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Biomedical subjects

P Pozzilli

Publications and source records attributed to P Pozzilli.

At least 163 records · Page 9Linked to original sources

[Isolated persistent left superior vena cava. Detection of cause during central venous catheterization].

The Authors report the causal discovery of isolated persistent left superior vena cava (IPLSVC) during a central venous incannulation with a Groshong's catheter, in a patient undergoing bone marrow transplant. After a short introduction about the IPLSVC ontogenesis, they stress the need for fluoroscopy during the central venous incannulation. The Authors conclude that the possibility of angiocardiography has been very helpful, in this case, for diagnosis and prognosis.

Angiocardiography↗

Raised temperature reduces the incidence of diabetes in the NOD mouse.

An association between the incidence of childhood Type 1 (insulin-dependent) diabetes mellitus and the average yearly temperature in different countries has been reported, the incidence being higher in countries with a lower mean temperature. We have studied the effect of environmental temperature on the incidence of diabetes in an animal model of Type 1 diabetes, the non-obese diabetic (NOD) mouse. Female NOD mice were divided at weaning, with one group placed at a higher temperature (mean 23.7 +/- 1.7 degrees C) and the other at a lower temperature (21.0 +/- 1.8 degrees C). At 20 weeks of age 6 of 16 mice at lower temperature and 1 of 17 mice at higher temperature had developed diabetes (p less than 0.02); at 30 weeks 10 of 16 and 5 of 17 mice had developed diabetes (p less than 0.05). Non-diabetic animals in the low temperature group had a higher food intake than those in the high temperature group between 13-15 weeks of age (28.0 +/- 1.2 g/week vs 24.8 +/- 0.7 g/week, p less than 0.05). In a parallel experiment, histological examination showed that there were similar degrees of insulitis in the high and low temperature groups at seven weeks of age. We conclude that environmental temperature can affect the incidence of diabetes in the NOD mouse and that this may be related to alterations in food intake.

Animals↗

Retinol binding protein: a short half life determinant of protein non enzymatic glycation in diabetes.

The non enzymatic glycation of circulating and structural proteins is the main biochemical consequence of the chronic hyperglycaemia of diabetes mellitus. Retinol binding protein (RPB) is a 21K plasma globulin with an half life of 12 hr; its non enzymatic glycation may reflect the variation of short term metabolic control (1-4 days). In this study two blood samples were withdrawn at four days interval from 24 non insulin dependent diabetic patients. Glycated RBP was measured by a two-site immunoradiometric assay and its variations correlated with the correspondent changes in the blood glucose level. A significant correlation (r = 0.471; p less than 0.02) was found between the time 4/time 0 ratios of glycated RBP and the time 4/time 0 ratios of blood glucose. These data suggest that measurement of non-enzymatically glycated RBP may be a useful tool to evaluate the short term state of non enzymatic glycation in diabetes.

Biomarkers↗

[Impedance plethysmography, Doppler echography and phlebography in deep venous thromboses of the lower limbs].

Computerized impedance plethysmography (CIP) and phlebography were performed on 165 consecutive outpatients with clinical suspicion of deep venous thrombosis (DVT) and on 220 consecutive asymptomatic patients hospitalized for hip fracture. Ninety-two asymptomatic patients were examined also with real-time B-mode US. In orthopedic patients CIP sensitivity, specificity, accuracy, positive and negative predictive values were 19.4%, 90.5%, 64.4%, 53.8% and 66.3%, respectively, for proximal and distal DVT, versus 19.7%, 88%, 77.5%, 77% and 86% for proximal DVT. In symptomatic patients CIP sensitivity, specificity, accuracy, positive and negative predictive values were 83%, 87%, 85%, 87% and 82%, respectively, for proximal and distal DVT, versus 91%, 88%, 89%, 82% and 94% for proximal DVT. CIP had great diagnostic utility in symptomatic DVT, whereas its diagnostic efficacy was low in asymptomatic patients. In orthopedic patients US sensitivity, specificity positive and negative predictive values were 44%, 99.2%, 95.7% and 81.6%, respectively. US diagnostic value was relatively high, but further investigation is needed. To date, phlebography seems to be the only effective method in the diagnosis of DVT in asymptomatic high risk patients.

Diagnosis, Computer-Assisted↗

The natural history of lymphocyte subsets infiltrating the pancreas of NOD mice.

