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Biomedical subjects

R Vock

Publications and source records attributed to R Vock.

At least 19 recordsLinked to original sources

A post mortem study on neurochemical markers of dopaminergic, GABA-ergic and glutamatergic neurons in basal ganglia-thalamocortical circuits in Parkinson syndrome.

Functional models of the circuitry of the basal ganglia have recently been proposed to account for the vast spectrum of motor disorders associated with the loss of anatomical or neurochemical integrity within the basal ganglia. On the basis of these hypothetical models, hypokinetic disorders such as Parkinson's disease, are thought to be associated with excessive tonic and phasic inhibition of the output from the basal ganglia to the thalamus. In the present study we have attempted to determine the validity of the proposed model by measuring neurochemical markers of inhibitory and excitatory neurotransmission in post mortem human brain tissue. We have determined the concentrations of the excitatory neurotransmitters aspartate/glutamate and of the inhibitory neurotransmitter GABA in 18 relevant regions of the thalamocortical circuits of the basal ganglia of patients who had manifested Parkinsonian symptoms, and compared them with controls of individuals who had died without any history of neurological or psychiatric disorders and had no neuropathological abnormalities. Additionally, the receptor subtype for the excitatory amino acid N-methyl-D-aspartate (NMDA) was studied in the same brain tissue in which neurotransmitter concentrations had been analysed as neurochemical markers of post-synaptic excitatory neurotransmission. In patients who had manifested Parkinsonian symptoms, glutamate and aspartate levels were found to be unchanged in all examined brain regions. In contrast, the binding of [3H]MK-801, which identifies the NMDA receptor, was reduced in the head (-42%) and body (-38%) of the caudate nucleus. In parkinsonian patients, GABA levels were diminished by 36% in the centromedial thalamus, compared to control values. These results do not confirm the changes in neurotransmitter concentrations predicted according to the model, although we cannot rule out that the predicted changes might have been observed if the Parkinsonian group had been further subdivided into groups diagnosed on the basis of the patients' clinical picture (akinetic-rigid, tremor-dominant, equivalent type) and compared with the control group.

3,4-Dihydroxyphenylacetic Acid

Bordetella pertussis infections and sudden unexpected deaths in children.

UNLABELLED: From December 1990 to November 1993 nasopharyngeal specimens were obtained for culture from 50 children (mean 4.9 +/- 3.3 months of age) who had died suddenly. Bordetella pertussis was not isolated. Subsequently, nasopharyngeal specimens for polymerase chain reaction (PCR) analysis were obtained from another 51 victims of sudden death (mean 5.4 +/- 4.4 months of age); nine (18%) were B. pertussis positive. CONCLUSION: Our findings support previous epidemiological studies which noted an association between epidemic pertussis and sudden infant death syndrome. Further PCR studies with both internal and external controls should be performed.

Cell Culture Techniques

Design of the oxygen and substrate pathways. I. Model and strategy to test symmorphosis in a network structure.

This first paper in a series develops a model of structure-function relationships for the oxygen and substrate pathways of oxidative metabolism in working muscle. This will be used in the subsequent experimental papers in asking how biological structures are designed if they serve more than one function and whether one function can be served by more than one structural pathway. We have used the concept of symmorphosis to address this question; in its original form, it postulates that no more structure is built and maintained at each step in a pathway than is required to meet functional demands. The concept of symmorphosis was developed to deal with the problem of modelling the pathway for oxygen from the environment to mitochondria, essentially a single series of interconnected transfer steps. In the present context, the application of this concept is more complex. Both oxygen and substrates are transported directly from the blood to the mitochondria in what appear to be shared steps. The flows along this direct pathway are adjusted during muscular work. However, substrates have an additional option. They can be stored intracellularly as lipid droplets or glycogen, and thus their supply to mitochondria can occur in two steps separated in time: from capillaries to stores during rest, and from stores to mitochondria during work. The integrated pathways have a network structure and the functional flows are partitioned to different branches of the network, and we must ask whether the partitioning of fluxes is related to design constraints. The principle of symmorphosis predicts that the best use is made of the available options and that the design of each step is matched to the specific functional demand in view of a balance to be achieved over the entire network. This will be tested in subsequent papers by determining maximal flows for oxygen, carbohydrates and lipids through each of the transport steps and their respective structural capacities, comparing dogs and goats, animals of the same size whose maximal oxidative capacities differ by more than twofold. Finally, we will ask whether the principle of symmorphosis can be extended to apply to network systems.

Animals

Design of the oxygen and substrate pathways. III. Partitioning energy provision from carbohydrates.

