G. Garosi

Peritoneal Sclerosis: One or Two Nosological Entities?

The frequency, pathology, animal models, pathogenesis, clinical manifestations, diagnostic criteria, therapy and prevention of peritoneal sclerosis are reviewed. Many of these aspects have a bimodal configuration which suggests that peritoneal sclerosis, usually considered a single pathology in peritoneal dialysis, is actually two distinct nosological entities: simple sclerosis and sclerosing peritonitis. The former is very frequent, with minor anatomical alterations and low clinical impact; it is reproducible in animals by means of peritoneal dialysis, and is clearly due to the poor biocompatibility of peritoneal dialysis solutions. The latter is rare, with radical anatomical alterations and high mortality requiring valid methods of diagnosis, therapy and prevention; it can only be reproduced in animal models by means other than peritoneal dialysis and seems to be due to factors both related and unrelated to peritoneal dialysis.

Morphological and Morphometric Changes in Mesothelial Cells during Peritoneal Dialysis in the Rabbit

The morphometric and morphological changes in the mesothelial cell population were studied in rabbits in peritoneal dialysis with lactate and bicarbonate buffer solution. During dialysis the mesothelial population underwent radical changes in morphology and morphometric analysis showed a significant increase in cell size. Light microscope examination showed two types of changes: hyperplasia of the mesothelial cell with diameters of up to 80 microns, nucleus proportional to the cytoplasm, a large nucleole giving an owls eye appearance and cytoplasm rich in granular material. The second change was multiple nuclei and arrest of cell division. Nuclear division occurred, but no separation of the cytoplasm. The cells became larger than 200 microns, packed with nuclei and relatively little cytoplasm. Electron microscopy confirmed that the hyperplastic cells had perfect structure whereas the polynucleate cells contained vacuoles and little cytoplasmic reticulum. Immunohistochemistry using monoclonal antibodies SK2-27 and SK 60-61 specific to cytokeratins 14, 16, 17 and 8, 18, respectively, identified the cells as mesothelial. The changes were related to the glucose content of the peritoneal dialysis solution. Glucose is therefore the bioincompatible agent that modifies the mesothelium during peritoneal dialysis, causing it to become hyperplastic or blocking replication.

Videothoracoscopic obliteration of pleuroperitoneal fistula in continuous peritoneal dialysis

Hydrothorax during peritoneal dialysis is a very tedious complication. Many authors have described techniques of performing diagnosis and therapeutic procedures to take care of these complications. We describe a method to perform diagnosis and therapy by videothoracoscopy. Videothoracoscopy permits identification and closure of the tiny flaws in the diaphragm.

Extracorporeal blood oxygenation and ozonation (EBOO) in man. preliminary report.

Autohemotherapy with ozone has been used for four decades with encouraging results but, owing to the lack of clinical studies, it has never been adopted by orthodox medicine. Confident of the valid principles of ozone therapy, we have endeavoured to increase its therapeutic efficacy. Over a ten-year period we have developed an apparatus that makes it possible to treat large quantities of blood with ozone in extracorporeal circulation (extracorporeal blood oxigenation and ozonation EBOO). One of us volunteered to test the system and after six treatments noted the disappearance of two lipomas. This prompted us to treat a patient with Madelung disease and several patients with atherosclerotic vasculopathy. Besides showing therapeutic effects, the preliminary results indicate that EBOO is clinically valid, without side-effects and worthy of testing in various diseases.

Ozonation of blood during extracorporeal circulation. I. Rationale, methodology and preliminary studies.

We investigated whether exposure of blood ex-vivo to oxygen-ozone (O2-O3) through a gas exchanger is feasible and practical. We first evaluated the classical dialysis-type technique but we soon realized that semipermeable membranes are unsuitable because they are hydrophilic and vulnerable to O3. We therefore adopted a system with hydrophobic O3-resistant hollow fibers enclosed in a polycarbonate housing with a membrane area of about 0.5 m2. First we tested the system with normal saline, determining the production of hydrogen peroxide (H2O2) at O3 concentrations from 5 to 40 μg/ml. We then evaluated critical parameters by circulating swine blood in vitro; this revealed that heparin is not an ideal anticoagulant for this system. Finally, we performed several experiments in sheep and defined optimal anticoagulant dose (sodium citrate, ACD), priming solution, volume of blood flow per min, volume and concentration of O2-O3 mixture flowing counter-current with respect to blood and the time necessary for perfusion in vivo. The biochemical parameters showed that an O3 concentration as low as 10 μg/ml is effective; this means that gas exchange and O3 reactivity are rapid and capable of inducing biological effects. The sheep showed no adverse effects even after 50 min of extracorporeal circulation at higher O3 concentrations (20 to 40 μg/ml) but the exchanger became less effective (low pO2 values) due to progressive clogging with cells.