A longitudinal study of lymphocytic infiltration in the endocrine pancreas of non-obese diabetic mice was performed to investigate the role of different lymphocyte subsets in the pathogenesis of diabetes. The incidence of insulitis and the percentage of mononuclear cell subsets in the pancreas were evaluated in non-obese diabetic mice of various ages (5, 9, 13, 17, 22, 29 and 36 weeks). Cryostat sections of pancreas were stained with heamatoxilin-eosin or with different monoclonal antibodies against total T lymphocytes, helper T lymphocytes, cytotoxic/suppressor T lymphocytes, activated interleukin 2 receptor positive lymphocytes and B lymphocytes. A monoclonal antibody against Class-II antigens was also used. Positive cells were revealed by the immunoperoxidase technique. Insulitis was found in 5 weeks old mice but to a lesser extent than in adult animals. No significant variation between infiltrating cell subsets was found in different age groups. T lymphocytes ranged between 20.4% and 28.1%, B lymphocytes between 28.8% and 30.8% and Class-II positive cells between 22.8% and 32.2%. Interleukin 2 receptor positive cells ranged between 5.5% and 8.5% as detected with AMT-13 monoclonal antibody which recognise the interleukin 2 binding site. A higher percentage of activated cells was observed using another monoclonal antibody (7D4) directed against a different epitope of the interleukin 2 receptor, suggesting the presence of activated lymphocytes with interleukin 2 receptors saturated by interleukin 2. No insulin-containing cells were found to express Class-II molecules as demonstrated by a double immunofluorescence technique. Most infiltrating mononuclear cells were found to be positive for Class-II and L3T4 antigens or to be Class-II positive and express surface immunoglobulins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Persistent reduction of CD4/CD8 lymphocyte ratio and cell activation before the onset of type 1 (insulin-dependent) diabetes.

Over a period of 5 years, lymphocyte subpopulations and their markers of activation were studied prospectively in 56 first degree relatives of Type 1 (insulin-dependent) diabetic probands. Lymphocytes were phenotyped using a panel of monoclonal antibodies which recognise CD3, CD4, CD8 lymphocytes, K/NK cells, HLA Class II products and IL-2 receptors (IL-2r). Twenty-six subjects were negative for islet cell antibody (ICA), 18 had complement fixing ICA (CF-ICA) and 12 only conventional ICA (ICA-IgG). The total number of observations (blood samples collected) was 386. Overall, changes in T cell data were observed in the three groups of first degree relatives compared to 70 normal subjects without a family history of diabetes. Six individuals developed Type 1 diabetes in the course of the study. They all possessed CF-ICA and five out of six showed a persistent reduction (less than 1.5) of the CD4/CD8 lymphocyte ratio before the clinical onset of the disease. Activated lymphocytes were found on two occasions in two of these subjects. We conclude that imbalance of lymphocyte immunoregulatory subsets is present before the onset of Type 1 diabetes in susceptible individuals; the persistence of a reduced CD4/CD8 lymphocyte ratio may reflect the ongoing process leading to B-cell destruction.

Antigens, Differentiation, T-Lymphocyte↗

Lessons from the NOD mouse for the pathogenesis and immunotherapy of human type 1 (insulin-dependent) diabetes mellitus.

Suitable animal models of human Type 1 (insulin-dependent) diabetes mellitus have long been sought, in particular a model that would permit detailed histological and immunological investigation of changes in the islet preceding the metabolic disorder. This would allow hypotheses as to pathogenesis of the condition to be examined and interventions such as immunotherapy to be tested. The most widely studied models include the low-dose streptozotocin induced diabetic mouse and the BB rat, but both differ in important respects from the human disease. In this review we describe one highly successful model, the non obese diabetic mouse. Selected aspects of pathogenesis and immunotherapy are presented and analogies with human Type 1 diabetes discussed.

Animals↗

Humoral and cellular immunological factors as possible markers of clinical relapse in HLA-typed Graves' patients followed with time.

