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Biomedical subjects

W M Grant

Publications and source records attributed to W M Grant.

At least 19 recordsLinked to original sources
PubMed1991

Outflow facility studies in the perfused human ocular anterior segment.

We have recently developed a tissue model of the human aqueous outflow pathway involving placement of the eviscerated anterior corneoscleral shell, [with lens and uveal tissue removed but trabecular meshwork (TM) attached] onto a specialized perfusion apparatus. The TM and associated outflow tissues are perfused with culture medium at a physiologically-relevant perfusion pressure in a 5% CO2 environment at 37 degrees C. Under these conditions, the perfused outflow tissues are similar for several days, to the human and/or subhuman primate outflow system in vivo with regard to morphology as well as several functional parameters. Measured facility of outflow (0.271 +/- 0.018 microliters min-1 mmHg-1, n = 79) is similar to facility values obtained by tonography in living human beings. Moreover, outflow facility decreases in a linear fashion with increased perfusion pressure by 1.4% mmHg-1. Finally the removal of the TM results in a 41% decrease in measured outflow resistance. The ability to study viable human outflow tissue for at least several days and the opportunity to establish a model which serves as an alternative to animal testing, point to the potential importance of this technique in investigating the biology of the aqueous outflow system.

Anterior Eye Segment↗
PubMed1989

Outflow resistance of enucleated human eyes at two different perfusion pressures and different extents of trabeculotomy.

Aqueous outflow resistance of enucleated human eyes was measured at 7 and 25 mm Hg before and after partial and complete (12 clock hours) internal trabeculotomy. Following complete trabeculotomy, 71% of the resistance was eliminated at 25 mm Hg while only 49% was eliminated at 7 mm Hg. In contrast to published findings in eyes with intact trabecular meshwork where the resistance increased with increasing IOP (1), following complete trabeculotomy, the resistance decreased 2% per mm Hg with increasing IOP. Experiments with trabeculotomy limited to part of the circumference showed that a one hour trabeculotomy produced 41% (25 mm Hg) to 60% (7 mm Hg) of the effect of a twelve hour trabeculotomy. The results indicate that a surprisingly high fraction of aqueous outflow resistance resides in the distal aspects of the outflow system at normal IOP, and that this distal resistance drops as IOP is increased.

Aged↗
PubMed1988

Outflow facility studies in the perfused bovine aqueous outflow pathways.

We have recently developed a technique for constant pressure perfusion of the aqueous outflow pathway of the eye. Our preliminary studies, conducted in the calf eye, show surprisingly that the manipulations necessary for preparing the outflow pathways and attached corneoscleral shell for perfusion do not greatly disrupt normal aqueous outflow physiology and anatomy according to the following criteria: 1. facility of outflow is similar before and during outflow pathway perfusion 2. as in the intact eye, facility of outflow decreases with increased IOP 3. removal of outflow resistance tissue greatly increases facility of outflow 4. morphology of outflow tissues remains normal Use of the perfused outflow pathway model may enable the creation of valuable in vitro preparations which may provide much needed information about the pathogenesis of primary open-angle glaucoma.

Animals↗
PubMed1986

Pigmentary dispersion syndrome and pigmentary glaucoma. A prospective study of the natural history.

The natural evolution of pigmentary dispersion syndrome and pigmentary glaucoma was studied in 55 patients for six to 43 months (mean, 27 months). Active dispersion of pigment was observed in 45 eyes in 31 patients and was associated with worsening of glaucoma in 32 eyes. Dispersion of pigment was defined as active when there was increase in iris transillumination, increase in corneal pigmentation, or appearance of pigment granules on the surface of the lens in the pupil. There were no differences in the frequency of active dispersion of pigment and worsening of glaucoma comparing patients aged less than 44, 45 to 64, and 65 or more years. This study demonstrates that active dispersion of pigment is clinically detectable, is correlated with elevation of intraocular pressure, and continues to occur in older patients.

Adult↗
PubMed1986

Optic disc cupping in arteritic anterior ischemic optic neuropathy resembles glaucomatous cupping.

Five cases of anterior ischemic optic neuropathy secondary to biopsy-proven giant cell arteritis are presented. In each case, cupping of the optic disc, which closely resembled glaucomatous cupping, was observed in the affected eye. The presence of glaucoma was ruled out on the basis of normal intraocular pressures and normal tonographic measurements of facility of outflow. These cases indicate that arteritic ischemic optic neuropathy can result in optic disc cupping, which closely resembles glaucomatous cupping. The similarities in the appearance of cupping of these discs with that seen in eyes with glaucoma suggest that the pathogenesis of cupping in glaucoma and in arteritic ischemic optic neuropathy may share some common mechanisms.

Aged↗
PubMed1986

The flow of aqueous humor through micro-porous filters.

