Ocular hypotensive effect of fixed-combination brinzolamide/brimonidine adjunctive to a prostaglandin analog: a randomized clinical trial.

PurposeTo determine whether intraocular pressure (IOP) lowering with fixed-combination brinzolamide/brimonidine (BBFC) adjunctive to a prostaglandin analog (PGA) was superior to that of vehicle+PGA in patients with open-angle glaucoma or ocular hypertension who were inadequately controlled with PGA monotherapyMethodsThis 6-week, multicenter, randomized, double-masked, parallel-group trial was conducted at 30 clinical sites in the United States between October 2013 and May 2014. Eligible patients were adults with open-angle glaucoma or ocular hypertension and with mean IOP ≥21 and <32 mm Hg, whereas receiving an open-label PGA (latanoprost, bimatoprost, or travoprost). Patients instilled a PGA once-daily in a run-in phase before randomization to masked BBFC or vehicle adjunctive treatment. Masked treatments were instilled 3 times daily for 6 weeks, and patients continued once-daily use of their PGA. The primary efficacy end point was the between-group difference in mean diurnal IOP (average of 0800, 1000, 1500, and 1700 hours time points) at week 6.ResultsAt week 6, mean diurnal IOP with BBFC+PGA was lower than with vehicle+PGA (17.1±0.4 mm Hg vs 20.5±0.4 mm Hg; between-group difference, -3.4±0.5 mm Hg; P<0.0001; 95% confidence interval, -4.5 to -2.4 mm Hg). BBFC+PGA reduced mean diurnal IOP by 5.7 mm Hg (25%) from the baseline IOP achieved with PGA monotherapy.ConclusionsTherapy with BBFC produced an additive IOP-lowering effect compared with a PGA alone or in conjunction with vehicle. BBFC may provide an effective treatment option for patients receiving PGA monotherapy who require additional IOP reduction.

Laser energy reaching the posterior pole during transscleral cyclophotocoagulation.

OBJECTIVE: To measure scattered laser energy reaching the posterior pole during transscleral cyclophotocoagulation. METHODS: Transscleral cyclophotocoagulation was performed on 4 cadaver eyes with Nd:YAG noncontact, Nd:YAG contact, and diode contact lasers. Energy was measured with a photodiode through a 7-mm trephined hole in the posterior pole. Average percentage power, average power, and average energy transmission were calculated. American Conference of Governmental Industrial Hygienists (ACGIH) guidelines were used to calculate allowable energy exposures for each laser. RESULTS: All 3 lasers transmitted 3% to 5% of the power to the posterior pole. The average energy transmission was 240 to 260 mJ for all lasers. The contact lasers had an average power transmission of 120 mW. The noncontact Nd:YAG laser, with shorter pulse duration, had an average power transmission of 13,000 mW, significantly greater than that of the other lasers. The ACGIH guidelines for allowable energy exposures were 93 mJ for the noncontact Nd:YAG laser, 1300 mJ for the contact Nd:YAG laser, and 440 mJ for the contact diode laser. CONCLUSIONS: Three percent to 5% of laser power delivered during cyclophotocoagulation reaches the posterior pole. Exposure energies may approach or exceed ACGIH guidelines. The clinical significance of these findings remains to be shown.

Complementary and alternative medicine for glaucoma.

Given the recent interest in complementary and alternative medicine (CAM), some patients may seek such treatments to supplement their traditional glaucoma management. The prevalence of CAM use for glaucoma is approximately 5%. We reviewed the literature to determine the potential benefit of various alternative treatments. Aside from a temporary osmotic effect from high dose intravenous ascorbic acid, there is no evidence that megavitamin supplementation has a beneficial effect on glaucoma. During exercise, autoregulation in healthy eyes seems to maintain a consistent blood flow rate to the optic nerve despite fluctuations in intraocular pressure (IOP). In a glaucomatous eye, the very modest IOP-lowering that follows exercise may be offset by the initial elevation in IOP that occurs when one first initiates exercise. At this time, there is no evidence to encourage or discourage the use of special diets, acupuncture, relaxation techniques, or therapeutic touch specifically for the treatment of glaucoma. Very little research has been done on the majority of herbal remedies with regard to their treatment of glaucoma. Marijuana can cause a profound lowering of IOP, but the high nonresponse rate, short half life, and significant toxicity are strong indicators that it is not an appropriate therapeutic agent. Ginkgo biloba and some other Chinese herbal remedies do not affect IOP, but may improve blood flow to the optic nerve and, as such, may have a beneficial effect on glaucoma. These agents have recognized toxicities. Although there are some well-designed studies of alternative treatments, many of the recommendations for using alternative treatments are currently unsupported by the data provided.

