A comparison of the adaptations of strains of Lymantria dispar multiple nucleopolyhedrovirus to hosts from spatially isolated populations.

The adaptation of pathogens to either their hosts or to environmental conditions is the focus of many current ecological studies. In this work we compared the ability of six spatially-distant Lymantria dispar (gypsy moth) multiple nucleopolyhedrovirus (LdMNPV) strains (three from eastern North America and three from central Asia) to induce acute infection in gypsy moth larvae. We also sequenced the complete genome of one Asian (LdMNPV-27/0) and one North American (LdMNPV-45/0) strain which were used for bioassay. We found that all of the North American virus strains, with the exception of one, demonstrated higher potency than the Asian virus strains, either in North American (Lymantria dispar) larvae or, in Asian (Lymantria dispar asiatica) larvae. Complete genome sequencing revealed two gene deletions in the LdMNPV-27/0 strain: the virus enhancin factor gene (vef-1) and the baculovirus repeated orf gene (bro-p). These deletions were not seen in the LdMNPV-45/0 strain nor in other American strains available in archiving systems. We also found deletions of the bro-e and bro-o genes in LdMNPV-45/0 strain but not in the LdMNPV-27/0 strain. The phylogenetic inference with an alignment of the 37 core gene nucleotide sequences revealed the close relationship of the LdMNPV-45/0 strain with other American strains accessed in GenBank (Ab-a624 and 5-6) while the LdMNPV-27/0 strain was clustered together with the LdMNPV-3054 strain (isolated in Spain) instead of predicted clustering with LdMNPV- 3029 (isolated in Asia). Our study demonstrated that first, different LdMNPV isolates from the same metapopulations of L. dispar exhibit little or no difference in the degree of virulence towards host larvae and second, that locality of host population is not an important driver of LdMNPV virulence. Virulence of LdMNPV is determined only by viral genetics. The genetic differences between North American and Central Asian virus strains are discussed.

Bone density in renal transplant recipients and in patients with chronic kidney disease: a follow-up study in children and adolescents.

AIMS: Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease. The purpose of this follow-up study was to compare the change of bone mineral density in patients with chronic kidney disease to those who have received the renal transplant. METHODS: The study included 47 children and adolescents: 16 with mild to moderate kidney disease, 14 on dialysis and 17 patients with renal transplant. At the baseline and follow-up visits, regular biochemistry, anthropometry and bone mineral density were measured. To minimize the effect of skeletal size, bone mineral apparent density (BMAD; g/cm3) was calculated. RESULTS: The mean height was below one standard deviation from reference values in patients on dialysis and in those with renal transplant. After correction for age, baseline and follow-up BMAD did not differ significantly between patients after transplantation and those with chronic kidney disease. The increase of BMAD between two measurements (mean period 16.0 +/- 4.4 months) was not significantly higher in patients with kidney transplant compared to those with chronic kidney disease. The significant predictors of BMAD were PTH in patients with chronic kidney disease and duration of steroid therapy in patients with renal transplant. CONCLUSIONS: The results showed that bone density in children and adolescents, even several years after kidney transplantation, did not significantly change over time comparing to patients with chronic kidney disease. Hyperparathyroidism and steroid therapy were the most important risk factors for the slow increase of bone density.

ECG body surface mapping changes in type 1 diabetic patients with and without autonomic neuropathy.

ECG body surface mapping (BSM) parameters in patients with diabetes mellitus Type 1 (DM1) are significantly different comparing to healthy non-diabetic subjects. Hypothesis that these changes are more pronounced in DM1 patients with autonomic neuropathy (AN) was tested. The parameters of BSM were registered by diagnostic system Cardiag 112.2 in 54 DM1 patients including 25 with AN and 30 control subjects. AN was diagnosed according to Ewing criteria when two or more Ewing tests were abnormal. In classic 12-lead ECG the heart rate was increased, QRS and QT shortened (p<0.01) and QT(C) prolonged in DM1 patients. The VCG measurement of QRS-STT angles and spatial QRS-STT angle showed non-significant differences. The absolute values of maximum and minimum in depolarization and repolarization isopotential, isointegral, isoarea maps were significantly different in DM1 patients in comparison with controls (p<0.01). The changes were more pronounced in DM1 patients with AN than in DM patients without AN (p<0.05). The QT duration measured in 82 leads of thorax was significantly shortened in 68 leads of both groups of DM 1 patients (p<0.01) when compared with controls. In 34 of them this shortening was more pronounced in DM1 patients with AN than in DM1 patients without AN (p<0.05). The results showed that the method of ECG BSM is capable to confirm the presence of autonomic neuropathy in diabetic patients.

