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Biomedical subjects

C Fischer

Publications and source records attributed to C Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2002

IgM-enriched immunoglobulin preparation for immunoprophylaxis in cardiac surgery.

OBJECTIVE: Evaluating the effects of prophylactic administration of IgM-enriched immunoglobulins (IVIG) on immunological- and clinical parameters in cardiac surgical patients. PATIENTS AND METHODS: 41 patients were randomized to receive either an IgM-enriched immunoglobulin (Pentaglobin(R)) preparation (1,300 ml immunoglobulin, equivalent to 65 g protein) combined with routine antibiotic prophylaxis (Group A; n = 20, 1 drop-out), or routine antibiotic prophylaxis plus placebo (Group B; n = 20). Patients were comparable with respect to their APACHE II score, comorbidity, coronary risk, operating time, clamp, and ischemic time. Endotoxin and endotoxin neutralizing capacity (ENC) were determined by a kinetic turbidimetric Limulus amebocyte lysate (LAL) assay with internal standardization. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF)-alpha, soluble TNF-Receptor I (sTNF-R1), and interleukin-10 (IL-10) were determined by ELISA. Data analysis was performed by area under the curve (AUC) calculation and ANOVA for endotoxin neutralizing capacity and by ANOVA for all other cases. RESULTS: All patients survived. Endotoxin plasma levels were generally but not significantly higher in group A than in controls, while the difference in endotoxin neutralizing capacity (ENC) reached significance. IL-6, TNF-alpha, IL-10 and TNF-R1 were not different between both groups, however. There were significantly less patients with signs of inflammation (fever, leukocytosis, hypotension) in group A (group A n = 2; group B n = 9; p<0.05). This was paralleled by a slightly reduced hospitalization period in group A patients compared to group B patients (A:12.05 +/- 3.66 vs. B:13.45 +/- 3.72 days; n.s.). All data are given as mean +/- standard deviation (SD). CONCLUSION: The results of this study support that IgM-enriched IVIG preparation are effective when used prophylactically in patients undergoing procedures with cardiopulmonary bypass. The mechanisms of endotoxin neutralization and the effect of the host immune status on the efficacy of IVIG treatment remain to be elucidated.

Adult↗
PubMed2002

Funipuncture for fetocide in late termination of pregnancy.

The most widely used method for fetocide in late termination of pregnancy for fetal abnormalities (TOPFA) consists of injecting of potassium chloride (KCl) into the fetal heart and is likely to be painful after 22 weeks of gestation. We studied ten consecutive women undergoing TOPFA between 22 and 38 weeks. This technique for fetocide consisted of a single umbilical vein puncture under ultrasound guidance with injections of sufentanil 5 microg followed by KCl 2 g. No electrocardiographic modifications could be observed and maternal plasma potassium levels did not show any significant variation throughout the procedure. Fetal umbilical phlebotomy for fetal analgesia followed by fetocide therefore appears to be a safe procedure for the mother and allows the fetus to die without pain when late termination of pregnancy (TOP) is indicated.

Abnormalities, Multiple↗
PubMed2002

[Traumatic brain injuries in adults: from coma to wakefulness. Neurophysiological data].

