Relations between thermodynamics, structures, and dynamics for modified water models in their supercooled regimes.

We use molecular dynamics simulations to study relations between thermodymamic, structural, and dynamical properties of TIP4P/2005 water models with systematically reduced partial charges and, thus, weaker hydrogen bonds. Observing a crossing of isochores in the P-T diagram, we show that these water-like models have a readily accessible liquid-liquid critical point (LLCP) associated with a transition between high-density liquid (HDL) and low-density liquid (LDL) forms and determine the dependence of the critical temperature Tc, pressure Pc, and density ρc on the charge-scaling factor from fits to a two-structure equation of states. The results indicate that the water-like models exhibit liquid polyamorphism in a wide range of interaction parameters. Considering elongated systems, we observe a decomposition into extended and stable HDL-like and LDL-like regions at appropriate pressures and low temperatures and analyze the respective structural and dynamical properties. We show that the diverse local order results in very different correlation times of local dynamics, while the fragility is hardly changed. The results yield insights into the origin of a dynamical crossover, which is observed when lowering the temperature along isobars and was previously interpreted in terms of a fragile-to-strong transition. Our findings imply that the effect does not involve two liquid phases with an exceptionally large difference of the fragility but rather a high temperature dependence near the LLCP results from a rapid conversion from HDL-like environments with faster dynamics to LDL-like ones with slower dynamics.

MD simulations of charged binary mixtures reveal a generic relation between high- and low-temperature behavior.

Experimental studies of the glassy slowdown in molecular liquids indicate that the high-temperature activation energy E∞ of glass-forming liquids is directly related to their glass transition temperature Tg. To further investigate such a possible relation between high- and low-temperature dynamics in glass-forming liquids, we analyze the glassy dynamics of binary mixtures using molecular dynamics simulations. We consider a binary mixture of charged Lennard-Jones particles and vary the partial charges of the particles and, thus, the high-temperature activation energy and the glass transition temperature of the system. Based on previous results, we introduce a phenomenological model describing relaxation times over the whole temperature regime from high temperatures to temperatures well inside the supercooled regime. By investigating the dynamics of both particle species on molecular and diffusive length scales along isochoric and isobaric pathways, we find a quadratic charge dependence of both E∞ and Tg, resulting in an approximately constant ratio of both quantities independent of the underlying observable, the thermodynamic ensemble, and the particle species, and this result is robust against the actual definition of Tg. This generic relation between the activation energy and the glass transition temperature indicates that high-temperature dynamics and the glassy slowdown are related phenomena, and the knowledge of E∞ may allow us to approximately predict Tg.

Effects of confinement on supercooled tetrahedral liquids.

We use molecular dynamics simulations to ascertain the effects of geometrical restriction on glass-forming tetrahedral liquids. Striving for a broad approach, we study families of waterlike and silicalike liquids, for which we systematically scale the partial charges and, hence, the relevance of the tetrahedral networks. The confined liquids and the confining matrices consist of the same type of particles to avoid disruptive interactions and distorted structures at the interfaces. Spatially resolved analyses show that these neutral confinements still impose static mobility gradients and density correlations on the liquids. We quantify the increasing degree and range of the altered properties upon cooling. For both families of models, common relations describe the confinement effects of all systems with tetrahedral order, while deviations occur for systems with lower polarities and different structures. The observations are rationalized by considering the fact that a pinned wall imprints a static energy landscape to a neighboring liquid. We explore the properties of this landscape based on changes in vibrational motion and structural relaxation and find that typical barrier heights amount to two to three times the activation energy of bulk dynamics. Combining the present and previous results, we predict the evolution of confinement effects down to the glass transition temperature for liquids without fragile-to-strong crossover. In addition, it is found for silicalike liquids that the temperature dependence of dynamic and static correlation lengths from confinement studies is not affected when cooling through fragile-to-strong transitions of the bulk materials, casting doubt on the relevance of these length scales for the glassy slowdown.

