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Biomedical subjects

A Doria

Publications and source records attributed to A Doria.

At least 127 records · Page 7Linked to original sources

Metabolic control of kidney hemodynamics in normal and insulin-dependent diabetic subjects. Effects of acetoacetic, lactic, and acetic acids.

Diabetes mellitus is associated with important changes in renal hemodynamics. The purpose of this study was to determine whether an increase in blood concentration patterns of ketone bodies and lactic acid, organic acids often elevated in poorly controlled insulin-dependent diabetes mellitus (IDDM), could contribute to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) regardless of changes in circulating levels of glucose and insulin. Six IDDM patients and six normal subjects were given a saline infusion (15 mumol.min-1.kg-1) for 2 h, an acetoacetic acid infusion (15 mumol.min-1.kg-1) for another 2 h, and then a saline infusion after an overnight fast during euglycemic insulin-glucose clamp. Acetoacetic acid infusion resulted in an increase of blood ketone bodies in the range of 0.7-1.5 mM from a basal value of 0.1-0.3 mM. GFR was 125 +/- 16 and 136 +/- 17 ml.min-1.1.73 m-2 in normal and IDDM subjects, respectively, during baseline saline infusion and 138 +/- 21 (P less than .01 vs. basal level) and 158 +/- 15 ml.min-1.1.73 m-2 (P less than .001 vs. basal level) during acetoacetic acid infusion. During the last saline infusion, renal hemodynamic patterns decreased again to baseline levels. Another six IDDM patients and six normal subjects were given saline, lactic acid, and saline infusions at the same rates of infusion after an overnight fast during euglycemic insulin-glucose clamp. Lactic acid concentration increased from approximately 0.5-0.8 to 1.0-1.5 mM in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Prevalence of anticentromere antibody in blood relatives of anticentromere positive patients.

Anticentromere antibody (ACA) was investigated in 116 blood relatives of 22 ACA positive patients affected with scleroderma and, for comparison, in 82 healthy subjects matched for age and sex who belonged to 25 families. No relative showed any evident scleroderma symptom although in 8 an unusual cold sensitivity of the extremities was present. ACA at a low titer (40), was found in 4 relatives (3.44%), while it was absent in control sera. The 4 ACA positive relatives were first as well as second degree relatives of probands. Two had familial disease: one idiopathic chronic hypoparathyroidism and the other mental retardation. The third had myasthenia gravis and the fourth unusual cold sensitivity and allergic dermatitis. At present we cannot explain the significance of ACA occurrence in relatives of ACA positive patients. Followup clinical and serological studies could show a possible association of low titer of ACA with subclinical scleroderma features in patients who later develop overt disease.

Adolescent↗

[Assay of rheumatoid factors by the indirect immunofluorescence method].

Sera from 69 patients affected with rheumatoid arthritis were examined for IgM, IgG and IgA rheumatoid factors (RF) by a indirect immunofluorescence method. The results were compared with those obtained from the classical rheumatoid factor latex test. By this technique we have demonstrated antigammaglobulin activity in a high proportion (23%) of sera from latex test seronegative rheumatoid patients. Moreover, by fractionated antisera it was possible to detect also IgG and IgA factors. Indirect immunofluorescence results to be a simple and available technique for detection of RF, also in many "seronegative" patients.

Adolescent↗

[Rheumatoid factors: value of their determination in patients with rheumatoid arthritis].

IgM, IgA, IgG rheumatoid factors were investigated by a indirect immunofluorescence method in three groups of patients affected with rheumatoid arthritis of various picture: 30 patients with mild articular disease, 20 with severe joint involvement and 19 with articular and systemic symptoms. Rheumatoid factors occurred more frequently in patients with articular and extraarticular severe rheumatoid arthritis; moreover these patients showed higher titres and higher incidence of different immunoglobulin class rheumatoid factors in comparison with rheumatoid patients having mild joint disease.

Adolescent↗

Ketone body kinetics in vivo using simultaneous administration of acetoacetate and 3-hydroxybutyrate labelled with stable isotopes.

Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single 14C tracer and the so called 'combined KB specific activity'. By definition, this approach does not allow to evaluate the individual kinetics of acetoacetate (AcAc) and 3-hydroxybutyrate (R-BHB) which is feasible only using the separate administration of 14C tracer AcAc and R-BHB. In the present study we followed a different approach using the simultaneous administration in vivo of [1,2,13C2] AcAc and m [1,2,3,4(13)C4] R-BHB which allows to evaluate the individual kinetics of the two KB in the some study, thus minimizing the magnitude of blood sampling and the potential changes in the metabolic conditions of each subject. The four isotopic 13C/12C KB ratios of AcAc and R-BHB tracer and tracee blood concentrations along with the fluorimetric measurement of 12C concentrations were determined in each blood sample. Using compartmental analysis following single dose bolus injection the production rate of KB was 206 +/- 57 mumol/min/1.73 m2 (mean +/- SD). The turnover rate of KB using noncompartmental analysis, during continuous infusion in a separate study was 294 +/- 41. The plasma clearance rates of AcAc and R-BHB were 1966 +/- 502 and 1443 +/- ml/min/1.73 m2, respectively. The mean residence time was 17 +/- 3 min and the total distribution volume 20 +/- 9.7 l/m2. We conclude that: (1) stable isotope tracer infusion allows the contemporary in vivo administration of the two KB and the simultaneous assessment of individual AcAc and R-BHB kinetics; (2) the estimated compartmental and noncompartmental parameters of KB turnover were similar to those observed in normal overnight fasting subjects following separate radioactive tracer injections.

