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Biomedical subjects

C E Miller

Publications and source records attributed to C E Miller.

At least 19 recordsLinked to original sources

Effect of increased tissue oxygen uptake on autoregulation in postnatal intestine.

To determine whether the rate of tissue oxygen utilization affects pressure-flow autoregulation in an age-dependent fashion in postnatal swine intestine, in vitro gut loops from 3- and 35-day-old swine were subjected to a 35% step reduction in arterial pressure under control conditions, during intra-arterial infusion of 2,4-dinitrophenol (DNP), and 30 min after luminal instillation of predigested artificial swine milk. Autoregulation was quantitated by determining the effect of pressure reduction on vascular resistance, and also by calculating Gf, a flow-controlling gain factor that relates pressure and flow. DNP infusion increased oxygen uptake 77 and 58% in gut from 3- and 35-day-old swine, respectively, whereas feeding increased oxygen uptake approximately 50% in both groups. Under control conditions, arterial pressure reduction had no effect on vascular resistance in either group. During DNP infusion and 30 min after feeding, however, intestine from 35- but not from 3-day-old swine demonstrated significant vasodilation in response to pressure reduction. Gf averaged -0.06 +/- 0.11 vs. 0.21 +/- 0.08 (P < 0.05) before vs. DNP infusion, and 0.06 +/- 0.03 vs. 0.22 +/- 0.06 (P < 0.05) before vs. 30 min after feeding in intestine from 35-day-old swine; these increases in Gf indicate that the intensity of the pressure-flow response increased during experimental treatments. In contrast, Gf averaged -0.11 +/- 0.07 vs. -0.23 +/- 0.08 before vs. DNP infusion, and -0.23 +/- 0.06 vs. -0.23 +/- 0.09 before vs. 30 min after feeding in intestine from 3-day-old swine.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dinitrophenol

Drug therapy of ventricular tachycardia: a cost comparison of randomized noninvasive and invasive approaches.

OBJECTIVE: Economic evaluation of noninvasive (suppression of ventricular arrhythmias detected by ambulatory monitoring) and invasive (suppression of arrhythmias induced by programmed stimulation) approaches to antiarrhythmic drug selection for ventricular tachyarrhythmias. DESIGN/SETTING: Randomized clinical trial/tertiary-care hospital. PATIENTS: Of 124 consecutive patients referred for treatment of symptomatic ventricular tachyarrhythmias, 57 consenting patients were eligible to have drug therapy selected by either noninvasive or invasive approaches. MEASUREMENTS: Costs of initial and follow-up (26 +/- 15 months) admissions for the two groups were compared. This economic evaluation also considered relative efficacies of the approaches using the primary outcome variable of symptomatic, sustained ventricular tachyarrhythmia recurrence (including sudden death). RESULTS: Initial hospitalization for therapy selection was less costly by the noninvasive approach ($6,869 +/- 4,019) than by the invasive approach ($13,164 +/- 6,740) (P less than 0.001). However, the noninvasive approach generated higher follow-up hospital costs ($9,204 +/- 9,217) than the invasive approach ($3,784 +/- 4,944) (P = 0.01). Thus, total hospital costs of the noninvasive ($16,073 +/- 9,423) and invasive approaches ($16,949 +/- 7,174) were equivalent. The two-year actuarial probability of a recurrent, sustained, symptomatic ventricular tachyarrhythmia was greater in noninvasive (0.50 +/- 0.10) than in invasive (0.20 +/- 0.08) approach patients (P = 0.02). CONCLUSIONS: The lower initial hospital costs of the noninvasive approach are offset by greater follow-up costs. Within two years the costs of the two approaches are equivalent. Thus, greater antiarrhythmic efficacy can be achieved by the invasive approach to drug selection without increasing total hospital costs.

Anti-Arrhythmia Agents

Periodontal status of individuals in early stages of human immunodeficiency virus infection.

