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Biomedical subjects

R Greene

Publications and source records attributed to R Greene.

At least 55 records · Page 3Linked to original sources
PubMed1997

Lactational transfer of volatile chemicals in breast milk.

Lactational transfer of chemicals to nursing infants is a concern for occupational physicians when women who are breast-feeding return to the workplace. Some work environments, such as paint shops, have atmospheric contamination from volatile organic chemicals (VOCs). Very little is known about the extent of exposure a nursing infant may receive from the mother's occupational exposure. A physiologically based pharmacokinetic model was developed for a lactating woman to estimate the amount of chemical that a nursing infant ingests for a given nursing schedule and maternal occupational exposure. Human blood/air and milk/air partition coefficients (PCs) were determined for 19 VOCs. Milk/blood PC values were above 3 for carbon tetrachloride, methylchloroform, perchloroethylene, and 1,4-dioxane, while the remaining 16 chemicals had milk/blood PC values of less than 3. Other model parameters, such as solid tissue PC values, metabolic rate constants, blood flow rates, and tissue volumes were taken from the literature and incorporated into the lactation model. In a simulated exposure of a lactating woman to a threshold limit value concentration of an individual chemical, only perchloroethylene, bromochloroethane, and 1,4-dioxane exceeded the U.S. Environmental Protection Agency non-cancer drinking water ingestion rates for children. Very little data exists on the pharmacokinetics of lactational transfer of volatile organics. More data are needed before the significance of the nursing exposure pathway can be adequately ascertained. Physiologically based pharmacokinetic models can play an important role in assessing lactational transfer of chemicals.

Air Pollution↗
PubMed1997

Comparison of nested PCR with immunofluorescent-antibody assay for detection of Ehrlichia canis infection in dogs treated with doxycycline.

A partial 16S rRNA gene was amplified in Ehrlichia canis-infected cells by nested PCR. The assay was specific and did not amplify the closely related Ehrlichia chaffeensis, Ehrlichia muris, Neorickettsia helminthoeca, and SF agent 16S rRNA genes. The assay was as sensitive as Southern hybridization, detecting as little as 0.2 pg of E. canis DNA. By this method, all blood samples from four dogs experimentally infected with E. canis were positive as early as day 4 postinoculation, which was before or at the time of seroconversion. One hundred five blood samples from dogs from Arizona and Texas (areas of E. canis endemicity) and 30 blood samples from dogs from Ohio (area of E. canis nonendemicity) were examined by nested PCR and immunofluorescent-antibody (IFA) test. Approximately 84% of dogs from Arizona and Texas had been treated with doxycycline before submission of blood specimens. Among Arizona and Texas specimens, 46 samples were PCR positive (44%) and 80 were IFA positive (76%). Forty-three of 80 IFA-positive samples (54%) were PCR positive, and 22 of 25 IFA-negative samples (88%) were negative in the nested PCR. None of the Ohio specimens were IFA positive, but 5 specimens were PCR positive (17%). Our results indicate that the nested PCR is highly sensitive and specific for detection of E. canis and may be more useful in assessing the clearance of the organisms after antibiotic therapy than IFA, especially in areas in which E. canis is endemic.

Animals↗
PubMed1996

Molecular indices of neuronal and glial plasticity in the hippocampal formation in a rodent model of age-induced spatial learning impairment.

Spatial learning ability was quantitated in young and aged Long-Evans rats, and molecular markers were assessed in the striatum and hippocampal formation using immunocytochemical, immunoblotting, and in situ hybridization histochemical procedures. The mRNA for beta-amyloid precursor protein (beta APP), most likely the transcript encoding the 695-amino acid form of this protein, was elevated in pyramidal and granule cells in the hippocampus of aged rats exhibiting poorer spatial learning. In immunoblots of hippocampal protein extracts, however, the level of beta APP-like immunoreactivity was depressed in the more impaired subjects. Similarly, the level in hippocampus of the mRNA for manganese-dependent superoxide dismutase (Mn-SOD), a marker of oxidative stress, was positively correlated with the degree of behavioral impairment, but immunoblotting revealed that Mn-SOD protein was depressed in the aged hippocampus compared with young. The mRNAs for the neuronal form of nitric oxide synthase and for the astrocyte marker glial fibrillary acidic protein (GFAP) were elevated in the hippocampus in correlation with the extent of learning impairment. In the striatum, the levels of mRNA and protein for several candidate genes, including GFAP, were elevated in parallel with the learning index, but these were age effects. Several hippocampal proteins were unchanged (GFAP) or depressed (beta APP and Mn-SOD) in level, despite elevations in corresponding mRNAs. In the aged cohort, hippocampal GFAP mRNA, Mn-SOD mRNA, and beta APP emerged as predictors of behavioral impairment, suggesting the involvement of these hippocampal systems in age-related cognitive impairment.

