[The tomb monuments of the Dukes of Brabant (12th-14th century)]. Godfrey with the Beard, Count of Louvain, acquired in 1106 the title of "Duke of Lower-Lorraine", together with the possession of the large margraviate of Antwerp. Ever since 1188, the title: "Duke of Brabant" became usual and the name "Brabant" stood for the whole of the Duke's territories. Duke John I completed the expansion-policy of his predecessors by annexing the Duchy of Limburg after the battle of Woeringen (1288). In 1430, Brabant was merged into the large Burgundian Duchy of Philip the Good. The tombs of the Dukes of Brabant were not concentrated in one dynastic necropolis, but located as well in abbeys (Affligem and Villers-la-Ville) as in churches belonging to cloisters or chapters, in Louvain and Brussels, the two towns successively used as the ducal residence. The Dukes were always buried in the most privileged part of the church, namely, the choir. Their remembrance was perpetuated by the building of a mausoleum on which the lying image of the decreased ("le gisant") was chiselled. Most mausolea did not escape damaging or even complete destruction. The following mausolea are reviewed: The tomb of Henry I (1235) in the St.-Peter's church at Louvain; it is erected in dark blue limestone from Tournai and was at first decorated with gilt. The tomb of Mathilde of Boulogne and Mary of Brabant (ca. 1260) in the St.-Peter's church at Louvain, also in dark blue limestone from Tournai, and at first, polychrome. The tomb of Henry II (1248) in the abbeychurch of Villers-la-Ville, nowadays disappeared. The tomb of Godfrey I (1139), in the abbeychurch of Affligem, probably built at the end of the 13th century and nowadays disappeared. Recently the "Service des Fouilles" of the Brussels University has been excavating on the site of the former Franciscan church in Brussels and discovered the foundations of the burial vault of John I.


[Identification of the first Duchess of Brabant. Anatomo-historical study]. After World War I, the St. Peter's church at Louvain had to be restored. When the floor of the choir was broken up, a vaulted tomb house, containing a heap of bones, was discovered. The study of the historical past of the church building was committed to Leo Van der Essen, Professor of History at the Louvain university, while Charles Nelis, Professor of Anatomy at the same university, was charged to identify, as far as possible, the discovered bones. Prof. Nelis succeeded in rebuilding three skeletons with bones that fitted together. He chiefly discovered on these skeletons a number of osteological variants, which in fact are known as being very rare; but their frequent existence on the three skeletons and their absence on the other bones, pointed towards an hereditary factor and the kinship of the three persons. By combining Prof. Van der Essen's historical data with his own heredomorphological findings, Prof. Nelis identified in the year 1930 the Dukes of Brabant from the twelfth and the thirteenth centuries, namely Godfrey II, Godfrey III and Henry I (father, son and grandson). With the help of the medical historian Dr. Tricot-Royer, Prof. Nelis extended his investigation to other members of the dukes' family, namely Saint Albert, Prince-bishop of Liège and brother of Henry I, whose shrine was preserved in Mechlin, and Henry II, son of Henry I, whose tomb was located in the ruins of the abbey of Villers-la-Ville. By measuring and digging in the gardens of the Affligem-abbey, according to historical documents, Dr. Tricot-Royer could find the graves and the skeletons of the first Duke Godfrey I with the Beard, of his daughter Queen Alice and of Godfrey of Gaesbeeck, brother of Henry II. Thanks to the unusual frequency of the same hereditary traits, the kinship with the first three skeletons was established and the historical indications could be confirmed by the anatomical science. The heredo-morphological pioneer research of Prof. Nelis on eight personages from five generations of the same family is unique.


[Revision of the Kaufman Assessment Battery for Children for German speaking regions. Part 2: Areas of application and criteria of reliability]. Adaptation, structure and standardization of the German version of the K-ABC, a test of intelligence and achievement in children comprising 16 subtests, were discussed in the first part of this article. Part 2 deals with aspects of test administration intended to make the procedure simple, objective and appealing to children. Also discussed are possibilities for internal and external comparison of test scores, approaches to interpretation and ideas for remedial measures that are an integrated feature of the K-ABC concept. Assessment of numerous psychometric properties of the K-ABC demonstrated the reliability and validity of this test.


[Prevalence and follow-up of psychiatric disorders in childhood and adolescence. Results of a prospective epidemiologic longitudinal study from ages 8-18 years]. In a prospective longitudinal epidemiological study with assessments at age 8, 13 and 18 the prevalence rate for psychiatric disorders remained constant at about 16%. The sex ratio for severe disorders was male dominated even in adolescence, which was a consequence of the high rate of unsocialized disturbances of conduct in boys. Persistence of psychiatric disorders between age 13 and 18 was about 50%, as had previously been the case between age 8 and 13. One child in four suffered from a psychiatric disorder for at least 10 years. In childhood, conduct disorders had a very poor prognosis and emotional disorders a very good one. In adolescence, the course of disorders depended on an interaction between diagnosis and gender. Boys with unsocialized disturbances and girls with emotional problems had a poor prognosis.


[Illness concepts of children. Validation of a modified locus of control test in illness and health]. We investigated the health and illness concepts of 53 healthy children aged 8 to 14 years using a modified illness and health locus of control scale (KKG, Lohaus and Schmitt, 1989) with the scales internal, external-p (powerful others) and external-c (chance). A comparison of the results with those on self-esteem (FSK 4-6), anxiety (CMAS-R) and hopelessness (HSC) scales showed a decrease in externality, but not an increase in internality, with increasing age and a correlation between self-confidence and a more internal locus of control. The influence of children's health locus of control on treatment compliance is discussed.


[Long-term course of dyslexia beyond the school years: catamnesis from pediatric psychiatric ambulatory care]. In our follow-up study 12 years after index admission we were able to examine 59 out of 115 male patients who had been diagnosed in our department as dyslexic (mean age: 10.1 years). Spelling skills at follow-up were more than one standard deviation below the norm for the subjects' age (T-value on the RT of only 24). About half of our patients had participated in a specific spelling remediation program lasting more than 6 months, but at follow-up no effect of therapy could be demonstrated. The patients with the higher IQs regressed in spelling less than those with the lower IQs. We assume that the effects of remediation programs do not survive therapy and school for long because later on good spelling is no longer either required or encouraged. Our patients were severely impaired in their school career: Although their average IQ was 112 only 6 out of 59 had completed a college-preparatory program (Abitur), all of them from middle-class families with well-educated parents. Our patients chose occupations corresponding to the type of high school diploma they had, often those requiring practical skills rather than reading or spelling skills. Patients who had completed no more than the nine obligatory years at school were less content with their work than expected. Emotional disorders during the past 6 months were no more frequent than expected. In a self-report about delinquency there was no difference compared to a random sample.


Skin disease and malignancy. An epidemiological study. The aim of this work was to develop a computer program (CANEST) to estimate the risk of cancer in patient populations and to use this program to investigate cancer risk associated with several dermatological disorders. Patients seen at the dermatology departments at the Karolinska Hospital and South Hospital were used for the study of chronic urticaria, condylomata acuminata, basal cell carcinoma, lichen planus and positive patch tests. The national Swedish In-Patient Register was used to find all patients hospitalized for dermatomyositis or polymyositis since 1964. From eleven large dermatological centers in Sweden, details of close to 5,000 PUVA-treated patients were obtained for study. The computer program CANEST was developed and used to calculate the expected number of malignant tumors in these patient populations, based on incidence data from the Swedish Cancer Register for the years 1958-1987. By matching the patients' records with the Cancer Register the actual number of cancers was obtained. Of 1,155 patients with chronic urticaria, a malignancy was diagnosed in 36, while the expected number was 41: clearly there is therefore no association between chronic urticaria and malignancy. In 3,260 patients with condylomata acuminata there was no increased risk of cancer in situ of the cervix (relative risk = 1.5; 95% confidence interval 0.9 to 2.5) and the number of genitourinary cancers in males was almost three times higher than expected (2.6; 1.2 to 5.0). These results indicate that the risk of developing cervical carcinoma in situ is less than previously thought, but the implications of the increase in genitourinary tumors in males are uncertain. Patients with basal cell carcinoma had an increased risk of malignancy in general. Melanoma risk was seven times greater in males (6.6; 3.0 to 12.5) after the basal cell carcinoma diagnosis. Risks of squamous cell carcinoma of the skin, lung cancer, thyroid cancer and cancer of the uterine cervix were also increased. No increased risk of cutaneous malignancy was found in 2,071 patients with lichen planus, but for oral cancer it was six times greater in males (5.9; 2.5 to 11.4). A slight general increase in malignancy risk was found in 2,183 males (1.3; 1.1 to 1.5) with positive patch tests, but not in 3,675 females. When individual sites were analyzed, cancers of the lung, larynx, uterine cervix and prostate were significantly increased. The implications of this are uncertain, but might indicate a common failure of the immune system which might predispose for both conditions, or be a marker of certain occupational exposure.(ABSTRACT TRUNCATED AT 400 WORDS)


[Digestive lesions related to N.S.A.I.D. (epidemiology and prevention)]. The frequency of gastrointestinal ulcers and ulcers complications induced by non steroidal anti inflammatory drugs (NSAID) increases continuously. This is a major health problem, since 1.5% of general population (mostly elderly people) take regularly NSAID'S. NSAID'S gastropathy is asymptomatic in nearly 50% of cases, even in case of big gastric ulcer. A severe hemorrhage or a gastric perforation can occurred in the absence of previous symptoms. When the patient had epigastric symptoms during a treatment with NSAID'S, upper GI endoscopy is normal in 50% of cases. NSAID'S are ulcerogenic by decreasing the capacity of the gastric mucosa to produce prostaglandin (PG) and by weakening gastric mucosal barrier. H2 blockers are not effective to prevent such lesions. Elderly women, are at high risk of gastric mucosal lesions and complications. In a prospective study, it was shown that misoprostol was effective to reduce the rate of NSAID'S induced gastric and duodenal ulcers. Up to date, epidemiologic studies don't show any population group at no risk of NSAID'S induced gastric lesions. The actual problem, now, is to determine which groups of patients are at high risk of complication in order to clarify the indications of preventive treatment. Today, in France, it's believed that old patients, with organic pathology (respiratory, cardiac, hepatic or urinary) and/or using two or more NSAID'S are at high risk.


