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Biomedical subjects

C Canavese

Publications and source records attributed to C Canavese.

At least 109 records · Page 6Linked to original sources

Three-year follow-up after withdrawal of iron therapy in uremic patients on regular dialytic treatment.

Iron supplementation is commonly recommended in uremic patients undergoing regular dialytic treatment in order to correct a presumed iron deficiency due to impaired absorption and dialytic losses. Serum ferritin levels show an iron overload in 83% of 136 patients on 1.25 g/year i.v. iron therapy. After the withdrawal of iron therapy, directly correlated ferritin levels and percentage transferrin saturation decreased slowly, except in carriers of HLA-A3 antigens and in polytransfused patients. In these latter patients, desferrioxamine reduced but did not normalize the iron balance. The 16 patients who never received iron therapy showed a normal iron balance over a 3-year follow-up. Despite iron-ferritin therapy, 11 patients with baseline ferritin values at the lower normal limits showed a tendency toward further depletion. Orally administered bivalent iron seems to be more promising in normalizing iron-deficient patients without potentially harmful overloading.

Adolescent↗

Leukocyte behaviour in chronic uraemic patients undergoing regular dialysis.

A review of the literature is followed by the presentation of data obtained during a study of white blood cell kinetics in patients undergoing regular dialysis treatment. It was found that contact between white blood cells and the dialyzer results in a very prompt 'neutropenia-neutrophilia' stage and the deposition of billions of white blood cells on the membranes at the end of each treatment. A comparison of intradialytic leukocyte behaviour and the mean baseline white blood cell values was made in a total of 49 patients subdivided in four groups: 1. patients using coil and parallel flow dialyzers; 2. patients using dialyzers of different surface area; 3. patients of different dialytic age; 4. patients employing monoused or re-usable filters. No differences were noted in groups 1 and 4. In contrast, employing large dialyzers and the increasing dialytic age led to a variety of white blood cell patterns. Contrary to the information in the literature on leukocyte adhesion, it was observed that the cell deposits on the membranes and on the bubble trap filters, while predominantly composed of neutrophils, also contained monocytes and lymphocytes in proportions similar to those of the normal differential blood count.

Adult↗

Dual effect of methylprednsolone pulses on apoptosis of peripheral leukocytes in patients with renal diseases.

It is well known that change in apoptosis may modulate the natural story of illness, and that many drugs may act through modulation of apoptosis, but the role of steroids in acting through apoptosis in different settings, including renal diseases, has still to be elucidated. We studied the in vivo effects of steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79 subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN, 19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22 (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A significant decrease in CD3+CD8+ cell count and a significant increase of the CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA fragmentation did not change after oral steroids, paralleling a 22 to 32% decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a deeper drop of all lymphocyte subsets was observed, while DNA fragmentation turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the presence of apoptosis in renal diseases is associated with decreased CD3+CD8+ cell count. Furthermore, steroid intravenous pulses, besides inducing a profound decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte apoptosis, eventually leading to a reversal of baseline patterns, either turning from negative to positive or from positive to negative. Oral steroid therapy did not influence baseline apoptosis.

Adult↗

[Quality of data or quality of care? Comparison of diverse standarization methods by clinical severity, based on the discharge form, in the analysis of hospital mortality].

