Effect of Corynebacterium parvum, methanol-extraction residue of BCG, and levamisole on macrophage random migration, chemotaxis, and pinocytosis.

Three parameters of macrophage function: random migration, chemotaxis, and pinocytosis, were studied in the guinea pig after administration of Corynebacterium parvum, methanol-extraction residue of BCG, and levamisole (LMS), a synthetic anthelmintic. Macrophage migration studies were performed with a modified Boyden chamber. Pinocytosis was assessed by the uptake of colloidal 198Au. After ip administration, each of the three immunostimulators induced an increase in macrophage chemotactic responsiveness and, to a lesser extent and duration, in random motility. Kinetic, dose-response, and time course data for the effect of each agent on macrophage movement were explored. LMS was the most effective stimulator of macrophage activation, which occurred earlier and persisted longer than it did with the other agents. Macrophages from animals receiving each of the agents showed enhanced pinocytosis. Measurement of macrophage random migration, chemotaxis, and pinocytosis appeared to provide a rapid and quantitative assessment of several parameters of macrophage function and, when studied with other immunologic parameters, may provide useful tools for the evaluation of potential immunoadjuvants.

Response of congenitally athymic (nude) mice to infection with Mycobacterium bovis (strain BCG).

Mice homozygous for the mutation "nude" (nu/nu) are athymic and lack thymus-dependent lymphocytes. Heterozygote (nu/+) controls, which are phenotypically and immunologically normal, and (nu/nu) mice were infected with 1.0 times 10-6 colony-forming units of Phipps strain BCG. In the spleens of nu/+ mice, there was a progressive increase in number of BCG up to the second week, followed by a gradual decline. However, in the nu/nu mice, BCG growth was gradual and continuous until termination of the experiment at 5 weeks. In the lung, significant differences were not noted until after the second week, at which time the nude mice showed a rapid increase (of more than 2 log10) in the number of BCG. However, the number of BCG was not significantly greater in the livers of either group. Changes in the normal histology of the lung included a massive influx of monocytes during the first 2 weeks which peaked at day 21. In the lungs of the nu/+ mice by day 28, there was considerable granuloma formation consisting of monocytes and small lymphocytes. However, in the lungs of nu/nu animals, the granulomas were made up primarily of monocytes with a lack of small lymphocytes. Acid-fast stains confirmed the presence of large numbers of organisms in the macrophages of nu/nu mice, with gradual destruction of these phagocytic cells.

The effect of Mycobacterium bovis (Bacillus Calmette-Guérin) on macrophage random migration, chemotaxis, and pinocytosis.

Macrophage random migration, chemotactic responsiveness, and pinocytosis were studied in the guinea pig after Bacillus Calmette-Guérin (BCG) administration. Oil-induced peritoneal exudate cells were evaluated for random migration and chemotaxis in modified Boyden chambers. Pinocytosis was measured by the in vitro uptake of colloidal 198Au. There was a parallel increase in random migration and chemotaxis after an i.p. dose of 1.0 X 10(7) COLONY-FORMING UNIts of BCG. This was seen as early as Day 4, sustained through Day 21, and absent by Day 44. A number of different strains and preparations of BCG vaccine exerted a similar augmentation of macrophage mobility. In parallel assays, aliquots of macrophages from BCG-treated animals showed increased pinocytosis, first noted at Day 14, peaking at Day 28, and no longer measurable at Day 44. These alterations in macrophage function following BCG administration may in part contribute to the antitumor effect of BCG adjuvant therapy.

Bilateral intraocular Nocardia asteroides infection.

A 38-year-old man with hypogammaglobulinemia and pulmonary Nocardia asteroides infection developed an intraocular Nocardia infection. The diagnosis was confirmed by examination of a specimen removed at pars plana vitrectomy. The chorioretinal infection in one eye resolved partially, with no organisms visible on histopathologic examination of the globe at autopsy. One month before the patient's death from disseminated nocardial infection, the previously uninvolved right eye developed a new metastatic nocardial chorioretinal lesion. This lesion rapidly progressed in size until the patient's death and showed on postmortem examination the presence of organisms characteristic of N asteroides.

The ocular manifestations in Fabry's disease.

We present the ocular manifestations in a series of 37 hemizygous male and 25 heterozygous female patients with Fabry's disease. The ocular findings typically do not impair vision, but are unique and diagnostic. Whorl-like corneal deposits were seen in almost all patients and were more severe in the heterozygotes. The lens showed cream-colored anterior capsular deposits, sometimes in striking "propeller" distribution, in one third of the hemizygotes, and in none of the heterozygotes. A faint but unique posterior capsular opacity with a branching radial pattern was seen in 37% of the hemizygotes and 14% of the heterozygotes. Conjunctival vessel aneurysmal dilations and retinal vessel tortuosity were both more frequent and severe in the hemizygotes. Severe visual loss occurred in two hemizygotes as a result of unilateral total central artery occlusions.