The purpose of this study was to evaluate the association of periodontal health and human immunodeficiency virus infection among individuals in the early stages of disease who were participating in randomized placebo-controlled clinical trials of zidovudine. Previous reports have described a rapidly progressive periodontitis and atypical gigivitis associated with late stages of infection by the human immunodeficiency virus. A health history was completed by each subject. Baseline oral examinations were completed on 97 asymptomatic patients and nine with AIDS-related complex (ARC) during their regular clinic visit. Follow-up examinations were conducted at 3-month intervals throughout the 48 weeks of the oral study. Evaluations of plaque, calculus, gingival abnormalities, caries, and periodontal disease were conducted. Periodontal measurements included plaque index (PI), gingival index (GI), bleeding index (BI), probing depth (PD), and observation for cratering, necrosis, and tooth mobility on six teeth in each patient. More than half of the subjects had visited their dentist during the previous year and had had an oral prophylaxis; less than 25% of them had had either restorative work or extractions. The mean scores for periodontal indices averaged over the course of the study in asymptomatic and ARC respectively were: PI: 0.9 (SE 0.04) and 0.9 (SE 0.08), 0.818; GI: 1.0 (SE 0.04) and 0.9 (SE 0.07), P = 0.412; BI: 0.6 (SE 0.04) and 0.4 (SE 0.07), P = 0.278; PD: 2.9 (SE 0.05) and 2.6 (SE 0.10), P = 0.140. There was no evidence of cratering, necrosis, or tooth mobility in either group. Few had calculus or dental caries. There were no clinically significant differences detected between ARC versus asymptomatic patients. Dental histories and oral examinations showed that two groups of patients in early stages of HIV-disease were in good periodontal health.

AIDS-Related Complex

Tributyltin-resistant bacteria from estuarine and freshwater sediments.

Resistance to tributyltin (TBT) was examined in populations from TBT-polluted sediments and nonpolluted sediments from an estuary and from fresh water as well as in pure cultures isolated from those sediments. The 50% effective concentrations (EC50s) for populations were higher at a TBT-polluted freshwater site than at a site without TBT, suggesting that TBT selected for a TBT-resistant population. In contrast, EC50s were significantly lower for populations from a TBT-contaminated estuarine site than for those from a site without TBT, suggesting that other factors in addition to TBT determine whether populations become resistant. EC50s for populations from TBT-contaminated freshwater sediments were nearly 30 times higher than those for populations from TBT-contaminated estuarine sediments. We defined a TBT-resistant bacterium as one which grows on trypticase soy agar containing 8.4 microM TBT, a concentration which prevented the growth of 90% of the culturable bacteria from these sediments. The toxicity of TBT in laboratory media was influenced markedly by the composition of the medium and whether it was liquid or solid. Ten TBT-resistant isolates from estuarine sediments and 19 from freshwater sediments were identified to the genus level. Two isolates, each a Bacillus sp., may be the first gram-positive bacteria isolated from fresh water in the presence of a high concentration of TBT. There was a high incidence of resistance to heavy metals: metal resistance indices were 0.76 for estuarine isolates and 0.68 for freshwater isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

Copper

Effect of sustained mesenteric nerve stimulation on intestinal oxygenation in developing swine.

The effects of sustained mesenteric nerve stimulation on intestinal oxygenation were determined in 3- and 35-day-old swine. Studies were conducted in pentobarbital-anesthetized animals during free-flow or constant-flow perfusion. Square-wave stimuli sufficient to induce maximal resistance vessel constriction were applied to postganglionic periarterial mesenteric nerves and each stimulation was sustained until measured variables reached steady state. When vascular resistance data were analyzed without data transformation, autoregulatory escape of intestinal vascular resistance was more complete in 3- than in 35-day-old animals when the escape process was complete; however, expression of these data as escape indexes revealed a similar degree of escape in both age groups. In 35-day-old animals, (a-v)O2 increased during sustained nerve stimulation under free-flow conditions; under constant-flow conditions, (a-v)O2, 86Rb extraction, and capillary permeability-surface area product were lower at completion of the escape process compared with baseline. In 3-day-old swine, these variables remained unchanged from baseline. Intestinal O2 uptake was compromised by sustained nerve stimulation, and this effect was similar in both age groups. We conclude that sustained nerve stimulation reduces intestinal oxygenation to a similar degree in 3- and 35-day-old swine. It is important to note, however, that the response of 3-day-old swine may be dissimilar from that which occurs during immediate postnatal life; indeed, the intestinal hemodynamic response of swine less than or equal to 1 day old should not be extrapolated from the response of 3-day-old animals.

