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Biomedical subjects

H Hotz

Publications and source records attributed to H Hotz.

At least 19 recordsLinked to original sources

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗

Ensembl 2004.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organize biology around the sequences of large genomes. It is a comprehensive and integrated source of annotation of large genome sequences, available via interactive website, web services or flat files. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. The facilities of the system range from sequence analysis to data storage and visualization and installations exist around the world both in companies and at academic sites. With a total of nine genome sequences available from Ensembl and more genomes to follow, recent developments have focused mainly on closer integration between genomes and external data.

Animals↗

[Minimal invasive surgery for pHPT--which patients will profit?].

BACKGROUND: Standard for treatment of pHPT has been the exploration of the neck and extirpation of the macroscopic identified adenoma for a long time. Since the Quick-PTH-Assay is available as intraoperative control of success, it is possible to extirpate a preoperativeley localized adenoma without identifying the normal parathyroid glands. Since the accuracy of the preoperative localization is essential for a minimally invasive or endoscopic procedure, we analyzed retrospectively the accuracy of ultrasound and mibiscan of our patients, operated due to pHPT in our facility. METHODS: Between 1995 and 2002 119 patients were operated due to HPT in our facility. Sensitivity, specificity, positive- and negative-predictive value for diagnosis and correct localisation of a singular adenoma by ultrasound and/or mibiscan were determined. RESULTS: We found a singular adenoma in 94 patients, a carcinoma in 1 patient, 6-times a double-adenoma and in 18 cases a hyperplasia of all parathyroid glands. Sensitivity, specificity, positive- and negative-predictive value for diagnosis and correct localisation of a singular adenoma were 52 %, 41 %, 60 % and 27 % rsp., when the results of mibiscan and ultrasound were used. DISCUSSION: Related to the preoperative imaging, a single gland exploration and extirpation would have been possible in 70 % of our patients with pHPT. However, in 40 % of these patients the 100 % reliable Quick-PTH-Assay would have shown, that the adenoma has not been removed successfully in the first attempt.

Adenoma↗

[Evaluation of passive cardiomyoplasty using left- and right-ventricular volume measurements by EBCT and MRI in patients with chronic congestive heart failure].

PURPOSE: To evaluate the efficacy of passive cardiomyoplasty with the determination of biventricular volumes, global systolic function as well as left-ventricular muscle mass. MATERIALS AND METHODS: In 19 patients with congestive heart failure of idiopathic or ischemic origin, a polyester mesh-graft was implanted around both ventricles for stabilization and functional support. Before and three months after surgery, 15 patients underwent EBCT and 4 patients with impaired renal function underwent MRI, for the evaluation of the volume and ejection fraction of both ventricles. RESULTS: EBCT demonstrated a decrease from 385 to 310 ml in LV-EDV, from 312 to 242 ml in LV-ESV, from 209 to 160 ml in RV-EDV and from 149 to 87 ml in RV-ESV, and an increase from 20 to 26% in LV-EF and from 37 to 50% in RV-EF as well as a reduction of LV-MM from 300 to 274 g (p < 0.05 each). Similar results were obtained by MRI. CONCLUSION: Following passive cardiomyoplasty, EBCT and MRI revealed an improvement of the global systolic function as well as a reduction of biventricular volumes and left-ventricular muscle mass.

Adult↗

Persistent multiple organ microcirculatory disorders in severe acute pancreatitis: experimental findings and clinical implications.

This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.

Acute Disease↗

Passive containment and reverse remodeling by a novel textile cardiac support device.

