Nafamostat as anti-coagulant for membrane plasmapheresis in high bleeding risk patients. Nafamostat mesilate (NM), an ultrashort-acting multi-enzymatic inhibitor, is a useful anti-coagulant in high bleeding risk patients needing hemodialysis. We applied NM as a membrane plasmapheresis (MP) anti-coagulant in patients with high bleeding risk. Eleven patients, the majority with hepatic failure and active hemorrhagic foci or severe bleeding diathesis, could be treated with MP 22 times under anti-coagulation by 20-40 mg/h/NM by continuous infusion without any trouble. Celite-activated coagulation time (CCT) at the plasma separator inlet and outlet was adequately prolonged during MP, but CCT in systemic blood showed no prolongation throughout the procedure, because NM was rapidly inactivated. There was no observable blood coagulation in the extracorporeal circuit including the plasma separator. No adverse reaction or exacerbation of hemorrhage was noted throughout the MP. NM thus appears to be a useful and safe anti-coagulant not only for hemodialysis but also for MP in high bleeding risk patients.


Mayer waves in dogs with total artificial heart. To assess the effect of a total artificial heart (TAH) on the autonomic nervous system a power spectral analysis of the hemodynamics in a TAH animal was done by the maximum entropy method. Two pneumatically driven sac-type ventricular assist devices were implanted as total biventricular bypass (BVB) in adult mongrel dogs to compare the differences between natural heart and TAH. Once the BVB was pumping, the natural heart was electrically fibrillated to constitute the BVB-type TAH model. In the arterial pressure waveform in animals with TAH, respiratory waves were not changed (97.7 +/- 24.6%) though Mayer waves were significantly decreased (47.5 +/- 22.6%) compared with the animal with a natural heart. These results suggest that prosthetic hemodynamics in the TAH animal affect fluctuations in the cardiovascular system.


Estimation of the following cardiac output using sympathetic tone and hemodynamics for the control of a total artificial heart. A sympathetic neurogram is potentially useful for the development of a real time total artificial heart (TAH) control system. We used sympathetic tone and hemodynamic derivatives to estimate the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was employed as a parameter of sympathetic tone. Equations for the following cardiac output were calculated using multiple linear regression analysis of the time series data. A significant correlation was observed between the estimated and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system.


Results of randomized mitral valve replacement with mechanical prostheses after 15 years. Between 1974 and 1976 150 consecutive patients (pts) were operated on for isolated mitral valve replacement (MVR). Björk-Shiley (BS), Lillehei-Kaste (LK), and Starr-Edwards (SE) (type 6210) prostheses were implanted at random. All survivors were prospectively followed by regular clinical examinations every 6 to 12 months for 15 years. The mean follow-up time was 14.8 years. A constant subjective improvement after 15 years was reported in 62% of pts with BS, 30% with LK, and 49% with SE. The cumulative 14-year survival rate was 0.62 +/- 0.13 (BS), 0.56 +/- 0.16 (SE), and 0.54 +/- 0.15 (LK), respectively. Late mortality was due to thromboembolic events (n = 3), bleeding complications (n = 3), congestive heart failure (n = 7), documented arrhythmias or sudden death (n = 6). Thrombotic valve thrombosis (1 BS, 1 LK, 2 SE) required reoperations. Linearized cumulative rates after 14 years for thromboembolic complications were 14.2 +/- 3.1 (BS), 15.8 +/- 3.7 (SE), 24.3 +/- 4.2 (LK). The cumulative risk of severe bleeding complications was not different: BS: 35.8, LK: 35.2, SE: 34.3. During the first years of observation no significant differences between these mechanical prostheses could be observed, however, after 14 years of long-term follow-up the cumulative event-free rates were more favorable for the BS prosthesis.


Hemocompatibility of titanium nitride.

Hemocompatibility of titanium nitride. The left ventricular assist device is based on the principle of the Maillard-Wenkel rotative pump. The materials which make up the pump must present particular mechanical, tribological, thermal and chemical properties. Titanium nitride (TiN) because of its surface properties and graphite because of its bulk characteristics have been chosen. The present study evaluated the in vitro hemocompatibility of TiN coating deposited by the chemical vapor deposition process. Protein adsorption, platelet retention and hemolysis tests have been carried out. In spite of some disparities, the TiN behavior towards albumin and fibrinogen is interesting, compared with the one of a reference medical grade elastomer. The platelet retention test gives similar results as those achieved with the same elastomer. The hemolysis percentage is near to zero. TiN shows interesting characteristics, as far as mechanical and tribological problems are concerned, and presents very encouraging blood tolerability properties.


Fast lysis by complement and uptake by liver of avidin-carrying biotinylated erythrocytes. The fate of 51Cr-labelled avidin-carrying biotinylated erythrocytes after intravenous injection in the rat was examined. Surface amino groups of the erythrocyte membrane were modified by biotin N-hydroxysuccinimide ester. The biodistribution and stability of biotinylated erythrocytes in the blood were similar to those of non-biotinylated cells. Both types of cells circulated in the bloodstream for prolonged periods of time without substantial lysis (about 2-3% of injected radioactivity per g of blood for 24-48 hours, no more than 2% of lysis). Both types of erythrocytes were cleared by the spleen. The clearance of biotinylated cells was faster and more pronounced (peak of spleen uptake at 3 hours after injection, up to 35% of injected radioactivity per g of spleen), than that of nonbiotinylated cells (peak of spleen uptake at 24 hours after injection, up to 25% of injected radioactivity per g of spleen). Attachment of avidin to biotinylated cells results in extremely rapid lysis and clearance from the bloodstream (0.17% of injected radioactivity per g of blood 30 min after injection, 100% lysis). Radioactivity was rapidly cleared by the liver (up to 80% of injected dose per g of tissue, 70% per organ). Uptake by the spleen plays only a minor role in the clearance. Considerable lung uptake of avidin-carrying biotinylated erythrocytes was observed. Avidin-carrying biotinylated erythrocytes were lysed by fresh homologous serum in vitro in contrast to biotinylated and native cells. Lysis was eliminated by pretreatment of serum with EDTA or heating, which indicates a complement-dependent mechanism of lysis.


Improved preparation of soluble dry oxyhemoglobin purified by carbontetrachloride treatment of outdated packed erythrocytes. A combination of treating outdated packed red blood cells (PRBCs) with carbontetrachloride, countercurrent dialysis and modified conditions of freeze-drying served to improve and standardize the technology of "stroma-free hemolysate" (SFH) in our laboratory. As a rule, proteins of the final product corresponded to 95% oxyhemoglobin, 3.5% methemoglobin and 1.5% non-hemoglobin ones. In freeze-dried samples stabilized with 0.24 molar saccharides, the weight proportions were 56% hemoglobin, 44% sucrose and/or 62% hemoglobin, and 38% fructose, respectively. If necessary, the saccharides could be rapidly removed from the easily reconstituted SFH by dialysis or chromatography. Analytical parameters were similar to those of chloroform-treated SFH stored dry at -12 degrees C for 4 months. However, the present procedure was easier and SFH samples remained unchanged after dry storage even at +4 degrees C for at least 13 months. This oxyhemoglobin product seems suitable for organ perfusion, further chemical modification and as an analytical standard.


Application of an essential data set based computer system in support of maternal and child care. A simple functional application software has been developed to support care providers in information management related to perinatal care activities, family planning encounters and the immunization of infants. This was distributed to some sites and was implemented with no organizational change, though the methods differed. An early assessment of the software after a period of implementation is made based on the observations and experiences reported. This is presented in a framework outlined earlier as the OUST model. The systems objective to enhance the value of information was observed to have been partially achieved. The utility to the users is observed in the ability of the end-users at the sites to identify the local community needs and adopt accordingly suitable strategies. The social impact was seen in the assistance provided by the sentinel action of the system in tracking dropouts from the immunization programme at a site, thereby ensuring quality in care and also economic benefits. From a technical standpoint, the application software was small yet functional and in it were incorporated features that ensured data quality. The application software was designed to generate a unique identity code to assist in follow-up of the target population. Based on the data entered it compiled reports to meet administrative requirements, reports that gave the care providers feedback and lists to coordinate in the follow-up of the target population. The application software is a common data collection tool that can assist in building a data registry for health outcomes research.


Multidimensional scaling of head and neck metastases. A mathematical analysis, called multidimensional scaling, was applied to two sets of data on metastases from head and neck cancers. The analysis places lymph nodes in an imaginary space (here termed a 'nodalgram') such that distances between nodal clusters are proportional to differences in the occurrence of tumor metastases. Two-dimensional scaling explains 93% of the variance in clinical data from 1008 patients and 91% of the variance in pathological data from a different set of 415 patients. These independent results are closely correlated, and both explain vastly more of the data than expected by chance. The dimensions of the nodalgram are not related to anatomical coordinates of the nodes, suggesting that a representation of these structures in an abstract space explains the spread of cancers better than an analysis of spread in real space. Surprisingly, a plot of the extent to which metastases from different primary sites spread along the nodalgram dimensions is closely related to the normal anatomical locations of the primaries. This shows that although the nodalgram may be difficult to interpret, it must have some biological significance. In conclusion, multidimensional scaling successfully quantifies a pattern in the spread of head and neck cancers.


Bodymap: an image processing system for the measurement of body surface profiles encountered in skin expansion surgery. A personal computer based image processing system for the mapping and subsequent analysis of local areas of the human body requiring no more than 180 degrees of vision is described. The operations of image capture and data extraction are undertaken in real time and photogrammetric reconstruction takes typically a further 30 s. Accuracy of the system has been assessed by photogrammetrically reconstructing 37 points whose coordinates had been precisely established by traditional survey techniques. An average discrepancy between surveyed and reconstructed positions of 0.485 mm was obtained; this level of accuracy compares highly favourably with results achieved using alternative methods and which do not have the level of automation inherent in the described system. The system has been developed specifically to provide quantitative values for parameters of particular interest in skin expansion surgery: consequently the post-reconstruction facilities available in this initial system are surface area and enclosed volume calculations and shaded surface display. Further development work currently in progress is also briefly discussed.


