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Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma.

BACKGROUND: The Raf/MEK/ERK (mitogen activated protein kinase-MAPK) signal transduction cascade is an important mediator of a number of cellular fates, including growth, proliferation, and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals. AIMS: The aim of this study was to elucidate a possible function of BRAF in liver tumours. METHODS: Mutations of BRAF and KRAS were evaluated in 25 hepatocellular carcinomas (HCC) and in 69 cholangiocarcinomas (CC) by direct DNA sequencing analyses after microdissection. The presence of active intermediates of the MAPK pathway was assessed immunohistochemically. The results obtained were correlated with histopathological variables and patient survival. RESULTS: Activating BRAF missense mutations were identified in 15/69 CC (22%) and in one case of tumour surrounding liver. KRAS mutations were found in 31 of 69 (45%) CC examined and in two cases of tumour surrounding non-neoplastic liver tissue. In HCC, neither BRAF nor KRAS mutations were detected. All 31 CC with KRAS mutations had an intact BRAF gene. We failed to observe a correlation between BRAF or KRAS mutations and histopathological factors or prognosis of patients. CONCLUSIONS: Our data indicate that BRAF gene mutations are a relatively common event in CC but not in HCC. Disruption of the Raf/MEK/ERK (MAPK) kinase pathway, either by RAS or BRAF mutation, was detected in approximately 62% of all CC and is therefore one of the most frequent defects in cholangiocellular carcinogenesis.

Base Sequence↗

The effect of an aerobic interval training program on intermittent anaerobic performance.

The effects of a 9-week aerobic interval training program on anaerobic intermittent performance were investigated. Intermittent work consisted of four repeat 30-sec maximal efforts on a cycle ergometer (Wingate test) with 3-min recovery intervals. Thirteen men trained 3 days a week on the cycle ergometer, completing 3-min work-to-rest intervals and progressing from 5 to 10 reps. Relative and absolute values of aerobic power increased significantly for the training group (p < .05). No significant change was observed for the control group (n = 11). The training group demonstrated significant increases in the four anaerobic variables of short-term peak power (SPP), short-term anaerobic capacity (SAC), intermediate-term peak power (IPP), and total work (TW), and across the four 30-sec maximal repeats for anaerobic performance (T1-T4) (p < .05). Greater percentages of increase occurred for IPP and TW, especially during Repeats 3 and 4. The control group only demonstrated a significant increase in SPP for Repeat 3. These data suggest that the type of interval training program used in the study increased aerobic power and also enhanced performance in repeated high intensity, short duration work.

Adult↗

Dysregulated human myeloid nuclear differentiation antigen expression in myelodysplastic syndromes: evidence for a role in apoptosis.

Reduced levels of human myeloid nuclear differentiation antigen (MNDA) gene transcripts have been detected in both familial and sporadic cases of myelodysplastic syndromes (MDS). Numerous reports implicate elevated apoptosis/programmed cell death and death ligands and their receptors in the pathogenesis of MDS. MNDA and related proteins contain the pyrin domain that functions in signaling associated with programmed cell death and inflammation. We tested the hypothesis that MNDA is involved in the regulation of programmed cell death in human myeloid hematopoietic cells. Clones of K562 cells (MNDA-null) that expressed ectopic MNDA protein were established using retroviral transduction. MNDA-expressing K562 clones were resistant to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis, but were not protected from programmed cell death induced with genotoxic agents or H(2)O(2). MNDA protein expression assessed in control and intermediate and high-grade MDS marrows showed several patterns of aberrant reduced MNDA. These variable patterns of dysregulated MNDA expression may relate to the variable pathophysiology of MDS. We propose that MNDA has a role regulating programmed cell death in myeloid progenitor cells, and that its down-regulation in MDS is related to granulocyte-macrophage progenitor cell sensitivity to TRAIL-induced programmed cell death.

Antigens, Differentiation, Myelomonocytic↗

Comparison of early thallium-201 scintigraphy and gated blood pool imaging for predicting mortality in patients with acute myocardial infarction.

