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Climacteric fruits display an increase in respiration and ethylene production during the onset of ripening, while such changes are minimal in non-climacteric fruits. Ethylene is a primary regulator of ripening in climacteric fruits. The ripening behavior and role of ethylene in blueberry ( Vaccinium sp.) ripening is controversial. This work aimed to clarify the fruit ripening behavior and the associated role of ethylene in blueberry. Southern highbush ( Vaccinium corymbosum hybrids) and rabbiteye ( Vaccinium ashei ) blueberry displayed an increase in the rate of respiration and ethylene evolution, both reaching a maxima around the Pink and Ripe stages of fruit development, consistent with climacteric fruit ripening behavior. Increase in ethylene evolution was associated with increases in transcript abundance of its biosynthesis genes, AMINOCYCLOPROPANE CARBOXYLATE ( ACC ) SYNTHASE1 ( ACS1 ) and ACC OXIDASE2 ( ACO2 ), implicating them in developmental ethylene production during ripening. Blueberry fruit did not display autocatalytic system 2 ethylene during ripening as ACS transcript abundance and ACC concentration were not enhanced upon treatment with an ethylene-releasing compound (ethephon). However, ACO transcript abundance was enhanced in response to ethephon, suggesting that ACO was not rate-limiting. Transcript abundance of multiple genes associated with ethylene signal transduction was upregulated concomitant with developmental increase in ethylene evolution, and in response to exogenous ethylene. As these changes require ethylene signal transduction, fruit ripening in blueberry appears to involve functional ethylene signaling. Together, these data indicate that blueberry fruit display atypical climacteric ripening, characterized by a respiratory climacteric, developmentally regulated but non-autocatalytic increase in ethylene evolution, and functional ethylene signaling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Acharya, Malladi, Tsai, NeSmith, Doyle and Nambeesan.)

The aim of this study was to determine the extent to which poor physical functioning, low participation in physical activity, and muscle atrophy observed among patients on hemodialysis are evident in the earlier stages of chronic kidney disease (CKD). We enrolled adults in three groups: no CKD, Stages 3 to 4 CKD, and hemodialysis. Outcomes measured were physical activity, muscle size, thigh muscle strength, physical performance, and self-reported physical function. Patients with CKD had muscle area intermediate between the no CKD and hemodialysis groups, but they had low levels of physical activity that were similar to the hemodialysis group. Physical activity and muscle size were significantly associated with all outcomes. Kidney function was not significantly associated with muscle strength or physical performance after adjustment for physical activity and muscle size. In conclusion, interventions aimed to increase muscle mass and energy expenditure might have an impact on improving physical function of CKD patients.

Blueberry (Vaccinium sp.) is thought to display a preference for the ammonium (NH 4 + ) form over the nitrate (NO 3 - ) form of inorganic nitrogen (N). This N-source preference has been associated with a generally low capacity to assimilate the NO 3 - form of N, especially within the shoot tissues. Nitrate assimilation is mediated by nitrate reductase (NR), a rate limiting enzyme that converts NO 3 - to nitrite (NO 2 - ). We investigated potential limitations of NO 3 - assimilation in two blueberry species, rabbiteye (Vaccinium ashei) and southern highbush (Vaccinium corymbosum) by supplying NO 3 - to the roots, leaf surface, or through the cut stem. Both species displayed relatively low but similar root uptake rates for both forms of inorganic N. Nitrate uptake through the roots transiently increased NR activity by up to 3.3-fold and root NR gene expression by up to 4-fold. However, supplying NO 3 - to the roots did not increase its transport in the xylem, nor did it increase NR activity in the leaves, indicating that the acquired N was largely assimilated or stored within the roots. Foliar application of NO 3 - increased leaf NR activity by up to 3.5-fold, but did not alter NO 3 - metabolism-related gene expression, suggesting that blueberries are capable of post translational regulation of NR activity in the shoots. Additionally, supplying NO 3 - to the cut ends of stems resulted in around a 5-fold increase in NR activity, a 10-fold increase in NR transcript accumulation, and up to a 195-fold increase in transcript accumulation of NITRITE REDUCTASE (NiR1) which codes for the enzyme catalyzing the conversion of NO 2 - to NH 4 + . These data indicate that blueberry shoots are capable of assimilating NO 3 - when it is directly supplied to these tissues. Together, these data suggest that limitations in the uptake and translocation of NO 3 - to the shoots may limit overall NO 3 - assimilation capacity in blueberry., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Unlabelled: Although sarcopenia is thought to underlie the manifestations of frailty, association of frailty with measures of body composition is underinvestigated., Methods: Eighty hemodialysis patients were included in the study. Performance-based frailty (PbF) used gait speed over 20 feet and 5 sit-to-stand (1 point each for lowest quintile) for the physical components of the frailty phenotype plus exhaustion (Short Form-36 [SF-36] vitality score <55) and physical activity (lowest quintile of weekly kcal energy expenditure on leisure activity on the Physical Activity Scale for the Elderly questionnaire; 1 point). Function-based frailty (FbF) defined by questionnaire measures of physical functioning (SF-36 Physical Function score <75; 1 point), exhaustion, and physical activity as for PbF. A score of 2 or greater was defined as frail. Outcomes related to muscle size included muscle area of the contractile tissue of the anterior tibialis and quadriceps muscles using magnetic resonance imaging, phase angle using bioimpedance analysis, lean body mass using dual energy X-ray absorptiometry, and body mass index (BMI). Linear regression was used to analyze associations between frailty and muscle size, with and without sex and age covariates., Results: Fifty-nine percent of individuals met PbF criteria, 63% met FbF criteria, and 55% met both. In univariate analysis, PbF and FbF were associated with smaller muscle area of the quadriceps, smaller phase angle, and higher BMI. Associations remained significant for the quadriceps after adjustment for age and sex. The magnitude of association of PbF with quadriceps muscle area was greater than 10 years of age (-30.3 cm(2)P = .02 vs. -6.6 cm(2)P < .0001) in multivariate analysis. There was no significant association between either measure of frailty and other measures of body composition after adjustment for age and sex., Conclusion: Frailty was associated with measurements related to muscle size in a population of individuals with chronic kidney disease, a known contributor to muscle wasting., (Published by Elsevier Inc.)

