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A P Evan

Publications and source records attributed to A P Evan.

At least 19 recordsLinked to original sources

Renal crystal deposits and histopathology in patients with cystine stones.

We have biopsied the papillae of patients who have cystine stones asking if this stone type is associated with specific tissue changes. We studied seven cystine stone formers (SF) treated with percutaneous nephrolithotomy using digital video imaging of renal papillae for mapping and obtained papillary biopsies. Biopsies were analyzed by routine light and electron microscopy, infrared spectroscopy, electron diffraction, and micro-CT. Many ducts of Bellini (BD) had an enlarged ostium, and all such were plugged with cystine crystals, and had injured or absent lining cells with a surrounding interstitium that was inflamed to fibrotic. Crystal plugs often projected into the urinary space. Many inner medullary collecting ducts (IMCD) were dilated with or without crystal plugging. Apatite crystals were identified in the lumens of loops of Henle and IMCD. Abundance of interstitial Randall's plaque was equivalent in amount to that of non-SF. In the cortex, glomerular obsolescence and interstitial fibrosis exceeded normal. Cystine crystallizes in BD with the probable result of cell injury, interstitial reaction, nephron obstruction, and with the potential of inducing cortical change and loss of IMCD tubular fluid pH regulation, resulting in apatite formation. The pattern of IMCD dilation, and loss of medullary structures is most compatible with such obstruction, either from BD lumen plugs or urinary tract obstruction from stones themselves.

Adolescent↗

Strategies for improved shock wave lithotripsy.

Research in lithotripsy that started with the effort to characterize acute shock wave damage to the kidney has led to advances on several fronts, including discovery of strategies that have improved clinical treatment. It is appreciated now that shock wave trauma is primarily a vascular lesion, that injury is dose dependent, and that hemorrhage can be severe and can lead to a permanent loss of functional renal mass. Studies of the renal functional response to lithotripsy have shown that shock wave treatment triggers vasoconstriction in the kidney. This finding has been turned to advantage, and it is now known that when treatment is begun using low amplitude pulses, subsequent high amplitude shock waves are far less damaging. Thus, when shock waves are delivered judiciously, treatment can have a protective effect. The finding that cavitation is a key mechanism in vessel rupture has led to the development of novel experimental methods of shock wave delivery that can suppress bubble expansion and minimize tissue damage. Progress has also been made in understanding the physical mechanisms involved in stone comminution, and it is seen that the forces generated by cavitation, shear stress and circumferential squeezing act synergistically to fragment stones. Recent work suggests that a broad focal zone may be an advantage, allowing stones to be broken with lower amplitude pulses. Cavitation has been shown to play a critical role in reducing stone fragments to a size that can be voided. Cavitation is also the factor that limits the rate at which treatment can be performed, as stones break significantly better at slow rate than at fast ratean observation from basic research that is now appreciated in clinical practice. The current environment in lithotripsy research is encouraging. There is great interest in developing new technology, and in finding ways to improve how lithotripsy is performed.

Animals↗

Sequential analysis of kidney stone formation in the Aprt knockout mouse.

BACKGROUND: We have previously shown that, as in human adenine phosphoribosyltransferase (APRT) deficiency, Aprt knockout mice form 2,8-dihydroxyadenine (DHA) renal stones. The disease develops earlier and is more severe in male than in female mice. To examine the biological bases for these differences, the area occupied by DHA crystals was quantified in kidney sections from male and female mice (strain 129) aged one day to eight months and this parameter was correlated with changes in renal histopathology. Aprt heterozygous and wild-type mice were used as controls. METHODS: Following anesthesia, the left kidney was removed and immediately frozen in dry ice. Unstained cryosections were examined by polarized light to determine total area of birefringent particles. The right kidney was perfused and embedded in plastic, and stained sections were viewed by light microscopy to examine the histopathology and to determine the location of the birefringent particles. A pathological score was assigned to the histological findings. The scores from the right kidney were compared with crystal/particle area in the left kidney, and the data were analyzed using two-way analysis of variance. The chemical composition of the particles was determined by x-ray diffraction analysis. Several stone fragments from the bladder were also examined by scanning electron microscopy (SEM). RESULTS: Crystals were detected in kidney sections from one- to two-day-old Aprt knockout mice. The crystal burden remained low in both sexes throughout the study except in males at the 120- to 240-day period. Furthermore, there was a substantial degree of renal pathology, primarily seen as interstitial fibrosis, in those males with a very high level of stone formation. The crystalline material was identified as 6-amino-2,8(3,9)-purine dione, a tautomeric form of DHA. SEM indicated that the crystals were spherical, with a diameter of 10 to 20 microm. Tissue staining and fixation procedures dramatically reduced the amount of birefringent material in kidney sections. Aprt heterozygotes of both sexes had low levels of crystalline material in the kidneys and no pathology. Birefringent material or pathological changes were not seen in kidneys from wild-type mice. CONCLUSIONS: Both male and female Aprt knockout mice accumulate DHA. However, the area occupied by DHA crystals was significantly greater in 120- to 240-day-old males compared with the females of similar age. Also, substantial renal pathology was detected in kidneys of male mice that had very high levels of stone material.

