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Biomedical subjects

J H Anderson

Publications and source records attributed to J H Anderson.

At least 73 records · Page 4Linked to original sources

Role of atrial contraction in diastolic pressure elevation induced by rapid pacing of hypertrophied canine ventricle.

The mechanism of diastolic pressure elevation induced by acute rapid pacing in pressure-load hypertrophied left ventricles (LVs) remains incompletely understood. It has been ascribed to abnormalities of coronary flow, metabolism, and calcium cycling. However, rapid pacing also alters the timing of atrial and ventricular stimulation relative to the diastolic filling period, and this could also influence diastolic pressures. To test the role of such mechanical factors, LV pressure-volume hemodynamics were measured in closed-chested anesthetized dogs during and after abrupt cessation of rapid atrial pacing. Twenty-one dogs were studied: 6 dogs with LV hypertrophy (LVH) induced by perinephritic hypertension, 5 sham-operated normotensive dogs, and 10 acute normotensive control dogs. In LVH dogs, but not in sham-operated or control dogs, end-diastolic pressure rose progressively with increasing heart rate from 5.6 +/- 3.1 mm Hg at baseline to 22.6 +/- 8.1 mm Hg at 220 beats per minute. In all hearts, rapid pacing shifted the timing of left atrial contraction so that it occurred near the onset of LV filling rather than at end diastole. However, in LVH hearts, early LV diastolic pressure and peak atrial pressure were also markedly elevated. Most striking, immediately after terminating the pacing, diastolic pressure declined to near baseline. This rapid pressure decline occurred just when atrial systole would have ensued and before ventricular activation would have followed had pacing continued. Thus, diastolic pressure elevation resolved before a change in ventricular pacing rate. The role of atrial contraction was further explored by simultaneous atrioventricular pacing. This shifted the time of atrial systole so that it occurred during LV isovolumic contraction, while maintaining the identical LV pacing rate. This change eliminated the diastolic pressure elevation found previously. Further analysis revealed that the pressure increase during rapid pacing was not due simply to partial LV filling imposed on a relaxing ventricle or to hypertension or an intact pericardium. These data indicate that mechanical effects of atrioventricular interaction play an important role in tachycardia-induced diastolic dysfunction in this model of LVH and can be more causative than ischemia or metabolic factors in this setting.

Animals↗

Vestibular and sensory interaction deficits assessed by dynamic platform posturography in patients with multiple sclerosis.

Vestibular impairments have not been routinely identified in patients with multiple sclerosis (MS), because of the confounding effects of deficits in other neural systems. In this study, 35 patients with MS were evaluated by means of a systematic alteration of the sensory environment (dynamic posturography) in order to identify those patients who became unstable when vestibular inputs were needed to maintain stance. Subjects were assigned to either a high-function (HF) or a low-function (LF) group on the basis of a functional status assessment score obtained prior to the posturography test. For the HF group, 30% (7/23) had abnormal posturography scores. Of those subjects, 3 had a vestibular dysfunction pattern or a somatosensory-vestibular impairment. In contrast, 58% of the LF group (7/12) had abnormal posturography scores. Nearly all of these LF patients (6/7) had a vestibular dysfunction pattern or a combined visual-vestibular or somatosensory-vestibular impairment. Posturography might serve as one method to evaluate the functional consequences of a vestibular deficit in patients with MS.

Adult↗

Hemilabyrinthectomy causes both an increase and a decrease in corticotropin releasing factor mRNA in rat inferior olive.

It was previously shown [NeuroReport, 3 (1992) 829-832] that unilateral labyrinthectomy (UL) induces Fos expression in several brainstem regions, including the beta subnucleus of the inferior olive. Using isotopic 33P in situ hybridization, the present results demonstrate significant changes in oligonucleotide-probed mRNA levels for corticotropin-releasing factor (CRF) in the rat inferior olivary nucleus 4 days following unilateral labyrinthectomy (UL). In the medulla of normal animals there was strong CRF mRNA labeling in the inferior olivary nucleus, and weaker labeling in the vestibular nuclei and prepositus hypoglossi. Following unilateral labyrinthectomy, the contralateral olivary beta subnucleus showed a significant increase in CRF message, similar to the contralateral Fos labeling observed after hemilabyrinthectomy [NeuroReport, 3 (1992) 829-832]. In addition, the contralateral A and B subnuclei (IOA/B) of the inferior olive showed a strong increase in CRF labeling, while the ipsilateral dorsal cap of Kooy (IOK) showed a decrease. This novel bidirectional alteration in CRF message in different subdivisions of the same nuclear group indicates the existence of both up and down regulatory mechanisms controlling CRF peptide expression, and reflects the dynamic neurochemical alterations occurring during vestibular compensation.

