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Biomedical subjects

N Di Paolo

Publications and source records attributed to N Di Paolo.

At least 19 recordsLinked to original sources

Inhaled mycotoxins lead to acute renal failure.

Mysterious deaths of archeologists after opening Egyptian tombs have been suspected, but never proved, to be secondary to inhalation of mycotoxin. We observed a case of acute renal failure (ARF) due to inhalation of ochratoxin A produced by a mould of the species Aspergillus ochraceus. After working 8 h in a granary closed for several months, a farmer and his wife suffered respiratory distress; the woman developed non-oliguric ARF and biopsy revealed tubulonecrosis. A strain of Aspergillus ochraceus producing ochratoxin was isolated from the wheat.

Acute Kidney Injury

Acute renal failure from inhalation of mycotoxins.

Mysterious deaths of archeologists after opening Egyptian tombs have been suspected to be secondary to inhalation of mycotoxin, however, the hypothesis has never been verified. Recently, we observed a case of acute renal failure (ARF) undeniably due to inhalation of ochratoxin of Aspergillus ochraceus. After spending 8 h in a granary which had been closed for several months, a farmer and his wife suffered temporary respiratory distress; 24 h later, the woman developed nonoliguric ARF and biopsy revealed tubulonecrosis which healed in 24 days. Toxic substances were not found, but a strain of A. ochraceus producing ochratoxin was isolated from the wheat.

Acute Kidney Injury

Autologous peritoneal mesothelial cell implant in rabbits and peritoneal dialysis patients.

Human and rabbit peritoneal mesothelial cells have been successfully cultured and autoimplanted. An original biopsy technique was used to take samples of peritoneal mesothelial cells and after culture they were characterized from the structural and caryological points of view. Staphylococcal peritonitis was induced in 12 rabbits with indwelling peritoneal catheters and after 4 days of antibiotics 6 of them were autoimplanted with cultured autologous mesothelial cells previously marked in 3 cases with thymidine (H3TdR). Direct morphological observation and autoradiography were used to compare the mesothelium of control rabbits and implanted rabbits sacrificed on days 3 and 6 and showed that the cell implants had taken. Four uremic CAPD patients recovering from severe peritonitis were implanted with about 300 million autologous peritoneal mesothelial cells, previously cultured and frozen. Morphological signs of taking were evident from peritoneal laparoscopy biopsies performed 3 and 6 days after implant. The aim of the study was merely to demonstrate that such implants are possible; however, the techniques may have interesting applications not only in peritoneal dialysis, but also in the vaster fields of medicine and surgery.

Adult

Autologous implant of peritoneal mesothelium in rabbits and man.

With the purpose of studying peritoneal physiology, original biopsy methods were devised and human and rabbit peritoneal mesothelial cells cultured and characterized. It was then decided to verify whether these cells could be implanted autologously during peritoneal dialysis in cases of acute loss of mesothelial surface. Staphylococcal peritonitis was induced in 12 rabbits and after 4 days of antibiotics, 6 of them were autoimplanted with cultured mesothelial cells, previously marked in 3 cases with thymidine (H3TdR). Implanted rabbits sacrificed after 3 and 6 days showed taking of the new mesothelial cells both by direct morphological observation and by autoradiography. Four uremic CAPD patients recovering from severe peritonitis were implanted with 300 million of their own peritoneal mesothelial cells, previously cultured and frozen. Morphological signs of taking were evident by laparoscopy and from peritoneal biopsies performed 3 and 6 days after implant. The fact that such implants are possible may have interesting applications in medicine and surgery.

Adult

Bleeding tendency of chronic uremia improved by vascular factor.

Complex hemostatic changes in uremic patients are characterized by platelet distress and prolonged bleeding time. Dialysis corrects platelet function and improves the bleeding time but introduces a tendency to thrombophilia. The uremic patient is thus an excellent model for the evaluation of hemostatic drugs. VUEFFE (VF) is a new hemostatic agent which reduces bleeding time without modifying clotting parameters. Changes in hemostasis and coagulation were studied in 42 hemorrhagic uremic subjects in dialysis or on conservative management. The patients were divided into two groups, one of which was given oral VF and the other oral placebo. 84% of those receiving VF ceased bleeding within 15 days (compared to 25% for placebo) and there was a significant reduction in bleeding time. The drug can be given orally or parenterally, is well tolerated and without side effects, making it suitable for administration to hemorrhagic uremic patients.

Adult

Peritoneal vascular changes in continuous ambulatory peritoneal dialysis (CAPD): an in vivo model for the study of diabetic microangiopathy.

Replication of the basement membrane of the peritoneal capillaries and the mesothelium is observed in all uremic patients after a period of continuous ambulatory peritoneal dialysis (CAPD). Biopsy specimens of the parietal peritoneum were taken in diabetic and non-diabetic patients on insertion or repositioning of the CAPD catheter. The basement membrane of the capillaries and mesothelium was normal in non-diabetics on insertion of the catheter, but after 2 to 66 months of CAPD, multiple replication was found. In nearly all the diabetics there was already replication of the basement membrane of the peritoneal capillaries before CAPD was begun but the basement membrane of the mesothelium was intact. After several months of CAPD thickening of the basement membrane of the capillaries was found in 36% of diabetics, sometimes to the point of occlusion. After CAPD, replication of the basement membrane of the mesothelium has been observed in both diabetics and non-diabetics although it is initially perfectly normal in both. CAPD is proposed as an experimental model for diabetic microangiopathy in man.

Basement Membrane

Implant of autologous mesothelial cells in animals and a peritoneal dialysis patient.

