repression. Because nucleosomal disruption and transcription produce topological changes in the chromatin substrate, the effect of topoisomerase activity was tested by the insertion of GAL-URABIB in topoisomerase mutant strains. The chromatin structure was analysed by nuclease digestion and psoralen crosslinking, and compared with that of the rDNA locus. In GAL-URARIB, neither the inactivation of topoisomerases I, II or I and II generated nucleosomal loss during transcription, nor was topoisomerase activity required for repositioning of the nucleosomes after repression. In contrast, the inactivation of topoisomerase I promoted an enhanced psoralen accessibility of the transcribed rDNA, possibly because of altered supercoiling, and the inactivation of topoisomerases I and II disrupted the chromatin structure of the whole rDNA locus by redistribution of the nucleosomes. The inactivation of topoisomerase II alone had no effect. These observations substantiate a differential participation of topoisomerases in the modulation of the chromatin structures of rDNA genes and of a single copy polymerase II gene. It is suggested that topological stress in genes transcribed by RNA polymerase II might diffuse away into flanking regions.

Chromatin↗

Peptic ulcer and its course in cirrhosis: an endoscopic and clinical prospective study.

The epidemiological and clinical characteristics of peptic ulcer were studied in 324 of 368 consecutive patients with cirrhosis of the liver during a mean period of 1.2 (+/- 0.61) years. Peptic ulcer prevalence rates in patients with cirrhosis were as follows: point prevalence 11.7%, period prevalence 15.1%, and life-time prevalence 24.2%. The annual incidence rate observed in 140 patients with cirrhosis undergoing endoscopic follow up was 4.3%. Ulcers were asymptomatic in more than 70% of patients. The peptic ulcer complication rate at entry was 20% in the whole group and 40% in those who had not a previous diagnosis of peptic ulcer when admitted to the study. Peptic ulcer was more frequent among HBsAg+ cirrhotics (p = 0.05). Patients with more severely decompensated cirrhosis also had a higher frequency of asymptomatic ulcers (p = 0.04), gastric ulcers (p = 0.01) and asymptomatic gastric ulcers (p = 0.005). After diagnosis, during endoscopic follow up, gastric ulcer in patients with cirrhosis tended to heal slowly and recurred with higher frequency than in controls without cirrhosis (p = 0.04). Seventy-nine per cent of peptic ulcer recurrences were asymptomatic in patients with cirrhosis. There were no complications during the follow-up period: this could be due to the regular timing of endoscopy, which permitted early detection and treatment of the recurrences, thus preventing further complications.

Endoscopy, Digestive System↗

Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe.

The methylation and transsulfuration pathways are intimately linked and have been implicated in the progression of neurologic damage and immune cell depletion caused by human immunodeficiency virus (HIV) infection. We studied the following metabolites related to these pathways: S-adenosylmethionine (SAMe), homocysteine, cysteine, cysteinyl-glycine, and glutathione (GSH) in blood and CSF of 16 HIV-infected patients with neurologic complications and 20 HIV-negative control patients undergoing lumbar punctures for other medical reasons. We confirmed recent studies of decreased CSF SAMe concentrations in HIV infection and demonstrated that diastereomers of SAMe are present in CSF but not in plasma or erythrocytes from both HIV-infected and HIV-negative patients. In HIV-infected patients, CSF GSH and cysteinyl-glycine, but not homocysteine or cysteine, were significantly reduced. This is the first report of decreased CSF GSH induced by HIV infection. GSH has a regulatory effect on the synthesis of SAMe in hepatic tissue, and the same mechanism may also apply in the CNS. Administration of SAMe-butanedisulphonate, 800 mg/d intravenously for 14 days, was associated with significant increases in CSF SAMe and GSH. These findings have potentially important therapeutic implications for the use of SAMe in protecting against SAMe and GSH deficiency in the CNS of HIV-infected patients.

Adult↗

Sonographic assessment of the distal end of the thoracic duct in healthy volunteers and in patients with portal hypertension.

