PubMed Health⌕ Search

Biomedical subjects

F Hartmann

Publications and source records attributed to F Hartmann.

At least 37 records · Page 2Linked to original sources
PubMed2001

Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: role of infusion schedule and costimulation with cytokines.

The natural killer cell-activating anti-CD16/CD30 bispecific monoclonal antibody (BiMAb) had shown efficacy in a Phase I/II trial of refractory Hodgkin's disease (HD). To gain additional information on clinical efficacy and to investigate the effects of different application schedules and the concomitant application of cytokines, we performed a second randomized pilot trial using this BiMAb in patients with refractory HD. Patients received 4 x 25 mg HRS-3/A9 either as a continuous infusion for 4 days or as a 1-h infusion every other day. In case of an objective response, retreatment was attempted after 4 weeks; in case of stable disease (SD), a second course was given after prestimulation with interleukin 2 and followed by granulocyte macrophage colony-stimulating factor s.c. A total of 16 heavily pretreated patients received one to four BiMAb courses. Overall, we observed one complete remission and three partial remissions lasting 5-9 months (three of four of these responses occurred after continuous BiMAb infusion) and four cases of SD for 3 to >6 months. Interleukin 2 pretreatment before the second BiMAb course resulted in a significant increase of circulating natural killer cells in all five patients treated. This coincided with the conversion of two cases of SD into one complete remission and one partial remission. HRS-3/A9-related side effects consisted of mild fever in only six patients. In summary, this second trial confirmed the antitumor efficacy of this BiMAb against HD and the minor toxicity of this BiMAb. Coadministration of cytokines might contribute to an augmented antitumor activity, and additional clinical trials are warranted to optimize this novel treatment modality.

Adult↗
PubMed2000

Heart rate variability in patients with acute myocardial infarction undergoing primary coronary angioplasty.

Depressed heart rate variability (HRV) has been associated with adverse outcome during and after acute myocardial infarction (AMI). The effects of reperfusion in AMI on the course of HRV have not been well characterized as yet. We analyzed 123 consecutive patients with a first AMI who underwent successful reperfusion (Thrombolysis In Myocardial Infarction grades 2 and 3) by primary percutaneous transluminal coronary angioplasty (PTCA). Time- and frequency-domain HRV was measured from 24-hour Holter monitoring, which began at hospital admission. Mean RR interval increased significantly after successful PTCA. Reperfusion immediately caused an immediate transient depression of HRV, which was followed by a significant increase of HRV. Quantitative markers of sympathetic activity and sympathovagal balance, such as SD of the averages of NN intervals in all 5-minute segments, and low- and/or high-frequency ratio continuously decreased within the observation period. Patients with anterior AMI exhibited the same pattern of temporal changes of HRV, with, however, lower absolute values for HRV and mean RR interval than patients with non-anterior AMI. Subgroup analysis in 21 patients with reperfusion > 12 hours after onset of pain showed that the biphasic profile of HRV and the marked increase of mean RR interval was absent. Furthermore, in patients with late reperfusion, HRV was significantly lower compared with those with early reperfusion. Thus, timely reperfusion in AMI leads to a biphasic effect on autonomic tone, characterized by a transient suppression, followed by a significant activation of the vagal tone, as well as an attenuation of sympathetic activity. Recovery of HRV may contribute to the benefits of early reperfusion in AMI.

Adult↗
PubMed2000

Immune recruitment by bispecific antibodies for the treatment of Hodgkin disease.

