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Biomedical subjects

D R Anderson

Publications and source records attributed to D R Anderson.

At least 181 records · Page 10Linked to original sources

Skeletal muscle ventricles for total heart replacement.

Skeletal muscle ventricles (SMV) were constructed from canine left latissimus dorsi muscle. The animals were divided into three groups: group A (n = 5), SMVs rested 4 weeks without electrical conditioning; group B (n = 6), SMVs rested 4 weeks and then electrically conditioned for 6 weeks; group C (n = 5), SMVs rested 18 weeks without electrical conditioning. At the end of each protocol, the SMVs were acutely tested by connecting them to a mock-circulation device. The SMVs in group C developed stroke work at physiologic preloads superior to any previously reported, as high as 194% of left ventricular stroke work at afterloads of 80 mmHg. The SMVs in group B developed work outputs equivalent to 53% of the left ventricle, which is still more than four times that of the right ventricle. The results show that it is possible to harvest sufficient work from skeletal muscle ventricles to fully replace cardiac function at physiologic preloads.

Adaptation, Physiological↗

Skeletal muscle ventricles in circulation as aortic diastolic counterpulsators: twelve-month update.

In previous studies, we have shown that canine skeletal muscle ventricles (SMVs) of various designs could develop stroke work intermediate between that of the canine left and right ventricle. We have subsequently reported that SMVs could be used as aortic diastolic counterpulsators. In some animals the SMVs pumped blood effectively for several weeks. Thromboembolism, however, caused renal failure, which was responsible for the demise of the longest surviving animals. More recently, we have studied a group of 15 dogs that had skeletal muscle ventricles constructed from their latissimus dorsi muscle and lined with autogenously derived tissues, either pleura, pericardium or fibrous tissue induced by a Teflon mandrel. We now report on one of those animals, that has survived more than 1 year. She remains active and in apparent good health with no clinical evidence of thromboemboli. Her SMV continues to generate effective aortic diastolic counterpulsation.

Animals↗

Acetylcholinesterase inhibition by (+)physostigmine and efficacy against lethality induced by soman.

The optical isomer (+)Physostigmine [(+)Phy] is a very weak anticholinesterase. In a recent report, pretreatment with (+)Phy, at a dose which failed to inhibit acetylcholinesterase (AChE), and atropine provided efficacy against a lethal dose of sarin (SYNAPSE:2, 139, 1988). It was of interest to see whether (+)Phy could protect against soman at a dose which caused only marginal inhibition of the whole blood (WB) AChE in guinea pigs (GPs). (-)Phy (0.15 mg/kg, im) and (+)Phy (10.0 mg/kg, im) produced nearly 70% inhibition of WB AChE at 30 min whereas (+)Phy (0.15 mg/kg, im) caused only marginal inhibition. Groups of guinea pigs (20/group) were dosed, im, with (-)Phy (0.15 mg/kg), (+)Phy (0.15 mg/kg), (+)Phy (10.0 mg/kg) or vehicle (0.5 ml/kg) respectively in one thigh while the mild anticholinergic trihexyphenidyl (THP), 2.0 mg/kg, was injected into the other thigh of 10 animals from each of the respective groups. Thirty min after pretreatment, all animals were challenged with soman (60 micrograms/kg, sc; 2 LD50s); this dose of soman is lethal in unprotected animals. (-)Phy or (+)Phy (10 mg/kg) alone protected nearly 50% from soman lethality, and in combination with THP, all animals survived. In contrast, (+)Phy (0.15 mg/kg; alone or together with THP) was completely ineffective against a 2 LD50 challenge of soman. These data support the hypothesis that protection against soman-induced lethality is related to the degree of carbamylation of the AChE just prior to challenge.

Acetylcholinesterase↗

Response of retinal vasculature to phenylephrine.

In a freshly enucleated bovine eye, the retinal arteries and veins constrict when phenylephrine is applied directly on the surface of the vessel walls. This "in situ" preparation allowed us to observe the reaction of retinal vessels without any surgical procedure that might alter the vascular response to agonists. These results indicate that alpha1-adrenergic receptors are present in the retinal vessels, which might therefore respond to vasoactive hormones. If, when, and how these reactions occur is still to be studied.

Animals↗

The influence of decreased retinal illumination on automated perimetric threshold measurements.