3-Hydroxybutyric Acid↗

Type I insulin-dependent diabetic patients show an impaired renal hemodynamic response to protein intake.

Human kidney responds to a meat meal with an increase in glomerular filtration rate (GFR), but the mechanisms regulating kidney hemodynamics following protein intake are poorly understood in Type I insulin-dependent diabetes. In the present study we investigated GFR response to protein intake (600 gr/1.73 m2 meat meal) in nine normal subjects and 21 Type I insulin-dependent diabetic patients with normal albumin excretion rates as well as proximal tubular sodium reabsorption rates and distal sodium delivery (PRNa and DDNa). The same study was reperformed in normal subjects and diabetic patients, with less than a 5 year diabetes duration, following one week of indomethacin treatment. Normal subjects showed a 38% increase in GFR following protein intake, whereas diabetic patients showed a significantly lower response (18%, p less than 0.01). The response of GFR to protein challenge was negatively related to diabetes duration but not to baseline glomerular filtration rate. Indomethacin treatment completely prevented the protein induced GFR increase in normal subjects but not in diabetic patients. Sodium reabsorption rate was increased following protein challenge both at the proximal and distal tubular level, as was net natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗

[Detection of serum anti-B/B' UsnRNP antibodies in patients with connective tissue diseases by immunoblotting].

OBJECTIVE: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B' polypeptides of U small nuclear ribonucleoproteins (UsnRNP) and to assess the significance of these antibodies in connective tissue disease (CTD) patients. METHODS: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjögren's syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD), of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV) infection with high titre of IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line) and Jurkat cells (a human T lymphoid cell line). Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. RESULTS: A high frequency of anti-B/B' antibodies was found in the sera of CTD patients, confined to SLE (54.4%) and overlap CTD with SLE features (55,2%). Anti-B/B' immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60%) anti-B/B' positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. CONCLUSIONS. The Sm B/B' proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and "lupus-like" overlap CTD. Moreover, anti-B/B' is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells is a reliable method, in terms of sensitivity and specificity, for the detection of anti-Sm B/B' antibodies.

Autoantibodies↗

[Myositis specific and myositis associated autoantibodies in idiopathic inflammatory myopathies: a serologic study of 46 patients].

OBJECTIVE: To characterize serum autoantibody profiles of patients with idiopathic inflammatory myopathies (IIM) by searching for myositis-specific (MSA) and myositis-associated (MAA) antibodies with sensitive and specific laboratory tests. METHODS: We tested the sera from 46 Caucasian patients diagnosed as affected with IIM at the Division of Rheumatology of Padova University (21 polimyositis, PM; 22 dermatomyositis, DM; 3 myositis overlap syndrome). All patients had definite IIM according to the criteria of Bohan-Peter. MSA including anti-tRNA synthetase (anti-Jo-1 and others) and anti-Mi-2 were determined by RNA immunoprecipitation and a modified immunoblot test, respectively. MAA (-U1RNP, -U2RNP, RoRNP, PM/Scl, Ku) were detected by counterimmunoelectrophoresis and immunoblot. RESULTS: Serum MSA and/or MAA were found in 30/46 (65%) patients with IIM. Twenty-three patients (50%) were positive for at least one MSA: anti-Jo-1 in 15 (33%), anti-Mi-2 in 6 (13%), and other anti-tRNA synthetase in 3 (6%). One patient was anti-Jo-1/Mi-2 positive. Moreover, 18 patients (39%) were positive for at least one MAA: anti-Ro/SSA in 13 (28%), anti-U1RNP in 4 (9%), anti-PM/Scl in 1 (2%) and anti-Ku in 1 (2%). Coexisting MSA and MAA were observed in 8 patients (17%), anti-Jo-1/SSA positive in most cases. Anti-Jo-1 was predominantly associated with PM (57% in PM vs 14% in DM), whereas anti-Mi-2 was exclusively found in DM patients (27%). Anti-synthetase antibodies were closely associated with interstitial lung disease and polyarthritis; anti-Mi-2 positive DM patients did not have lung involvement. Notably, anti-Ro/SSA antibody was frequently observed and almost equally detected in either PM or DM (about 30%): in more than 50% of cases the antibody was associated with one MSA. CONCLUSIONS: By means of analytically reliable methods, MSA was detected in 50% of our IIM patients. Searching for MSA in patients with IIM is recommended because of its diagnostic and prognostic value.

