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Biomedical subjects

M Hauser

Publications and source records attributed to M Hauser.

At least 37 records · Page 2Linked to original sources
PubMed2003

Impaired myocardial blood flow and coronary flow reserve of the anatomical right systemic ventricle in patients with congenitally corrected transposition of the great arteries.

OBJECTIVES: To investigate myocardial blood flow of the morphological right systemic ventricle in unoperated patients with congenitally corrected transposition of the great arteries (CCTGA) by positron emission tomography (PET). DESIGN: Prospective cross sectional clinical study. SETTING: Tertiary referral centre for paediatric cardiology. PATIENTS: 15 patients with CCTGA were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilatation. A subgroup of seven patients had isolated CCTGA (group A, mean (SD) age 30.3 (11.9) years) and the remaining eight patients had complex CCTGA associated with subpulmonary stenosis; four of this second group also had ventricular septal defect (group B, mean (SD) age 30.6 (16.4) years). Eleven healthy adults (mean (SD) age 26.2 (5.1) years) served as the control group. RESULTS: Resting myocardial blood flow was not different between both groups of patients with CCTGA and the controls. Hyperaemic blood flows were significantly lower in both groups of CCTGA than in the control group (mean (SD) 195 (21) ml/100g/min in group A, 201 (27) ml/100g/min in group B, 309 (74) ml/100g/min in the control group; p < 0.001). Thus, coronary flow reserve was significantly lower in both groups of CCTGA than in the control group (mean (SD) 2.5 (0.28) in group A, 2.6 (0.48) in group B, and 4.0 (0.73) in the control group; p < 0.001). CONCLUSION: Blood flow measurements suggest that coronary reserve is decreased in the absence of ischaemic symptoms in patients with CCTGA. The global impairment of stress flow dynamics may indicate altered global vasoreactivity, and quantitative changes in microcirculation suggest that their role in the pathogenesis of systemic right ventricular dysfunction is important.

Adenosine↗
PubMed2002

Study of the binding environment of alpha-factor in its G protein-coupled receptor using fluorescence spectroscopy.

Mating in Saccharomyces cerevisiae is induced by the interaction of alpha-factor (W1H2W3L4Q5L6K7P8G9Q10P11M12Y13) with its cognate G protein-coupled receptor (Ste2p). Fifteen fluorescently labeled analogs of alpha-factor in which the 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group was placed at the alphaN-terminus and in side-chains at positions 1, 3, 4, 6, 7, 12 and 13 were synthesized and assayed for biological activity and receptor affinity. Eleven of the analogs retained 6-60% of the biological activity of the alpha-factor, as judged using a growth arrest assay. The binding affinities depended on the position of NBD attachment in the peptide and the distance of the tag from the backbone. Derivatization of the positions 3 and 7 side-chains with the NBD group resulted in analogs with affinities of 17-35% compared with that of alpha-factor. None of the other NBD-containing agonists had sufficient receptor affinity or strong enough emission for fluorescence analysis. The position 3 and 7 analogs were investigated using fluorescence spectroscopy and collisional quenching by KI in the presence of Ste2p in yeast membranes. The results showed that the lambda max of NBD in the position 7 side-chain shifted markedly to the blue (510 nm) when separated by 4 or 6 bonds from the peptide backbone and that this probe was shielded from quenching by KI. In contrast, separation by 3, 5, 10 or more bonds resulted in lambda max ( approximately 540 nm) and collisional quenching constants consistent with increasing degrees of exposure. The NBD group in the position 3 side-chain was also found to be blue shifted (lambda max=520 nm) and shielded from solvent. These results indicate that the position 7 side-chain is likely interacting with a pocket formed by extracellular domains of Ste2p, whereas the side-chain of Trp3 is in a hydrophobic pocket possibly within the transmembrane region of the receptor.

Fluorescent Dyes↗
PubMed2001

High-altitude pulmonary edema is initially caused by an increase in capillary pressure.

