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Biomedical subjects

F Locatelli

Publications and source records attributed to F Locatelli.

At least 91 records · Page 5Linked to original sources
PubMed2001

Decreased serum aminotransferase activity in patients with chronic renal failure: impact on the detection of viral hepatitis.

Hepatitis C virus (HCV) infection is common in the dialysis population and patients with chronic renal failure (CRF) not requiring dialysis. HCV is the most important cause of chronic liver disease in dialysis patients; however, its role has been underestimated by the lower aminotransferase activity in the dialysis population. Aminotransferase activity in patients with CRF not requiring dialysis has not been adequately addressed to date. The aim of this study is to investigate whether serum aminotransferase levels in predialysis patients with CRF are less than those obtained in healthy individuals and dialysis patients. We also analyzed the potential association between serum aminotransferase activity and demographic, clinical, and biochemical parameters. Aspartate (AST) and alanine aminotransferase (ALT) activity was greater in antibody to hepatitis C (anti-HCV)-positive than anti-HCV-negative patients with CRF not requiring dialysis (AST, 32.3 +/- 19 versus 18.1 +/- 8 IU/L [P = 0.0001]; ALT, 32.9 +/- 28 versus 17.7 +/- 11 IU/L [P = 0.00001], respectively). Predialysis patients with CRF had lower AST and ALT activity in comparison to healthy individuals (AST, 19.7 +/- 11.2 versus 20.4 +/- 6.8 IU/L [P = 0.00001]; ALT, 19.5 +/- 15.1 versus 21.7 +/- 11.3 IU/L [P = 0.00001], respectively). The difference was much greater after correction for viral markers: AST and ALT levels in hepatitis B surface antigen (HBsAg)-negative anti-HCV-negative predialysis patients with CRF were less than those in the healthy population (AST, 17.9 +/- 8 versus 20.4 +/- 6.8 IU/L [P = 0.00001]; ALT, 17.5 +/- 10 versus 21.7 +/- 11.3 IU/L [P = 0.00001], respectively). Comparison of AST and ALT activity between age-matched healthy and predialysis seronegative CRF groups showed lower AST and ALT values in the study population. HBsAg-negative anti-HCV-negative dialysis patients had lower AST and ALT activity than seronegative predialysis patients with CRF (AST, 16.6 +/- 11.6 versus 17.9 +/- 8 IU/L [P = 0.01]; ALT, 16.3 +/- 9.4 versus 17.5 +/- 10 [P = 0.041], respectively). Multivariate analysis in the predialysis CRF population showed an independent association between AST (P = 0.00001) and ALT (P = 0.00001) activity and anti-HCV positivity, and age was negatively linked to AST (P = 0.011) and ALT levels (P = 0.001). AST level was negatively related to serum creatinine level (P = 0.0001). In conclusion, HCV infection causes significant liver injury in predialysis patients with CRF. These patients have decreased aminotransferase activity compared with the general population. Dialysis patients show lower aminotransferase activity than predialysis patients with CRF. Because serum aminotransferase levels are commonly used to screen for liver disease in the dialysis and predialysis CRF population, recognition of liver damage may be hampered by the reduction in aminotransferase values in these patients. Studies aimed to clarify the pathogenesis of this phenomenon are in progress.

Aged↗
PubMed2001

Dry weight and sodium balance.

To achieve good blood pressure control and minimal intradialytic patient discomfort, it is very important to define the correct dry weight and individualize the "adequate" dialysate sodium concentration. Given the highly variable amounts of sodium introduced during interdialytic periods, the use of the sodium and conductivity kinetic models guarantees adequate sodium removal in each patient with each treatment. According to our data, the imprecision of the sodium kinetic model was less than 0.84 mEq/L; that of the conductivity kinetic model, which has the advantage not requiring blood or dialysate samples, was less than 0.14 mS/cm. In paired filtration dialysis (PFD), the corresponding figures were less than 1.1 mEq/L and less than 0.1 mS/cm. A multicenter prospective, controlled and randomized trial has demonstrated that the application of the conductivity kinetic model in PFD makes it possible to improve cardiovascular stability in patients prone to dialysis hypotension. The sodium kinetic model is difficult to apply in routine clinical practice because of the need for blood and dialysate samples, but this may be overcome by the conductivity kinetic model, which is a very promising tool for achieving a zero intradialytic sodium balance and improving cardiovascular stability.

Blood Pressure↗
PubMed2001

Incidence of, and risk factors for, nosocomial infections among hematopoietic stem cell transplantation recipients, with impact on procedure-related mortality.