Decreased retinal illumination (such as can be caused by pupillary constriction or light absorption by ocular media opacities) was simulated with a randomly ordered series of neutral density filters in front of the right eyes of five subjects with dilated pupils. Threshold measurements were performed on Humphrey and Octopus perimeters at 0, 5, 10, 15, 20, and 25 degrees nasally along the 180-degree meridian. A 0.6-log unit neutral density filter, which reduces retinal illumination the equivalent of halving the pupillary diameter, decreased the mean Humphrey thresholds by 1.1 +/- 0.8 decibels (dB) (mean +/- standard deviation) and the mean Octopus thresholds by 1.7 +/- 1.4 dB. Statistically significant (P less than or equal to .05, Dunnett's test) threshold depressions were observed at all eccentricities with a 1.5-log unit neutral density filter on the Humphrey perimeter (-4.5 +/- 0.7 dB) and with a 1.0-log unit neutral density filter on the Octopus perimeter (-3.5 +/- 1.0 dB).

Adult↗

Glaucoma: the damage caused by pressure. XLVI Edward Jackson memorial lecture.

I discuss the condition of chronic glaucoma in terms that make high intraocular pressure simply one of several risk factors instead of an integral part of the disease definition. I review some of the clinical observations that constitute a basis for this perspective and explore the immediate therapeutic implications of this manner of conceptualizing the disease.

Glaucoma↗

Threshold equivalence between perimeters.

To determine equivalence between perimeters, 49 eyes of 35 subjects underwent static threshold testing of the central 30 degrees twice on each of three automated perimeters and twice by manual kinetic threshold testing with the Goldmann perimeter. The Octopus-Humphrey difference was 3.3 dB (2.3 dB in the upper two rows for programs 32 and 30-2). The Dicon-Octopus difference was 3.5 dB and the Dicon-Humphrey, 6.5 dB. The I4e stimulus of the Goldmann perimeter was equivalent to 17.1 dB, 13.6 dB, and 10.8 dB on the Humphrey, Octopus, and Dicon perimeters, respectively. The III4e stimulus of the Goldmann perimeter, used for visual impairment determination, was roughly equivalent to 7 to 10 dB, 4 to 7 dB, and 0 to 6 dB on the Humphrey, Octopus, and Dicon perimeters, respectively. The prediction when converting from one instrument to another was only 10% less reliable than the ability of a perimeter to predict the values on a second examination with the same perimeter. Validity of the conversion formulas was confirmed by the age-corrected normal values available for the Octopus, Humphrey, and Goldmann perimeters.

Adult↗

Evaluation of phototoxic retinal damage after argon laser iridotomy.

We performed several visual function tests in 17 eyes (ten patients) before and after argon laser iridotomy in an effort to detect diffuse photochemical damage to photoreceptors caused by exposure to the intense, blue-green light that is transmitted into the posterior segment as the iridotomy is created and enlarged. No change was detected in static threshold sensitivity in the central 30 degrees of the field (Octopus perimeter), color sensitivity (Farnsworth-Munsell 100-Hue test), or visual acuity. Contrast sensitivity showed a small increase at low spatial frequencies and a small decrease at high spatial frequencies. The latter change was small and not necessarily laser related, but precautions to limit laser exposure of the posterior pole are prudent.

Argon↗

The relationship between oxime-induced reactivation of carbamylated acetylcholinesterase and antidotal efficacy against carbamate intoxication.

The efficacy of the oximes pyridinium-2-aldoxime methochloride (2-PAM) and 1-[[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydro xyimino) methyl]pyridinium dichloride (HI-6), in combination with atropine (At), against lethality by either carbaryl (CA) or physostigmine (Phy) was investigated in rats. The protection by At, 8 mg/kg, iv, against CA intoxication was reduced by 2-PAM (22 mg/kg, iv) and HI-6 (50 mg/kg, iv) from a protective ratio (PR) of 6.6 to 3.5 and 2.3, respectively. However, in Phy-intoxicated rats, the administration, iv, of At alone, At + 2-PAM, or At + HI-6 at 1 min following Phy provided good protection and resulted in PRs of 7.2, 8.8, and 23.3, respectively. In experiments on decarbamylation of inhibited acetylcholinesterase (AChE), HI-6 and 2-PAM accelerated (p less than 0.05) the decarbamylation of Phy-inhibited AChE in vitro, and HI-6 decreased (p less than 0.05) the inhibition of whole blood AChE in Phy-intoxicated rats. These findings show that the protection was increased substantially by the use of either 2-PAM or HI-6 against Phy-induced lethality, whereas the use of oximes against carbaryl poisoning was contraindicated. Furthermore, even though CA and Phy are both N-methyl carbamates, the data indicate that there is no adverse interaction between 2-PAM or HI-6 and Phy.

