5-Fluorouracil and mitomycin C in pseudophakic patients.

PURPOSE: Previous studies have shown that 5-fluorouracil (5-FU) and mitomycin C enhance the success rate of filtration surgery in aphakic eyes. However, eyes with posterior chamber implants have not been specifically studied. This study was performed to compare the safety and efficacy of 5-FU with that of mitomycin C in eyes that have posterior chamber implants and undergo filtration surgery for uncontrolled glaucoma. METHODS: Eighty eyes of 74 patients who had previous cataract surgery with posterior chamber implants and who subsequently required trabeculectomy for uncontrolled open-angle glaucoma were randomized to receive either subconjunctival postoperative 5-FU or intraoperative mitomycin C. RESULTS: Twelve months after surgery, intraocular pressures (IOPs) averaged 12.8 +/- 5.5 mmHg (mean +/- standard deviation) in the mitomycin C group and 14.8 +/- 3.8 mmHg in the 5-FU group (P = 0.001). Mitomycin C-treated eyes received an average of 0.6 medications for IOP control, and 5-FU-treated eyes received an average of 1.05 medications (P = 0.03). There was no significant difference in complications between the two groups. CONCLUSION: Mitomycin C appears to be a viable alternative to 5-FU in patients with posterior chamber implants with uncontrolled glaucoma who require filtration surgery.

A double-masked comparison of betaxolol and dipivefrin for the treatment of increased intraocular pressure.

Noncardioselective beta-adrenoceptor antagonists are used for treatment of increased intraocular pressure. Because these agents may be absorbed systemically, their use is of concern in patients with restricted pulmonary function. We compared the efficacy of betaxolol, a cardioselective beta-adrenoceptor antagonist, and dipivefrin, an alpha/beta-adrenergic agonist. Seventy-six patients with open-angle glaucoma or ocular hypertension were randomly assigned to receive either betaxolol 0.5% or dipivefrin 0.1%. Patients were examined at two weeks, one month, two months, and three months. Intraocular pressure reductions were similar, with a mean decrease of 4.1 mm Hg in the betaxolol group and 3.5 mm Hg in the dipivefrin group. Both treatments caused similar minor increases in heart rate, typical with alpha-adrenergic agonists but atypical with beta-blockers. Stinging or burning in the betaxolol group was significantly (P = .008) greater than in the dipivefrin group. Our findings suggest that betaxolol and dipivefrin therapy are effective, equivalent ocular hypotensive agents.

A canine model of thrombin-induced coronary artery thrombosis: effects of intracoronary streptokinase on regional myocardial blood flow, contractile function, and infarct size.

The present investigation was undertaken to produce and to validate a canine model of experimental coronary artery thrombosis. In anesthetized, open-chest dogs, thrombin (150-200 U) was injected through an intracoronary catheter proximal to a brief (1 min) left anterior descending coronary artery occlusion. After 1 min, the mechanical occlusion was released, but no reperfusion occurred. Intracoronary thrombus was limited to the large coronary artery proximal to the site of mechanical occlusion. In two groups of dogs (n = 8), 15 min following thrombosis, vehicle (saline) or streptokinase (20,000 IU) was administered as an intracoronary bolus followed by an intracoronary infusion for 1 hr. None of the vehicle-treated dogs demonstrated antegrade coronary flow for up to 4 hr following intracoronary thrombin, whereas seven of eight had return of antegrade flow among streptokinase-treated dogs. Following streptokinase, thrombus size was reduced from control (25.1 +/- 5.3 mg versus 1.8 +/- 1.3 mg), perfusion to the subepicardium, midmyocardium, and subendocardium was increased, and infarct size was reduced. The results of the present study indicate the usefulness and reproducibility of this model in evaluating the beneficial actions of thrombolytic therapy.

Long-term evaluation of initial filtration surgery.

