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Biomedical subjects

H Haller

Publications and source records attributed to H Haller.

At least 37 records · Page 2Linked to original sources

[Modern differential therapy with diuretics].

Diuretics block different electrolyte transporters in renal tubular cells. Their predominant action is inhibition of renal sodium chloride reabsorption, however, and achievement of a negative body sodium balance is the principal goal of diuretic therapy in patients with hypertension and edema. Several classes of diuretics can be distinguished with respect to the sites of sodium reabsorption along the nephron, but loop diuretics and distal-tubular diuretics (incl. thiazides) are the most widely used. The latter have a less potent natriuretic effect than loop diuretics, but their long duration of action predispose them for treatment of patients with uncomplicated hypertension. In conditions of gross edema, e.g. heart and/or renal failure, distal-tubular diuretics lose their efficacy and must be replaced by or combined with loop diuretics ("sequential nephron blockade"). Aldosterone antagonists are unique among diuretics because they improve survival in patients with heart failure independently of their effect on sodium metabolism.

Benzothiadiazines↗

A novel multimedia tool to improve bedside teaching of cardiac auscultation.

Training in cardiac auscultation is a core element of undergraduate teaching but recent studies have documented a remarkable decline in auscultatory skills. Therefore there is an interest in new ways to teach cardiac auscultation. In analogy to phonocardiography, an electronic system for simultaneous auscultation and visualisation of murmurs was sought. For this purpose, an electronic stethoscope was linked to a laptop computer and software created to visualise auscultatory findings. In a preliminary trial in undergraduate students, this approach greatly facilitated teaching. Amalgamating traditional phonocardiography with a multimedia approach, this system represents a novel tool for bedside teaching of cardiac auscultation.

Education, Medical, Undergraduate↗

Low dialysance of asymmetric dimethylarginine (ADMA)--in vivo and in vitro evidence of significant protein binding.

BACKGROUND: Increased blood levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) predict cardiovascular mortality in patients with end-stage renal disease. Despite its low molecular weight, available information on the impact of hemodialysis (HD) on ADMA plasma levels is controversial. METHODS: We assessed plasma concentrations, dialyzer clearance and total amount of ADMA removed in 30 patients with end-stage renal disease during regular HD. In addition, plasma ADMA levels were assessed in 10 patients with acute renal failure treated with extended HD. RESULTS: Regular HD decreased plasma creatinine (from 774 +/- 42 to 312 +/- 17 micromol/l) and urea (from 24.5 +/- 1.5 to 8.4 +/- 0.5 mmol/l) concentrations significantly (both p < 0.001), whereas plasma ADMA remained unchanged (4.35 +/- 0.19 vs. 4.76 +/- 0.24 micromol/l). ADMA clearance was 92 +/- 6 ml/min, and the total amount removed in the spent dialysate was 37 +/- 4 micromol. The clearances of creatinine (161 +/- 3 ml/min) and of urea (173 +/- 3 ml/min) were significantly higher. Furthermore, even during extended HD, plasma ADMA concentrations did not decrease significantly (1.73 +/- 0.22 vs. 1.63 +/- 0.18 micromol/l). CONCLUSION: In conclusion, dialysance of ADMA is markedly lower than expected from its molecular weight because of significant protein binding of the substance. Since markedly increased ADMA blood concentrations have been linked to cardiovascular complications due to atherosclerosis in patients with ESRD, new strategies should be evaluated to remove this putative uremic toxin.

Arginine↗

[Simultaneous reimplantation of both lower legs--5-year follow-up (case report)].

We are reporting the case of a 29 year old male in whom we performed successful reimplantaton of both lower legs following trauma inflicted by a railroad boxcar. Five years after this accident, the patient's walk is almost normal and both deep sensitivity and two point discrimination on the soles of his feet are sufficient. The patient can walk, run and stand very well on one leg, both on even and on uneven ground.He returned to his job with the railroad 8 months after his accident. Originally the patient was employed as a railroad workman, and is now an office employee. His private life is normal and he enjoys hiking and dancing. In our opinion, sufficient function of the tibial nerve in the reconstructed extremity is important for clinically satisfactory long-term results. Both the Mangled Extremity Severity Score (MESS) and the NISSSA are helpful in making the decision on whether to primarily amputate or reconstruct Gustillo IIIC cases. Good long-term results as well as general cost reduction are achievable following reconstruction of extremities. Amputation of an extremity can be predicted with 100% certainty when MESS is 9 or more. Primary shortening and secondary lengthening of an extremity is a good method of treating Gustillo III C fractures.

