Keeping pace with implanted defibrillators.
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Biomedical subjects
Publications and source records attributed to A Wagner.
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Since iron deficiency is associated with abnormal erythrocyte rheology, we investigated relationships between plasma ferritin and blood rheology in 36 male elite sportsmen (age: 22.38+/-0.9 years). On the whole, ferritin was negatively correlated with blood viscosity (r = -0.36, p < 0.05). When 23 subjects with low ferritin levels suggesting mild iron deficiency were compared with 13 matched sportsmen with normal ferritin levels, iron-deficient sportsmen were shown to have a higher blood viscosity at 1000 s(-l) (3.17+/-0.09 vs. 2.85+/-0.06 mPas, p < 0.05), explained by a higher plasma viscosity (1.38+/-0.02 vs. 1.31+/-0.02 mPa s, p < 0.05), while hematocrit and RBC rigidity index Tk were similar in the two groups. RBC aggregability index M (4.59+/-0.58 vs. 2.95+/-0.43 mPas, p < 0.05) and M1 (8.46+/-0.58 vs. 6.07+/-0.55, p < 0.01) were higher in iron-deficient subjects. Serum zinc was lower in iron-deficient sportsmen (0.73+/-0.02 vs. 0.83+/-0.02 mg/l, p < 0.01), but the score of early signs of overtraining was higher in this group (10.84+/-1.61 vs. 4.08+/-1.11, p < 0.01). These data suggest that mild iron deficiency as commonly seen in athletes, before anemia occurs, is associated with an increase in plasma viscosity and RBC aggregation, together with an increased subjective feeling of exercise overload.
To delineate the astronomical number of possible interactions of all genes in a genome is a task for which conventional experimental techniques are ill-suited. Sorely needed are rapid and inexpensive methods that identify candidates for interacting genes, candidates that can be further investigated by experiment. Such a method is introduced here for an important class of gene interactions, i.e., transcriptional regulation via transcription factors (TFs) that bind to specific enhancer or silencer sites. The method addresses the question: which of the genes in a genome are likely to be regulated by one or more TFs with known DNA binding specificity? It takes advantage of the fact that many TFs show cooperativity in transcriptional activation which manifests itself in closely spaced TF binding sites. Such 'clusters' of binding sites are very unlikely to occur by chance alone, as opposed to individual sites, which are often abundant in the genome. Here, statistical information about binding site clusters in the genome, is complemented by information about (i) known biochemical functions of the TF, (ii) the structure of its binding site, and (iii) function of the genes near the cluster, to identify genes likely to be regulated by a given transcription factor. Several applications are illustrated with the genome of Saccharomyces cerevisiae , and four different DNA binding activities, SBF, MBF, a sub-class of bHLH proteins and NBF. The technique may aid in the discovery of interactions between genes of known function, and the assignment of biological functions to putative open reading frames.
Viral persistence in the central nervous system is the driving force behind the chronic progressive disease caused by natural canine distemper virus (CDV) infection in dogs. Persistence of CDV is associated with non-cytolytic spread and impaired viral budding. Since budding is to a large extend dependent on the nucleocapsid-(N) and matrixproteins (M) of the virus, we analyzed the nucleotide- and deduced amino acid sequences of the corresponding genes of a spectrum of CDV strains, that differ with respect to virulence and persistence in vivo and in vitro. The wild type CDV (A75/17), which is capable of causing a persistent infection in vivo was compared to two tissue culture adapted CDV strains (passaged A75/17-CDV and Rockborn-CDV), which CDV strains, that differ with respect to virulence and persistence in vivo and in vitro. The wild type CDV (A75/17), which is capable of causing a persistent infection in vivo was compared to two tissue culture adapted CDV strains (passaged A75/17-CDV and Rockborn-CDV), which retain a residual virulence and the capacity to spontaneously persist in vitro. A modified distemper virus (Snyder Hill-CDV), which is neurovirulent but not capable of causing a persistent infection in vivo, and an avianized virus (Onderstepoort-CDV) which is completely apathogenic and spreads by budding in cell cultures were also examined. Differences were found in the C-terminal of the nucleocapsid protein, which--comparing the two extremes of the spectrum (wild A75/17-CDV and OP-CDV)--lead to changes of the predicted protein structure. Such changes could affect the budding process and thus play a role in persistence. Marked changes in the M-gene were found in its non-coding region: the nucleotide sequences of the SH-CDV and OP-CDV differed considerably from the other three strains. Moreover, an additional second open reading frame was detected in the 'non-coding' region of the M gene in the wild A75-CDV, the two tissue culture adapted CDV strains and SH-CDV, but not in OP-CDV. The presence of this additional open reading frame correlated with the ability to cause a spontaneous persistent infection in vitro. Our findings support the notion that both N- and M-genes of CDV harbor determinants of viral persistence.
