Martin Radespiel-Tröger

The Effect of Continuous Positive Airway Pressure Treatment on Insulin Sensitivity in Patients with Obstructive Sleep Apnoea Syndrome and Type 2 Diabetes

Background: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. Objectives: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. Methods: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 ± 21.3; body mass index (BMI) 37.3 ± 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 ± 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. Results: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 ± 2.94 vs. 2.74 ± 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 ± 0.6%; not significant). Fasting leptin levels showed no significant changes. Conclusions: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.

Agreement of two different methods for measurement of heart rate variability

Abstract.Background: The widespread use of affordable devices with sufficient precision for measurement of heart rate variability (HRV) might lead to early detection of abnormalities in a large number of high-risk patients and athletes. The purpose of this study was to determine the limits of agreement of two devices for measuring HRV parameters differing in price and assumed precision. Subjects and methods: 36 healthy subjects (22 men and 14 women) with a mean age of 27.4 (SD 11.1) years were included. The two devices used for comparison were PowerLab® with Chart® software as the reference golden standard, and Polar® Transmitter®/Advantage® with Precision Performance® software, respectively. Measurements included the following heart rate variability parameters: heart rate, range of R-R-interval duration, SDNN, rMSSD, total Power, VLF power, LF power, and HF power. Measurements were taken during metronomic respiration over a total period of 3 minutes. Statistical analysis was performed according to Bland and Altman and by means of scatterplots and Spearman correlation coefficients. Results: Good agreement was found for heart rate (95 % CI of limits of agreement: −0.7–0.6 bpm; r = 0.999), range of duration of R-R-intervals (95 % CI: −18.9–17.0 ms; r = 0.997), rMSSD (95 % CI: −1.5–2.5 ms; r = 0.999), and SDNN (95 % CI: −3.0–3.1 ms; r = 0.997). Correlation of measurements was high for the variables total Power, VLF power, LF power, and HF power. Analysis of method agreement for frequency domain variables was statistically not feasible. Conclusion: The level of agreement for the analyzed time domain variables between the reference golden standard and the inexpensive device is sufficient to permit initial screening by family doctors, and self-administration by high-risk patients and athletes.

Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.

BACKGROUND Studies suggest that heparin has anti-inflammatory effects that could prevent acute post-ERCP pancreatitis. The aim of this investigator-initiated, prospective, randomized, double-blind, multicenter study was to determine whether low-molecular-weight heparin can prevent acute post-ERCP pancreatitis. METHODS Patients at increased risk for acute post-ERCP pancreatitis based on assessment of known risk factors were randomized to receive low-molecular-weight heparin (Certoparin 3000 IU subcutaneously) or placebo (saline solution 0.3 mL subcutaneously) the day before ERCP. The drug was given 2 hours before and 22 hours after ERCP. Documentation and follow-up included patient history, risk factors for acute post-ERCP pancreatitis, procedure-related data, assessment of pain (visual analogue scale, need for pain medication), laboratory findings before and after ERCP (0, 4, and 24 hours), as well as post-ERCP complications. The two-sided Fisher exact test was used for statistical comparison, and a p value < or =0.05 was considered significant. RESULTS A total of 458 patients were enrolled in the study. Data from 10 patients could not be evaluated, leaving 221 patients in the low-molecular-weight heparin group and 227 in the placebo group (total 448 patients; 135 men, 313 women; mean age 58 [15] years). Low-molecular-weight heparin and placebo groups were comparable with regard to risk factors for acute post-ERCP pancreatitis (gender distribution, age <65 years, history of pancreatitis, pancreas divisum, disorders of sphincter of Oddi) and procedure-related data (difficult cannulation, diagnostic or therapeutic ERCP, needle-knife papillotomy, endoscopic sphincterotomy, biliary or pancreatic procedure, pancreatic contrast injection, success and final diagnosis of ERCP). Acute post-ERCP pancreatitis occurred in 8.5% (38/448), with one death resulting from severe pancreatitis. Low-molecular-weight heparin offered no benefit compared with placebo based on the frequency of acute post-ERCP pancreatitis (low-molecular-weight heparin, 18/221 vs. placebo, 20/227; p=0.87) and the severity of acute post-ERCP pancreatitis (low-molecular-weight heparin, 14 mild, 3 moderate, one severe; placebo, 18 mild, two moderate, 0 severe). The 24-hour serum amylase values and 24-hour pain scores did not differ significantly between the low-molecular-weight heparin group and the placebo group. Bleeding complications occurred in two patients, both in the low-molecular-weight heparin group (one mild, one moderate). CONCLUSIONS Prophylactic subcutaneous administration of low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.