Animals↗

Quantitative proton spectroscopy of canine brain: in vivo and in vitro correlations.

Quantitative, single-voxel proton NMR spectroscopy of normal brain was performed in five adult beagle dogs using the cerebral water signal as an internal intensity reference. The same brain regions were then rapidly isolated and frozen using a pneumatic biopsy drill, perchloric acid extracted, and analyzed by biochemical assay and high-resolution NMR spectroscopy. The concentrations of the major resonances in the in vivo and in vitro spectra were compared, and good agreement was found between the different measurements. The in vivo spectra contained three peaks at 3.21, 3.04, and 2.02 ppm, which are usually assigned to trimethylamines (TMA), creatines, and N-acetyl derivatives (NAc), which corresponded to be the following metabolite concentration values: 1.7 +/- 0.6, 7.7 +/- 2.1, and 10.9 +/- 2.7 mumol/g wet weight respectively. In vitro, the following metabolite concentrations were measured: glycerophosphocholine (GPC) 1.3 +/- 0.2, phosphocholine (PC) 0.5 +/- 0.1, phosphocreatine (PCr) 2.6 +/- 0.4, creatine (Cr) 5.9 +/- 1.4, and N-Acetyl aspartate (NAA) 8.9 +/- 1.8 mumol/g wet weight. Therefore, the 3.21 ppm resonance observed in the in vivo spectrum is predominantly GPC and PC in a ratio of 2.6:1, the 3.04 ppm resonance is Cr and PCr in a ratio of 2.3:1, and the 2.02 ppm resonance is predominantly (approximately 80%) NAA with small contributions from N-acetylaspartylglutamate (NAAG) and glutamate. The data presented here validate the technique of water referencing as a simple and convenient means of quantitating single-voxel in vivo proton NMR spectra of the brain.

Animals↗

High performance liquid chromatography of carbon-11 labeled thymidine and its major catabolites for clinical PET studies.

The identity and pharmacology of the rapidly formed radiolabeled metabolites formed following i.v. injection of C-11 thymidine (TdR) labeled in the 5-methyl-position are being studied in animal models and patients with cancer. A high performance liquid chromatographic (HPLC) procedure has been developed for the separation of these metabolites including thymine, dihydrothymine, beta-ureidoisobutyric acid, and beta-aminoisobutyric acid from plasma and tissue extracts. Information obtained regarding the pharmacokinetics of the metabolites are being used to generate mathematical models for C-11 TdR incorporation rates into DNA.

Animals↗

Splanchnic blood flow changes in the presence of hepatic tumour: evidence of a humoral mediator.

Intrahepatic tumour is associated with alterations in splanchnic haemodynamics. To investigate the hypothesis that these are the result of a circulating vasoactive agent, rat small bowel segments were cross-perfused with arterial blood from groups (n = 12) of paired tumour-bearing (intrahepatic HSN sarcoma) and control rats. The vascular resistance of the segment was significantly greater during perfusion by tumour-bearing animals (91.6 mmHg ml-1 min, s.e. 21.5, vs 51.7 mmHg ml-1 min, s.e. 7.4, P < 0.05), suggesting that intrahepatic tumour may be associated with a circulating vasoactive agent. A similar mechanism may underlie changes in the hepatic perfusion index in patients with liver metastases.

Animals↗

A phase II study of regional 5-fluorouracil infusion with intravenous folinic acid for colorectal liver metastases.

Regional chemotherapy, delivered via the hepatic artery, may significantly increase tumour response rates in patients with colorectal liver metastases. However, survival is limited by extrahepatic disease progression. We have developed a novel therapeutic approach for patients with metastases confined to the liver. In order to achieve high local response rates and also inhibit extrahepatic progression, 5-fluorouracil (5-FU) was infused intra-arterially at a dose previously calculated to achieve both high-dose regional therapy and adequate systemic levels. To enhance efficacy further, 5-FU was combined with high-dose systemic folinic acid (FA). Thirty-one patients were evaluated in a phase II study. 5-FU (1.5 g m2) was infused via a surgically implanted hepatic artery catheter over a 24 h period; FA (total 400 mg m-2) was infused intravenously during the initial and final 2 h. Treatments were given weekly for cycles of 6 weeks' duration. To date, median duration of treatment is 6 months and the median follow-up period is 17 months. The overall response rate was 48% with two complete and 13 partial responses. Predicted median time to progression is 8 months. The site of first progression was hepatic in 10 (42%) and extrahepatic in 14 (58%) patients. Seven patients developed local complications; one required emergency surgery. Side-effects were limited to grade 3 toxicity (four patients) or less. Predicted median survival is 19 months. This approach, which is associated with a high response rate and low systemic toxicity, warrants further evaluation. A phase III study is planned.