Common behaviors associated with the glass transitions of water-like models.

We perform molecular dynamics simulations to ascertain effects of the molecular polarity on structural and dynamical properties of water-like systems, in particular, on their glassy slowdown. To systematically vary the molecular dipole moments, we scale the partial charges of the established SPC/E and TIP4P/2005 models. In broad ranges of the molecular polarity, the studied SPC/E and TIP4P/2005 descendants show a density anomaly, which can be attributed to the removal of water molecules interstitial between the first and the second neighbor shells upon cooling. While all considered modified water models behave as typical glass formers, the structural relaxation time τ heavily depends on the molecular dipole moment. This large dynamical diversity is exploited to systematically ascertain characteristic properties of glass-forming liquids. For all studied water-like systems, we observe a close relation between the activation energy E∞ describing the Arrhenius behavior of the regular liquid and the glass transition temperature Tg characterizing the supercooled liquid, explicitly, E∞/Tg≈10. Moreover, decomposing the activation energy of the structural relaxation according to E(T)=E∞+Ec(T), we show that the glassy slowdown of all modified water molecules can fully be traced back to an exponential temperature dependence of the contribution Ec(T) related to cooperative dynamics. Extrapolation of this behavior suggests a common value at the glass transition temperature, Ec(Tg)/Tg≈25. Finally, we discuss links between the structural relaxation and the vibrational displacement, as proposed in various theoretical approaches to the glass transition.

Lacosamide cardiac safety: a thorough QT/QTc trial in healthy volunteers.

OBJECTIVE: To determine whether lacosamide prolongs the corrected QT interval (QTc). MATERIALS AND METHODS: In this randomized, double-blind, positive- and placebo-controlled, parallel-design trial, healthy volunteers were randomized to lacosamide 400 mg/day (maximum-recommended daily dose, 6 days), lacosamide 800 mg/day (supratherapeutic dose, 6 days), placebo (6 days), or moxifloxacin 400 mg/day (3 days). Variables included maximum time-matched change from baseline in QT interval individually corrected for heart rate ([HR] QTcI), other ECG parameters, pharmacokinetics (PK), and safety/tolerability. RESULTS: The QTcI mean maximum difference from placebo was -4.3 ms and -6.3 ms for lacosamide 400 and 800 mg/day; upper limits of the 2-sided 90% confidence interval were below the 10 ms non-inferiority margin (-0.5 and -2.5 ms, respectively). Placebo-corrected QTcI for moxifloxacin was +10.4 ms (lower 90% confidence bound >0 [6.6 ms]), which established assay sensitivity for this trial. As lacosamide did not increase QTcI, the trial is considered a negative QTc trial. There was no dose-related or clinically relevant effect on QRS duration. HR increased from baseline by ~5 bpm with lacosamide 800 mg/day versus placebo. Placebo-subtracted mean increases in PR interval at tmax were 7.3 ms (400 mg/day) and 11.9 ms (800 mg/day). There were no findings of second-degree or higher atrioventricular block. Adverse events (AEs) were dose related and most commonly involved the nervous and gastrointestinal systems. CONCLUSIONS: Lacosamide (≤ 800 mg/day) did not prolong the QTc interval. Lacosamide caused a small, dose-related increase in mean PR interval that was not associated with AEs. Cardiac, overall safety, and PK profiles for lacosamide in healthy volunteers were consistent with those observed in patients with partial-onset seizures.

Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures.

