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Biomedical subjects

R Auer

Publications and source records attributed to R Auer.

At least 19 recordsLinked to original sources
PubMed2000

Co-localisation of CCG repeats and chromosome deletion breakpoints in Jacobsen syndrome: evidence for a common mechanism of chromosome breakage.

Folate-sensitive fragile sites are associated with the expansion and hypermethylation of CCG-repeats. The fragile site in 11q23.3, FRA11B, has been shown to cause chromosome deletions in vivo, its expression being associated with Jacobsen (11q-) syndrome. However, the majority of Jacobsen deletions are distal to FRA11B and are not related to its expression. To test the hypothesis that other unidentified fragile sites might be located in 11q23.3-24 and may cause these deletions, we have identified and characterised CCG-trinucleotide repeats within a 40 Mb YAC contig spanning distal chromosome 11q. Only eight CCG-repeats were identified within the entire YAC contig (not including FRA11B ), six of which map to the region of 11q23.3-24 that includes Jacobsen deletions. We have previously collated the deletion mapping data of 24 Jacobsen patients with the physical map of chromosome 11q, and accurately localised six breakpoints to short intervals corresponding to individual YAC clones. We now show that in each of these cases, YAC clones found to contain a deletion breakpoint also contain a CCG-repeat. The improved analysis of one of these deletions, together with those of several new Jacobsen cases, further strengthens this association by localising five breakpoints to individual PAC clones containing CCG-repeats. These data provide strong evidence for the non-random clustering of chromosome deletion breakpoints with CCG-repeats, and suggests that they may play an important role in a common mechanism of chromosome breakage.

Abnormalities, Multiple↗
PubMed1999

The role of intra-abdominal pressure on splanchnic and pulmonary hemodynamic and metabolic changes during carbon dioxide pneumoperitoneum.

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.

Abdomen↗
PubMed1999

A novel immunosuppressant, FTY720, induces peripheral lymphodepletion of both T- and B cells and immunosuppression in baboons.

OBJECTIVE: FTY720, a new immunosuppressant active in transplantation models, modulates lymphocyte re-circulation, leading to peripheral lymphopenia and increased lymphocytes in lymph nodes and Peyer's patches. Here, we investigated the susceptibility of baboons to FTY720 as an introductory study to transplantation protocols. METHODS: FTY720 was administered orally to Chacma baboons at 0.3 or 0.1 mg/kg/day for 3 days or at 0.03 mg/kg/day for 10 days. Haematological parameters, lymphocyte phenotype (CD3, CD4, CD8, CD20), cell apoptosis, ex vivo blood cell proliferation in response to mitogens and drug blood levels were monitored during treatment and up to 4 weeks thereafter. MAIN FINDINGS: FTY720 administered p.o. in baboons at 0.3 mg/kg/day caused a marked decrease in circulating lymphocytes within 4 h of treatment, reaching 60-80% decrease within 24-48 h. The effect of FTY720 was seen both on T- and B cells, although it was slightly more rapid/pronounced on T cells. CD4+ cells were slightly more affected than CD8+ cells. The response onset was faster and the duration longer at higher dose, but the maximal peripheral lymphodepletion achieved was similar within the dose range 0.03-0.3 mg/kg tested. Ex vivo mitogen-induced lymphoproliferation was drastically decreased after FTY720 treatment, corresponding to the reduced blood lymphocyte counts. The blood drug levels measured after FTY720 administration correlated well with the dose applied but there was a poor correlation between FTY720 blood levels and the extent of peripheral lymphodepletion, suggestive of a high tissue distribution of the drug. When compared with cynomolgus monkeys treated in the same way, baboons had a lower initial exposure and a slightly lower response 24 h after one or two doses of FTY720 0.03-0.3 mg/kg. However, the stabilized drug blood levels and peripheral lymphodepletion achieved after 7 days of FTY720 0.03 mg/kg/day were similar in both nonhuman primate species. CONCLUSIONS: FTY720 was well tolerated and was effective in terms of peripheral T- and B lymphodepletion in baboons, indicating that it could be used in protocols of allo- and xenotransplantation. The pharmacokinetic and pharmacodynamic profiles of FTY720 in baboons suggest the use of high induction doses to optimize immediate response followed by a reduced dose regimen for drug maintenance.