Adult↗

Dose requirements for a nonionic contrast agent for spiral computed tomography of the liver in rabbits.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the relationship between intravenous dose of a nonionic contrast agent and hepatic enhancement using spiral computed tomography. METHODS: The enhancement of the liver, hepatic vein, inferior vena cava, and aorta was evaluated in the New Zealand male rabbit after intravenous injection of iohexol, 300 mg iodine (I)/mL, at 2 mL/sec. Spiral computed tomography scans of 10 animals were evaluated at each of nine different contrast doses (857, 771, 686, 600, 514, 429, 343, 257, and 171 mg I/kg) for a total of 90 spiral scans. RESULTS: Hepatic attenuation was linearly proportional to the contrast dose over the range of doses examined. The average change in attenuation of the liver from the first to the last scanned portion of the liver ranged from 0 to 7 Hounsfield Units (HU) (standard deviation ranging from 4 to 11 HU). Hepatic venous enhancement was greater than that of the liver for doses greater than 171 mg I/mL. The aortocaval difference in enhancement was greater than 10 HU in all cases. CONCLUSION: A dose of 429 mg I/kg, providing an average hepatic enhancement greater than 30 HU, is predicted to be the lower dose limit for hepatic parenchymal enhancement using spiral computed tomography.

Animals↗

Multimodality correlative study of canine brain tumors. Proton magnetic resonance spectroscopy, positron emission tomography, and histology.

RATIONALE AND OBJECTIVES: Structural/functional relationships in an induced canine brain tumor were studied using proton-magnetic resonance spectroscopy (1H-MRS), positron emission tomography (PET), and histology. METHODS: Proton-MRS and PET data of implanted canine brain tumors were correlated with quantitative analysis of the tissue composition within the MRS and PET regions of interest (ROIs). Linear regression analysis was employed to correlate the 1H-MRS and PET data with the percent tumor and the percent total lesion (comprising tumor plus associated pathology ie, edema, cysts, hemorrhage, inflammation) within the ROI. RESULTS: Using 1H-MRS, N-acetyl aspartate concentrations were indirectly correlated with the amount of tumor (P = .058), as well as the amount of tumor plus associated pathology (P = .032) within the ROI. Total creatine concentrations were indirectly correlated with the amount of tumor and the amount of tumor plus associated pathology within the ROI (P < .05). Lactate concentrations were directly correlated with the amount of tumor (P = .053) and the amount of tumor plus associated pathology (P = .058) within the ROI. Using PET, Oxygen metabolic rates were indirectly correlated with the amount of tumor and with the amount of tumor plus associated pathology within the ROI (P < .05). Glucose metabolic rates were directly correlated with both the amount of tumor and with the amount of tumor plus associated pathology at P < .05. Proton-MRS measured concentrations of choline and PET measured values for blood flow, and oxygen extraction showed correlations with the amount of tumor and with the amount of tumor plus associated pathology at P > or = .08. CONCLUSIONS: The PET and MRS data were complementary with respect to suggesting anaerobic glucose metabolism for the tumor. Unlike other tumors, no increase in choline was noted in the canine tumor.

Animals↗

Palmaz stent in the treatment of central venous stenosis: safety and efficacy of redilation.

PURPOSE: To assess the safety and efficacy of redilation of central venous stents in a growing animal model. MATERIALS AND METHODS: Palmaz stents were placed in the inferior vena cava (IVC) in 18 newborn lambs. After 5 months, vena cavography was performed. Those animals in which growth of the IVC adjacent to the stent and/or neointimal hyperplasia had resulted in a stenosis were considered candidates for redilation. Repeat vena cavography, intravascular ultrasound, and histologic examination were performed at 2 or 6 months. RESULTS: A stenosis of > 20% was demonstrated in 13 animals. Redilation was performed, and a 50% mean increase in stent diameter was achieved. There were no immediate complications. Late complications included nonocclusive laminar clot (n = 2), and a bar of tissue dividing but not occluding the caval lumen (n = 1). Moderate neointimal hyperplasia occurred in all stents. Stent compression (unrelated to redilation) occurred in seven animals. CONCLUSION: Palmaz stents can be redilated safely and effectively in an animal model of growing central veins.

Animals↗

Clinical pharmacokinetic advantages of new drug delivery methods for the treatment of liver tumours.

