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Biomedical subjects

D R Anderson

Publications and source records attributed to D R Anderson.

At least 199 records · Page 11Linked to original sources

Skeletal muscle ventricles: improved performance at physiologic preloads.

We attempted to construct skeletal muscle ventricles (SMVs) so that they would develop optimal stroke work at physiologic preloads of 5 to 15 mm Hg. Thirty-one SMVs were constructed in mongrel dogs. The effects of electrical preconditioning with 2 Hz continuous and 25 Hz burst patterns were evaluated, as well as the application of passive stretch to the muscle fibers during preconditioning. We evaluated the stroke work developed by these SMVs at afterloads of 30 mm Hg and 80 mm Hg in vivo, using a mock circulation device. During mock circulation studies, the SMVs were stimulated via the thoracodorsal nerve with either a 25 Hz or 85 Hz burst pattern. SMVs with 2 Hz preconditioning developed significantly higher stroke work than SMVs with 25 Hz preconditioning under all conditions of afterload, preload, and stimulation frequency (p less than or equal to 0.001). Under these conditions, for the 2 Hz preconditioned SMVs, passive stretch during preconditioning resulted in a further significant increase in developed stroke work (p less than 0.05). For these SMVs, with an 85 Hz stimulation frequency, stroke work averaged 410% of canine RV stroke work, and 59% of canine LV stroke work at physiologic preloads and afterloads.

Animals↗

Bridge flexor tendon grafts.

In adults, when flexor tendons cannot be repaired until weeks or months after injury or when tendons have ruptured and part of the tendon is nonviable, it is often inadvisable to suture the tendon ends together. When a primary repair has failed, when there has been a delay in tendon reconstruction to allow skin coverage or joint mobilization, or when repair has been delayed because of infection, continuity of a profundus tendon or flexor pollicis longus tendon can often be restored by using a free graft to bridge the defect. Many patients treated by this procedure will have a satisfactory result providing that the flexor tendon is undamaged within its digital sheath and the muscle is intact and has adequate amplitude. In the study reported here, satisfactory function was restored to 28 of 37 fingers and to eight of ten thumbs treated by this method.

Adult↗

Possibly reduced prevalence of peripapillary crescents in ocular hypertension.

We studied optic disc photographs from 137 healthy subjects and 195 subjects with ocular hypertension. The prevalence of peripapillary crescents was lower among hyperopes than among myopes (p less than 0.05). Moreover, the ocular hypertensive subjects had a statistically significant tendency toward a hyperopic median refraction (p less than 0.01). In keeping with this, we observed a lower prevalence rate of crescents in the ocular hypertensive group (35%) than among the healthy subjects (41%). This difference is in the expected direction and magnitude if the absence of a crescent decreases the risk of glaucomatous damage from elevated intraocular pressure, but the number of subjects was too small to obtain statistical significance; however, the evidence is suggestive. Further study, such as in a large population survey or by comparison of two groups with matched genetic heritage, is needed to substantiate the relation between the presence of a crescent and increased risk of glaucomatous damage.

Female↗

Biochemical evidence for cholinergic activity in retinal blood vessels.

Blood vessels from human, cat, pig and bovine retinas were analyzed for their contents of choline acetyltransferase (ChAT) and muscarinic binding sites. ChAT was measured by the synthesis of 3H-acetylcholine in the presence of 3H-acetyl CoA and choline. Muscarinic binding sites were determined by the specific binding of 3H-quinuclidinyl benzylate (3H-QNB). Tissue levels of ChAT varied from 39-850 nmol/g/hr, the lowest values being in human tissues. Muscarinic binding sites were less different (0.5 to 1.8 fmol/mg net weight) among the species studied, being the highest values in human retinal vessels. It appears that retinal blood vessels not only have sites to bind acetylcholine, perhaps to mediate physiologic responses, but might be capable of supplying acetylcholine for local vascular tone control.

Animals↗

Thymoxamine reverses phenylephrine-induced mydriasis.

