Thermal effects of a novel electrosurgical device for focused preparation in breast surgery tested in a specified porcine tissue ex vivo breast model using infrared measurement.

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.

Selective tissue elevation by pressure for endoscopic mucosal resection of colorectal adenoma: first clinical trial.

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.

Effectiveness and Safety of PRECISE APC for the treatment of bleeding gastrointestinal angiodysplasia--a retrospective evaluation.

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.

Comparison of standard endoscopic submucosal dissection (ESD) versus an optimized ESD technique for the colon: an animal study.

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.

Fragmentation of bile duct stones: a prospective systematic in vitro evaluation of argon plasma coagulation, cryotechnology, and water-jet technology.

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.

Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study.

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.

Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study.

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.

Pain sensation and neuromuscular stimulation during argon plasma coagulation in gastrointestinal endoscopy.

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.

Submucosal cushioning with water jet before endoscopic mucosal resection : Which fluids are effective?

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.

Prospective nonrandomized comparison of two modes of argon beamer (APC) tumor desobstruction: effectiveness of the new pulsed APC versus forced APC.

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.

Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance.

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 or =7.8 mL. kg(-1). min(-1), and borderline with an MCR of 5.9 to 7.7 mL. kg(-1). min(-1). Flow-associated dilation was 4.1+/-0.9% in insulin-resistant FDRs, 6.7+/-1.1% in borderline FDRs, 9.0+/-1.2% in insulin-sensitive FDRs (P=0.002), 7.7+/-2.9% in control subjects (P=NS versus FDRs), and 3.8+/-1.0% in DM patients (P=0.03). In multiple regression analysis, low MCR was significantly correlated with ED independent of age, sex, smoking, body mass index, percent body fat, serum insulin, and lipids. CONCLUSIONS: There is a significant association between ED and insulin resistance in young FDRs of DM subjects independent of the classic cardiovascular risk factors.

Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes.

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.

Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects.

OBJECTIVE: To examine endothelial function (EF) noninvasively in IDDM and NIDDM patients with long diabetes duration. RESEARCH DESIGN AND METHODS: We studied EF in 17 IDDM patients without diabetic complications and in 25 NIDDM patients with comparable glycemic control and with diabetic complications and compared both with nondiabetic control subjects matched for age, sex, and lumen diameter. Using high-resolution ultrasound, we measured the endothelial-dependent (FAD%) and independent vasodilation (GTN%); the blood flow at rest, postocclusive, and after application of 400 micrograms glyceroltrinitrate of the branchial artery; and the intima media thickness (IMT) of the common carotid artery. RESULTS: In the IDDM patients, neither FAD% (8.2 +/- 4.6 vs. 7.6 +/- 4.2%), GTN% (16.3 +/- 4.9 vs. 18.4 +/- 6.4%), nor postocclusive blood flow (40.6 +/- 19.1 vs. 39.3 +/- 23.6 cm/s) differed from the control subjects. IMT (0.59 +/- 0.10 vs. 0.55 +/- 0.14 mm) was slightly, but not significantly, elevated. In contrast, the NIDDM patients showed an impaired FAD% (3.8 +/- 3.3 vs. 6.9 +/- 4.4%, P < 0.01), no difference in GTN%, and a decreased postocclusive blood flow (18.5 +/- 13.8 vs. 32.7 +/- 20.0 cm/s, P < 0.01). IMT was significantly increased in NIDDM patients (0.77 +/- 0.14 vs. 0.62 +/- 0.10 mm, P < 0.001). CONCLUSIONS: In contrast to NIDDM patients with cardiovascular complications, IDDM patients with long diabetes duration and good long-term metabolic control do not have impaired EF compared with control subjects.

Correlation of imaging techniques to histopathology in patients with diabetic foot syndrome and clinical suspicion of chronic osteomyelitis. The role of high-resolution ultrasound.

OBJECTIVE: To investigate the role of ultrasound in the diagnosis of osteomyelitis in the diabetic foot compared with magnetic resonance imaging (MRI), bone scintigraphy (BS), and plain film radiography (PFR). RESEARCH DESIGN AND METHODS: We investigated 19 consecutive diabetic patients (2 women, 17 men, age 60.7 +/- 9.8 years, BMI 27.0 +/- 3.8 kg/m2) with clinical suspicion of bone infection of the foot. A high-resolution ultrasound system (Esaote/Biosound, Munich) with a linear array transducer up to 13.0 MHz was used. The prospective and blinded results of each method were compared with histopathology as the reference method after metatarsal resection. RESULTS: In 14 of 19 patients, histopathology confirmed osteomyelitis. Ultrasound showed a sensitivity of 79% (PFR, 69%; BS, 83%; MRI, 100%), a specificity of 80% (PFR, 80%; BS, 75%; MRI, 75%), a positive predictive value of 92% (PFR, 90%; BS, 91%; MRI, 93%), and a negative predictive value of 57% (PFR, 50%; BS, 60%; MRI, 100%). CONCLUSIONS: Our data indicate that ultrasound might have a better diagnostic power for detecting chronic osteomyelitis in the diabetic foot than PFR and has similar sensitivity and specificity as BS. MRI is superior to the other three methods. We conclude that the use of ultrasound in the management of the diabetic foot is worthy of further investigation.

Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease.

OBJECTIVE: Flow associated dilatation (FAD%) and intimal media thickness are established markers of early atherosclerosis. This study aimed to compare the ability of the non-invasive measurements FAD% and intimal media thickness to predict coronary artery disease. METHODS: FAD% and intimal media thickness were determined using high resolution ultrasound in 122 patients with clinically suspected coronary artery disease before coronary angiography. Results are given as mean (SD). RESULTS: Patients with coronary artery disease had reduced FAD% compared with those with angiographically normal coronary vessels (3.7 (4.1) v 7.0 (3.5)%, p < 0.001), whereas intimal media thickness tended to be increased in patients with coronary artery disease (0.58 (0.35) v 0.47 (0.11)mm, p = 0.054). There was a negative correlation between FAD% and intimal media thickness (R = -0.317, p = 0.0004). Receiver operating characteristic analysis showed that FAD% < or = 4.5% predicted coronary artery disease with a sensitivity of 0.71 (95% confidence interval 0.61 to 0.80) and a specificity of 0.81 (0.58 to 0.95). In contrast, intimal media thickness showed a positive correlation with the extent of coronary artery disease (number of vessels with a lesion > or = 50%) (R = 0.324, p = 0.0003), without a clear cut off point. CONCLUSIONS: In patients with clinically suspected coronary artery disease, FAD% discriminates between the presence or absence of coronary artery disease, whereas intimal media thickness is associated more with the extent of coronary artery disease.

Paraoxonase 1 192 Gln/Arg gene polymorphism and cerebrovascular disease: interaction with type 2 diabetes.

Paraoxonase 1 (PON1) is an HDL-associated enzyme which protects HDL and LDL particles from lipid peroxidation. Its enzymatic serum activity varies 10-40-fold between individuals, and its biallelic gene polymorphism at codon 192 (glutamine-->arginine, Gln/Arg) has been associated with coronary artery disease in diabetic patients. To evaluate the role of this PON1 gene polymorphism in cerebrovascular disease, we determined the PON1 192 genotype in 149 patients with hemodynamically relevant extracranial artery stenosis and in 241 controls. The PON1 192 Gln/Arg genotype was determined using polymerase chain reaction followed by Alw I digestion and polyacrylamide gel electrophoresis. Among all subjects, there was no association between the PON1 192 Gln/Arg genotype and cerebrovascular disease (Odds ratio for Arg/Arg and Gln/Arg vs Gln/Gln 0.99, 95%-CI 0.70-1.39). In contrast, in the subgroup of type 2 diabetic patients the PON1 192 Arg allele conferred about twice the risk of cerebrovascular stenosis compared to those homozygous for the Gln allele (Odds ratio 2.00, 95%-CI 0.92-4.38). Our data indicate that in the general population the PON1 192 Gln/Arg gene polymorphism cannot be regarded as a major risk marker for cerebrovascular disease. The observed interaction with type 2 diabetes, however, is supporting the hypothesis that the effect of the PON1 192 Arg allele on atherosclerosis is modulated by other risk factors like diabetes.

Acute improvement of peripheral endothelial function in postmenopausal women with coronary artery disease after single oral intake of 17beta-estradiol valerate.

Chronic estrogen supplementation is known to improve endothelial function in postmenopausal women. We studied the acute effect of a single dose of orally administered 17beta-estradiol valerate (E2) on the peripheral endothelial dependent and independent vasodilatation in postmenopausal women with coronary artery disease (CAD). 20 postmenopausal women (age: 64.9 (7.2) y, height: 1.61 (0.04) m. weight: 68.6 (10.6) kg) with angiographically confirmed CAD were randomly examined for flow-associated vasodilatation (= FAD%, a marker for endothelial dependent vasodilatation) and for glyceryltrinitrate (400 microg, p.o.) induced vasodilatation (= GTN%, representing endothelial independent vasodilatation) two hours after placebo controlled, randomized crossover intake of 4 mg E2 p.o. After placebo FAD% was impaired (3.5 (1.7)%) compared to historic controls. After the oral intake of 4 mg E2, FAD% improved to 5.0 (2.8)% (P=0.02). GTN% was not significantly influenced by the oral E2 (E2: 12.6 (5.7) v placebo: 11.2 (6.9)%, P=0.14). Endothelial dysfunction can partially be restored by a single oral dose of 4 mg E2. This indicates an acute vasoprotective effect of E2 beyond its genomic and lipid modifying actions. It remains to be investigated if estrogen might play a beneficial role in the acute treatment of symptomatic coronary artery disease such as angina pectoris or preinfarct syndrome.