Aging

Effects of hypoxia and ischemia on autoregulation in postnatal intestine.

Pressure-flow autoregulation was quantified within in vitro intestine from 3- and 35-day-old swine before and after lowering arterial PO2 (hypoxia) or lowering baseline blood flow by means of norepinephrine infusion (ischemia). Autoregulation was elicited by reducing arterial pressure approximately 33% from an age-appropriate baseline pressure. In 3-day-old intestine, autoregulation was unaffected by hypoxia or ischemia: vascular resistance was unchanged after pressure reduction, while Gf averaged -0.33 +/- 0.15 vs. -0.26 +/- 0.05 under control vs. hypoxic conditions, and -0.48 +/- 0.15 vs. -0.46 +/- 0.11 under control vs. ischemic conditions, respectively. In 35-day-old intestine, autoregulation was enhanced by hypoxia and ischemia. Under both experimental conditions, vasodilation was noted in response to pressure reduction: Gf averaged -0.04 +/- 0.14 vs. 0.38 +/- 0.08 under control vs. hypoxic conditions, and -0.12 +/- 0.10 vs. 0.28 +/- 0.08 under control vs. ischemic conditions, respectively. Regression analysis revealed a significant inverse linear correlation between Gf and venous PO2 in older, but not younger, subjects. Significant relationships between Gf and blood flow were not demonstrated in either group under any experimental condition. We conclude that autoregulation is enhanced within in vitro intestine from 35-, but not 3-day-old, swine during hypoxia or ischemia, and that reduction of venous PO2 is the principal factor responsible for the effect noted in older subjects.

Analysis of Variance

Effect of O2 availability on intrinsic vascular response to venous pressure elevation in postnatal swine intestine.

The goal of these experiments was to determine whether the intrinsic vascular response of postnatal intestine to acute venous pressure elevation was dependent on the preexisting level of oxygen availability. To this end, acute venous hypertension was applied to denervated loops of small intestine from 3- and 35-day-old swine anesthetized with pentobarbital during free-flow and controlled-flow perfusion. During controlled-flow perfusion, the base-line blood flow rate was set slightly above (+5%; high flow) or significantly below (-50%; low flow) the rate noted during free-flow perfusion so as to directly alter intestinal oxygen availability. The vascular response to venous hypertension noted under controlled high-flow perfusion was similar in both age groups and generally consistent with that noted under free-flow perfusion. In contrast, the response noted during low-flow perfusion was clearly age dependent. In the older group, vascular resistance decreased (27%), while arteriovenous oxygen content difference [(a-v)O2] and tissue oxygen uptake remained unchanged. In the younger group, vascular resistance remained unchanged, whereas (a-v)O2 and oxygen uptake decreased (14%). We conclude that the intrinsic vascular response to venous pressure elevation is dependent on the preexisting level of oxygen availability in intestine from 35- but not from 3-day-old swine. We speculate that the local metabolic vascular response to venous hypertension is more effective in intestine from older than from younger swine.

Aging

Finite element analysis of bioelectric phenomena.

