Intrafamilial variability of the ocular phenotype in a Polish family with a missense mutation (A63D) in the Norrie disease gene.

PURPOSE: To describe the phenotypic variability in a Polish Norrie disease (ND) family associated with the missense mutation A63D. METHODS: A patient with spared vision from a Polish ND family underwent detailed ophthalmological examinations including slit-lamp biomicroscopy, ultrasound (USG), angiography, Goldmann kinetic visual field, and electroretinography (ERG). Mutation screening was carried out using the single-strand conformation polymorphism (SSCP) technique and subsequent DNA sequencing of the coding part of the ND gene. RESULTS: A mutation was detected (exon 3, A63D) in a large Polish family with 12 affected males, all but one presenting with classical ND symptoms. In one male, partially preserved vision was observed up to 40 years of age (distance acuity of the right eye 1/50 and left eye 2/50). Slit-lamp examination revealed remnants of a persistent primary vitreous and hyaloid artery. Upon angiography, the retina was vascularized within the posterior pole but not in the periphery. The ERG revealed pathological changes characteristic for chorioretinal degenerations. CONCLUSION: Within one family, individuals with identical sequence alterations in the ND gene can show remarkable phenotypic variability of the ocular symptoms. These findings indicate the involvement of additional factors (epigenetic or genetic) in ocular pathogenesis of ND.

[Diagnosis and treatment of eye infections caused by the canine ascaris larva Toxocara canis]. / Diagnostyka i leczenie postaci ocznej infekcji larwa glisty psiej toxocara canis.

UNLABELLED: In the years 1990-1993 the authors diagnosed and treated 48 children on account of uveitis probably caused by Toxocara canis. This etiology was established in 43 cases based on the characteristic clinical picture and presence of antibodies as determined by the ELISA test for Toxocara in serum, anterior chamber fluid and vitreous. Diagnostic punction of anterior chamber was done in 30 cases (in 18 titres were positive, in 7 higher than in serum), in 3 the level of antibodies were determined in vitreous. In 30 patients Hetrazan, in 3 Hetrazan and Mintezol was applied; in 31 together with Encorton. SURGICAL TREATMENT: vitrectomy and lensectomy were done in 9 children. Improvement of visual acuity was achieved in 41.9% of cases, deterioration in 9.3%. In 33 cases the active signs of vitritis recovered after 2-6 months of treatment, recurrence was observed in 4. An increase of serum titres was found in 10 children in early period after treatment, in 15 they decreased after 6-18 months and in 18 treatment had no influence on the titres level. A relationship was found between the level of titres in anterior chamber and vitreous and the activity and duration of intraocular inflammation.

[Ocular problems in children with homocystinuria]. / Problemy okulistyczne u dzieci z homocystynuria.

Homocystinuria was diagnosed in 12 patients, aged 3-12 years. Myopia, ranged from -5.0 D to -20.0 D, and bilateral subluxation of lens were found in all children. In 8 eyes during follow-up luxation of lens was observed in 8 eyes, in 5 complicated by acute glaucoma. Surgical treatment, mostly pars plana lensectomia, was applied in 20 eyes. Normalisation of the intraocular pressure was achieved after surgery in 4 cases and improvement of visual acuity in 16 eyes. In 1 case of a boy after cerebral vessels infarct the intraocular pressure remained elevated and optic nerve atrophy developed. In 3 cases anterior scleral staphyloma was found.

[Results of vitrectomy in children]. / Wyniki witrektomii u dzieci.

Presented are the results of vitrectomy in children operated in the Ophthalmological Department of Children Health Centre. The procedure was preformed in 110 eyes including 32 vitrectomies and 78 vitrectomies connected with lensectomy. Operated were eyes with chronical uveitis of various etiology, with posttraumatic changes, after vitreal haemorrhages in Eales' disease, in persistent vitreal artery cases. Improvement of the visual acuity was achieved in 68 cases (61.8 p.c.), deterioration was observed in 28 (25.5 p.c.); the visual acuity did not change in 14 cases (12.7 p.c.). Retinal detachment was the most frequent complication--38 cases (34.5 p.c.); from this number 10 cases (9 p.c.) improved after a repeated operation.

[Metabolic cataract among the children from the Children's Health Center]. / Zacmy metaboliczne w materiale Centrum Zdrowia Dziecka.

The investigations concerned 385 children with a congenital cataract. It was not possible to establish the causes of the condition in 46.5 p.c. of examined children. The set of examinations which was used was sufficient for an explicit determination of the cause of the metabolic part of congenital cataracts. In galactosaemia opacification of the lens appeared in 64 p.c. of cases, in hypofunction of the parathyroids in 17.8 p.c., in hypoglycaemia in 6.6 p.c., in Lowe's syndrome in 100 p.c. of cases.

