Correlates of Physical Functioning and Performance Across the Spectrum of Kidney Function.

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.

Postdialysis fatigue is associated with sedentary behavior.

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.

Human skeletal muscle responses vary with age and gender during fatigue due to incremental isometric exercise.

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.

Use of tissue plasminogen activator to revive blebs following intraocular surgery.

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.

Enhanced short-term plasmid transfection of filtration surgery tissues.

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.

Effect of phacoemulsification surgery on hypotony following trabeculectomy 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]

Results of another modality for extending glaucoma drainage tubes.

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.

Intraocular pressure reduction following phacoemulsification cataract extraction with posterior chamber lens implantation in glaucoma patients.

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.

Cataract surgery in the glaucoma patient: advances and modifications.

Cataract removal in the glaucoma patient is a less arduous task today than it was a decade ago, because of technological advances and modifications in surgical technique. These technological advances include excellent phacoemulsification instrumentation. Useful modifications in surgical technique include the use of combined phacotrabeculectomy with antimetabolite supplementation, when necessary. Anticipated advances in the next decade include superior viscoelastics and the widespread availability of capsular tension rings.

New aqueous inflow inhibitors.

Several new aqueous inflow inhibitors have been introduced over the past few years. These new agents include two alpha agonists, two topical carbonic anhydrase inhibitors, and a novel combination agent. All of these agent compare favorably with timolol in terms of aqueous suppression, though each has its own relative advantages and disadvantages.

Modified aqueous drainage implants in the treatment of complicated glaucomas in eyes with pre-existing episcleral bands.

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.

IL-10 and GM-CSF expression and the presence of antigen-presenting cells in chronic venous ulcers.

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.

Comparison of IL-10 levels in chronic venous insufficiency ulcers and autologous donor tissue.

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.

Treatment of bleb leaks with transforming growth factor-beta in the rabbit model.

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.

Biochemical assessment of cellular damage after adipocyte harvest.

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.

Results of intraoperative 5-fluorouracil or lower dose mitomycin-C administration on initial trabeculectomy surgery.

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.

Effects of calcium alginate on cellular wound healing processes modeled in vitro.

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.

Injection of autologous blood for bleb leaks in New Zealand white rabbits.

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.

The effects of radiation on neovascularization in a rat 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.