Biomedical subjects

M Studer

Publications and source records attributed to M Studer.

At least 19 recordsLinked to original sources

PubMed1998

[Surgery of mitral valve insufficiency. Results of 10 years].

From 1987 to 1996 we operated on 263 patients for mitral insufficiency. Multiple valve operations were excluded, with the exception of tricuspid reconstruction for functional regurgitation. The perioperative mortality was 3%, while the late mortality rate during a mean follow-up period of 3.5 years amounted to 2% per patient year and 1.7% if only cardiac causes were considered. The prognosis for patients with rheumatic, endocarditic and ischemic valvular disease was much worse compared to that for a degenerative cause. The latter group consisted of 209 patients with an operative mortality of 1.4% and a late mortality rate per patient year of 1.4% and 0.9% for cardiac causes only. Further analysis showed a significant prognostic improvement for patients with a preoperative ejection fraction of more than 60% and a repairable valve.

Adult↗

PubMed1998

Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning.

In the developing vertebrate hindbrain Hoxa1 and Hoxb1 play important roles in patterning segmental units (rhombomeres). In this study, genetic analysis of double mutants demonstrates that both Hoxa1 and Hoxb1 participate in the establishment and maintenance of Hoxb1 expression in rhombomere 4 through auto- and para-regulatory interactions. The generation of a targeted mutation in a Hoxb1 3' retinoic acid response element (RARE) shows that it is required for establishing early high levels of Hoxb1 expression in neural ectoderm. Double mutant analysis with this Hoxb1(3'RARE) allele and other targeted loss-of-function alleles from both Hoxa1 and Hoxb1 reveals synergy between these genes. In the absence of both genes, a territory appears in the region of r4, but the earliest r4 marker, the Eph tyrosine kinase receptor EphA2, fails to be activated. This suggests a failure to initiate rather than maintain the specification of r4 identity and defines new roles for both Hoxb1 and Hoxa1 in early patterning events in r4. Our genetic analysis shows that individual members of the vertebrate labial-related genes have multiple roles in different steps governing segmental processes in the developing hindbrain.

Animals↗

PubMed1998

Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch.

The analysis of Hoxa1 and Hoxb1 null mutants suggested that these genes are involved in distinct aspects of hindbrain segmentation and specification. Here we investigate the possible functional synergy of the two genes. The generation of Hoxa1(3'RARE)/Hoxb1(3'RARE) compound mutants resulted in mild facial motor nerve defects reminiscent of those present in the Hoxb1 null mutants. Strong genetic interactions between Hoxa1 and Hoxb1 were uncovered by introducing the Hoxb1(3'RARE) and Hoxb1 null mutations into the Hoxa1 null genetic background. Hoxa1(null)/Hoxb1(3'RARE) and Hoxa1(null)/Hoxb1(null )double homozygous embryos showed additional patterning defects in the r4-r6 region but maintained a molecularly distinct r4-like territory. Neurofilament staining and retrograde labelling of motor neurons indicated that Hoxa1 and Hoxb1 synergise in patterning the VIIth through XIth cranial nerves. The second arch expression of neural crest cell markers was abolished or dramatically reduced, suggesting a defect in this cell population. Strikingly, the second arch of the double mutant embryos involuted by 10.5 dpc and this resulted in loss of all second arch-derived elements and complete disruption of external and middle ear development. Additional defects, most notably the lack of tympanic ring, were found in first arch-derived elements, suggesting that interactions between first and second arch take place during development. Taken together, our results unveil an extensive functional synergy between Hoxa1 and Hoxb1 that was not anticipated from the phenotypes of the simple null mutants.

Animals↗

PubMed1998

[Early postoperative nutrition after elective colonic surgery].

UNLABELLED: Our intent was to show that immediate postoperative oral feeding of a regular diet after elective open colorectal surgery is safe, feasible and can be tolerated by the patients. Our prospective study included 96 consecutive patients, and their results were compared with those of the literature. CONCLUSION: Early oral feeding after elective colorectal surgery is safe (morbidity: 12.5%; mortality: 2%); it can be tolerated without symptoms by a majority of patients (85%); it is easy, feasible, and shortens the postoperative length of hospital stay (10.6 days).