The extent of abnormality in early thallium-201 and gated cardiac blood pool scintigrams has been reported to be useful for predicting mortality in patients with acute myocardial infarction (AMI). To compare the two techniques, 91 patients admitted consecutively with evident or strongly suspected AMI underwent both imaging studies within 15 hours of the onset of symptoms. Patients with pulmonary edema or shock were excluded. AMI developed in 84% of patients, and 6-month mortality for the entire group was 16%. A thallium defect score of 7.0 or greater (corresponding to at least a moderate reduction of activity involving 40% of the left ventricular circumference) identified a subgroup of 14 patients with 64% 6-month mortality rate. Similarly, a left ventricular ejection fraction of 35% or less identified a high-risk subgroup of 10 patients with a 6-month mortality of 60%. Mortality in the remaining patients was 8% for thallium score less than 7 and 11% for ejection fraction greater than 35%. The mortality rate was highest among patients who had concordant high-risk scintigrams (five of six, 83%), lowest in those with concordant low-risk studies (five of 64, 8%) and intermediate in those with discordant results (four of 11, 36%). Of a number of clinical variables, only the appearance of Q waves, peak creatine kinase greater than 1000 IU/I, and history of infarction were significantly associated with mortality. High-risk thallium or blood pool scintigraphic results were significantly more predictive and a thallium score of 7 or greater was more sensitive for detecting nonsurvivors than ejection fraction 35% or less at a similar level of specificity. Stepwise multiple logistic analysis showed that the thallium score was the best predictor of mortality, but that appearance of Q waves and ejection fraction were additive. Using these three variables, 11 patients were calculated to have a 50% or greater chance of dying and eight (73%) actually died, compared with six of 70 (9%) with a calculated chance of death of less than 50%. These results in a prospectively identified and consecutive group of patients support the value of early thallium and blood pool scintigraphy for separating high- and low-risk subgroups of hemodynamically stable infarct patients.

Adult↗

Epitheliocystis infection in cultured white sturgeon (Acipenser transmontanus): antigenic and ultrastructural similarities of the causative agent to the chlamydiae.

A mild to moderate branchial epitheliocystis infection was diagnosed in subyearling (11 months old, 250-300 g) white sturgeon (Acipenser transmontanus) from a private culture facility with a 4-8% mortality in the population. Infected branchial epithelial cells contained the coccoid to coccobacillary epitheliocystis organisms, which appeared as cytoplasmic inclusions composed of a fine, homogeneous, dense, basophilic, granular material. The infected cells were variably enlarged with spherical to oval profiles and were randomly distributed throughout the branchial epithelium. The cytoplasmic inclusions stained positive with Macchiavello stain but negative with Brown and Brenn, periodic acid-Schiff, and Gimenez stains. Expression of chlamydial antigen was demonstrated within the cytoplasmic inclusions using a standard peroxidase-antiperoxidase immunohistochemical technique. Three stages of coordinated intracellular development were recognized by electron microscopy. The reticulate bodies were oval to spherical and 0.4-0.8 x 0.5-1.4 microns but often exhibited a pleomorphic and convoluted appearance because of variable membrane invaginations and evaginations suggestive of uneven fission and budding. Separate host cells contained intermediate bodies that were spherical to oval and 0.2-0.4 x 0.3-0.6 microns although often observed in the process of apparent uneven division. The presence of a cap or plaque composed of hexagonally arrayed fibrillar surface projections was initially recognized in this stage. A homogeneous population of 0.3-0.4 microns oval elementary bodies were observed separately in individual host cells. This developmental stage had a single, dense, compact, eccentrically located cytoplasmic condensation that occurred opposite to the location of the cap of hexagonally arrayed fibrillar surface projections. Morphologic characteristics of the epitheliocystis organism in these white sturgeon were similar to those previously described in other teleosts and expands the species catalogue of epitheliocystis infection. Furthermore, the ultrastructural similarities to the chalmydiae and the immunohistochemical detection of chlamydial antigen provides further evidence that the epitheliocystis agent is related to members of the Chlamydiales. Although the infection was considered mild to moderate and could not be definitively attributed to the mortality in this population, the potential adverse impact of epitheliocystis infection on sturgeon culture should be considered especially in intensive fish culture operations.

Animals↗

Comparative morphology of the pectinate ligaments of domestic mammals, as observed under the dissecting microscope and the scanning electron microscope.