Reliability of the measurement of intrarenal haemodynamics in the dog, as determined by the radioactive microsphere technique.

In the anaesthetized dog total renal blood flow (RBF) and its intrarenal distribution were investigated by the radioactive microsphere technique under control conditions and after various experimental interventions. (i) In five control series performed within the last four years, there was a small but significant scatter in total RBF, due entirely to changes in inner cortical (IC) perfusion, while outer cortical (OC) perfusion proved to be constant. (ii) Repeated measurements in the same dog, performed after 1 h interval revealed constancy of total RBF with some inward shifting in cortical perfusion. (iii) Surgical intervention or manipulation of the kidney did not alter total RBF but led to an increase in IC, compensated by a decrease in OC perfusion (iv) The possible role of local intrarenal hormones (angiotensin and prostaglandin) in the above changes is discussed.

Prostaglandin-dependent changes in renal haemodynamics and excretory patterns before and after release of 24 hours bilateral ureteral ligation.

In the anesthetized dog during and 1 hr after release of 24 h bilateral ureteral ligation (BUL) renal blood flow (RBF) decreased to 44 and 51%, respectively, as compared with normal controls. After release there was a marked increase in sodium and water excretion, so-called postobstructive diuresis (POD), in spite of a considerably reduced glomerular filtration rate (GFR). Radioactive microspheres revealed a proportionate decrease of perfusion in all cortical layers before, and inward shifting after release of the ligature. Inhibition of intrarenal prostaglandin (PF) synthesis by indomethacin (IM) before release of BUL led to a further pronounced decrease in RBF both in the pre- and postrelease phases, characterized by a proportionate decrease of perfusion in all cortical layers. Fractional excretion of sodium and water remained moderately increased in spite of a very pronounced hypofiltration. It is assumed that, in contrast to PG-dependent changes in renal haemodynamics due to BUL, enhanced sodium and water excretion (POD) are due to a PG-independent mechanism, most probably to some natriuretic substance produced and/or accumulated during 24 h complete retention.

Intrarenal haemodynamics in postobstructive diuresis in the dog.

Intrarenal haemodynamics were investigated in the dog prior to and after relief of 24 hr bilateral ureteral ligation (BUL), by the radioactive microsphere technique. Prior to release of 24 hr BUL there was an about 50% reduction in total blood flow (RBR), with a nearly proprotional decrease in the perfusion of the four cortical layers. Following release of the obstruction, total renal and outer cortical (zones 1 and 2) blood flow remained diminished, while perfusion of the inner (juxtamedullary) layers (zones 3 and 4) increased as compared to its prerelease values and equalled controls. Glomerular filtration rate (GFR) amounted to about 27% of controls in the postrelease phase. A marked increase in absolute and fractional sodium water excretion was observed after release of 24 hr BUL, as contrasted to normal controls and dogs after 24 hr unilateral ureteral ligation (UUL). This state, designated as postopstructive diuresis, might be explained by redistribution of intrarenal blood flow towards the juxtamedullary zones, and by a powerful natriuretic substance accumulated during complete obstruction.

Intrarenal haemodynamics in uranyl nitrate-induced acute renal failure.

Intrarenal haemodynamics were investigated in the dog at various intervals after the iv. injection of 10 mg/kg uranyl nitrate (UN). Renal blood flow (RBF), as determined by measuring the renal venous effluent and by radioactive microspheres, decreased by about 23% at 6 hr after UN administration, as compared to normal controls, then rose and reached controls at 24 to 48 hr; subsequently, RBF increased and surpassed controls by about 36% at 96 hr. Thus, the early phase (6 hr) and the late phase (96 hr) of uranyl nitrate-induced acute renal failure (UNARF) were characterized by an increase and by a decrease, respectively, in overall renal vascular resistance. Glomerular filtration rate (GFR) diminished to about 37% of controls at 6 hr, with no change in urinary output (V). In the following hours, however, GFR and V fell quickly and reached practically zero at 12 to 24 hr. Approximate calculations revealed a predominantly preglomerular vasoconstriction in the early phase and post-glomerular vasodilatation in the late phase. Radioactive microspheres showed a nearly proportionate decrease in perfusion of all cortical layers in the early phase (6 hr); in the late phase (96 hr), however, blood flow to the outermost layer remained unaltered, while perfusion of the inner cortical and juxtamedullary layers increased significantly.

Functional changes in compensatory hypertrophy of the canine kidney after uninephrectomy.