ECG body surface mapping (BSM) in type 1 diabetic patients.

Diabetes mellitus is a risk factor of cardiovascular diseases. ECG of patients with diabetes mellitus type 1 (DM 1) shows tachycardia (block of parasympathetic innervation) and abnormal repolarization (increased QT interval and QT dispersion (QTd)) indicating a risk of ventricular tachycardia and sudden death in young people with DM 1. The aim of the present report was to measure 145 parameters of the heart electric field in 22 patients (14 men, 8 women) with DM 1 without complications (mean age 32.8+/-11.4 years) and in 22 controls (11 men, 11 women, mean age 30.1+/-3.4 years). The duration of diabetes was 13.9+/-7.8 years. The parameters were registered by the diagnostic system Cardiag 112.2 and statistically evaluated by the Student and Mann-Whitney test. Tachycardia (86.3+/-2.7 beats.min(-1)), shortening of both QRS (79.9+/-1.6 ms) and QT (349.0+/-5.9 ms) and increased QT dispersion (115+/-36 ms) were observed in DM 1 when compared with the controls (75.0+/-2.1 beats. min.(-1), QRS 89.9+/-2.7 ms, QT 374.0+/-4.4 ms, QTd 34.0+/-12.0 ms, p<0.01). The QTc was 415.2+/-4.1 ms in DM 1 and 401.4+/-6.6 ms in controls (NS). Other significant findings in DM 1 were: higher maximum of depolarization isopotential maps (DIPMmax) in the initial phase of QRS and less positive in the terminal phase, more negative minimum (DIPMmin) during QRS similarly as the minimum in depolarization isointegral maps (DIIMmin) and the minimum in isointegral map of the Q wave (Q-IIMmin), lower maximum in repolarization isopotential maps (RIPMmax) and less negative minimum (RIPMmin), more negative amplitude of Q wave (Q-IPMAM) and more pronounced spread of depolarization (activation time). Our results confirmed a decreased parasympathetic to sympathetic tone ratio (tachycardia, shortening of the activation time) and revealed different depolarization and repolarization patterns in DM 1. The differences in heart electric field parameters measured by the BSPM method in DM 1 and in the controls indicate the importance of ECG examination of diabetic patients type 1 in the prevention of cardiovascular diseases.

Temporal analysis and spatial mapping of Lymantria dispar nuclear polyhedrosis virus transcripts and in vitro translation polypeptides.

Genomic expression of the Lymantria dispar multinucleocapsid nuclear polyhedrosis virus (LdMNPV) was studied. Viral specific transcripts expressed in cell culture at various times from 2 through 72 h postinfection were identified and their genomic origins mapped through Northern analysis. Sixty-five distinct transcripts were identified in this analysis. Most viral transcripts were expressed late in infection, and originated from throughout the viral genome. Viral polypeptides expressed in infected 652Y cells were labeled with [35S]methionine and identified by autoradiography after separation by SDS polyacrylamide gel electrophoresis. Viral protein synthesis was found to occur in a sequential manner. Four proteins were identified in the early phase of viral replication (4-12 h p.i.), 24 proteins in the intermediate phase (12-24 h p.i.), and 5 proteins during the late phase (greater than 24 h p.i.). Cytoplasmic RNAs were isolated from LdMNPV infected cells at 16, 24, and 48 h p.i., and used for hybrid selections with overlapping DNA fragments that covered the entire LdMNPV genome. The selected RNAs were translated in vitro, and 61 distinct viral polypeptides were identified and their genomic origins mapped. Temporal and spatial transcription and translation maps of the LdMNPV genome were generated with these data, and the expression pattern of the LdMNPV genome was compared to that of the Autographa californica nuclear polyhedrosis virus.