Time trends of smoking cessation: a micro-population computer simulation model. The Micro-population model of Risk-group Dynamics (MRD) approaches smoking behavior at the level of the individual and integrates physiological and social factors to describe the evolution of behavior change in the population. MRD is innovative in several ways: (1) the model describes mathematically the interactions among these behavioral factors; (2) the model accounts for both the variability of these factors among different persons and the universality of basic rules describing these factors in all individuals; and (3) the model can be applied to various types of populations and a wide range of intervention strategies. MRD combines the physiological, psychological and social determinants into a hazard function for relapse to smoking. This hazard function is then organized into a three term expression incorporating: a baseline hazard characteristic to each individual, a decreasing term for the diminishing aspect of the initial hazard and an effect of external interventions. The model gives promising results when applied to the Multiple Risk Factors Intervention Trial (MRFIT) data using the assumptions of a Weibull distribution for the baseline hazard, a negative exponential for the decrease in the initial hazard and a constant intensity for the external intervention.


An application of computer conferencing in dental education. A computer conference was used as an instructional tool in a dental school course on health education. Second year students (N = 84) were divided into 17 groups to design community education programs. A student from each group participated in the conference to electronically discuss their program with peers. The conference operated for 52 days. The 28 conference topics were displayed 1028 times. There were 279 conferencing uses lasting 8125 min (135.4 h); a mean of 29.1 min/use. Mean responses per students was 25. Mean student terminal time was 7.8 h. Instructor terminal time was 20.8 h; 5.4 h were spent managing the conference. Of the available conferencing funds ($440.00), $218.35 was expended with students using $168.24. Mean dollars spent per student was $9.90. Quantitative evaluation of participation was based on: (a) number of individual responses made compared to mean responses; (b) timely item placement on the conference; and (c) the percentage of responses made in other students' items. Student evaluation of conferencing was positive and acknowledged the value of computer skills.


Simulation of a diffusion process with randomly distributed jumps in neuronal context. In stochastic neuronal models, an interspike interval corresponds to the time interval during which the process imitating the membrane potential reaches a threshold from an initial depolarization. For neurons with an extensive dendritic structure, a stochastic process combining diffusion and discontinuous development of its trajectory is considered a good description of the membrane potential. Due to a lack of analytical solutions of the threshold passage distribution for such a process, a method for computer simulation is introduced here. For the diffusion Ornstein-Uhlenbeck process with exponentially distributed moments of constant jumps a program is given. The relation between the simulation step, accuracy of simulation and amount of computing time required is discussed.


Application of autoregressive analysis to 20 MHz pulsed Doppler data in real time. The real time application of autoregressive (AR) spectral analysis to a 20-MHz pulsed Doppler blood flowmeter is presented. The system consists of a TMS 320C25 digital signal processor with a 80286 based PC/AT microcomputer and associated interfacing circuitry. The AR method was used for in vivo spectral analysis of the signals obtained from a 20-MHz pulsed Doppler flowmeter in real time. The data obtained from digital and coronary arteries were processed using both AR and FFT spectral analysis methods. Also the data obtained from a stenosis coronary artery under surgical operation were processed using both methods. When the results are compared, it is seen that autoregressive analysis has given better results. Therefore the technique can be used in the examining of small vessels such as renal, iliac, mesenteric, coronary and digital arteries.


Seasonal variation and meteotropism in various self-rated psychological and physiological features of a normal couple. Recently, true seasonal variation with significant periodicities (circannual, semiannual, circatrimensual, circabimensual) and a significant meteotropism have been observed in a number of self-rated characteristics of normal man (arousal, mood, physiology and social behaviour). In order to replicate these findings, two normal controls (a married couple) were asked daily to complete a self-rating scale concerned with the characteristics mentioned above during one calendar year. By means of time series analysis, significant rhythmicities with recurrent cycles in the autorhythmometric data of all of the above characteristics were found. An important part of the variance in these characteristics was found, using multiple regression, to be related to various weather variables, such as mean atmospheric pressure, temperature, relative humidity, wind speed, minutes of sunlight/day and precipitation/day. These results support the hypothesis that temporal variations in human psychological and physiological characteristics may be dictated by the composite effects of past and present atmospheric activity.


Mast cells in the human lung at high altitude. Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were Mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6-8.8 cells/mm2). In the Aymara Indians the mast cell counts were raised (25.6-26.0 cells/mm2). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm2 lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema.


Effect of air temperature and humidity on ingestive behaviour of sheep. Thirty-two Polwarth ewes, of ages up to 1 year, were observed in a climatic chamber (24 to 45 degrees C) for eight periods of 5 h each. The observations were made through a window in the chamber wall. All animals were observed four times, then shorn and observed four times again. The animals were given weighed quantities of water and feed consisting of commercial concentrate plus Rhodes grass (Chloris gayana) hay. The water and feed remaining after 5 h of observation were weighed. The following traits were analysed: time eating hay (TEH), time eating concentrate (TEC), time drinking water (TDW), weight of hay eaten (WHE), weight of concentrate eaten (WCE), volume of ingested water (VIW), ruminating time standing up (RTS), ruminating time lying down (RTL), idling time standing up (ITS), and idling time lying down (ITL). Shearing had a significant effect for all traits except ITS. Shearing resulted in higher values for all traits except for ITS and ITL. Ingestion of hay (TEH and WHE) decreased with increased air temperature and humidity, while the ingestion of concentrate (TEC) and WHE) and water (TDW and VIW) increased. Rumination decreased with increased air temperature and humidity, and was higher in shorn than in unshorn sheep.


Influence of hot environments on some blood variables of sheep. Thirty-two Polwarth sheep of ages up to 1 year were observed under temperatures varying from 10.5 to 46.5 degrees C. The following blood cell counts were made: erythrocyte (RBC), leucocyte (WBC), eosinophil (EOS), neutrophil (NEU), lymphocyte (LYM) and monocyte (MON). Other traits measured were: haemoglobin (HB), haematocrit (HT), blood glucose (GLU) and serum protein (PROT). Multivariate analysis of variance was used and the results showed a significant (P < 0.001) effect for the interaction of shearing and temperature treatment. Under temperatures > 25 degrees C, sheep presented a decrease of RBC, WBC, HB and HT, these differences being greater in the shorn than in the unshorn animals. Unshorn animals presented higher variations in EOS, NEU, LYM, MON and GLU. Blood glucose increased under high temperatures in the shorn animals (from 56.36 +/- 0.65 mg/100 ml to 60.52 +/- 0.69 mg/100 ml) as in the unshorn animals (from 54.72 +/- 0.74 mg/100 ml to 57.56 +/- 0.77 mg/100 ml).


Geomagnetic activity and enhanced mortality in rats with acute (epileptic) limbic lability. Presumably unrelated behaviors (e.g. psychiatric admissions, seizures, heart failures) have been correlated with increased global geomagnetic activity. We have suggested that all of these behaviors share a common source of variance. They are evoked by transient, dopamine-mediated paroxysmal electrical patterns that are generated within the amygdala and the hippocampus of the temporal lobes. Both the probability and the propagation of these discharges to distal brain regions are facilitated when nocturnal melatonin levels are suppressed by increased geomagnetic activity. In support of this hypothesis, the present study demonstrated a significant correlation of Pearson r = 0.60 between mortality during the critical 4-day period that followed induction of limbic seizures in rats and the ambient geomagnetic activity during the 3 to 4 days that preceded death; the risk increased when the 24 h geomagnetic indices exceeded 20 nT for more than 1 to 2 days.


Lung cancer following Hodgkin's disease: a case-control study. It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer. A collaborative group of population-based cancer registries and major treatment centers carried out a case-control study, in which 98 cases of lung cancer were identified in patients who had survived at least 1 year following a diagnosis of Hodgkin's disease. A total of 259 matched controls were selected from patients with Hodgkin's disease who did not develop subsequent lung cancer, and for both cases and controls detailed information was abstracted from medical records concerning stage and treatment of Hodgkin's disease. Patients treated with chemotherapy alone had about twice the risk of developing lung cancer than those treated by radiotherapy alone or both modalities. There was no increase in risk with cumulative number of cycles of chemotherapy. Among patients treated with radiotherapy alone, there was an increase in risk related to estimated radiation dose to the lung. There was also a strong association between cigarette smoking and the risk of lung cancer. The finding of a higher risk following chemotherapy than following radiotherapy was unexpected, but could not be explained by any identified methodological flaws. A plausible inference from the study is that all forms of Hodgkin's disease therapy are carcinogenic to the lung and that, in particular, chemotherapy is associated with an increase in risk which is at least comparable to and perhaps higher than the risk produced by radiotherapy.


Variations in the ganglioside profile of uveal melanoma correlate with cytologic heterogeneity. Gangliosides may play an important role in the proliferation and spread of human malignant melanoma. Because the frequency of metastases in uveal and cutaneous melanoma differs, it is possible that they may express different gangliosides. We analyzed the ganglioside profiles of primary uveal melanoma in 14 cases and of cutaneous melanoma metastasis in 19 cases. In cutaneous melanoma, GM3 ranged from 4.2% to 74.6% and GD3 from 22.1% to 91.8% of total lipid-bound sialic acid. GM2 (found in 13 of 19 cases, ranging from 0.5% to 11.7%), GD2 (11/19, 0.5%-22.0%) and 9-O-acetyl-GD3 (13/19, 0.5%-12.6%) were also frequently observed. By contrast, in 11 cases of uveal melanoma, GM3 was > 90%, GD3 was < 10%, GM2 was < 1.1%; neither GD2 nor 9-O-acetyl-GD3 were detected. The ganglioside profiles of these uveal melanomas were virtually identical to those of normal melanocytes obtained from foreskins. Histological examination of these 11 biopsies showed a monomorphous cell composition, but neither infiltration of lymphocytes or melanophages nor cell necrosis was observed. In 3 other cases, GD3 was increased to 19.5%-46.0%. Histological examination of these 3 biopsy specimens showed at least 2 populations of tumor cells that were separable based on morphological grounds, and mononuclear inflammatory cells interspersed among the tumor cells. An increase in GD3 appears to be related to tumor polyclonality and infiltration of the tumor by lymphocytes and macrophages. These results suggest that ganglioside expression of uveal melanoma is associated with host immune responses to the tumor. Furthermore, the low metastatic capacity of uveal melanoma, in contrast to the high metastatic rate of cutaneous melanoma, may be a result of its differentiated ganglioside expression, which is strikingly similar to that of normal melanocytes.


