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Biomedical subjects

A Gabrielli

Publications and source records attributed to A Gabrielli.

At least 73 records · Page 4Linked to original sources
PubMed1996

Hepatitis C virus infection and mixed cryoglobulinaemia: assessment of HCV RNA copy numbers in supernatant, cryoprecipitate and non-liver cells.

The aim of this study was to characterize hepatitis C virus (HCV) infection in patients with mixed cryoglobulinaemia (MC). The HCV RNA copy number was assayed in clinical specimens from 15 consecutive patients with MC and HCV infection. Absolute quantification of HCV RNA molecules was performed using a competitive reverse transcription-polymerase chain reaction (cRT-PCR). Specific HCV RNA sequences were detected and quantified in plasma samples from all patients (mean HCV RNA copy number 4.9 x 10(6) ml-1 plasma). A high concentration of HCV RNA molecules was detected in the cryoprecipitates of eight of the 15 patients, who had a cryoprecipitate/supernatant ratio higher than 3.0 (range 3.60 to 186.80): in the remaining seven patients this ratio was close to or lower than 1.0 (range 0.13 to 1.60). Quantitative analysis of HCV RNA molecules in cells other than hepatocytes (i.e. peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs), in which the HCV replicative intermediate was detected using strand specific RT-PCR, demonstrated that infection is detectable in nearly 60% of these extrahepatic cells. Quantitative analysis of HCV RNA in PBMCs and BMCs revealed low levels of viral nucleic acids.

Aged↗
PubMed1996

[Neuro-SLE. Models of its clinical expression].

In this paper we considered different models concerning the clinical expression of neuropsychiatric involvement in course of systemic lupus erythematosus (SLE). These models describe pathological conditions as multifocal cerebropathy, transverse myelitis, peripheral neuropathy and panic attacks. We have chosen these cases as clinical example of different pathogenic mechanisms responsible of CNS-lupus, as hypercoagulation due to antiphospholipid syndrome, immune-complex vasculitis, complement-mediated autoantibody damage and antibody-induced cytotoxicity. The prevalence of neuropsychiatric manifestations in 122 SLE patients is also reported. Finally, the paper reports some guidelines about diagnostic and therapeutic behaviour in course of CNS-lupus.

Adolescent↗
PubMed1995

Carbon monoxide intoxication during pregnancy: a case presentation and pathophysiologic discussion, with emphasis on molecular mechanisms.

In carbon monoxide (CO) poisoning, the mortality and morbidity risk does not always correlate with the level of carboxyhemoglobin (COHb). Recent studies confirm that the mitochondrial cytochrome portion of the respiratory chain is susceptible to CO toxicity at concentrations traditionally considered nontoxic. These laboratory findings correlate with subtle neurologic symptoms detected by psychometric studies in individuals many days from the time of acute intoxication. Additionally, in the pregnant patient, a time lag for both uptake and elimination of CO between the mother and fetus has been demonstrated, with the fetus at risk for hypoxia even when the mother's blood level of CO is nontoxic. Hyperbaric oxygen (HBO) therapy in pregnant patients has not been shown to have adverse effects on the fetus. We present a case of CO intoxication in late pregnancy treated with HBO therapy without adverse consequences.

Adolescent↗
PubMed1995

Granulocytopenia after combined therapy with interferon and angiotensin-converting enzyme inhibitors: evidence for a synergistic hematologic toxicity.

