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Purpose: The aim of this study was to report clinical observations suggesting the efficacy of topical 1% 5-fluorouracil (5-FU) in treating Demodex -associated blepharitis., Methods: An observational retrospective review of 13 eyes from 13 individuals with conjunctival neoplastic lesions and concomitant Demodex lash infestation that received topical 1% 5-FU eye drops. Patients underwent slit-lamp examination at each follow-up visit. Clinical photographs of the lash line were obtained after treatment initiation. In a subset of patients, lashes were epilated bilaterally and microscopically analyzed for presence of Demodex mites before and after treatment initiation., Results: The mean age of the population was 68 ± 14 years (range: 30-84 years) and 92% were male. In all 13 patients, a marked reduction in cylindrical dandruff was noted in the treated eye by slit-lamp examination after 2 cycles of 5-FU. There was complete resolution of cylindrical dandruff in 10 of 13 treated eyes compared with 0 resolution of cylindrical dandruff in untreated eyes ( P = 0.0001). In the 6 patients who received epilation, the lashes from the treated eye showed no Demodex , whereas lashes from the fellow untreated eye revealed persistent Demodex ., Conclusions: Topical 1% 5-FU shows efficacy in treating Demodex -associated blepharitis. Further studies are indicated to reproduce our findings and evaluate the potential use of 5-FU as a treatment ingredient., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The benefit of loco-regional treatments such as hepatic arterial infusion (HAI) in terms of survival and response rate is unclear. The aim of this work is to quantitatively summarize the results of both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing fluoropyrimidine-HAI (F-HAI) to systemic chemotherapy (SCT) for the treatment of colorectal liver metastases (CRLMs)., Methods: We searched the Cochrane Library, PubMed, EMBASE, and Web of Science up to July 1, 2021. The outcome measures were tumor response rate and overall survival (OS). Both RCTs and NRSIs comparing HAI to SCT for patients with unresectable CRLMs were included. The outcome measures were tumor response rate and OS. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2., Results: A total of 16 studies including 11 RCTs and 5 NRSIs were identified for the present meta-analysis. Nine RCTs compared F-HAI to SCT for patients with unresectable CRLMs and the pooled result indicated that patients who received F-HAI experienced more than twofold response rate than SCT, with a pooled risk ratio of 2.10 (95%CI 1.59-2.79; P < .00001). In addition, the pooled result based on RCTs showed that F-HAI had a significant benefit regarding OS, with a pooled HR of 0.83 (95% CI 0.70-0.99; P = .04). Similarly, the benefit of F-HAI in terms of OS was also observed in the results of NRSIs., Conclusions: Our results indicated that the F-HAI regimen had a greater tumor response rate and survival advantage than SCT for patients with unresectable CRLMs. Future propensity score-matched analyses with a large sample size should be conducted to support the evidence of our results based on RCTs and NRSIs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Hyperuricemia has been epidemiologically associated with multiple comorbidities including chronic renal failure and cardiovascular disease. Cause and effect are difficult to address, given comorbidities associated with and prevalence of metabolic syndrome. One impediment to achieving serum uric acid (sUa) levels less than or equal to 6.0 mg/DL is the concept that allopurinol might be nephrotoxic. We examined the relation of sUa less than or equal to 6.0 mg/dL to renal function over time., Methods: This is a medical records review study of 348 hyperuricemia patients identified in 2015, as having been followed with serial uric acid measurements. After 1 year of serial urate levels, to allow for treatment, patient cohorts were defined: sUa less than or equal to 6.0 mg/dL and sUa greater than 6.0 mg/dL. A repeated measure model was used to test for an association between uric acid level and serum creatinine, while adjusting for covariates., Results: There was a significant difference in the least square means of serum creatinine comparing those who achieved an sUa less than or equal to 6.0 mg/dL versus sUa greater than 6.0 mg/dL (1.39 mg/dL [95% confidence interval, 1.30-1.48] vs 1.57 mg/dL [95% confidence interval, 1.46-1.69]; p = 0.0015). This is a between-group difference in creatinine of 0.18 mg/dL. If a change in serum creatinine of 0.2 is considered significant, this short-term between-group progression of renal failure approaches clinical significance., Conclusions: Given that most serial measures were within the first few years of follow-up, and change in renal function occurs slowly over time, the between group difference of sUa of 0.18 mg/dL is close to a clinically significant creatinine difference of 0.2 mg/dL.