UNLABELLED: Mechanical restraints in agitated, violent psychiatric patients are still sometimes in use in the initial phase of emergency treatment, especially when patients are taken to hospital by law enforcement. Sudden death has occurred in persons in hobble restraint. Cardiopulmonary response to prone or upright hobble restraint for three minutes was investigated in six male volunteers in randomised crossover trial. RESULTS: No change was observed in the investigated cardiopulmonary parameters after hobble restraint in the upright position. After hobble restraint in the prone position, mean forced vital capacity decreased by 39.6%, mean forced exspiratory volume by 41%, mean end-tidal carbon dioxide increased by 14.7%, mean heart rate decreased by 21.3%, mean systolic blood pressure decreased by 32.3%, mean diastolic blood pressure decreased by 26.1% and mean cardiac output decreased by 37.4% (P for all reported changes < 0.01). CONCLUSION: Hobble restraint in the prone position leads to a dramatic impairment of hemodynamics and respiration. Upright position and frequent control of vital parameters are necessary to prevent a possibly fatal outcome in persons in hobble restraint.
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The presence of a haemoglobin protein which does not exhibit a Bohr effect has been found only in fish living in fast flowing waters. We report the cloning of the first non-Bohr effect beta-globin cDNA from an adult Atlantic salmon kidney bank. Nucleotide sequence analysis of this cDNA shows that the predicted beta-globin peptide comprises 147 amino acids with a calculated molecular mass of 15 975 Da and an overall amino acid homology of 40 to 50% to higher vertebrates and 60-90% to fish sequences. This sequence confirms the important amino acid residues which are changed thus causing loss of the Bohr effect [Powers, D.A. and Edmunson, A.B. (1972) Multiple hemoglobins of catostomid fish. J. Biol. Chem. 247, 6686-6693; Brunori, M. (1975) Molecular adaptation to physiological requirements: the hemoglobin system of trout. Curr. Topics Cell. Regul. 9, 1-39]. This loss allows the haemoglobin protein to have a higher oxygen affinity, as it does not release oxygen when the pH of the surrounding environment decreases, which is an important ability for the fish in times of stress.
OBJECTIVE: To assess the value of a computer-assisted three-dimensional guidance system (Virtual Patient System) in maxillofacial operations. DESIGN: Laboratory and open clinical study. SETTING: Teaching Hospital, Austria. SUBJECTS: 6 patients undergoing various procedures including removal of foreign body (n=3) and biopsy, maxillary advancement, and insertion of implants (n=1 each). INTERVENTIONS: Storage of computed tomographic (CT) pictures on an optical disc, and imposition of intraoperative video images on to these. The resulting display is shown to the surgeon on a micromonitor in his head-up display for guidance during the operations. MAIN OUTCOME MEASURES: To improve orientation during complex or minimally invasive maxillofacial procedures and to make such operations easier and less traumatic. RESULTS: Successful transferral of computed navigation technology into an operation room environment and positive evaluation of the method by the surgeons involved. CONCLUSIONS: Computer-assisted three-dimensional guidance systems have the potential for making complex or minimally invasive procedures easier to do, thereby reducing postoperative morbidity.