For the treatment of Hodgkin lymphoma, bispecific monoclonal antibodies (bi-mAbs) were established which recognize the Hodgkin-associated CD30 antigen with one arm and the CD3 or CD28 antigen on T lymphocytes or the CD16 antigen on natural killer (NK) cells with the second arm. The NK cell-activating alpha-CD16/CD30 antibody was able to retarget human NK cells toward CD30- target cells and induce their lysis. Sixty percent of Hodgkin tumor-bearing severe combined immunodeficient mice responded to a combined treatment with bi-mAb and human NK cells, leading to a final cure rate of 20%. T cell-activating bi-mAbs were more effective, resulting in the cure of all mice treated. The in vivo administration of both alpha-CD3/CD30 and alpha-CD28/CD30 antibodies resulted in the specific activation of resting human T cells infiltrating the CD30+ Hodgkin tumors. Tumor-infiltrating lymphocytes in the group of mice treated with both T cell-activating bi-mAbs expressed high levels of cytokines and cytotoxic molecules such as perforin and the cytotoxic serine esterases granzyme A and B. More importantly, activated T cells did not home to CD30 tissue and did not enter the circulation. Encouraged by these preclinical data, 15 patients with treatment-refractory Hodgkin lymphoma were included in a phase I/II dose-escalation study and treated four times every 3 or 4 days with increasing doses of the alpha-CD16/CD30 bi-mAb ranging from 1 mg/m2 to 128 mg/m2. No dose-limiting toxicity occurred even at the highest doses. Of these 15 patients, one had a complete response, one a partial response, three a mixed response, two stable disease, and eight patients had progressive disease. Treatment with immunological effector cell-recruiting bi-mAbs is a promising new approach to the treatment of Hodgkin disease refractory to standard therapy.

Animals↗
PubMed2000

Initiation of humoral and cellular immune responses in patients with refractory Hodgkin's disease by treatment with an anti-CD16/CD30 bispecific antibody.

Fifteen patients with refractory Hodgkin's disease were treated in a dose-escalation trial with the bispecific monoclonal antibody (bi-mAb) HRS-3/A9, which is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's-associated CD30 antigen. Treatment consisted of four cycles of four bi-mAb infusions given over 1 h every 3-4 days at different dose levels ranging from 1 mg/m2 to 64 mg/m2. Measurable serum levels (above 0.1 microgram/ml) of circulating bi-mAb could be detected in patients treated with doses above 4 mg/m2, reaching peak levels of 9.5 micrograms/ml immediately after the end of antibody infusion on the highest dose level. Bi-mAb elimination corresponded to second-order kinetics with a terminal half-life time (t1/2, beta) of 28-32 h. Bi-mAb treatment induced the occurrence of human anti-(mouse Ig) antibodies (HAMA) in 6 out of 13 patients initially testing negative. All 6 patients not only developed anti-isotypic anti-(mouse Ig) but also anti-idiotypic and anti-anti-idiotypic antibodies. While no consistent changes of peripheral blood cell counts, or of any lymphocyte subpopulation including natural killer (NK) cells, has been observed, 4 out of 6 evaluable patients treated with doses of at least 4 mg/m2 showed an increase of NK cell activity within 2 weeks after treatment, which lasted for a maximum of 12 weeks. Circulating amounts of soluble CD30 antigen could be detected in the serum of 6 patients. However, like the results and time courses of all the other immunological parameters evaluated, this was not predictive for treatment outcome.

Animals↗
PubMed2000

Clinical and angiographic outcome of patients with acute inferior myocardial infarction.