We performed a randomized double-masked evaluation of the alpha-adrenergic blocking agent thymoxamine (0.1%) as compared to placebo for the reversal of phenylephrine-induced mydriasis. Topically applied thymoxamine reversed the mydriasis from a single drop of 2.5% phenylephrine in 36 of 40 eyes (90%) within one hour. The mydriasis was completely reversed in 25 of 40 eyes (63%). Eyes with blue irides responded more quickly and more completely than did those with brown irides. The 40 contralateral eyes, which had also been dilated with phenylephrine, remained dilated or dilated further after receiving a placebo eyedrop. Twenty subjects (50%) reported mild transient ocular irritation upon instillation of thymoxamine. Thymoxamine was useful in individuals with narrow anterior chamber angles who were at risk of acute closed-angle glaucoma following dilation with an adrenergic agent.

Adult↗

Correlation of asymmetric damage with asymmetric intraocular pressure in normal-tension glaucoma (low-tension glaucoma).

If intraocular pressure plays a role in producing visual field loss in normal-tension glaucoma, there may be a possible benefit from therapeutic efforts to lower the pressure. To see whether pressure plays a role in the production of damage, we studied 14 cases of normal-tension glaucoma with asymmetric intraocular pressure (1- to 6-mm Hg interocular difference in pressure). In 12 of these 14 cases, we found that glaucomatous cupping and field loss (damage) was greater in the eye with higher pressure. This statistically significant correspondence of the higher pressure with the greater visual damage suggests that the level of pressure is a factor in producing optic nerve damage. Other factors also must contribute to account for the few instances in which damage asymmetry did not reflect interocular pressure-difference and for the occurrence of injury at such low levels of pressure in the first place. Although benefit may be expected from therapeutic lowering of pressure in this condition, the degree of benefit, as well as the side effects from treatment required for successful lowering of pressure, remains to be documented by a future clinical trial.

Glaucoma↗

The configuration of peripapillary tissue in unilateral glaucoma.

We compared the peripapillary scleral and choroidal halos and crescents in the two eyes of 42 patients with unilateral glaucoma. In most cases, the edge of the three tissue layers (the retinal pigment epithelium [RPE], the choroid, and the sclera) that encircle the optic nerve head of the glaucomatous eye superimposed exactly on the mirror images of the edges in the fellow nonglaucomatous eye. Although the size of the peripapillary crescent or halo was the same in both eyes, it and the scleral rim were often more conspicuous in the eye with glaucomatous damage because the tissue edges were seen more easily through the reduced thickness of nerve fiber layer tissue. There were nine exceptions. In five cases, the peripapillary choroidal crescent (the area of choroid not covered by RPE) was larger in the glaucomatous eye. In four eyes, however, the crescent was larger in the nonglaucomatous eye, although the magnitude of the asymmetry was less in these four cases. Thus, in late stages of optic nerve damage, there was some RPE atrophy, but in most cases of glaucoma, the area of bared choroid was the inherent anatomic configuration of the optic nerve exit canal.

Choroid↗

The influence of simulated light scattering on automated perimetric threshold measurements.

The effect of light scattering by ocular media opacities on OCTOPUS and Humphrey perimeter threshold measurements was simulated with randomly ordered sequences of six ground-glass diffusers in the right eyes of five subjects. Threshold measurements were performed at 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 25 degrees nasally along the 180 degrees meridian with the F4 program on an OCTOPUS perimeter, and with twice-repeated profiles on a Humphrey perimeter. The reduction in differential light sensitivity correlated well with the 2.7-dB to 16.7-dB reduction in stimulus intensity caused by the 46% to 98% scattering of incident light by the diffusers. Contrast sensitivity in the presence of a glare source (Miller-Nadler glare test) was also affected by the diffusers, such that a 75% contrast target was not visible through the strongest diffuser whereas a 5% contrast target was visible without a diffuser. Conversely, the diffusers had very little effect on visual acuity measurements that were performed with projected high-contrast targets in a darkened room. Our data suggest that even minimal light scattering, such as might be caused by a cataract that has a relatively insignificant effect on visual acuity, may influence threshold measurements.

Adult↗

Acquired peripapillary changes and progression in glaucoma.