PURPOSE: The objective of this study was to apply virtual reality technology to osteotomies of the facial skeleton. MATERIALS AND METHODS: Augmented reality can be considered a hybrid of virtual and real environment spaces, which are coregistered and simultaneously visualized. Using a see-through HMD (head-mounted display) and Interventional Video Tomography intraoperatively, partial visual immersion into a patient-related virtual data space augments the surgeon's perception as shown in an experimental study and clinical applications. RESULTS: Without limiting the surgical judgment, offering continuous observation of the operating field, the presented technology additionally provides visual access to invisible data of anatomy, physiology, and function and thus guarantees unencumbered and fluent surgery. CONCLUSION: Despite current shortcomings, augmented reality technology proved to be particularly well suited for use in osteotomies of the facial skeleton.
We report a case of acute inhalation injury of nitric acid in a 56-year old white male. The patient presented conscious and dyspnoic at the emergency department after cleaning a copper chandelier with nitric acid. He had to be intubated 2 h after admission and mechanically ventilated because of fulminant respiratory insufficiency. As all sources of mechanical ventilation failed, extracorporeal membrane oxygenation had to be established 7 h after admission. With the additional use of surfactant and low dose inhalation therapy with nitric oxide (NO), the patient could be stabilised for 3 days and lung function improved temporarily. Despite all efforts the patient died at the fourth day from refactory respiratory failure. Pathologic examination revealed massive pulmonary edema without signs of inflammation. Thus, nitric acid inhalation induced pulmonary edema appears to be a most severe situation in which even most modern therapeutic interventions fail. As, in respect of recent literature and our case no promising therapy for nitric acid inhalation pulmonary edema is available, our efforts have to be directed towards prevention of nitric acid exposure.
The synthesis and the SAR study of imidazo[4,5-b]pyridine biphenyl sulfonylureas and -carbamates as highly potent AT1-selective ANG II receptor antagonists are described. Several members of this new class of antagonists efficiently inhibited the ANG II-induced pressor response in pithed rats after iv and intraduodenal (id) administration.
Additional data from imaging sources using computer navigation assistance enables virtual visualization of anatomical structures in three dimensions for stereotactic navigation during an operation. Recent developments in communication technology enable the broadcasting not only of video data, but also of stereotactic navigation data via the network. By telepresence/teleconsulting, the composite images and overlapping graphics (instrument, target structure, landmark, contour) can be seen in connected clinics, with the possibility of interactive graphic assistance. In cranio-maxillofacial surgery, the first surgical teleconsultation in real time via telecommunication of stereotactic data was performed in August 1996. A patient suffering from a post-traumatic deformity following multiple comminuted midface fractures was re-osteotomized with the aid of image-guided surgery using teleconsultation: the intraoperative position achieved could be discussed with different surgeons with regard to symmetry, hard/soft tissue relationships and occlusal details, with the possibility of on-screen planning interaction and real time evaluation of the results, over a distance of 500 km.
We present 6 selected cases of extensive facial vascular anomalies extending to the skull base or actually involving it. These patients are compared with other cases in the literature. The spontaneous course of these vascular lesions is different and so variable treatment modalities are suggested depending on the age of the patient and the type of lesion. In young children, haemangiomas are common and spontaneous involution is characteristic. Conservative treatment in the sense of a wait-and-see approach is thereby favoured if there is no urgent indication such as involvement of essential structures, e.g. blockage of an orifice as demonstrated in one case or complications such as excessive bleeding. Vascular malformations most commonly appear in adults, there is no tendency to spontaneous involution and resection is usually necessary, especially in arteriovenous malformations. Nowadays, preoperative superselective embolization is recommended to minimize intraoperative blood loss. Superselective embolization is the treatment of choice in cases of a-v fistulae. Proximal ligation of the supplying arteries should be avoided because this may make embolization more difficult, and may be responsible for the common occurrence of rapid revascularization.
