Topiramate induced acute angle closure glaucoma.

Topiramate is an oral sulphamate medication primarily used for seizure, migraine and neuropathic pain. It has been associated with secondary angle closure, which can mimic acute angle closure glaucoma. Suspicion for medication induced angle closure glaucoma should be higher whenever angle closure presents bilaterally. We present two cases of bilateral angle closure glaucoma secondary to topiramate.

Protegrin-1 enhances bacterial killing in thermally injured skin.

OBJECTIVE: Septic complications and the emergence of drug-resistant microbes represent serious risks to patients. Recently, naturally occurring peptides have been discovered that possess potent and broad-spectrum antimicrobial activity. Protegrin-1 is particularly attractive for clinical use in human wounds because, unlike defensins, protegrin-1 retains broad antimicrobial and antifungal activity at physiologic salt concentration and in the presence of serum. The objective of this study was to examine the efficacy of protegrin-1 in killing multiple drug-resistant microbes isolated from human burn patients. DESIGN: For thein vitroexperiment, bilayer radial diffusion was performed comparing standard antibiotics with protegrin-1 on multiple-drug-resistant microbial organisms isolated from infected burn wounds. In vivo, rats received a 20% total body surface area partial-thickness burn by immersion in 60 degrees C water for 20 secs followed by wound seeding with 106 colony forming units of Silvadene-resistant Pseudomonas aeruginosa. SETTING: University of Michigan research laboratory. SUBJECTS: Adult, male Sprague-Dawley rats. INTERVENTIONS: Rats were randomized into three groups: those receiving synthetic protegrin-1, acetic acid (carrier), or gentamicin (positive control). Protegrin-1 was administered by topical application or intradermal injection. Wound tissues were harvested aseptically at different time points for quantitative bacterial counts. MEASUREMENTS AND MAIN RESULTS: In vivo and in vitro experiments revealed rapid and significant decreases in bacterial counts for protegrin-1-treated groups compared with controls. CONCLUSIONS: This study shows that protegrin-1 potentially may be used as an alternative or adjunct therapy to standard agents used to treat wound infections.

Feasibility of biolistic gene therapy in burns.

Skin is an especially attractive target for genetic manipulation because it is readily accessible and easily monitored for both the presence and the expression of inserted genes. This study was designed to assess the feasibility of particle mediated gene transfer to burned skin and to compare the transfection efficiency, anatomic distribution, and duration of transgene expression achievable in normal versus burned skin. Two days following scald injury of varying depths in 60 degrees C water (10 s: superficial partial; 20 s: deep partial; 40 s: full thickness) reporter gene (beta-galactosidase) constructs were delivered using a gene gun at various helium pressures (200-600 psi) to normal and burned skin. A time course study was performed to examine the kinetics of transgene expression. Animals received a superficial partial thickness burn and were sacrificed 12 h, 1, 3, 5, 7, 14, or 21 days after gene transfer. India Ink injection and immunohistochemistry were used to assess the depth of the scald injury. Transfection efficiency was measured in skin homogenates 24 h after gene transfer by morphometric and chemoluminescent assays. We found that the extent of tissue damage was directly related to the duration of heat source exposure. Reporter gene activity was significantly higher in superficial partial thickness burns compared to normal controls and gradually declined with increasing tissue injury. No activity was seen in the full thickness burn group. Beta-galactosidase activity reached a maximum level 12 h after gene transfer in both normal and superficial partial thickness burned skin with no levels seen after 5 days post-transfection. These findings indicate that particle-mediated gene transfer in thermally injured skin is feasible and may provide a means of introducing biologic agents into injured tissue capable of enhancing bacterial clearance and improving wound healing.

Lipopolysaccharide-binding protein accelerates and augments Escherichia coli phagocytosis by alveolar macrophages.

BACKGROUND: The first step in bacterial clearance by leukocytes is attachment and phagocytosis. Although lipopolysaccharide-binding protein (LBP) is best known for potentiating LPS-induced cytokine production through a CD14-dependent pathway, recent studies suggest that LBP plays a critical role in clearance of gram-negative bacteria and is essential for survival after bacterial challenge. We therefore sought to examine LBP's effect on Escherichia coli phagocytosis by alveolar macrophages (AMs) and to determine if this effect is mediated through CD14. MATERIALS AND METHODS: Phosphatidylinositol-specific phospholipase C (PIPLC)-treated and untreated rat AMs were incubated in the presence of increasing doses of recombinant LBP or negative control protein (choramphenicol acetyltransferase) prior to E. coli-FITC (Ec-F) BioParticle challenge. Phagocytosed bacteria were assayed by fluorescence measurement. A time course study was also performed. RESULTS: LBP potentiated phagocytosis of Ec-F BioParticles by AMs in a dose-dependent fashion. Kinetic studies showed that LBP augmented Ec-F phagocytosis by 76% at 30 min. Treatment of AMs with PIPLC to remove CD14 resulted in only a partial decrease in LBP-mediated enhancement of phagocytosis. CONCLUSION: These results clearly demonstrate that LBP plays an important role in enhancing Ec-F binding and phagocytosis in a time- and dose-dependent manner. This observed increase may not require the presence of CD14 as significant potentiation of phagocytosis still occurred after PIPLC treatment. We postulate that the LBP-mediated increase in Ec-F phagocytosis can occur in the absence of CD14 through the presence of another receptor.

