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Biomedical subjects

G Martina

Publications and source records attributed to G Martina.

At least 19 recordsLinked to original sources

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort.

Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease (ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular (CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients (244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events (morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one (hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1-3.5) or more (HR 3.9, 95% CI 2.1-7.1) CV accidents before starting dialysis. Both lipoprotein(a) (HR 1.67, 95% CI 1-2.5) and total plasma homocysteine at cutoff 30 micromol/l (HR 1.7, 95% CI 1.1-2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine < 30 micromol/l, methylenetetrahydrofolate reductase (MTHFR) TT was the sole biological parameter predictive of CV event outcome (HR 2.5, 95% CI 1.1-10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.

Adult↗

Renal transplantation from cadaveric donor after myocardial revascularization: still a matter of concern?

Renal transplantation in patients who have undergone coronary revascularization remains a matter of concern, few experiences have been reported in literature. From January 1997 to March 2003, 23 previously revascularized patients underwent renal transplants from cadaveric donors. We analyzed patient survival and cardiac events in this group of patients (group A) versus a similar population of 38 revascularized patients who were still on dialysis (group B) on the active waiting list (awl). After a similar follow-up (29.30 +/- 21.34 months versus 32.98 +/- 31.33 months; P = .56), survival was 100% for renal transplant patients and 94.74% for dialysis patients, two of whom (5.26%) died from acute myocardial infarction and four (10.52%) were excluded from the waiting list because of cardiac problems. The event-person ratio was 0.51 for group A patients (75% of events clustered within the first 6 months) and 0.71 for group B. The need for therapy with nitrates decreased from 11/23 (47.8%) to 6/23 (26%) after transplant. The ejection fraction remained stable (53.82% +/- 10.4% vs pre-Tx value of 54.8% +/- 9.4%). Renal survival was 100% (sCr = 1.4 +/- 0.4 mg/dL). Although no statistical significance has emerged, there was a general trend in favor of transplanted patients. On the basis of this experience we believe that coronary revascularization per se should no longer be a matter of concern for renal transplantation, which could be superior to dialysis for this type of patient.

Angioplasty, Balloon, Coronary↗

The influence of autonomic neuropathy on hypotension during hemodialysis.

UNLABELLED: Many patients with chronic renal failure experience profound hypotension during hemodialysis. This phenomenon may be caused by hypovolemia, autonomic or cardiac dysfunction, vascular resistance defects or vasoactive substances such as nitric oxide or adrenomedullin. The aim of the study was to evaluate the influence of autonomic neuropathy on the occurrence of hypotension during hemodialysis. Fifty-three patients with chronic renal failure on maintenance hemodialysis underwent a standard battery of cardiovascular tests for the diagnosis of autonomic neuropathy. The study population was then divided into two groups, with (AN+) and without (AN-) autonomic neuropathy. Blood pressure (BP) was recorded before, during and after hemodialysis for 10 consecutive dialysis sessions and the mean value was calculated. RESULTS: Of the patients, 38% were AN+. During hemodialysis, systolic BP was lower in AN+ than in AN- patients at the third hour (110.0 +/- 17.5 vs 128.0 +/- 26.2; p = 0.049). Systolic BP reduction during hemodialysis was greater in AN+ than AN-patients (-21.2 +/- 10.9 vs -13.5 +/- 10.6% change, p = 0.013). CONCLUSION: The presence of autonomic neuropathy is associated with a more severe BP fall during hemodialysis. Routine evaluation of autonomic function may be helpful in defining patients at risk for dialysis-induced hypotension.

Adult↗

Clinical relevance of hemochromatosis-related HFE C282Y/H63D gene mutations in patients on chronic dialysis.