OBJECTIVE: To analyse relevant literature and to express an expert point of view concerning the interest of electroencephalography and evoked potentials recordings in the evaluation of severe head trauma in adults in the context of a consensus conference. MATERIAL AND METHODS: Scientific databases have been checked on the Internet using key-words. The summaries of 340 papers have checked out. Consequently 94 papers have been thoroughly analysed. Fifty-nine of them are cited in the text of this paper. RESULTS: Electroencephalography (EEG) and evoked potentials (Eps) evaluate the functional status of the brain. They augment the clinical examination. They are non invasive and easy to perform at patient's bedside. The EEG evaluate globally the functional status of the brain but it is very sensitive to sedative and anaesthetic drugs. It can disclose subclinical or electroclinical epileptic seizures. When reactivity to sensory stimulations can be elicited, this can be considered a prognostic indicator for a good outcome. Evoked potentials are less influenced by sedative drugs. There are several types of evoked potentials, each one with a different localizing value. Brainstem auditory evoked potentials (or short-latency Eps) evaluate the auditory nerve and brainstem. When normal they have no specificity. When abnormal they are an indicator of a poor or bad outcome. Somatosensory and auditory middle-latency Eps evaluate the primary cortex. In coma due to traumatic brain injury the presence of primary cortex components is an indicator of a good outcome and its absence is an indicator of a poor outcome at least when there is no focal brain lesion as to have the primary cortex component to be absent. Event-related potentials evaluate associative brain areas. When they are present in a comatose patient they favor the idea that some cognitive processes are active and they have a high positive predictive value for a return to consciousness. The electrophysiological evaluation can help to identify atypical situations and pathologies close to coma, disclose nonconvulsive seizures and localize certain complications or dysfunctions in atypical cases.

Adult↗
PubMed2002

Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts.

NF-kappaB/Rel transcription factors are modulators of immune and inflammatory processes and are also involved in malignancy. Phosphorylation of the IkappaB inhibitors by the IkappaB kinase (IKK) complex leads to their proteasomal degradation, resulting in activated NF-kappaB. Here, we investigated the activation status of NF-kappaB and the IKK complex in acute myeloid leukemia (AML). Gelshift assays revealed an increased level of activated nuclear NF-kappaB in myeloid blasts. Both bone marrow and peripheral blood blasts from AML patients showed enhanced IKK activity relative to controls, whereas the IKK protein concentrations were comparable. In addition, an increased level of IkappaB-alpha was detected in AML blast cells, although this appeared to be insufficient to block nuclear translocation of NF-kappaB, also confirmed by immunofluorescence. In subtype M4 and M5 AML cells a more extensive NF-kappaB activation and higher IKK activity was found than in M1/M2 specimens. Isolated AML blasts cultured ex vivo responded to external stimulation (TNF, LPS) by further IKK activation, IkappaB degradation and NF-kappaB activation. Preincubation with the proteasome inhibitor PSI inhibited the NF-kappaB system in isolated AML blasts. This study established for the first time a dysregulation of IKK signaling in AML leading to increased NF-kappaB activity suggesting potential therapeutic avenues.

Acute Disease↗
PubMed2002

Marginal adaptation of partial crowns cast in pure titanium and in a gold alloy - an in vivo study.

The aim of the present study was to assess in vivo the marginal integrity of partial crowns cast in pure titanium and in a gold alloy. For this purpose, two groups of 25 molars were prepared for partial crowns and then restored with partial crowns cast in Degulor M gold alloy and in pure titanium. At a subsequent session, replicas were produced using a special impression-taking technique. The scanning electron microscope (SEM) technique was used to perform quantitative margin analysis (Tiffmess 1.8 program). The gold alloy partial crowns displayed significantly (P < 0.05) more continuous margin (marginal quality A, <50 microm), and the titanium partial crowns significantly more marginal quality B (50-100 microm) and C (>100 microm). The results show that better marginal integrity can be achieved with gold alloy than with titanium partial crowns. However, in practical terms the difference in marginal quality is only slight, so that the use of pure titanium for single-tooth restorations is justified.

Cementation↗
PubMed2001

Cloning and mutation analysis of the human potassium channel KCNQ2 gene promoter.

Benign familial neonatal convulsions (BFNC) have been previously found to be associated with mutations within the coding region of KCNQ2. We have now cloned and analyzed the promoter region of the human KCNQ2 gene. 5'-RACE identified a transcription start site (TSS) located 200 bp upstream of the ATG start codon. The TSS is located close to a repetitive region containing seven copies of a degenerate 42-mer repeat. Several different luciferase (LUC) reporter plas- mids containing fragments from the KCNQ2 5'-flanking region were constructed and expressed in NT2N and SH-SY5Y cell lines. A core promoter region was found to be located between bp 20 and bp 74 upstream of the TSS. Neither the promoter region nor the repetitive region showed any mutations in 13 index patients from unrelated BFNC families.

