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Biomedical subjects

P Ulrich

Publications and source records attributed to P Ulrich.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cerebral blood flow autoregulation during hypobaric hypotension assessed by laser Doppler scanning.

Hypobaric hypotension was used to reduce systemic blood pressure in rats below the lower threshold of CBF autoregulation to evaluate a new laser Doppler (LD) "scanning" technique. Spontaneously breathing male Wistar Kyoto rats (n = 8) were anesthetized with chloral hydrate and the head fixed in a stereotaxic head holder. A cranial window with intact dura mater was introduced to assess local CBF (lCBF) by LD. One stationary probe served to detect rapid flow changes, whereas the second probe was used to sample lCBF recordings from many cortical locations by means of a stepping motor-controlled micromanipulator to obtain lCBF frequency histograms. Advantages are an improved spatial resolution together with the easy detection of low-flow areas and a better comparison of data from individual experiments. Arterial blood pressure was stepwise reduced by exposing the lower body portions to subatmospheric pressures (hypobaric hypotension), thus avoiding the use of drugs or heparinization. The lower threshold of CBF autoregulation was detected by "scanning" at arterial pressures between 50 and 46 mm Hg, with low-flow spots occurring immediately. The data suggest LD scanning as a method suited particularly for studies where lCBF inhomogeneities are expected, e.g., the ischemic penumbra or sinus vein thrombosis.

Animals↗
PubMed1994

Aneurysm surgery of patients in poor grade condition. Indications and experience.

Out of a total of 196 patients admitted with aneurysmal subarachnoid haemorrhage (SAH) to the neurological department in Mainz over a 42 month period, 48 patients (24.5%) were considered as grade IV or V on admission. Aneurysm surgery within 48 hours after SAH was performed in 56.3% of these patients, 2% were operated between day 3 and 7 and 16.6% were operated after day 7. 25% did not undergo operation because of severe neurological deficit and brain damage. The overall outcome according to the Glasgow outcome scale in the surgically treated group was full recovery in 11.1%, moderate disability in 16.7%, severe disability in 47.2%, vegetative state in 2.8% and death in 22.2%. All patients in the not operated group died. Good and moderate outcome was mainly seen in patients grade IV, which justify an aggressive strategy. Severe disability was mainly attributed to primary brain damage, while vasospasm played a minor role. Improvement may only be achieved by early referral of SAH patients to neurosurgical centres.

Adult↗
PubMed1994

Reoperation in the management of post-operative disc space infection.

Post-operative intervertebral disc space infection had been recognised as a clinical entity with its own characteristics. Various treatments have been described. During the last six years 3127 open lumbar intervertebral disc operations were performed of which 15 (0.5%) showed a post-operative discitis. We treated our patients by reoperation of the infected intervertebral disc space. The reason of reoperation consists of acquiring material for bacteriological culture and removing loose fragments. It appears to us that reoperation is facilitating early mobilisation of patients. Also attention is paid to new diagnostic possibilities.

Adult↗
PubMed1991

Evaluation of collateral flow capacity in patients with vascular or tumorous lesions of the skull base by Doppler sonography.

In 12 patients with vascular or tumorous lesions of the skull base, the collateral flow capacity was examined by transcranial Doppler sonography and carotid compression studies. In four patients no cross flow mechanism was found, in two patients the test remained unclear, and in six patients the examination suggested a good collateral flow capacity. However, for this application of Doppler sonography no borderlines have yet been defined and thus interpretation is difficult. Intraoperative Doppler sonography was used in five patients and proved to be helpful for localisation of the internal carotid artery within skull base tumors.

Adult↗
PubMed1991

Transient and lasting effects of reproductive episodes on NaCl intake of the female rat.

Following recovery from experimental sodium depletion, both the need-free and the future need-induced NaCl intakes of the rat are increased. The present experiments asked whether a naturally occurring episode of sodium need, pregnancy and lactation, would also enhance NaCl intake. The daily 0.3 M NaCl intake of Long-Evans rats increased from 18.2 ml (prior to pregnancy) to 28.7 ml during pregnancy, and increased further to 36.2 ml during lactation. The daily intakes remained increased after the weaning of the second litter, at 28.5 ml/24h for females which had access to 0.3 M NaCl during the reproductive episodes (DAM + Na) and at 27.6 ml/24h for those which did not (DAM). When they were subsequently sodium depleted, the need-induced NaCl intake of the DAM, but not the DAM + Na group, was significantly increased compared to virgin female rats. The sodium depletion-induced water intakes of both groups were significantly increased. Neither the need-free nor the need-induced intakes of their offspring (as adults) were increased. In summary, pregnancy and/or lactation, in the absence of a sodium deficit, produced increased intakes of NaCl which persisted beyond the reproductive episodes.

