Effect of a combination of nitazoxanide, ribavirin, and ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-19.

This trial compared the rate and time of viral clearance in subjects receiving a combination of nitazoxanide, ribavirin, and ivermectin plus Zinc versus those receiving supportive treatment. This non-randomized controlled trial included 62 patients on the triple combination treatment versus 51 age- and sex-matched patients on routine supportive treatment. all of them confirmed cases by positive reverse-transcription polymerase chain reaction of a nasopharyngeal swab. Trial results showed that the clearance rates were 0% and 58.1% on the 7th day and 13.7% and 73.1% on the 15th day in the supportive treatment and combined antiviral groups, respectively. The cumulative clearance rates on the 15th day are 13.7% and 88.7% in the supportive treatment and combined antiviral groups, respectively. This trial concluded by stating that the combined use of nitazoxanide, ribavirin, and ivermectin plus zinc supplement effectively cleared the SARS-COV2 from the nasopharynx in a shorter time than symptomatic therapy.

Design of polysaccharidic nano-in-micro soft agglomerates as primary oral drug delivery vehicle for colon-specific targeting.

Microencapsulation of polysaccharidic nanoparticles is met with nanoscale and biological performance changes. This study designs soft agglomerates as nanoparticle vehicle without nanoparticles undergoing physical processes that alter their geometry. The nanoparticles were made of high molecular weight chitosan/pectin with covalent 5-fluorouracil/folate. Nanoparticle aggregation vehicle was prepared from low molecular weight chitosan. The nanoparticles and aggregation vehicle were blended in specific weight ratios to produce soft agglomerates. Nanoparticles alone are unable to agglomerate. Adding aggregation vehicle (< 2 µm) promoted soft agglomeration with nanoparticles deposited onto its surfaces with minimal binary coalescence. The large and rough-surfaced aggregation vehicle promoted nanoparticles deposition and agglomeration. A rounder vehicle allowed assembly of nanoparticles-on-aggregation vehicle into agglomerates through interspersing smaller between larger populations. Soft agglomeration reduced early drug release, and was responsive to intracapsular sodium alginate coat to further sustain drug release. The soft agglomerates can serve as a primary oral colon-specific vehicle.

Outcomes of Combined Ahmed Glaucoma Valve and Trabeculectomy Revision With Adjunctive Antimetabolite.

PURPOSE: Evaluate the intraocular pressure (IOP) control in combined Ahmed Glaucoma Valve (AGV) implantation and trabeculectomy revision with adjunctive antimetabolite compared with AGV alone in patients who failed prior trabeculectomy. METHODS: Consecutive cases of combined AGV implantation and trabeculectomy revision with adjunctive antimetabolite (combined group) after January 3, 2014 were case-matched to cases of AGV implantation alone (AGV-alone group) before January 3, 2014. Primary outcome measures were qualified success with stratified IOP targets based on criteria: (A) IOP≤18 mm Hg and 20% IOP reduction; (B) IOP≤15 mm Hg and 25% IOP reduction; (C) IOP≤12 mm Hg and 30% IOP reduction, and hypertensive phase (HP) rate. Secondary outcome measures were 1-year postoperative IOP and number of glaucoma medications and complications. RESULTS: Twenty eyes (20 patients) in each group were included. Cumulative success for combined group and AGV-alone group at 1-year were: 74.0% versus 59.2% (criterion A, P=0.221), 61.9% versus 49.5% (B, P=0.183), and 54.2% versus 30.0% (C, P=0.033), respectively. In total, 50% (10 eyes) in the AGV-alone group developed HP compared with 15% (3 eyes) in the combined group (P=0.041). At 1-year follow-up, combined group had statistically significantly lower IOP than AGV-alone group (10.1±4.4, 13.3±2.9 mm Hg, respectively; P=0.028). There were no cases of bleb-related infections, choroidal effusion or hemorrhage, persistent hypotony, or hypotony maculopathy in either group. CONCLUSIONS: Combining AGV implantation with trabeculectomy revision with antimetabolite was associated with better tonometric success compared with AGV implantation alone in patients with previously failed trabeculectomy, particularly when a low IOP target (≤12 mm Hg) is required. Revised trabeculectomy may provide complimentary outflow facility to AGV.

The combination use of 1-O-acetylbritannilactone (ABL) and gemcitabine inhibits cell growth and induces cell apoptosis in lung adenocarcinoma cells.

