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Biomedical subjects

G Graziani

Publications and source records attributed to G Graziani.

At least 73 records · Page 4Linked to original sources

Validation study of thoracic fluid bioimpedance for assessing the haemodialysis-induced changes in total body fluids.

Thoracic fluid bioimpedance (TFB) has been proposed as a noninvasive technique for monitoring both haemodynamics and fluid homeostasis in patients on regular dialysis. To validate the reliability of TFB in assessing the haemodialysis (HD)-induced changes in plasma volume (PV) in these patients, we examined the changes of TFB during and after HD in relation to those in total plasma protein (TP) concentration, haematocrit (Ht), heart rate (HR), total body water (TBW) and plasma angiotensin II (A-II) concentration. Data were recorded in 13 HD patients with a wide range of interdialytic weight gains before, at the end, and 4, 8, 24, 48 h after the HD session. We found that the percent TFB changes were closely and inversely related with those of TP, Ht and TBW (r = -0.54, r = -0.45 and -0.68, respectively, p < 0.001 for all). Similar relations were found between the percent changes in TFB and those in absolute TP and Ht. In addition, a direct relation was found between the percent changes of TFB and those of HR and of A-II (r = 0.33 and r = 0.31, respectively, p < 0.01 for both). These data indicate that TFB is a reliable method for evaluating the HD-induced changes of intra- and extravascular fluids and, with respect to the conventional techniques, has the advantage of providing this information dynamically, and in conjunction with the haemodynamic data of patients.

Adult↗

High prevalence of silent gallstone disease in dialysis patients.

Gallstone disease was detected in 28% of 119 patients on regular dialysis treatment. The disease was silent in 82% of the patients. Stones were radiolucent in 88% of the cases, radioopaque in 8% and mixed in 4%. Among 49 variables considered, increasing age was the only variable that correlated significantly with increasing prevalence of gallstone disease. Since no relationships were found between gallstones and age or modes of dialysis, it is conceivable that some mechanism(s) linked with the preexisting chronic nephropathy might have been involved in the development of cholelithiasis. End-stage renal disease could be another so far unrecognized risk factor for cholelithiasis.

Adult↗

Chemoembolization in liver malignant involvement. Experiences on 17 cases.

INTRODUCTION: Liver invasion is the major cause of organ failure in patients with primary liver cancer and metastatic large bowel cancer. Furthermore it causes high morbidity in many other carcinomas. The normal liver presents a double circulation: 75% from portal circulation and 25% from hepatic artery. In malignant primary and secondary lesions the blood support is given by hepatic artery. Antineoplastic drugs mixed to selectively injecting embolic particles, such as polyvinyl alcohol and gelatin powder (Gelfoam), can be injected to infarct tumors and to obtain a therapeutical advantage. Chemoembolization using an emulsion of Lipiodol ultra-fluid (LUF) and drugs is a recent tool in liver regional therapy. LUF has been shown to be taken up hepatocellular carcinoma and retained for a long period of time in the tumor bed. Chemoembolization causes massive shrinkage due to ischemia and increasing the local drug intensity and drug exposure. Our study reports the results of multi-agents chemoembolization (MACHEM) in 17 patients bearing massive liver involvement. MATERIAL AND METHODS: From January 1988 we treated 17 patients (5 HCCs, 7 large bowell carcinomas, 1 gastric cancer, 1 ocular melanoma, 1 pancreas, 1 soft tissue sarcoma, 1 carcinoid) using a transfemoral approach to cannulate the celiac axis and then the hepatic artery. The catheter was advanced into the vessel responsible for the majority of the tumor blood supply and a mixture of Gelfoam, radiopaque contrast media, followed by chemotherapy (mitomycin 10 mg/sqm, cisplatin 20 mg/sqm, epirubicin 20 mg/sqm) mixed to LUF was injected until vascular stasis occurred. After chemoembolization, analgesics and anti-pyretics were administered. Liver function tests were monitored daily. RESULTS: Objective tumor regression was observed in 11 out 15 full evaluable patients; the median duration of survival was 9.5 months. Within 8 weeks shrinkage, due to development of necrosis, appeared in the tumors. One patient with high levels of 5-HIAA due to carcinoid, demonstrated more than 75% decreasing in urinary excretion. In 6 patients out 8 with CEA elevation a clear reduction was documented as well in 2 HCCs out 5 with alfa-fetoprotein elevation. DISCUSSION: The palliation of HCC and metastatic liver disease have been extremely disappointing. Systemic chemotherapy produces in HCC a response rate of no more than 20% and does not increase the median survival. Venook obtained 24% of PRs and liquefaction in 35 out 50 HCC treated with chemoembolization. Some results have been also demonstrated in the treatment of metastatic liver tumors by Carrasco, Daniels and Modiano. Moertel stressed that chemoembolization could be incorporated in the initial management of carcinoid. Because of the difference in chemoembolization protocols it is difficult to compare the relative efficacy of this tool, although encouraging response rates have been reported in palliation of bulky tumors. In our study Gelfoam given before LUF and antineoplastic agents mixture produce a distal arteriolar occlusion and this would facilitate the migration of the polychemotherapy emulsion toward the tumor. Our MACHEM program has been shown to have significant activity even in heavily pretreated patients with an acceptable toxicity. We conclude that hepatic arterial chemoembolization will be improved by mean of better combination of chemotherapy with embolizing agents in well selected patients.

