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Biomedical subjects

M M Wright

Publications and source records attributed to M M Wright.

At least 19 recordsLinked to original sources

Design, synthesis, and biological evaluation of potent and selective amidino bicyclic factor Xa inhibitors.

Thrombotic diseases are a major cause of death and morbidity. Factor Xa (fXa) plays a vital role in the regulation of normal homeostasis and abnormal intravascular thrombus development in the blood coagulation cascade. A novel series of fXa inhibitors incorporating an amidino 6,5-fused bicyclic moiety at the P1 position has been designed and synthesized based on molecular modeling studies. Structure-activity relationship (SAR) studies have led to selective subnanomolar fXa inhibitors. The most potent fXa inhibitor in this series (72, SE170) has a potent inhibition constant (K(i) = 0.3 nM), is 350-fold selective for fXa over trypsin, and also shows good in vivo efficacy in a rabbit arterio-venous thrombosis model (ID(50) = 0.14 micromol/kg/h). An X-ray crystal structure of 72 complexed to bovine trypsin was completed, and a binding mode of 72 with fXa has been proposed based on modeling with human des-Gla-fXa.

Amidines↗

Resuscitation of the multitrauma patient with head injury.

Head injury remains the leading cause of death from trauma. The definitive method for eliminating preventable death from traumatic brain injury remains elusive. New research underscores the danger of inadequate or inappropriate support of oxygenation, ventilation, and perfusion to cerebral tissues. The belief that sensitivity to hypotension makes the patient with head injury fundamentally different is critical to nursing strategies. The conventional concept that fluid restriction decreases cerebral edema in patients with head injury must be weighed against mounting evidence that aggressive hemodynamic support decreases the incidence of subsequent organ system failure and secondary brain injury. New evidence has triggered a scrutiny of conventional interventions. A search for optimal treatments based on prospective randomized trials will continue. Development of neuroprotective drugs and use of hypertonic saline may be on the horizon. In an effort to ensure optimal outcome, contemporary trauma nursing must embrace new concepts, shed outmoded therapy, and ensure compliance with the basic tenets of critical care for the multitrauma patient with head injury.

Acute Disease↗

Laser-cured fibrinogen glue to repair bleb leaks in rabbits.

OBJECTIVE: To determine whether laser-cured fibrinogen glue can close bleb leaks in rabbits. METHODS: Full-thickness filtration surgery with intraoperative mitomycin and a sutured limbus-based conjunctival flap was performed in 1 eye each of 19 New Zealand albino rabbits. On the second postoperative day, a 2- to 3-mm hole was made in the bleb. In 9 rabbits, the hole was glued using fibrinogen glue with indocyanine green dye added. The glue was "cured" with a diode laser. Eyes that had been glued and developed a subsequent leak had the glue reapplied on the day the leak was detected. RESULTS: The glue remained on the conjunctiva for an average (mean+/-SD) of 1.9+/-1.8 days (range, 0-5 days). The last day of bleb leak for the rabbits with glued eyes was 1.6+/-2.4 days; for the control rabbits, it was 8.0+/-4.4 days (P=.001, Mann-Whitney U test). CONCLUSION: Laser-cured fibrinogen glue is effective in closing bleb leaks in rabbits.

Animals↗

The efficacy of goniotomy/trabeculotomy in early-onset glaucoma associated with the Sturge-Weber syndrome.

PURPOSE: To assess the efficacy of goniotomy/trabeculotomy as the initial surgical procedure in early-onset glaucoma associated with Sturge-Weber syndrome. METHODS: We retrospectively analyzed 16 eyes of 14 consecutive patients with Sturge-Weber syndrome-associated glaucoma diagnosed before 4 years of age. All subjects were seen at a single institution from 1978 to 1996 and underwent goniotomy or trabeculotomy as their initial surgical procedure. RESULTS: Twelve eyes underwent initial goniotomy, and 4 eyes underwent initial trabeculotomy. One subject was lost to follow-up after surgery, resulting in 15 eyes for analysis. Of the initial goniotomy eyes, two thirds required a second surgical procedure. In the initial trabeculotomy eyes, half required a second procedure. Intraocular pressure was controlled (intraocular pressure < or = 22 mm Hg) in 66.7% of the eyes (10 of 15) after one or more goniotomy or trabeculotomy procedures for a median follow-up of 5.4 years (range, 1.4 to 15 years). For eyes with only one surgical procedure, 4 of 6 eyes had controlled intraocular pressure over a median follow-up of 3.4 years (range, 3 to 12 years). Seven of the 9 eyes that required more than one procedure had controlled intraocular pressure after all procedures over a median follow-up of 4.5 years (range, 1.4 to 15 years). CONCLUSION: Initial or repeated goniotomy or trabeculotomy may be an effective management choice for treatment of glaucoma associated with Sturge-Weber syndrome presenting in early childhood.