Background: Current guideline recommendations for immunosuppression reduction after diagnosis of posttransplant lymphoproliferative disorder (PTLD) include stopping antimetabolites, reducing calcineurin inhibitors, and maintaining corticosteroids. However, the effect of immunosuppression on PTLD relapse risk after up-to-date therapy is unclear., Methods: This is a retrospective analysis of immunosuppression, patient baseline characteristics, and relapse risk measured as landmark time to progression (TTP) starting 1 year after start of therapy in 159 patients with B cell PTLD after solid organ transplantation treated in the prospective, international, multicenter PTLD-1 trials with either sequential treatment (rituximab followed by cyclophosphamide (CHOP-21 chemotherapy) 750 mg/m intravenously [IV] day (d) 1, doxorubicin 50 mg/m IV d1, vincristine 1.4 mg/m (maximum, 2 mg) IV d1, and prednisone 50 mg/m PO d1-5, every 21 days) or risk-stratified sequential treatment (rituximab followed by rituximab or rituximab (R-CHOP-21 immunochemotherapy) 375 mg/m IV day (d) 1, cyclophosphamide 750 mg/m IV d1, doxorubicin 50 mg/m IV d1, vincristine 1.4 mg/m (max. 2 mg) IV d1, and prednisone 50 mg/m PO d1-5, every 21 days)., Results: Patient baseline characteristics at diagnosis of PTLD differed significantly depending on immunosuppression before diagnosis. Compared with immunosuppression before diagnosis, significantly fewer patients received an antimetabolite or a calcineurin inhibitor (CNI) after diagnosis of PTLD. Relapse risk measured as landmark TTP was significantly higher for patients on corticosteroids compared to all others (P = 0.010) as well as for patients on ciclosporin compared with those on tacrolimus (P = 0.002), but similar for those on antimetabolites compared with all others (P = 0.912). In a Cox regression analysis of landmark TTP, corticosteroid-containing immunosuppression after diagnosis of PTLD (P = 0.002; hazard ratio, 11.195) and age (P = 0.001; hazard ratio, 1.076/year) were identified as independent, significant risk factors for PTLD relapse., Conclusions: In the prospective PTLD-1 trials, corticosteroid use after diagnosis of PTLD is associated with an increased risk of relapse, whereas the use of antimetabolites is not. These findings require prospective validation.

Background: Hyperuricemia is associated with development of gout, hypertension, and renal disease. The impact of allopurinol, a urate-lowering therapy, on renal function is unclear, especially in patients with chronic kidney disease who are at higher risk of hypersensitivity reaction., Objectives: The aim of this study was to determine the effect of allopurinol on kidney function in hyperuricemic male veterans., Methods: This is a retrospective cohort study using pharmacy, medical, and laboratory records of veterans enrolled at the Veterans Administration New York Harbor Healthcare System, Brooklyn campus. Fifty patients with hyperuricemia defined as a serum uric acid greater than 7 mg/dL (average of ~9 mg/dL), newly started on allopurinol for any reason, with evidence of treatment compliance, were matched by age, race, sex, and estimated glomerular filtration rate (EGFR) to 50 hyperuricemic control subjects. The retrospective cases were observed from October 2000 until November 2006, at which time there was a change in the laboratory analyzer, making further comparisons inappropriate., Results: On average, patients treated with a mean 221 (SD, 96) mg/d dose of allopurinol achieved 11.9 mL/min higher GFR (95% confidence interval, 4.8-11.9 mg/d dose; P = 0.01) than did the control group. Treatment effect was found to depend on the initial EGFR, as indicated by the significant treatment by initial EGFR interaction (P = 0.004) and increased with a higher initial EGFR. The allopurinol-treated group had a 0.10 mg/dL lower final creatinine level (95% confidence interval, 0.003-0.20 mg/dL; P = 0.04) than did the control subjects, adjusted for initial creatinine and age. The average length of follow-up was 3.4 years. There were 5 mild adverse events in the treated cases., Conclusions: Treatment of hyperuricemic patients with allopurinol over an average of 3.4 years resulted in a significant improvement of kidney function in this male cohort from the Veterans Administration Healthcare System. Clinicians should consider this potential benefit of allopurinol in the treatment of patients with hyperuricemia, those with overall maintained renal function.