BACKGROUND: Progressive remodeling and dilation of cardiac chambers is responsible in part for myocardial dysfunction in chronic heart failure. Preclinical studies with suitable animal models indicate that a passive cardiac constraint device can promote reverse remodeling, with improvement in cardiac function. We hypothesize that such a device could provide benefit for stable heart failure patients in New York Heart Association (NYHA) class II and III. METHODS AND RESULTS: From April 1999 to March 2000, 27 patients received Acorn's Cardiac Support Device (CSD) during an initial safety/feasibility study. In 11 patients, the only surgical measure was CSD placement. Most patients suffered from idiopathic cardiomyopathy; 4 were in NYHA class II, one was in class II/III, and 6 were in class III. All were stable on intensive medical treatment. The CSD, a textile polyester device, was fitted snugly around the heart during surgery. All patients survived surgery and recovered smoothly. Three months after surgery, 56% of patients were in NYHA class I, 33% were in class II, and 11% were in class II/III. Echocardiography showed an improvement in left ventricular ejection fraction from an average of 22% to 28% and 33% at 3 and 6 months, respectively. Simultaneously, the left ventricular end-diastolic dimension decreased from 74 mm to 68 mm and 65 mm, respectively. Mitral valve regurgitation (on a scale of 0 to 4+) decreased from 1.3 to 0.7 by 3 months. Quality-of-life indices correlated with the apparent reversal of ventricular remodeling. Preoperative cardiac medications remained virtually unchanged after implant. CONCLUSIONS: In the short- and intermediate-term, CSD implantation seems to ameliorate symptoms and improve cardiac and functional performance in heart failure patients. Worldwide randomized trials are currently underway.

Adult↗

Risk factors for prolonged ventilation after cardiac surgery using APACHE II, SAPS II, and TISS: comparison of three different models.

OBJECTIVE: To identify the risk for prolonged mechanical ventilation in cardiac surgical patients. DESIGN: Prospective study with retrospective combination of a second database. PATIENTS: Six hundred and eighty-seven patients after cardiac surgery over a period of 12 months. MEASUREMENTS: Demographic data were recorded preoperatively, and surgical procedures intraoperatively using a surgical database designed for quality control. Length of ICU and hospital stay, and hospital outcome were recorded. Severity of illness was assessed daily using APACHE II, SAPS II, and Organ Failure Score. Intensity of treatment and nursing care was monitored by means of the Therapeutic Intervention Scoring System (TISS). Univariate and multivariate analyses were performed using logistic regression. The predictive value of the identified variables was tested by the Wilcoxon test using the receiver operating characteristic curve. MAIN RESULTS: Sixty-two patients (9.0%) were ventilated for > 48 h and accounted for 42.8% of the total costs in the ICU. The pre- and intraoperatively collected data produced a model with weak predictive capacity for prolonged ventilation [area under curve (AUC) 73.22 and 71.08, respectively]. The use of TISS and SAPS postoperatively resulted in an effective model of prediction (AUC 93.76). Adding the occurrence of reoperation, reintubation, emergency transfusion, intraaortic balloon pumping, and need for total parenteral nutrition to the model further improved its predictive capacity (AUC 94.74). CONCLUSIONS: The present results strongly suggest that data collected postoperatively using established scoring systems as well as documented events of high clinical impact for risk assessment and quality control are reliable predictors of prolonged ventilation.

APACHE↗

[Indications, technique and initial results of passive cardiomyoplasty].

The cardiac support device (CSD, Acorn Cardiovasc. Inc.), a knitted polyester tissue, is surgically placed over the ventricles to prevent further dilatation of the heart. The aim of this study was to evaluate the feasibility and safety of CSD implantation in patients with advanced heart failure from cardiomyopathy of either idiopathic or ischemic origin. From April 1999, 23 patients received the CSD. In 8 patients the CSD implantation was the only surgical measure; in 12 patients a concomitant mitral valve repair was performed. In three more patients, the CSD implantation was combined with other surgical procedures. The CSD was placed while on bypass with the heart beating, attached to the AV groove and tailored anteriorly to snugly fit the ventricles. There were no intraoperative deaths or complications. Two patients died early postoperatively (4 d, 21 d); 1 late death occurred (44 d postop). The deaths were not considered to be device related. There were no CSD-related adverse events. Six months postoperatively all patients improved by at least one NYHA class. Echocardiography at 6 months revealed an increase in LVEF; the LVEDD decreased accordingly. Mitral valve regurgitation improved in all patients. These findings indicate that the CSD is safe, and improves heart failure symptoms and left ventricular function. Additional studies have to confirm these results.