OBJECTIVES: This study sought to determine the procedural success and the in-hospital outcome after primary coronary angioplasty in patients with acute inferior myocardial infarction and right ventricular involvement (RVI). BACKGROUND: RVI represents an easily detectable, highly prevalent subset of acute inferior infarction associated with poor outcome even in the era of thrombolysis. Primary PTCA may offer advantages in patients with inferior infarction involving the right ventricle. METHODS: Primary coronary angioplasty with optimal stenting was performed in 87 of 88 consecutive patients presenting within 24 hours after onset of acute inferior myocardial infarction. On the basis of right precordial ST segment elevations at admission, patients were classified into those without (n=61) and those with RVI (n=27). The patients were followed prospectively for angiographic success at 10 days and for in-hospital clinical outcome. RESULTS: Baseline characteristics including age, severity of coronary artery disease, proportion of stent implantation, and occurrence of cardiogenic shock were comparable. Patients with RVI had larger infarct sizes (lactate dehydrogenase level: 962 vs 580 U/l, P=0.03), developed more often complete atrioventricular block (18.5 vs. 2%, p=0.0038), needed more often parasympatholytics (48.1 vs 18.8%, p<0.001), and had a substantially higher incidence of the Bezold-Jarisch reflex (29.6 vs 6.6%, p<0.01) following reperfusion. Success of recanalization therapy acutely and at 10 days, as well as in hospital mortality were similar in patients with and without RVI (88.5 vs. 85.2%, 79.3 vs. 84.7%, 7.4 vs 9.8%). However, patients with RVI revealed a greater lumen gain acutely after PTCA (2.49 vs. 2.13 mm, p=0.025) and experienced less frequently major cardiac events (14.8 vs. 36.1%, p=0.04) which included reinfarction, re-ischemia, coronary bypass grafting, stent thrombosis, and cardiac death. In addition, procedural success was established more rapidly (fluoroscopy time: 10 vs 15 min., p=0.032) and with less contrast material (242 vs 295 ml, p=0.015) in patients with RVI. This is probably due to the more proximal location (84.6 vs 6.6%, p<0.0001) and the larger reference diameter (3.17 vs. 2.79 mm, p=0.03) of the occluded right coronary artery. CONCLUSIONS: Primary PTCA is an appropriate reperfusion strategy in patients with RVI. Further comparative studies are required to compare the effectiveness of primary PTCA with early thrombolytic therapy in this high risk setting.

Aged↗
PubMed2000

[Intracoronary stent implantation and left ventricular function in primary PTCA in acute myocardial infarct].

In acute myocardial infarction intracoronary stenting is superior to PTCA regarding interventional success and occurrence of cardiac events. It is, however, uncertain whether myocardial function also improves with stenting. We, therefore, assessed angiographic parameters of myocardial function in patients with acute myocardial infarction who were treated with primary PTCA and received additional stenting in case of an unsatisfactory angiographic result (provisional stenting). Nineteen patients with acute myocardial infarction, in whom a "stent-like" angiographic result was achieved by PTCA alone, were compared with an equal number of patients receiving provisional stenting. The groups were exactly matched with respect to severity of coronary heart disease, segment of coronary occlusion, Killip class, and TIMI flow after intervention. We only included patients without inhospital cardiac events, in whom repeat angiography after ten days revealed a patent target vessel. There were no differences between both groups regarding age, gender, enzymatic infarction size, duration of ischemia (< or = 12 h), and cardiac risk factors. Myocardial function was assessed by ventriculography and was analyzed quantitatively by the center-line method. The group treated by intracoronary stenting showed a significantly improved ejection fraction (60.3 +/- 2.1% vs. 52.6 +/- 2.9%). All parameters of regional wall motion also indicated significantly less functional disturbance in the stented group compared to PTCA alone (circumferential extend of hypokinesia: 7.4 +/- 2.4% vs. 16.1 +/- 3.4% chords, maximum hypokinesia in the central infarct region: -0.98 +/- 0.20 vs. -1.52 +/- 0.15 SD, severity of regional hypokinesia: 7.3 +/- 2.6 vs. 21.9 +/- 5.4 area). In summary, these results in patients undergoing primary PTCA in acute myocardial infarction indicate that intracoronary stenting is superior to PTCA alone with respect to myocardial recovery, even if an angiographically "stent-like" result can be achieved. Probably, stenting results in a more efficient reperfusion.

Aged↗
PubMed2000

Risk factors for early reocclusion and luminal renarrowing in patients with acute coronary syndromes treated by direct PTCA with provisional stenting.