Skin lipopolysaccharide-binding protein and IL-1beta production after thermal injury.

In response to a burn injury, skin can have an inflammatory response characterized by the production of inflammatory cytokines, recruitment of immune cells, containment of invading organisms, and clearance of noxious substances from the wound. Lipopolysaccharide-binding protein (LBP) is a molecule that is capable of coordinating all 4 functions; we previously found evidence that suggested that LBP is produced within surgical wounds. Because of the central role of LBP in the response to bacterial infection, as well as in the high rate of infection after burn injuries, we sought to determine whether a thermal injury could affect wound LBP production and thereby affect host responses against bacterial infection. Rats were given either a burn or a sham burn and were killed 24, 48, and 72 hours after the injuries. Wound specimens were assayed for bacterial counts and for the presence of LBP, messenger (m)RNA, and interleukin (IL)-1beta mRNA. Wound LBP mRNA was significantly upregulated at 24 hours in the group with burn injuries (P < .05; burn vs sham burn); this was followed by decreases at 48 and 72 hours. Immunohistochemistry showed LBP protein in the epidermis of animals with burns. Bacterial counts increased in the group with burn injuries (P < .05; burn vs sham burn) and continued to rise for 72 hours. IL-1beta mRNA levels were elevated at all time points in the group with burn injuries (P < .05). These results suggest an inverse correlation between burn wound LBP expression and bacterial wound counts. This failure to maintain local LBP production after severe thermal injury despite localized inflammation shown by high IL-1beta levels may predispose local wounds to bacterial invasion.

Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4.

Lipopolysaccharide (LPS) binding protein (LBP) is a key serum factor that mediates LPS activation of mononuclear cells. In the presence of LBP, 1/1,000 the concentration of LPS is sufficient to activate peripheral blood monocytes. Previous studies with Kupffer cells have shown a variable effect of serum on LPS activation of these cells and led to the conclusion that, unlike extrahepatic mononuclear cells, Kupffer cells do not respond to LPS in an LBP-dependent fashion. Because there are multiple components in serum other than LBP that might affect LPS activation, these reports with serum are difficult to interpret. To investigate the specific role of LBP in LPS activation of Kupffer cells, we produced a functional recombinant rat LBP using a baculovirus expression system, which we used to selectively examine the role of LBP's on Kupffer-cell function. Isolated Kupffer cells exposed to increasing concentrations of LPS (0, 1, 10 ng/mL) showed a dose-dependent increase in TNF-alpha production, which was augmented and accelerated by the presence of LBP. The effects of LBP on Kupffer cell activation by LPS are dependent on a functional Toll-like receptor 4 (Tlr 4) because Kupffer cells from C3H/HeJ mice failed to respond to LPS in the presence of LBP. LBP plays an important role in mediating Kupffer cell activation by LPS, and these effects are dependent on the presence of functioning Tlr 4.

Pulmonary LPS-binding protein (LBP) upregulation following LPS-mediated injury.

BACKGROUND: The acute respiratory distress syndrome (ARDS) causes significant morbidity and mortality among trauma patients. Although multiple factors have been implicated, pulmonary injury in this population may be due to inflammatory mediators released in response to stimuli such as endotoxin (LPS). LBP plays an integral part in LPS-mediated release of inflammatory cytokines and increased local expression of LBP as the result of a primary injury may prime the lung to secondary LPS-mediated damage. MATERIALS AND METHODS: To determine the magnitude of pulmonary LBP upregulation following LPS injury we challenged rats with either intravenous (IV) or intratracheal (IT) LPS. Animals from each group were euthanized at 1, 2, 4, and 8 h postchallenge. Lung LBP and CD14 mRNA levels were assayed by Northern blot. Serum and bronchoalveolar lavage (BAL) fluid were assayed for inflammatory cytokines (TNF-alpha, MCP-1, IL-1beta, IL-6, and IL-10) by ELISA. RESULTS: LBP and CD14 mRNA levels were found to increase significantly in lung tissue after both IV and IT LPS with the IV LPS animals having a greater increase over 8 h. Serum TNF-alpha was significantly elevated in the IV LPS group whereas very low levels were detected in the BAL. Only BAL TNF-alpha was increased in the IT group at 8 h. CONCLUSION: Local pulmonary LBP and CD14 mRNA are both upregulated after either systemic or local LPS exposure. Such upregulation may render thelung more susceptible to local immune overactivation and injury during subsequent exposures to LPS.

Traumatic cataract and Wieger's ligament.

