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We measure the mode-resolved direction of the precessional motion of the magnetic order, i.e., magnon polarization, via the chiral term of inelastic polarized neutron scattering spectra. The magnon polarization is a unique and unambiguous signature of magnets and is important in spintronics, affecting thermodynamic properties such as the magnitude and sign of the spin Seebeck effect. However, it has never been directly measured in any material until this work. The observation of both signs of magnon polarization in Y_{3}Fe_{5}O_{12} also gives direct proof of its ferrimagnetic nature. The experiments agree very well with atomistic simulations of the scattering cross section.
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PURPOSE: This article investigates the qualities and thermal effects of a novel electrosurgical device (PT) which has been designed by ERBE Elektromedizin GmbH, Germany, for the preparation of critical locations such as in skin-sparing or nipple-sparing techniques and compares it to a standard device (SD) in a porcine ex vivo breast model using an heat map generated by infrared thermography. METHODS: In total, 42 abdominal wall specimens of porcine tissue consisting of the skin and the underlying subcutaneous and muscle layer were alternately dissected using one of the devices and pre-settings. During the preparation with the two devices, the epicutaneous temperature was measured by an infrared camera (VarioCam, Jenoptik, Germany) and the maximum temperature as well as the slope of the temperature rise was analysed. RESULTS: The use of PT shows significantly lower values for [Formula: see text] compared to SD. This effect was independent from the chosen mode. Using the same instrument in different modes, the use of AutoCut mode showed a significant reduction of [Formula: see text] at all indicated time points (SD: p < 0.0001 and PT: p < 0.0001). In summary, the combination of AutoCut + PT showed the lowest rise in temperature, whereas the combination of DryCut + SD led to the highest rise in temperature. The temperature difference between these two settings was 13.84 °C, which means a possible temperature reduction of 67% can be achieved by the right choice of device and its tailored mode. CONCLUSIONS: The novel PT shows a significant reduction in epicutaneous temperature and a significant reduction of the slope of temperature rise most probably by a more focused application of energy compared to SD.
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Mama/cirugía , Electrocirugia/métodos , Termografía/métodos , Animales , Mama/patología , Modelos Animales de Enfermedad , Femenino , PorcinosRESUMEN
The need for both high electrical conductivity and low thermal conductivity creates a design conflict for thermoelectric systems, leading to the consideration of materials with complicated crystal structures. Rattling of ions in cages results in low thermal conductivity, but understanding the mechanism through studies of the phonon dispersion using momentum-resolved spectroscopy is made difficult by the complexity of the unit cells. We have performed inelastic X-ray and neutron scattering experiments that are in remarkable agreement with our first-principles density-functional calculations of the phonon dispersion for thermoelectric Na(0.8)CoO2, which has a large-period superstructure. We have directly observed an Einstein-like rattling mode at low energy, involving large anharmonic displacements of the sodium ions inside multi-vacancy clusters. These rattling modes suppress the thermal conductivity by a factor of six compared with vacancy-free NaCoO2. Our results will guide the design of the next generation of materials for applications in solid-state refrigerators and power recovery.
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The structure of solid deuterium confined in 9 nm wide tubular silicon nanochannels has been studied by means of elastic neutron scattering techniques. As a result we report the formation of fcc D(2) as the stable solid phase in confinement in contrast to the hcp bulk structure. Further, a preferred alignment of D(2) nanocrystals with respect to the surrounding crystalline silicon matrix is discussed in terms of heteroepitaxial growth of solid D(2) on crystalline pore walls.
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Polarized and unpolarized neutron scattering experiments on the frustrated ferromagnetic spin-1/2 chain LiCuVO4 show that the phase transition at H(Q) of 8 T is driven by quadrupolar fluctuations and that dipolar correlations are short range with moments parallel to the applied magnetic field in the high-field phase. Heat-capacity measurements evidence a phase transition into this high-field phase, with an anomaly clearly different from that at low magnetic fields. Our experimental data are consistent with a picture where the ground state above H(Q) has a next-nearest neighbor bond-nematic order along the chains with a fluidlike coherence between weakly coupled chains.