Accidents, Occupational↗

Treatment of chronic neuropathic pain after traumatic central cervical cord lesion with gabapentin.

Central cord syndrome may be associated with severe pain, resistant to conventional pain therapy regimens. Chronic pain may be a persistent problem in rehabilitation of spinal cord injuries. These pain syndromes are long lasting and challenging to treat. Gabapentin has been shown to be useful in treatment of different conditions which may be caused by increased neuronal excitability. This report describes a case where central cord syndrome and its chronic neuropathic pain associated with allodynia was successfully treated with gabapentin.

Acetates↗

Endogenous nitric oxide synthase inhibitors and renal perfusion in patients with heart failure.

BACKGROUND: Patients with heart failure are characterized by impaired nitric oxide-dependent endothelial vasodilation and, in addition, by reduced renal perfusion. DESIGN: We assessed blood concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal haemodynamics to compare normotensive patients with mild heart failure (n = 12, seven males, 70 +/- 1 years, 72.0 +/- 2.7 kg, 92 +/- 2 mmHg, NYHA I/II) and healthy subjects matched with respect to gender, age and body weight (n = 12, seven males, 69 +/- 2 years, 72.7 +/- 2.5 kg, 88 +/- 2 mmHg). RESULTS: Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (P < 0.01) and effective renal plasma flow (ERPF) significantly lower (P < 0.01) in the patients with heart failure (ADMA 4.18 +/- 0.42 micro mol L-1, RVR 159 +/- 12 mmHg mL-1 min-1, ERPF 381 +/- 26 mL min-1 1.73 m-2) as compared with the healthy controls (ADMA 2.38 +/- 0.11 micro mol L-1, RVR 117 +/- 8 mmHg mL-1 min-1, ERPF 496 +/- 19 mL min-1 1.73 m-2). In contrast, plasma concentrations of l-arginine, homocysteine, symmetric dimethylarginine (i.e. the biologically inactive stereoisomer of ADMA) and plasma renin activity were not significantly different in both groups studied. In the multiple regression analysis, only plasma ADMA concentrations independently predicted reduced ERPF (r = -0.57; P < 0.003). CONCLUSIONS: In normotensive patients with heart failure plasma ADMA concentrations are markedly increased and related to reduced renal perfusion. Thus accumulation of this endogenous nitric oxide inhibitor may play a role in renal pathology in these patients.

Aged↗

Efficiency of high-flux hemodialysis in the treatment of valproic acid intoxication.

Recently, highly efficient (i.e., high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit. They also can be a safer, more effective, and less costly alternative to traditional extracorporal techniques in the treatment of severe intoxication. This holds true even if the substance to be eliminated is believed to be a poor candidate for dialysis treatment. We report a case of successful treatment of potentially life-threatening intoxication, with valproic acid (VPA) using a GENIUS batch dialysis system for combined standard and extended high-volume hemodialysis therapy. Concentration of VPA in the total collected dialysate were measured.

Adult↗

Modelling human burn injuries in a three-dimensional virtual environment.

