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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 235 records · Page 13Linked to original sources

Adverse events in primary care identified from a risk-management database.

BACKGROUND: The inevitability of adverse events in medicine arises from human fallibility, negligent care, limits of medical knowledge, risks inherent in medical practice, and biological variability among individuals. A better understanding of the nature and causes of adverse events is necessary to reduce their occurrence and limit their harm. This study describes adverse events identified from a risk-management database that occurred in an out-patient primary care setting. METHODS: Incident reports filed with the risk-management office of an academic medical center between January 1, 1991, and June 30, 1996, by eight primary health care clinics affiliated with the center were eligible for the study. Two independent reviewers assessed the incidents to determine whether there were adverse medical events. Incidents classified as adverse events were analyzed to determine the cause, potential preventability, and outcome. RESULTS: The prevalence of adverse events was 3.7 per 100,000 clinic visits over a period of 5 1/2 years. Twenty-nine of 35 (83%) adverse events were due to medical errors and were considered preventable. The causes of the adverse events included 9 diagnostic errors (26%), 11 treatment errors (31%), and 9 other errors (26%). Of the adverse events attributed to medical errors, 4 (14%) resulted in a permanent, disabling injury and 1 (3%) resulted in a death. CONCLUSIONS: Serious adverse events appear to occur infrequently in primary care outpatient practice, although these data probably underestimate the overall prevalence. To reduce or prevent the occurrence of adverse events in primary care, better systems for recognizing and tracking them and for assessing their causes are needed.

Academic Medical Centers↗

[Spinal cord astrocytomas and ependymomas: therapeutic strategy].

Ependymomas and astrocytomas are the most frequent spinal cord tumors. They have the same clinical expression and the only treatment is surgery. We report the experience of two neurochurgical teams working in Lyon and Brussels with 171 operated patients, focusing on therapeutic strategies. Spinal cord ependymomas usually present as circumscribed benin tumors, complete exeresis is the best strategy. Long-term follow-up in 40 patients who were not given adjuvant radiotherapy showed no recurrence and satisfactory functional results. Astrocytomas are classically less well circumscribed but when exeresis is macroscopically complete, results are comparable with those of ependymomas as was found in 22 patients with long-term follow-up. Inversely, for infiltrating astrocytomas, pathology is usually malignant and prognosis is unfavorable despite radiotherapy or chemotherapy.

Astrocytoma↗

Localized facial flushing in infancy. Auriculotemporal nerve (Frey) syndrome.

BACKGROUND: Patients with auriculotemporal nerve syndrome (Frey syndrome) have facial flushing, sweating, or both localized to the distribution of the auriculotemporal nerve that occurs in response to gustatory stimuli. In adults, the syndrome usually results from surgical injury or trauma to the parotid gland. The condition is rare in infants, but usually manifests during infancy with the introduction of solid food, thus leading to the misdiagnosis of food allergy by physicians unfamiliar with the syndrome. OBSERVATIONS: We describe 8 children with auriculotemporal nerve syndrome who manifested with flushing only. The reaction was erroneously attributed to food allergy in most cases. Six of the 8 patients were delivered with forceps assistance. The remaining 2 patients, with disease onset during the first 3 months of life, had bilateral involvement without known trauma. CONCLUSIONS: Auriculotemporal nerve syndrome may manifest during infancy as flushing with eating food. In contrast to the syndrome in adults, gustatory sweating is rarely associated. The known use of forceps to assist in the delivery of at least 14 of the 28 previously reported pediatric cases and in 6 of our 8 patients suggests that trauma to the parotid region may be responsible for the condition in most infants, as it is in adults. Auriculotemporal nerve syndrome in infancy should be recognized as a benign condition that often resolves spontaneously. Treatment is ineffective and unnecessary.

Birth Injuries↗

Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro.

The interaction of Ro 25-6981 with N-methyl-D-aspartate (NMDA) receptors was characterized by a variety of different tests in vitro. Ro 25-6981 inhibited 3H-MK-801 binding to rat forebrain membranes in a biphasic manner with IC50 values of 0.003 microM and 149 microM for high- (about 60%) and low-affinity sites, respectively. NMDA receptor subtypes expressed in Xenopus oocytes were blocked with IC50 values of 0.009 microM and 52 microM for the subunit combinations NR1C & NR2B and NR1C & NR2A, respectively, which indicated a >5000-fold selectivity. Like ifenprodil, Ro 25-6981 blocked NMDA receptor subtypes in an activity-dependent manner. Ro 25-6981 protected cultured cortical neurons against glutamate toxicity (16 h exposure to 300 microM glutamate) and combined oxygen and glucose deprivation (60 min followed by 20 h recovery) with IC50 values of 0.4 microM and 0.04 microM, respectively. Ro 25-6981 was more potent than ifenprodil in all of these tests. It showed no protection against kainate toxicity (exposure to 500 microM for 20 h) and only weak activity in blocking Na+ and Ca++ channels, activated by exposure of cortical neurons to veratridine (10 microM) and potassium (50 mM), respectively. These findings demonstrate that Ro 25-6981 is a highly selective, activity-dependent blocker of NMDA receptors that contain the NR2B subunit.

