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Biomedical subjects

M Bonello

Publications and source records attributed to M Bonello.

At least 19 recordsLinked to original sources

Successful use of sodium hypochlorite pack plus systemic and local antibiotic therapy for the treatment of pseudomonas infection of peritoneal dialysis catheter exit-site.

Peritoneal catheter exit-site and tunnel infections remain critical problems in patients undergoing peritoneal dialysis. Catheter-related peritonitis occurs in about 20% of patients and exit-site infections are responsible for catheter removal in more than one-fifth of the cases. For the last 2 years in the Department of Nephrology, San Bortolo Hospital, Vicenza, Italy, we have been treating exit-site infections caused by Pseudomonas with sodium hypochlorite packs as well as systemic and local antibiotic therapy. Considering the encouraging results obtained on Pseudomonas infection, we decided to utilize the same schedule for the treatment of exit-site infections caused by other germs which are generally difficult to eradicate to prevent peritonitis and catheter removal. Between 2003 and 2004, 10 patients contracted infection of the exit-site. All patients underwent a swab test because of the reddening and the purulent secretion of the exit-site. The swab resulted positive for Pseudomonas in 7 patients, Corynebacterium sp. in 2 patients, and Candida albicans in 1 patient. All patients were treated with systemic antibiotic therapy or antifungal therapy, local sodium hypochlorite 50% packs. After 15 days all patients were submitted to a swab test of the exit site. In all patients, the swab test resulted negative after 15 days and 1 month, and they could continue peritoneal dialysis. This procedure avoided peritoneal catheter removal and temporary switch to hemodialysis in all patients with exit site infection. The mechanism of action is related to the wide antimicrobial spectrum and the rapid action of sodium hypochlorite possibly creating a protective barrier on the exit-site.

Anti-Bacterial Agents↗

Management of fluid overload in congestive heart failure: learning from a case report.

A case of refractory fluid overload due to congestive heart failure and consequent renal insufficiency is reported. The case was approached multidisciplinarily, at the beginning with conservative and pharmacological therapy, subsequently with extracorporeal fluid removal in which a specific attention was payed to the maintenance of circulating blood volume and achievement of dry weight, and finally with chronic peritoneal dialysis as a maintenance therapy. The case seems to summarize the pathway of many patients seen initially in intensive care and cardiology departments and subsequently in nephrological wards.

Aged↗

Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line.

Transplant patient plasma produces an increased rate of mononuclear cell apoptosis despite a normal serum creatinine value. Immunosuppressive medications may be one factor that causes an altered apoptotic pattern. We evaluated the in vitro effects of various doses of cyclosporine, mycophenolate mofetil, and steroids on apoptosis of a cultured human monocytic U937 cell line, using estimates by fluorescence microscopy and annexin V assays. Increasing cyclosporine concentrations (100 to 800 ng/mL) progressively increased apoptosis rates (16% to 32%). The combination of steroid (0.01 microg/mL) and cyclosporine increased the apoptosis rate to 45%. Mycophenolate mofetil alone (0.3 microg/mL) led to an apoptosis rate of 34%. Therapeutic levels of mycophenolate mofetil from 3 to 7 microg/mL led to apoptosis rates from 56% to 67%. The combination of cyclosporine, steroid, and mycophenolate mofetil increased the rate of apoptosis to 95%. Immunosuppressive therapy may contribute to the high rate of apoptosis observed among mononuclear cells of transplanted patients. This effect may alter patient susceptibility to infections and contribute to a unique mechanism of immunosuppression.

Annexin A5↗

Sequential hemofiltration-hemodiafiltration technique: all in one?