PURPOSE: The purpose of this study was to assess whether granulocytopenia observed in 3 of 38 patients with essential mixed cryoglobulinemia who were treated with low-dose interferon was due to the underlying disease or to synergistic toxicity of interferon with other drugs. PATIENTS AND METHODS: Adverse effects of interferon therapy were monitored in 38 patients affected with type II essential mixed cryoglobulinemia. Patients were treated with 3 million units (MU), daily or on alternate days, of recombinant interferon-alpha 2a (35 patients) or with natural interferon-beta (3 patients). The duration of treatment ranged between 6 and 15 months; the total duration of follow-up, including after therapy, ranged between 8 and 93 months. RESULTS: None of 35 patients treated with interferon alone developed significant hematologic alterations. In addition, none of 7 patients treated with angiotensin-converting enzyme (ACE) inhibitors alone showed hematologic toxicity. Three patients who were treated with a combination of interferon and ACE inhibitors developed severe granulocytopenia a few days after starting treatment. Granulocytopenia subsided within 1 to 2 weeks after suspending therapy. Resumption of treatment with this drug combination produced a granulocytopenia relapse in 1 patient. In these 3 patients, interferon treatment alone, or ACE inhibitor monotherapy, was not followed by granulocytopenia. CONCLUSION: Although severe hematologic toxicity rarely develops in patients treated with low-dose interferon, granulocytopenia occurred in all 3 of our patients with mixed cryoglobulinemia who were treated with a combination of low-dose interferon-alpha 2a and ACE inhibitors. Neither drug alone was toxic in any of our cryoglobulinemic patients, indicating a high risk of severe hematologic toxicity for this drug combination, at least in patients with this disease. Physicians should be aware of this danger when using interferon treatment in patients with this, or possibly other, disorder(s) that also require antihypertensive therapy.

Adult↗
PubMed1994

Active hepatitis C virus infection in bone marrow and peripheral blood mononuclear cells from patients with mixed cryoglobulinaemia.

The presence of hepatitis C virus (HCV) genomic sequences was checked in plasma, liver, peripheral blood mononuclear cells (PBMC) and bone marrow cells from 11 patients with mixed cryoglobulinaemia positive for anti-HCV antibodies, and from 11 patients with chronic HCV hepatitis without serological evidence of cryoglobulinaemia. HCV RNA sequences were demonstrated by reverse transcription polymerase chain reaction in seven plasma samples, in six PBMC samples, and in seven bone marrow cell samples from the 11 cryoglobulinaemic subjects; otherwise, viral specific nucleic acids were detected in 10 plasma samples, in one PBMC sample, and in two bone marrow cell samples from the 11 patients with chronic hepatitis. The HCV replicative intermediate was evidenced in four of the six PBMC and in five of the seven bone marrow aspirate HCV RNA-positive samples. Analysis of subpopulations isolated from bone marrow and peripheral blood samples showed HCV RNA sequences in mononuclear cells belonging either the CD2+ subset or to the CD19+ subpopulation or to the adherent cells. Finally, we compared the nucleotide sequences of a large portion (-270 to -59) of the HCV 5'-untranslated region from five patients with mixed cryoglobulinaemia and from seven patients with chronic hepatitis without cryoglobulinaemia; the degree of heterogeneity, compared with the prototype HCV sequence, was similar in both groups. These findings from two groups of HCV-infected patients indicate that transient or permanent active HCV infection of bone marrow and PBMC is frequent in anti-HCV-positive patients with mixed cryoglobulinaemia, and suggest that extra-hepatic infection may play a major role in influencing the pathophysiology of this infection as well as the viral persistence.

Aged↗
PubMed1994

Presence of hepatitis C virus (HCV) genomic RNA and viral replicative intermediates in bone marrow and peripheral blood mononuclear cells from HCV-infected patients.

The cellular tropism of hepatitis C virus (HCV) was studied in vivo in samples from patients with persistent HCV infection. Plasma, liver, peripheral blood mononuclear cell (PBMC), and bone marrow cell (BMC) samples from 15 subjects positive for anti-HCV antibodies were tested for the presence of HCV RNA sequences by reverse transcription PCR. Virus-specific RNA sequences were found to be present in liver samples from all subjects (100%), in plasma samples from 13 of 15 patients (86.7%), in PBMC samples from 3 patients (20%), and in BMC samples from 9 (60%) of the 15 anti-HCV-positive patients enrolled in this study. The presence of the molecular intermediate of HCV replication (the negative-stranded HCV RNA) was evident in the two of the three PBMC and in five of the nine BMC HCV RNA-positive samples. Finally, we studied the nucleotide sequence of a large portion (-270 to -59) of the 5'untranslated region of HCV amplified from plasma samples of 12 of the 15 patients with and without HCV in BMCs; the degree of heterogeneity compared with the prototype HCV sequence was similar in both groups. The data principally indicate that HCV infection of PBMCs and BMCs is frequent in persistently infected patients, as shown by the occurrence of positive- and negative-stranded HCV RNA, thus suggesting the possibility of extrahepatic replication of HCV.

