An uncommon pattern of polyneuropathy induced by lifetime exposures to drift containing organophosphate pesticides.

The natural history of chronic peripheral polyneuropathy following lifetime low-level organophosphate (OP) exposure was investigated. A pilot study (1984-1987) conducted in rural communities in Israel detected subtle reversible in-season changes in nerve conduction patterns of 17 field workers out of 214 residents exposed to seasonal drift containing OP's. We examined 60 individuals (males: 50/60; 83.3%) from the original cohort still residing (more than 40 years) in the same communities. Exposure assessment was based on reports by Israeli institutions and the Bureau of Statistics. Information on personal status, work experience, exposures and symptoms was collected by questionnaires. The nervous system was systematically studied, evaluating cortical upper motor neurons, corticospinal tracts, lower motor neurons and peripheral nerves. Electrophysiological studies included conduction velocities, amplitudes and distal latencies of sensory and motor median, ulnar, tibial and sural nerves; F-waves for proximal nerve functions; thermal and pain thresholds for small thinly-myelinated and non-myelinated fibers; transcranial magnetic stimulation for large fibers. Clinical and electrophysiological features of Carpal Tunnel Syndrome were found in 18% of the subjects, atypically in males only. Fingertips' tingling correlated with both axonal and myelin-dependent parameters (lower wave amplitudes and prolonged latency periods, respectively) in the sensory median nerves bilaterally. OP exposure significantly correlated to prolonged distal latency in the right median sensory nerve (r=0.29; p=0.052; n=45) and lower wave amplitude in the right sural nerve (p=0.031). These findings attest to subtle, predominantly sensory peripheral polyneuropathy following lifetime low-level exposures to drifts containing OP.

Stability and dynamics of forebrain vasopressin receptor and oxytocin receptor during pregnancy in prairie voles.

During pregnancy, females undergo several physiologically driven changes that facilitate adaptive behaviours and prepare the mother to care for her developing offspring. The nonapeptide hormone oxytocin is best recognised for its involvement in mammalian pregnancy and has been tightly associated with maternal care, in addition to its roles in pregnancy, parturition and lactation. A closely-related nonapeptide hormone, arganine vasopressin, has received considerably less attention for its role in pregnancy, although it has recently been implicated in modulating maternal care and aggression. In the present study, we examined the expression patterns of receptors for oxytocin (OXTR) and vasopressin (V1aR) over the course of pregnancy, ranging from non-mated virgin to immediately postpartum female prairie voles (Microtus ochrogaster). Unexpectedly, we found that OXTR was highly stable in all measured structures in the forebrain. V1aR was also stable throughout most of the brain. Two exceptions to this were found in the ventral pallidum (VPall) and the paraventricular nucleus of the hypothalamus (PVN); both significantly correlated with the length of time that females were pregnant. Changes in the PVN may reflect functional feedback in vasopressin release, or preparatory changes for ensuing maternal behaviour. The results also indicate an unappreciated role for VPall V1aR in pregnancy, which may relate to the function of the VPall in hedonic 'liking' and motivational 'wanting.' Taken together, our data indicate that, with a few compelling exceptions, nonapeptide dynamics during prairie vole pregnancy are largely limited to changes in the synthesis and release of oxytocin and vasopressin, and not the receptors to which they bind.

Vitreous traction and epiretinal membranes in diabetic macular oedema using spectral-domain optical coherence tomography.