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BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection of large lateral spreading tumors currently are technically limited by complications such as bleeding, perforation, and disturbed large procedural sites, leading to incomplete resection and secondary surgery. Further technical improvements are necessary. The authors previously demonstrated the effectiveness of a focused water jet for elevation of the lamina submucosa in animal studies. For the first time, the clinical application of selective tissue elevation by pressure (STEP) for the treatment of colorectal adenomas as a prospective single-arm human trial is presented. METHODS: This trial evaluated 59 patients who had primary colorectal adenomas with diameters exceeding 12 mm classified as 0-IIa or 0-IIb according to Paris classification. A submucosal cushion was created with a flexible water jet applicator using the Helix HydroJet. The adenoma was subsequently resected with a mucosal resection snare. All results were recorded. The resected specimens were assessed histologically. RESULTS: A total of 59 patients underwent resection of 70 lesions with a maximum diameter of 80 mm (mean, 27 mm). Submucosal elevation with the water jet dissector was possible in all cases and locations from the pectinate line to the ileocecal valve. Of the 70 lesions, 64 (91%) were resected completely in one session. Histologically, the resected specimens were found to be adenocarcinomas (n = 2, 3%), adenomas with high-grade intraepithelial neoplasia (n = 24, 34%), adenomas with low-grade intraepithelial neoplasia (n = 38, 54%), and hyperplastic polyps (n = 6, 9%). Hemostasis during the resection was necessary in 24 cases (34%). No perforation required surgical intervention. CONCLUSION: This first clinical trial to analyze STEP technique demonstrated that STEP used to elevate large mucosal lesions in any location is feasible and facilitates EMR for colorectal adenoma.
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Adenoma/cirugía , Neoplasias Colorrectales/cirugía , Endoscopía Gastrointestinal/métodos , Anciano , Estudios de Factibilidad , Femenino , Humanos , Inyecciones a Chorro , Mucosa Intestinal/cirugía , Masculino , Presión , Estudios Prospectivos , AguaRESUMEN
The spin-wave excitations emerging from the chiral helically modulated 120° magnetic order in a langasite Ba3NbFe3Si2O14 enantiopure crystal were investigated by unpolarized and polarized inelastic neutron scattering. A dynamical fingerprint of the chiral ground state is obtained, singularized by (i) spectral weight asymmetries answerable to the structural chirality and (ii) a full chirality of the spin correlations observed over the whole energy spectrum. The intrinsic chiral nature of the spin waves' elementary excitations is shown in the absence of macroscopic time-reversal symmetry breaking.
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BACKGROUND: APC is a thermal coagulation technique that uses ionized argon to transmit high-frequency electrical current, contact-free, to tissue. Precise APC is one of the new modes and is characterized by a small and distinctive energy input, higher reproducibility of tissue effects which is almost independent of the probe distance. The aim of the study was the evaluation of precise APC in patients with bleeding angiodysplasia's in the cecum or the small bowel. AIM/METHODS: Patients (pts.) with bleeding angiodysplasia of the cecum or small bowel were prospectively enrolled. Effectivity and safety of APC was assessed by evaluating the local coagulation effect, number of rebleedings and transfusions and complications (perforation, infection). RESULTS: There were 50 males and 44 females, median age 65.5 ± 8.5 years. 58 pts. (62 %) had lesions in the small bowel, 28 pts. (30 %) lesions in the cecum and 8 pts. (8 %) lesions in small bowel and cecum. All 234 visible lesions in 94 pts. were coagulated successfully. There was no perforation, active bleeding and tissue carbonization after the procedure. Re-bleeding was recognized in 18 pts. (19 %) after a mean follow-up of 6.1 months and new lesions in the same area were seen in 15 / 18 pts (16 %). CONCLUSION: In a historical comparison to forced or pulsed APC, precise APC may be a more appropriate option for the treatment of bleeding angiodysplasia's in critical locations like the cecum or small bowel. The coagulation effect seems to be comparable and due to its better depth control we assume a better safety, especially in preventing perforations.
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Angiodisplasia/complicaciones , Angiodisplasia/terapia , Coagulación con Plasma de Argón/métodos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Anciano , Anciano de 80 o más Años , Coagulación con Plasma de Argón/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Inelastic neutron scattering measurements show the existence of a strong two-spinon continuum in the frustrated ferromagnetic spin-1/2 chain compound LiCuVO4. The dynamic magnetic susceptibility is well described by a mean-field model of two coupled interpenetrating antiferromagnetic Heisenberg chains. The extracted values of the exchange integrals are in good agreement with the static magnetic susceptibility data and an earlier spin-wave description of the bound state near the lower boundary of the two-spinon continuum. In addition, there is clear evidence for a four-spinon continuum at high energies.
