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Biomedical subjects

S Holm

Publications and source records attributed to S Holm.

At least 109 records · Page 6Linked to original sources
PubMed1996

Transport of D-glucose and 2-fluorodeoxyglucose across the blood-brain barrier in humans.

The deoxyglucose method for calculation of regional cerebral glucose metabolism by PET using 18F-2-fluoro-2-deoxy-d-glucose (FDG) requires knowledge of the lumped constant, which corrects for differences in the blood-brain barrier (BBB) transport and phosphorylation of FDG and glucose. The BBB transport rates of FDG and glucose have not previously been determined in humans. In the present study these transport rates were measured with the intravenous double-indicator method in 24 healthy subjects during normoglycemia (5.2 +/- 0.7 mM). Nine subjects were restudied during moderate hypoglycemia (3.4 +/- 0.4 mM) and five subjects were studied once during hyperglycemia (15.0 +/- 0.7 mM). The global ratio between the unidirectional clearances of FDG and glucose (K1*/K1) was similar in normoglycemia (1.48 +/- 0.22), moderate hypoglycemia (1.41 +/- 0.23), and hyperglycemia (1.44 +/- 0.20). This ratio is comparable to what has been obtained in rats. We argue that the global ratio is constant throughout the brain and may be applied for the regional determination of LC. We also determined the transport parameters of the two hexoses from brain back to blood and, assuming symmetrical transport across the BBB, we found evidence of a larger initial distribution volume of FDG in brain (0.329 +/- 0.236) as compared with that of glucose (0.162 +/- 0.098, p < 0.005). The difference can be explained by the very short experimental time, in which FDG may distribute both intra- and extracellularly, whereas glucose remains in a volume comparable to the interstitial fluid of the brain.

Adult↗
PubMed1996

Rate dependence of regional cerebral activation during performance of a repetitive motor task: a PET study.

Using repeated positron emission tomography (PET) measures of regional cerebral counts, we investigated the regional cortical activations induced in eight normal subjects performing eight different frequencies of fingertapping (0.5-4 Hz) with the right index finger. The task was auditorially cued and the performance recorded during the scanning procedure. Performance evaluation showed increased error rates, during fingertapping, of high and low frequencies, and the best tapping performance was measured in the midrange of frequencies. Significantly activated areas (p < 0.05) of normalized cerebral counts were located in the left sensorimotor cortex (MISI), right motor cortex, left thalamus, right insula, supplementary motor area (SMA), and bilaterally in the primary auditory cortex and the cerebellum. Statistical evaluation showed a significant (p < 0.01) and positive dependence of cerebral activation upon movement rate in the contralateral MISI. There was no significant rate dependence of cerebral activation in other activated motor areas. The SMA and the right cerebellar hemisphere showed a more uniform activation throughout the tapping frequency range. Furthermore, we found a stimulus rate dependence of cerebral activation in the primary auditory cortex. We believe that the present data provide useful information for the preparation and interpretation of future motor activation studies of normal human subjects and may serve as reference points for studies of pathological conditions.

Adult↗
PubMed1996

Evaluation of mitral regurgitation by pulmonary venous blood flow patterns. Relation to angiographic and haemodynamic parameters in subgroups of patients.

OBJECTIVES: To study the relationship between pulmonary venous systolic flow fraction (PVSFfr) recorded using pulsed Doppler transesophageal echocardiography and angiographic grading and haemodynamic parameters in subgroups of patients with mitral regurgitation. BACKGROUND: Reversed systolic pulmonary venous flow is a sensitive sign of severe mitral regurgitation. Scarse data are available regarding the effects of atrial fibrillation and coronary artery disease. METHODS: PVSFfr was calculated as the systolic flow velocity integral divided by the total inflow integral. PVSFfr is negative when systolic flow is dominantly reversed. 111 patients were studied. RESULTS: PVSFfr < 0 was 91% sensitive for angiographic severe mitral regurgitation (MR) (specificity 75%). In patients with sinus rhythm and without coronary artery disease the sensitivity was 100% and specificity was 86% (n = 25). PVSFfr correlated to angiographic grade (r = -0.63, P = 0.0001), mean PCW (r = -0.63, P = 0.0001), v-wave (r = -0.72, P = 0.0001), systolic blood pressure (r = 0.28, P = 0.003) and left atrial diameter (r = -0.42, P = 0.0001) (n = 111). Stepwise linear regression analysis revealed the v-wave, angiographic grading, left atrial diameter and systolic blood pressure to be independent predictors of PVSFfr. Subgroup analysis revealed a correlation (r = 0.85, n = 25) between angiographic grading and PVSFfr in patients with sinus rhythm without CAD and (r = 0.35, n = 23) in patients with CAD in atrial fibrillation. CONCLUSIONS: PVSFfr is valuable in assessing mitral regurgitation. In the presence of atrial fibrillation and coronary artery disease the correlation with angiographic grading decreases indicating the dynamic nature of this valvular lesion.