1-O-acetylbritannilactone (ABL), a natural chemical component obtained from Chinese traditional medicine, Inula britannica, has been demonstrated to have anticancer activities. In the present study, we evaluated the anti-proliferative and the pro-apoptotic abilities of ABL alone or in combination with gemcitabine in human NSCLC cell line. A549 cells were treated, in vitro, with ABL, gemcitabine, and the combination of ABL and gemcitabine for 72 h. Our results showed ABL and gemcitabine inhibited cell growth and induced apoptosis of A549 cells. These effects after the combination of ABL and gemcitabine were superior to those of each alone. Furthermore, signal transduction analysis revealed NF-κB expression was significantly decreased by ABL and the combination treatment. IκBα and Bax levels were up regulated whereas Bcl-2 was substantially downregulated after all treatments. Our findings suggest that ABL combined with gemcitabine elicits a potent apoptosis of lung cancer cell and hence ABL has the potential to be developed as a chemotherapeutic agent.

Increased Systemic Exposure of Methotrexate by a Polyphenol-Rich Herb via Modulation on Efflux Transporters Multidrug Resistance-Associated Protein 2 and Breast Cancer Resistance Protein.

Scutellariae radix (SR, roots of Scutellaria baicalensis Georgi), a popular Chinese medicine, contains plenty of flavonoids such as baicalin, wogonoside, baicalein, and wogonin. Methotrexate (MTX), an important immunosuppressant with a narrow therapeutic index, is a substrate of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). This study investigated the effect of SR on MTX pharmacokinetics and the underlying mechanisms. Rats were orally administered MTX alone and with 1.0 or 2.0 g/kg of SR. The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. Cell models were used to explore the involvement of MRP2 and BCRP in the interaction. The results showed that 1.0 g/kg of SR significantly increased Cmax, AUC(0-30), AUC(0-2880), and mean residence time (MRT) of MTX by 50%, 45%, 501%, and 347%, respectively, and 2.0 g/kg of SR significantly enhanced the AUC(0-2880) and MRT by 242% and 293%, respectively, but decreased AUC(0-30) by 41%. Cell line studies indicated that SR activated the BCRP-mediated efflux transport, whereas the serum metabolites of SR inhibited both the BCRP- and MRP2-mediated efflux transports. In conclusion, SR ingestion increased the systemic exposure and MRT of MTX via modulation on MRP2 and BCRP.

Keloids and Hypertrophic Scars: A Spectrum of Clinical Challenges.

Since their earliest description, keloids and hypertrophic scars have beleaguered patients and clinicians alike. These scars can be aesthetically disfiguring, functionally debilitating, emotionally distressing, and psychologically damaging, culminating in a significant burden for patients. Our current understanding of keloid pathophysiology has grown and continues to advance while molecular biology, genetics, and technology provide ever-deepening insight into the nature of wound healing and the pathologic perturbations thereof. Greater understanding will lead to the development and application of refined therapeutic modalities. This article provides an overview of our current understanding of keloids, highlighting clinical characteristics and diagnostic criteria while providing a comprehensive summary of the many therapeutic modalities available. The proposed mechanism, application, adverse events, and reported efficacy of each modality is evaluated, and current recommendations are summarized.

Needle Revision With 5-fluorouracil for the Treatment of Ahmed Glaucoma Valve Filtering Blebs: 5-Fluoruracil Needling Revision can be a Useful and Safe Tool in the Management of Failing Ahmed Glaucoma Valve Filtering Blebs.

PURPOSE: To determine the outcome of needling with adjunctive 5-fluorouracil (5-FU) in patients with a failing Ahmed glaucoma valve (AGV) implant, and to identify predictors of long-term intraocular pressure (IOP) control. METHODS: A prospective observational study was performed on consecutive patients with medically uncontrolled primary open-angle glaucoma (POAG) with AGV encapsulation or fibrosis and inadequate IOP control. Bleb needling with 5-FU injection (0.1 mL of 50 mg/mL) was performed at the slit-lamp. Patients were examined 1 week following the needling, and then at months 1, 3, and 6. Subsequent follow-up visits were scheduled at 6-month intervals for at least 2 years. Needling with 5-FU was repeated no more than twice during the first 3 months of the follow-up. Procedure outcome was determined on the basis of the recorded IOP levels. RESULTS: Thirty-six patients with an encapsulated or fibrotic AGV underwent 67procedures (mean 1.86 ± 0.83). Complete success, defined as IOP ≤ 18 mm Hg without medications, was obtained in 25% at 24 months of observation. The cumulative proportion of cases achieving either qualified (ie, IOP ≤ 18 mm Hg with medications) or complete success at 24 months of observation was 72.2%. In a univariate Cox proportional hazards model, age was the only variable that independently influenced the risk of failing 5-FU needling revision. Fourteen eyes (38.8%) had a documented complication. CONCLUSIONS: Needling over the plate of an AGV supplemented with 5-FU is an effective and safe choice in a significant proportion of POAG patients with elevated IOP due to encapsulation or fibrosis.