Beta-endorphin-immunoreactive cells in the human fetal pancreas. This investigation has been carried out on 50 samples of fetal pancreata from the 10th to the 32nd week of gestation using the PAP technique. beta-Endorphin-reactive cells were morphometrically recorded by means of the point-counting method. beta-Endorphin reactivity occurred for the first time during the 15th week. During further development, beta-endorphin cells were found inside and outside the islets. From the 18th to 23rd week, these cells were primarily localized in the islet periphery. From the 24th week, they rearranged and occurred in irregular positions mixed with other islet cells. This rearrangement took place with a 4 week delay compared with the basic cell types of the islet organ. The extrainsular portion of these cells in the exocrine parenchyma varied between 0.3% in the 27th week and up to 10% in the 22nd week. Concerning the adult human pancreas, it has been suggested whether beta-endorphin cells may be a 6th basic cell type of the islet organ. Previous studies on the coexistence of somatostatin, glucagon and beta-endorphin in the same islet cell and the morphometric analysis would support this assumption. Biochemical examinations indicate that beta-endorphin is a modulator of insulin, glucagon, and somatostatin secretion in the islet organ. This is supported by the fact that beta-endorphin cells have extended cell bodies which is typical of cells with paracrine function.


Recent progress in cholera vaccination.

Recent progress in cholera vaccination. Cholera disease remains an important cause of morbidity and mortality in the third world. The parenteral cholera vaccine actually used offers only a 50% protection during 6 months. As Vibrio cholerae and its toxin don't cross the gut wall, the aim of new vaccines is to prevent the colonization and growth of the vibrio in the jejuno-ileum and to inhibit the fixation of cholera toxin (CT) on its enterocyte membrane receptor. This can be afforded by stimulation of the gut local immune system mainly represented by secretory IgA antibodies (Abs). New vaccines should comprise both bacterial and CT antigens and must be given by the oral route to induce the production of specific secretory IgA Abs in the gut. Four different ways are actually under study to produce an oral cholera vaccine. 1. Combination of CT-B subunit and killed vibrios. 2. Live recombinant Vibrio cholerae in which the CT coding gene has been deleted. 3. Synthetic peptides reproducing some immunodominant CT-epitopes. 4. Manipulation of the idiotypic network to induce the production of Abs mimicking CT-epitopes. This paper reviews the actual developments and advantages of these four approaches.


Light and electron microscopic studies of lectin binding to the glycocalyx of rat pancreatic cells. II. Light microscopic changes after induction of an olive-oil pancreatitis. Using a battery of 7 horseradish peroxidase marked lectins (WGA, RCA I, PHA, LCA, PNA, UEA I, LPA) or 2 unmarked lectins (Con A, VAA I) and HRP-marked antibodies, the binding to acinar cells with a postembedding technique on semithin sections of rat pancreatic tissue after olive-oil pancreatitis was studied light microscopically. The lectin binding of the normal healthy rat pancreatic tissue (Jonas et al. 1991) changed remarkably. Whereas the apical glycocalyx of acinar cells with the strong binding of WGA, RCA I, and PHA remained unchanged within the first 10 min of damage, the basolateral cell surface lost the typical specific binding of UEA I within the initial phase of pancreatitis just 2 min after injection of olive-oil. Con A and VAA I were found to be very reactive with the necrotic cells 60 min after administration of oil. The results were discussed in relation to the possible functions of the 2 main domains of the pancreatic acinar cell glycocalyx.


[Oxygen metabolism and toxicity in the phenomenon of ischemia-reperfusion]. One of the major cause of human disease results from the compromise of blood flow and oxygen delivery to tissues. Ischemia phenomenon is defined as blood flow that is inadequate to maintain normal tissue function. Prolonged ischemia ultimately results in irreversible changes in cell metabolism and cell death. Historically, it was felt that if ischemia results in altered cell function and injury, then reoxygenation or reperfusion leading to a restoration of a normal blood flow was expected to have a beneficial effect and promote salvage of tissue depending on the extent of ischemia. Recent studies have, however, revealed that reoxygenation leads to an oxygen metabolism resulting in the generation of active and toxic oxygen intermediates (free radicals) which play an important role in the pathophysiology of reperfusion injury.


Histochemical characterization of carbohydrate residues during the morphogenesis of gastrointestinal and respiratory systems of Caretta caretta. The distribution of carbohydrates in the gastrointestinal and respiratory tract of Caretta caretta during embryogenesis and postnatal development was investigated by histological and histochemical techniques and using fluorescein-labelled lectins. The results indicate that the compartmentalised expression of glycoconjugates found in the juvenile Caretta caretta is acquired during development. The occurrence of neutral carbohydrates in cells and extracellular matrix was dependent on the developmental stage of the animal. In general, periodic acid Schiff positive glycoconjugates of the respiratory tract occurred at an earlier stage of development than those from the gastrointestinal system. The lectin binding pattern of both organ systems revealed a more refined pattern of the types of carbohydrates present during development. Wheat germ agglutinin showed the broadest binding pattern, whereas Soy bean agglutinin and phythaemagglutinin were more limited in their binding to tissue structures. The terminal carbohydrates detected in the gastrointestinal and respiratory tract of Caretta caretta were similar to those observed in mammals; this finding emphasises the suitability of Caretta caretta as a model system for amniote development.


Immune mechanisms in alcoholic liver disease. This paper reviews the potential role of immune factors in alcoholic liver diseases. They can either be involved in liver damage and hepatocyte's neurons or in the development of liver fibrosis, or in the sequellae of the disease. Cytokines, as mediators of the relationships between circulating monocytes, Kupffer cells, sinusoidal cells, Ito cells and hepatocytes, seem to play a crucial role in the development of the disease. Studies are now ongoing which try to identify the alcohol-related cofactor which triggers immune activation and the development of liver damage.


Localization of proteins immunologically related to erythrocyte protein 4.1, spectrin and ankyrin in thyroid gland. Analogues of erythrocyte protein 4.1, spectrin and ankyrin were examined in the thyroid gland of pig and rat by immunohistochemical techniques. Analysis with immunofluorescence microscopy revealed that the peripheral cytoplasm and apical-lateral plasma membrane of follicle epithelial cells of thyroid glands were stained with antibodies against erythrocyte protein 4.1, spectrin, or ankyrin. The results indicate that membrane skeletal protein lattice might exist in thyroid follicle epithelial cells.


Comparison of three histochemical methods for assaying lactate dehydrogenase in liver. The mean activity of lactate dehydrogenase (LDH) in hepatocytes near the central vein region of unfixed sections of mouse liver was determined and compared with 3 different histochemical methods: conventional method, polyvinyl alcohol (PVA) method, and gel film method. An image analysis system was used for measuring the enzyme activity in single hepatocytes. The mean activities were approximately 1.4 and 2.7 times higher with the PVA and a gel film techniques respectively than with conventional aqueous media. The highest activity of LDH was obtained with gel media; this can be explained by the lowest diffusion late of this soluble cytoplasmic enzyme from the secretion into the medium. In the conventional technique, the apparent activity was found to be about 16% lower when sections were incubated vertically in a large volume of medium than when they were incubated horizontally in a small volume of medium.


Nucleolar organizer regions in acute and chronic leukaemias. A silver staining technique for nucleolar organizer regions (NORs) has been applied to bone marrow biopsies of various types of acute and chronic leukaemias. This method could be easily evaluated on resin-embedded bone marrow obtained from acute lymphocytic leukaemia (n = 12), acute myelogenous (n = 16), chronic lymphocytic (n = 16) and chronic granulocytic (n = 20) leukaemia. A significant difference (p < or = 0.1) was only found between the AgNOR numbers in nuclei of lymphocytes from acute and chronic leukaemia (mean of 1.23 to 1.40 and 1.58) and those of cells from acute and chronic myelogenous leukaemia (from a mean of 5.00 to 9.17 per nucleus). However, no significant difference was observed among cells of various types of acute and chronic myelogenous leukaemias, despite of their markedly higher staining intensity and proliferative activity. The greatest mean of AgNOR numbers was counted in monoblasts of acute myelomonocytic leukaemia. It is suggested, that higher AgNOR counts in nuclei of more malignant leukaemic cells are in parallel with their mitotic activity and could be related to their elevated cell turn-over.


Effect of flumecinol (Zixoryn) on the cytochrome P450 and cytochrome P448 dependent hepatic microsomal monooxygenase activities in male rats. The effect of three-day oral administration of 50 mg/kg bw. and 100 mg/kg bw. flumecinol (Zixoryn, Gedeon Richter Chemical Works Ltd., Budapest, Hungary) and intraperitoneal administration of 50 mg/kg bw. phenobarbital as well as the single intraperitoneal administration of 20 mg/kg bw. 3-methylcholanthrene on various cytochrome P450 and P448 dependent hepatic microsomal enzyme activities was studied in male albino Wistar rats. 50 mg/kg bw. flumecinol had no significant effect. 100 mg/kg bw. flumecinol had an inducing effect comparable to the one of phenobarbital. The activity of the cytochrome P448 dependent 7-ethoxyresorufin O-deethylase was enhanced by all three substances, but flumecinol's effect was by far behind that of 3-methylcholanthrene, so the carcinogenic promoter effect of flumecinol can be questioned.


Possible role of bile deficiency in the development of intestinal syndrome of acute radiation disease. Experimentally induced bile deficiency significantly accelerates the development of acute gastrointestinal syndrome in the irradiated rat. The usual 11 days of survival is reduced to 5 days. In view of the experimental results it seems justifiable to conclude that endotoxins play an important role in the development of this syndrome.