Aging↗
PubMed1996

Computation of vascular flow dynamics from intravascular ultrasound images.

Analysis of three-dimensional velocity profiles and wall shear stress distribution in a segment of an artery reconstructed from in vivo imaging data are presented in this study. Cross-sectional images of a segment of the abdominal aorta in dogs were obtained using intravascular ultrasound (IVUS) imaging employing a constant pull back technique. Simultaneous measurement of pressures distal and proximal to the vessel segment along with gated pulsed Doppler velocity measurements were also obtained. The three-dimensional geometry of the vascular segment was reconstructed from the IVUS images during peak forward flow phase, and a computational mesh was constructed from the data. A quasi-steady analysis of incompressible Newtonian fluid was performed with a finite difference general purpose computational analysis program FLOW3D. The velocity at the inlet and pressure at the outlet measured at the corresponding time (time referenced to ECG) were used to specify the boundary conditions for the computational flow model. The computed results compared favorably with previously reported results. The purpose of the present study was to analyze the hemodynamics in vascular segments from morphologically realistic three-dimensional reconstructions. The method can be potentially employed in analyzing the hemodynamics in the region of atherosclerotic plaques at various stages of development and the reactivity of the vessel in response to pharmacological and mechanical interventions.

Animals↗
PubMed1996

Differential effects of physiological versus pathophysiological plasma concentrations of epinephrine and norepinephrine on ketone body metabolism and hepatic portal blood flow in man.

Few studies that have examined the effects of catecholamines on ketogenesis have considered the effects of catecholamines on hepatic portal blood flow. Since hepatic blood flow is a major determinant of hepatic ketogenesis (via modification of free fatty acid availability), interpretation of these studies is difficult. To better define the relative contributions of these variables, we studied the effects of physiological and pathophysiological plasma concentrations of epinephrine and norepinephrine on plasma ketone body concentrations and hepatic portal blood flow in controlled paired studies in young healthy male volunteers. To assess the effects of physiological catecholamine concentrations, each of eight subjects received 60-minute sequential infusions of epinephrine (10 ng/kg/min) and norepinephrine (32.5 ng/kg/min) together with a control infusion of heparin (0.4 U/kg/min) separated by 60-minute washout periods. Similar increments in plasma nonesterified fatty acid ([NEFA] to approximately 1 mmol/L) were observed during each infusion. The ketotic ratios, calculated as the ratio of plasma ketone bodies to fatty acids integrated above baseline for 90 and 120 minutes, respectively, for epinephrine and norepinephrine infusions were both significantly greater (P < .005 for each) than for the heparin control infusion. To assess the effects of pathophysiological plasma catecholamine concentrations, each of eight subjects also received sequential 60-minute infusions of epinephrine 60 ng/kg/min, norepinephrine 80 ng/kg/min (plus heparin 0.1 U/kg/min), and a separate control infusion of heparin with or without Intralipid (KabiVitrum, Alameda, CA). Whereas integrated plasma fatty acid levels were approximately twofold greater than those observed in the physiological protocol, the absolute integrated ketone body response to the pathophysiological concentration of epinephrine was significantly lower than that observed for the physiological dose of the hormone (P < .05). In contrast, the ketotic ratio for norepinephrine was significantly greater (P < .005) than for both epinephrine and the control infusion of heparin with or without Intralipid. Significant (P < .01) increases above baseline fasting levels were observed in plasma glucose and immunoreactive insulin concentrations during infusion of pathophysiological concentrations of epinephrine. Because of the technical difficulties of simultaneously measuring portal blood and sampling blood frequently, studies were repeated in six additional subjects using noninvasive image-guided flowmetry to measure percentage changes in hepatic portal blood flow during catecholamine infusion. Norepinephrine reduced hepatic portal blood flow significantly at the low-physiological concentration by 12% (P < .05) and at the pathophysiological concentration by 18% (P < .05). In summary, (1) both epinephrine and norepinephrine were associated with significant ketotic effects at physiological plasma concentrations; and (2) when infused at pathophysiological concentrations, only norepinephrine exerted a significant additional ketotic effect. Since norepinephrine has a significant simultaneous effect of reducing hepatic portal blood flow, we conclude that previous studies may have underestimated the effect of norepinephrine on hepatic ketogenesis.