Background: Declines in 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels and physical functioning follow the course of chronic kidney disease (CKD). Although the molecular actions of vitamin D in skeletal muscle are well known, and muscle weakness and atrophy are observed in vitamin D-deficient states, there is little information regarding vitamin D and muscle function and size in CKD., Objective: To examine associations of vitamin D with physical performance (PF) and muscle size., Design: Cross-sectional., Setting: CKD clinic., Subjects: Twenty-six patients (61 ± 13 years, 92% men) with CKD stage 3 or 4., Main Outcome Measures: Gait speed, 6-minute walk, sit-to-stand time, 1-legged balance, and thigh muscle cross-sectional area (MCSA), measured by magnetic resonance imaging (MRI)., Results: Overall, 73% were 25-hydroxyvitamin D (25(OH)D) deficient (n = 10) or insufficient (n = 9) (Kidney Disease Outcomes Quality Initiative guidelines). 25(OH)D level was associated with normal gait speed only (r = 0.41, P = .04). Normal and fast gait speed, the distance walked in 6 minutes, and sit-to-stand time were best explained by 1,25(OH)₂D and body mass index (P < .05 for all) and 1-legged stand by 1,25(OH)₂D (r = 0.40, P < .05) only. There were no associations of age, estimated glomerular filtration rate (eGFR), intact parathyroid hormone (iPTH), or albumin with any PF measures. MCSA was associated with eGFR (r = 0.54, P < .01) only. Variance in MCSA was best explained by a model containing 1,25(OH)₂D, plasma Ca²⁺, and daily physical activity (by accelerometry) (P < .05 for all). Once these variables were in the model, there was no contribution of eGFR., Conclusion: These results suggest that 1,25(OH)₂D is a determinant of PF and muscle size in patients with stage 3 and 4 CKD., (Copyright © 2012 National Kidney Foundation, Inc. All rights reserved.)

Postdialysis fatigue (PDF) is a common and debilitating phenomenon that adversely affects the quality of life of hemodialysis patients. Excessive ultrafiltration and rapid osmolar flux are implicated in the pathogenesis of PDF, but simple adjustments do not always ameliorate this symptom. Increased physical activity has long been associated with reduced fatigue in sedentary fatigued patients. The aim of the study was to examine the extent to which physical activity is associated with PDF. This was a retrospective cross-sectional study of hemodialysis patients (n = 58, age 55 ± 13 years, 38 M, 20 F). Physical activity was measured by self-report using the Human Activity Profile (HAP) (n = 58) and accelerometry (n = 26). Postdialysis fatigue was assessed by a questionnaire rating frequency, severity, and duration of symptoms. 86% (50/58) of patients reported PDF ranging from mild to severe. The PDF index was inversely correlated with the adjusted score of the HAP (p < 0.05). Least squares linear regression was used to assess the association of physical activity with PDF, controlling for Kt/V and dialysis vintage. In the adjusted model (R2 = 0.40), physical activity remained the most significant predictor (p < 0.01) of PDF after adjusting for Kt/V and/or vintage. Further studies are needed to evaluate whether increasing habitual physical activity can mitigate PDF symptoms.

Background: Progressive resistance exercise training (PRT) improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients., Methodology/principal Findings: This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo) enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance). The main outcome measurements included muscle strength (one repetition maximum), energetics ((31)P magnetic resonance spectroscopy), composition and size (magnetic resonance imaging), as well as total body composition (dual-energy X-ray absorptiometry). Thirty-three subjects completed the study (17 creatine, 16 placebo). Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9%) in creatine and placebo, respectively). There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM) increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved muscle size, strength and function in HIV-infected men. While creatine supplementation produced a greater increase in LBM, it did not augment the robust increase in strength derived from PRT., Trial Registration: ClinicalTrials.gov NCT00484627.

Objective: Vitamin D has various actions in skeletal muscle. The purpose of this study was to compare lower-limb muscle size and strength in hemodialysis (HD) patients being treated with 1,25-dihydroxyvitamin D (calcitriol) or a 1,25-dihydroxyvitamin D analogue (paricalcitol) with lower-limb muscle size and strength in HD patients who were receiving none., Design: This was a retrospective, cross-sectional study., Setting: This study was performed in outpatient HD centers., Patients: Hemodialysis patients receiving calcitriol or paricalcitol (active vitamin D) for control of secondary hyperparathyroidism (VitD, n = 49) were compared with HD patients who were not (n = 30)., Main Outcome Measures: The main outcome measures included the cross-sectional areas (CSAs) of the thigh and tibialis anterior muscles by magnetic resonance imaging, and three measures of strength: the three-repetition maximum (3RM) for knee extension (isotonic), the peak torque of knee extensors (isokinetic), and maximal voluntary contraction of the ankle dorsiflexor muscles (isometric)., Results: There were no differences in age, weight, dialysis vintage, or intact parathyroid hormone levels between groups, although serum albumin was higher in the VitD group (P < .05). Patients in the VitD group had a larger thigh-muscle CSA (P < .05) and were stronger across all strength measures (P < .05) after controlling for age and gender (by analysis of covariance). When all analyses were subsequently adjusted for serum albumin concentration, only the difference in 3RM knee-extension strength lost significance. There were no significant differences in any measurements between patients who received calcitriol or paricalcitol., Conclusion: Treatment with active vitamin D was associated with greater muscle size and strength in this cohort of HD patients.

Background and Objective: To evaluate the effect of pseudophakia on the success of selective laser trabeculoplasty in lowering intraocular pressure (IOP)., Patients and Methods: In this retrospective, nonrandomized clinical trial, a chart review of all patients who underwent selective laser trabeculoplasty from September 2002 to June 2004 using a frequency-doubled Q-switched 532-nm Nd:YAG laser was performed. Changes in IOP and statistical significance were determined at each follow-up period. Average decrease in IOP and success rates for phakic and pseudophakic eyes were compared statistically at each time period., Results: In the phakic group, mean IOP decreased from 18.1 to 15.5 mm Hg (P < .0005) and mean glaucoma medication use decreased from 2.1 to 1.6 medications after 24 months of follow-up. In the pseudophakic group, mean IOP decreased from 18.3 to 15.2 mm Hg (P < .005) and mean glaucoma medication use decreased from 2.2 to 1.6 medications. Success rates ranged from 54% to 67% in the phakic group and 52% to 65% in the pseudophakic group. No statistically significant difference between phakic and pseudophakic eyes in decreased IOP or success rates was seen at any time point (P > .05). No significant complications occurred in either group., Conclusions: Selective laser trabeculoplasty is effective in lowering IOP in both phakic and pseudophakic patients.