Animals↗
PubMed1989

RCBF-quantification with 99mTc-HMPAO-SPECT: theory and first results.

The activity concentrations of 99mTc-HMPAO in brain after intravenous injection were evaluated in 25 patients using SPECT. With additional first pass studies of heart and brain with the short lived isotope 195mAu, the cardiac output and the mean cerebral transit times of the patients were measured a short time before the HMPAO injection. The time dependence of 99mTc-HMPAO activity in the brain was registered during the first 5 min after injection over both hemispheres. Using a simplified three compartment model it was possible to calculate the mean retention fraction of HMPAO in brain from the time activity curves. It could be shown that the regional cerebral blood flow in ml/min per 100 g can be calculated from the activity concentration of HMPAO in the brain, the cardiac output and the retention fraction. In 15 of the 25 cases the rCBF was measured using the planar 133Xe inhalation method as a reference. We found a significant correlation between the mean hemisphere CBF from our method and the mean hemisphere grey matter CBF from the Xenon method with a correlation coefficient of 0.73.

Adolescent↗
PubMed1988

Characterisation of two differently processed forms of human recombinant factor IX synthesised in CHO cells transformed with a polycistronic vector.

A stable transformed cell line constitutively expressing human factor IX has been established. Wild-type Chinese hamster ovary cells (CHO cells) were transformed using a polycistronic expression vector carrying a previously isolated factor IX cDNA and a selection gene encoding the Escherichia coli xanthine-guanine phosphoribosyl transferase. One clone, CHO 622.4, contains a high number of genomically integrated plasmids and secretes 1-3 mg factor IX l-1 day-1 into the culture medium with a biological activity ranging from 25% to 40%. The recombinant molecule was purified either by conventional chromatography or by immunoaffinity chromatography using antibodies specific to a calcium-induced factor IX conformer. The purified recombinant protein migrates as a single band with the same mobility as that of natural factor IX on SDS/polyacrylamide gels. N-terminal sequencing shows tow differently processed forms of recombinant factor IX: whereas the majority of the zymogen is correctly processed, approximately 20% of the purified recombinant molecule contains an 18-amino-acid NH2-extension corresponding to the precursor form of factor IX. Analysis of the 4-carboxyglutamic acid content indicates a high but incomplete carboxylation (70%) of the recombinant molecule as compared to natural factor IX. The carbohydrate composition of both the natural and recombinant molecules has been determined. Both molecules have a N-glycan structure of similar complexity, indicating that factor IX contains all the information to direct the same glycosylation pattern in human liver cells and in an unrelated cell line such as CHO-K1.

Amino Acid Sequence↗
PubMed1988

Immunohistochemical detection of HIV structural proteins and distribution of T-lymphocytes and Langerhans cells in the oral mucosa of HIV infected patients.

Seventeen biopsies taken from oral mucosa of HIV infected patients were analysed for the distribution of CD4+/CD8+ T-lymphocytes and Langerhans cells. The results were evaluated statistically. An increase in the absolute number of CD4+ and CD8+ cells in HIV infected patients without clinical symptoms, ARC or AIDS was seen in the connective tissue stroma when compared with normal oral mucosa from sero-negative patients. However, the ratio between CD4+/CD8+ cells was decreased due to the disproportionate increase of CD8+ cells. These findings did not show statistical correlation with the clinical status of the infection. In contrast to the increase in absolute number of CD4+/CD8+ cells the number of Langerhans cells was unchanged when compared with the control group. Using four different monoclonal antibodies against virus structural proteins (2 X anti p24, gp41, gp120) two of 26 patients showed labelled cells in consecutive sections in the same connective tissue areas. It was assumed that latently infected mononuclear cells invaded the oral mucosa together with uninfected cells of the cellular immune system.

AIDS-Related Complex↗
PubMed1988

Tissue elastance and fluid conduction in normotensive and hypertensive intracerebral mass haematomas.