Carbon dioxide laser plus topical 5-fluorouracil: a new combination therapeutic modality for acral vitiligo.

BACKGROUND: Acral vitiligo (AV) is resistant to treatment. AIM: To evaluate efficacy and safety of combining carbon dioxide (CO2) laser and 5-fluorouracil (5FU) in treating AV. METHODS: This study included 68 adult patients with AV. After randomly assigning patients into 3 groups, patients in group I were treated using 5FU, group II were treated using CO2 laser, and group III were treated using CO2 laser followed by 5FU for a maximum period of 5 months. The lesions were then evaluated both qualitatively and quantitatively. RESULTS: Almost half (49.8%) of the lesions in group III achieved G4, and 6.1% of lesions achieved G3 re-pigmentation. This response was statistically significantly higher than that in the other two groups. This was not achieved in periungual areas in the hands and feet. The pain was tolerable during sessions or at sites of 5FU application. Transient hyperpigmentation, brownish spot on nail plates, itching, and infection were temporary side effects; however, Koebnerization was not detected. CONCLUSION: We concluded that prior use of CO2 laser skin ablation, followed by 5FU application for AV is a safe and tolerable technique that improves the outcome and increases patient compliance.

Comparison of two plasma urate assays in patients receiving vitamin C supplementation.

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.

Cross talk between angiotensin-(1-7)/Mas axis and sirtuins in adipose tissue and metabolism of high-fat feed mice.

Angiotensin-(1-7) and resveratrol have been described as new potential therapeutic tools on treating and preventing metabolic disorders. In the present study we aimed to evaluate the effect of an oral formulation of angiotensin-(1-7) [Ang-(1-7)] included in HPB-cyclodextrin and resveratrol (RSV), in modulation of sirtuin and renin-angiotensin system (RAS) in adipose tissue of mice treated with a high-fat diet (HFD). We observed that HFD+Ang-(1-7) and HFD+RSV groups presented marked decrease in the adipose tissue mass. Furthermore, these animals showed improved insulin-sensitivity and glucose tolerance as well as lower plasma levels of fasting glucose and lipids. The RT-PCR analysis revealed decreased expression of ACE and an increase of ACE2 [Ang-(1-7) marker] in group treated with resveratrol and also an increased expression of SIRT1 in groups that received Ang-(1-7). We showed for the first time that improved metabolic profile is associated with increased expression of GLUT4 and high expression of AMPK/FOXO1/PPAR-γ pathway in adipose-tissue. Finally, adipocyte primary cell-culture incubated with and without sirtuin and Ang-(1-7)/Mas antagonists pointed out for a cross-talking between RAS and sirtuins. We conclude that oral administration of Ang-(1-7) and RSV improved metabolic profile through a cross-modulation between RAS and Sirtuins.

Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments.

PURPOSE: It is advantageous to individualize high-dose methotrexate (HDMTX) to maintain adequate exposure while minimizing toxicities. Previously, we accomplished this through within-course dose adjustments. METHODS: In this study, we evaluated a strategy to individualize HDMTX based on clearance of each individual's previous course of HDMTX in 485 patients with newly diagnosed acute lymphoblastic leukemia. Doses were individualized to achieve a steady-state plasma concentration (Cpss) of 33 or 65 µM (approximately 2.5 or 5 g/m(2)/day) for low- and standard-/high-risk patients, respectively. RESULTS: Individualized doses resulted in 70 and 63 % of courses being within 20 % of the targeted Cpss in the low- and standard-/high-risk arms, respectively, compared to 60 % (p < 0.001) and 61 % (p = 0.43) with conventionally dosed therapy. Only 1.3 % of the individualized courses in the standard-/high-risk arm had a Cpss greater than 50 % above the target compared to 7.3 % (p < 0.001) in conventionally dosed therapy. We observed a low rate (8.5 % of courses) of grade 3-4 toxicities. The odds of gastrointestinal toxicity were related to methotrexate plasma concentrations in both the low (p = 0.021)- and standard-/high-risk groups (p = 0.003). CONCLUSIONS: Individualizing HDMTX based on the clearance from the prior course resulted in fewer extreme Cpss values and less delayed excretion compared to conventional dosing.