Adult↗

Hepatorenal syndrome. New perspectives in pathogenesis and treatment.

Hepatorenal syndrome is a life-threatening complication of severe liver disease. It is generally accepted that the syndrome is the final stage of complex hemodynamic derangements associated with portal hypertension, ie, peripheral arterial vasodilation, effective hypovolemia, and hyperkinetic status. In spite of reduced systemic resistances, intrarenal vascular resistances are increased. This is probably the consequence of the activation of systemic vasoactive factors, such as the renin-angiotensin system, the sympathetic nervous system, and vasopressin aimed at restoring arterial filling pressure. Recently, it has been shown that intrarenal vasoconstrictors, such as leukotrienes and endothelins, are activated with the progression of liver disease. The renal vasoconstriction is counterbalanced by the intrarenal hyperproduction of vasodilating prostaglandins and kallikreins. When this balance is lost, for whatever mechanism, the renal vascular resistances dramatically increase and the hepatorenal syndrome develops. In spite of increased knowledge about pathogenesis, the treatment of hepatorenal syndrome remains unresolved. Low-dose dopamine or ornipressin are currently employed in many liver units to avoid further deterioration of renal function in patients with severe liver disease who are waiting for liver transplantation that remains, at present, the only effective treatment for hepatorenal syndrome.

Hepatorenal Syndrome↗

Emergence of double-positive CD4/CD8 cells from adult peripheral blood mononuclear cells infected with human T cell leukemia virus type I (HTLV-I).

It is known that the human T lymphotropic retrovirus type I (HTLV-I) preferentially selects lymphocytes expressing the CD4 phenotype in vivo and in vitro. The present study shows that the emergence of double-positive (DP) CD4/CD8 cells was a constant, even if transient, phenomenon occurring in early phases after the in vitro HTLV-I infection of adult human peripheral blood mononuclear cells (PBMC). Moreover, purified CD8+ lymphocytes, isolated from human PBMC after challenge with HTLV-I, gave origin to a relatively stable DP CD4/CD8 cell line after a few weeks in culture. Conversely, isolated CD4+ T lymphocytes did not show DP emergence during either the early phases of HTLV-I infection or long-term culture. One of the DP cell lines was maintained in culture for more than 1 year and was characterized on the basis of virological and phenotypic features. This cell line bore HTLV-I sequences as demonstrated by PCR analysis, and 60-90% of the DP cells expressed the virus core protein p19. In addition the phenotype of this DP cell line infected with HTLV-I highly expressed antigens associated to activation such as CD45R0, CD18, and CD54.

Antigens, CD↗

Transient HTLV-I infection of a human glioma cell line following cell-free exposure.

The human T-lymphotropic virus type I (HTLV-I) has been recently associated with cases of tropical spastic paraparesis and human myelopathy. In order to study whether cells of neuroectodermic origin were susceptible to HTLV-I infection, a human glioma cell line T67 was exposed in vitro to HTLV-I by a cell-free method of virus transmission. The presence of HTLV-I proviral DNA was analyzed by polymerase chain reaction 3, 7, and 14 days after infection. The results showed the presence of LTR, pol, and tax sequences within glioma cell line 3 days after the infection. However after 7 and 14 days, detection of HTLV-I sequences remarkably decreased. P19 expression peaked 7 days after infection and decreased in the following week. These data provide evidence that cell-free transmission of HTLV-I results in transient infection of cells of glial origin.