In a long-term study of 252 eyes that had initial glaucoma filtration surgery, there was an overall success rate of 85%. Rigid criteria for success included an intraocular pressure equal to or less than 19 mmHg, no further visual field loss or disc damage, and no glaucomatous etiology for a decrease in visual acuity. The success rate was evaluated over an extended postoperative period with a range of 2 to 14 years and a mean follow-up of five years (61 months). Full thickness procedures had a higher success rate for a greater length of time, 88% (6 years) than did trabeculectomy, 76% (4 years). If an eye was considered successful at two years, the probability of success at five years was 94.5% for full thickness procedures and only 82% for trabeculectomies. Choroidal effusion associated with hypotony and shallow anterior chamber was the most frequent postoperative complication. There was no difference in the incidence between full thickness procedures and trabeculectomies. Cataract extraction was indicated more often following full thickness procedures, 34%, than trabeculectomies, 21%. However, the performance of a choroidal tap or subsequent cataract extraction did not appear to influence the success of the filtration operation. Bleb leaks and bleb infection occurred only after full thickness operations and were associated with a high 5/8 (62%) rate of bleb failure and loss of glaucoma control. Full thickness filtering operations appeared to insure a lower pressure from a longer period of time than does trabeculectomy.

Enhanced subendocardial perfusion distal to a flow-limiting coronary artery stenosis in dogs: comparative effects of nicorandil, a potential new antianginal agent, and nitroglycerin.

The purpose of this study was to compare the effects of nicorandil [SG-75; 2-nicotinamidoethyl nitrate (ester)] and nitroglycerin on the distribution of blood flow between subendocardium and subepicardium [endocardial/epicardial blood flow ration (endo/epi)] distal to a proximal flow-limiting coronary artery stenosis in anesthetized dogs. Myocardial blood flow distribution was determined by use of 15-micron radioactive microspheres. Various indices of reactive hyperemia (peak flow, duration, volume) and poststenotic coronary pressures were used to assess the severity of ischemia in the area distal to the stenosis. Partial ischemia was produced by a 10-s total left circumflex coronary occlusion followed by 110 s of reflow to 50-60% of the control flow. Microspheres were injected during steady-state conditions during the partial reflow period. In the absence of drug, coronary artery stenosis produced marked underperfusion of the subendocardium (endo/epi, 0.55 +/- 0.05). Following administration of nicorandil (60 micrograms/kg i.v.) or nitroglycerin (15 micrograms/kg i.v.), the endo-epi during a subsequent partial reflow (stenosis present) period was significantly increased (0.67 +/- 0.06). The duration of reactive hyperemia and reactive hyperemic flow were also decreased by both compounds following release of the stenosis. These results suggest that nicorandil and nitroglycerin reduce subendocardial ischemia distal to a flow-limiting coronary artery stenosis. This beneficial effect may partially explain the efficacy of these two compounds in the therapy of angina pectoris.

Melanotic neuroectodermal tumor of infancy (retinal anlage tumor).

Six cases of the melanotic neuroectodermal tumor of infancy, including light and electron microscopic findings, are presented. The tumor, now believed to originate from neural crest, is usually cured by wide excision; however, malignant cases have been reported. Histopathologically, this lesion resembles neural retina and retinal pigment epithelium. It may involve the orbit but most frequently occurs in the maxilla. One case presented involved the orbit, another the anterior fontanelle, and four presented in the maxilla.

Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine.

The effects of nicorandil [SG-75, 2-nicotinamidoethyl nitrate (ester)] and nifedipine on the recovery of myocardial segment shortening were compared to a vehicle-treated group following a short occlusion (15 min) of the left anterior descending coronary artery (LAD) and reperfusion (5 h). The relationship between myocardial blood flow and myocardial segment shortening was examined by means of the radioactive microsphere technique and sonomicrometry. Nicorandil (100 micrograms/kg followed by 25 micrograms/kg/min, i.v.) or nifedipine (3 micrograms/kg followed by 1 microgram/kg/min, i.v.) was administered 10 min prior to and throughout the occlusion period. Both drugs produced similar decreases in mean arterial pressure (approximately 25 mm Hg) during LAD occlusion. Similar degrees of ischemia (flow deprivation) were produced in the vehicle, nicorandil, and nifedipine groups; however, nicorandil produced a significantly greater decrease in the heart rate-left ventricular systolic pressure product during coronary occlusion. During reperfusion of the LAD there was no difference in the hemodynamics of the vehicle, nicorandil, or nifedipine groups. Neither drug altered myocardial blood flow to the ischemic region during the occlusion or reperfusion period when compared to the vehicle-treated group; however, both nicorandil and nifedipine pretreatment significantly improved recovery of percentage of segment shortening of the ischemic region. Nicorandil improved the recovery of function (percentage of segment shortening) to a greater extent than did nifedipine throughout the reperfusion period, most likely because of the greater decrease in afterload produced by nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)

Actions of two new bradycardic agents, AQ-AH 208 and UL-FS 49, on ischemic myocardial perfusion and function.