PURPOSE: The purpose of this study was to present an association between diabetic macular oedema (DME) and vitreoretinal interface abnormalities using 3D spectral domain optical coherence tomography (SD-OCT). METHODS: In a retrospective study, charts and SD-OCT of consecutive patients with diffuse or focal DME were reviewed. Only one randomly chosen eye per patient with DME was included, and eyes that had another retinopathy that could affect the study analysis or that underwent vitreoretinal surgery were excluded. RESULTS: Out of 58 eyes (58 patients) with DME, 11 eyes (19.0%) had vitreofoveal traction (Group A), either unifocally (n=6) or multifocally; that is, associated with additional extrafoveal traction site(s). Group B comprised 20 eyes (34.5%) that had sole extrafoveal vitreous traction, at either retinal and/or papillary sites. In each, the retinal oedema underlying extrafoveal traction was in continuum in at least one site with that at the central macula, as verified by the macular maps, thus presented as diffuse macular oedema. In Group C, 13 eyes (22.4%) had an epiretinal membrane (ERM), 1.5 × 3 mm to ≥6 × 6 mm in size that overlaid diffuse oedematous macula. Group D included 14 eyes (24.1%) that had neither vitreous traction nor ERM; 12 (20.7%) of them had DME secondary to leaking microaneurysms with or without leaking capillary beds, and the remaining two had leakage from non-microaneurysms sources. CONCLUSIONS: DME was detected by the SD-OCT to be associated with sole extrafoveal vitreous traction in one-third of the patients. Further studies are required to evaluate the clinical consequences of these observations.

Energetic cost of calling: general constraints and species-specific differences.

The energetic cost of acoustic signalling varies tremendously among species. Understanding factors responsible for this heterogeneity is important for understanding the costs and benefits of signalling. Here, we present a general model, based on well-established principles of bioenergetics, which predicts the energetic cost of call production across species. We test model predictions using an extensive database of resting and calling metabolic rates of insects, amphibians and birds. Results are largely supportive of model predictions. Calling metabolic rates scale predictably with body mass and temperature such that calling and resting metabolic rates are directly proportional to each other. The cost of acoustic signalling is approximately 8 times higher than resting metabolic rate in ectotherms, and approximately 2 times higher in birds. Differences in the increase in metabolic rate during calling are explained by the relative size of species' sound-producing muscles. Combined with published work, we quantify call efficiency and discuss model implications.

Extrafoveal vitreous traction associated with diabetic diffuse macular oedema.

PURPOSE: To present an association between diabetic diffuse macular oedema and extrafoveal vitreous traction by optical coherence tomography (OCT). METHODS: In a retrospective study, charts and OCT scans of diabetic patients with macular oedema were reviewed. Eyes with either vitreofoveal or extrafoveal traction were included. Eyes that had vitreoretinal adherence with no sign of traction, idiopathic vitreomacular traction syndrome, or vitreoretinal surgery were excluded. Macular maps were compared with normal controls (n=12). RESULTS: Of the 186 eyes of 122 consecutive patients, 45 eyes (41 patients) were analyzed. Vitreofoveal traction was detected in 25 eyes (56%) and extrafoveal traction in 20 (44%), either at the retina (16; 35%) or at the optic nerve head (4; 9%). Of these 20 eyes, related extrafoveal retinal oedema was in continuum with the central macular oedema, manifesting as diffuse macular oedema, in 16 (36% of all 45) eyes. Vitreous adherence was detected by the centrally fixated Automatic 6-radial lines program in 26 eyes (58%): 5 (25%) of 20 with extrafoveal traction and 21 (84%) of 25 with vitreofoveal traction. In the other 19 (42%) eyes, the vitreous traction site was detected only by the Line group OCT-2000 program, which is manually controllable during the scanning process. CONCLUSIONS: Diabetic diffuse macular oedema may be related to an extrafoveal vitreous traction. The traction sites were detected in a large proportion of eyes only by the OCT Line group program and not by the Automatic 6-radial lines program. Further studies are required to validate the clinical consequence of these findings.

Cystoid foveal oedema in symptomatic inner lamellar macular holes.

PURPOSE: Inner lamellar macular hole (LMH) was considered a relatively risk-free condition that rarely progresses or worsens. Nowadays, at the optical coherence tomography (OCT) era, increasing evidence seems to position it differently. The aim of the study was to describe morphologic abnormalities associated with symptomatic LMH using OCT that may explain reduced visual acuity in these patients. METHODS: In a retrospective study on consecutive symptomatic patients with LMH, OCT scans were compared with normal controls. Analysis was referred to LMH-associated abnormalities at the residual fovea, mainly cystoid spaces that manifested as cystoid foveal oedema. RESULTS: A total of 22 eyes of 20 patients (mean age, 68 years; range, 22-94) were included in the study. Best-corrected visual acuity ranged from 6/9 to 6/120. Cystoid foveal oedema that contained cystoid spaces of various sizes was found in 21 (95%) of eyes; an intraretinal split was seen in 18 eyes (82%) and epiretinal membrane was detected in 16 eyes (73%). CONCLUSIONS: The appearance of cystoid oedema at the residual fovea in symptomatic LMHs may explain in part a reduced visual acuity and/or metamorphopsia. The old notion on the low incidence of LMH progression may probably be related in part to (a) lower diagnostic accuracy before OCT was available and to (b) the already spontaneously peeled inner limiting membrane. Further studies are required to verify these observations, which may merit clinical and surgical considerations.