Response rates following systemic chemotherapy for hepatic tumours are disappointing. The drugs used have a narrow therapeutic ratio, which limit the scope for dose escalation of these potentially toxic agents. Therefore, alternative delivery methods that optimise the efficacy of currently available cytotoxic agents have been explored. Several novel approaches have attempted to 'target' treatment so that it reaches the tumour whilst minimising systemic exposure. There is some evidence to suggest that certain agents, including monoclonal antibodies and liposomes, selectively lodge in tumours following intravenous administration. Alternatively, the route of administration may be modified to enhance targeting of the administered drug. Delivery via the hepatic arterial, portal venous, and peritoneal routes as well as drug delivery via direct implantation may provide certain pharmacokinetic advantages. Infusion rates may be adjusted to optimise the pharmacokinetic profile. Chemoembolisation with microspheres, microcapsules or macromolecules might enhance targeting further. Variations in particle characteristics or by modifying hepatic arterial blood flow with vasoactive substances may be used to further refine this technique. The ultimate 'magic bullet', which allows total delivery of treatment to malignant cells whilst eliminating exposure of healthy tissues to these toxic agents, has not been developed as yet. However, currently available techniques allow considerable dose escalation that, whilst not providing a significant survival advantage, certainly improves response rates.

Antibodies, Monoclonal↗

Quantitative proton spectroscopy and histology of a canine brain tumor model.

Quantitative, single voxel proton nuclear magnetic resonance (NMR) spectroscopy and histological analysis was performed in eight dogs implanted with the transplantable canine glioma model of Wodinsky (Proc. Am. Assoc. Cancer Res. 10, 99 (1969)). Signals from choline, creatine, N-Acetyl Aspartate (NAA) and lactate were converted to molar concentration units and correlated with the quantitative analysis of histologically determined tissue types within the localized volume selected for NMR spectroscopy. In general, compared with normal brain, the lesions were associated with reductions in all metabolite concentrations, with the exception of lactate, which was increased. NAA and creatine decreases were most significantly correlated with the total lesion volume (P < 0.01), suggesting that these compounds are present in normal brain only. Changes in choline levels did not correlate strongly with any particular tissue type. Lactate was found to increase with increasing total lesion volume (P < 0.01), but not with increasing percent tumor, suggesting that it accumulates in abnormal tissue other than the tumor. The spectra reported were similar to those observed in human glioblastomas, with the exception that elevations of choline were not observed. The transplantable canine gliosarcoma system appears to be a suitable tumor model for evaluation by clinical radiological techniques such as magnetic resonance imaging (MRI) and proton NMR spectroscopy.

Animals↗

Sensory organization of balance responses in children 3-6 years of age: a normative study with diagnostic implications.

The effect of altered sensory environments on balance was studied in 82 healthy children between 3 and 6 years of age. The purpose was to obtain normative measurements of postural stability during early stages of development for use in clinical posturography. Subjects were tested in three visual conditions (eyes open, blind-folded, and sway-referenced visual enclosure) during stance on either a fixed or sway-referenced force platform (EquiTest). During sway-referenced conditions, spontaneous changes in the subject's center of force (COF) drove rotational displacements of the platform and/or visual surround. The gain of platform/COF or surround/COF displacement was altered from 0.00 to 1.5. An equilibrium score (ES) was calculated based on the amount of postural sway compared to the maximum sway possible without falling. A higher ES reflected greater postural stability. An improvement in postural stability was observed between 4 and 5 years of development when the sensory environment was fixed (sway referenced gain = 0.0). In a dynamic sensory environment, however, age-related improvements in postural stability were not uniform and depended upon the specific sensory condition. For example, while 6 year olds generally showed the greatest postural stability of any age group, all ages showed statistically equivalent equilibrium scores during stance on a compliant surface with eyes closed, at all sway gains. The ability to ignore misleading sensory inputs to maintain balance was observed at 3 years of age; 76% of the 3 year olds (n = 16) were able to maintain stance in altered sensory environments at the 1.0 sway gain. In addition, postural stability was greater when visual inputs were sway-referenced compared to conditions that manipulated the support surface compliance. These data suggest that the predominance of visual-vestibular control of balance gives way to a somatosensory-vestibular dependence by age 3, but that the transition to adult-like balance responses is not complete for all sensory conditions even by age 6. The use of posturography to enhance the assessment of pediatric vestibular and sensory integration deficits is discussed.

Age Factors↗

Clinical application of captopril renal scintigraphy in Takayasu's arteritis.