The aim of the study was to assess the effects of bevacizumab in augmenting trabeculectomy for glaucoma. We searched the databases of Cochrane Library, PubMed, Embase, CNKI, and VIP. All the databases were retrieved from the time databases established to September, 2015. The keywords we used were as follows: "bevacizumab," "anti-VEGF," "avastin," "trabeculectomy," "glaucoma," and so on. We used a method of the freedom word search and the MeSH search combined, which was recommended by Cochrane Systematic Review Manual 5.1.2. Randomized controlled trails (RCTs) of frequently used bevacizumab in trabeculectomy for glaucoma were included. Study selection, data extraction, quality assessment, and data analysis were performed according to the Cochrane standards. Eight randomized controlled trails involving 212 eyes in the experimental (bevacizumab or bevacizumab + mitomycin C) groups and 214 eyes in the control (mitomycin C or placebo) groups were selected. Compared with placebo, bevacizumab significantly increased the complete success rate [OR = 2.79, 95%CI, (1.47, 5.29), P = 0.002], what else, bevacizumab also significantly decreased the intraocular pressure (IOP) [MD = 3.07, 95% CI, (0.87, 5.27), P = 0.006] at the 6-month after trabeculectomy and the number of antiglaucoma medications [MD = 1.23, 95% CI, (0.66, 1.80), P < 0.0001]. Additionally, it also increased the risk of bleb leak [OR = 5.24, 95% CI, (1.30, 21.10), P = 0.02]. When compared with mitomycin C (MMC), bevacizumab significantly increased the rate of encysted blebs [OR = 4.62, 95% CI, (1.02, 20.91), P = 0.05]. However, there was no significantly difference between the bevacizumab + MMC groups and MMC groups whatever the items were. Bevacizumab was an effective way in trabeculectomy concerning the complete success rate, IOP, and anti-glaucoma medications reduction when compared with placebo; however, it increased the risk of bleb leakage. And it significantly increased the rate of encysted blebs compared with MMC.

6-Mercaptopurine (6-MP) is the mainstay of treatment for acute lymphoblastic leukemia and lymphoblastic lymphoma. It is metabolized into the pharmacologically active, 6-thioguanine nucleotide (6-TGN), and 6-methyl mercaptopurine nucleotides (6-MMPN), which is associated with hepatotoxicity that jeopardizes antileukemic therapy. Allopurinol alters the metabolism of 6-MP to increase 6-TGN levels and decreases 6-methyl mercaptopurine nucleotides levels. We report 2 cases in which combination therapy of allopurinol with 6-MP was used successfully to avoid hepatotoxicity while delivering adequate 6-TGN levels. We suggest that this combination therapy can be used safely to change the metabolite production in patients who develop excessive hepatotoxicity.