BACKGROUND: The actual prevalence and the clinical relevance of gene mutations of HFE (which are linked to hemochromatosis) have not yet been established in patients on chronic dialysis. On the basis of theoretical premises, it could be hypothesized that these genetic determinants might influence the response to iron intake and the susceptibility for iron overload in patients in parenteral iron therapy. Furthermore, carriers for these mutations might be prone to develop sporadic porphyria cutanea tarda and cardiovascular events. METHODS: C282Y/H63D mutations of HFE gene were evaluated in 132 patients (34 in peritoneal dialysis, 98 in HD) and correlated with biochemical parameters of iron status (ferritin (FER) concentration and transferrin saturation (TSAT)), red cell parameters (red cell size and hemoglobin content), erythropoietin (EPO) dosage, major cardiovascular events and C-reactive protein as marker of chronic inflammation, in patients without iron therapy and after i.v. iron supplementation (< or = 60 mg/week) and with the presence of biopsy-proven porphyria. RESULTS: C282Y heterozygous mutation was found in 8/132 (6.6%); H63D homozygous and heterozygous mutations were found in 3/132 (2.3%) and 22/132 (16%) patients, respectively. Two patients (1.5%) showed double heterozygosis. No differences in baseline serum FER and TSAT and the other biochemical and clinical parameters were found in patients bearing mutations alleles nor after continuous iron therapy at low dosages. However, the prevalence of patients capable of maintaining normal hemoglobin (Hb) level without EPO therapy is increased in the C282Y-mutated patients. Only 1 patient out of the 4 with biopsy-proven porphyria cutanea tarda was bearing gene mutations (H63D heterozygosis). CONCLUSION: C282Y/H63D HFE gene mutations do not seem to be related to major abnormalities in biochemical parameters of iron status in dialysis patients without iron therapy or after i.v. iron supplementation, granted that low dosages are employed. Obviously, as our patients were exposed to a relatively uniform iron regimen in our clinical center (< or = 60 mg/week), it is unclear if other dosing regimens will unmask clinically significant differences between the heterozygotes and normals. The fact that the C282Y-mutated patients more frequently maintain high Hb values without EPO is interesting as could suggest a better use of available iron for erythopoiesis, but needs to be confirmed in larger samples. No clear association is demonstrated with porphyria cutanea tarda and major cardiovascular events.

Aged↗

Limits of aortic stop flow infusion chemotherapy in the treatment of advanced cancer.

BACKGROUND: Advanced and relapsed tumors remain a challenging disease with a poor and dismal prognosis. Our choice for inoperable tumors consists in a percutaneous treatment strategy involving intra-arterial chemotherapy and hemofiltration, with previous blood stop-flow, which allows high doses of Cisplatin-cisplatinum, cis-diammine-dichloroplatinum (CDDP) and Mitomycin C (MMC) in the tumor-bearing area with minimal systemic toxicity. METHODS: We analyse the morbidity and mortality associated with stop-flow in 20 patients with unresectable and/or metastatic thoraco- abdominal tumors, non responders to prior systemic chemotherapy. RESULTS: In our experience, the rate of major side effects of the procedure was 31% with a mortality of 5%. The side effects were related to the radiological procedure and to the chemotherapic treatment. A 74-year-old patient died for acute kidney toxicity within 15 days after the procedure. The other transient toxicity symptoms recorded were: nausea, vomiting, increasing of creatinine levels, diplopia and appearance of necrotic ulcer associated to chemotherapic drugs. Concerning the complications related to the radiological technique, the main problem was the rupture of the balloon stop-flow catheter in four patients. CONCLUSIONS: Stop-flow is a new procedure that could develop in the future, thanks to the possibility of obtaining a higher dose intensity of chemotherapic drugs in districts or organs affected by advanced tumors, with less systemic side effects. Unfortunately, the uncertain results in terms of increasing survival and the default of effective devices are to be resolved for a wider application of the procedure.

Adult↗

Association between elevated prolactin levels and circulating erythroid precursors in dialyzed patients.

The prolactin (PRL) receptor (R), a member of the cytokine hemopoietin receptor superfamily, has been shown to activate early differentiation steps along the erythroid pathway. In particular PRL, a product of bone marrow stroma, induces functional erythropoietin (EPO)-R on CD34+ hemopoietic progenitors. In this study, expression of EPO-R mRNA and responsiveness to EPO were assessed on enriched hemopoietic progenitor cells (HPC) from seven hyperprolactinemic and three normoprolactinemic patients and two normal subjects. Expression of EPO-R mRNA by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was found in HPC of four out of seven hyperprolactinemic patients but not in normoprolactinemic patients or normal donors. Development of EPO-dependent Colony Forming Unit-Erythroid (CFU-E) colonies in semi-solid medium was observed only in hyperprolactinemic patients (six out of seven). A much higher number of CFU-E colonies was observed in the four patients with a positive EPO-R message. We conclude from these data that abnormally high levels of PRL may increase the number of EPO-responsive hemopoietic precursors in vivo as they do in vitro. Since hyperprolactinemia associates in these patients with depressed EPO production, it may be regarded as a compensatory mechanism for the reduced availability of the hemopoietic factor.

