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Biomedical subjects

B Greger

Publications and source records attributed to B Greger.

At least 19 recordsLinked to original sources
PubMed2004

Cognitive control signals for neural prosthetics.

Recent development of neural prosthetics for assisting paralyzed patients has focused on decoding intended hand trajectories from motor cortical neurons and using this signal to control external devices. In this study, higher level signals related to the goals of movements were decoded from three monkeys and used to position cursors on a computer screen without the animals emitting any behavior. Their performance in this task improved over a period of weeks. Expected value signals related to fluid preference, the expected magnitude, or probability of reward were decoded simultaneously with the intended goal. For neural prosthetic applications, the goal signals can be used to operate computers, robots, and vehicles, whereas the expected value signals can be used to continuously monitor a paralyzed patient's preferences and motivation.

Animals↗
PubMed2002

[Information deficits and hesitant acceptance of combined pancreas-kidney transplantation in Germany. A survey at German dialysis centers].

BACKGROUND AND OBJECTIVE: The pancreas kidney transplantation (PKTx) currently is the only treatment for cure for patients with diabetes mellitus Type 1. Despite the availability of organs and the need for therapy the PKTx rate is much lower in Germany than it is in the United States. Is this attributable to an information gap?. MATERIAL AND METHODS: A questionnaire contrasting 16 statements pro and con PKTx was sent to 960 dialysis centres in Germany. RESULTS: 397 out of 960 questionnaires were returned, resulting in an response rate of 41.4 %. Regional representation was established. The central argument against combined PKTx was an assumed lack of organs (89 %). Other con-arguments were assuming a long waiting list (60 %), lack of qualified transplantation centres (40 %) and poor long-time transplant function (38 %). The most important moderator variable of the distribution of correct/incorrect answers was the direct contact to a cooperating transplant centre. Respondents with direct contact (n = 230) were significantly (p < 0.05 to < 0.001) more likely to hold correct answers with respect to 14 out of 16 single PKTx-related statements. The size of the dialysis centre as determined by the number of patients treated did not alter the distribution of correct/incorrect answers. CONCLUSION: The majority of nephrologists treating patients with Type 1 diabetes underestimate the potential of PKTx. More efforts to increase information are necessary.

Attitude of Health Personnel↗
PubMed2001

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol of a controlled clinical trial developed by consensus of an international study group. Part three: individual patient, complication algorithm and quality manage.

GENERAL DESIGN: Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). A randomised, placebo controlled, double-blinded, single-centre study is performed at an University Hospital (n = 40 patients for each group). This part presents the course of the individual patient and a complication algorithm for the management of anastomotic leakage and quality management. OBJECTIVE: In part three of the protocol, the three major sections include: The course of the individual patient using a comprehensive graphic display, including the perioperative period, hospital stay and post discharge outcome. A center based clinical practice guideline for the management of the most important postoperative complication--anastomotic leakage--including evidence based support for each step of the algorithm. Data management, ethics and organisational structure. CONCLUSIONS: Future studies with immune modifiers will also fail if not better structured (reduction of variance) to achieve uniform patient management in a complex clinical scenario. This new type of a single-centre trial aims to reduce the gap between animal experiments and clinical trials or--if it fails--at least demonstrates new ways for explaining the failures.

Algorithms↗
PubMed1998

An apyrimidinic site kinks DNA and triggers incision by endonuclease VII of phage T4.

Apurinic/apyrimidinic lesions (AP-sites) occur frequently in DNA, generated by physically and chemically induced or spontaneous loss of bases. Repair mechanisms have evolved in organisms to deal efficiently with AP-sites by first incising the DNA at the lesion, followed by excision and resynthesis of the damaged strand. Here we report that endonuclease VII (endo VII) of phage T4, which was originally classified as a debranching and Holliday structure resolving enzyme, also recognizes AP-sites with high efficiency. The enzyme cleaves both strands of double-stranded DNA in a stepwise fashion a few nucleotides 3' of the lesion. In a search for a recognition signal shared by all known endo VII substrates, kinking of DNA has earlier been suggested as such a signal. In support of this hypothesis, we demonstrate here that AP-sites induce distinct kinks in synthetic oligonucleotides allowing efficient intramolecular ring closure by ligation.

