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Biomedical subjects

M Engel

Publications and source records attributed to M Engel.

At least 19 recordsLinked to original sources

Dynamic shunt testing applying short lasting pressure waves--inertia of shunt systems.

Laboratory shunt testing often comprises only static pressure flow and flow pressure tests. We applied shorter acting pressure waves using a computerised shunt testing rig to investigate shunt behaviour under conditions that might occur in the clinical situation, e.g. during nocturnal vasogenic pressure waves or shorter rises in ICP at movements or exercise. Additionally the influence of a human-like compliance situation compared to a fixed pressure/volume relationship was investigated. Shunts behaved very differently than seen in static tests and demonstrated a marked inertia the shorter pressure waves acted. Although some valves opened at higher pressure, all valves showed marked hysteresis and none did close--if at all--at the specified pressure level. This behaviour might be a cause of shunt overdrainage not related to siphoning. The simulation of a human-like variable pressure-volume relationship with higher compliance at lower pressures had a positive effect on shunt function by decreasing the amount of drained volume. We therefore suggest to include dynamic pressure wave testing if hydrodynamic properties of shunts are to be evaluated.

Cerebrospinal Fluid↗

Epicardial echocardiography for correct placement of the intracardial biventricular assist device (Impella).

BACKGROUND: Correct placement of the intracardial biventricular assist device (Impella) as a supporting system for off-pump coronary surgery is routinely checked by transesophageal echocardiography and invasive pressure measurements. However, it remains difficult to verify the accurate position of the right heart system when the posterior wall is exposed. METHODS: In 23 patients undergoing augmented beating heart CABG surgery, the correct placement of the lmpella-system was controlled by TEE as well as by a new 15-6 L epicardial echotransducer (EE) (Agilent, Andover, MA). RESULTS: TEE assisted well in inserting the system in all patients. The correct placement of the distal end of the right heart system 1.5 cm behind the pulmonary valve was verified in 18/23 cases by TEE vs. 23/23 cases by EE. Dislocation of the devices during tilting of the heart could only be verified by EE. CONCLUSIONS: Epicardial echocardiography is a useful, innovative method for monitoring the correct placement of the new intracardial biventricular assist device during beating-heart surgery.

Coronary Artery Bypass↗

A new intracardiac microaxial pump: first results of a multicenter study.

As coronary artery bypass grafting (CABG) surgery in the beating heart technique is progressing, new devices have been developed to overcome hemodynamic instabilities while tilting the heart for exposure of back wall vessels. A new device for in heart biventricular intracorporeal circulation was applied in 42 patients undergoing CABG surgery (Group 1). The control group consisted of 38 patients operated on using a conventional cardiopulmonary bypass setup (Group 2). The study protocol of the prospective, randomized multicenter study was approved by the local ethics committees. Patients were included following inclusion criteria and patient informed consent. Mean age, procedure time, mean arterial pressure (MAP), and hemolysis by means of plasma free hemoglobin (fHb) were assessed preoperatively, perioperatively, on postoperative Days 1 to 3, at discharge, and at a 3 month follow-up. The mean age was 62.1 (range 59-74) years (Group 1), 62.7 (range 48-72) years (Group 2); procedure time was 112 min +/- 31.9 min (Group 1), 137.4 min +/- 36.2 min (Group 2); and 2.3 +/- 0.6 (Group 1), 2.2 +/- 0.7 (Group 2), vessels were revascularized. The flow on pump was 3.7 (2.5/4.4) L/min (Group 1), 4.9 (3.6/6.2) L/min (Group 2) which resulted in a MAP of 69.8 (4.0/143) mm Hg (Group 1), 58.3 (5.3/94) mm Hg while assessing the vessels of the back wall. Hemolysis defined by fHB was lower than 20 mg/dl at all times pre- and postoperatively. Intraoperative maximum values were up to 100 mg/dl in 4 patients (2 in Group 1 and 2 in Group 2). Body mass index was 26.4 +/- 2.6 (Group 1), 27.9 +/- 3.2. New York Heart Association Class was II to III in both groups. There were no pump related life threatening or severe adverse events. Beating heart procedures with ICC can be reliably and safely achieved. As the device is easy to use, it may deserve a more widespread use in the future.

Aged↗

[Patient-adapted valve selection: biological vs. mechanical heart valve replacement in aortic valve diseases].