BACKGROUND: High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation. It is not known, however, whether the primary event is an increase in pressure or an increase in permeability of the pulmonary capillaries. METHODS AND RESULTS: We studied pulmonary hemodynamics, including capillary pressure determined by the occlusion method, and capillary permeability evaluated by the pulmonary transvascular escape of 67Ga-labeled transferrin, in 16 subjects with a previous HAPE and in 14 control subjects, first at low altitude (490 m) and then within the first 48 hours of ascent to a high-altitude laboratory (4559 m). The HAPE-susceptible subjects, compared with the control subjects, had an enhanced pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean pulmonary artery pressures (37 +/- 2 versus 26 +/- 1 mmHg, P<0.001) and pulmonary capillary pressures (19 +/- 1 versus 13 +/- 1 mmHg, P < 0.001) at high altitude. Nine of the susceptible subjects developed HAPE. All of them had a pulmonary capillary pressure >19 mm Hg (range 20 to 26 mmHg), whereas all 7 susceptible subjects without HAPE had a pulmonary capillary pressure < 19 mm Hg (range 14 to 18 mm Hg). The pulmonary transcapillary escape of radiolabeled transferrin increased slightly from low to high altitude in the HAPE-susceptible subjects but remained within the limits of normal and did not differ significantly from the control subjects. CONCLUSIONS: HAPE is initially caused by an increase in pulmonary capillary pressure.

Adult↗
PubMed2001

Myocardial blood flow and flow reserve after coronary reimplantation in patients after arterial switch and ross operation.

BACKGROUND: Coronary reimplantation is used in therapy for congenital heart disease, such as in the arterial switch (ASO) and Ross operations. The adequacy of myocardial perfusion may remain a matter of concern. The aim of the present study was to stratify the effect of coronary reimplantation on myocardial perfusion and to highlight the clinical relevance of any attenuation in myocardial perfusion. METHODS AND RESULTS: A total of 21 children with transposition of the great arteries at a mean interval of 11.2+/-2.9 years after ASO and 9 adolescents at a mean interval of 4.2+/-2.1 years after the Ross procedure were investigated. All patients were asymptomatic and had a normal exercise capacity. On stress echocardiography, 2 of the ASO patients had dyskinetic areas within the left ventricular myocardium, and 5 had adenosine-induced perfusion defects on positron emission tomography. No coronary obstruction was detected on coronary angiography in any patient, but a common finding was right coronary dominance and a small caliber of the distal part of the left anterior descending artery. Coronary flow reserve (CFR) was significantly reduced in all patients after ASO when compared with 10 normal healthy volunteers (age, 25.6+/-5.3 years). CFR was normal in the 9 patients who had the Ross operation (age, 19.2+/-7.6 years); exercise-induced perfusion defects were not detected in the Ross patients. CONCLUSIONS: Children after ASO are asymptomatic, without clinical signs of coronary dysfunction. In contrast to patients who had the Ross operation, stress-induced perfusion defects and an attenuated CFR were documented. The prognostic implications of these findings and the clinical consequences are unclear; nevertheless, close clinical follow-up of ASO patients is mandatory.

Adolescent↗
PubMed2001

Probing the binding domain of the Saccharomyces cerevisiae alpha-mating factor receptor with rluorescent ligands.

Three analogues of the alpha-mating factor pheromone of Saccharomyces cerevisiae containing the 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group were synthesized that had high binding affinity to the receptor and retained biological activity. The fluorescence emission maximum of the NBD group in [K7(NBD),Nle(12)]-alpha-factor was blue shifted by 35 nm compared to buffer when the pheromone bound to its receptor. Fluorescence quenching experiments revealed that the NBD group in [K7(NBD),Nle(12)]-alpha-factor bound to the receptor was shielded from collision with iodide anion when in aqueous buffer. In contrast, the emission maximum of NBD in [K7(ahNBD),Nle(12)]-alpha-factor or [Orn7(NBD),Nle(12)]-alpha-factor was not significantly shifted and iodide anion efficiently quenched the fluorescence of these derivatives when they were bound to receptor. The fluorescence investigation suggests that when the alpha-factor is bound to its receptor, K7 resides in an environment that has both hydrophobic and hydrophilic groups within a few angstroms of each other.

4-Chloro-7-nitrobenzofurazan↗
PubMed2001

Spontaneous volume changes in gastric banding devices: complications of a semipermeable membrane.

