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Biomedical subjects

M Funk

Publications and source records attributed to M Funk.

At least 19 recordsLinked to original sources

Frequency of long-term lower limb ischemia associated with intraaortic balloon pump use.

Lower limb ischemia is a frequent complication of intraaortic balloon pump (IABP) use. The incidence and risk factors for acute ischemia have been well-defined, but little is known about long-term ischemic complications. This prospective study evaluated the incidence, nature, progression and predisposing factors for long-term lower limb ischemia in 151 patients who were previously treated with the IABP. These persons were interviewed and their lower extremities examined 12 to 20 months after undergoing IABP counterpulsation. Limb ischemia, characterized primarily by ipsilateral discomfort and diminished pulses, occurred in 18% of those evaluated. Evidence of ischemia worsened over time in 14%. Logistic regression analysis, which was based on variables found to be significant in bivariate analysis, revealed that the occurrence of limb ischemia acutely, cardiogenic shock as an indication for IABP insertion, and smoking (at the time of hospitalization or having quit < 10 years previously) were risk factors for long-term lower limb ischemia. The adjusted odds ratio for acute limb ischemia was 8.89 (95% confidence interval 2.80 to 28.21), for cardiogenic shock 3.59 (95% confidence interval 1.01 to 12.75), and for smoking 2.87 (95% confidence interval 1.10 to 7.46). Increasing numbers of patients are undergoing IABP counterpulsation and a greater proportion of these are surviving their acute event and resuming active lives. It is essential to recognize that detrimental consequences of this device can persist long after hospitalization.

Adult

Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs.

The development of factor VIII:C inhibitors remains one of the most serious complications of repeated transfusion in patients with haemophilia A. The proportion of patients affected has been reported to range from 3.6% to 25%, but these figures have been derived mainly from retrospective data and from total numbers of known haemophiliacs instead of number at true risk. The assessment here is based on a prospective study, started in 1976, on the incidence of inhibitor development in haemophiliacs born after 1970 whose FVIII or FIX activity was 5% or less, and who had received replacement therapy at least once. 46 of 63 children with haemophilia A and 13 of 17 with haemophilia B fulfilled the enrollment criteria. Inhibitors developed only in haemophilia A patients who had previously been treated with FVIII products--inhibitor concentrations were high in 12 and low in 3. Inhibitors developed in 24% (15/63) of all haemophilia A patients, and in 52% (14/27) of those with severe disease. The incidence of inhibitor development for all haemophilia patients was 39.1 per 1000 patient-years of observation. All inhibitors were first detected when patients were aged 0.08-5.2 years. The cumulative risk was 33% at age 6 years. The findings indicate that previous reports have underestimated the risk of acquiring FVIII inhibitors. Prospective, standardised studies, especially in children, are needed for the assessment of the true risk of this complication.

Age Factors

Portable image-manipulation software: what is the extra development cost?

A hospital-wide picture archiving and communication system (PACS) project is currently under development at the University Hospital of Geneva. The visualization and manipulation of images provided by different imaging modalities constitutes one of the most challenging component of a PACS. It was necessary to provide this visualization software on a number of types of workstations because of the varying requirements imposed by the range of clinical uses it must serve. The user interface must be the same, independent of the underlying workstation. In addition to a standard set of image-manipulation and processing tools, there is a need for more specific clinical tools that can be easily adapted to specific medical requirements. To achieve this goal, it was elected to develop a modular and portable software called OSIRIS. This software is available on two different operating systems (the UNIX standard X-11/OSF-Motif based workstations and the Macintosh family) and can be easily ported to other systems. The extra effort required to design such software in a modular and portable way was worthwhile because it resulted in a platform that can be easily expanded and adapted to a variety of specific clinical applications. Its portability allows users to benefit from the rapidly evolving workstation technology and to adapt the performance to suit their needs.

Costs and Cost Analysis

Glutathione conjugation of trans-3,4-dihydroxy 1,2-epoxy 1,2,3,4-tetrahydrobenzo[c]phenanthrene isomers by human glutathione transferases.