Colony-Forming Units Assay↗

Limited value of zinc protoporphyrin as a marker of iron status in chronic hemodialysis patients.

BACKGROUND: In an attempt to find new parameters able to evaluate the actual iron availability by bone marrow cells, zinc protoporphyrin (ZnPP), a metabolic intermediate generated in the red blood cell by the incorporation of zinc instead of iron, has been proposed. ZnPP is a good marker of iron-deficiency anemia in non-uremic people, as red blood cell ZnPP concentration rises specifically (except for lead intoxication) in this condition. Existing data on ZnPP as a marker of iron deficiency in uremic patients comes mainly from cross sectional studies on chronic hemodialysis and has produced conflicting results. SUBJECTS AND METHODS: Therefore, we prospectively studied 42 HID patients, 28-88 years old, 13-346 months of dialysis age, beginning from a period of maximal iron deficiency, due to the lack of parenteral iron compounds (T0) up to the end of more than one year of follow-up with continuous parenteral iron supplementation (T4). ZnPP, hemoglobin, transferrin saturation and ferritin were serially determined before and after six weeks (T1), four months (T2), seven months (T3) and 14 months (T4) of parenteral iron supplementation at a maintenance dose of 0.5-1 mg/kg/week. RESULTS: In comparison with baseline values (95+/-37 micromol/mol heme) there were no significant changes in ZnPP levels at T1 and T2 despite a continuous increase in both transferrin saturation and ferritin values, while ZnPP significantly decreased at T4 (63+/-37 micromol/mol heme, p<0.001). There was no correlation between ZnPP and both transferrin saturation and ferritin at any time during the study, the same was true for ZnPP and zinc and lead serum concentration, fibrinogen and reactive C protein levels at T1 and T4, respectively. At T4, only 2/10 patients who still showed ZnPP levels >80 micromol/mol heme had absolute or functional iron deficiency, when the percentage of hypochromic red cells were measured. CONCLUSION: We conclude that ZnPP untimely parallels a change in iron balance in only a proportion of uremic people, in as much as confounding factors, such as chronic inflammation and uremia in itself may obscure its relationship with iron status. Therefore, ZnPP cannot be assumed to be a first-line diagnostic marker of iron balance in uremic patients.

Adult↗

Effect of acetate, bicarbonate dialysis, and acetate-free biofiltration on nitric oxide synthesis: implications for dialysis hypotension.