Newly identified steady-state potassium channels in rat hippocampal neurons. We report two new types of potassium channels in cultured hippocampal neurons of rat. Both channels occurred in the soma membrane of these cells at very low density. They were active in steady-state conditions, within a wide voltage range that included the resting membrane potential. Their open probability was enhanced by membrane depolarization, but not influenced by Ca ions. In symmetrical 150 mM KCl the channels showed a slope conductance of ca. 40 and 80 pS, respectively. Current-voltage relations of both K channels show a negative slope at high positive voltages.


Impact of single neonatal allylestrenol treatment on the estrus cycle of rats treated with FSH+LH or TSH. Neonatal allylestrenol treatment administered to female rats significantly increases the duration of estrus phase in the sexual cycle. Treatment with follicle stimulating hormone (FSH) + luteinizing hormone (LH) in adulthood prolongs the duration of estrus even on its own; the effect, however, is more pronounced in those animals who were treated (imprinted) with allylestrenol neonatally. When administered to the control animals, the chemically related thyreotrop hormone (TSH) is either indifferent or it even decreases the estrus index. In animals having received neonatal allylestrenol treatment, however, TSH administration increases significantly the duration of the estrus phase. Either with or without FSH+LH treatment, the ratio of estrogenic to gestagenic phase increases following neonatal allylestrenol treatment. The experiments call attention to the potential functional risks inherent in neonatal allylestrenol treatment. The actual risks, however, seem to be smaller than the effects seen at the receptor level.


Hemodynamic observations following orthotopic cardiac transplantation: hemodynamic responses to upright exercise at 1 year. Central hemodynamic responses during upright exercise were studied at 1 year in 40 orthotopic cardiac transplant recipients. Hemodynamic responses were characterized by slow rise in heart rate and blunted peak exercise heart rate response, a significant early increase in stroke index followed by a plateau phase, and a steady increase in ventricular filling pressures and pulmonary artery pressure. In spite of exclusive utilization of the Frank-Starling mechanism to augment cardiac output during early exercise, the pressure responses were comparable to those reported in normal subjects. Our observations also indicate that similarly to normal subjects, the heart rate response plays an important role in the cardiac output achieved at maximum exercise. Although patients with younger donor hearts achieved a more favorable maximum heart rate, the other hemodynamic parameters showed no correlation with the donor heart age. Thus, no hemodynamic disadvantage of older donor hearts could be demonstrated. These data provide further enlightenment regarding the mechanisms of the well-preserved functional capacity noted in these patients.


Hemodynamic observations following orthotopic cardiac transplantation: evolution of rest hemodynamics in the first year. The evolution of resting hemodynamics was studied at 1 week and 1 year in 40 patients following orthotopic cardiac transplantation. Abnormal hemodynamics after transplantation, characterized by elevated ventricular filling pressures (indicating diastolic dysfunction) and also by pulmonary hypertension, showed normalization by 1 year. In the absence of innervation, the resting heart rate of heart transplant recipients should theoretically be close to the intrinsic heart rate predicted by the age of the donor heart. In this study, a high incidence of relative sinus bradycardia (an indicator of sinus node dysfunction) was noted in the first post-operative week, although again there was a tendency to normalization by 1 year. These beneficial changes help to explain the dramatic and sustained improvement in the functional capacity of these patients late after transplantation.


Impact of combined hormonal pretreatment (insulin+TSH) on the imprinting of hormones administered in combination to Chinese hamster ovary cell culture. Cultured Chinese hamster ovary (CHO) cells were treated (imprinted) with insulin and with thyrotropin (TSH) related to gonadotropins (FSH+LH). When one week later the treatment was repeated with one of the hormones, considerable differences could be observed in the binding capacity of the cells. In the hormone combination TSH was able to evoke persistent imprinting only to a markedly lesser degree than insulin, meanwhile the imprintatory effect of insulin was of greater extent even on the cell regarded to be unspecific for insulin. Hormone treatment of one hour duration--when investigated immediately after--did not extinct the binding capacity to TSH but enhanced that to insulin. With the deterioration of the conditions of culturing, the enhanced binding capacity disappeared.


Histochemical study on adrenal delta 5-3 beta-hydroxysteroid dehydrogenase activity in cadmium treated toad (Bufo melanostictus). Effect of a single subcutaneous injection of cadmium chloride at the dose of 0.5 mg/toad on adrenal delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) was observed after 7 days. The activity of delta 5-3 beta-HSD was measured histochemically. The experiments indicate that cadmium chloride resulted in a significant decrease in the activity of adrenal delta 5-3 beta-HSD in toad during breeding season (June-July).


Immunoglobulin-G and creatinine levels in rabbits in altitude adaptation. The changes of immunoglobulin-G and creatinine levels in mid-altitude were investigated in rabbits. The animals living at sea level were exposed to 2240 m altitude for 22 days period. When compared with sea level values; immunoglobulin-G levels were significantly low. Serum creatinine level decreased significantly in the 2nd day, then reached the sea level amount on the 12th day. On the 22nd day a significant increase was observed. It was concluded that the decrease in immunoglobulin-G values may be due to the depression of protein synthesis. The increase in plasma creatinine level would be explained by the decrease in urine.


Morphometric and time lapse analyses of rapid-onset neurites stimulated by cycloheximide in NG108-15 cells. We previously reported that the laminin-induced outgrowth of neurites in the first 4 hr after plating ('rapid-onset neurites') is markedly stimulated by inhibitors of protein and RNA synthesis, including cycloheximide, puromycin and actinomycin D. Our original interpretation of this finding was that inhibiting protein synthesis led to metabolic changes in the cell which converged upon the intracellular pathway used by laminin to stimulate neurite formation. Alternatively, Preston et al. (1987, Proc. natn. Acad. Sci. U.S.A. 84, 5247-5251) suggested that cycloheximide acts by inhibiting neurite retraction. In order to resolve these conflicting interpretations, we decided to re-examine the effects of cycloheximide using time lapse analyses of NG108-15 cells grown on laminin, together with morphometric analyses of cultures fixed at 1.5 or 3 hr after plating. Cycloheximide was found to cause both an increase in neurite initiation within the first 1.5 hr after plating, and a decrease in the occurrence of neurite retractions between 1 and 3 hr. Investigators should be aware of the effects of biosynthetic inhibitors on neurite growth, since these agents are employed widely in studies of cultured neural cells, particularly those involving receptor metabolism and phenotypic differentiation.


NCAM as a differentiation marker of postmigratory immature neurons in the developing human nervous system. The regional distribution and cellular localization of the neural cell adhesion molecule were investigated in the developing nervous system of human embryos and fetuses, by using immunocytochemistry with antibodies against the human neural cell adhesion molecule. Embryos and fetuses with crown-rump lengths ranging from 15 to 80 mm (corresponding approximately to 6-12 ovulation weeks) were examined. In the telencephalon, immunoreactivity was found in the primordial plexiform layer and in the early cortical plate. During later stages, immunoreactivity was present in the marginal zone, cortical plate, developing subplate zone and radiations of the internal capsule. In the mesencephalon and rhombencephalon, neuronal perikarya were outlined and strong staining was present in fiber bundles. In the spinal cord, strong immunostaining was present in fiber tracts and in dorsal and ventral roots. Immunostaining outlined perikarya of dorsal and ventral gray columns; the neuropil of the developing gray matter was also stained. Contrary to findings in some other species, precursor cells in the proliferating zones, i.e. all cells of ventricular zones and the external granular layer in the proliferation were not stained. Reactivity, however, was also observed in single mature-looking nerve cell bodies and their processes, which were localized in proliferating zones. All peripheral nervous structures including nerve fibers and peripheral nervous tissue components derived from the neural crest (i.e. sensory and autonomic ganglia) expressed the neural cell adhesion molecule. At the cellular level staining always appeared to be associated with the entire cell membrane of a given neuron including its outgrowing processes. Immunocytochemical staining for neural cell adhesion molecule is an excellent method for the identification of single nerve fibers, nerves and nerve cell bodies in situ in the developing peripheral and early central nervous system. The neural cell adhesion molecule is suggested as a marker of postmigratory immature neurons in the developing human nervous system.


Expression in murine and human neuroblastoma cell lines of VGF, a tissue specific protein. Screening by different means has demonstrated the presence, in human and murine neuroblastoma cell lines, of VGF, a gene product identified in a limited number of neuronal and endocrine cells. Indirect immunofluorescence and Western and Northern blot analyses have shown the presence of this protein in some of the tested lines, confirming that VGF is not an ubiquitous molecule. Further studies, using human SK-N-BE and murine N18TG2 lines, showed that VGF expression is upregulated during differentiation, suggesting that various species, including man, express VGF and regulate it in a similar manner. The subcellular localization of the protein, which is associated with vesicles, its electrophoretic molecular profile and its specific release under different conditions are all consistent with results reported in other cells. Neuroblastomas are thus added to the class of VGF-positive cells and provide a new in vitro model for investigation of the structural and functional properties of this protein.


Neuronal sprouting and synapse formation in response to injury in the mouse organ of Corti in culture. The effect of mechanical injury on induction of regenerative phenomena within the neurosensory epithelium was investigated in cultures of neonatal mouse cochlea. The oldest examined culture in which new neuronal growth followed insult, was injured at 13 days in vitro and fixed 24 h later. By far, the most vigorous regenerative reaction was observed in a 3-day culture 4 h post-injury. The reaction included sprouting of nerve fibers injured directly, synapse formation between the surviving hair cells and sprouting neuronal growth cones, wrapping of growing nerve fibers by extending processes of hair cell cytoplasm, and collateral sprouting of synaptically-engaged nerve endings and of nerve fibers in passage.


[Personality disorders in patients with panic disorder]. The relationship between personality disorders and panic disorder in adults is analyzed in this study. The patients included in this work presented anxiety disorder with agoraphobia and were compared with a group of normal controls. The percentage of patients with personality disorder was 46% significantly higher than those encountered in the control group (16%). The existence of these disorders do not seem to modify the severity of panic disorder.


[Profile of psychiatric and psychosomatic symptoms in medical students]. In this paper the features, pattern profile and frequency of psychiatric and psychosomatic symptomatology of a sample constituted by 40 medical students during the usual academical period--free fron examination--are analyzed. Results suggest that there are no significant differences between the symptomatic patterns of the students of our sample and those belonging to the general population in our context. The Possible role played by stress associated to "examination" in reaching a high level of psychopathology in these students is discussed.


