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Biomedical subjects

S Heller

Publications and source records attributed to S Heller.

At least 19 recordsLinked to original sources

Percutaneous vascular interventions in the superficial femoral artery. A review.

The superficial femoral artery (SFA) is a frequent target of atherosclerotic disease predominantly in the proximal section near the bifurcation to the deep femoral artery and in the distal section where the adductor muscles tend to compress the artery. In the past, SFA revascularization was the domain of vascular surgery (femoropopliteal and femorodistal bypasses). However, with the development of endovascular treatment and advancing techniques as well as more sophisticated stenting material and balloons, endovascular treatment is nowadays not just a treatment option but, in most cases, preferable at least as initial revascularization procedure in the treatment of peripheral artery vascular disease. In the last years, many efforts have been made to fight restenosis in revascularized artery segments after stenting and/or angioplasty. This article aims to give a review on this topic including the most recent experience with the various latest revascularization techniques such as drug eluting stents, coated stent grafts, brachytherapy, cryoplasty, cutting balloons, and drug coated balloons.

Angioplasty, Balloon↗

[Pulmonary endarterectomy--the surgical treatment of chronic thromboembolic pulmonary hypertension].

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) in indicated cases can be successfully treated by the endarterectomy of pulmonary arteries (PEA). Symptomatically not treated CTEPH has highly unfavourable prognosis. Five years survival of patients with mean pulmonary pressure over 50 mmHg is only 10%. PEA was not available in the Czech Republic till 2004, when PEA program was initiated it the Cardiocenter of the General teaching hospital in Prague in collaboration with leading clinics in that field (Prof. Mayer, University of Mainz, BRD). METHODS AND RESULTS: Up-to-date surgical technique, which in various modifications has been used at majority of clinics, was elaborated by Jamieson and Daily at University of California in San Diego. It is based on reverse endarterectomy performed during complete circulatory arrest with brain protection by deep hypothermia. Till September 2005 twelve patients were operated with zero mortality. In one patient a suture of atrial septum defect was necessary to perform along. Average time of the circulatory arrest was 45 minutes; duration of the extracorporal circulation was 334 minutes. Average duration of the operation was 450 minutes. Duration of the mechanical ventilation was in average 45.5 hours. After one month already haemodynamic parameters (mPA, CI, PVR) significantly improved or normalized and the average length in the test of six minutes walking increased by 132 meters. CONCLUSION: PEA represents a treatment method for patients with CTEPH and surgically accessible pulmonary artery obstruction. Centralized care of those patients is a rational necessity enabling to get maximum experience with complicated diagnostics and treatment of those patients. Multidisciplinary collaboration is the essential condition for the success of the program.

Adult↗

[Endovascular treatment of acute vascular occlusions].

Acute vascular occlusion is a medical emergency and often a life threatening situation. It is caused by embolization into local arteries, by thrombosis or by occlusion of peripheral arterial bypass grafts. Percutaneous thrombectomy and local thrombolysis represent well established techniques for the treatment of acute limb ischemia and massive deep venous thrombosis especially for ileofemoral and ileocaval occlusion. The new techniques of thrombectomy allow very effective and minimally invasive therapy of acute vascular occlusions.

Acute Disease↗

Identification of chicken transmembrane channel-like (TMC) genes: expression analysis in the cochlea.

Mutations of the human gene encoding transmembrane channel-like protein (TMC)1 cause dominant and recessive nonsyndromic hearing disorders, suggesting that this protein plays an important role in the inner ear. In this study, we cloned chicken Tmc2 (GgTmc2) from a cochlear cDNA library and we annotated four additional TMC family members: GgTmc1, GgTmc3, GgTmc6, and GgTmc7. All chicken TMCs possess the defining TMC signature motif and display high conservation of their genomic structure when compared with other vertebrate TMC genes. GgTmc1 is localized on the chicken sex chromosome Z at a locus that displays conserved synteny with the loci of mammalian orthologues residing on autosomes. In contrast, the locus of GgTmc2 does not exhibit conserved synteny with its mammalian orthologues. Because murine TMC1 and TMC2 are restrictively expressed in cochlear hair cells, we determined the expression of the chicken orthologues in the basilar papilla, the avian equivalent of the organ of Corti. While GgTmc2 was present throughout the basilar papilla and in other tissues, GgTmc1 transcript was detected specifically in the basal portion of the basilar papilla and was not detectable in any other tissue or organ studied. GgTmc3 and GgTmc6 were detectable in all organs analyzed. Antibody labeling revealed that GgTmc2 is predominantly associated with the lateral membranes of hair and supporting cells. The expression of GgTmc2 by both cell types was further confirmed by RT-PCR using isolated cells. This expression and subcellular localization of GgTmc2 is in agreement with the proposed potential role of this novel class of transmembrane proteins in ion transport.