The goal of this study was to prove that adjustable laparoscopic gastric banding (LAP-BAND) is semipermeable and that luminal adjustment with saline leads to spontaneous fluid loss, luminal widening, and effect loss which makes repeated readjustments necessary. In 64 patients stoma adjustment was performed with saline according to the guidelines of the manufacturer (group 1). In 32 patients hyperosmolar contrast material was used for stoma readjustments with the intention to detect a system leakage after spontaneous fluid loss and spontaneous luminal widening was observed (group 2). After spontaneous luminal narrowing had occurred in group 2, all patients from group 2 and all additional patients (n = 148) underwent stoma (re-) adjustment with iso-osmolar contrast material (group 3). Spontaneous fluid changes which led to spontaneous changes of the luminal width were then analyzed for the different filling substances in each group. Fifty-two patients from group 1 presented with effect loss because a spontaneous luminal widening had occurred secondary to a fluid loss of 0.1-0.2 ml/month. All 32 patients from group 2 presented with increasing obstruction and food intolerance because a spontaneous luminal narrowing had occurred secondary to a spontaneous fluid gain of 0.1-0.3 ml/month. In our patients from group 3, where stoma adjustment was performed with iso-osmolar contrast material, no spontaneous fluid changes were observed and luminal width/degree of obstruction did not change. The LAP-BAND is semipermeable. Stoma adjustment should not be performed with saline in order to avoid spontaneous luminal widening and the need for repeated readjustments. Stoma adjustments with hyperosmolar contrast material are clearly contraindicated since osmotic fluid gain leads to increasing obstruction. Stoma adjustments should be performed using iso-osmolar filling media which provide a stable luminal obstruction.

Contrast Media↗
PubMed2001

Diagnosis of anthracycline-induced late cardiomyopathy by exercise-spiroergometry and stress-echocardiography.

UNLABELLED: Anthracyclines are used in the therapy of several of the most common paediatric oncological disorders. The usefulness of these agents is limited by cardiotoxicity, with congestive heart failure developing in up to 20% of patients. To stratify possible risk factors, we investigated 38 children with acute lymphoblastic leukaemia for signs of late cardiomyopathy. Exercise-spiroergometry and stress-echocardiography with measurement of fractional shortening (FS) and ejection fraction (EF) as indicators of left ventricular function were performed. ECG, 24 h Holter monitoring, chest X-ray, virus serology and carnitine were analysed. Control subjects were 38 healthy children matched for age and body surface area. All 38 patients had normal echocardiographic findings at rest (EF: 0.73 +/- 0.06; FS: 0.35 +/- 0.05). ten patients had a significant attenuation of left ventricular function after exercise assessed by stress-echocardiography compared to the remaining 28 patients and 38 healthy control subjects (EF: 0.52 +/- 0.08 versus 0.77 +/- 0.06 and 0.80 +/- 0.08; FS: 0.29 +/- 0.06 versus 0.39 +/- 0.05 and 0.41 +/- 0.02); patients with reduced ventricular function after exercise had significant low anaerobic threshold, subnormal maximal oxygen uptake and decreased carnitine levels. The findings were not related to the dosage of administered doxorubicin. There exists no correlation between ECG, 24 h ECG, chest X-ray, virology and left ventricular dysfunction. The benefit of angiotensin converting enzyme inhibitors and the administration of carnitine remains speculative. CONCLUSION: exercise-spiroergometry and stress-echocardiography are sensitive investigations for diagnosing subclinical cardiomyopathy late after completion of chemotherapy. Investigative findings of cardiomyopathy are not dose related and may provide information for therapeutic prevention before clinical symptoms of cardiomyopathy appear.

Antibiotics, Antineoplastic↗
PubMed2001

Spontaneous representation of number in cotton-top tamarins (Saguinus oedipus).

The "violation of expectancy" looking-time methodology has proven a powerful tool for exploring prelinguistic mental representations in human infants as well as in nonhuman primates. Four studies applying this methodology to the question of spontaneous number representations in cotton-top tamarins (Saguinus oedipus) are reported here. Monkeys were shown 1 + 1 events in which objects were placed behind a screen, 1 by 1. The screen was removed, revealing consistent (2 objects) and inconsistent (1, 3, or 1 large object twice the mass of original object) outcomes. In all studies, monkeys looked longer at the inconsistent than at the consistent outcome. When the monkeys view a 1 + 1 operation, they expect exactly 2 objects. It is likely that these numerical representations are spontaneously available to a variety of primate species and could provide a foundation on which humans' number sense was constructed over evolution and development.

