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Biomedical subjects

S Krag

Publications and source records attributed to S Krag.

At least 19 recordsLinked to original sources
PubMed2005

The use of transgenic animals in the study of diabetic kidney disease.

Diabetic nephropathy is one of the most common diseases leading to fibrosis and end-stage renal disease (ESRD) world wide. Under normal conditions, a delicate equilibrium exists between synthesis, composition, and removal of extracellular matrix (ECM). If this is disturbed, ECM accumulation and fibrosis may result. The fragile balance between synthesis and removal of ECM is crucial for the prognosis of glomerular as well as interstitial pathological processes. Some features may favor ECM accumulation and progression to ESRD (dialysis and transplantation), whereas other elements may favor ECM removal and resolution (recovery). Pathogenetic mechanisms and the cellular sources of ECM in the glomerular basement membrane as well as in the tubulointerstitial space are still under investigation. Among several growth factors, transforming growth factor beta1 (TGF-beta1) plays a major role. We consider the use of living animals necessary for our understanding of the complex biological processes that occur during the development of ESRD. The present review will discuss the glomerular as well as interstitial accumulation of ECM and the use of transgenic animals in studying the pathogenetic mechanisms with special emphasis on diabetic kidney disease and TGF-beta1.

Animals↗
PubMed2000

TGF-beta1-induced glomerular disorder is associated with impaired concentrating ability mimicking primary glomerular disease with renal failure in man.

Transforming growth factor-beta1 (TGF-beta1) may play a major role in the pathogenesis of glomerulopathy and end-stage renal disease (ESRD). The aim of this study was to explore the functional consequences of localized overproduction of TGF-beta1 in relation to glomerular ultrastructure and the composition of the extracellular matrix (ECM) in the inner medulla. We used a transgenic mouse with overexpression of TGF-beta1 targeted to the juxtaglomerular apparatus (JGA) by the Ren-1c promoter. The kidney function was evaluated using urine production and metabolite excretion over a 24-hour period, glomerular filtration rate (GFR), and concentrating ability. The glomerular structure was analyzed in terms of volume, ie, the volume of the mesangium per glomerulus (Vv[mes/glom]) and the volume of the matrix per glomerulus (Vv[matrix/glom]), ECM per glomerulus, the area of the filtration surface, and the thickness of the peripheral basement membrane (PBM). Immunohistochemistry or in situ hybridization was used to examine the expression of aquaporin 2 (AQP2), plasminogen activator inhibitor-1 (PAI-1), and the composition of the ECM in the inner medulla. The mice exhibited polyuria, reduced concentrating ability, decreased GFR, and albuminuria paralleled by increased glomerular volume, with increased volume of ECM, decreased filtration surface, and thickening of the PBM being detectable between 1 and 2 months of age. The deposition of glomerular ECM was accompanied by increased levels of PAI-1. As estimated by excretion of Clara cell protein-1 (CC16) and lysozyme, tubular damage occurred only in older mice. Collagen Type I was deposited in the inner medulla in the presence of normal AQP2-expression in the collecting ducts. This study reached the following conclusions: (a) TGF-beta1 reduces the GFR and the glomerular filtration surface, (b) TGF-beta1 induces albuminuria in association with widening of the PBM, (c) expansion of the mesangial volume seems to precede the widening of the PBM, (d) TGF-beta1-induced accumulation of glomerular ECM is partly explained by increased PAI-1 expression, (e) Decreased concentrating ability and polyuria caused by accumulation of ECM in the inner medulla may be an early marker of glomerular diseases associated with increased expression of TGF-beta1 in man.

Aldosterone↗
PubMed2000

High plasma concentrations of prorenin in a transgenic animal model of nephropathy with overexpression of transforming growth factor-beta1 in the kidneys.

1. Plasma concentrations of prorenin were determined in a transgenic animal model of nephropathy induced by overexpression of transforming growth factor (TGF)-beta1 in the juxtaglomerular apparatus. 2. In both female and male mice, plasma concentrations of prorenin were higher in transgenic than in non-transgenic animals. In sexually mature mice, plasma prorenin concentrations were higher in males than in females in both transgenic and non-transgenic animals in accordance with a sexual dimorphism of the plasma concentration of prorenin. 3. The results indicate that TGF-beta1-like androgens increase prorenin secretion in the kidneys and may explain the increased plasma prorenin concentrations in patients with diabetic nephropathy.