Osseointegration of endodontic endosseous conesZirconium oxide vs titanium

OBJECTIVE The purpose of this investigation was to investigate the osseointegration of zirconium oxide (ZrO(2)) ceramic cones in comparison with that of titanium cones in apicectomy. STUDY DESIGN To evaluate the bone/implant interface, 20 ZrO(2) cones and 20 titanium cones were inserted into the mandibles of 4 Göttinger minipigs. During the 6-month healing period, intravital polychrome sequence marking was performed. Qualitative light microscopic, fluorescence microscopic, and quantitative histomorphometric assessment was carried out. Differences between continuous histomorphometric measures were tested through use of a 2-way analysis of variance. RESULTS Light microscopy revealed zones of direct bone contact with the ZrO(2) and titanium surfaces. Fluorescence microscopy revealed remodeling processes directly adjacent to both material surfaces. There was no significant difference in the distances of the fluorescence bands of each fluorescence marker for either the ZrO(2) surfaces or the titanium surfaces. Quantitatively and histomorphometrically, the mean ratio between the total cone/bone contact and the total cone/fibrous tissue contact was 0.95 (SD 1.10) on the titanium surface (n = 38) and 1.47 (SD 1.12) on the ZrO(2) surface (n = 78; P =.02). CONCLUSIONS The qualitative results show that the biocompatibility of ZrO(2) was similar to that of titanium. The use of ZrO(2) cones for sealing purposes in resected teeth after apicectomy appears to be acceptable.

Improved prediction of recurrence after curative resection of colon carcinoma using tree‐based risk stratification

Patients who are at high risk of recurrence after undergoing curative (R0) resection for colon carcinoma may benefit most from adjuvant treatment and from intensive follow‐up for early detection and treatment of recurrence. However, in light of new clinical evidence, there is a need for continuous improvement in the calculation of the risk of recurrence.

Histomorphologische Strukturveränderungen von Kopf-Hals-Gefäßen nach prä- oder postoperativer Radiotherapie