Colonic Diseases↗

PubMed1997

Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1.

Correct regulation of the segment-restricted patterns of Hox gene expression is essential for proper patterning of the vertebrate hindbrain. We have examined the molecular basis of restricted expression of Hoxb2 in rhombomere 4 (r4), by using deletion analysis in transgenic mice to identify an r4 enhancer from the mouse gene. A bipartite Hox/Pbx binding motif is located within this enhancer, and in vitro DNA binding experiments showed that the vertebrate labial-related protein Hoxb1 will cooperatively bind to this site in a Pbx/Exd-dependent manner. The Hoxb2 r4 enhancer can be transactivated in vivo by the ectopic expression of Hoxb1, Hoxa1, and Drosophila labial in transgenic mice. In contrast, ectopic Hoxb2 and Hoxb4 are unable to induce expression, indicating that in vivo this enhancer preferentially responds to labial family members. Mutational analysis demonstrated that the bipartite Hox/Pbx motif is required for r4 enhancer activity and the responses to retinoids and ectopic Hox expression. Furthermore, three copies of the Hoxb2 motif are sufficient to mediate r4 expression in transgenic mouse embryos and a labial pattern in Drosophila embryos. This reporter expression in Drosophila embryos is dependent upon endogenous labial and exd, suggesting that the ability of this Hox/Pbx site to interact with labial-related proteins has been evolutionarily conserved. The endogenous Hoxb2 gene is no longer upregulated in r4 in Hoxb1 homozygous mutant embryos. On the basis of these experiments we conclude that the r4-restricted domain of Hoxb2 in the hindbrain is the result of a direct cross-regulatory interaction by Hoxb1 involving vertebrate Pbx proteins as cofactors. This suggests that part of the functional role of Hoxb1 in maintaining r4 identity may be mediated by the Hoxb2 gene.

Animals↗

PubMed1996

[Cerebral insult in heart surgery].

The aim of the study was to identify causes for perioperative stroke in cardiac surgery in order to reduce its occurrence. From 1989 to 1994, 3593 open heart operations were performed in adult patients. In 59 patients carotid endarterectomy for high grade stenosis was combined with the cardiac operation. There were a total of 68 (2%) focal strokes, 41 of which were considered minor and 14 major; 13 were lethal. The etiology of the 27 major and lethal events was most probably an embolus from the ascending aorta (6), from the ascending aorta or a cardiac valve (5), a thrombus in the left heart (6), air (1), cardiac arrest and resuscitation (4), cerebral hemorrhage (1), preoperatively unknown but high grade internal carotid stenosis (3), and a 50% stenosis of both internal carotid arteries preoperatively known but not operated on (1). There were 2 minor but no major neurologic complications in patients undergoing a combined carotid and cardiac procedure. A wide indication for preoperative neuroangiologic examination, echocardiography and careful intraoperative management may help to identify sources of possible emboli. Endarterectomy of high grade carotid stenosis is recommended simultaneously with the cardiac procedure.

Adult↗

PubMed1996

Retinoids and Hox genes.

The vertebrate embryonic body plan is constructed through the interaction of many developmentally regulated genes that supply cells with the essential positional and functional information they require to migrate to their appropriate destination and generate the proper structures. Some molecular cues involved in patterning the central nervous system, particularly in the hindbrain, are interpreted by the Hox homeobox genes. Retinoids can affect the expression of Hox genes in cells lines and embryonic tissues; the hindbrain and branchial region of the head are particularly sensitive to the teratogenic effects of retinoic acid. The presence of endogenous retinoic acid, together with the distribution of retinoid binding proteins and nuclear receptors in the developing embryo, strongly suggest that retinoic acid is a natural morphogen in vertebrate development. The molecular basis for the interaction between retinoic acid and the Hox genes has been aided in part by approaches using deletion analysis in transgenic mice carrying lacZ reporter constructs. Such studies have identified functional retinoic acid response elements within flanking sequences of some of the most 3' Hox genes, suggesting a direct interaction between the genes and retinoic acid. Furthermore, as demonstrated using transgenic mice carrying Hoxb-1/lacZ constructs, multiple retinoic acid response elements may cooperate with positive and negative regulatory enhancers to specify pattern formation in the vertebrate embryo. These types of studies strongly support the normal roles of retinoids in patterning vertebrate embryogenesis through the Hox genes.