[The influence of personality on suicidal behavior]. With the purpose of studying the influence of personality on suicidal behavior, 63 female suicide attempters were assessed by means of standardized interviews, Eysenck's personality questionnaire (EPQ-R) and other psychometric scales. Personality disorders (DMS III-R) were found in almost 70 per 100 and associated with previous attempts, higher hopelessness, suicide ideation, and to a more severe attempt. The most relevant dimensions were psychoticism and extraversion. The first one correlated to repetition, hopelessness, and suicide ideation; the second exerted a moderating effect, showing association with feelings of conformity towards survival. Neuroticism showed a rather unspecific effect on studied factors. Results confirm a relationship between personality disorders and suicidal behavior, and suggest possible mediating variables.


[Validity of the Spanish version of the Diagnostic Interview Schedule. Third revision (DIS-III-R)]. After a brief description of the Diagnostic Interview Schedule, versión III, spanish, we studied the agreement between diagnoses by a clinical standard and diagnoses by the DIS. As clinical standard we used the lifetime diagnoses given by expert psychiatrists to 135 patients who had been longitudinally assessed, with follow up periods amounting to 14 years. Sensitivities, for the fourteen diagnostic categories, varied between 64 per 100 and 100 per 100. Specificity was above 93 per 100 for all diagnoses, and K values ranged from .50 to 1.00, surpassing .60 for eleven of the fourteen categories.


Photothrombosis in rabbit brain cortex: follow up by continuous pO2 measurement. Continuous recording of changes in local pO2 during and after brain infarction in surviving animals which can be followed for months or years, may provide interesting information concerning pathophysiology and treatment of stroke and thrombosis. We performed such measurements before, during and till 4 weeks after photochemical induction of a cerebrocortical infarction in three rabbits. Rose bengal--a photosensitive dye which sticks to endothelial cells and gives rise to endothelial damage and thrombosis when illuminated--was injected intravenously. After injection, a circular area (diameter 3 mm) of the brain cortex was illuminated using an optic fiber conducting light from a halogen lamp, whether or not filtered by heat and colour filters. In order to enable pO2 measurement in and near the infarct zone, we constructed a transparent plastic frame in which pO2 electrodes were fixed beneath and 1 mm besides a shaft permitting mounting of the optic fiber. A black adhesive ring (inner diameter 3 mm) was attached to the bottom of the frame providing a perfectly demarcated illumination area. After fixation the electrodes were calibrated and the frame was implanted in the rabbit's skull. Ten days later an infarction was induced; pO2 was monitored continuously before, during and till 4 hours after this induction. Furthermore, pO2 was recorded 24 hours, 48 hours, 5 days, 14 days and 4 weeks after infarction. Parameters describing the time course of pO2 were determined. In the illuminated area pO2 decreased after a certain latency time to reach a very low level, probably zero level, where it remained for at least 24 hours. Gradually, recovery was observed during the following days, and four weeks after infarction both level and pattern of electrode current appeared to be normal again. In the border zone pO2 decreased but did not reach zero level. Recovery was observed earlier than in the illuminated area.


[Brief psychotherapy in clinical medicine patients]. The criteria that "illness is biographical crisis od the individual" and that the only medicine is "personal medicine" is stressed. Clinical medicine, which covers medicine in its entirety, demands conceptual and doctrinal reaffirmations so that gradually the patient can come to be dealt with as a human being fron a holistic point of view, which commences with his complaint and consultation, continues with the interview and semiology, to finish with the diagnosis and therapy which, although in some cases it may be surgical, is still medical and integral. All the steps mentioned are bio-socio-cultural thus, whether in the practice of general clinical medicine or in the most specialized and technologically sophisticated clinical medicine, the animist component is not lacking and demands a minimum degree of "psychosomatic" Knowledge. The use of a psychotherapeutic technique is proposed which, while based on the psychoanalysis theory, is distanced technically from it as a "psychotherapy on limited time and goals", which abbreviates the disease, and is projected not as the "focus" of therapeutic work, but as a re-evaluation of the "life style" of each individual, and tends to help to develop a "project for life" suited to the possible personal, familiar and social well-being of the "patient". Technically speaking, this modality of brief psychotherapy is based on the nonuse of transferential interpretations, on impeding the regression od the patient, on facilitating a cognitice-affective development of his conflicts and thus obtain an internal object mutation which allows the transformation of the "past" into true history, and the "present" into vital perspectives. This technique is within reach of every health professional.


Intravitreal and intraretinal oxygen tension in the rat eye. We have successfully measured the intravitreal and intraretinal oxygen distribution in normal rats, during both normoxia and hyperoxia. The feasibility of such measurements in the very small rat eye has opened up the opportunity for the use of the many rat models of vascular disease in physiological experiments of retinal oxygen supply and consumption.


[Psychopathologic manifestations in the sphere of subjectivity: disorders of self]. As much as it strives to be "scientific" psychiatry can not obviate its necessary bonds to the subjectivity of the subject. The attempt has been made to reflect the richness of manifestation of subjectivity by means of a formalization process based on the traditional concept of it. This has led to the concept of disorders of self (Ichstörungen). They are of central importance in clinical psychiatry and psychopathology, as can be seen in the attempts to conceptualize schizophrenia. However, the presumed degree of precisión reached runs parallel to the apartness of the fidelity to the effective vivification of the patient. This discord is interpreted as a fault in the conceptualization of the disorders of self and the possibilities originates by corporality point to the need to redefine, once again and in depth, the concept of subjectivity which is the foundation of psychiatry.


[Psychophysiologic and psychopathologic aspects associated with sexual dysfunction]. The authors review the relations between anxiety and sexual dysfunctions in base of studies that, in general, suggest the anxiety is common among subjects with sexual dysfunctions, but the level and the nature of the anxiety could vary much in the interindividual pattern. It revises experimental and clinical works that describe the anxiety provides the sexual arousal, studying the neurophysiological and neurochemical substratum which compares anxiety and sexual responses. It discusses the presence of psychopathology associated with sexual dysfunction.


Experimentally measured optical pathlengths for the adult head, calf and forearm and the head of the newborn infant as a function of inter optode spacing. The Differential Pathlength Factor (DPF) has been measured for several different tissues. The results showed that the DPF varied with the type of tissue studied, and in the case of the adult calf with sex. However, the DPF for all tissues studied was constant once the inter optode spacing exceeded 2.5 cm. Thus, measurements can be made by NIR spectroscopy at a range of inter optode spacings, and a single DPF used in the calculation of chromophore concentration. The results also showed that the major source of error in the DPF lay in the measurement of the inter optode spacing. To improve accuracy, two options are possible. Firstly, some means of continuous measurement of inter optode spacing could be incorporated in the NIR instrumentation. The better alternative would be an instrument incorporating a method of directly measuring the optical pathlength at each wavelength. This could be done either by time of flight measurement, or if it can be validated, by phase shift measurement.


Near-infrared imaging in vivo (I): Image restoration technique applicable to the NIR projection images. To enhance spatial resolution of NIR projection images in vivo, we performed refocusing of NIR projection images of human forearm of about 50 mm thickness. A volunteer's forearm was illuminated by parallel light beam-flux, and then projection images at 750 nm was measured with a Pertier-cooled CCD video camera and digitized. For refocusing computation, PSF of the light transmitted through the tissue was calculated by general equation proposed by van der Zee and Delpy (1988). Simple inverse, constrained least squares, and Wiener filters were tested as refocusing algorithms. Wiener filter gave the best result in terms of image quality and computation time. By applying Wiener filter to the image refocusing of NIR projection images of human forearm, we obtained enhanced spatial resolution.


Muscle oxygenation by fast near infrared spectrophotometry (NIRS) in ischemic forearm. Fast scanning near infrared spectroscopy (680-1050nm) was utilized to evaluate human forearm muscle oxygenation in 15 adults volunteers. Spectra were recorded in hypoxic hypoxia, ischemia and venous outflow restriction. Derivative spectra were performed with the aim to obtain a quantitative information of Hb/Mb oxygen saturation free from volume and scattering changes. The absorption spectra O.D. demonstrate an increase of deoxy-Hb/Mb in hypoxic condition with a moderate volume changes. In ischemia a rapid Hb/Mb desaturation occurred until a plateau was reached at 4th min. The cuff release was followed by hyperemia with Hb volume raise and oxy-Hb/Mb increase above the control. Spectral data support the hypothesis that derivative NIRS can be used to identify muscle oxygenation changes.


Near-infrared imaging in vivo (II): 2-Dimensional visualization of tissue oxygenation state. By measuring NIR projection images at 700 and 800 nm, we examined 2-dimensional visualization of Hb oxygenation state in the human forearm of about 50 mm thickness. Equations for selective quantification of oxy-Hb, deoxy-Hb, and SO2 were derived from in vitro experiment, and validity of the equations were checked by using a test phantom which simulates optical properties of living tissues. Forearm occlusion caused increase in 2-dimensional O.D. image at 700 nm, while slight decrease was observed in the image at 800 nm. These results were consistent with changes in NIR spectra caused by the forearm occlusion and explained by Hb deoxygenation and slight decrease in blood volume. Although several uncertain errors seemed to remain in our results, we obtained an essentially reasonable image which demonstrates 2-dimensional changes in Hb oxygenation in the human forearm caused by forearm ischemia.


Monitoring of the oxygen pressure in the blood of live animals using the oxygen dependent quenching of phosphorescence. Oxygen dependent quenching of phosphorescence is a powerful new method for measuring oxygen pressure in biological systems (see Vanderkooi et al, J. Biol. Chem. 262 (1987) 5476; Wilson et al, J. Biol. Chem. 263 (1988) 2712). This technology has now been extended to include measurements of the phosphorescent of oxygen probes dissolved in the blood as a complex with albumin. In this communication, we report on a new microcomputer controlled phosphorimeter in which the tissue is illuminated by a flash lamp and the phosphorescence observed through flexible light guides designed to make measurements in regions down to approximately 1 mm in diameter. Measurements of the phosphorescence lifetimes of these probes in regions of tissue necessarily report a distribution of oxygen pressures due to the presence of blood in veins and arteriols as well as that present in the capillaries. Thus the phosphorescence decay is the sum of a continuum of exponentials with different decay constants and initial intensities. The complete phosphorescence decay curve is digitized using a 12 bit, 1 MHz A/D board and deconvoluted using numerical methods to yield a distribution of exponentials contributing to the total decay curve.