Aging↗
PubMed1999

Circadian intraocular pressure variation with beta-blockers.

PURPOSE: To investigate circadian intraocular pressure variation in patients treated with topical beta-blockers as monotherapy. METHOD: Circadian IOP curves were measured on 25 patients (47 eyes) treated with topical beta-blockers. IOP was recorded 4 times during the day and twice at night. All IOP measurements were taken using a non-contact tonometer. RESULTS: IOP at night was significantly higher than IOP during the day. Thirty-four percent exhibited an increase in IOP of more than 5 mmHg at night, and 15% exhibited an increase of 10-18 mmHg at night. The median range of circadian IOP variation was 7 mmHg. Determined separately by day, the range of IOP variation was 4 mmHg. CONCLUSION: Patients treated with beta-blockers as monotherapy may experience greater variations in IOP than can be detected by conventional daytime IOP measurements.

Administration, Topical↗
PubMed1998

Thermal and mechanical stability of the lens capsule.

PURPOSE: Several procedures in cataract surgery carry the risk of high temperature increases in the capsular bag. The present study was undertaken to determine the shrinkage temperature of the human lens capsule and to investigate the effect of temperature on the mechanical behavior of the lens capsule. METHOD: Thermal-shrinkage characteristics of the lens capsule were determined during gradual heating of circular specimens (2 mm in diameter) prepared from anterior lens capsules from 25 human donors, ranging in age from 20 to 98 years. Uniaxial mechanical testing was carried out at 22 degrees C, 36 degrees C and 61 degrees C on ring-shaped test specimens prepared from anterior lens capsules from 5- to 6-month-old pigs. RESULTS: The mean shrinkage temperature (Ts) for the human lens capsule was 51.5 degrees C (range 49.3-54.3) and the mean shrinkage area in percent of the original area (AST) was 49% (36-66). Ts was significantly associated with the age of the donors and decreased 0.1 degree C per year until age 65 after which Ts was found to increase. AST showed no association with age. The mechanical effect of temperatures below the shrinkage temperature was modest. The capsule became slightly more extensible with increasing temperature. The effect of temperatures above the shrinkage temperature was an increased ultimate strain, a reduced ultimate stiffness and a slightly reduced ultimate stress. CONCLUSION: Thermal stability of the human lens capsule (type IV collagen) seems to be considerably lower than that of fibrous connective tissue (type I collagen). A potential risk of capsular shrinking has to be taken into account when the capsule is exposed to thermal stress during cataract surgery.

Adult↗
PubMed1998

Effect of freezing on lens capsule mechanical behavior.

Postmortem storage of lens capsules by freezing was found to increase capsular thickness slightly (5%). The effect on mechanical properties was minor. Ultimate tensile strength and ultimate stiffness were not changed by freezing. Ultimate strain was slightly increased (2%) and the elastic modulus calculated at 40% strain was decreased (20%). Frozen capsules were found to relax to a slightly lower value than fresh ones (2%). The results show that freezing tends to soften the tissue, possibly due to an increased hydration. In spite of this effect, which has to be kept in mind, postmortem freezing seems to be an acceptable storage method when collecting tissue for biomechanical research.

Animals↗
PubMed1997

One-handed phacoemulsification with low settings.

We describe a technique in which one-handed phacoemulsification with low aspiration flow and vacuum is performed with a peristaltic pump machine. With this technique, ultrasonic energy can be used for nucleus segmentation without the need for a second instrument. Measurements in cadaver eyes and clinical experience showed the technique to be simple, effective, and safe.

Humans↗
PubMed1997

Biomechanical characteristics of the human anterior lens capsule in relation to age.