Adult↗
PubMed1996

Autonomic regulation of heart rate and peripheral circulation: comparison of high altitude and sea level residents.

1. To evaluate the activity of the autonomic nervous system on the heart and peripheral circulation in native high-altitude residents, during a Himalayan expedition we studied 12 men (age: 48 +/- 4, mean +/- SEM), life-long resident in a village at 4800 m (Sumdo village, Zanskar, India) and 7 healthy sea-level residents (age: 37 +/- 4) after 7 days of acclimatization (acclimatized lowlanders) at the same altitude. Furthermore 25 sea level residents (age: 46 +/- 2) underwent the same protocol at sea level. 2. R-R interval (RR), respiratory signal, non-invasive blood pressure, and skin arteriolar blood flow were evaluated in three different conditions: during free breathing in supine position and during controlled breathing (at 0.15 Hz), in supine and upright position, and analysed by autoregressive spectral analysis [low- (around 0.1 Hz) and high-frequency (respiratory) fluctuations, LF and HF, markers of sympathetic and vagal activity, respectively]. 3. High-altitude residents showed in supine position a higher RR than acclimatized lowlanders, similar to sea-level residents. RR variability was reduced in acclimatized lowlanders compared to both high-altitude residents and sea level residents. Systolic blood pressure (SBP) did not show significant differences between the three groups. High altitude residents showed in supine lower LF in RR signal compared to sea-level residents, and, compared to acclimatized lowlanders, higher HF and lower LF/HF ratio; high-altitude residents showed a reduction in skin microcirculation variability compared to sea-level residents, but this was eight fold greater than in acclimatized lowlander, thus indicating a much greater vasoconstriction in acclimatized lowlanders than in high-altitude residents. 4. In upright position, high-altitude residents showed the same behaviour as sea-level residents, with increase in LF-RR, and decrease in HF and LF-SBP. Acclimatized lowlanders showed similar directional trends though not significant changes for RR-LF. 5. After one week of acclimatization, lowlanders still manifested sympathetic activation and skin vasoconstriction; high-altitude residents did not show reduced vagal tone compared to sea-level residents, but a mild vasoconstriction appeared to be present. In conclusion, normal or enhanced vagal tone and preserved vasomotion are probably evidence of adaptation at high altitude hypoxia.

Adaptation, Physiological↗
PubMed1996

Articular muscle of the knee: a muscle seldom recognized on MR imaging.

OBJECTIVE: We studied the MR imaging characteristics of the articular muscle of the knee, an important but seldom recognized structure of the distal thigh and knee. SUBJECTS AND METHODS: We used a 1.5-T system to prospectively evaluate the articular muscle of the knee in five healthy volunteers (10 knees); then we retrospectively studied the knee examinations of 24 patients (30 knees). One reader made duplicate readings to prospectively assess the sagittal proton density-weighted and axial T1-weighted images of the healthy volunteers. Three independent readers retrospectively evaluated the sagittal proton density-weighted images of the 24 patients. RESULTS: The articular muscle of the knee was identified in 100% of prospective studies (10/10) and in 83% of retrospective studies (25/30). For the prospective study group, measurements (mean +/- SEM) were as follows: number of bundles, 2.4 +/- 0.68 (range, 1-4); length of uppermost bundle, 47.2 +/- 4.06 mm; width of origin, 8.6 +/- 0.79 mm; angle of origin, 11.4 degree +/- 1.29 degree; and cross-sectional bundle width, 19.8 +/- 2.05 mm2. CONCLUSION: The articular muscle of the knee can usually be identified by MR imaging as an independent entity, separate from the great (vastus) muscle group.