Animals↗

Bone-dust in autopsies: reduction of spreading.

During autopsies, an open oscillating saw produces large quantities of respirable bone-dust, which is able to carry microbes over several metres. Experiments were done using a modified (open) undulation saw (spray tube to moisten the saw-blade with water). Saw-dust was asservated with culture media. Colonies were identified macroscopically. Microbes in the air were quantified (per unit of time). A remarkable reduction of saw-dust is done by an integrated spray tube using water. There remains a contamination at the head of the autopsy table in the level of the table top. We found a complete decontamination 150 cm above the floor. No spreading of particles carrying microbes was seen over distances of more than 1.5 m. The risk of an airborne infection is minimal when using a manual saw (absence of grinding-dust). The modified type of an 'oscillating saw with a spray-tube' may be considered a practicable compromise between a manual saw and an unprotected undulation saw. It is necessary to complete the precautions against airborne infections by breath masks and safety-goggles.

Air Microbiology↗

Extended binding sites of cyclophilin as revealed by the interaction with HIV-1 Gag polyprotein derived oligopeptides.

Oligopeptides derived from the gag polyprotein (Pr55gag) of human immunodeficiency virus type 1 (HIV-1) segment were used to evaluate the extension of the putative binding region for the complex of Pr55gag and the human cytosolic peptidyl prolyl cis/trans isomerase (PPIase) 18 kDa cyclophilin (Cyp18). Five N-terminally acetylated, C-terminally amidated oligopeptides containing one (HIV-1 Gag218-224; 1), two (HIV-1 Gag218-226 and HIV-1 Gag217-224; 2 and 3, respectively), three (HIV-1 Gag217-226; 4) or four (HIV-1 Gag213-237; 5) proline residues were synthesized. Using competition experiments with a standard substrate the binding affinities to Cypl8 of the synthesized peptides were determined. The IC50 value of 184 microM for the 25-mer peptide 5 was fivefold or more lower than those of the peptides 1-4 lacking one or more prolines. Failure of competition in assays containing enzymes of other PPIase families by millimolar concentrations of 5 revealed a Cyp18 specific interaction involving the active site of the enzyme. In its far UV circular dichroism, aqueous solutions of 5 display properties of random coil conformation, but spectra were also consistent with a small contribution of proline specific secondary structures. However, a proline-rich peptide typical of forming left-handed polyproline II helices did not compete for the active site of Cypl8. The results demonstrate that the putative binding region of HIV-1 gag polyprotein has a certain degree of binding affinity to the PPIase site of Cyp18, and may add a previously unrecognized topological component to the known subsite specificity of cyclophilins.

Amino Acid Isomerases↗

Mapping of the ribosomal operons on the linear chromosomal DNA of Streptomyces ambofaciens DSM40697.

Streptomyces ambofaciens DSM40697 possess six rRNA gene clusters which can be distinguished by probing BfrI-digested total DNA with the PCR-amplified l6S-23S ribosomal genet internal transcribed spacer. The six rrn loci of S. ambofaciens were cloned as recombinant cosmids and located on the AseI-Dŕal physical map of the linear chromosomal DNA. For five of the six ribosomal gene sets, the transcriptional orientation was determined relative to the physical map and was shown to be divergent away from an oriC-like locus.

Base Sequence↗

Isolation and amino acid sequence of a new 22-kDa FKBP-like peptidyl-prolyl cis/trans-isomerase of Escherichia coli. Similarity to Mip-like proteins of pathogenic bacteria.

We identified a periplasmic peptidyl-prolyl cis/trans-isomerase (PPIase) of the (FK506-binding protein (FKBP) type in Escherichia coli (FK506 represents a natural peptidomacrolide containing an acylated pipecolic acid residue). After purification to homogeneity, its complete amino acid sequence was determined by a combination of Edman degradation and electrospray mass spectrometry of the authentic protein and peptides generated by proteolysis. The molecular mass calculated from the amino acid sequence of the protein was 22,085.53 Da, which corresponded perfectly with the value of 22,084 +/- 1.47 Da as determined by mass spectrometry. The corresponding gene was cloned and analyzed, and Southern blot experiments revealed the existence of similar genes in various Gram-negative bacteria. The amino acid sequence of the novel FKBP22 shows similarity to Mip (macrophage infectivity potentiator)-like proteins produced by a number of pathogenic bacteria. However, FKBP22 is inhibited more strongly by FK506 than are other Mip-homologues, as indicated by the Ki value of 25 nM. The subsite specificity regarding the P1 position of the substrate resembles that for Mip-FKBP25 from Legionella pneumophila. The mature FKBP22 enzyme of 205 amino acids exists as a dimer in solution.