Adenine↗

Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells.

Calciphylaxis or calcific uremic arteriolopathy (CUA) is a fatal disease in dialysis patients due to calcification of cutaneous blood vessels. The pathogenesis has been attributed to elevated parathyroid hormone (PTH). However, recent studies evaluating vascular calcification in nondialysis patients have found that the smooth muscle cells play an active role, including production of the bone matrix protein osteopontin. To examine the involvement of various clinical parameters and smooth muscle cells of CUA, we performed a case-control analysis comparing 10 CUA patients with our current dialysis patients. Available histologic sections were immunostained for osteopontin, markers of smooth muscle cells, endothelial cells, and macrophages. Compared with our current dialysis population, patients with CUA were more likely to be obese, white, and female (P < 0.02). Comparison of laboratory values found CUA patients with lower serum albumin, greater serum phosphorus, and greater calcium X phosphorus product (P < 0.01). In contrast, there was no difference in the concentration of PTH or calcium between the 2 groups. Immunostaining of calcified blood vessels showed that all calcified vessels stained positive for osteopontin, whereas all the noncalcifed vessels showed no osteopontin localization. Staining for smooth muscle alpha-actin decreased in the medial layer with calcification, with cells appearing to be sloughed off, leading to near occlusion of the vessel lumen. Our case-control study demonstrates that hyperphosphatemia and an elevated calcium X phosphorus product is associated with CUA. Histologic examination suggests that the calcification is associated with increased expression of osteopontin by smooth muscle cells.

Adult↗

Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine nephrolithiasis.

BACKGROUND: We have developed a knockout mouse model for adenine phosphoribosyltransferase (APRT) deficiency, a condition that often leads to 2,8-dihydroxyadenine (DHA) nephrolithiasis in humans. Aprt knockout male mice develop severe renal damage by three months of age, but this is strain specific. Renal damage in female mice is less pronounced than in males. The gene level changes that promote renal injury in APRT-deficient mice are not known. METHODS: We used mRNA differential display polymerase chain reaction (DD-PCR) to analyze renal gene expression changes in APRT-deficient male and female mice (strain C3H) compared with age- and sex-matched Aprt heterozygote controls. The differentially amplified bands were reamplified, cloned, sequenced, and queried against the National Center for Biotechnology Information nonredundant databases using the Basic Alignment Search Tool. Relative quantitative reverse transcription-polymerase chain reaction was used to confirm the results of DD-PCR for a selected number of genes in one-, three-, and six-month-old male and female mice. RESULTS: Sixty-three differentially amplified bands were identified, including 21 for known genes, and 8 of these were examined further. In three-month-old APRT-deficient male mice, the expression of C10 was increased tenfold, and there was a fourfold to sevenfold increase in the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), MGP (matrix Gla protein), and lysyl oxidase (LOX). The expression of cholecystokinin-A receptor (CCKAR), imprinted multimembrane-spanning polyspecific transporter-like gene 1 (IMPT-1), and kidney androgen-regulated protein (KAP) was diminished twofold to fourfold, but there was little or no change in the expression of organic anion transporter (OATP). Except for a more than tenfold increase in C10 expression and up to tenfold decrease in KAP expression, APRT-deficient female mice did not show significant changes in gene expression compared with controls. CONCLUSIONS: These findings suggest that (1) there are sex-related differences in gene expression in DHA lithiasis, possibly caused by increased deposition of DHA crystals in male compared with female kidneys; and (2) the expression of certain genes (for example, C10) may simply be an indication of nonspecific cellular stimulation and may not be related to renal injury.

Adenine↗

Studies of renal injury III: lipid-induced nephropathy in type II diabetes.