Adolescent↗
PubMed1996

Visualization of the lymphatics of the heart and the mediastinal drainage pathways in the living cynomolgous (Macaca mulatta) monkey.

Our interest in the effects of impaired cardiac lymph drainage on coronary atherosclerosis led us to study the cardiac lymphatic anatomy in the monkey, generally considered the ideal experimental animal for examining coronary artery disorders. Short-term and long-term studies to visualize the cardiac lymphatic system and its mediastinal drainage pathways in 14 living monkeys confirmed that the epicardial collecting lymphatic anatomy is comparable to that of man, dog, and pig. These lymphatics, and particular lymphatic drainage to the cardiac lymph node in the right mediastinum, are difficult to visualize, in good part, because lymph uptake of such tracers as India Ink and T1824 blue dye is extremely slow. By modifying our techniques and taking cognizance of the slow lymphatic uptake of the tracers, we have been more successful in visualizing the mediastinal cardiac lymph node. Though our studies confirm that the lymphatic drainage of the monkey heart is similar to that in other mammals, we conclude that the "monkey model" has several drawbacks to study the effects of impaired cardiac lymph flow because of the laborious requirements to visualize successfully the cardiac lymph node. Perhaps the development of new markers would make this lymphatic system more approachable for experimental investigation.

Animals↗
PubMed1995

Discovery of a brain promoter from the human transferrin gene and its utilization for development of transgenic mice that express human apolipoprotein E alleles.

Transgenic mice carrying heterologous genes directed by a 670-bp segment of the regulatory sequence from the human transferrin (TF) gene demonstrated high expression in brain. Mice carrying the chimeric 0.67kbTF-CAT gene expressed TF-CAT in neurons and glial cells of the nucleus basalis, the cerebrum, corpus callosum, cerebellum, and hippocampus. In brains from two independent TF-CAT transgenic founder lines, copy number of TF-CAT mRNA exceeded the number of mRNA transcripts encoding either mouse endogenous transferrin or mouse endogenous amyloid precursor protein. In two transgenic founder lines, the chloramphenicol acetyltransferase (CAT) protein synthesized from the TF-CAT mRNA was estimated to be 0.10-0.15% of the total soluble proteins of the brain. High expression observed in brain indicates that the 0.67kbTF promoter is a promising director of brain expression of heterologous genes. Therefore, the promoter has been used to express the three common human apolipoprotein E (apoE) alleles in transgenic mouse brains. The apoE alleles have been implicated in the expression of Alzheimer disease, and the human apoE isoforms are reported to interact with different affinities to the brain beta-amyloid and tau protein in vitro. Results of this study demonstrate high expression and production of human apoE proteins in transgenic mouse brains. The model may be used to characterize the interaction of human apoE isoforms with other brain proteins and provide information helpful in designing therapeutic strategies for Alzheimer disease.

Alleles↗
PubMed1995

Electrical activation during ventricular fibrillation in the subacute and chronic phases of healing canine myocardial infarction.