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BACKGROUND AND STUDY AIM: Choledocholithiasis is a common disease in the West. Lithotripsy by mechanical methods using baskets and by laser or electrohydraulic methods varies in effectiveness. With argon plasma coagulation (APC), high temperatures are used for devitalization and fragmentation; cryogenic techniques use the selective controlled application of freeze-thaw cycles to devitalize pathological tissue; and the dissecting water jet exploits the high pressure action of a thin laminar jet. We aimed to assess the feasibility and effectiveness of APC, cryotechnology, and the dissecting water jet as options for the fragmentation of bile duct stones. METHODS: In an in vitro feasibility study, we evaluated the fragmentation of 120 bile duct stones treated with the three methods. Primary measures were assessment of the fragmentation rate, fragmentation effect, and energy application for each technology. RESULTS: Fragmentation was seen in only 10 % of stones treated cryogenically using liquid nitrogen. APC at a power setting of 30 - 50 W fragmented all the cholesterol stones, but results with hard pigment stones were unsatisfactory even at high energies of a 100 W setting and long application time. Using the water jet, all 40 stones (100 %) were cracked effectively and completely with a pressure of 10 - 50 bar. CONCLUSION: In this feasibility study, the first of its kind, only the water-jet device demonstrated efficient fragmentation of large bile duct stones in vitro. APC and cryotechnology are not suitable for the treatment of bile duct stones; the fragmentation rate with these methods was inadequate.
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Coledocolitiasis/terapia , Criocirugía , Electrocoagulación , Cálculos Biliares/terapia , Litotricia/métodos , Argón , Criocirugía/métodos , Electrocoagulación/métodos , Estudios de Factibilidad , Humanos , Técnicas In Vitro , Presión , Agua/administración & dosificaciónRESUMEN
BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a promising therapeutic technique for en bloc resection of large gastrointestinal tumors. However, this technique has disadvantages such as a long intervention time, complexity of the procedure, and a higher rate of complications. The primary aims of the study were to show the feasibility of ESD in the pig colon and to evaluate a new ESD technique comprising the use of a newly developed hybrid knife for colon procedures combining RF (radiofrequency) application and a distance-dependent water-jet application. MATERIALS AND METHODS: ESD was conducted at three different locations in the colon according to the computer-generated randomization list, using either the standard technique (injection needle, flex knife, and hook knife as therapeutic instruments and DRY CUT and SWIFT COAG as RF currents), or the new ESD technique (hybrid knife as the therapeutic instrument combined with the new cutting mode ENDO CUT D) in 12 healthy pigs. The perforation and bleeding rates were documented and statistically analyzed. Intervention time, resected specimen size, thermal and mechanical damage of the resection bed, and number of instrument changes required were also recorded. RESULTS: A total of 16 and 18 ESD procedures were performed by the standard and new techniques, respectively. Complete en bloc resection was achieved in all cases. The standard ESD technique showed a perforation rate of 25 % (4/16) whereas the new ESD technique resulted in a 5.5 % perforation rate (1/18) ( P = 0.035); bleeding rates were similar. The new ESD technique was significantly safer compared with the standard ESD technique. CONCLUSIONS: A new ESD technique for the successful en bloc resection in thin-walled regions such as pig colon has been described. This procedure is as effective as the standard procedure but is easier to handle and significantly safer.
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Ablación por Catéter/métodos , Colon/cirugía , Gastroscopía/métodos , Mucosa Intestinal/cirugía , Animales , Quemaduras/etiología , Ablación por Catéter/efectos adversos , Ablación por Catéter/instrumentación , Colon/lesiones , Estudios de Factibilidad , Gastroscopía/efectos adversos , Perforación Intestinal/etiología , Estudios Prospectivos , Distribución Aleatoria , PorcinosRESUMEN
BACKGROUND AND STUDY AIMS: Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS: 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS: The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P < 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS: Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.
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Ablación por Catéter/instrumentación , Criocirugía/instrumentación , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Animales , Proyectos Piloto , Complicaciones Posoperatorias , Análisis de Regresión , Estadísticas no Paramétricas , Porcinos , UltrasonografíaRESUMEN
BACKGROUND AND STUDY AIMS: In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS: Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16-18 W) and simultaneous cooling with CO(2) (standardized pressure: 675 psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS: For both organs the correlation between EUS and gross pathology was good (correlation coefficient R(liver) = 0.71; R(spleen) = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 (P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS: Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.