Adult↗

[Left ventricular reduction surgery: pre- and postoperative evaluation by cine MRI].

AIM: To evaluate the role of cine magnetic resonance imaging (MRI) in the preoperative assessment and postoperative follow-up of patients undergoing left ventricular (LV) reduction surgery. PATIENTS AND METHODS: 6 patients with cardiomegaly were examined on a 1.5 T MR imager before and after LV reduction surgery. The heart was imaged along the short and long axes using a breath-hold ECG-triggered cine gradient-echo sequence for assessing ventricular and valvular morphology and function and performing volumetry (end-diastolic and end-systolic volumes, ejection fraction). RESULTS: Postoperatively, the mean ejection fraction increased from 21.7% to 33.4% and the end-diastolic and end-systolic left ventricular volumes decreased in all patients (304.0 and 252.5 ml before to 205.0 and 141.9 ml after surgery). Mean myocardial mass decreased slightly from 283.8 g to 242.7 g. Differences were significant for all parameters (p < 0.05). MRI allowed for the reliable assessment of post-operative valve morphology and yielded additional findings such as the presence of mitral valve insufficiency or ventricular thrombus. CONCLUSIONS: Cine MRI provides relevant information prior to left ventricular reduction surgery and reliably depicts functional and morphological changes in the early post-operative follow-up.

Aged↗

Magnetic resonance imaging of stentless xenografts for reconstruction of right ventricular outflow tract.

The objective was to overcome allograft shortage during the Ross operation; stentless xenografts were carefully evaluated for hemodynamic behavior and valve deterioration during medium term follow-up. Between January 10, 1994 and January 4, 1996 nine adult patients (age 31-51 years) underwent aortic valve replacement with an autologous pulmonary valve and right ventricular outflow tract reconstruction with the Edwards Prima or Medtronic Freestyle xenograft. One patient was dead early and one late, both from noncardiac reasons. Forty-eight to 66 months follow-up was available for 7 patients and was performed with physical examination in the outpatient clinic, transthoracic echocardiography (TTE), and magnetic resonance imaging (MRI). Two patients received 29-mm valves and the remaining 27-mm valves. No reoperation became necessary during follow-up. Preoperative left ventricular ejection fraction ranged from 20% to 84%, median 61%, mean 59% +/- 18%. At latest follow-up left ventricular ejection fraction was 49% to 70%, median 57%, mean 58% +/- 8%. TTE showed no calcification of the xenograft wall or cusps. MRI revealed good autograft function with no evidence of stenosis in any patient. Four patients showed no and three trivial regurgitation. Right ventricular outflow tract-stenosis could not be seen in any patient. Calculated gradients of the xenograft valves ranged from 2 to 6 mm Hg, median 3 mm Hg (mean 3.1 +/- 2.4 mm Hg) and calculated EOA ranged from 2.0 to 4.0 cm(2), median 2.8 cm(2). MRI supported these findings and showed pliable xenograft cusps in all patients. Right ventricular function was well preserved in all patients. In adult patients right ventricular outflow tract reconstruction with stentless xenografts can be performed safely and intermediate-term results are encouraging. During medium-term (5-7 years) follow-up no calcification or deterioration of valve function occurred with excellent hemodynamic behavior.

Adult↗

Differential performance among LDH-B genotypes in Rana lessonae tadpoles.