Flow resistance was measured as bovine and primate aqueous humor was passed through Nuclepore polycarbonate filters having flow dimensions similar to those found within the juxtacanalicular meshwork of the aqueous outflow network. The results indicate that aqueous humor has a greater flow resistance than isotonic saline; this greater resistance is attributable to proteins or glycoproteins in aqueous humor that obstruct the filters. If the same phenomenon is operative in the aqueous outflow network, it would help to explain discrepancies between calculated and measured aqueous outflow resistance.

Animals↗
PubMed1985

Race as a risk factor for progressive glaucomatous damage.

Retrospective analysis of black and white men with glaucoma indicated that open-angle glaucoma may be a more severe disease in blacks than in whites. Disk damage and visual field loss at initial diagnosis appeared to be worse in the eyes of blacks. Progression of disease as evidenced by further disk damage and visual field loss was more marked in the eyes of blacks. Furthermore, at initial diagnosis blacks were younger than whites, suggesting an earlier onset of open-angle glaucoma among blacks.

Adult↗
PubMed1983

High fetal estrogen concentrations: correlation with increased adult sexual activity and decreased aggression in male mice.

In the house mouse (Mus musculus), fetuses may develop in utero next to siblings of the same or opposite sex. The amniotic fluid of the female fetuses contains higher concentrations of estradiol than that of male fetuses. Male fetuses that developed in utero between female fetuses had higher concentrations of estradiol in their amniotic fluid than males that were located between other male fetuses during intrauterine development. They were also more sexually active as adults, less aggressive, and had smaller seminal vesicles than males that had developed between other male fetuses in utero. These findings raise the possibility that during fetal life circulating estrogens may interact with circulating androgens both in regulating the development of sex differences between males and females and in producing variation in phenotype among males and among females.

Aggression↗
PubMed1982

Why do some people go blind from glaucoma?

Retrospective analysis of patients blinded by glaucoma has revealed a need to educate patients to the significance of premonitory symptoms, to investigate a higher incidence of blindness from open-angle glaucoma among blacks than whites, and to define the goals of therapy in relation to presenting pathology. Responding to this third need, circumstances of patients followed for 20 to 40 years with extensive documentation relating to open-angle glaucoma were analyzed. Some eyes with normal discs and fields were found to tolerate a tension of 30 mm Hg for many years without need of treatment. But, when abnormalities ranging from early glaucomatous cupping to advanced visual field defects were present on initial evaluation, progressive loss of field tended to occur at lower tensions. It appears that the worse the initial condition of the eye, the lower the tension needs to be to prevent further loss or blindness.

Adult↗
PubMed1982

Effect of delta 9-tetrahydrocannabinol on monoamine oxidase activity in bovine eye tissues, in vitro.

An investigation was undertaken to analyze the effects of delta 9-tetrahydrocannabinol (THC) on monoamine oxidase (MAO) activity from calf ocular tissues. Ciliary processes, retina, trabecular meshwork, choroid, and iris all demonstrated significant MAO activity in decreasing order of magnitude. THC in concentrations from 10(-8)M to 10(-12)M stimulated MAO activity in extracts from all five tissues, except for iris at 10(-8)M. Maximum stimulation of MAO activity occurred at the 1 x 10(-12)M level for all tissues. Retina, followed next by trabecular meshwork and then ciliary processes, exhibited the largest increase in MAO activity at 10(-12)M THC. This latter effect could possibly by related to the influence of THC on intraocular pressure.

Animals↗
PubMed1982

Progressive low-tension glaucoma: treatment to stop glaucomatous cupping and field loss when these progress despite normal intraocular pressure.

Our thesis, inspired by the experience and teaching of Paul A. Chandler, is that after the optic discs have developed cupping and atrophy from elevated intraocular pressure they tend to become abnormally vulnerable and, in some cases, may continue to deteriorate even if the intraocular pressure is brought to the teens. At this stage they behave the same as in eyes with so-called low-tension glaucoma, which have developed progressive cupping and atrophy with pressures always in the teens. In either case, we find that the progression of cupping and field loss can be stopped by reducing the intraocular pressure to lower levels, preferably to 10 mm Hg or less. We have found that such low pressures are most reliably attained by surgery, using a special technique we call the shell tamponade filtration procedure, which involves the use of a glaucoma shell in conjunction with standard (full-thickness sclerostomy) filtration operations and certain specific operative and perioperative maneuvers. We present nine case reports illustrating our thesis. Glaucomatous cupping and loss of visual field were progressing relentlessly at normal pressures in each case. This progressive deterioration was shown to be arrested by reduction of the pressure to less than 12 mm Hg in 13 eyes.

Aged↗
PubMed1981

The influence of supplemental sodium acetate on carbonic anhydrase inhibitor-induced side effects.

