Intravitreal tissue plasminogen activator in submacular haemorrhage.

Submacular haemorrhage is a major cause of sudden visual loss in age-related macular degeneration (AMD). If left untreated it often results in permanent central visual loss. We present our experience in the use of intravitreal tissue plasminogen activator (tPA) in a 65-year-old male with submacular haemorrhage.

Glucose affects the severity of hypoxic-ischemic brain injury in newborn pigs.

BACKGROUND AND PURPOSE: The administration of glucose has been shown to worsen brain injury in adult animals but has no effect on the severity of injury in newborn rats. We wished to see whether the results in newborn rats could be extended to another newborn animal. METHODS: In 44 0- to 3-day-old piglets, hypoxic-ischemic central nervous system damage was induced by ligation of both carotid arteries and reduction of their blood pressure to two-thirds normal for one-half hour. In the last 15 minutes of this half hour, oxygen concentration was reduced to 6%. The piglets were randomized to receive either 2 mL/kg 50% dextrose in water followed by 2 mL/kg per hour for 2.5 hours beginning before ischemia or enough insulin to reduce their resting blood sugar to approximately 2 mmol/L. RESULTS: Neurological exam scores in the glucose-treated piglets at 1 day after injury were significantly worse than those in the insulin-treated group. Pathological examination scores were poorer in the glucose-treated group (13.6 +/- 1.9 [mean +/- SEM]) than in the insulin-treated group (24.7 +/- 1.4, P < .01). CONCLUSIONS: Increasing serum glucose during hypoxic-ischemic injury to the newborn piglet's brain worsens brain injury.

Use of polyethylene glycol-bound superoxide dismutase, polyethylene glycol-bound catalase, and nimodipine to prevent hypoxic ischemic injury to the brain of newborn pigs.

OBJECTIVE: To determine if polyethylene glycol-bound superoxide dismutase and catalase and nimodipine, alone or in combination, will ameliorate hypoxic ischemic injury to the brain. SUBJECTS: A total of 78 newborn (0 to 3 days) pigs were used. DESIGN: Prospective, blinded, randomized, controlled trial. INTERVENTIONS: The piglets were subjected to hypoxic ischemic brain injury. Carotid arteries were ligated at time 0 and BP was reduced one third by hemorrhage. At 15 mins, FIO2 was reduced to 0.6. At 30 mins, carotids were released, blood was reinfused, and FIO2 was increased to 1.0. Pigs were randomly assigned at time 35 mins to receive either: 10,000 U/kg of polyethylene glycol-bound superoxide dismutase and catalase (group 1); 0.5 mg/kg of nimodipine (group 2); both 10,000 U/kg of superoxide dismutase and catalase and 0.5 mg/kg of nimodipine (group 3); or no drugs (controls). MEASUREMENTS: The time after reoxygenation for return of electroencephalogram, respiration, blink and pain were recorded in minutes as well as a neurologic examination at 1, 2, and 3 days and pathologic examination of the brain at 3 days, both by blinded observers. MAIN RESULTS: There were no significant differences in the four groups. CONCLUSIONS: Polyethylene glycol-bound superoxide dismutase and catalase, and nimodipine, either alone or in combination, do not ameliorate hypoxic ischemic injury to the brain in the newborn pig when given 5 mins after reoxygenation.

Fructose-1,6-bisphosphate does not ameliorate hypoxic ischemic injury to the central nervous system in the newborn pig.

BACKGROUND AND METHODS: Fructose-1,6-bisphosphate has been shown to improve the outcome of hypoxic ischemic brain injury in adult rabbits. We wished to see if these results could be extended to a newborn animal. Twenty-four 0- to 3-day-old piglets were randomized to receive 300 mg/kg of fructose-1,6-bisphosphate 5 mins before injury, followed by a continuous infusion of 15 mg/kg/min of fructose-1,6-bisphosphate for the next 90 mins, or the equivalent volume of normal saline. Hypoxic ischemic central nervous system damage was induced by ligating both carotid arteries and reducing their BP to two thirds of the normal value for 30 mins. In the last 15 mins of this 30 mins, the FIO2 was reduced to 0.6. At 30 mins, the piglets were resuscitated with an FIO2 of 1.0, the carotid ligatures were released, and the removed blood was reinfused. RESULTS: The neurologic examination scores at 1, 2, and 3 days after injury and pathologic examination scores at 3 days after injury were not different in the fructose-1,6-bisphosphate-treated and the control animals. CONCLUSION: Fructose-1,6-bisphosphate does not ameliorate hypoxic ischemic brain injury in the newborn pig.