OBJECTIVE: To evaluate the cardiac safety of adjunctive lacosamide in a large pool of adults with partial-onset seizures (POS). METHODS: Post-randomization changes from baseline for electrocardiographic (ECG) measurements, diagnostic findings, and relevant adverse events (AEs) were compared for pooled data from three randomized, placebo-controlled trials of adjunctive lacosamide for the treatment of POS. RESULTS: Lacosamide did not prolong the QTc interval or affect heart rate as determined by an analysis of data from patients randomized to lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). After 12-week maintenance treatment, mean changes from baseline for QRS duration were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, respectively). First-degree atrioventricular (AV) block was reported as a non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective groups. Second- or higher degree AV block was not observed. There was no evidence of a PR-interval-related pharmacodynamic interaction of lacosamide with either carbamazepine or lamotrigine. CONCLUSIONS: Evaluation of the pooled cardiac safety data from patients with POS showed that adjunctive lacosamide at the maximum recommended dose (400 mg/day) was not clearly associated with any cardiac effect other than a small, dose-related increase in PR interval that had no evident symptomatic consequence.

[Molecular diagnostics of hereditary fever syndromes. Familial Mediterranean fever (FMF), hyperimmunoglobulin D syndrome (HIDS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS: FCAS, MWS, NOMID/CINCA)]. / Molekulargenetische Diagnostik erblicher Fiebersyndrome. Familiäres Mittelmeerfieber (FMF), Hyperimmunglobulin-D-Syndrom (HIDS), TNF-rezeptorassoziiertes periodisches Syndrom (TRAPS), Cryopyrin-assoziiertes periodisches Syndrom (CAPS: FCAS, MWS, NOMID/CINCA).

Periodic episodes of fever and inflammation can have a genetic origin. Nowadays, the identification of the causative genetic variants in the majority of cases allows molecular genetic confirmation of the clinical diagnosis, which enables approaches with specific drug treatment and improves patient compliance as well as genetic counseling. Besides a detailed clinical examination a medical history including family history and an assessment of the ethnic origin are required. In order to make genetic testing straightforward and cost effective an iterative procedure should be followed which should include, in addition to clinical data, the frequencies of causative mutations in the various gene segments involved.

A structural variant of the human interferon-gamma gene.

The first structural IFNG variant, G54D (c.287G>A, ss105106770), located in the second exon, was identified.

Thorough QT/QTc study in patients with advanced Parkinson's disease: cardiac safety of rotigotine.

The potential effects of the dopamine agonist rotigotine on cardiac repolarization were studied in patients with Parkinson's disease, which affects electrocardiogram (ECG) quality. The parallel-group trial was double-blind and placebo- and positive (moxifloxacin 400 mg)-controlled. After two 24-h baseline ECGs, patients were randomized to rotigotine (n = 66) or placebo (n = 64). Twenty four-hour ECGs were recorded on days 14/15, 21/22, 28/29, 35/36, and 42/43 of a regimen involving weekly dose escalations of 4 mg/24 h (4 mg/24 h-24 mg/24 h). In 10-s ECGs (n = 357,948) selected from 24-h records, QT measurements were manually verified and individually rate-corrected (QTc). Assay sensitivity showed maximum mean 13.5 ms QTc prolongation after moxifloxacin with 95% confidence interval (CI) 11.8-15.2 ms. Rotigotine vs. placebo differences in time-matched changes from baseline (54 data points/24 h) showed mean effects close to zero with upper one-sided 95% CI <5 ms. Accurate, thorough QTc studies are possible even in patients with diseases that profoundly affect ECG quality. Rotigotine in supra- and therapeutic doses was shown not to affect cardiac repolarization.

[Laparoscopic inguinal herniorrhaphy in children--experiences in a primary medical care center]. / Die laparoskopische herniorrhaphie des leistenbruches im kindesalter--erfahrungen in einem krankenhaus der grund--und regelversorgung.