PURPOSE: The purpose of the study was to investigate the influence of age on the biomechanical properties of the human anterior lens capsule. METHODS: The material comprised 67 lens capsules obtained from human donors ranging in age from 7 months to 98 years. Test specimens were prepared from the anterior lens capsule as tissue rings by means of excimer laser technique using a metal ring (mask) to shape the laser output (outer diameter = 3.2 mm, width = 100 microns). Capsular thickness was measured under microscope as the difference in focus between microspherules placed on the outer and inner surfaces of the capsule. The rings were slipped over two pins connected to a motorized micropositioner and a force transducer, respectively, and stretched at constant speed until rupture, with continuous recording of load and elongation. RESULTS: Capsular thickness was associated significantly with age of the donors and increased gradually (1.2% per year) until age 75, after which a slight decrease was observed. The elastic response curves showed a high degree of nonlinearity and were influenced markedly by age. Ultimate strain decreased 0.5% per year (range, 108% to 40%). Ultimate tensile strength decreased 1% per year (range, 17.5 N/mm2 to 1.5 N/mm2), and ultimate elastic stiffness (tangent modulus) decreased 0.9% per year (range, 44.8 N/mm2 to 4.4 N/mm2), whereas elastic stiffness corresponding to a specific strain level (30%) increased until age 35, after which a slight decrease was observed. CONCLUSIONS: Aging of the human anterior lens capsule is associated with a progressive loss of mechanical strength. The young capsule is strong, tough, and highly extensible, whereas the older, thicker capsule is less extensible and much more brittle, and it has a markedly reduced breaking strength.

Adolescent↗
PubMed1996

Biomechanical measurements of the porcine lens capsule.

Biomechanical measurements were carried out on capsular rings prepared from the anterior lens capsule by means of photoablation technique (excimer laser). The outer diameter of the metal ring used to shape the laser output was 3.2 mm and the width (wall thickness) was 100 microns. Thickness of the lens capsule (depth of the tissue ring) was measured with a microscope coupled to an electronic length gauge as the difference in focus between latex spherules placed on the upper and lower surfaces of the capsular rings. For mechanical measurements the capsular rings were mounted around two pins connected to a motorized micropositioner and a force transducer, respectively, and stretched at a constant rate until rupture. Estimates of the precision of the test method were based on differences between measurements of paired eyes from 15 6-month-old pigs. Thickness of the lens capsules was 59 microns (50-66) (median, range). Repeatability of a single measurement was +/- 2 microns for a probability of 95%. Maximum strain as a percentage of the initial length was 78% [68-89] with a repeatability of +/- 6%. Maximum stiffness (elastic modulus) was 23.0 N mm-2 [10.0-31.5] with a repeatability of +/- 4.3 N mm-2, and maximum stress was 4.4 N mm-2 [2.8-7.7] with a repeatability of ./:1.27 N mm-2. There were no significant differences between paired eyes, but a significant variance component between individuals. The experimental set-up described in this paper seems reliable and useful for biomechanical measurements of the lens capsule, in the physiological as well as the surgical function range.

Animals↗
PubMed1994

Biomechanical aspects of the anterior capsulotomy.

We used the finite element method to evaluate different capsulotomy techniques. Nucleus expression was simulated in a computer model to visualize stress distribution in the anterior capsule. The finite element model demonstrated that the capsulorhexis edge is strong because of low and uniform stress distribution in the tissue. With can-opener and envelope capsulotomies, areas of high stress accumulation create the risk of tears during surgery.

Cataract Extraction↗
PubMed1993

Strength of the lens capsule during hydroexpression of the nucleus.

In planned extracapsular cataract extraction, hydroexpression of the nucleus has been introduced to facilitate nucleus delivery when performing capsulorhexis. The hydroexpression technique induces a fluid pressure in the capsular bag, which may rupture the posterior capsule. In a human cadaver eye model the pressure at the capsule's rupture point was determined in 16 cadaver eyes and compared to the fluid pressure in the capsular bag during hydroexpression of the nucleus in 32 eyes. The posterior capsule was able to withstand a pressure of 59 +/- 10 mm Hg (mean +/- SD) without rupturing. During hydroexpression of the nucleus the pressure was less than 12 mm Hg (3 mm Hg to 12 mm Hg) when the diameter of the capsulorhexis opening was 5.5 mm or more (measurement in the anterior chamber). Thus hydroexpression of the nucleus seems to be a safe technique when the diameter of the capsulorhexis is 5.5 mm or more.