This article reviews the application of finite element methods to models of bioelectric phenomena. The models represent the electrical fields created in the body as a result of membrane current sources or external current applied for diagnostic or therapeutic purposes. We formulate the governing equations for these models and then derive the finite element equations for the generalized bioelectric problem. The 32 papers reviewed here, all those appearing in the literature to date, cover the areas of electrocardiology, therapeutic and functional electrical stimulation in the cerebellum, cochlea, spinal cord, and peripheral nerves, cardiac defibrillation, electrical impedance tomography, bidomain cardiac models, electroporation, and therapeutic electrical stimulation of bone. For each, we summarize the purpose of the study, the model details and assumptions, the major results, and the applicability of the study. The models are then considered as a group to critique the appropriateness of the finite element method, the means of implementation, and the factors affecting accuracy, thus providing an overview of the state of finite element modeling of bioelectric phenomena.

Central Nervous System Diseases

Dissimilar plasmids isolated from Pseudomonas diminuta MG and a Flavobacterium sp. (ATCC 27551) contain identical opd genes.

The opd (organophosphate-degrading) gene derived from a 43-kilobase-pair plasmid (pSM55) of a Flavobacterium sp. (ATCC 27551) has a sequence identical to that of the plasmid-borne gene of Pseudomonas diminuta. Hybridization studies with DNA fragments obtained by restriction endonuclease digestion of plasmid DNAs demonstrated that the identical opd sequences were encoded on dissimilar plasmids from the two sources.

Base Sequence

Autoregulation in the developing postnatal intestinal circulation.

The relationships among perfusion pressure, blood flow, and oxygen uptake were determined in in vitro ileal loops from 3- and 35-day-old swine. Arterial perfusion of the ileal loops was achieved using a reservoir perfusion apparatus that allowed direct manipulation of perfusion pressure. The hematocrit, partial pressure of oxygen, and partial pressure of carbon dioxide of the blood used to perfuse the gut loops were standardized. During steady-state perfusion at an arterial pressure of 100 mmHg and venous pressure of 0 mmHg, ileal loops from 3-day-old swine demonstrated a higher blood flow (55 vs. 27 ml.min-1.100 g-1, 3 vs. 35 day old) and lower arteriovenous oxygen content difference (3.5 vs. 6.6 ml O2/dl). Oxygen uptake was not statistically different between groups (1.99 vs. 1.76 ml O2.min-1.100 g-1). During perfusion pressure reduction from 150 to 25 mmHg (in successive decrements of 25 mmHg), pressure-flow autoregulation was present in ileal loops from 35-day-old swine but not in ileal loops from 3-day-old swine. Similarly, tissue oxygen uptake was more effectively maintained in ileal loops from older swine during perfusion pressure reductions. We speculate that the efficacy of intrinsic regulation of intestinal hemodynamics and oxygenation is dependent, in part, on postnatal age.

Aging

Effects of arterial hypoxia and isoproterenol on in vitro postnatal intestinal circulation.

We have previously speculated that intestinal vasodilation and hyperemia that occur in response to moderate arterial hypoxia in newborn swine in vivo are mediated by factors intrinsic to the intestinal circulation. To test this speculation, we vascularly perfused in vitro loops of jejunum from postnatal swine with control (PO2 98 +/- 4 mmHg) and hypoxic (PO2 38 +/- 2 mmHg) blood obtained from donor swine. In response to hypoxic perfusion, jejunal vascular resistance decreased 12 +/- 2, 13 +/- 3, 33 +/- 5, and 42 +/- 3% in in vitro loops from 1-, 7-, 14-, and 30-day-old swine, respectively, whereas jejunal oxygen uptake decreased 53 +/- 6, 29 +/- 6, 31 +/- 4, and 13 +/- 6% in these age groups. To clarify whether this age-dependent vasodilation was unique to the stimulus of arterial hypoxia or a response characteristic of the postnatal swine intestine to other vasodilator stimuli, we also determined the effect of intra-arterial isoproterenol infusion at rates of 0.01, 0.1, and 1.0 micrograms/min on jejunal hemodynamics and oxygenation in vitro. In jejunal loops taken from 7- and 30-day-old swine, isoproterenol caused a similar degree of vasodilation at each drug-infusion rate. We conclude that vasodilation of the postnatal swine intestine in response to moderate arterial hypoxia is mediated, at least in part, by intrinsic vascular regulation. We speculate that the age dependency of hypoxic vasodilation may reflect a relative inability of the intestine from very young swine to respond to the stimulus of arterial hypoxia.