Using discharge abstract data, we analysed hospital mortality comparing four different methods of risk adjustment. All patients discharged from the S. Giovanni Battista (Molinette) hospital in Turin (Italy) between January 1996 and June 1999 (n = 169,746) were classified with All Patient Refined--Diagnosis Related Groups (APR-DRG). A first analysis evaluated the time trend of hospital mortality by semester. A second analysis compared hospital mortality during the last 12 months among eight units of internal medicine (n = 5592). All comparisons were made through logistic regression models. As the quality of discharge abstracts increased during time and showed variation among units with similar patients, all comparisons were repeated using four models, characterised by increasing predictivity and sensitivity to quality of data. In addition to crude comparisons (A), the other models included as risk factors: B) age and emergency admission; C) same as 'B' plus expected mortality by APR-DRG; D) same as 'B' plus expected mortality by APR-DRG and risk of death subclass. If no risk factors were considered (A), hospital mortality showed an increasing trend, with an odds ratio (OR) of 1.02 by semester, with a 95% confidence interval (CI) between 1.01 and 1.03. The association was weakened when age and mode of admission were taken into account (B) and disappeared when the APR-DRG expected mortality was also considered (C) (OR = 1.00; CI = 0.98-1.01). Finally, if the comparisons were adjusted also for the expected mortality by APR-DRG and risk of death subclass (D) a reversed trend appeared (OR = 0.95; CI = 0.94-0.97). The comparison among the units of internal medicine gave discordant results according to the method used to adjust for confounders. The most striking variations were detected for those units with the best and the worst clinical data. The unit with the poorer clinical data (average number of diagnoses per patient = 2.9) showed a crude OR of 1.38 (CI = 0.99-1.93) and an adjusted OR (D) of 1.71 (CI = 1.10-2.66); the unit with the best quality of data (average number of diagnoses per patient = 4.4) changed the OR from 1.55 (CI = 1.06-2.26) (A) to 0.66 (CI = 0.37-1.17) (D). In conclusion, these results confirm the high sensitivity of the APR-DRG classification to the quality of data and, more in general, suggest to be prudent when using powerful instruments like this to assess quality of care, especially if the quality of data among the units compared is less than optimal or not homogeneous.

Hospital Mortality↗

Extrahepatic immunological manifestations of hepatitis C virus in dialysis patients.

BACKGROUND: Hepatitis C virus (HCV) infection may be associated with various extrahepatic immunological disorders. Uremic patients on chronic regular dialytic treatment (RDT) frequently develop immunological abnormalities. The aim of this study was to evaluate the probability that HCV infection creates an increased risk for extrahepatic immunological abnormalities in chronic RDT patients. SUBJECTS AND METHODS: In a series of one hundred sixteen chronic RDT patients, HCV status was determined by anti-HCV antibodies, polymerase chain reaction (PCR) RNA and viral genotyping. After excluding four anti-HCV negative/PCRRNA positive patients, a comparison was made between 51 anti-HCV negative/PCR-RNA negative and 61 anti-HCV positive patients, this latter group including seventeen PCR-RNA negative, fifteen genotype 1, thirteen genotype 2, three genotype 3, four genotype 4, four undeterminable genotype and five mixed genotypes. The following investigations were performed: cryoglobulinemia (presence, titer and, when possible, identification), monoclonal gammopathy, antineutrophil cytoplasm antibodies, antidouble stranded DNA antibodies, circulating immunocomplexes and immunoglobulin levels. RESULTS: Cryoglobulinemia was found in 77% of anti-HCV positive versus 29% of anti-HCV negative patients, and cryocrit > 1% in 50% versus 9.8% respectively, p=<0.01. Also cryoglobulin concentration was higher (logarithmic transformation: 4.38 +/- 0.94 vs 3.11 +/- 1.06, p =< 0.001) in anti-HCV positive versus negative patients. Multivariate logistic regression analysis showed a significantly increased odds ratio (12.0, confidence interval 3.0 to 48.3) for having high levels of cryoglobulins (cryocrit >1%) after adjusting for age and dialytic age. The prevalence of this abnormality did not differ significantly among patients infected with different genotypes, but a tendency towards a lower frequency was observed in the anti-HCV positive/PCR negative subgroup. Cryoglobulins were identified as type I (2 anti-HCV positive case), type II (2 anti-HCV positive and 1 anti-HCV negative case) and type 3 (1 anti-HCV negative case). The frequency of monoclonal gammopathy was not significantly different between anti-HCV positive and anti-HCV negative patients (6.5% versus 2%) as well as that of the other parameters evaluated except for IgG concentration which was higher in the anti-HCV positive group (1,685 +/-605 versus 1349 +/- 352 mg/dl, p 0.006). Five events, potentially linked to HCV infection, occurred in our anti-HCV positive patients: 2 cases of porphyria cutanea, 1 case of unexplained peripheral neuropathy, 1 cutaneous leukocytoclastic vasculitis, 1 death for non-Hodgkin's lymphoma. In one anti-HCV positive patient treated with interferon-alpha, the presence of cryoglobulins, monoclonal gammopathy and high IgG levels strictly paralleled that of viremia, disappearing during the recovery phase under treatment and reappearing shortly after stopping treatment. CONCLUSIONS: HCV infection provides a significantly increased risk for developing extrahepatic immunological abnormalities also in chronic RDT patients. It is possible that the clinical relevance of this event might be scant because of the low level of these abnormalities, but an awareness of its possibility should to be taken into account.