Bacteriophage T4↗
PubMed1998

Enzymatic mutation detection. Phosphate ions increase incision efficiency of endonuclease VII at a variety of damage sites in DNA.

The ability of endonuclease VII (endo VII) to cleave at mispairings in double-stranded DNA has recently been used for enzymatic mutation detection (EMD) [R. Youil, B.W. Kemper, R.G.H. Cotton, Proc. Natl. Acad. Sci. USA 92 (1995) 87-91]. The method is based on mapping cleavages in heteroduplex DNAs obtained from mutant and wildtype sequences. Despite the capability of endo VII to cleave at all possible mispairings, relative cleavage efficiencies vary considerably for individual mismatches and may escape detection if located in an unfavorable sequence surrounding. We report here improved reaction conditions which can increase the selectivity of the enzyme for mismatches up to 500-fold, as demonstrated with a mutation in a 247 nt long fragment from exon 7 of human gene p53. The new conditions involve replacement of Tris/HCl buffer by phosphate buffer and change from pH 8.0 to 6.5. Various concentrations of phosphate ions should be tried in the assay to meet individual requirements of the substrate.

Base Composition↗
PubMed1997

Pancreas-specific protein (PASP), serum amyloid A (SAA), and neopterin (NEOP) in the diagnosis of rejection after simultaneous pancreas and kidney transplantation.

A reliable, noninvasive indicator of pancreatic allograft rejection is urgently needed. In this study, serum (S), plasma (P), and urine (U) levels of pancreas-specific protein (P-PASP, U-PASP), neopterin (S-NEOP, U-NEOP), amylase (U-AMYL), and amyloid A (SAA) were measured daily in ten type I diabetic patients following simultaneous pancreas and kidney transplantation (SPK). Rejection episodes occurred in three isolated pancreas, nine isolated kidney, and five simultaneous pancreas and kidney transplants. In the case of the eight pancreas rejections, SAA was the rejection marker with the highest diagnostic accuracy (94%). Using P-PASP and U-PASP, an accuracy of 81% and 79%, respectively, was achieved. During viral infections, U-NEOP levels increased to a maximum level of 1904 mumol/mol creatinine, whereas during bacterial infections, SAA levels increased to a maximum value of 43 mg/dl. SAA, measured for the first time in SPK, appears to be a valuable rejection parameter. In combination with U-NEOP and U-AMYL, a differential diagnosis between rejection, bacterial infection, and viral infection was possible. Neither U-PASP nor P-PASP monitoring led to a significant improvement in the results.

Acute Disease↗
PubMed1997

[Evaluation models for therapy planning/standardization exemplified by infection].

Models of evaluation in therapeutic management pathways (practice guidelines, clinical algorithms) are demanded today, both by public health research and health policy. However, practical achievements are lacking. To overcome this controversy, the Lucerne Study Group on Sepsis Research was founded to develop guidelines in accordance with a series of official groups. It was shown that there was no agreement between the providers and the daily users. However, every surgeon has a firm, personal view about sepsis.

Algorithms↗
PubMed1995

Detection and partial purification of a cruciform-resolving activity (X-solvase) from nuclear extracts of mouse B-cells.

We have identified a cruciform-resolving enzyme (X-solvase) in nuclear extracts from mouse B-cells, called EMX1, by using an exonuclease-resistant cruciform DNA as a substrate. The cruciform was a 104-nt oligonucleotide that spontaneously adopted a branched conformation with four arms, each arm protected by a terminal loop of five T residues. A ligatable nick was left in one arm. After ligation, the covalently closed substrate was used to follow an 1800-fold purification of the mouse X-solvase (EMX1) from crude nuclear extracts by chromatography on DEAE-cellulose, MonoQ and heparin-Sepharose. The purest fractions containing EMX1 show high specificity for cruciform DNA. The cleavage pattern is indistinguishable from that found in the same substrates after treatment with endonuclease VII from phage T4 or endonuclease X3 from the yeast Saccharomyces cerevisiae. EMX1 and yeast endonuclease X3 were also found to be sensitive to anti-(endonuclease VII) antibodies which inhibited their reactions with cruciform DNAs in vitro.