DNA, Viral↗

In vitro combined effects of human interferons and interleukin-2 on natural cell-mediated cytotoxicity.

In vitro modulation of natural cell-mediated cytotoxicity (NCMC), following sequential treatment of human mononuclear cells (MNC) with cytokines was investigated. Recombinant Interleukin-2 (IL2) used in combination with interferons (IFNs) induced variable effects on the cytolytic function of different MNC preparations obtained from 16 healthy donors. When MNC were treated with IFNs on day 4, after IL2 induction of LAK cells, increase or no change in cytotoxic activity was found. On the other hand, either no change or decrease in LAK activity occurred when MNC were treated with IFNs on day 0 before exposure to IL2. In this case the effect of IFNs on NCMC did not correlate with their activity on cell proliferation or on TAC antigen expression. In conclusion the present study points out that the NCMC of MNC of healthy donors, subjected to IL2 treatment in vitro, can be significantly increased by IFNs. However this effect is largely schedule-dependent (i.e. detectable with IL2-IFNs but not with IFNs-IL2 sequence), and can be obtained in a relatively limited number of cases. Moreover it is suggested that these in vitro studies could provide preclinical bases for a rational approach to in vivo treatment with cytokine cascade in a clinical setting.

Cell Division↗

Hypertension and chronic renal insufficiency: the experience of the Northern Italian Cooperative Study Group.

There is general agreement that hypertension is a prognostic index of the progression of chronic renal insufficiency (CRI), although it remains to be clarified whether this is related to the hypertension per se, or to the underlying disease and the level of CRI. In an attempt to clarify this important point, an inductive analysis was made of the behavior of blood pressure values and their relationship to the progression of CRI in 456 patients (pts) who participated in a multicenter prospective formal randomized trial, designed to compare the effects of a restricted and a controlled protein diet on CRI progression. An analysis was also made (on the population as a whole and by separating the pts into fast progressive and slowly progressive groups) of the type and frequency of the antihypertensive drugs used, the number and type of drugs used in association, and their possible relationship to the progression of CRI. Of the 456 enrolled pts, 406 (89%) were defined as hypertensive at entry (mean blood pressure > 107 mm Hg); 324 out of the 380 pts (85.3%) who completed the 24-month follow-up or reached an end point were treated with antihypertensive drugs. There was a significant difference at entry between the supine blood pressure values of the pts with fast progressive CRI (182 pts), and those of the pts with slowly progressive CRI (198 pts). During the follow-up period, no significant differences were observed between the two groups. There was no difference in the blood pressure levels reached with the different drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Abnormal hemodynamics and elevated angiotensin II plasma levels in polydipsic patients on regular hemodialysis treatment.

To investigate the cause and the mechanisms responsible of the compulsive thirst and excessive fluid intake observed in many patients on chronic dialysis treatment, we measured plasma antidiuretic hormone (ADH), angiotensin II (Ang II) and some hemodynamic parameters in seven polydipsic and in six normodipsic patients before hemodialysis, at the end of it and several times during the interdialytic interval. Before dialysis we found that ADH was elevated in both groups (6.9 +/- 1.9 vs. 6.9 +/- 1.3 pg/ml, respectively in polydipsics and controls), whereas Ang II was abnormally high only in polydipsics (51 +/- 12 vs. 11 +/- 3 pg/ml, P < 0.01); these patients also had significantly higher heart rate and cardiac indices and lower total peripheral resistances than control patients. Overall these hemodynamic indices were related with Ang II but not with ADH. Ang II rose markedly in polydipsics after dialysis, reaching a peak at the fourth hour after its termination (136 +/- 12 pg/ml) and remained consistently elevated throughout the interdialytic period, whereas in controls Ang II was practically unchanged with respect to baseline. In contrast, ADH had minor and similar modifications in both groups, in whom also the hemodynamic changes were superimposable. Significant correlations were found between the absolute and percent changes of Ang II and those of plasma volume during the interdialytic interval (P < 0.001 for both), and between the individual values of Ang II measured during the whole study and the interdialytic weight gain (P < 0.05). These results demonstrate that polydipsic patients have abnormally high levels of Ang II before and after the hemodialysis-induced volume depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma exchange in systemic lupus erythematosus. Experience in thirty-seven patients.

