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PubMed1996

Comparative scanning, transmission and atomic force microscopy of the microtubular cytoskeleton in fenestrated liver endothelial cells.

Endothelial fenestrae control the exchange of fluids, solutes and particles between the sinusoidal lumen and the microvillous surface of the parenchymal cells. Fenestrae have a critical dimension in the order of 150-200 nm, making it necessary to use microscopes with a resolution better than the light microscope. Comparative whole-mount preparations of isolated, purified and cultured rat liver sinusoidal endothelial cells (LEC) were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). Examination of detergent-extracted LEC by SEM and TEM shows an integral cytoskeleton: sieve plates are delineated by a sieve plate-associated cytoskeleton ring and fenestrae by a fenestrae-associated cytoskeleton ring. By using microtubule altering agents we could demonstrate: (1) the architectural role of microtubules in arranging fenestrae, (2) the existence of a population of microtubules resistant against low temperature and colchicine, (3) the ability of LEC to shift the microtubule assembly-disassembly steady state under various conditions, (4) and the necessity of an intact microtubular cytoskeleton to support the increase in the number of fenestrae after cytochalasin B. Topographical examinations of AFM images revealed that sieve plates are delineated by elevated borders, probably projections of the underlying tubular cytoskeleton.

Animals↗
PubMed2004

Highly symptomatic adult polycystic liver disease: options and results of surgical management.

BACKGROUND: The majority of patients afflicted with adult polycystic liver disease (APLD) are asymptomatic. For those who are symptomatic, there are a variety of treatment procedures that have been proposed but these lack verification through long-term studies with respect to safety and long-term effectiveness. Choice of surgical procedure is related to the severity of APLD and morphology of the cysts within the liver. The aim of the present study was to analyse the immediate and long-term results of fenestration and combined resection-fenestration at Singapore General Hospital. METHODS: A retrospective analysis of clinical, operative, imaging and follow-up data was carried out for 12 patients (10 women and two men) with symptomatic APLD who underwent surgery from January 1992 to December 2000. The primary outcome measures assessed were postoperative alleviation of symptoms, performance status, complications, mortality and long-term recurrence of symptoms. RESULTS: Nine patients underwent 12 fenestration procedures and three patients had combined resection-fenestration. Fenestration was carried out for eight of nine patients with a dominant cyst morphology and combination resection-fenestration was carried out for those three patients with diffuse cyst morphology. There was no operative mortality and all patients were discharged from hospital free of their preoperative symptoms. Overall morbidity rate was 58%. The mean follow up for the present cohort was 29.3 months. Only two patients had recurrence of symptoms. One patient with dominant cyst morphology who underwent laparoscopic fenestration had recurrence at 26 and 43 months but this was successfully treated finally with open fenestration. The other patient had diffuse cyst morphology and was treated with fenestration for recurrent cyst infection that recurred 1 month postoperatively. This required subsequent intravenous antibiotics and percutaneous drainage for resolution of symptoms. CONCLUSION: Treatment for symptomatic APLD should be based on the morphology of the liver cysts. Fenestration is a safe and acceptable procedure for patients with a dominant cyst pattern where liver size can be reduced after the cysts collapse. A combination of resection-fenestration is suitable for those with a diffuse cyst pattern where grossly affected segments are resected in combination with fenestration to allow for reduction in liver size.

Adult↗
PubMed1987

An analysis of the permeability of a fenestra.