The pectinate ligaments of ten horses, two donkeys, five oxen, five sheep, ten goats, five dogs, five cats, thirty pigs and two rabbits were studied under the stereomicroscope and the scanning electron microscope. In the horse and the donkey, the pectinate ligament was very prominent and was characterized by sturdy interconnected strands and relatively small intertrabecular spaces. The pectinate ligaments of ruminants were composed of shorter strands, separated by relatively larger spaces. Fusion between adjacent strands, resulting in the formation of fenestrated sheets, was regularly observed in these species, in particular in the superior and inferior ocular segments. In the dog and the cat, the pectinate ligament consisted of slender strands that were separated by large intertrabecular spaces. The strands of the pectinate ligaments of the pig and the rabbit were shorter and their diameters were intermediate between those of the herbivores and the carnivores. The clinical relevance of the normal variability in the structure of the pectinate ligament and proposals for a uniform anatomical nomenclature are discussed.

Animals↗

A conserved supergene locus controls colour pattern diversity in Heliconius butterflies.

We studied whether similar developmental genetic mechanisms are involved in both convergent and divergent evolution. Mimetic insects are known for their diversity of patterns as well as their remarkable evolutionary convergence, and they have played an important role in controversies over the respective roles of selection and constraints in adaptive evolution. Here we contrast three butterfly species, all classic examples of Müllerian mimicry. We used a genetic linkage map to show that a locus, Yb, which controls the presence of a yellow band in geographic races of Heliconius melpomene, maps precisely to the same location as the locus Cr, which has very similar phenotypic effects in its co-mimic H. erato. Furthermore, the same genomic location acts as a "supergene", determining multiple sympatric morphs in a third species, H. numata. H. numata is a species with a very different phenotypic appearance, whose many forms mimic different unrelated ithomiine butterflies in the genus Melinaea. Other unlinked colour pattern loci map to a homologous linkage group in the co-mimics H. melpomene and H. erato, but they are not involved in mimetic polymorphism in H. numata. Hence, a single region from the multilocus colour pattern architecture of H. melpomene and H. erato appears to have gained control of the entire wing-pattern variability in H. numata, presumably as a result of selection for mimetic "supergene" polymorphism without intermediates. Although we cannot at this stage confirm the homology of the loci segregating in the three species, our results imply that a conserved yet relatively unconstrained mechanism underlying pattern switching can affect mimicry in radically different ways. We also show that adaptive evolution, both convergent and diversifying, can occur by the repeated involvement of the same genomic regions.

Animals↗

Large-scale gene expression differences across brain regions and inbred strains correlate with a behavioral phenotype.

Behaviors are often highly heritable, polygenic traits. To investigate molecular mediators of behavior, we analyzed gene expression patterns across seven brain regions (amygdala, basal ganglia, cerebellum, frontal cortex, hippocampus, cingulate cortex, and olfactory bulb) of 10 different inbred mouse strains (129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ tf/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and FVB/NJ). Extensive variation was observed across both strain and brain region. These data provide potential transcriptional intermediates linking polygenic variation to differences in behavior. For example, mice from different strains had variable performance on the rotarod task, which correlated with the expression of >2000 transcripts in the cerebellum. Correlation with this task was also found in the amygdala and hippocampus, but not in other regions examined, indicating the potential complexity of motor coordination. Thus we can begin to identify expression profiles contributing to behavioral phenotypes through variation in gene expression.

Amygdala↗

The influence of genetic variation on the splenic T cell cytokine and specific serum antibody responses to Porphyromonas gingivalis in mice.

