Paternal obesity and its transgenerational effects on gastrointestinal function in male rat offspring

The interplay between obesity and gastrointestinal (GI) motility is contradictory, and the transgenerational influence on this parameter is unknown. We aimed to evaluate the GI function in a model of paternal obesity and two subsequent generations of their male offspring. Newborn male rats were treated with monosodium glutamate (MSG) and composed the F1 generation, while control rats (CONT) received saline. At 90 days, male F1 were mated with non-obese females to obtain male offspring (F2), which later mated with non-obese females for obtaining male offspring of F3 generation. Lee Index analysis was adopted to set up the obesity groups. Alternating current biosusceptometry (ACB) technique was employed to calculate GI transit parameters: mean gastric emptying time (MGET), mean cecum arrival time (MCAT), mean small intestinal transit time (MSITT), and gastric frequency and amplitude of contractions. Glucose, insulin, and leptin levels and duodenal morphometry were measured. F1 obese rats showed a decrease in the frequency and amplitude of gastric contractions, while obese rats from the F2 generation showed accelerated MGET and delayed MCAT and MSITT. Glucose and leptin levels were increased in F1 and F2 generations. Insulin levels decreased in F1, F2, and F3 generations. Duodenal morphometry was altered in all three generations. Obesity may have paternal transgenerational transmission, and it provoked disturbances in the gastrointestinal function of three generations.

Brain damage resulting from postnatal hypoxic-ischemic brain injury is reduced in C57BL/6J mice as compared to C57BL/6N mice.

Perinatal hypoxia is a critical complication during delivery and is mostly studied in animal models of postnatal hypoxic-ischemic brain injury. We here studied the effects of postnatal hypoxic-ischemic brain injury in two different sub-strains of C57BL/6 mice, i.e. C57BL/6J and C57BL/6N mice. These two sub-strains show different metabolic properties, for instance an impaired glucose tolerance in C57BL/6J mice. Genetically, this was linked to differences in their nicotinamide nucleotide transhydrogenase (Nnt) genes: In C57BL/6J mice, exons 7-11 of the Nnt gene are deleted, resulting in the absence of functional Nnt protein. The mitochondrial Nnt-protein is one of several enzymes that catalyses the generation of NADPH, which in turn is important for the elimination of reactive oxygen species (ROS). As ROS is thought to contribute to the pathophysiology of hypoxia-ischemia, the lack of Nnt might indirectly increase ROS levels and therefore result in increased brain damage. We therefore hypothesize that lesion score and lesion size will increase in C57BL/6J mice as compared to C57BL/6N mice. Surprisingly, the results showed exactly the opposite: C57BL/6J mice showed a decrease in lesion score and size, associated with a reduced number of apoptotic cells and activated microglia. In contrast, the number of cells with ROS-induced DNA modifications (detected by 8OHdG) was higher in C57BL/6J than C57BL/6N mice. In conclusion, C57BL/6J mice showed reduced ischemic consequences after postnatal hypoxic-ischemic brain injury compared to C57BL/6N mice, with the exception of the amount of ROS-induced DNA-damage. These differences might relate to the lack of Nnt, but also to a modified metabolic setting (cardiovascular parameters, oxygen and glucose metabolism, immune function) in C57BL/6J mice.

Cardiac surgery in Germany during 2013: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

On the basis of a voluntary registry of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS), data of all cardiac surgical procedures performed in 79 German cardiac surgical units during the year 2013 are presented. In 2013, a total of 99,128 cardiac surgical procedures (implantable cardioverter defibrillator [ICD] and pacemaker procedures excluded) were submitted to the registry. More than 13.8% of the patients were older than 80 years, which remains equal in comparison to the previous year. In-hospital mortality in 40,410 isolated coronary artery bypass grafting procedures (84.5% on-pump and 15.5% off-pump) was 2.9%. In 29,672 isolated valve procedures (including 7,722 catheter-based procedures), an in-hospital mortality of 4.7% was observed. This long-lasting registry of the GSTCVS will continue to be an important tool for quality control and voluntary public reporting by illustrating current facts and developments of cardiac surgery in Germany.

[GSTCVS certificate for cardiac pacemaker, ICD and CRT therapy]. / DGTHG-Zertifizierung zur Herzschrittmacher-, ICD- und CRT-Therapie.