Differences in expression of SPan-1 and CA15-3 antigens in blood and tissues. Pancreatic and mammary cancer cells are reported to have different oligosaccharides on the same apomucin, the MUCI gene product. A better understanding of the tissue specificity of these sugar structures may help in identifying the source of mucins when they are found in the sera. Serum levels of 3 pancreatic-cancer-associated carbohydrate epitopes identified by monoclonal antibodies (MAbs) SPan-1, 19-9 and DU-PAN-2, were compared to those of CA15-3 in a variety of malignant conditions. CA15-3 identifies both carbohydrate and peptide determinants associated with the MUC1 apomucin in breast tissues. SPan-1 antigen was elevated in a high percentage of patients with pancreatic, gastric and colorectal cancer but in only a few of the patients with malignancies of non-GI origin such as breast, ovary and lung. The 19-9 and DU-PAN-2 antigens had a similar pattern of much greater sensitivity for pancreatic cancer than for these non-gastrointestinal cancers. The levels of these 3 markers showed significant correlations in pancreatic cancer. In contrast, CA15-3 was elevated in a large number of patients with breast, lung, ovarian and pancreatic cancers. There was no correlation of CA15-3 with the 3 other markers in pancreatic cancer. SPan-1 and DF3/115D8 antigens in blood have different mobilities in SDS-PAGE and buoyant densities. Moreover, SPan-1 and DF3 antigenic determinants are localized in different regions of the same normal and malignant pancreas and breast tissues. Thus the SPan-1 determinant can be dissociated from the breast peptide and/or carbohydrate determinants.


Effect of DNA ploidy classification on prognosis in breast cancer. A series of 327 breast cancers was analyzed for DNA ploidy by flow cytometry from paraffin-embedded tissue, and the resulting DNA histograms were classified independently by 6 researchers in the field as DNA diploid (Di), aneuploid (An), tetraploid (Te), multiploid (Mu), or technically uninterpretable. The frequency of diploid, aneuploid, tetraploid and multiploid cancers varied from 28 to 41%, 33 to 49%, 8 to 21% and 2 to 6%. According to the scale Di-An-Te-Mu, DNA ploidy was not significantly associated with breast-cancer mortality by 2 classifiers, but if DNA euploid cancers (Di+Te) were tested against non-euploid, or diploid cancers against non-diploid, all classifiers found DNA euploid and diploid cancers to have better prognosis. Mortality associated with diploid or tetraploid cancers decreased with improving histogram quality and increasing uniformity of classification, whereas that associated with aneuploid cancers remained unaltered. Among the cases where all classifiers agreed on ploidy, tetraploid, diploid and aneuploid cancers were associated with 100%, 88% and 68% 5-year survival rates. In this sub-set the S-phase fraction and possibly DNA ploidy were independent prognostic factors, together with histological grade, axillary node status, and primary tumor size.


Breast cancer and timing of surgery during menstrual cycle. A 5-year analysis of 385 pre-menopausal women. It has been proposed that the timing of breast-cancer surgery in relation to menstrual phase has a prognostic impact on outcome. We carefully evaluated a combined 2-center series of 385 pre-menopausal women operated on for stage-I and stage-II breast cancer with a median follow-up of 5 years for a possible impact on outcome of the date of their last menstrual period (LMP) before surgery. The distribution of risk factors of the study cohort as well as prognostic indicators corresponded to previously published results. Nodal status, grading, and (in part) hormone-receptor status differentiate well between patient subgroups with high and low risk of relapse and death after breast-cancer surgery. In neither univariate nor multivariate analysis was any impact of the so-called "unopposed" estrogen secretion detected. We did not observe any effect of LMP on long-term survival in any of several prognostic subgroups, in particular in hormone-receptor-positive patients. From our results and from the literature, we conclude that LMP does not provide any prognostic information for outcome after breast-cancer surgery and therefore the proposed modification of scheduling of breast-cancer operations is not justified.


H-2Db gene transfer into highly metastatic D122 cells results in tumor rejection in allogeneic recipients, but does not affect metastasis in syngeneic recipients. Implications for mechanisms of allorejection. Highly metastatic, weakly immunogenic Lewis lung carcinoma clones express very low levels of H-2Kb and moderate levels of H-2Db class-I major histocompatibility complex antigens. These cells metastasize spontaneously in mice with C57BL/6 genetic background possessing the H-2Db locus, and grow as local tumors across allogeneic barriers. Transfection of the H-2Db genes into the highly metastatic clone D122 did not alter the growth or metastatic capacity of these cells in syngeneic mice. However, these cells were rejected in allogeneic mice. Transfection of the H-2Kd or H-2Kk genes into D122 elicited a CTL population that cross-reacted with cells bearing native H-2Db antigens. These data suggest that overlapping allo-CTL populations are induced by a native alloantigen and by alloantigen peptides presented through self class-I molecules.


Regulation of androgen receptor gene expression by steroids and retinoic acid in human breast-cancer cells. Although the androgen receptor (AR) has been detected by ligand-binding assays, there is little known about the expression and regulation of the AR gene in human breast-cancer cells. AR mRNA, measured by Northern analysis in 18 cell lines, was found to be expressed predominantly in oestrogen- and progesterone-receptor-positive (ER+, PR+) lines as a single species of approximately 10.5 kb but was also comparatively abundant in I ER- and PR-negative cell line, MDA-MB-453. Dexamethasone (Dex), Organon 2058 (Org 2058), dihydrotestosterone (DHT), and all-trans-retinoic acid (RA) down-regulated AR mRNA levels in T-47D (ER+, PR+) cells 6 hr after treatment, whereas oestradiol (E2) had no effect. In MDA-MB-453 (ER-, PR-) cells, regulation of AR mRNA by RA differed from the other cell lines: RA increased the level of AR mRNA. DHT-binding assays indicated a corresponding increase in AR protein. Transfection of the androgen-responsive mouse mammary tumour virus long-terminal repeat (MMTV LTR) linked to a chloramphenicol acetyltransferase (CAT) reporter gene was used to examine the effect of altered AR levels on androgen action. The increased level of AR following RA pre-treatment in MDA-MB-453 cells resulted in enhanced induction of CAT activity by DHT and, conversely, a decrease in the level of AR following RA pretreatment in T-47D cells resulted in reduced induction of CAT activity by DHT. These data demonstrate that AR is expressed predominantly in ER+ and PR+ cell lines and its expression is regulated by ligands also known to regulate ER or PR, including progestins and retinoids. Androgen responsiveness measured by a transfected reporter gene was altered according to the extent of up- or down-regulation of AR expression, demonstrating that responsiveness is dependent on receptor concentration.


Specific cytogenetic abnormalities and k-ras mutation in two new human colorectal-adenoma-derived cell lines. Two new human epithelial cell lines from sporadic colorectal adenomas designated S/RR and S/BR are reported. Both cell lines have extended growth capacities in vitro, reaching passages 38 and 40 respectively and show no sign of senescence. S/RR and S/BR cell lines have retained the ability to differentiate in vitro, as shown by mucin production from goblet-like cells. S/BR was derived from a large colonic tubular villous adenoma (3 to 4 cm), whereas S/RR was derived from a small rectal adenoma (< 1 cm), and may represent a relatively early-stage adenoma. The parent S/RR cell line has given rise to a clonogenic variant, designated S/RR/Cl, which also has shown no sign of senescence and has currently reached passage 43. Both the S/BR and the S/RR cell lines had mutations in codon 12 of the K-ras gene, while retaining one normal allele. The presence of this mutation, particularly in the cell line S/RR derived from a small adenoma, is consistent with ras mutation being a relatively early event in colorectal carcinogenesis and is perhaps involved in the ability of the adenoma cells to progress and to give rise to an immortal cell line in vitro. The clonal derivatives of the S/RR cells have an isochromosome 1q and abnormalities of chromosome 13 which include an isochromosome 13q. The S/BR cells have a deletion on the short arm of chromosome 1 and trisomy 7. The common abnormality for S/RR and S/BR cells involves chromosome 1. The involvement of different chromosomes in the 2 cell lines also suggests different pathways for malignant progression of the premalignant adenoma cells.


Effect of IL-1 on experimental bone/bone-marrow metastases. Bone metastasis is a common event and a major cause of morbidity in cancer patients. The hematopoietic marrow of the bones, rather than the bone tissue per se, is the target organ in bone metastasis. In the bone marrow, IL-1 induces the release of hematopoietic growth factors that may affect tumor-cell growth. We treated groups of mice with rhuIL-1 alpha to examine its role in the establishment of experimental bone/bone-marrow metastasis. We found that injection of 2 micrograms of rhuIL-1 alpha 24 hr prior to, simultaneously with or 24 hr after the injection of 10(4) B16 melanoma cells into the left cardiac ventricle of mice resulted in a 2-fold increase in the average number of colonized bones per mouse. GM-CSF is produced by bone-marrow stromal cells in response to IL-1, and its receptor has been found on tumor cells, including melanoma cells. However, the administration of rmuGM-CSF to mice by either multiple injections or continuous infusion did not affect the number of colonized bones. Many of the biologic effects of IL-1 are mediated by prostaglandins. Treatment of mice with 100 micrograms of indomethacin, a potent inhibitor of prostaglandin synthesis, prior to the injection of rhuIL-1 alpha, prevented the increase in number of bone metastases. To determine whether constitutive productions of IL-1 and/or prostaglandins are involved in the pathogenesis of bone/bone marrow metastasis, we treated mice with antimouse IL-1 alpha neutralizing antibodies, rhuIRAP (an inhibitor of IL-1 activity) or indomethacin. We found no difference in the average number of colonized bones per mouse between treated and control mice. We conclude that exogenous administration of IL-1 enhances experimental bone/bone-marrow metastases, and that this phenomenon is mediated through prostaglandins. However, neither the constitutive production of IL-1 nor that of prostaglandins appear to play a role in the pathogenesis of bone/bone-marrow metastasis in our murine model system.


Inhibition by 6-hydroxydopamine of enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in spontaneously hypertensive rats. The effects of chemical sympathectomy induced by 6-hydroxydopamine (6-OHDA) on the enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in spontaneously hypertensive rats (SHR), and the norepinephrine (NE) concentrations in their gastric wall and the labeling index of gastric epithelial cells were investigated. SHR rats and normotensive Wistar Kyoto rats (WKY) as controls were given MNNG (25 micrograms/ml) in their drinking water for 25 weeks and then i.p. injections of 6-OHDA (42 mg/kg twice within 24 hr, and then 105 mg/kg every 2 weeks from 1 week later). In control group (WKY rat + NaCl), gastric cancers were found in 2 (11%) of 18 rats examined in week 52. In SHR rats treated with NaCl solution only, the incidence of gastric cancers significantly increased, to 53% compared with that in control WKY rats. Treatment of SHR rats with 6-OHDA significantly decreased its incidence to 12% compared with the value in SHR rats treated with NaCl solution only. Prolonged administration of 6-OHDA to SHR rats significantly reduced the NE concentration in the antral portion of the gastric wall and the labeling index of antral epithelial cells. These findings indicate that prolonged i.p. treatment with 6-OHDA attenuated the normally higher incidence of MNNG-induced gastric cancer in SHR rats.