Hintergrund: Patienten mit Plattenepithelkarzinomen im Kopf- und Halsbereich werden zumeist multimodal strahlen-, chemotherapeutisch und/oder chirurgisch behandelt. Die Erfolgsrate einer mikrovaskulären Hart- und Weichgeweberekonstruktion nach vorausgegangener Radiotherapie ist neben anderen Faktoren limitiert durch die strahleninduzierten Veränderungen der mikrochirurgisch genutzten Anschlussgefäße im Kopf- und Halsbereich. Ziel der Untersuchungen war es daher, das Ausmaß pathomorphologischer Gefäßveränderungen in Abhängigkeit von der Gesamtreferenzdosis und dem Intervall zwischen Radiotherapie und/oder Chemotherapie zu erfassen. Patienten und Methoden: Im Zeitraum von Oktover 1995 bis März 2002 wurden insgesamt 348 Patienten mit 356 freien mikrovaskulären Hart- und Weichgewebetransplantaten primär oder sekundär rekonstruiert. In Abhängigkeit von der strahlentherapeutischen Vorbehandlung wurde folgende Gruppeneinteilung vorgenommen: Gruppe 1 = Patienten (n = 27) mit ausschließlich chirurgischer Behandlung. Gruppe 2 = Patienten (n = 29) mit einer neoadjuvanten Radiochemotherapie (40–50 Gy; 800 mg/m2 5-Fluorouracil [5-FU] und 20 mg/g2 Cisplatin) und primärer Rekonstruktion. Grupp3 = Patienten (n = 20) mit vorausgegangener Radiotherapie (60–70 Gy) und sekundärer Rekonstruktion. 209 Gefäßproben der Anschluss- und Transplantatgefäße wurden qualitativ histologisch auf Veränderungen der Media und Intima sowie quantitativ histomorphometrisch (NIH-Image) auf eine anteilige Zu- oder Abnahme der Media, der Intima oder des Lumens am Gesamtquerschnitt des Gefäßes untersucht (ANOVA SPSS V9). Ergebnisse: Die Ergebnisse zeigten ein signifikantes Überwiegen von Gefäßveränderungen des Grade II (Hyalinose der Media und Intima und eine Intimaablösung, p = 0,009) an den Anschlussarterien in der Gruppe 3 (präoperative Radiotherapie mit 60–70 Gy). An Transplantatarterien (p = 0,127), Anschluss- (p = 0,43) und Transplantatvenen (p = 0,54) wurden keine signifikanten qualitativen Gefäßwandveränderungen zwischen einer vorausgegangenen Radiotherapie und keiner Bestrahlung gesehen. Bei der Analyse der Anschlussarterien war die Ratio Media/Gesamtfläche in Gruppe 3 (Median 0,51; IQR 0,10) signifikant kleiner als in Gruppe 1 (p = 0,02) (Median 0,61; IQR 0,29) und Gruppe 2 (p = 0,046) (Median 0,58; IQR 0,19). Ein signifikanter Unterschied der Ratio Lumen/Gesamtfläche zeigte sich zwischen Gruppe 1 und 3 (p = 0,01) (Gruppe 1: Median 0,24; IQR 0,15; Gruppe 2: Median 0,34; IQR 0,15; Gruppe 3; Median 0,40; IQR 0,18). Schlussfolgerung: Nach einer Vorbestrahlung mit 60–70 Gy wurden signifikante qualitative und quantitative Gefäßwandveränderungen an den Anschlussarterien, nicht aber an den Anschlussvenen, den Transplantatarterien oder den Transplantatvenen festgestellt. Im Gegensatz zeigte eine neoadjuvante Radiochemotherapie (40–50 Gy, 5-FU und Cisplatin) bei der primären vaskulären Rekonstruktion 1,5 Monate nach neoadjuvanter Vorbehandlung keine signifikanten histologischen Gefäßveränderungen der vorbestrahlten Anschlussgefäße.Background: Patients with squamous cell carcinomas of the oral cavity are being increasingly treated by multimodal interdisciplinary regimes using a combination of surgery, chemo- and radiotherapy. Inflammatory alterations of the vascular endothelium following preoperative radiotherapy frequently cause healing delays of free flaps in the irradiated graft bed. The aim of the study was to investigate quantitative and qualitative changes of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses in free flaps in patients undergoing preoperative radiotherapy or radiochemotherapy. Patients and Methods: In 348 patients (October 1995–March 2002) receiving primarly or secondarly 356 microvascular hard- and soft tissue reconstruction, a total of 209 vessels were obtained from neck recipient vessels and transplant vessels during anastomosis. Three groups were analysed: group 1 (27 patients) treated with no radiotherapy or chemotherapy; group 2 (29 patients) treated with preoperative irradiation (60–70 Gy) and chemotherapy (800 mg/m2/day 5-FU and 20 mg/m2/day cisplatin) 1.5 months prior to surgery; group 3 (20 patients) treated with radiotherapy (60–70 Gy) (median interval 78.7 months; IQR: 31.3 months) prior to surgery. From each of the 209 vessel specimens, 3 sections were investigated histomorphometrically, qualitatively and quantitatively (ratio media area/total vessel area) by NIH-Image-digitized measurements. To evaluate these changes as a function of age, radiation dose and chemotherapy, a statistical analysis was performed using an analysis of covariance and 2tests (p > 0.05, SPSS V10). Results: In group 3, qualitative changes (intima dehiscence, hyalinosis) were found in recipient arteries significantly more frequently than in groups 1 and 2. For group 3 recipient arteries, histomorphometry revealed a significant decrease in the ratio media area/total vessel area (median 0.51, IQR 0.10) in comparison with groups 1 (p = 0.02) (median 0.61, IQR 0.29) and 2 (p = 0.046) (mdeian 0.58, IQR 0.19). No significant difference was found between the vessels of groups 1 and 2 (p = 0.48). There were no significant differences in transplant arteries and recipient or tansplant veins between the groups. Age and chemotherapy did not appear to have a significant influence on vessel changes in this study (p > 0.05). Conclusions: Following irradiation with 60–70 Gy, significant qualitative and quantitative histological changes to the recipient arteries, but not to the recipient veins, could be observed. In contrast, irradiation at a dose of 40–50 Gy and chemotherapy given at a median interval of 1.5 months prior to operation did not lead to significant histological changes to the recipient vessels.

Traffic hypoglycaemias and accidents in patients with diabetes mellitus treated with different antidiabetic regimens

Objectives.  Insulin‐treated patients with diabetes are at a higher risk than the general population in causing traffic accidents due to hypoglycaemias. Preceeding investigations focused on insulin‐treated patients and hypoglycaemia‐induced accidents as ‘end‐points’. We studied the incidence of symptomatic hypoglycaemia and hypoglycaemia‐induced accidents during driving and put it in relation to the different treatment modes of insulin therapy (Conventional Insulin Treatment = CT, Intensified Conventional Insulin Treatment = ICT, Continuous Subcutaneous Insulin Infusion = CSII) as well as to patients treated with oral hypoglycaemia‐inducing agents and the two main types of diabetes mellitus.