On-line oxygen uptake measurement (VO2): a computer feed-back controlled rebreathing circuit for long term oxygen uptake registration. A totally closed feed back controlled anesthesia- and ventilation circuit has been developed feasible to be applied for artificial ventilation with tidal volumes as low as 5 ml at a rate of up to 60/min and for spontaneous ventilation with on-line measurement of physiological lung parameters (pressure, volume, flow). Oxygen inflow is regulated via actual-set value comparison, oxygen inflow is measured and recorded on-line (= oxygen uptake by the connected subject). On-line oxygen uptake (consumption) measurement furnishes a valuable, so far not available parameter to monitor changes in the oxygen transport chain to the tissue and to register physiological oxygen consumption values and derangement of metabolism. First results show that total body oxygen consumption of man in rest is lower than so far expected in the high weight and body surface area groups and that oxygen consumption is decreasing with length and age. Metabolic derangements such as in developing hyperthermia crisis are noticed in a very early stage when therapy is still possible before severe damage has occurred.


Interaction of blood flow, diffusive transport and cell metabolism in isovolemic anemia. 1) High blood flow can compensate for half-normal hematocrit, leaving the rate at which O2 is offered to the capillaries unchanged. Nevertheless, intracellular PO2 is lower in anemia, indicating impaired diffusive transport. 2) Anemia increases O2 flux per red cell and decreases functional capillary surface area. These changes increase flux density and the extracellular component of resistance to diffusive O2 transport, in accord with current theory (Federspiel and Popel, 1986; Groebe, 1990; Hellums, 1977). 3) Maintenance of diffusive flux in presence of anemia required a larger delta PO2 between Hb and Mb, and higher intracellular O2 conductance brought about by greater Mb-facilitated diffusion. Both compensations depend on lower PmbO2. 4) PmbO2 and creatine charge fall with increasing VO2 and ATP demand. These responses, as well as adaptive changes in redox help maintain VO2 in the presence of a lower O2 drive on electron transport. 5) Greater engagement of reserves of both transport and metabolism limits the range of aerobic performance in anemia. 6) The match between the transcapillary and mitochondrial O2 fluxes depends on interaction of transport and metabolism as a system.


Microtopographic analysis of oxidative stress in organ microcirculatory units. Current approaches for visualization of oxidative stress in organ microcirculatory units were summarized. Recent development of digital imaging photonic microscopy has made it possible to analyze spatial and temporal alterations of oxyradical generation during tissue injury. Luminol-dependent photonic imagery revealed granulocyte-mediated oxidative stress during microvascular damages, suggesting that the interface between venular endothelium and sticking granulocytes may be the most critical site of oxidative stress. Fluorographic analysis assisted by dichlorofluorescin (DCFH) diacetate is a powerful tool to visualize intracellular hydroperoxide formation. This method demonstrated intralobular heterogeneity of oxidative stress in the isolated perfused hepatic microcirculatory units exposed to either CCl4 or low-flow hypoxia. CCl4 caused the activation of dichlorofluorescein (DCF) predominantly in perivenular areas, while the 25% low-flow perfusion induced periportal or midzonal DCF activation. Refinement of the present technique will provide further insight into the microtopographic correlation between oxidative stress and tissue breakdown in microcirculation.


Estimation of the oxygen gradient across phospholipid bilayers of mitochondria from reperfused rabbit hearts after ischemia. Mitochondria isolated from myocardium exposed to 30 minute ischemia followed by 30 minute reperfusion showed an increase in membrane viscosity and a decrease in wobbling angle of phospholipids, compared with those from the normally perfused myocardium in anesthetized open-chest rabbits. The values for the membrane viscosity were used to estimate the oxygen gradient across the lipid bilayers of mitochondrial membranes with a model of cylindrical diffusion. The effective diffusion coefficient for oxygen, DO2, was approximated to be 6.5 and 6.3 x 10(-5) cm2/sec in the control and ischemic-reperfused area, respectively, by comparing reported DO2 values with values for membrane viscosity. For the surface area of the inner mitochondrial membrane including cristae and for the oxygen consumption rate of the myocardium, reported values for rats and cats, respectively, were employed. Using these values, oxygen gradients across the lipid bilayers of mitochondrial lipid membranes were estimated to be only 0.055 and 0.057 nM in the control and 30 minute ischemic-reperfused myocardium, respectively. If the mitochondrial membranes are hydrated because of the ischemia-reperfusion, the absorption coefficient of the membrane to oxygen will decrease and the oxygen gradient will be increased. In the present study, however, the fluorescence life time of DPH, the hydrophobic fluorophore, showed no shortening despite the ischemia-reperfusion. Hence, no indication of membrane hydration was obtained.


The oxygen dependence of mitochondrial oxidative phosphorylation and its role in regulation of coronary blood flow. The oxygen dependence of mitochondrial oxidative phosphorylation measured in isolated cells of cardiac and non-cardiac origin are affected by the metabolic state of the cells. The contribution of oxygen diffusion to the measured P50 value in resting cells is small. In cardiac myocytes, and possibly in the other cells as well, this contribution may become significant near maximal levels of respiration. The influence of cellular energy metabolism on the oxygen dependence of respiration in cardiac myocytes suggests strongly that mitochondrial oxidative phosphorylation in these cells is an oxygen sensor for adjusting coronary vascular tone during normal cardiac function.


Oxygen penetration in and release from lung surfactant. The kinetics of oxygen penetration from the air into an oxygen free human BAL/saline and of its release from the oxygenated BAL/saline into a nitrogen environment was studied. Time-dependent oxygen concentration at constant temperature was monitored by recording the direct polarographic current of the second reduction wave of oxygen at a dropping mercury electrode. The obtained kinetic curves showed that not only uptake and release were quicker in BAL than in saline but also the corresponding equilibrium values were higher. Release and uptake curves in BAL were markedly different. The release was faster than the uptake but its maximal value was about 30% under the maximal uptake level. We suggest that the differences in oxygen uptake and release kinetics might contribute to explain the previously found accumulation of oxygen in BAL. The positive difference between the release and uptake kinetics at the beginning of the curves is consistent with a steady oxygen penetration through the BAL. The difference in the maximal oxygen uptake level and the maximal release level indicates a partial retention of the oxygen in the system.


Improvement of pulmonary gas exchange after surfactant replacement in rats with Pneumocystis carinii pneumonia. The effect of intratracheal surfactant instillation on pulmonary function in rats with pneumocystis carinii pneumonia (PCP) was investigated. In these animals which developed PCP with severe respiratory failure after s.c. administration of cortisone acetate over 8-12 weeks, pulmonary function could be improved by surfactant instillation, as measured by an increase in PaO2. Histological examination showed that alveoli of rats with PCP which received no surfactant treatment are filled with foamy edema, whereas after surfactant treatment alveoli are stabilized and well-aerated. These results indicate that surfactant therapy could be used in patients with severe PCP to overcome an acute stage of respiratory distress while at the same time surfactant could serve as a carrier substance for antimicrobial drugs to attain high intra-alveolar and low systemic antimicrobial drug concentrations.


Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids. To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a significant rise in arterial PO2 from 84 to 99 Torr. The findings are highly compatible with the idea that HPV is distinctly attenuated in diseases areas induced by oleic acid probably due to a local accumulation of vasodilator prostanoids. Inhibiting prostanoid biosynthesis may selectively enhance the vascular reactivity to O2 in shunt vessels and may redistribute the perfusion from shunt to relatively normal areas, thereby improving gas exchange at alveolar region without altering the total amount of extravascular lung water.


Modeling of oxygen transport to skeletal muscle: blood flow distribution, shunt, and diffusion. By injection of embolizing microspheres, by local radioactive xenon clearance and by inert gas washout in resting and stimulated gastrocnemius dog preparation, experimental evidence for unequal blood flow distribution and for shunt flow has been provided. Model calculations show that in some respect unequal blood flow and shunt produce effects predicted for a homogeneous model with diffusion limitation of O2 supply. This finding must be taken into account when the role of diffusion limitation to O2 supply is to be ascertained.


The role of wall shear stress in microvascular network adaptation. The possible role of wall shear stress in microvascular network adaptation was investigated by computer simulation in planar polygonal model networks. Adaptation of vessel diameter to local wall shear stress resulted in false geometry and excessive rarefaction of the networks. Adaptation to mean wall shear stress decreased the range of shear stress, decreased the total power dissipation, and prevented network rarefaction. A measure of mean wall shear stress may serve as a control signal for the adaptation of vessel diameter to blood flow in microvascular networks.


Estimation of respiratory mechanics in dogs with acute lung injury. In mechanically ventilated anesthetized dogs with acute lung injury induced by intravenous infusion of oleic acid (OA), changes in airflow, lung volume, and tracheal (Pao), transpulmonary (Ptp) pressures were measured. Changes in lung mechanics were studied before and after OA infusion at intervals, during an observation period lasting 4-5 hours, by using the interrupter technique and identification technique, and by measuring the pressure-volume (PV) characteristics. The main results are listed as follows: (1) compliance and FRC showed a marked decrease, Pao and Ptp showed a marked increase within 2 hours after OA. (2) airflow resistance estimated by the identification technique showed a marked increase after OA. (3) static PV characteristics of both the lungs and total respiratory system showed similar changes 4 hours after OA, characterized by the presence of an inflexion on the inflation limb, increased hysteresis and a rightward and downward shift of the loop. (4) the trend of changes of dynamic PV characteristics obtained by changing the PEEP value in a stepwise manner, with the ventilation uninterrupted, was similar to that of the static PV curve. It is suggested that an on-line identification technique with one-compartment model to track the slow changes in combination with serial measurements of the dynamic PV characteristics of the total respiratory system would be more appropriate for monitoring lung mechanics of ventilated patients with ARDS.