Amino Acid Sequence↗

Adolescents' and their parents' views on the acceptability and design of a new diabetes education programme: a focus group analysis.

BACKGROUND: The present study was conducted as part of an ongoing project to develop an innovative educational intervention for young people with type 1 diabetes. We aimed to seek the views of children and adolescents with type 1 diabetes and their parents regarding (i) the acceptability of the new programme and (ii) practical aspects regarding course design and delivery. METHODS: Twenty-four children and 29 parents attended one of eight separate focus groups. Semi-structured interview schedules were developed around two main areas of discussion: views on the education programme; and views on the design and delivery of current and future education. Discussions were tape-recorded and transcribed, before undergoing systematic qualitative analysis. RESULTS: Participants agreed that the proposed intervention was feasible, and were enthusiastic that it could improve quality of life and 'normality'. Potential problems included self-management during school-time and parental anxiety. In terms of course design/delivery, participants emphasized the need to maximize enjoyment on the course (e.g. integrating fun and practical sessions, holding parts of the course outside of the clinic setting), and encourage effective learning and adherence to the regimen (e.g. including separate parent education, and using IT-based reference material). CONCLUSIONS: The qualitative methodology proved an effective way of eliciting child and parent views and informing the development of the proposed intervention. These findings can now be incorporated into the development of the education programme.

Adolescent↗

A new autologous keratinocyte dressing treatment for non-healing diabetic neuropathic foot ulcers.

AIMS: To evaluate the use of a new cell-tailored carrier surface (TranCell) for delivery of autologous keratinocytes to promote wound healing in patients with chronic neuropathic foot ulcers. METHODS: TranCell is a sterile medical grade polymer coated with a plasma-polymerized functional surface containing 20% carboxylic acid which enables keratinocytes to attach and proliferate. Six diabetic patients with neuropathic ulcers resistant to conventional therapy were treated with weekly applications of autologous keratinocytes delivered on TranCell. A split-thickness skin biopsy was taken from each patient followed by isolation, expansion and freezing down of keratinocytes. Keratinocytes were thawed and seeded on TranCell 48 h prior to application. This procedure was repeated weekly in addition to conventional therapy until wound healing was achieved. RESULTS: Complete healing was achieved in six out of nine ulcers in six patients, a reduction in ulcer size was achieved in one ulcer and no response was seen in one ulcer. Treatment was discontinued in one patient due to development of Methicillin-Resistant Staphylococcus aureus (MRSA) after only three applications of TranCell. Wound healing took 6-17 applications over 6-20 weeks. There were no recurrences in the healed ulcers after a follow-up of 6 months. CONCLUSIONS: TranCell delivery of autologous cells is a promising treatment for chronic diabetic foot ulcers with no side-effects and no recurrence in the healed ulcers.

Adult↗

Cost-effectiveness of flexible intensive insulin management to enable dietary freedom in people with Type 1 diabetes in the UK.

AIMS: To determine the cost-effectiveness of a structured treatment and teaching programme (STTP) combining dietary freedom with insulin adjustment for Type 1 diabetes. METHODS: Incremental cost-effectiveness analysis based on effectiveness data from three RCTs in Germany, Austria, and Dose Adjustment for Normal Eating (DAFNE) in the UK, to model the long-term microvascular complications of Type 1 diabetes. RESULTS: The STTP approach yields effectiveness gains at a lower cost compared with current standard practice for treatment of Type 1 diabetes. STTPs are likely to save 0.05 life years, yield 0.12 EuroQol 5 dimensions (EQ-5D) and 0.09 visual analogue scale (VAS) incremental quality-adjusted life years, and save approximately pound 2200 per patient treated discounted over 10 years. CONCLUSIONS: Introducing STTPs as standard treatment for people with Type 1 diabetes in the UK may help to achieve the primary goal of the National Service Framework (NSF) for Diabetes by enabling individuals to manage their own lifestyle and condition. In doing so it could save valuable resources for the NHS and yield important morbidity and mortality gains.