Use of latanoprost in the treatment of glaucoma associated with Sturge-Weber syndrome.

PURPOSE: To determine if latanoprost reduces intraocular pressure in eyes with glaucoma associated with Sturge-Weber syndrome. METHODS: We conducted a prospective study in which eyes with uncontrolled intraocular pressure associated with Sturge-Weber syndrome were treated with latanoprost 0.005% once daily. All eyes were already receiving at least two other antiglaucoma medications. Intraocular pressure was measured at baseline and after treatment for at least 1 month. All intraocular pressure measurements were taken within 24 hours of drug instillation. RESULTS: Six eyes of six patients received latanoprost. Two (28%) of the six eyes demonstrated an intraocular pressure decrease that averaged 8.8 mm Hg. These two responders had juvenile onset glaucoma, whereas the four nonresponders had congenital onset glaucoma. CONCLUSIONS: Latanoprost may significantly reduce intraocular pressure in selected patients with glaucoma associated with Sturge-Weber syndrome.

Effect of transforming growth factor beta 1 on stromal haze following excimer laser photorefractive keratectomy in rabbits.

BACKGROUND: Transforming growth factor beta (TGF-beta) has been shown to affect wound repair. Anti-transforming growth factor beta 1 antibodies have been shown to neutralize its activity. METHODS: Seventeen New Zealand White rabbits underwent unilateral photorefractive keratectomy followed by corneal staining with dichlorotriazinyl fluorescein. Three groups received topical transforming growth factor beta 1: 1 microgram/ml, 10 micrograms/ml, and 100 micrograms/ml; one group topical anti-transforming growth factor beta antibody (200 micrograms/ml); and a control group vehicle only. Corneal haze was graded from 0 to 4, weekly. Rabbits were sacrificed at 5 weeks and histopathological analysis and fluorescence microscopy performed. RESULTS: All treated eyes developed haze and had epithelial erosions. No statistically significant differences in haze score were seen among individual treatment groups (Kruskal Wallis p > 0.05). The anti-transforming growth factor beta antibody group had less haze than all other groups at every week after the first. Comparing all transforming growth factor beta 1 treated eyes as one group to the antibody group, significantly less haze was seen at weeks 3 and 4 in the antibody treated group (p = 0.028 and 0.013, respectively). This study is limited by small group size and further studies are needed to confirm these results. CONCLUSION: TGF-beta may be involved in stromal haze formation, and topical anti-TGF-beta 1 antibody may help reduce the development of stromal haze.

Effect of topical anti-transforming growth factor-beta on corneal stromal haze after photorefractive keratectomy in rabbits.

PURPOSE: To determine the relationship between anti-transforming growth factor-beta (anti-TGF-beta) antibodies and the amount of corneal stromal haze after excimer laser photorefractive keratectomy (PRK). SETTING: Wills Eye Hospital, Philadelphia, Pennsylvania, USA. METHODS: Nineteen rabbits had bilateral PRK. Dichlorotriazinyl fluorescein was used to stain the exposed stroma; all rabbits were then treated with antibiotic ointment for 4 days. Ten rabbits were randomized to treatment with topical anti-TGF-beta1, -beta2, and -beta3 antibody 50 microg three times a day for 4 days; the others received diluent three times a day for 4 days. Stromal haze was graded weekly for 8 weeks on a 0 to 4+ scale. At the end of the study, all corneas were examined histopathologically. RESULTS: All treated eyes developed appreciable haze. Seven control rabbits and one antibody-treated rabbit had an epithelial erosion (P = .00001). Antibody-treated rabbits had significantly less haze at 3, 4, and 5 weeks (right eyes) and 3, 4, 5, 7 and 8 weeks (left eyes) (P < .05). Histopathology and fluorescence microscopy showed subepithelial collagen deposition consistent with clinical haze. CONCLUSIONS: Topical anti-TGF-beta antibody reduced stromal haze after PRK in the rabbit model and may be clinically beneficial in humans.

Comprehensive analysis of a large genomic sequence at the putative B-cell chronic lymphocytic leukaemia (B-CLL) tumour suppresser gene locus.