AIM: Children undergoing laparoscopic herniorrhaphy may benefit from a minimally invasive access and the possible exploration of the contralateral groin. In this prospective feasibility study, the experiences and results after introduction of this method in a tertiary referral medical center are reported. METHODS: 50 laparoscopic herniorrhaphies were performed in 44 children (32 boys and 12 girls, range: 17 months-11 years) with open inner inguinal rings between January 2001 and March 2007. In 6 children (13.6 %) an additional contralateral open inner inguinal ring was detected. Laparoscopic access was obtained with a 5-mm laparoscope which was inserted transumbilically and two 2-mm needle holders were inserted through the inferolateral abdominal wall. The open inner inguinal rings were closed in 8 children using a resorbable Z-suture and in 36 children using a monofilamentous non-absorbable suture. Follow-up examinations included records of intra- and postoperative complications, recurrence rate and economic aspects. RESULTS: No intra- or perioperative complications occurred. Median operation time was 19 minutes. 43 / 44 operations were carried on an outpatient basis. Average material costs were about 20 Euro without any difference from the open access. During 36 months the follow-up rate was 91 %. Two children who had previously received an absorbable suture suffered from a recurring groin hernia within the first 6 months. CONCLUSION: Laparoscopic herniorrhaphy in children represents a safe and effective surgical method that can be recommended for tertiary referral medical centers with training facilities and experience in minimally invasive surgery.

Randomized clinical trial of the influence of intraperitoneal local anaesthesia on pain after laparoscopic surgery.

BACKGROUND: There is controversy about the effectiveness of intraperitoneal local anaesthesia (LA) in laparoscopic surgery. The aim of the present randomized clinical trial was to compare the analgesic effect of pre-emptive (preoperative) versus postoperative intraperitoneal LA in two different types of laparoscopic surgery. METHODS: Between July 2004 and January 2005, 133 consecutive patients scheduled to undergo laparoscopic fundoplication or hernia repair were randomly assigned to one of three treatments: placebo solution (50 ml 0.9 per cent saline) or LA (50 ml 0.5 per cent lidocaine) administered immediately after creation of the pneumoperitoneum, or LA (50 ml 0.5 per cent lidocaine) at the end of the operation. Analgesic requirements were analysed, and pain was assessed using a visual analogue scale (VAS) from 0 to 100 at 6, 12, 24 and 48 h after surgery. RESULTS: The duration of pneumoperitoneum (median 66 versus 46 min respectively; P < 0.001) and overall pain intensity (median VAS score 46.7 versus 6.5; P < 0.001) were higher for laparoscopic fundoplication than for hernia repair. Preoperative application of LA reduced abdominal pain (median 28.6 versus 74.9; P < 0.005), shoulder pain (median 24.3 versus 43.8; P = 0.004) and analgesic consumption (mean(s.d.) 11.1(5.0) versus 18.5(5.4) mg piritramide per 48 h; P = 0.002) after fundoplication, but had no analgesic effects after hernia repair. CONCLUSION: Pre-emptive application of LA reduced postoperative pain and analgesic requirements after laparoscopic fundoplication.

Focussing cellular function. Metabolic monitoring in perioperative and Intensive Care Medicine.

In the clinical field microdialysis today is a routine technique for monitoring the chemistry of tissues and organs in physiological and pharmacological research on animals. In more than 10.000 papers on microdialysis research it is used to uncover physiological mechanisms and the influence of drugs in almost every organ of the body. Since the first papers describing microdialysis in the human brain microdialysis has become a technique for routine monitoring of energy metabolism especially in neurointensive care. This paper gives an account of the microdialysis technique describing its practical use and interpretation in monitoring energy metabolism and ischemia in different organs with respect to the field of perioperative and intensive care medicine. This article gives an overview over current results of clinical studies using microdialysis in critical care medicine and tries to focus on possible indications for clinical biochemical monitoring. However, despite numerous publications available microdialysis has not been shown to improve outcome of the patients yet.

[Anti-reflux surgery in patients with adequate response to proton pump inhibitors - is there an indication?]. / Antirefluxchirurgie bei patienten mit adäquatem ansprechen auf protonenpumpeninhibitoren - sinnvoll oder übertherapiert?