Protection of the conjunctival flap from contact with mitomycin C during tunnel-trabeculectomy.

AIM: The mid-term appearance of the filtering bleb and surgical outcome following tunnel-trabeculectomy, in which protective measures were carried out to avoid contact between the mitomycin C (MMC) and the conjunctival flap, are presented. METHODS: In a retrospective study the records of 20 consecutive patients who had undergone tunnel-trabeculectomy >/=24 months earlier, using fornix-based conjunctival flap and MMC (0.4 mg/ml) application were evaluated. Inclusion criteria were patients in whom: (I) the MMC-socked sponge was applied without contact with the conjunctival flap; (II) during MMC washout, a second Weck cell sponge was held anterior to the conjunctival flap, to protect the flap from mitomycin contact during its back-flow. Excluded were five patients who either did not complete 24 months of follow-up (n=4) or underwent an intraocular surgery during that period (n=1). RESULTS: After 24-32 (26.9+/-2.2) months, the filtering bleb was completely vascularized and thick in 13/15 patients (86.7%), mostly vascularized with some para-limbal thick cysts in one and avascular and cystic in another. Mean intraocular pressure (IOP) dropped from a preoperative level of 25.3+/-7.0 mmHg with 3.5+/-0.9 hypotensive medications to 13.9+/-2.9 mmHg with 0.9+/-1.1 medications (P<0.0001, Wilcoxon test). Of the five excluded patients, the IOP ranged between 10 and 16 mmHg with 0-1 medications at the last examination, 1-15 months postoperatively. CONCLUSION: In this pilot study, an intraoperative protection of the conjunctival flap from mitomycin contact was mostly associated with a vascularized and thick filtering bleb after mid-term follow-up. Further controlled prospective studies are required to confirm these observations.

Diabetic vitreopapillary traction and macular oedema.

PURPOSE: To describe an association between optic disc traction and diabetic macular oedema (DME) unresponsive to laser treatment. METHODS: A retrospective review of all patients with DME who attended our clinic between September 2001 and November 2003 was undertaken. The patients had undergone ophthalmic history and examination, fluorescein angiography, and optical coherence tomography (OCT) of the macular area and optic nerve head (ONH). A total of 10 nonvitrectomized eyes that were found to have an elevation of the ONH secondary to vitreopapillary traction were included in the analysis. Eyes with additional traction at the posterior pole were excluded. RESULTS: Out of the 10 eyes (seven patients, aged 47-79 years) with vitreo-papillary traction, nine had previously undergone argon laser photocoagulation(s) for DME. In seven eyes (seven patients), OCT verified the vitreopapillary traction as the sole traction, whereas in the fellow eyes of three patients vitreomacular traction was evident as well. In the seven eyes with only vitreopapillary traction, OCT demonstrated parapapillary serous retinal detachment in two eyes and a diffuse DME in all eyes (mean foveal thickness, 396+/-144 microm). Maximal thickness of the papillo-macular bundle site was adjoining the elevated ONH in three eyes, and was maximal at the central macula in the other four eyes. Ultrasonography (n=5) revealed an incomplete detachment of the posterior hyaloid in each, adherent only at the ONH. CONCLUSIONS: Diffuse DME unresponsive to laser treatment may be associated with vitreopapillary traction. Further studies should indicate whether these two phenomena could suggest a cause and effect in such eyes.

Spontaneous expulsive suprachoroidal hemorrhage.