Since the first aortic valve replacement performed by Harken in 1960, the operation of aortic valve disease by replacing the native valve with a heart valve prosthesis has become one of the most frequently performed procedures in cardiac surgery. For valve replacement there are biological (xenografts and homografts) and mechanical heart valve prostheses available. When choosing the most suitable prosthesis the limited durability of a biological prosthesis and the risks of lifelong anticoagulation for a mechanical prosthesis have to be balanced. In this article the indication for operation of aortic valve stenosis and aortic regurgitation are discussed first. Based on the literature of the last 2 years the advantages and disadvantages of mechanical and biological heart valve prostheses (xenograft, homograft and ROSS procedure) are discussed. In addition rarely used techniques like aortic valve reconstruction are presented. Due to the fact that a biological prosthesis has a durability of 12-15 years and the risk of bleeding complications under anticoagulation grows with increasing age, the choice of a biological prosthesis can be recommended from the age of 65 years. Results of long-term studies at to whether this limit can be diminished by using a stentless biological prosthesis have to be awaited.

Aged↗

Application of clinically recorded ICP patterns--an extension of conventional shunt testing.

Various methods of laboratory testing are currently being used to explore the hydrodynamic properties of shunts. We constructed a novel shunt-testing rig with a human-like compliance to be able to subject shunts to in-vivo recorded ICP patterns. The human-like situation was realized with a pear-shaped glass container with a non-linear, third-order pressure/volume characteristic similar to the CSF system. The new device also allows conventional shunt testing. Shunt performance in conventional pressure/flow tests (linear compliance) was compared to tests with human-like compliance. No clinically relevant differences were seen. Clinically recorded ICP waves (Lundberg type A and B) were reproduced before and after shunt implementation. Shunt insertion reduced pressure in the A-wave pattern to slightly negative values. Reproducing B-waves, the shunt dampened wave amplitude and pressure decreased below the opening pressure of the valve. In conclusion, the presented device allows a standardized reproduction of ICP patterns. The effects of shunt implantation can be studied.

Cerebrospinal Fluid↗

Improved prognosis of Epstein-Barr virus associated childhood Hodgkin's lymphoma: study of 47 South African cases.

AIM: To study the distribution of Hodgkin's lymphoma in South African children and report the incidence of Epstein-Barr virus (EBV) as regards age, race, sex, and histological subtype; to investigate whether EBV is relevant to survival. METHODS: Immunohistochemistry (IHC) and in situ hybridisation (ISH) to detect EBV were performed on 47 South African children with classical Hodgkin's lymphoma, ranging in age from 3 to 14 years and coming from different ethnic backgrounds. The correlation between the presence of the virus and clinical outcome was assessed. RESULTS: The nodular sclerosing subtype predominated, comprising 89% of cases; the remaining 11% were of the mixed cellularity subtype. EBV was present in 68%. Full clinical data were available for 36 cases; EBV positive patients presented with less aggressive symptoms at diagnosis and had a significantly longer median survival than EBV negative patients. CONCLUSIONS: The distribution of EBV in South African childhood Hodgkin's lymphoma follows a pattern intermediate to that of industrialised and non-industrialized countries. Furthermore, our data suggest that there is an association between poor prognosis and the non-detection of EBV products in South African childhood Hodgkin's lymphoma.

Adolescent↗

Aortic rupture and concomitant transection of the left bronchus after blunt chest trauma.

We report a patient with traumatic aortic rupture and preoperatively unrecognized complete disruption of the bronchus for the left lower lobe. Preoperative state was complicated by inadequate oxygenation due to total atelectasis of the unventilated collapsed left lower lobe with consequent significant shunting of the unoxygenated blood. The patient had no massive pneumothorax because the intact peribronchial tissue and pleura covered the injured place, preventing important air leakage. The suspicion of possible concomitant tracheobronchial injury and early diagnostic bronchoscopy are important in patients with aortic rupture after blunt chest trauma.

Adult↗

CAPN 8: isolation of a new mouse calpain-isoenzyme.

Recent molecular biological approaches indicate that calpain, also named CANP for calcium-activated neutral protease and originally characterized as an intracellular cytoplasmatic nonlysosomal cysteine protease that requires calcium ions for activity, constitutes a large superfamily consisting of ubiquitous and tissue specific homologues, which are widely distributed in cells of various organisms from human to fungus. Due to the increasing number of substrates along with the involvement of calpain isoenzymes in mammalian diseases, especially in malignancies, members of the calpain superfamily seem to be important biomodulators in physiological as well as pathological cell function. Here we report the characterisation of a new calpain, named CAPN 8 with a different C-terminal domain, implicating a putative new regulatory mechanism. Northern blot analysis revealed an ubiquitous expression with different RNA levels in all tissues examined. Highest levels were found in brain, kidney, and digestive tract, suggesting a specific regulatory function of CAPN 8 in these tissues.

