Hemofiltration in septic ARDS. The artificial kidney as an artificial endocrine lung

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.     

Hemodialysis-related pruritus and associated cutaneous manifestations

BACKGROUND: Uremic pruritus is one of the most common disabling problems in patients with chronic renal failure. Few studies have evaluated itching and cutaneous manifestations in hemodialysis-dependent patients. OBJECTIVES: The aim of this prospective study was to identify the prevalence of pruritus and cutaneous changes affecting patients undergoing hemodialysis. METHODS: The degree of itching in 70 patients treated at the Haemek Medical Center Hemodialysis Unit, in northern Israel, was scored according to presence and severity. We examined the relationship between the quality of dialysis and the frequency of pruritus, and identified concurrent cutaneous disorders. RESULTS: Pruritus was a common problem in the study cohort and affected 74.3% of hemodialysis patients at some point. The main characteristics of pruritus were a general pattern in 65.7% and mild intensity in 78.3% of observed patients. Duration of hemodialysis varied between 3 months and 13 years. There was no correlation between occurrence of pruritus and demographic or medical parameters (sex, type of kidney disease, regular medications or duration of hemodialysis) of the patients. Higher dialysis efficacy, as expressed by dialyser clearance, volume distribution of area, dialysis duration (Kt/v), may reduce the prevalence of pruritus (P < 0.02). None of the blood and chemical values considered (hemoglobin, creatinine, urea, phosphorus, calcium, albumin, parathormone and alkaline phosphatase) revealed any statistically relevant differences between pruritus groups. The appearance of foot ulcers was different between diabetic and nondiabetic individuals undergoing hemodialysis (P < 0.001). CONCLUSIONS: Pruritus is still a common problem in hemodialysis-dependent patients. The prevalence of xerosis and excoriations was high in patients undergoing replacement therapy. Efficient replacement hemodialysis may provide a clinical benefit.     

Hemofiltration in severe high microvascular permeability pulmonary edema secondary to rickettsial spotted fever

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.     

Heterogeneous density and ultrastructure of rabbit's peritoneal microvasculature

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.     

Subunit stoichiometry of staphylococcal alpha-hemolysin in crystals and on membranes: a heptameric transmembrane pore.

Elucidation of the accurate subunit stoichiometry of oligomeric membrane proteins is fraught with complexities. The interpretations of chemical cross-linking, analytical ultracentrifugation, gel filtration, and low-resolution electron microscopy studies are often ambiguous. Staphylococcal alpha-hemolysin (alpha HL), a homooligomeric toxin that forms channels in cell membranes, was believed to possess six subunits arranged around a sixfold axis of symmetry. Here, we report that analysis of x-ray diffraction data and chemical modification experiments indicate that the alpha HL oligomer is a heptamer. Self-rotation functions calculated using x-ray diffraction data from single crystals of alpha HL oligomers show a sevenfold axis of rotational symmetry. The alpha HL pore formed on rabbit erythrocyte membranes was determined to be a heptamer by electrophoretic separation of alpha HL heteromers formed from subunits with the charge of wild-type alpha HL and subunits with additional negative charge generated by targeted chemical modification of a single-cysteine mutant. These data establish the heptameric oligomerization state of the alpha HL transmembrane pore both in three-dimensional crystals and on a biological membrane.     

Fenestrated capillaries in human parietal and rabbit diaphragmatic peritoneum

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.     

Fenestrated capillaries in mice submesothelial mesenteric microvasculature

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.     

Decreased density distribution of mesenteric and diaphragmatic microvascular anionic charges during murine abdominal sepsis

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.