Enhancement of cisplatin activity by lonidamine in human ovarian cancer cells. The ability of lonidamine, an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxicity of cisplatin was investigated in human ovarian-cancer cell lines sensitive (A2780) or with experimentally induced resistance (A2780/cp8) to the alkylating agent. A 24-hr post-incubation with 300 microM lonidamine significantly potentiated the activity of a 1-hr cisplatin treatment in both cell lines. In particular, the cisplatin IC50 value was reduced 4-fold in the sensitive line and 5-fold in the resistant line. Flow cytometric analysis showed that, in the resistant cell line, lonidamine alone did not affect cell kinetics, but when given after cisplatin it was able to transform the temporary G2 + M cell accumulation induced by the alkylating agent to a persistent block in S/G2 + M. In the A2780/cp8 cell line, lonidamine was also able to significantly enhance the accumulation of cisplatin-induced DNA interstrand cross-links. Our results suggest that lonidamine can positively modulate the anti-tumor activity of cisplatin in ovarian cancer cells and also indicate that the drug is potentially useful in combination therapy including the alkylating agent for ovarian cancer patients.


Percutaneous transluminal coronary angioplasty in patients aged 70 years and older: immediate and long-term results. We analyzed all coronary angioplasty procedures performed in patients aged greater than 70 yr since 1987. There were a total of 92 patients with a mean age of 74 +/- 4 yr (range 70-82). The clinical diagnosis was unstable angina in 79%. Single-vessel disease was present in 41%, double-vessel in 29% and triple-vessel in 30% of patients. A left ventricular ejection fraction of less than 40% was present in 18 patients. Angioplasty was attempted on one vessel in 52 patients (56%), on two vessels in 29 patients (32%) and in three vessels in 10 patients (11%). Angiographic success was achieved in 96% of stenoses and in 53% of chronic total occlusions attempted. Complete revascularization was achieved in 56% of patients. Complications included three patients (3.2%) who underwent emergency coronary artery bypass grafting, 1 patient (1.1%) who sustained a myocardial infarction and 5 patients (5.4%) who died. During hospitalization, which averaged 3 +/- 2 days, 1 patients sustained reversible renal failure and 5 patients required blood transfusion for a large groin hematoma. Clinical success at discharge was 83%. At a mean follow-up of 13 months (range 3-45 months), symptomatic improvement was observed in 59 of the 76 patients who had achieved clinical success, with 42 of these patients (55%) being asymptomatic. The following clinical events occurred: myocardial infarction in 1 patient, new percutaneous transluminal coronary angioplasty in 9 and 3 patients died of cardiac reasons.(ABSTRACT TRUNCATED AT 250 WORDS)


Metabolic adaptation of myocardial mitochondria to mild altitude hypoxia. We studied the metabolic parameters of myocardial mitochondria (respiration, respiratory control index, oxidative phosphorylation rapidity and coefficient of oxidative phosphorylation) in two groups of rats: one living at an altitude of 140 m above sea level (control group) and the other living from birth at an altitude of 1350 m above sea level for 2 and 4 months (experimental group). Compared with the control rats, the experimental rats during 2 and 4 months of mild altitude acclimatization increased their basal and stimulated respiration, as well as the rapidity of energy production by myocardial mitochondria. The coefficient of oxidative phosphorylation under mild altitude hypoxia decreased but the respiratory control index did not change. We explain these alterations of heart muscle metabolism at the mitochondrial level as an adaptation to the mild hypoxic conditions.


Cardiac tamponade as presentation of systemic amyloidosis. We present a patient with pericardial tamponade due to amyloid heart disease. A 64-yr-old man was admitted to the hospital because of fatigue and the abrupt development of chest pain and dyspnea. Echocardiography showed severe pericardial effusion and total pericardiectomy was necessary. Ten months later laboratory studies revealed proteinuria and high serum creatinine. A rectal biopsy showed amyloid deposition that was also found in the pericardial tissue. Pericardial tamponade is an extremely rare complication of cardiac amyloidosis. To our knowledge, only one previous case of cardiac tamponade due to amyloid heart disease has been reported.


"Serpentine heart". Direct observation of the human heart during profound hyperkalemia. We observed cardiac contractility in a patient who had inadvertently received a massive overdose of potassium chloride during open heart surgery. Slowly advancing waves of contraction were present while the surface electrocardiogram showed the sine wave configuration typical of severe hyperkalemia. This is the first report of such an observation and may serve to promote proper diagnosis and treatment of similar cases.


Coronary-cameral fistula in association with Klinefelter syndrome: exercise-induced ventricular tachycardia late after surgical ligation. Twenty two years after surgical ligation of a large coronary-cameral fistula originating from the circumflex artery and terminating to the right atrium, non-sustained exercise-induced ventricular tachycardia occurred in a 26-year-old male with known Klinefelter (XXY) syndrome. Cardiac catheterization showed satisfactory closure of the defect, but also revealed occlusion of the circumflex coronary artery, associated with inferolateral infarction.


Absence of the right superior caval vein associated with disease of the sinus node. Absence of the right superior caval vein has been shown by postmortem studies of infants and children to be associated with histological abnormalities of the sinus node. We report the case of a 32-yr-old man who presented with syncope due to disease of the sinus node and was found to have absence of the right superior caval vein. He was successfully managed with implantation of an epicardial atrioventricular sequential pacemaker.


Common arterial trunk with absence of the left pulmonary artery in a 32-year-old man. We report a case of common arterial trunk with absence of the left pulmonary artery who was diagnosed at the age of 32 years. Pulmonary vascular disease made the condition inoperable. He does well with medical management after a follow-up of 20 months.


Left internal thoracic artery bypass graft in arterial switch with coronary transfer for transposition of the great arteries. The left internal thoracic artery was anastomosed to the circumflex coronary artery to treat myocardial ischemia during an arterial switch procedure for transposition of the great arteries in a 6-month-old infant. Follow-up angiography revealed complete patency of the anastomosis.


Assessment of coronary stent by intravascular ultrasound. The use of intravascular ultrasound to assess the adequacy of the deployment of an intracoronary stent is described. Although angiographically a good result was suggested, intravascular ultrasound showed this to be misleading.


Exercise-induced bradycardia after Mustard repair for complete transposition. Impairment of sinus rhythm has been reported after the Mustard procedure for complete transposition. We observed two patients who developed severe bradycardia during or after exercise. The first had a 2.8 s sinus pause in the recovery period, the second had a drop in heart rate during exercise. Both eventually had a pacemaker implanted. Exercise testing can be helpful in detecting sick sinus syndrome.


Intermediate-term clinical and hemodynamic results of the neonatal arterial switch operation for complete transposition of the great arteries. We prospectively evaluated 49 consecutive hospital survivors of the arterial switch operation for complete transposition and intact ventricular septum by clinical examination, echocardiography, cardiac catheterization, 12-lead and 24-h Holter ECG. The mean length of follow-up was 40 +/- 18 months. Forty-six children are clinically asymptomatic without medication, 2 died due to coronary related left ventricular dysfunction 3 and 12 months after surgery, and 1 required reoperation because of severe bilateral pulmonary branch stenoses. Except for this case, cardiac catheterization (n = 23) revealed a mean gradient of only 17 +/- 8 mmHg between the right ventricle and distal pulmonary arteries. Left ventricular end-diastolic volume was within normal limits except for 2 cases with volumes slightly below normal, the mean ejection fraction was 78 +/- 5%, and end-diastolic and end-systolic ventricular shapes were normal. The mean cardiac index was 4.14 +/- 0.69 l/min/m2. Left ventricular end-systolic wall stress to velocity of fiber shortening relation was normal in all cases examined (n = 15), indicating normal myocardial contractility. Significant neoaortic valve insufficiency was never observed despite considerably enlarged aortic roots. Twenty-four-hour Holter ECG records (n = 46) provided no evidence of serious atrial arrhythmias, especially sinus node dysfunction. These encouraging intermediate-term results make the arterial switch operation the treatment of choice at present, for neonates with simple transposition.


Social adaptation of young adults with congenital heart disease. The social status of 71 young adults (30 females, 41 males, aged 22.9 +/- 1.9 yr) with congenital heart disease was compared with that of 211 (106 females, 105 males, mean age 23.2 +/- 1.4 yr) randomly selected controls. The clinical examinations included clinical study with ultrasonic visualization, electrocardiography, X-ray and measurement of exercise capacity. In the study group 87% had completed school at the secondary level and another 21% at high school level, while the corresponding figures in the control group were 98% and 51%. About half of both groups continued to vocational training and a fifth to a higher level. Those without any vocational education made up 32% of the study group (95% confidence interval 21-43%) and 11% of the controls (95% confidence interval 7-15%). State benefits were the main source of income for 13% of the study group as compared to 2% among the controls. The employment status of the actual labour force showed no significant difference between the groups. Among patients with congenital heart disease there were significantly more of those who had developed a dependent life style, living with their parents without a marital or quasi-marital relationship. A cyanotic type of severe heart defect is one of the factors predisposing to poor success at school and a dependent lifestyle. Congenital heart disease, even when treated, is a significant factor which influences adult life. The results call for more practical support to assist psychosocial maturation, especially in patients with residual defects.