Amino Acid Sequence↗

Expression of calpain I messenger RNA in human renal cell carcinoma: correlation with lymph node metastasis and histological type.

Calpain, also named CANP (for calcium-activated neutral protease), is an intracellular cytoplasmatic non-lysosomal cysteine endopeptidase that requires calcium ions for activity. Many substrates of the calpain isoenzymes, such as the transcription factors c-Fos and c-Jun, the tumor supressor protein p53, protein kinase C, pp60c-src and the adhesion molecule integrin, have been implicated in the pathogenesis of different human tumors, suggesting an important role of the calpains in malignant diseases. We now report differential expression of the calpain I gene (CL I) in a variety of tumors, extending our study to a larger series of renal cell carcinomas. Using Northern-blot analysis, we studied calpain I expression in 30 renal cell carcinomas as compared with matched healthy tissues. Tumor samples were classified according to their histological type: 21 clear cell carcinomas, 4 chromophobe carcinomas, 3 papillary carcinomas and 2 oncocytomas. In renal tumor samples, calpain I gene mRNA was expressed at highly variable levels, significantly depending on the different histological types. Moreover, there was a correlation of higher calpain I expression with increased malignancy: within the clear cell carcinoma subset, tumor samples with advanced nodal status (N1 and N2) showed a significantly higher calpain I expression than tumors without metastasis to regional lymph nodes. Our data suggest an important role of calpain isoenzymes in carcinogenesis and tumor progression.

Biomarkers, Tumor↗

Patterns of seroconversion to Aujeszky's disease virus in unvaccinated chronically infected Swedish weaner pig-producing herds.

This study was carried out in nine unvaccinated Swedish weaner pig-producing herds, ranging in size from 20 to 134 breeding animals, which had experienced a previous outbreak of Aujeszky's disease (AD) and in which seropositive sows were still present. The objective was to quantify the seroconversion rate to Aujeszky's disease virus (ADV) in breeding animals and to find out whether unvaccinated herds could become free from ADV by using only seronegative animals for replacement. Serum samples were initially obtained from all adult pigs in the herds. Animals testing negative, as well as replacement animals, were subsequently tested every second or third month and the herds were followed for 10-28 months. The herd owners were advised to keep seropositive and seronegative animals separate whenever possible and to implement sanitary measures against the reintroduction of the virus into the herds. All herds experienced long consecutive periods (> or = 4 months, median 9 months) without seroconversion. Three herds became free from ADV during the serological study; in two of these herds no seroconversion was observed. In those seven herds where seroconversion occurred, between 9 and 86% of the susceptible pigs became infected. The reinfection was indicative of the reactivation of latent virus in all herds but two, where the reintroduction of the virus was most likely. The pattern of seroconversion was either sporadic, involving not more than three animals at a time, or epidemic, involving a large proportion of the susceptible animals in the herd. Severe clinical outbreaks hit the two largest herds and these only became ADV-free after the conclusion of the study when vaccine was used, which reduced the incidence of seroconversion to zero. The results from the present study show that it is possible for smaller herds to achieve freedom from ADV without any radical control methods, provided that only ADV-free replacement animals are used and the virus is not reintroduced. Moreover, the finding that long periods can elapse without transmission suggests that when infection is discovered in a herd, the risk of massive spread is not necessarily imminent.

Animal Husbandry↗

Diagnosing genetic anomalies by inspection.

Several readily identifiable syndromes that have a genetic basis consist of mental retardation, hyperactivity or other abnormal behaviors, and characteristic physical signs. These disorders are not only an opportunity for clinical diagnosis, but they reflect the neurologic underpinning of intellect and behavior. Moreover, the wide variations in their phenotypes suggests that genetic testing be considered in children with abnormal appearance and mental retardation.

Child↗

Vaccination and eradication programme against Aujeszky's disease in five Swedish pig herds with special reference to herd owner attitudes.

A vaccination eradication programme against Aujeszky's disease (AD), based on the use of gE-negative killed vaccine, was carried out between 1987 and 1992 in 5 Swedish weaner pig producing or farrow-to-finish herds, with 63 to 398 breeding animals. All breeding animals were tested at the start and the end of the programme. Seroprevalence to Aujeszky's disease virus (ADV) ranged between 47% and 100% in the herds at the first test. During the programme, all breeding animals were vaccinated simultaneously every 4 months and ADV-free replacement animals were vaccinated shortly after arrival and boostered within a month. In one herd only, a limited number of fatteners were vaccinated. The herds were declared free (gE-negative) 12 to 53 months after the start of the programme. When all seropositive breeding animals had been culled, the programme ended after 2 negative tests of the breeding animals. Seroconversion was limited in all herds but one, where initially no isolation unit was available for replacement animals. The attitude of the herd owners towards the programme and the special conditions prevailing in the herds are discussed. It is suggested that vaccination may promote risk behaviour of herd managers.