OBJECTIVE: Our study assessed the feasibility of detecting and measuring by sonography the diameter of the thoracic duct in healthy subjects and in patients with cirrhosis and portal hypertension. We also evaluated the relationship of thoracic duct size with age and with clinical, endoscopic, and sonographic signs of portal hypertension. SUBJECTS AND METHODS: The left supraclavicular area of 24 patients with cirrhosis and 23 healthy subjects was examined with high-frequency probes using transverse and oblique scans to visualize the distal end of the thoracic duct. All patients with cirrhosis, diagnosed by liver biopsy or clinical and biochemical data, had endoscopic or sonographic signs of portal hypertension. The severity of the liver disease was determined by Child-Pugh's criteria; the diameter of portal vessels and the size of esophageal varices were also considered. RESULTS: The thoracic duct was visualized in 19 of 24 patients with cirrhosis and in 18 of 23 control subjects (percent of visualization was 79% and 78%, respectively). The diameter of the duct was larger in patients with cirrhosis than in healthy subjects (3.1 +/- 1.2 mm versus 1.9 +/- 0.5 mm; p < .0001), but no relationship was found among clinical, endoscopic, and sonographic signs of portal hypertension. A direct relationship between age and the size of the thoracic duct was found only among healthy subjects. CONCLUSION: This is the first report of the sonographic visualization of the distal end of the thoracic duct. Its diameter is small in healthy young subjects, whereas in patients with cirrhosis its increased diameter seems to be associated only with the presence of portal hypertension and not with its severity.

Humans↗

Evidences of 4-hydroxynonenal involvement in modulation of phagocyte activities.

The peroxidative breakdown of membrane polyunsaturated fatty acids leads to the production of various carbonylic compounds: among these, 4-hydroxynonenal (HNE) displays many biological properties related to neutrophil functions. It stimulates rat and human polymorphonuclear (PMN) cell migration and has been detected during inflammation. The aim of this study was to elucidate and well characterize the mechanism of action of HNE. We observed that micromolar HNE concentrations that influence migration do not stimulate differently from many other chemoattractants the human PMN chemiluminescence (CL) induced by opsonized zymosan or phorbol 12-myristate 13-acetate (PMA). Higher HNE concentrations inhibit the light emission of stimulated PMN. Addition of 0.5 mM L-arginine (L-arg), the substrate of nitric oxide synthase, into the incubation medium had the effect of modifying human CL. In fact, HNE at 10-6 M, a concentration which is ineffective in absence of L-Arg, at 10-5 M reduces CL emission of PMA-stimulated human PMN. These observations have been confirmed by electron-spin resonance (ESR) analysis. HNE, according to other stimuli, induced PMN phosphoinositide-specific phospholipase C (PL-C). All these results considered together suggest the conclusion that HNE represents an interesting endogenous molecule that plays a role as an inflammatory mediator involved a) in the recruitment of phagocytic cells at the inflamed area, and b) in the modulation of respiratory burst and of nitric oxide (NO) production.

Aldehydes↗

Timing of the first variceal hemorrhage in cirrhotic patients: prospective evaluation of Doppler flowmetry, endoscopy and clinical parameters.

We followed 87 cirrhotic patients with esophageal varices and without previous hemorrhage for a mean period of 24 mo to prospectively evaluate the occurrence of variceal bleeding within (early) or after (late) 6 mo from entry and the contribution of portal Doppler ultrasound parameters to the prediction of early and late hemorrhage. Clinical, biochemical, endoscopic and portal Doppler ultrasound parameters were recorded at entry. Variceal bleeding occurred in 22 patients (25.3%). Nine (40.9%) bled within the first 6 mo. Cox regression analysis identified variceal size, cherry-red spots, serum bilirubin and congestion index of the portal vein (the ratio of portal vein [cross-sectional area] and portal blood flow velocity) as the only independent predictors of first variceal hemorrhage. Discriminant analysis was used to find the prognostic index cut off points to identify patients who bled within 6 mo (prognostic group 1) or after 6 mo (prognostic group 2) or remained free of bleeding (prognostic group 3). The cumulative proportion of patients correctly classified was 73% in prognostic group 1, 47% in prognostic group 2 and more than 80% in prognostic group 3. The addition of Doppler ultrasound flowmetry to clinical, biochemical and endoscopic parameter only improved the classification of patients with early bleeding.

Adult↗

The relationship of endoscopy, portal Doppler ultrasound flowmetry, and clinical and biochemical tests in cirrhosis.

The relationship of the endoscopic aspect of esophageal varices, portal quantitative Doppler ultrasound parameters and clinical and biochemical findings was assessed in 149 patients with cirrhosis stratified according to the presence of esophageal varices (n = 115) and the absence of previous bleeding (n = 96). In this series of patients the presence of esophageal varices and red signs proved to be significantly correlated with the severity of cirrhosis. However, in the group of patients with varices, no correlation was found between variceal size and the degree of liver failure. Portal blood flow velocity was significantly different in the endoscopic subgroups, but not in the clinical and biochemical subgroups. Furthermore, portal blood flow velocity was found to correlate only with the presence and size of esophageal varices. The Congestion Index of the portal vein (derived from the ratio between the cross-sectional area of the portal vein and the mean velocity of portal flow) was significantly different in most clinical, biochemical and endoscopic subgroups and was correlated with liver function, presence and size of varices, and presence and degree of red signs. We conclude that the Congestion Index of the portal vein, the clinical status and the endoscopic aspect of varices are not independent features in patients with cirrhosis. As for liver function and endoscopic findings, portal Doppler ultrasound parameters, in particular the Congestion Index, may contribute to a better clinical assessment in patients with cirrhosis.