Clinical signs and medical therapy of early Acanthamoeba keratitis.

Several diagnostic signs of Acanthamoeba keratitis have been reported recently. We treated three patients who developed a dendritiform epithelial pattern seen early in the course of Acanthamoeba keratitis that likely represents epithelial infection by Acanthamoeba before any stromal involvement. In these three cases, the early diagnosis of Acanthamoeba keratitis coupled with wide epithelial debridement and medical therapy proved effective in eradicating the protozoan. In two additional cases, Acanthamoeba keratitis was not diagnosed until significant stromal involvement was present. Medical therapy was effective in eradicating the organism in one case, although penetrating keratoplasty was necessary for visual rehabilitation. In the other case, medical therapy was ineffective, as corneal perforation resulted and Acanthamoeba cysts were demonstrated by fluorescent staining in the host corneal button.

Central retinal artery occlusion complicating Fabry's disease.

A 16-year-old boy had a central retinal artery occlusion and was subsequently diagnosed as a hemizygote with Fabry's disease. The typical ocular manifestations in males with this inborn error of glycosphingolipid metabolism include whorl-like corneal epithelial infiltrates, retinal and conjunctival vessel tortuosity, and lenticular changes. The present case represents the first report of a retinal artery occlusion as an ocular complication of Fabry's disease.

The use of the 193-nm excimer laser for myopic photorefractive keratectomy in sighted eyes. A multicenter study.

Photorefractive keratectomy was performed at three centers using the 193-nm excimer laser on 31 sighted myopic eyes. Preoperative refractive errors (spherical equivalent) ranged from -12.00 to -4.00 diopters (D) (mean, -6.49 +/- 1.75 D). Peribulbar anesthesia, a 5.2- to 6.0-mm beam diameter, and topical corticosteroids were used for up to 6 months after surgery. The epithelium healed within 3 to 4 days, and all patients returned to their best corrected visual acuity within 1 line of their preoperative acuity. There was minimal subepithelial reticular haze, peaking at 3 weeks and diminishing over the next 3 to 4 months, which was not felt to be visually significant. At 6 months, the average residual refractive error was -1.85 +/- 2.5 D. Sixty-eight percent of eyes were corrected within 2 D and 55% within 1 D of attempted correction. There was no significant change in astigmatism, contrast sensitivity, corneal sensation, or endothelial cell counts. This preliminary work shows that photorefractive keratectomy has promise in the reduction of moderate myopia.

Excimer laser photorefractive keratectomy in high myopia. A multicenter study.

Excimer photorefractive keratectomy was performed at three centers on 16 highly myopic eyes (8 diopters [D] or more) and followed up for 6 months. Ablation depths ranged from 137 to 230 microns. The preoperative spherical equivalent of myopia ranged from -8.62 D to -14.50 D (mean +/- SD, -11.57 +/- 1.62 D). Six months after surgery, the mean refraction (spherical equivalent) was -0.90 +/- 2.13 D. Eleven of 16 eyes achieved refractions within 2 D of that attempted. All eight patients at one site were treated with a maximum-beam diameter of 6.0 mm and were corrected to within 2 D of that attempted, and all were 20/40 or better uncorrected. Three of eight eyes at the other two sites were treated with a 5.5- or 5.6-mm maximum-beam diameter, which achieved corrections within 2 D of that attempted. The epithelium healed within 3 to 4 days, and there were no erosions. Mild subepithelial reticular haze, similar to that seen with excimer photorefractive keratectomy for lower myopia, was seen in all patients, with two patients experiencing more significant corneal haze. This peaked at 3 to 6 weeks and then gradually diminished. All but two patients had a return of their best corrected preoperative visual acuity to within one Snellen line at 6 months. This preliminary study shows excimer photorefractive keratectomy to be a promising surgical treatment for patients with higher myopia.

Clinical use of the 193-nm excimer laser in the treatment of corneal scars.

Phototherapeutic keratectomy using a 193-nm excimer laser was performed at four centers on 33 sighted patients with corneal opacity and/or irregular astigmatism. Pathologic conditions included anterior stromal and superficial scarring from postinfectious and posttraumatic causes, including inactive herpes simplex virus, anterior corneal dystrophies, recurrent erosions, granular dystrophy, and band keratopathy. Most patients received peribulbar anesthesia and underwent removal of the epithelium prior to laser ablation. A majority of patients had a reduction in the amount of corneal scarring and approximately half had improved visual acuity. No intraocular reaction or changes in endothelial counts were seen, and some patients avoided the need for penetrating keratoplasty. Reepithelialization usually occurred within 4 or 5 days and we noted no significant scarring secondary to use of the laser. It was difficult to eliminate preexisting irregular astigmatism despite the use of surface modulators, such as methylcellulose. A hyperopic shift secondary to corneal flattening was encountered in approximately 50% of the patients. A combination of myopic ablation, followed immediately by a secondary hyperopic steepening, may minimize this refractive change. The 193-nm excimer laser is an effective new tool in the treatment of selected patients with superficial corneal opacity from a variety of conditions.