BACKGROUND: The indication for anti-reflux-surgery in patients with gastroesophageal reflux disease (GERD) who are totally symptom-free under conservative treatment with proton pump inhibitors (PPI) is still seen controversially. Arguments for PPI-treatment include the missing trauma and few side-effects, arguments against include the life-time-long drug intake. We prospectively observed the indication of anti-reflux-surgery in symptom-free patients in comparison to patients with remaining symptoms under treatment with PPI. PATIENTS AND METHODS: Between January 1999 and December 2001, 317 patients with GERD were treated by laparoscopic hemifundoplication and grouped in patients with adequate response to PPI (n = 103) and patients with residual discomfort in spite of or by PPI (n = 214). Preoperative diagnostic included endoscopy, ph-testing, manometry and quality of life scoring by a standardized questionnaire. Peri- and postoperative morbidity as well as quality of life were analyzed and compared with healthy individuals (n = 50). RESULTS: Patient demographics and surgical procedures did not differ between the two groups. After a median follow-up of 49 months and a follow-up rate of 89.9 %, the recurrence rate was 2.5 % and perioperative complication rate was 6.3 % without any significant differences between the groups. Patients with GERD and adequate response to PPI showed preoperatively during PPI omission a significant lower incidence of esophagitis (3.9 % vs. 18.2 %) and higher quality of life score (93.7 +/- 11.3 vs. 75.3 +/- 12.6), which significantly decreased in comparison to healthy individuals (132.9 +/- 10.5). After anti-reflux surgery the quality of life has been increased in both groups (130.5 +/- 11.4 vs. 121.8 +/- 13.2). However, only patients with adequate response to PPI reached the quality of life score of healthy individuals. CONCLUSION: Patients with preoperatively adequate response to PPI profit of anti-reflux surgery in terms of postoperative quality of life. Concerning the indication for anti-reflux surgery in these patients, one has to balance between the individual inconvenience due to the long-lasting drug intake on the one hand and the operative risk, morbidity and outcome of a specialized surgical department on the other hand.

[Risk management in the operation room. Results of a pilot project of interdisciplinary "incident reporting"]. / Risikomanagement im Operationsbereich. Ergebnisse eines pilotprojektes zum interdisziplinären "incident-reporting".

BACKGROUND: Methods for error analysis are suitable to increase patients' safety as well as staff satisfaction and may avoid, in a sense of process control, financial damage to the hospital. The aim of the presented pilot study was to establish and evaluate an incident reporting system as a first step towards a new safety culture. METHODS: In June 2003 an incident reporting system was introduced in the central surgical suite, in which the surgical and anaesthesiologic departments took part as well medical and nursing staff. Besides conceiving a report form, a "board of confidence" was elected, kick-off meetings were held and a baseline study on the basis of industrial psychological knowledge was initialised. RESULTS: The process of creating confidence is arduous and depends elementarily on sincere cooperation of management staff, especially of the heads of the departments. The exclusive participation of only two medical departments led to conflicts. Therefore, after finishing the pilot study, the system was expanded to the whole surgical suite including all operating departments. In order to increase the motivation for the strictly voluntarily participation, the frequency of regular echoes to the staff was optimised. To achieve high acceptance in the whole staff, the board of confidence needs a clearly defined position within the system of quality management. CONCLUSIONS: For the first time in Germany an incident reporting system under participation of several medical departments has been installed. After finishing the pilot project, in future we will be able to evaluate changes caused by this system. Simultaneously an electronic database for reported adverse events and strategies to avoid them are being developed based on similar systems in aviation industry. In near future, the system will be of increasing importance likewise for inpatient units and non-operative departments.

YAC/BAC contig spanning the MHC class III region of cattle.

A contig of the class III region of the bovine major histocompatibility complex (MHC) was established from bacterial and yeast artificial chromosomes using PCR and BAC-end sequencing. The marker content of individual clones was determined by gene and BAC-end specific PCR, and the location of genes and BAC-ends was confirmed analyzing somatic hybrid cells. A comparative analysis indicated that the content and order of MHC class III genes is strongly conserved between cattle and other mammalian species. Fluorescence in situ hybridization localized the bovine class III region to BTA23q21-->q22. The results show that the collection of sequenced BAC-ends is a powerful resource for generating high-resolution comparative chromosome maps.