Animals↗
PubMed2001

Treatment of autonomous and toxic thyroid adenomas by percutaneous ultrasound-guided ethanol injection.

PURPOSE: To evaluate the feasibility and efficacy of US-guided percutaneous ethanol injection (PEI) in the treatment of autonomous and toxic thyroid adenomas. MATERIAL AND METHODS: PEI was performed in 42 patients with solitary, scintigraphically "hot" nodules (n=37) or toxic nodular goiter (n=5). The nodular volume ranged from 2.5 to 38 cm3 (mean volume, 20.7+/-14.1 cm3). Ethanol was injected using a free-hand technique, usually in multiple sessions, using color and power Doppler US guidance. Treatment success was evaluated following 3-4 months after PEI by scintigraphy, hormonal status, and US findings. RESULTS: The procedure was technically successful in 39 patients (93%). Three patients were lost to follow-up. Minor complications were pain (all patients), subcutaneous hematoma (n=6), and transitory dysphonia (n=1). A complete cure was achieved in 22 patients (52%), and a partial cure in 10 patients (24%). In 4 cases (9%), the result was unsatisfactory since only moderate hormonal remission was observed. A satisfactory results was thus achieved in 32/42 patients (76%). Significant nodular volume reduction was observed in all cases. Better results were observed in smaller nodules and in cases of autonomous adenomas. There were no cases of recurrent hyperthyreosis. CONCLUSION: US-guided PEI is an efficient and safe method in the treatment of autonomous thyroid nodules and it enables inactivation of nodules with minimal or transitory complications.

Adenoma↗
PubMed2001

WdChs2p, a class I chitin synthase, together with WdChs3p (class III) contributes to virulence in Wangiella (Exophiala) dermatitidis.

The chitin synthase structural gene WdCHS2 was isolated by screening a subgenomic DNA library of Wangiella dermatitidis by using a 0.6-kb PCR product of the gene as a probe. The nucleotide sequence revealed a 2,784-bp open reading frame, which encoded 928 amino acids, with a 59-bp intron near its 5' end. Derived protein sequences showed highest amino acid identities with those derived from the CiCHS1 gene of Coccidioides immitis and the AnCHSC gene of Aspergillus nidulans. The derived sequence also indicated that WdChs2p is an orthologous enzyme of Chs1p of Saccharomyces cerevisiae, which defines the class I chitin synthases. Disruptions of WdCHS2 produced strains that showed no obvious morphological defects in yeast vegetative growth or in ability to carry out polymorphic transitions from yeast cells to hyphae or to isotropic forms. However, assays showed that membranes of wdchs2Delta mutants were drastically reduced in chitin synthase activity. Other assays of membranes from a wdchs1Deltawdchs3Deltawdchs4Delta triple mutant showed that their residual chitin synthase activity was extremely sensitive to trypsin activation and was responsible for the majority of zymogenic activity. Although no loss of virulence was detected when wdchs2Delta strains were tested in a mouse model of acute infection, wdchs2Deltawdchs3Delta disruptants were considerably less virulent in the same model, even though wdchs3Delta strains also had previously shown no loss of virulence. This virulence attenuation in the wdchs2Deltawdchs3Delta mutants was similarly documented in a limited fashion in more-sensitive cyclophosphamide-induced immunocompromised mice. The importance of WdChs2p and WdChs3p to the virulence of W. dermatitidis was then confirmed by reconstituting virulence in the double mutant by the reintroduction of either WdCHS2 or WdCHS3 into the wdchs2Deltawdchs3Delta mutant background.

Amino Acid Sequence↗
PubMed2001

Molecular cloning and characterization of WdPKS1, a gene involved in dihydroxynaphthalene melanin biosynthesis and virulence in Wangiella (Exophiala) dermatitidis.