The aim of this study was to compare plasma urate (PU) concentrations using two different assays in patients receiving vitamin C supplementation. PU was measured using two routinely available enzymatic uricase methods: (1) uric acid plus method (ascorbate oxidase assay), and (2) uric acid method (non-ascorbate oxidase assay). Twenty patients receiving allopurinol were randomised to an increase in allopurinol dose or commence vitamin C 500  mg/d on a 1:1 ratio. Twenty patients not receiving allopurinol were randomised to start allopurinol or vitamin C 500  mg/d on a 1:1 ratio. Trough fasting samples for plasma ascorbate and urate were measured weekly until week 8. There was no significant difference in the mean PU measured by the two assays. In patients not receiving supplemental vitamin C the mean PU concentrations were identical for both assays. For patients receiving supplemental vitamin C the mean PU concentrations for the ascorbate oxidase assay was 0.525  mmol/L (SE 0.034) and for the non-ascorbate oxidase assay 0.510  mmol/L (SE 0.033), p = 0.079.There is a small non-significant difference in measured PU in patients receiving supplemental vitamin C between the two assays. The assay which does not include ascorbate oxidase results in consistently lower PU concentrations compared to the assay which includes ascorbate oxidase.

Objectives: Autism spectrum disorders (ASDs) have core impairments in social communication as well as the presence of repetitive, stereotypic behaviors and restricted interests. Older adolescents and young adults are particularly impacted by these deficits. Preclinical data implicate glutamatergic dysfunction in the pathophysiology of ASDs. D-Cycloserine (DCS), a partial glycineB agonist at the N-methyl-D-aspartic acid receptor site, has been shown to improve sociability in mouse models and a small human study. The sensitivity of the obligatory glycineB co-agonist binding site may change with daily administration of DCS as a result of agonist-induced desensitization. The efficacy of a "pulsed" once-weekly administration versus "daily" administration of DCS was compared., Methods: Males and females, ages 14 to 25 years, with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis of an ASD were enrolled in a double-blind, randomized 10-week trial consisting of 8 weeks of active drug with either weekly or daily administration of 50 mg of DCS followed by a 2-week follow-up visit., Results: For the purposes of this study, no statistical or clinical differences existed between the 2 dosage groups on the Aberrant Behavior Checklist subscale 3, which measures stereotypies/repetitive movements. When combining groups, a statistically significant decrease of 37% was found from baseline to week 8 when study drug was completed using a linear mixed effects model (P = 0.003)., Conclusions: D-Cycloserine was shown to be effective in improving stereotypic symptoms in older adolescents and young adults with ASDs measured by the Aberrant Behavior Checklist subscale 3. In addition, DCS was safe and well tolerated.

Objective: To assess the outcome of elderly patients with primary CNS lymphoma (PCNSL) treated within the G-PCNSL-SG-1 trial., Methods: We reviewed response, toxicity, and survival of patients with PCNSL aged 70 or more enrolled in the G-PCNSL-SG-1 trial., Results: A total of 126 of the 526 eligible patients (24%) and 66 of 318 patients (21%) in the per protocol population were aged 70 or more. Among all eligible patients, the rate of complete and partial responses (CR+PR) to HD-MTX-based chemotherapy was 44% in the elderly vs 57% in the younger patients (p = 0.016). Toxicity was age-independent except for a higher rate of grade III/IV leukopenia in the elderly (34% vs 21%, p = 0.007). Death on therapy was more frequent (18% vs 11%; p = 0.027), and progression-free survival (PFS) (4.0 vs 7.7 months, p = 0.014) and overall survival (12.5 vs 26.2 months, p < 0.001) inferior, in the elderly. A striking difference between younger and elderly patients was the PFS of CR patients of 35.0 in the younger vs 16.1 in the elderly patients (p = 0.024). Elderly patients were treated less often and less aggressively at salvage. However, age was not associated with survival from salvage whole brain radiotherapy in patients progressing during primary HD-MTX-based chemotherapy (p = 0.633)., Conclusions: Lower response rate and higher mortality on HD-MTX-based chemotherapy as well as lower PFS of CR patients and less salvage therapy contribute to the poor prognosis of elderly patients with PCNSL.

