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M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed2001

Electroanatomical Mapping (CARTO) of ectopic atrial tachycardia: impact of bipolar and unipolar local electrogram annotation for localization the focal origin.

UNLABELLED: Electroanatomical Mapping (CARTO) allows a tridimensional localization of ectopic atrial tachycardia (EAT). No standardized recommendation exists for annotation the local activation time in EAT using this new technology. In the present study bipolar local electrogram were used for CARTO guided RF ablation of EAT. In comparison the same maps were retrospectively analyzed by annotation the unipolar local electrogram. METHODS: In 15 consecutive patients (6m, 51+/-14 y) with EAT CARTO mapping was guided by annotation the earliest onset of the bipolar local electrogram. Following successful RF ablation the obtained EAT maps were subsequently evaluated by annotation of the earliest steepest negative intrinsic deflection of the unipolar local electrogram. Both CARTO maps were compared with regard to the region of focal EAT origin. RESULTS: RF ablation of all 15 EAT foci guided by annotation the bipolar local electrogram with CARTO was successful with a median of 3 [1-18] pulses and a median fluoroscopy time of 10 min [4-25]. All but one focus was located in the right atrium: posterior to posteroinferior region of the terminal crest in 6, septal region in 5, anterior superior region in 3 cases. One left sided EAT was located at the septum. The bipolar CARTO map demonstrated a "small territory" location of earliest activation (extension of the focus < or =0.4 cm(2)) in 14 out of 15 patients. In a single patient the bipolar map showed several sites of earliest local activation (extension >0.4 cm(2)). On the other side the retrospectively achieved unipolar maps demonstrated an extended region of earliest local activation in 6 out of 15 patients (>0.4 cm(2)). CONCLUSIONS: CARTO maps of EAT by annotation the earliest onset of the bipolar local electrogram provide an efficacious guide for location the focal origin. Extended regions of earliest local activation in EAT might be rather determined by annotation the unipolar in comparison to the bipolar local electrogram.

Adult↗
PubMed2001

The human delta opioid receptor activates G(i1)alpha more efficiently than G(o1)alpha.

To assess the relative capacity of the human delta opioid receptor to activate closely related G proteins, fusion proteins were constructed in which the alpha-subunits of either G(i1) or G(o1), containing point mutations to render them insensitive to the actions of pertussis toxin, were linked in-frame with the C-terminus of the receptor. Following transient and stable expression in HEK 293 cells, both constructs bound the antagonist [(3)H]naltrindole with high affinity. D-ala(2),D-leu(5) Enkephalin effectively inhibited forskolin-stimulated adenylyl cyclase activity in intact cells in a concentration-dependent, but pertussis toxin-insensitive, manner. The high-affinity GTPase activity of both constructs was also stimulated by D-ala(2),D-leu(5) enkephalin with similar potency. However, enzyme kinetic analysis of agonist stimulation of GTPase activity demonstrated that the GTP turnover number produced in response to D-ala(2),D-leu(5) enkephalin was more than three times greater for G(i1)alpha than for G(o1)alpha. As the effect of agonist in both cases was to increase V:(max) without increasing the observed K:(m) for GTP, this is consistent with receptor promoting greater guanine nucleotide exchange, and thus activation, of G(i1)alpha compared with G(o1)alpha. An equivalent fusion protein between the human mu opioid receptor-1 and G(i1)alpha produced a similar D-ala(2),D-leu(5) enkephalin-induced GTP turnover number as the delta opioid receptor-G(i1)alpha fusion construct, consistent with agonist occupation of these two opioid receptor subtypes being equally efficiently coupled to activation of G(i1)alpha.

Adenylyl Cyclases↗
PubMed2001

Differential capacities of the RGS1, RGS16 and RGS-GAIP regulators of G protein signaling to enhance alpha2A-adrenoreceptor agonist-stimulated GTPase activity of G(o1)alpha.