The European pool frog, Rana lessonae, is widely polymorphic for two common alleles (b,e) at the lactate dehydrogenase-B (LDH-B) locus. We compared fitness-related larval life-history traits among LDH-B genotypes, which originated from segregation in heterozygous parents, in an artificial pond experiment where tadpoles of R. lessonae from a Swiss population were raised together with tadpoles of the hemiclonal hybrid R. esculenta at two densities. In R. lessonae, LDH-B e/e homozygotes at each density had a higher proportion of metamorphs among survivors, reached metamorphosis earlier, and were heavier at metamorphosis than b/b homozygotes; b/e heterozygotes had intermediate values. That e/e individuals were superior to b/b in both time to and mass at metamorphosis is surprising because these two life-history traits are thought to reflect a performance trade-off; e/e genotypes apparently compensated for shorter time to metamorphosis by a higher growth rate. The two alleles showed the same performance ranking when combined in hybrids with a R. ridibunda allele: When R. esculenta from Swiss populations reared in the same ponds had received the e allele rather than the b allele from their R. lessonae parent, they reached metamorphosis earlier, but did not differ in mass at metamorphosis. The degree of linkage disequilibrium in the source population of the eight R. lessonae used as parents of the R. lessonae tadpoles is unknown, so we cannot exclude the possibility that the performance differences are caused by some anonymous tightly linked gene, rather than the LDH-B locus, that constitutes the genomically localized target of natural selection. A causal involvement of LDH-B is plausible, nevertheless, because this enzyme takes part in the central energy-metabolizing processes and has been reported to underlie fitness differences in other animals; also, differential performance of LDH-B genotypes has been observed in R. lessonae larvae from another population. The present results suggest strong directional selection for allele e; the sum of available data, including an independent laboratory experiment, suggests that partial environment-dependent overdominance combined with balancing selection favoring e/e homozygotes under some and b/b homozygotes under other conditions may be partially responsible for the broad maintenance of the LDH-B polymorphism in R. lessonae.

Alleles↗

Spontaneous heterosis in larval life-history traits of hemiclonal frog hybrids.

European water frog hybrids Rana esculenta (Rana ridibunda x Rana lessonae) reproduce hemiclonally, transmitting only their ridibunda genome to gametes. We compared fitness-related larval life-history traits of natural R. esculenta from Poland with those of the two sympatric parental species and of newly generated F1 hybrids. Compared with either parental species, F1 hybrid offspring had higher survival, higher early growth rates, a more advanced developmental stage by day 49, and earlier metamorphosis, but similar mass at metamorphosis. R. esculenta from natural lineages had trait values intermediate between those of F1 offspring and of the two parental species. The data support earlier observations on natural R. esculenta that had faster larval growth, earlier metamorphosis, and higher resistance to hypoxic conditions compared with either parental species. Observing larval heterosis in F1 hybrids in survival, growth rate, and time to metamorphosis, however, at an even higher degree than in hybrids from natural lineages, demonstrates that heterosis is spontaneous and results from hybridity per se rather than from subsequent interclonal selection; in natural lineages the effects of hybridity and of clonal history are confounded. This is compelling evidence for spontaneous heterosis in hybrid clonals. Results on hemiclonal fish hybrids (Poeciliopsis) showed no spontaneous heterosis; thus, our frog data are not applicable to all hybrid clonals. Our data do show, however, that heterosis is an important potential source for the extensively observed ecological success of hybrid clonals. We suggest that heterosis and interclonal selection together shape fitness of natural R. esculenta lineages.

Animals↗

Effect of different immunosuppressive agents on acute pancreatitis: a comparative study in an improved animal model.

