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Biomedical subjects

Michael Grimm

Publications and source records attributed to Michael Grimm.

44 records · Page 3Linked to original sources

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1.

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.

Adult↗

Plant 7SL RNA and tRNA(Tyr) genes with inserted antisense sequences are efficiently expressed in an in vitro transcription system from Nicotiana tabacum cells.

RNA polymerase III-driven cassettes for the expression of antisense RNAs and ribozymes have recently attracted much attention because (1) pol III genes are transcribed abundantly in all kinds of tissues and (2) the transcripts are very stable by virtue of their small and compact size. We have designed two types of pol III-based expression vehicles. Antisense RNA sequences targeted against conserved structural elements or domains in the RNAs of potato spindle tuber viroid, hop latent viroid and potato virus S were either embedded in the anticodon region of a Nicotiana tRNA(Tyr) gene or near the 3' end of an Arabidopsis 7SL RNA gene. Both classes of chimeric genes were transcribed in vitro in a homologous plant extract. Our studies clearly revealed that the modified tRNA and 7SL RNA genes, carrying insertions of up to 90 and 120 bp, respectively, were expressed efficiently in the tobacco nuclear extract, resulting in high levels of stable chimeric transcripts. 7SL RNA (also termed SRP RNA) represents the RNA component of the signal recognition particle. This is the first report of demonstrating the employment of 7SL RNA genes as potential cassettes for the expression of antisense RNA and ribozyme sequences and might be helpful in future experiments to control their localization in specific sub-cellular compartments.

Base Sequence↗

Intrapulmonary shunt after cardiopulmonary bypass: the use of vital capacity maneuvers versus off-pump coronary artery bypass grafting.

OBJECTIVES: It has been proved in human subjects and animals that atelectasis is a major cause of intrapulmonary shunting and hypoxemia after cardiopulmonary bypass. Animal studies suggest that shunting can be prevented entirely by a total vital capacity maneuver performed before termination of bypass. This study aimed to test this theory in human subjects and to evaluate possible advantages of off-pump coronary artery bypass grafting. METHODS: Twenty-four patients scheduled for coronary artery bypass grafting were randomly assigned to receive no total vital capacity maneuver (control group, n = 12) or standard total vital capacity maneuvers (TVCM group, n = 12). Additionally, 12 consecutive patients undergoing off-pump coronary artery bypass grafting (off-pump group) were studied. Systemic and central hemodynamics, the pattern of breathing, and ventilatory mechanics were evaluated after induction of anesthesia, after sternotomy, after cardiopulmonary bypass and skin closure, and 4 hours after extubation. RESULTS: The use of total vital capacity maneuvers reduced (P <.05) intrapulmonary shunting after termination of cardiopulmonary bypass. However, shunting increased (P <.05) in all groups (control group, 8.2% +/- 3.3% vs 25.6% +/- 8.1%; TVCM group, 8.7% +/- 3.4% vs 24.4% +/- 8.5%; and off-pump group, 7.8% +/- 2.8% vs 14.0% +/- 5.3%) after extubation, but the increase was significantly (P <.05) less pronounced in the off-pump group. Furthermore, pulmonary compliance decreased (P <.05) in all groups except the off-pump group after extubation. Duration of hospital and intensive care unit stay was significantly shorter (P <.05) in the off-pump group than in the other groups. CONCLUSION: The development of intrapulmonary shunting and hypoxemia after coronary artery bypass grafting can be substantially reduced by performance of total vital capacity maneuvers while patients are mechanically ventilated. However, off-pump coronary artery bypass surgery is superior in preventing shunting and hypoxemia after bypass grafting in the immediate and early postoperative periods, probably leading to substantially shorter intensive care unit and hospital stays.

Aged↗

The University of Vienna experience in heart transplantation.

Since the University of Vienna Cardiac Transplant Program began in 1984, 892 heart transplant procedures have been performed through the end of 2001. One- and five-year survival has increased steadily over time to 80% and 75%, respectively, in the most recent cohort. Ten-year survival is 55%. Over the past 10 years our program has seen dramatic changes in patient selection, accepting now patients with more risk factors (age, diabetes, elevated pulmonary resistance,..). Developments in immunosuppression have decreased the incidence of infection, rejection and graft arteriosclerosis continuously. Our program continues to pursue novel strategies to improve the survival and quality of life of our heart transplant patients.