This paper quantifies maximal fluxes through the pathway supplying carbohydrates to the mitochondria of muscle cells. Continuous infusions of D-[3-(3)H]glucose together with indirect calorimetry were used to investigate the partitioning of the supply of carbohydrates through the two branches of the pathway: from circulating glucose and from glycogen stores within the muscle cells to the mitochondria. The relative contribution of circulating glucose to total carbohydrate oxidation was small, accounting for only 13% and 23% of the carbohydrate oxidized at exercise intensities approaching MO2max in dogs and goats, respectively. Unexpectedly, maximal rates of circulating glucose oxidation were nearly the same in the two species (when expressed in absolute terms; dog:goat ratio = 1.2), despite the 2.2-fold difference in aerobic capacity. We conclude that the glycogen stores in the muscle cells are the major source of substrates at maximal rates of oxidation, supplying 60-70% of the total energy. Furthermore, it is this branch of the carbohydrate pathway that is adapted to the large difference in aerobic capacity between dogs and goats.

Animals

Design of the oxygen and substrate pathways. V. Structural basis of vascular substrate supply to muscle cells.

This paper quantifies the structural capacity of the transport steps for oxygen, glucose and fatty acids from the blood in capillaries to the cytosol of muscle cells and compares it with maximal rates of oxygen and substrate transport measured in the same animals and reported in the preceding papers of this series. Dogs have relatively more muscle per unit body mass than goats (37 versus 26%), but the maximal rate of oxidation per gram of muscle is still larger in the dog by a factor of 1.55. The maximal rates of substrate supply from the circulation are similar in both species. We predict that these differences in physiological parameters should be matched by proportional differences in structural capacity. We find that capillary volume and surface area are matched to maximal oxygen demand. The rate of vascular substrate supply is proportional neither to the capillary surface area nor to the length of intercellular junctions. The sarcolemmal surface area per gram of muscle is the same in both species. Using the physiological data presented in the companion papers of this series, we have calculated the maximal flux densities of circulatory glucose and fatty acids across the capillary wall and the sarcolemma. We find, for both substrates, that the flux densities across the sarcolemma reach a maximum at nearly the same level and at low exercise intensities in both species. In contrast, the flux densities across the capillary surface and the endothelial junctions are higher in goats than in dogs. We conclude that the capillaries are designed for O2 supply up to maximal rates of oxidation but not for the supply of the substrates (glucose and fatty acids) at the rates required at high exercise intensities. These are limited by the transport capacities of the sarcolemma.

Animals

Design of the oxygen and substrate pathways. VI. structural basis of intracellular substrate supply to mitochondria in muscle cells.

This paper quantifies the structures involved in the transport and oxidation of carbohydrates and fatty acids within the muscle cell. The structural capacity is measured on whole-body random samples of the musculature of dogs and pygmy goats and compared with maximal rates of oxygen consumption and substrate oxidation. Comparing dogs and goats of the same body size provided a 1.55-fold difference in the maximal rate of oxidation when related to muscle mass. As in previous studies, we found that the volume of mitochondria was approximately proportional to aerobic capacity. The maximal glucose flux from intracellular stores to mitochondria is 1.6 times greater in the dog than in the goat; we find that the amount of glycogen stored in the muscle cells is 4.2 times as great in the dog, but part of the intracellular glycogen pool is used for anaerobic rather than for oxidative metabolism. The maximal fatty acid flux from intracellular stores to mitochondria is 1.5 times larger in the dog, and the amount of lipid stored is 2.3 times as great in the dog. Every lipid droplet is in direct contact with the outer membrane of a mitochondrion and the contact surface area is 3.6 times greater in the dog than in the goat. Additional measurements are needed to investigate the role of structural limitation at this step. The amount of substrates stored intracellularly in the muscle cells of the dog is about twice as much as would match the differences in the maximal rates of utilization. This allows the endurance-specialized dogs to run for longer periods at higher rates of oxidation.

Animals

Design of the oxygen and substrate pathways. VII. Different structural limits for oxygen and substrate supply to muscle mitochondria.

This paper integrates the results of a series of studies on the supply of O2 and substrates for oxidative muscle metabolism and draws conclusions on the role of structural design in partitioning and limiting substrate supply. The studies compared dogs and goats exercising at different intensities and combined physiological, biochemical and morphometric investigations. In both species, the rate of fatty acid oxidation reached an upper limit at low exercise intensities, and only glucose consumption was increased at higher exercise intensities. The supply of both glucose and fatty acids from the capillaries reached maximal rates at low exercise intensities; this limitation is related to the design of the sarcolemma as calculations suggest that the endothelium introduces only a small resistance to substrate flux. From these findings, it appears that the capillaries are designed to satisfy O2 supply up to maximal O2 demand. The increase in substrate supply to the mitochondria at higher exercise intensities is achieved by drawing on intracellular stores of glycogen and lipids. The size of these stores is larger in dogs than in goats, providing the athletic species with twice the fuel reserves. These findings are interpreted on the basis of a network model with fluxes partitioned between direct and indirect pathways and with some structures shared by more than one function. Whereas O2 is supplied through a direct pathway, the supply of both substrates is split temporally to allow, during exercise, immediate fuel supply to the mitochondria from intracellular stores; these are replaced from the vasculature, during periods of rest, to a size commensurate with high rates of combustion. Considering this complexity, we conclude that the results are compatible with the principle of symmorphosis applied to a network structure and that the adjustment of design to functional demand involves different structures for O2 and for substrates.