In this analysis of published data we evaluate the permeabilities of unit area of fenestral pathway to water and small solutes. These properties are then used to assess the functional significance of the fenestral diaphragm which, along with the glycocalyx and basement membrane, makes up the fenestral pathway. Endothelial hydraulic conductance and permeability to small lipophobic solutes increase with fenestral density in a variety of mammalian tissue. The increase in conductance per unit increment in fenestral area (Kfen) averages 0.38 micron X s-1 X mm Hg-1 (regression analysis). This value means that a single fenestra (diam 0.06 micron, area 0.003 micron2) has a greater conductance than 1 micron2 of continuous (skeletal muscle) endothelium. Similarly the diffusional permeability of unit fenestral area (Pfen) to B12 and inulin is high. But neither Kfen nor Pfen is as great as might be expected from the extreme thinness of the diaphragm (less than or equal to 5 nm). Pfen depends on diffusivity (D) and pathlength (delta chi): Pfen = D'/delta chi. D' depends on the fraction of the fenestral surface available for exchange and on restriction to diffusion. These relations were applied to test the view that the diaphragm, rather than the glycocalyx or basement membrane, is the major barrier to fluid and small solutes in the fenestral pathway. If this were turn, over 98 1/2% of the diaphragm's area would have to be totally impermeable in order to yield the observed values of Pfen--a result consequent upon the extreme thinness of the diaphragm. In this event there would be less than one equivalent pore (radius 5-11 nm) per diaphragm on average-which is incompatible with ultrastructural evidence. The resistance of a 5-nm-thick diaphragm containing one or more pores is not high enough to account for fenestral resistance. It is concluded that much thicker structures, such as the glycocalyx and/or basement membrane, and not the diaphragm, account for fenestral resistance to small-solute and water transport.

Animals↗
PubMed1998

Fluid uptake by the renal medullary vasa recta: an estimate based on a quantitative analysis of the distribution of fenestrae in the vasa recta of young Sprague-Dawley rats.

Transmission electron microscopic techniques were used to carry out a quantitative analysis of the density of fenestration in the inner medullary vasa recta of the rat kidney. Measurements were made at 200 microns intervals from the tip to the base of the papilla (1800 microns from the tip). Fenestral diaphragms were estimated to be 65.4 +/- 0.78 nm in diameter (mean +/- S.E.M.), and were arranged in plaques with a mean interfenestral distance of 114.8 +/- 2.6 nm. Near the tip of the papilla there was no correlation between vessel size and degree of fenestration; density of fenestration, however, began to decrease about 1400 microns from the tip. The ratio of fenestrated to non-fenestrated profiles of vasa recta was found to be linear with respect to distance from the tip (r = 0.991), with values ranging from about 40:1 near the tip to 2:1 near the base of the papilla. We have estimated the proportion of the total surface area of a fenestrated vasa recta occupied by fenestral diaphragms to be 0.057 at 1000 microns from the tip. The total potential conductance (K) of a 200 microns segment of fenestrated vessel at 1000 microns from the tip was calculated to be 0.319 microns 3 s-1 cmH2O-1, giving a hydraulic conductivity (Lp) of 0.030 micron s-1 cmH2O-1. We have also examined the reverse question of the conductance of a single fenestra if all the fluid flux across the vessel wall occurred through the fenestrae and none via the intercellular clefts or water channels; single fenestral conductance was estimated to be 1.94 x 10(-3) microns 3 s-1 cmH2O-1.

Animals↗
PubMed1996

Surgical treatment of 95 children with 102 intracranial arachnoid cysts.

Our review of 95 children with 102 intracranial arachnoid cysts treated surgically from 1976 to 1996 is presented. These patients are divided into two groups, those initially treated from 1976 to 1986 and those treated from 1987 to May 1996, to see whether any improvement in outcome had occurred. There were 31 patients (20 males/11 females) with 34 cysts treated from 1976 to 1986 and 64 patients (45 males/19 females) with 68 cysts treated from 1987 to 1996. The mean age at presentation for all cases was 4.9 years (range from 3 days to (7.8 years). The most common cyst location was the middle fossa. Treatment options for the management of intracranial arachnoid cysts include fenestration or shunting. We consider the avoidance of a shunt as a primary goal in the management of these patients. Accordingly, 82 (80%) of the cysts in our series were treated initially by fenestration. Fifty percent of those initially fenestrated from 1976 to 1986 required no further treatment as compared with 60% fenestrated from 1987 to 1996. The success rate of fenestration among those patients without associated hydrocephalus was significantly higher than in those with hydrocephalus; 73% without hydrocephalus required no additional treatment versus 32% with hydrocephalus. Seventeen percent of the patients treated from 1976 to 1986 required a subsequent ventriculoperitoneal shunt as compared with 22% treated from 1987 to 1996. Twenty-nine percent of those patients initially fenestrated from 1976 to 1986 required a subsequent cystoperitoneal shunt as compared with only 12% treated from 1987 to 1996. Although not statistically significant, the second group of patients had a lower rate of reoperation, fewer complications, and a better clinical outcome than the first group. We recommend that in patients without evidence of hydrocephalus, cyst fenestration be considered as the primary procedure, as 73% of the patients in the two series remain shunt free. In those patients with hydrocephalus, we still recommend cyst fenestration, but with a ventriculoperitoneal shunt inserted before fenestration if the hydrocephalus is marked or after fenestration if the hydrocephalus is progressive.