UNLABELLED: Angioplasty in acute coronary syndromes is complicated by a high rate of early vessel reocclusion and restenosis. Therefore, it is recommended to achieve a "stent-like" result by percutaneous transluminal coronary angioplasty (PTCA) or otherwise use coronary stenting (provisional stenting). This study sought to determine angiographic and patient-related factors that are associated with early target vessel reocclusion or luminal renarrowing after coronary intervention in acute coronary syndromes (ACS). In an observational prospective study we investigated 161 patients with ACS (acute myocardial infarction and unstable angina) submitted to PTCA. In 140 patients a follow-up angiography after 10 days was obtained. All angiograms were quantitatively evaluated by computerized measurements. Target vessel reocclusion and early luminal renarrowing was observed in 10 patients (7.1%) and 19 patients (13.6%), respectively. Using univariate analysis, significant risk factors (P < 0.05) for early reocclusion and renarrowing were diabetes mellitus (relative risk [RR] 6.1 and 5.0), arterial hypertension (RR 7.7 and 3.3), postprocedural lesion length > or = 2.5 mm (RR 6.8 and 7.1), postprocedural minimal lumen diameter < or = 2.5 mm (RR 9.0 and 5.8), residual stenosis > or = 25% (RR 4.8 and 3.5) and absence of stents (RR 4.1 and 3.2). Moreover, in multivariate analysis hypertension and postprocedural lesion length could be identified as independent risk factors for reocclusion and renarrowing. Diabetes mellitus was found to be an independent risk factor for renarrowing. CONCLUSIONS: In a consecutive series of patients with ACS undergoing PTCA with provisional stenting the occurrence of early target vessel reocclusion and luminal renarrowing is lower than previously reported for this subset of patients treated by PTCA alone. Adverse outcome is related to absence of stents, angiographic factors (residual stenosis, lesion length, minimal lumen diameter after procedure) and patient-related factors such as diabetes and hypertension.

Acute Disease↗
PubMed2000

Gene-modified spontaneous Epstein-Barr virus-transformed lymphoblastoid cell lines as autologous cancer vaccines: mutated p21 ras oncogene as a model.

The transfer of genes coding for tumor antigens (Ags) into Ag-presenting cells is a promising strategy to develop cancer vaccines for patients not limited by major histocompatibility complex restriction. To test whether autologous lymphoblastoid cell lines (LCL) can be used as an alternative to dendritic cells for Ag presentation, we established LCL by spontaneous growth in cyclosporin-containing medium in vitro (SP-LCL). SP-LCL, which have an advantage over B95-8-transfected LCL in that they carry no risk of introducing a new infectious agent when used for vaccination, served as a permanent source for transfection with an episomal Epstein-Barr virus-based expression vector encoding the Ki-ras p21 oncogene carrying a point mutation at codon 12 (muRas) as a model tumor Ag. The ability of muRas-transfected SP-LCL (muRas-LCL) to induce immunoreactivity was determined in vitro. After electroporation with an optimized protocol, muRas-LCL expressed mutated ras peptides for a considerable period of time (at least 8 weeks) on the cell surface. The transfection procedure did not affect the expression of the costimulatory molecules B7.1, intercellular adhesion molecule-1, and leukocyte function associated Ag-3 by SP-LCL. muRas-LCL were able to induce muRas-specific cytotoxic T lymphocytes from three of three healthy donors and one of one patient with pancreatic carcinoma. Our results suggest that the gene transfer of muRas sequences to SP-LCL leads to an endogenous processing of this Ag in the major histocompatibility complex class I pathway and to functional presentation of antigenic peptides to CD8+ T lymphocytes. Autologous SP-LCL can serve as an unlimited renewable source for autologous cellular vaccines and appear to be good candidates as presenters for a wide range of human tumor Ags.

B7-1 Antigen↗
PubMed2000

Differential effects of carvedilol on norepinephrine release in normoxic and ischemic heart.