PURPOSE: To present a 90-year-old patient with spontaneous expulsive suprachoroidal hemorrhage (SESCH). This unique case suggests a mechanism of SESCH, which is still under debate. METHODS: The patient, who had corneal inflammatory disease and diabetes mellitus, atherosclerosis, and glaucoma, presented with active ocular bleeding and expulsion of intraocular tissues. Almost the entire cornea was absent, except for several small and irregular areas in its periphery. Histopathologic evaluation of the eviscerated contents was performed. RESULTS: Clinicopathologic evaluation revealed acute inflammation of the corneal remains as well as intraocular inflammation. Inflammatory necrosis of choroidal vessels was evident. CONCLUSION: The findings point to the assumption that choroidal bleeding, secondary to vascular inflammatory necrosis, was the initial event in this case of spontaneous expulsive suprachoroidal hemorrhage. Presumedly, the intraocular pressure level was very high owing to continuous bleeding, which could result in a very large, rather than localized, tearing of the peripherally inflamed cornea.

Mini-trabeculectomy as initial surgery for medically uncontrolled glaucoma.

PURPOSE: To report on the surgical outcome after at least 12 months of follow-up of mini-trabeculectomy (without radial incisions) as an initial surgery. METHODS: In a prospective, institutional study, mini-trabeculectomy was performed as the initial surgical therapy on 41 eyes with medically uncontrolled glaucoma of 41 consecutive patients aged 40 years or older. Mini-trabeculectomy consists of a 3-mm fornix-based conjunctival flap, sclerostomy at 1 mm from the limbus, and a sclerocorneal tunnel without radial incisions. Of the 41 eyes, four eyes did not complete 12 months of follow-up. Of the remaining 37 eyes, one eye underwent cataract extraction 5 months postoperatively and was evaluated only for surgical complications. Thirty-six patients with a mean age of 70.3 +/- 7.4 standard deviation years (range, 54 to 87) completed 12 months or more of follow-up. RESULTS: In the 36 eyes, mean preoperative intraocular pressure was 30.2 +/- 9.3 mm Hg (range, 19 to 54) with 3.0 +/- 1.2 hypotensive medications (range, 1 to 4). After postoperative mean follow-up of 25.0 +/- 9.2 months (range, 12 to 43), intraocular pressure was at or below the planned target intraocular pressure in 35 eyes (97.2%; P <.0001) and mean intraocular pressure was 16.0 +/- 2.8 mm Hg (range, 11 to 21) with 0.8 +/- 1.0 medications (range, 0 to 3). Postoperative complications in the 37 eyes included early postoperative aqueous leakage with moderately shallow or deep anterior chamber in two eyes (5.4%) and rapid cataract progression in one eye (2.7%). The four eyes that were excluded from the study had intraocular pressures of 10 to 16 mm Hg with 0 to 1 hypotensive medications, 3 to 9 months after surgery, respectively. CONCLUSIONS: Mini-trabeculectomy, which may offer clinical and technical advantages over the standard trabeculectomy, was generally efficacious and relatively safe, based on outcome observed at a mean of 25 months follow-up. A controlled study is required to confirm these observations.

Hollow bandage contact lens.

OBJECTIVE: To report on the use of a new bandage contact lens (BCL) for a leaking filtering bleb. PATIENTS AND METHODS: A hollow BCL, with an internal central opening of 6 mm, has been applied on three eyes that had leaking blebs shortly after either trabeculectomy or combined cataract extraction and trabeculectomy, each with a fornix-based conjunctival flap. RESULTS: The treatment with this lens was found beneficial: the leakage subsided and the patients were comfortable with the lens. The internal hollow of the BCL enabled us to monitor the intraocular pressure throughout the entire follow-up period without transient and repeated removal of the BCL. CONCLUSION: The new hollow BCL was found efficacious. The study suggests that this lens may have advantages over the commonly used BCLs that are related to the elimination of the need for its frequent removal and reinsertion for tonometry. This decreases the risk of both the exposure of the lens and the filtering bleb to contamination and the interference with the continuity of the process of conjunctival epithelial closure.

Halting pterygium recurrence by postoperative 5-fluorouracil.