UNLABELLED: Studies of renal injury III: Lipid-induced nephropathy in type II diabetes. BACKGROUND: Nephrotoxicity from elevated circulating lipids occurs in experimental and clinical situations. We tested the hypothesis that lipid-induced nephropathy causes advanced renal failure in rats with type II diabetes and dyslipidemia. METHODS: First generation (F1) hybrid rats derived from the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) and the LA/NIH-corpulent rat (LA/N-fa) were studied for 41 weeks while being on specific diets. Group 1 (14 rats) ingested 11.5% protein, 47.9% fat, and 40.6% carbohydrate. Group 2 (8 rats) ingested 26.9% protein, 16.7% animal fat, and 56.4% carbohydrate, and group 3 (20 rats) ingested 20.2% protein, 40.4% soy and coconut oil, and 39.4% carbohydrate. RESULTS: Hyperglycemia was more severe in rat groups 1 and 2 than in group 3. In contrast, circulating cholesterol and hydroperoxide levels were highest in group 3, intermediate in group 2, and lowest in group 1. Group 3 had severe renal failure secondary to glomerulosclerosis and tubulointerstitial disease, with striking deposition of the lipid peroxidation stress biomarker 4-hydroxynonenal in glomeruli and renal microvessels. Moreover, in group 3, increased arterial wall thickness also connoted vascular injury. In contrast, the glycoxidation stress biomarkers pentosidine and carboxymethyl-lysine were preferentially localized to renal tubules of hyperglycemic rats in groups 1 and 2 and did not segregate with the most severe renal injury. Glomerular and interstitial fibrosis was accompanied by proportional increases in renal transforming growth factor-beta1 levels, which were threefold higher in the hypercholesterolemic rats of group 3 than in the hyperglycemic rats of group 1. CONCLUSIONS: Acquisition of non-nodular glomerular sclerosis and tubulointerstitial disease is dependent on lipoxidation stress in rats with type II diabetes. On the other hand, in the absence of hypercholesterolemia, prolonged glycoxidation stress does not appear to be uniquely nephrotoxic.

Animals↗

Effect of macroscopic air bubbles on cell lysis by shock wave lithotripsy in vitro.

In studies of cells or stones in vitro, the material to be exposed to shock waves (SWs) is commonly contained in plastic vials. It is difficult to remove all air bubbles from such vials. Because SWs reflect at an air-fluid interface, and because existing gas bubbles can serve as nuclei for cavitation events, we sought to determine in our system whether the inclusion of small, visible bubbles in the specimen vial has an effect on SW-induced cell lysis. We found that even small bubbles led to increased lysis of red blood cells (1- to 3-mm diameter bubbles, 9.8+/-0.5% lysis, n = 7; no bubbles, 4.4+/-0.8%, n = 4), and that the degree of lysis increased with bubble size. Damage could not be reduced by centrifuging the cells to the opposite end of the vial, away from the bubble. B-scan ultrasound imaging of blood in polypropylene pipette bulbs showed that, with each SW, bubbles were recruited from the air interface, mixing throughout the fluid volume, and these appeared to serve as nuclei for increased echogenicity during impact by subsequent SWs; thus, bubble effects in vials could involve the proliferation of cavitation nuclei from existing bubbles. Whereas injury to red blood cells was greatly increased by the presence of bubbles in vials, lytic injury to cultured epithelial cells (LLC-PK1, which have a more complex cytoarchitecture than red blood cells) was not increased by the presence of small air bubbles. This suggests different susceptibility to SW damage for different types of cells. Thus, the presence of even a small air bubble can increase SW-induced cell damage, perhaps by increasing the number of cavitation nuclei throughout the vial, but this effect is variable with cell type.

Epithelial Cells↗

Cell damage by lithotripter shock waves at high pressure to preclude cavitation.

Acoustic cavitation has been implicated as a cause of cell damage by lithotripter shock waves, particularly under in vitro conditions. When red blood cells were exposed to shock waves (from an electrohydraulic lithotripter) while under high hydrostatic pressure (> 80 atm), cell lysis was dramatically reduced over that seen at atmospheric pressure, which is consistent with damage due to acoustic cavitation. However, even at > 120 atm of pressure, lysis was still 97% above that of cells not exposed to shock waves, revealing significant damage that apparently was due to mechanisms other than cavitation. Hydrostatic pressure alone did not cause cell lysis, and shock-wave-dependent damage occurred when the cells were in fluid suspension, or when they were centrifuged to the end of the vial. Shock-wave damage at high pressure increased with increasing shock-wave number, and was seen at 24 and 20 kV, but not at 16 kV. This shock-wave damage at high pressure makes up a noteworthy portion of the total cell injury seen at atmospheric pressure (about 10% at 24 kV), suggesting significant noncavitational injury to cells in vitro. Because cavitation occurs far more readily in vitro than in vivo, the noncavitational damage seen in the present study could represent a substantial portion of cell injury seen in vivo with shock-wave lithotripsy.