BACKGROUND: Little information is available regarding the effects of myocardial infarction on the characteristics of ventricular fibrillation (VF). Epicardial activation during VF can be characterized by the cycle length and by the characteristics of activation wave fronts. METHODS AND RESULTS: VF was induced by programmed stimulation in 6 dogs with subacute healing (1 week) myocardial infarction (MI), 5 dogs with chronic (8 week) healing MI, and 6 dogs without MI. Using a plaque electrode array with a 2.5-mm interelectrode distance, 112 electrograms were recorded and 91 vector loops were created for each cycle of VF from either the anterior (infarcted) or lateral (noninfarcted) wall. Direction of maximum epicardial activation was determined at each site for the first 10 cycles of VF (early) and for 10 cycles after 5 seconds of VF (late). Wave front size was determined based on a similarity in epicardial activation directions within a given area and by a statistical analysis that determined the degree of spatial linking at varying distances over the recording plaque. VF cycle length was defined as the mean interval of 10 consecutive local activation times. Differences among groups and differences between the anterior and posterolateral walls were determined by ANOVA. The mean wave front area was significantly larger in the presence of subacute MI (97 +/- 4 mm2, early; 78 +/- 3 mm2, late) or chronic MI (94 +/- 5 mm2, early; 78 +/- 5 mm2, late) than in noninfarcted animals (73 +/- 5 mm2, early; 61 +/- 3 mm2, late). The degree of linking of epicardial activation directions was similar in the three groups at distances of 2.5 and 5.0 mm but was lower at a distance of 7.5 mm among animals without infarction, confirming a smaller wave front size and suggesting less organization of activation. VF cycle length was significantly longer in the presence of infarction (98 +/- 5 ms, normal control animals; 121 +/- 13 ms, subacute MI; 127 +/- 13 ms, chronic MI). VF cycle length was significantly longer over the anterior than the lateral wall in the presence of subacute MI (131 +/- 8 ms, anterior; 109 +/- 5 ms, lateral) or chronic MI (136 +/- 9 ms, anterior; 119 +/- 6 ms, lateral) but not in noninfarcted animals (99 +/- ms, anterior; 97 +/- 5 ms, lateral). The prolongation of VF cycle length among animals with infarction was associated with slower estimated conduction velocities during VF. CONCLUSIONS: During VF, in animals with subacute or chronic healing MI, (1) the size of activation wave fronts is larger, (2) the cycle length of VF is longer, (3) the conduction velocities are slower, and (4) the degree of organization is greater than in control animals. Thus, the characteristics of VF throughout the heart are altered by the presence of regional myocardial infarction. The implications of these findings for the initiation and maintenance of VF in the presence of different underlying myocardial substrates require further study.

Animals↗
PubMed1995

Prevalence of Bartonella henselae antibodies in pet cats throughout regions of North America.

Cat exposure has been directly associated with the development of human Bartonella henselae infections, resulting in cat-scratch disease, bacillary angiomatosis, or bacteremia. The prevalence of serum antibody titers to B. henselae was determined for selected pet cats from 33 geographic locations throughout the United States and several areas in western Canada. Seroprevalences paralleled increasing climatic warmth (P < .02) and annual precipitation (P < .03). These warm, humid areas with the highest seroprevalence would also have the highest number of potential arthropod vectors. The southeastern United States, Hawaii, coastal California, the Pacific Northwest, and the south central plains had the highest average prevalences (54.6%, 47.4%, 40.0%, 34.3%, and 36.7%, respectively). Alaska, the Rocky Mountain-Great Plains region, and the Midwest had low average prevalences (5.0%, 3.7%, and 6.7%, respectively). Overall, 27.9% (175/628) of the cats tested were seropositive. The seroprevalence of B. henselae in cats varies throughout the United States and appears to be influenced by climate.

Animals↗
PubMed1995

In vivo assessment of nonlinear myocardial deformation using finite element analysis and three-dimensional echocardiographic reconstruction.

In vitro data have shown that the myocardium exhibits nonlinear passive stress-strain relationship and a non-linear pressure-volume relationship. A finite element (FE) analysis and optimization algorithm was used on three-dimensional reconstructed left ventricular (LV) geometry using echocardiographic images, along with hemodynamic measurements, in seven closed-chest dogs to show a nonlinear stress-strain relationship in vivo. Our analysis included the computation of Poisson's ratio from the measured volumetric strain of the myocardium and a simulated pericardial pressure load ("equivalent pericardial pressure") applied to the epicardial surface of the reconstructed LV. LV geometry was reconstructed in three or four incremental time steps in diastasis and the myocardium was assumed to be homogeneous, isotropic, and linearly elastic during these short intervals in this initial study. Simultaneous LV chamber pressure and equivalent pericardial pressure were incorporated into the algorithm to predict actual LV expansion. Computations were performed iteratively at each interval to compute the optimized elastic modulus. By performing the FE analysis and optimization at each interval (a step-wise linear analysis approach), a linear relationship between the myocardial elastic modulus and LV chamber pressure was derived (r = .87 to .98). Such a linear relationship is equivalent to an exponential myocardial stress-strain relationship in vivo. Detailed measurement of nonhomogeneous regional deformation are becoming possible with the advent of sophisticated imaging techniques. The methodology described in this study, with appropriate modifications in the FE analysis and optimization algorithms, can be applied to assess the complex three-dimensional pressure-deformation characteristics in vivo.