Animals↗
PubMed1997

Deletions at 11q identify a subset of patients with typical CLL who show consistent disease progression and reduced survival.

Eighty-four patients with typical chronic lymphocytic leukemia (CLL) (by morphological and immunophenotypic criteria) on whom karyotypes were available were studied. Binet stage at diagnosis and follow-up were defined. Survival was calculated from diagnosis. Fifty-one percent of patients had a karyotypic abnormality, the commonest being abnormalities at 13q14 (16%); these patients did not have significantly different survival from patients with normal karyotype. The second commonest abnormality was del(11q) (13%); these patients had significantly worse survival when compared both with patients with normal karyotype (P < 0.0001) and with other patients with karyotypic abnormality (P = 0.0012). All patients with del(11q) had progressed to stage C at follow-up while only 20% of the other patients had shown any disease progression (P < 0.0001). Del(11q) may identify a subset of patients with typical CLL who have worse survival and consistent disease progression and in future may help define a group of patients with CLL who could benefit from earlier or more intensive therapy.

Adult↗
PubMed1987

MRI CT, and plain film appearance of anterior spina bifida.

Anterior spina bifida or butterfly vertebral body has a well known and characteristic appearance on plain film and CT. Its appearance on magnetic resonance imaging also appears to be characteristic and should not be mistaken for more serious abnormalities.

Humans↗
PubMed1985

Lesions of the glutamatergic cortico-striatal projections in the rat ameliorate hypoglycemic brain damage in the striatum.

Unilateral ablations of the motor cortex were performed on rats. One to two weeks following the ablation they were subjected to 30 min of reversible insulin-induced hypoglycemic coma. The levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), taurine, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and phosphocreatine (PCr) were determined in frozen tissue sections from the superior half of the caudate nucleus. The lesions induced a specific reduction in the levels of glutamate by approx. 10% in the dorsal caudate nucleus ipsilateral to the lesion, while no significant differences in the levels of aspartate, GABA, taurine, ATP, ADP, AMP or PCr were noted. Neuronal necrosis in the caudate nucleus in animals subjected to 30 min of insulin-induced hypoglycemic coma and one week recovery was assessed by light microscopy. Contralateral to the lesion, extensive neuronal necrosis, mainly affecting small and medium-sized neurons, was observed in the dorsal and lateral caudate nucleus. In the caudate ipsilateral to the lesion a complete amelioration of necrosis was noted in areas subjacent to the lesion. The data suggest that hypoglycemic brain damage is induced by excitotoxins such as glutamate or related compounds.

Animals↗
PubMed1985

Status epilepticus in well-oxygenated rats causes neuronal necrosis.

Neuronal necrosis in the brain resulting from status epilepticus of 15 to 120 minutes duration in ventilated and well-oxygenated rats was assessed. Seizures were induced by inhalation of the convulsant gas flurothyl, and terminated by withdrawal of flurothyl and a single injection of thiopental. The animals were allowed to recover for one week, and neuronal damage was assessed by cell counts following subserial sectioning of the brain and microscopical examination of the sections. Infarction of the pars reticulata of the substantia nigra occurred in 5 of the 6 animals with seizure duration of 30 minutes, and in all animals with longer seizure durations. There also was a common affectation of the central parts of the globus pallidus. The pars compacta of the substantia nigra was never affected. After 45 to 120 minutes of seizures, moderate neuronal necrosis was observed in the neocortex (layers 3 and 4), and after 60 to 120 minutes was seen in amygdaloid and thalamic nuclei, as well as in CA4 and CA1 hippocampal pyramidal cells. Notably, CA3 neurons were not damaged nor were dentate granule cells affected. After 120 minutes of seizures, damage regularly affected the neocortex and the ventral-posterior nuclei of the thalamus. A conspicuous feature was the localization of neuronal necrosis at sites close to the ventricles.

Animals↗
PubMed1985

The dentate gyrus in hypoglycemia: pathology implicating excitotoxin-mediated neuronal necrosis.