Carvedilol is a beta-adrenoceptor antagonist with multiple actions, which may contribute to superior cardioprotection in heart failure and myocardial infarction. We hypothesized that carvedilol may modulate presynaptic norepinephrine release in the heart. Therefore, we compared the effects of carvedilol (racemate and both enantiomers) and beta1-selective as well as nonselective beta-adrenoceptor blockers on norepinephrine release in isolated perfused rat hearts under normoxic and brief ischemic conditions. Exocytotic release of endogenous norepinephrine was induced by paired electric field stimulations to compare the release before (S1) and after (S2) beta-adrenoceptor blocker application. Metoprolol, bisoprolol, and pindolol (0.1-10 microM) had essentially no effect on exocytotic norepinephrine release under normoxic and ischemic conditions. In contrast, carvedilol exerted a biphasic concentration-response curve (increase followed by suppression) on norepinephrine release. The increase in norepinephrine release was more pronounced with R-carvedilol than with S-carvedilol, indicating an effect independent from beta-receptor antagonism. During ischemia, the facilitatory effect of carvedilol on norepinephrine release was lost, resulting in a concentration-dependent suppression of the release. These results indicate that carvedilol in contrast to classic beta1-selective and -nonselective beta-adrenoceptor blockers has pronounced effects on cardiac norepinephrine release with a remarkable difference between normoxic and ischemic conditions. Whereas a facilitation of norepinephrine release prevailed in normoxia, we observed a suppression of the release in ischemia. It remains to be established whether this unique action of carvedilol on cardiac sympathetic neurotransmission is of clinical relevance.

Adrenergic beta-Antagonists↗
PubMed2000

New Pathways in Plastics Recycling.

The catalytic degradation of polyethylene to short-chain hydrocarbons is possible with zirconium hydride compounds (see picture), and represents the first step in the reversal of Ziegler - Natta polymerization. Thus, even in the case of polyolefins the important target of plastics recycling, the recovery of reusable monomers from polymer waste, may be achieved.

Journal Article↗
PubMed1999

Methicillin-resistant Staphylococcus aureus infections in 11 dogs.

Methicillin-resistant Staphylococcus aureus infection was identified in 11 dogs. The infection was associated with surgical treatment especially orthopaedic surgery. Infection after traumatic wounding, and recurrent pyoderma was also seen. Oral antibiotic treatment improved or resolved the infection in nine of the 11 dogs, although the methicillin-resistant isolates were susceptible to relatively few antibiotics.

Animals↗
PubMed1999

Is glutamine essential for the maintenance of intestinal function? A study in the isolated perfused rat small intestine.

Glutamine has received considerable interest as a gut-targeted nutrient due to its proposed key role in the maintenance of intestinal structure and function. We used a preparation of isolated vascularly perfused rat small intestine to investigate whether glutamine is essential for the maintenance of intestinal function. When glutamine was available, arterial glutamine was extracted at 15 +/- 2%, and net uptake was -89 +/- 5 nmol min-1 g-1. Nitrogenous metabolites ammonia, alanine, and citrulline (41 +/- 7, 41 +/- 4, and 11 +/- 2 nmol min-1 g-1, respectively) were released into the venous perfusate, but only ammonia was also excreted into the lumen (36 +/- 3 nmol min-1 g-1). In the absence of exogenous glutamine alanine release was halved and that of citrulline and ammonia nullified. Additional inhibition of glutamine synthetase yielded the same results. In all cases variables of tissue function were fully maintained also in the absence of exogenous and/or endogenous glutamine. The inhibition of glutaminase/amidotransferase reactions, however, was accompanied by a reduction in glutamine consumption and a graded deterioration in tissue function. In conclusion, glutamine seems to be dispensable as a metabolic fuel to be fully oxidized by the mucosa. However, the inhibition of major glutamine consuming pathways was associated with impaired tissue function and viability. Therefore the role of intestinal glutamine metabolism seems to be threefold: (a) providing affluent amounts of nitrogen precursors for mucosal anabolic pathways to maintain intestinal structure and function, (b) feeding the liver with an optimal substrate mix, and (c) providing citrulline and thereby arginine for the whole organism.