Thirty-seven (37) SLE patients submitted to therapeutic plasmapheresis were examined. The results were good in the active stage of the disease. Various types of antibody, anti-DNA, anti nucleus, anti-cardiolipine, I.C. (Clq and C3d) were removed. The values of IgG, coagulation factors, creatinine and proteinuria were assessed. Close collaboration with the clinicians is urged, with the aim of applying immunosuppressive therapy immediately after P.E. to consolidate the results obtained.

Adolescent↗

Treatment of pelvic osteosarcoma.

Pelvic osteosarcoma is a very rare disease, with poor prognosis affecting young people. Since June 1987 we have observed 26 patients, F/M: 12/14, median age 23 years (range 14-55), 7 with lung metastases at diagnosis. Four patients underwent surgery as first line treatment; 4 patients received intravenous (i.v.) chemotherapy; eighteen out of 26 received 1-3 cycles of neoadjuvant chemotherapy consisting of high dose i.v. methotrexate plus leucovorin rescue, intraarterial cisplatin and i.v. epidoxorubicin. We obtained 8 PR, 9 SD, 1 PD. Hemipelvectomy has been performed in 4 cases (0%, 0%, 50%, 70% necrosis). The other 14 patients, judged not operable, received radiotherapy plus daily low doses of cisplatin. All patients have been treated with i.v. epidoxorubicin, ifosfamide, high dose methotrexate, cisplatin and etoposide. Two out of four patients who underwent surgery died at 17 and 18 months, 2 are alive and free of disease at 28+ and 17+ months from surgery. Among the 14 patients treated with radiotherapy, 9 died with a median survival of 18 months (5-22); 5 are alive with a median survival of 20 months (14-31). Although pelvic osteosarcoma has a limited cure rate at present, results could be improved in the future by means of earlier diagnosis and better combined treatment.

Adolescent↗

Prevalence of hepatitis C virus antibodies in hemodialysis patients in the area of Milan.

We studied the seroprevalence of antibodies to hepatitis C virus (HCV Ab) in a cohort of 229 chronic hemodialysis patients followed by 6 Dialysis Units in the Milan area. HCV Ab was present in 51 (22.3%) of 229 examined patients. Previous blood transfusions and surgery did not clearly influence HCV seroconversion, whereas duration of dialysis treatment seems to be strictly related to HCV Ab positivity.

Adult↗

Induction of Xenopus oocyte meiotic maturation by the dbl oncogene product.

The dbl oncogene was originally identified by transfection of NIH3T3 cells with DNA from a human diffuse B-cell lymphoma. The dbl oncogene product is a cytoplasmic phosphoprotein distributed between the cytosolic and cytoskeletal matrix-associated membrane fractions. Nucleotide sequence analysis has indicated that the predicted dbl product is very hydrophilic with no detectable similarity to known oncogene products. We have more recently discovered that a region of dbl essential for its transforming activity shows significant sequence similarity to a yeast cell cycle gene, CDC24, which is involved in cell polarity and bud formation in the division cycle of Saccharomyces cerevisiae. This sequence similarity suggests a possible role for dbl in cell division. We report here that the dbl oncogene product is able to induce maturation of Xenopus oocytes. Germinal vesicle breakdown (GVBD) was observed when oocytes were microinjected with the soluble fraction of SF9 insect cells infected with a dbl recombinant baculovirus as well as with the in vitro-transcribed dbl mRNA. Moreover, extracts of oocytes microinjected with dbl mRNA showed activation of H1 histone kinase activity. These findings define a new biologic activity of the dbl product and provide the opportunity to analyse dbl interactions with other components of signaling pathways involved in oocyte maturation.

Animals↗

Factors affecting chronic renal failure progression: results from a multicentre trial. The Northern Italian Cooperative Study Group.