Characterization of the replication cycle of the Lymantria dispar nuclear polyhedrosis virus.

The life cycle of the Lymantria dispar nuclear polyhedrosis virus (LdMNPV) was characterized through analysis of budded virus (BV) release, the temporal formation of polyhedra, the temporal transcription pattern of representative early, late, and hyper-expressed late genes, and the onset of DNA replication in the Ld652Y cell line. Transcripts from the LdMNPV immediate early gene G22 were detected 4 h post infection (h p.i.). The late and hyper-expressed late p39 capsid and polyhedrin genes were initially transcribed at approximately 20 and 24 h p.i., respectively. Viral DNA replication initiated at approximately 18-20 h p.i. Budded virus was released from infected cells between 24 and 36 h p.i., and polyhedra were first detected at approximately 48 h p.i.

Microbial conversion of steffimycin and steffimycin B to 10-dihydrosteffimycin and 10-dihydrosteffimycin B.

It has been shown that steffimycin (1) and steffmycin B (2) are reduced at the C-10 carbonyl by Actinoplanes utahensis, UC-5885 and Chaetomium sp., UC-4634, respectively. Using cell-free extracts of the latter organism, the optimum conversion time, pH, and enzyme concentration have been determined for the conversion of 2 to 4. The biochemical conversion of 2 has been found to be TPNH linked.

Electrocardiographic dose-dependent changes in prophylactic doses of dosulepine, lithium and citalopram.

Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium carbonicum (Li) have different cardiovascular side-effects. We compared them in the prophylactic therapy of periodic affective disorder in remission with TCA, SSRI and Li. Our previous papers confirmed the most prominent effects of heart electric field parameters in TCA patients (Slavícek et al., 1998). In the present work we studied for the first time the dose-dependent changes of ECG, body surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40 SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMDL10; age 40+/-5 years; treated for depressive disorders or bipolar disorders). The daily doses of dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66+/-0.08 meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were measured and calculated by the Cardiag 112.1 diagnostic system. The results have shown a relation between the dose of dosulepine and extremum (maximum and minimum) of depolarization isoarea map in dosulepine, but not in citalopram patients. The repolarization BSPM changes were most pronounced in SSRI patients. Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM changes. The present results correspond with our previous observations.

Antidepressant drugs and heart electrical field.

Some antidepressant drugs, especially tricyclic ones--(TCA), have cardiovascular side effects. To compare the effects of antidepressant drugs, the electrocardiogram (ECG), vectorcardiogram (VCG), and body surface maps (BSM) were recorded in psychiatric patients without cardiovascular diseases treated by a) TCA amitriptyline or dosulepin (daily dose 50-200 mg, 22 patients), b) lithium (serum level 0.66 +/- 0.08 meq/l, 21 patients), c) selective serotonine reuptake inhibitor citalopram (daily doses 20-60 mg, 30 patients), and in 23 control patients. In the TCA-treated patients, the heart rate was increased, QT and RR intervals shortened (p < 0.01, antimuscarinic effect). This was not observed in lithium- and citalopram-treated patients. All antidepressants decreased the absolute maximum values of depolarization isointegral maps, lithium and TCA reduced the initial and citalopram the later phase of depolarization. Citalopram slightly diminished the amplitude of the R wave. The results confirm the antimuscarinic effects of TCA in therapeutic doses and specify the intraventricular effects of antidepressants.

Plasma levels of dosulepine and heart electric field.