A double-masked, randomly assigned, crossover trial of the effect of supplemental two-weak courses of sodium acetate (90 mEq/day) and placebo on carbonic anhydrase inhibitor (CAI)-induced side effects of malaise, fatigue, and others ("malaise symptom complex") was performed in 28 patients. Fifteen patients (54%) experienced significant improvement while receiving supplemental sodium acetate compared with five (18%) receiving a placebo. A relationship was observed between the clinical efficacy of the acetate supplementation and the measured improvement in serum carbon dioxide combining power. No changes in intraocular pressure were observed when supplemental sodium acetate was given. The results confirm the beneficial effect of supplemental alkalinization for such CAI-induced symptoms in somewhat less than half of the affected patients and suggest the need for long-term studies in which the dosage of sodium acetate is titrated in relation to measured changes in the level of metabolic acidosis.

Acetates↗
PubMed1981

Effect of iodoacetamide perfusion on outflow facility and metabolism of the trabecular meshwork.

Freshly enucleated eyes were quantitatively perfused via the anterior chamber with varying dosages of iodoacetamide at constant pressure. Iodoacetamide caused a significant increase in facility of outflow in a dose-response manner in calf and monkey eyes. Almost complete inhibition of glycolysis in the calf trabecular meshwork was produced by a dosage of iodoacetamide that was too low to appreciably alter the facility. A similar response was produced by a higher dosage, which did significantly increase the facility. Our results, taken together with what is known of the properties of iodoacetamide, suggest that cellular sulfhydryl groups may be involved in a mechanism for aqueous flow through the trabecular meshwork and that iodoacetamide probably acts directly on cellular permeability rather than by inhibition of glycolysis or interference with the production of energy in the trabecular meshwork.

Animals↗
PubMed1980

Acetazolamide dosage forms in the treatment of glaucoma.

Patients with chronic glaucoma had a carefully scheduled series of intraocular pressure measurements before and after taking acetazolamide for one week at the following dosages: none, 500 mg of sustained-release capsules once a day, 500 mg of capsules twice a day, and 250 mg of tablets four times a day. A capsule taken once a day, which is better tolerated than one taken twice a day by some patients, offers a substantial pressure-lowering effect that lasts at least 23 hours, although the magnitude of the pressure lowering is less than with higher dosages. One capsule twice a day appears to be as effective in the regulation of IOP as one tablet four times a day. The 45% reduction in outflow pressure is achieved with an acetazolamide serum concentration in the range of 15 to 20 micrograms/mL.

Acetazolamide↗
PubMed1980

Chloroprocaine vs. bupivacaine for lumbar epidural analgesia for elective cesarean section.

The incidence and degree of hypotension, time to establish surgical analgesia, and several other maternal and fetal variables were studied when 2-chloroprocaine, 3 per cent, and bupivacaine, 0.5 per cent, were used for epidural analgesia in 30 women undergoing elective cesarean section. Surgical analgesia occurred 8 min sooner (P less than 0.001) with chloroprocaine (14 +/- 1 min) than with bupivacaine (22 +/- 2 min). Blood pressure values were significantly lower with chloroprocaine than with bupivacaine during the 18--to-32 min interval after local anesthetic injection, while pulse rates were higher (P less than 0.05) at 18, 20, and 22 min. Hypotension necessitating treatment with ephedrine occurred in 33 per cent of chloroprocaine-treated subjects, compared with 13 per cent of those receiving bupivacaine. Newborn outcome was excellent in both groups, as reflected by umbilical vessel blood-gas values, times to sustained respiration, and 5-min Apgar scores. The authors conclude that chloroprocaine disturbs maternal cardiovascular status more than does bupivacaine when used for cesarean section epidural analgesia. However, chloroprocaine can be employed safely in normal pregnancies if maternal hypotension is corrected rapidly.

Analgesia↗
PubMed1979

Experimental perfusions through the anterior and vitreous chambers with possible relationships to malignant glaucoma.

Enucleated eyes were perfused alternately via the anterior and vitreous chambers. At low intraocular pressure (IOP), vitreous humor presented considerable resistance to forward flow of perfusion fluid in calf eyes, but not in human eyes. In human eyes when the perfusion pressure was increased to 60 mm Hg, the resistance to flow forward from the vitreous body increased, but became practically nil again when the IOP was decreased. At high pressure the volume of the vitreous body apparently increases and the anterior hyaloid membrane probably presses against the ciliary body, reducing the area of hyaloid membrane through which fluid can flow. Whether increased perfusion pressure can in some other manner change the permeability of human vitreous to resemble that of the calf remains unanswered. Our results suggest that factors other than, or in addition to, simple diversion of aqeous humor must be important in malignant glaucoma.

Animals↗
PubMed1979

Scanning electron microscopy of trabeculectomy specimens in open-angle glaucoma.

We examined trabeculectomy specimens obtained at the time of surgery for inadequately controlled open-angle glaucoma by scanning electron microscopy. Of the 50 specimens ten included a broad area of the trabecular meshwork. In these ten specimens the meshwork was obscured by material. We believe the degree of occlusion was significant in these specimens, which would lead to obstruction of aqueous outflow. No similar material was found in control specimens from persons of similar age.

Aged↗