Anterograde tracing and immunohistochemical characterization of potentially mechanosensitive vagal afferents in the esophagus

Vagal mechanosensitive afferents with an important functional role in esophageal peristalsis are well known from physiological studies. It is not known whether these fibers represent a separate subpopulation among all vagal afferents projecting to the esophageal wall. A morphological and immunohistochemical description of vagal afferents was undertaken to define their possible homo‐ or heterogeneity. The peripheral projections of vagal afferents were anterogradely labeled by injection of wheatgerm agglutinin conjugated to horseradish peroxidase into the nodose ganglion of rats. The anterogradely transported tracer was detected by tyramide amplification in conjunction with immunohistochemistry for Ca2+‐binding proteins recently identified in different types of mechanosensory endings. It was found that vagal afferents represented a morphologically and structurally homogeneous population projecting to the myenteric ganglia of the esophagus, where they terminated as highly branched endings. Vagal afferent terminals, however, were different in their staining intensity for calretinin and calbindin, which ranged from intense to no detectable immunofluorescence. The fluorescence intensity of Ca2+‐binding proteins within the vagal terminating branches was graded and the average staining intensity determined of all terminating branches in the upper, middle, and lower thirds of the esophagus. The average staining intensity was highest in the upper third of the esophagus and then declined in a statistically significant manner in the middle and lower thirds. This result suggests different requirements for intracellular Ca2+‐buffering capacities in vagal afferents depending on their position along the esophageal axis and corroborates studies reporting a segmental organization of esophageal motility. Immunohistochemical evidence of substance P (SP) in a subset of vagal terminals was demonstrated. Hence, an effector role of vagal afferents on esophageal peristalsis by the release of SP, as has been proposed by physiological studies, is also supported by immunohistochemical data. J. Comp. Neurol. 412:161–172, 1999.

Histomorphometric analysis of irradiated recipient vessels and transplant vessels of free flaps in patients undergoing reconstruction after ablative surgery

The aim of the study was to investigate, histomorphometrically, quantitative and qualitative changes in irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses in free flaps in patients undergoing preoperative radiotherapy and chemotherapy. In 55 patients receiving 42 radial forearm flaps, 6 latissimus dorsi flaps, 6 osteomyocutaneous fibula grafts and 1 lateral arm flap, a total of 220 vessels were obtained from neck recipient vessels and transplant vessels during anastomosis. Three groups were formed: Group 1 (16 patients) treated with no radiotherapy or chemotherapy; Group 2 (20 patients) treated with preoperative irradiation (40-50 Gy) and chemotherapy (800 mg/m2 5-FU and 20 mg/m2 cisplatin) 1.5 months prior to surgery; Group 3 (19 patients) treated with radiotherapy (60-70 Gy) (median interval 78.7 months; IQR 31.3 months) prior to surgery. From each of the 220 vessel specimens, 3 sections each were histomorphometrically investigated, both qualitatively and quantitatively. To evaluate these changes as a function of age, radiation dose and chemotherapy, a statistical analysis was performed using analysis of covariance and chi-square tests. In Group 3, qualitative changes (intima dehiscence, hyalinosis) were found in recipient arteries significantly more frequently (25%, P=0.009) than in Groups 1 and 2. For Group 3 recipient arteries, histomorphometry revealed a significant decrease in the ratio of media area/total vessel area (median 0.53, IQR 0.10) in comparison with Group 1 (P= 0.02) (median 0.60, IQR 0.29) and Group 2 (P=0.046) (median 0.59, IQR 0.10). No significant differences were found between the vessels of Groups 1 and 2 (P= 0.48). Age and chemotherapy did not appear to have a significant influence on vessel changes in this study.

Transforming growth factor ß1 and ß2 (TGFβ2 / TGFβ2) profile changes in previously irradiated free flap beds†

Following preoperative radiotherapy prior to ablative surgery of squamous epithelial carcinomas of the head and neck region, inflammatory changes and the expression of cytokines involved in wound healing could be observed. These processes lead to a delayed healing of free flaps in the graft bed. The aim of the present experimental study was to analyze the expression profiles of transforming growth factor (activated TGFβ1, TGFβ2) and latency‐associated peptide (LAP) in the irradiated graft beds and the transition area between grafts and irradiated graft beds.