Purpose: To assess the changes in the conjunctival cytology of patients given a subconjunctival injection of 5-fluorouracil (5-FU) to treat failed filtering blebs., Methods: The patients were classified into 3 groups. The first group included 15 eyes in 15 patients who were given subconjunctival injections of 5-FU after unsuccessful glaucoma surgery. The second group consisted of 15 eyes of 15 patients with primary open angle glaucoma treated with antiglaucomatous eyedrops. Twelve healthy age- and sex-matched volunteers formed the third group. Impression cytology specimens were obtained from the bulbar conjunctiva just beside the injection sites using cellulose acetate filter paper. The samples were fixed in 95% ethanol, stained with Papanicolaou stain, and evaluated under light microscopy and graded., Results: In the first group, grade 0-3 cytological changes were seen in 1 eye (6.6%), 9 eyes (60%), 4 eyes (26.6%), and 1 eye (6.6%). Apoptosis was observed in 2 eyes (13%) and nuclear atypia in 7 eyes (47%). In the second group, 9 eyes (60%) were grade 0, 4 eyes (27%) were grade 1, and 2 eyes (13%) were grade 2. Also, nuclear atypia was observed in 1 eye (6.6%). In the third group, 10 eyes (83%) were grade 0 and 2 eyes (17%) were grade 1. There was no significant difference in terms of the impression cytology grades between the groups because of small sample size., Conclusions: The use of subconjunctival 5-FU injections after glaucoma surgery may lead to squamous metaplastic changes and nuclear atypia and apoptotic cell death in the conjunctival epithelium in short-term period.

Background: Immunological demyelination is a proposed strategy to improve nerve regeneration in the peripheral nervous system. To investigate the remyelinating potential of Schwann cells in vivo in the peripheral nervous system, the authors have reproduced and expanded upon a novel model of immunological demyelination in the adult rat sciatic nerve. The authors demonstrate (1) the peripheral nervous system's quantitative, regenerative response to immunological demyelination and (2) whether Schwann cells within a region of demyelination are induced to divide in the presence of demyelinated axons., Methods: The sciatic nerves of female Sprague-Dawley rats were exposed and injected with demyelinating agent bilaterally. At 3 days (n = 3), 7 days (n = 3), and 14 days (n = 3), the animals were euthanized for histological evaluation. A second group of animals (n = 3) was similarly injected with demyelinating agent and then exposed to bromodeoxyuridine between 48 and 72 hours after the onset of demyelination. These animals were euthanized soon after the last injection of bromodeoxyuridine. The tissue was analyzed for Schwann cells (labeled with antibodies to S100) and bromodeoxyuridine assay., Results: A single epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 3 days after injection, peripheral nerve demyelination and Schwann cell proliferation were evident. Maximum demyelination was seen at 7 days; however, Schwann cell proliferation and remyelination peaked at 14 days after injection., Conclusions: These studies demonstrate an immunological model of demyelination and remyelination in the peripheral nervous system and quantitatively measure regenerative potential. This model will be used to isolate nerve segments and to measure their regenerative potential when given demyelinating agent after acute contusion and transection injuries.

Background: Cardiopulmonary bypass (CPB) is associated with pulmonary inflammation and dysfunction. This may lead to acute lung injury and acute respiratory distress syndrome with increased morbidity and mortality. The authors hypothesized that inhaled carbon monoxide before initiation of CPB would reduce inflammatory response in the lungs., Methods: In a porcine model, a beating-heart CPB was used. The animals were either randomized to a control group, to standard CPB, or to CPB plus carbon monoxide. In the latter group, lungs were ventilated with 250 ppm inhaled carbon monoxide in addition to standard ventilation before CPB. Lung tissue samples were obtained at various time points, and pulmonary cytokine levels were determined., Results: Hemodynamic parameters were largely unaffected by CPB or carbon monoxide inhalation. There were no significant differences in cytokine expression in mononuclear cells between the groups throughout the experimental time course. Compared with standard CPB animals, carbon monoxide significantly suppresses tumor necrosis factor-alpha and interleukin-1beta levels (P < 0.05) and induced the antiinflammatory cytokine interleukin 10 (P < 0.001). Carbon monoxide inhalation modulates effector caspase activity in lung tissue during CPB., Conclusions: The results demonstrate that inhaled carbon monoxide significantly reduces CPB-induced inflammation via suppression of tumor necrosis factor alpha, and interleukin-1beta expression and elevation of interleukin 10. Apoptosis induced by CPB was associated with caspase-3 activation and was significantly attenuated by carbon monoxide treatment. Based on the observations of this study, inhaled carbon monoxide could represent a potential new therapeutic modality for counteracting CPB-induced lung injury.