Blood Glucose↗

[Basic epidemiologic indicators of venous diseases].

Venous diseases are among the major causes of morbidity and mortality in The Czech Republic. The incidence of venous diseases increases rapidly with age, especially in those older than 65 years. Among discussed entities is the most important deep venous thrombosis and its complications--pulmonary embolism and postthrombotic syndrome. We discuss epidemiology of acute and chronic venous diseases in context of risk factors and offer a short outline of currently applied therapy. Then we focus on the new perspective possibilities of treatment of venous diseases especially in acute states (including local thrombolysis), on its influence of quality of life, on the progression of diseases into chronic states and on its socioeconomic consequences.

Aged↗

[Interventional therapy of the inferior vena cava syndrome].

Interventional procedures are becoming increasingly popular in the treatment of impaired patency of deep venous system caused most often by extensive phlebothrombosis. Restoration of patency to affected venous segments while preserving the valvular function with a high degree of success in a relatively short period of time can be achieved by combination of endovascular methods such as catheter guided thrombolysis followed by percutaneous transluminal angioplasty and stenting. This approach enables not only the resolution of acute vascular complications but also the prevention of postthrombotic syndrome. This case report of a 52-year-old man with retroperitoneal fibrosis causing chronic compression of vena cava inferior further complicated by travelling associated bilateral ileofemoral thrombosis clearly demonstrates the wide ranging applications of the endovascular techniques.

Angioplasty, Balloon↗

Reducing hypoglycaemia with insulin analogues.

Numerous studies have demonstrated that tight glycaemic control reduces long-term complications in both Type 1 and Type 2 diabetes. However, current intensive insulin regimens increase the risk of hypoglycaemia, dissuading many attempting this approach. Normal physiological insulin profiles consist of a stable, basal component and meal-related surges in secretion. Conventional insulin regimens cannot mimic this profile accurately due to pharmacokinetic limitations. Human insulin has a slow onset of action, thus patients are advised to inject about 30 min before a meal, ensuring peak insulin concentrations coincide with postprandial glucose excursions. This is clearly impractical for many and can lead to pre-meal hypoglycaemia if the meal is delayed. Furthermore, it only partially overcomes the unphysiological insulin profile and patients experience postprandial hyperglycaemia and are vulnerable to postabsorptive hypoglycaemia. Insulin aspart and insulin lispro are rapid-acting analogues that allow a more physiological replacement of mealtime insulin secretion. They reduce postprandial glucose and usefully reduce the incidence of hypoglycaemia when used in a basal-bolus regimen in tightly controlled patients. Pre-mixed insulins, containing a combination of rapid-acting and intermediate-acting insulin, are widely used, particularly in Type 2 diabetes. They have limitations achieving tight glucose targets but early data suggest that the combination of 30% insulin aspart and 70% protaminated insulin aspart may also reduce severe hypoglycaemia. On-going clinical trials will establish whether they can be used to achieve better glycaemic control with less hypoglycaemia.

Blood Glucose↗

Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors.

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.

Adult↗

Association analysis of Arg16Gly polymorphism of the beta2-adrenergic receptor gene in offspring from hypertensive and normotensive families.