Erythrocytes↗

Renal disease potentiates the injury caused by SWL.

PURPOSE: The present study tested the hypothesis that renal disease potentiates the structural/functional changes induced by a clinical dose of shockwaves. MATERIALS AND METHODS: Experimental pyelonephritis was induced in 6- to 8-week-old pigs before treatment with 2,000 shocks at 24 kV. These pigs were divided into two groups according to whether they were infected with a highly virulent (Group 1) or less virulent (Group 2) inoculation of E. coli. All animals were imaged by MR prior to SWL as a means of documenting the extent of pyelonephritis and immediately after SWL to examine the lesion produced by the shockwaves. The glomerular filtration rate (GFR), renal plasma flow (RPF) and para-aminohippurate (PAH) extraction were determined bilaterally on day 30 (Group 1) or day 80 (Group 2). RESULTS: In group 2, urine flow and sodium excretion were reduced by 50% from baseline in the shocked kidneys at both 1 and 4 hours post-SWL. A sustained reduction in RPF through 4 hours post-SWL was noted in the shocked kidneys in Group 1, but RPF was significantly reduced only at the 1-hour determination in Group 2. Large, consistent reductions in GFR were evident at 1 and 4 hours post-SWL in shocked and unshocked kidneys of Group 2 and in the shocked kidneys of Group 1. No significant changes were noted in PAH extraction. CONCLUSION: Acute pyelonephritis exaggerated the effect of a clinical dose of shockwaves on renal hemodynamics. This effect suggests that renal disease may be risk factor for SWL-induced injury.

Animals↗

Metabolic evaluation of stone disease patients: a practical approach.

In the last three decades, minimally invasive techniques have progressed significantly, replacing traditional open surgery as the mainstay of stone disease surgical treatment. The challenge for the next millennium remains medical prevention of calcium urolithiasis, a field where less dramatic progress has been achieved during the same period of time. The purpose of this article is to provide the practicing urologist with current practical guidelines for the assessment and management of calcium urolithiasis patients. The recommendations are based on the latest available information regarding the pathogenesis, medical treatment options, and decision-making rationale when managing these challenging patients. Every urolithiasis patient should undergo a basic evaluation, which is considered the minimal essential diagnostic work-up, in order to rule out obvious, treatable systemic causes of urinary stone disease. All patients should be advised about conservative nonspecific preventive measures. High-risk stone patients should have a more extensive metabolic evaluation based on two 24-hour urine samples. Treatment protocols for each patient are tailored individually according to the metabolic evaluation findings.

Humans↗

Relationship between kidney size, renal injury, and renal impairment induced by shock wave lithotripsy.

The relationship between kidney size and impaired renal function induced by shock-wave lithotripsy (SWL) was examined in 6- and 10-wk-old anesthetized pigs. Each pig received 2000 shock waves, 24 kV, or sham SWL to the lower pole calyx of one kidney. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate extraction was measured 1 h before and 1 and 4 h after SWL. The kidneys were then removed for morphometric analysis. Mean kidney weights were 66.1+/-2.7 g (n = 9) and 103.1+/-3.3 g (n = 8) in the SWL groups, and 60.1+/-2.6 g (n = 9) and 82.3+/-4.0 g (n = 9) in the sham-SWL groups. SWL-induced lesions occupied a significantly greater volume of the small kidneys (6.1+/-1.7 vol % versus 1.5+/-0.2 vol% in the large kidneys). RPF was significantly reduced by SWL in small and large kidneys, but to a significantly greater extent in small kidneys. RPF was also significantly reduced in the contralateral kidneys of both groups, but only at 1 h after SWL. SWL significantly reduced GFR to similar degrees in both kidneys of both groups, regardless of kidney size. Para-aminohippurate extraction was likewise reduced to similar degrees in both groups, but this effect was evident only in the SWL-treated kidneys, and only in the pole to which the shock waves had been applied. The injury induced by SWL affected a larger fraction of small kidneys than large ones, and the renal vasoconstriction induced by SWL was greatest in small kidneys.