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats. METHODS: Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. RESULTS: Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats. CONCLUSIONS: These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.

Comparison of the use of 5-fluorouracil and bevacizumab in primary trabeculectomy: results at 1 year.

BACKGROUND: The present study compared the effects of adjuvant bevacizumab and 5-fluorouracil on the efficacy and safety of trabeculectomy. DESIGN: A nonrandomized, prospective, interventional case study. PARTICIPANTS: A total of 62 patients in two groups undergoing primary trabeculectomy. METHODS: In Group 1 (21 primary open-angle glaucoma, nine pseudoexfoliative glaucoma), trabeculectomy was performed with an adjuvant 5% solution of 5-fluorouracil administered for 4 min, intraoperatively. In Group 2 (21 primary open-angle glaucoma, 11 pseudoexfoliative glaucoma), trabeculectomy was enhanced with 1.25 mg of bevacizumab applied subconjunctivally immediately before and after surgery and again 1 and 7 days after surgery. MAIN OUTCOME MEASURES: Intraocular pressure, best corrected visual acuity, visual field index, bleb morphology, cornel endothelial cell count. RESULTS: Mean intraocular pressure was 28.0 ± 8.0 mmHg before 5-fluorouracil-augmented trabeculectomy and 27.8 ± 9.5 mmHg before bevacizumab-augmented trabeculectomy. After 12 months, mean intraocular pressure was 13.6 ± 4.4 mmHg in the 5-fluorouracil group and 14.7 ± 4.7 mmHg in the bevacizumab group. A 30% reduction of initial intraocular pressure was attained in 86.7% of patients in the 5-fluorouracil group and 78.1% of patients in the bevacizumab group at the end of follow up. No significant differences were noted between the two studied groups with respect to corneal endothelial density, visual field indices and postoperative complications. CONCLUSIONS: The 12-month intraocular pressure results showed no significant differences between the two groups of patients after bevacizumab or 5-fluorouracil to augment trabeculectomy. However, to obtain successful intraocular pressure control more patients in bevacizumab group needed medical therapy.

Exacerbation of hereditary warfarin resistance by azathioprine.

A 39-year-old Afro-Caribbean man with Crohn disease with recurrent deep vein thromboses and pulmonary emboli was commenced on lifelong warfarin treatment. The patient required high-dose warfarin (>140 mg/wk), which increased further during azathioprine treatment. Cessation of azathioprine resulted in an increase in the international normalized ratio (INR). Mutation analysis identified a Val66Met substitution in vitamin K epoxide reductase complex subunit 1 (VKORC1), consistent with severe warfarin resistance. This report is the first presentation where the patient had a defined hereditary resistance to warfarin, which was aggravated by concomitant azathioprine. It is important for clinicians to be aware of the interaction between warfarin and azathioprine, to monitor clinical response closely, and to manage the doses of both drugs accordingly.

Age dependence of oval cell responses and bile duct carcinomas in male fischer 344 rats fed a cyclic choline-deficient, ethionine-supplemented diet.

UNLABELLED: The age dependence of the oval cell response and bile duct carcinomas of male F344 rats exposed to a cyclic choline deficiency-ethionine (CDE) diet (2 weeks on, 1 week off) supports the concept of loss of potential of liver stem cells to form cancers with aging. Livers of rats exposed at 3 weeks of age demonstrated a robust and widespread oval cell proliferation followed by cholangiofibrosis and bile duct metaplasia with extensive mucinous cysts throughout all lobes, and induction of cholangiocarcinomas (CCAs) in seven of eight rats. Livers of rats exposed beginning at 8 weeks of age had much less oval cell response and cholangiofibrosis with only 1 of 15 rats developing a CCA. Livers in old (10-12 months when started) rats remained virtually unaffected, with minimal oval cell proliferation, only occasional and small foci of ductular dysplasia, and none of 16 rats developed CCAs. In contrast to most published studies using uninterrupted choline deficiency plus a carcinogen, hepatocellular carcinoma (HCC) was not observed under the conditions of this study. CONCLUSION: With aging, male F344 rats exposed to cyclic CDE diet display a diminished oval cell response and fewer CCAs. The absence of HCC is possibly due to the fact that during cyclic CDE, the week off may allow putative liver stem cells to avoid death or differentiation and survive to give rise to CCAs, whereas with continuous CDE exposure, the stem cells are forced to differentiate and develop into HCCs with relatively few CCAs.