Animals

(3H)dipyridamole and (3H)nitrobenzylthioinosine binding sites at the human parietal cortex and erythrocyte adenosine transporter: a comparison.

We compared the binding sites of the adenosine transport inhibitors (3H)dipyridamole (DPR) and (3H)nitrobenzylthioinosine (NBI) in human parietal cortex and erythrocytes. In comparison with guinea pig (3H)DPR marked only slightly more binding sites than (3H)NBI with a Bmax of 1080 +/- 29 and 780 +/- 7 fmol/mg protein respectively in parietal cortex and 24288 +/- 2725 and 20875 +/- 1905 fmol/mg protein respectively in erythrocytes. NBI displaced (3H)DPR binding completely from its binding sites at about KD/2 concentrations in parietal cortex as well as erythrocytes with inhibition constants comparable to its dissociation constants. Lineweaver-Burke analysis in erythrocytes indicated a competitive inhibition of (3H)DPR binding by NBI. Pharmacological characterization of (3H)DPR binding sites in human erythrocytes is consistent with their localization on adenosine transporters. These findings provide evidence that as opposed to guinea pig (3H)DPR and (3H)NBI largely label binding sites to the same adenosine transporter in human erythrocytes and parietal cortex.

Adenosine

Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity.

The pulmonary diffusing capacity is related to the quantitative design characteristics of the pulmonary gas exchanger. The current model for estimating DLO2 from morphometric data breaks the diffusion path for O2 into four steps, three of which represent the membrane part of DLO2. A critique of this model on the basis of newer evidence leads to a modification of the model where the path from the alveolar surface to the erythrocyte membrane is considered as a single step. The structural determinant of this model for DMO2 is the ratio of effective diffusion surface to effective total barrier thickness. The effective surface is formulated as a fraction of the alveolar surface area, the most robust measure of lung design, whereas the effective barrier thickness is the harmonic mean distance--or mean proximity--between alveolar surface and erythrocyte surface. The methods for obtaining the morphometric measurements are discussed. The results show that the new morphometric estimates of DMO2 are 33% lower than those obtained with the old model, resulting in a reduction of the estimates of DLO2 by 10-20%.

Animals

How to run a brain bank. A report from the Austro-German brain bank.

The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the concept and practice of our brain bank. Both brain tissue and information are handled by standardized procedures and flow in parallel from pathology to neuropathology and neurochemistry. Data concerning brain material are updated with clinical information gained by standardized procedures.

Austria

[Liver and splenic ruptures as a complication of heart pressure massage].

UNLABELLED: Injuries of the abdominal organs, especially liver and spleen, which were caused by resuscitative measures, can occasionally raise problems if an expert opinion on death is obtained particularly with regard to previous traumatization and if the question arises whether the trauma could have been avoided or not. These questions will be discussed from different points of view by means of ten cases. RESULT: Even when lege-artis-cardiac massage is made, the above mentioned complications cannot always be avoided. In none of the ten cases the trauma caused by resuscitative measures was the cause of concomitant cause of fatal outcome.

Adolescent

[Physical capacity following blunt thoracic trauma].

In order to extend the knowledge of possibility of action after blunt thoracic injuries 43 patients with largely isolated collar-bone fractures, rib and serial rib fractures as well as vertebral column fractures were questioned about their posttraumatic possibility of action. Essential result: In general, there is a close correlation between the acuteness of pain, the patient's judgment of severity of the injury and the extent of his ability to act during the first posttraumatic minutes. In the further course the ability to act was limited by the extent and the developmental speed of the hematothorax and/or pneumothorax, unless it was primarily limited or completely missing due to pain. Casualties having sustained collar-bone fractures were fully able to act except for a considerably diminished arm-swing. Patients with vertebral column fractures mostly remained lying at the place of accident for fear of a deterioration of the injury sustained and because of severe pain. The casualties' deliberate behavior was the predominant posttraumatic feature. In view of the various forms of rib and/or serial rib fractures with and without a hematothorax/pneumothorax there was a varying posttraumatic clinical picture ranging from freedom from pain to severe pain and non-restricted possibility of action to complete inability to act.

Arousal

[Performing ability after kidney contusions and kidney ruptures].