Algorithms↗
PubMed1994

Doppler catheter tip localization using color enhancement.

The objective of this research was to determine if the ultrasound emissions of the Doppler catheter can be used to locate its position in 3 dimensions by conventional echocardiography. A Doppler catheter has previously been shown to permit nonfluoroscopic retrograde catheterization of the aortic root and left ventricular chamber by using velocity waveform polarity for directional guidance. A significant difficulty in providing ultrasound catheter guidance, however, has been the inability to recognize the Doppler catheter tip, because each point at which a flexible catheter crosses the image plane can be misinterpreted as the catheter tip. Initial in vitro water bath trials were performed using the Doppler catheter attached to a standard velocimeter. Using a 5 MHz imaging transducer and color Doppler methods, the presence or absence of a banded color pattern which could demarcate the Doppler catheter tip was recorded at various angles in and out of the scanning plane. Using Doppler retrograde guidance and transesophageal echocardiography, color Doppler banded patterns, which could identify the Doppler catheter tip, were investigated in the dog aorta. In order to understand the physical mechanisms involved, a series of water bath trials were then conducted using the Doppler catheter attached to a velocimeter which was synchronized to the echo machine. Initial nonsynchronized water bath trials revealed distinct banded color patterns demarcating the Doppler catheter tip when it pointed in any direction within the beam width, except for a 40 degrees blind cone directly away from the imaging transducer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Detection of pooled secretions above endotracheal-tube cuffs: value of plain radiographs in sheep cadavers and patients.

OBJECTIVE: Mechanical ventilation is thought to increase the risk of nosocomial pneumonia by permitting leakage of bacteria-laden gastro-oropharyngeal secretions into the upper airways. The goal of this study was (a) to validate radiographic signs of pooled secretions above endotracheal-tube cuffs (supracuff liquid) in an animal model and (b) to determine whether suctionable pooled supracuff liquid can be identified on bedside radiographs of intubated patients. MATERIALS AND METHODS: Diagnostic criteria for supracuff liquid were initially validated by three radiologists interpreting 162 randomized radiographs made in an intubated sheep cadaver. The primary criteria included (a) replacement of the normal supracuff lucency with liquid opacity and (b) the formation of a sharp interface between the lucency of the upper edge of the cuff below and the liquid above. Graded infusions of 0, 3, 8, 13, and 23 ml of saline were made in triplicate into the space above the cuff, and radiographs were evaluated for the presence or absence of saline. The validated diagnostic criteria were used by two radiologists to estimate the frequency with which pooled liquid was seen on portable chest radiographs of 47 patients undergoing elective short-term postanesthetic mechanical ventilation. RESULTS: In the sheep-cadaver model, the diagnostic criteria for supracuff liquid allowed successful differentiation between no liquid, a small amount of liquid (3-8 ml), and a large amount of liquid (13-23 ml; c2, p < .0001). In a clinical study, radiographic signs of supracuff liquid were identified in 57% of 47 patients. In a small subset of patients (n = 18), the estimated liquid volume (mean +/- SEM) was calculated to be 7.8 +/- 1.1 ml (range = 2.1-18.4 ml). CONCLUSIONS: Radiography is a sensitive means of identifying small volumes of supracuff liquid above the inflated cuffs of endotracheal tubes. Potentially contaminating liquid pooled above the cuff of an endotracheal tube can be identified in about half of patients undergoing short-term mechanical ventilation. Our results suggest the suction of the supracuff space may be a reasonable prophylactic maneuver against nosocomial pneumonia. A much larger study is suggested to investigate the actual relation between pooled supracuff liquid and the development of nosocomial pneumonia.

Adult↗