A paired comparison of the accuracy of two impedance plethysmographs.
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Humans↗
Biomedical subjects
D R Anderson
Publications and source records attributed to D R Anderson.
Oxygen modulation of guanylate cyclase-mediated retinal pericyte relaxations with 3-morpholino-sydnonimine and atrial natriuretic peptide.
PURPOSE: This study explores at which level of the guanylate cyclase pathway oxygen modulates retinal pericyte relaxation induced by nitric oxide (NO). METHODS: Bovine retinal microvascular pericytes were grown on silicone. On silicone, pericyte contractile tone induces wrinkles. Drug-induced relaxation was quantified as a reduced number of wrinkles after exposure to 3-morpholino-sydnonimine (SIN-1) or atrial natriuretic peptide (ANP) in the absence or in the presence of either 0.3 microM methylene blue (MB), a guanylate cyclase inhibitor, or 10 microM hemoglobin, a NO scavenger; and under 100% oxygen (hyperoxia), ambient air (normoxia), or 100% nitrogen (hypoxia). RESULTS: Pericytes were relaxed with SIN-1 and ANP in a concentration-dependent manner (EC50: 0.1 microM and 0.01 microM, respectively). Relaxations induced by SIN-1 or ANP were inhibited (P < 0.001) by MB, whereas hemoglobin inhibited only SIN-1 relaxations (P < 0.001). Relaxations induced by SIN-1, but not by ANP were increased (P < 0.001) under hypoxia and decreased (P = 0.002) under hyperoxia. CONCLUSIONS: SIN-1 and ANP relax pericytes through the activation of guanylate cyclase (inhibited by MB), but only SIN-1 through an extracellular release of NO (inhibited by hemoglobin). That oxygen only modulates pericyte relaxations induced by SIN-1 (NO-mediated) but not those induced by ANP suggests that an interaction between oxygen and NO might participate in the capillary network's blood-flow modulation according to local tissue oxygen tension.
Animals↗
Reproducibility of laser Doppler flowmetry in the human optic nerve head.
PURPOSE: We sought to demonstrate reproducibility of the noninvasive laser Doppler flowmetry technique for measuring microvascular hemodynamics of the optic nerve head in human subjects. METHODS: Laser Doppler flowmetry was performed by four examiners on four human optic nerve heads during multiple sessions. Intersubject, interexaminer, intersession, and intrasession variabilities were calculated for velocity, blood volume, and blood flow (flux). RESULTS: Initial variability of measurements improved after 3 months' experience. The standard deviation of the intrasession variation for single readings was 18% of the velocity mean value and 24% of the flow (flux) mean value. Based on this, a sample size of 17 (power beta = 0.8, alpha = 0.05, paired t test) will demonstrate a 10% physiologic change in flux within a session if the average of five readings is used before and after the experimental perturbation. The intersession variation was 12% and 32% for velocity and flux, respectively. Because of this, a larger sample size or additional measurement sessions are required for detection of an experimental influence between two sessions. The coefficient of variation among subjects for single readings was 7% and 10% for velocity and flux, respectively. CONCLUSIONS: Reproducibility of velocity measurements is better than reproducibility of flux measurements. After experience with the method, laser Doppler flowmetry is sufficiently precise to permit feasible studies of human optic nerve head microvascular hemodynamics when physiologic perturbations are applied.
Adult↗
Glaucomatous optic nerve cupping as an optic neuropathy.
Intraocular pressure (IOP), which causes the lamina cribrosa to bulge backward, produces a pressure gradient along the axoplasm of exiting optic nerve axons, and challenges the circulation, interacts with presently unknown physiologic or anatomic factors to harm the optic nerve and causes loss of vision. Present treatment of glaucoma is limited to efforts to lower IOP. Future treatments may be directed at other contributing anatomic or physiologic abnormalities that permit IOP to be harmful, or at some step in the pathway from insult to mortal injury of the axon or cell body.
Animals↗
Adenosine-induced relaxation of cultured bovine retinal pericytes.