Purpose of Review: Current treatments for schizophrenia target the dopamine system. Developments of new treatments that target the glutamate system, however, are under progress, in particular, for the N-methyl-D-aspartate-type glutamate receptor. Compared with dopaminergic treatments, these treatments may show improved efficacy in the treatment of persistent negative symptoms., Recent Findings: During the past year, clinical trials have been published with several agonists at the glycine site of the N-methyl-D-aspartate receptor, including glycine, D-serine, D-alanine and with the glycine transport inhibitor, sarcosine. Studies published during the past year indicate highly significant beneficial effects on negative symptoms when these compounds are added to both conventional and newer atypical antipsychotics in efficacy models although an effectiveness trial of current formulations of glycine and D-cycloserine failed to show an overall benefit. Relevant issues across studies may include the compound chosen, its formulation and tolerability, populations studied, and the nature and dose of the base antipsychotic treatment., Summary: The present findings continue to support the use of N-methyl-D-aspartate/glycine site agonists as potential new treatments for persistent negative symptoms of schizophrenia. Ongoing work with novel compounds and new formulations may assist in the translation of these advances into clinic-ready pharmacotherapies.

Background: Fibroproliferative disorders, such as Dupuytren's contracture of the hand, are characterized by excessive production of collagen. 5-Fluorouracil has been used to treat fibroproliferative disorders of the eye and skin and is thought to inhibit thymidylate synthetase blocking DNA replication. 5-Fluorouracil has been shown to down-regulate fibroblast proliferation and differentiation in vitro., Methods: This study investigated the dose-dependent effect of 5-fluorouracil on fibroblast extracellular matrix production. Fibroblasts were derived from tendon and primary Dupuytren's disease of the hand, a fibroproliferative disorder of the palmar aponeurosis (n = 4 patients). Total collagen synthesis was determined by means of the incorporation of radiolabeled proline. Fibroblast secretion of the profibrotic factor transforming growth factor-beta1 (TGF-beta1) was measured by a sandwich enzyme-linked immunosorbent assay. Gene expression of collagen types I and III and TGF-beta1 were quantified by means of reverse-transcriptase polymerase chain reaction assays., Results: The authors found that 5-fluorouracil caused a dose-dependent, selective, and specific decrease in collagen production by Dupuytren's fibroblasts compared with noncollagenous protein synthesis. By contrast, procollagen types I and III mRNA were unaffected by 5-fluorouracil treatment. These changes did not appear to be mediated by alterations in the endogenous secretion of TGF-beta1 or its autocrine effect on collagen metabolism., Conclusions: The clinical implication is that 5-fluorouracil could possibly reduce extracellular matrix production and therefore reduce recurrence of Dupuytren's disease of the hand.