Amino Acid Isomerases↗

Autocatalytic folding of the folding catalyst FKBP12.

Prolyl isomerases are folding enzymes and thus have the potential to catalyze their own folding. We show here that the folding of cytosolic FKBP12 (FK 506 binding protein) is an autocatalytic process both for the mature protein and for a fusion protein with an amino-terminal extension of 16 residues. Native FKBP contains seven trans-prolyl peptide bonds, and the cis-to-trans isomerizations of some or all of them constitute the slow, rate-limiting events in folding. The rate of an autocatalytic reaction increases with reactant concentration, because the product catalyzes its own formation. Accordingly, the folding of the fusion protein was more than 10-fold accelerated when the protein concentration was increased from 0.05 microM to 10 microM. At high concentrations of both forms of FKBP12 autocatalysis was very efficient, and the observed folding rate seemed to approach the rate of the fast direct folding reaction of the protein molecules with the correct (all trans) peptidyl-prolyl bond conformation.

Amino Acid Isomerases↗

An 11.8 kDa proteolytic fragment of the E. coli trigger factor represents the domain carrying the peptidyl-prolyl cis/trans isomerase activity.

The 48 kDa trigger factor (TF) of E. coli was shown to be a peptidyl-prolyl cis/trans isomerase (PPIase). Its location on a ribosomal particle is unique among the PPIases described so far, and suggests a role in de novo protein folding. The trigger factor was investigated with regard to a domain carrying the catalytic activity. An enzymatically active fragment could be isolated after proteolysis by subtilisin. The resulting polypeptide was analysed by N-terminal sequencing and MALDI-TOF mass spectrometry revealing an 11.8 kDa fragment of TF encompassing the amino acid residues Arg-145 to Glu-251. The nucleotide sequence encoding the amino acid residues Met-140 to Ala-250 of the TF was cloned into vector pQE32. After expression in E. coli the resulting His-tagged polypeptide was isolated on an Ni2+-NTA column. Subsequent digestion with subtilisin and anion-exchange chromatography yielded a TF fragment encompassing amino acids Gln-148 to Thr-249. This fragment may represent the catalytic core of TF since PPIase activity with a specificity constant kcat/Km of 1.3 microM(-1) s(-1) could be demonstrated when using Suc-Ala-Phe-Pro-Phe-NH-Np as a substrate. Moreover, as was observed for the complete, authentic TF the PPIase activity of the fragment was not inhibited by the peptidomacrolide FK506.

Amino Acid Isomerases↗

Effectiveness of vaginal Papanicolaou smear screening after total hysterectomy for benign disease.

OBJECTIVE: Using literature review, we assessed (1) Papanicolaou smear screening recommendations after hysterectomy for benign disease, (2) total hysterectomy for benign disease as a risk for vaginal dysplasia or carcinoma, and (3) effectiveness of screening for vaginal carcinoma after total hysterectomy for benign disease. DATA SOURCES: We considered (1) organizations' recommendations about screening, (2) references from major textbooks of gynecology, and (3) MEDLINE searches of English-language studies published from 1966 through 1995 using the search strategy (hysterectomy and vaginal smears) or (vaginal smears and vaginal neoplasms). STUDY SELECTION: Published or verbal confirmations of screening recommendations were eligible. Criteria for assessing risk of vaginal dysplasia or carcinoma included original research, documented reports of hysterectomy as an exposure, and evidence of preinvasive vaginal disease or vaginal carcinoma outcomes. We sought data assessing burden of suffering, screening efficacy, and effectiveness of early detection. DATA EXTRACTION: Descriptive and analytic data from each study were abstracted. DATA SYNTHESIS: Screening recommendations were categorized by the organizations' positions: two opposed screening, two supported screening, and six lacked specific guidelines. Data on the risk between total hysterectomy for benign disease and subsequent vaginal carcinoma were organized by study design (three case control, two cohort, and 13 case series) and described. Data on screening effectiveness were organized to address the criteria advocated by the US Preventive Services Task Force. CONCLUSIONS: There are conflicting guidelines on screening after hysterectomy and conflicting data on the risk of vaginal carcinoma after total hysterectomy for benign disease, though the best-designed research suggests no association. There is insufficient evidence to recommend routine vaginal smear screening in women after total hysterectomy for benign disease.

Carcinoma in Situ↗