Adult↗
PubMed1994

Partially and totally unloading respiratory muscles based on real-time measurements of work of breathing. A clinical approach.

OBJECTIVE: To evaluate the clinical feasibility of using real-time measurements of work of breathing obtained at the bedside with a portable, commercially available respiratory monitor as an objective and quantifiable guideline for appropriately setting pressure support ventilation (PSV) to partially and totally unload the respiratory muscles in patients with respiratory failure. DESIGN: In vivo measurements of work of breathing were performed on a consecutive series of patients after applying incremental levels of PSV. SETTING: University teaching hospital in a surgical ICU. PATIENTS: Thirty adults (18 men and 12 women, ages 20 to 77 years) who had acute respiratory failure were studied. All patients had an endotracheal or a tracheostomy tube in place and were breathing spontaneously, receiving continuous positive airway pressure and PSV. INTERVENTIONS: Intraesophageal pressure (indirect measurement of intrapleural pressure) was measured with an esophageal balloon catheter positioned in the mid- to lower-third of the esophagus. Tidal volume was obtained by positioning a flow sensor between the "Y" piece of the breathing circuit and the endotracheal or tracheostomy tube. Airway pressure was measured from a catheter attached to the flow sensor. Data from these measurements were directed to the respiratory monitor (CP-100, Bicore Monitoring Systems) which calculates work of breathing performed by the patient using the Campbell diagram. Work of breathing performed by the ventilator to inflate the respiratory system was calculated by the monitor by integrating the change in airway pressure and tidal volume. Initially, the level of PSV was set to 0 cm H2O and work measurements were obtained. Pressure support ventilation was then increased until the work performed by the patient decreased to a range of 0.3 to 0.6 J/L, which corresponds to a normal range for physiologic work of breathing (ie, partial respiratory muscle unloading), and then until the work decreased to 0 J/L (ie, total respiratory muscle unloading). RESULTS: Work performed by the patient varied inversely (r = -0.83; p < 0.001) and work performed by the ventilator varied directly with the level of PSV (r = 0.94; p < 0.001). Work performed by the patient was 1.5 +/- 0.3 J/L at zero pressure support ventilation and decreased significantly to 0.50 +/- 0.1 J/L (p < 0.05) as the level of PSV was increased to 18 +/- 7 cm H2O. The respiratory muscles were partially unloaded under these conditions. Patient work decreased to 0 J/L and ventilator work increased when the muscles were totally unloaded at a PSV level of 31 +/- 8 cm H2O. CONCLUSION: We propose an objective and goal-oriented clinical approach for using PSV by directly measuring the work of breathing performed by the patient with an easy to operate, bedside respiratory monitor and then applying pressure support ventilation to decrease the work to appropriate levels. Partially or totally shifting the workload from the respiratory muscles to the ventilator is appropriate under specific clinical conditions.

Acute Disease↗
PubMed1994

Prognostic significance of basement membrane antigens and of soluble interleukin 2 receptor serum concentrations in heart transplant rejection.