Sequential dialysis techniques (i.e. pure ultrafiltration followed by dialysis) have been used in the past, due to their capability to remove large volumes of fluids without inducing hemodynamic instability. The disadvantages of the inadequate dialysis and the lack of technology lead to the decline such methods. Hemofiltration (HF) and hemodiafiltration (HDF) are recently being utilized in a greater proportion thanks to the on line fluid preparation systems. Each process (HF and HDF) has its own benefits in the removal of small, medium and high-molecular weight substances and in the hemodynamic stability. Sequential hemofiltration/ hemodiafiltration (SHF/HDF), may combine the benefits and eliminate the disadvantages of each method. Furthermore they can be easily applied nowadays, due to the development of new high technological hemodialysis machines. In order to evaluate the feasibility and the effects of SHF/HDF we studied 7 chronic hemodialysis patients (6 months of treatment with SHF/HDF switched to 6 months of SHDF/HF), using the same machine (AK200 ULTRA), with on line fluid preparation system and the same type of dialyzer (Polyflux 210). The feasibility of such techniques (SHF/HDF or vice versa) resulted excellent. All sessions left the patients in a condition of well-being making fulltime work. No difference was observed between the different period of treatment, but a reduction in pre value was observed in calcium-phosphorous product, C-reactive protein and beta2-microglobulin, at the end of the sequential techniques. SHF/HDF therapy is a very promising technique. Further studies are needed to better explore the potential of such a therapeutic approach in the quality of life, the hemodialysis adequacy and the hemodynamic stability of our patients.

Adult↗

Sequential convective therapies (SCT): a prospective study on feasibility, safety, adequacy and tolerance of on-line hemofiltration and hemodiafiltration in sequence.

Sequential dialysis techniques (i.e pure ultrafiltration followed by dialysis) have been used in the past, due to their capability to remove large volumes of fluids without inducing hemodynamic instability. The disadvantages of inadequate efficiency and lack of technology lead to the decline of such methods. Hemofiltration (HF) and hemodiafiltration (HDF) are recently being utilized in a greater proportion thanks to on-line fluid preparation systems. Each process (HF and HDF) has its own benefits in the removal of small, medium and high-molecular weight substances and in hemodynamic stability. Sequential convective therapies (SCT) such as hemofiltration-hemodiafiltration in sequence (HF-HDF) may combine the benefits and eliminate the disadvantages of each method and should be studied in order to explore their potential application in modern dialysis. Furthermore they can be easily applied nowadays, due to the development of new sophisticated dialysis machines. In order to evaluate the feasibility, safety, efficiency and tolerance of different SCT methods we studied 3 schedules: SCT1: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 25% of the total fluid that had to be removed). SCT2: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). SCT3: 2h pre-dilution HF followed by 2h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). We studied 6 chronic hemodialysis patients using the same machine (AK200 ULTRA), with on-line fluid preparation system and the same type of dialyzer (Polyflux 210). SCT schedules were compared to on-line HF, on-line HDF and high flux dialysis performed with the same dialyzers. The treatments resulted safe, easy, feasible and well tolerated with an improved hemodynamic response to high volume convective therapies. Adequacy of treatment was satisfactory in all SCT schedules while middle molecular weight solute clearance and removal resulted higher in treatments with higher convective component. SCT might represent an interesting option for the future especially in patients with hemodynamic instability and requirements for interventions during treatment.

Blood Pressure↗

Pulse high volume hemofiltration.

The sepsis syndrome is the most common cause of acute renal failure and multiple organ dysfunction in critically ill subjects and continues to have an alarmingly high mortality. Normal immune homeostasis is interrupted by a complex storm of inflammatory mediators responsible for the deleterious effects. Extracorporeal blood purification techniques can confer benefits in sepsis by proven non-specific removal of these mediators (pro- or anti-inflammatory), and provide a logical and adequate approach to treat this syndrome. High volume hemofiltration (HVHF) has had the most dramatic effect conferring benefits in hemodynamics, reduction in vasopressor doses and improvement in survival. "Pulse HVHF" is the latest approach which may offer the most efficient results: a daily schedule of 6-8 hours followed by standard CVVH. This paper describes the rationale and potential of this technique. Reliability and tolerance of this technique and biological effects are described.

Acute Kidney Injury↗

First clinical trial for a new CRRT machine: the Prismaflex.

A new CRRT machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called "Prismaflex" (Gambro-Dasco, Mirandola, Modena) and it is the natural evolution of the Prisma machine that has been utilized worldwide for CRRT in the last decade. We performed a preliminary "alfa trial" to establish usability, flexibility and realiability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities. Forty-one runs were conducted on 13 patients and the difference between delivered and prescribed parameters was always lower than 2%. We concluded that the new Prismaflex is a well designed new machine for CRRT and can be safely and effectively utilized in the critical care nephrology setting.