This is an investigation into the prognostic factors of 117 patients with spontaneous normo- and hypertensive intracerebral haematomas, supported by animal experiments. Preserved tissue elastance and fluid conduction enables the drainage of intrinsic haematoma serum into the CSF spaces in normotensive patients, who showed an increased extension of a perifocal hypodensity in the CT. Arterial hypertension decreased the possibility of fluid resolution. Our experimental studies showed that in hypertensive cases the serum remained trapped in the haematoma, which explains the small hypodense area around the haematoma in most of the hypertensive cases. If as an exception in hypertensives of perifocal hypodensity develops then it acts as additional space-occupying factor. Corresponding observations were made in hypertensive animals which showed a reduced serum movement out of the haematoma, but an increased Evans-Blue content in the perifocal tissue. Both pathological mechanisms explain the poorer prognosis in patients with intracerebral haematomas associated with high arterial blood pressure.

Adult↗
PubMed1988

"Subversive" substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas disease.

The trypanosomatid flavoprotein disulfide reductase, trypanothione reductase, is shown to catalyze one-electron reduction of suitably substituted naphthoquinone and nitrofuran derivatives. A number of such compounds have been chemically synthesized, and a structure-activity relationship has been established; the enzyme is most active with compounds that contain basic functional groups in side-chain residues. The reduced products are readily reoxidized by molecular oxygen and thus undergo classical enzyme-catalyzed redox cycling. In addition to their ability to act as substrates for trypanothione reductase, the compounds are also shown to effectively inhibit enzymatic reduction of the enzyme's physiological substrate, trypanothione disulfide. Under aerobic conditions, trypanothione reductase is not inactivated by these redox-cycling substrates, whereas under anaerobic conditions the nitrofuran compounds cause irreversible inactivation of the enzyme. When tested for biological activity against Trypanosoma cruzi trypomastigotes, many of the test compounds were trypanocidal, and this activity correlated with their relative ability to act as substrates for trypanothione reductase. The activity of the enzyme with these redox-cycling derivatives constitutes a subversion of its normal antioxidant role within the cell. For this reason these compounds may be termed "subversive" substrates for trypanothione reductase.

Aerobiosis↗
PubMed1988

A new recombinant procoagulant protein derived from the cDNA encoding human factor VIII.

We have constructed new B domain deletion derivatives of human factor VIII (FVIII) by manipulating the cDNA using recombinant DNA techniques. One of these new derivatives, FVIII delta II, in which amino acids 771(pro)-1666(asp) have been deleted, no longer contains the protease cleavage site at amino acid position 1648(arg)-1649(glu) known to be involved in the initial step of FVIII processing. We have expressed this molecule in both baby hamster kidney (BHK) 21 cells using the vaccinia virus (VV) expression system and have established Chinese hamster ovary (CHO) derived permanent cell lines expressing either recombinant (r)FVIII or FVIII delta II. The characteristics of FVIII delta II have been compared to those of rFVIII and/or plasma derived (pd) FVIII. FVIII delta II has the following properties: (i) it exhibits FVIII procoagulant activity; (ii) it is expressed at 5-fold higher levels than is the complete molecule in comparable systems; (iii) it migrates for the most part as a single major band on SDS-PAGE, in contrast to the complete molecule; (iv) it is activated to a greater extent by thrombin than is either rFVIII or pdFVIII; and (v) it retains the ability to bind von Willebrand factor (vWf).

Antibodies, Monoclonal↗
PubMed1987

Substrate specificity of the flavoprotein trypanothione disulfide reductase from Crithidia fasciculata.

The substrate specificity of the trypanosomatid enzyme trypanothione reductase has been studied by measuring the ability of the enzyme to reduce a series of chemically synthesized cyclic and acyclic derivatives of N1,N8-bis(glutathionyl)spermidine disulfide (trypanothione). Kinetic analysis of the enzymatic reduction of these synthetic substrates indicates that the mutually exclusive substrate specificity observed by the NADPH-dependent trypanothione disulfide reductase and the related flavoprotein glutathione disulfide reductase is due to the presence of a spermidine binding site in the substrate binding domain of trypanothione reductase. Trypanothione reductase will reduce the disulfide form of N1-monoglutathionylspermidine and also the mixed disulfide of N1-monoglutathionylspermidine and glutathione. The Michaelis constants for these reactions are 149 microM and 379 microM, respectively. Since the disulfide form of N1-monoglutathionylspermidine and the mixed disulfide of N1-monoglutathionylspermidine and glutathione could be formed in trypanosomatids, the binding constants and turnover numbers for the enzymatic reduction of these acyclic disulfides are consistent with these being potential alternative substrates for trypanothione reductase in vivo.