Adult↗
PubMed1996

Cerebral metabolism in a case of multiple sclerosis with acute mental disorder.

Acute mental disorder in early Multiple Sclerosis (MS) is rare and little is known about the structural and metabolic changes in this relation. We present an MS patient with discrete motor and sensory deficits, who developed severe behavioral changes over a period of nine months during the initial course of the disease. The cerebral metabolic rate of glucose (CMRglc) was measured using positron emission tomography (PET), and the patient underwent MRI as well as a comprehensive battery of neuropsychological tests. Significantly reduced values of CMRglc were found bilaterally in the frontal and temporal cortex, the putamen, the thalamus and the hippocampus. The MRI revealed progression of MS lesions in the frontal lobes during the development of mental symptoms. Neuropsychological examination showed wide spread cognitive dysfunction, and a pronounced frontal lobe syndrome. The study demonstrates the remote metabolic effects of lesions affecting subcortical neural connections in an MS patient with severe cognitive dysfunction.

Acute Disease↗
PubMed1996

Ethical reasoning in mixed nurse-physician groups.

OBJECTIVES: To study the ethical reasoning of nurses and physicians, and to assess whether or not modified focus groups are a valuable tool for this purpose. DESIGN: Discussion of cases in modified focus groups, each consisting of three physicians and three nurses. The discussion was taped and analysed by content analysis. SETTING: Five departments of internal medicine at Danish hospitals. SAMPLE: Seven discussion groups. MAIN MEASUREMENTS: Ethical content of statements, style of statements, time used by each participant. RESULTS: Danish physicians and nurses do not differ in the kind of ethical reasoning they use, but physicians use more of the discussion time than nurses, they use a more assertive style of argumentation, and the solutions chosen are usually first put forward by physicians. CONCLUSION: The results and informal comparisons with similar data from long qualitative interviews indicate that groups of this kind are a useful tool for gathering data on ethical reasoning.

Aged↗
PubMed1996

Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia.

During starvation, brain energy metabolism in humans changes toward oxidation of ketone bodies. To investigate if this shift is directly coupled to circulating blood concentrations of ketone bodies, we measured global cerebral blood flow (CBF) and global cerebral carbohydrate metabolism with the Kety-Schmidt technique before and during intravenous infusion with ketone bodies. During acute hyperketonemia (mean beta-hydroxybutyrate blood concentration 2.16 mM), cerebral uptake of ketones increased from 1.11 to 5.60 mumol.100 g-1.min-1, counterbalanced by an equivalent reduction of the cerebral glucose metabolism from 25.8 to 17.2 mumol.100 g-1.min-1, with the net result being an unchanged cerebral uptake of carbohydrates. In accordance with this, global cerebral oxygen metabolism was not significantly altered (144 vs. 135 mumol.100 g-1.min-1). The unchanged global cerebral metabolic activity was accompanied by a 39% increase in CBF from 51.0 to 70.9 ml.100 g-1.min-1. Regional analysis of the glucose metabolism by positron emission tomography-[18F]fluoro-2-deoxy-D-glucose indicated that mesencephalon does not oxidize ketone bodies to the same extent as the rest of the brain. It was concluded that the immediate oxidation of ketone bodies induced a decrease in cerebral glucose uptake in spite of an adequate glucose supply to the brain. Furthermore, acute hyperketonemia caused a resetting of the coupling between CBF and metabolism that could not be explained by alterations in arterial CO2 tension or pH.

Adult↗
PubMed1996

Cerebral glucose metabolism is decreased in white matter changes in patients with phenylketonuria.

Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MRI changes in patients with PKU. Four patients with PKU and nine healthy volunteers with an average age of 23 y (range 19-26 y) and 23 y (range 20-27 y), respectively, were studied. The IQ of patients with PKU was between 58 and 97. Cerebral MRI and positron emission tomography images with 18F-deoxyglucose were obtained, and arteriovenous differences for oxygen and glucose as well as cerebral blood flow was measured simultaneously to determine global cerebral oxygen and glucose metabolism. Cerebral MRI revealed that all patients with PKU had white matter changes with characteristic localization. In patients with PKU, regional glucose metabolism was 36% lower in the anterior periventricular areas, 0.14 +/- 0.06 compared with 0.22 +/- 0.04 mumol.g-1.min-1 in controls (mean +/- SD, p < 0.05, Mann-Whitney). Further, the ratio between glucose metabolism in the affected white matter and the cortex was 14% lower in the patients, decreasing from 0.57 +/- 0.05 to 0.48 +/- 0.06 (p < 0.05). Global cerebral blood flow, oxygen and glucose consumption were similar in the two groups. In conclusion, regional glucose metabolism is lower in MRI-demonstrated white matter changes. In mildly intellectually impaired patients with PKU, global cerebral glucose and oxygen metabolism remain intact.

Adult↗
PubMed1996

Intervertebral disc response to cyclic loading--an animal model.

The viscoelastic response of a lumbar motion segment loaded in cyclic compression was studied in an in vivo porcine model (N = 7). Using surgical techniques, a miniaturized servohydraulic exciter was attached to the L2-L3 motion segment via pedicle fixation. A dynamic loading scheme was implemented, which consisted of one hour of sinusoidal vibration at 5 Hz, 50 N peak load, followed by one hour of restitution at zero load and one hour of sinusoidal vibration at 5 Hz, 100 N peak load. The force and displacement responses of the motion segment were sampled at 25 Hz. The experimental data were used for evaluating the parameters of two viscoelastic models: a standard linear solid model (three-parameter) and a linear Burger's fluid model (four-parameter). In this study, the creep behaviour under sinusoidal vibration at 5 Hz closely resembled the creep behaviour under static loading observed in previous studies. Expanding the three-parameter solid model into a four-parameter fluid model made it possible to separate out a progressive linear displacement term. This deformation was not fully recovered during restitution and is therefore an indication of a specific effect caused by the cyclic loading. High variability was observed in the parameters determined from the 50 N experimental data, particularly for the elastic modulus E1. However, at the 100 N load level, significant differences between the models were found. Both models accurately predicted the creep response under the first 800 s of 100 N loading, as displayed by mean absolute errors for the calculated deformation data from the experimental data of 1.26 and 0.97 percent for the solid and fluid models respectively. The linear Burger's fluid model, however, yielded superior predictions particularly for the initial elastic response.

Animals↗
PubMed1995

Electromyographic response of the porcine multifidus musculature after nerve stimulation.

STUDY DESIGN: In this study, a porcine model was used to study whether a nerve reaction in the anulus fibrosus of a lumbar disc or in a facet joint capsule could cause a muscular response in the multifidus musculature. OBJECTIVES: To determine if there is an interrelationship between the intervertebral disc and facet joint innervation and the multifidus musculature as a possible pain mechanism. SUMMARY OF BACKGROUND DATA: The innervation of the anulus fibrosus of the intervertebral disc and the capsule of the facet joint is well described in the literature, although the functions of these nerves are poorly understood. An interrelationship between this innervation and the paraspinal musculature has not been previously described. METHODS: Fifteen adult pigs were used to measure the electromyographic response in the multifidus musculature to electrical stimulation of the lateral region of the disc anulus and the facet joint capsule in the L1-L2 motion segment. Motor unit action potentials were recorded using three sets of bipolar needle electrodes placed into the deepest fascicles of the multifidus, bilateral to the L2, L3, and L4 spinous processes. The effect of lidocaine injection into the facet joint and subperiosteal muscle detachment on the electromyographic response were studied. RESULTS: Stimulation of the disc anulus fibrosus induced reactions in the multifidus on multiple levels and on the contralateral side, whereas stimulation of the facet joint capsule induced reactions predominantly on the same side and segmental level as the stimulation. Introduction of lidocaine into the facet joint resulted in a significantly reduced electromyographic response to either stimulation, with the most drastic reduction seen when stimulating the facet joint capsule. Subperiosteal detachment of the paraspinal muscles prevented any muscular response. CONCLUSIONS: Stimulation of the disc and the facet joint capsule produced contractions in multifidus fascicles. The clinical implications are that there may be interactive responses between injured or diseased structures, i.e., disc or facet joints, and the paraspinal musculature. Activation of the multifidus muscles may have a stabilizing effect, constraining the motion of the lumbar spine. Longstanding muscular contraction may produce ischemic conditions and may be a potential source of pain.