BACKGROUND: T cell cytokine profiles in the spleens and anti-Porphyromonas gingivalis antibodies in the sera of P. gingivalis-immunized BALB/c (H-2d), CBA/CaH (H-2k), C57BL6 (H-2b), and DBA/2J (H-2d, C5 deficient) mice were examined. METHODS: Mice were immunized either by intraperitoneal injections of P. gingivalis outer membrane antigens and Freund's incomplete adjuvant weekly for 3 weeks or sham-immunized with PBS and adjuvant, followed by subcutaneous challenge with live organisms 1 week after the final immunization. Spleens were excised and blood samples collected by heart puncture at 0 and 7 days after challenge. Splenic CD4 and CD8 cells were stained for intracytoplasmic interleukin (IL)-4, interferon (IF)-gamma, and IL-10 and levels of anti-P. gingivalis antibodies in the serum samples determined by ELISA. RESULTS: Lesion sizes in immunized BALB/c mice remained stable for the 7-day experimental period. Immunized CBA/CaH and C57BL6 mice exhibited large lesions at day 1 reducing by day 7 particularly in the latter strain. Lesions in immunized DBA/2J mice were still larger than the other strains at day 7. With the exception of DBA/2J mice, sham-immunized mice demonstrated lesions which did not show signs of healing by day 7. T cell cytokine responses in sham-immunized mice at day 0 were low, increasing to a variable degree by day 7 after challenge in the 4 strains. Immunized BALB/c mice demonstrated intermediate T cell responses while generally exhibiting a stronger IFN-gamma response than IL-4 or IL-10. Immunized CBA/CaH and C57BL6 mice showed weak T cell cytokine responses while immunized DBA/2J displayed the strongest T cell responses particularly in regard to IL-4 positive cells. Sham-immunized mice had low levels of serum anti-P. gingivalis antibody levels at day 0 with levels increasing significantly by day 7 after challenge. Antibody levels in immunized mice seemed to correlate with lesion sizes. Immunized C57BL6 mice had the highest antibody levels followed by CBA/CaH, BALB/c with DBA/2J exhibiting low levels. The T cell and B cell antibody responses in each strain appeared to exhibit an inverse relationship. CONCLUSIONS: This study has shown that genetic differences at the level of H-2 haplotype induce variations in the local and T and B cell responses to P. gingivalis antigens. The responses of DBA/2J mice which have the same haplotype as BALB/c mice suggest that factors other than H-2 haplotype such as the C5 deficiency may influence this immune response. The significance of the specific antibody and T cell responses and of their inverse relationship to susceptibility to periodontal disease remains to be determined.

Analysis of Variance↗

Diets during far-off and close-up dry periods affect periparturient metabolism and lactation in multiparous cows.

The objectives of this study were to determine the effects of far-off and close-up diets on prepartum metabolism, postpartum metabolism, and postpartum performance of multiparous Holstein cows. From dry-off to -25 d relative to expected parturition (far-off dry period), cows were fed a control diet to meet National Research Council (NRC) recommendations for net energy for lactation (NE(L)) at ad libitum intake (100NRC; n = 25) or a higher nutrient density diet, which was fed for either ad libitum intake to provide at least 150% of calculated NE(L) requirement (150NRC; n = 25) or at restricted intake to provide 80% of calculated NE(L) requirements (80NRC; n = 24). From -24 d relative to expected parturition until parturition (close-up period), cows were fed a diet that met or exceeded NRC nutrient recommendations at either ad libitum intake (n = 38) or restricted intake (n = 36) to provide 80% of the calculated NE(L) requirement. After parturition, all cows were fed a lactation diet and measurements were made through 56 d in milk (DIM). Prepartum metabolism was consistent with the plane of nutrition. During the first 10 DIM, far-off treatments had significant carryover effects on dry matter intake, energy balance, serum nonesterified fatty acid (NEFA) concentration, and serum beta-hydroxybutyrate concentration. Cows with the lower energy balance during the far-off period (100NRC and 80NRC) had higher dry matter intake and energy balance and lower serum NEFA and beta-hydroxybutyrate during the first 10 DIM. There were no effects of close-up diet and no interactions of far-off and close-up treatments. During the first 56 DIM, there were no residual effects of far-off or close-up diets on dry matter intake, milk yield or composition, body weight, body condition score, serum glucose and insulin concentrations, or muscle lipid concentration. Serum NEFA was higher for 150NRC than 80NRC; 100NRC was intermediate. Thus, the effects of far-off and close-up treatments on postpartum variables diminished as lactation progressed. Overfeeding during the far-off period had a greater negative impact on peripartum metabolism than did differences in close-up period nutrition.

3-Hydroxybutyric Acid↗

Does finasteride alter the pathology of the prostate and cancer grading?

All forms of androgen-deprivation therapy, including finasteride, induce distinctive histologic changes in benign and neoplastic prostatic epithelial cells, including cytoplasmic clearing, nuclear and nucleolar shrinkage, and chromatin condensation. Treated cancer has a significantly higher architectural (Gleason) grade, lower nuclear grade, and smaller nucleolar diameter than untreated controls, creating the potential for grading bias. Recognition of these changes may be difficult in needle biopsies and lymph node metastases with treated cancer because of the subtle infiltrative pattern and inconspicuous nucleoli. The effects of finasteride may be less pronounced than other forms of therapy with variable distribution throughout the prostate; further, there may be greater sensitivity of low and intermediate-grade cancer than high-grade cancer. The Gleason grading system for cancer should not be used after finasteride treatment as it is not validated in this setting and is likely to overestimate the biologic potential of high-grade cancer observed after therapy. Chemoprevention trials with agents such as finasteride that alter morphology should not rely on cancer grading as a secondary endpoint owing to grading bias.