Influence of vessel size, age and body mass index on the flow-mediated dilatation (FMD%) of the brachial artery.

BACKGROUND: The non-invasive determination of the endothelial dysfunction (ED) of the brachial artery is a widely used method in clinical research. It remained, however, unclear, whether the test-results are influenced by the anatomical vessel size, the patients age, body mass index (BMI) or gender. METHODS: The flow-mediated vasodilatation (FMD%) of the brachial artery was determined in 122 consecutive (88 male, 34 female) patients. FMD% was measured using high resolution ultrasound (13 Mhz) at rest, during reactive hyperaemia and after the sublingual administration of glycerolnitrate (GTN%). RESULTS: Lumen diameters at rest varied from 2.48 mm to 6.33 mm (4.46+/-0.74 mm). The extent of FMD% as well as of GTN% showed an inverse correlation to the resting lumen diameters (r=-0.33, P<0.001/r=-0.51, P<0.001). This correlation was even more distinct in females (females: FMD% r=-0.54, P<0.001; GTN% r=-0.64, P<0.001 vs. males: FMD% -0.23, P<0.001; GTN% -0.59, P<0. 001). No significant influence of age (61+/-9 years, FMD%: r=-0.04, P=0.68, GTN%: r=-0.18, P=0.05) and BMI (27.03+/-3.43 kg/m(2), FMD%: r=0.16, P=0.08, GTN%: r=0.09, P=0.3) on the test results were found. CONCLUSIONS: FMD% was found to be rather independent of age or BMI. The anatomical vessel size had an influence on the test results, which was more obvious in female patients. Our data indicate the necessity of further methodological studies, in larger, community-based populations. In particular, it needs to be clarified, whether vessel size or even gender-specific correction factors are required when using this technique in routine clinical practice.

Real-time detection of vessel diameters with ultrasound.

Transcutaneous vessel imaging is a frequently used ultrasound imaging modality in medicine. The measurement of vessel diameters can be done with conventional B-mode imaging systems, which work at frame rates up to 100 Hz. Furthermore, there are special systems available, which can track vessel walls very precisely using the phase of signals that are sent at frame rates up to several thousand Hz. Though, such systems are usually not able to provide the examiner with 2D images of the object. With respect to brachial artery flow-mediated vasodilatation (FMD), which is frequently used as a measure of endothelial function, it is necessary to observe diameter changes of small arterial vessels noninvasively for several minutes at a high resolution. In the past, the diameter had to be measured manually in tedious postprocessing of ECG-gated image sequences. We developed a system composed of a Siemens Omnia ultrasound system with a VF13-5 transducer (9 MHz center frequency) and a personal computer, that is capable of calculating vessel diameter changes with an accuracy below the wavelength of the ultrasound system in real-time at a frame rate of 27 Hz. We implemented a two-dimensional active contour model using the Viter-bi-algorithm and a phase-sensitive vessel wall tracking algorithm, in order to guarantee both, geometric information and accuracy. Results from carotid and brachial arteries show that arterial pulsations below 0.1 mm can be visualized reliably over several minutes. With this system we want to find out, if FMD is suitable for an individual assessment of the risk for cardiovascular diseases.

Forms of energy delivery during cryo-cooled radiofrequency ablation for optimization of the ablation result.

PURPOSE: Energy transfer from radiofrequency (RF) applicator to tissue is both precondition and limiting factor. The purpose of this ex vivo study was to examine the influence of form of energy delivery on ablation result during RF ablation with cryo-cooled applicators. MATERIALS AND METHODS: One hundred eight ablations were performed in ex vivo bovine liver under continuous energy delivery (A), pulsed energy delivery with reduced current during ablation pause (B) and impedance-dependent energy delivery. Maximum ablation time was 20 min. Early termination of ablation in case of loss of conductivity. Optimal ablation parameters were assessed. Short axis diameter of the ablation zone and ablation duration were determined. Ablation results under mode A, B and C were compared with analysis of variance and Tukey-Kramer HSD test. Influence of ablation duration on short axis diameter was evaluated with regression analysis. RESULTS: Significantly largest short axis diameter (51.1 mm ± SD 2.3; p = 0.01) was reached with impedance-dependent energy delivery (pulsed: 46.1 mm ± SD 5.6; continuous: 44.4 mm ± SD 4.1). Significantly longest ablation duration (1061.6 s ± SD 42.4; p = 0.01) was reached with impedance-dependent energy delivery (pulsed: 815.7 s ±â€Š41.3; continuous: 715.3 s ± SD 82.2). Linear correlation between ablation duration and short axis diameter was calculated (R = 0.7). CONCLUSION: Modification of energy delivery during RF ablation with cryo-cooled applicators improves energy transfer to tissue and enables larger ablation zones. KEY POINTS: • Impedance-dependent energy delivery prevents early termination in kryo-based RF-ablation,• Impedance-dependent energy delivery enables larger ablation zones than continuous energy delivery,• Reduced current during ablation pause does not improve ablation results.