OBJECTIVES: To determine the incidence of, and risk factors for, nosocomial infections (NIs) occurring among hematopoietic stem cell transplantation (HSCT) recipients during hospitalization and to evaluate the impact of these NIs on patient outcome. DESIGN: A two-year prospective observational study in two HSCT units. PATIENTS: All patients admitted to the HSCT units between February 1997 and March 1999. SETTING: A teaching hospital. METHODS: After admission to the HSCT units, the patients were followed prospectively on a daily basis to collect all pertinent variables for the development of NIs. RESULTS: 49 NIs were identified in 34 of the 143 patients screened. The incidence of NIs and infected patients was 34.2% and 23.7%, respectively. The incidence density of NI was 8.96 per 1,000 patient-days. The most frequent NIs were bloodstream infections ([BSIs], 42.8%) and respiratory tract infections (28.6%). Other sites involved were as follows: eye (8.2%), urinary tract (6.1%), gastrointestinal tract (6.1%), skin (4.1%), ear (2%), and central venous catheter ([CVC], 2%). Because of the predominance and clinical relevance of BSIs, we examined both intrinsic and extrinsic risk factors associated with these infections. Independent risk factors for BSIs were allograft from matched unrelated or partially matched family donor, graft-versus-host disease (GVHD) prophylaxis without methotrexate (MTX), type of CVC, and duration of total parenteral nutrition. Four variables were independently associated with mortality occurring during hospitalization: culture-proven BSIs, advanced disease phase at transplant, type of transplant, and absence of MTX for GVHD prophylaxis. CONCLUSIONS: The study identified several factors associated with increased risk of BSIs among HSCT patients. Because BSIs are life-threatening complications for HSCT recipients, preventive measures aimed at reducing the incidence of these infections among patients given HSCT should be adopted.

Adolescent↗
PubMed2001

Cardiovascular disease determinants in chronic renal failure: clinical approach and treatment.

INTRODUCTION: Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice. METHODS: Consensus was reached on key points relating to the clinical approach and treatment of the main cardiovascular risk factors in RRT patients (hypertension, anaemia, hyperparathyroidism, dyslipidaemia, new emerging risk factors). In addition, the role of convective treatments on cardiovascular outcomes was examined. RESULTS: Hypertension should be managed by aiming at blood pressure values of < or =140/90 mmHg (< or =160/90 mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No single class of drug has proved superior to others in RRT patients, provided that the blood pressure target is achieved, although ACE inhibitors have shown specific organ protection in high-risk patients (HOPE study) and are well tolerated. Anaemia should be managed by using erythropoietin and iron supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin levels < 500 ng/ml. The management of hyperparathyroidism is currently unsatisfactory, as calcium supplements have the potential to increase cardiovascular calcification. While awaiting new calcium- and aluminium-free phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies are in progress to assess the real impact of lipid-lowering drugs in RRT. In the meantime, serum LDL-cholesterol < 160 mg/dl and triglycerides < 500 mg/dl may be desirable targets. The impact of new emerging risk factors (inflammation and chronic infection, hyperhomocysteinaemia, metabolic waste-product accumulation) and their proper management are still under research. Convective dialysis treatments may confer some degree of protection from dialysis-related amyloidosis and mortality, but clinical data on this important issue are still controversial and no definitive conclusions can be drawn at present. CONCLUSION: CVD prevention and treatment is a great challenge for the nephrologist. Achieving evidence-based consensus can help in encouraging the implementation of best clinical practice in line with the progress of current knowledge.

Anemia↗
PubMed2001

The epidemiology of end-stage renal disease in the Baltic countries: an evolving picture.

INTRODUCTION: The epidemiology of end-stage renal disease (ESRD) and renal replacement therapy (RRT) is under continuous evolution all over the world. Of particular interest is the development of RRT in the countries of the former Soviet bloc which underwent great political and socio-economical changes in the last decade. We report here the epidemiological analysis of ESRD and RRT in the three Baltic countries: Lithuania, Estonia, Latvia. Subjects and methods. This epidemiological report is based on data from centre questionnaires which were collected from 1996 onwards, with a response rate of 98-99%. RESULTS: The prevalence/incidence of RRT patients in 1999 were 213/99.5 p.m.p. in Lithuania, 186/45.5 p.m.p. in Estonia and 172/55.8 p.m.p. in Latvia. Haemodialysis (HD) was the most common RRT modality in Lithuania (60% of prevalent patients), but not in Estonia (29%), while in Latvia it was nearly as common as renal transplantation (45 and 46%, respectively). Home HD was not performed. The proportion treated by peritoneal dialysis (PD) was very low in Lithuania (4% of RRT patients), while the percentage was higher in Latvia (9%) and Estonia (20.4%). The percentage of patients on RRT treated by renal transplantation was high throughout, representing the main modality of treatment in Estonia (50.5% of RRT prevalent patients, 94 p.m.p.) and in Latvia (46%, 79 p.m.p.) and being high in Lithuania (36%, 77 p.m.p.). The main renal diseases leading to ESRD were glomerulonephritis, pyelonephritis and diabetes. CONCLUSION: The epidemiology of RRT in the Baltic countries is undergoing rapid changes. Transplantation has reached an impressive level. A high percentage of RRT patients live with a functioning graft.

Estonia↗
PubMed2001

Dialysis: its role in optimizing recombinant erythropoietin treatment.