Effect of hyperventilation on oxygenation of the brain cortex of neonates. A new phosphorescence imaging method (Rumsey et al, Science (1988) 1649) has been used to continuously monitor the oxygen pressure in the blood of the cerebral cortex of newborn pigs. The animals' blood pressure was continuously measured and PaCO2, PaO2 and arterial blood pH were measured periodically. The oxygen pressure in the blood was quantitatively determined for regions of about 100 um square within the image (from a total field of about 3 mm diameter). It was observed that during hyperventilation, which lowered PaCO2 and increased pH of the blood, oxygen pressure decreased in proportion to the decrease in PaCO2. For example, hyperventilation which decreased PaCO2 from its normal value of 40 Torr to 10 Torr caused a rapid (within 5 minutes) decrease in oxygen pressure in the blood of capillaries and veins to approximately 1/4 of normal.


Hypoxia and the "reaction theory" of central respiratory chemosensitivity. In peripherally chemodenervated and vagotomized cats and rabbits, either spontaneously breathing or artificially ventilated, we studied the reaction of the respiratory control system to changes in the extracellular fluid (ECF) pH at the ventral surface of the medulla oblongata. The brainstem ECF-pH was varied either by alternating periods of hypoxia and hyperoxia or by intravenous infusion of lactic acid to achieve endogenous or exogenous lactacidosis, respectively. Additionally, the arterial PCO2 was changed by varying the inspiratory CO2-fraction or the respirator's pumping rate. When pulmonary ventilation or central respiratory drive (in terms of phrenic nerve activity) was related to brainstem ECF-pH, no unique function resulted for respiratory (CO2-induced) and metabolic (lactic acid induced) acid-base changes, thus contradicting the "reaction theory" for central respiratory chemosensitivity. Under steady state conditions, there was no ventilatory reaction to endogenous or exogenous metabolic brainstem acidosis at all. However, the apneic threshold was shifted towards the acid range, although the sensitivity of the respiratory system to CO2 remained nearly unchanged, no matter whether CO2 was inhaled or increased by acetazolamide. This points to a dominating role of CO2 or at least carbonic acid over fixed acids for the central chemosensitive control of pulmonary ventilation.


Oxygenation of mammary tumors: from isotransplanted rodent tumors to primary malignancies in patients. As a result of a compromised and anisotropic microcirculation, isotransplanted mammary tumors in mice exhibit hypoxic and anoxic tissue areas which are heterogeneously distributed within the tumor mass. Similarly, in poorly perfused human breast cancer xenografts, hypoxia develops at early growth stages and expands with tumor growth. In contrast, breast cancer xenografts with high perfusion rates exhibit an oxygenation status comparable to that of most normal organs. There is clear experimental evidence that the efficiency of tumor blood flow in isotransplanted tumors and in xenografted human breast cancers is the principal modulator of tissue oxygenation. The pO2 distribution found in primary lesions in patients ranged from the pO2 histograms obtained in "low-flow" isotransplants and xenografts to those measured in "high-flow" breast cancer xenografts or normal tissues. From our extended and systematic clinical studies there is clear indication that the oxygenation status of human breast cancers in situ does not correlate with the clinical stage and/or histological grade of an individual tumor.


Measurements of tumor blood flow using intraperitoneal deuterium and 2H-NMR spectroscopy. Using i.p. delivered deuterated water, and 2H NMR spectroscopy, it is possible to non-invasively, serially, and quantitatively measure blood flow through tissue volumes as small as 0.05 ml. Measurements made with this technique show that changes in total tumor blood flow reflect local changes measured superficially by laser Doppler flowmetry, and that tumors of identical histology and size have heterogeneous blood flow rates. Finally, we have shown that tumors growing in an irradiated normal tissue have a lower blood flow rate which is manifest when tumors grow beyond 0.1 ml.


Apparent heterogeneity between leukemic lymphocyte cell lines. 31P-NMR and polarographic techniques were used to investigate glycolytic versus aerobic oxidative activity in normal and leukemic lymphocytes, and to investigate possible heterogeneity in these parameters between two leukemic cell lines. Molt 3 cells showed a 10-fold higher rate of glutamine-dependent respiration than Molt 4 cells, and an increased level of glutamine-uptake. Molt 3 demonstrated a high intracellular buffering capacity, manifested by constant pHi after addition of glucose, while the same treatment applied to Molt 4 cells induced a change in internal pH of up to 1.23 pH units. This data raises the possibility of heterogeneity of leukemic lymphocytes within the patient from whom the isolation was conducted, or of gross metabolic adaptation by the cell lines in culture.


Whole body and regional O2 uptake/delivery and lactate flux in endotoxic dogs. We infused endotoxin into anesthetized dogs while maintaining cardiac output. Whole body O2 uptake and arterial lactate concentration were measured at the same time with regional O2 uptake and lactate fluxes in muscle and gut. Even though whole body O2 uptake increased, so did arterial lactate levels. The different behavior of organ systems was marked by the fact that muscle took up lactate while its O2 uptake didn't change whereas gut produced lactate as it decreased its O2 uptake. Comparison with critical levels of O2 delivery and O2 extraction ratio for whole body and the two regions opened considerable doubt that generalized and significant hypoxia explained the rise in arterial lactate. Addition of mild hypoxic hypoxia also neither caused O2 uptake to fall nor lactate to rise which reinforced our conclusion that there was little or no tissue hypoxia in endotoxin treated animals given adequate resuscitation with red blood cells and colloid solutions.


Resuscitation fluids and oxygen transport in haemorrhagic shock. This study examined the cardiovascular and oxygen transport/consumption relationships in haemorrhagic shock and resuscitation using Human Albumin and Gelatin solutions in a porcine haemorrhagic shock model. Immature pigs (17-25 kg) were anaesthetised and ventilated with nitrous oxide, oxygen and isoflurane. Aortic pressure monitoring and monitoring of pulmonary pressures and cardiac output via a Swan-Ganz catheter were instituted. A controlled haemorrhage of 40% of blood volume at 1% blood volume per minute was followed 30 minutes later by resuscitation with 60% of blood volume of 4.5% Human Albumin (Immuno) or 4% Modified Fluid Gelatin (Gelofusine). Haemorrhage caused marked decreases in (CI), mean arterial pressure and oxygen delivery (DO2). Oxygen consumption (V02) remained unchanged. Resuscitation with Albumin and Gelatin raised CI to values 60% to 70% above control though only Albumin restored DO2. Deterioration was more rapid in the Gelatin group due to the estimated half a life of 3 hours in this model. Oxygen extraction was 10% higher in the Gelatin group 2 hours after resuscitation. The role of oxygen radicals in haemorrhagic shock is discussed.


Changes in tissue histology associated with adaptation and acclimation to hypoxia. Newborn kittens are adapted to hypoxia by having an oxygen department respiration rate. In part, this is due to the structure of the liver which results in a great reduction of oxygen consumption in this organ in response to hypoxia. Older animals possess an oxygen independent respiration rate which is not lost when they acclimate to hypoxia. Instead, there are histological changes which permit the liver to consume oxygen at the same rate as before by facilitating intracellular oxygen transport.


Impact of ischemia on tissue oxygenation and wound healing: improvement by vasoactive medication. The influence of vasoactive medication on tissue oxygenation and wound healing was investigated in the ear model of the hairless mouse. Ischemia was induced to the ears by ligating 2 of the 3 main vessel bundels and verified by measurements of tcpO2. Reduced tissue oxygenation was followed by a prolongation of the time required for complete healing of standardized wounds. Treatment with the vasoactive drug Buflomedil (3 mg/kg/day iv.) resulted in enhanced recovery of the tissue from reduced oxygenation and likewise reversed the adverse effects of ischemia on wound healing. These results warrant the use of the drug in patients suffering from delayed wound healing due to peripheral arterial disease.


PAF-acether induced arterial thrombosis and the effect of specific antagonists. Platelet-vessel wall interactions and local thrombosis are investigated in vivo in a branch of the mesenteric artery of the guinea pig, using optoelectronic registration and ultrastructural control. Following an electrical challenge resulting in changes of cell membrane polarization, subsequent superfusion by PAF-acether or a stable analogue, (1-O-alkyl-2-N-methylcarbamyl-sn-glycero-3-phosphocholine, 10(-8) M focal concentration (f.c.)) for a restricted period results in endothelial cell retraction and bleb formation followed by platelet adhesion and the development of a thrombus which over time becomes invaded by leukocytes and eventually occludes the vascular lumen. It was demonstrated in a previous investigation that these phenomena are triggered by the generation of endogenous PAF-acether by the endothelial cells. Specific PAF-acether-antagonists, such as BN 52021 a ginkgolide, but also synthetic molecules, derivatives of the triazolo-pyridino-diazepine group (BN 50727, BN 50755 and BN 50789), significantly inhibit platelet-vessel wall interactions and thrombosis, but not the formation of blebs in the endothelial cells. Hydrogen peroxide (10(-5)M f.c.) not only primes the effect of PAF-acether, but is by itself capable of inducing thrombosis through a PAF-acether-mediated mechanism. Inhibition of acetyl hydrolase by PMSF (phenyl-methyl-sulfonyl-fluoride, 10(-5)M f.c.) invariably results in a significant enhancement of thrombosis, while conversely, inhibition of acetyl transferase by 27584 RP (4-(naphtylvinyl)pyridine hydrochloride, 10(-6)M f.c.) inhibits thromboformation indicating that the remodeling pathway is involved.


Transcutaneous measurements of skin O2 supply and blood gases. The data of the O2 exchange through the surface of the skin show that a part of the normal upper skin can be supplied with O2 from the surrounding atmosphere. This may be important in pathological situations although probably simultaneous disturbances of the substrate supply may be more serious. The noninvasive continuous registration of skin surface pO2 (and pCO2) allows to monitor skin oxygen supply under different conditions. The new optical sensing of pssO2 and of the local O2 flux into the skin opens up new promising possibilities for quantification of the skin oxygen supply.