Adolescent↗
PubMedDate not supplied

A physical model for the formation of evaginations: a prospective precursor to the creation of saccular aneurysms.

The actual spatial geometry of separate regions of normal and enlarged fenestrations from the internal elastic lamina of human cerebral arteries have been replicated in sheets of latex rubber from scanning electron microscope (SEM) photomicrographs. Geometrical models which assume a constant diameter for the fenestrations, a constant ligament efficiency for the regions of fenestrations and a uniform array of rows and columns have also been created in sheets of latex rubber. The stress (load per unit of cross-sectional area) and strain (percent elongation) were computed for each of the samples during uniaxial stretching. The elongation of the sample representing the region of enlarged fenestrations increased an average of 47% compared to the similar representation of normal fenestrations, at the same increments of stress. This suggests that regions of enlarged fenestrations would form a bulge, indicative of an evagination of the internal elastic lamina. The model configurations demonstrate very similar stress/strain characteristics to the replications. This finding justified the use of the modelling technique using equivalent ligament efficiencies, to represent the actual spatial geometry. During elongation, the average area of the enlarged fenestrations increased at a rate which was an order of magnitude greater than the normal fenestrations. Since a number of observations associated with the development of intracranial saccular aneurysms can be correlated to a region of enlarged fenestrations, the region of enlarged fenestrations may be a defect in the internal elastic lamina which could play a prominent role in the development of intracranial saccular aneurysms.

Elasticity↗
PubMed1985

Surface densities of diaphragmed fenestrae and transendothelial channels in different murine capillary beds.

Fenestrated capillaries are provided with two types of regular discontinuities: fenestrae with negatively charged diaphragms, and transendothelial channels fitted with two diaphragms, of which the luminal one is uncharged. These structures are expected to affect macromolecular exchanges on the basis of size and charge. We have detected variations in the surface density of fenestrations and transendothelial channels (normalized to 1 micron of capillary endothelial profiles in sections) in selected areas of different murine organs, i.e., kidney cortex, duodenal mucosa, and exocrine pancreas. The survey was limited to endothelial segments less than or equal to 400 nm thick, and covered a total length of endothelial profiles of 1180 microns, 730 microns, and 1189 microns in the exocrine pancreas, intestinal mucosa, and kidney cortex, respectively. At least 1000 transendothelial openings were recorded by scoring for easily recognizable fenestrations, transendothelial channels, and unknowns, the latter representing either of the above in grazing sections. The linear density of all transendothelial openings taken together was found to vary among the different capillary beds (kidney cortex greater than intestinal mucosa greater than exocrine pancreas). This same sequence was observed for the linear densities of fenestrations, transendothelial channels, and unknowns considered individually. The values obtained were as follows: kidney cortex, 1.35 fenestrations per micron, 0.25 transendothelial channels per micron, 0.52 unknowns per micron; intestinal mucosa, 0.92 fenestrations per micron, 0.10 transendothelial channels per micron, 0.38 unknowns per micron; exocrine pancreas, 0.58 fenestrations per micron, 0.04 transendothelial channels per micron, 0.27 unknowns per micron. The differences in distribution of transendothelial openings among fenestrated capillary beds probably reflect capillary permeability modulations connected with the functions of these various organs.

Animals↗