Peritoneal dialysis and recovery from acute renal failure in a 847-gram newborn infant.
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Biomedical subjects
Publications and source records attributed to L Gotloib.
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Previous studies showed that murine septic peritonitis induced a substantial reduction of the anionic site density distribution in mesenteric and diaphragmatic microvessels. The present study shows that acute experimental septic peritonitis induces a severe reduction of the anionic site density distribution along the submesothelial basement membrane. Five days after induction of peritonitis, there was a partial recovery of anionic sites which even at 13 days was not completed. This observation suggests that the increased protein losses observed during peritonitis are the consequence of increased microvascular and mesothelial permeability to anionic plasma proteins secondary to neutralization and/or disappearance of the anionic sites located in the microvascular wall and in the mesothelial layer.
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This study demonstrates the existence of fenestrated capillaries in the microvascular bed of mice mesentery. The 26.6% incidence of fenestrated capillaries observed in this study is similar to that found in rabbit diaphragmatic peritoneum. Fenestral diameters are too large to be identified as the large pore of Pappenheimer's theory. They appear to be too frequent to become the predicted large pore. Peritoneal permeability should be analyzed on the basis that molecular transfer occurs through multiple ways.
Pulmonary edema of sepsis is a consequence of increased transmural conductance for water and proteins at the level of lung microvessels induced by vasoactive endogenous mediators, liberated after activation of complement by bacterial endotoxins. Intermittent opening of interendothelial junctions at the level of post-capillary venules has been implicated as being the pathway for the leaking plasma proteins and water. Microvascular basement membranes and endothelial cell surfaces have fixed anionic charges (AS) which prevent the escape of plasma proteins from the circulation as well as the adhesion of blood cells to the luminal endothelium. The density distribution of these AS was substantially reduced in visceral and systemic microvessels during murine abdominal sepsis. This observation suggest that MOF secondary to sepsis is the consequence of a severe and generalized alteration of the microvascular electronegative charge, induced by liberation of inflammatory mediators.
The peritoneum has been classically considered to be an inert passive membrane. Previous studies demonstrated the presence of fixed anionic charges at the level of the peritoneal microvasculature and the subserosal interstitium. The present study describes the selective distribution of fixed anionic charges in the mesothelial cell plasmalemma and organelles as well as in the submesothelial basal lamina of rat and mice visceral, parietal and diaphragmatic peritoneum. These data support the idea that the peritoneum should be considered a negatively charged biological dialyzing membrane with selective capabilities. Therefore, transperitoneal transfer of charged solutes cannot be analyzed just on the basis of their molecular weight, size and shape.
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This study shows that the luminal surface of peritoneal microvascular endothelium, coated pits and coated vesicles are all negatively charged, unlike the limiting membrane of pinocytotic vesicles and transcellular channels. Our findings suggest that these cellular organelles have different functions as well as a different chemical composition. Anionic sites were observed along the subendothelial and subperithelial basal laminae of peritoneal capillaries and post capillary venules, respectively. Electric charge is a new parameter to be considered when analyzing transperitoneal transfer of charged macromolecules.
Twenty-four patients with high microvascular permeability pulmonary edema were initially treated by means of conventional supportive therapy for 1-12 days. Continued deterioration was treated by predilutional hemofiltration and induced a dramatic improvement in 22/24 patients. Survival was 92%. Sieving coefficients for autacoids and middle molecular weight vasoactive peptides involved in the development of high microvascular permeability pulmonary edema were higher than 0.88 indicating that clearing from blood of these peptides during one pass through the hemofilter is similar to that obtained during one pass through the pulmonary normal microvasculature. Hemofiltration seems to be a significant breakthrough in the treatment of ARDS secondary to severe sepsis.
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One case of severe varicella pneumonia with high microvascular permeability pulmonary edema and signs of multiple system organ disfunction was successfully treated by means of hemofiltration. The patient was discharged from the Intensive Care Unit 6 days after admission. Peptides showing molecular weight ranging between 600 (prostaglandins) and 4000 (B-endorphin) daltons were cleared from blood at the same rate as urea. Hemofiltration appears to be a valuable tool for treating septic ARDS.
Two patients, affected by spotted fever, developed low pulmonary capillary wedge pressure (PCWP) pulmonary edema with severe hypoxemia. Conventional specific and supportive therapy, including mechanical ventilation, failed to induce significant respiratory and hemodynamic improvement which was dramatically reached by means of hemofiltration. Removal of circulating middle molecular weight peptides by the convective mass transfer, characteristic of hemofiltration, offers a new and effective therapeutic approach for the adult respiratory distress syndrome secondary to rickettsial diseases.