PURPOSE: To investigate the effect of adenosine on the contractile tone of cultured bovine retinal pericytes. METHODS: Changes in the contractile tone were quantified as the changes in the summed length of wrinkles induced by pericytes on the silicone surface on which the cells were grown. RESULTS: Adenosine at 10(-9) M had no effect. In the range of 10(-8) to 10(-4) M, adenosine caused relaxation of pericytes in a concentration-dependent manner. Complete relaxation was induced by 10(-5) M to 10(-4) M adenosine. The concentration of adenosine that produced 50% relaxation was 3 x 10(-7) M. At all concentrations, relaxation began within 1 minute, reached the maximum within 5 to 10 minutes, and persisted for at least 30 minutes. After a washout of 3 x 10(-7) M adenosine, the reduced contractile tone recovered to the original level in 10 minutes. The adenosine-induced relaxation (3 x 10(-7) M) was completely abolished in the presence of 8-phenyl theophylline (10(-5) M), a nonselective adenosine receptor antagonist. The selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) at 10(-6) M did not reduce the effect of adenosine (3 x 10(-7) M). Conversely, the selective A2 receptor antagonist CP-66,713 at 10(-8) M partially inhibited (and at 10(-7) M, completely inhibited) the relaxation induced by adenosine (3 x 10(-7) M). The adenosine receptor antagonists-8-phenyl theophylline (10(-5) M), DPCPX (10(-6) M), and CP-66,713 (10(-7) M) by themselves had no effect on the contractile tone of pericytes. CONCLUSIONS: Adenosine causes relaxation of pericytes through the activation of the adenosine A2 receptor. Adenosine, which accumulates under ischemic conditions, may help to regulate local capillary blood flow.
Adenosine↗
Pulmonary artery sarcoma mimicking pulmonary embolism: successful surgical intervention.
Because of its rarity and the similarity of its presentation to that of pulmonary thromboembolic disease, the diagnosis of pulmonary artery sarcoma is often not considered early in patients presenting with recurrent or chronic pulmonary emboli. We present a case of pulmonary artery sarcoma that was treated as pulmonary embolism for 3 years before surgical resection was carried out. Two years after the resection the patient is well with no clinical or radiologic evidence of recurrent or metastatic disease.
Adult↗
Automated suprathreshold static perimetry screening for detecting neuro-ophthalmologic disease.
PURPOSE: To devise and evaluate a rapid, accurate, and cost-effective method of detecting neuro-ophthalmologic visual field defects. METHODS: One hundred fifty-nine consecutive patients were evaluated with 76-point, central 30 degree automated static threshold perimetry on the Humphrey Visual Field Analyzer, as well as by a 76-point, central 30 degree suprathreshold examination with the central reference levels set at 2 or 4 dB lower than the estimated normal median central reference level adjusted for age. Six masked readers reviewed the fields. Their readings were compared with those of the other observers, as well as with the final diagnoses as determined from all available clinical information. RESULTS: In detecting abnormality, the full-threshold 30 degree test had a sensitivity (percent of eyes with true field defects identified by the field test) of 93 percent or 99 percent (depending on whether borderline results were counted as a positive or negative test) and a specificity (percent of cases without true field defects appropriately identified by the field test) of 71 percent or 91 percent. In comparison, the 4-dB offset suprathreshold test had a sensitivity (averaged over all reviewers) of 79 percent or 87 percent and a specificity of 81 percent or 89 percent, whereas the 2-dB test had a sensitivity of 87 percent or 94 percent and a specificity of 73 percent or 85 percent. The mean duration of the suprathreshold tests was 3.5 +/- 1.0 minute, compared with 14.8 +/- 2.8 minutes for the full-threshold technique. CONCLUSION: The central 30 degree, 76-point, 2-dB offset suprathreshold automated perimetry is more rapid and nearly as effective as the full-threshold test in detecting visual field abnormalities due to neuro-ophthalmologic disease. More quantitative, full-threshold perimetric strategies should be used in all equivocal cases and to follow progression of established disease.
Adult↗
Silicone granuloma in acral skin in a patient with silicone-gel breast implants and systemic sclerosis.