Medical qualifications to perform operations with cardiac electronic implantable devices as well as for preoperative and postoperative therapy, including follow-up in this patient population are not well defined. Based on recommendations which have been worked out and published by an interdisciplinary consensus of cardiac surgeons, cardiologists and electrophysiologists, a certificate with three modules has been developed by the Working Group for Electrophysiologic Surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS, Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie, DGTHG). First examinations for this certificate will be held in 2013 and transitional regulations apply until 1st April 2014. Further details are available on the homepage of the GSTCVS.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

Cardiac surgery in Germany during 2010: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

All cardiac surgical procedures performed in 79 German cardiac surgical units throughout the year 2010 are presented in this report, based on a voluntary registry which is organized by the German Society for Thoracic and Cardiovascular Surgery. In 2010 a total of 95,734 cardiac surgical procedures (ICD and pacemaker procedures excluded) have been collected in this registry. More than 12.4% of the patients were older than 80 years compared to 11.8% in 2009. Hospital mortality in 42,804 isolated CABG procedures (14.2% off-pump procedures) was 2.8%. In 25,127 isolated valve procedures (including 3660 transcatheter-valve implantations) a mortality of 4.9% has been observed. This voluntary registry of the German Society for Thoracic and Cardiovascular Surgery will continue to be an important tool enabling quality control and illustrating the development of cardiac surgery in Germany.

Cardiac surgery in Germany during 2009. A report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

All cardiac surgical procedures performed in 80 German cardiac surgical units throughout the year 2009 are presented in this report, based on a voluntary registry which is organized by the German Society for Thoracic and Cardiovascular Surgery. In 2009 a total of 96 129 cardiac surgical procedures (excluding ICD and pacemaker procedures) were collected in this registry. More than 11.8 % of the patients were older than 80 years compared to 10.3 % in 2008. Hospital mortality in 45 171 isolated CABG procedures (13.1 % off-pump) was 2.8 %. In 23 556 isolated valve procedures (including 2216 catheter-based procedures) a mortality of 4.7 % was observed. This voluntary registry of the German Society for Thoracic and Cardiovascular Surgery continues to be an important tool for quality control and illustrates the development of cardiac surgery in Germany.

Cardiac surgery in Germany during 2008. A report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

All cardiac surgical procedures performed in 79 German cardiac surgical units throughout the year 2008 are illustrated in this report, based on a voluntary registry which is organized by the German Society for Thoracic and Cardiovascular Surgery. In 2008 a total of 99 176 cardiac surgical procedures (ICD and pacemakers procedures excluded) have been collected. More than 10.3 % of the patients were older than 80 years compared to 9.8 % in 2007. Hospital mortality in 47 337 isolated CABG procedures (11.3 % off-pump) was 2.8 %. In 22 243 isolated valve procedures a mortality of 4.7 % has been observed. This voluntary registry of the German Society for Thoracic and Cardiovascular Surgery continues to be an important tool enabling quality control and illustrating the development of cardiac surgery in Germany.

EuroSCORE overestimates the risk of cardiac surgery: results from the national registry of the German Society of Thoracic and Cardiovascular Surgery.

OBJECTIVE: The EuroSCORE risk stratification model has been developed in 1995 and is still widely used to assess individual patient risk prior to cardiac surgery. Furthermore, the score advanced to a decision tool to determine so-called "high-risk patients" and in consequence serves as an important selection criterion in new technologies, such as the catheter-based aortic valve replacement. Several studies with relatively small patient numbers showed a substantial overestimation of risk by the EuroSCORE. The aim of our study was to evaluate whether the nationwide data support this finding. METHODS: A subgroup of the registry of the German Society of Thoracic and Cardiovascular Surgery from 2006 and 2007, with 32,806 patients undergoing isolated coronary surgery and isolated aortic valve replacement was investigated. RESULTS: The overall hospital mortality in isolated coronary surgery in this patient cohort (n = 26,501 patients) was 2.6% (n = 695). The overall hospital mortality in isolated aortic valve replacement in this patient cohort (n = 6,305 patients) was 3.9% (n = 245). The logistic EuroSCORE predicted a proportion of 5.2% for patients with isolated CABG and 7.3% for patients with isolated aortic valve replacement. The area under the receiver operating characteristic curve was 0.77 for isolated CABG procedures and 0.69 for isolated valve procedures, supporting the substantial lack of predictive value of the EuroSCORE. CONCLUSION: The logistic EuroSCORE insufficiently evaluates the risk of the current patient population and therefore should be carefully used as a tool for important therapeutic decision-making.