Endoscopy, Digestive System↗

Quantitative analysis of intrahepatic bile duct component in normal adult human liver and in primary biliary cirrhosis.

The volume density of bile ducts in adult normal liver has been analyzed in order to provide stereometric parameters to which refer on performing quantitative evaluations of bile duct loss in acquired liver diseases. Five livers were studied by applying a semi-automatic image analysis system (ASM 68K Leitz) to histological sections. No significant differences (P > 0.10) were found for all measures and the following values were derived from the pooled data: (1) mean % volume of bile ducts in liver = 0.318 +/- 0.171; (2) mean % volume of portal tracts in liver = 4.351 +/- 2.860; (3) mean % volume of bile ducts in portal tracts = 6.567 +/- 3.813. The parallelism of bile duct to arterial components of portal tracts was also investigated and expressed as the ratio of their respective volume fractions (mean ratio = 1.72). The validity of the obtained parameters was tested by comparing them with values determined in five cases of primary biliary cirrhosis (PBC). All PBC cases showed a marked decrease in both bile duct % volume in liver (ranging between 0.028 and 0.057) and bile duct % volume in portal tracts (ranging between 0.673 and 0.914), as well as inversion of the bile duct to artery volume ratio in portal tracts (ranging between 0.246 and 0.437).

Adult↗

[Does aortic insufficiency influence Doppler-derived calculation of the valvular area in patients with mitral stenosis?].

BACKGROUND: The evaluation of mitral valve area (MVA) in patients with mitral stenosis represents the main purpose of any diagnostic method, provided that MVA is a key parameter to indicate the need for valve surgery. The aim of this study was to assess whether the presence of aortic regurgitation associated with mitral stenosis affects the MVA measurement by left atrial pressure half time (PHT). METHODS: Eighty-nine patients with mitral valve stenosis (68 females and 21 males, mean age 53.6 +/- 12.1 years), were studied. Fourty-eight patients (36 females and 12 males) had a concomitant aortic regurgitation (AR group), whereas 41 patients (32 females and 9 males) did not reflect any aortic valve involvement (no-AR group). Aortic regurgitation was graded on the basis of color flow analysis. The majority of patients had a slight to moderate regurgitation. MVA determination was carried out using both Hatle formula (220/PHT) and planimetric measurement in parasternal short axis view. RESULTS: Statistical analysis demonstrated a good correlation between the 2 MVA measurement in both groups (IA group: r = 0.9, p < 0.0001, SSE = 0.21 cm2, y = 0.91x + 0.05; no-IA group r = 0.92, p < 0.0001, SSE = 0.22 cm2, y = 0.92x + 0.04). The concomitant aortic valve disease did not affect in any way the MVA measurement by means of the PHT method. CONCLUSIONS: The Doppler derived method appears to be reliable for estimating the mitral valve area in patients with mitral stenosis even in the presence of aortic regurgitation.

Adult↗

[Tricuspid insufficiency and pulmonary hypertension in mitral disease: an echocardiographic study].

Tricuspid valve regurgitation and pulmonary hypertension have been evaluated with echo-color-Doppler technique in 100 patients (80 females and 20 males, mean age 54 years) affected by mitral valve stenosis. Pure mitral stenosis was present in 13 patients; 87 had an associated mitral regurgitation. The severity of mitral valve disease was based on the planimetric and functional (Doppler-derived) evaluation of valvular area. No relationship was found between extent of tricuspid regurgitation and severity of mitral valve disease, whereas pulmonary artery hypertension was significantly related to mitral valve involvement, above all Doppler mean gradient (r: 0.63, p < 0.005) and valvular area (r: -0.52, p < 0.01). The study suggests that in patients with mitral valve disease tricuspid regurgitation is independent of the degree of mitral valve involvement, whereas pulmonary hypertension is related to transvalvular gradient and to mitral valve area, but does not depend on the duration of the disease. This is evident only in patients who maintain the sinus rhythm.

Adult↗

Chromatin transitions during activation and repression of galactose-regulated genes in yeast.