Ultrasound biomicroscopy in nonperforating filtering surgery with intraoperative 5-fluorouracil and no implant: long-term results.

PURPOSE: To evaluate the long-term morphologic changes in the anterior segment structures after nonpenetrating filtering surgery (NPFS) supplemented with 5-fluorouracil (5-FU) and no scleral implant using ultrasound biomicroscopy (UBM). METHODS: Thirteen eyes of 13 consecutive patients who underwent NPFS with intraoperative 5-FU under the conjunctiva and the scleral flap and no implant were evaluated in an observational nonrandomized, consecutive case series study conducted 2 years postoperatively. Patients were assessed for the presence of a subconjunctival filtering bleb, the volume of an intrascleral cavity, and a suprachoroidal hypoechoic area. The intraocular pressure(IOP) was measured preoperatively and postoperatively at the time of UBM. RESULTS: The IOP decreased significantly (p=0.01) from 24-/+7.6 mmHg to 13.7-/+4.1 mmHg. In most patients (69.2%), the postoperative IOP decreased at least 30% from the preoperative value without medications and in 84.6% with medication. UBM showed a subconjunctival empty space in 92.3% of eyes. In 84.6% of patients, an intrascleral cavity was seen, the mean volume of which was 1.68 mm(3) (range, 0-4.07). We found a negative correlation between the height, width, and volume of the intrascleral lake and the IOP. In 92.3% of eyes, a hypoechoic area in the suprachoroidal space also was seen. CONCLUSIONS: UBM showed a filtering intrascleral cavity, subconjunctival filtering bleb, and a suprachoroidal space after NPFS supplemented with 5-FU under the conjunctiva and the scleral flap without an implant.

Expression of extracellular matrix genes in cultured hepatic oval cells: an origin of hepatic stellate cells through transforming growth factor beta?

BACKGROUND: Hepatic oval cells, progenitor cells in the liver, can differentiate into hepatocytes and bile duct cells both in vitro and in vivo. Although hepatic stellate cells are another important cell component in the liver, less attention has been focused on the relationship between hepatic oval cells and hepatic stellate cells. METHODS: Hepatic oval cells were isolated from rats fed a choline-deficient diet supplemented with 0.1% ethionine for 6 weeks and characterized by electron microscopy, flow cytometry, reverse transcription polymerase chain reaction, Western blot and bi-direction differentiation. After treatment with transforming growth factor-beta1 (TGF-beta1), changes in cell viability, morphology, extracellular matrix (ECM) expression and immune phenotype were analysed in these cultured and adherent hepatic oval cells. RESULTS: The primary cultured hepatic oval cells were positive for the oval cell-specific markers OV-6, BD-1/BD-2 and M2PK as well as the hepatocyte markers albumin and alpha-foetoprotein. These hepatic oval cells differentiated bipotentially into hepatocytes or bile duct-like cells under appropriate conditions. It is noteworthy that these bipotential hepatic oval cells expressed ECM genes stably, including collagens, matrix metalloproteinases and tissue inhibitor of mellatoproteinase. Furthermore, except for growth inhibition and morphological changes in the hepatic oval cells after exposure to TGF-beta1, there was an increased expression of ECM genes, the onset expression of snail and loss expression of E-cadherin. During this process, TGF-beta1 treatment induced an upregulation of marker genes for hepatic stellate cells in hepatic oval cells, such as desmin and GFAP. CONCLUSION: Except for the expression of ECM, the cultured hepatic oval cells could induce an increased expression of hepatic stellate cell markers by TGF-beta1 through an epithelial-mesenchymal transition process, which might indicate the contribution of hepatic oval cells to liver fibrosis.

Endogenous cortisol suppression with metyrapone enhances acoustic startle in healthy subjects.