In order to evaluate the prognostic factors concerning the rate of progressive deterioration of renal function, we made an inductive analysis of the behaviour of 456 patients in a multicentre, formal prospective trial aimed at clarifying the possible role of protein restriction in retarding the progression of chronic renal insufficiency (CRI). The main clinical and laboratory findings in patients whose plasma creatinine (PCr) levels doubled in comparison with baseline randomization values or who needed dialysis within 24 months after onset of the study were compared with those of the other patients. In addition, independently of the assigned diet, we tested the main variables that might affect CRI progression (sex, systolic and diastolic blood pressure, change in body weight, hematocrit, calcium-phosphate product, proteinuria, protein catabolic rate, total cholesterol and triglycerides). We used multiple regression analyses and also plotted the mean values of these parameters in each patient against an estimate of the deterioration of chronic renal failure based on the difference between the final and the initial reciprocal of the PCr and the creatinine clearance (CCr) levels. A descriptive analysis of the behaviour of PCr in the three CRI groups and in the four underlying diseases groups was made. PCr levels at entry, underlying disease and proteinuria were prognostic factors for CRI progression. The increase in PCr was 0.0102 mg/dl/month in patients with nephrosclerosis, 0.0203 mg/dl/month in interstitial nephropathy, 0.0360 mg/dl/month in glomerulonephritis and 0.0704 mg/dl/month in polycystic kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prospective, randomised, multicentre trial of effect of protein restriction on progression of chronic renal insufficiency. Northern Italian Cooperative Study Group.

A multicentre, prospective trial was organised to clarify the role of protein restriction in the progression of chronic renal insufficiency (CRI). 456 adult patients were assigned either a low-protein diet (0.6 g/kg body weight daily; n = 226) or a "normal" controlled-protein diet (1.0 g/kg daily; n = 230) and were stratified into three groups (A-C) with increasing baseline plasma creatinine concentrations. Each patient was followed up for 2 years or until an endpoint (a doubling of the baseline plasma creatinine or a need for dialysis) was reached. The difference between the diet groups in cumulative renal survival defined by these endpoints (27 low-protein, 42 controlled-protein) was of borderline significance (p less than 0.06). The difference in renal survival between the low-protein and controlled-protein diet groups was of borderline significance in group A (0 vs 4 endpoints), significant in group B (10 vs 21 endpoints; p less than 0.025), and not significant in group C. There were no differences among the diet groups or subgroups in mean plasma creatinine concentrations, creatinine clearance, the slope of the plasma creatinine reciprocal, or mean blood pressures. Compliance was good in the controlled-protein group but poor for the low-protein diet: the difference in protein intake between the groups was substantially less than that required by the protocol. However, there was no correlation between the progression of renal failure and protein catabolic rate. These findings offer little, if any, support to the hypothesis that protein restriction retards CRI progression: careful medical care and a "normal" controlled protein intake also allow very slow progression of CRI.

Actuarial Analysis↗

Requirement of phospholipase C-catalyzed hydrolysis of phosphatidylcholine for maturation of Xenopus laevis oocytes in response to insulin and ras p21.

Recent studies have demonstrated the activation of phospholipase C-mediated hydrolysis of phosphatidylcholine both by growth factors and by the product of ras oncogene, ras p21. Also, evidence has been presented indicating that the stimulation of this phospholipid-degradative pathway is sufficient to activate mitogenesis in fibroblasts. In Xenopus laevis oocytes, microinjection of transforming ras p21 is a potent inducer of maturation, whereas microinjection of a neutralizing anti-ras p21 antibody specifically inhibits maturation induced by insulin but not by progesterone. The results presented here demonstrated that microinjection of phosphatidylcholine-hydrolyzing phospholipase C is sufficient to induce maturation of Xenopus laevis oocytes. Furthermore, microinjection of a neutralizing anti-phosphatidylcholine-hydrolyzing phospholipase C specifically blocks the maturation program induced by ras p21/insulin but not by progesterone.

Animals↗

Role of GTPase activating protein in mitogenic signalling through phosphatidylcholine-hydrolysing phospholipase C.

Recent evidence has accumulated showing that activation of PLC-catalysed hydrolysis of phosphatidylcholine (PC-PLC) is a critical step in mitogenic signal transduction both in fibroblasts and in oocytes from Xenopus laevis. The products of ras genes activate PC-PLC, bind guanine nucleotides, have intrinsic GTPase activity, and are regulated by a GTPase-activating protein (GAP). It has been suggested that, in addition to its regulatory properties, GAP may also be necessary for ras function as a downstream effector molecule. In this study, evidence is presented that strongly suggests that the functional interaction between ras p21 and GAP is sufficient and necessary for activation of maturation promoting factor (MPF) H1-kinase activity in oocytes, and that PC hydrolysis is critically involved in this mechanism. Therefore, we identify GAP as a further step required for signalling through PC-PLC, and necessary for the control of oocyte maturation in response to ras p21/insulin but not to progesterone.

Animals↗