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Biomedical subjects

C Kolb

Publications and source records attributed to C Kolb.

At least 19 recordsLinked to original sources

Modes of initiation of paroxysmal atrial fibrillation from analysis of spontaneously occurring episodes using a 12-lead Holter monitoring system.

Although new, possibly curative radiofrequency ablation techniques for atrial fibrillation (AF) have been developed in recent years, little is known about the mechanisms of spontaneous onset of AF episodes. Using a 12-lead 24-hour Holter monitoring system, we aimed to characterize such episodes. A total of 297 spontaneous episodes of AF in 33 patients with intermittent AF (mean age of 59 +/- 11 years) were analyzed. Two hundred seventy-six episodes (93%) were initiated by atrial premature complexes (APCs), whereas 19 episodes (6.4%) were preceded by typical atrial flutter and 2 (0.7%) by atrial tachycardia. Based on 12-lead electrocardiographic criteria, the origin of ectopic beats initiating AF was classified in 230 episodes (77.5%) as being of left atrial origin, in 6 episodes (2.0%) as being of right atrial origin and in 40 episodes (13.5%) the exact location could not be determined. In 16 of 23 patients (70%) with multiple episodes of AF, ectopic beats that initiated AF were consistently monomorphic. In the 120 seconds (6.2 APCs/min for a 30-second period) before onset of AF, frequency of ectopic beats increased from 0.8 APCs/min in AF-free intervals to 4.1/min (6.2 APCs/min for a 30-second period), (p = 0.003 and p = 0.016, respectively). In 209 of 254 episodes (82%), AF onset occurred during normal sinus rate (60 to 100 beats/min). Thus, paroxysmal AF is triggered most frequently by monomorphic left APCs. In most AF episodes, the increase in the number of ectopic beats that initiated episodes of AF occurred at a normal sinus rate.

Adult↗

Incidence of electromagnetic interference in implantable cardioverter defibrillators.

Electromagnetic interference (EMI) with ICDs can lead to temporary inhibition of the device or to inappropriate delivery of antitachycardia pacing and shocks. The incidence of interactions between electronic devices and the current generation of ICDs is not known. In a retrospective study of 341 patients (665 patient-years) who underwent a regular follow-up every 3 months, five episodes of EMI were detected in four different patients. The risk for receiving inappropriate shocks due to EMI is < 1% per year and patient. In conclusion, although inappropriate delivery of shocks by ICDs due to EMI rarely occurs, patient information should emphasize the avoidance of situations of possible interference. Further efforts concerning lead technology and detection algorithms are necessary to minimize the risk of EMI.

Aged↗

Inappropriate shock delivery due to ventricular double detection with a biventricular pacing implantable cardioverter defibrillator.

This report describes a patient with advanced heart failure, pronounced intraventricular conduction delay, and ventricular tachycardias who underwent implantation of a multisite pacing ICD. Pacing leads were placed in the right atrium, right ventricular apex, and to the left ventricular posterior wall via a coronary sinus vein. The system proved to have correct sensing and pacing function in an atrial synchronized biventricular pacing mode and an appropriate detection of ventricular fibrillation. However, 1 month after implantation the patient received an inappropriate shock delivery due to double detection of ventricular premature beats. The inherent detection problem of dual ventricular sensing is discussed.

Defibrillators, Implantable↗

Pseudotermination of intermittent atrial fibrillation by a pacemaker algorithm: antitachycardia pacing without capture miscounted as successful termination of fibrillation episodes.

A patient is described with intermittent AF and an implanted pacemaker which provides preventive pacing and overdrive stimulation designated to terminate atrial arrhythmias. The case highlights the possibility of false estimation of therapeutic efficacy and possible proarrhythmic effect of this therapeutic modality.

Algorithms↗

Do current dual chamber cardioverter defibrillators have advantages over conventional single chamber cardioverter defibrillators in reducing inappropriate therapies? A randomized, prospective study.