Adolescent↗

[Acute cardiotoxicity from 5-fluorouracil: un underestimated toxicity].

The most common toxicity in clinical trials with 5-FU, in mono or polychemotherapy, is stomatitis, diarrhea, hand-foot syndrome. In this case report, the 5-fluorouracil (5-FU) cardiotoxicity, an uncommon 5-FU-related toxicity, has been investigated. Cardiotoxicity reports are uncommon because the problem is not well known. This study is also a review of the recent literature and it recommend to take care in prescribing chemotherapy to patients with heart disease history.

Antineoplastic Combined Chemotherapy Protocols↗

[Non SLE connective tissue diseases: general aspects and kidney].

Connective tissue diseases represent a group of heterogeneous disorders that share certain common features, including inflammation of the skin, joints and other structures rich in connective tissue, as well as altered immunoregulation patterns, including autoantibody production and cell-mediated immunity abnormalities. While certain distinct clinical entities can be defined, manifestations can vary considerably from patient to patient, and the overlap of clinical features between and among specific diseases is common. Genetic, environmental and sex hormonal factors are likely to be of pathogenic importance. Among these diseases, systemic lupus erythematosus is the most frequent, followed by systemic sclerosis or scleroderma (SSc), Sjogren's disease, polymyositis and dermatomyositis and mixed connective tissue disease. Systemic sclerosis involves multiple organs in a process consisting of disseminated sclerosis affecting all compartments. Prominent vascular lesions typify the renal lesions. Scleroderma crisis is a major complication of SSc, characterized by severe hypertension, rapidly progressive renal failure, thrombotic microangiopathy with hemolitic anemia and low platelet count: the prompt use of angiotensin-converting enzyme (ACE) inhibitors significantly increased the 1-yr survival rate from 15 to 76%. Sjogren's syndrome is an immunologic disorder characterized by progressive lymphocytic destruction of the exocrine gland, frequently resulting in symptomatic eye and mouth dryness. The interstitial lesions constitute the principal renal manifestations: interstitial infiltrates and small lymphocytes, which can be homogenous and massive. In polymyositis and dermatomyositis renal involvement is rare.

Connective Tissue Diseases↗

Lupus erythematosus and the skin.

Cutaneous manifestations of patients with lupus erythematosus (LE) are very frequent, show a great variety and can occur at any stage of the disease. The most consistent environmental trigger factors so far recognized are exposure to ultraviolet light and certain drug classes known to be capable of inducing LE in otherwise healthy individuals. A classification system has been established including clinical, histologic, photobiologic, serologic, and immunogenetic findings to better define the different cutaneous subtypes of LE. During their clinical evolution, the cutaneous manifestations vary considerably, and, therefore, the diseases which should be considered in differential diagnosis are different, according to the stages of disease development. Furthermore, 25 years of experience worldwide have revealed that individuals whose disease presentation is dominated by subacute cutaneous LE skin lesions and the presence of circulating anti-Ro/SS-A antibodies represent a rather homogeneous immunogenetic subphenotype of LE that enjoys a good prognosis over time. Treatment should be individualized according to disease severity. The majority of patients with cutaneous manifestations of LE do not require systemic immuno-suppressive/ immunomodulatory therapy and the advent of recombinant biologicals has given hope to the small percentage of patients that suffer from particularly severe skin disease activity.

Humans↗

The antiphospholipid antibody syndrome: diagnosis, skin manifestations and current therapy.

Antiphospholipid antibody syndrome is characterized by venous and/or arterial thrombosis and/or pregnancy morbidity associated with antiphospholipid antibodies (aPL), such as anticardiolipin antibodies, anti beta 2 glycoprotein I antibodies and positive lupus anticoagulant test. This syndrome may potentially affects any organ system including the skin. Livedo reticularis is the most frequently observed cutaneous lesion; other lesions, by order of frequency, are ulcerations, digital gangrene, subungueal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis and primary anetoderma. Skin lesions are more frequently observed in the catastrophic antiphospholipid syndrome, characterized by widespread microvascular occlusions involving multiple organs simultaneously. Patients with antiphospholipid associated thrombosis should receive long-term oral anticoagulants. The intensity of anticoagulation should be guided according to the nature of the thrombotic event (venous vs. arterial thrombosis). Patients with aPL-associated pregnancy morbidity should be treated with aspirin plus heparin and closely monitored during pregnancy. The treatment of the catastrophic antiphospholipid syndrome remains unsatisfactory. High dose intravenous steroids and parenteral anticoagulation should be supplemented by intravenous gammaglobulin and repeated plasma exchanges using fresh frozen plasma early on in the course of the syndrome.

Antiphospholipid Syndrome↗