Recombinant RGS1, RGS16 and RGS-GAIP, but not RGS2, were able to substantially further stimulate the maximal GTPase activity of G(o1)alpha promoted by agonists at the alpha2A-adrenoreceptor in a concentration-dependent manner. Kinetic analysis of the regulation of an alpha2A-adrenoreceptor-G(o1)alpha fusion protein by all three RGS proteins revealed that they had similar affinities for the receptor-G protein fusion. However, their maximal effects on GTP hydrolysis varied over threefold with RGS16 > RGS1 > RGS-GAIP. Both RGS1 and RGS16 reduced the potency of the alpha2A-adrenoreceptor agonist adrenaline by some 10-fold. A lower potency shift was observed for the partial agonist UK14304 and the effect was absent for the weak partial agonist oxymetazoline. Each of these RGS proteins altered the intrinsic activity of both UK14304 and oxymetazoline relative to adrenaline. Such results require the RGS interaction with G(o1)alpha to alter the conformation of the alpha2A-adrenoreceptor and are thus consistent with models invoking direct interactions between RGS proteins and receptors. These studies demonstrate that RGS1, RGS16 and RGS-GAIP show a high degree of selectivity to regulate alpha2A-adrenoreceptor-activated G(o1)alpha rather than G(i1)alpha, G(i2)alpha or G(i3)alpha and different capacities to inactivate this G protein.

Adrenergic alpha-Agonists↗
PubMed2001

Long-term results after repair of total anomalous pulmonary venous connection.

BACKGROUND: Operative strategies and early results concerning repair of Total Anomalous Pulmonary Venous Connection (TAPVC) are relatively well known. Less well defined data are available to evaluate the long-term outcome. We would therefore like to contribute our long-term data in this presentation. PATIENTS AND METHODS: Between 1958 and 1992 52 consecutive patients aged two days to 42 years (15 neonates, 16 infants, 9 children and 12 adults) with TAPVC were operated on. The data were collected retrospectively from the records. In 24 patients, a current follow-up study was performed, including clinical evaluation, echocardiography, and a twenty-four-hour ambulatory ECG. RESULTS: Early mortality was 34.6% (n = 18). The postoperative follow-up period ranged from 4 months to 28 years (mean 10.7 years). There were 4 late deaths, yielding an overall long-term mortality of 7.7% (4/52). Causes of death were severe hypoplasia of central pulmonary veins in 1, ventricular fibrillation (2) and non-cardiac in one case. 80% of the operative survivors were available for assessment. Preoperatively, 11 of these patients were in NYHA functional class II, six in class III and seven in class IV. After treatment, 22 patients were in class I and two in class II. Ventricular function was evaluated by echocardiography and invasive catheterization. Only two of 24 patients (8%) showed an abnormal IVS-motion and enlargement of the right ventricle. Cardiac catheterization revealed a mean PA pressure of 26 mmHg, the peak systolic pressure in the RV was 34 mmHg. All 24 long-term survivors underwent assessment of cardiac rhythm by 24 h electrocardiogramm (ECG) monitoring. Significant arrhythmias were recorded in 11 of 24 cases (46%), including sinus node dysfunction in 3 patients. Multiform ventricular ectopic beats were evaluated in 9 cases. According to the Lown classification, 7 patients were class I while 2 cases were considered to be class IV. CONCLUSIONS: A normal hemodynamic state can be achieved in most cases. Significant arrhythmias may exist in asymptomatic patients late after surgical correction of TAPVC, and therefore, long-term follow-up of these patients, including 24 h ECG monitoring, is recommended, even if they are asymptomatic.

Adolescent↗
PubMed2001

[Legionellas in domestic warm water--effects on the health of residents].