A detailed light- and electron-microscopic study of the damage to the rat dentate gyrus in hypoglycemia was undertaken, in view of the previously advanced hypothesis that hypoglycemic nerve cell injury is mediated by a released neurotoxin. The distribution of neuronal necrosis showed a relationship to the subarachnoid cisterns. Electron microscopy of the dentate granule cells and their apical dendrites revealed dendrosomal, axon-sparing neuronal pathology. Dentate granule cells were affected first in the dendrites in the outer layer of the stratum moleculare, sparing axons of passage and terminal boutons. Subsequently, the neuronal perikarya were affected, and Wallerian degeneration of axons followed. Cell membrane abnormalities preceded the appearance of mitochondrial flocculent densities and degradation of the cytoskeleton, and are suggested to be early lethal changes. The observed early dendrotoxic changes, and the dendrosomal, axon-sparing nature of the lesion implicate an excitotoxin-mediated neuronal necrosis in hypoglycemia.

Animals↗
PubMed1985

The EPICS C analyzer. An ergometrically designed flow cytometer computer system.

A description is presented of a new flow-cytometer (FCM) computer system, the EPICS C analyzer, which was developed to be used by a moderately trained technician as opposed to an FCM expert. The system was made robust and user-friendly by the use of menu-based rather than command-driven software. The user primarily interacts with the self-explanatory menus by depressing one of the eight membrane selector switches located on each side of the screen. The minimizing of typing and restriction of the user's responses greatly simplify the use and design of the software. The EPICS C operates in two modes: as a reliable clinical instrument and as a research tool. The instrument settings are stored on disk files rather than manually logged into a book. The settings for the predefined tests are read from the disk.

Cell Separation↗
PubMed1975

[Prophylactic measures in general dental practice. An inquirly on their state and frequency].

Questionnaires concerning the type of oral examinations and preventive measures used in private practice were sent to 500 randomly selected dentists in the german-speaking part of Switzerland. 300 were returned completed, the majority of these anonymously. In the examination of new patients, bite-wing radiographs were the most commonly used diagnostic aid. This was reported in 60% of the offices--more often by younger than by older pracitioners, more frequently in urban than in rural offices and more often in surgeries treating less than 12 patients a day. Concerning oral restauration itself, the most frequently frequently reported procedures were the treatment of clinically visible carious lesions, polishing and the replacement of defective fillings. A broad spectrum of prophylactic oral hygiene aids were reported. Toothbrush and dental floss combined with oral hygiene instruction, however, were still the most commonly used. There was considerably correlation between the type of prophylactic acids used and the type of the dental practice. According to the questionnaires, fluoride prophylaxis is very regulary carried out and recommended. The ways in which this fluoride prophylaxis is carried out differs from practice to practice. Nutritional prophylaxis counseling was considered in the majority of the offices irrespective of the type of office. Relatively little emphasis was placed upon cooperation of the patient. From the questionnaries we calculated a need for about 550 DH for Switzerland. Younger dentists mentioned this need relatively moe often than older practitioners. A recall system was used in 70% of the practices, whereby annual and semi-annual intervals were reported with equal frequency. It is obvious that the emphasis placed upon prevention is not the same in all practices. This statement is valid also for the carious and periodontal diagnostic measures utilized. Much work as well as maybe a certain resignation resulting from previous failures may prevent the dentist from instituting more preventive measures in his practice. It is obvious that the graduates of the new dental hygiene school can help in this regard. However, because as yet these new graduates cannot supply even one half of the 550 required hygienists, it is discussed whether or not dental chair-side assistants with special training could motivate our patients toward a more satisfactory oral hygiene.

Adult↗
PubMedDate not supplied

[Status of dental preventive efforts in Switzerland].

Regarding schools, the first endeavours of preventive dentistry based on the results of modern scientific results were made in the early fifties in the Canton of St. Gall. Great efforts have been made since then and it is impossible to keep track of all activities. At the schools it is the teachers on one hand and specialized or lay auxiliary personnel on the other who organize and perform supervised toothbrushing exercises with fluorides. In Switzerland there are now some 30 full-time positions for auxiliaries charged with preventive measures at Kindergarten or school. An estimate of the population reached by the various methods of prevention is presented. The costs of prevention are but a small fraction of the cost of conservative treatment. In the majority of the private dental offices prevention is part of the activity, but with varying intensity. As to public clinics, the preventive programm run by the Volkszahnklinik Basel is most advanced. It is important that prevention is introduced in all regions of Switzerland and that it reaches the children of all ages. The future depends strongly on the availability of auxiliary personnel working at the schools and in the dental offices.

Child↗