In many haematological diseases, and more particularly in B-cell chronic lymphocytic leukaemia (B-CLL), the existence of a tumour suppressor gene located within the frequently deleted region 13q14.3, has been put forward. A wide candidate region spanning from marker D13S273 to D13S25 has been proposed and an extensive physical map has been constructed by several teams. In this study, we sequenced a minimal core deleted region that we have previously defined and annotated it with flanking available public sequences. Our analysis shows that this region is gene-poor. Furthermore, our work allowed us to identify new alternative transcripts, spanning core regions, of the previously defined candidate genes DLEU1 and DLEU2. Since their putative involvement in B-CLL was controversial, our present study provide support for reconsidering the DLEU1 and DLEU2 genes as B-CLL candidate genes, with a new definition of their organisation and context.

Vestiges of life in the oldest Greenland rocks? A review of early Archean geology in the Godthabsfjord region, and reappraisal of field evidence for > 3850 Ma life on Akilia.

The Godthåbsfjord region of West Greenland contains the most extensive, best exposed and most intensely studied early Archean rocks on Earth. A geological record has been described of numerous magmatic events between ~3.9 and 3.6 Ga, and evidence of life at >3.85 Ga and ~3.8-3.7 Ga has been proposed from two widely-separated localities. Some of these claims have recently been questioned, and the nature of the best preserved remnants of the oldest known terrestrial volcanic and sedimentary rocks in the Isua greenstone belt are being reinvestigated and substantially reinterpreted. The first part of this article reviews the evolution of geological research and interpretations, outlining the techniques by which the geological history has been determined and the ensuing controversies. The second part re-examines crucial field evidence upon which the antiquity of the oldest terrestrial life is claimed from the island of Akilia.

Excisional bleb revision to correct overfiltration or leakage.

OBJECTIVES: To evaluate the effectiveness of excisional revision of filtering blebs for hypotony or leakage when more conservative measures have failed. PATIENTS AND METHODS: Retrospective review of all patients who underwent excisional revision of a filtering bleb for hypotony (intraocular pressure [IOP] < 5 mm Hg) or leakage during a 3 year period. The revision consisted of excision of the avascular bleb, mobilization of the surrounding conjunctiva, and suturing of the conjunctiva at the limbus. RESULTS: Sixteen patients were included in the study. The average age was 66.3 +/- 14.8 years (range, 39-83). Revision followed trabeculectomy in 11 cases, combined phacoemulsification-trabeculectomy in three cases, and inadvertent blebs in two cases. Five cases had bleb leaks without hypotony, four cases had hypotony alone, and seven cases had both hypotony and a bleb leak. Average follow-up after bleb revision was 25 +/- 11 months (range, 9-43). Average IOP increased from 3.8 +/- 5.6 mm Hg (range, 0-22) to 11.9 +/- 4.1 mm Hg (range, 3-18), with an average of 1.1 +/- 1.1 medication (range, 0-3). The IOP at the last visit was < 15 mm Hg in all but two patients, with 10 of the 16 patients requiring medications. At the last follow-up examination, visual acuity had improved > or = two lines in nine patients and was reduced two lines in one patient. Five patients had early postoperative limbal wound leaks; resuturing was required in one case. CONCLUSIONS: Excisional bleb revision is an effective technique to correct hypotony or leakage after filtering surgery when other methods have failed. Intraocular pressure control is often maintained with the use of medications.

A randomized trial of the long-term effects of digital ocular compression in the late postoperative period.

PURPOSE: To determine whether digital ocular compression is a viable technique to lower intraocular pressure in patients at least 3 months after trabeculectomy. PATIENTS AND METHODS: A 6-month prospective, randomized, controlled, single-masked trial of 29 patients who underwent a trabeculectomy at the Glaucoma Service of Wills Eye Hospital. Patients were assigned to two groups: ocular compression or cheekbone compression (control group). The ocular compression group performed compression to the operated eye three times a day in the pattern of 10 seconds of pressure, 5 seconds of rest, and 10 seconds of pressure. Pressure was applied with the index finger through the closed lid to the center of the cornea. Pressure was steady and firm, but not painful. No massaging was performed. The cheekbone compression group applied pressure to the zygomatic arch with an identical style and frequency. RESULTS: At 6 months, the change in mean intraocular pressure for the ocular compression group was 0.25 mm Hg compared with -0.44 mm Hg for the control group (P = 0.7). A few patients in both groups experienced large swings in intraocular pressure and mild to moderate discomfort. CONCLUSION: Ocular compression had little to no success in the long-term management of increased intraocular pressure in the late postoperative period in this study.