OBJECTIVE: Since beta2-adrenergic receptors (beta2AR) can influence blood pressure not only by vasodilation, but also participate in noradrenaline release from sympathetic nerve endings, we have studied whether Arg16Gly polymorphism of the beta2AR gene is associated with predisposition to essential hypertension and increased plasma noradrenaline concentration in offspring from normotensive (SN) and hypertensive parents (SH). DESIGN AND METHODS: The study population consisted of 105 young SN and 101 SH subjects matched for age and body mass index. Arg16Gly polymorphism of the beta2AR gene was determined by polymerase chain reaction (PCR) technique and subsequent incubation with NcoI restriction enzyme. Resulting fragments were separated using electrophoresis on a 4.2% Metaphor agarose gel. RESULTS: SH already had significantly higher systolic BP, and a tendency to higher diastolic BP than the SN group. The frequency of Arg/Arg homozygotes was significantly increased in SH when compared to SN (25% vs 15%). Results of logistic regression analysis showed the highest relative risk for the Arg/Arg genotype and suggested a recessive action of the Arg16 variant. There was an increased diastolic BP in Arg/Arg homozygotes of the SN group (p = 0.029). This genotype also had a tendency to increased heart rate in both groups (p = 0.049). There was no relationship of this polymorphism with plasma noradrenaline concentration. CONCLUSION: Our findings suggest that genetic variability of the beta2AR gene is implicated in predisposition to essential hypertension. However, the contradictory results between individual studies indicate that the action of the beta2AR gene is indirect, through multiple intermediate phenotypes and gene interactions.

Adult↗

[Is mild essential hypertension without obvious organ complications and risk factors associated with increased levels of circulating markers of endothelial dysfunction? Effect of ACE inhibitor therapy].

The objective of the investigation was to assess whether circulating adhesion molecules, von Willebrand factor (vWf) and endothelin-1 are elevated in patients with mild uncomplicated essential hypertension without further risk factors of atherosclerosis and whether they could serve as indicators of endothelial dysfunction in this form of hypertension. Furthermore the authors investigated the effect of ACE inhibitor treatment (ACEI), quinapril, on the level of these markers of endothelial dysfunction. The level of adhesion molecules [intercellular cytoadhesion molecule-1 (ICAM-1), E-selectin, P-selectin], von Willebrand s factor (vWf) and endothelin-1 were assessed in patients with mild essential hypertension without further cardiovascular risk factors or clinical manifestations of atherosclerosis before and after quinapril treatment (n = 25) and compared with normotensive controls (n = 29). The results of the examinations provided evidence that contrary to controls the hypertensive subjects had significantly higher ICAM-1 levels (237.8 vs. 207.8 ng/ml, P = 0.02) vWf (118 vs. 106 IU/dl, p < 0.05) and endothelin-1 (5.81 vs. 5.15 fmol/ml, p < 0.05). Three-month treatment of hypertensive patients with ACEI led to a significant drop of endothelin-1 levels (5.81 vs. 5.26 fmol/ml, p = 0.01). The authors proved also an unequivocal declining trend of other cytoadhesion molecules and vWf after ACEI treatment, the changes however were not statistically significant. From the investigation it may be concluded that also patients with uncomplicated essential hypertension without other cardiovascular risk factors or clinical manifestations of atherosclerosis have significantly elevated plasma levels of ICAM-1, vWf and endothelin-1. Higher concentrations of these factors suggest endothelial dysfunction already in mild forms of essential hypertension without further risk factors or cardiovascular complications. A significant drop of endothelin-1 and declining trend of the other investigated indicators suggest that ACEI treatment can favourably influence endothelial dysfunction in hypertensive patients also independently on reduction of the BP.

Angiotensin-Converting Enzyme Inhibitors↗

Interventional stent implantation in a child with patent ductus venosus and pulmonary hypertension.

UNLABELLED: We report on the rare case of a 4-year-old boy with patent ductus venosus and pulmonary hypertension presenting with progressive fatigue, tachypnoea at rest and tachycardia. Cardiac catheterisation revealed suprasystemic pressure in the pulmonary arteries with severely elevated pulmonary vascular resistance. In order to reduce the diameter of the ductus venosus, a stent was implanted interventionally, which closed, as expected, spontaneously 2 years later. Pulmonary arterial pressure and pulmonary vascular resistance decreased significantly and the general condition of the boy improved dramatically. CONCLUSION: To the best of our knowledge, this represents the first report of successful interventional stent occlusion of a patent ductus venosus associated with severe pulmonary hypertension. The future will tell whether this intervention is curative or represents a bridging procedure for subsequent liver transplantation.

Child, Preschool↗

Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.

The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the central nervous system, the channel is expressed in neurons of the circumventricular organs, neurosensory cells responsive to systemic osmotic pressure. The channel also occurs in other neurosensory cells, including inner-ear hair cells, sensory neurons, and Merkel cells.

Amino Acid Sequence↗