5' Flanking Region↗
PubMed2001

Oscillatory synchrony between human extrastriate areas during visual short-term memory maintenance.

How do we keep an object in mind? Based on evidence from animal electrophysiology and human brain-imaging techniques, it is commonly held that short-term memory relies on sustained activity in a network distributed over sensory and prefrontal cortices. How does neural firing persist in such a distributed network in the absence of visual input? Hebb's influential but so far unproved proposal, developed more than 50 years ago, is that sustained activation in short-term memory networks is maintained by reverberating activity in neuronal loops. We hypothesized that synchronized oscillatory activity, proposed to provide a dynamic link between distributed areas, could not only coordinate activity in the network but also establish reentrant loops in the system to enable both sustained firing and temporal coincidence of inputs. We show in human intracranial recordings that limited regions of extrastriate visual areas, separated by several centimeters, become synchronized in an oscillatory mode during the rehearsal of an object in visual short-term memory. Synchrony occurs specifically in the beta range (15-25 Hz) and disappears in a control condition. These findings thus confirm experimentally the hypothesis of a functional role of synchronized oscillatory activity in the coordination of distributed neural activity in humans, and support Hebb's popular but unproved concept of short-term memory maintenance by reentrant activity within the activated network.

Action Potentials↗
PubMed2001

Treatment of American cutaneous leishmaniasis with miltefosine, an oral agent.

There is no recognized oral treatment for American cutaneous leishmaniasis. A rising-dose, open-label phase I/II trial of the oral agent miltefosine against Colombian cutaneous leishmaniasis was conducted. Seventy-two male Colombian soldiers (mean weight, 67 kg) received miltefosine at 50-100 mg/day for 3 weeks (for 32 evaluable patients) or at 133-150 mg/day for 3-4 weeks (for 32 evaluable patients). The per-protocol cure rate for 50-100 mg/day was 21 (66%) of 32 patients. The per-protocol cure rate for 133-150 mg/day was 30 (94%) of 32 patients (P =.01, by use of Fisher's exact test). The historic per-protocol cure rate for standard injections of antimony is 93%. "Motion sickness" that did not interfere with normal duties was experienced by 40% of patients and was dose related. Vomiting and diarrhea were reported on approximately 2% of treatment days. In this uncontrolled study of oral miltefosine for treatment of patients with American cutaneous leishmaniasis, a dosage of approximately 2.25 mg/kg/day for 3-4 weeks was effective and tolerated.

Administration, Oral↗
PubMed2001

Chromosomal aberrations in sporadic pituitary tumors.

Pituitary adenomas are common intracranial neoplasms that may be hormone-secreting or nonfunctional. Genetic defects associated with some pituitary tumors have been identified, although our understanding of the underlying molecular mechanisms remains incomplete. We have studied 75 sporadic pituitary tumors, representing the major clinical subtypes, by comparative genomic hybridization (CGH) with the aim of assessing for DNA copy number changes. CGH revealed chromosomal imbalances in 34 adenomas (45.3%), whereby gains were 4.9 times more frequently observed than losses. Most of the genetic alterations detected by CGH affected entire chromosomes (108/131, 82.4%). Gain of genetic material was observed predominantly on chromosomes X (24/75, 32%), 19 (12/75, 16%), 12 (6/75, 6.7%), 7 and 9 (5/75, 6.7%), whereas loss of DNA sequences most frequently affected chromosomes 11 (4/75, 5.3%), 13 and 10 (3/75, 4%). There were no significant differences in the CGH results for the individual clinical subtypes of pituitary tumors. These results reveal a nonrandom pattern of chromosomal alterations in pituitary tumors, in particular gains of entire chromosomes, and this may contribute to the development of such neoplasms.

Adenoma↗
PubMed2001

Deoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceus. Characterization of three methyltransferase genes.