Objective: The effects of topical application of Mitomycin-C (MMC) and 5-fluorouracil (5-FU) for maintaining myringotomy patency were investigated in this experimental study., Study Design: We performed simple myringotomy with a knife on 140 tympanic membranes of 70 rats. Rats were divided in two study groups and a control group. Each study group had 60 tympanic membranes, and the control group had 20. We applied Mitomycin-C (0.4 mg/ml) in Group A, 5-fluorouracil (50 mg/ml) in Group B topically, and sterile saline in the control group for 10 minutes. Examination was made with otoendoscope on days 1, 3, 5, 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, and 70, and patency rates were recorded., Results: MMC and 5-FU Groups remained open for a mean of 46.17 days and 14.62 days, respectively. The control ears healed within 10.4 days. Fibrosis of the MMC-treated group was the same as that of 5-FU-treated groups. Fibrosis of both study groups was significantly lower than that of the control group., Conclusions: MMC is more effective than 5-FU, which is more effective than the simple myringotomy procedure in extending the patency of myringotomies in rat tympanic membranes (p < 0.05). Both medications are useful as an adjunct in preventing myringotomy closure.

Background: Bone loss has been reported as a complication after heart transplantation (HTx), and the increase in bone fractures is an effective problem. Treatment of osteoporosis has obtained mixed results. In this study we evaluate the effect of treatment with an oral bisphosphonate., Methods: Sixty-four patients with low mineral density 6 months after HTx were randomized as follows: Group A received oral clodronate (1600 mg/day in two divided doses), and Group B received placebo. Every patient was also treated with 2000 mg/day of oral calcium carbonate. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at the lumbar spine, 1/3 and 1/10 of the distal nondominant forearm before and after 12 months of treatment. Laboratory tests were performed at 3, 6, and 12 months of treatment., Results: All patients demonstrated manifest bone loss 6 months after HTx compared with normal non-HTx controls (P=0.0001). After 1 year of clodronate therapy, BMD at the lumbar spine increased from 0.77+/-1.4 g/cm(2) to 0.86 g/cm(2) (P=0.02). Laboratory tests did not show any significant variation, except for the bone isoenzyme of alkaline phosphatase, which showed a significant decrease after 1 year of treatment. The incidence of new fractures was 9.3% in the placebo group and 0% in the clodronate group. Therapy was well tolerated without impact on graft function., Conclusions: One year of clodronate therapy induced a significant increase in BMD at the lumbar spine in our HTx patients. Treatment was well tolerated without onset of new bone fractures.

The healing process after glaucoma filtration is the main determinant of surgical failure and, even more important, the final intraocular pressure. The ability to fully control wound healing may ultimately give us the ability to set the intraocular pressure in the low teens for all patients undergoing glaucoma filtration surgery. The authors review the changes in how to use antimetabolites to improve safety, and many of the exciting new areas of progress, including growth factor neutralization and future molecular therapies to control wound healing.

Leaking blebs may be encountered in the early postoperative period, or months to years after filtering surgery. Early postoperative bleb leaks are most often related to surgical trauma to the conjunctiva and can be avoided by careful surgical technique. Spontaneous late bleb leaks occur more frequently in glaucoma filtering surgery following adjunctive use of antimetabolites and full-thickness procedures. As we endeavor to achieve better long-term success with filtering surgery, antimetabolites have gained increasing popularity. With this change in clinical practice, a higher rate of bleb leaks is being recognized. These leaks may be uncomplicated or may be associated with sight-threatening complications such as endophthalmitis. The plethora of treatment options for bleb leaks described in the literature reflects the widespread nature of this problem. It also reflects the failure of any one particular approach not only to resolve bleb leaks but also to prevent their recurrence. This paper reviews the contemporary surgical management of leaking blebs and formulates a practical approach to their management.

Using an animal model, the effect of a single intraoperative application of 5-fluorouracil on digital flexor tendon adhesions was assessed. After a standard partial division of the tendon and immobilization with a stitch, the synovial sheath in 30 rabbit tendons was treated with 5-fluorouracil solution (50 mg/ml)-soaked sponge pledgets for 5 minutes. Buffered saline was substituted for 5-fluorouracil in 30 control tendons. The tendons were harvested 1 week postoperatively, and histologic sections were assessed with a light microscope. There was a significant reduction in synovial sheath thickening (p < 0.001), cell counts (p < 0.001) and proportional length of adhesions (p < 0.001) in the treated tendons. The reduction in synovial reaction and adhesion formation using this "one touch" technique presents a novel strategy for the management of the clinical problem of postoperative adhesions complicating tendon injury and repair.