Cardiac surgery in Germany during 2007: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

All cardiac surgical procedures performed in 80 German cardiac surgical units throughout the year 2007 are presented in this report, based on a voluntary registry which is organized by the German Society for Thoracic and Cardiovascular Surgery. In 2007 a total of 99,990 cardiac surgical procedures (ICD and pacemaker procedures excluded) have been collected in this registry. More than 9.8% of the patients were older than 80 years compared to 9.6% in 2006. Hospital mortality in 49,788 isolated CABG procedures (10.1% off-pump) was 2.7%. In 21,312 isolated valve procedures a mortality of 5.1% has been observed. This voluntary registry of the German Society for Thoracic and Cardiovascular Surgery will continue to be an important tool enabling quality control and illustrating the development of cardiac surgery in Germany.

Cardiac surgery in Germany during 2006: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

All cardiac surgical procedures performed in 81 German cardiac surgical units throughout the year 2006 are presented in this report, based on a voluntary registry which is organized by the German Society for Thoracic and Cardiovascular Surgery. In 2006 a total of 97,123 cardiac surgical procedures (ICD and pacemakers procedures excluded) have been collected in this registry. More than 9.6 % of the patients were older than 80 years compared to 8.4 % in 2005. Hospital mortality in 51,273 isolated CABG procedures (10.1 % off-pump) was 3.1 %. In 20,028 isolated valve procedures a mortality of 4.9 % has been observed. This registry will continue to be an important tool of the German Society for Thoracic and Cardiovascular Surgery enabling a continuous and voluntary quality assurance and illustrating the development of cardiac surgery in Germany.

Cardiac surgery in Germany during 2005: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery.

All cardiac surgical procedures performed in 79 German cardiac surgical units throughout the year 2005 are presented in this report, based on a voluntary registry, which is organized by the German Society for Thoracic and Cardiovascular Surgery. In 2005, a total of 98 860 cardiac surgical procedures (ICD and pacemaker procedures excluded) were collected in this registry. More than 8.4 % of the patients were older than 80 years, compared to 7.8 % in 2004. Hospital mortality in 54 126 isolated CABG procedures (9.7 % off-pump) was 2.9 %, while a mortality of 4.5 % was observed in 19 203 isolated valve procedures. This registry is an important tool of the German Society for Thoracic and Cardiovascular Surgery to ensure a continuous and voluntary quality assurance and illustrate the development of cardiac surgery in Germany.

Inflammatory infiltrates in the spinal cord of patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is defined as an acute inflammatory demyelinating polyradiculoneuropathy (AIDP) of the peripheral nervous system. Reports on central nervous system involvement in patients with GBS are rare and the histopathological analysis was usually restricted to conventional staining techniques. We were able to investigate four cases with GBS at autopsy in respect to the inflammatory infiltrates and histopathological changes in the spinal cord by immunohistochemistry using a panel of antibodies recognizing lymphocytes and different macrophage-activation antigens. There were increased inflammatory cell infiltrates comprising lymphocytes and macrophages in the spinal cord of two cases. In one of these two cases, GBS predominantly affecting the motor system similar to acute motor axonal neuropathy (AMAN) developed following hepatitis B vaccination; in the second one, GBS developed rapidly 4 days after onset of intravenous purified GM1-ganglioside application affecting the motor as well as the sensory system, resembling acute motor sensory axonal neuropathy (AMSAN). Impairment of the spinal anterior horn cells with their axons was suggested to be responsible for prolonged motor symptoms and the predominantly axonal type of neuropathy at least as a late-stage feature in these two cases with fatal outcome. Insignificant cellular infiltrates in the spinal cord were noted in the other two GBS cases. Focal cellular infiltration of spinal nerve roots and meninges was similar in all cases.

Genetic characterisation of invasive breast cancer: a comparison of CGH and PCR based multiplex microsatellite analysis.