The anthracycline-like polyketide drug elloramycin is produced by Streptomyces olivaceus Tü2353. Elloramycin has antibacterial activity against Gram-positive bacteria and also exhibits antitumor activity. From a cosmid clone (cos16F4) containing part of the elloramycin biosynthesis gene cluster, three genes (elmMI, elmMII, and elmMIII) have been cloned. Sequence analysis and data base comparison showed that their deduced products resembled S-adenosylmethionine-dependent O-methyltransferases. The genes were individually expressed in Streptomyces albus and also coexpressed with genes involved in the biosynthesis of l-rhamnose, the 6-deoxysugar attached to the elloramycin aglycon. The resulting recombinant strains were used to biotransform three different elloramycin-type compounds: l-rhamnosyl-tetracenomycin C, l-olivosyl-tetracenomycin C, and l-oleandrosyl-tetracenomycin, which differ in their 2'-, 3'-, and 4'-substituents of the sugar moieties. When only the three methyltransferase-encoding genes elmMI, elmMII, and elmMIII were individually expressed in S. albus, the methylating activity of the three methyltransferases was also assayed in vitro using various externally added glycosylated substrates. From the combined results of all of these experiments, it is proposed that methyltransferases ElmMI, ElmMII, and ElmMIII are involved in the biosynthesis of the permethylated l-rhamnose moiety of elloramycin. ElmMI, ElmMII, and ElmMIII are responsible for the consecutive methylation of the hydroxy groups at the 2'-, 3'-, and 4'-position, respectively, after the sugar moiety has been attached to the aglycon.

Amino Acid Sequence↗
PubMed2001

Comparative genomic hybridization in childhood acute lymphoblastic leukemia: correlation with interphase cytogenetics and loss of heterozygosity analysis.

We used comparative genomic hybridization (CGH) to study DNA copy number changes in 71 children with acute lymphoblastic leukemia (ALL) including 50 B-lineage and 21 T-ALLs. Forty-two patients (59%) showed genomic imbalances whereby gains were more frequently observed than losses (127 vs. 29). Gains most commonly affected the entire chromosomes 21 and 10 (19.7% each), 6, 14, 18, X (15.5% each), 17 (14.1%) and 4 (11.3%). Highly hyperdiploid karyotypes (chromosome number >50) occurred more frequently in B-lineage than in T-lineage ALL (24% vs. 4.8%). In both cell lineages deletions were mainly detected on 9p (14.1%) and 12p (8.4%), and on 6q in T-lineage ALL (4.2%). These findings were compared with loss of heterozygosity (LOH) of 6q, 9p, 11q, and 12p previously performed in 56 of the 71 patients. Among 54 sites of LOH, CGH revealed losses of the respective chromosome arms in 17 LOH-positive regions (31.5%). G-banding analysis and interphase cytogenetics with subregional probes for 14 loci confirmed the presence of genomic imbalances as detected by CGH. We, therefore, conclude that, in the absence of cytogenetic data, CGH represents a suitable method for identifying hyperdiploid karyotypes as well as prognostically relevant deletions in ALL patients.

Adolescent↗
PubMed2001

Exploring haplotype sharing methods in general and isolated populations to detect gene(s) of a complex genetic trait.

We applied a new haplotype sharing method to the simulated Genetic Analysis Workshop 12 data for both isolated and general populations without knowledge of the disease model, using affection status as phenotype and three different sample sizes. The highest peak for the mean sharing of the haplotypes was found in the isolated population for the markers D06G034 and D06G035, which flank the candidate genes located on chromosome 6, with -log10(p) values of 2.9 and 7.0 in the moderate and large study samples, respectively. The whole genome screen detected three further loci with -log10(p) values of 3.0, which turned out to be false positives. None of the true gene loci were detected in the general population even in the largest sample. The test of linkage disequilibrium based on excess haplotype sharing over the linkage equilibrium expectation revealed z-values one order of magnitude higher in the isolated than in the general population. This approach appears to be promising for mapping genes of complex diseases depending on population characteristics.

Chromosome Mapping↗
PubMed2001

Shanxi Province Cervical Cancer Screening Study: a cross-sectional comparative trial of multiple techniques to detect cervical neoplasia.

