Rapid genetic diversification within dog breeds as evidenced by a case study on Schnauzers.

As a result of strong artificial selection, the domesticated dog has arguably become one of the most morphologically diverse vertebrate species, which is mirrored in the classification of around 400 different breeds. To test the influence of breeding history on the genetic structure and variability of today's dog breeds, we investigated 12 dog breeds using a set of 19 microsatellite markers from a total of 597 individuals with about 50 individuals analysed per breed. High genetic diversity was noted over all breeds, with the ancient Asian breeds (Akita, Chow Chow, Shar Pei) exhibiting the highest variability, as was indicated chiefly by an extraordinarily high number of rare and private alleles. Using a Bayesian clustering method, we detected significant genetic stratification within the closely related Schnauzer breeds. The individuals of these three recently differentiated breeds (Miniature, Standard and Giant Schnauzer) could not be assigned to a single cluster each. This hidden genetic structure was probably caused by assortative mating owing to breeders' preferences regarding coat colour types and the underlying practice of breeding in separate lineages. Such processes of strong artificial disruptive selection for different morphological traits in isolated and relatively small lineages can result in the rapid creation of new dog types and potentially new breeds and represent a unique opportunity to study the evolution of genetic and morphological differences in recently diverged populations.

On ancestors of dog breeds with focus on Weimaraner hunting dogs.

Paternally inherited Y chromosomal markers and maternally inherited mitochondrial (mt) DNA sequences were investigated in 27 dog breeds (Canis familiaris), of which the Weimaraner hunting dog was studied in greater detail. Altogether, nine potentially polymorphic markers of the Y chromosome were examined as well as parts of the canine mt genome (1947 base pairs) in 111 male dogs and four wolves for comparison. Twenty Y chromosomal and fifty-nine mitochondrial DNA (mtDNA) haplotypes were identified in the canine breeds and wolves. In 34 Weimaraners, four distinct Y chromosomal haplotypes were observed as well as three mtDNA types thus reflecting at least four male and three female ancestors for the current population in Germany. Tracing patri- and matrilineages, several entries in the Weimaraner stud book cannot be reconciled with the male-only, Y chromosomal neither the female-only, mt inheritance patterns, respectively. The investigated breeds represent 9 of 10 groups defined by the Fédération Cynologique Internationale (FCI). The level of Y chromosomal and especially mtDNA diversity was immense considering the relatively small number of individuals investigated per breed. Unique haplotypes were found only in a few breeds and the wolf. Other haplotypes were shared among several breeds, also across different FCI groups, suggesting that these canine breeds had common male and female ancestors.

Neuroendocrinological effects of acupuncture treatment in patients with irritable bowel syndrome.

OBJECTIVES: Quality of life (QoL) improvement in patients with irritable bowel syndrome (IBS) during acupuncture (AC) treatment seems to be due to a placebo effect. The aim was to explore if acupuncture has some specific influence on the neuroendocrinic and autonomic nervous system (ANS). DESIGN/SETTING: Patients with IBS were randomly assigned to receive either acupuncture (AC) or sham acupuncture (SAC) using the so-called "Streitberger needle". QoL was measured with the functional quality of life diseases quality of life questionnaire (FDDQL) and SF-36. The effect on ANS was evaluated by measuring salivary cortisol and by cardiovascular responses on a tilt table before and after 10 AC treatments. Complete data sets of tilt table and salivary morning cortisol were available for 9 patients in the AC and 12 in SAC group. RESULTS: QoL increased in both groups (p=0.001) with no group differences. Salivary cortisol decreased in all groups (F=10.55; p=0.006). However, the decrease was more pronounced in the AC group (F=4.07; p=0.033) (ANOVA repeated measures model). Heart rate response decreased during orthostatic stress in the AC group while it increased in the SAC group (F=9.234; p=0.005), indicating an increased parasympathetic tone in the AC group. Improvement of pain was positively associated with increased parasympathetic tone in the AC group (F=10.1; p=0.006), but not in the SAC group. CONCLUSIONS: The acupuncture specific physiological effects are in contrast to the unspecific improvement of QoL in both AC and SAC groups. Thus, different mechanisms seem to be involved in placebo and real-acupuncture driven improvements. The specific mechanism of action of acupuncture on the ANS remains unclear and deserves further evaluation.

Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting.

BACKGROUND: There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms. OBJECTIVES: The objective was to assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain, Palliative Care and Supportive Care Specialized Register, Cochrane Cancer Specialized Register, and conference abstracts. SELECTION CRITERIA: Randomized trials of acupuncture-point stimulation by any method (needles, electrical stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea or vomiting, or both. DATA COLLECTION AND ANALYSIS: Data were provided by investigators of the original trials and pooled using a fixed effect model. Relative risks were calculated on dichotomous data. Standardized mean differences were calculated for nausea severity. Weighted mean differences were calculated for number of emetic episodes. MAIN RESULTS: Eleven trials (N = 1247) were pooled. Overall, acupuncture-point stimulation of all methods combined reduced the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99; P = 0.04), but not acute or delayed nausea severity compared to control. By modality, stimulation with needles reduced proportion of acute vomiting (RR = 0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not; delayed symptoms for acupuncture were not reported. Acupressure reduced mean acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to -0.01; P = 0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. AUTHORS' CONCLUSIONS: This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

High Resolution Imaging of Viscoelastic Properties of Intracranial Tumours by Multi-Frequency Magnetic Resonance Elastography.

PURPOSE: In recent years Magnetic Resonance Elastography (MRE) emerged into a clinically applicable imaging technique. It has been shown that MRE is capable of measuring global changes of the viscoelastic properties of cerebral tissue. The purpose of our study was to evaluate a spatially resolved three-dimensional multi-frequent MRE (3DMMRE) for assessment of the viscoelastic properties of intracranial tumours. METHODS: A total of 27 patients (63 ± 13 years) were included. All examinations were performed on a 3.0 T scanner, using a modified phase-contrast echo planar imaging sequence. We used 7 vibration frequencies in the low acoustic range with a temporal resolution of 8 dynamics per wave cycle. Post-processing included multi-frequency dual elasto-visco (MDEV) inversion to generate high-resolution maps of the magnitude |G*| and the phase angle φ of the complex valued shear modulus. RESULTS: The tumour entities included in this study were: glioblastoma (n = 11), anaplastic astrocytoma (n = 3), meningioma (n = 7), cerebral metastasis (n = 5) and intracerebral abscess formation (n = 1). Primary brain tumours and cerebral metastases were not distinguishable in terms of |G*| and φ. Glioblastoma presented the largest range of |G*| values and a trend was delineable that glioblastoma were slightly softer than WHO grade III tumours. In terms of φ, meningiomas were clearly distinguishable from all other entities. CONCLUSIONS: In this pilot study, while analysing the viscoelastic constants of various intracranial tumour entities with an improved spatial resolution, it was possible to characterize intracranial tumours by their mechanical properties. We were able to clearly delineate meningiomas from intraaxial tumours, while for the latter group an overlap remains in viscoelastic terms.

Randomised clinical trial comparing the effects of acupuncture and a newly designed placebo needle in rotator cuff tendinitis.

Acupuncture has gained increasing attention in the treatment of chronic pain. The lack of a satisfying placebo method has made it impossible to show whether needling is an important part of the method or whether the improvement felt by the patient is due to the therapeutic setting and psychological phenomena. Also, the effectiveness of acupuncture has not been demonstrated sufficiently. We treated 52 sportsmen with rotator cuff tendinitis in a randomised single-blind clinical trial using a new placebo-needle as control. Patients were treated for 4 weeks. The primary endpoint of the trial was the change in the modified Constant-Murley-score from the baseline. Assessment of the treatment outcome was made by experienced orthopaedists not informed of the treatment allocation. Acupuncture with penetration of the skin was shown to be more effective than a similar therapeutic setting with placebo needling in the treatment of pain. The acupuncture-group improved 19.2 Constant-Murley-score points (SD 16.1, range from -13 to 50), the control-group improved 8.37 points (SD 14.56, range from -20 to 41), (P=0.014; C.I. 2.3;19.4). This study showed that needling is an important part of the acupuncture effect in the treatment of chronic shoulder pain in athletes. No conclusions can be derived from this study concerning the importance of choosing points and the rules of Traditional Chinese Medicine. Using the new placebo method as control for other ailments could improve the evidence of specific acupuncture effects beyond pain treatment.