A 68-year-old white woman was referred to us by her rheumatologist for possible participation in a clinical study of photopheresis for scleroderma. In February 1993, she noticed edema of her distal phalanges, Raynaud's phenomenon in both hands, flu-like symptoms, fatigue, intermittent diarrhea, abdominal pain, tearing in both eyes, dyspnea on exertion, dysphagia, and odynophagia. Bilateral silicone-gel breast implants had been placed 12 years before; 2 months before her present evaluation, they were removed and found to be ruptured. Physical examination revealed edema, limited to the fingers and hands bilaterally, and slight induration of the skin on the dorsum of both hands and distal forearms. The remainder of the physical examination was normal. According to our study protocol, a skin biopsy specimen from the dorsum of the right hand was taken, but all other laboratory investigations were refused. Histopathologic examination revealed multiple clear spaces of varying sizes in the dermis and multinucleated macrophages containing small refractile particles, characteristic of silicone granuloma (Figs. 1 and 2); however, the specimen showed no evidence of scleroderma. X-ray energy dispersive analysis by scanning electron-microscopy confirmed the presence of elemental silicon in the small refractile particles. The patient did not receive any treatment after her diagnosis and shortly thereafter, she was lost to follow-up.
Aged↗
Direct interactions of coxsackievirus B3 with immune cells in the splenic compartment of mice susceptible or resistant to myocarditis.
In vitro replication of coxsackievirus B3 (CVB3) in cells of the immune system derived from uninfected adolescent A/J and C57BL/6J mice and replication of CVB3 in and association with immune cells from spleens of infected animals in vivo were assessed. Nonstimulated or mitogen-stimulated spleen cells were minimally permissive for viral replication during an 8-h period. Three days postinfection (p.i.), CVB3 RNA was localized in vivo to B cells and follicular dendritic cells of germinal centers in both A/J and C57BL/6J mice; however, extrafollicular localization was greater in C57BL/6J mice (P = 0.0054). Although the pattern of CVB3 RNA localization was different, the total load of infections virus (PFU per milligram of tissue) was not different. Splenic CVB3 titers (PFU per milligram of tissue) in both strains were maximal at day 3 or 4 p.i. and were back to baseline by day 7 p.i., with most infectious virus being non-cell associated. CVB3 titers (PFU per milligram of tissue) correlated directly with in situ hybridization positivity in splenic follicles and extrafollicular regions in both murine strains; however, follicular hybridization intensity was greater in A/J mice at day 5 p.i. (P = 0.021). Flow cytometric analysis demonstrated that 50.4% of total spleen cells positive for CVB3 antigen were B cells and 69.6% of positive splenic lymphocytes were B cells. Myocardial virus load in C57BL/6J mice was significantly lower than that in A/J mice at days 4 and 5 p.i. These data indicate that CVB3 replicates in murine splenocytes in vitro and in B cells and extrafollicular cells in vivo.
Animals↗
Glaucoma, capillaries and pericytes. 1. Blood flow regulation.
Blood flow autoregulation may be deficient in patients with glaucoma, making the optic nerve circulation susceptible to the challenge of intraocular pressure (IOP). Adequacy or inadequacy of autoregulation may be a factor that decides whether a patient with elevated IOP develops glaucomatous optic nerve damage. Hypothetically, capillaries may assist arteries and veins in the regulation of blood flow. Our attention has become focused on the pericytes, particularly abundant in the optic nerve and retina, which are a contractile component of capillaries and may therefore be the cells responsible for the capillary's role in autoregulation.
Animals↗
Glaucoma, capillaries and pericytes. 2. Identification and characterization of retinal pericytes in culture.
As cell cultures of pericytes derived from bovine retina are in regular use by a number of investigators, we decided to confirm the identity of these cells, to show them different from other cells that might contaminate cultures derived from retinal tissue, to characterize the properties they share with pericytes in situ and to establish a practical and effective means for confirmation of the cell type of each batch of cultured cells used in scientific studies. Cultured pericytes differed in immunocytochemical reactions and phagocytic properties from vascular smooth muscle, vascular endothelial cells, astroglia, conjunctival fibroblasts or retinal pigment epithelium. Like vascular smooth muscle, pericytes in situ and those in culture have the contractile proteins actin and myosin, which implies a potential role in blood flow control. In routine studies of cultured pericytes, they can be identified by their unique reaction in situ and in vitro with the antiganglioside monoclonal antibody 3G5. The presence of any contaminating endothelial cells can be recognized by their ability to take up acetylated low-density lipoprotein.