The effects of continuous infusions (30 min) of two new bradycardic agents, AQ-AH 208 (3,4-dihydro-6,7-dimethoxy-2-(3-((2-(3,4 dimethoxyphenyl) ethyl)-amino methyl) propyl)-1(2H)-isochinolinon) (10 and 25 micrograms/kg/min) and UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3(3((2-(3,4-dimethoxyphenyl) ethyl) methylimino) propyl)-2H-3-benzazepin-2 on) (1.0 and 2.5 micrograms/kg/min) on ischemic myocardial perfusion and function were studied in anesthetized open chest dogs. Coronary stenosis was induced by narrowing an extracorporeal shunt between the carotid and left anterior descending coronary artery. Regional perfusion was measured by use of radioactive microspheres and regional myocardial function (% segment shortening) was assessed by sonomicrometry. AQ-AH 208 and UL-FS 49 produced dose-dependent reductions in heart rate of 13 to 55 beats/min without prominent effects on left ventricular dP/dt, aortic blood pressure, and % segment shortening of the normally perfused area. In nonischemic myocardium, AQ-AH 208 did not change transmural blood flow in spite of the bradycardia, whereas UL-FS 49 decreased flow. At the high infusion rate, ischemic subendocardial perfusion increased from 0.43 to 0.58 ml/min/g following UL-FS 49 and from 0.57 to 0.84 ml/min/g after treatment with AQ-AH 208. Consequently, endo/epi rose from 0.52 to 0.80 and 0.62 to 0.96, respectively. Atrial pacing abolished the effects of UL-FS 49 on ischemic myocardium whereas the effects of AQ-AH 208 were only partially reduced. Ischemic myocardial function deteriorated less during treatment with UL-FS 49 and was significantly improved following AQ-AH 208 as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicotinic acid, free fatty acids and myocardial function during coronary occlusion and reperfusion in the dog.

The effect of nicotinic acid on regional myocardial blood flow, percentage of segment shortening and myocardial uptake of free-fatty acids during a 15-min occlusion of the left anterior descending coronary artery and 3-hr reperfusion period was compared to a saline-treated control group. Nicotinic acid (2.4 mumol/kg/min i.v.) was infused 30 min before and throughout the occlusion period. Heart rate, arterial blood pressure and left ventricular systolic and end diastolic pressures were not different during occlusion and reperfusion in the nicotinic acid or saline-treated groups. However, left ventricular dP/dt, an index of global myocardial function and percentage of segment shortening in the ischemic region were greater during occlusion and reperfusion after nicotinic acid. Even though myocardial blood flow was unaltered in the normal or ischemic region during nicotinic acid infusion, subendocardial blood flow during reperfusion was enhanced significantly when compared to the control group. Nicotinic acid also decreased free-fatty acid uptake by the heart during occlusion which returned gradually to the pretreatment control during 3 hr of reperfusion. Thus, the improvement in percentage of segment shortening, dP/dt and subendocardial blood flow during reperfusion may be related to the ability of nicotinic acid to reduce free-fatty acid uptake by the heart during coronary occlusion.

Comparative effects of a new nicotinamide nitrate derivative, nicorandil (SG 75), with nifedipine and nitroglycerin on true collateral blood flow following an acute coronary occlusion in dogs.