Patient-activated three-dimensional multifrequency magnetic resonance elastography for high-resolution mechanical imaging of the liver and spleen.

PURPOSE: To introduce a novel in-vivo three-dimensional multifrequency magnetic resonance elastography (3D-MMRE) method for high-resolution mechanical characterization of the liver and spleen. MATERIALS AND METHODS: Ten healthy volunteers were examined by abdominal single-shot 3D-MMRE using a novel patient-activated trigger system with respiratory control. 10 contiguous slices with 2.5  mm cubic voxel resolution, 3 wave components, 8 time steps, and 2 averages were acquired at 7 mechanical excitation frequencies from 30 to 60  Hz. The total imaging time was approximately 15  min. For postprocessing, multifrequency dual elasto-visco (MDEV) inversion was used to calculate high-resolution mechanical parameter maps of the abdomen including the liver and spleen. RESULTS: Two parameters maps were generated from each image slice to capture the magnitude and the phase angle of the complex shear modulus. Both parameters depicted the mechanical structures of the abdomen with unprecedented high spatial resolution. Spatially averaged group mean values of the liver and spleen are 1.27 ±â€Š0.17 kPa and 2.01 ±â€Š0.69 kPa, indicating a significantly higher asymptomatic stiffness of the spleen compared to the liver. CONCLUSION: Patient-activated respiratory-gated 3D-MMRE combined with MDEV inversion provides highly resolved mechanical maps of the liver and spleen that are superior to previous elastograms measured by abdominal MRE.

The prevalence of widespread central hypersensitivity in chronic pain patients.

BACKGROUND: Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. METHODS: We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. RESULTS: Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. CONCLUSIONS: Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment.

Double-blinded, randomized controlled trial comparing real versus placebo acupuncture to improve tolerance of diagnostic esophagogastroduodenoscopy without sedation: a study protocol.

BACKGROUND: Sedation prior to performance of diagnostic esophagogastroduodenoscopy (EGDE) is widespread and increases patient comfort. But 98% of all serious adverse events during EGDEs are ascribed to sedation. The S3 guideline for sedation procedures in gastrointestinal endoscopy published in 2008 in Germany increases patient safety by standardization. These new regulations increase costs because of the need for more personnel and a prolonged discharge procedure after examinations with sedation. Many patients have difficulties to meet the discharge criteria regulated by the S3 guideline, e.g. the call for a second person to escort them home, to resign from driving and working for the rest of the day, resulting in a refusal of sedation. Therefore, we would like to examine if an acupuncture during elective, diagnostic EGDEs could increase the comfort of patients refusing systemic sedation. METHODS/DESIGN: A single-center, double blinded, placebo controlled superiority trial to compare the success rates of elective, diagnostic EGDEs with real and placebo acupuncture. All patients aged 18 years or older scheduled for elective, diagnostic EGDE who refuse a systemic sedation are eligible. 354 patients will be randomized. The primary endpoint is the rate of successful EGDEs with the randomized technique. INTERVENTION: Real or placebo acupuncture before and during EGDE. Duration of study: Approximately 24 months. DISCUSSION: Organisation/Responsibility The ACUPEND--Trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The Interdisciplinary Endoscopy Center (IEZ) of the University Hospital Heidelberg is responsible for design and conduct of the trial, including randomization and documentation of patients' data. Data management and statistical analysis will be performed by the independent Institute for Medical Biometry and Informatics (IMBI) and the Center of Clinical Trials (KSC) at the Department of General, Visceral and Transplantation Surgery, University of Heidelberg. TRIAL REGISTRATION: The trial is registered at Germanctr.de (DRKS00000164) on December 10th 2009. The first patient was randomized on February 2nd 2010.