To study the fate of nucleosomes during transcription, a yeast gene 'GAL-URARIB' was constructed which is tightly regulated by the GAL1 promoter and shows in its inactive state a series of positioned nucleosomes that are sensitive for monitoring structural changes by micrococcal nuclease. Upon transcriptional activation, nucleosome positions were lost, but a residual nucleosomal repeat with an altered repeat length and no changes in psoralen accessibility measured by a band shift assay indicated that nucleosomes were present but rearranged on the transcribed gene. When chromatin was prepared 10 or 50 min after glucose repression, nucleosomes were repositioned in a large fraction of the population by a rapid process which most likely did not depend on histone synthesis or DNA replication. However, complete regeneration of the inactive structure and repeat length was observed after one cell generation (2.5 h) suggesting that in this step some missing histones were replaced. The results are consistent with a local dissociation of nucleosomes at the site of the polymerase followed by a rapid reassembly into nucleosomes behind it. The data are further supported by analysis of the chromosomal GAL1, GAL7 and GAL10 genes.

Blotting, Northern↗

Soluble interleukin-2 receptors and beta 2-microglobulin in patients with primary glomerulonephritis.

Serum levels of soluble interleukin-2 receptors (IL2R) and of beta 2-microglobulin (beta 2M) were studied with the immunoenzymatic technique in 38 patients with primary glomerulonephritis (GN), in 10 patients with essential hypertension (EH) and in 30 healthy subjects. IL2R correlated with beta 2M (p < 0.05). IL2R and beta 2M were higher in patients with GN (p < 0.003, p < 0.001, respectively) and in patients with EH (p < 0.003, p < 0.01, respectively) than in healthy subjects. IL2R and beta 2M correlated with serum creatinine, but not with proteinuria. Our data would suggest the existence of lymphocyte activation in patients with GN. Only speculations can be advanced with regard to the observed increase in these parameters in EH patients.

Adult↗

Glomerular permselectivity to macromolecules in reflux nephropathy: microalbuminuria during acute hyperfiltration due to aminoacid infusion.

Reflux nephropathy is an important cause of chronic renal failure in children. After the parenchymal scar, the progression is thought to be mediated by glomerular hypertension in remnant nephrons resulting in modifications in permselectivity to macromolecules. Proteinuria correlates with a progressive course. The glomerular permselectivity to macromolecules in basal conditions and after acute hemodynamic stress was investigated in 28 children whose bilateral vesico-ureteric reflux (VUR) had been previously surgically corrected (meanly 5.6 years before) and with normal creatinine clearance (CrCl). Bilateral renal scarring (0 to 8 scale for both kidneys) was 4.3 +/- 1.6. Albuminuria (UAE) was evaluated in basal conditions and under acute hyperfiltration induced by amino acid (Aa) infusion. After isotonic saline at 310 ml/hour/1.73 m2, 6 mg/kg/min of Aa were infused for 2 hrs. UAE was significantly higher than controls in basal conditions (p < 0.01), and further increased after Aa infusion (p < 0.02). Microalbuminuria was detectable in 53.5% of the children in basal conditions and in 64.3% after Aa. Also urinary beta 2 microglobulin significantly increased at the end of the test (p < 0.001). CrCl significantly increased at the first hour (p < 0.05). Children with severe renal parenchymal scarring had greater UAE (p < 0.01) and beta 2M (p < 0.02) values after provocative test than those with mild renal damage. In 8 children GFR and ERPF were measured by means of inulin and p-hippurate clearance respectively. The variations in UAE during Aa infusion were significantly correlated with GFR dynamics (p < 0.05) while they were not influenced by ERPF modifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

Serum and intracellular detection of cytokines in patients undergoing chronic hemodialysis.

Tumor necrosis factor (TNF) was detected, before and after dialysis, in sera from 69 patients and, at various times during dialysis, in 28 patients carefully selected for the absence of intercurrent illness. Blood samples were also sequentially collected for separation of monocytes, and cells were sonicated to detect intracellular TNF. Compared with serum levels obtained from 41 healthy subjects, basal TNF values of the unselected group of 69 patients were significantly higher (p < 0.01), independent of the dialyzer membrane. A significant increase in TNF levels by the end of dialysis was found only with Cuprophan (p < 0.01). In the selected group of 28 patients, no significant changes in TNF values were observed in sequential samples. However, a significant increase of intramonocyte TNF levels was found in Cuprophan patients (p < 0.025). Soluble interleukin-2 receptor (IL-2R) levels, measured in parallel in sera from unselected and selected patients, were found to be very much higher than healthy controls without significant changes during the dialysis procedure. While the diverse profiles of TNF obtained from differently selected patients suggest that mechanisms other than membrane biocompatibility play a role in the appearance of these low cytokine levels, the possible nature of uremic toxin for soluble IL-2R can be envisaged by detection in dialysis patients.

Adult↗