Acute Kidney Injury↗

Continuous renal replacement technology: from adaptive devices to flexible multipurpose machines.

OBJECTIVE: To review the evolution of technologies in the development of renal replacement therapies. DATA SOURCES: Articles and published reviews on renal replacement therapies. SUMMARY OF REVIEW: Continuous arterio-venous haemofiltration (CAVH) was the first continuous renal replacement technique capable of overcoming the traditional haemodialysis-related side effects, making possible the treatment of critically ill patients safely and with less physiological instability. The evolution of technology and the progress experienced in intensive care units (ICUs) has made it possible to start renal replacement therapy programs in the absence of a chronic dialysis facility or a trained nephrological team. Initial limitations and draw-backs of CAVH, stimulated the ICU staff to explore new avenues for better therapy. Extracorporeal therapies are today a routine experience in the ICUs: continuous renal replacement therapies are a broadly accepted treatment for acute renal failure. Furthermore, alternative indications for extracorporeal blood circulation (e.g. sepsis, liver failure, congestive heart failure, drug intoxications, hyperthermia, immuno-mediated syndromes) are becoming more and more popular. The ideal machine has yet to be completed, but progress has occurred and has opened a new era for critical care nephrology and the further expansion of blood purification technology in the ICU. CONCLUSIONS: Technical advances in renal replacement therapies have increased their functionality (i.e. used in hepatic failure, sepsis, cardiac failure and immuno-mediated syndromes), are easier to operate and have less side-effects compared with their standard extracorporeal counterparts. Further improvements may see them become a routine part in the management of the critically ill patient.

Journal Article↗

Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model.

Pro-apoptotic molecules are generated during sepsis which may be responsible for alteration of organ function in sepsis. Removal of systemic apoptotic activity may affect recovery from sepsis. Current high flux membranes might not be sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the elimination of pro-apoptotic factors induced by LPS in human whole blood by a super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka, Japan) in comparison to a standard high flux cellulose triacetate membrane (UT 700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola Italy) in an in vitro blood circulation. We spiked human whole blood with lipopolysaccharide from Escherichia coli (Serotype 026-86, 10 mg/ml), incubated it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for 3 hours. The UF line was first returned to the blood module at 10 min. After this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance was obtained by re-infusion of bicarbonate buffered hemofiltration fluid. Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate) by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFalpha were determined by commercially available ELISAs. Sieving coefficients and clearances were determined for the different cytokines. Caspase-3 and Caspase-8 were activated by LPS and remained either stable or increased during in vitro circulation. Apoptosis activity of U937 cells, when incubated with the ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700 = 23.1%; Sureflux FH150 = 42.5%). However, by 60 min the apoptotic activity recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for Uf: UT700 = 19.8%; Sureflux FH150 = 11.2%). Sieving coefficients in the super-permeable membrane were significantly higher for all measured cytokines in comparison to the standard high flux membrane (e.g. TNFalpha 0.72 vs 0.03 p < 0.001) and close to the values observed for the plasmafiltration membrane. Nevertheless protein losses measured by albumin leakage were much lower with the Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic factors can be eliminated by dialytic membranes with the removal rate maximized by using super high flux dialysers which may represent a compromise between hemofiltration and plasmafiltration membranes.

Apoptosis↗

Continuous flow peritoneal dialysis: a new double lumen catheter.

Continuous flow peritoneal dialysis (CFPD) is a therapy originally utilized in the sixties. It was then abandoned because of technical reasons, but, today, a new interest in this technique is emerging, because of new technical solutions and new hardware capabilities. CFPD is a peritoneal dialysis technique in which a certain amount of fluid is maintained in the peritoneal cavity, while a continuous inflow and outflow is provided via twin catheters or through a double lumen catheter. In this paper a new double lumen catheter is presented. The catheter is characterized by the presence of a diffuser in the inflow lumen, while a standard coiled shape characterizes the outflow lumen. The diffuser allows the use of high dialysate flows without peritoneal damage and with an excellent distribution of the fluid. The other feature of the catheter is the removable hub which allows for an easy subcutaneous tunneling of the catheter with a subsequent connection to the y segment. The special shape also guarantees a minimum recirculation during treatment. Data obtained in the first implanted catheter showed a progressive increase in small solute clearances in relation to an increase of the flow and the tidal volume in the peritoneal cavity. In particular, urea clearances up to 48 ml/min and creatinine clearances up to 39 ml/min were obtained. No major complications were observed after one year of use of the catheter.