1,8-Dihydroxynaphthalene (1,8-DHN) is a fungal polyketide that contributes to virulence when polymerized to 1,8-DHN melanin in the cell walls of Wangiella dermatitidis, an agent of phaeohyphomycosis in humans. To begin a genetic analysis of the initial synthetic steps leading to 1,8-DHN melanin biosynthesis, a 772-bp PCR product was amplified from genomic DNA using primers based on conserved regions of fungal polyketide synthases (Pks) known to produce the first cyclized 1,8-DHN-melanin pathway intermediate, 1,3,6,8-tetrahydroxynaphthalene. The cloned PCR product was then used as a targeting sequence to disrupt the putative polyketide synthase gene, WdPKS1, in W. dermatitidis. The resulting wdpks1Delta disruptants showed no morphological defects other than an albino phenotype and grew at the same rate as their black wild-type parent. Using a marker rescue approach, the intact WdPKS1 gene was then successfully recovered from two plasmids. The WdPKS1 gene was also isolated independently by complementation of the mel3 mutation in an albino mutant of W. dermatitidis using a cosmid library. Sequence analysis substantiated that WdPKS1 encoded a putative polyketide synthase (WdPks1p) in a single open reading frame consisting of three exons separated by two short introns. This conclusion was supported by the identification of highly conserved Pks domains for a beta-ketoacyl synthase, an acetyl-malonyl transferase, two acyl carrier proteins, and a thioesterase in the deduced amino acid sequence. Studies using a neutrophil killing assay and a mouse acute-infection model confirmed that all wdpks1Delta strains were less resistant to killing and less virulent, respectively, than their wild-type parent. Reconstitution of 1,8-DHN melanin biosynthesis in a wdpks1Delta strain reestablished its resistance to killing by neutrophils and its ability to cause fatal mouse infections.

Amino Acid Sequence↗
PubMed2001

Anterior versus posterior slippage: two different types of eccentric pouch dilatation in patients with adjustable laparoscopic gastric banding.

PURPOSE: To describe two different types of band dislocation that may occur in morbidly obese patients following adjustable laparoscopic gastric banding (ALGB) with the LAP-BAND. MATERIALS AND METHODS: 170 morbidly obese patients were treated with an LAP-BAND at our institution. In the first 20 patients the band was positioned transbursally, which means that the lesser sac is penetrated during laparoscopic band implantation. In the following 150 patients the operation technique was changed to suprabursal band positioning where the lesser sac is not penetrated. Plain radiographs and single contrast studies of all patients who developed band instability in the follow-up were analyzed retrospectively and compared to the clinical and intraoperative findings and to the operation technique used. RESULTS: Over a time period of 3.5 years 'posterior slippage' occurred in all 20 patients with transbursal band placement, but it never occurred after suprabursal band placement. Never- theless 4 patients with suprabursal band placement presented with an eccentric pouch dilatation, secondary to 'anterior slippage' after the seromuscular stitches had burst on the anterior and superior surface of the band. All these patients presented with food intolerance and all of them had to be reoperated. The radiographic findings were pathognomonic for each type of band dislocation. CONCLUSION: Band dislocation is a known major complication that may occur following ALGB and it may present in two different forms. While 'posterior slippage' can be avoided if the band is placed suprabursally, 'anterior slippage' may still occur. It is important to be familiar with both types of band dislocation since they require early detection and surgical band replacement or band refixation.

Body Mass Index↗
PubMed2001

Pseudo-achalasia following laparoscopically placed adjustable gastric banding.