Only few epidemiological data on legionella diseases are available in Germany and studies on the prevalence of legionella antibody response in the population are scarce. We report on an epidemiological study on immune response in residents of homes with heavy and with minor legionella contamination in their hot-water system. 53 inhabitants of houseblocks with central hot-water system and high legionella contamination (6,049 +/- 17,995 cfu/l; 40% > 1,000 cfu/l) were studied. 92 persons living in 1-2 family houses with decentral hot water systems (244 +/- 1,434 cfu/l; 3% > 1,000 cfu/l) served as controls. All persons filled in a questionnaire on bronchial and fever diseases etc; blood specimen were tested for legionella antibodies (different methods: immunofluorescence, and ELISA), and urine specimens were analysed for legionella antigen. During this investigation in the population exposed to Legionella no cases of legionellosis were reported. The prevalence of legionella antibodies was twice as high in the exposed versus the control persons. Significant correlation between cfu/l and legionella antibody titer in the inhabitants were found. One person with high antibody titer and with legionella-free hot-water system in his home had reported about pulmonary problems after having stayed in a hotel. The positive antibodies of the other persons are most likely the result of asymptomatic infections caused by permanent exposure in their home hot-water supply. In conclusion, with regard to the increased prevalence of antibody titers against legionellae in the exposed inhabitants and the significant correlation between antibody titers and cfu/l in hot-water samples, the necessity to control and redevelop hot-water systems in homes is confirmed--even though no cases of legionelloses in the exposed population were reported.

Adult↗
PubMed2001

Hepatosplenomegaly and progressive neurological symptoms - Late manifestation of Niemann-Pick disease type C - a case report -.

Niemann-Pick disease type C is an inborn error of metabolism that affects lipid degradation and storage. Hepatosplenomegaly and progressive neurological symptoms are the main clinical features. We present a case of an adult-onset type of Niemann-Pick disease in a 33-year-old woman who initially presented with dysarthria. At first, laboratory findings suggested Wilson's disease. Laparoscopy showed macroscopic signs of liver cirrhosis and histology did not confirm Wilson's disease. After bone marrow biopsy showed characteristic sea-blue histiocytes, Niemann-Pick disease was suspected and confirmed by filipin stain of cultured fibroblasts. Though rarely encountered, lipid storage disease should be suspected especially in younger patients with organomegaly and progressive signs of neurologic disease.

Adult↗
PubMed2001

Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis.

BACKGROUND: There are already many effective topical therapies available for use in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are often associated with a rather significant risk of undesirable effects. OBJECTIVE AND METHODS: In this randomized, prospective clinical trial, the effects of the vitamin D(3) analog calcipotriol were evaluated against those of a recently developed vitamin B(12) cream containing avocado oil in an intraindividual right/left-side comparison. The trial population consisted of 13 patients, 10 men and 3 women, with chronic plaque psoriasis. The observation period was 12 weeks; the effects of therapy were assessed on the basis of a PASI score adapted to the right/left-side comparison technique, the subjective evaluations of the investigator and patients and the results of 20-MHz sonography. RESULTS: There was a more rapid development of beneficial effects with the use of calcipotriol in the initial 8 weeks, although differences in effects were significant only at the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI score nor 20-MHz sonography showed significant differences between the two treatments. While the efficacy of the calcipotriol preparation reached a maximum in the first 4 weeks and then began to subside, the effects of the vitamin B(12) cream containing avocado oil remained at a constant level over the whole observation period. This would indicate that the vitamin B(12) preparation containing avocado oil may be suitable for use in long-term therapy, a hypothesis further supported by the fact that the investigator and the patients assessed the tolerability of the vitamin B(12) cream containing avocado oil as significantly better in comparison with that of calcipotriol. CONCLUSION: The results of this clinical trial provide evidence that the recently developed vitamin B(12) cream containing avocado oil has considerable potential as a well-tolerated, long-term topical therapy of psoriasis.

Adult↗
PubMed2001

Gene expression in a pure population of odontoblasts isolated by laser-capture microdissection.

Studies of odontoblast differentiation and function have been limited due to difficulties in obtaining sufficient numbers of intact cells. We describe a novel approach of laser-capture microdissection to obtain homogenous populations of pre-odontoblasts and odontoblasts from tissue sections of mouse molar cusp tips. Fixation, processing, and staining conditions were assessed for the optimal retrieval of total RNA from microdissected odontoblasts. Fluorometric assays and RT-PCR analysis of alpha1(I) collagen, dentin sialophosphoprotein (Dspp), and osteocalcin (OC) confirmed that the total RNA from three-day-old captured odontoblasts was sufficient in quantity and quality. Odontoblast-specific gene expression was studied by RT-PCR analysis performed in a single streptavidin-coated tube. At E15.5, Days 0 and 3, gene expression in laser-captured odontoblasts resembled that seen in vivo by in situ hybridization. The use of LCM is thus a valuable means of retrieving quality RNA from discrete populations of odontoblasts at different stages of dentinogenesis.

