Electrophysiological effects of dridocainide on isolated canine,guinea-pig and human cardiac tissues

The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel class I antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibres and papillary muscle preparations obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6–2 mol/l) decreased the maximum velocity of action potential upstroke (V_max) in a frequency-dependent manner, although marked differences were observed in its effects in Purkinje fibre and ventricular muscle preparations. In canine Purkinje fibres, action potential duration measured at 50% and 90% of repolarization was decreased, while action potential duration measured at 10% of repolarization was increased by dridocainide. In addition, the plateau of the action potential was depressed by the drug. These changes in action potential configuration were not observed in guinea pig or human papillary muscles. The offset kinetics of the dridocainide-induced V _max block were different in Purkinje fibres and in ventricular muscle: the slow time constant of recovery of V _max was estimated to be 2.5 s in dog Purkinje fibre and 5–6 s in human and guinea-pig papillary muscle. In guinea-pig papillary muscle, the rate of onset of the V _max block was 0.15 and 0.2 per action potential in the presence of 0.6 and 2 mol/l dridocainide, respectively. Dridocainide also decreased the force of contraction in this preparation. On the basis of the present results, dridocainide appears to posess mixed class LC and LA properties, with LC predominance in human and guinea-pig ventricular muscle. Present results also indicate that results of conventional classification of class I drugs may depend on the parameters chosen, as well as on the preparation selected.     

Presence of antibodies to human herpesvirus type 6 and 7 in Hungarian children]

Prevalence of antibodies to variants HHV-6A and B as well as HHV-7, the time of primary infections are not know in Hungarian children. Therefore, antibodies to these viruses were studied in 21 healthy children aged between 6 and 18 months. Lymphoid cultures were infected with standard virus strains for indirect immunofluorescence. IgM, IgG and high avidity IgG after 8M urea treatment were quantified in serial dilutions of sera. It was established that, three of 13 boys had low level (1:20) IgG or IgM antibodies to HHV-6A, but all girls were negative. With exception of one girl and one boy, all had antibodies to HHV-6B in different titres (1:20 to 1:640 by immunofluorescence), in 9 cases only IgM, in further 4 cases only low avidity IgG were detected. Children studied gradually acquired symptom-free HHV-6B infection between age of 8 and 18 months. Antibodies to HHV-7 were found in 3 boys and one girl before their age of 12 months, but the majority were infected after that age. Approximately three quarters of children acquired either HHV-6B or HHV-7 before age of 18 months. More than half of the children were infected with HHV-6B prior to HHV-7. Antibody level to HHV-6B was slightly higher in boys, while that to HHV-7 was higher in girls. In Hungary, childhood infection with HHV-6A seems to be a very rare event. Epidemiology of HHV-6B primary infection is similar to that of industrial countries, while that of HHV-7 resembles data of developing world: onset of antibodies occurs 1 or 2 years earlier than in the industrial nations.     

An analytical model of a kilovoltage beam phase space.

Our aim in this project was to quantify a kilovoltage beam phase space for use in dose calculations. The phase space was modeled by incorporating the following analytically derived x-ray beam production properties: the intensity variation due to the heel effect, the energy variation due to the differing amount of target material traversed by the photons, and the finite source size. The initial energy spectrum used was generated using a computer program. A Monte Carlo code was adapted in order to examine the validity of the calculated phase space. Dose distributions calculated using the modeled phase space for 10x10 and 20x20 cm2 fields show agreement with experimental values to within 2% and 4%, respectively, for the central 80% of the field size. Within the field but outside this range a maximum of 6% difference (for the 20x20 cm2 field) was observed, however, these values were in a region of sharp gradient and hence small geometric shift. The "tails" of the profiles were underpredicted by up to 6%. Due to uncertainties in experiment (3%) and Monte Carlo (1.5%), the modeled phase space is deemed acceptable for phantom and in-vivo dosimetric calculations within the field boundaries.     

温血心停跳液与冷晶体心停跳液对狗心率变异性的影响

为探讨体外循环（ＣＰＢ）导致心脏植物神经系统（ＣＡＳ）损伤的机理,了解温血心停跳液能否防止ＣＰＢ后心率变异性（ＨＲＶ）的降低,采用对照方法观察了温血心停跳液与冷晶体心停跳液对狗ＨＲＶ的影响。结果显示：ＣＰＢ后温血心停跳液组（ＷＢ组）和冷晶体心停跳液组（ＣＣ组）的全频谱（ＴＰ）、低频（ＬＦ）和高频（ＨＦ）均较术前明显降低（Ｐ＜０．０５）,而且ＣＣ组比ＷＢ组降低更明显（Ｐ＜０．０５）,但ＬＦ／ＨＦ在组内及组间均无明显变化（Ｐ＞０．０５）。ＣＰＢ后２４小时平均心率（ＭＨＲ）明显增加（Ｐ＜０．０５）,且ＣＣ组高于ＷＢ组（Ｐ＜０．０５）。本研究表明：采用温血心停跳液或冷晶体心停跳液的ＣＰＢ不会干扰ＣＡＳ平衡,但均能使ＨＲＶ降低,温血心停跳液不能防止ＨＲＶ损害。     

A pilot study on the antibodies to HHV-6 variants and HHV-7 in CSF of MS patients

In the possible role for human herpesviruses (HHV) in the pathogenesis of multiple sclerosis (MS) neither clear distinction between the two variants of HHV-6, nor the involvement of HHV-7 have been described. Therefore, we quantitated HHV-6 variant specific and HHV-7 reacting antibodies in the CSF of 13 patients with MS or other neurological disorders by ELISA. Predominance in the positivity of IgG (67%) and IgM (44%) to HHV-6B over that of IgG (44%) with no detectable IgM to HHV-6A, and no antibodies to HHV-7 were found in the CSF of MS patients. None of these antibodies were found in the CSF of controls. This suggests that, intrathecal chronic active or primary HHV-6B infection might contribute to MS progression, while the local effects of HHV-6A and HHV-7 seem to be less important.     

Nerve growth factor and its high-affinity receptor in chronic pancreatitis

OBJECTIVE: To study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP). SUMMARY BACKGROUND DATA: Chronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves. METHODS: Nerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters. RESULTS: By Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p < 0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p < 0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84). CONCLUSION: Activation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.     

Iliorenal bypass for the treatment of type-3 Takayasu's disease. A case report with 10-year follow-up

The case of a 16-year old female with severe renovascular hypertension resulting from type-3 Takayasu's arteritis is reported. The entire thoracic and abdominal aorta was affected by an active inflammatory process and all its branches were stenotic or occluded. After the early failure of a percutaneous balloon angioplasty of the left renal artery, an iliac to renal artery bypass graft using a reversed autologous saphenous vein was performed through a retroperitoneal tunnel The patient is asymptomatic and the graft is patent at 10-year follow-up.