OBJECTIVE: The aim of this study was to design a cervical cancer screening algorithm for the developing world that is highly sensitive for cervical intraepithelial neoplasia (CIN) II, III, and cancer and highly specific for CIN II and III, making it possible to ablate the transformation zone without histologic confirmation. METHODS: In rural Shanxi Province, China, we examined 1997 women ages 35-45. Each subject underwent a self-test for intermediate and high-risk HPV (by HC-II assay), fluorescence spectroscopy, a liquid-based Pap (read manually and by computer and used as a direct test for HPV), a visual inspection (VIA) diagnosis, and colposcopy with multiple cervical biopsies. RESULTS: Mean age was 39.1 +/- 3.16 years, mean number of births was 2.6 +/- 0.93. Based on tests administered, 4.3% subjects had > or =CIN II. All subjects with > or =CIN II had either a ThinPrep Pap (> or =ASCUS) or a positive HPV direct test. The sensitivity and specificity for the detection of > or =CIN II were, respectively, 83 and 86% for the HPV self-test, 95 and 85% for the HPV direct test, 94 and 78% for the ThinPrep Pap (> or =ASCUS), 77 and 98% for the ThinPrep Pap (> or =HGSIL), 94 and 9% for fluorescence spectroscopy, 71 and 74% for VIA, and 81 and 77% for colposcopy. CONCLUSION: Based on these data and the existing healthcare infrastructure in China, we believe that further refinement of primary HPV screening using centralized labs is indicated. Self-testing in the local villages may be effective with improvements in the devices and techniques.

Adult↗
PubMed2001

Development status of miltefosine as first oral drug in visceral and cutaneous leishmaniasis.

An oral treatment for visceral and cutaneous leishmaniasis has been searched for over the last decades. An oral drug would facilitate treatment and lower costs. Oral miltefosine (Zentaris/ASTA Medica AG, Germany), an alkylphosphocholine, is under clinical development for treatment of leishmaniasis. Phase I, II and III clinical trials have been performed in visceral leishmaniasis in India; the overall response rate with 100 mg/day over 4 weeks is 96%. A first clinical trial in New World cutaneous leishmaniasis has shown a final cure rate of 94% at a dose of 150 mg/day over 3 or 4 weeks. Side effects are mainly gastrointestinal (vomiting, diarrhoea). Furthermore, transient elevation of transaminases or urea/creatinine has been observed. The clinical results suggest that miltefosine is the first oral therapy that is effective and safe in visceral and cutaneous leishmaniasis.

Administration, Oral↗
PubMed2001

Evidence of peripheral auditory activity modulation by the auditory cortex in humans.

At the auditory periphery, the medial olivocochlear system is assumed to be involved in complex sound processing and may be influenced by feedback from higher auditory nuclei. Indeed, the descending auditory pathway includes fibers coming from the auditory cortex that are anatomically well positioned to influence the superior olivary complex, and thus the medial efferent system. The aim of the present study was to verify the hypothesis of an implied influence of the auditory cortex on the peripheral auditory system. In three rare cases of patients presenting with intractable temporal lobe epilepsy, Heschl's gyrus (i.e. the temporal superior gyrus) was surgically removed in the right hemisphere in two patients and in the left hemisphere in a third patient, in order to minimize epilepsy attacks, as preoperative stereoencephalography had shown the epileptic focus or tumor to be situated in those locations. In all three cases, several weeks after the operation the medial olivocochlear system was clearly less functional on both sides, but especially on the side contralateral to the resection. In healthy controls, no such pattern was obtained. In four other epileptic patients, who were operated unilaterally at the anterior temporal pole, amygdala and hippocampus with the temporal gyrus partially spared, efferent suppression grew stronger in the ear ipsilateral to surgery. These results revealed that, in humans, the primary and secondary auditory cortex play a role in modulating auditory periphery activity through direct or indirect efferent fibers. In accordance with previous findings, this descending influence may improve the auditory afferent message by adapting the hearing function according to cortical analysis of the ascending input.

Adult↗