Relating measuring signals from PO2 electrodes to tissue PO2: a theoretical study. Organ surface PO2 measurement by oxygen sensitive electrodes has proved to be an efficient tool for monitoring changes in tissue oxygenation status. A parameter giving more direct information is the PO2 distribution within tissue cells which, however, can only be assessed by more invasive methods. The present study addresses the problem of relating electrode measured surface PO2 to muscle cell PO2. To that end, the magnitude of tissue volumes the PO2 in which electrodes are sensitive to, has been reassessed. It turned out that the measuring signal of current membrane covered PO2 electrodes is only sensitive to the PO2 within the muscle surface and not any deeper, thus rendering the measured PO2 an area weighted average over the surface PO2 rather than a spatial average. The consequences of this finding are illustrated in an example of a maximally working muscle. Under the assumption that there are capillaries located on the muscle surface or immediately beneath it, the PO2 predicted to be measured by a surface electrode is almost four times the average muscle fiber PO2. However, PO2 values actually measured by surface PO2 electrodes are even higher calling for further explanation, in which superficial blood vessels and surface fascia may play an important role. Quantitative information on vascular morphology near muscle surfaces is needed in order to more definitely determine the importance of mechanisms discussed, for experimental results.


A new catheter for quasi-continuous measurement of arterial partial oxygen pressure. Recently a catheter has been developed based on amperometric measurement principle for in vivo monitoring of PaO2. A study in pigs was performed to compare the cell with a standard method for measuring PaO2. The results show that the cell is capable to accurately measure PaO2.


Continuous intra-arterial PO2 monitoring during thoracic surgery. Intermittent blood gas sampling has several disadvantages, the most important being that samples are usually taken at set intervals, or when changes in oxygenation are suspected--when it is too late. Another problem is inaccuracy caused by careless blood sample handling. Continuous intravascular PaO2 monitoring eliminates these problems. This study shows that the Continucath sensor is an easy-to-use and reliable monitor, with specific early warning capabilities for hypoxia, thereby improving anesthetic and intensive care management. Its characteristics are: a stabilization period of 10 minutes, a 90% response time of 90 seconds, temperature dependence of 4% per degree celsius, a flow dependence of less than 1% if the flow is more than 5 cm/sec, a drift of less than 0.7% per hour, a correlation coefficient of 0.92 when compared to blood gas analysis during surgery.


Construction, calibration and evaluation of pO2 electrodes for chronical implantation in the rabbit brain cortex. Aiming at continuous polarographic measurement of the mean pO2 in the rabbit brain cortex before, during and after photochemically induced infarction, we designed and constructed monopolar platinum oxygen electrodes of the open type for chronical implantation. The measuring tip (length 1 mm, diameter 0.1 mm) is covered with a homogenous membrane of cellulose acetate. The electrode currents are measured by a four-channel amplifier of proper design; the device permits accurate and stable polarisation, identical for each channel. Moreover, a calibration device has been constructed. It consists of a Buchner funnel filled with Ringer solution and mounted in a temperature-controlled bath. In order to create a specific partial pressure of oxygen in the calibration chamber, predetermined gasmixtures are bubbled through the solution using computer controlled mass flow regulators. The calibration device thus permits the determination of primary and secondary electrode parameters, i.e. linearity, oxygen sensitivity and residual current, and polarisation dependency, temperature dependency, sensitivity to CO2, electrode stability, dynamic behaviour and oxygen consumption. Three groups, each of them containing ten electrodes, have been tested with regard to electrode parameters: the first group contains bare electrodes, the second and the third group contain membrane covered electrodes, with a membrane thickness of 10 and 20 microns respectively. In order to evaluate acute and long-term effects of implantation on the brain cortical tissue and on the sensors' measuring qualities, electrodes have been implanted for different time periods (51 days, 30 days, 9 days, 5 min). pO2 was recorded regularly and polarograms have been registered. The effects on cortical tissue have been studied with the aid of light microscopy.


Skeletal muscle PO2 in anaerobic soft tissue infections during hyperbaric oxygen therapy. In the present study skeletal muscle PO2 measurements were performed in patients with gas gangrene and anaerobic soft tissue infections before, during and after hyperbaric oxygen therapy. Polarographic PO2 needle electrodes appeared to be suitable for application during different ambient pressures. We found that patients with gas gangrene revealed higher skeletal muscle PO2 values than patients with an anaerobic soft tissue infection. This may be explained by a higher metabolic rate within the anaerobically infected soft tissues. The higher PO2 values in gas gangrene may be caused by alpha toxins, affecting cellular and intracellular membranes thus destroying PO2 diffusion barriers.


Effect of hyperbaric oxygen treatment and perfluorochemical administration on glutathione status of the lung. Exposure to hyperoxia, especially under hyperbaric conditions, causes an enhanced oxidative stress particularly in lung tissue. To test the potential hazardous effect of either a single or repeated hyperbaric oxygen treatment (HBO) on the cellular defence system the glutathione status of lung tissue from rats exposed to HBO was investigated. When daily exposed to 2.5 ATA of > 95% O2 for 90 min over 8 or 14 days the content of reduced glutathione in lung tissue (GSH) increased by 16-19%. Oxidized glutathione (GSSG) tended to increase after 8 days and was 56% higher after 14 days. While the GSSG/GSH ratio was unchanged after 8 days, it increased by 39% after 14 days. Thus, the GSH increase after 8 days can be understood as a adaptive process to protect the lung from oxidative stress. The distinct increment of the cellular GSSG that lead to an increase of the GSSG/GSH ratio after 14 days reflects a situation, in which the cellular defence system is overwhelmed by oxidative stress. The additional pretreatment with perfluorochemicals in a dose of 2g/kg every second day aggravated the observed changes (GSH +39-19%, GSSG +118%). In a second experiment rats were exposed to a single session with 7 ATA of O2 for 60 min. GSH in the lungs increased for 40%, it was not elevated by PFC. However, GSSG increased to a much higher degree in untreated as well as in PFC-treated animals (+240%, +163%), elevating the ratio GSSG/GSH markedly (+145%, +176%). Allopurinol given as radical scavenger in a dose of 50 mg/kg was able to suppress the increased oxidative stress widely. Thus adaptive and overloading processes are involved under the treatment with increased oxygen pressures. As the administration of PFC aggravates the observed changes, a still increased blood oxygen offer must be considered as the causative agent. A radical scavenger is capable to suppress the increased oxidative stress widely.


Computerized histographic oxygen tension measurements of murine tumors. As further work on tumor oxygenation results in the development of agents capable of modulating hypoxic cell radiosensitivity, and chemotherapeutic agents capable of targeting hypoxic cells, knowledge of relative tumor oxygenation takes on greater importance. The pO2 Histograph was used to characterize the oxygen tension of a murine sarcoma (RIF1) and a murine carcinoma (SCCVII), each with different hypoxic fractions. These tumors were studied sequentially to assess the suitability of the Histograph both as a research tool and, ultimately, as a clinical monitor of tumor hypoxia.


Oxygen dependent quenching of phosphorescence: a perspective. Oxygen quenches phosphorescence by energy transfer from the phosphor when oxygen molecules collide with molecules of the phosphor in the excited triplet state. Thus increasing oxygen pressure causes an increase in the rate of decay of phosphorescence (shorter lifetimes) and a decrease in total phosphorescence intensity. Phosphors have been selected which decay with a single exponential and for which the relationship between phosphorescence lifetime and oxygen pressure is quantitatively described by the Stern-Volmer equation. The use of phosphorescence lifetime as the measure of oxygen pressure makes the method insensitive to the absorbance changes of other chromophores in the system. This method has permitted quantitative, rapid (less than 10 msec) and sensitive (to less than 10(-8) Torr) measurements of oxygen pressure in suspensions of cells or subcellular organelles. In tissues, oxygen pressure has been evaluated by measuring phosphorescence using an intensified CCD camera. Maps of oxygen pressure in the vasculature of the cortex of the brain and of other tissues demonstrate the method is limited only by the optics of the system and resolutions of a few microns are readily attained.


Quantitation of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry. Photon migration in highly scattering tissues such as muscle and brain gives optical pathlengths that are dependent upon absorption and scattering parameters, mu a, mu s'. Determination of these parameters gives the correct concentration of principal absorber such as hemoglobin in the red region of the spectrum. Determinations of scatter factor in functioning and pathological tissues are made.


Non-invasive, on-line measurement of oxygen consumption during anesthesia. Oxygen consumption is usually derived from values measured by a thermodilution catheter, i.e. an invasive procedure, with associated risks and calculation errors. Closed circuit ventilation provides a reliable, non-invasive means of access to this parameter of metabolism. Routine application of closed circuit ventilation requires overcoming many, mainly technical, difficulties (e.g. leakage problems, valve malfunctions, and calculations of gas uptake). We developed a computerized closed circuit anesthesia ventilator without these problems. With this system non-invasively measured oxygen uptake is continuously presented on-line. We discuss three representative patients presenting for surgical repair of an abdominal aneurysm. Besides actual changes in metabolism and depth of anesthesia, success or failure of the operation is visible in the pre- and direct post-clamping period. With resuscitative therapeutic interventions, increase in oxygen consumption gives valuable information under changing conditions. We conclude that closed circuit anesthesia is a safe and valuable method for measurement of oxygen consumption.


Oxygen transport through a model lung surfactant surface layer: influence of the film compression on the kinetics. The influence of the compression state of a model Lung Surfactant Surface Layer LSSL on the oxygen permeation kinetics was studied in vitro at 37 degrees C. In an attempt to mimic in vivo conditions, the oxygen from the air was allowed to cross a dipalmitoylphosphatidylcholine DPPC layer situated at an air/deaerated saline interface in an electrochemical vessel. The time dependent concentration change of the oxygen diffusing through this layer into the deaerated saline hypophase was measured electrochemically using a Hanging Mercury Drop Electrode HMDE, situated at a definite depth in the bulk of the saline. The surface pressure in the monolayer was monitored using a Wilhelmy balance. The oxygen permeability was measured through two differently compressed DPPC layers in which the area/phospholipid molecule differed by 30%. This is consistent with the difference in the alveolar area at the end-points of the compressed and expanded lung. The results, submitted to a linear regression analysis, showed that the DPPC film compression influences the oxygen permeation kinetics. The denser the lipid film, the slower the oxygen uptake by the deaerated hypophase. The results suggest that the LSSL might play an important role in the oxygen transport kinetics, the oxygen permeation through it being dependent on the actual lung area.