Kidney weight and renal functional parameters were investigated in dogs 7 to 68 days after uninephrectomy. Average enlargement of the remaining kidney amounted to 35.1%. Renal blood flow (RBF) and glomerular filtration rate (GFR) calculated per 100 g actual kidney weight were identical in the non-hypertrophied controls and in the hypertrophied kidneys, i.e. structural and functional changes were strictly proportional. Calculation of mean nephron parameters (MNRBF and MNGFR) revealed an increase of about 43% in the hypertrophied kidneys, with an appropriate decrease in nephronal vascular resistance. The hypertrophied kidney showed an enhanced responsiveness to mannitol; increased MNRBF under stop flow conditions was due to a pronounced dilatation of the postglomerular vessels. There was no difference between control and hypertrophied kidneys in cortical zonal blood flow, as investigated by the labelled microsphere technique. Increase in parallel-connected cortical resistances towards the inner (juxtamedullary) zones was pronounced.

Renal haemodynamics prior to and after release of 24 hr unilateral ureteral ligation in the dog.

Renal functional parameters were investigated prior to and following release of 24 hr unilateral ureteral ligation (UUL). In the obstructd kidney renal blood flow (RBF) and glomerular filtration rate (GFR) decreased to about 50% and 14%, respectively, as compared to normal controls. Relief of the obstruction did not cause any change in renal haemodynamic parameters in the ligated kidney. Urine flow rate and urine osmolality in the previously obstructed kidney were decreased, the excreted fraction of filtered sodium increased as compared to the undisturbed kidney. The excretory lesion of the obstructed kidney is due to arteriolar, presumably preglomerular, vasoconstriction. Radioactive microspheres revealed that the decrease of RBF in the obstructed kidney was caused by diminished perfusion of the outer cortical zones, while blood flow to the inner cortical zones was unaltered. Fractional flow to the outer cortex was decreased, that to the inner cortex increased as compared with normal controls. In the undisturbed kidney there was a shifting of flow from the outer towards the inner cortex, while total blood flow remained unaltered.

Pathomechanism of postischaemic renal failure in the dog induced by temporary occlusion of the renal artery.

Intrarenal haemodynamics were investigated in previously uninephrectomized dogs, immediately after release and on the third day following two hours clamping of the renal artery. Postischaemic renal failure (PIRF) was considered moderate or severe, if three days after clamping plasma NPN values were under or over 150 mg/dl, respectively. Renal blood flow (RBF) as determined by measuring the renal venous effluent and by radioactive microspheres did not differ significantly from controls either immediately after release, or three days following arterial occlusion. Glomerular filtration rate (GFR) was, however, severely depressed in all postischaemic kidneys. An increase in preglomerular and a decrease in postglomerular resistance was assumed, resulting in unaltered total vascular resistance and a sharp drop in glomerular capillary pressure. Radioactive microspheres revealed a shifting of intrarenal blood flow from the superficial cortex towards the deeper (juxtamedullary) cortical layers. Fractional flow to the outer cortex was decreased, that to the inner cortex increased, as compared with uninephrectomized controls.

Quantitative aspects of autoregulation in the canine kidney.

Autoregulatory changes in series connected vascular resistances were studied in the normal canine kidney. Two sets of observations were made: a) ureter pressure was increased by ureteral obstruction and b) arterial pressure was decreased by aortic clamping. It was assumed that in both experimental panels the decrement in intrarenal resistance is solely due to dilatation of the preglomerular vessels. Proximal tubular pressure is thought to equal deep venous (wedged) pressure under free flow and ureteral pressure under stop flow conditions. Calculation of the glomerular filtration coefficient yielded the same value in both sets of observations: k similar to 2 ml/min/100 g per 1 mm Hg effective filtration pressure. Glomerular capillary pressure rises steeply and roughly parallels arterial pressue below the autoregulatory range (about 40-80 mm Hg), whereas in the autoregulatory range (about 90-150 mm Hg) its value is stabilized at 74 plus or minus 1 (S.E.)mm Hg. Afferent resistance is negligible in the hypotensive range and increases progressively in the normotensive range. Changes in efferent and venular resistance are insignificant in the whole pressure range considered, i.e. 40 to 150 mm Hg.

Autoregulation of renal circulation in mannitol-loaded dogs.

Renal haemodynamics and autoregulatory behaviour of the renal vessels have been investigated in mannitol-loaded dogs both for free-flow and for stop-flow conditions. Arterial pressure has been decreased by aortic clamping. For free-flow conditions: (i) relative constancy of RBF and GFR are well preserved in the entire autoregulatory pressure range, i.e., over 80 mm Hg arterial pressure; (ii) decreased GFR is due to enchanced intratubular pressure; (iii) autoregulation is connected with a sharp rise in afferent resistance, accompained by a passive decrease in efferent resistance. For stop-flow conditions: (i) enchancement of total vascular resistance is due to an increase in the passive resistance of the postglomerular vessels; (ii) afferent resistance drops to minimal values as casused by the relaxation of the corresponding arterioles; (iii) autoregualation is abolished: pressure-flow relations are linear over the entire arterial pressure range examined.