Humoral and cellular immune factors were studied in 33 newly diagnosed Graves' patients at diagnosis and in 12 of these patients at regular intervals thereafter. All the patients were treated with carbimazole for 15 months (initially 60 mg and then 20 mg supplemented with L-Thyroxine). The incidence of relapse after treatment was 42%. Thyrotropin receptor antibodies (TRAb), T-cell subsets, K and NK cells and mononuclear cells expressing surface antigen markers of different activation were evaluated respectively by the use of a radioimmunoassay and a panel of monoclonal antibodies. Patients in the follow-up study were HLA-A, B, C and D typed. TRAb levels (91%) and levels of 4F2-positive cells (73%) and class II-positive lymphocytes (69.6%) were significantly increased in newly diagnosed Graves' patients in comparison with normal controls, whereas CD8 cells were significantly decreased. There was a significant inverse correlation between the increase in 4F2-positive cells and TRAb values. In the follow-up study both humoral and cellular immunological parameters showed a wide variation in levels, but TRAb, 4F2 and L243 values declined on average with respect to diagnosis. After 15 months some patients still showed abnormal values of activated T cells and TRAb values. All patients who relapsed (42%) after medical treatment showed a significant increase of 4F2-positive cells, and some of TRAb, some time before the appearance of clinical symptoms. Finally, no correlation was found between HLA type and relapse of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Nonenzymic glycation of isolated human glomerular basement membrane changes its physicochemical characteristics and binding properties.

The chronic hyperglycemia in diabetes mellitus enhances the nonenzymic glycation of structural proteins possibly increasing the formation of highly reactive advanced glycation end products (AGE). These protein changes might be involved in tissue-damaging mechanisms leading to diabetic complications, including diabetic nephropathy. To simulate these events, an in vitro model, based on isolated human glomerular basement membrane (hGBM), has been developed. In this study we have investigated the extent of AGE formation and the binding changes induced by the nonenzymic glycation of hGBM. An enriched fraction of hGBM was isolated from normal human kidneys and glycated in vitro by incubation with glucose (500 mmol/l) at 37 degrees C for 10 days. The presence of AGE was investigated by two methods - spectrofluorescence and the diazonium salt reaction - both specific for this type of chemical entity. The binding capacity of glycated hGBM was tested by a 10-day incubation with human insulin, albumin, immunoglobulin G and fibrinogen. Higher relative spectrofluorescence values at 440 nm emission (20.0 +/- 2.0 vs. 12.5 +/- 5.0) and higher absorbance values at 492 nm (0.798 +/- 0.063 vs. 0.429 +/- 0.228) indicated the presence of increased levels of AGE in glycated vs. native hGBM. Insulin and the three proteins were bound to hGBM in increased amounts after its glycation (p less than 0.05). The results obtained in this in vitro model confirm that enhanced nonenzymic glycation of hGBM induces the formation of AGE and possibly, through these compounds, alters its physicochemical and binding properties. This reaction might contribute to the mechanisms eventually leading to diabetic nephropathy.

Basement Membrane↗

[24-hour behavior of T-lymphocyte subpopulations in patients with stable heart transplants receiving cyclosporin therapy].

In 10 heart transplanted subjects (HTS) undergoing conventional immunosuppressive cyclosporine therapy, in comparison with 10 normal subjects, the 24 hour patterns of T lymphocyte subpopulations, namely, OKT3 (total T lymphocytes), OKT4 (helper lymphocytes) and OKT8 (cytotoxic or suppressor) in relation to the circadian rhythms for plasma cortisol (marker rhythm) and to circulating levels of cyclosporine were studied. From the collected data, it can be deduced that the OKT3, OKT4, OKT8 subpopulations and the plasma cortisol level show 24-hour non-periodic variations. The lymphocyte subpopulations show a negative correlation with circulating levels of cyclosporine. The negative correlation is "selective" and "delayed" in that it is detectable at particular and non-coinciding hours. Plasma cortisol is also negatively correlated to plasma cyclosporine. Assessing the meaning of the lack of a circadian rhythm of the lymphocyte subpopulation in HTS undergoing conventional cyclosporine therapy, and taking into account the pharmacological time-stage dependency, we can emphasize the idea that the optimization of anti-rejection therapy with cyclosporine may and should be performed as a time-modulated treatment.

Adult↗

Thymopentin administration and increase of sero-conversion after B-hepatitis vaccine in diabetic patients.

We have previously reported that 40% of diabetic patients have an impaired specific immune response after vaccination against B-hepatitis. Thymopentin (TP5), the active site of thymopoietin hormone, has been shown to increase antibody response (HbsAb) following B-hepatitis vaccination in several disease conditions. In the present study TP5 (50 mg) was administered subcutaneously three times per week to 17 diabetic patients for a week prior B-hepatitis vaccination and for three weeks afterwards. Sero-conversion was observed after the third dose of vaccine in 15 out of 17 (88%) patients and in 94% of a group of normal subjects acting as control. Although the median HbsAb titre was significantly lower in diabetics compared to normal subjects, we conclude that administration of TP5 in diabetic patients increases the rate of sero-conversion following B-hepatitis vaccination.

Adjuvants, Immunologic↗