Adult↗

Rubidium deficiency in dialysis patients.

BACKGROUND: Since dialysis has brought long-term survival to uremic patients, we can now speculate on more subtle problems derived from imbalance or sub-optimal regulation of some elements such as trace metals. We focused on the rubidium (Rb) status in dialysis patients (HD), as concerns about its possible deficiency have been raised. METHODS: Rb in uremic patients was evaluated by: A) serum concentration (graphite furnace atomic absorption spectroscopy) from blood samples of 70 patients on chronic hemodialysis (HD) in comparison with 75 controls; B) tissue concentration (neutron activation analysis) from autopsy or biopsy samples (20) of HD patients in comparison with 21 controls; C) in vivo intradialytic mass balance during standard bicarbonate dialysis in 8 HD patients. RESULTS: A) Serum Rb concentrations in HD patients significantly were lower than in normal controls (304 +/- 81 micrograms/L versus 350 +/- 74 micrograms/L p < 0.001, log-transformed 5.68 +/- 0.28 versus 5.84 +/- 0.20, p < 0.001). Univariate logistic regression analysis found a significantly higher risk of serum Rb < 250-300 and 350 micrograms/L in uremic patients than in controls (Odd ratios or 12.6, 95% CI 2.77-57.04; 4.0, 95% CI 1.92-8.4; 2.08, 95% CI 1.02-4.25, respectively). B) Rb was significantly lower in tissues of HD patients, including brain (2250 +/- 1520 ng/g versus 5490 +/- 1250 ng/g, p = 0.0002) than normal controls. C) Rb was transferred from the patients' blood to the dialysis bath during a standard bicarbonate dialysis session, giving mean intradialytic Rb removal of 4.0 +/- 1.1 mg/session. CONCLUSIONS: These results confirm that Rb deficiency may arise in uremic patients, and indicate that diffusive dialysis treatments allow Rb removal which, however, with a standard bicarbonate schedule does not seem to be any greater than that expected with normal urine output (20 mg/week). Further studies are needed to clarify the roles of many factors in this Rb deficiency, including the effects of uremia by itself, pre-dialysis factors (diet, impaired renal function and drugs), dialysis procedures (frequency, hours, diffusive/convective components) or other biochemical/clinical parameters (hemoglobin, body mass index, age). The finding of a Rb deficiency in uremia is important as it has a role in neurobehavioural functions, mainly as an antidepressant. As Rb deficiency may be implicated in central nervous system alterations which strongly influence the quality of life, we believe that monitoring serum Rb in uremic patients and clarifying the causal mechanisms of deficiency will facilitate future therapeutic approaches.

Adult↗

Silica and renal diseases: no longer a problem in the 21st century?

Silicosis and other occupational diseases are still important even in the most developed countries. In fact, at present, silica exposure may be a risk factor for human health not only for workers but also for consumers. Furthermore, this exposure is associated with many other different disorders besides pulmonary silicosis, such as progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, glomerulonephritis and vasculitis. The relationships between these silica-related diseases need to be clarified, but pathogenic responses to silica are likely to be mediated by interaction of silica particles with the immune system, mainly by activation of macrophages. As regards renal pathology, there is no single specific clinical or laboratory finding of silica-induced nephropathy: renal involvement may occur as a toxic effect or in a context of autoimmune disease, and silica damage may act as an additive factor on an existing, well-established renal disease. An occupational history must be obtained for all renal patients, checking particularly for exposure to silica, heavy metals, and solvents.

Humans↗

[Nephrologists and porphyrias].