Aging

Decreased gestational sac volumes in pregnancies induced by human menopausal gonadotropin.

Mean gestational sac volumes of 9 singleton pregnancies induced by human menopausal gonadotropin (hMG) measured by ultrasound were compared with mean gestational sac volumes obtained from 37 normal singleton pregnancies, 6 to 8 weeks from the last menstrual period. HMG-induced gestational sacs were smaller at 6 and 7 weeks of gestation, compared with normal pregnancies. Despite the initial lag in gestational sac volume, hMG-induced pregnancies subsequently demonstrated appropriate fetal growth as measured by crown-rump length measurements between 8 and 12 weeks. These pregnancies also demonstrated normal fetal growth patterns in the second and third trimesters of pregnancy, as assessed by clinical evaluation and ultrasound. These preliminary data suggest that early growth development in hMG-induced pregnancies may be different from that in spontaneously occurring pregnancies.

Embryonic and Fetal Development

Structural implications of basilar membrane compliance measurements.

Static point-load measurements of basilar membrane compliance were made in the basal region of the excised guinea pig cochlea. Points on a radial line across the basilar membrane were displaced in one-half micron increments and the force required to maintain each increment recorded. The results are interpreted in terms of the material layers of the basilar membrane and displayed as compliance curves. In addition, a beam model of the basilar membrane, including the arches of Corti and the actual geometry of the pectinate zone, is constructed from anatomical data. The free parameters in this model are the modulus of elasticity of the transverse filaments and the effective spring stiffness of the arches. Compliance curves for the model are generated with a finite element approach and the parameters are obtained by requiring optimal agreement with the experimental measurements. The results show that the separation between fiber layers in the pectinate zone is relevant to the effective moment of inertia of the cross section and that the longitudinal coupling between the heads of the arches provides a rigidity to the arcuate zone not seen in the pectinate zone where longitudinal coupling is minimal. The elastic modulus calculated for the filaments is 1.8 GPa, approximately one-half that of keratin, while the cells and ground substance are five orders of magnitude softer.

Animals

Deformation and creep in the human chorioamniotic sac.

This paper presents a review of physical principles involved in deformation and creep in the human chorioamniotic membrane. These are definable rheological properties found in many materials. Experimental data are presented on 66 human fetal membranes. A difference in the stress tolerance between preterm and term membranes is demonstrated. A computer model has been devised which allows for the calculation of changes in thickness of the membrane at the point of fracture. This computer model allows for the study of the physical property of the tissue in ways which have not previously been suggested. The model suggests that the pathophysiology related to rupture of the membrane is based on changes in the thickness of this tissue occurring secondary to acute and chronic stress applications. The data derived in these experiments suggest a possible physical model for rupture of the membranes; they also introduce questions regarding the anatomic and biochemical makeup of the chorion and the amnion and the respective role that each plays in maintaining the integrity of the human chorioamniotic sac.

Extraembryonic Membranes

Probabilistic theories of coalition formation in groups.

Chertkoff's (1967) and Walker's (1973) theories of coalition formation for decision making, which attempt to predict the probabilities of the occurrence of coalitions in three-person group systems, are extended to apply to certain situations involving groups larger than these triads. These two extended theories and Komorita's (1974) weighted probability theory, which attempts to predict the probabilities of occurrence of coalitions in groups of any size, are compared according to how well they can account for the results of a number of previously reported experiments, both on triads and on larger groups. In general, this comparison shows that: (a) Chertkoff's theory cannot account for the results; (b) Walker's theory can account only for the results of experiments in which all the minimal winning coalitions are equal in size; and (c) Komorita's theory can account only for the results of experiments in which there is some difference in size among the minimal winning coalitions. It is suggested that the theories of Chertkoff and Walker do not attribute enough importance to size as a factor in coalition formation, while weighted probability theory attributes too much importance to this factor.

Decision Making