Purpose: Glaucoma drainage devices, on rare occasions, need repositioned and the intraocular portion of the implant tube is found to be "too short" to do so. Previously, a technique was described for "extending" the tube with angiocatheter material (rather than replacing the entire apparatus), and had been performed successfully without complication for 7 years. This case describes the first known complication: trauma causing anterior chamber migration of the tube extension requiring retrieval and reconstruction of the tube extension apparatus., Patient and Methods: One eye of 1 patient (age 8) with a prior glaucoma drainage device and tube extension with angiocatheter material with elevated intraocular pressure after direct trauma to the eye from a pencil. Office examination revealed inferior corneal edema and no tube segment visible in the anterior chamber on limited examination due to age-related compliance. Gonioscopy under anesthesia revealed the tube extender in the inferior anterior chamber. The tube extender was retrieved from the anterior chamber. The glaucoma drainage device was surgically exposed and the tube extension was reconstructed, including securing the tube extension with a suture placed through the lumens of both the angiocatheter extender and the tube extension., Results: The reconstructed tube extension maintained good draining function with the secured extension and no further migration of the tube extension into the anterior chamber was seen., Conclusions: Tube extension using angiocatheter material continues to be a viable, cost-effective option in difficult cases. Placing a securing suture in patients prone to eye trauma can be considered.

The objective of this study was to determine whether the viral reduction processes of nanofiltration and solvent/detergent treatment used in the manufacture of alpha-1 proteinase inhibitor (API) cause neoantigenic changes. Polyclonal antibodies were raised in rabbits against the treated API and quantitatively absorbed with an affinity column containing API that had not undergone viral reduction treatment. Antibodies before and after absorption were measured in a validated ELISA using the immunogen for antibody capture. Antibodies against novel API epitopes were not found after antiserum from rabbits inoculated with treated API was absorbed with untreated API. A positive control, consisting of serum obtained from rabbits inoculated with trinitrophenylated API, showed substantial amounts of measurable antibody following absorption with untreated API. The results suggest that the viral reduction process used does not result in the creation of API neoantigens.

Background: Diabetes mellitus (DM) is a potential contributor to the muscle abnormalities and poor physical functioning of the dialysis population., Methods: Thirty-three dialysis patients without DM (non-DM group) were compared with 25 dialysis patients with DM (DM group). Measures were made of cross-sectional area and composition of the leg muscles by using proton T1-weighted magnetic resonance imaging; body composition by means of dual-energy X-ray absorptiometry; leg muscle strength by means of isokinetic knee extension; isometric dorsiflexor maximum voluntary contraction by means of force plate; physical activity by means of 3-dimensional accelerometry; and functional capacity by using various functional tests., Results: The DM group was older, weaker, more atrophic, and had a greater amount of intramuscular fat compared with the non-DM group. However, when the overall analysis was adjusted for age and sex, there were no differences between the 2 groups with respect to muscle cross-sectional area, leg strength, or physical activity. To further account for sex and age differences, a paired analysis was performed after matching patients by age (within 5 years) and sex (N = 16/group). In the matched analysis, only intramuscular fat and leg adipose tissue were different between the 2 groups., Conclusion: DM is associated with more fat within muscles of dialysis patients, but is unrelated to muscle size or strength. Demographic differences between the DM and non-DM groups on dialysis therapy likely are responsible for the general perception that patients with DM are more debilitated.

We compared the hemostatic efficacy of a production version of a dry fibrin sealant dressing (DFSD) to a prototype that was previously successful in large animal studies. The results were used to improve manufacturing processes. Grade-V liver injuries were induced in swine and treated with gauze sponges (GAU), the prototype dressings (DFSD-1), or the scaled-up production version dressings (DFSD-2 in experiment 1 and DFSD-3 in experiment 2). Blood loss, hemostasis, resuscitation volume, and 60-min survival were quantified. In experiment 1, the DFSD-1 treatment reduced blood loss (p < 0.01), increased hemostasis at 4 min (p < 0.05), and improved survival (p < 0.05) compared with GAU. The DFSHD-2 decreased blood loss (p < 0.05) but did not increase hemostasis or survival significantly. Based on these results, manufacturing processes were altered, producing DFSD-3. In experiment 2, the DFSD-1 and DFSD-3 were equally effective in reducing blood loss (p < 0.01) and resuscitation volume (p < 0.05) compared with GAU. Hemostasis occurred more frequently in both the DFSD-1 and DFSD-3 groups (p < 0.01) compared with GAU. The structural design of DFSD-2 did not meet the efficacy requirement for release of the product. The subsequent change incorporated in DFSD-3 improved all hemostatic parameters of the dressings equal to those of the prototype product., (Copyright 2004 Wiley Periodicals, Inc.)

The purpose of this study was to compare the magnitude and mechanisms of ankle dorsiflexor muscle fatigue in 20 young (33 +/- 6 yr, mean +/- SD) and 21 older (75 +/- 6 yr) healthy men and women of similar physical activity status. Noninvasive measures of central and peripheral (neuromuscular junction, sarcolemma) muscle activation, muscle contractile function, and intramuscular energy metabolism were made before, during, and after incremental isometric exercise. Older subjects fatigued less than young (P < 0.01); there was no effect of gender on fatigue (P = 0.24). For all subjects combined, fatigue was modestly related to preexercise strength (r = 0.49, P < 0.01). Neither central (central activation ratio) nor peripheral (compound muscle action potential) activation played a significant role in fatigue in any group. During exercise, intracellular concentrations of P(i) and H(2)PO increased more and pH fell more in young compared with older subjects (P < 0.01) and in men compared with women (P < 0.01). These varied metabolic responses to exercise suggest a greater reliance on nonoxidative sources of ATP in young compared with older subjects and in men compared with women. These results suggest that the mechanisms of fatigue vary with age and gender, regardless of whether differences in the magnitude of fatigue are observed.

Background: To review costs of the wide array of glaucoma medications available today as well as patient-assistance programs., Methods: Potential yearly costs for current frequently used single and multiple drug therapies were determined, taking into account the actual (not labeled) volume of drops in the bottled medications. Alternative modes for obtaining medications, such as compassionate-use programs, were also surveyed., Results: "Maximum" medical therapy may cost over $2000 per year. Allergan, Ciba, Merck, Pharmacia-Upjohn, and Alcon offer patient-assistance programs of variable simplicity of use., Discussion: The cost of maximum glaucoma medical therapy can assume a significant proportion of an elderly patient's yearly income.

Purpose: Surgeons may use various materials, including donor sclera, dura, or pericardium grafts to cover glaucoma drainage implant tubes, prior to repositioning conjunctiva. We reviewed our experience with these materials., Patients and Methods: Sixty-four eyes with at least 24 months follow-up status post glaucoma drainage implant surgery were evaluated for signs of tube erosion, as well as patch graft thinning, after initial placement of donor sclera (23), dura (18), or pericardium (23) patch grafts., Results: Sixty-two eyes required no intervention for conjunctival and patch graft melting with subsequent tube erosion. Three cases (two eyes) of erosion requiring reoperation (1-dura at 6 months, 1-sclera at 15 months, and in the same eye 21 months later, 1-pericardium) were noted. Significant thinning of the donor patch graft such that the tube was visible beneath intact conjunctiva ocurred in 6 out of 23 donor sclera eyes, 4 out of 18 donor dura eyes, and 6 out of 23 donor pericardium eyes., Conclusion: No material was more prone to melting than another. Donor sclera may be slightly more cost-efficient, but gamma-irradiated pericardium has sterility advantages.