BACKGROUND: Immunosuppressive drugs have been associated with the development and progression of acute pancreatitis after organ transplantation. Consequently, a reduction or a change in immunosuppressive therapy has been recommended once posttransplantation pancreatitis has been suspected. However, it is not known which of the available immunosuppressive agents is most harmful to the pancreas and which may be used safely in this situation. The objective of this study was to investigate the effect of different immunosuppressive drugs in various dosages on intrapancreatic protease activation, acinar cell necrosis, and mortality in an improved model of acute necrotizing pancreatitis in the rat. The rat model of acute necrotizing pancreatitis, like posttransplantation pancreatitis, is characterized by ischemia and microcirculatory disorders. METHOD: Acute pancreatitis was induced in rats by using a combination of low-dose controlled intraductal glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. Six hours thereafter, animals were randomized to intravenous therapy with 2, 10, or 50 mg/kg/day prednisolone (PRED); 3, 15, or 60 mg/kg/day cyclosporine A (CsA); 10 mg/kg/day azathioprine (AZA); 0.6 mg/kg/day orthoclone OKT3 (OKT3); or saline. After 36 hr, surviving animals were killed to determine acinar cell necrosis and trypsinogen activation peptides levels (TAP) in blood and ascites. RESULTS: Compared with saline-treated control rats, animals treated with 60 mg/kg/day CsA developed significantly more acinar cell necrosis and had increased amounts of TAP in ascites. Likewise, there was more extensive acinar cell necrosis in animals subjected to AZA therapy. However, this was not associated with incremental TAP. Animals treated with 3 or 15 mg/kg/day CsA, OKT3, or PRED showed no significant changes in these target parameters. Animals given 10 or 50 mg/kg/day PRED even had decreased hematocrit values and produced significantly less ascites than animals in the other groups. CONCLUSION: The present results suggest that AZA and high doses of CsA aggravate acute pancreatitis and should, therefore, be avoided once posttransplantation pancreatitis has been suspected, whereas lower doses of CsA, OKT3, and PRED may be used safely. PRED can even be used at higher doses as may be required when graft rejection is suspected.

Acute Disease↗

Retinoic acid receptor alpha mediates growth inhibition by retinoids in rat pancreatic carcinoma DSL-6A/C1 cells.

During carcinogenesis, pancreatic acinar cells can dedifferentiate into ductal adenocarcinoma of the pancreas. DSL-6A/C1 cells represent an in vitro model of this carcinogenic sequence. This study was designed to examine the effects of retinoids on cell growth in DSL-6A/C1 cells and to characterize further the molecular mechanisms underlying the antiproliferative actions of retinoids. Treatment of DSL-6A/C1 cells with retinoids results in a time- and dose-dependent inhibition of cell growth, paralleled by a retinoid-mediated transactivation of a pTK::betaRAREx2-luciferase reporter construct transiently transfected into DSL-6A/C1 cells. Retinoid receptor expression was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) using subtype-specific primers and demonstrated expression of retinoic acid receptor alpha (RAR-alpha), RAR-beta and retinoid X receptor alpha (RXR-alpha). Using a panel of receptor subtype-specific agonists, the RAR-alpha specific agonist Ro 40-6055 was the most potent retinoid in terms of growth inhibition. Furthermore, all-trans-retinoic acid-mediated growth inhibition and transactivation was completely blocked by the RAR-alpha-specific antagonist Ro 41-5253. In summary, the RAR-alpha subtype predominantly mediates the antiproliferative effects of retinoids in DSL-6A/C1 cells. Furthermore, this cell system provides a feasible tool to study the molecular mechanisms underlying the growth inhibitory effects of retinoids in ductal pancreatic carcinoma cells derived from a primary acinar cell phenotype.

Animals↗

Pediatric circulatory support.

BACKGROUND: Mechanical circulatory support in infants and small children is still a crucial issue. Until recently technological advances have been limited to the adult population. METHODS: Between February 1994 and December 1996, 553 infants or children underwent operation at our institution. Ten of them were treated with cardiac assist systems. Their ages ranged from 4 days to 8 years (median 5 months). In 8 patients we used a pulsatile circulatory support system available in 6 sizes (9, 10, 22.5, 25, 54, and 60 mL). A centrifugal pump was used in 2 additional infants. In 3 children cardiac assist was considered as a bridge to transplantation; in the remaining patients postcardiotomy failure or cardiogenic shock led to mechanical support. RESULTS: Median duration of assist was 4 days (range 8 hours to 17 days). In all cases we could observe recovery of renal, hepatic, and cardiac function in the immediate postimplantation period. Six patients survived and could be discharged either after successful transplantation or after myocardial recovery from postcardiotomy failure. The cause of death in 4 cases was bleeding and multiorgan failure. No technical failures occurred with either system. CONCLUSIONS: The pulsatile circulatory support system seems to be feasible and effective for pediatric extracorporeal support. If the anatomic situation does not permit implantation, centrifugal pumps are an alternative.