Generally, the incidence of peritonitis in maintenance peritoneal dialysis programs is calculated as a percentage of the total number of treatments or as the number of episodes per patient-months. Both statistical methods give the wrong impression that peritonitis is seldom observed. However, peritonitis is still the major and unsolved challenge to successful long-term peritoneal dialysis. The lack of a standard and homogeneous definition of peritonitis is another critical point that prevents a rational interpretation of the published experiences. In the present study, dialysate cell counts of greater than 1,100 cells/mm3 were assumed to be the first sign of peritoneal infection. As long as more signs and symptoms are required for recognizing peritonitis (fever, abdominal pains, positive cultures), the statistical probability of making such a diagnosis shows the characteristics of a Poisson distribution. It is concluded that in long-term peritoneal dialysis, the currently used statistical methodology for evaluation of the incidence of peritonitis, including the clinical definition of this complication, is misleading. Dialysate cell counts appear to be the more sensitive sign for early diagnosis of peritonitis.
Samples of parietal peritoneum from 20 patients (11 of them chronic uremics) and biopsies of diaphragmatic peritoneum from 5 apparently normal female New Zealand rabbits were examined by electron microscopy. One out of 20 patients and 3 out of 5 rabbits showed fenestrated capillaries. This report is the first published demonstration of the existence of fenestrated capillaries in human parietal and rabbit diaphragmatic peritoneum. They represented a small fraction of the peritoneal microvascular bed which was mainly formed by capillaries of the continuous type. Fenestrae of the observed fenestrated capillaries showed diaphragms. Results of this study indicate that different peritoneal microvascular segments can show different microvascular ultrastructures and possibly have a different physiology and different mechanisms of transperitoneal transfer of water and solutes.
Sixteen chronic uremics who showed exhausted bone marrow iron stores and mean hematocrit values of 20.9 +/- 4.2% at the time of starting maintenance hemodialysis (HD) were treated by means of intramuscular iron dextran (IMD) (400 mg/month) for six months. By the end of this replenishment period, stainable bone marrow iron was observed and mean hematocrit values increased to 27.2 +/- 4.9% (p greater than 0.001). At this time, 200 mg of IMD/month and testosterone enanthate (1.5 g/month) were prescribed for the whole follow-up period (up to 8 years). The observed mean hematocrit values were up to 46.1 +/- 1.6%. Major side effects were not observed. The process of slow iron reabsorption from the intramuscular injection site (up to 4 weeks) also implies the splitting of iron from dextran, therefore preventing bone marrow deposits of iron dextran complexes which make iron unavailable for erythropoiesis. High doses of testosterone enanthate can normalize hematocrit values of maintenance hemodialysis patients with replenished bone marrow iron stores.
Five patients with nonoliguric adult respiratory distress syndrome (ARDS) secondary to severe sepsis showed improved blood oxygenation after up to 36 h of conventional therapy and mechanical ventilation with optimal positive end-expiratory pressure. However, metabolic acidosis was unchanged, and blood urea had increased. Some patients showed hemodynamic signs of incipient heart failure. After sequential hemofiltration, the altered physiologic shunt and blood pH returned to normal. Chest x-rays showed clearing of interstitial pulmonary edema. Patients recovered from ARDS in spite of fluid accumulation. Mechanical ventilation was stopped up to 8.5 h after the last hemofiltration. We postulate that convective ultrafiltration clears the blood of circulating low- and middle-weight vasoactive molecules implicated in the development of high microvascular permeability acute pulmonary edema secondary to sepsis.
In this study, samples of mesenteric diaphragmatic peritoneum and peritoneum covering the inner side of the ventral abdominal wall of apparently normal rabbits were examined under electron microscopy. Mesentery appeared as the most vascularized peritoneal segment (71.1% of the total number of observed capillaries). Diaphragmatic and parietal peritoneum contributions to the total examined microvascular bed were of 17.9% and 10.9% respectively. Only 3.2% of peritoneal diaphragmatic capillaries were of the fenestrated type. This qualitative and quantitative heterogeneity of the peritoneal microcirculation combined with the different contribution of each peritoneal segment to the total peritoneal surface area, the different mesothelial cell density of visceral and parietal peritoneum, and the different permeability of parietal visceral peritoneum suggest that, in vivo, whole organ permeability studies would eventually show just an average of an unknown distribution of segmental peritoneal permeabilities.