PURPOSE: To investigate the efficacy of postoperative 5-fluorouracil (5-FU) in halting recurrence of pterygium. METHODS: Early recurrence of pterygium was detected in six eyes of six patients aged 40 to 66 years that, over a 3-year period, had undergone pterygium excision in our institution, using the "bare sclera" technique. Each of the hyperemic fibrovascular tissues was found to override the cornea by 1.5 mm or less in length. Five of these eyes had undergone a primary excision and one, a second operation (with intraoperative mitomycin C). Upon diagnosis, each eye was treated with two to four injections of 5-FU, administered into the dome of the fibrovascular tissue. The dose of 5-FU per injection was 1 to 3 mg (mean, 2.1 +/- 0.8 mg). Of all 126 eyes that underwent pterygium surgery during that 3-year period, pterygium recurred in nine additional eyes but was found to be 2 mm or more in length in each. These eyes were not treated by 5-FU. RESULTS: In five of the six treated eyes, the pterygium became clinically atrophic and the recurrence process was stopped. No renewal of the recurrence process was detected after 12 months or more of follow-up. No major complications were related to the use of 5-FU. CONCLUSION: This pilot study suggests that when early recurrence of pterygium is already evident, 5-FU treatment into the dome of the fibrovascular tissue may be beneficial in halting its progression, by rendering it atrophic. A prospective, randomized, controlled study is required to confirm the efficacy of this approach.

Quantitative analysis of hydroxyl radicals in the anterior optic nerve of the cat following transient ischemia.

PURPOSE: Ischemic insults in the optic nerve are relatively common ocular disorders. This study provides quantitative data on the generation of hydroxyl radicals in the anterior optic nerve of the cat during the early reperfusion phase following 90 minutes of ischemia. MATERIALS AND METHODS: Cats were injected intravenously with sodium salicylate that by acting as an hydroxyl radical trap, forms 2,3-dihydroxybenzoic acid (2,3-DHBA). Ischemia was achieved by intraocular pressure (IOP) elevation via cannulation of the anterior chamber. Ischemia was maintained for 60 minutes in 6 eyes and 90 minutes in 12 eyes, followed by 5 minutes of reperfusion. In an additional 6 eyes, ischemia was maintained for 90 minutes without reperfusion. RESULTS: After 90 minutes of ischemia and reperfusion, mean normalized levels of 2,3-DHBA (ie, ng 2,3-DHBA/microg salicylate/mg protein) that represent the levels of hydroxyl radicals were 2.47 times (at least) higher in the anterior optic nerves than in the fellow sham-operated controls (P = 0.03). These levels were 3.9 times (at least) greater than in the corresponding levels after 90 minutes of ischemia without reperfusion (P= 0.005). CONCLUSION: This study provides a quantitative analysis and evidence for the generation of hydroxyl radicals in the optic nerve of the cat following transient ischemia. A quantitative analysis may provide an important tool to detect even relatively small levels of free radicals in the tissues, and to evaluate the relative efficacy of various therapeutic agents in the inhibition of free radical generation following ischemia and reperfusion.

Mini-trabeculectomy in eyes with high risk of scarring: midterm follow-up.

PURPOSE: To report on the surgical outcome after at least 1 year of follow-up of mini-trabeculectomy (without scleral radial incisions), which took place in eyes at high risk of postoperative filtering bleb scarring. METHODS: In a prospective, institutional study, mini-trabeculectomy was performed on 26 eyes of 26 consecutive patients aged 40 years and older who had undergone a previous intraocular surgery or had had a post-traumatic recessed anterior chamber angle. The surgical procedure, a modification of the standard trabeculectomy, involved a 3-mm fornix-based conjunctival flap, sclerostomy at 1 mm from the limbus, and a sclerocorneal tunnel without radial incisions. During surgery, 0.4 mg per ml of mitomycin C was applied in the scleral pocket of each eye for 3 minutes. Of the 26 eyes, each of two eyes underwent an intraocular intervention during the first postoperative year and therefore was evaluated only for surgical complications. Another eye underwent inferior mini-trabeculectomy, and three other eyes did not complete 12 months of follow-up. Twenty eyes have completed 12 months or more of follow-up and were included in the midterm calculations of intraocular pressure control. RESULTS: Mean preoperative intraocular pressure (n = 20) was 32.2 +/- 9.5 mm Hg with 3.3 +/- 0.9 hypotensive medications. After 12 to 37 months (mean, 22.1 +/- 6.6) of follow-up, intraocular pressure was 20 mm Hg or less in 18 of 20 eyes (90%) and the mean intraocular pressure was 17.4 +/- 2.9 mm Hg (range, 12 to 23) with 1.1 +/- 1.2 hypotensive medications (range, 0 to 4). At that time, the filtering bleb was low and fleshy in appearance in 15 eyes (75%). Postoperative complications of the 22 eyes included early postoperative aqueous leakage in one eye (4.5%); cataract extraction took place in one eye and vitrectomy was performed in another eye, 7 and 3 months postoperatively, respectively. The four eyes that were excluded from the study had controlled intraocular pressure at the last examination. CONCLUSION: Mini-trabeculectomy in eyes with high risk of scarring was found efficacious and relatively safe. The relatively small peritomy, the tunnel approach, and the avoidance of radial incisions seem to offer important advantages over the standard trabeculectomy.