Child, Preschool↗

Intermediate-term outcome of variable dose mitomycin C filtering surgery.

PURPOSE: Trabeculectomy with adjunctive mitomycin C is associated with high success rates in studies with follow-up of less than 1 year. This report evaluates the visual and intraocular pressure (IOP) outcome in eyes after trabeculectomy with adjunctive mitomycin C 1 to 3 years after surgery in a predominantly white group (98.1%). METHODS: The records of 157 eyes of 157 consecutive patients, aged 18 or older, who underwent mitomycin C trabeculectomies for uncontrolled glaucoma of various causes were reviewed. All surgeries were performed between April 1991 and June 1993. The concentration of mitomycin C varied from 0.2 to 0.5 mg/ml and was applied for 30 seconds to 5 minutes (only one patient received 0.2 mg/ml). Of the 157 eyes, 110 eyes were at high risk for failure (previous surgeries or inflammatory glaucoma). Thirty-nine eyes had preoperative IOP < or = 21 mmHg. RESULTS: The mean preoperative IOP was 29.4 +/- 10.3 mmHg. This was reduced to 13.0 +/- 7.6 mmHg at 1 year, 11.5 +/- 6.4 mmHg at 2 years, and 13.4 +/- 7.3 mmHg at 3 years. Cumulative survival rate by life-table analysis was 94.2% +/- 1.9% at 1 year, 92.1% +/- 2.4% at 2 years, and 88.7% +/- 4.0% at 3 years, where failure was defined as reoperation for control of IOP. Complications included cataract formation-progression (n = 31), hyphema (n = 26), choroidal detachment (n = 21), hypotony maculopathy (n = 5), and endophthalmitis (n = 2). Vision deteriorated in 29 eyes and improved by 2 or more Snellen visual acuity lines in 29 eyes. CONCLUSION: The IOP reduction after mitomycin C filtering surgery is sustained in the intermediate-term, 1 to 3 years, follow-up period.

Adult↗

Measurement of intraocular pressure after epikeratophakia.

AIMS: To assess the accuracy of three commonly used tonometers in eyes after epikeratophakia. METHODS: Five eye bank eyes with sutured epikeratophakia buttons were connected to a manometer and a pressure transducer. Intraocular pressure was adjusted in 5 mm Hg increments from 0 to 50 mm Hg. The intraocular pressure was measured at each increment using a Goldmann tonometer, a pneumatonometer, and a Tono-pen. RESULTS: The difference between the manometer (actual pressure) and the Goldmann tonometer ranged from -19 to +9 mm Hg (mean (SD) overestimation 2.6 (5.8) mm Hg). The pneumatonometer error ranged from -27.5 to +5.5 mm Hg (mean (SD) overestimation 4.7 (6.1) mm Hg), and for the Tono-pen the range was -18 to +11 mm Hg (mean (SD) overestimation 0.05 (7.9) mm Hg). The correlation coefficients for the three tonometers were 0.94, 0.92, and 0.87 for the Goldmann tonometer, pneumatonometer, and Tono-pen respectively. CONCLUSION: The Goldmann tonometer had the best correlation with the manometer in eye bank eyes with epikeratophakia (correlation coefficient 0.94), but none of the tonometers was accurate over the entire range of pressures tested. Detection of glaucoma in eyes with epikeratophakia cannot rely on tonometry alone, but requires examination of the optic nerve and visual field.

Case-Control Studies↗

Intraoperative mitomycin-C for glaucoma associated with ocular inflammation.

