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.

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.

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.

A randomized study of trabeculectomy and subconjunctival administration of fluorouracil in primary glaucomas.

Forty-one adult patients with primary open angle glaucoma and nine adult patients with chronic angle closure glaucoma underwent trabeculectomy in one eye each. Twenty-one eyes with primary open angle glaucoma and four with chronic angle closure glaucoma were randomly assigned to receive four to six subconjunctival injections of fluorouracil for 10 days after surgery. Twenty-five control eyes did not receive fluorouracil. Intraocular pressure was 20 mm Hg or lower in 24 eyes (96%) in the treatment group after mean follow-up of 17.8 months and in 19 control eyes (76%) after mean follow-up of 17.5 months (P less than .05). Encapsulated bleb developed in three (12%) of the fluorouracil-treated eyes vs two (8%) of the control eyes. A few injections of fluorouracil adequately inhibited scarring. This might be explained by its toxic effect on existing fibroblasts. Overall, trabeculectomy with injection of fluorouracil was found to be efficacious and relatively safe. Further studies regarding late complications are required.

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.

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.

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.

Late complications after glaucoma filtering surgery with adjunctive 5-fluorouracil.

We studied 105 patients (105 eyes) operated on for glaucoma with adjunctive fluorouracil, who were followed up for 12 to 48 months (mean, 34.6 +/- 12.9 months). Fifty eyes that had previous glaucoma or cataract extraction or had inflammatory glaucoma had a high risk for postoperative scarring (high-risk group), and 55 eyes had glaucoma surgery as an initial procedure (initial surgery group). An intraocular pressure of 20 mm Hg or less, with or without hypotensive medications, was found in 42 eyes in the high-risk group (84.0%) and in 53 of the eyes in the initial surgery group (96.4%). Of the 105 eyes, an intraocular pressure of 12 mm Hg or less without medication was achieved in 17 eyes in the high-risk group (34.0%) and in 35 eyes in the initial surgery group (63.6%). Late complications in both groups were as follows: endophthalmitis in four eyes (3.8%) (two of the infected blebs were located superiorly and two inferiorly), transient leaking bleb in two eyes (1.9%), hypotony of an extended period with 180 to 360 degrees of filtration in three eyes (2.9%), giant bleb extending over the cornea in two eyes (1.9%), and a transient, mild iridocyclitis in nine eyes (8.6%). Thus, adjunctive fluorouracil after filtering surgery may entail various, mainly bleb-related, late side effects and complications.

Experimental intraocular proliferation and neovascularization.

An experimental model of massive periretinal proliferation and intraocular neovascularization, produced in rabbits by the intravitreal injection of 250,00 cultured heterologous fibroblasts, showed no significant difference in the detachment rate (69% to 100%) or neovascularization rate (45% to 88%) between the animals injected with autologous cells and those injected with heterologous cells. Dermal fibroblasts produced a slightly higher detachment rate than conjunctival fibroblasts and were equally effective after reconstitution and subculture from liquid nitrogen storage in 7% dimethyl sulfoxide. Heterologous cells produced no clinical or histologic evidence of rejection when compared with autologous cells in the same animal and had the following advantages: (1) elimination of several biopsies and extended cell culture time; (2) a ready source of cryopreserved cells is available; (3) multiple injections of many animals can be performed within a short time; (4) in vivo and in vitro drug testing can be correlated on the same cell line.

Fluorouracil for the treatment of massive periretinal proliferation.

A single intravitreal injection of fluorouracil was effective in the treatment of an experimental model of massive periretinal proliferation. When given with an intravitreal injection of 250,000 heterologous fibroblasts, fluorouracil decreased the rate of tractional retinal detachment from 36.8% in controls (seven of 19 eyes) to 5.2% in treated animals (one of 19 eyes) at one week, and from 73.6% in controls (14 of 19 eyes) to 31.5% in treated animals (six of 19 eyes) after four weeks (P less than .05). Intraocular neovascularization was reduced from 52.6% in controls (ten of 19 eyes) to 5.2% in treated animals (one of 19 eyes) after one week and 36.8% in controls (seven of 19 eyes) to 5.2% in treated animals (one of 19 eyes) after four weeks. When supplemented by repeated 10-mg subconjunctival injections of fluorouracil, or in combination with intravitreally administered indomethacin, this effect appeared to be enhanced. Intravitreal and subconjunctival injections of fluorouracil were well tolerated and may prove to be of significant value in the treatment of human disease.

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.

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.

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.

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.

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.

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.

[Treatment of anterior uveitis with 5-fluorouracil].

Filtering surgery with use of 5-fluorouracil (5FU) was performed in 5 eyes (4 patients) with inflammatory glaucoma to prevent filtering bleb scarring. Postoperative injections of 5FU were given once or twice a day, according to the degree of anterior chamber inflammation. Complete remission of the uveitis was achieved in all 5 eyes after 7-14 days of postoperative injections of 5FU. There were no recurrences of uveitis during a minimum of 8 months of follow-up.

[Prevention of scarring of filtering bleb by 5-fluorouracil].

Scarring of the filtering bleb is the most common cause of failure of surgery for glaucoma. It is much more common when the surgery is for certain types of glaucoma, such as aphakic glaucoma, cases of previously failed filtering surgery and neovascular and uveitic glaucoma. In 31 such high-risk cases we injected 5-fluorouracil subconjunctivally for 7-16 days after operation to prevent scarring of the filtering bleb. The success rate was 83%. After a follow-up of 3-12 months, there was statistically significant improvement in each group as compared to cases in which the drug was not administered. Further indications should be considered for the use of 5-fluorouracil in glaucoma.

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.