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Ablación por Catéter/instrumentación , Criocirugía/instrumentación , Endoscopía/métodos , Hígado/diagnóstico por imagen , Hígado/cirugía , Bazo/diagnóstico por imagen , Bazo/cirugía , Animales , Diseño de Equipo , Estudios de Factibilidad , Hígado/patología , Modelos Animales , Bazo/patología , Porcinos , UltrasonografíaRESUMEN
BACKGROUND: Argon plasma coagulation (APC) is a thermal coagulation technique that uses ionized argon for contact-free transmission of high-frequency electrical current to tissue. Prospective data on complications with the new APC-2 (VIO) system are lacking. METHODS: A prospective trial was conducted with 152 patients treated for various gastrointestinal diseases using three modes of the APC-2. The study aimed to assess complications, focusing on the pain and neuromuscular stimulation (NMS) experienced during and after treatment. Patients reported pain and NMS using a scale ranging from 0 to 10 and were interviewed for symptoms such as tingling, paresthesia, muscle pain, and cramping or twitching. The endoscopists also graded NMS using a separate questionnaire. RESULTS: A total of 85 males and 67 females (median age, 66 years) were enrolled in the study. All APC therapies were completed successfully. Two peri-interventional perforations were recorded. Of the 152 patients, 26 (17%) reported pain sensation during or after APC. The median pain sensation reported by the patients on the standardized scale was 3.7. The findings showed NMS in 14 (9.2%) of the 152 patients. Significantly more NMS events were seen with pulsed APC than with forced or precise APC. Additional risk factors for NMS were gender (female) and type of sedation (combination midazolam and pethidine). No complications were noted among patients with intracardiac defibrillators or cardiac pacemakers. CONCLUSIONS: According to the findings, APC may be associated with minor complications such as pain sensation and NMS. These complications were rarely seen, but occurred more often with pulsed APC than with forced or precise APC. Physicians should be aware of these complications.
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Estimulación Eléctrica/métodos , Electrocoagulación/métodos , Endoscopía Gastrointestinal/métodos , Enfermedades Gastrointestinales/terapia , Dolor/prevención & control , Anciano , Electrocoagulación/efectos adversos , Endoscopía Gastrointestinal/efectos adversos , Femenino , Humanos , Láseres de Gas/efectos adversos , Láseres de Gas/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Dolor/etiología , Dimensión del DolorRESUMEN
BACKGROUND: Several new techniques have recently been described that allow the endoscopic mucosal resection even of broad-based flat lesions in the gastrointestinal tract. The technique recently described by us of using a water jet dissector (Helix HydroJet) for a selective deposition of liquid in the submucosal lamina has now been combined with different substances, and their effects have been compared. MATERIAL AND METHODS: Gastroscopies were carried out in 8 pigs under intubation anesthesia, and 2 submucosal cushions each were created in the stomach using one out of 4 test substances (gelatin, glucose 50, hydroxyethyl starch [HES] 10%, dextran 40), as well as one cushion of isotonic saline solution placed in each area via the Helix HydroJet). The height of the submucosal cushions was intermittently measured over a period of 40 or 20 min, respectively, by miniprobe endosonography. In 7 of the animals the stomach was subsequently subjected to mucosal resection. The specimens and the gastric wall were histologically assessed to evaluate the localization of the liquid cushion and the effect on adjacent layers of the gastric wall. RESULTS: All test substances produced strictly selective liquid cushions in the submucosa. With HES 10% and dextran the maximum height of the cushions initially increased and then decreased during the further course to an average of 90% of the initial height within 40 min. Isotonic saline solution showed the most rapid decrease in height (72% after 20 min). The histological assessment confirmed the selective nature of the liquid deposit in the submucosa. DISCUSSION: Plasma expanders produced cushions that initially increased in height but then remained constant for a longer period than cushions produced using glucose 50, gelatin, or isotonic saline solution. The combination of transmucosal jet application for elevation of the mucosa with plasma expanders is therefore an interesting approach to optimize endoscopic mucosal resections.
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Dextranos , Mucosa Gástrica/cirugía , Gastroscopía , Gelatina , Glucosa , Derivados de Hidroxietil Almidón , Cuidados Preoperatorios/métodos , Animales , PorcinosRESUMEN
BACKGROUND AND STUDY AIM: Argon plasma coagulation (APC) has become an established noncontact method of tumor palliation in a variety of locations. The present prospective study evaluated a new APC system (APC-2) using amplified power settings and different application modes, such as intermittent energy delivery (pulsed APC) in comparison with the conventional technique (forced APC). PATIENTS AND METHODS: A total of 100 patients with esophageal, gastric, or rectal tumors were alternately (but not randomized) enrolled and treated with either pulsed APC (n = 46) or forced APC (n = 54). Parameters to assess the palliative effect were: amount of lumen restoration ((1/3), (2/3), complete), objective planimetry, stenosis length, treatment time, and number of APC sessions. RESULTS: Overall response rate was similar in both groups (pulsed 83 %, forced 87 %), the same was found in the subgroups with different amounts of lumen restoration and for the other objective parameters. However, the tumor debulking effect was achieved in a significantly shorter median treatment time with forced compared with pulsed APC (13.6 vs. 18.2 minutes, P = 0.03), with a similar number of treatment sessions in both groups. Complications also occurred with similar frequency in both groups. CONCLUSIONS: There was no significant difference in overall local tumor response between the two modes of APC application. However, data from this nonrandomized study suggest a faster achievement of response with forced APC. A combination of both modes may be superior.