Animals↗
PubMed1995

Is there a moral obligation not to infect others?

The emergence of HIV infection and AIDS has refocused concern on the obligations surrounding the carrying and transmission of communicable diseases. This article asks three related questions: Is there a general duty not to spread contagion? Are there special obligations not to communicate disease in the workplace? And does the mode of transmission of the disease affect the ethics of transmission and, if so, how and to what extent? There seems to be a strong prima facie obligation not to harm others by making them ill where this is avoidable, and this obligation not to communicate disease applies as much to relatively trivial diseases like the common cold as it does to HIV disease. The reasonableness of expecting people to live up to this obligation, however, depends on society reciprocating the obligation in the form of providing protection and compensation.

Communicable Diseases↗
PubMed1995

On the quantitative structure-activity relationships of meta-substituted (S)-phenylpiperidines, a class of preferential dopamine D2 autoreceptor ligands: modeling of dopamine synthesis and release in vivo by means of partial least squares regression.

The quantitative structure-activity relationship between physicochemical properties and effects on dopamine (DA) synthesis and release in the rat brain, in a series of meta-substituted (S)-phenylpiperidines, has been investigated by means of partial least squares regression (PLS). The effect on DA synthesis caused by the drugs, in both non-pretreated and reserpine-pretreated rats, was assessed by measurements of tissue levels of L-DOPA accumulated in the striatum following treatment with a decarboxylase inhibitor. Assessment of effects on DA release was performed by analysis of perfusates collected from implanted microdialysis probes. The numerical characterization of the variation in physicochemical features of the phenylpiperidines used in the regression modeling was accomplished by using common tabulated aromatic and aliphatic substituent constants in combination with a set of property descriptors derived from molecular mechanics and semiempirical calculations. It was found that the biochemical responses could be accurately predicted by the regression models based on these molecular feature measures. The molecular features exerting influence on DA synthesis were found to be markedly different from those influencing DA release. This finding is discussed in terms of the possible existence of a dopamine receptor-mediated DA release-controlling mechanism, which may not involve the synthesis regulating DA D2 autoreceptor. Some findings regarding the impact of the piperidine N substituent on agonist properties of the drugs are reported. The regression models were also used for guidance in the search for a phenylpiperidine with a lower intrinsic activity, at the DA D2 type autoreceptor, than the partial DA agonist preclamol (3).

Animals↗
PubMed1995

Effects of tiaprofenic acid and indomethacin on proteoglycans in the degenerating porcine intervertebral disc.

STUDY DESIGN: Eighteen pigs were stabbed with a scalpel in the anterior part of the anulus fibrosus of a lumbar disc. After surgery, the pigs received either tiaprofenic acid or indomethacin daily, and a third group did not receive any medication. OBJECTIVES: Nonsteroidal anti-inflammatory agents are widely used in the treatment of low back patients, but their long-term effects on the matrix molecules in the degenerate disc are unknown. SUMMARY OF BACKGROUND DATA: Several in vitro and in vivo studies on articular cartilage have suggested that tiaprofenic acid may not have adverse effects on matrix metabolism, whereas indomethacin probably does. METHODS: Uronic acid, DNA, and water contents were determined from five different locations in each injured disc. Transport and incorporation of sulfate were examined by in vivo radioactive tracer analysis, and proteoglycan structures were analyzed by gel electrophoresis. RESULTS: Morphologically, there were no differences between the treatments. Tiaprofenic acid maintained a higher uronic acid content in the nucleus pulposus and outer anulus compared with that of the nonmedicated animals. Tiaprofenic acid decreased the incorporation of sulfate in the injured area and the water content at most sites. Indomethacin had no adverse effects compared with the nonmedicated group, and it increased water content in the posterior anulus fibrosus. CONCLUSIONS: Long-term administration of tiaprofenic acid and indomethacin did not have harmful effects on matrix metabolism after disc injury. On the contrary, tiaprofenic acid may slightly protect proteoglycans in the degenerating disc.