This paper gives a work-in-progress report on our research project BurnCase, a virtual environment for modelling human burn injuries. The goal of the project is to simplify and improve the diagnosis and medical treatment of burns. Due to the lack of electronic and computational support for current diagnosis methods, enormous variations regarding the approximated size of burned skin regions exist. And although Simplifications like the Rule-Of-Nines-Method ([Weidringer, 2002]), Lund and Browder ([LundBrowder, 1944]) and others try to compensate for these errors, the fact remains that different physicians overestimate the BSA (Body Surface Area) by 20% up to 50%, depending on the different experience and subjectivity of the approximation process. Nevertheless, different supporting mechanisms have been developed to assist the process of burn region transfer so that after transferring all burned regions on the virtual human body, calculations can be applied in order to evaluate standard indices like the ABSI (Abbreviated Burn Severity Index), and Baux ([Baux, 1989]) as well as ICD10 (International Classification of Diseases) diagnosis encoding. The virtual body simulation is based on state-of-the-art 3D computer graphics (OpenGL). Thus a simulation system, providing a graphical user interface, allows surgeons to transfer a patient's burn injury regions onto an appropriate 3-dimensional model. As such, the BurnCase system improves surface determination by calculating region surfaces up to a precision of one cm2. This improves the average variation to less than 5%, limited by the precision of the surface transfer onto the virtual model. The system already allows the transfer of burned regions by using standard input devices. For this purpose different reference models of human bodies have been created in order to receive appropriate results based on measured physical data of different patients. Moreover, an underlying database stores all entered case studies so that it is possible to perform comparisons of burn cases and animation sequences of the healing process of single wounds or whole bodies. When used as centralized burn accident registration service, a huge knowledge base of burn diagnoses and consequent medical treatment will emerge. This knowledge base will allow medical advices and diagnosis support for any kind of burn accidents, and it will consequently improve and support the primary diagnosis process of burn accidents. Thus, an enormous reduction of time and costs of medical burn treatment will be reached.

Burns↗

Vertebral osteomyelitis and endocarditis of a pacemaker lead due to Granulicatella (Abiotrophia) adiacens.

Systemic infection due to Granulicatella (formerly Abiotrophia), a species of nutrition-deficient gram-positive cocci, is rare. We present the case of a 68-year-old diabetic male who presented with back pain and a history of fever and chills. Imaging studies revealed vertebral osteomyelitis of the Th 10/11 region. Transesophageal echocardiography disclosed a vegetation adjacent to the pacemaker lead and blood cultures grew Granulicatella adiacens. A diagnosis of vertebral osteomyelitis and endocarditis due to G. adiacens was made and the patient improved with bed rest and medical treatment alone. Granulicatella ssp. should always be part of the differential diagnosis of fastidious bacteria in vertebral osteomyelitis and endocarditis.

Aged↗

Endothelial dysfunction, hypertension and atherosclerosis. A review of the effects of lacidipine.

Lacidipine, a third generation dihydropyridine calcium antagonist, has demonstrated pronounced anti-atherosclerotic activity in preclinical studies. The drug can act at several stages within the atherosclerotic process, utilising its antihypertensive and antioxidant properties to protect hypertensive animals against mortality and vascular damage, to reduce cholesterol levels from the vessel wall of hypercholesterolaemic animals, and to reduce the progression of existing atherosclerotic lesions. The clinical benefit of lacidipine in atherosclerosis has recently been confirmed in humans in a large, multicentre, comparative, 4-year clinical trial involving patients with mild to moderate hypertension. The European Lacidipine Study on Atherosclerosis (ELSA) showed that lacidipine was able to slow the progression of atherosclerosis, measured as carotid intimato-media thickness, by 40% compared with atenolol (p = 0.0073). Although further comparative trials are needed, based on the results of ELSA, lacidipine is likely to become a promising therapeutic agent for atherosclerosis.

Animals↗

Adenovirus-mediated gene transfer as a tool to study angiogenesis in the chick embryo.

Abstract. An adenoviral construct encoding a nuclear-localized beta-galactosidase marker protein was injected into the heart of chick embryos at Hamburger-Hamilton (HH) stage 14-15 (approximately 52-56 h of incubation). Reporter gene expression was determined 48-54 h after injection. Efficient gene transfer into endothelial cells (ECs) of intraembryonic and yolk sac vessels was observed. ECs of vessels in the head region, which undergo massive expansion around the time of injection, were efficiently labeled. However, limb bud vasculature, which starts to develop around stage 16 (HH), carried scarce (wing bud) or no (leg bud) lacZ marker. In contrast, ECs of the allantois, a structure that develops even later (around stage HH 18), expressed lacZ reporter. This observation suggests that EC precursors infected at an earlier time migrated into the allantois. A few non-endothelial cell types were also labeled by the reporter. These results suggest that adenovirus-mediated gene transfer provides a powerful tool to study angiogenesis in the developing chick embryo.