Acetylcholinesterase↗

The effect of medial meniscectomy and coronal plane angulation on in vitro load transmission in the canine stifle joint.

The purpose of this study was to determine the in vitro load transmission characteristics of the canine stifle joint, paying particular attention to the positioning effect of the meniscus in the coronal plane. The intact joint was first loaded, and then tested under two different loading conditions after a complete medial meniscectomy. The first set of test conditions attempted to simulate those used by previous investigators, by ignoring the spacer effect of the meniscus and not repositioning the joint after its removal. The second set of tests was carried out after the joint was repositioned in the coronal plane to allow initial contact to occur in both tibiofemoral compartments. It is presumed that this occurs subsequent to a meniscectomy in vivo, following the application of any weight-bearing load. As with previous investigators, it was found that after meniscectomy the joints produced slightly larger displacements and lower stiffnesses than when intact (no significant differences from intact). However, repositioning the meniscectomized joint produced markedly smaller displacements (35-49%, p less than 0.01) and greater stiffnesses (47-123%, p less than 0.05) over the range of forces analyzed, compared with the intact joint. The ratio of dissipated to input energy was 42% for the intact joint, and rose following meniscectomy to 54% (p less than 0.05) with repositioning and 55% (p less than 0.05) without repositioning. Measured contact area decreased by 17% (p less than 0.05) following meniscectomy alone, and by 12% (p less than 0.05) following meniscectomy with repositioning. Since repositioning of the joint subsequent to meniscectomy (accounting for the loss of the meniscal spacer) resulted in an increase in structural stiffness, it was concluded that the medial meniscus decreases the structural stiffness of the intact stifle joint. In addition, the meniscus has a role in elastic energy storage and increasing contact area. This study is intended to serve as a baseline comparison for future in vivo studies on meniscectomy, meniscal repair, and meniscal replacement, in addition to more fully elucidating the mechanism of load transmission. A model is presented to explain both the decrease in stiffness after meniscectomy without repositioning and the increase in stiffness after meniscectomy with repositioning, employing linear springs of unequal length and different stiffnesses. After removal of the softer meniscal element and allowing joint approximation to occur, loading of the stiffer articular element results in an initially stiffer preparation.

Animals↗

Effects of subacute administration of physostigmine on blood acetylcholinesterase activity, motor performance, and soman intoxication.

Subacute administration of carbamates is under study as pretreatment against soman, a toxic anticholinesterase agent. In this study, the sustained release of physostigmine salicylate (Phy) in rats was achieved via osmotic minipumps; each pump contained 2 ml of Phy solution (0.4, 10, or 50 mg/ml) and delivered 2.5 microliter/hr for 28 days. At the corresponding dosage rates, rat whole blood acetylcholinesterase (AChE) activity was suppressed by approximately 11, 42, and 66%, respectively. These levels of Phy administration caused no decrement in performance on an accelerating rotarod (ARR) when tested between Days 3 and 27 of the 28-day exposure. The highest level of Phy caused a mean weight loss of 11% initially, with recovery by the 17th day. On Day 27 the rats were given 0.08 mg/kg, im, of scopolamine (SCP), 30 min before exposure to soman (58 micrograms/kg; 1 LD50, iv). In combination with SCP, the two highest levels of Phy prevented lethality and a decrement in ARR performance by soman, while the lowest level showed 40% lethality after soman and the survivors exhibited partial recovery to their own presoman control performance by 24 hr. These results suggest that, in a pretreatment mode, 42-66% inhibition of AChE by sustained exposure to Phy, with an acute dose of cholinolytic, would suffice to protect against lethality and motor performance decrement by a toxic level of soman.

Acetylcholinesterase↗

Post-infarction ventricular septal defect: the importance of site of infarction and cardiogenic shock on outcome.

Sixty-eight patients operated upon for post-infarction VSD from 1980-1987 have been reviewed to identify incremental risk factors which influence survival. Univariate and multivariate analysis was performed on 19 parameters and showed the following in decreasing order of importance to be significantly associated with non-survival: (1) operation within 24 h of occurrence of the VSD; (2) inferior infarct preceding the VSD; (3) requirement for inotropic support preoperatively; (4) preoperative cardiogenic shock; (5) a lower mean pulmonary artery pressure; (6) a lower mean wedge pressure; (7) a lower mean systolic pressure. The presence of a graft to the right coronary artery was associated with a better prognosis. Age, sex, diastolic blood pressure, balloon pumping, mean plasma urea, right atrial pressure, extent of coronary disease, number of coronary grafts, grafts to the left coronary system and method of myocardial preservation had no influence on survival.