Background: Tissue plasminogen activator (tPA) is a serine protease with thrombolytic-fibrinolytic activity. In the anterior segment of the eye, it has been used to lyse blood and fibrin clots immediately following trabeculectomy., Objective: To review our experience using tPA to revive previously functional but newly failing blebs following secondary surgical procedures (cataract extraction or penetrating keratoplasty)., Methods: A retrospective medical record review of all eyes receiving tPA to revive a failing bleb after a later anterior segment surgery was performed. Blebs were functional for at least 9 months before tPA, 12.5 microg, was injected into the anterior chamber. Eyes had longer than 6 months of follow-up after tPA use., Results: Six eyes that had undergone phacoemulsification and 1 that had undergone penetrating keratoplasty were identified. Before the secondary surgery, blebs had been in place for 20.4 +/- 9.3 months, with an intraocular pressure of 10.7 +/- 3.6 mm Hg. New bleb failure in these eyes was observed following phacoemulsification or penetrating keratoplasty between postoperative days 4 and 14, with the intraocular pressure increasing to 27.7 +/- 9.5 mm Hg. One day after tPA use, the intraocular pressure had decreased to 11.0 +/- 3.7 mm Hg (P =.002). In 5 of the 7 patients, the bleb height improved following tPA use. The final intraocular pressure was 10.7 +/- 3.6 mm Hg at a follow-up of 13.4 +/- 6.4 months. (All data are given as mean +/- SD.), Conclusion: Tissue plasminogen activator can be a useful adjunct for reviving newly failing blebs after other anterior segment surgery.

Purpose: To quantify and localize plasmid transfection of filtration surgery tissues using two delivery techniques., Methods: Full-thickness filtering procedures were performed on eyes of New Zealand albino rabbits. In 10 eyes, naked plasmid DNA in saline was either injected beneath Tenon's capsule at the filtration site or absorbed into a collagen shield that was then placed external to the sclerostomy and under the Tenon's capsule. Forty-eight hours after surgery, levels of the reporter gene, chloramphenicol acetyltransferase (CAT) were measured in samples of ocular tissues. In two additional eyes, the ss-galactosidase (ss-GAL:) reporter gene expression was localized histologically., Results: Injection of plasmid DNA in saline vehicle into the filtration bleb produced readily detectable CAT activity in bleb tissue (conjunctiva, Tenon's capsule, and sclera) whereas CAT activity was nearly undetectable in samples of the cornea, iris-ciliary body, and tissues located opposite the bleb site. Delivery of the plasmid DNA into the bleb through a collagen shield increased CAT activity 30-fold over injection of plasmid in saline (2711 +/- 567 mU/mg versus 92 +/- 38 mU/mg). ss-Gal activity was imaged only in the region of the bleb, and microscopic examination showed ss-Gal activity localized to Tenon's capsule fibroblasts, with minimal ss-Gal activity observed in inflammatory cells or scleral fibroblasts., Conclusions: Transfection of filtration tissues is enhanced by absorption of naked DNA into a collagen shield. Furthermore, transfection is localized to the fibroblasts and inflammatory cells of the filtration bleb site. Gene therapy using naked plasmid DNA and a simple collagen shield delivery vehicle may be useful for regulating wound healing after glaucoma surgery.

Objective: To review the effect of phacoemulsification surgery in eyes with chronic hypotony following trabeculectomy with mitomycin C., Design: Retrospective analysis of all eyes that underwent phacoemulsification surgery for symptomatic cataracts and had a preoperative diagnosis of chronic hypotony (intraocular pressure [IOP]

Purpose: For a variety of reasons, on rare occasions a surgeon needs to reposition the intraocular portion of a glaucoma drainage implant tube, but finds the tube "too short" to do so. This study describes results of a different technique for "extending" the tube (rather than replacing the entire apparatus)., Methods: Four eyes of four patients required a tube "extender," for either tube tip blockage associated with uncontrolled intraocular pressure (IOP; n = 3), or to avoid total seton replacement after tube "cheesewiring" (n = 1). An extender was fashioned from common angiocatheter material. Postoperative complications, IOP, and need for further surgery were reviewed., Results: None of the four patients required further, more invasive surgery or experienced any related postoperative complications. Final IOP averaged 11.5 +/- 4.2 mmHg (range 6-16 mmHg)., Conclusion: Tube extension using angiocatheter material is a viable, cost-effective option in these difficult cases, saving the surgeon from having to explant and replace the entire implant.

Background and Objective: To evaluate changes in intraocular pressure (IOP) following uneventful phacoemulsification cataract extraction with posterior chamber intraocular lens implantation (Phaco/PC IOL) in primary open-angle glaucoma (POAG) patients., Patients and Methods: The authors retrospectively reviewed preoperative and postoperative IOP in 31 consecutive medically-controlled POAG patients who underwent uneventful Phaco/PC IOL. None of the patients had prior intraocular surgery., Results: The mean preoperative IOP in the POAG group was 18.1+/-3.1 mm Hg with patients receiving a mean of 1.7 antiglaucoma medications. With a mean follow-up of 16.4 months, the average postoperative IOP in the POAG group was 15.2+/-2.9 mm Hg (P < .001, Student's t test) with patients receiving a mean of 0.7 antiglaucoma medication (P < .001)., Conclusion: Phaco/PC IOL may be associated with a significant decrease in IOP in POAG patients, allowing for decreased postoperative antiglaucoma medication.

In previous immunohistochemical studies, chronic venous insufficiency (CVI) ulcers have been shown to display positive staining for interleukin-10 (IL-10), while other wounds (including autologous donor wound tissue) show a reduced staining level. IL-10 inhibits the synthesis of many proinflammatory cytokines, while also inhibiting antigen presentation by antigen-presenting cells. It is possible that abnormally high amounts of IL-10 in chronic wounds may be related to the failure of these wounds to progress to final wound healing. The purpose of this study was to quantify the levels of IL-10 in CVI ulcers and autologous donor tissue using Western blotting. Extracts were prepared from frozen wound tissue samples and equal amounts of protein were concentrated by immune-precipitation for Western blot analysis. Densitometric analysis was performed on nonsaturated chemilumigraphs and normalized to an IL-10 standard run on each gel. The quantity of IL-10 in CVI ulcers was found to be 490% of the quantity in autologous donor tissue. This study provides confirmatory quantitative data which supports previous immunohistochemical findings showing elevated levels of IL-10 in CVI ulcers.

