[Transanal extraction vs. minilaparotomy : For laparoendoscopic left-sided colon resection]. / Transanale Bergung vs. Minilaparotomie : Bei laparoendoskopischer linksseitiger Kolonresektion.

BACKGROUND: Recent developments in classical minimally invasive surgical procedures for colon resection aimed to minimize or even eliminate abdominal wall incisions, thus improving postoperative pain, patient recovery and aesthetics. A promising approach is the total laparoendoscopic colectomy (LEC) with transanal sample extraction. The aim of this study was the comparison of total LEC with conventional laparoscopic assisted surgery (LAS) and extraction incision. METHOD: We included 168 consecutive patients (LEC:112; LAS:56) with diverticular disease, rectal prolapse, benign or malignant tumors and analyzed retrospectively. The specimen was extracted transanally by LEC with a specially developed rectoscope; the LAS group required a minilaparotomy of 5 cm. The primary outcome was postoperative pain. Secondary outcomes included operating time, minor and major complication rates, number and length of extracted specimens, additional pain medication and duration of hospital stay. RESULTS: The measured postoperative pain score values did not significantly differ between the two groups; however, consumption of postoperative pain medication was significantly higher in the LAS-group (p < 0.001). Due to the learning curve, the median operating time in the LEC group (120 min) was slightly longer than in the LAS group (100 min); however, it was reduced to 95 min in the last 50 operations. Patients in the LEC group were discharged from hospital one day earlier (median duration of hospital stay 6 days, p = 0.003). Compliaction rates were similar in both groups. CONCLUSION: The technique of total LEC with transanal specimen extraction is designed to avoid a minilaparotomy and its associated morbidities. The LEC operation is feasible for a large group of patients, including overweight patients. The superiority of LEC in terms of reduced pain medication, shorter hospital stay and faster patient recovery, as shown in this study, needs to be confirmed by randomized controlled trials with longer follow-up periods.

Performance of the Peto odds ratio compared to the usual odds ratio estimator in the case of rare events.

For the calculation of relative measures such as risk ratio (RR) and odds ratio (OR) in a single study, additional approaches are required for the case of zero events. In the case of zero events in one treatment arm, the Peto odds ratio (POR) can be calculated without continuity correction, and is currently the relative effect estimation method of choice for binary data with rare events. The aim of this simulation study is a variegated comparison of the estimated OR and estimated POR with the true OR in a single study with two parallel groups without confounders in data situations where the POR is currently recommended. This comparison was performed by means of several performance measures, that is the coverage, confidence interval (CI) width, mean squared error (MSE), and mean percentage error (MPE). We demonstrated that the estimator for the POR does not outperform the estimator for the OR for all the performance measures investigated. In the case of rare events, small treatment effects and similar group sizes, we demonstrated that the estimator for the POR performed better than the estimator for the OR only regarding the coverage and MPE, but not the CI width and MSE. For larger effects and unbalanced group size ratios, the coverage and MPE of the estimator for the POR were inappropriate. As in practice the true effect is unknown, the POR method should be applied only with the utmost caution.

The Peto odds ratio viewed as a new effect measure.

Meta-analysis has generally been accepted as a fundamental tool for combining effect estimates from several studies. For binary studies with rare events, the Peto odds ratio (POR) method has become the relative effect estimator of choice. However, the POR leads to biased estimates for the OR when treatment effects are large or the group size ratio is not balanced. The aim of this work is to derive the limit of the POR estimator for increasing sample size, to investigate whether the POR limit is equal to the true OR and, if this is not the case, in which situations the POR limit is sufficiently close to the OR. It was found that the derived limit of the expected POR is not equivalent to the OR, because it depends on the group size ratio. Thus, the POR represents a different effect measure. We investigated in which situations the POR is reasonably close to the OR and found that this depends only slightly on the baseline risk within the range (0.001; 0.1) yet substantially on the group size ratio and the effect size itself. We derived the maximum effect size of the POR for different group size ratios and tolerated amounts of bias, for which the POR method results in an acceptable estimator of the OR. We conclude that the limit of the expected POR can be regarded as a new effect measure, which can be used in the presented situations as a valid estimate of the true OR.

Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern.