Aged↗

Visual outcome in cystic craniopharyngiomas treated with intracavitary phosphorus-32.

Seven patients with cystic craniopharyngiomas were treated with stereotactic instillation of radioactive phosphorus-32 (32P). Five patients had been previously treated with various combinations of surgery and external beam irradiation, whereas two had the 32P instillation at a primary therapy. Visual acuity improved in 13 eyes and remained stable in 1. Visual fields normalized in three patients, improved in two, and remained stable in two. Two patients received single treatments with 32P, whereas five required multiple instillations for recurrent cyst expansion.

Adolescent↗

Static threshold asymmetry in early glaucomatous visual field loss.

Ten normal subjects underwent static threshold visual field testing of both eyes with the Humphrey perimeter, with one eye tested twice. The mean sensitivity of the field seemed virtually identical in the two eyes, with the average difference between the right and left eyes (0.65 decibels [dB]) being no greater than the testing error as reflected in the difference between the same eye tested twice (0.7 dB). The authors provide the mathematical basis for recognizing that a right eye-left eye difference in mean sensitivity might be abnormal. Additional information is needed about the variance of the right eye-left eye difference in the population at large, but present information suggests that a 2-dB difference may be meaningful on a single examination. A 1.5-dB difference is statistically significant if confirmed on a second test, and a difference as small as 1 dB may be meaningful if shown consistently in a series of four examinations. In all cases, nonglaucomatous causes of field abnormality needs to be ruled out, and the generalized asymmetry is most meaningful if it is consistent with asymmetry of cupping or intraocular pressure. Several cases are reported in which a mild (1 dB) generalized depression of the visual field is the only recognizable abnormality in the visual field in eyes with early glaucoma.

Adult↗

Optic tract injury after anterior temporal lobectomy.

Three patients had complete homonymous hemianopia with clinical and neuroimaging characteristics of ipsilateral optic tract infarction after anterior temporal lobectomy for seizure control. This injury presumably resulted from irritative vasospasm of the anterior choroidal artery. The features of this pure optic tract syndrome should be distinguished from the more common compressive optic tract syndrome which generally also impairs ipsilateral optic nerve function.

Adult↗

Clinical histologic correlation of human peripapillary anatomy.

The various types of peripapillary crescents which are observed clinically are generally interpreted to represent misalignments of the edges of the neural retina, retinal pigment epithelium (RPE), choroid, and sclera at the disc margin. In order to test the validity of conventional assumptions about the anatomic basis for each type of crescent, the authors compared histologic sections to previously obtained clinical photographs and fluorescein angiograms of 21 eyes enucleated for choroidal melanomas. The authors' results define several configurations of peripapillary tissue, but also show that there can be more than one anatomic basis for some appearances. A scleral lip, which consists of an anterior extension of sclera to separate the choroid from the optic nerve head, is nearly always present, and ophthalmoscopically appears as a white rim that marks the disc margin and accumulates fluorescein after the vascular transit in an angiogram. A chorioscleral crescent occurs when the RPE is retracted from the disc margin, most prominent when associated with a tilted exit canal for the axon bundles through the sclera. In such a crescent, the choroid may be thinned or absent next to the disc, exposing to view some of the underlying sclera. Malposition of the embryonic fold occurs when the boundary between the neural retina and the RPE does not coincide with the embryologically formed fold in the neuroectoderm that occurs at the disc. When this occurs, there is either a double layer RPE (forming a very dark pigment crescent) or a double layer of incompletely formed neural retina adjacent to the disc.(ABSTRACT TRUNCATED AT 250 WORDS)

Choroid↗

Peripapillary crescents and halos in normal-tension glaucoma and ocular hypertension.

In normal-tension glaucoma ("low-tension" glaucoma), 21 of 33 eyes (64%) had a peripapillary chorioscleral crescent or halo, compared with 13 of 38 eyes (34%) with ocular hypertension. The average area of bared choroid and sclera was greater in normal-tension glaucoma (5.8 arbitrary units of area) than in ocular hypertension (1.4 units). Myopic eyes were prevalent among the normal-tension glaucoma group. When eyes with more than 4 diopters (D) of myopia were excluded from the analysis, the difference in prevalence and size of chorioscleral crescents and halos remained. Thus, the presence of a crescent correlates with disc damage, but further work is needed to determine if the correlation represents peripapillary atrophy that accompanies glaucomatous nerve atrophy or represents a greater susceptibility of discs with preexisting peripapillary abnormality.

Female↗