INTRODUCTION: Supraventricular tachyarrhythmias are the main cause of inappropriate therapies in patients with conventional single chamber implantable cardioverter defibrillators (VVI-ICD). It was anticipated that dual chamber cardioverter defibrillators (DDD-ICD), with their capacity to analyze atrial and ventricular rhythm, could substantially reduce inappropriate therapies. METHODS AND RESULTS: Our prospective study included 92 patients (87 men; mean age 61 +/- 12.7 years) who were randomly assigned to a VVI-ICD (45 patients) or a DDD-ICD (47 patients). Both groups were followed for 7.5 +/- 3.5 and 7.6 +/- 4.1 months, respectively. During the follow-up period, overall 725 ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes were recorded in 45 (49%) of 92 patients. Of these episodes, 404 (56%) occurred in the VVI-ICD group and 321 (44%) episodes occurred in the DDD-ICD group. Twenty-three (51%) patients in the VVI-ICD group and 22 (47%) patients in the DDD-ICD group (P = 0.8) developed VT/VF. Overall, 73 (10%) of 725 treated episodes were inappropriate in 6 (13%) patients in the VVI group and in 10 (21%) patients in the DDD-ICD group (P = 0.2). There were 22 (31%) inappropriately treated episodes in the VVI-ICD group and 51 (69%) in the DDD-ICD group. Thirty-two of the 51 inappropriate episodes in the DDD-ICD patients resulted from intermittent atrial sensing problems that led to failure of the respective dual chamber algorithms. Nonfatal complications occurred in 6 (13%) patients in the VVI-ICD group and in 3 (6%) patients in the DDD-ICD group (P = 0.7). CONCLUSION: We conclude that the implanted DDD-ICD and conventional VVI-ICD are equally safe and effective for therapy of life-threatening ventricular tachyarrhythmias. Although DDD-ICDs allow better rhythm classification, the applied detection algorithms do not offer benefits in avoiding inappropriate therapies during supraventricular tachyarrhythmias.

Aged↗

The murine ortholog of matrix metalloproteinase 19: its cloning, gene organization, and expression.

We have isolated a murine cDNA orthologous to the human matrix metalloproteinase 19 (hMMP-19). The murine MMP-19 cDNA was amplified by RT-PCR using specific primers whose DNA sequences were derived from both murine MMP-19 genomic DNA and partial cDNA sequences. The murine MMP-19 (mMMP-19) is 79% identical to the human ortholog and encodes a protein of 527 amino acids with a deduced molecular mass of 59.1kDa. Analyzing the exon/intron junctions we revealed that the murine MMP-19 gene consists of nine exons and eight introns, and thus differs from the gene organization of other matrix metalloproteinases. Furthermore, a 587bp fragment of the mMMP-19 promoter containing a TATA box and an AP-1 binding motif was cloned, and 3.3kb transcripts of the MMP-19 gene were identified in liver, kidney, spleen, and colon. Finally, immunostaining of murine heart cryosections showed that mMMP-19, like its human counterpart, is expressed in the arterial tunica media of large blood vessels. By cloning mMMP-19 and unraveling its genomic structure, we have obtained valuable information for further study of the function of this MMP in vivo.

3T3 Cells↗

Matrix metalloproteinase-19 in capillary endothelial cells: expression in acutely, but not in chronically, inflamed synovium.

Matrix metalloproteinase-19 (MMP-19), originally isolated as an autoantigen from the synovium of a patient suffering from rheumatoid arthritis (RA), is expressed in smooth muscle cells of the tunica media of large blood vessels of an RA patient, but not in the endothelial cell layer. By contrast, in acutely inflamed tissue, synovial capillaries strongly express MMP-19 in the cytoplasm, as shown by immunofluorescence of cryostat sections. In MMP-19-producing capillaries the beta3 integrin chain was found at the endothelial cell surface, as was the vascular endothelial cell growth factor receptor-2 (KDR). The specific tissue inhibitor of metalloproteinases TIMP-1 was absent or faintly stained in MMP-19-expressing capillaries, whereas TIMP-1, but not TIMP-2, was strongly expressed in large vessels and in MMP-19-negative capillaries of RA synovia. In the spontaneously transformed human umbilical vein endothelial cell line ECV304 neither MMP-19 transcripts nor protein could be detected. By contrast, primary cultures of human endothelial cells of either dermal or adipose tissue origin produced MMP-19 mRNA and protein. The results strongly suggest the regulated induction of matrix metalloproteinase-19 in capillary endothelial cells during acute inflammation and hint at a role of MMP-19 in angiogenesis.