Animals↗
PubMed1994

[Routine intravenous urography before colorectal resections?].

The value of preoperative intravenous urography (IVU) to prevent iatrogenic damage to the urogenital tract was investigated in a series of 236 females and 188 males (mean age 54 [5-87] years) who underwent an operation on the colon or rectum between April 1988 and March 1992. The operations were: 101 right and 49 left hemicolectomies, 125 sigmoid resections, 74 anterior rectum resections, 58 abdomino-perineal rectum amputations and 17 total colectomies. Preoperative IVU was performed in 279 patients (65.8%), while in 145 (34.2%) urgency of the operation or intolerance to contrast medium prevented the procedure being done. The results were abnormal in 75 of the 279 IVUs (26.9%). Of the latter, only 19 (6.8%) of the abnormalities were related to the colorectal disease (renal obstruction due to tumour: 9, malignant invasion of the bladder: 5, ureter displacement: 5). Other diagnostic procedures had given abnormal results in six patients, although the preoperative IVU had been unremarkable. Iatrogenic damage to a ureter occurred in only one patient: the IVU had been normal. No ureteral damage occurred in any of the patients who had not had an IVU. These data indicate that the decisive factor in preventing intraoperative damage to a ureter is not a preoperative IVU but careful intraoperative dissection and visualization of the ureter. There is, therefore, no need for routine preoperative IVU in these cases.

Adolescent↗
PubMed1994

[Standardized combined pancreas and liver explantation].

Maximum use of organs from a single donor is mandatory as a result of the current organ shortage. In combined liver and pancreas allograft retrieval, it is vital that one remember the variability in the anatomy of vessels. Based on our experience, we describe a new technique of dividing the celiac trunk horizontally with subsequent arterial reconstruction, depending on the anatomical situation. Vascular division of the grafts can be performed either in situ or in an ex situ fashion in cases where cardiovascular function has deteriorated.

Arteries↗
PubMed1991

Isolation and structure elucidation of urinary metabolites of mitoxantrone.

Three 13C-labeled 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]-ethyl)amino-9,10- anthracenedione dihydrochloride (mitoxantrone) isotopomers were synthesized to prove the proposed chemical structures of human urinary metabolites by means of nuclear magnetic resonance spectroscopy. After application of labeled mitoxantrone to an anesthetized pig, urine was collected by way of a vesicourethral catheter. The urinary metabolites were isolated by liquid chromatography using a new procedure developed for extraction of mitoxantrone metabolites. Structural elucidation by nuclear magnetic resonance spectroscopy and tandem mass spectrometry confirmed the proposed mono- and dicarboxylic acid structures of the metabolites. High-performance liquid chromatography of native pig urine showed an additional metabolite detected by its UV-visible absorption. The new metabolite was identified as a glucuronic acid conjugate of mitoxantrone by means of nuclear magnetic resonance spectroscopy and tandem mass spectrometry. Incubation with beta-glucuronidase under high-performance liquid chromatography control revealed mitoxantrone as the sole product. Quantitative high-performance liquid chromatography analyses showed that the new urinary metabolite represents the main biotransformational pathway of mitoxantrone in pigs, indicating significant interspecies variation in mitoxantrone biotransformation. Expressed in equivalents of mitoxantrone, the new metabolite amounts to 25% and 31%, respectively, of urinary excreted drug-related material. Extraction of patient urine using the same procedure led to the isolation of pure metabolite B. Tandem mass spectrometric data delivered definitive evidence for the structure of metabolite B as monocarboxylic acid of mitoxantrone.

Animals↗