Animals↗

In vivo pressure measurements of lithotripsy shock waves in pigs.

Stone comminution and tissue damage in lithotripsy are sensitive to the acoustic field within the kidney, yet knowledge of shock waves in vivo is limited. We have made measurements of lithotripsy shock waves inside pigs with small hydrophones constructed of a 25-microm PVDF membrane stretched over a 21-mm diameter ring. A thin layer of silicone rubber was used to isolate the membrane electrically from pig fluid. A hydrophone was positioned around the pig kidney following a flank incision. Hydrophones were placed on either the anterior (shock wave entrance) or the posterior (shock wave exit) surface of the left kidney. Fluoroscopic imaging was used to orient the hydrophone perpendicular to the shock wave. For each pig, the voltage settings (12-24 kV) and the position of the shock wave focus within the kidney were varied. Waveforms measured within the pig had a shape very similar to those measured in water, but the peak pressure was about 70% of that in water. The focal region in vivo was 82 mm x 20 mm, larger than that measured in vitro (57 mm x 12 mm). It appeared that a combination of nonlinear effects and inhomogeneities in the tissue broadened the focus of the lithotripter. The shock rise time was on the order of 100 ns, substantially more than the rise time measured in water, and was attributed to higher absorption in tissue.

Acoustics↗

Alterations in predicted growth rates of pediatric kidneys treated with extracorporeal shockwave lithotripsy.

The long-term effects of extracorporeal shockwave lithotripsy (SWL) on the kidneys of children treated for renal calculi are unclear. In order to determine if SWL has any negative effects on renal growth rates, we reviewed long-term (mean 9-year) follow-up data on 29 pediatric patients treated between 1984 and 1988 with an unmodified Dornier HM3 lithotripter. Changes in renal length, serum creatinine, and blood pressure were analyzed. Predicted renal growth was calculated using a formula for age-adjusted renal length. Treated kidneys were stratified into normal and abnormal groups based on a history of renal surgery, evidence of recurrent infection, and obvious anatomic abnormalities. Fifty-six upper urinary tract calculi were treated in 34 renal units. Twenty-two renal units (68%) were rendered stone free, and 65% of the patients continue to be stone free. At follow-up, one patient was classified as having new-onset hypertension, and the mean serum creatinine was 0.93 +/- 0.08 mg/dL. Both at treatment and at follow-up, no significant differences were found in the sizes of the treated and untreated kidneys. However, at treatment, the abnormal group of kidneys seemed to be smaller than expected (mean Z -1.30 +/- 1.10), whereas the group of normal kidneys was very close (mean Z 0.18 +/- 0.54) to the predicted length. At follow-up, the deviations between actual and predicted renal length were significantly more negative. Treated kidneys were an additional 1.26 +/- 0.49 SD units below their expected length (p = 0.02). Untreated kidneys were further below normal as well but possibly to a lesser degree (-0.82 +/- 0.36; p <0.04). Although there was a trend for the abnormal group to have smaller kidneys than the normal group, both groups showed the same trend toward an age-adjusted reduction in renal growth at follow-up. The alterations in renal growth patterns observed in this population are unsettling and could be secondary to either treatment effect (SWL) or, more likely, to some underlying pathology intrinsic to pediatric kidneys with urolithiasis. Until further data are available, SWL in the pediatric population should be applied with caution and at the lowest dosage sufficient to achieve stone comminution.

Adolescent↗

Quantitation of shock wave lithotripsy-induced lesion in small and large pig kidneys.

BACKGROUND: Shock wave lithotripsy (SWL) is known to cause injury to the kidney. However, it is not known how lesion size varies as the parameters of SWL treatment (number of shocks, kilovoltage, kidney size) are changed. This hypothesis could not be tested because there was no method available to quantitate accurately the SWL-induced renal lesion. METHODS: A dosage of 2,000 shocks at 24 kV delivered by an unmodified Dornier HM3 lithotripter was applied to the lower pole calyx of the right kidney of small and large pig kidneys. A new method was developed to embed a whole pig kidney for serially sectioning, recording, and digitization. Automated computer color recognition made it possible to discriminate regions of hemorrhage from undamaged tissue and allowed quantitation of the lesion in single sections and in the entire kidney. RESULTS: The new protocol resulted in an accurate identification of sites of hemorrhage and calculations of the volume fraction of injured renal tissue. Lesion size induced in small kidneys was significantly larger than that induced in the larger kidneys (7.6 +/- 1.2% and 1.6 +/- 0.7%, respectively). CONCLUSIONS: Computer segmentation of serially sectioned SWL-treated kidneys has determined that kidney size is a risk factor for enhanced renal injury.