[Spectrum of patients in prehospital emergency services. What has changed over the last 20 years?]. / Patientenspektrum im Notarztdienst. Was hat sich in den letzten 20 Jahren geändert?

BACKGROUND: In Germany the physician staffed emergency systems have announced an increase in rescue missions over the years. The aim of this study is to analyse the development of the spectrum of patients in an emergency system over the last 20 years in order to highlight the significant changes. METHODS: In a retrospective study we analyzed the prehospital chart views from 2004, 1992 and 1984 with respect to patients' demography, type of rescue mission, degree of internal disease or injury (NACA), state of consciousness (GCS), as well as prehospital interventions performed by prehospital emergency physician. RESULTS: In 2004 (3,825), the absolute number of missions was 2 and 4 times higher than 1992 (2,114) and 1984 (957), resp. In all of these investigated time periods non-trauma missions (74%; 2,812 vs. 66%; 1,390 vs. 51%; 485) were leading, followed by trauma missions (18%; 690 vs. 22%; 464 vs. 39%; 375), aborted missions (3%; 126 vs. 7%; 154 vs. 6%; 56), and dead on arrival (5%; 197 vs. 5%; 106 vs. 4%; 41). Although, the percentage of patients with NACA IV-VI (39% vs. 50%) or patients with GCS < or =8 (18% vs. 34%) was lower in 2004, the absolute number of patients in each category was higher than in 1984 (NACA IV-VI: 1,434 vs. 448, p<0.01; GCS: 672 vs. 303, p<0.01). CONCLUSIONS: The results of this study demonstrate, that the percentage of trauma, severely ill/injured or unconscious patients is lower than in previous years. However, the higher absolute numbers of patients demonstrate that the emergency physician now encounters more critically ill/injured, unconscious and trauma patients. It does not seem necessary to question the qualifications for an emergency physician, which have previously been considered essential for the management of acute life-threatening situations.

Acupuncture treatment in irritable bowel syndrome.

BACKGROUND AND AIMS: Despite occasional positive reports on the efficacy of acupuncture (AC) on functions of the gastrointestinal tract, there is no conclusive evidence that AC is effective in the treatment of irritable bowel syndrome (IBS). PATIENTS AND METHODS: Forty three patients with IBS according to the Rome II criteria were randomly assigned to receive either AC (n = 22) or sham acupuncture (SAC) (n = 21) using the so-called "Streitberger needle". Treatment duration was 10 sessions with an average of two AC sessions per week. The primary end point was improvement in quality of life (QOL) using the functional digestive diseases quality of life questionnaire (FDDQL) and a general quality of life questionnaire (SF-36), compared with baseline assessments. QOL measurements were repeated three months after treatment. RESULTS: Both the AC and SAC groups improved significantly in global QOL, as assessed by the FDDQL, at the end of treatment (p = 0.022), with no differences between the groups. SF-36 was insensitive to these changes (except for pain). This effect was partially reversed three months later. Post hoc comparison of responders and non-responders in both groups combined revealed a significant prediction of the placebo response by two subscales of the FDDQL (sleep, coping) (F = 6.746, p = 0.003) in a stepwise regression model. CONCLUSIONS: Acupuncture in IBS is primarily a placebo response. Based on the small differences found between the AC and SAC groups, a study including 566 patients would be necessary to prove the efficacy of AC over SAC. The placebo response may be predicted by high coping capacity and low sleep quality in individual patients.

[German Acupuncture Trials (gerac) address problems of methodology associated with acupuncture studies]. / Zur Problematik von Akupunkturstudien am Beispiel der Methodik von gerac.