Effect of diltiazem on norepinephrine-induced acute left ventricular dysfunction. The present study has examined the role of diltiazem as a protective agent in a canine model of norepinephrine cardiotoxicity. Effects of diltiazem, 20 micrograms/kg/min x 5 min pretreatment followed by 10 micrograms/kg/min x 90 min, or saline infusion were examined at baseline and 1 h after infusion of norepinephrine, 4 micrograms/kg/min for 90 min, in closed-chest anesthetized dogs. Left ventricular function was assessed by equilibrium radionuclide angiogram and two-dimensional echocardiogram. In 7 saline experiments, hypotension and increased heart rate were observed at 1 h post infusion. In the diltiazem-treated group (n = 7), mean arterial pressure and heart rate were unchanged. In the saline group, left ventricular ejection fraction fell from 0.50 +/- 0.04 to 0.28 +/- 0.04. Left ventricular ejection fraction was unchanged in the diltiazem-treated group: 0.52 +/- 0.03 to 0.55 +/- 0.07. Left ventricular end-diastolic volume was increased at 1 h post infusion in saline controls but not in the diltiazem-treated group. Measurement of fractional shortening from two-dimensional echocardiograms also indicated left ventricular dysfunction in the saline but not diltiazem-treated groups. Left ventricular end-systolic wall stress following norepinephrine infusion was significantly increased in the saline but not diltiazem-treated groups: 122.7 +/- 18.7 vs 67.6 +/- 19.7 g/cm2, respectively. In dogs receiving saline without norepinephrine infusion, no significant changes occurred over the course of the experiment. Histologic examination showed mild contraction band necrosis in saline controls but not in sham saline dogs. Diltiazem showed intermediate histologic evidence of injury, which was not further quantified. This study suggests that effects of norepinephrine on left ventricular function in the canine model of norepinephrine cardiotoxicity may be largely due to increased wall stress following a prolonged increase in afterload. Diltiazem pretreatment afforded significant protection of left ventricular function.


The effect of antiplatelet therapy on platelet accumulation after experimental angioplasty in the rabbit iliac model. Antiplatelet therapy is routinely used in balloon angioplasty. Yet recent clinical trials have not shown these agents to reduce the incidence of restenosis. As this might be due to inadequate antiplatelet effect, this study was designed to evaluate the effectiveness of antiplatelet therapy in reducing platelet accumulation immediately after angioplasty. Sixty-six atherosclerotic rabbits underwent angioplasty of a focal (50-99%) iliac stenosis after pretreatment with an antiplatelet drug. The animals were randomly given aspirin (10 mg/kg orally) (n = 10), aspirin (10 mg/kg intravenously) (n = 7), aspirin (10 mg/kg per os) plus dipyridamole (25 mg orally) (n = 8), a thromboxane synthetase inhibitor (GS13080, 1 mg/kg/h intravenously) (n = 9) or heparin (500 U/kg intravenously) (n = 9). Platelet accumulation, determined by 51Cr-labeled platelet counts 30 min after angioplasty disclosed a significant reduction from control (44.1 +/- 51.2 platelets/cm x 10(6)) with intravenous aspirin (3.3 +/- 1.9; p less than 0.007) and the thromboxane synthetase inhibitor CGS13080 (15.1 +/- 16.6, p less than 0.04). Aspirin plus dipyridamole reduced platelet accumulation as well (10.4 +/- 9.8, p = 0.076), while oral aspirin (109.5 +/- 240) and heparin (34.7 +/- 35.5) were ineffective. The results of this study demonstrate that pretreatment with antiplatelet agents can reduce platelet accumulation significantly after experimental angioplasty. However, the wide variability in effectiveness particularly with oral aspirin may have important clinical implications. Further investigation into more effective antiplatelet therapy may help to reduce the incidence of abrupt vessel closure and restenosis.


Young infarct patients with single-vessel occlusion do not have an underlying prothrombotic state to explain their coronary occlusion. To determine the importance of a prothrombotic state in the pathogenesis of coronary occlusion in young infarct patients, assessment of risk factor profile and thrombotic tendency was undertaken in 25 young male patients (age less than 45 yr) who were shown at angiography, following myocardial infarction, to have occlusion of a single coronary. Comparison was made with a control group of symptomatic males aged greater than 55 yr, who at angiography had significant disease in two or more coronary arteries (multi-vessel disease control group). At the time of the study more patients in the single-vessel disease study group smoked cigarettes (n = 12) compared to the control group (n = 5) (p less than 0.01). Serum cholesterol and triglycerides were higher, and high density lipoprotein-cholesterol lower, in the single-vessel disease group but the difference reached significance only with the high density lipoprotein-cholesterol. Quantitative platelet aggregability was similar in the two groups. Although the level of beta-thromboglobulin, was higher in the single-vessel disease study group the difference was not significant. There were also no significant differences between these groups in levels of fibrinogen, Factor XII and alpha-2 antiplasmin. Patients in the multi-vessel disease group, however, had increased Factor VII levels (p less than 0.01). There were no significant differences between the two groups in fibrinolytic potential or in levels of antithrombin III. Coronary occlusion in the young appears likely to be due primarily to an arterial (plaque) related event as opposed to an abnormal coagulation response to minor arterial plaque damage.


A low plasma selenium is a risk factor for peripartum cardiomyopathy. A comparative study in Sahelian Africa. A specific selenium deficiency is a risk factor for Keshan disease, an endemic cardiomyopathy observed in China. In a Sahelian area of Niger, plasma selenium concentration was measured by neutronic activation and particle induced X-ray emission in 35 black African women with peripartum cardiomyopathy and 36 breast-feeding women without cardiac failure as controls. The plasma selenium concentration in patients was lower (48 +/- 25 ng/ml, mean +/- standard deviation) than in controls (77 +/- 16 ng/ml) (P less than 0.0001). Moreover, 40% (14/35) patients with peripartum cardiomyopathy had very low plasma selenium concentrations, below 45 ng/ml, versus none in controls. A low plasma selenium concentration is a risk factor for the Sahelian peripartum cardiomyopathy.


Transesophageal echocardiography in adults with a continuous precordial murmur. In order to assess the ability of echocardiography in the detection of intracardiac and extracardiac shunts, we studied 11 patients (aged 22-64 yr) with a continuous precordial murmur using transthoracic and transesophageal echocardiography, and correlated the results with the subsequent angiographic and surgical findings. We found that only in 5 of 6 patients with a patent arterial duct could the continuous flow pattern be detected in pulmonary artery using transthoracic echocardiography, whereas it could be readily and accurately identified by transesophageal echocardiography in all patients. The diameters of the patent arterial duct were also measured and found to be in good correlation with subsequent surgical findings (r = 0.98, p less than 0.05). In 2 patients with a ruptured aneurysm of sinus of Valsalva which originated from the right coronary sinus and perforated into the right ventricle, transesophageal echocardiography gave a better image than transthoracic echocardiography. In 2 patients with coronary artery fistula, the origin and site of drainage of the coronary artery could be imaged using transesophageal echocardiography, but the course of coronary artery fistula was more easily detected by transthoracic echocardiography. In one patient with aortopulmonary window, the defect between ascending aorta and main pulmonary artery could readily be imaged by transesophageal echocardiography. We therefore recommend transesophageal echocardiography when evaluating patients with precordial continuous murmur in whom intracardiac and extracardiac shunts or defects are suspected.


Electrophysiology and long-term efficacy of pentisomide in patients with supraventricular tachycardia. The electrophysiologic effects of pentisomide were investigated after intravenous (5 mg/kg) and oral (900-1200 mg three times a day) application in 9 patients with drug refractory atrioventricular nodal tachycardia and 6 patients with orthodromic atrioventricular re-entrant tachycardia. Pentisomide did not change sinus cycle length, effective refractory period of the right ventricle and the atrioventricular node. AH, HV interval, effective refractory period of the right atrium, QRS duration and QTc duration were (p less than or equal to 0.01) increased. Tachycardia cycle length was only increased after intravenous application of pentisomide, antegrade effective refractory periods of the accessory pathways and shortest fully pre-excited R-R intervals during atrial fibrillation were increased after the oral treatment phase (p = 0.054). Intravenous pentisomide prevented tachycardia in 6/9 patients with atrioventricular nodal tachycardia and in 2/6 patients with atrioventricular re-entrant tachycardia. If intravenous pentisomide did not prevent induction of the tachycardia, oral pentisomide was not effective either. During long-term follow-up 2/7 patients with atrioventricular nodal tachycardia and 1/4 patient with atrioventricular re-entrant tachycardia had a recurrence. Long-term treatment with pentisomide had to be discontinued because of possible side effects in 2 patients. It is concluded, that the electrophysiological effects of pentisomide are similar to those of flecainide and propafenone.


Effects of phenytoin on the ventricular tachyarrhythmias of chronic Chagas' disease. The effects of phenytoin on the ventricular tachyarrhythmias of 11 patients with chronic chagasic myocarditis were investigated, and correlated with the serum phenytoin levels. Physical examination, laboratory tests and 24- to 48-h ambulatory electrocardiographic recordings were performed before, during (7-14 days) and after treatment with phenytoin (4-6 mg/kg/day, orally, in three divided doses). Significant (greater than 90%) reduction of couplets, bigeminy and runs of ventricular tachycardia were observed in 50-67% of the patients, whereas the frequency of isolated premature ventricular contractions was significantly (greater than 70%) reduced in only 2 patients (18%). Proarrhythmic activity was not observed and adverse side effects were of mild intensity and usually transient, except in one patient, who developed pruritus and skin rash in the presence of toxic phenytoin serum levels (27 micrograms/ml). It is suggested that phenytoin may be useful for the control of repetitive forms of ventricular tachyarrhythmias in selected patients with chronic chagasic myocarditis.


Congenitally corrected transposition of the great arteries associated with hypoplasia of the morphological left ventricle in the setting of atrial situs inversus. Hypoplasia of the morphological left ventricle associated with severe pulmonic stenosis and an intact ventricular septum in the setting of congenitally corrected transposition of the great arteries is a rare lesion. We report the clinical and echocardiographic findings of this lesion in a patient with atrial situs inversus.


Electrophysiologic effects of selective B1 adrenergic stimulation in the late phase of myocardial infarct healing. Nonspecific adrenergic stimulation plays an important role in the genesis of ventricular tachyarrhythmias in the postinfarction period. However, the role of selective B1 adrenergic stimulation in the aggravation of reentrant ventricular tachycardia is still poorly understood. The purpose of this investigation was to study the regional electrophysiologic actions and arrhythmogenic effects of the B1 adrenergic agonist dobutamine in a postinfarction canine model. Eleven dogs with 4-week-old anterior wall myocardial infarctions, chronic indwelling intramyocardial electrodes and no inducible sustained ventricular tachycardia at baseline, were studied in the closed-chest state at baseline (control) and during intravenous infusion of dobutamine 10 micrograms/kg/min. Dobutamine caused reductions in the effective and absolute refractory periods in the infarct, peri-infarct and noninfarcted regions of the myocardium which were similar in magnitude at each region. With dobutamine, only 1 dog had inducible sustained ventricular tachycardia (polymorphic). No spontaneous arrhythmias were seen. In summary, selective B1 adrenergic stimulation alone does not cause dispersion of myocardial refractoriness and does not cause significant proarrhythmia in the chronically infarcted canine heart. Additional metabolic, electrolyte or ischemic abnormalities may be required for B1 adrenergic stimulation to aggravate arrhythmias in this model.