No associations of human pulmonary tuberculosis with Sp110 variants.

BACKGROUND: After a recent report on the role of the Ipr1 gene in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, the human Ipr1 homologue, Sp110, was considered a promising candidate for an association study in human tuberculosis. METHODS: In a sample of >1000 sputum positive, HIV negative West African patients with pulmonary tuberculosis and >1000 exposed, apparently healthy controls, we have genotyped 21 Sp110 gene variants that were either available from public databases, including HapMap data, or identified by DNA re-sequencing. RESULTS: No significant differences in the frequencies of any of the 21 variants were observed between patients and controls. This applied also for HapMap tagging variants and the corresponding haplotypes, when including sliding window analyses with three adjacent variants, and when stratifying controls for positivity and negativity according to the results of intradermal tuberculin (purified protein derivative, PPD) skin tests. DNA re-sequencing revealed 13 novel Sp110 variants in the 5'-UTR, exons, and adjacent intronic regions. CONCLUSIONS: Based on the results obtained in this case-control study, the hypothesis that Sp110 variants and haplotypes might be associated with distinct phenotypes of human M tuberculosis infection is doubtful.

Long-term experience of treating 185 patients with gastroesophageal reflux disease (GERD) by anti-reflux surgery respecting the functional-morphological restoration of the esophagus.

BACKGROUND: According to anatomical investigations the whole esophagus plays a crucial role as reflux barrier in the pathogenesis of gastroesophageal reflux disease (GERD). Morphologically, the spirally arranged muscle fibres present a tension-dependent "stretch closure" and in the event of any reduction of tension, as for example caused by an axial hiatus hernia, the organ may become inefficient. The aim of this study was to evaluate quality of life as the main success criterion after anti-reflux surgery based strictly on the restoration of functional morphology. METHODS: Between January 1999 and December 2000, 185 patients with GERD were treated by surgery in accordance with functional-morphological principles. After dissecting the mediastinum, the gastroesophageal junction was displaced into the abdomen with consecutive retensioning the esophagus. The esophageal hiatus was reconstructed with non-absorbable single knot sutures and strengthened with alloplastic material. The application of a 180 degrees fundus cuff around the posterior esophageal circumference served as a "spacer" and also restored the angle of His. Preoperatively, all patients underwent endoscopy, pH metry and manometry. During postoperative follow-up, recurrence rate and quality of life were evaluated via a disease-specific scale. RESULTS: Preoperatively, 85% of the patients had an elevated DeMeester Score with a median of 81.4; 64% had reflux esophagitis and 37% had reduced lower esophageal sphincter pressure. All 185 operations were performed without conversion in a median operating time of 74 min. In one patient a lesion of the esophagus was treated during the operation; two patients had lesions of the splenic capsule which were also dealt with during the operation. Postoperatively, pleural effusions occurred in 15 patients and puncture was deemed necessary in one subject. Ninety-three percent were followed up for a median of 45 months and the recurrence rate was 2.3%. The quality of life index was 81.6+/-12.4 points preoperatively, and had significantly improved to 125.2+/-12.7 points in the follow-up. CONCLUSION: Through the functional-morphological concept of anti-reflux surgery comprising the restoration of the tension-dependent "stretch closure" of the esophagus, significant long-term improvement in quality of life with a low recurrence rate and perioperative morbidity can be achieved.

Pre-treatment with chloroquine and parasite chloroquine resistance in Ghanaian children with severe malaria.