Objective: Control of intraocular pressure (IOP) after retinal surgery with scleral band placement may be problematic. In this study, outcome after silastic drainage implant placement is reviewed., Design/participants: A retrospective chart review of 11 eyes in 11 patients with severe glaucoma after multiple surgeries, including scleral buckle procedures., Intervention: Patients received silastic drainage implant surgery, either a long Krupin Denver valved implant (7) or a trimmed Baerveldt seton (4)., Main Outcome Measures: Vision, IOP, and need for further glaucoma medication or glaucoma surgery were measured., Results: One- and 2-year life-table success rates (either complete or qualified success) were 82% and 73%, respectively, defining success as final IOP of 21 mmHg or less without need for further glaucoma surgery and no loss of visual acuity. Half of the successful eyes required antiglaucoma medication., Conclusions: Silastic drainage implants may be a viable option in the treatment of complicated glaucoma after retinal surgery.

Background: White cell trapping and activation occurs in the legs of patients having chronic venous insufficiency (CVI), and it is thought that this process may be important in the development of CVI ulcers. This study has compared the tissue distribution of proinflammatory (GM-CSF) and anti-inflammatory cytokines (IL-10) and inflammatory cell markers (CD68, HLA-DR) between CVI ulcers, other chronic and acute wounds, and autologous nonwounded skin to determine whether cell-mediated immunity (CMI) is impaired in CVI ulcers., Methods: Wound and donor site tissue was obtained from 10 patients with CVI ulcers and 10 patients with other chronic and acute wounds. Serial Formalin-fixed sections were processed by standard hematoxylin and eosin staining or by indirect immunoperoxidase histochemical staining., Results: HLA-DR-positive antigen-presenting cells (APC), including CD68-positive macrophages and dermal dendritic cells, were found with greater frequency in CVI ulcers than in other chronic or acute wounds (P = 0.0015) or in the autologous CVI donor site tissue (P = 0.006). CVI ulcers also demonstrated increased IL-10 staining of the entire epidermis compared to non-CVI wounds (P = 0.0019) or autologous donor site tissue (P = 0.004), whereas there was no significant change in the presence of the counteracting cytokine, GM-CSF., Conclusions: These findings suggest that although the cellular components of CMI are present in CVI ulcers, their function may be impaired by the increased level of IL-10. Future studies will examine whether IL-10-mediated suppression of CMI and/or inhibition of GM-CSF-stimulated keratinocyte proliferation may contribute to the chronic nature of CVI ulcers., (Copyright 1998 Academic Press.)

Purpose: The mechanism through which peribleb injection of autologous blood results in resolution of bleb leak in the rabbit model remains unclear. This study evaluates the clinical and histologic effects of peribleb injection of transforming growth factor-beta (TGF-beta) after leak induction in mitomycin-C-treated blebs., Method: Posterior lip sclerectomies treated with mitomycin-C were created in New Zealand White rabbits. On postoperative day 7, a standardized stab incision was performed on all blebs, and the eyes were randomized to receive a peribleb injection of either TGF-beta or of a balanced salt solution., Results: Injection of TGF-beta was associated with the resolution of bleb leak and maintenance of a functioning bleb in 50% (4 of 8) of treated eyes. The remaining TGF-beta-treated eyes and control eyes demonstrated continued bleb leaks or bleb failures with intraocular pressure returning to preoperative levels. Histologic examination revealed increased peribleb cellularity and denser collagen deposition in the TGF-beta-treated eyes compared with that observed in control eyes., Conclusions: Peribleb TGF-beta injections may contribute to healing bleb leaks, but the injections do not appear in this model to be as useful as whole-blood injections.

Free fat transplantation for soft tissue augmentation yields variable results, which may be related to the technique of fat harvest. To compare the viability of adipocytes harvested by liposuction (sal) or by excision (exc), fat harvested by both techniques from seven lipectomy patients was analyzed by glycerol-3-phosphate dehydrogenase (G3PDH) enzyme assay. Leakage of this lipogenic enzyme through the plasma membrane is a potential indicator of fat cell damage. Preliminary experiments showed this assay to be sensitive and specific for adipocyte G3PDH activity. Treatment of fat tissue with collagenase H resulted in complete release of the component fat cells for analysis with less loss of G3PDH activity, compared to other collagenase preparations. Each sample was digested and separated into three compartments: mature adipocytes-floating layer (F), acellular supernatant (S), and stromal pellet (P). Samples from each compartment were assayed for G3PDH activity, normalized to DNA content, and represented as a percentage of the whole (F + S + P). Within the subgroups, the fat cell fraction of the liposuction samples (Fsal) showed statistically more activity than the excised samples (Fexc) by paired Student's t test (P = 0.004). The supernatant (representing leaked G3PDH) and pellet fractions of excised samples revealed more G3PDH activity than the same fractions from liposuctioned tissue; the former (Sexc) to a significant degree (P = 0.036). Using this assay, the results indicate that liposuction fat harvest does not result in increased fat cell damage compared to fat harvested by excision.

Purpose: This study was conducted to review outcomes in eyes following primary trabeculectomy supplemented intraoperatively with 5-fluorouracil (5-FU) or lower dose mitomycin-C (MMC)., Patients and Methods: We retrospectively reviewed the medical records of 73 eyes of 63 patients with progressive, far advanced open angle glaucoma who had undergone initial trabeculectomy with intraoperative application of 5-FU, 50 mg/mL for 5 min (N = 37), or MMC, 200 micrograms/mL for 3-5 min (N = 36), and with at least 12 months follow-up., Results: Mean preoperative intraocular pressures (IOPs) in the MMC and 5-FU groups were 24.3 +/- 7.6 and 24.6 +/- 9.3 mm Hg, respectively. Postoperatively, IOPs were similar at 6-month interval follow-up examinations in the MMC and 5-FU groups. At an average follow-up of 20.9 months, mean final visit postoperative IOPs were 10.2 +/- 3.6 (p < 0.001) and 9.7 +/- 3.4 mm Hg (p < 0.001) in the MMC and 5-FU groups, respectively, requiring an average of 0.25 and 0.22 antiglaucoma medications per eye, respectively. Interval follow-up complications were similar between groups and included four bleb leaks in the MMC group, and three bleb leaks in the 5-FU group. Visual acuity remained stable in 71 of 73 eyes., Conclusions: Both antifibrosis agents provide good intermediate term IOP control and may be appropriate for use in those eyes requiring final "target" IOPs in the low teens or single digits.