Catheters, Indwelling↗

Extracorporeal treatments in sepsis: are there new perspectives?

Sepsis continues to provide a major challenge to clinicians. Despite vast advancements achieved in the understanding of its pathways and mechanisms, the incidence of sepsis is increasing and the mortality and morbidity rates remain high, generating a considerable burden to health budgets worldwide. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the non-selective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extra-corporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials which lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. We will also review novel information related to other blood purification techniques using largo pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.

Acute Kidney Injury↗

Nephrotic syndrome and plasmapheresis.

We studied 15 patients suffering from nephrotic syndrome (NS) in bioptically-accertained primary and secondary glomerulopathies responding poorly to the common pharmacological treatment. They were monitored for one year by assessing their immunological and kidney functionality parameters, especially proteinuria. The patients underwent 3 apheretic sittings using the cascade double-filtration technique. After the third apheretic sitting the patients received metilprednisolone 300 mg/m2. This therapy was repeated every month for 6 months. At the end of the apheretic cycle it was shown that all patients had responded well to the therapy with a dramatic decrease in proteinuria, maintenance and/or recuperation of kidney functionality and improvement of lipidic asset; these data remained unchanged over time. Considering our preliminary results, we believe that therapeutic apheresis has a precise function in refractory nephrotic syndrome and, in particular, we propose the use of the cascade double-filtration technique.

Adult↗

[Efficacy of recombinant erythropoietin on the quality of life in patients over 60 years of age undergoing hemodialysis].

We followed for a period of six months, 54 patients of over 60 years old, submitted to hemodialitic treatment. We gave human recombinant erythropoietin, average dosage 50 UI/Kg subcutaneously on alternative days, folic acid and iron supplements together with a proteic supply of 1.2 g/Kg/die (35 Kcal/Kg). The medullary response has been monitored with hematochemical tests; blood pressure and nutritional conditions have been evaluated. Furthermore, the patients were given a questionnaire to evaluate their quality of life. At the end of the follow up, 50 patients responded positively to therapy. These patients showed an increase of RBC (from 2,789,780 +/- 259,310 to 3,313,110 +/- 472,780 p < 0.001) of HCT (from 21.86% +/- 2.16% to 27.18 +/- 2.74% p < 0.0001) and of Hb (from 7.72 +/- 1.12 g/dl to 9.28 +/- 0.98 g/dl p < 0.006). Total protein and albumin increased too. Furthermore they showed a progressive increase of "performance status". Our results confirm efficacy of erythropoietin in the treatment of anemia in elderly hemodialized patients.

Age Factors↗

[Plasmapheresis combined with pharmacology in the treatment of lupus nephritis: a new therapeutic protocol].

Systemic Lupus Erythematosus (SLE) is a pathology of unknown cause, characterized by tissue and cellular damage, secondary to production of autoantibodies and to deposition of immunocomplexes. Lupus nephritis is one of the most common complications of SLE. Our purpose is to propose a therapeutic protocol for patients suffering from Lupus nephritis. This consists of Plasmapheresis associated with pharmacological therapy so that dosage of immunosuppressors can be reduced and consequently also the side effects of the pharmacological therapy.

Adolescent↗

[Rationale for the use of extracorporeal treatments for sepsis].

Sepsis is the leading cause of disability and mortality among critical patients; moreover, it causes high economic expenditures. Although very much is known about the pathophysiology of this condition and its mediators despite great investments directed to its control, mortality rates remain high. Recent treatment manuals emphasize the value of early goal-oriented therapy and also point to the high efficacy of activated protein C. Extracorporeal blood clearance may potentially become a new approach to treating this condition. There are reports on its positive clinical results that are likely associated with the effective removal of septic mediators. Human and animal studies, few and rather alike as they are, have yielded promising results. It is evident that the use of these procedures is justified; however, their efficiency in sepsis requires large-scale, correctly conducted studies.

Extracorporeal Circulation↗