Prematurity and early-onset juvenile myasthenia gravis.

A child manifested ocular myasthenia gravis at age 16 months which progressed to bulbar and mild systemic weakness over a 3-year period. The medical history was significant for premature birth at 32 weeks gestation and birth weight 940 gm. A review of reported patients with juvenile myasthenia gravis with adequate documentation of the birth history, noncongenital onset, typical clinical course and diagnostic findings, and elevated titers of antiacetylcholine receptor antibodies revealed that 55% with onset before age 3 years had a history of prematurity. This association of myasthenia gravis and prematurity may provide insights to the pathogenesis of the disease.

MK-801 does not protect against hypoxic-ischemic brain injury in piglets.

BACKGROUND AND PURPOSE: The excitatory amino acid inhibitor MK-801 has been shown in many animals species to protect against hypoxic-ischemic brain injury. We sought to determine whether hypoxic-ischemic injury to the newborn pig's brain could be prevented by the use of MK-801. METHODS: Hypoxic-ischemic injury to the brain was induced in forty 0-3-day-old piglets. They were randomized to receive either 3 mg/kg MK-801 (MK-801 group, n = 20) or vehicle (control group, n = 19) prior to insult. At time 0, the carotid arteries were ligated and the blood pressure was reduced by one third by hemorrhage. At 15 minutes, inspired oxygen was reduced from 50% to 6%. At 30 minutes, inspired oxygen was changed to 100%, carotid ligatures were released, and the withdrawn blood was reinfused. An additional 14 piglets received 3 mg/kg MK-801 but not hypoxic-ischemic injury (drug-only group), and a final group of 11 piglets were subjected to only a sham operation (sham group). RESULTS: Neurological examination scores at 24, 48, and 72 hours showed that MK-801 and drug-only piglets were significantly worse than the controls. Pathological examination of the brains at 72 hours showed significantly greater damage in the brains of the MK-801 and control pigs relative to the sham and drug-only groups. No differences were found between the control and the MK-801 groups. No differences were found between the sham and drug-only groups. CONCLUSIONS: MK-801, at a dose of 3 mg/kg, causes neurological dysfunction in piglets lasting at least 72 hours, but neither causes brain damage nor ameliorates the effects of hypoxic-ischemic injury to the brain of the newborn pig.

Fructose-1,6-bisphosphate, when given immediately before reoxygenation, or before injury, does not ameliorate hypoxic ischemic injury to the central nervous system in the newborn pig.

BACKGROUND AND METHODS: We demonstrated earlier in our laboratories that fructose-1,6-bisphosphate (FDP) would improve the outcome of hypoxic ischemic injury to the brain in the adult rabbit. Since many human newborns suffer hypoxic injury to the brain, with a secondary ischemic component due to hypoxic cardiac failure, we set out to reproduce similar experiments in newborn piglets. Hypoxic ischemic CNS damage was induced by ligating both carotid arteries and reducing BP to 66% of normal for 30 min; in the last 15 min, FIO2 was reduced to 0.6. Twelve piglets were randomized to receive either 175 mg/kg of FDP in the last 5 min before reoxygenation or the equivalent volume of saline. The other 20 piglets received 75 mg/kg of FDP in the 5 min immediately before carotid ligation, followed by 1.8 mg/kg.min continuous infusion for the 30 min of hypoxia and ischemia or an equivalent volume of saline. RESULTS: There were no significant differences in the neurologic exam scores or pathologic exam scores between the FDP and control animals at either dose level. CONCLUSIONS: In this animal model, FDP at the doses given was not effective in ameliorating hypoxic ischemic injury to the CNS.