Needling with intra-bleb 5 fluorouracil for intractable neovascular glaucoma.

BACKGROUND AND OBJECTIVE: Trabeculectomy for neovascular glaucoma (NVG) often results in filtering bleb scarring. The outcome of a needling procedure with intra-bleb 5-fluorouracil (5-FU) administration in NVG eyes is presented. PATIENTS AND METHODS: Following trabeculectomy with mitomycin C (MMC), intraocular pressures (IOPs) ranged between 36 to 56 mm Hg in 3 painful, neovascular glaucomatous eyes despite treatment. Each eye was then injected subconjunctivally with 1.0 mg of 5-FU, adjacent to and within the filtering bleb. The needle was advanced and penetration into the anterior chamber through the bled, anterior to the scleral flap, followed. RESULTS: In each eye, the IOP dropped immediately. After 18 to 29 months, IOPs were 11 to 22 mm Hg, and in two eyes-without hypotensive medications. Cataract progression was evident in the 2 eyes that had had cataracts preoperatively. CONCLUSION: The postoperative needling, in conjunction with the dual effect of intraoperative MMC and intra-bleb 5-FU, was found efficacious and saved further surgery in these intractable cases.

Noncontact tonometry in perforating corneal injuries.

PURPOSE: To report on one of the possible complications induced by puff noncontact tonometry and to discuss various aspects such as safety, other optional methods, rationality, and the need for tonometry in cases of perforating corneal injuries. PATIENTS AND METHODS: We report a case of traumatic, self-sealed, midperipheral corneal perforation, where puff tonometry was performed upon admission, 30 minutes after the injury. RESULTS: The integrity of the wound was temporarily distorted by the air-jet of the puff tonometer, the wound was opened, and an air-bubble filled the anterior chamber. CONCLUSION: Puff tonometry in patients with self-sealed midperipheral corneal perforation and a negative Seidel test does not seem sufficiently safe during the immediate posttraumatic period.

Surgical outcome after early intraocular pressure elevation following combined cataract extraction and trabeculectomy.

BACKGROUND AND OBJECTIVES: We report on the incidence and course of early postoperative intraocular pressure (IOP) elevation and related surgical outcome following combined manual extracapsular cataract extraction (ECCE), using a sclerocorneal tunnel incision and trabeculectomy. PATIENTS AND METHODS: The combined procedure was the initial surgery in each eye. Intraocular pressure was measured during the first 4 days, at 1 week, and thereafter following surgery. RESULTS: Of 38 eyes (38 consecutive adults), postoperative IOP elevation to > 25 mm Hg was found in 7 eyes (18.4%) during the first 3 postoperative days. The IOP was reduced to < or = 20 mm Hg without hypotensive medication in 3 of them within the first 3-7 postoperative days, and remained so after 7-16 months (mean, 10.3 +/- 4.9 months). Each of the other 4 eyes underwent argon-laser suture lysis 8-10 days after surgery due to unstable IOP which rose to > 30 mm Hg. Two weeks after the operation and thereafter, ie, after 8-22 months (mean, 12.8 +/- 6.4 months), each of these 4 eyes necessitated 1-4 (mean, 2.5 +/- 1.3) hypotensive medications. CONCLUSION: This study raises the possibility that in eyes with early IOP elevation, a delay in promoting aqueous outflow beyond a critical period during the first postoperative week might become a risk factor for full surgical success.