AIMS: Comparative genomic hybridisation (CGH) is a reliable tool to gain an overview of all unbalanced chromosomal alterations within a tumour. Nevertheless, the high numbers of tumour cells required and the comparatively low resolution are drawbacks of this technique. Polymerase chain reaction (PCR) based multiplex microsatellite analysis represents a semi-automated, highly reproducible method, which requires small amounts of tumour cells. This is a comparative study of CGH and microsatellite analysis. METHODS: Eighty one samples of invasive breast cancer were investigated by two sensitive multiplex PCRs containing three microsatellites each of six markers (D6S261, D11S907, D6S300, D11S927, D8S272, and D11S925), and two additional microsatellite markers located within intron 1 of the epidermal growth factor receptor gene (egfr) and p53 (p53CA). RESULTS: At least one example of loss of heterozygosity was detectable in all breast cancer tissues. However, the overall rate of accordance between the two methods tested was only 61%. An increasing rate of the number of genetic alterations in each case was mirrored by a constantly increasing fractional allelic loss index. CONCLUSIONS: PCR based multiplex microsatellite analysis using this panel of eight microsatellite markers not only enables the characterisation of cells that have malignant potential in a high frequency of patients with breast cancer, but can also give an estimate of the degree of genetic progression.

Double- and competitive-differential PCR for gene dosage quantitation.

An association of a loss of DNA replication control and the activation of erbB oncogenes can be deduced from studies with different cancers (1-5). In the first study on ovarian cancer 26% of the tumors had c-erbB-2 amplifications (6). The correlation between c-erbB-2 amplification and expression on mRNA and protein level was perfect. The median survival time of patients with ovarian cancers was negatively correlated to the degree of amplification. The association of egfr (c-erbB-1) amplification and overexpression with ovarian cancer prognosis has not been investigated as extensively as for c-erbB-2. EGF-R is expressed in normal ovarian epithelium and patients whose ovarian cancer continues to express EGF-R have a worse prognosis (7). Rearrangements of the egfr gene in ovarian cancer were also described, as identified by Southern blot analysis (8). Bauknecht submitted that a failure of chemotherapy was seen for ovarian cancers with low EGF-R expression (8).

Screening for Charcot-Marie-Tooth type 1A and hereditary neuropathy with liability to pressure palsy in archival nerve biopsy samples by direct-double-differential PCR.

Chromosomal imbalance of the peripheral myelin protein-22 gene (PMP22) is known to be the most frequent genetic abnormality in Charcot-Marie-Tooth disease type 1 (CMT1) and hereditary neuropathy with liability to pressure palsy (HNPP). We applied a new quantitative PCR method, the direct-double-differential PCR (dddPCR), to the gene dosage determination of PMP22. The method allows the quantification of the PMP22 gene copy number independently from DNA fragmentation, even in highly degraded DNA from up to 12-year-old sural nerve biopsy samples. Chromosomal imbalance of the PMP22 gene, which had been detected by examination of four microsatellites located directly adjacent to the PMP22 gene, between the CMT1A-repetition (CMT1A-REP) elements was reliably confirmed by the dddPCR. Using this method we unexpectedly identified two cases with PMP22 imbalance, although morphologically the neuropathies were of a neuronal or axonal type and not of a demyelinating type as usual. One sural nerve biopsy was from a 58-year-old male diabetes mellitus patient with a disproportionately severe polyneuropathy showing a heterozygous duplication of PMP22. The second biopsy exhibiting a heterozygous deletion of PMP22 was from a 58-year-old female patient with a more axonal than demyelinating type of neuropathy without typical tomaculous changes seemingly altered by exogenous, possibly traumatic factors other than diabetes mellitus. Thus, the dddPCR provides a fast and reliable diagnostic tool for the screening and identification of CMTIA and HNPP cases, which is fast and may be essential even when nerve biopsies show morphologically atypical changes.

Blood-borne cancer cells--quo vadis?

The detection of blood-borne cancer cells may help in clinical staging and further understanding of cancer metastasis. We developed a cytokeratin-based immunomagnetic method to isolate epithelium-derived cells from the circulating blood of patients. The number of cell clusters positive for cytokeratin/prostate-specific antigen (PSA) from the peripheral blood of prostate cancer patients and cytokeratin/p185c-erbB-2 from the peripheral blood of breast cancer patients has been related to stage of the disease. Breast cancer patients who presented cytokeratin/p185c-erbB-2-positive cell clusters showed a decrease in such cells under adriamycin adjuvant therapy with Further molecular characterization by a highly sensitive microsatellite multiplex-PCR enabled reproducible detection of microsatellite alterations. The impact of these individually targeted results may contribute to an individual diagnostic and therapeutic strategy.