In a review of fundus photographs, changes in the degree of depigmentation or atrophy of the retinal pigment epithelium (RPE) were observed near the disc over time in 21% of cases with progressive glaucomatous cupping, but they also occurred as a natural phenomenon over time in 4% of eyes with nonprogressive glaucoma and in 3% of nonglaucomatous eyes. Thus, the peripapillary RPE shows some progressive alteration in normal individuals, but also may sometimes suffer along with the axons during glaucomatous damage. The acquired changes observed in the progressive glaucomatous eyes seem too small and too infrequent to account for the high prevalence of large haloes and crescents seen around the optic disc in glaucoma.

Adolescent↗

Mitral incompetence associated with lipoma infiltrating the mitral valve.

A 54 year old man presented with presyncopal symptoms. Echocardiography and subsequently computed tomography showed a mass in the posterior mitral annulus causing incompetence of the valve. At operation a lipoma was found which could not be resected. Mitral incompetence was the result of chordal rupture where the lipoma had engulfed the papillary muscle. The valve was replaced and the patient made an uneventful recovery. This case report shows a potential danger of an otherwise benign lesion.

Heart Neoplasms↗

A comparison of in vivo and in vitro rates of aging of soman-inhibited erythrocyte acetylcholinesterase in different animal species.

This study was conducted to assess differences in the rate of aging of soman-inhibited erythrocyte (RBC) acetylcholinesterase (AChE) from different species and to determine whether the rate of aging in vitro approximates that in vivo following a single exposure to soman. The logarithm of the percentage RBC AChE reactivated by 2-PAM after soman exposure was plotted as a function of time. Linear regression analysis was used to determine the half-time (t1/2) for aging. In the in vivo experiments, the rapidity of aging increased from rat to guinea pig to marmoset; the corresponding t1/2 values (mean +/- standard error) were 8.6 (+/- 0.94) min, 7.5 (+/- 1.7) min and 0.99 (+/- 0.10) min. The in vitro values of t1/2 in marmoset and guinea pig were 1.1 (+/- 0.08) min and 8.0 (+/- 0.82) min, respectively. Other t1/2 values computed for in vitro experiments were 1.4 (+/- 0.11) min for cynomolgus monkeys and 0.88 (+/- 0.03) min for squirrel monkeys. The results indicate that, for marmoset and guinea pig, the in vitro values closely approximate the in vivo. Since aging of soman-inhibited human and monkey RBC AChE occurs rapidly (1 min) in vitro, it is reasonable to assume that in man rapid aging will be crucial in delimiting successful treatment of soman intoxication.

Acetylcholinesterase↗

Angiotensin-converting enzyme in bovine, feline, and human ocular tissues.

Angiotensin-converting enzyme was shown to be present in retinal vessels and neural retina of feline, bovine, and human eyes. It was also demonstrated in the other ocular tissues of feline eyes, in especially high concentration in the highly vascular uveal layer. Its role in the physiology of ocular blood flow and neurophysiology is uncertain, especially in the retina where circulating angiotensin and bradykinin are confined to the intravascular space by the blood-retina barrier, and sufficient data are not available to describe these peptides as transmitters or modulator molecules in the retina.

Angiotensin-Converting Enzyme Inhibitors↗

A method for improved biometry of the anterior chamber with a Scheimpflug technique.

A new method is described for obtaining cross-sectional images of the anterior chamber. Photographs are obtained with a Scheimpflug slit-lamp camera. After cornea, iris, and lens surfaces are digitized, mathematical corrections are made for the camera distortion and for the refractive effects of the cornea. The reproducibility and accuracy of the method were tested and found to be adequate for clinical study of human eyes in physiologic or diseased states.

Analog-Digital Conversion↗

Threshold variability with an automated LED perimeter.

The CooperVision Dicon AP 2000 does not project the stimulus onto an existing background, but produces the test stimuli with light emitting diodes (LEDs) recessed in a dark cavity in the perimetric bowl. Nearly everywhere in the visual field, the visibility threshold with the Dicon instrument seems equivalent to that obtained with projection perimeters, but in the most sensitive retinal areas we found the threshold stimulus (Is) to be sometimes dimmer than the "background" (Ib), which surrounds the stimulus, making a negative differential threshold (delta L = Is - Ib). In other words, where a dark cavity is imaged on a very sensitive portion of the retina, the visual mechanism may perceive the switching on of a stimulus of a lower intensity (Is) than the "background" light (Ib) that floods only the surrounding retina. In retinal regions where this happens, we found the variability of retesting of threshold to be much greater than at locations with threshold stimuli that are more intense than the "background". When we modified the instrument by placing a diffuser over the LED to provide a preexistent "background" at the test location equivalent to that of the surround, the greater variability disappeared, and the threshold results resembled those of projection perimetry even at the most sensitive retinal areas. Variability was also reduced with shortened stimulus durations.