Alanine↗
PubMed1999

Effects of vascular or luminal administration and of simultaneous glucose availability on glutamine utilization by isolated rat small intestine.

This study examined whether the route of glutamine administration and the simultaneous availability of glucose affect intestinal glutamine metabolism. We measured net substrate exchange rates of glutamine and its nitrogenous products in the isolated vascularly and luminally perfused rat small intestine (a) as a function of glutamine provision from either the vascular or the luminal or simultaneously from both sides and (b) as a function of simultaneous availability of glucose from various routes. When glutamine was provided from the lumen, only 19-32% of absorbed glutamine appeared intact in the venous effluent, but the release of metabolic products was 170 +/- 5 nmol N min-1 g-1. This measure of intestinal glutamine metabolism was unchanged when glutamine was available only in the vascular perfusate (164 +/- 6 nmol N min-1 g-1). It increased, however, to 271 +/- 14 nmol N min-1 g-1 (P < 0.001) when glutamine was available simultaneously from both the luminal and the vascular perfusate. Glutamine consumption (-110 +/- 6 vs. -70 +/- 5 or -91 +/- 5 vs. -73 +/- 7 nmol min-1 g-1; P < 0.05 each) and the production of citrulline (11.4 +/- 0.7 vs. 10.0 +/- 0.8 or 9.8 +/- 0.5 vs. 7.8 +/- 0.4 nmol min-1 g-1; P < 0.05 each) or ammonia (124 +/- 7 vs. 88 +/- 4; P < 0.01 or 78 +/- 4 vs. 68 +/- 5 nmol min-1 g-1) decreased when glucose (vascular or luminal perfusate) became available in addition to glutamine. We conclude that glutamine is utilized by the small intestine very efficiently regardless of the route of administration being enteral or parenteral. The two routes can be used interchangeably to provide the intestinal mucosa with glutamine. Glucose and glutamine may partially substitute each other, most likely for the purpose as a metabolic fuel.

Ammonia↗
PubMed1999

Regional patterns of myocardial sympathetic denervation in dilated cardiomyopathy: an analysis using carbon-11 hydroxyephedrine and positron emission tomography.

OBJECTIVE: To assess presynaptic function of cardiac autonomic innervation in patients with advanced congestive heart failure using positron emission tomography (PET) and the recently developed radiolabelled catecholamine analogue carbon-11 hydroxyephedrine (HED) as a marker for neuronal catecholamine uptake function. DESIGN AND PATIENTS: 29 patients suffering from dilated cardiomyopathy with moderate to severe heart failure were compared with eight healthy controls. Perfusion scan was followed by HED dynamic PET imaging of cardiac sympathetic innervation. The scintigraphic results were compared with markers of disease severity and the degree of sympathetic dysfunction assessed by means of heart rate variability. RESULTS: In contrast to nearly normal perfusions, mean (SD) HED retention in dilated cardiomyopathy patients was abnormal in 64 (32)% of the left ventricle. Absolute myocardial HED retention was 10.7 (1.0)%/min in controls v 6.2 (1.6)%/min in dilated cardiomyopathy patients (p < 0.001). Moreover, significant regional reduction of HED retention was demonstrated in apical and inferoapical segments. HED retention was significantly correlated with New York Heart Association functional class (r = -0.55, p = 0. 002) and ejection fraction (r = 0.63, p < 0.001), but not, however, with plasma noradrenaline concentrations as well as parameters of heart rate variability. CONCLUSIONS: In this study, using PET in combination with HED in patients with dilated cardiomyopathy, not only global reduction but also regional abnormalities of cardiac sympathetic tracer uptake were demonstrated. The degree of abnormality was positively correlated to markers of severity of heart failure. The pathogenetic mechanisms leading to the regional differences of neuronal damage as well as the prognostic significance of these findings remain to be defined.

Adult↗
PubMed1998

[The languages of pains].