BACKGROUND: The complication of pseudo-achalasia may occur after laparoscopic adjustable gastric banding (LAGB) in patients with normal band position and normal stomal width. We hypothesized that this complication occurs especially in patients with preexisting insufficiency of the lower esophageal sphincter (LES), who show poor compliance secondary to lacking the sensation of satiety and who therefore also have insufficient weight loss at follow-up. METHODS: Early and late postoperative barium meal studies of 120 LAGB patients were retrospectively analyzed to identify patients who developed esophageal widening and dysmotility despite normal band position and normal stomal width. Results were compared with preoperative endoscopies, clinical findings, each patient's compliance with dietary instructions and postoperative weight loss. RESULTS: 9/120 patients developed pouch dilatation, esophageal widening and esophageal dysmotility as a late complication, despite normal band position and normal stomal width. All these patients had shown preexisting insufficiency of their LES endoscopically. They all showed bad compliance with dietary instruction, and they all abused their distal esophagus as an additional pouch. 7 of these patients presented with insufficient weight loss at follow-up, whereas of 3 other patients with pre-existing LES insufficiency who had shown good compliance, only 1 showed insufficient weight loss. Insufficient weight loss after 1 year was significantly more common in patients with pre-existing LES insufficiency (8/12 patients, 67%) than in patients with a competent LES (26/108 patients, 24%). CONCLUSION: Patients with pre-existing LES insufficiency appear to be at risk for pouch dilatation and esophageal decompensation despite normal band position and normal stomal width. These patients are prone to show lack of satiety and poor compliance with dietary instruction, use of their lower esophagus as additional space for food, and tend to have insufficient weight loss. Preoperative manometry should be used to identify such patients, where the indication for gastric banding should be discussed very critically.

Adult↗
PubMed2001

Factor V Leiden mutation in postthrombotic and non-postthrombotic venous ulcers.

OBJECTIVE: To determine the prevalence of the factor V Leiden mutation in patients with postthrombotic and non-postthrombotic venous ulcers. DESIGN: Case-control study. SETTING: Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. PARTICIPANTS: Seventy-three consecutive outpatients and inpatients with venous ulcers and 45 age- and sex-matched control subjects (matched to the 42 patients with postthrombotic syndrome). MAIN OUTCOME MEASURES: Frequency of postthrombotic and non-postthrombotic findings in patients with venous ulcers. Prevalence of the factor V Leiden mutation in these different subgroups. RESULTS: Postthrombotic syndrome was identified as the cause of 42 (58%; 95% confidence interval [CI], 45%-69%) of 73 venous ulcers, and the remainder were caused by primary valvular insufficiency. In postthrombotic ulcers, the prevalence of the factor V Leiden mutation was 38% (95% CI, 24%-54%) (16/42), which corresponds to an odds ratio of 13.2 (95% CI, 2.8-62.3; P<.001). In non-postthrombotic venous ulcers, the prevalence was 16% (95% CI, 5%-34%) (5/31), which corresponds to an odds ratio of 3.2 (95% CI, 1.0-10.0; P =.07). CONCLUSIONS: The factor V Leiden mutation is highly prevalent in patients with postthrombotic venous ulcers. Even patients with non-postthrombotic venous ulcers show a moderately elevated prevalence of the factor V Leiden mutation. Some of the latter might be misclassified because of near-to-perfect revascularization after asymptomatic deep venous thrombosis. However, as long as the therapeutic consequences of the factor V Leiden mutation are not established, systematic screening cannot be recommended in patients with venous ulcers.

Aged↗
PubMed2000

[The value of bronchoalveolar lavage in the clarifying of HIV-associated lung diseases].

BACKGROUND AND OBJECTIVE: Examination of sputum is the first diagnostic step in the evaluation of HIV-infected patients with pulmonary complications. We were interested in the indications and the diagnostic value of subsequent bronchoscopy and bronchoalveolar lavage (BAL) and especially the importance of so-called atypical bacteria. PATIENTS AND METHODS: We analysed 59 consecutive BALs performed in HIV positive patients with pulmonary symptoms (48 men, 11 women, age 22-70 years, 36 in stage C). Culture for Legionella pneumophila and PCR analysis for Mycoplasma pneumoniae and Chlamydia pneumoniae were done in all cases. RESULTS: In 50 patients (85%) there was a clear indication for performing a BAL because either an infectious agent could no be detected on sputum examination (n = 36), or the patient's sputum production was insufficient (n = 14). In 30 (60%) of these cases bronchoscopy and BAL were able to establish a diagnosis. The most frequent agent was Pneumocystis carinii (n = 12). In contrast, BAL was able to establish coinfection in patients with positive sputum samples in one case only. So-called atypical bacteria were not found. CONCLUSION: In patients with a clear indication, especially a non-diagnostic sputum examination, BAL plays an important role in the work-up of HIV-associated pulmonary disease. The search for so-called atypical bacteria yields unsatisfactory results.

AIDS-Related Opportunistic Infections↗