Macrophage migration inhibition factor activity in the aqueous humor during experimental corneal xenograft and allograft rejection.

Macrophage migration inhibition factor (MIF), a soluble mediator of delayed hypersensitivity, was assayed for in the aqueous humor of rabbits undergoing corneal graft rejection. Penetrating and interlamellar xenografts and interlamellar allografts were performed in rabbits, and aqueous humor early in the course of xenograft and allograft rejection, and MIF activity was present during the course of the active rejection. This activity returned to near normal after the active rejection resolved. No significant MIF activity could be measured during the nonspecific inflammations produced by alkali burns, multiple paracenteses, intracorneal clove oil, mechanical debriding of the endothelium.

Results one year after using the 193-nm excimer laser for photorefractive keratectomy in mild to moderate myopia.

As part of a clinical trial, photorefractive keratectomy using the VISX 2015 193-nm excimer laser was performed on 91 healthy eyes of 91 patients. Preoperative refractive errors (spherical equivalent) ranged from -1.00 to -7.50 diopters (mean, -4.16 +/- 1.41 diopters). No patient had more than 1 diopter of refractive astigmatism. Six months postoperatively, the average residual refractive error was +0.09 +/- 0.63 diopters (range, -2.13 to +1.63 diopters). Correction within 1 diopter of that attempted was attained in 85 eyes (93%). Uncorrected visual acuity of 20/40 or better was attained in 86 eyes (95%) and was 20/25 or better in 67 eyes (74%). At one year, follow-up information was available on 85 eyes of 85 patients. The average residual refractive error was -0.15 +/- 0.65 diopters (range, -2.50 to +1.63 diopters). Correction within 1 diopter of that attempted was attained in 85 eyes (93%). Uncorrected visual acuity was 20/40 or better in 83 eyes (98%) and was 20/25 or better in 68 eyes (80%). One patient lost three lines of best-corrected visual acuity because of corneal haze, dropping from 20/15 to 20/30, whereas all other patients returned to best-corrected visual acuity within one line of their preoperative best-corrected visual acuity. Photorefractive keratectomy with the 193-nm excimer laser appears to be a useful treatment modality for the reduction of mild to moderate myopia.

The effect of various methods of eye immobilization on corneal topography.

BACKGROUND: Accurate, predictable, and safe refractive surgery requires immobilization of the eye. We measured the effects of current eye fixation techniques on human cadaver eyes. MATERIALS AND METHODS: Central to our study was a device specially designed to secure cadaver eyes and stabilize intraocular pressure. Topographical measurements were made with a modified Model 2 Corneal Analysis System (EyeSys Technologies, Houston, Tex) mounted vertically to allow analysis of a cadaver eye mounted in the artificial orbit. The effect on human cadaver eyes of six fixation instruments was assessed: forceps, U-shaped fixation forceps, a full Hofman-Thornton ring, a VISX vacuum fixation ring, a Meditec suction ring, and a new instrument, the Eye Fixation Speculum. RESULTS: The circular vacuum fixation rings caused minimal distortion, resulting in less than 1.00 diopter (D) of change. Forceps and U-shaped fixation forceps, which apply force at one or two points, caused significantly more distortion. Single-point fixation forceps distorted the cornea at the point of application a mean of +5.50 +/- 3.50 D, and, at 180 degrees from the point of instrument application, a mean of +2.00 +/- 1.90 D. U-shaped forceps apply force at two points, 90 degrees and 270 degrees, from the axis of instrument application. At these axes, the cornea was distorted a mean of +9.40 +/- 3.70 D and +8.30 +/- 3.10 D, respectively. CONCLUSIONS: Single- and multi-point fixation instruments, due to an asymmetric application of fixation force, significantly distort the cornea. Ring fixation instruments, which apply a more equally distributed force, cause less distortion.

Use of the 193 nm excimer laser for photorefractive keratectomy in low to moderate myopia.

As part of a Phase III clinical trial, photorefractive keratectomy using the VISX 2015 193 nm excimer laser was performed on 91 sighted eyes of 91 patients. Preoperative refractive errors (spherical equivalent) ranged from -1.00 diopters (D) to -7.50 D (mean -4.11 D +/- 1.43 D). At six months, average residual refractive error was 0.02 D +/- 0.64 D (range -2.21 D to +1.38 D). Ninety-three percent of eyes were within 1.00 D of attempted correction, 93% had uncorrected visual acuity of 20/40 or better, and 72% achieved uncorrected visual acuity of 20/25 or better. All patients returned to their best corrected visual acuity within one line of their preoperative best corrected visual acuity. Photorefractive keratectomy with the 193 nm excimer laser appears to be useful in reducing low to moderate myopia.