Although the clinical experience with calcium alginate has been generally good, well-controlled studies examining the effect of such dressings on the processes of wound healing have not been conducted. The healing of cutaneous ulcers requires the development of a vascularized granular tissue bed, filling of large tissue defects by dermal regeneration, and the restoration of a continuous epidermal keratinocyte layer. These processes were modeled in vitro in the present study, utilizing human dermal fibroblast, microvascular endothelial cell (HMEC), and keratinocyte cultures to examine the effect of calcium alginate on the proliferation and motility of these cultures, and the formation of capillarylike structures by HMEC. This study demonstrates that the calcium alginate tested increased the proliferation of fibroblasts but decreased the proliferation of HMEC and keratinocytes. In contrast, the calcium alginate decreased fibroblast motility but had no effect on keratinocyte motility. There was no significant effect of calcium alginate on the formation of capillarylike structures by HMEC. The effects of calcium alginate on cell proliferation and migration may have been mediated by released calcium ions. These results suggest that the calcium alginate tested may improve some cellular aspects of normal wound healing, but not others.

Purpose: Bleb leaks after trabeculectomy with antimetabolites can be recalcitrant to therapy. Peribleb autologous blood injections are a moderately successful new treatment modality for such leaks. However, it is unclear what mechanism the injections work to achieve leak resolution., Methods: A randomized, prospective study in the rabbit model was undertaken to evaluate further the clinical and histologic effects of peribleb autologous blood injection after leak induction in mitomycin-C exposed blebs, compared to controls that received only peribleb balanced salt solution injections., Results: In the blood-treated eyes, all bleb leaks healed. Control eyes either demonstrated persistent bleb leaks with shallow anterior chambers or failed blebs that were Seidel negative. Histologic results were remarkable for increased peribleb cellularity and collagen deposition in the blood-treated eyes, compared to controls., Conclusions: Peribleb autologous blood injections are associated with bleb leak resolution, increased peribleb cellularity, and collagen deposition in the rabbit model.

It is thought that radiation treatment inhibits neovascularization of recipient and/or graft tissues, and this may account in part for abnormalities in wound healing associated with radiation therapy. We have examined this hypothesis using a model that measures the neovascularization of an implanted foreign material. Expanded polytetrafluoroethylene (PTFE) sheets were implanted adjacent to both superficial epigastric vascular pedicles of 63 rats distributed into 7 groups (n = 7) that differed with respect to dose and timing of irradiation. Zero to 10 daily fractions of electron-beam radiation (300 cGy each) were delivered to the implant in the right groin, while the implant in the left groin served as a nonirradiated internal control. Unirradiated animals showed equal neovascularization of both implants. Rats that were irradiated twice (single fractions at 0 and 24 hours after implantation) did not show a significant decrease in the neovascularization of the irradiated implant compared with the contralateral control implant. In contrast, the implants that were irradiated three times (single fractions at 0, 24, and 48 hours after implantation) demonstrated significantly diminished ( > 25 percent, p < 0.05) neovascularization beyond day 7, whereas implants irradiated only at 48 hours after implantation did not. Interestingly, neovascularization of the implants irradiated with 10 fractions (3000 cGy) was not significantly decreased compared with irradiation with three fractions (900 cGy). Irradiation delivered before implantation (900 cGy) inhibited neovascularization significantly less than the same dose administered after implantation. The results of this study suggest that a subclinical cumulative dose of 900 cGy is the threshold for impaired tissue revascularization provided that treatment is delivered immediately after implantation over a 48-hour interval.

Background and Objective: Initial overdrainage following filtration surgery can be frustrating to manage. The authors reviewed the records of 10 patients with early postoperative hypotony following filtration surgery who were treated with application of an oversized 17.0-mm bandage soft contact lens (BSCL)., Patients and Methods: Nine eyes had undergone trabeculectomy with either mitomycin-C or 5-fluorouracil intraoperative application, and one eye had undergone tenonectomy 4 years following trabeculectomy. On postoperative day 1, seven eyes were hypotonous, and three other eyes became hypotonous following suture removal or lysis. An oversized 17.0-mm BSCL was placed immediately following the diagnosis of hypotony on all eyes except one, which had the BSCL applied after 24 hours of observation., Results: In 9 of 10 cases intraocular pressure rose 5 to 12 mm Hg following placement of the BSCL. During a 6- to 18-months follow-up, all successfully treated eyes had final intraocular pressures of 5 to 11 mm Hg, with extensive low to moderate height blebs., Conclusion: Oversized BSCLs can be a useful tool in the management of early hypotony following filtration surgery.

Purpose: To evaluate the use of Scheimpflug photography in the examination of iris configuration and anterior chamber depth in eyes with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG)., Methods: The Nidek EAS 1000 Scheimpflug camera was used to photograph the anterior segment of 12 eyes with PDS/PG, as well as 12 age-matched controls and four eyes with primary open-angle glaucoma (POAG). Anterior chamber depth, iris insertion angle, and iris configuration were evaluated. Five eyes of three patients were serially photographed over 10 min while blinking was prevented., Results: Patients with PDS/PG showed deeper anterior chambers than age-matched controls or patients with POAG. Nine of 12 PDS/PG eyes showed a concave iris configuration. There were no concave irides noted in control or POAG eyes. Preventing blinking resulted in significant anterior excursion of concave irides in three of the five eyes studied., Conclusions: Scheimpflug photography is a useful modality to study iris configuration. These photographs document the presence of a concave iris configuration in some patients with PDS/PG, and support the hypothesis that blinking may be significant in producing this configuration.

Background: Managing filtration surgery bleb leaks can be difficult as well as frustrating. Treatment options traditionally have included aqueous suppressants, patching, and bleb compression devices. Previously, if conservative management failed, surgical revision was considered., Methods: Six patients with thin avascular blebs and discrete leaking holes (2 had had full-thickness procedures, 4 had had trabeculectomy with mitomycin C) underwent subconjunctival injection of approximately 1 ml of whole autologous blood. Injections were made just lateral and just medial to the domed cystic elevation of the blebs., Results: Five of six eyes were leak-free by the second day after the procedure. No complications occurred. After 4 to 12 months of follow-up, four eyes are currently leak-free. In these eyes, intraocular pressure is between 8 and 12 mmHg., Conclusion: Subconjunctival peribleb injection of autologous blood may be a safe and helpful adjunct in treating selected postfiltration surgery bleb leaks.