BACKGROUND: The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases. OBJECTIVE: To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP. METHODS: We ascertained ERP on the basis of electrocardiograms in 3 large community-based cohorts from Europe and the United States: the Framingham Heart Study, the Health 2000 Study, and the KORA F4 Study. We analyzed genome-wide association studies in participants with and without ERP by logistic regression assuming an additive genetic model and meta-analyzed individual cohort results. We then sought to strengthen support for findings that reached P ≤ 1 × 10(-5) in independent individuals by direct genotyping or in-silico analysis of genome-wide data. We meta-analyzed the results from both stages. RESULTS: Of 7482 individuals in the discovery stage, 452 showed ERP (ERP positive: mean age 46.9 ± 8.9 years, 30.3% women; ERP negative: 47.5 ± 9.4 years, 54.2% women). After meta-analysis, 8 single nucleotide polymorphisms reached P ≤ 1 × 10(-5): The most significant finding was intergenic rs11653989 (odds ratio 0.47; 95% confidence interval 0.36-0.61; P = 6.9 × 10(-9)). The most biologically relevant finding was intronic to KCND3: rs17029069 (odds ratio 1.46; 95% confidence interval 1.25-1.69; P = 8.5 × 10(-7)). In the replication step (7151 individuals), none of the 8 variants replicated, and combined meta-analysis results failed to reach genome-wide significance. CONCLUSIONS: In a genome-wide association study, we were not able to reliably identify genetic variants predisposing to ERP, presumably due to insufficient statistical power and phenotype heterogeneity. The reported heritability of ERP warrants continued investigation in larger well-phenotyped populations.

Polymorphisms of the drug transporter gene ABCB1 predict side effects of treatment with cabergoline in patients with PRL adenomas.

INTRODUCTION: Treatment with dopamine agonists in patients with prolactin (PRL) adenomas and Parkinson's disease is associated with central side effects. Central side effects may depend on a substance's ability to pass the blood-brain barrier, which can be actively controlled by transporter molecules such as the P-glycoprotein (P-gp) encoded by the ABCB1 gene. MATERIALS AND METHODS: We aimed to determine whether cabergoline is transported by the P-gp and whether polymorphisms of its encoding ABCB1 gene predict central side effects of cabergoline therapy in patients with PRL adenomas. i) In an experimental mouse model lacking the homologues of the human ABCB1 gene (Abcb1ab double knockout mouse model), we examined whether cabergoline is a substrate of the P-gp using eight mutant and eight wild-type mice. ii) In a human case-control study including 79 patients with PRL adenomas treated with cabergoline at the Max Planck Institute of Psychiatry in Munich, we investigated the association of four selected ABCB1 gene single nucleotide polymorphisms (SNPs) (rs1045642, rs2032582, rs2032583 and rs2235015), with the occurrence of central side effects under cabergoline therapy. RESULTS: i) In the experimental mouse model, we observed that brain concentrations of cabergoline were tenfold higher in the mutant mice compared with their wild-type littermates, implying that cabergoline is indeed a substrate of the transporter P-gp at the blood-brain barrier level. ii) In the human study, we observed significant negative associations under cabergoline for the C-carriers and heterozygous CT individuals of SNP rs1045642 with two central side effects (frequency of fatigue and sleep disorders) and for the G-carriers of SNP rs2032582 with the enhancement of dizziness. For the SNPs rs2235015 and rs2032583, no associations with central side effects under cabergoline were found. DISCUSSION: This is the first study demonstrating that individual ABCB1 gene polymorphisms, reflecting a different expression and function of the P-gp, could predict the occurrence of central side effects under cabergoline. Our findings can be viewed as a step into personalised therapy in PRL adenoma patients.

Interrelated neuropsychological and anatomical evidence of hippocampal pathology in the at-risk mental state.

BACKGROUND: Verbal learning and memory deficits are frequent among patients with schizophrenia and correlate with reduced magnetic resonance imaging (MRI) volumes of the hippocampus in these patients. A crucial question is the extent to which interrelated structural-functional deficits of the hippocampus reflect a vulnerability to schizophrenia, as opposed to the disorder per se. METHOD: We combined brain structural measures and the Rey Auditory Verbal Learning Test (RAVLT) to assess hippocampal structure and function in 36 never-medicated individuals suspected to be in early (EPS) or late prodromal states (LPS) of schizophrenia relative to 30 healthy controls. RESULTS: Group comparisons revealed bilaterally reduced MRI hippocampal volumes in both EPS and LPS subjects. In LPS subjects but not in EPS subjects, these reductions were correlated with poorer performance in RAVLT delayed recall. CONCLUSIONS: Our findings suggest progressive and interrelated structural-functional pathology of the hippocampus, as prodromal symptoms and behaviours accumulate, and the level of risk for psychosis increases. Given the inverse correlation of learning and memory deficits with social and vocational functioning in established schizophrenia, our findings substantiate the rationale for developing preventive treatment strategies that maintain cognitive capacities in the at-risk mental state.