Anaemia in children following cardiac transplantation: treatment with low dose human recombinant erythropoietin. Anaemia is common in children following cardiac transplantation. In a series of 5 children with anaemia beyond the immediate post-operative period one had a hypochromic, microcytic anaemia which corrected with oral iron. The other four had normochromic, normocytic anaemias unresponsive to iron or folate supplementation and associated with inappropriately low levels of erythropoietin. Subcutaneous administration of low dose human recombinant erythropoietin to these four patients resulted in correction of their anaemia. Our findings suggest that erythropoietin deficiency is an important cause of anaemia in transplant recipients and should be sought in cases of anaemia refractory to conventional haematinic therapy. In cases of proven erythropoietin deficiency, treatment with erythropoietin is effective, acceptable to patients and preferable to repeated blood transfusion.


Is a parental history of coronary arterial disease in children as discriminating as their lipoprotein profile? Niño Jesus Group. The relationship between hyperlipidemia and a parental history of heart attack and other related disorders was studied in 2224 two- to 18-yr-old children in Madrid (Spain). Children were divided into three groups: those with a parental history of heart attack (first group), a parental history of stroke, hypertension, diabetes mellitus or hypercholesterolemia (second group), and no parental history of disease (third group). The number of children with higher than normal levels of total cholesterol (greater than 200 mg/dl), LDL-cholesterol (greater than 135 mg/dl) and/or apolipoprotein B100 (greater than 75 mg/dl) was significantly higher in the first and second group (positive parental history) than in the third (no parental history). Children and adolescents with a parental history of heart attack (first group) had significantly higher mean levels of total cholesterol and LDL-cholesterol; in the 2- to 13-yr age group a significantly higher level of apolipoprotein B was also found. Children and adolescents belonging to the second group had a significantly higher level of LDL-cholesterol, and a significantly higher level of apolipoprotein B was also found in the 2- to 13-yr age group. However, only 15% of children with hypercholesterolemia had a parental history of heart attack or other related disorders. This percentage was 41% when second-degree relatives were included in the family history. We conclude that a parental history is not enough to detect children with an abnormal lipid profile who might be at risk for early development of coronary arterial disease.


Balloon angioplasty for native coarctation of the aorta in children and adults: factors determining the outcome. Balloon angioplasty was performed in 46 patients (age 2-40 yr) with discrete native coarctation of aorta. Patients with associated patent ductus arteriosus, aberrant subclavian artery and aneurysms were excluded. The peak systolic gradient across the coarcted segment decreased from 52.1 +/- 18.5 mmHg to 18.6 +/- 14.8 mmHg (p less than 0.001), and the diameter of the coarcted segment increased from 3.6 +/- 1.7 mm/m2 to 9.1 +/- 3.2 mm/m2 (p less than 0.001). Follow-up haemodynamic and angiographic studies performed in 21 patients at 13.1 +/- 6.9 months after angioplasty, showed good results in 15 patients. Four patients undergoing haemodynamic study and 4 other patients undergoing noninvasive evaluation were graded as having bad results at follow-up. In 5 of these patients the poor results were due to primary failure of angioplasty in relieving the gradient, and three developed re-coarctation after initial fall in the trans-coarctation gradient. Four risk factors were identified on univariate analysis, which were associated with significantly larger residual gradients at follow-up: (1) size of isthmus/size of coarcted segment ratio less than 3.0; (2) size of post-coarctation descending aorta/size of isthmus ratio greater than 1.75; (3) size of coarcted segment after angioplasty/size of coarcted segment before angioplasty ratio less than 2.0; and (4) size of balloon/size of coarcted segment ratio less than 3.0. The presence of one or more risk factors was associated with bad late results. On multivariate analysis the ratio of balloon size/coarcted segment size was found to be the sole independent predictor of the late outcome (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


Ventricular late potentials: another expression of cardiotoxicity of cytostatic drugs in children? With the aim of finding a sensitive method to detect early anthracycline-induced myocardial damage ultimately resulting in cardiomyopathy, we studied the occurrence of ventricular late potentials, using a signal averaged electrocardiogram, in 68 children with cancer during or after chemotherapy. Ten (15%) of the children showed late potentials; in addition, patients treated with cytostatic drugs had significantly lower voltages of the last 40 ms of the QRS complex (RMS40) and a longer duration of low amplitude signals in the terminal QRS (LAS) than control patients. The occurrence of late potentials was not significantly correlated with anthracycline therapy or dosage, nor with the presence of echocardiographic abnormalities; in none of the patients we found late potentials during therapy with anthracyclines. We therefore conclude that late potentials are not helpful for early detection of myocardial injury. The occurrence of late potentials, however, does show another expression of cardiotoxicity not specifically related to anthracycline therapy. The occurrence of these late potentials may have prognostic significance with regard to the risk of ventricular arrhythmias during longer follow-up of these patients.


Effects of dietary supplementation with fish oil on prostanoid metabolism during acute coronary occlusion with or without reperfusion in diet-induced hypercholesterolemic rabbits. We studied the changes in myocardial and aortic concentrations of prostacyclin and thromboxane A2 during acute coronary occlusion with or without reperfusion in rabbits fed with a cholesterol-enriched diet with or without fish oil supplementation for a short (5 days) or long period (6 weeks). New Zealand white male rabbits were divided into 5 groups: Group I, 15 control rabbits fed with a laboratory standard rabbit chow. In addition to the standard chow, the 4 study groups were treated with cholesterol or fish oil. Group II, 17 rabbits fed with a 1% high cholesterol diet for 5 days. Group III, 16 rabbits fed with a diet containing 1% cholesterol and 10% fish oil for 5 days. Group IV, 17 rabbits fed with the same diet as group II for 6 weeks. Group V, 18 rabbits fed with the same diet as group III for 6 weeks. Each group of rabbits was randomly divided into the coronary occlusion or occlusion-reperfusion mode of experiment. Acute coronary occlusion was induced by ligating the marginal branch of the left circumflex coronary artery for 1 h. Subsequent reperfusion for 4 h was performed in the occlusion-reperfusion rabbits. The aortic tissue above the aortic valve and the ischemic and normal (nonischemic) areas of the left ventricle were excised for the measurement of 6-keto-PGF1 alpha and thromboxane B2 levels by radioimmunoassay. Both during coronary occlusion and occlusion-reperfusion, rabbits showed higher myocardial concentrations of 6-keto-PGF1 alpha and thromboxane B2 in the ischemic area than in the normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)


Atrial natriuretic factor and concomitant hormonal, hemodynamic and renal function changes after slow continuous ultrafiltration. We treated a patient with refractory biventricular heart failure, dilutional hyponatremia and prerenal azotemia, by means of ultrafiltration. After ultrafiltration, gas exchange and cardiac output improved, with concomitant reduction of systemic and pulmonary vascular resistances. Despite a decrease of right atrial and wedge pressure, atrial natriuretic factor rose and plasma renin activity decreased.


Repair of asymptomatic aortic valve disease during other cardiac surgery. Repair of asymptomatic aortic valve disease was performed in 12 patients (9 female, 3 male, mean age 57.5 years) undergoing other cardiac surgery. Stenosis was the predominant aortic valve lesion in 7 (group A) with a mean gradient of 33.4 mmHg and regurgitation of mean grade 1.4 was predominant in 5 (group B). Cusp debridement +/- commissurotomy was performed in 9; commissural resuspension in 6 and repair of cusp perforation in 2. Perioperative transoesophageal echocardiography was used to assess the adequacy of repair in 4 patients. Prospective precordial echocardiographic follow-up is complete (mean 4.3 months). In group A there has been a significant reduction is peak aortic pressure gradient (33.4 vs 22.1 mmHg, p less than 0.05) and in cusp thickness (2.25 to 1.64 mm, p less than 0.05). In group B the degree of incompetence has improved in 3 of the 5 patients. Three patients have worsened valve disease following repair; in all these there was mixed valve disease of rheumatic origin. Aortic valve repair of asymptomatic disease during other cardiac surgery is a feasible technique which does not accelerate the disease process in the short term. Long-term follow-up is in progress to assess the prognosis of this preventive intervention.


The sensitivity of intracoronary injection of acetylcholine in inducing coronary spasm differs in patients with stable and unstable angina. In an attempt to clarify the role of coronary artery spasm in the pathogenesis of unstable angina, acetylcholine (20 and 50 micrograms) was injected directly into the coronary arteries of 19 patients with unstable effort angina (group 1), 30 patients with unstable spontaneous angina (group 2), and 15 patients with stable effort angina due to coronary artery organic stenosis (greater than or equal to 75%) (group 3). Coronary spasm was defined as severe vasoconstriction (greater than or equal to 90% of luminal diameter) with chest pain and/or ischemic ST-segment changes. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in 19 patients (100%) of group 1 and 28 (93%) of group 2 but only 3 (20%) of group 3 (p less than 0.01). When acetylcholine was injected into the left and right coronary arteries separately, multivessel spasm (spasm of both coronary arteries) was induced in 5 of 12 (42%) patients of group 1 and in 9 of 23 (39%) patients of group 2. In contrast, intracoronary acetylcholine did not cause multivessel coronary spasm in any of 15 patients of group 3 (0%). These results suggest that coronary arteries in patients with unstable effort angina as well as spontaneous angina are susceptible to spasm and that coronary artery spasm may be responsible at least in part for the genesis of attacks in these patients.


The influence of captopril on intrahospital mortality and duration of hospitalization in Nigerians with congestive heart failure. A retrospective study was undertaken to evaluate the impact of captopril on intrahospital mortality and the duration of hospitalization in Nigerians with congestive heart failure. In 1989 and 1990, the mortality rates were 13.7% and 15.2%, respectively, and it appeared to be reduced to 6.6% in 1991 after the introduction of captopril. There was a significant (p less than 0.001) increase in the proportion of patients with early discharges (less than 10 days hospitalization) following the addition of captopril to the standard antifailure regime in Nigerians.