Although iron deficiency is probably the most important factor affecting response to recombinant erythropoietin (Epo, epoetin), other factors are of significance, including dialysis adequacy. Additionally, water treatment and distribution, sterilizants and the quality of the dialysate in terms of trace elements (particularly chloramine) are of importance in relation to erythropoiesis inhibition. Microbiological or pyrogenic contamination can cause or aggravate anaemia in haemodialysis patients, and the impact of enhanced production of cytokines should be taken into consideration. By removing small and (possibly) medium/large molecules, adequate dialysis is of paramount importance in correcting anaemia and optimizing epoetin therapy. The biocompatibility of dialysis membranes and flux are other important factors. As yet unknown uraemic toxins may suppress erythropoiesis and contribute towards the development of anaemia. It is reasonable to hypothesize that, because anaemia improves after the start of dialysis with cellulose membranes, low molecular weight erythropoiesis inhibitors are involved, as well as medium/large molecular weight inhibitors, which are removed by more permeable membranes. However, in highly selected, adequately dialysed patients without iron or vitamin depletion, the effects of dialysis membrane type on haematological parameters and epoetin efficacy are smaller than might be expected from the results of uncontrolled studies. Improvement in anaemia has been observed using on-line haemofiltration, haemodiafiltration, and sterile dialysate. The results of prospective, randomized trials examining the impact of these factors on anaemia and the effectiveness of epoetin treatment are eagerly awaited.

Anemia↗
PubMed2001

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease.

BACKGROUND: Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. METHODS: Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/- anti-thymocyte globulin +/- total body irradiation. The median duration of follow up was 12 months (3-55). RESULTS: An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. CONCLUSION: Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Adolescent↗
PubMed2001

Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed?

STUDY OBJECTIVES: To evaluate early and late lung function abnormalities and their predictors in a large sample of children who underwent bone marrow transplantation (BMT) for leukemias in the 1990s, highlighting changes with respect to the 1980s. DESIGNS: Prospective cohort. SETTING: A university department of pediatrics. PARTICIPANTS: Seventy-five consecutive children who underwent BMT were enrolled in the study (median age, 11 years; range, 6 to 19 years; 45 male and 30 female children). Twenty-three children received autologous BMT, and 52 children received allogeneic BMT; 50 children completed the study. MEASUREMENTS: Clinical examinations and lung function tests were performed before BMT, and 3 to 6 months, 12 months, and 24 months after BMT. RESULTS: Before BMT, at 3 to 6 months after BMT, and at 24 months after BMT, 44%, 85%, and 62% of children, respectively, had altered lung function in the absence of persistent respiratory symptoms. Between 3 months and 6 months after BMT, a restrictive pattern was the most frequent abnormality. The only predictive factors for late abnormalities were transplantation performed in the advanced disease phase (odds ratio [OR], 6.75; p = 0.005) and bronchopulmonary infections (OR, 3.9; p < 0.05). CONCLUSIONS: These data suggest that a significant proportion of children who undergo BMT, especially if for leukemia in advanced phase, have early and late pulmonary abnormalities. These abnormalities, especially the late ones, seem to be more severe than patients reported in studies analyzing children undergoing BMT in the 1980s. This could be due to the more intensive front-line treatment protocols employed for treatment of children with acute leukemia in the 1990s.

Adolescent↗
PubMed2001

Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Group (GITMO).

BACKGROUND AND OBJECTIVES: Unrelated donor bone marrow transplant (UD-BMT) has become an attractive alternative source of hematopoietic cells for patients lacking a matched sibling. The aim of this paper was to report on results of the 696 UD BMTs performed in 31 Italian institutions during the first 10 years of activity of the Italian Bone Marrow Donor Registry (IBMDR). EVIDENCE AND INFORMATION SOURCES: In 1989 the Italian Bone Marrow Transplant Group (GITMO) established the IBMDR to facilitate donor search and marrow procurement for patients lacking an HLA identical sibling. By end of December 1999, 260,000 HLA-A, B typed volunteer donors had been cumulatively registered and 2,620 searches had been activated for Italian patients. At least one HLA-A, B, DRB1 matched donor was found for 54% of the patients and 696 UD BMTs were performed. In 50% of cases the donor was found in the IBMDR and in 50% in 15 other Registries. The average time from search activation to transplant was 6 months for disease other than CML. For CML it was 14 months. Actuarial 12-month transplant-related mortality (TRM) was 68% in patients grafted between 1979 and 1992 and 44% for patients grafted after 1993. Twenty-eight per cent of patients developed grade III or IV acute GvHD and 24% developed extensive chronic GvHD. The rate of disease free survival at three years was 57% for patients with 1st chronic phase CML, 37% for patients with 1st or 2nd CR ALL, 31% for AML or MDS patients 18 years of age and 54% for patients with inborn errors. PERSPECTIVES: We conclude that the IBMDR has benefited a substantial number of patients lacking a matched sibling and has facilitated the recruitment of UDs into the international donor pool. The long time required for the search is the major obstacle to the success of this programme. This suggests that early transplant and a decrease in TRM could further improve these encouraging results.

Adolescent↗