Remembering or knowing: electrophysiological evidence for an episodic memory deficit in schizophrenia.

BACKGROUND: In schizophrenia, impaired conscious retrieval of past events and facts may represent a selective cognitive deficit of declarative memory against a background of a generalized neuropsychological impairment. We aimed to disentangle the neural subprocesses leading to this deficit applying the 'Remember/Know procedure'. METHOD: Event-related potentials (ERPs) were recorded as 14 schizophrenic patients and 14 controls recognized an equal mixture of previously presented old and new words. For recognized old words, participants were required to judge whether recognition was associated with recollection ('Remember') or familiarity ('Know'), either reflecting episodic or semantic memory. RESULTS: Patients showed a lack of 'Remember responses', which led to more opportunities to make 'Know responses'. ERPs for 'Remember' compared to 'New responses' differed consistently in controls over left temporo-parietal and right frontal electrode sites. Although schizophrenic patients showed the same topography for this Remember old/new effect, it was apparent over temporoparietal sites for only 800 ms and over right frontal sites for 1100 ms post-stimulus. For controls, the Know old/new effect was elicited over temporo-parietal sites between 500 and 800 ms. For patients, it showed a widespread maximum over frontal sites between 500 and 1100 ms. CONCLUSIONS: The shorter time course of the left temporo-parietal Remember old/new effect suggests that the patients' episodic memory impairment was possibly mediated by a dysfunction of the mediotemporal regions. The more widespread frontal Know old/new effect in the patients suggests that the prefrontly mediated processes associated with retrieval of semantic memory may be enhanced compensatorily.

Methohexital-induced changes in spectral power of neuromagnetic signals: beta augmentation is smaller over the hemisphere containing the epileptogenic focus.

Previous research has suggested that methohexital, a short-term barbiturate, alters activity in the primary epileptogenic area. It can be assumed that drug-induced activation of the epileptogenic focus provides a rapid and safe method to obtain a sufficient amount of information relevant for the lateralization and localisation of the primary epileptogenic area. This study shows that methohexital changes spectral power in the beta band derived from magnetoencephalographic (MEG) signals over the hemisphere ipsilateral to the primary epileptogenic area. This effect was demonstrated for 10/13 of the investigated patients suffering from unilateral temporal lobe epilepsy (TLE). The side and location of the primary epileptogenic area of these patients (5 left TLE, 8 right TEL) was determined invasively during presurgical evaluation. During a 1-2 minute interval after intravenous bolus injection of 100 mg methohexital a clear lateralization effect in the beta band was observed, which differed marginally between fronto-central, fronto-temporal and temporo-parietal brain regions. In addition, bilateral spectral power changes were obtained in the theta, alpha and gamma bands that differed between brain regions. Analyses of simultaneously recorded scalp electroencephalographic (EEG) data revealed effects consistent with those of the MEG analysis. The reduced enhancement of beta band spectral power of MEG recordings provides a potential application for the non-invasive lateralization of the primary epileptogenic area.

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.

Human temporal lobe potentials in verbal learning and memory processes.

Animal experiments and lesion studies have shown the importance of temporal lobe structures for language and memory. We recorded intracranial cognitive potentials from the human lateral and medial temporal lobe in 26 patients with temporal lobe epilepsy undergoing presurgical evaluation, using a word- and a picture-recognition paradigm. Neuropsychological testing included word fluency, verbal reasoning, sustained attention and a verbal learning memory test (VLMT), which was an adapted version of the Rey auditory verbal learning test. Word-specific N400-potentials elicited in the middle temporal gyrus of the dominant left hemisphere (LTL-N400) predicted immediate recall performance after learning, whereas N400s, elicited by words but not pictures in the left anterior medial temporal lobe (AMTL-N400), predicted delayed recall. The number of words that were learned but forgotten after a 30-min delay correlated only with N400s elicited by words in the left anterior medial temporal lobe. Thus, intracranial recordings indicated that different electrophysiological responses in different temporal lobe structures were linked to memory scores from specific neuropsychological tests.