Different Aspects of Peritoneal Damage: Fibrosis and Sclerosis

Peritoneal sclerosis is very common in peritoneal dialysis patients. It can vary from the mild, clinically silent simple sclerosis always present after years of peritoneal dialysis, to rare but dramatic and often fatal cases of encapsulating peritoneal sclerosis. Their frequency, pathology, animal models, pathogenesis, clinical manifestations, therapy, and prevention are reviewed. Peritoneal fibrosis and sclerosis is a complex phenomenon. At one end of the spectrum we have simple sclerosis: the mild, clinically silent sclerosis always present after years of peritoneal dialysis. At the other end, we have encapsulating peritoneal sclerosis, which is rare but dramatic and fatal.

Uremia, dialysis and aluminium

Few studies have dealt with assaying aluminium levels in different tissues of uremic patients; so far a comparison has never been made between its accumulation in the various tissues of uremic patients and controls. Aluminium levels were determined in the following biological samples: 1)111 serum samples from hemodialysis patients and 55 serum samples from normal subjects; 2) 47 urine samples from the same dialysis patients and 45 from the controls; autopsy tissue specimens (blood, bile, brain, rib, cartilage, cranium, lung, spleen, kidney, aorta, vena cava, liver, muscle) from 12 deceased dialysis patients undergoing post-mortem diagnosis and 10 autopsy cases in which death was not associated with uremia. In living subjects, both serum and urinary levels of aluminium are significantly higher in hemodialysis patients than in controls; a significant positive correlation was found between serum and urinary levels of aluminium. In autopsy specimens, aluminium levels were higher in the dialysis group than controls for all tissues; the differences were statistically significant except in heart and urine. Tissue concentrations of aluminium in the two groups were then analysed separately both in uremic patients and controls. The highest values found in dialysis cases were in the bile, followed by blood, urine and lung; levels in the other tissues were considerably lower. In controls, the distribution was somewhat different, due to much lower levels in the liver and bile with respect to dialysis cases. Again we found surprisingly high levels in the lung. The results show that aluminium storage in uremic patients occurs in all organs and tissues, albeit to different degrees.

Fibrosis and Sclerosis: Different Disorders or Different Stages?

Peritoneal sclerosis is very common in peritoneal dialysis (PD) patients. It can vary from the mild, clinically silent sclerosis always present after years of PD, to rare but dramatic and often fatal cases. In our opinion, peritoneal sclerosis is a single disorder, so its variable manifestations are different stages of one nosological entity: this opinion relies mainly on strong connections in pathophysiology. In our view, the frequency, pathology, animal models, etiology and pathogenesis often show a bimodal configuration with suggests that peritoneal sclerosis is actually two distinct nosological entities: simple sclerosis and sclerosing peritonitis. The former is very frequent, with minor anatomical alterations and low clinical impact; it is reproducible in animals by means of PD, and is clearly due to the poor biocompatibility of PD. The latter is rare, with radical anatomical alterations and high mortality; it can only be reproduced in animal models by means other than PD and seems to be due to factors both related and unrelated to PD.

Simple peritoneal sclerosis and sclerosing peritonitis: related or distinct entities?

Aim The etiopathogenesis of sclerosing peritonitis is still debated, with some sustaining that it is a rare form of progression of simple peritoneal sclerosis and others that it is a primitive form. The aim of the present research was to clarify this question. Material and Methods 438 peritoneal biopsies from 253 patients were re-examined. 174 were obtained prior to peritoneal dialysis and 224 after various periods of dialysis. Forty biopsies were from peritoneal dialysis patients who developed sclerosing peritonitis. Peritoneal morphology was studied for signs of transition from simple sclerosis to sclerosing peritonitis. Results Evidence was found sustaining the hypothesis that simple sclerosis to sclerosing peritonitis patients have distinct pathologies. Conclusions The results confirm previous observations, excluding the existence of any type of relation between simple peritoneal sclerosis to sclerosing peritonitis.

State of the art on autologous mesothelial transplant in animals and humans.

Sixteen years ago rabbit and human mesothelial cells were successsfully cultured and autoimplanted. The aim of the study was merely to demostrate that mesothelial implant was possible and interesting not only in peritoneal dialysis, but also in the vaster field of medicine and surgery concerning all the mesothelial districts of the body. The aim of this paper is to recollect the steps which have led to autolougous mesothelial transplantation and verify if the tecnique has been validated and adopted by others. Review of the literature published in the last 15 years shows that intraperitoneal transplantation of mesothelial cells has been effective in reducing the formation of peritoneal adhesions, and in remodeling the area of mesothelial denudation. New studies on the mesothelial cell opened the way to costruction of transplantable tissue-engineered artificial peritoneum, to the utilization of mesothelial progenitor cells and to find simple metods to collect autologous mesothelial cells. Finally mesothelial trasnsplantation may represent a new neovascular therapy in the prevention and treatment of ischemic coronaric heart disease.