The effects of nicorandil (NC), nifedipine (NF), and nitroglycerin (GTN) on true collateral blood flow were studied following an acute occlusion of the left anterior descending (LAD) coronary artery in anesthetized dogs. Ischemic tissue samples contaminated with overlap blood flow from the normal region were eliminated by using a special balloon reservoir technique for administration of radioactive microspheres. The effects of each drug on true collateral blood flow were determined following 1 h of coronary occlusion with the radioactive microsphere technique and an indirect index of collateral perfusion, retrograde pressure. NC (25 micrograms/kg/min, i.v.), NF (1.0 micrograms/kg/min, i.v.), and GTN (1.5 micrograms/kg/min, i.v.) infusions reduced mean arterial and left ventricular systolic pressures similarly (10-20 mm Hg). None of the drugs had any effect on true collateral blood flow in the presence of a decrease in aortic blood pressure. However, when aortic pressure was maintained by use of a cuff around the descending thoracic aorta, NC and NF increased collateral flow as measured by the microsphere technique as well as retrograde pressure. In addition, NC produced a significant increase in subendocardial blood flow, which resulted in an increase in the endocardial-epicardial blood flow ratio (endo/epi). GTN had no significant effect on any index of collateral function. These results indicate the importance of aortic pressure in determining the effects of vasodilators on coronary collateral function. Furthermore, NC may have more desirable effects on collateral blood flow than NF or GTN when hypotension is minimized, since this was the only agent that selectively increased subendocardial blood flow.

Effects of nicorandil and nifedipine on protection of ischemic myocardium.

The effects of nicorandil and nifedipine on ischemia--reperfusion-induced myocardial infarct size following a 2-h occlusion and 30-min reperfusion period of the left anterior descending coronary artery (LAD) were compared in anesthetized dogs. Myocardial blood flow was measured using the radioactive microsphere technique, and infarct size was determined using triphenyl tetrazolium chloride histochemical stain. Vehicle, nicorandil (100-micrograms/kg bolus followed by 25 micrograms/kg/min), or nifedipine (10-micrograms/kg bolus followed by 1 microgram/kg/min) was administered intravenously 10 min after LAD occlusion and infused throughout the occlusion and reperfusion periods. Nicorandil and nifedipine reduced mean arterial blood pressure similarly (15 mm Hg) during infusion. However, neither drug altered collateral blood flow to the ischemic region during occlusion. In all three groups, left ventricular mass, area at risk mass, percentage of the left ventricle at risk, and retrograde flow during occlusion were similar. As compared with the control group, nicorandil reduced myocardial infarct size as determined by absolute mass, percentage of the area at risk infarcted, and percentage of the left ventricle infarcted. Nifedipine had no significant effect on infarct size. This beneficial effect of nicorandil was not related to an improvement in myocardial blood flow or a change in global hemodynamics.

Effects of nicorandil, a new antianginal agent, and nifedipine on collateral blood flow in a chronic coronary occlusion model.

The effects of nicorandil and nifedipine on collateral blood flow were compared in anesthetized dogs with a well-developed collateral circulation produced by Ameroid constriction (6-8 weeks) of the left anterior descending (LAD) coronary artery. The radioactive microsphere technique was used to determine myocardial perfusion in the normal left circumflex (LC) region and in the LAD region distal to the Ameroid constrictor. Low and high doses of nicorandil (25 and 50 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min) were infused i.v. to reduce mean arterial and left ventricular systolic pressure approximately 10 and 25 mm Hg, respectively. A low dose of nicorandil had no effect on myocardial perfusion whereas nifedipine increased subepicardial blood flow in both the LC and LAD regions. The high dose of nifedipine further increased both subepicardial and subendocardial perfusion to the LC region and subepicardial blood flow to the LAD region whereas nicorandil had no effect. When aortic blood pressure was returned to control by occluding a snare around the descending thoracic aorta during infusion of the high dose, nicorandil and nifedipine increased subepicardial and subendocardial blood flow to LAD and LC regions. Whereas nicorandil increased flow to both tissue layers equally, nifedipine increased subepicardial perfusion primarily. In summary, nifedipine increased collateral blood flow in a chronic coronary occlusion model despite the presence of systemic hypotension, whereas nicorandil only increased flow when aortic blood pressure was maintained. However, nicorandil increased myocardial blood flow equally across the left ventricular wall, whereas nifedipine primarily increased subepicardial blood flow.

Oxyphil cell adenomas. Three case reports.

The clinical and histopathologic features of three cases of oxyphil cell adenomas (oncocytomas) include two cases involving the lacrimal sac and one involving the caruncle. These lesions generally occur in the caruncle of elderly women, although they have been reported to involve the conjunctiva, lacrimal sac, and rarely the lacrimal gland. They are usually controlled by wide local excision.