Animals↗

PubMed1996

[Long-term course of medullary thyroid gland carcinoma].

UNLABELLED: To obtain information on the outcome of medullary thyroid carcinoma (MTC) in the Berne area, a retrospective analysis of the 28 MTCs diagnosed by the Institute of Pathology of the University of Berne in the 25-year period between 1969 and 1994 was done. These 28 MTCs represented 2.4% of all thyroid malignancies diagnosed at the Bernese Institute of Pathology in the 25-year period mentioned above. 25 MTCs were sporadic and 3 associated with a multiple endocrine neoplasia (MEN) syndrome. Follow-up data were available from 27 of the 28 MTC patients. After a follow-up period of between 2 and 275 months 7 of these 27 patients had died form the MTC (among them all 4 patients with T4 tumors) and two were alive with tumor. 18 patients, including all 14 patients with T1 or T2 tumors without lymph node or distant metastases at the time of diagnosis, were alive and without evidence of tumor at the end of the follow-up period. CONCLUSIONS: MTCs are rare malignant tumors and comprise only a small fraction of all thyroid carcinomas in the Berne area. Most MTCs were sporadic, only a small minority was associated with a MEN syndrome. The TNM stage was the most important prognostic factor for patient survival. These data are in accordance with the results of similar MTC surveys done in other areas.

Adult↗

PubMed1995

Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx.

Comparison of Hoxb-1 regulatory regions from different vertebrates identified three related sequence motifs critical for rhombomere 4 (r4) expression in the hindbrain. Functional analysis in transgenic mice and Drosophila embryos demonstrated that the conserved elements are involved in a positive autoregulatory loop dependent on labial (lab) family members. Binding of Hoxb-1 to these elements in vitro requires cofactors, and the motifs closely resemble the consensus binding site for pbx1, a homolog of the Drosophila extradenticle (exd) homoedomain protein. In vitro exd/pbx serves as a Hoxb-1 cofactor in cooperative binding and in Drosophila expression mediated by the r4 enhancer is dependent on both lab and exd. This provides in vivo and in vitro evidence that r4 expression involves direct autoregulation dependent on cooperative interactions of Hoxb-1 with exd/pbx proteins as cofactors.

Animals↗

PubMed1995

[Acquired heart diseases and pregnancy].

Understanding of the mechanisms of cardiovascular and hemodynamic adaptation during pregnancy helps to prevent or manage complications in cardiac patients during gestation. Manifestations of coronary heart disease are exceptional during pregnancy and delivery. The same is true of disorders of the pericardium. Peripartal cardiomyopathy is a myocardial disorder of undetermined cause occurring shortly before, during or after delivery, which may take a fatal course. Hypertrophic obstructive or non-obstructive cardiomyopathy is compatible with gestation and delivery without serious complications in most cases. Rheumatic mitral stenosis was the most common cardiac disorder until the 1950s. Nowadays it is rarely seen in this country. Surgical and other interventional therapies have greatly changed the outlook in pregnant women with valvular heart disease. A highly controversial issue is heart valve replacement in young women and management of anticoagulation during pregnancy. Like any other drug therapy, anticoagulation during gestation requires careful weighing of the benefit for the mother against toxic and teratogenic effects for the fetus. In women with heart disease the management of pregnancy should start, if possible, before conception. Thorough counseling and proper planning of pregnancy and of therapeutic measures is essential in order to avoid or manage complications.