Augmented reality technology was used in 5 patients for secondary reconstruction of post-traumatic unilateral deformities of the zygomaticomaxillary complex. Three electromagnetic sensors interfaced to a computer-aided navigation system (ARTMA Biomedical Inc.) were utilized. The computer navigation procedure was planned by drawing graphic lines on the CT scan at the level of the zygomatic arch, representing the outer surface of the zygoma. The desired position of the displaced zygoma was planned by mirroring from the healthy side, using a virtual mid-sagittal plane. These virtual graphics were presented intraoperatively on a TV monitor and also on the surgeon's see-through head-mounted display. Correct reduction was assumed when the virtual line representing the position of the zygoma before the osteotomy reached the virtual line defined preoperatively as the desired position. The advantages of the technique presented are that a complete exposure of the zygomatic bone is no longer necessary, and coronal and subciliary incisions may be avoided unless enophthalmos correction has to be carried out, which was in fact necessary in 2 patients. The results of zygomatic reconstruction have been satisfactory in all 5 patients.
Apoptosis seems to be the predominant type of active cell death in the liver (type I), while in other tissues cells may die via biochemically and morphologically different pathways (type II, type III). Active cell death is under the control of growth factors and death signals. In the liver, endogenous factors, such as transforming growth factor beta 1 (TGF-beta 1), activin A, CD95 ligand, and tumor necrosis factor (TNF) may be involved in induction of apoptosis. Release and action of these death factors seems to be triggered by exogenous signals such as withdrawal of hepato-mitogens, food restriction, etc. During stages of hepatocarcinogenesis, not only DNA synthesis but also apoptosis gradually increase from normal to preneoplastic to adenoma and carcinoma tissue. Also, in human carcinomas, birth and death rates of cells are several times higher than in surrounding liver. (Pre)neoplastic liver cells are more susceptible than normal hepatocytes to stimulation of cell replication and of cell death. Consequently, tumor promoters may act as survival factors, i.e., inhibit apoptosis preferentially in preneoplastic and even in malignant liver cells, thereby stimulating selective growth of (pre)neoplastic lesions. On the other hand, regimens favoring apoptosis and lowering cell replication may result in selective elimination of (pre)neoplastic cell clones from the liver. Finally, we have studied the first stage of carcinogenesis, namely the appearance of putatively initiated cells after a single dose of the genotoxic carcinogen N-nitrosomorpholine (NNM). Most of these cells were found to be eliminated by apoptosis, suggesting that initiation, at the organ level, can be reversed at least partially by preferential elimination of initiated cells. These events may be regulated by autocrine or paracrine actions of survival factors.
Spinal cord injured (SCI) individuals most often contract their injury at a young age and are deemed to a life of more or less physical inactivity. In addition to the primary implications of the SCI, severe SCI individuals are stigmatized by conditions related to their physically inactive lifestyle. It is unknown if these inactivity related conditions are potentially reversible and the aim of the present study was, therefore, to examine the effect of exercise on SCI individuals. Ten such individuals (six with tetraplegia and four with paraplegia; age 27-45 years; time since injury 3-23 years) were exercise trained for 1 year using an electrically induced computerized feedback controlled cycle ergometer. They trained for up to three times a week (mean 2.3 times), 30 min on each occasion. The gluteal, hamstring and quadriceps muscles were stimulated via electrodes placed on the skin over their motor points. During the first training bouts, a substantial variation in performance was seen between the subjects. A majority of them were capable of performing 30 min of exercise in the first bout; however, two individuals were only able to perform a few minutes of exercise. After training for 1 year all of the subjects were able to perform 30 min of continuous training and the work output had increased from 4 +/- 1 (mean +/- SE) to 17 +/- 2 Kilo Joules per training bout (P < 0.05). The maximal oxygen uptake during electrically induced