The efficacy of combined surgery for the treatment of concurrent glaucoma and cataract has long been under scrutiny. Comparisons between sequential surgery and combined procedures have shown mixed results, and current guidelines have been drawn for the indication of combined surgery. The evolution of combined triple surgery--cataract extraction, intraocular lens implantation, and filtering procedure--has evolved from planned extracapsular cataract extraction to small-incision phacoemulsification. The improvements of phacoemulsification over extracapsular surgery have naturally given rise to improvements in the results of combined procedures; good outcomes in both intraocular pressure control and visual acuity have been reported along with low complication rates. The techniques of combined phacoemulsification-trabeculectomy are under continual development as new sutureless incisions, filtration procedures, and antimetabolite use are studied. The results of numerous studies show that the combined procedure is an effective method of treatment of glaucoma and cataract. This review examines various recent aspects of the combined procedure, phacoemulsification-trabeculectomy, antimetabolites, results and complications, as well as current developments of new techniques. In addition, we review studies on combined cataract extraction and trabeculectomy, including older literature on planned extracapsular extraction plus trabeculectomy as well as newer studies on phacoemulsification-trabeculectomy.

The refinements of small incision cataract surgery by phacoemulsification with foldable intraocular lens implantation and the pharmacologic modulation of wound healing have brought new options for the combined procedure. Phacoemulsification combined with filtering surgery has the potential advantage of requiring a smaller conjunctival and scleral incision, which may reduce inflammation and bleb scarring with the possibility of enhanced bleb formation and long-term intraocular pressure control. The smaller phacoemulsification incision also helps to reduce postoperative astigmatism and improve visual results. Following combined phacoemulsification and filtering surgery, a larger area of undisturbed or virginal tissue in the conjunctiva and at the limbus is spared for further glaucoma surgeries or revision if the initial procedure fails. The risk of suprachoroidal hemorrhage during phacoemulsification in this susceptible group of patients is minimized by maintaining a closed chamber during the procedure.

Combined phacoemulsification and trabeculectomy has become a common procedure in the management of coincident cataract and glaucoma. As the medical options to treat glaucoma continue to improve, more patients may not require surgical intervention until the time of cataract extraction. Current techniques using small-incision phacoemulsification and trabeculectomy with antimetabolites have vastly improved the results of combined glaucoma surgery. This article discusses many of the important issues as they relate to this subject. This is not a comprehensive review, but rather a discussion of the literature in the scanning period of this issue.

After injury, adhesions may develop between the digital flexor tendons and their sheaths. Fibroblasts are key cells in this fibrotic adhesive process, and two possible sources for these cells are the synovial sheath and the endotenon tissue (tendon core). Fibroblasts seeded into a collagen lattice will contract the collagen. This fibroblast-populated collagen lattice contraction was used to investigate the ability of the fibroblasts from the synovial sheath and endotenon to reorganize collagen (an important function in the formation of adhesions). Endotenon and synovial fibroblasts isolated from 30 animals were used in the study. Synovial fibroblasts produced significantly greater collagen lattice contraction compared with endotenon fibroblasts (p < 0.05). The possibility of preventing collagen lattice contraction with a single, nontoxic 5-minute treatment of the fibroblast-populated collagen lattices with the antimetabolite 5-fluorouracil was investigated. Compared with controls the degree of fibroblast-populated collagen lattice contraction was significantly inhibited (p < 0.05) with the use of 5-fluorouracil for endotenon and synovial cells. These results demonstrate the potential for locally targeted therapy in tendon healing. Because of the different contractile properties of the two cell lines, a change in the balance between intrinsic and extrinsic healing might be achieved with this method of therapy; in turn, this might lead to better functional results following surgery.