Each of the four stereoisomers of trans-3,4-dihydroxy 1,2-epoxy 1,2,3,4-tetrahydrobenzo[c]phenanthrene [(+)- and (-)-anti-BPhDE and (+)- and (-)-syn-BPhDE] has been incubated with the human glutathione transferase (GST) isoenzymes GST A1-1, GST M1-1 and GST P1-1, representing class alpha, mu and pi respectively, and glutathione (GSH). The conjugates formed were analyzed by HPLC and the results demonstrate that all GST isoenzymes catalyze the formation of GSH conjugates of all BPhDE isomers. However, a marked variation in catalytic efficiencies was observed (0.122-1.28/mM/s). These values are considerably lower than those previously estimated for the bay-region diol epoxides of benzo[a]pyrene (B[a]P) and human GSTs. The (+)-syn and (-)-anti-BPhDE (1R,2S-epoxide absolute configuration) were in general better substrates than the corresponding 1S,2R-epoxides. In accordance with previous observations with the diolepoxides of B[a]P, GST P1-1 was highly selective towards the BPhDE isomer with 4R,3S-diol 2S,1R-epoxide absolute configuration, i.e. (-)-anti-BPhDE, whereas GST A1-1 and M1-1 preferentially catalyzed the conjugation of (+)-syn-BPhDE (4R,3S-diol 2R,1S-epoxide absolute configuration). Overall, the most active isoenzyme was GST A1-1. Analysis by NMR spectroscopy of the GSH conjugates of BPhDE demonstrate that the reaction with GSH generally takes place by trans-addition of the thiol group at the benzylic C-1 carbon. The low catalytic efficiencies of human GSTs with BPhDE as compared to diolepoxides of B[a]P may be explained in part by the more crowded bay-region and substantially lower chemical reactivity (e.g. delta Edeloc/beta) of the former compounds.

Carcinogens

Caring.

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Aged

Electrocardiographic considerations in right ventricular infarction.

Right ventricular infarction frequently occurs in the setting of infarction of the inferior wall of the left ventricle. Although there are several protective mechanisms that may limit the size of the infarction, right ventricular damage can result in right ventricular failure and cardiogenic shock. ECG manifestations of right ventricular infarction can facilitate the early recognition of this syndrome. The standard 12-lead ECG may provide some evidence of infarction of the right ventricle. ST-segment elevation in right precordial leads, however, is far more reliable in establishing a diagnosis. These leads should be recorded immediately if the standard 12-lead ECG reveals an acute inferior wall MI. Continuous ST-segment monitoring may be useful in the early detection of ongoing right ventricular ischemia. ECG markers can aid in the prompt institution of appropriate treatment. It is clear that early recognition of right ventricular infarction can have important diagnostic and therapeutic implications.

Electrocardiography

[Physiologic blood coagulation studies in idiopathic arterial thrombosis].

QUESTIONING: The prevalence of inherited thrombotic syndromes in the general population appears to be higher than that of inherited bleeding disorders. However, the most important candidates for screening are patients with unexplained thromboembolism at ages of less than 40 years: In 19 children suffering from "idiopathic" arterial thrombosis laboratory screening has been performed. METHODS: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand-factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin have been investigated. RESULTS: Compared to an age matched healthy control group we could demonstrate in children with arterial thrombosis in vitro platelet activation with significant enhanced platelet aggregation, elevated levels of von Willebrand-factor and alpha-1-antichymotrypsin at the onset of disease. Protein C and alpha-2-antiplasmin were significantly decreased. These changes turned back to normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, c1-inactivator and alpha-2-macroglobulin showed no alterations compared to controls. CONCLUSIONS: Platelet activation and alteration of platelet function have been shown in vivo and in vitro to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The lowering of protein C levels at the onset of thrombotic diseases is discussed to be due to an increased turnover, whereas the decreased levels of alpha-2-antiplasmin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.

Adolescent

The MELANIE project: from a biopsy to automatic protein map interpretation by computer.

The goals of the MELANIE project are to determine if disease-associated patterns can be detected in high resolution two-dimensional polyacrylamide gel electrophoresis (HR 2D-PAGE) images and if a diagnosis can be established automatically by computer. The ELSIE/MELANIE system is a set of computer programs which automatically detect, quantify, and compare protein spots shown on HR 2D-PAGE images. Classification programs help the physician to find disease-associated patterns from a given set of two-dimensional gel electrophoresis images and to form diagnostic rules. Prototype expert systems that use these rules to establish a diagnosis from new HR 2D-PAGE images have been developed. They successfully diagnosed cirrhosis of the liver and were able to distinguish a variety of cancer types from biopsies known to be cancerous.

Biopsy

From biopsy to automatic diagnosis.

High resolution two-dimensional gel electrophoresis is a very powerful biochemical tool for analysis of complex protein mixtures. In well defined situations, protein maps, obtained from tissue biopsies or biological fluids by this technique, can be automatically analyzed by computer. Some polypeptide patterns are the fingerprints of diseases. Applying clustering algorithm and learning techniques, the prototype expert system MELANIE recognized patterns and associated the correct diagnosis to the specific pattern.