Cardiac Surgical Procedures↗

Genomes of two water frog species resist germ line exclusion in interspecies hybrids.

Abundant natural interspecies hybrids between the European water frog Rana ridibunda and at least three other taxa reproduce hemiclonally, by hybridogenesis: the non-ridibunda genome is excluded in the germ line before meiosis, and the unrecombined ridibunda genome is transmitted to haploid gametes. In contrast, natural hybrids between Rana ridibunda and either of two Balkan species (Rana shqiperica and Rana epeirotica) do not show such genome exclusion. This plausibly results from failure of Balkan Rana ridibunda genomes to "induce" such exclusion in the germ line of hybrids, from "resistance" of Rana shqiperica and Rana epeirotica genomes to such exclusion in hybrids with an "inducing" Rana ridibunda genome, or both. We tested the second hypothesis by examining lampbrush chromosome patterns in oocytes of hybrids that in the soma contain one "inducing" ridibunda genome and one genome of either of the two Balkan species. Several lampbrush chromosome markers (e.g., presence and location of certain giant loops and conspicuousness and width of centromeres) discriminate sets of Rana ridibunda chromosomes from those of Rana shqiperica and Rana epeirotica. Based on such markers, nine diploid female hybrids between Rana ridibunda or Rana esculenta from natural hybridogenetic lineages (Rana ridibunda x Rana lessonae, making ridibunda gametes) from central Poland and either Rana shqiperica or Rana epeirotica each contained both parental genomes in primary oocytes; the bivalents showed reduced numbers of chiasmata compared with parental species. It follows that none of these hybrids was hybridogenetic. This conclusion is confirmed, for two hybrids between Rana epeirotica and either Rana ridibunda or Rana esculenta, by protein electrophoretic comparison of somatic tissues with primary oocytes, all of which evidenced allelic markers of both parental species. Because Rana ridibunda genomes that are known to induce germ line genome exclusion when combined in hybrids with Rana lessonae genomes were used, these data provide the first compelling evidence for resistance of Rana shqiperica as well as Rana epeirotica genomes to such exclusion.

Animals↗

Clinical experience with the MEDOS HIA-VAD system in infants and children: a preliminary report.

BACKGROUND: The need of pediatric cardiac assist is growing because of the complexity of the congenital conditions operated on and the increasing number of pediatric transplantations. We evaluated the newly developed pediatric MEDOS HIA-VAD ventricular assist device. METHODS: The pneumatic paracorporeal ventricular assist device has three left ventricular sizes (10-, 25-, and 60-mL maximum stroke volume) and three right ventricular sizes (9, 22.5, and 54 mL) and can be operated effectively with up to 180 cycles/min. We used this device in 6 consecutive pediatric patients. Intention of treatment was to bridge to transplantation in 3 patients and to aid in recovery from a cardiac operation in 3. Age ranged from 5 days to 8 years. RESULTS: Two children died during assist, 2 were weaned from the system and discharged home, and 2 had successful transplantation. During assist, laboratory variables indicative of impaired renal, hepatic, or pulmonary function normalized or showed a trend toward normalization. Both deaths were related to infection. CONCLUSIONS: With the new MEDOS HIA-VAD ventricular assist device system, pediatric mechanical cardiac assist can be performed successfully. It requires timely implantation, careful monitoring, and adequate size-matched devices.

Antibiotic Prophylaxis↗