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Biomedical subjects

S Holm

Publications and source records attributed to S Holm.

At least 145 records · Page 8Linked to original sources
PubMed1994

Fatigue development during electrical stimulation in the masseter muscle of rhesus monkeys (Macaca mulatta).

Fatigue development was investigated in five adult female rhesus monkeys, 9-11 yr old (mean weight, 4.6 kg). After sedation and anaesthesia, silver electrodes were implanted in the anterior and posterior parts of the right masseter; the contralateral muscle was used as a control. The bite force was monitored. Muscle biopsies were obtained from the central part of the masseter and were immediately frozen in liquid nitrogen. After freeze-drying a fluorometric analysis using enzymatic methods for measuring levels of glycogen, glucose, lactate, pyruvate, creatine phosphate, creatine, NADH and NAD was made. The masseters were stimulated for 3 min (100 V, 4 Hz and 2 ms). After a 5-min rest period the stimulation was repeated with the same voltage, frequency and duration. The rhesus monkey masseters were easy to fatigue. After the stimulations 25% of the initial bite force remained. A marked substrate depletion was evident. The precontraction values of glycogen, glucose and phosphocreatine were reduced. The NADH concentration increased and the NAD content decreased. An accumulation of waste products was observed; the pyruvate increased by 92% and the lactate increased by a factor of 3. The substantial substrate depletion in combination with a prominent metabolic waste-product accumulation may induce a decrease in bite-force production.

Animals↗
PubMed1994

Effects of chronic imipramine on exploration, locomotion, and food/water intake in rats.

Three groups of rats were subjected to 15 daily injections of imipramine (10 or 20 mg/kg) or vehicle control injections, respectively. During the treatment period, both imipramine groups failed to grow while the control group gained weight normally. Both dosages of imipramine suppressed food intake significantly, while water intake was only reduced by 20 mg/kg of imipramine and only during the first 5 days of treatment. Twenty-four hours after the last imipramine injection, the animals were subjected to a test battery designed to demonstrate potential changes in locomotion and/or exploration. While locomotion appeared unaffected by both dosages of imipramine, the group receiving 20 mg/kg of imipramine demonstrated a significantly reduced exploration. The exploration of the group receiving imipramine in the concentration of 10 mg/kg was only marginally changed. The temporal pattern of exploration of the animals receiving 20 mg/kg of imipramine revealed that chronic imipramine treatment was associated with an initial "hyperexploration" followed by an "overhabituation," resulting in an overall reduction of exploration during a 15-min period.

Animals↗
PubMed1994

Regional cerebral blood flow distribution in newly diagnosed schizophrenia and schizophreniform disorder.

Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used to study subjects under resting conditions and during performance of the Wisconsin Card Sorting Test. The study is a replication of a previous investigation in an independent series of patients and healthy volunteers. The patients had significantly lower relative blood flow in prefrontal regions during activation than did the healthy volunteers. An earlier series of 19 patients and 7 healthy volunteers was studied using exactly the same procedure. Analyses of the combined samples from the two studies (43 patients and 24 healthy volunteers) showed the patients to have significantly lower relative flow in prefrontal regions both at rest and during activation and higher flow in the left striatum during activation. The same finding emerged when analyses were confined to drug-naive patients and patients educationally matched to the healthy volunteers. The study suggests a defective frontostriatal interrelationship in schizophrenia and schizophreniform disorder.

Adolescent↗
PubMed1994

Brain metabolism during short-term starvation in humans.

During prolonged starvation, brain energy requirements are covered in part by the metabolism of ketone bodies. It is unknown whether short-term starvation of a few days' duration may lead to reduced brain glucose metabolism due to the change toward ketone body consumption. In the present study we measured the cerebral metabolism of glucose and ketone bodies in nine healthy volunteers before and after 3.5 days of starvation. Regional glucose metabolism was measured by dynamic positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. The mean value of K1* in gray and white matter increased by 12% (p < 0.05), whereas k2* and k3* were unchanged compared with control values. Regional glucose metabolism in cortical gray matter was reduced by 26% from 0.294 +/- 0.054 to 0.217 +/- 0.040 mumol g-1 min-1 (p < 0.001). White matter glucose metabolism decreased by 27% (p < 0.02). The decrease was uniform in gray and white matter with regional decreases ranging from 24 to 30%. A determination using Fick's principle confirmed the reduction in glucose metabolism yielding a decrease of 24% from 0.307 +/- 0.050 to 0.233 +/- 0.073 mumol g-1 min-1 (p < 0.05), whereas CBF did not change (0.57 +/- 0.07 vs. 0.57 +/- 0.06 ml g-1 min-1). The global net uptake of beta-hydroxybutyrate increased 13-fold from 0.012 +/- 0.024 to 0.155 +/- 0.140 mumol g-1 min-1 (p < 0.05). Net uptake of acetoacetate and net efflux of lactate and pyruvate did not change significantly during starvation. The present study shows that the human brain adapts to the changes in energy supply as early as 3 days following initiation of starvation, at which time ketone bodies account for approximately one-fourth of the cerebral energy requirements.