Animals↗
Glaucoma, capillaries and pericytes. 3. Peptide hormone binding and influence on pericytes.
To test the potential for vasoactive neuropeptide receptors to affect capillary resistance, we have begun to study the plausibility that pericytes might be equipped to respond to a representative peptide vasoconstrictor and a representative peptide vasodilator. Pericytes cultured from the bovine retinal vasculature specifically bind the angiotensin II (Ang II) antagonist saralasin (1 nM125I-saralasin bound at 2.2 +/- 0.41 fmol/mg protein) and 125I-vasoactive intestinal peptide (VIP; Kd of 0.5 nM with a population of 30 fmol/mg protein). Incubation with 100 microM Ang II induced minimal cAMP synthesis, while VIP (1 microM, 10 microM) did not induce any change in cAMP concentration. Ang II (10 microM and 100 microM) caused contraction of pericytes cultured on an elastic silicone surface. Circulating or locally produced vasoactive neuropeptides might affect pericyte contractile tone via several intracellular pathways, moderated by indirect effects of these peptides through endothelial stimulation, with the net effect on local blood flow resulting from the effects on arteries and veins as well as capillaries.
Angiotensin II↗
Glaucoma, capillaries and pericytes. 4. Beta-adrenergic activation of cultured retinal pericytes.
To characterize the relaxation of pericytes induced by beta-adrenergic stimulation, changes in the contractile tone of pericytes were quantified as a change in the wrinkling of an elastic silicone surface on which they were cultured. Isoproterenol produced relaxation of pericytes in a dose-dependent manner over a range of 5 nM to 1 microM. Low concentrations of the nonselective beta-blockers propanolol and timolol blocked the relaxation produced by isoproterenol. The specific beta 2-adrenergic component of isoproterenol-induced relaxation was shown by blockage with bromoacetyl alprenolol menthane. In contrast, atenolol and betaxolol, as relatively selective beta 1-adrenergic blockers, had no effect on the isoproterenol-induced relaxation.
Adrenergic beta-Agonists↗
Glaucoma, capillaries and pericytes. 5. Preliminary evidence that carbon dioxide relaxes pericyte contractile tone.
We undertook this study to determine if pericytes respond to carbon dioxide in a manner such that they could help control capillary blood flow and that their physiologic responses to pCO2 might be worthy of detailed study. Pericytes were isolated from bovine retinas and grown in cell culture. Changes in the contractile tone of the pericytes upon changing the ambient pCO2 were observed by noting changes in the wrinkling of an elastic silicone surface on which they were grown. An increase in pCO2 caused acidosis of the medium and relaxation of the pericytes in a reversible, concentration-dependent manner. These findings suggest that the regulation of blood flow to meet local metabolic needs does not reside entirely in the arterioles and precapillary sphincters, but at least in part in the capillary bed through the contractile properties of pericytes. The local pCO2 is one of several potential indicators of whether or not local blood flow is adequate for local tissue needs. The response to local conditions may modulate or be modulated by the effect of neurotransmitters and hormones on the local rate of blood flow.
Animals↗
The effect of ondansetron on pyridostigmine-induced blood acetylcholinesterase inhibition in the guinea pig.