Animals↗
PubMed1987

Cerebral blood flow, computerized tomography and angiography in 562 cases of cerebrovascular insufficiency.

The measurement of cerebral blood flow (CBF) in addition to cerebral computerized tomography (CT) and angiography is most reliable in cases of transient ischemic attacks (TIA) and prolonged reversible ischemic neurologic deficits (PRIND). Alterations of CBF can be detected in symptom-free intervals. The cerebrovascular reactivity to CO2 stimulus is regarded as an especially suitable tool to prove the cerebrovascular reserve. If it is diminished, cerebral angiography should be carried out since it will often show major obstructive lesions. Angiography shows no sure correlation between CBF and collateral circulation. Strong opthalmic pathways in unilateral occlusion of the internal carotid artery (ICA) often coincide with compensated or only slightly alterated CBF and relatively small infarcts in CT. In about 70% of cases of ICA occlusion, CT shows an infarct mostly in region of the middle cerebral artery (MCA). Largest infarct volumes were found in the anterior area. Although resting CBF was normal in 55% of cases of unilateral ICA occlusion, CO2 reactivity was impaired in 68% of these Cases.

Adolescent↗
PubMed1987

Cerebral blood flow in autogenic training and hypnosis.

In 12 healthy volunteers with at least an experience of six months in autogenic training (AT), the cerebral blood flow (CBF) was measured at rest, in AT and in hypnosis (H). The results were correlated with individual test profiles. The cortical flow pattern at rest of our AT trained volunteers did not show the hyperfrontality which is described in the literature. This may be interpreted as an effect of better and habitualized relaxation in long trained AT practitioners. This flow pattern corresponds to the low grades of neuroticism and aggressivity found in the tests. Furthermore an activation in central cortical areas and a deactivation in regions which are associated with acoustic and autonomous functions occur. Possible explanations for these phenomena as well as for the relatively low perfusion of the left hemisphere at rest and activation in AT are discussed. The global rise of CBF in H may be an activation effect caused by resistance against the hypnotizer: the deeper the trance, the smaller the CBF increase in the motor cortical area needed for maintaining catalepsy of the right arm and in temporal cortical fields processing acoustic inputs.

Adult↗
PubMed1987

Epidermal growth factor--interactions with normal and malignant urothelium: in vivo and in situ studies.

Epidermal growth factor (EGF) is excreted in urine in high concentrations and thus incubates with bladder epithelial cells continuously. However, it is not known whether any urothelial cells can bind urinary EGF or respond to it. Using a monoclonal antibody (528) to the binding portion of the human EGF receptor, immunoperoxidase staining demonstrated that the basal cell layer of normal urothelium is richly endowed with cell surface EGF receptors while the superficial cell layer is not. Alternatively, superficial cells of premalignant and malignant urothelium have many surface EGF receptors. Intravesical EGF induces in vivo activity of ornithine decarboxylase and DNA synthesis in rat bladders, with nuclear thymidine incorporation being limited to the basal epithelial cell layer. These studies indicate that urothelium can respond to urinary EGF and that this response parallels the distribution of EGF receptors. These findings combined with the difference in EGF-receptor expression between malignant and normal cells indicate that urinary EGF may play a role in bladder tumor development and/or growth.

Animals↗
PubMed1987

Chemotherapy of trypanosomiasis: the use of guanylhydrazone compounds in the treatment of experimental murine trypanosomiasis.

The efficacy of 1,3,5-triacetylbenzene tris(guanylhydrazone) trihydrochloride i.e. [(TBG)] in the treatment of early and late stage infections of Trypanosoma brucei in mice was investigated. Successful treatment on day 3 after infection could be achieved by doses of 2 X 2.5 mg kg-1. If treatment was delayed to 21 days after infection then the mice had to be given either suramin (1 X 20 mg kg-1) or difluoromethyl-ornithine (DFMO) 2% solution for 14 days in addition to either 15 mg kg-1 (TBG) daily for 4 days or 10 mg kg-1 twice daily for 4 days to obtain permanent cures. Other guanylhydrazone compounds were investigated for the treatment of chronic T. brucei infections and, at the limited dose levels used, failed to give any permanent cures. The use of (TBG) in the treatment of early and late stage infections of T. congolense and T. evansi indicated that treatment on day 3 after infection could be successful but on day 21 after infection the results were disappointing.

Animals↗