Endomyocardial biopsy is still considered the only reliable method for diagnosing acute rejection. However, because of its invasive nature, this procedure cannot be performed on a daily basis. Therefore, for the noninvasive monitoring of transplanted patients, we tested the sensitivity of serum levels of basement membrane antigens, type IV collagen fragment NC1 and laminin fragment P1 (LP1), of antibodies against laminin and type IV collagen, and of soluble interleukin 2 receptor (sIL2R). In 17 patients who underwent heart transplantation no correlation was found between the degree of rejection and the levels of antibodies to type IV collagen and laminin. Serum laminin P1 and sIL2-R values were found increased in all the study groups even in absence of rejection; however, sIL2R levels were higher in patients with more severe rejection. NC1 levels were found significantly higher in patients with mild or moderate rejection than in those with no rejection or in controls. These preliminary data suggest a possible predictive role of basement membrane antigens in cardiac rejection, but further studies in a larger group of transplanted patients are needed.

Adolescent↗
PubMed1993

Immunohistochemical localization of intracellular and extracellular associated TGF beta in the skin of patients with systemic sclerosis (scleroderma) and primary Raynaud's phenomenon.

We have investigated the distribution of TGF beta using antibodies specific for its intracellular and extracellular forms in full-thickness biopsies of patients with SSc, primary Raynaud's phenomenon (PRP), systemic lupus erythematosus (SLE), and from normal subjects. Nine of 11 SSc biopsies demonstrated intracellular TGF beta in endothelial cells while only 6 exhibited extracellular TGF beta. Endothelial cells in skin biopsies of all PRP patients displayed both intracellular and extracellular TGF beta. All other control biopsies were negative. In patients with PRP, some positively staining fibroblasts were found scattered throughout the dermis. Lastly, extracellular TGF beta was localized in the papillary dermis of PRP and SSc biopsies and in all the dermal layers of SLE patients. No significant staining of TGF beta was observed in the endothelial cells, fibroblasts, or in the extracellular matrix of the majority of biopsies from normal subjects. These data suggest that TGF beta may be one of the cytokines involved in the early stages of pathogenesis of SSc, and that endothelial cells in SSc and PRP may be a source and/or a target of TGF beta.

Aged↗
PubMed1993

Antibodies against terminal galactosyl alpha(1-3) galactose epitopes in patients with idiopathic myelofibrosis.

Sera from patients with myelofibrosis were analysed for circulating antibodies against an antigenic determinant characterized by two molecules of galactose in alpha 1-3 linkage (anti-Gal antibodies). 50% of patients were found to have values above the 90th percentile of the values of control sera chosen as a cut-off. The median level of the antibodies was significantly higher than the value detected in normal controls, but no difference could be found between patients with idiopathic myelofibrosis and those with myelofibrosis associated to a chronic myeloproliferative disorder. Anti-Gal antibodies were found to correlate with disease activity and with platelet count whereas no correlation was detected with other haematological parameters. Furthermore, for evaluation of disease activity, determination of serum anti-Gal antibodies was a sensitive and specific parameter. We conclude that humoral immunity against Gal alpha 1-3Gal may provide a sensitive tool to detect disease activity in patients with idiopathic myelofibrosis and may be important for understanding its pathogenesis.

Aged↗
PubMed1993

Serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and systemic idiopathic vasculitis.

Soluble interleukin 2 receptor (sIL2R) may be used as an index of immune perturbation. We report on the correlation between the serum levels of sIL2R, as assessed with a sandwich-ELISA, and disease activity in 61 patients with Systemic Lupus Erythematosus (SLE) and in 15 with systemic idiopathic vasculitis (SIV). The mean levels of sIL2R in SLE and SIV patients were significantly higher than in healthy controls and higher values were detected in patients with active disease or severe organ involvement or infection. We also studied patients with clinically silent SLE, characterized by the presence of several immunologic abnormalities. The sIL2R mean level in this group did not differ from that of quiescent SLE patients, suggesting that immunologic alterations are present even in inactive SLE. Finally, the sIL2R assay showed higher sensitivity and specificity than most of the common immunologic parameters.

Adolescent↗
PubMed1992

Juvenile rheumatoid arthritis patients manifest immune reactivity to the mycobacterial 65-kDa heat shock protein, to its 180-188 peptide, and to a partially homologous peptide of the proteoglycan link protein.