Specific conversion of D-galactose into D-galacturonic acid residues in glycoproteins: a facile method for carbohydrate linkage-analysis.

The terminal D-galactopyranosyl residues of asialoglycopeptides isolated from human alpha1-acid glycoprotein were oxidized in nearly quantitative yield to the corresponding uronic acid residues by a two-step sequence employing D-galactose oxidase followed by treatment with Tollens reagent, Ag(NH3)+2. Mild acid hydrolysis of the oxidized glycopeptides led to the isolation of the corresponding aldobiuronic acid(s). Structural and colorimetric analysis revealed that only one aldobiuronic acid 2-amino-2-deoxy-4-O-(beta-D-galactopyranosyluronic acid)-D-glucose, was isolated from the oxidized glycopeptides of alpha1-acid glycoprotein. This method can readily distinguish between the (1 leads to 3), (1 leads to 4), and (1 leads to 6) isomers of the corresponding aldobiuronic acids.

Vicarious calibration of the moderate-resolution imaging spectroradiometer airborne simulator thermal-infrared channels.

We made an experimental vicarious calibration of the Moderate Resolution Imaging Spectroradiometer (MODIS) Airborne Simulator (MAS) thermal infrared (TIR) channel data acquired in the field campaign near Mono Lake, Calif. on 10 March 1998 to demonstrate the advantage of using high-elevation sites in dry atmospheric conditions for vicarious calibration. With three lake-surface sites and one snow-field site, we estimated the MAS noise-equivalent temperature difference as 0.7-1.0 degrees C for bands 30-32 in the 3.68-4.13-microm region and 0.1-0.5 degrees C for bands 42, 45, 46, and 48 in the 8-13.5-microm region. This study shows that the MAS calibration error is within +/-0.4 degrees C in the split-window channels (at 11 and 12 microm) and larger in other TIR channels based on the MAS data over Mono Lake and in situ measurement data over the snow-field site.

Hypersensitivity reaction to paclitaxel: nursing interventions.

Paclitaxel, a mitotic inhibitor, is used to treat a variety of cancers. A significant incidence of paclitaxel-related hypersensitivity reactions (HSRs) occurs because of the diluent used. Premedication with dexamethasone, diphenhydramine, and H2-histamine antagonists has markedly decreased the incidence of HSRs. Paclitaxel-related HSRs should be managed immediately and appropriately by (a) stopping the infusion, (b) administering oxygen, (c) infusing fluids, (d) continuously monitoring blood pressure, pulse, and oxygenation, and (e) initiating standing orders for i.v. corticosteroids and diphenhydramine or other emergency medications. Oncology nurses are key to the rapid recognition and treatment of paclitaxel-related HSRs.

The impact of domestic violence on children: an adolescents' story.

The authors in this paper illustrate how growing up in a violent household impacts the emotional and psychological development of one college-aged student who confronts her father in a letter about his violent behavior as she was growing up. The Williams Assessment of Unresolved Issues (WAUI) survey instrument is briefly discussed as a tool in gathering data about violent episodes experienced by college-aged students during their childhood.

Matrix metalloproteinase inhibition in atherosclerosis and stroke.

Matrix metalloproteinases (MMPs) are a family of tightly regulated, zinc-dependent proteases that degrade extracellular matrix (ECM), cell surface, and intracellular proteins. Vascular remodeling, whether as a function of normal physiology or as a consequence of a myriad of pathological processes, requires degradation of the ECM. Thus, the expression and activity of many MMPs are up-regulated in numerous conditions affecting the vasculature and often exacerbate vascular dysfunction. A growing body of evidence supports the rationale of using MMP inhibitors for the treatment of cardiovascular diseases, stroke, and chronic vascular dementia. This manuscript will examine promising targets for MMP inhibition in atherosclerosis and stroke, reviewing findings in preclinical animal models and human patient studies. Strategies for MMP inhibition have progressed beyond chelating the catalytic zinc to functional blocking antibodies and peptides that target either the active site or exosites of the enzyme. While the inhibition of MMP activity presents a rational therapeutic avenue, the multiplicity of roles for MMPs and the non-selective nature of MMP inhibitors that cause unintended side-effects hinder full realization of MMP inhibition as therapy for vascular disease. For optimal therapeutic effects to be realized, specific targets for MMP inhibition in these pathologies must first be identified and then attacked by potent and selective agents during the most appropriate timepoint.