Animals↗
PubMed1995

Collagen synthesis and types I, III, IV, and VI collagens in an animal model of disc degeneration.

STUDY DESIGN: The present study sought to elucidate the changes that occur in collagen chemistry in the early phases of disc degeneration. OBJECTIVE: To monitor the healing process of the injured anulus fibrosus and the secondary degenerative reactions in the nucleus pulposus. SUMMARY OF BACKGROUND DATA: Despite the importance of collagen chemistry under pathologic conditions in the intervertebral disc, knowledge of this aspect is very limited. METHODS: Fourteen pigs were stabbed with a scalpel blade in the anterior part of the anulus fibrosus of a lumbar disc. The animals were killed 2 weeks to 5 months after injury. The activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, the total collagen content, and staining patterns for Types I, III, IV, and VI collagens were analyzed from different parts of the disc. RESULTS: The most active phase of the healing process, assessed from the activities of enzymes involved in collagen biosynthesis, took place during the first month postoperatively. The anular lesion was found to cicatrize through formation of disorganized granulation tissue in which Type I, III, and, IV collagens were deposited. In the nucleus pulposus, activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase and total collagen content increased, and the originally rounded cells became more elongated, resembling fibroblasts. CONCLUSIONS: The results of this study suggest that the altered composition of collagens observed in the degenerate porcine nucleus pulposus results from changes in cell phenotype: Notochondral cells were replaced by fibroblast-like cells. It is likely that trauma to the anulus fibrosus can initiate a progressive degenerative process in the disc tissue.

Animals↗
PubMed1995

Prefrontal cortical mediation of rats' place learning in a modified water maze.

The acquisition of a place learning task in a water maze modified from the "standard" set-up by restriction of distal cues and addition of "proximal" cues (ping-pong balls in fixed positions on the surface of the water) was tested in three groups of rats: (I) animals subjected to bilateral ablation of the anteromedial prefrontal cortex, (II) rats in which the parietal "association" cortex had been removed bilaterally, and (III) a sham operated control group. The task acquisition of the prefrontally ablated group was significantly impaired, whereas the animals in which the parietal cortex had been removed acquired the task as quickly as the control group. Upon reaching criterion level performance all animals were tested on "challenge" sessions on which the cues were manipulated. Such "challenges" demonstrated that the animals of all three groups discriminated between the distal cues and utilized such a discrimination for navigational purposes.

Animals↗
PubMed1995

Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety-Schmidt technique.

Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation showed that the activation-induced resetting of the relation between CMRglc and CMRO2 persisted virtually unaltered for > or = 40 min after the mental activation task was terminated. The activation-induced increase in cerebral lactate efflux measured over the same time period accounted for only a small fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic stress indicators returned to baseline values. Activation-induced resetting of the cerebral oxygen/glucose uptake ratio is not necessarily accounted for by increased lactate production from nonoxidative glucose metabolism.

Adult↗
PubMed1995

Effect of milk and fermented milk on iron absorption in ileostomy subjects.

This study was undertaken to determine whether milk with its high calcium content adversely affects the absorption of nonheme iron from the diet as greatly as single-meal studies indicate. Nine ileostomy subjects ate a low-fiber, low-phytate diet for 8 consecutive weeks. During the first and eight weeks they drank a 250-mL soft drink with three main meals and an evening snack each day (0.16 g Ca/d). During the two intervening 3-wk periods, they drank the same amount of low-fat milk or fermented low-fat milk (Verum; Hälsofil, Norrmejerier, Umeä, Sweden) according to a formally randomized crossover design (1.4 g Ca/d). During the last 2 d in each of the four periods, apparent iron absorption (balance) from a test diet together with that period's beverage was measured and the plasma ferritin concentration was determined. There was no decrease in apparent iron absorption during the milk diet periods.

Adult↗
PubMed1995

"Socialized medicine," resource allocation and two-tiered health care--the Danish experience.

This paper describes the present resource allocation problems in the Danish tax-based public health care system and presents an analysis of the two policy options put forward as a solution to these problems: (1) explicit rationing of services, and (2) the introduction of two-tiered health care. It is argued that a two-tiered system with a private second tier is unlikely to be acceptable and viable in Denmark, whereas an introduction of a second tier within the public system may be more acceptable. It is further argued that present implicit rationing methods may be unethical and ought to be replaced by explicit rationing.

Delivery of Health Care↗