Animal Husbandry↗

Glyceraldehyde-3-phosphate dehydrogenase and Nm23-H1/nucleoside diphosphate kinase A. Two old enzymes combine for the novel Nm23 protein phosphotransferase function.

We have recently discovered an alternative function of the putative metastasis suppressor protein Nm23, which is identical to nucleoside diphosphate kinase, as a protein phosphotransferase in vitro. While purified native Nm23 protein did not phosphorylate other proteins, we could purify a Nm23-associated protein that activates the protein phosphotransferase function; it was identified as a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzyme. Co-expression and purification of (His)6-tagged GAPDH in combination with either Nm23-H1 or Nm23-H2 in baculovirus-infected Sf9 cells showed that only Nm23-H1, but not Nm23-H2, forms a stable complex with GAPDH. Protein phosphotransferase activity was confirmed for the recombinant GAPDH.Nm23-H1 complex but not for either of the enzymes alone, nor was this activity observed after simple mixing of the purified proteins in vitro. The molecular mass of the highly purified recombinant GAPDH.Nm23-H1 complex suggests that a dimer of GAPDH interacts with a dimer of Nm23-H1. In contrast to the complex with GAPDH, co-expression of Nm23-H1 with antioxidant protein (MER-5) or creatine kinase did not activate the protein phosphotransferase function, indicating that this activation may specifically require GAPDH as a binding partner.

Creatine Kinase↗

Enhanced prostaglandin E2 production by monocytes in atopic dermatitis (AD) is not accompanied by enhanced production of IL-6, IL-10 or IL-12.

AD is associated with a bias of the T helper cells to show increased IL-4 and reduced interferon-gamma (IFN-gamma) production. The production of IFN-gamma and IL-4 and the development of Th cells into either high IFN-gamma or high IL-4 producers is strongly influenced by factors produced by antigen-presenting cells (APC), like IL-12 and prostaglandin E2 (PGE2). IL-12 selectively enhances IFN-gamma production and favours the development of IFN-gamma-producing Th cells, whereas PGE2 selectively inhibits IFN-gamma production by Th cells. The aim of this study was to test whether the increased IL-4/IFN-gamma production ratio by Th cells in AD can be explained by an increased PGE2/IL-12 production ratio by the APC. Monocytes were used as APC source. PGE2 and IL-12 production by lipopolysaccharide (LPS)-stimulated monocytes from 12 AD patients and 12 non-atopic controls was determined using two complementary experimental systems, whole blood cultures and purified monocytes. In addition, we determined IL-6 production as a measure of monocyte activation, and IL-10 production because IL-12 production by monocytes is highly influenced by endogenously produced IL-10. The monocytes from AD patients showed normal production levels of IL-6 and IL-10, a two-fold, but non-significant decrease in IL-12 production, and a significantly (three-fold) higher PGE2 production than those from non-atopic controls. Here we show for the first time that enhanced PGE2 production by monocytes in AD is not accompanied by a general rise in cytokine production. We conclude that AD is indeed associated with an increased PGE2/IL-12 production ratio by monocytes.

Adolescent↗

Molecular characterization of a new whitefly-transmissible bipartite geminivirus infecting tomato in Panama.

The nucleotide sequence of infectious clones of a tomato-infecting geminivirus from Panama [named tomato leaf curl virus (ToLCV-Pan) because of symptoms produced in infected tomato (plant stunting and mild leaf curling)] was determined. ToLCV-Pan has a bipartite genome (DNAs A and B) and computer analysis showed that the genome resembles that of other bipartite, whitefly-transmitted geminiviruses. DNA A (2584 nt) and B (2542 nt) have little sequence homology other than within the common region. ToLCV-Pan clones were introduced into Lycopersicon esculentum and infected plants developed the same symptoms as naturally infected tomatoes. Homology analysis of DNA A and B showed that ToLCV-Pan is most closely related to potato yellow mosaic virus (PYMV) from Venezuela. Pseudorecombination between ToLCV-Pan and PYMV did not give viable pseudorecombinant viruses. However, in some plants infected with the pseudorecombinant virus produced by ToLCV-Pan DNA A and PYMV DNA B, systemic movement of ToLCV-Pan DNA A was observed.

Base Sequence↗