Adult↗
PubMed1994

Relationship between brain structure and function in disorders of the schizophrenic spectrum: single positron emission computerized tomography, computerized tomography and psychopathology of first episodes.

Fifty newly diagnosed, briefly treated or drug-naive patients with schizophrenia or schizophreniform disorder were examined by psychopathology scales for positive (SAPS), negative (SANS) and overall psychotic symptoms (PSE and BPRS). CT-scan and regional cerebral blood flow (rCBF) measurement by 99mTc-HMPAO SPECT during rest and mental activation by Wisconsin Card Sorting Test was performed as well. Twenty-five age-matched normal healthy volunteers served as controls. Thought disorders and fundamental symptoms correlated positively with relatively high, though subnormal prefrontal (PFC) rCBF and high rCBF in temporal cortex; positive symptoms correlated positively with high rCBF in the striatum and temporal cortex during activation. Negative symptoms correlated with high prefrontal rCBF. The patients had sulcal enlargement and smaller brain volume compared with the healthy volunteers. There were no signs of ventricular enlargement. Neither total negative symptoms, thought disorder nor fundamental symptoms correlated with any CT measurements. Total positive symptoms correlated negatively with the size of the temporal horns. The relatively high rCBF in PFC and temporal cortex of cases with pronounced positive and negative symptoms and thought disorder may imply that an aberrant cortical network has to be active to express a malattuned clinical output. The striatal hyperfunction mainly in productive cases may be a secondary phenomenon and more pronounced in cases where no signs of subcortical atrophy has (yet?) ensued.

Adolescent↗
PubMed1994

Moral reasoning in biomedical research protocols.

An analysis was performed of the ethics section in 134 biomedical research protocols submitted for review to a Danish Research Ethical Committee (REC) in 1990. The statements made in the ethics sections were identified and classified. It was found that 20% of the protocols lack an ethics section despite a specific requirement for such a section in the Helsinki-II declaration and the guidelines issued by the REC. The ethics sections have a median length of 6 lines of text and contain a median of 3 ethically relevant statements, thereby comprising 1.13% of the total research protocol. An analysis of the statements made show that 32% are purely formal and 30% are concerned with the area of information, consent and voluntariness. The remaining 38% are spread over a wide range of considerations. It is hypothesized that this relatively meager result reflects the researchers perception of the research review procedure as a mostly formal procedure.

Clinical Protocols↗
PubMed1994

Fiber types and diameters in the porcine masseter muscle. A histochemical study.

Type I, I:B, II:A, and II:C fibers were identified by adenosine triphosphatase histochemistry in masseter muscles from 22 female pigs (1 year old, 70-90 kg body weight). Type II:B fibers were not found. This was in contrast to the findings of five fiber types in the porcine soleus muscles. In the porcine masseter the most prominent fiber type was II:A (75%). Type I fibers constituted 15% of the fiber types on average. Type I:B and II:C fibers were less frequent (4-6%). No significant difference was found between various biopsy locations, but there was a tendency towards more type I fibers in the deeper part of the masseter muscle. The mean fiber diameters were larger in the masseter muscles than in the soleus; however, the differences were significant only for fiber type I:B.

Adenosine Triphosphatases↗
PubMed1994

Expression of type I, III, and VI collagen mRNAs in experimentally injured porcine intervertebral disc.

Young domestic pigs were incised with a scalpel blade into the anterior part of annulus fibrosus of lumbar discs in order to study the reparative processes in the annulus fibrosus and the secondary reactions in the nucleus pulposus. Northern and slot-blot hybridizations were used to investigate type I, III, and VI collagen gene expression in the disc tissue. For this purpose a method for RNA isolation was modified so as to be applicable to the intervertebral disc, which has a low cell density and a high proteoglycan content in its extracellular matrix. The amount of total RNA was found to be very low, particularly in the nucleus pulposus. Intact RNA could be isolated from most parts of the injured discs, but only from the outer annulus of the control discs. Hybridizations showed that healing of the wound in the annulus fibrosus involves an increase in the synthesis of particularly type I and type III collagens. However, no changes in the collagen gene expression were detectable in the nucleus pulposus two weeks after the injury.

Animals↗
PubMed1994

Absence of transsynaptic transport in cerebello-thalamo-cortical path of the rat.