Diagnosis, Computer-Assisted

CPF1, a yeast protein which functions in centromeres and promoters.

Centromeres and several promoters of Saccharomyces cerevisiae contain a highly conserved octanucleotide, RTCACRTG, called CDEI. Using biochemical, genetic and structural analyses, we show that the same protein binds in vivo to CDEI sites in centromeres and in promoters. This protein, called CPF1 for centromere promoter factor, binds DNA as a dimer. Inactivation of the gene is not lethal but leads to a partial loss of the centromere function and to a Met- phenotype. Changes of the chromatin structure due to inactivation of CPF1 are seen at centromeres and at several CDEI-carrying promoters (e.g. MET25, TRP1, GAL2). However promoter activities are affected in diverse ways making it presently difficult to describe a function for CPF1 in gene expression. The sequence of the cloned gene reveals in the carboxy-terminal part two potential amphipathic helices preceded by a positively charged stretch of amino acids very similar to the helix-loop-helix domains recently identified in factors controlling tissue specific transcription in higher eukaryotes. Carboxy-terminal truncations of CPF1 lacking this domain no longer bind to CDEI. The amino-terminal half of CPF1 carries two clusters of negatively charged amino acid residues. Surprisingly, deletions of these clusters still render cells Met+ and lead only to a marginal decrease in centromere activity.

Amino Acid Sequence

Chromatin digestion with restriction endonucleases reveals 150-160 bp of protected DNA in the centromere of chromosome XIV in Saccharomyces cerevisiae.

Isolated nuclei of Saccharomyces cerevisiae were incubated with five restriction nucleases. Out of the twenty-one recognition sequences for these nucleases in the centromere region of chromosome XIV, only five are accessible to cleavage. These sites map 11 bp and 74 bp to the left and 27 bp, 41 bp and 290 bp to the right, respectively, of the boundaries of the 118 bp functional CEN14 DNA sequence. The distance between the sites accessible to cleavage and closest to CEN14 is 156 bp, suggesting this is the maximal size of DNA protected in CEN14 chromatin. The DNA in CEN14 chromatin protected against cleavage with DNase I and micrococcal nuclease overlaps almost completely with this region. Hypersensitive regions flanking both sides are approximately 60 bp long. Analyses of other S. cerevisiae centromeres with footprinting techniques in intact cells or nucleolytic cleavages in isolated nuclei are discussed in relation to our results. We conclude that structural data of chromatin obtained with restriction nucleases are reliable and that the structure of CEN14 chromatin is representative for S. cerevisiae centromeres.

Blotting, Southern

Technology versus clinical evaluation for fluid management decisions in CABG patients.

An exploratory study was designed to determine whether data made available by a pulmonary artery catheter or data obtained by nonivasive clinical evaluation were used as a basis for fluid management decisions in stable coronary artery bypass graft patients approximately 18 hours postoperatively and beyond. The sample consisted of 40 fluid management decisions made on 33 patients. The data were collected on all of the factors that influenced the decision. In no instance was information provided by the pulmonary artery catheter used as a basis for a fluid management decision; only noninvasive clinical measures were influential. The study questions the prolonged use of this medical technology with its attendant cost and risk. Nurses' roles in managing technology are highlighted.

Catheterization, Swan-Ganz

Lower limb ischemia related to use of the intraaortic balloon pump.

In this prospective study we sought to establish the incidence and nature of lower limb ischemia in patients undergoing treatment with intraaortic balloon pump (IABP) counterpulsation and to determine risk factors for its development. The sample was composed of all 258 balloon catheter insertions or attempted insertions for IABP therapy in 249 patients during a 16-month period. Assessment of the lower limbs, hemodynamic status, and pertinent medications were recorded daily throughout the patient's hospitalization. Lower limb ischemia was present in 47%, with 14% having major ischemic complications. Multivariate logistic regression, which was based on variables found to be significant in univariate analysis, revealed that preexisting peripheral vascular disease, female sex, and diabetes mellitus were related to the development of the whole range of lower limb ischemic problems. Diabetes mellitus, cardiogenic shock, and a history of smoking were associated with major ischemia. Evaluation of risks and benefits before treatment with IABP counterpulsation and careful lower limb assessment before, during, and after counterpulsation may help reduce the complications associated with this lifesaving device.

Adolescent