Differential effects of intravenous vs. intracoronary nifedipine on myocardial segment function in ischemic canine hearts.

The direct effects of nifedipine (NF) on the heart, in an acute stenosis model, were separated from its peripheral effects by comparing the actions of each after intracoronary (i.c.) or systemic (i.v.) administration in the anesthetized dog. Myocardial blood flow and myocardial contractility [percent segment shortening (% SS)] were measured with radioactive microspheres and piezoelectric crystals in a normal and partially ischemic region, respectively. A stenosis was placed on the left anterior descending coronary artery which abolished autoregulation and reduced diastolic perfusion pressure to 20 to 25 mm Hg. Intravenous NF (0.5-1.0 microgram/kg/min) reduced mean arterial pressure (104 +/- 4 to 94 +/- 5 mm Hg) and distal coronary perfusion pressure (37 +/- 2 to 34 +/- 1 mm Hg). Transmural blood flow to the normal region was significantly increased (1.04 +/- 0.12 to 1.44 +/- 0.19 ml/min/g). Although subendocardial blood flow was not altered, subepicardial blood flow to the ischemic region was decreased (0.86 +/- 0.12 to 0.72 +/- 0.14 ml/min/g) after i.v. nifedipine. Despite the small decrease in subepicardial perfusion, % SS in the ischemic region was increased (3.0 +/- 2.6 to 7.4 +/- 2.3%, 147% increase). In contrast, i.c. NF (10 micrograms) had no effect on hemodynamics or myocardial blood flow to the normal or ischemic region. Myocardial contractility to the ischemic region was depressed [7.4 +/- 1.5 to (-)-1.1 +/- 2.6%, 115% decrease]. These data suggest that alterations in myocardial blood flow do not necessarily correlate with changes in myocardial contractility after NF administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Resection of solitary metastasis. Approach to palliative treatment of hepatic involvement with choroidal melanoma.

Local resection was performed as palliative treatment of solitary hepatic metastases from choroidal melanoma in two patients. One patient survived three years after partial hepatectomy, and the second patient was in excellent clinical condition one year after hepatic resection despite radiologic evidence of possible recurrent metastases elsewhere. Our review suggests that local resection of solitary hepatic metastases may constitute an effective approach to palliation of hepatic involvement with uveal melanoma and may possibly lead to longer survival.

The Harrower collection and its place in the history of ophthalmic pathology.

A set of ophthalmic pathology slides made in 1882 by Dr. David Harrower, a Massachusetts physician who studied at Moorfields Eye Hospital, and Mr. W. Jennings Milles, the curator of Moorfields, are reviewed. They are of historical significance, as they were made at a time when microscopic examination of ocular tissues was first being introduced, and they represent one of the earliest examples of the use of celloidin for embedding ocular tissue. The slides are well preserved and contain cases demonstrating a wide spectrum of ocular pathology. The Harrower collection is possibly the oldest existing slide collection of ophthalmic histopathology.

The slow-channel calcium blocking agent, nitrendipine, and coronary collateral blood flow.

The effects of a new dihydropyridine slow-channel calcium blocking agent, nitrendipine, on hemodynamics and myocardial blood flow in normal and ischemic areas distal to either an acute or chronic coronary artery occlusion were studied in anesthetized dogs. Nitrendipine produced significant and dose-related decreases in mean aortic blood pressure and increases in flow through the nonobstructed coronary artery. In acute coronary artery occlusion experiments, only small changes in perfusion of the ischemic zone were observed following nitrendipine. On the other hand, in dogs with a chronic coronary artery occlusion and well-developed collateral circulation, nitrendipine produced significant and dose-related increases in subepicardial perfusion within the central ischemic zone. No change in subendocardial blood flow during drug-induced hypotension was observed, but when aortic pressure was held constant, there was an increase in subepicardial, subendocardial, and overall transmural myocardial perfusion. The data demonstrate that nitrendipine improves oxygen supply to collateral-dependent myocardium via an increase in coronary collateral blood flow in a model of chronic coronary occlusion.