Attempts to visualize the cerebello-thalamo-cortical path in the rat were made with different approaches. We tried (1) double labelling with somatopetal tracing from the motor cortex and somatofugal from the cerebellar nuclei, (2) transmembrane labelling by depositing biocytin or wheat germ agglutinin (WGA) into the motor cortex or cerebellum. WGA was either iodinated with 125I or conjugated with horseradish peroxidase (HRP). The double labelling technique showed an overlap of the tracers in the same thalamic region but no evidence of transsynaptic transport in either direction was obtained. Our results indicate a difference in the organization of this system in primates and rodents, since transsynaptic labelling in the cerebellar nuclei after injections of WGA-HRP conjugate in the monkey motor cortex has been found.

Animals↗
PubMed1994

Proteoglycan chemistry in experimentally injured porcine intervertebral disk.

An animal model of disk degeneration was used to study the concentration levels and types of proteoglycans in the different parts of the intervertebral disk. An annular incision was made with a scalpel blade into the anterior part of the porcine lumbar intervertebral disks via a retroperitoneal approach. Three months after injury the morphology of the injured disk had changed considerably. Disk height was diminished, and in the injured segment osteophytes had formed at the ventral edges of the vertebral body. The nucleus was small, fibrous, and yellowish. The annular lesion had healed by formation of granulation tissue, but the lamellar structure was partially destroyed. The concentration of inorganic [35S]sulfate had decreased across the whole disk, reflecting a decrease in the rate of solute transport. The concentration of incorporated [35S]sulfate had also decreased in the injured disks. The DNA concentration in the anterior annulus and in the nucleus had increased, whereas both the concentration of uronic acid and the ratio of chondroitin-6-sulfate to chondroitin-4-sulfate in the nucleus had decreased. Agarose gel electrophoresis combined with chondroitinase B digestion suggested the presence of dermatan sulfate proteoglycans in the injured annulus fibrosus. The morphology and chemical composition of the disks adjacent to the injured one were normal, and only a slight increase in the concentration of incorporated [35S]sulfate was observed in the disks above the injured one.

Animals↗
PubMed1994

Use of 99mTc-bicisate in activation studies by split-dose technique.

The properties of the brain single photon emission computed tomography (SPECT) tracer 99mTc-bicisate (ethyl cysteinate dimer) were examined in regard to its use in test-retest studies with short-interval, split-dose studies. The stimulus applied in these tests was a visual activation by a "flickering chessboard" pattern. We used a fast dynamic SPECT (Tomomatic 232) recording eight slices. Twelve volunteers were assigned to two groups for reproducibility control and stimulation experiments, respectively. All were examined on 2 days. On the first day, only one injection was given in the resting state (t = 0), while two recordings were performed (t = 30 and t = 100), simulating the course and timing of a full split-dose study. The average washout of 8.3 +/- 1.0% was used as a correction on the second-day study. On that day the first injection was given during rest exactly as on day 1, allowing an estimate of day-to-day reproducibility. The second injection was made either in a resting state identical to the first or during visual stimulation. All images were normalized to mean brain count value. Results were analyzed in predefined anatomical regions of interest (ROIs). The day-to-day reproducibility was fair, with only one ROI (inferior frontal cortex) showing a significant 2% decrease. The studies of day 1 revealed a regional difference in observed washout ranging in the applied cortical ROIs from 7.9 to 11.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Retention of 99mTc-bicisate in the human brain after intracarotid injection.

99mTc-bicisate (ECD) was injected as a bolus into the internal carotid artery, and cerebral uptake and retention were recorded with fast-rotating single photon emission computed tomography (SPECT) equipment in four patients suffering from temporal lobe epilepsy. Quantitative regional cerebral blood flow (rCBF) was measured tomographically with the 133Xe inhalation technique. We applied a three-compartment kinetic model and algorithms modified from a previous analysis of 99mTc d,l-hexamethylpropyleneamine oxide (HM-PAO) kinetics. The bicisate brain uptake and retention curve was very similar to that of HM-PAO, and it can be described by a triexponential function including an initial steep component representing the vascular transmitted spike, a second less steep component representing back-diffusion from brain tissue to blood, and a third, very slow component, representing the very slow loss due to incomplete retention of the deesterified hydrophilic metabolites. Computerized curve-fitting on data from three patients gave average kinetic values for the first-passage (unilateral) extraction of E = 0.60 (range, 0.59-0.61); the overall retained fraction of the tracer supplied was R = 0.44 (0.43-0.45), and the conversion/clearance ratio was alpha = k3/k2 = 2.59 (2.38-2.77). This alpha is higher than that for HM-PAO, and therefore bicisate uptake as a function of blood flow is more linear than in HM-PAO. Less correction for backdiffusion is therefore needed. From 1 to 24 h there was an average loss of hydrophilic tracer of 3.5%/h, but the late distribution images were essentially unchanged over time, pointing to practically the same rate of loss in all regions.