The plural words "languages" and "pains" emphasize the variety of the conditions and the locations from which pain emerges of the conduction and processing of pain stimuli in the central nervous system, and of the subjective gestalt of pain feeling. The personal expression in speaking, facial expression, gestures, and posture is, like words, a mixture of measurable and understandable elements. The verb "to hurt" should therefore be understood and used transitively and intransitively, passively and actively by suffering and by acting-forming. The concept--called isopathy--of the analysis of the conditions of possible understanding of the affective expressions of a person by an empathic-participating observer and listener should be applied to the understanding of pains in one individual person.

English Abstract↗
PubMed1998

Isolation and analysis of two strongly transforming isoforms of the Epstein-Barr-Virus(EBV)-encoded latent membrane protein-1 (LMP1) from a single Hodgkin's lymphoma.

Two genes encoding the latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) were isolated from a single case of Hodgkin's disease (HD) and were tested for their biological activities. The LMP1 gene from the Reed-Sternberg cells contained point mutations relative to the prototype LMP1 gene, leading to amino-acid exchanges. The LMP1 gene from passenger lymphocytes showed identical point mutations, but also had an in-frame insertion of 132 base pairs within the 33-bp repeat region. This insert encoding 44 amino acids contained the sequence PSQQS, corresponding to the potential TRAF-binding motif PXQXT/S. When compared to the B95.8 gene, both HD-derived LMP1 genes showed an increase in the transformation of Rat-1 rodent fibroblasts. The transforming ability of the LMP1 gene with the insertion was greater than that of the other HD-derived LMP1, and was comparable with the highly transforming LMP1-Cao gene derived from a nasopharyngeal carcinoma. The HD-derived genes stimulated expression of the cell-surface markers, CD40 and CD54, similarly to the LMP1-B95.8 gene, while the LMP1-Cao gene had a significantly reduced ability to induce these proteins. In contrast, the LMP1-Cao transactivated an NF-kappaB-response element more efficiently than did the HD-derived genes. Transfer of the 132-bp insert alone into the B95.8 gene did not increase its transforming activity to the LMP1-Cao level, indicating that additional mutations in the LMP1 gene are necessary for modulating this function.

Adult↗
PubMed1998

Regional in vivo and in vitro characterization of autonomic innervation in cardiomyopathic human heart.

BACKGROUND: In contrast to healthy volunteers, regional differences of cardiac autonomic innervation have been described through the use of C11-hydroxyephedrine positron emission tomography (HED-PET) in the left ventricles of patients with dilated cardiomyopathy. The goal of the present study was to correlate HED-PET images with biochemical analysis of tissue samples. METHODS AND RESULTS: To assess the significance of altered HED uptake, we used HED-PET to examine eight patients with dilated cardiomyopathy before heart transplantation. After explantation, we measured the density and affinity of uptake1 (3H-mazindol binding) and tissue norepinephrine content as markers of presynaptic function, and we determined beta-receptor density and affinity (3H-CGP 12177 binding) in the corresponding areas of the same patients. The density of uptake1 and norepinephrine content showed marked regional variation, with highest values in the anterior septal wall and lowest in inferoapical and apical areas. Both parameters were closely correlated (r=.65, P=.05). Similarly, uptake1 density or norepinephrine content and HED retention (PET) showed clear correlations (r=.63 and .60, respectively). Uptake1 affinities did not vary significantly and were not correlated to the other parameters. Beta-Adrenergic receptor density showed some, albeit less pronounced, regional variation and was weakly correlated to uptake1 density and local HED retention (r=.38 and .31, respectively). CONCLUSIONS: Uptake1 density and tissue norepinephrine content showed marked regional variation in cardiomyopathic left ventricles. HED-PET is significantly correlated to the density but not the affinity of uptake1 sites in the human heart, suggesting either loss of neurons or downregulation of uptake1 in dilated cardiomyopathy. HED-PET is a valuable marker for alterations of the presynaptic sympathoadrenergic system in humans.

Adult↗