The purpose of this study was to assess the compatibility, in terms of red blood cell acetylcholinesterase (AChE) inhibition, of ondansetron (OND; a 5-hydroxytryptamine subtype-3 receptor antagonist) with the organophosphorus pretreatment compound pyridostigmine (PYR) after simultaneous oral (p.o.) administration to guinea pigs. The time-course of PYR-induced (0.94 mg/kg, p.o.) AChE inhibition was determined in the absence and presence of OND. Ondansetron (10, 20 and 30 mg/kg; p.o.) did not modify AChE inhibition, whereas concurrent administration of PYR with OND (10 or 20 mg/kg; p.o.) produced significantly greater decreases in AChE activity than PYR alone. The decreases in AChE activity for PYR plus OND, 10 and 20 mg/kg, (between 30 -240 min) were 12.3 +/- 2.8% and 16.1 +/- 2.3% (mean +/- SD) respectively relative to PYR alone. The slope for recovery of AChE activity (120 - 240 min) was 0.0914 for PYR alone; recovery rates (slopes) for PYR plus OND, 10 and 20 mg/kg, were 0.0796 and 0.0433 respectively. Additionally, altered PYR-induced AChE activity profiles were ameliorated when PYR and OND (20 mg/kg) were administered 150 min apart. Since the results of this study provided evidence that the oral administration of OND alone did not inhibit AChE, the changes in PYR-induced AChE activity by the simultaneous administration of OND suggest mechanisms other than a direct action on the enzyme. The significance of these findings is that the increased AChE inhibition resulting from simultaneous oral administration of both component could result in undesirable cholinergic toxicities and subsequent perform decrements.
Acetylcholinesterase↗
Skeletal muscle as a myocardial substitute.
During the last several years, there has been intense worldwide interest concerning the use of skeletal muscle as a form of cardiac assistance. For over 10,000 people in the United States diagnosed each year with irreversible heart failure, the 1-year mortality approaches 50%. This comes despite recent advances in medical therapy, heart transplantation, and the artificial heart program. Because of the limitations of these treatments in terms of effectiveness, cost, and availability, we have used a different approach for cardiac augmentation. Skeletal muscle is shaped into the form of a pumping chamber and then used to aid the function of the failing myocardium. Another approach is cardiomyoplasty, where the latissimus dorsi muscle is wrapped around the heart and stimulated to contract in synchrony with the patient's failing myocardium. More than 500 patients have undergone cardiomyoplasty worldwide. These two areas of investigation represent the principle methods for skeletal muscle cardiac assistance.
Animals↗
Laser Doppler flowmetry measurement of changes in human optic nerve head blood flow in response to blood gas perturbations.
PURPOSE: The objective of this study was to establish the ability of laser Doppler flowmetry to detect relative changes in human optic nerve head hemodynamics caused by physiologic blood gas perturbations. METHODS: Laser Doppler flowmetry permits the noninvasive assessment of relative blood velocity, volume, and flow (flux) in a sample volume of the nerve head. Such measurements were performed in two groups of healthy subjects. The first group (n = 11) was tested during normal room air breathing and then while breathing 100% oxygen (isocapnic hyperoxia). The second group (n = 10) was also tested under normal conditions as well as during isoxic hypercapnia (+ 15% end-tidal carbon dioxide). Results were analyzed by paired t tests. RESULTS: Hyperoxia created a significant 25% (p = 0.002) decrease in optic nerve head blood flow, with blood volume decreased by 9% (p = 0.095) and blood velocity reduced by 13% (p = 0.154) compared to the room air condition. During hypercapnia, optic nerve head blood flow was increased by 28% (p = 0.012), with blood volume increased by 22% (p = 0.017) and blood velocity increased by 9% (p = 0.218) as compared to the normal room air condition. CONCLUSION: Blood flow in the optic nerve head capillaries changes in response to hyperoxia and hypercapnia as demonstrated in the brain and retina. Laser Doppler flowmetry permits the noninvasive assessment of these responses in humans under conditions within the physiologic range.
Adult↗
Idiopathic hypertrophic cranial pachymeningitis: clinical-radiological-pathological correlation of bone involvement.
We present the clinical, radiological, and pathological findings in an elderly man who developed a progressive superior orbital fissure syndrome due to idiopathic hypertrophic cranial pachymeningitis. The unique aspect of this case concerned the increased density of the sphenoid ridge and lateral orbital wall observed by using computed tomography, and the enhancement of the marrow signal seen on magnetic resonance imaging. These neuroimaging abnormalities of bone resulted from an indirect nonspecific response of the marrow to the adjacent soft tissue and dural inflammatory process.
Aged↗