Acute Disease↗

[In Process Citation]

Since 1996 thoracic surgery has been invoiced according to fixed reimbursement rates (Sonderentgelte, SE). The legislator argues that fixed reimbursement rates cover operation costs and justify a 20% reduction in reimbursement for nursing. In order to examine this assumption we performed a cost analysis of thoracic surgery. Taking into account the staff, equipment, and operating theatre supplies, we analyzed 30 cases of five different types of operation prospectivly: wedge resections with more than three wedges (AR: n = 8), lobectomies (LE: n = 8), pneumonectomies (PE: n = 5), thoracoscopic wedge resections (VR: n = 6) and resections of mediastinal tumors (MR: n = 3). Then we calculated the overall costs for each operation. The costs for a LE amounted to DM 9,927, which is DM 4,904 more than the corresponding fixed reimbursement rate. The costs were DM 11,562 for a PE, DM 12,477 for a VR and DM 7,532 for a MR. Thus the costs were DM 5,539, DM 2,435 or DM 1,907 higher than the corresponding fixed reimbursement rates. The fixed reimbursement rate for an AR was DM 866 higher than the actual cost of DM 6,922. Only for a small number of cases do the fixed reimbursement rates cover the actual costs of thoracic surgery. Thus operation costs still need to be at least partly covered by the reimbursement for nursing.

Journal Article↗

Apparent trans-chromosomal antibody class switch in mice bearing an Igh(a) mu-chain transgene on an Igh(b) genetic background.

Native high molecular weight dextran induces a thymus-independent response in BALB/c mice. When the dextran epitope is linked to a protein carrier the response becomes thymus-dependent. IgG antibodies produced after secondary immunization had epitope specificity and idiotope of myeloma M104E. The antibody of M104E (mu, lambda1) is representative for antibodies produced by mice with immunoglobulin haplotype Igh(a) in response to immunization with dextran B1355S. Myeloma product and physiological antibodies share specificity for the alpha(1-3) glucosidic linkage and have idiotopes in common. Mice with haplotypes other than Igh(a) (e.g. Igh(b)) are unable to yield this type of response. A complete rearranged immunoglobulin mu-chain gene with a VDJ-region from BALB/c (Igh(a)) myeloma protein M104E had been introduced into the genome of BALB/c congenic mice having the haplotype Igh(b). As was shown previously in our laboratory the M104E mu-chain transgene confers Igh(a)-type reactivity to Igh(b) mice. In experiments described in this report we used the thymus-dependent form of the antigen to immunize mice bearing the M104E mu-chain, either alone or together with the lambda1-chain, as a transgene on an Igh(b) genetic background. Serological analysis revealed a class switch to IgG very similar to that seen in BALB/c mice with respect to magnitude, kinetics, epitope and idiotope specificity. The pattern of IgG subclass expression was indistinguishable in mu-chain transgenic Igh(b) and normal BALB/c mice. The class switch occurred even though, as is shown here, the transgene had become incorporated in a site not linked to the Igh locus on chromosome 12. We propose a model for this apparent trans-chromosomal class switch recombination which is based on mechanisms known for conventional switch recombination.

Animals↗

Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and CagA protein expression, cytotoxin production, and associated diseases.