30 casualties who had sustained a kidney contusion (23 patients) or a kidney rupture (7 patients) were questioned about their posttraumatic possibility of action after their recovery. Essential result: Fundamental differences were detected between the two groups. The high degree of the ability to act for a longer period of time may be explained by the comparatively low acuteness of pain after kidney contusions and the impression of most casualties of not being seriously injured. In contrast to kidney contusions, kidney ruptures are generally accompanied by moderate to severe pain. Accordingly, the possibility of action in cases of kidney ruptures is restricted more frequently and to a greater extent than in cases of kidney contusions. The two groups had one thing in common: the casualties' mostly deliberate posttraumatic reaction; there were only 3 patients in a state of helplessness.

Arousal

[Performance following liver, spleen and intestinal ruptures].

In order to extend the knowledge about posttraumatic possibility of action after blunt abdominal traumas, 34 patients mostly having sustained isolated ruptures of the liver, spleen and the intestines, were interviewed after their recovery; the results obtained were separated by the organs involved. Essential result: In general, there is a close correlation between the acuteness of pain, the patient's assessment of severity of the injury and the degree of the ability to act during the first posttraumatic minutes. In the further course of the injury, the capacity to act was limited by the extent and the developmental speed of the loss of blood into the abdominal cavity, provided that it was not limited or cancelled primarily by the acuteness of pain. No correlation could be detected between the extent of rupture and the acuteness of pain. The casualties' thoughtful, deliberate behavior was the predominant posttraumatic characteristic. There was a varying posttraumatic clinical picture ranging from freedom from pain to severe pain and non-restricted possibility of action to the inability to act.

Arousal

[Statistics of blunt abdominal trauma in an autopsy sample at the Institute of Forensic Medicine of the Würzburg University].

The autopsy material of the Institute for Forensic Medicine of the University of Wuerzburg, comprising 2512 post-mortem examinations between 1981 and 1988, was statistically analyzed. Blunt abdominal traumas could be detected in 424 (= 17%) of the 2512 deceased. Essential results: In 3/4 of the cases a traffic accident was the harmful event, followed by occupational accidents and suicide. In 9 cases the blunt abdominal trauma was caused by resuscitative measures. 96.6% suffered from severe extraabdominal secondary injuries which, in 72% of the cases, occurred as craniocerebral traumas frequently determining the quoad vitam prognosis. In more than 90% death was caused by cranio-cerebral traumas, exsanguination, polytraumas as well as injuries of the cervical spine and the cervical spinal cord. Approx. 2/3 of the casualties died within 1 hour after having sustained the trauma. Only 31 injured persons did survive the harmful event more than 10 days; just 5 of them did not die before a period of more than 30 days. Late death was predominantly caused by secondary injuries adding up, peritonitis, pneumonia or pulmonary embolism.

Abdominal Injuries

[Alcohol drinking experiments with men over 60 years of age].

Alcohol drinking experiments (exposure: 0.68 g alcohol per kg body weight; type of drink: hard liquor and wine) was carried out in 20 men over 60 years old. The peak alcohol concentration, the course of the alcohol curve, co, r and beta 60 were compared with the results of drinking experiments with young persons published in the literature. No appreciable differences between the two age groups could be detected.

Aged

[Do elastic corpuscles appear prenatally? Histological studies of the skin of embryos and fetuses].

There have been descriptions of corpuscular structures in the human skin since the turn of the century. These bodies 3-20 micron in size are situated in the zone connecting the epidermis and corium. They can be readily visualized with resorcinol-fuchsin staining according to Weigert and are regarded as morphological variants of the elastic fiber system. According to the investigations we have carried out so far on the skin of babies, infants and adults, these elastic globes exhibit the following distribution pattern: abundant occurrence on the limbs, only scanty occurrence on the trunk and the hands. With increasing age, a numerical increase of elastic globes can be demonstrated in babies and in infants. In adults, there is an opposite tendency in the hands and feet. Here, the frequency of elastic globes decreases with increasing age. To clarify the question as to whether precursors of elastic globes are present, the skin of 35 embryos and fetuses was systematically examined for their occurrence and the results of the investigation are discussed.

Elastic Tissue

[Fatal poisonings with propoxur].

The insecticide propoxur (2-isopropoxyphenyl-N-methylcarbamate) acts by blocking cholinesterase. This inhibition is fast and, unlike that brought about by organophosphorus compounds, reversible. The toxicity of propoxur to man is stated to be low compared with that of parathion. Only a small number of fatal intoxications have been published; at the Würzburg University Institute of Legal Medicine eight cases have been observed since 1978. In seven cases death occurred after deliberate oral ingestion of solutions of propoxur with suicidal intent, while in the other, intoxication was accidental, following inhalation of an aerosol containing propoxur. Organs and body fluids were investigated toxicologically and histologically. The results are presented and discussed. Special attention is paid to the combination of propoxur and alcohol.

Adult