Animals↗
PubMed2001

Molecular insights into the lineage-specific determination of odontoblasts: the role of Cbfa1.

The role of stable transcription complexes in initiating and consolidating programs of gene expression during lineage specification has been extensively studied. Despite the progress made in the identification of key molecules of tooth initiation and patterning, the mechanisms leading to cell differentiation during odontogenesis are unknown. Odontoblasts are exclusive dentin-producing cells that are phenotypically and functionally distinct from osteoblasts. However, not much is known about the precise determinants of odontoblast terminal differentiation--in particular, how the fate of these cells becomes delineated from that of osteogenic mesenchyme. Cbfa1(-/-) mice completely lack osteoblasts and bone, while tooth development arrests at the time of odontoblast differentiation. The purpose of this paper is to overview our studies on the role of Cbfa1 in odontoblast determination and differentiation using the Cbfa1(-/-) mouse model and various experimental approaches. Our expression analyses confirm the down-regulation of Cbfa1 expression in newly differentiated and functional odontoblasts. Second, we demonstrate that Cbfa1(-/-) incisor organs arrest at a later stage than molars, and that alpha 1 (I) collagen, a marker of odontoblast differentiation shared in common with osteoblasts, is not significantly affected by the absence of the transcription factor. Interestingly, Dspp expression in Cbfa1(-/-) appeared markedly down-regulated in putative odontoblasts. The overexpression of Cbfa1 in an odontoblast cell line (MDPC-23) results in the selective down-regulation of Dspp and not type I collagen. It is likely that, in addition to its influence on tooth epithelial morphogenesis, Cbfa1 plays a non-redundant and stage-specific role in the lineage determination and terminal differentiation of odontoblasts from dental papilla mesenchyme.

Animals↗
PubMed2001

Higher cortical function deficits after stroke: an analysis of 1,000 patients from a dedicated cognitive stroke registry.

OBJECTIVE: Despite spectacular success of animal model neuroprotective therapy in stroke, these agents have been uniformly unsuccessful in humans. One possible explanation is the crudity of cerebral measurement by insensitive of stroke scales comprising scant or absent higher cortical-function parameters and the heterogeneity of stroke syndromes and etiology. We sought to determine the frequency and extent of cognitive disorders after stroke and their relation to stroke risk factors, syndromes, lesion site, and etiology. METHODS: We used hospital-based consecutive stroke cases. A tiered, hierarchic, cerebrovascular investigative protocol and a battery of predefined, validated bedside higher cortical function deficit (HCFD) tests with comparison to neuropsychological. Quantification according to the World Health Organization levels of disease model was achieved by a clinical neurologic deficit scale, etiologic scale, and disability scale. RESULTS: Stroke deficit, disability and etiology: In patients evaluated (n = 1,000), the admission Canadian Neurological Scale deficit grading was mild, 11.5-9.5 (n = 696); moderate, 9.5-5.5 (n = 204); and severe, 5.0-0 (n = 86); with correlation to Rankin scale of independent (n = 467), mild disability (n = 345) and severe disability (n = 174) with moderate agreement (kappa = 0.54) between the two measurements. The etiologic subtypes included large-vessel atherothrombosis (n = 264), small-vessel atherothrombosis (n = 262), cardioembolic (n = 122), other (dissection, vasculitis, prothrombotic states; n = 253), and unknown (n = 99). Cognitive Data: 1. One or more higher cortical function abnormalities was detected in 607 (63.5%) of 955 nondrowsy patients. The most numerous categories were aphasias (25.2%), apraxias (14.5%), amnesias (11.6%), and frontal network syndromes (9.2%), with the other categories less frequent (3%). Cognitive impairment occurred without elementary neurologic deficits (motor, sensory, or visual impairment) in 137 (22.5%) of 608. The cardioembolic, other, and unknown stroke mechanistic groups differed significantly from the other groups in terms of HCFD (p = 0.01) frequency. HCFD did not differ between younger (younger than 49 years) and older patients (p = 0.194). 3. Univariate and multivariate analyses of risk factors and likelihood of developing an HCFD revealed increasing age, black race, being overweight, and recent infection to be independent variables (p = 0.05). 4. In 76 patients, neuropsychological testing was performed and comparison with the HCFD test revealed a sensitivity of 80.2% (CI, 72-88%) and specificity of 100%. CONCLUSIONS: 1. Cognitive impairment is present in the majority of all types of stroke. 2. Cognitive impairment may be the sole presentation of stroke, unaccompanied by long-tract signs. 3. Stroke etiologic subtype differed significantly among the subgroups, but in comparison of young versus older patients, no significant differences in HCFD frequency were recorded. 4. Risk factors for developing cognitive impairment in the indigenous stroke population included increasing age, black race, overweight body habitus, and recent infection.