Objective: To compare the 350-mm2 Baerveldt implant with the double-plate Molteno implant in the treatment of eyes with complicated glaucoma., Design: Retrospective chart review of a consecutive series of drainage implants., Setting: University-based referral practice., Patients: Thirty-four consecutive patients (37 eyes) undergoing glaucoma drainage device implantation because of uncontrolled, complicated glaucoma., Intervention: Eighteen eyes underwent 350-mm2 Baerveldt implantation and 19 eyes underwent double-plate Molteno implantation., Main Outcome Measures: Intraocular pressure (IOP) control, visual acuity outcome, and complication rate., Results: Mean preoperative IOP was 30.2 mm Hg in the Baerveldt group, with an average of 2.7 antiglaucoma medications, and 28.4 mm Hg in the Molteno group, with an average of 2.4 antiglaucoma medications. With an average follow-up of 11.3 months (range, 5 to 16 months), mean IOP at the final visit was 13.1 mm Hg (range, 7 to 21 mm Hg) in the Baerveldt group, with an average of 1.3 medications, and 13.4 mm Hg (range, 8 to 25 mm Hg) in the Molteno group, with an average of 0.8 medications. Final IOP was between 7 and 19 mm Hg in 16 of 18 Baerveldt eyes and in 17 of 19 Molteno eyes. Visual acuity (when it could be checked) remained stable (+/- 2 Snellen lines) in 17 of 17 eyes in the Baerveldt group and in 17 of 19 eyes in the Molteno group. Complications in the Baerveldt group included two cases (11%) of flat anterior chamber after stent removal, one case (6%) of intermittently symptomatic diplopia, and one case (6%) of endophthalmitis. In the Molteno group there were two graft failures (11%) and one eye (5%) with loss of central field., Conclusions: Both types of drainage implants provide excellent postoperative IOP control. Early stent removal should be avoided if possible in eyes with Baerveldt implants.

Purpose: To examine the stability of retinoic acid administered to cultured bovine retinal pigment epithelial (RPE) cells and to determine if RPE cells metabolize retinoic acid by a cytochrome P-450 mechanism., Methods: Retinoic acid metabolism was examined in cultured RPE cells and subcellular fractions quantitatively by a thin-layer chromatography procedure and qualitatively by normal and reverse phase high-performance liquid chromatography., Results: Cultured bovine RPE cells were found to have an activity that converts retinoic acid into more polar metabolites rapidly released from the cell. The highest specific activity for this process is found in the post-mitochondrial pellet (100,000g), is induced by retinoic acid, and is inhibited by ketoconazole. The major product of the RPE cell-mediated metabolism of retinoic acid is 4-oxo-retinoic acid, a known P-450 monooxygenase product of retinoic acid. The retinoic acid metabolizing activity is greatest in primary RPE cultures and decreases with aging in culture., Conclusions: These data suggest that a cytochrome P-450 monooxygenase is involved in the metabolism of retinoic acid in RPE cells, and this is similar to the findings of other investigators using other cells and tissues. The authors' findings suggest that the RPE may be important in the deactivation of this biologically potent retinoid in the retina.

Glaucoma after penetrating keratoplasty remains a management problem. The incidence is significant because of the status of those eyes undergoing PKP. Many have had multiple previous surgeries, and aqueous outflow may be compromised before the PKP. The surgery itself causes additional damage to the angle, often inducing peripheral anterior synechiae formation, with further impediment to aqueous outflow. Control of postkeratoplasty glaucoma is complicated by the need to preserve graft clarity for visual function. Medical treatment with aqueous suppressants is the first line of care. Since the introduction of apraclonidine 0.5%, and with topical carbonic anhydrase inhibitors soon to be introduced, perhaps medical management will become easier. When medical management fails, if the angle is open and viable, argon laser trabeculoplasty may be an option. If further intervention is indicated, the authors recommend a drainage seton (double-plate Molteno, or Baerveldt tube) in those eyes with good visual potential. For those eyes with poor visual potential (or those patients who cannot undergo surgery), we recommend contact Nd: YAG CPC.

We treated a persistent, brisk bleb-leak after trabeculectomy with mitomycin C by bleb injection of autologous blood. Following preparation with povidone iodine, approximately 0.5 cc of whole autologous blood was injected into the bleb at the slit lamp. The leak resolved after 36 hours, and after 9 months' follow up, continued to function well.

Purpose: Postoperative subconjunctival injections of 5-fluorouracil (5-FU) improve the success rate of filtration surgery, but there is still a 20% or greater failure rate at 1 year in pseudophakic and repeat trabeculectomy cases. The injections are inconvenient to give and may produce corneal epithelial toxicity and other side effects. An alternative method for administration of 5-FU is investigated., Methods: A masked, randomized, prospective study was undertaken to compare bleb survival and complications in a rabbit model, after either a single intraoperative exposure to 5-FU (50 mg/ml concentration for 5 minutes) or five postoperative injections of 5-FU (5 mg injection on postoperative days 1, 3, 5, 7, and 9), or a combination of both, with controls that received only a 5-minute exposure to distilled water, intraoperatively., Results: For the control eyes, all blebs were "flat" to masked grading, and intraocular pressure returned to preoperative levels by postoperative day 11. In the group receiving postoperative injections of 5-FU only, blebs were flat and the pressure normalized by postoperative day 14. Rabbits receiving intraoperative 5-FU only, or combined intraoperative and postoperative 5-FU, had consistently higher blebs than the former two groups, and some blebs survived until postoperative day 25. The mean intraocular pressure remained depressed in these groups until postoperative day 21 (P < 0.05 for days 5 through 18). A combination of intraoperative and postoperative 5-FU produced significantly higher blebs than intraoperative 5-FU alone on days 7 to 14., Conclusions: Intraoperative application of high-dose 5-FU to the filtration site either as a single 5-minute treatment, or in conjunction with postoperative injections of 5-FU greatly prolongs bleb function after filtration surgery in the rabbit.

Previously we showed that CHO cell growth is arrested in the G1 or G0 phase within 24 h after the biosynthesis of mevalonic acid is blocked. The growth-limiting factor under these conditions appeared to be dolichyl phosphate or one of its glycosylated derivatives with consequent decrease in the synthesis of N-linked glycoproteins (Doyle, J.W., and A.A. Kandutsch, 1988, J. Cell Physiol. 137:133-140; Kabakoff, B., J.W. Doyle, and A.A. Kandutsch, 1990, Arch. Biochem. Biophys. 276:382-389). We show herein that cell surface glycoproteins are depleted in the inhibited cultures and that growth arrest is delayed when supraphysiological concentrations of insulin, insulin-like growth factor-1 (IGF-1) and bFGF are added to the culture medium. Apparently an elevated level of a growth factor increases the length of time during which a threshold level of occupied receptor is maintained as the number of glycosylated receptor molecules declines. The results support the idea that cellular levels of dolichyl phosphate and its derivatives may limit cell division by controlling the numbers of functional receptors for growth factors and of other glycoproteins on the cell surface.