Antidepressants, particularly tricyclic (TCA) antidepressants, may have cardiotoxic effects, such as cardiac arrhythmias, especially in patients with cardiovascular diseases. For most of TCA, no exact correlation between dosage, plasma levels and changes of ECG parameters of standard ECG has been found. So far, no relationship between dosulepine plasma levels and heart electric field parameters has been studied. We selected 18 female outpatient subjects diagnosed with recurrent depressive disorders, currently in the remission phase (HAMD < 10), without any cardiovascular disease. Patients were treated with daily dosulepine doses of 25-125 mg for 4-8 weeks. 30 heart electric field parameters were analyzed by Cardiag 128.1 diagnostic system as part of BSPM (Body Surface Potential Mapping). Acquired data were correlated with dosulepine plasma levels by means of Spearman's rank order correlation test. Four ECG parameters showed a significant correlation with dosulepine plasma levels: QRS axis deviation in frontal plane (p=0.01), DIAM 40 max (p<0.05), QRS-STT angle in transversal and left sagittal plane (p<0.05). The demonstrated changes confirmed dosulepine influence on the early myocardium depolarization phase and the correlation of this effect with dosulepine dose (its plasma concentration). The higher the dosulepine level, the more marked are the changes of the QRS-STT angle in transversal and sagittal planes and the changes in the QRS axis deviation in frontal plane. Repeatedly recorded changes in the heart electric field were dosulepine-specific and dependent on its plasma levels.

Citalopram inhibits L-type calcium channel current in rat cardiomyocytes in culture.

Selective serotonine reuptake inhibitors (SSRI) are believed to be less dangerous in the treatment of depressive disorder in comparison with tricyclic antidepressants (TCA) due to their relative lack of cardiotoxicity. Thus, we investigated the effect of citalopram (SSRI) on membrane electrophysiology in rat cardiomyocytes in tissue culture. The results were compared with those from amitriptyline (TCA). The whole-cell configuration patch-clamp technique was used. Both citalopram and amitriptyline exhibited the concentration-dependent inhibition of the L-type calcium channel current (ICa). Citalopram in concentrations of 3 microM and 10 microM inhibited peak calcium current by 2.7% and 8%, respectively. We demonstrated the same potency of citalopram and amitriptyline to inhibit ICa. These observations led us to conclude that citalopram and amitriptyline are drugs, which exhibit a similar potency for causing concentration-dependent inhibition of ICa.

QT dispersion and T-loop morphology in late pregnancy and after delivery.

The aim of the study was to detect changes of both the QT dispersion and T-loop morphology resulting from the changed spatial position of the heart during pregnancy. Electrocardiographic and vectorcardiographic recordings were obtained from 37 healthy women 19-36 years old in the 36th to 40th week of physiological pregnancy and 2 to 6 days after delivery. The same recordings were obtained from 18 healthy women of the same age. The average QT dispersion (+/- S.D.) in normal subjects was significantly lower (34 +/- 12 ms) than in those in late pregnancy (73 +/- 18 ms) (P < 0.001). The average amplitude of T-loop (Ta) in women in late pregnancy was significantly (P < 0.001) smaller (532 +/- 98 microV) and the width of T-loop (Tw) was wider (21.24 +/- 11.48 deg) than in the control group (793 +/- 114 microV and 7.17 +/- 3.02 deg, respectively). The partial post-partum restoration of all parameters was not significant. In all groups, the QT dispersion was significantly correlated with Tw but not with Ta. According to these results we can conclude that the QT dispersion is an indirect reflection of the complete process of ventricular repolarization, reflected in the morphology of the T-loop.

Electrocardiogram, vectocardiogram and body surface maps in patients with panic disorder.