Abnormalities, Drug-Induced↗

PubMed1994

Role of a conserved retinoic acid response element in rhombomere restriction of Hoxb-1.

After activation in mesoderm and neuroectoderm, expression of the Hoxb-1 gene is progressively restricted to rhombomere (r) 4 in the hindbrain. Analysis of the chick and mouse Hoxb-1 genes identified positive and negative regulatory regions that cooperate to mediate segment-restricted expression during rhombomere formation. An enhancer generates expression extending into r3 and r5, and a repressor limits this domain to r4. The repressor contains a conserved retinoic acid response element, point mutations in which allow expression to spread into adjacent rhombomeres. Retinoids and their nuclear receptors may therefore participate in sharpening segment-restricted expression of Hoxb-1 during rhombomere boundary formation.

Animals↗

PubMed1994

A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1.

Within the Hoxb homeobox gene complex, Hoxb-1 is the earliest member expressed in the mesoderm and neuroectoderm of primitive streak and presomite embryos, preceding rhombomere-restricted expression in the hindbrain. Ectopic exposure of embryos to retinoic acid alters spatial aspects of Hox gene expression patterns. However, the role of retinoids in regulating these genes during normal development is unclear. We have now identified two enhancers, 3' of the mouse Hoxb-1 gene, which together reconstruct the early endogenous expression pattern and mediate the early ectopic response to retinoic acid. Furthermore, these regions are functionally conserved in both chicken and pufferfish (Fugu rubripes) Hoxb-1 genes. The enhancer that controls the retinoic acid response, and regulates expression predominantly in neuroectoderm, contains a retinoic acid response element (RARE). Point mutations in the RARE abolish expression in neuroectoderm. Therefore, this RARE is not only involved in the ectopic response to retinoic acid, but is also essential for establishing aspects of the early Hoxb-1 expression pattern.

Animals↗

PubMed1994

[Quality assurance in nursing: nursing standard. Nausea, gagging and vomiting during emetogenic cytostatic therapies. Report of research into the development and introduction of nursing standards].

This report documents the introduction of standard-setting in the haemato-oncological reverse-isolation unit of the Kanton hospital, Basle. The topic is the prevention or reduction of nausea, choking and vomiting, and the treatment of patients who are receiving prolonged chemotherapy. The objective was quality assurance in nursing care. The definition of the desired outcome was the well-being and safety of patients. In addition the wish of the staff to increase their security in dealing with antiemetics was taken into consideration. The authors describe the basic problems they encountered in their strategies and actions for standard setting. By extensive use of measurement and evaluation it was possible, in cooperation with medical leadership, to develop instructional leaflets and checklists. Approximation to the intended outcome was achieved. The well being of patients and satisfaction of the safety-needs of staff and patients reached a high level. The report shows that the introduction of nursing standards requires great effort and a high level of commitment of the entire team. It also shows that the effort is worthwhile for patients and staff.

Antineoplastic Agents↗

PubMed1993

[Work load in occupations].

Fewer subjects return to work after acute myocardial infarction or a cardiac surgical procedure than one would expect from the results of their medical examinations and cardiac tests. To decide whether a patient is able to return to work, one has to assess his individual prognosis and measure his maximal physical working capacity without cardiac dysfunction. Psychological and socioeconomic aspects have also to be considered. Recommendations are presented for practical procedure in assessing the ability of a patient to return to work.

Adaptation, Psychological↗

PubMed1993

Hox homeobox genes and regionalisation of the nervous system.

The Hox family of homeobox-containing genes are intimately associated with the processes of axial patterning in vertebrate embryos. This family of transcription factors is widely conserved in evolution and by analogy with their Drosophila counterparts, the HOM-C homeotic genes, may play a role in establishing regional identity in a number of embryonic systems, including the CNS. The patterns of expression of these genes are linked with the generation of rhombomeres and neural crest in the developing hindbrain, and suggest that they provide a molecular system for generating a combinatorial patterning mechanism. Analysis of mouse Hox mutants generated by homologous recombination have clearly demonstrated that the genes have important roles in normal regionalisation of the hindbrain and branchial arches, and this has lead to interest in how their early patterns are established in the nervous system. The Hox genes and their relation to hindbrain segmentation therefore provide a means of examining the cascade of events which regulates pattern formation in early neural development.