Mini-trabeculectomy without radial incisions.

PURPOSE: To describe a new modification of Cairns trabeculectomy. METHODS: Surgical adjustment includes a small, 3-mm, fornix-based conjunctival flap, a circumferential scleral incision at a distance of only 1 mm from the corneoscleral limbus, and a sclerocorneal tunnel without scleral radial incisions. RESULT: Among the various clinical and technical advantages of the procedure is the possibility of performing more operations through the superior limbus rather than reverting to an inferior trabeculectomy or implantation of an aqueous shunt. CONCLUSION: The reduced surgical area and manipulations of the current procedure appear to offer advantages over the standard approach.

Protection of the transiently ischemic cat retina by zinc-desferrioxamine.

PURPOSE: A previous study indicated that hydroxyl radicals are generated in the cat retina during the early reperfusion phase after 90 minutes of ischemia. Salicylate was injected intravenously, and its conversion to 2,3-dihydroxybenzoic acid (2,3-DHBA) served as a marker of hydroxyl radicals. The authors attempted to prevent this free radical generation during reperfusion. METHODS: After salicylate administration, both eyes (15 minutes apart) of 15 cats were subjected to 90 minutes retinal ischemia. Following 5 minutes of reperfusion in the control eye, it was enucleated and processed for DHBA quantitation. Then, 7.5 mg of Zn-desferrioxamine (Zn-DFO) was injected intravenously into nine cats and saline into six cats. Five minutes later, reperfusion was induced in the experimental eye for 5 minutes, followed by enucleation. In one eye each of 12 other cats, scotopic electroretinographic (ERG) studies were carried out during 90 minutes of ischemia and 16 to 18 hours of reperfusion. Five minutes before termination of the ischemia, six animals were injected with 7.5 mg Zn-DFO and six with saline. RESULTS: The normalized levels of 2,3-DHBA were lower in the experimental eyes than in their fellow controls only after Zn-DFO treatment (P = 0.01). In the ERG studies, after 16 to 18 hours of reperfusion, the mean b-wave-ERG amplitudes in the eyes of the saline-treated cats (n = 6) were 8.4% +/- 4.0% of the preischemic stage, and 70.5% +/- 6.7% of the Zn-DFO-treated cats (n = 6, P = 0.004). CONCLUSIONS: Protection of the cat retina against ischemia and reperfusion injury by Zn-DFO was evident, most probably through its inhibitory effect on the generation of hydroxyl radicals during reperfusion.

5-fluorouracil and mast cell precursors in mice.

In the mouse hematopoietic system, 5-fluorouracil (5-FU) reversibly inhibits the generation of multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage. To determine the effect of 5-FU on mastopoiesis in vitro, bone marrow cells were obtained from mice, cultured, and treated with 5-FU for 14 days in an interleukin-3 (IL-3)-enriched medium. A dose-related inhibitory effect of 5-FU on mastopoiesis was found. When an inhibitory dose (1 microgram/mL) of 5-FU was supplemented to the cultures for only 2, 4, or 8 days and the cells were then recultured without the drug, we observed inhibition of mastopoiesis directly related to the time of exposure of the cells to 5-FU. To determine the effect of 5-FU on mastopoiesis in vivo, bone marrow cells from mice that had received a single intravenous (i.v.) 5-FU injection (150 mg/kg) were cultured. A virtually total absence of mast cells was noted at days 1 and 2 following 5-FU administration. A gradual reappearance of mast cells was later observed. Whether mice were injected with the drug once or with four once-daily (100 mg/kg 5-FU) injections, a similar pattern of delay of mast cell appearance was observed. The findings suggest (1) an irreversible, nonadditive, toxic effect of 5-FU on mast cell precursors and (2) that most or all of the mast cell precursors are nonquiescent cells, continuously activated or cycling. In addition, the use of 5-FU may serve as a unique model system for controlling and studying mastopoiesis in normal mice, rather than the mutated mice currently studied.