As usually occurs for rare diseases, the word "PORPHYRIA" often recalls a confused topic with shaded boundaries, presenting "bullous" skin lesions, rare opportunity of diagnosis in clinical practice, unknown pathogenesis, and almost absent therapeutic options. The goal of this review is to draw attention to this topic, as new diagnostic and therapeutic tools might change the natural history of this disease. Porphyrias are disorders resulting from abnormalities of porphyrin metabolism. Porphyrins are molecules made up of four pyrrol rings, which constitute haeme-proteins, including haemoglobin. Following the "trigger" enzyme delta-aminolevulinic acid (ALA) synthase, which is capable of condensing succynil CoA and glycine, seven additional enzymes are involved in the process that eventually leads to haeme biosynthesis. Porphyrias are the result of total or partial deficiencies in these seven enzymes involved in haeme synthesis. Usually, the final haeme product exerts a negative feed-back on its synthesis. The enzyme deficiency that occurs in porphyrias is responsible for reduced haeme production, which, in turn, allows the cascade to be stimulated by increased activity of the trigger enzyme, ALA-synthase (ALA-s). However, due to the subsequent enzyme defects, notwithstanding increased ALA-s activity, haeme synthesis is blunted and intermediate metabolites accumulate. Clinical manifestations depend on which step the enzymatic defect occurs: if enzymatic defects are in the initial steps of the metabolic cascade, early metabolic intermediates will accumulate [i.e. ALA and porphobilinogen (PBG)] responsible for attacks of neurological dysfunction; if the enzymatic defects are in the final steps, sunlight-induced cutaneous lesions (phtotosensitivity) due to porphyrin accumulation in the skin will develop. The seven major human porphyrias may be classified into "hepatic or erythropoietic porphyrias" depending on the organ/tissue where metabolic alterations are more evident, or "acute or chronic porphyrias" depending on the prevalence of clinical symptoms, if neurologic (acute) or cutaneous (chronic). Only a small number of people with inherited enzyme deficiency will develop overt clinical disease, mainly because of the role of acquired aggravating and precipitating factors, such as drugs, hormonal causes, infection, caloric restriction, alcohol. The biochemical diagnosis of porphyrias relies on the detection of the consequences of increased ALA-s activity in the liver: overproduction, accumulation and increased excretion of early (ALA, PBG) or late (porphyrins) intermediate compounds in plasma, faeces and urine. A major difficulty arises from the knowledge that such abnormalities may be completely absent during the remission phases of the disease. Only in very specialised Centres it is now possible to measure specific haeme synthesis enzyme defects, and to perform molecular diagnosis by DNA analysis. The true prevalence of the diseases is unknown, ranging from 1:500 to 1:50,000. Therapeutic strategies include withdrawal of all common precipitants (drug, alcohol, fasting, infection), use of opiates and chlorpromazine, carbohydrates (300-400 g/day) and infusion of human haemine. Genetic therapies are being studied for the future.

Adult↗

[Guidelines on water and solutions for dialysis. Italian Society of Nephrology].

The National Society of Nephrology has promoted the development of specific Italian Guidelines for dialysis fluids. Two previous national inquiries showed a wide variety in the type and frequency of both microbiological and chemical controls concerning dialysis water, reinforcing the need for specific standards and recommendations. An optimal water treatment system should include tap water pre-treatment and a double reverse osmosis process. Every component of the system, including the delivery of the treated water to the dialysis machines, should prevent microbiological contamination of the fluid. Regular chemical and microbiological tests and regular disinfection of the system are necessary. 1. Chemical quality (Table: see text). Treated tap water used to prepare dialysis fluid should be within European Pharmacopoeia limits at the water treatment system inlet and at the reverse osmosis outlet. In addition dialysate, concentrate and infusion fluids must comply with specific Pharmacopoeia limits. The physician in charge of the dialysis unit is advised to institute a multidisciplinary team to evaluate the requirement for added chemical controls in the presence of local hazards. 2. Microbiological quality (Table: see text). High microbiological purity of dialysis fluid--regularly verified--is a fundamental prerequisite for dialysis quality and every dialysis unit should aim as a matter of course to obtain "ultra-pure" dialysate (microbial count <0.1 UFC/mL, endotoxins <0.03 U/mL). On-line dialysate ultrafiltration and regular disinfection of dialysis machines greatly enhance microbiological purity. On-line dialysate reinfusion requires specific devices used according to corresponding instructions and to more frequent microbiological tests. Dialysis fluids for home dialysis should comply with the same chemical and bacteriological quality. The appendix reports the water treatment system's technical characteristics, sampling and analytical methods, monitoring time-tables, as well as the origin and effects of the main toxic substances. Suggestions and questions concerning these guidelines are welcome to nefrologia@sin-italy.org.

Colony Count, Microbial↗