Adult↗

Oxime-induced decarbamylation and atropine/oxime therapy of guinea pigs intoxicated with pyridostigmine.

The generally accepted explanation for the effects of oximes in countering organophosphorus (OP) anticholinesterase is reactivation of the inhibited acetylcholinesterase (AChE). With soman, the inhibited AChE rapidly becomes resistant to oxime reactivation due to a phenomenon called aging. Thus, pretreatment with pyridostigmine (Py) or physostigmine (Ph) followed by atropine sulfate therapy is required to achieve significant protection against soman; the effectiveness of a pretreatment/therapy (P/T) regimen can be further increased against certain OPs (e.g. sarin and VX) by including an oxime in the therapy regimen. The P/T regimen is clouded by a controversy concerning the use of oximes in the treatment of carbamate intoxication, because 2-PAM has been reported to exacerbate intoxication by some carbamates and to have no effect on decarbamylation rates. To better understand the role of oxime therapy in the theory of pretreatment of OP intoxication we examined the effects of 2-PAM and HI-6 on the rate of decarbamylation of Py-inhibited erythrocyte AChE in vitro and in vivo, and studied the effects of atropine plus 2-PAM or HI-6 on Py toxicity. In decarbamylation experiments, Py-inhibited guinea pig erythrocytes were washed free of excess Py and incubated with vehicle or oxime (2 X 10(-4) M, pH 7.3 and 37 degrees C). Aliquots were assayed for AChE activity at various times during a 60 min incubation period. Rate constants were calculated and compared to determine whether the presence of oxime affected decarbamylation. The data from in vitro and in vivo experiments revealed that oximes accelerated the decarbamylation (p less than 0.05) of inhibited AChE. Lethality data for Py-treated guinea pigs showed that treatment with atropine (23 mumoles/kg, im) plus 2-PAM or HI-6 (145 mumoles/kg, im) at one min after injection of Py increased the protective ratio from 4.2 (atropine only) to 5.1 and 12.2, respectively. It is suggested that the enhanced therapeutic efficacy of atropine by oximes against Py intoxication is related to oxime-induced reactivation.

Acetylcholinesterase↗

The influence of refraction accuracy on automated perimetric threshold measurements.

The effect of refraction accuracy on the differential light threshold of a Goldmann size III (0.43 degrees diameter) stimulus was evaluated in the right eyes of five normal subjects with randomly ordered sequence of plano, +1.00-, +2.00-, +3.00-, +4.00-, +5.00-, and +6.00-diopter (D) spherical overcorrections. Threshold measurements were performed at 0 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 25 degrees eccentricity nasally along the 180 degrees meridian with the F4 program on the Octopus 201 perimeter. The +1.00- through +6.00-D overcorrections decreased the threshold values by an average of 1.4, 2.9, 4.2, 5.6, 6.7, and 7.6 dB, respectively, compared with the plano overcorrection. The depression of the differential light threshold was of similar magnitude at all eccentricities within the central 25 degrees.

Adult↗

Accommodation of an endocapsular silicone lens (Phaco-Ersatz) in the nonhuman primate.

In owl monkeys, as a model of endocapsular cataract extraction, the lens material was removed through a small hole in the capsule and was replaced with a silicone polymeric gel. The ability of this endocapsular implant (Phaco-Ersatz) to accommodate was documented when pilocarpine produced an increase in the curvature of the lens surface and a decrease in the anterior chamber depth, just as occurs with the untouched natural lens. Refinements of the surgical technique are required to achieve a controlled degree of filling of the capsular bag and inhibit postoperative epithelial proliferation on the inner capsular surface.

Accommodation, Ocular↗