The vacuolating cytotoxin and the cytotoxin-associated protein, encoded by vacA and cagA, respectively, are important virulence determinants of Helicobacter pylori. Sixty-five H. pylori strains were isolated from dyspeptic patients (19 with peptic ulcer disease, 43 with chronic gastritis, and 3 with gastric cancer) and studied for differences in the vacA and cagA genes and their relationship to VacA and CagA expression, cytotoxin activity, and the clinical outcome of infection. By PCR, fifty-four (83.1%) of 65 strains had the vacA signal sequence genotype s1 and only 10 (15.4%) had the type s2. After primer modification, the vacA middle-region types m1 and m2 were detected in 24 (36.9%) and 41 (63.1%) strains, respectively. The combinations s1-m2 (31 [47.7%]) and s1-m1 (23 [35.4%]) occurred more frequently than s2-m2 (10 [15.4%]) (P = 0.01). No strain with the combination s2-m1 was found. All 19 patients with peptic ulcers harbored type s1 strains, in contrast to 32 (74.4%) of 43 patients with gastritis (P = 0.02). The vacA genotype s1 was associated with the presence of cagA (P < 0.0001), VacA expression (P < 0.0001), and cytotoxin activity (P = 0.003). The cagA gene was detectable in 48 (73.8%) of 65 isolates and present in 16 (84.2%) of 19 ulcer patients and 29 (67.4%) of 43 patients with gastritis (P = 0.17). The vacA genotypes of German H. pylori isolates are identical to those previously reported. H. pylori strains of vacA type s1 are associated with the occurrence of peptic ulceration and the presence of cagA, cytotoxin activity, and VacA expression.

Antigens, Bacterial↗

[Acute water intoxication as a complication of therapy refractory schizophrenia].

A patient with chronic paranoid schizophrenia with delusions of infestation and of grandeur type, developed polydipsia in the course of his illness which ended up in acute life-threatening water intoxication. Apart from somatic causes like SIADH, which are discussed in literature, water-intoxication could psychodynamically be interpreted in the sense of acting on delusions.

Acute Disease↗

The matrix metalloproteinase RASI-1 is expressed in synovial blood vessels of a rheumatoid arthritis patient.

RASI-1 is a novel matrix metalloproteinase which we isolated from an expression cDNA library representing the mRNA of an inflamed synovium obtained from a patient with rheumatoid arthritis (RA). To investigate the involvement of RASI-1 in the pathology of RA, we examined synovial specimens from RA patients with antibodies directed against an unique RASI-1-derived peptide. In comparison to interstitial collagenase, gelatinase A and B, and stromelysin 1, the RASI-1 expression in the RA-synovium is located mainly in the tunica media of blood vessel walls and its synovial localization is not as ubiquitous as that of other MMPs. The tissue inhibitor of metalloproteinases (TIMP-1), although also widely expressed in the synovium, exhibits strong colocalization with RASI-1 in blood vessel walls. While RASI-1 is expressed in blood vessels of the inflamed synovium of an RA patient, its expression was not found in control synovial specimens from patients with luxation and arthrosis. However, RASI-1 expression can also be found in non-inflamed blood vessels of uterine ligaments and skin. RASI-1, although its function and substrates are unknown, could be involved in processes such as neovascularization and angiogenesis or lymphocyte extravasation and thus may participate in joint tissue destruction during RA.

Amino Acid Sequence↗

Serum antibodies against Helicobacter pylori proteins VacA and CagA are associated with increased risk for gastric adenocarcinoma.

Infection with Helicobacter pylori is associated with the development of gastric cancer. To study whether the infection with H. pylori strains expressing the vacuolating cytotoxin (VacA) and/or the cytotoxin-associated protein (CagA) is associated with an increased risk of developing gastric adenocarcinoma, sera of 90 patients with gastric cancer and 90 matched controls with cardiovascular diseases were investigated for the presence of antibodies to VacA and CagA by immunoblot. Although no significant difference in the overall H. pylori seropositivity was found between cancer patients and controls, antibodies against VacA or CagA were significantly more frequent in cancer patients than in control subjects. Seventy-five (97.4%) of 77 H. pylori-positive patients in the cancer group, but only 60 (84.5%) of 71 H pylori-positive control patients had antibodies against either VacA or CagA (chi 2 = 6.63; relative risk, 2.00; 95% confidence interval, 1.18-3.39; P = 0.01). The presence of antibodies against VacA or CagA alone was also associated with an increased cancer risk (92.2% vs 80.3%; chi 2 = 5.30; relative risk, 1.74; 95% confidence interval, 1.08-2.78; P = 0.021, for VacA; and 87.0% vs 74.6%; chi 2 = 4.90; relative risk, 1.61; 95% confidence interval, 1.06-2.45; P = 0.037, for CagA). The relative risk for gastric cancer was mainly elevated in patients under 65 years, but not in patients at or over 65 years. There is evidence that infection with VacA- or CagA-producing H. pylori strains increases the risk of developing gastric cancer, especially in younger patients.