The objective of this study was to determine the relationship between posterior subcapsular contusion cataract and Wieger's ligament. Two clinical cases of traumatic cataract, occurring in young patients, were analyzed. In neither case was there evidence of penetrating or perforating injuries to the globe. During cataract extraction a smooth oval defect in the posterior capsule was observed; however, there was no evidence of intraoperative capsular damage. The outline of the defect was consistent with the border of Wieger's ligament. It appears that blunt trauma avulsed this region of lens capsule, resulting in these findings.

Hypotonus cyclodialysis cleft following anterior chamber intraocular lens removal.

Inadvertent cyclodialysis cleft formation is a rare complication of intraocular surgery. We report a patient in whom a hypotonus cyclodialysis cleft developed following the removal of an anterior chamber intraocular lens. The cleft closed and the hypotony resolved after 1 month of topical atropine therapy.

Inadvertent cyclodialysis cleft.

We report four patients with functionally significant inadvertent cyclodialysis cleft. In three, the cleft followed uneventful extracapsular cataract extraction with posterior chamber intraocular lens implantation; in the fourth, blunt trauma with hyphema. Ocular hypotony resolved in three patients with medical therapy; the fourth required argon laser photocoagulation. Causes, clinical findings, and treatment of inadvertent cyclodialysis cleft are reviewed.

Effect of intermittent versus continuous patient monitoring on reliability indices during automated perimetry.

PURPOSE: This prospective, randomized study was undertaken to determine the effect of intermittent versus continuous patient monitoring on reliability indices (fixation losses, false-positive errors, and false-negative errors) during automated static perimetry. METHODS: A practice Humphrey Program C30-2 visual field was administered to 169 subjects (mean age +/- standard deviation, 56 +/- 18 years) for 1.5 minutes, during which time trained technicians continuously monitored all subjects and assessed patient fixation as noted on the eye monitor. The computer-generated reliability indices during the 1.5 minute practice test were recorded. After completion of the practice test, the 169 eyes were randomized to either intermittent or continuous monitor for the permanent C30-2 test. During intermittent monitoring, the technician returned periodically to the examination room to assess the subject's performance. For continuous monitoring, the technician continually assessed the subject's performance while remaining in the examination room throughout the test duration. RESULTS: The mean number of visits per visual field test during intermittent monitoring was 4.0, and mean test duration was 15.8 minutes. There was no difference in the mean deviation, pattern standard deviation, and short-term fluctuation (P = 0.85, 0.98, and 0.41, respectively) of the visual fields for intermittent and continuous monitoring, suggesting similar diffuse depression and localized defects in the visual fields for each group. The mean fixation losses (6.9%), false-positive errors (1.8%), and false-negative errors (5.8%) for the intermittently monitored group were not different from the mean fixation losses (7.8%), false-positive errors, (3.1%) and false-negative errors (5.0%) for the continuously monitored group (P = 0.40, 0.24, and 0.36, respectively). CONCLUSION: Although recommended, continuous monitoring does not appear necessary for all patients undergoing automated perimetry. Error-free reliability indices combined with the technician's judgment of patient reliability during the first 1.5 minutes of C30-2 testing may be a guideline for choosing intermittent monitoring.

Simultaneous bilateral malignant glaucoma following laser iridotomy.

A case of bilateral malignant glaucoma is described in a 50-year-old white woman 4 weeks after successful bilateral laser iridotomy for angle-closure glaucoma. The malignant glaucoma may have been precipitated by systemic hydrochlorothiazide therapy. The condition was worsened by pilocarpine; however, atropine and cyclopentolate opened the angle and deepened the anterior chamber, resulting in resolution of the malignant glaucoma. The clinician must be alert to the possibility of malignant glaucoma following laser iridotomy for angle-closure glaucoma.

Use of a symblepharon ring for treatment of over-filtration and leaking blebs after glaucoma filtration surgery.

We report the use of a symblepharon ring in the treatment of seven cases of flat anterior chamber (six cases of total iridocorneal touch, and one of corneallens touch) secondary to overfiltration or to bleb leak. In all cases, the anterior chamber reformed within 24 hours after the symblepharon ring was used. Advantages of using the ring are: (a) it permits testing of visual acuity, tonometry, and intraocular examination without removing it; (b) it does not require suturing to the conjunctiva; (c) it does not disturb the corneal epithelium; (d) it may be available at institutions lacking other shells; and (e) it is cost-effective.

Correlation of ocular findings and plain skull roentgenogram in pituitary adenoma.

A review of the conditions of 44 consecutive patients diagnosed as having pituitary tumor is presented. In none of those with abnormal visual acuity, visual field defect, or extraocular muscle palsy was the plain skull roentgenogram normal. In all but one patient who had an abnormality on ocular examination), there was erosion of the clinoids on the plain lateral skull roentgenogram and, in that one patient, erosion was found on the side of the visual loss by the use of tomography. Based on these observations, we have stressed primarily the early use of simple plain skull roentgenograms in the evaluation of the conditions of patients with unexplained visual loss or extraocular movement palsy. We have also presented a scheme for evaluation of the conditions and the follow-up of patients suspected of having pituitary tumors.