Impaired neurotrophin-3 signaling in a TrkAII mutant associated with hereditary polyneuropathy.

Mutations of the neurotrophin receptor tyrosine kinase TrkA (NTRK1) cause congenital sensory neuropathy with insensitivity to pain and anhydrosis (CIPA), also called hereditary sensory and autonomous neuropathy type IV (HSAN IV). The neuronal splice variant of TrkA, TrkAII, binds two neurotrophin ligands, nerve growth factor (NGF) and neurotrophin-3 (NT3). Several studies have demonstrated NGF signaling defects in CIPA-associated TrkA mutants. To date, however, no study has examined NT3/TrkA signaling of CIPA mutants. As the interaction of NT3 and TrkA temporally and spatially precedes the interaction of NGF with TrkA, we examined the signaling of NT3 in a CIPA-associated TrkA mutant. Intriguingly, we revealed remarkable defects in NT3-induced ERK1/2 phosphorylation and neurite outgrowth. The impact of our findings is twofold. First, our data call for a re-examination of previously described TrkAII CIPA mutants regarding their NT3 signaling capability. Second, we envision that CIPA/HSAN IV polyneuropathies might fall into two different subgroups: one with diminished NT3/TrkAII signaling, in which axons actually do not reach their targets, and a second group with sufficient NT3/TrkAII signaling but diminished NGF/TrkAII signaling, in which axons do reach their targets, yet degenerate after successful target engagement.

[Immunologic studies in patients with dilated cardiomyopathy]. / Immunologische Untersuchungen bei Patienten mit dilatativer Kardiomyopathie.

In 10 cases of dilated cardiomyopathy the HLA-loci (A, B, C, DR) and marker expression on lymphocytes were studied. In this group the T4/T8-ratio was decreased and interleukin-2-expression was increased in relation to normals or patients with chronic coronary heart disease, respectively. 9 patients had the HLA-A1 or HLA-A2-locus in their siblings. In correlation analysis between immunological and hemodynamic parameters a good correlation of the number of NK-cells to the ejection fraction (r = 0.79) and negative correlation of helpercells (CD4) to the cardiac output were found (r = -0.80). The results of this attempt suggest an immunological pathogenesis of the dilated cardiomyopathy.

[Echocardiography evaluation of the surgical result in hypertrophic obstructive cardiomyopathy]. / Echokardiographische Beurteilung des Operationsergebnisses bei hypertrophisch obstruktiver Kardiomyopathie (HOCM).

Despite the small cohort of patients with HOCM could be shown that the routine application of the conventional and colour Doppler echocardiography after myectomy is indicated and reasonable. The modern echocardiography is able to assess with high individual reliability the therapeutic aim of myectomy--drastic reduction of the intracavitary pressure gradient. Significant changes were also the results in the systolic acceleration time (TPVS/LVET standardized on the LVET and the diastolic measuring parameters VmaxE, ATE and TVIE/TVIA), the importance of which is partly still fully open.

[Hypertrophic obstructive cardiomyopathy]. / Die hypertrophisch obstruktive Kardiomyopathie.

Today, with the help of modern echocardiographic techniques we are able not only to describe the characteristic changes when a HOCM is present and to determine the intracavitary pressure gradient, but also recognize the functional irregularities typical for the HOCM. Thus, the methodical progress of the echocardiography has essentially enlarged our knowledge about the pathophysiology of this clinical picture. Today, the echocardiography is the method of choice for the diagnostics of the HOCM and for the judgment of the functional consequences of therapeutic interventions.

[Emergency coronary surgery in patients with unstable angina pectoris. Results and place in the total concept of the treatment of this group of patients]. / Die dringliche Koronarchirurgie bei Patienten mit instabiler Angina pectoris. Ergebnisse und Stellenwert im Gesamtkonzept der Behandlung dieser Patientengruppe.

The urgent coronary surgery performed in patients with high risk unstable angina (rest pain greater than 48 h) shows still different results. We found in 57 urgent operated patients the same functional and clinical results as after elective bypass grafting. A higher in hospital mortality after urgent coronary surgery based on a higher number of grafts are occluded in the early postoperative period. The better prognosis concluded that the use of urgent coronary surgery is the therapy of choice in patients with refractory unstable angina pectoris.

[The relation of anthropometric parameters and echocardiography findings in the evaluation of left ventricular form and function in extreme obesity]. / Beziehungen zwischen anthropometrischen Parametern und echokardiographischen Befunden zur Beurteilung linksventrikulärer Form und Funktion bei extremer Adipositas.

For the characterization of the left-ventricular thickness of the wall, of the diameter and of the functional parameters in obesity in a short-term investigation on 18 extremely adipose female normotonics and 17 normotonics with normal weight the echocardiographic investigation in the M-mode in the short parasternal axis was performed. The women with overweight had a by 28% (p less than 0.001) greater fractional shortening, a by 8% (p less than 0.01) greater ejection fraction, a by 23% (p less than 0.05) greater stroke volume and a by 34% (p less than 0.001) greater cardiac output as well as a by 13% smaller left-ventricular end-systolic volume than normotonic women with normal weight. Index of stroke volume and cardiac output did not differ. The women with overweight had a significantly larger left-ventricular end-diastolic diameter and a thicker interventricular septum as well as a larger thickness of the left-ventricular posterior wall in the systole. The results allowed the conclusion that changed left-ventricular parameters both with regard to the form and to the function in obesity per se might be the expression of the physiological adaptation to an increased requirement and the borderlines to the transition into a disturbed left-ventricular function and development of a left-ventricular hypertrophy were not fixed. Long-term studies should bring further explanation concerning these problems.