An increased risk of myocardial ischemic changes was demonstrated in patients suffering from panic disorder (PD). Using classical ECG methods, this risk cannot be evaluated in most patients. We measured the vectocardiogram (VCG) using Frank orthogonal leads and body surface maps (BSM) including 12-lead ECG. In our study of 11 PD patients (2 men, 9 women), without any seizures and pharmacological treatment and without cardiovascular symptoms, we found marked sinus tachycardia (heart rate 90.1 +/- 12.2 min(-1)) and a shorter R-R interval (678 +/- 93.6 ms) than in 27 controls (heart rate 73.6 +/- 7.7min(-1), R-R 822.7 +/- 86.4 ms) (5 men, 22 women) (p<0.001). The VCG measured spatial QRS-STT angle was more opened (70.3 +/- 24.5 degrees) than in the control group (49.5 +/- 19.5 degrees) (p<0.05). The maximum (extremum) in depolarization (DIAM max 30, 40) and repolarization (RIAM max 35) of body surface isoarea and isointegral (RIIM max) maps was less positive (p<0.001) and the minimum (DIAM min 40) was less negative than in the controls (p<0.05) even in the period free of a panic attack. Our results showed the changes in the heart electric field parameters occurred in PD patients when compared to the control group.

Repolarization pattern of body surface potential maps (BSPM) in coronary artery disease.

The aim of our study was to assess if repolarization BSPM were able to evaluate the site, size and severity of chronic ischaemic damages and if BSPM were in any way related to the regional attenuation of myocardial contractility or to the site of coronary artery occlusion. The BSPM were obtained from 69 patients suffering from coronary artery disease confirmed by coronarography, with at least 75% occlusion of at least one coronary artery. According to the site of single occlusion, or a combination of the sites of multiple occlusions, the patients were divided into 6 subgroups. According to the region of attenuated kinetics the same group of 69 patients was also divided into other 6 subgroups. As in the polarity distribution there was only a limited accordance in BSPM with coronarographic and echocardiographic findings, in the localization of extreme values there were very important specific changes in patients with normal kinetics as determined by both contrast ventriculography and two-dimensional echocardiography. The repolarization maps can distinguish patients with coronary artery disease and normal echocardiography from healthy persons with a sensitivity of 85% and a specificity of 65% in the case of the isoareal map from the ST segment (RIAM) and 90% and 85%, respectively, in the case of the isointegral map from the whole ST-T segments (RIIM).

QT dispersion and electrical heart field morphology in patients treated with dosulepin.

The aim of the study was to detect the changes of QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and vectorcardiographic recordings were obtained using Cardiag 112.2 diagnostic system from 28 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings following parameters were evaluated: QTd, spatial QRS-STT angle and amplitude of T-wave. The acquired data were correlated with the dosulepin plasma levels using Spearman's rank order correlation test. The average QTd (+/-S.D.) in the dosulepin group was significantly higher (70+/-21 ms) than that in the control group (34+/-12 ms) (P<0.001). Moreover, the correlation between QTd and the dosulepin plasma levels was highly significant (r = 0.7871, P<0.001). Similar results were obtained when QTc dispersion was used. On the contrary, the QRS-STT space angle did not correlate with the dosulepin plasma levels. Furthermore, the T-wave amplitude was not significantly correlated to the QT-interval. Thus we can conclude that the QT dispersion could be used as a simple marker of the dosulepin effect on the myocardium.

QT dispersion estimated from 80 body surface potential map leads and from standard 12-leads ECG in psychiatric patients treated with dosulepin.

The aim of the study was to detect changes of the QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and body surface potential mapping (BSPM) recordings were obtained using Cardiag 112.2 diagnostic system from 27 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings the QTd and the dispersion of heart rate-corrected QT interval QTc were evaluated. These parameters were estimated both from 80 BSPM leads and from 12 standard ECG leads. Acquired data were statistically correlated by Spearman rank order correlation coefficient with dosulepin plasma levels. The average QTd evaluated from BSPM leads (+/-SD) in the dosulepin group was significantly higher [70 (+/-21) ms] than that in the control group [34 (+/-12) ms] (P< 0.001). Moreover, the correlation between QTd and the dosulepin plasma level was statistically significant as well (P< 0.001) with the value of correlation coefficient 0.7871. The QTd evaluated from standard 12 ECG leads was increased in dosulepin group as well [46 (+/-18) ms vs. 28 (+/-10) ms - P< 0.05] but we have not found any significant correlation of the QTd with the dosulepin plasma level. According to the above-mentioned results we can conclude that the QTd estimated from BSPM leads (but not that estimated from 12-lead ECG) could be used as a marker of the dosulepin effect on the myocardium.