5-alpha Reductase Inhibitors↗

Management of suspected giant cell arteritis: a decision analysis.

We used decision analysis to compare 4 strategies for managing suspected giant cell arteritis (GCA): treat no patients, treat all patients, perform temporal artery biopsy and only treat positive cases, or biopsy and treat all cases irrespective of the result. The "treat no patients" strategy is preferred only if the likelihood of disease is less than 2%. The "biopsy and treat positive cases" strategy predominates for intermediate likelihood of disease (50%) and is insensitive to altering the probability of any key variables. The "biopsy but treat irrespective of the result" strategy becomes preferred at likelihood of disease of 81%. However, this result was sensitive to alteration of the key variables. Empirical therapy without biopsy would only be preferred if the likelihood of disease exceeded 90% and the disutility one attaches to treating under uncertainty is low at high probability of disease. Management of suspected GCA should be guided by the results of temporal artery biopsy in the majority of cases. At high likelihood of disease, temporal artery biopsy may be of value independent of its usefulness in determining management strategy. Further research should be directed towards improving the accuracy of diagnosis, defining the risk of iatrogenic complications and estimating utilities for the outcomes.

Adrenal Cortex Hormones↗

[Extent of the gastric antrum in duodenal ulcer patients].

The extent of the gastric antrum in duodenal ulcer patients and the relationship between the first antral branch of the vagal nerve and proximal delimitation of antrum were examined using resected gastric specimens of 46 duodenal ulcer patients. It has been demonstrated that: (1) There was a variable extent of measured distance from the pyloric ring to the antrum-corpus boundary (intermediate zone), and it ascended with age along the lesser curvature. (2) The intermediate zone was a transitional change of the fundic and pyloric gland area. The change on the lesser curvature was abrupt, but on the greater curvature it was gradual. It displaced distally on the greater curvature, and was found to be symmetrical on the anterior and posterior walls. (3) The proximal delimitation of the antrum lay on the lesser curvature where the first antral branch of the vagal nerve reached the lesser curvature topographically. (4) At the lesser curvature, the antrum-corpus boundary was found to be located within +/- 2 cm from the first antral branch in 93.5% of the cases. It may be a useful landmark to decide the proximal boundary of gastric antrum while performing antrectomy. (5) The shrinkage factor for specimens after 10% formalin fixation appeared to be between 0.7 and 0.9.

Adolescent↗

[Usefulness of coronary angioplasty (PTCA) of the infarct-related artery in patients with prior myocardial infarction--follow up of infarct zone pre- and post-angioplasty by stress thallium scan].

We studied the efficacy of coronary angioplasty (PTCA) of the infarct-related artery in 29 patients with prior myocardial infarction by stress thallium scan. Twenty-seven patients had anterior myocardial infarction (single LAD disease), one had inferior (single RCA disease) and one had posterior (single LCX disease). According to the stress-redistribution thallium scintigraphic finding before PTCA, the patients were classified in 4 groups; (A): three patients with complete redistribution. (B): fourteen patients with incomplete redistribution. (C): seven patients with partial redistribution. (D): five patients with no redistribution. After PTCA, the parameters of residual ischemia in the infarct area (% RD and Thallium ischemic score = TIS) were improved significantly but those of infarct size (RD% uptake and Defect Score = DS) were improved slightly in group A. In group B and C, % RD, TIS, RD% uptake and DS were all improved significantly. In group D, TIS was improved slightly and DS was improved slowly 3 months after PTCA. Group A had high probability of viable muscle and group D had high probability of scar at the infarct zone. Group B and C showed intermediate type between group A and D. The change of infarct area after PTCA was variable in 4 groups but both residual ischemia and infarct size decreased in all groups. Thus, PTCA of infarct-related coronary artery is useful even in the patients with prior myocardial infarction.

Adult↗

Essentials of insulin pharmacokinetics.