The effect of acetate dialysis (AD), bicarbonate dialysis (BD), and acetate-free biofiltration (AFB) on nitric oxide (NO) synthesis and the implications for dialysis hypotension was studied. The finding that uremic plasma is a potent inducer of NO synthesis by endothelial cells in vitro suggested that the cardiovascular instability of dialysis patients might result from excessive NO formation. Cardiovascular instability is more frequent in patients undergoing AD than BD. To see whether these differences were attributable to NO, we studied the NO synthetic pathway ex vivo in patients undergoing different dialysis procedures. Five patients were treated, in a random order, with AD, BD, and AFB, a technique using a buffer-free dialysate and postdilution of a sterile bicarbonate solution. Each type of dialysis was used for 1 week, comprising three dialysis sessions. A polyacrylonitrile dialyzer was used for all three methods. Before and after the third dialysis, plasma was collected, added to [3H]L-arginine, and incubated with human umbilical vein endothelial cells (HUVECs) for 24 hours. NO synthesis was evaluated as [3H]L-citrulline formation. Plasma concentrations of interleukin-1beta (IL-1beta), a potent inducer of inducible NO synthase (iNOS) in endothelial cells, were also measured. Plasma collected from patients after AD stimulated endothelial NO synthesis more than plasma from the same patients before the dialysis session (pre-AD, 0.173+/-0.028 nmol/10(5) cells v post-AD, 0.280+/-0.093 nmol/10(5) cells; P < 0.05). A slight, although not significant, increase was also observed when HUVECs were incubated with plasma drawn after BD (pre-BD, 0.151+/-0.014 nmol/10(5) cells; post-BD, 0.230+/-0.055 nmol/10(5) cells). AFB did not aggravate the stimulatory effect of uremic plasma on endothelial NO synthesis (pre-AFB, 0.184+/-0.038 nmol/10(5) cells; post-AFB, 0.189+/-0.040 nmol/10(5) cells). Plasma IL-1beta was greater (P < 0.01) after AD than after BD and AFB (post-AD, 0.234+/-0.028 pg/mL; post-BD, 0.124+/-0.019 pg/mL; post-AFB, 0.120+/-0.013 pg/mL). With AD, there was a greater intradialytic decrease in systolic blood pressure than with BD or AFB. Weight and blood volume loss and sodium balance were similar in AD, BD, and AFB. These data were consistent with the possibility that NO and cytokines, released in excessive amounts during AD, may contribute to hemodynamic instability.

Acetates↗

Intradialytic cytokine gene expression.

Along with the numerous technological improvements in molecular biology, polymerase chain reaction, which permits analysis of sequences of a very small amount of biological material, enables evaluation of hemodialysis-induced gene transcription of inflammatory cytokines. Blood samples drawn from 22 hemodialysis patients, treated with cellulose-derived or synthetic membranes, were collected at 0 and 15 min of hemodialysis. Total RNA, purified from mononuclear cells, was reverse transcribed and cDNA amplified by polymerase chain reaction primed with specific oligomers in order to determine tumor necrosis factor alpha (TNF alpha), interleukin (IL) 1 beta and IL6 gene expression. Plasma samples were collected at 0 and 180 min for detection of mature cytokines by enzyme immunoassay with plates pre-coated with monoclonal antibodies to TNF alpha, IL1 beta and IL6. A significant increase in TNF alpha mRNA was detected at 15 min of hemodialysis in 12 of 22 patients: 5 of 9 treated with cuprophan; 3 of 3 with cellulose triacetate; 3 of 5 with polysulfone, and only 1 of 5 treated with polymethyl-methacrylate membranes. A parallel increase in IL1 beta or IL6 mRNA was detected, and significant relationships were found between TNF alpha and IL1 beta (p < 0.001), and IL1 beta and IL6 gene expression (p < 0.05). Increased levels of mature TNF alpha and IL1 beta molecules in plasma were detected in the majority of patients showing an increased cytokine gene expression. However, the absolute amount of cytokine mRNA transcription at 15 min did not predict the levels of mature molecules reached in plasma at 180 min. Cytokine mRNA transcription is quite common at the beginning of a dialysis run. Possibly due to intracellular degradation of critical sequences of cytokine mRNA, gene expression does not necessarily imply translation into mature protein. It is suggested that mechanisms related to cell-to-cell interaction, which may possibly involve procytokine biology, are needed to drive phenomena of cytokine activation to clinical effectiveness.

Adult↗

Early increase in blood nitric oxide, detected by electron paramagnetic resonance as nitrosylhaemoglobin, in haemodialysis.