Adenoviridae↗

Regulation of calcium sparks and spontaneous transient outward currents by RyR3 in arterial vascular smooth muscle cells.

Intracellular Ca(2+) levels control both contraction and relaxation in vascular smooth muscle cells (VSMCs). Ca(2+)-dependent relaxation is mediated by discretely localized Ca(2+) release events through ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). These local increases in Ca(2+) concentration, termed sparks, stimulate nearby Ca(2+)-activated K(+) (BK) channels causing BK currents (spontaneous transient outward currents or STOCs). STOCs are hyperpolarizing currents that oppose vasoconstriction. Several RyR isoforms are coexpressed in VSMCs; however, their role in Ca(2+) spark generation is unknown. To provide molecular information on RyR cluster function and assembly, we examined Ca(2+) sparks and STOCs in RyR3-deficient freshly isolated myocytes of resistance-sized cerebral arteries from knockout mice and compared them to Ca(2+) sparks in cells from wild-type mice. We used RT-PCR to identify RyR1, RyR2, and RyR3 mRNA in cerebral arteries. Ca(2+) sparks in RyR3-deficient cells were similar in peak amplitude (measured as F/F(0)), width at half-maximal amplitude, and duration compared with wild-type cell Ca(2+) sparks. However, the frequency of STOCs (between -60 mV and -20 mV) was significantly higher in RyR3-deficient cells than in wild-type cells. Ca(2+) sparks and STOCs in both RyR3-deficient and wild-type cells were inhibited by ryanodine (10 micromol/L), external Ca(2+) removal, and depletion of SR Ca(2+) stores by caffeine (1 mmol/L). Isolated, pressurized cerebral arteries of RyR3-deficient mice developed reduced myogenic tone. Our results suggest that RyR3 is part of the SR Ca(2+) spark release unit and plays a specific molecular role in the regulation of STOCs frequency in mouse cerebral artery VSMCs after decreased arterial tone.

Animals↗

Altered gene expression in cerebral capillaries of stroke-prone spontaneously hypertensive rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) are a well-characterized, genetic model for stroke. We showed earlier that the structure and function of the tight junctions in SHRSP blood-brain barrier endothelial cells is disturbed prior to stroke. To investigate the molecular events leading to endothelial dysfunction in SHRSP cerebral capillaries, we carried out suppression subtractive hybridization (SSH) in combination with a cDNA filter screening step. We identified two cDNA fragments that were upregulated in SHRSP, compared to stroke-resistant spontaneously hypertensive rats (SHR), and found open reading frames of 133 and 138 amino acids, respectively. These peptides did not match any known proteins in public databases. A third upregulated SHRSP cDNA fragment was identified as the rat sulfonylurea receptor 2B (SUR2B). We also isolated and cloned the cDNA of the rat homologue for the mouse G-protein signaling 5 (RGS5) regulator. This regulator was downregulated in SHRSP. We used in situ hybridization to show that rat RGS5 is expressed in the brain capillary endothelium and in the choroid plexus. Our findings may lead to the identification of new stroke-related genes.

ATP-Binding Cassette Transporters↗

Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice.

Caveolae are plasma membrane invaginations that may play an important role in numerous cellular processes including transport, signaling, and tumor suppression. By targeted disruption of caveolin-1, the main protein component of caveolae, we generated mice that lacked caveolae. The absence of this organelle impaired nitric oxide and calcium signaling in the cardiovascular system, causing aberrations in endothelium-dependent relaxation, contractility, and maintenance of myogenic tone. In addition, the lungs of knockout animals displayed thickening of alveolar septa caused by uncontrolled endothelial cell proliferation and fibrosis, resulting in severe physical limitations in caveolin-1-disrupted mice. Thus, caveolin-1 and caveolae play a fundamental role in organizing multiple signaling pathways in the cell.

Albumins↗

Amelioration of angiotensin II-induced cardiac injury by a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. METHODS AND RESULTS: We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription-polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-kappaB and AP-1 were substantially less activated, although plasma cholesterol was not decreased. CONCLUSIONS: These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.

Angiotensin II↗