Pharmacokinetic methods are a powerful tool for the investigation of the insulin system in health and disease; the underlying formalisms are simple and straight-foreward. Following intravenous injection the plasma concentration of insulin declines with at least two exponentials, the rapidly disappearing component (half-time 2.4 min) represents elimination from the intravascular space, whereas the most slowly disappearing component (half-time 50-130 min) reflects elimination from the interstitial fluid and the tissues that utilize insulin. Total clearance of insulin, which is the result of metabolic degradation, ranges between 700 and 800 ml/min. The sites of degradation are primarily the liver (hepatic insulin clearance: 320-400 ml/min) and the kidneys (renal insulin clearance: 190-270 ml/min), hence insulin disposal depends on the function of these organs. The apparent volume of distribution for insulin is approximately equal to the extracellular space. Insulin absorption from the subcutaneous tissue is slow (half-times of 0.5-2.7, 6.6-13.8, and 15-48 hours for fast-, intermediate-, and long-acting insulins, respectively). The bioavailability of insulin after subcutaneous administration is variable. Insulin kinetics appear not to be altered in diabetes mellitus, except in cases with insulin antibodies or in insulin-resistant patients, in which insulin removal may be retarded. Optimization of functional insulin replacement requires knowledge of the pharmacokinetic properties of the insulin preparation used.

Humans↗

A multifactorial analysis of melanoma. II. Prognostic factors in patients with stage I (localized) melanoma.

Stage I melanoma encompasses an extraordinary diversity of biologic behavior. In such a setting where numerous parameters appear to influence survival, a multifactorial analysis using Cox's regression model is a valuable statistical model. Using a computerized data base of 394 clinical stage I melanoma patients treated at this institution during the past 20 years, a multifactorial analysis was used to compare the relative prognostic strength of 11 parameters. Two pathological factors (tumor thickness and ulceration) and two clinial factors (initial surgical treatment and anatomic location) were identified as the dominant prognostic variables. Other factors examined simultaneously that did not provide additional predictive influence on survival included the level of invasion, pigmentation, growth pattern, lymphocyte infiltration, pathological state, sex, and age. Melanoma thickness was the most important factor for predicting survival in patients with stage I melanoma (P less than 10(-8). This parameter is easy to measure and provides a quantitative estimate of clinically occult regional and distant metastases. Contrary to other reports using single factor analysis, the type of initial surgical treatment, in fact, did influence survival after other variables were taken into consideration. Thus the multifactorial analysis supports the observation that patients with intermediate thickness melanoma thickness of 1.5 to 3.99 mm had a 78% 8-year survival rate with wide excision of the melanoma and elective node dissection, while none survived more than 8 years if a melanoma of the same thickness was only widely excised. Multifactorial analysis is a useful and important statistical method when comparing treatment alternatives and prognostic factors in patients with melanoma.

Adult↗

Fetal blood and tissue pH with variable deceleration patterns.

Continuous tissue pH, scalp blood pH, and umbilical artery pH were studied in 89 patients with variable decelerations and 5 control patients in labor. The characteristics of the variable decelerations were analyzed. The deceleration pattern was classified as variable without late component (V), variable with late onset (VLO), or variable with late recovery (VLR). The patterns with a late component showed a greater incidence of falling pH during the decelerations. The VLR pattern was very likely to show a tendency to fetal acidosis and a high incidence of low Apgar scores. Variable decelerations without a late component were found to be innocuous. The VLO was an intermediate pattern, often progressing to the potentially more hazardous pattern of VLR.

Apgar Score↗

[Relationship between ventricular extrasystole and parasystole].

Monomorphic ventricular extrasystoles, no less than 30 within an hour, were revealed in 89 of 300 patients with chronic ischemic heart disease during continuous 24-hour ECG recording on magnetic tape. A fixed type of the linkage interval (oscillations of no more than 0.1 sec) was established in 58 (62%) and the variable tupe (oscillations of more than 0.1 sec) in 31 (38%) patients. Oscillations in the linkage interval of more than 0.1 sec gave grounds to suspect parasystole. A deeper analysis revealed parasystole in 8 cases (2.6% of the total number of patients), the remaining cases were included in the group of extrasystoles with a variable non-parasystolic type of the linkage interval. This group of extrasystoles occupies an intermediate position between para- and extrasystole. The large number of transitional forms between extra- and parasystole suggests their common origin.

Aged↗