The objective of this study was to determine intradialytic blood levels of nitric oxide (NO), in patients undergoing chronic haemodialysis. This was done by detection of nitrosylhaemoglobin by a sensitive technique of spin trap electron paramagnetic resonance at 0, 5, 15, 60, 180 and 240 min of a 4-h standard bicarbonate dialysis, using the same dose (6000 U) of heparin and different dialysis membranes. The study group included 12 patients treated with cellulose-derived dialysis membranes (nine with cuprophan and three with cellulose triacetate) and 10 patients treated with synthetic membranes (five with polysulfone and five with polymethylmethacrylate). Control groups included 11 normal subjects and six patients with end-stage renal failure who were receiving intermittent peritoneal dialysis. Basal blood levels of nitrosylhaemoglobin in haemodialysis patients were significantly higher than normals, but similar to peritoneal dialysis patients. A significant increase (P < 0.01) in nitrosylhaemoglobin level was detected at 15 min of haemodialysis irrespective of the membrane used. A decrease to basal levels at 180 min was observed in all but two cuprophan-treated patients who, in contrast to the others, had a symptomatic hypotension at the end of the session and a further increase in blood nitric oxide. Patients undergoing peritoneal dialysis did not show any change in blood levels of nitrosylhaemoglobin during the first 180 min of the procedure. Thus, a constant increase in nitrosylhaemoglobin levels was observed early in haemodialysis, but not in peritoneal dialysis patients. Very preliminary evidence was obtained for a role of nitric oxide in the vascular instability at the end of haemodialysis in a few patients who had hypotensive episodes.

Adult↗

[Partial cystectomy versus TUR in T1G3 tumors].

Authors report their experience in conservative treatment of 41 patients with bladder cancer and they compare partial cytectomy with turv. They hold that partial cystectomy can represent a good therapeutical option in treatment of bladder cancer T1G3.

Carcinoma, Transitional Cell↗

[Is HCV RNA detectable in the ultrafiltrate?].

We investigated by molecular biology the possibility that the HC virus passes by the dialysis membranes into the ultrafiltrate, making the HD monitor a way of HCV transmission. HCV-RNA was tested in blood and in UF samples during 2 HD sessions at T-0, 30, 60, 120 min and at HD end. HCV-RNA was measured by RT-PCR. Viraemia in patients was > 10(-4) gen Eq/ml and remained unchanged along HD, HCV-RNA was not found in whole UF and its x100 concentrates during the HD. We failed to prove the passage of the HCV into the UF, at least in standard conditions.

Hemofiltration↗

[Report of a case of traumatic avulsion of the penile skin with amputation of the glans].

OBJECTIVES: A case of traumatic avulsion of penile skin with amputation of the penis and sectioning of the urethra is described. METHODS/RESULTS: Surgical management included embedding the penis without scrotal skin and subsequent reconstruction utilizing scrotal skin. The patient has recovered sexual activity, although sensitivity has been reduced as a consequence of penile amputation. Six months postoperatively, the patient has reported orgasm during intercourse. CONCLUSIONS: The surgical technique of embedding the penis is safe and preserves elasticity for subsequent reconstruction of the urethral meatus.

Adult↗

HCV viremia in hemodialysis patients: detection by a DNA enzyme immunoassay for amplified HCV sequences.

The aim of this study was the detection of HCV viremia in both anti-HCV antibody positive and negative hemodialysis patients. Sera from 75 patients on extracorporeal blood purification in the same dialysis unit were analyzed. Anti-HCV antibodies were detected using a 2nd-generation ELISA assay and in all positive cases a RIBA 3rd-generation test was performed. HCV-RNA was tested by a reverse transcription-nested polymerase chain reaction (RT-PCR) assay with primers located in the 5' region. PCR products were analyzed by a nonradioactive hybridation assay. The presence of anti-HCV antibodies was detected in 30 (40%) patients by means of ELISA II test; 28 of them were RIBA III positive and two indeterminate. Twenty-four of the 30 HCV Ab ELISA II positive patients (80%) were HCV-RNA positive (23 RIBA III positive and 1 indeterminate). Six anti-HCV Ab ELISA II positive patients tested negative for HCV-RNA (20%); 5 of these patients were also positive for anti-HCV antibodies with a RIBA III test and 1 was indeterminate. None of the anti-HCV negative patients was HCR-RNA positive. In two cases we documented the disappearance of viremia after an acute HCV infection, with the persistence of antibody reactivity. In conclusion, anti-HCV antibody positive hemodialysis patients should be considered as potentially infectious.

Adult↗

[Usefulness of echography in the diagnosis of urachal cancer].

Authors report a case of urachal carcinoma diagnosed with ultrasonography linear probe 7.5 mhz. With this work they want underline the importance to use a superficial probe in all those situation in which the sonography shows a neoformation in the posterior wall of the bladder; it should be the spy of a urachal neoformation.

Aged↗