BACKGROUND AND OBJECTIVE: The authors studied the efficacy and complications of intraoperative mitomycin-C in glaucoma associated with ocular inflammation. PATIENTS AND METHODS: The authors retrospectively reviewed the medical records of 24 consecutive patients (24 eyes) with glaucoma and ocular inflammation who had been treated with trabeculectomy and intraoperative mitomycin-C. Patient ages ranged from 10 to 83 years (mean 43 years). All patients were observed for at least 6 months. RESULTS: With a mean follow-up time of 14.6 months, 18 of the 24 patients (75%) retained vision and had an intraocular pressure of 21 mm Hg or lower with or without medications (range 4 to 21 mm Hg; mean 13.4 mm Hg). Fifteen of 24 patients (62%) had an intraocular pressure of 21 mm Hg or lower with no medications. Three patients required tube shunt implants. One patient had a retinal detachment and lost light perception. One patient had endophthalmitis 14 months after surgery. Seven of 24 patients lost two or more lines of Snellen acuity. CONCLUSION: Trabeculectomy with mitomycin-C can control intraocular pressure in glaucoma associated with ocular inflammation, but complications are frequent.

Adolescent↗

Attempted autoenucleation.

PURPOSE: A 24-year-old man had visual acuity of no light perception in the left eye after attempted autoenucleation. METHODS: An urgent lateral canthotomy was performed, followed by treatment with high-dose intravenous corticosteroids. RESULTS: Visual acuity improved to L.E.: 20/30. Visual field testing disclosed recovery of the central visual field with persistent arcuate visual field defects. CONCLUSION: Visual acuity of no light perception after attempted autoenucleation does not preclude the return of good visual acuity.

Adult↗

A prospective study of ocular hypertension and glaucoma after pediatric cataract surgery.

BACKGROUND: Late-onset glaucoma can occur after pediatric cataract surgery. However, no large prospective study of the prevalence of ocular hypertension and glaucoma after pediatric cataract surgery has been performed. METHODS: A prospective glaucoma evaluation was offered to all eligible subjects at least 5 years after automated lensectomy and vitrectomy for pediatric cataracts. RESULTS: Sixty-two (58%) of 107 eligible subjects received a glaucoma evaluation. One (4.5%) of 22 patients with bilateral cataracts had glaucoma, and a much higher percentage (45%) had ocular hypertension. Five (12.5%) of 40 patients with unilateral cataracts had glaucoma, and an additional 32.5% had ocular hypertension. For patients with monocular cataracts, the age and corneal diameter at the time of cataract surgery were related to the subsequent development of ocular hypertension or glaucoma. The majority of subjects were able to cooperate with a comprehensive glaucoma examination that included cycloplegic refraction, determination of intraocular pressure, examination of the optic nerve, and fundus photography, without requiring sedation. CONCLUSIONS: There is a high prevalence of ocular hypertension after pediatric cataract surgery. Children who are 5 years of age and older usually are able to cooperate with a glaucoma evaluation. The natural history of ocular hypertension after pediatric cataract surgery will be determined with longitudinal studies in the future.

Aphakia, Postcataract↗

The physiologic characteristics of relative pupillary block.

In biometric photographs of 13 patients, we quantified the iris contour in eyes with central anterior chamber depths ranging from 1.9 to 3.4 mm (epithelium to lens surface). This actual profile was compared to that predicted by a theoretical analysis of the forces acting on the iris. The average discrepancy between the calculated actual and the theoretically predicted iris position was only -0.01 to +0.03 mm. The close agreement validates the model under normal conditions and in the presence of relative (nonsynechial) pupillary block. The theoretical iris shape may not occur under conditions that violate the underlying physical assumptions of the mathematical model, such as when iridectomy eliminates the pressure difference between the anterior and posterior chamber or when synechiae introduce additional forces on the iris other than the ones included in the analysis.

Anterior Chamber↗

Measurement of intraocular pressure with a flat anterior chamber.

When a flat chamber develops in an eye after filtration surgery, management depends on whether the cause is excessive filtration or aqueous misdirection (ciliary block or malignant glaucoma). This diagnosis is often based on the intraocular pressure: low pressure in excessive filtration, high pressure in aqueous misdirection. To determine the accuracy of tonometry when the lens is in contact with the cornea, flat anterior chambers were created in 5 eyes obtained from an eye bank. The pressure in the vitreous cavity was raised and lowered with an infusion line and monitored with a pressure transducer. The intraocular pressure was estimated with a Goldmann applanation tonometer, a Pneumatonometer, and a Tono-pen. The readings poorly represented the actual pressure in the vitreous cavity. The error was 0 to 51 mmHg (mean, 12.8 mmHg) with the Goldmann tonometer, 0 to 33 mmHg (mean, 9.0 mmHg) with the Pneumatonometer, and 1 to 28 mmHg (mean, 13.5 mmHg) with the Tono-pen. Therefore, in the face of a flat anterior chamber, pressure measurements made on the cornea cannot be relied on to distinguish excessive filtration from aqueous misdirection.