exercise increased from 1.20 +/- 0.08 litres per minute measured after a few weeks habituation to the exercise to 1.43 +/- 0.09 litres per minute after training for 1 year (P < 0.05). Magnetic resonance cross sectional images of the thigh were performed to estimate muscle mass and an increase of 12% (mean, P < 0.05) was seen in response to 1 year of training. In biopsies taken before exercise various degrees of atrophy were observed in the individual muscle fibres, a phenomenon that was partially normalized in all subjects after training. The fibre type distribution in skeletal muscles is known to shift towards type IIB fibres (fast twitch, fast fatiguable, glycolytic fibres) within the first 2 years after the spinal cord injury. The muscle in the present investigation contained of 63% myosin heavy chain (MHC) isoform IIB, 33% MHC isoform IIA (fast twitch, fatigue resistant) and less than 5% MHC isoform I (slow twitch) before training. A shift towards more fatigue resistant contractile proteins was found after 1 year of training. The percentage of MHC isoform IIA increased to 61% of all contractile protein and a corresponding decrease to 32% was seen in the fast fatiguable MHC isoform IIB, whereas MHC isoform I only comprised 7% of the total amount of MHC. This shift was accompanied by a doubling of the enzymatic activity of citrate synthase, as an indicator of mitochondrial oxidative capacity. It is concluded that inactivity-associated changes in exercise performance capacity and skeletal muscle occurring in SCI individuals after injury are reversible, even up to over 20 years after the injury. It follows that electrically induced exercise training of the paralysed limbs is an effective rehabilitation tool that should be offered to SCI individuals in the future.
Radiation-induced intracranial aneurysm formation is a rare but life-threatening condition with a high mortality rate secondary to rupture of the aneurysm. Furthermore, this condition can mimic tumour recurrence. Only 10 months after craniospinal radiation therapy for medulloblastoma, a 9-year-old boy developed a subarachnoid haemorrhage secondary to a ruptured saccular aneurysm arising from the distal part of the right anterior cerebral artery. The development of intracranial aneurysms and rupture following radiation damage of the arteries has been reported previously, but in no case as soon as 10 months after radiation therapy. It is important to diagnose these aneurysms as they can be successfully treated.
BACKGROUND: A plunge in platelet count if often observed after massive blood transfusions during major surgery. This study was designed to assess whether the prophylactic administration of prostaglandin E1 (PGE1) might prevent this drop in platelet count. METHODS: Forty-five patients receiving massive transfusions of packed red blood cells (> 10 units) during major orthopedic surgery were enrolled in a prospective, randomized, double-blind, placebo-controlled study and divided into two groups: group 1 (therapy group) received intravenous PGE1 up to 30 ng/kg/min for 72 hours after surgery, and group 2 (placebo group) received a placebo during the same time period. RESULTS: The patients in group 1 suffered no reduction in platelet count and thus required no platelet concentrate transfusions. In contrast, a significant postoperative drop in platelet count (p < 0.05) was observed in the placebo group between days 3 and 5 after surgery when compared to the therapy group, necessitating transfusions of platelet concentrates in this group. Similarly, red blood cell count and hemoglobin were far more stable in the therapy group, which required fewer transfusions of red blood cells than did the placebo group (p < 0.05). There seemed to be a tendency toward a consumptive coagulation disorder in the placebo group as indicated by a decrease of fibrinogen levels, prothrombin time, and antithrombin III activity, and an increase of partial thromboplastin time. The incidence of adult respiratory distress syndrome was slightly lower in the therapy group. Last but not least, the length of intensive care unit stay was significantly shorter in the therapy group (p < 0.05). CONCLUSION: In our study, the administration of PGE1 prevented a reduction in platelet count. Furthermore, measurements of clotting activity furnished the possibility that PGE1 might inhibit transfusion-induced coagulation disturbances. We recommend that PGE1 should be considered in patients requiring massive transfusion during major surgery.