BACKGROUND: Self-medication with anti-malarial drugs is widespread, and chloroquine (CQ) resistance is increasing. The effect of these factors on the incidence and presentation of severe malaria is uncertain. AIM: To investigate subtype of severe malaria, duration of illness, previous CQ treatment and prevalence of Plasmodium falciparum CQ-resistance markers among children presenting with severe malaria to a teaching hospital in Ghana. DESIGN: Prospective clinical study. METHODS: Consecutive patients (n = 189) presenting with severe malaria were examined clinically, and blood was taken for routine haematology and malaria films. Plasma and blood cells were stored and subsequently analysed by ELISA for CQ levels (n = 168) and by PCR and restriction digest for P. falciparum chloroquine resistance transporter gene (pfcrt) mutations (n = 139). RESULTS: Of 47 presenting with cerebral malaria, 21 had severe anaemia and 13 respiratory distress (RDS). Twenty-nine had prostration or RDS alone, 41 severe anaemia with prostration or RDS, and 72 severe anaemia not associated with coma, prostration or RDS. Of the patients studied, 77% had CQ in their plasma, and 88% were carrying P. falciparum with a CQ-resistance genotype. Significant associations were found (i) between the CQ-resistance genotype of parasites and plasma CQ levels, (ii) between the presence of CQ in plasma and the reported duration of illness, and (iii) between the reported duration of illness and the occurrence of severe but otherwise uncomplicated anaemia. DISCUSSION: There was extensive prior CQ use in our patients presenting with severe malaria, and a high prevalence of parasites with the CQ-resistance genotype. CQ resistance in P. falciparum may contribute to the development of severe but otherwise uncomplicated anaemia in this setting.

[Telemedical-supported screening of retinal vessels ("talking eyes")]. / Telemedizinisch unterstütztes Screening der retinalen Gefässe ("Talking Eyes").

BACKGROUND: Cerebral and retinal vessels behave similarly under the influence of vascular risk factors. Several groups have shown that retinal microvascular abnormalities represent an independent risk factor with regard to strokes and heart attacks. AIM OF THE STUDY: The aim of this study was to perform a prospective screening examination with regard to retinal microvascular abnormalities as well as an extended vessel diagnosis in a subgroup of patients with lower arteriovenous risk values. METHODS: In the course of a prospective cross-sectional study ("Talking Eyes") between 1.9.2001 and 1.8.2002 a telemedical-supported screening of the retina (study I) was carried out in 7,163 subjects. The patients were selected without any inclusion or exclusion criteria. The mean age was 48.2 +/- 8 years (18 - 83 years) with a sex distribution of 39.2 % females to 60.8 % males. Digital fundus photos of the right and left eyes were taken for all patients. The pictures were taken without pupil dilation using a CANON-NM camera. The pictures and case histories were stored in a central server using web-based software (MedStage, Siemens). In a central reading centre, the arteriovenous ratio of both eyes was determined telemedically using the Parr-Hubbard formula and the retinas subjected to a standardised examination by an ophthalmologist. The retinal risk factor was calculated on the basis of the arteriovenous ration, the presence of microvascular abnormalities and the case history. The reproducibility of measurement of the arteriovenous ratio (Kronbach alpha coefficient) was evaluated by double measurements on 1,332 images. In a subgroup of study I with arteriovenous ratio values < 0.76 (N = 107), an extended vessel diagnosis with measurement of 24-h blood pressure and vessel-relevant blood values (homocysteine, cholesterol, LDL, HDL, CRP, TG, HbA1c) was carried out (study II). RESULTS: Study I: The Kronbach alpha coefficient as a measure of reproducibility amounted to 0.77. The mean arteriovenous ratio of the retinal vessels was 0.83 +/- 0.09 and showed a pronounced age dependence (R = 0.9, p < 0.0001). On multivariate testing the arteriovenous ratio correlated significantly (R = 0.33, p < 0.001) with the factors age, systolic blood pressure, diastolic blood pressure and body mass index. Diastolic blood pressure followed by age had the largest influence. The prevalence of microvascular abnormalities in the right (RE) and left (LE) eyes, respectively were: cotton wool foci RE 0.0015 %, LE 0.003 %, retinal haemorrhage RE 0.1 %, LE 0.1 %, focal stenoses RE 3.4 %, LE 3.4 %, tortuositas vasorum RE 4.1 %, LE 4.0 %, arteriovenous crossing signs RE 11.2 %, LE 11.2 %. On multivariate testing the occurrence of microvascular abnormalities correlated significantly (R = 0.38, p < 0.001) with the factors high blood pressure known from case history, body mass index, and gender. Arterial hypertension had the strongest influence followed by diastolic blood pressure. The calculated retinal risk factor correlated with the prevalence of angina pectoris. Study II: 2/3 of the subjects with arteriovenous risk factor values < 0.76 exhibited pathologically high 24-h blood pressure values. For these patients there were significant correlations between the arteriovenous ratio and the low-density lipoprotein concentration as well as the Framingham risk score. CONCLUSION: In the course of a prospective, telemedical-supported screening examination of the retinal vessels of more than 7,000 subjects the arteriovenous ratio exhibited a strong dependence on age and blood pressure. Among the subjects with lowered arteriovenous ratio values, 2/3 exhibited arterial hypertension in the 24-h blood pressure determination.