Adolescent↗

Classifying 'drug-likeness' with kernel-based learning methods.

In this article we report about a successful application of modern machine learning technology, namely Support Vector Machines, to the problem of assessing the 'drug-likeness' of a chemical from a given set of descriptors of the substance. We were able to drastically improve the recent result by Byvatov et al. (2003) on this task and achieved an error rate of about 7% on unseen compounds using Support Vector Machines. We see a very high potential of such machine learning techniques for a variety of computational chemistry problems that occur in the drug discovery and drug design process.

Artificial Intelligence↗

Neurocognitive function in patients with ventricular assist devices: a comparison of pulsatile and continuous blood flow devices.

The effect of successful ventricular assist device (VAD) implantation on neurocognitive function in terminal heart failure is uncertain. Additionally, the different impact of continuous versus pulsatile blood flow devices is unknown. A total of 29 patients (mean age 53 years), surviving implantation of a ventricular assist device as bridge to transplantation were prospectively followed (continuous flow: Micromed DeBakey, n = 11; pulsatile flow: Thoratec and Novacor, n = 18). Normative data were obtained in 40 age- and sex-matched healthy subjects (mean age 54 years). Neurocognitive function was objectively measured by means of cognitive P300 auditory evoked potentials before operation (baseline), at intensive care unit (ICU) discharge, and at the 8-week and 12-week follow-up. Before implantation of the VAD, cognitive P300 evoked potentials were impaired (prolonged) compared with age- and sex-matched healthy subjects (p < 0.001). After successful VAD implantation, P300 evoked potentials markedly improved compared with before operation (ICU discharge, p = 0.007; 8-week follow-up, p = 0.022; 12-week follow-up, p < 0.0001). Importantly, there was no difference between continuous and pulsatile VADs (before operation, p = 0.676; ICU discharge, p = 0.736; 8-week follow-up, p = 0.911 and 12-week follow-up, p = 0.397; respectively). Nevertheless, P300 peak latencies did not fully normalize at 12-week follow-up compared with healthy subjects (p = 0.012). Successful VAD implantation improves neurocognitive impairment in patients with terminal heart failure. Importantly, this effect is independent of the type of VAD (pulsatile vs. continuous blood flow).

Austria↗

Pre-operative intercostal nerve blockade for minimally invasive coronary bypass surgery: a standardised anaesthetic regimen for rapid emergence and early extubation.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCAB) has become a popular adjunct to cardiac bypass surgery in selected patients. Although MIDCAB without cardiopulmonary bypass is considered to be a relatively noninvasive procedure, the trauma to the muscle tissue caused by the anterolateral thoracotomy often leads to more pain than that of patients undergoing routine sternotomy. The purpose of our study was to evaluate the pre-operative application of an intercostal nerve blockade, combined with general anaesthesia for peri- and postoperative pain control, and its efficacy for early extubation. METHODS AND RESULTS: Nine consecutive patients undergoing MIDCAB surgery were evaluated. Pre-operative ipsilateral intercostal nerve blockade was employed in all patients. After induction, isofluran (0.4-0.8%) and nitrous oxide in combination with the pre-operative nerve blockade provided sufficient anaesthesia throughout the procedure (mean operative time: 147 min). Only 2/9 patients required additional small doses of narcotics. All patients could be safely extubated within 15 minutes of skin suture. Postoperative discomfort and pain were minimal. CONCLUSION: From our initial experience with preoperative intercostal nerve blockade for the MIDCAB procedure, we concluded that it provides profound somatic analgesia as an effective adjunct to general anaesthesia with reduced doses of narcotics and sedatives. MIDCAB impresses with its ease of technical performance, its reliability and safety. The minimised chest-wall pain improves patients' chances of early tracheal extubation. In accordance with the minimally invasive surgical approach, it provides a contribution towards 'minimally invasive anaesthesia'. The surgeons' and the patients' acceptance is excellent. Because the results of this study are based on observation and verbalisation of the investigators' impressions, and no objective measurements were made which would have allowed a comparison between the MIDCAB technique and the golden standard of general anaesthesia with opioid analgesia, a further study should be conducted to prove our theory.

Adult↗