The apolipoprotein E epsilon 4 allele is not associated with early onset temporal lobe epilepsy.

A polymorphism of the apolipoprotein E gene, in particular the epsilon 4 allele (ApoE4), has been associated with impaired neuronal phospholipid metabolism and synapse reorganization and has been implicated in several neurodegenerative disorders. Since selective neuronal cell lose and aberrant axonal reorganization represent hall-marks of Ammon's horn sclerosis (AHS) in patients with chronic temporal lobe epilepsy (TLE), the ApoE polymorphism was studied in 125 patients with TLE. The genotype analysis revealed a frequency of 15.5% for epsilon 4, and 74.8% and 9.8% for epsilon 3 and epsilon 2, respectively. These figures were not significantly different from those reported in the normal European population. In addition, no correlation was found between the ApoE4 allelotype and the age of epilepsy onset, seizure type, febrile seizures, family history of epilepsy, surgical outcome and neuropathological findings in patients with TLE. These data virtually exclude ApoE as a susceptibility gene involved in the pathogenesis of early onset TLE or AHS.

[Lead and cadmium content in deciduous teeth of children of Stolberg and other cities of North-Rhine-Westphalia: a chronological trend 1968-1993]. / Blei- und Cadmiumgehalte in Milchschneidezähnen von Kindern aus Stolberg und anderen Städten Nordrhein-Westfalens: Entwicklungstrend 1968-1993.

The levels of lead and cadmium were determined in deciduous teeth (incisors only) of children living in Stolberg and some other cities located in North-Rhine-Westfalia, Germany. The Stolberg children were born in 1968-1973 (group 1; n = 103) and 1982/1983 (group 2; n = 103). The other children (n = 109) were born between 1979 and 1986. All teeth were analysed within the same analytical series by atomic absorption spectrometry (AAS). The results show that the average levels of lead and cadmium in milk teeth have decreased significantly in the time period from 1970 to 1990. Considering the Stolberg children the fall of tooth lead was about 50% and the fall of tooth cadmium was about 60%. Children from other cities show a comparable decrease of tooth lead and tooth cadmium. The results indicate that a significant decrease of the lead body burden and cadmium body burden of children and probably also of the general population of Germany has occurred during the last years.

Complex partial seizures of temporal lobe origin in children of different age groups.

The semiology of complex partial seizures (CPS) of temporal lobe origin in adults is well known and is important in establishing seizure localization in patients considered for epilepsy surgery. In contrast, the behavioral features of temporal lobe seizures (TLS) in children described in the literature have not been consistent. In the present study, we investigated children with TLS to compare their attacks to TLS occurring in adults. The study was based on video recordings of 29 children with TLS aged 18 months to 16 years. Children were included, if they became seizure-free after temporal lobectomy (except 4 children with a marked reduction in seizure frequency and 1 with isolated auras), and if clear unitemporal seizure onset in ictal EEG-recordings, unilateral radiological lesions, and corresponding histopathological findings were detected. Children aged > 6 years had TLS with features similar to those of adults. In younger children, typical semiology included symmetric motor phenomena of the limbs, postures similar to frontal lobe seizures in adults, and head nodding as in infantile spasms. We concluded that the clinical features of TLS in younger children can be misleading and should therefore be considered with caution in selecting patients for surgical procedures on the temporal lobe.

[Heavy metal pollution of soil and garden products of Stolberg home gardens and lead and cadmium pollution of small farms in Stolberg]. / Untersuchungen zur Schwermetallbelastung von Böden und Gartenprodukten aus Stolberger Hausgärten und zur Blei- und Cadmiumbelastung von Kleingärtnern aus Stolberg.

Cadmium, lead and zinc were determined in garden soils and vegetable products from private gardens located in a lead/zinc smelter area (Stolberg, Germany). At the same time lead and cadmium were measured in blood and urine samples collected from 90 garden owners. Inspite of extraordinary high levels of cadmium and lead in garden soils and vegetables, blood lead, blood cadmium and urine cadmium levels were not or only slightly elevated in the gardeners when compared to a reference group of subjects from the same area who did not consume home-grown vegetables and fruits. The results show that high levels of pollutants in soil and vegetables are not necessarily associated with an increased burden of pollutants in the human body, and that the transfer of pollutants from soil to humans might have been overestimated in some cases. Moreover, the results underline the preventive character of the guideline values presently applied with respect to the evaluation of soil contaminants.