Adolescent↗
PubMed2000

Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits.

The paradox of blunted parathormone (PTH) secretion in patients with severe hypomagnesemia has been known for more than 20 years, but the underlying mechanism is not deciphered. We determined the effect of low magnesium on in vitro PTH release and on the signals triggered by activation of the calcium-sensing receptor (CaSR). Analogous to the in vivo situation, PTH release from dispersed parathyroid cells was suppressed under low magnesium. In parallel, the two major signaling pathways responsible for CaSR-triggered block of PTH secretion, the generation of inositol phosphates, and the inhibition of cAMP were enhanced. Desensitization or pertussis toxin-mediated inhibition of CaSR-stimulated signaling suppressed the effect of low magnesium, further confirming that magnesium acts within the axis CaSR-G-protein. However, the magnesium binding site responsible for inhibition of PTH secretion is not identical with the extracellular ion binding site of the CaSR, because the magnesium deficiency-dependent signal enhancement was not altered on CaSR receptor mutants with increased or decreased affinity for calcium and magnesium. By contrast, when the magnesium affinity of the G alpha subunit was decreased, CaSR activation was no longer affected by magnesium. Thus, the paradoxical block of PTH release under magnesium deficiency seems to be mediated through a novel mechanism involving an increase in the activity of G alpha subunits of heterotrimeric G-proteins.

Animals↗
PubMed2000

Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in patients with head-and-neck squamous-cell carcinoma.

Human papillomaviruses (HPVs) have been recognized as an essential pathogenic factor in anogenital cancer. HPV DNA has also been found in a subgroup of head-and-neck squamous-cell carcinomas (HNSCCs), and a causative role of the virus in the development of these tumors has been suggested by the concomitant inactivation of the tumor-suppressor protein pRb. Using 4 second-generation ELISAs, we found antibodies against at least 1 of the oncoproteins E6 and E7 of the high-risk HPV types 16 and 18 in 11 of 92 sera (12%) taken from HNSCC patients at or near diagnosis, in 1 of 52 sera (2%) taken from HNSCC patients >6 months after diagnosis and in 10 of 288 sera (3. 5%) taken from sex- and age-matched healthy control individuals of the normal population. In 11 of the 12 seropositive HNSCC cases, antibodies were directed against HPV16 proteins. In patients, the HPV16 antibodies were mostly of high titer, and in 6 cases, antibodies against both HPV16 oncoproteins were present. Seven of the 8 HPV16 antibody-positive sera from the control group were of low titer, and none of the 10 antibody-positive sera reacted with both oncoproteins of the same HPV type. The HPV type of the antigens detected by the antibodies in HNSCC patients correlated well with that of the HPV DNA found in the tumor. Of 19 patients known to have HPV16 DNA-positive tumors, 7 (37%) also had HPV16 E6 and/or E7 antibodies. Our finding suggests that the antibodies were formed in an immune response against HPV E6 and E7 proteins expressed in the HNSCC and thus strongly supports the concept of a biologically active role of HPV in the development of a subgroup of HNSCC.

Adult↗
PubMed2000

Does (99m)Tc-Sestamibi in high-grade malignant brain tumors reflect blood-brain barrier damage only?