Amiodarone reduces QT dispersion in patients with hypertrophic cardiomyopathy. To compare QT interlead variability (dispersion) in patients who receive a class III antiarrhythmic with those not on antiarrhythmic therapy, we measured QT in all 12 leads of a standard ECG in 24 patients with hypertrophic cardiomyopathy, 12 (50%) of whom were on amiodarone monotherapy and 12 (50%) who were not on amiodarone or other cardioactive medication which could affect QT. Age, functional class, chamber dimension or the degree of left ventricular hypertrophy expressed by maximal wall thickness (21 +/- 5 vs 20 +/- 4 mm; p = NS) was not different between the amiodarone and the non-amiodarone group. Maximal corrected QT (QTc) was greater in patients receiving (488 +/- 25 ms) compared to those not receiving amiodarone (451 +/- 23 ms) (p less than 0.001). However, QTc dispersion defined as the difference of maximum minus minimum QTc was decreased in the amiodarone (48 +/- 10 ms) compared to the non-amiodarone group (78 +/- 17 ms) (p less than 0.001). We conclude that in patients with hypertrophic cardiomyopathy, amiodarone prolongs QTc but reduces QTc dispersion. These results agree with expected changes in ventricular recovery time in patients who receive Class III antiarrhythmic agents and provide further support to the theory that QTc dispersion reflects regional differences in ventricular recovery time.


Relationship between stature and coronary heart disease in a German male population. Short stature in men has previously been associated with a higher risk of coronary heart disease. In order to further investigate this observation, the physical characteristics of 4470 German men admitted to the Klinik Roderbirken between 1978 and 1989 with a documented myocardial infarction and with a stenosis greater than or equal to 75% in at least one vessel were compared to those of 711 male controls. Results indicated that the myocardial infarct group was significantly shorter by 1.8 cm than the control group (p less than 0.001). However, discriminant function analysis indicated that height accounted for only 1% of the variance between the cardiac and control patients. Classification analysis further indicated that on the basis of height, the percentage of subjects correctly classified for grouping was no better than 54% for the myocardial infarct patients and 57% for the controls. It was concluded that height exerted a minimal influence on coronary heart disease in this population.


Transoesophageal Doppler pulmonary venous flow pattern and left atrial spontaneous contrast in mitral stenosis. The relationship between transoesophageal Doppler pulmonary venous flow pattern and spontaneous left atrial contrast was studied in 23 patients with isolated severe mitral stenosis (mitral valve area = 0.8 +/- 0.2 cm2). The patients with none or minimal (1+) spontaneous contrast (n = 15, group I) were compared with those with significant spontaneous contrast (grade 2+, n = 8, group II) with regard to peak systolic velocity (33 +/- 14 cm/s vs 28 +/- 12 cm/s, p = NS), peak diastolic velocity (36 +/- 14 cm/s vs 28 +/- 8 cm/s, p = NS) and peak atrial reversal velocity (19 +/- 4 cm/s vs 19 +/- 8 cm/s, p = NS), systolic forward flow velocity time integral (3.37 +/- 1.73 cm vs 2.78 +/- 0.9 cm, p = NS), diastolic forward flow velocity time integral (2.85 +/- 1.2 cm vs 2.65 +/- 1.87 cm, p = NS), ratios of peak systolic and diastolic velocity (0.91 +/- 0.21 vs 0.95 +/- 0.29, p = NS) and duration of diastolic deceleration (117 +/- 59 ms vs 132 +/- 106 ms, p = NS). The results show that the occurrence of spontaneous contrast in the left atrium in patients with mitral stenosis is not related to the Doppler-estimated pulmonary venous flow.


Discordance between abdominal and atrial arrangement in a case of complex congenital heart disease. The report describes a rare case of a complex congenital heart disease wherein the splenic status and the relationship of the suprarenal abdominal great vessels strongly suggested right isomerism, but atrial morphology demonstrated usual atrial arrangement. It emphasises the increasing recognition that the arrangement of the abdominal organs need not accurately reflect atrial arrangement.


The syndrome of absent or faint second heart sound, rapid systole and forward collapsing pulse. A syndrome consisting of an absent or faint second heart sound, prominent cardiac impulse and non-regurgitant or forward collapse of the pulse is described. There was, moreover, no second sound or flow murmur audible in either the aortic or the pulmonary area even though the impulse and collapsing pulse suggested a hyperdynamic circulation; the upstroke was sharp but without the full waterhammer knock. It is argued that the dominant cause of the collapsing pulse will usually be vasodilation, that absence or faintness of the second sound is due to a narrow angle of divergence between the ventricular and arterial pressure decay curves, and that in marked contrast to aortic regurgitation the quality of the impulse derives from rapid systole of lightly loaded ventricles. Although they described its separate elements, pre-homeostatic era clinicians may have overlooked the syndrome in the belief that the heart regulated a largely passive circulation, regarding only primary intracardiac events and the first heart sound as important. Sir William Stokes nevertheless foresaw that alterations in the second sound might be due to changes in vascular tone as well as in elasticity. Wider recognition, deeper understanding and appropriate correction of this syndrome may prove both useful and enlightening.


A case of multiple pericardial hydatid cysts. Pericardial cysts are rare developmental benign intrathoracic lesions and constitute 7% of all mediastinal tumors. As many as 70% of the cysts are found in the right cardiophrenic angle. Unusual locations include the left costophrenic angle, the hilum and the superior mediastinum at the level of the aortic arch. Cysts arising inside the pericardial cavity and attached to the heart are exceedingly rare. We describe a case of multiple pericardial hydatid cysts.


Ventricular septal aneurysm in a case of Ehlers-Danlos syndrome. Cardiac abnormalities are a recognised feature of connective tissue disorders. We report a case of Ehlers-Danlos syndrome associated with an aneurysm of the membranous ventricular septum and mitral valve prolapse. To our knowledge this is the first reported association of Ehlers-Danlos syndrome and ventricular septal aneurysm.


Mechanism of cyanotic spells in tetralogy of Fallot--the missing link? The mechanism of cyanotic spells in patients with tetralogy of Fallot is not clear. Increases in infundibular contractility or hyperpnoea have been considered as the key factors, but this explanation appears inadequate. In this review, arguments are presented against these commonly held views. Preliminary evidence is synthesised in favour of another more plausible hypothesis that cyanotic spells may result from mechanoreceptor stimulation from the right ventricle. Increased contractility (due to catecholamines) and decreased right ventricular size (due to various factors) can trigger a reflex resulting in hyperventilation, some peripheral vasodilation without bradycardia, and this may initiate a spell. This mechanism explains most of the precipitating events and many other issues about cyanotic spells more satisfactorily.


Hypertrophic cardiomyopathy and myocardial bridging. Two patients are reported in whom hypertrophic cardiomyopathy was associated with myocardial bridging of the left anterior descending coronary artery. One had a history of angina and recurrent syncope, the other had chest pain and exertional dyspnoea. In each case the diagnosis was made by cross-sectional echocardiography and coronary angiography.


Mycotic aneurysm of the descending aorta diagnosed by echocardiography. We present a 3-yr-old girl with coarctation of aorta and patent ductus arteriosus in whom mycotic aneurysm and bacterial endarteritis developed postoperatively and was diagnosed by two-dimensional and Doppler echocardiography. Five weeks after the operation of ligation of ductus and resection of coarctated segment, the patient was readmitted with complaints of vomiting, fever and coughing. Bacterial endarteritis, empyema and septic arthritis were diagnosed. Suprasternal echocardiographic examination demonstrated an aneurysmatic appearance 60 x 65 mm in size at the location of coarctation. The patient died, most probably due to aortic rupture, before surgical treatment could be undertaken. Autopsy study confirmed our diagnosis.


Giant epicardial lipoma.

Giant epicardial lipoma. A patient undergoing coronary artery bypass was found to have a giant epicardial lipoma weighing 1.36 kg which was excised uneventfully. The radiological and pathophysiological features are considered, and the options for management discussed.


Radiofrequency ablation of incessant ventricular tachycardia to prevent multiple defibrillator shocks. In a patient who received frequent shocks from an implantable defibrillator, a slow ventricular tachycardia originating in a large left ventricular aneurysm was ablated with radiofrequency current. Pacemapping perfectly matched the spontaneous, incessant arrhythmia. Local entrainment was present, along with a mid-diastolic potential of 65 microV. Application of 30 W terminated tachycardia within 12 s. He had no more recurrences during follow-up.


Recurrent acute myocardial infarction during sport. A 48-yr-old well conditioned man developed acute myocardial infarction twice during sporting activities. After both events right coronary angiography showed a moderate proximal stenosis and, 5 months later, a subtotal obstruction at the site of prior slight lumen irregularity. This case suggests a causal relationship between sport and the occurrence of acute coronary events.


Lung function in atrial septal defect after heart surgery. Lung volume, indices of lung elasticity and airway patency were measured in 74 patients, 9-21 yr old (15.0 +/- 2.5 yr) with atrial septal defect (secundum type) from 2-11 (5.1 +/- 2.5) yr after successful surgical correction. Clinical condition in all patients was classified as excellent. Heart surgery was performed at the age of 4-14.8 (9.9 +/- 3.0) yr. Lung function abnormalities were found in 35 (47.3%) patients. Lung recoil pressure was significantly increased in 24 (32.4%) patients. The mean value of lung recoil pressure at 100% of total lung capacity reached 123 +/- 31% of the predicted value (P < 0.0001). Specific static compliance was within normal limits. Specific airway conductance was significantly reduced in 13 (17.6%) patients. Maximum expiratory flow at 25% of vital capacity was significantly reduced in 4 (5.4%) patients. Static lung volumes did not differ from reference values. Since various abnormalities of lung function tests (most frequently the tests suggested increased lung stiffness and obstruction of larger airways) were revealed in almost half of the studied children and adolescents after successful surgery for atrial septal defect, we propose to carry out lung function tests routinely as another criterion of health conditions in these patients.


Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features. To investigate the clinical background and the electrocardiographic features of marked alternans of the elevated ST segment during coronary angioplasty, we examined 12-lead electrocardiograms recorded continuously during occlusion of the left anterior descending coronary artery by balloon inflation in 41 patients. The incidence of marked ST alternans was 27% of 41 patients and 15% of 117 balloon occlusions. The incidence decreased progressively from the first to the third occlusion. The time course of ST alternans was determined. Compared with patients without ST alternans, patients with ST alternans had a shorter history of angina, less severe stenosis of the target lesion before coronary angioplasty, more leads showing ST elevation during occlusion, higher ST elevation during occlusion and lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. ST alternans recorded on the surface electrocardiogram may thus be considered a marker of acute severe and extensive myocardial ischemia.