OBJECTIVE: Conflicting or ambivalent findings on the effectiveness of body acupuncture in pain treatment are often attributed to flaws in study methodology. The paper describes the methodology used for the German Acupuncture Trials (gerac), which demonstrates that it is possible to design acupuncture studies in accordance with the standards of good clinical practice. METHOD: Approximately 1000 chronic pain sufferers per indication (migraine, tension-type headache, low back pain (cLBP), or gonarthrosis) are randomly allocated to one of three treatment groups (verum acupuncture, sham acupuncture, or established conservative therapy). Patients are blind to the type of acupuncture. All patients receive ten sessions of treatment (two per week) with an option of adding five more treatments in cases of slight but insufficient improvement (number of headache days or von Korff pain score). Participating physicians are in private practice, representing a variety of specialties. All have completed at least a 140-hour training course in acupuncture. Mandatory and optional verum and sham points are predefined. The point selection is individualized according to the criteria of traditional Chinese medicine (TCM). Primary outcome measures are number of headache days per month, von Korff Graded Chronic Pain Scale or Hannover Functional Ability Questionnaire (cLBP), or WOMAC scores (gonarthrosis). Data are assessed by trained telephone interviewers not involved in treatment and blind to types of acupuncture. PRESENT STATUS: Over 500 participating physicians in ten urban areas of Germany. Patient recruitment for cLBP and gonarthrosis was completed in November 2003 and March 2004 respectively. Recruitment for chronic headaches will be completed in autumn 2004. CONCLUSIONS: The gerac trials prove that it is possible to design and carry out acupuncture studies in accordance to stringent standards of methodology and clinical practice. The results will form a basis for the assessment of acupuncture effectiveness in Germany and abroad.

Introducing a placebo needle into acupuncture research.

BACKGROUND: A problem acupuncture research has to face is the concept of a control group. If, in control groups, non-acupoint needling is done, physiological acupuncture effects are implied. Therefore the effects shown in this group are often close to those shown in the acupuncture group. In other trials, control groups have received obviously different treatments, such as transcutaneous electrical nervous stimulation or TENS-laser treatment; it is not clear if the effects of acupuncture are due only to the psychological effects of the treatment. METHODS: We developed a placebo acupuncture needle, with which it should be possible to simulate an acupuncture procedure without penetrating the skin. In a cross-over experiment with 60 volunteers we tested whether needling with the placebo needle feels any different from real acupuncture. FINDINGS: Of 60 volunteers, 54 felt a penetration with acupuncture (mean visual analogue scale [VAS] 13.4; SD 10.58) and 47 felt it with placebo (VAS 8.86; SD 10.55), 34 felt a dull pain sensation (DEQI) with acupuncture and 13 with placebo. None of the volunteers suspected that the needle may not have penetrated the skin. INTERPRETATION: The placebo needle is sufficiently credible to be used in investigations of the effects of acupuncture.

Acupuncture compared to placebo-acupuncture for postoperative nausea and vomiting prophylaxis: a randomised placebo-controlled patient and observer blind trial.

This randomised, placebo-controlled, patient and observer blinded trial was conducted to determine whether acupuncture at the acupuncture point P6 is effective in preventing postoperative nausea and vomiting (PONV) compared to placebo acupuncture. Female patients (n = 220) scheduled for gynaecological or breast surgery were randomly assigned to two groups receiving either acupuncture (n = 109) or placebo acupuncture (n = 111). Each group was stratified for type of surgery and included two subgroups receiving intervention either before or after induction of anaesthesia. The incidence of PONV and/or antiemetic rescue medication within 24 h after surgery was the main outcome measure which showed no statistically significant difference between groups (43.7% acupuncture, 50.9% placebo, p = 0.27). The differences were more pronounced for patients having gynaecological surgery (48.9% acupuncture, 67.6% placebo, p = 0.07) than for those having breast surgery (38.7% acupuncture, 40.3% placebo, p = 0.86). The secondary outcome, vomiting, was significantly reduced by acupuncture from 39.6% to 24.8% (p = 0.03). Subgroup analysis showed no difference between applications of acupuncture before compared to after induction of anaesthesia.