Adenocarcinoma↗

Stimulation of the same B-cell population by thymus-independent dextran and by thymus-dependent oligosaccharide-carrier.

The immune response of adult BALB/c mice against the bacterial antigen dextran B1355S (Dex) is well characterized as thymus independent (TI type 2) and Igha linked. The antisera consist of mainly IgM/lambda antibodies directed against the alpha(1-->3) glucosidic linkage. This study describes the immune response against the alpha(1-->3) linkage in the thymus dependent form (TD), i.e. tetra- or heptasaccharides (N4 or N7) of glucose as hapten coupled to chicken serum albumin (CSA) as carrier. Whereas athymic BALB/c-nu/nu mice did not respond to the TD antigens N4-CSA and N7-CSA, euthymic BALB/c showed high anti-Dex antibody titres of IgM and, after 2 degrees immunization, a class switch to IgG (mainly IgG1) isotypes with lambda light chains. The hapten N4 inhibited Dex-binding of M104E or of antisera from Dex or N4-CSA or N7-CSA immunized mice at 1.7-10 x 10(-4)M. The idiotype composition of these antibodies resembled those after Dex immunization. We conclude that the same Dex-specific precursor B cells have been stimulated by either form of antigen. The ontogenic development of a Dex-specific response could not be accelerated by the aid of T cells, even of adult origin. It seems, therefore, that the maturation of antigen specific B cells is the limiting step in ontogeny.

Age Factors↗

The thymus-independent antigen alpha(1-3) dextran elicits proliferation of precursors for specific IgM antibody-producing cells (memory cells), which are revealed by LPS stimulation in soft agar cultures and detected by immunoblot.

Single antibody-forming cells (AFC) specific for alpha(1-3) dextran (Dex) from i.p.-immunized BALB/c mice were enumerated in soft agar cultures by blotting on antigen-precoated membranes and subsequent staining via enzyme-coupled anti-IgM antibodies. Short cultures (2 h) revealed AFC as harvested ex vivo, while in long-term cultures (4 days), in the presence of lipopolysaccharide (LPS) as B cell mitogen, cells or colonies developed by differentiation in vitro. Whereas the spleen contained most AFC ex vivo in a sharp-peak response at 4 and 5 days after i.p. injection of Dex in aqueous solution, peritoneal exudate cells (PEC) contained only very few AFC. However, the same PEC population developed Dex-specific cells or colonies after 4 days of culture. The isotype of antibodies was IgM. The frequency of these Dex-specific LPS-inducible precursor cells rose exponentially in the course of the immune response to a broad plateau and was still, 11 weeks after Dex injection, approximately 40-fold higher than in non-immunized mice. Since these cells increased in frequency after antigen injection, and since they could not be detected as AFC during 2 h ex vivo, they were regarded as memory cells. They seemed to be arrested in vivo, but could be induced to differentiation and/or proliferation in vitro. Although these cells had the functional characteristics of memory cells as defined above, they produced anti-Dex antibodies of IgM isotype. Their population might be critical for the protection of the peritoneal cavity against microbial invasion from the intestines, and it may be significant in this context that we could evoke a peritoneal memory cell response only when antigen was injected intraperitoneally, but not intravenously. In athymic BALB/c-nu/nu mice only few of these Dex-specific memory cells were found. It is possible that T cells exert a regulatory influence on this pathway of differentiation.

Animals↗