Oxygen supply dependency in the critically ill--a continuing conundrum. There was little dispute that endotoxin treatment of experimental animals could recreate the O2 extraction defect that had been observed in critically ill patients. The remaining question was whether or not this necessarily signified pervasive tissue hypoxia. Some limitation to O2 diffusion in the tissues had been postulated because of known effects of endotoxin that ultimately result in damage to endothelium. We were unable to alter the critical DO2 or 0(2)ER in endotoxic dogs by manipulating the arterial PO2. This tended to rule against there being a diffusion limitation created by the endotoxin as a result of endothelial disruption or microvascular dysfunction. The results of the DCA and dopexamine experiments served to remind us that arterial lactate measurements may or may not indicate widespread tissue hypoxia. Sepsis, as emulated by endotoxin infusions, is also a metabolic disease that can cause inactivation of PDH and thus cause lactacidosis without tissue hypoxia. Regional measurements of lactate flux indicated that gut was hypoxic in spite of DO2 above critical because of maldistribution of blood flow between muscularis and mucosa. The questions persist of how much tissue hypoxia is caused by sepsis or endotoxin when DO2 is supported at supposedly adequate levels and whether there are marked regional differences. Such questions still await answers. Newer technological advances that permit assessment of tissue oxygenation by noninvasive methods, such as near infrared spectrophotometry or nuclear magnetic resonance measurement of tissue energy potential, may soon be feasible in critically ill patients. This kind of information will be of vast importance in designing the most effective therapeutic regimen.


Alterations of the respiratory minute volume cause changes in muscle oxygenation of rats. In the anesthetized, open-chest rat, alterations of the respiratory minute volume were induced by changes of the respiratory frequency. Mean tissue pO2 of skeletal muscle in healthy and distressed rats did not change significantly. 10 minutes after a ventilation stop lasting 60 seconds, healthy rats showed an approximately normalized pO2 histogram, whereas distressed rats did not seem to recover. The results indicate an independent regulation mechanism which maintains a sufficient oxygen supply to skeletal tissue of anesthetized rats. The efficacy of this mechanism seemed to be reduced in distressed rats after the ventilation stop.


Myocardial oxygen supply under critical conditions, the effects of hemodilution and fluorocarbons. This article reviews the factors influencing myocardial oxygen supply and demand. The regulative mechanisms in coronary blood flow, especially in critical conditions, are explained. Myocardial oxygenation in coronary artery disease is discussed with special reference to pharmacological intervention. An extensive evaluation of the effects of hemodilution on both the healthy and diseased heart is presented. Effects of hemodilution with fluorocarbons for the treatment or prevention of myocardial ischemia are shown with the aid of intramyocardial oxygen partial pressure measurements.


Computer simulation of erythrocyte transit in the cerebrocortical capillary network. The relationship between erythrocyte flow path length and transit time was studied using a probabilistic computer simulation of erythrocyte transit in morphometrically reconstructed cerebrocortical microvascular network of the rat. The results suggest (1) a near-cubic relationship between erythrocyte flow and vessel diameter, (2) preferential pathways of erythrocyte flow, (3) an exponential relationship between erythrocyte transit time and flow path length.


Classification of oxygen transport to tissue with neural networks. In the current stage of the development of the EMPHO II it was shown that the transport of oxygen to tissue can be classified for all applications in real time by using neural networks. The resolution of the oxygen classification is 1%. The implementation of the neural network is possible on a commercial signal processor TMS 320C30 board which is compatible with an IBM PC. The implementation of the neural network is done fully in software and no special neurocomputer is necessary. The results are very promising so that the neural network design goals will be established in the future. In the future further efforts will be made in order to increase the data base and to train the network in more detail.


Adaptation of O2 transport and utilization at altitude in man. All stages of the O2 transport pathway are affected in some way by both acute and chronic altitude exposure. At any one stage, the effects are multiple, sometimes subtle, and frequently opposing. Clear-cut differences in responses to acute and to chronic altitude exposure are detectable but not in every case explainable, leaving important and perplexing problems still to be solved. Perhaps the most interesting of these relate to control of cardiac output and to determinants of O2 diffusion from muscle capillary red cells to the muscle mitochondria.


Distribution pattern of capillary and venular red blood cell velocity following ischemia-reperfusion in striated muscle. Ischemia-reperfusion induced changes in distribution pattern of RBC-velocity of nutritive capillaries and postcapillary venules was analyzed in striated muscle using intravital fluorescence microscopy in awake hamsters. Four hours of ischemia to striated muscle contained in the dorsal skinfold preparation (n = 10) revealed a significant (p < 0.01) decrease of capillary, but only a slight decrease of mean venular RBC-velocity during the entire reperfusion period. However, analysis of distribution pattern of single values revealed a shift of the histograms to the left, including pronounced skewness as mean values approached zero. This characteristic phenomenon may be due to an increase of microvascular hematocrit and/or decrease in deformability of red blood cells during ischemia-reperfusion. Beside other factors, the impairment of flow properties and flow conditions of the blood may contribute to the development of microvascular reperfusion injury.


Oxygen tension and blood flow in the retina of normal and diabetic rats. The use of microelectrode techniques for studying oxygen distribution and blood flow in the eye of a physiologically well maintained rat provides a very convenient model in which to study oxygen supply to the retina. The availability of rat models of vascular disease such as diabetes and hypertension, and the existence of several models of retinal degeneration, make studies of oxygen supply in the rat eye of particular relevance. The experiments reported in this paper demonstrate changes in oxygen distribution and blood flow very early in STZ induced diabetes. Thus, we have established a preparation in which the role of changes in oxygen supply can be correlated with the pathological events that are apparent later in the disease.


Oxygen uptake and static lung compliance during automatic ventilation. Oxygen uptake is an important parameter to control proper tissue oxygen delivery. Oxygen uptake is dependent on adequate lung function and easily disturbed by changes in lung compliance and related parameters such as the tidal volume controlling pressure support. Simultaneous on-line registration of oxygen uptake and lung compliance together with ventilatory pressures applied to achieve preset tidal volumes has been made possible using the computer feedback controlled closed circuit ventilatory system Physio-Flex (Physio Co, Hoofdorp, The Netherlands). The system guarantees for leakage free functioning (maximal leakage 7 mL gas loss/minute) and, therefore, patient oxygen consumption measurements with an accuracy of more than 95%. A specially developed membrane ventilation mode registers on-line flow and displaced volume automatically corrected for temperature, pressure and compressible volume. The current investigation has shown: Decrease oxygen consumption versus oxygen delivery supply dependency may be induced by reflectory decreases of heart rate and cardiac output; in this case a reactive pulmonary parameter change is preceding the event in form of a drop in compliance and corresponding changes in ventilatory pressures necessary to maintain the preset tidal volume. In contrast, decrease of oxygen uptake following changes in cardiac output due to acute hypovolemia has no effect on pulmonary function parameters. This can be diagnostically used as moderate changes of tidal volume also have no significant influence on pulmonary parameters. However, changes due to reduction in depth of anesthesia and relaxation have some influence and need to be excluded.


pO2-profiles in human muscle tissue as indicator of therapeutical effect in septic shock patients. Automatically stepwise driven pO2 electrodes were transcutaneously inserted into muscle tissue of severely ill septic shock patients. The pO2 profile was plotted from 200 individual measurements registered during 5 minutes and a histogram plotted for documentation. Arterial and venous blood gases, cardiac output, systemic and pulmonary vascular resistance were measured continuously on-line. In septicemia multiple drug schemes are suggested all intending to increase oxygen supply to the tissue and to improve oxygen demand/supply mismatch. So far the attending physician is bound to conclude and continue respectively change the treatment scheme according to the above described macrophysiological parameters. Perfusion distribution and local inhomogenities of tissue oxygen supply remain undetected. In the described study pretreatment pO2 profiles in musculus quadriceps femoris were obtained and measurements repeated in intervals of 10 minutes after start of pharmacological treatment. The changes of pO2 profiles of 20 patients, monitored in such a way over days and weeks, were carefully correlated to the described cardiocirculatory parameters and blood gas analyses. Dopamine was used to improve cardiac function and tissue oxygen supply as well. The investigations show that resulting changes of cardiovascular and blood gas parameters do not always indicate that tissue oxygen supply has really improved. On the other hand there was never an improvement in tissue oxygen supply when no changes of the other parameters had occurred. It is advised to add as a further diagnostic parameter tissue pO2 measurements to get insight if improvement in cardiac and pulmonary function really has the intended effect of improvement of tissue oxygen supply.


[ESWL treatment of urinary stones at an outpatient clinic]. A total of 107 patients (age: mean 51.6, range 17-85, sex: male 71, female 36) with urinary stones in 112 renoureteral units were subjected to extracorporeal shockwave lithotripsy (ESWL) in situ using an EDAP LT-01 at an outpatient clinic between June 1990 and July 1991. All patients were given an analgesic suppository before ESWL. One ESWL session required 20-60 minutes with a repetition rate of 1.25 Hz, 2.5 Hz or 5 Hz. The effectiveness of the treatment was evaluated in 94 cases consisting of 50 renal units (R1 2, R2 46, R3 2) and 44 ureteral units (U1 16, U2 1, U3 27) three months after the final session according to the criteria reported by Sonoda. Of the 94 cases, 80 cases (85.1%) were stone free and 12 cases (12.8%) had residual fragments of less than 4 mm in diameter. Macroscopic hematuria was seen in all cases. Fever or colicky pain occurred in 3 cases. Outpatient ESWL using the EDAP LT-01 is considered to be safe and efficient for the initial treatment of urinary stones.