[Laparoscopic versus open appendectomy: which factors influence the decision between the surgical techniques?]. / Laparoskopische vs. offene Appendektomie: Welche Faktoren beeinflussen die Wahl der Operationsmethode?

BACKGROUND: Although in hospitals focussing on minimal invasive surgery laparoscopic appendectomy (LA) is widely practiced as method of choice in patients with acute appendicitis, the decision for the laparoscopic or the conventional technique (OA) is usually ensued by individual viewpoints. Aim of this prospective observation study was to analyse the decision algorithm for both procedures in patients with the presumptive diagnosis "appendicitis". PATIENTS AND METHODS: Between January 1996 and July 2001 512 patients with the presumptive diagnosis "acute appendicitis" underwent surgery and, assigned by intention-to-treat, were subdivided in a laparoscopic (I) and a conventional group (II). The choice of surgical procedure was analysed with regard to patient characteristics (age, gender, comorbidity), severity of appendicitis (clinical manifestation, preoperative inflammation signs), surgeon (clinical experience) and daytime (during the day, in the evening, at night). Furthermore, the outcome of either method was related to postoperative diagnosis, perioperative morbidity, analgesia, length of hospital stay and cosmetic results. RESULTS: In group I 265 patients and in group II 247 patients underwent surgery. Conversion from LA to OA was necessary in 6.4 %. Group I consisted of significantly more female (67.9 % vs. 45.7 %) and younger patients (21 yrs. vs. 30 yrs.) with less medical history as well as minor severity of tissue inflammation and significantly lower preoperative serum inflammation parameters (leukocytes (1000/ml): 10.6 +/- 4.3 vs. 13.5 +/- 4.9; CRP (mg/l): 2.3 +/- 3.3 vs. 5.6 +/- 7.5, I vs. II: p < 0.001). In group I more patients underwent surgery during day-time as well as by more laparoscopic-experienced surgeons. In the postoperative histopathologic evaluation there were significantly fewer cases with complicated appendicitis (33.2 % vs. 52.2 %, p < 0.001). Additionally, patients after LA revealed a lower postoperative complication rate (9.3 % vs. 18.3 %), length of hospital stay (median 3 vs. 4 days) and duration of analgesia (2.1 +/- 1.8 vs. 4.1 +/- 7.1 days). CONCLUSIONS: Important factors for decision algorithm between a laparoscopic or an open appendectomy include severity of appendicitis, gender, day-time as well as the surgeon's individual laparoscopic experience. With appropriate indication for each technique, both procedures are of equal value in the treatment of acute appendicitis. Furthermore the positive patient selection for laparoscopic appendectomy contributed to a better postoperative outcome in this study.