Takayasu's disease (pulseless disease) is an uncommon chronic inflammatory disease primarily affecting the medium and large arteries, with a strong predilection for the aortic arch and its branches; hence, it sometimes is referred to as aortic arch syndrome. The etiology is unknown, although a systemic immunologic process seems most likely. About half the reported cases also revealed involvement of the pulmonary and renal arteries. The involvement is more marked in the origin of the vessel than distally. Although it is more common among Orientals, its distribution is worldwide, without racial boundary. A case is presented in which captopril renal scintigraphy and digital subtraction angiography were used to show renal artery stenosis as the cause of the patient's hypertension.

Adult↗

Otolith-brain stem connectivity: evidence for differential neural activation by vestibular hair cells based on quantification of FOS expression in unilateral labyrinthectomized rats.

1. The effects of acute and chronic labyrinthectomies on Fos-defined neuronal activity induced by rotation were determined with the use of quantitative image analysis procedures. Unilateral sodium arsanilate labyrinthectomies (UL) were performed either 24 h (acute) or 2 wk (chronic) before exposure to a 90 min, 2-G centripetal acceleration along the interaural axis that stimulated the intact otolith organs. The results obtained from both acute and chronic UL animals subjected to centripetal acceleration were compared with data obtained from nonrotated UL animals and fully intact, normal animals exposed to centripetal acceleration. Such comparisons allowed the definition of functional projections from the otolith organs of one labyrinth to vestibular related and inferior olivary brain stem nuclei in the rat. 2. The effect of the labyrinthectomy on nonrotated animals was first assessed. After acute UL, asymmetric Fos expression was present in the medial and inferior vestibular nuclei, the prepositus hypoglossi (bilaterally), the ipsilateral (with respect to the side of UL) dorsolateral periaqueductal gray, and the contralateral inferior olivary beta subnucleus, as previously described (Kaufman et al., 1992b). Except for minimal labeling in the contralateral prepositus hypoglossi and the dorsolateral periaqueductal gray, the Fos labeling that was present in the brain stem of acute UL animals was absent in chronic UL animals. Thus Fos neuronal activity appears to define a pattern of brain stem activation associated with the initial events that underlie vestibular compensation. 3. In acute UL rats, which were rotated, the contralateral beta subnucleus of the inferior olive had greater labeling (compared with nonrotated UL animals) when the lesion was away from the axis of rotation. In contrast, the ipsilateral beta subnucleus labeled when the lesion was towards the axis of rotation. Fos expression was observed bilaterally in the prepositus hypoglossi when the lesioned side was oriented toward the axis of rotation but was observed only in the contralateral prepositus nucleus when the lesioned side was oriented away from the axis of rotation. Finally, the dorsomedial cell column of the inferior olive (DMCC) was heavily labeled when the lesioned side was oriented towards the axis of rotation but was unlabeled when the lesioned side was oriented away from the axis of rotation. In acute UL nonrotated animals the DMCC was only lightly labeled. All other brain stem nuclear labeling was similar between the acute UL rotated and nonrotated animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Acceleration↗

Evaluation of patients with acoustic neuroma with dynamic posturography.

The purpose of the present work was to consider the use of posture tests in patients who had known acoustic tumors. The results suggest that it might be possible to determine whether the tumor is on the inferior or superior branch of the vestibular nerve. This would have clinical significance for planning a surgical approach to the tumor.

Aged↗

Effect of sway-referenced visual and somatosensory inputs on human head movement and postural patterns during stance.

The purposes of this study were to (1) evaluate the effects of sway-referenced visual and ankle somatosensory inputs on head movement and body sway during stance and (2) determine how sway-referenced sensory inputs might influence the selection of postural patterns. Seventeen healthy adult subjects were evaluated while attempting to maintain standing balance. Ankle somatosensory inputs were altered during stance by creating support surface rotations which were continuously adjusted ("referenced") to the center of force. In selected trials, ankle somatosensory or visual inputs were distorted further by increasing the platform/body sway gain or by increasing the sway-referenced gain of a rotating visual enclosure. The results showed that spontaneous body sway in a given direction was generally associated with head displacement in the opposite direction. The slope of the sway vs. sagittal head position linear regression line was statistically greater at a sway-referenced gain of 1.5 compared to a gain of 1.0. This finding was observed specifically when mechanical compliance of the support surface was increased and occurred whether the eyes were open or closed. Horizontal shear force was generated in the same direction as head displacement and the linear regression slope was greatest with eyes open and at a sway gain of 1.5. These findings indicate that (1) destabilization of the ankles altered displacement of the head independently from visual input, and (2) visual information was necessary to produce specific postural patterns utilizing horizontal shear forces to maintain stance on a mechanically compliant surface. The results provide evidence for a neural mechanism linking ankle somatosensory inputs and head control.

Adult↗