Anterior Chamber↗

5-Fluorouracil after trabeculectomy and the iridocorneal endothelial syndrome.

Nine patients (nine eyes) with iridocorneal endothelial (ICE) syndrome underwent trabeculectomy and received postoperative subconjunctival injections of 5-fluorouracil (5-FU) to enhance bleb formation (total 5-FU dose, 30-105 mg; mean, 53.8 mg). Eight eyes had undergone prior unsuccessful trabeculectomy. Four eyes had intraocular pressure (IOP) less than or equal to 21 mmHg on zero to two glaucoma medications after 6 to 54 months of follow-up (mean, 25.3 months). Five eyes required repeat surgery within 2 to 13 months and were considered failures. All five eyes that failed received a Molteno drainage implant. Progressive endothelial proliferation may explain late onset bleb failure and the relative ineffectiveness of 5-FU in this condition.

Adult↗

Nd:YAG cyclophotocoagulation: outcome of treatment for uncontrolled glaucoma.

We reviewed the records of 35 patients (35 eyes) treated with Nd:YAG cyclophotocoagulation for uncontrolled glaucoma and followed for 6 to 36 months or until treatment was declared a failure (loss of light perception, or intraocular pressure (IOP) greater than 21 mm Hg). The mean pretreatment intraocular pressure was 37.9 mm Hg (range, 20 to 61 mm Hg). The total energy in the initial treatment session ranged from 50.4 to 372.4 J (191.7 +/- 66.3 J). After the treatment, the mean IOP was 21.2 mm Hg (range, 0 to 53 mm Hg). The Kaplan Meier survival analysis demonstrated that failures occurred throughout the follow-up period and that the majority of patients required further intervention or lost all vision if followed long enough. Visual outcome was not correlated with energy used. Eleven eyes (31%) lost two or more lines of acuity or lost all light perception. These findings suggest that Nd:YAG cyclophotocoagulation may control IOP but cannot always save vision.

Adolescent↗

Time course of thymoxamine reversal of phenylephrine-induced mydriasis.

We conducted a randomized, double-masked, paired comparison of 0.1% thymoxamine vs placebo for the reversal of phenylephrine-induced mydriasis. Mydriasis was induced with 2.5% phenylephrine in each eye of 74 subjects (148 eyes). Each subject then received 0.1% thymoxamine in one eye and placebo in the other eye. Pupillary measurements were obtained at regular intervals during the ensuing 8 hours. At all intervals, a greater percentage of thymoxamine-treated eyes returned to baseline pupillary diameters compared with placebo-treated eyes (P less than or equal to .01). For subjects in whom both pupils returned to baseline, thymoxamine-treated eyes returned to baseline in a mean of 2.2 hours, vs 5.2 hours for placebo (P less than .0001). Among thymoxamine-treated eyes, those with light irides responded more rapidly than those with dark irides, returning to baseline in 1.6 vs 2.8 hours, respectively (P = .0046). After constriction to baseline pupillary diameter had been achieved, no patients experienced a rebound dilation.

Adolescent↗

Efficacy of the primary dye test.

A primary dye test was performed on the right lacrimal system of 25 normal subjects by three physicians of differing levels of experience in performing the test. The frequency of positive primary dye tests for each of the three examiners was higher than previously reported. The most experienced examiner had the highest percentage (100%) of positive primary dye tests, and the least experienced examiner had the lowest percentage (80%) of positive tests. However, variation between the most experienced examiner and the other two was due, at least in part, to a difference in fluorescein instillation. Therefore, the effect of experience could not be ascertained. The most experienced examiner used four moistened fluorescein strips medially and each used a 10-minute interval after dye instillation before looking for evidence of dye passage through the nasolacrimal duct. Twenty-one (84%) of the subjects had a positive primary dye test on initial blowing of the nose. This indicates that even inexperienced examiners can expect to detect a high percentage of functioning lacrimal drainage system with the method of the experienced examiner.

Adult↗