Animals↗

Aldose reductase and IGF-I gene expression in aortic and arteriolar smooth muscle during hypo- and hyperinsulinemic diabetes.

Two genes whose expression is likely to be altered during diabetes mellitus are aldose reductase (AD) and insulin-like growth factor-I (IGF-I). We proposed that gene expression of AD is increased in vascular smooth muscle during diabetes mellitus due to hyperglycemia, while IGF-I expression is decreased in insulin-deficient diabetes and elevated in insulin-resistant diabetes. The mRNA for both was measured in the renal glomerulus, in the vascular smooth muscle of large arterioles from the brain, kidney, and small intestine, and in the aorta of hypoinsulinemic streptozotocin (STZ)-treated rats and hyperinsulinemic Zucker diabetic fatty (ZDF) rats. Quantitative in situ hybridization was used to determine variations in expression. Expression of the AD gene was unchanged in STZ and ZDF rats, except for a decrease of about 50% in glomeruli and renal smooth muscle of STZ diabetic rats. Expression of IGF-I generally decreased in vascular smooth muscle of insulin-depleted STZ diabetic rats, but was normal in hyperinsulinemic ZDF rats. The data indicate that decreased expression of the AD gene is a specific problem in renal vascular smooth muscle and glomeruli in the insulin-depleted STZ model of diabetes. The expression of the IGF-I gene in vascular muscle was decreased in hypoinsulinemic diabetic animals, but did not increase in hyperinsulinemic diabetic rats.

Aldehyde Reductase↗

Quantitation of shock wave cavitation damage in vitro.

Acoustic cavitation damage was quantitated using aluminum foil targets placed within 2-mL polypropylene cryovials. The vials contained various media tested for their potential to support cavitation and were exposed to shock waves using an unmodified Dornier HM3 lithotripter. Foil damage, expressed in terms of a "damage index," was measured from digitized light microscopy images by quantitating the spread of gray-scale histograms. Target sensitivity was demonstrated by reproducible dose-response curves over the range (1-200 shock waves) commonly used for in vitro cell injury studies. Increased shock wave repetition rate reduced the damage index. Untreated foils showed a very low damage index (0.001% +/- 0.001%), while treated foils submerged in Ringer buffer yielded significant damage (2.2% +/- 0.3%, p < 0.001). Degassing the buffer reduced damage to 0.3% +/- 0.1% (p < 0.001). Foils submerged in castor oil showed virtually no damage. These results implicate acoustic cavitation in target damage. Targets immersed in biological fluids (blood and urine) had significantly less damage than in Ringer. The effect of degassing was also evaluated in a red blood cell lysis assay. Hemoglobin release in degassed preparations was significantly reduced compared to nondegassed controls (p < 0.001) and correlated with reduced foil damage index in cell-free vials. These findings characterize a sensitive method to quantitate acoustic cavitation and implicate a role for cavitation in shock wave lithotripsy-induced cell lysis.

Body Fluids↗

Intraoperative sponge 5-fluorouracil to reduce postoperative scarring in strabismus surgery.

INTRODUCTION: To determine whether 5-fluorouracil is effective in reducing scarring after strabismus surgery we used rectus muscle surgery in experimental animals to compare a single intraoperative dose of 5-fluorouracil with mitomycin C and to compare results in similarly treated controls not receiving these antimetabolites. METHODS: Muscle resections were performed on eight rabbits (16 eyes). Four eyes had 5-fluorouracil (50 mg/ml), and four eyes received mitomycin C (0.2 mg/ml), each of which was applied during surgery on an ophthalmic sponge for 5 minutes. Eight eyes served as controls. Six weeks after surgery conjunctival vascularity, muscle length-tension curves, muscle disinsertion force, and the histologic degree of scarring were assessed. RESULTS: The mitomycin C-treated eyes clearly had more conjunctival avascularity and a lower disinsertion force. Both treated groups had flatter length-tension curves and less scarring on histologic examination than the control eyes. CONCLUSIONS: Antifibroproliferative therapy with intraoperative sponge 5-fluorouracil appears as effective as, and is possibly safer than, mitomycin C. It may be a useful adjunct in recurrent strabismus surgery or in other situations where a risk of excessive postoperative scarring exists.

Administration, Topical↗