Success in culturing human and animal peritoneal mesothelial cells for the purpose of study, led us to determine whether these cells could be autoimplanted in animals and man during peritoneal dialysis in cases of acute and extensive loss of mesothelial surface area. Using an original biopsy technique, we were able to cultivate and characterize from the structural and caryological point of view, human and rabbit peritoneal mesothelial cells. Staphylococcal peritonitis was provoked in 12 rabbits with in-dwelling peritoneal catheters and after 4 days of antibiotic therapy, 6 of them were autoimplanted with cultured mesothelial cells. In the animals sacrificed on the third and sixth days, direct morphological observation and autoradiographic techniques showed that the transplanted cells had taken and revealed a different picture from that in the non-transplanted rabbits. In a 56 year old female diabetic patient, upon insertion of the first peritoneal catheter, a specimen of mesothelial cells was cultured and then frozen. Seven months later after an episode of peritonitis from candida which dictated removal of the peritoneal catheter, since there was a sufficient number of cultured mesothelial cells and the patient consented, the implant was performed. Peritoneal biopsy by laparoscopy three and six days later showed that the cells had taken. The purpose of the study was merely to show that autoimplant of mesothelium in man and animals is possible.

Animals

Morphology of the peritoneal membrane during continuous ambulatory peritoneal dialysis.

In the last 3 years we performed 52 peritoneal biopsies (PB) in 31 patients on continuous ambulatory peritoneal dialysis (CAPD). Samples of the parietal peritoneum were obtained either during insertion of the catheter or while it was being repositioned or removed. PB was performed in 13 patients before initiating CAPD and in 27 after 7-49 months of CAPD while 7 had PB during peritonitis, and, again, in 5 of these cases, PB was repeated after 1-4 months for light, electron transmission, and scanning electron microscopy. BP after CAPD showed that mesothelial cells were irregularly spaced, and at times we observed alterations in the cellular structure. Rarely were these cells degenerating, while rarefaction and in many cases complete absence of microvilli were observed. In some cases the submesothelial layers showed rarefaction of the connective tissue and sclerosis. During peritonitis, PB showed more alterations with marked degeneration and in some cases necrosis of the mesothelium and alterations of connective tissue. PB performed some months after peritonitis showed only a partial regression of these alterations and sclerotic patches, and no microvilli were noted in the mesothelium.

Ascitic Fluid

Phosphatidylcholine and peritoneal transport during peritoneal dialysis.

Peritoneal effluent of patients on chronic ambulatory peritoneal dialysis (CAPD) contains a surface-active material (SAM) made up of phospholipids and showing phosphatidylcholine on thin-layer chromatography. This substance drastically lowers surface tension, helps to repel water and has a lubricating effect. The presence of stratified phosphatidylcholine on the peritoneum might narrow the stagnant dialysate fluid layer and situations which can alter the quantity or composition of SAM may affect peritoneal transport and also, perhaps, the formation of adherences. This led us to verify, experimentally, the presence of phospholipids in basal conditions, after CAPD and during peritonitis and to check if addition of phosphatidylcholine to dialysis liquid is able to modify water transport in patients with low ultrafiltration and peritonitis. Phospholipids in the dialysis effluent of patients who have been on CAPD for a long time are lower than observed in the first days of peritoneal dialysis. A more drastic, significant decrease in phospholipids was observed in patients with low ultrafiltration and in patients with peritonitis. Mean ultrafiltration significantly increases in patients with low ultrafiltration and in those with peritonitis during dialysis exchanges containing phosphatidylcholine (50 mg/l) indicating that the latter is able to restore normal physiological conditions.

Biological Transport

A new technique for insertion of the Tenckhoff peritoneal dialysis catheter.

To eliminate the discomfort caused by surgical methods and the risks involved using the trocar, for 1 year we have been using a new technique for insertion of peritoneal catheters (PC). We devised a steel instrument, vaguely resembling a rhinoscope, composed of two semicones. The handles are connected by a screw to permit dilatation of the semicones. After local anesthesia, an introducer needle is inserted into the peritoneal cavity. A guide-wire is passed through the needle which is then withdrawn and our instrument is placed around the guide and gently pushed into the peritoneal cavity. The guide is now removed and squeezing the handles of the instrument we introduce the PC up to 2 cm beyond the first Dacron cuff. When the catheter is in place, the instrument is removed and a subcutaneous tunnel may be made. We have used this method for 25 patients. 14 were new cases while 11 underwent PC repositioning. For all patients this new method proved to be excellent with practically no leakage and PC were utilized immediately or after only 24 h. We emphasize the brief time for PC insertion, the minimum discomfort and the simplicity of the technique.

Catheterization

[Effects of reduction of blood viscosity at constant hematocrit on the cerebral blood flow].

It is well established that cerebral blood flow (CBF) is low in patients with high hematocrit and is high in anemic patients. An inverse relationship between CBF and hematocrit has been found. Furthermore, if hematocrit is reduced, CBF increases. There is some debate as to whether these observations are due to viscosity or to oxygen carrying capacity of the blood. In order to further elucidate this problem, CBF, blood viscosity and hematocrit were measured in 4 patients with paraproteinemias before and after paraproteins had been removed by plasmapheresis without changes in hematocrit. After plasmapheresis, blood viscosity significantly decreases and CBF increases by a mean of 24.4 ml/100 g/min. Mean arterial blood pressure and hematocrit were not influenced by plasmapheresis. These results indicate that blood viscosity is an important factor in determining CBF. This does not exclude the role of oxygen transport as an associated factor, but it is evident that oxygen transport and blood viscosity are independent variables in the control of CBF.

Blood Viscosity