Animals↗

PubMed1993

The internal mammary artery 'string phenomenon'. Analysis of 10 cases.

The internal mammary artery (IMA) string sign has been described as a narrowing of IMA grafts in the late course after coronary artery bypass grafting. It has been assumed that this phenomenon was due to competitive flow in grafts connected to only mildly stenosed coronary arteries. We analyzed 10 cases of IMA string sign operated on between March 1988 and June 1991. Bilateral IMA was used in six cases and unilateral IMA in four. The mean interval between operation and reangiography was 14 +/- 11 months. String sign of the whole length of the IMA was detected in nine cases, and of the distal part between two sequential anastomoses in one. In all cases, the stenosis of the vessel bypassed with the narrowed graft proved to be only mild (50% or less) at reangiography. In all six cases with bilateral IMA grafts, the contralateral IMA was widely patent. These were all connected to highly stenosed or occluded coronary arteries. With respect to this observation, there is a high index of suspicion that the string phenomenon occurs due to competitive flow in only mildly stenosed coronary arteries. We decided, for our strategy in coronary artery surgery, still to aim at complete revascularization using IMAs as much as possible, but to avoid connecting IMA grafts to only mildly or moderately stenosed coronary arteries.

Coronary Angiography↗

PubMed1992

Similar endothelium-dependent relaxation, but enhanced contractility, of the right gastroepiploic artery as compared with the internal mammary artery.

The right gastroepiploic artery is an alternative coronary bypass graft. The excellent graft function of the internal mammary artery has been related to its physiologic properties, particularly to endothelial function. Isolated artery rings were suspended in organ chambers for recording of isometric tension. Norepinephrine and potassium chloride evoked threefold greater contractions in the gastroepiploic artery than in the mammary artery (p less than 0.01 to 0.05), whereas the sensitivity to the catecholamine was comparable. Acetylcholine induced endothelium-dependent relaxations, but the sensitivity (pD2: 6.7 +/- 0.3) and maximal relaxation (81% +/- 9%) were slightly less in the gastroepiploic artery than in the mammary artery (pD2: 7.6 +/- 0.2; 100% +/- 0%; p less than 0.05). Histamine induced endothelium-dependent relaxations with a similar sensitivity (pD2: 7.5 +/- 0.3 and 7.2 +/- 0.1), whereas the maximal relaxation was slightly enhanced in the gastroepiploic artery. The relaxation to the nitric oxide donor SIN-1 was identical in the two arteries. Thus the right gastroepiploic artery exhibits better contractility than the internal mammary artery but comparable endothelium-dependent and endothelium-independent relaxations. The good endothelial function of the gastroepiploic artery might be important for graft function and patency, whereas the enhanced contractility may facilitate vasospasm, especially in the presence of high circulating levels of catecholamines.

Acetylcholine↗

PubMed1991

Characterization of a second promoter for the mouse liver/bone/kidney-type alkaline phosphatase gene: cell and tissue specific expression.

The second leader exon and the relative promoter of the mouse liver/bone/kidney-type alkaline phosphatase gene were identified and characterized. The transcription initiation site was determined by S1 mapping analysis. The differential expression of the two alternatively spliced transcripts was assessed in cell lines of different origin and in various tissues by polymerase chain reaction and RNase mapping analysis. The first promoter is active in embryo derived cells, whereas the second promoter is silent in basal conditions but it is activated by dibutyryl cAMP in fibroblastic cells. In the whole animal, the transcript driven by the first promoter is found in most tissues albeit at different levels, while the one driven by the second promoter is specifically expressed at high levels only in the heart.

Alkaline Phosphatase↗