(99m)Tc-Sestamibi (MIBI) has been successfully applied in recurrent glioblastoma. The aim of this study was to evaluate the incremental diagnostic information of MIBI as a tumor-avid radiopharmaceutical compared with (99m)Tc-pertechnetate ((99m)Tc) as sole indicator of the integrity of the blood-brain barrier. Twenty-five patients with confirmed recurrent brain tumors were included. MIBI SPET was performed 10 min after injection of 555 MBq MIBI intravenously with a triple-headed gamma camera equipped with LE-UHR-PAR collimators over 360 degrees (3 degrees /step) and stored in a 128(2) matrix. Identical acquisition parameters were used for (99m)Tc SPET, which was acquired 3 h after injection of 740 MBq (99m)Tc. Normalized tumor uptake (NU) was calculated from attenuation-corrected transaxial slices. In addition, tumor/plexus, tumor/nasopharynx, and tumor/parotid gland ratios were assessed in both studies. No statistically significant differences were detected for the mean NU of tumor tissue with MIBI (0.26 +/- 0.10) and (99m)Tc (0.39 +/- 0. 33) and for the tumor/nasopharynx and tumor/parotid gland ratios; only the tumor/plexus ratio was significantly higher for (99m)Tc than for MIBI (p < 0.05). In conclusion, our data indicate that MIBI scintigraphy in brain tumors at 10 min postinjection reveals no additional visual information over that provided by the conventional (99m)Tc-pertechnetate brain scan, and in addition, tracer retention reflects primarily blood-brain barrier damage.

Adult↗
PubMed2000

Change of sternal perfusion following preparation of the internal thoracic artery--a scintigraphical study.

BACKGROUND: Today the internal thoracic artery (ITA) is the bypass graft of choice due to its superior long-term patency rate. It was the aim of this present prospective study to investigate possible perfusion disturbances and consecutive impaired wound healing induced by the ITA preparation. The sternal perfusion was assessed by bone scintigraphy. METHODS: Forty-four patients were included in the study. There were three groups: group I (control, no ITA preparation; n = 12); group II (preparation of the left ITA; n = 21); group III (preparation of both ITAs; n = 11). In all patients a median sternotomy was performed. A bone scintigraphy was performed 4 days before and 12 days after the bypass procedure. Scintigraphical pictures of all patients were assessed visually (one specialized investigator) and the impulse rate was counted by the aid of a computer program. RESULTS: Results of both evaluation methods showed congruently that neither the use of the left nor of both ITAs causes a statistically significant impairment of sternal perfusion. The percentage of postoperative increase of the rate of impulses was in group I: total sternum 55%; right side 56%; left side 55%. The respective numbers for group II were 58, 63 and 53%, and for group III 54, 52 and 56%. Surprisingly, perfusion scans in group II revealed an increase in the right sternal half after left ITA preparation. This may be due to the additional blood flow demand of collaterals branching between the right ITA and contralateral intercostal arteries representing a compensatory mechanism of the loss of the left ITA. During the observed postoperative time frame (mean 15 days) no healing disturbance of the sternal wound occurred in any patient. CONCLUSION: According to the present data the use of one or both ITAs does not cause an increase of healing disturbances, consecutive to a postoperatively decreased sternal blood perfusion.

Adult↗
PubMed2000

IVIG-bound IgG and IgM cloned by phage display from a healthy individual reveal the same restricted germ-line gene origin as in autoimmune thrombocytopenia.

Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigate this, we cloned previously a large number of phage displayed IgG Fab fragments derived from three patients with autoimmune thrombocytopenia (AITP) that were specifically bound by IVIG molecules. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used germ-line gene segments of all IVIG-bound Fabs were identical to those observed for many other autoantibodies. Particularly, the loci 3-30 or 3-30/3-30. 5, 3-23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (VH) and light chain V region (VL), respectively. This suggested a specific interaction of IVIG molecules with B cells that present B cell receptors derived from these germ-line genes. In the current study we determined the genetic origin of IVIG-reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ-line origins as in AITP was observed. Because 3-30 and 3-23 are the most frequently rearranged VH germ-line gene segments among human B cells, our results suggest that this favoured anti-idiotypic interaction may have an important role for the development and control of the normal B cell repertoire.

Adult↗