Electrocardiographic body surface maps (BSM) in patients with ischemic heart disease examined by coronary angiography.

ECG body surface maps (BSM) is one of the noninvasive methods for the detection of ischemic heart disease. In the present work we registered the BSM in 25 patients, 18 men, mean age 56.8 (31-83) years, 7 women, mean age 58.7 (43-72) years with coronary artery disease and in 23 healthy persons, 17 men, mean age 55 (46-60) years, 6 women, mean age 57 (42-70) years. Using diagnostic system Cardiag we measured 32 parameters of heart electric field (ECG, VCG, isopotential, isointegral, and isoarea maps). The results of BSM examination were compared with the results of coronary angiography (CAG) and other noninvasive methods. Twenty-four patients were BSM positive, 5 of them with negative CAG. In one case both BSM and CAG were negative. None of persons with positive CAG were BSM negative. The values of positive BSM in patients with negative CAG approached more to the values of positive CAG persons than to controls. Despite of small number of persons examined in our study one can conclude that the BSM method detects the damage of myocardium by another way than the CAG.

Three-dimensional finite element computer model of the forward problem of electrocardiology.

This study analyses forward problem of electrocardiology. Premature beats originated from subepicardial layer of myocardium were simulated in order to analyse their shape dependence on the site of origin. The equation governing the propagation of the electrical wave through human thorax together with transition and boundary conditions is derived under the clearly stated simplifying assumptions. The weak formulation of the forward problem of electrocardiology is introduced, too. The Galerkin method as a convenient tool for looking for the numerical solution is mentioned and its practical implementation--finite element method--then used in order to obtain numerical results. The obtained results were presented in the form of isopotential maps and compared with actually measured body surface isopotential maps of the depolarization phase. The parameters of the model were then optimalized in accordance with the measured data. In spite of the lack of quantitative data the model has proved that the presented method was able to be used for the simulation studies of ventricular ectopic beats. It was shown that only a small difference between the site of beat origin can be well distinguished on the simulated body surface maps. (Fig. 3, Ref. 3.)

[Mycetismus in children--report of an epidemic of poisoning]. / Micetizam u djece--u povodu jedne epidemije otrovanja.

In the autumn of 1988 an outbreak of mushroom poisoning occurred in the surroundings of Zagreb. In less than 3 week period about 140 cases of poisoning were recorded, 17 of whom were children treated at the Department of Pediatrics. Nine children developed gastrointestinal and 18 phalloid syndrome. In the differential diagnosis of each gastroenterocolitis, mushroom poisoning should be taken into consideration, especially during warm and wet summer and autumn. The detection and identification of the poison is the main principle in diagnostics and medical treatment of each poisoning, thus of mushroom poisoning. Incriminated mushroom was identified in 21 of 27 patients (77.8%). Timely application of general therapeutic procedures, especially thorough gastric lavage in each patient, and application of plasmapheresis in case of Amanita phalloides poisoning have been found effective in reducing lethality and in rapid clinical recovery. Of the total number of 18 Amanita phalloides poisoned children, 4 died which is a lethality rate of 22%. In health education it should be pointed out that there are no simple methods for distinguishing edible mushrooms from poisonous ones.

[The nail-patella syndrome]. / Nail-patella sindrom.

The nail-patella syndrome (synonym of onychoosteodysplasia) is considered to be an autosomal dominant hereditary disease affecting numerous tissues of ectodermal and mesodermal origin. The changes are mostly found on nails, patellae, eyes and joints. The symptoms of nephropathy are present in 30% to 40% of patients, and renal insufficiency with typical signs of the syndrome in 25% of patients. This report describes a female patient with renal insufficiency on chronic hemodialysis treatment, in whom diagnosis of the nail-patella syndrome has been made at 36 years of age. The incidence of the syndrome has been noted in 11 members of the patient's family, but without clinical signs of nephropathy.