Adult↗
PubMed1993

Hydroexpression and viscoexpression of the nucleus through a continuous circular capsulorhexis.

When a continuous circular capsulorhexis (CCC) is performed, conventional nucleus expression may be impossible because of the strong capsular rim. Hydroexpression of the nucleus seems to overcome the problem if the capsulorhexis opening is large enough. Because a viscoelastic material may be an even more gentle tool than balanced salt solution (BSS), hydroexpression and viscoexpression were evaluated in 16 pairs of human cadaver eyes. The diameter of the capsulorhexis opening ranged from 4 mm to 6 mm; it was the same in each pair of eyes. Hydroexpression was performed in one eye using BSS and viscoexpression was performed in the fellow eye using sodium hyaluronate (Healon Yellow). The fluid pressure in the capsular bag was measured during both procedures. The pressure was higher during hydroexpression than during viscoexpression. The pressure difference between fellow eyes ranged from 0 to 32 mm Hg and was most marked when the CCC opening was small. This correlation was significant (P < .05). Viscoexpression may enhance the safety in cases with a small CCC opening or in those that are otherwise difficult.

Adult↗
PubMed1992

Excimer laser treatment of pterygium.

Primary experience with the use of excimer laser in pterygium therapy is presented. Twenty-two pterygia (11 primary and 11 recurrent) were surgically removed using the bare-sclera technique followed by excimer laser ablation to smooth the corneal surface. As recurrence was observed in 20 eyes (91%) during the first year, supplementary excimer laser treatment of a pterygium does not seem to reduce the recurrence rate. The high recurrence rate in this series may to a certain extent reflect the surgical technique used (bare-sclera).

Adult↗
PubMed1991

[Clinical experience with a bifocal intraocular lens].

At cataract operation, the opaque cataractous lens is removed from the eye and is replaced by an artificial intraocular lens. Employing modern technology, development of a bifocal intraocular lens based on diffraction optic has now proved possible. The lens contains correction for distant vision and also for close work so that the patients may be independent of glasses. Sixty-two eyes with bifocal intraocular lenses were followed-up for approximately one year. The results are promising. 84% of the patients could read small print without corrective glasses. The accuracy by which the intraocular lens power can be calculated preoperatively and the surgical control of astigmatism in the eye are of decisive importance for the success of the lens.

Adult↗
PubMed1991

Stretching capacity of capsulorhexis and nucleus delivery.

The stretching capacity of the continuous circular capsulorhexis was studied in 30 human cadaver eyes. The capsulorhexis was found to have a remarkable stretching capacity, allowing safe nucleus delivery in planned extracapsular cataract extraction using hydroexpression. The difficulties encountered when trying to deliver the nucleus by external pressure to the sclera are discussed.

Adult↗
PubMed1991

Secondary IOL power calculation. A comparison of an optical and a biometric method.

In 40 aphakic eyes undergoing secondary IOL implantation, the axial length was calculated optically as well as measured by ultrasound, and the two methods of axial length determination were compared to evaluate the accuracy in the calculation of secondary IOL power. The mean refractive prediction error (+/- SD) was 0.18 diopters (+/- 0.96) and -0.37 diopters (+/- 0.83) using the optical and the biometric method, respectively. The difference in mean value was significant, whereas the variation around the mean value was not found to be significantly different between the two methods. A calculated axial length may offer a valuable alternative to biometry in the aphakic eye, increasing the accuracy of secondary IOL power calculation.

Adolescent↗
PubMed1990

New multifocal intraocular lens design.

The first clinical experience with a new diffractive multifocal intraocular lens implanted in 55 eyes of 53 patients is reported. Excluding four patients with preoperative senile macular degeneration, the best corrected visual acuity was 20/40 or better and the near vision without any add to the best distance correction was J2 or better in all cases three, six, and 12 months postoperatively.

Cataract Extraction↗