Adolescent↗
PubMed1993

Benzodiazepine receptor equilibrium constants for flumazenil and midazolam determined in humans with the single photon emission computer tomography tracer [123I]iomazenil.

This study is based on the steady state method for the calculation of Kd values recently described by Lassen (J. Cereb. Blood Flow Metab. 12 (1992), 709), in which a constant infusion of the examined nonradioactive ligand is used with a bolus injection of tracer. Eight volunteers were examined twice, once without receptor blockade and once with a constant degree of partial blockade of the benzodiazepine receptors by infusion of nonradioactive flumazenil (Lanexat) or midazolam (Dormicum). Single photon emission computer tomography and blood sampling were performed intermittently for 6 h after bolus injection of [123I]iomazenil. The tracer in plasma was determined by high-pressure liquid chromatography and also by a simple octanol extraction procedure. The free concentration of flumazenil and midazolam in plasma water averaged 52% and 3.5% of that in whole plasma. The Kd values for the entire cortical rim for flumazenil were 7.4, 10.0, 10.3 and 17.7 nmol/l plasma water and, for midazolam, 73, 76, 58 and 30 nmol/l plasma water. The variation exceeds random methodological error and is probably due to interindividual differences in receptor affinity. The Kd level of midazolam is considerably higher than expected from the results of in vitro studies.

Adolescent↗
PubMed1993

[Ethical problems of the emergency room work].

We studied the incidence of ethical problems occurring in the emergency room of a large Danish provincial hospital. During a period of two months, 3620 unselected patients were treated, and in 190 (5.2%) of these cases the attending physician identified one or more ethical problems. The three most common problems identified were a. potentially suboptimal treatment due to communication difficulties, b. potentially suboptimal treatment due to a high work-load in the emergency room, and c. questions raised by patients who presented with minimal lesions not requiring any treatment. It is suggested that a reduction of the number of ethical problems encountered in the emergency room can be obtained by allocation of more resources, education of the staff, and education of the general public explaining the role of the emergency room.

Communication Barriers↗
PubMed1993

Electrical sensitization of the meso-limbic dopaminergic system in rats: a pathogenetic model for schizophrenia.

To study whether it was possible to modify mesolimbic dopaminergic activity by intermittent electrical stimulations (IES), 44 rats were either electrically stimulated or sham-stimulated in the ventral tegmental area (VTA) once daily for 70 days. This was done through chronically implanted intracranial electrodes. The intensity of electrical stimulation was determined by the lowest current that elicited a definite motor response. Stimulated rats demonstrated a significantly potentiated behavioral response after 70 stimulations. Seven months after IES rats still demonstrated an increased sensitivity to electrical stimulations in the VTA. A new stimulation period only resulted in a modest additional fall in threshold values. There was a highly significant difference between the current needed to provoke a given response in sensitized rats and in sham-stimulated rats. The behavioral response to stimulation was suppressed both by the dopamine (DA) D2 receptor antagonists haloperidol and raclopride and by the DA D1 receptor antagonist SCH 23390. Furthermore, stimulated rats showed an enhanced response to stimulation with amphetamine and to a lesser extent with apomorphine. Between stimulation periods sensitized animals demonstrated a reduced social interaction. In conclusion intermittent electrical stimulations of the VTA resulted in a syndrome characterized by a hypersensitive response to electrical and pharmacological DA provocation combined with abnormal social interaction. This animal model has points of resemblance with recent interpretations of the DA hypothesis for schizophrenia.

Amphetamine↗
PubMed1993

Double-level cauda equina compression: an experimental study with continuous monitoring of intraneural blood flow in the porcine cauda equina.

Compression of the spinal nerve roots may occur clinically at multiple levels at the same time; however, the basic pathophysiology of multi-level compression is largely unknown. In this study, the intraneural blood flow was analyzed continuously in the uncompressed segment between two compression balloons, with a pig used as an experimental model and a thermal diffusion method. At 10 mm Hg compression, there was a 64% reduction of total blood flow in the uncompressed segment compared with pre-compression values. Total ischemia occurred at pressures 10-20 mm Hg below the mean arterial blood pressure. After two-level compression at 200 mm Hg for 10 min, there was a gradual recovery of the intraneural blood flow towards the baseline. Recovery was less rapid and less complete after 2 h of compression. Double-level compression of the cauda equina can thus induce impairment of blood flow, not only at the compression sites, but also in the intermediate nerve segments located between two compression sites, even at very low pressures. These findings may have clinical importance in the understanding of the pathophysiology of multiple-level cauda equina compression.

Animals↗