[Mercury exposure of the population. IV. Mercury exposure of male dentists, female dentists and dental aides]. / Untersuchungen zur Quecksilberbelastung der Bevölkerung. IV. Quecksilberbelastung von Zahnärzten, Zahnärztinnen und Zahnarzthelferinnen.

Urinary mercury levels were determined in 22 dentists and 46 dental nurses and assistants working in 15 private dental offices in West-Germany. For comparison, urinary mercury levels of 29 subjects without occupational mercury exposure were studied. On average, urinary mercury in dental personnel was higher than in the reference group. Individual mercury levels, however, were all significantly below present occupational exposure limits. Urinary mercury was significantly correlated with the number of amalgam fillings in dental personnel as well as in the reference group. Following administration of Dimaval a significant increase of mercury excretion was observed in both groups. Regarding total exposure to mercury in dental personnel, the contribution of mercury exposure from the occupational environment is of the same order of magnitude as their exposure from their own amalgam fillings. Dental nurses were found to be more exposed than dentists. This finding seems to be related predominantly to the larger number of amalgam fillings in dental nurses.

[The mercury exposure of the population. III. Mercury mobilisation by DMPS (Dimaval) in subjects with and without amalgam fillings]. / Untersuchungen zur Quecksilberbelastung der Bevölkerung. III. Quecksilbermobilisation durch DMPS (Dimaval) bei Personen mit und ohne Amalgamfüllungen.

The urinary excretion of mercury (per 24 h) was determined in 29 subjects before and after application of DMPS (2.3-dimercapto-1-propane sulfonic acid, 300 mg per os). A 6-7 fold increase of mercury excretion was noted after application of DMPS. Subjects with amalgam fillings excreted significantly more mercury before as well as after application of DMPS than subjects without amalgam fillings. Urinary mercury excretion was significantly correlated with the number of amalgam fillings. About 50% of the variance of urinary mercury can be explained by the number of amalgam fillings. The results show that the release of mercury from amalgam fillings represents the main source of mercury exposure in subjects with amalgam fillings.

High lead content of deciduous teeth in chronic renal failure.

Lead is suspected to contribute to the progression of kidney disease. Lead content of blood and deciduous teeth was determined in 22 children aged 5-14 years at different stages of chronic renal failure (CRF). In addition, individual lead exposure was estimated from histories. The results were compared with a control group of 20 siblings or neighbours of patients living in the same environment (C1), and to a group of children known to be free of excessive lead exposure (C2). The mean blood lead concentration of patients was normal (mean 2.9 micrograms/dl, range 1.1.-10.1). Mean dental lead content was 2.8, 1.7 and 1.4 micrograms/g in CRF, C1 and C2, respectively. It always exceeded that of healthy peers. Increased dental lead content was associated with a high risk of exposure. It is suggested that both an increased lead uptake and renal dysfunction may contribute to the increased lead burden in children with CRF.

Hypalgesic efficacy of acupuncture on experimental pain in man. Comparison of laser acupuncture and needle acupuncture.

The analgesic effect of acupuncture on cutaneous heat stimuli of 43 degrees C has been evaluated in a controlled experimental study with healthy, informed volunteers. Laser acupuncture was administered to 39 probationers using a helium-neon laser under double-blind conditions. The point Hegu (L.I.4) and Jianqian (Extra.) on both sides were each irradiated for 1 min. Forty probationers were needled with stainless steel needles in the point Hegu (L.I.4) on both sides under single-blind conditions. Pain threshold was measured in terms of the time (in msec) that the probationers needed to perceive the cutaneous heat stimulus of 43 degrees C. The painful stimulus was generated by a computer-controlled standardized procedure. The Wilcoxon test was used for the statistical evaluation. Laser acupuncture did not change the pain threshold. Needle acupuncture did, however, increase the pain threshold compared with the initial value (alpha = 0.1%). The difference compared with the control group, where a placebo point was needled, was also significant (alpha = 5%). This controlled experimental study proves the analgesic effect of needle acupuncture on painful heat stimuli. Laser acupuncture had no effect on pain threshold in this study.