Immune reactivity to the 65-kDa mycobacterial heat shock protein (hsp65) has been associated with arthritis in rats and humans. In this report we evaluated patients with juvenile rheumatoid arthritis for such immunity. A high proportion of affected children showed both antibody and T lymphocyte responses to hsp65 and to two related peptides: the nonapeptide 180-188 sequence of hsp65 and a partially homologous peptide of the cartilage proteoglycan link protein. The titer of circulating antibodies was generally higher in patients with clinically active disease. In contrast to the juvenile rheumatoid arthritis patients, patients with adult rheumatoid arthritis tended to have lower responses of their peripheral blood T lymphocytes to the whole hsp65 molecule. Moreover, the adult rheumatoid arthritis patients did not respond to the peptides. Thus, there appear to be immunological differences between juvenile and adult forms of rheumatoid arthritis related to hsp65 reactivity.

Adolescent↗
PubMed1992

Antibodies to mycobacterial 65 kDa heat shock protein in systemic sclerosis (scleroderma).

It has been reported that immunity to the 65 kDa heat shock protein of Mycobacterium tuberculosis (MT-hsp65) not only accompanies rheumatoid arthritis (RA), but may also be characteristic of chronic inflammation. We now report serum antibodies to MT-hsp65 in 47% of systemic sclerosis (SSc), 38% of primary Raynaud's phenomenon (PRP) and 5% of systemic lupus erythematosus (SLE). Antibody levels were higher in patients with active or progressive SSc and correlated with the degree of skin fibrosis. Thus, immunity to MT-hsp65 appears in SSc and is not limited to RA. However, it does show some degree of specificity beyond chronic inflammation: PRP patients have a higher reactivity than do SLE patients.

Adolescent↗
PubMed1991

Oropharyngeal and esophageal function in scleroderma.

Fifty-one patients with systemic sclerosis (scleroderma) underwent videofluoroscopy during barium swallow to evaluate the incidence of oropharyngeal deglutition abnormalities and to correlate the radiologic patterns of esophageal motility abnormalities with patients' clinical features. Thirteen patients (26%) showed swallowing dysfunction, (e.g., oral leakage, retention, penetration, mild or moderate aspiration, and upper esophageal sphincter incoordination). These dysfunctions were more severe in patients with prominent esophageal dysmotility. Normal esophageal motility was not associated with swallowing alterations. Patients with an oropharyngeal disorder had a higher incidence of pulmonary disease. The clinical picture of the above-mentioned 13 patients was more severe, based on the duration of Raynaud's phenomenon and duration of skin sclerosis. Patients with primary Raynaud's phenomenon had no oral or esophageal abnormalities. The esophageal phase of swallowing was abnormal in 80% of the patients with scleroderma. Esophageal dysfunction, therefore, seems to be frequent in the early stages of the disease. However, patients with advanced or extensive disease may have normal esophageal function.

Adult↗
PubMed1991

Antibodies to mouse laminin in patients with systemic sclerosis (scleroderma) recognize galactosyl (alpha 1-3)-galactose epitopes.

Employing radioimmunoinhibition assays with distinct oligosaccharides as inhibitors, this study demonstrates that the epitope recognized on mouse laminin by sera from patients with systemic sclerosis (scleroderma) is a terminal galactosyl (alpha 1-3)-galactose disaccharide. The reaction with this alpha-digalactose was further confirmed when the sera were tested in radioimmunoassay (RIA) binding assay and in ELISA with synthetic galactose alpha 1-3 galactose coupled to human serum albumin. The circulating antibody appeared restricted to the IgG class and mostly to the subclass IgG3 and IgG4. Antibodies with the same specificity can be found in patients with American cutaneous leishmaniasis and Chagas disease; however, whilst in these diseases the antibody production is triggered by antigenic determinants present on the surface of the parasites, the events eliciting their appearance in systemic sclerosis are unknown.

Disaccharides↗