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Endoscopía Gastrointestinal/métodos , Estenosis Esofágica/cirugía , Obstrucción de la Salida Gástrica/cirugía , Obstrucción Intestinal/cirugía , Coagulación con Láser/instrumentación , Cuidados Paliativos/métodos , Anciano , Diseño de Equipo , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/cirugía , Estenosis Esofágica/etiología , Femenino , Estudios de Seguimiento , Obstrucción de la Salida Gástrica/etiología , Humanos , Obstrucción Intestinal/etiología , Masculino , Estudios Prospectivos , Neoplasias del Recto/complicaciones , Neoplasias del Recto/cirugía , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
Recent experiments indicate that static stripe-like charge order is generic to the hole-doped copper oxide superconductors and competes with superconductivity. Here we show that a similar type of charge order is present in La5/3Sr1/3CoO4, an insulating analogue of the copper oxide superconductors containing cobalt in place of copper. The stripe phase we have detected is accompanied by short-range, quasi-one-dimensional, antiferromagnetic order, and provides a natural explanation for the distinctive hourglass shape of the magnetic spectrum previously observed in neutron-scattering measurements of La2-xSrxCoO4 and many hole-doped copper oxide superconductors. The results establish a solid empirical basis for theories of the hourglass spectrum built on short-range, quasi-static, stripe correlations.
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BACKGROUND: Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Among the pathogenetic factors leading to atherosclerosis, the role of insulin resistance and hyperinsulinemia as independent risk factors is still under debate. In this study, we examined the association between ED and insulin resistance in normotensive and normoglycemic first-degree relatives (FDRs) of patients with type 2 diabetes mellitus (DM). METHODS AND RESULTS: Endothelium-dependent and -independent vasodilation of the brachial artery was measured with high-resolution ultrasound (13 MHz) in 53 normotensive FDRs (21 men, 32 women; mean age, 35 years) with normal oral glucose tolerance, 10 age- and sex-matched normal control subjects, and 25 DM patients (mean age, 57 years). According to the tertiles of the clamp-derived glucose metabolic clearance rate (MCR), the FDRs were further classified as insulin resistant with an MCR
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Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Endotelio Vascular/fisiopatología , Resistencia a la Insulina/fisiología , Adolescente , Adulto , Anciano , Presión Sanguínea/fisiología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Diabetes Mellitus/fisiopatología , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , Estadísticas no Paramétricas , VasodilataciónRESUMEN
Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic gene polymorphism at codon 192 (glutamine/arginine) has been associated with coronary artery disease (CAD). To further evaluate the role of this paraoxonase gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase genotype in 288 type 2 diabetic patients (170 with and 118 without angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was assessed using polymerase chain reaction followed by AlwI digestion. The frequency of the Gln allele was 0.656 in the CAD patients and 0.746 in the controls (chi2 = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age-adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects carrying at least one Arg allele. In the multivariate analysis, this association was even stronger after correction for the possible confounders age, sex, smoking history, and hypertension. Among current and former smokers, the odds ratio (OR) for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P < 0.01). The paraoxonase Arg allele was not associated with the history of myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not myocardial infarction in type 2 diabetic patients, a risk factor further modified by cigarette smoking. This risk could possibly be explained by a reduced ability of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.
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Arginina , Enfermedad Coronaria/genética , Diabetes Mellitus Tipo 2/genética , Angiopatías Diabéticas/genética , Esterasas/genética , Glutamina , Infarto del Miocardio/genética , Polimorfismo Genético , Arildialquilfosfatasa , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/enzimología , ADN/sangre , Diabetes Mellitus Tipo 2/enzimología , Angiopatías Diabéticas/enzimología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/enzimología , Reacción en Cadena de la PolimerasaRESUMEN
Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the 0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2-mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.