Purpose: To establish the effects of single intraoperative exposures to either 5-fluorouracil (5-FU) or two different concentrations of mitomycin C (MMC) on filtration surgery in the rabbit., Methods: A prospective, randomized, masked-observer, placebo-controlled study was performed to compare the effects on filtration surgery in rabbits of a single 5-minute intraoperative exposure to 5-FU (50 mg/ml), MMC (0.2 mg/ml), or MMC (0.4 mg/ml) with control eyes treated with distilled water., Results: Intraocular pressures (IOPs) remained lower for longer and bleb survival was increased (P < 0.05) with all three treatments compared with control eyes. The effect of 5-FU was more transient than MMC. Bleb survival was prolonged in the following order: MMC 0.4 > MMC 0.2 > 5-FU 50 mg/ml. At 30 days, blebs were present in 100% of eyes treated with MMC 0.4 mg/ml, 60% of eyes treated with MMC 0.2 mg/ml, and 0% of eyes treated with 5-FU 50 mg/ml or distilled water. The blebs in the eyes treated with MMC were thinner, and significant complications (endophthalmitis, transient corneal opacification and neovascularization, and a presumed bleb leak) only occurred in the eyes treated with MMC 0.4 mg/ml., Conclusions: The authors' results suggest that 5-FU and MMC at these concentrations, delivered as a single intraoperative dose, prolong the survival of filtration surgery for different lengths of time in the rabbit, which is a model that normally exhibits aggressive healing and rapid failure of filtration surgery. The implications of these potentially titratable effects for filtration surgery in different categories of patients are discussed.

Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90 degrees and 180 degrees from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed.

The success rate of filtration surgery has been increased by the postoperative subconjunctival injection of 5-fluorouracil, a potent antimetabolite. However, the optimal route of administration has not been determined. Trabeculectomy was performed on one eye each of 14 patients. Topical 5-fluorouracil was applied intraoperatively (50 mg/ml for five minutes) and subconjunctival 5-fluorouracil was injected postoperatively (an average of 5.8 injections) (mean total dose, 29 mg). Seven of the 14 eyes had primary open-angle glaucoma, and seven eyes had open-angle glaucoma with either uveitis, aphakia, or previous failed trabeculectomy. Mean preoperative intraocular pressure was 24.7 mm Hg during treatment with an average of three antiglaucoma medications, and mean final intraocular pressure was 11.9 mm Hg during treatment with an average of 0.2 medication. Thirteen of 14 eyes (93%) had final intraocular pressure of 18 mm Hg or less. Mean follow-up was 6.4 months (range, four to nine months). No remarkable complications occurred. Visual acuity remained stable in 13 of 14 eyes (93%). Intraoperative 5-fluorouracil may be a helpful adjunct in achieving low final intraocular pressure after trabeculectomy.

Rabbits undergoing full thickness glaucoma filtering surgery were exposed to one of 4 treatments. Group 1 received intraoperative distilled water, group 2 received intraoperative mitomycin-c 0.2 mg/ml for 5 minutes, group 3 received 5 post operative injections of 5-Fluorouracil (5-FU) 5 mg in 0.1 ml, and group 4 received intraoperative 5-FU 50 mg/ml followed by 5 post operative injections of 5-FU. 30 days after the operation tissue biopsies were taken from the subconjunctival and scleral tissue at the treated area and 90 and 180 degrees from the treated area. The biopsies were then placed in tissue culture media and the outgrowths quantitated. The fibroblast outgrowths from all areas did not differ significantly from each other except for the outgrowths from the areas directly treated with mitomycin 0.2 mg/ml which were significantly smaller. In addition then cells were morphologically abnormal although there were foci of normal cells which appeared to be growing from localised areas in the tissue biopsies. The outgrowths from the areas 90 and 180 degrees from the treated area were normal. Intraoperative treatments with mitomycin-c result in long term inhibition of fibroblast proliferation limited to the treated area, when compared with intraoperative and postoperative treatment with 5-FU. Failure of filtration surgery in eyes treated with intraoperative mitomycin may in part be due to unaffected cells reproliferating.

The effect of several naturally-occurring retinoids and 13-cis-retinoic acid on the proliferation of cultured bovine retinal pigment epithelial (RPE) cells was investigated. None of the retinoids tested were toxic to the cultures and all, except retinylpalmitate, inhibited cell proliferation when given for more than 3 days. The relative potencies of the retinoids were; all-trans-retinoic acid greater than 13-cis-retinoic acid greater than all-trans-retinol approximately equal to all-trans-retinaldehyde. Uptake of retinoic acid by cultured RPE cells was 10-fold less than the uptake of retinol. Although retinoic acid-treated cultures showed strong density-dependent growth inhibition, cellular proliferation was inhibited more in sparse cultures than in dense ones. Retinoic acid did not significantly inhibit the proliferation of first passage bovine or rabbit RPE cells, but partially inhibited the proliferation of first passage human RPE cells. The sensitivity of all these cultures to growth inhibition by retinoic acid increased in subsequent subcultures, yet there was no effect of passage number on retinoic acid uptake. This study demonstrates that RPE cell proliferation can be inhibited by retinoic acid but the sensitivity of these cells to the retinoid's effects are modulated by incubation time, in vitro aging, and cell density.

We examined two patients with monocular frosted branch angiitis. The patients were young and healthy; they rapidly developed severe visual loss with thick, white sheathing of the retinal veins and responded promptly to systemic corticosteroids. The fluorescein angiograms showed late leakage from the retinal veins, without evidence of stasis or occlusion. Frosted branch angiitis can be either a unilateral or a bilateral condition. We believe the potential for visual loss and the prompt response to systemic corticosteroids make early, accurate diagnosis and institution of therapy desirable.

Following treatment of Chinese hamster ovary cells with inhibitors of mevalonate biosynthesis in the presence of exogenous cholesterol, the cellular concentration of phosphorylated dolichol and the incorporation of [3H]mannose into dolichol-linked saccharides and N-linked glycoproteins declined coincident with a decline in DNA synthesis. Addition of mevalonate to the culture medium increased rates of mannose incorporation into lipid-linked saccharides and restored mannose incorporation into N-linked glycoproteins to control levels within 4 h. After an additional 4 h, synchronized DNA synthesis began. Inhibition of the synthesis of lipid-linked oligosaccharides and N-linked glycoproteins by tunicamycin prevented the induction of DNA synthesis by mevalonate, indicating that glycoprotein synthesis was required for cell division. The results suggest that the rate of cell culture growth may be influenced by the level of dolichyl phosphate acting to limit the synthesis of N-linked glycoproteins.