Previous human studies have shown that excess cortisol sufficient to fully occupy central nervous system (CNS) corticosteroid receptors may reduce startle eye blink. The present study tested whether cortisol depletion and the resulting reduction in activity of CNS corticosteroid receptors has the opposite effect. In a single-blind, placebo-controlled, randomized study, eye blink EMG responses to 105 dB acoustic startle stimuli were assessed in 25 healthy subjects who received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. As expected, metyrapone significantly reduced salivary cortisol, indicating effective endogenous cortisol suppression. Startle eye blink responses were significantly increased in the metyrapone group. Short-term habituation of the startle reflex was not different between groups. Our results suggest that startle is enhanced during depletion of cortisol. This effect may be mediated by CNS mechanisms controlling cortisol feedback.

Long-term comparison of primary trabeculectomy with 5-fluorouracil versus mitomycin C in West Africa.

PURPOSE: To compare the long-term efficacy and safety of intraoperative 5-fluorouracil (5-FU) versus mitomycin-C (MMC) used adjunctively with primary trabeculectomy in a Black West African population. DESIGN: Retrospective comparative study supplemented with cross-sectional follow-up data. METHODS: Review of 68 eyes of 68 Black West African subjects that underwent primary trabeculectomy with the use of intraoperative 5-FU or MMC between January 1, 1988 and January 1, 2002 and had at least 3 years postoperative follow-up. Postoperative outcome measures included intraocular pressure (IOP) control, number of glaucoma medications, visual acuity, and complications. RESULTS: Thirty-eight of sixty-eight eyes received 5-FU and 30 received MMC. Mean postoperative follow-up was 7.5 and 6.5 years in the 5-FU and MMC groups, respectively (P=0.17). A higher proportion of eyes in the MMC group achieved "qualified" (with or without medical therapy) success with varying IOP targets relative to the 5-FU group, but the differences were not statistically significant. "Complete" (without medical therapy) postoperative success was greater in the MMC group with a significantly higher proportion achieving an IOP <21 mm Hg (P=0.02). MMC use was also associated with a lower likelihood of receiving IOP-lowering medications postoperatively (P=0.01). Baseline demographic characteristics, preoperative and postoperative IOP, visual acuity, and complications did not differ significantly between the 2 groups. CONCLUSIONS: Intraoperative MMC use is associated with a lower likelihood of requiring postoperative medications and a greater likelihood of achieving IOP lowering without medications relative to the use of 5-FU in a Black West African population.

Review of consecutive phacotrabeculectomies supplemented with early needle revision and antimetabolites.

BACKGROUND: To describe the results of a novel postoperative management approach for patients undergoing combined cataract and glaucoma surgery supplemented with early needle revision and antimetabolites. METHODS: Consecutive retrospective chart review identified 66 patients who had undergone combined cataract and glaucoma surgery with early needling and antimetabolite injections between January 2002 and May 2003; 8 patients were excluded from analysis because of missing data or inadequate follow-up time. Single-site phacotrabeculectomy was performed followed by subconjunctival antimetabolite injections of 5-fluorouracil (5-FU). Needling was performed as an office procedure if early evidence of subconjunctival scarring was observed 2-6 weeks after surgery. Additional subconjunctival 5-FU injections were administered after needling, and repeat needling was performed with 5-FU or mitomycin-C if subconjunctival scarring recurred. A complete success was defined as a reduction in intraocular pressure (IOP) to <18 mm Hg without the use of antiglaucoma medications or further surgical procedures to control IOP. The outcome was considered a qualified success when antiglaucoma medications were required to achieve the same result. RESULTS: The mean preoperative IOP was 21.9 (SD 6.3) mm Hg, and the mean postoperative IOP at 6 months was 13.0 (SD 6.7) mm Hg. The mean number of medications was reduced from 2.9 (SD 1.3) preoperatively to 0.5 (SD 0.9) postoperatively at 6 months. Needling was performed because of early evidence of subconjunctival scarring in 34 patients. The 6-month outcomes of 37 patients (64%) were a complete success and of 47 patients (81%) were a complete or qualified success. A longer follow-up of 10-23 months was attained in 25 of the 58 patients. At latest visit, the mean postoperative IOP of this group was 13.0 (SD 5.5) mm Hg, the mean number of postoperative medications was 0.7 (SD 1), and 21 of the 25 (84%) had achieved a complete or qualified success. The most common complication for all 58 patients was an early, self-limited postoperative wound leak that was unrelated to the needling intervention and was observed in 26 patients (45%). INTERPRETATION: Phacotrabeculectomy supplemented with early needle revision and antimetabolites may improve outcomes of combined cataract and glaucoma surgery.