Percutaneous transluminal coronary angioplasty in patients more than 75 years old: early and long-term results. Over 4 yr, 102 consecutive patients more than 75 yr old (56 men, 46 women; mean age 78 +/- 3 years, range: 76-89 years) underwent 120 percutaneous transluminal coronary angioplasty procedures. At baseline, 86% had severe anginal symptoms (Canadian class III or IV), 43% had a history of prior myocardial infarction; 61% had multivessel coronary artery disease, and mean left ventricular ejection fraction was 60 +/- 11%. Calcifications were observed on 66% of the dilated arteries. A total of 158 vessels (1.3 vessel per procedure) were attempted: 1 vessel in 89 procedures (74%), 2 vessels in 24 (20%) and 3 vessels in 7 (6%). The primary success rate was 80% per lesion (126/158) and 77% per procedure (92/120). Complications included 3 deaths (3%), 9 Q-wave infarctions (7.5%) and there was no emergency coronary bypass surgery. The primary success rate was significantly related to the absence of coronary calcifications on the dilated segment (88% versus 75%, p < 0.05) and to the initial patency of the dilated artery (subtotal stenosis: 83% versus total occlusion: 53%, p < 0.05). Follow-up data were obtained in the 79 consecutive patients with a duration of follow-up exceeding 8 months. The mean duration of follow-up was 23 +/- 13 months (range 8 to 61 months). No patient was lost to follow-up; 11 patients died (cardiac causes: 7), 2 had a non-fatal infarction, 7 had aortocoronary bypass surgery and 18 had repeat percutaneous transluminal coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)


Electrophysiological abnormalities of the atrial muscle in patients with sinus node dysfunction without tachyarrhythmias. The duration and the number of fragmented deflections of the right atrial electrograms were assessed and quantitatively measured in 74 patients who underwent endocardial catheter mapping during sinus rhythm. The bipolar electrograms were recorded at 12 sites in the right atrium. An abnormal atrial electrogram was defined as a duration of 100 ms or longer, and/or 8 or more fragmented deflections, according to our previous criteria. The patients were divided into two groups. The control group consisted of 41 age-matched patients with normal sinus node function and without paroxysmal atrial fibrillation. The study group comprised 33 patients with sinus node dysfunction but without tachyarrhythmias. Abnormal atrial electrograms were observed in 8 (19.5%) control patients, and in 16 (48.5%) sinus node dysfunction patients; p < 0.02. The total number of abnormal electrograms was 14 (2.89%) of 483 atrial electrograms in controls, and 36 (9.38%) of 384 in the study group; p < 0.0002. The mean duration (75.6 +/- 17) and the mean number of fragmented deflections (4.1 +/- 2) of the total atrial electrograms in the sinus node dysfunction group was significantly greater than that in controls (70.9 +/- 11 and 3.6 +/- 1, respectively); p < 0.01. The mean number of abnormal electrograms per patient in the study group (1.06 +/- 1.8) was significantly higher than that in the control group (0.3 +/- 0.8); p < 0.05. These data suggest that: (1) there is a significantly greater electrophysiological abnormality of the atrial muscle in patients with sinus node dysfunction but without paroxysmal atrial fibrillation than in age-matched controls, and (2) not only the sinus node but also the atrial muscle is electrophysiologically altered in patients with sinus node dysfunction but without tachyarrhythmias.


Reappraisal of electrical cure of atrioventricular nodal reentrant tachycardia--lessons from a modified catheter ablation technique. A modified catheter ablation technique was studied prospectively in 29 patients with atrioventricular (AV) nodal reentrant tachycardia. A His bundle electrode catheter was used for mapping and ablation. Cathodic electroshocks (100-250 J) were delivered from the distal two electrodes (connected in common) of the His bundle catheter to the site selected for ablation. The optimal ablation site recorded the earliest retrograde atrial depolarization, simultaneous or earlier than the QRS complex, with absence of a His bundle deflection during AV nodal reentrant tachycardia. One additional electrical shock was delivered if complete abolition of retrograde VA conduction persisted for more than 30 min and AV nodal reentrant tachycardia was not inducible during isoproterenol and/or atropine administration. With a cumulative energy of 323 +/- 27 J and a mean of 2.3 +/- 0.5 shocks interruption or impairment of retrograde nodal conduction was achieved. Antegrade conduction, although modified, was preserved in 27 patients, with persistence of complete AV block in 2 patients. Two of the 27 patients still need antiarrhythmic agents to control tachycardia, the other 25 patients were free of tachycardia within a mean follow-up period of 13 +/- 2 months (range 7 to 20 months). Twenty-three patients received late follow-up electrophysiological studies (3-6 months after the ablation procedures), and the AV nodal function curves were classified into 4 types. The majority of the patients (15/23) had loss of retrograde conduction. Among the 8 patients with prolongation of retrograde conduction, 4 patients still had antegrade dual AV nodal property but all without inducible tachycardia. In conclusion, preferential interruption or impairment of retrograde conduction was the major, but not the sole, mechanism of electrical cure of AV nodal reentrant tachycardia.


Alterations in cardiac diastolic function in patients with ankylosing spondylitis. Ankylosing spondylitis is associated with a decreased survival that appears attributable to cardiovascular causes. To determine whether alterations in systolic or diastolic cardiac function precede overt cardiac disease, 20 ankylosing spondylitis patients without clinical evidence of cardiovascular disease and 25 healthy age and gender matched controls were studied by cross-sectional and Doppler echocardiography. Systolic function was assessed by wall motion analysis and ejection velocities. Diastolic function was measured by the peak velocity of early ventricular inflow, peak velocity in late diastole during atrial systole, the ratio of these velocities and the diastolic filling time. Atrial, ventricular and aortic dimensions were similar in patients and controls. Ejection indexes and systolic wall motion were normal in both groups. Diastolic function differed in patients as evidenced by a shorter diastolic filling period [405 +/- 68 ms vs 548 +/- 136 ms, p = 0.0001], a reduced velocity of early mitral inflow [0.55 +/- 0.09 m/s vs 0.63 +/- 0.11 m/s (p = 0.005)], and lower ratios of early/late inflow velocities [1.21 +/- 0.33 vs 1.60 +/- 0.35 (p = 0.0005) for mitral and 1.36 +/- 0.34 vs 1.71 +/- 0.42 (p = 0.016) for tricuspid]. These changes are consistent with impaired ventricular relaxation in some patients with ankylosing spondylitis.


Cardiopulmonary exercise testing early after catheter-balloon mitral valvuloplasty in patients with mitral stenosis. Seven female patients (age 27 to 53 yr) with significant mitral stenosis performed continuous, incremental, maximal treadmill exercise tests the day before and within 3-5 days after catheter-balloon valvuloplasty. Mitral valve area determined by the echo-Doppler method increased from 0.9 +/- 0.3 cm2 to 1.9 +/- 0.7 cm2 (p < 0.02). Mean left atrial pressure was reduced from 24 +/- 8 to 13 +/- 7 mmHg (p < 0.01) and mean pulmonary artery pressure from 36 +/- 13 to 28 +/- 10 mmHg (p < 0.02) with a non-significant increase in cardiac output from 3.6 +/- 1.2 to 4.0 +/- 1.7 l/min. After catheter-balloon valvuloplasty all patients reached a higher maximal workload during exercise, and mean value of oxygen consumption and pulmonary ventilation were significantly lower in submaximal workloads. The calculated ventilatory equivalent for oxygen was significantly reduced in submaximal and in maximal workloads after catheter-balloon valvuloplasty. Peak oxygen consumption and the ventilatory anaerobic threshold were not changed after catheter-balloon valvuloplasty (pre 15.59 +/- 2.72 vs post 16.90 +/- 3.44 and pre 12.10 +/- 2.55 vs post 12.62 +/- 2.71 ml/kg/min, respectively). We concluded that after catheter-balloon valvuloplasty the cost of breathing was reduced and the oxygen consumed was more effectively utilized during exercise. Increases in peak oxygen consumption and in ventilatory anaerobic threshold would require circulatory and metabolic adaptations in response to increased physical activity and were not observed when cardiopulmonary tests were performed early after catheter-balloon valvuloplasty.


Doppler echocardiographic determination of aortic and pulmonary valve orifice areas in normal adult subjects. Cross-sectional and Doppler echocardiography were performed in 36 healthy adult subjects (aged 19 to 50 yr, mean 28 +/- 9; male 23, female 13) to establish normal values for aortic and pulmonary valve orifice areas. Standard continuity equation using echo-determined ventricular outflow tract diameters and Doppler-determined flow-velocity integrals from the outflow tracts and the corresponding great arteries, was employed to calculate the valve areas. Mean left ventricular outflow tract diameter was 1.92 +/- 0.17 cm (range 1.5-2.3 cm) and right ventricular outflow tract diameter was 1.80 +/- 0.18 cm (range 1.5-2.2 cm). Calculated aortic valve orifice area was 2.63 +/- 0.31 cm2 (1.76 +/- 0.2 cm2/m2) and correlated poorly with body surface area (r = 0.31, p > 0.05). Mean pulmonary valve orifice area was 3.01 +/- 0.36 cm2 (2.02 +/- 0.20 cm2/m2) and had a modest correlation with body surface area (r = 0.38, p < 0.05). No difference was observed between males and females for indexed aortic and pulmonary valve orifice areas. These data provide normal values for echocardiographically determined semilunar valve orifice areas and question the practice of indexing valve area for body surface in adult subjects.


Surgical pathology of the mitral valve: gross and histological study of 1288 surgically excised valves. A consecutive series of 1288 mitral valves surgically excised from 1981 through 1989 were studied macroscopically and histologically. The explanted valves were affected by: chronic rheumatic disease (1179, 91.5%), floppy mitral valve (84, 6.5%), bacterial endocarditis (19, 1.5%), and post-ischemic mitral incompetence (6, 0.5%). Among 1179 post-rheumatic cases, mixed mitral stenosis and incompetence was the most frequent malfunction (747, 58%). Isolated mitral incompetence was diagnosed in 72 (6.11%) cases only, and isolated stenosis in 360 cases. In 52 valves, excised because of chronic rheumatic disease, the histology showed unexpected signs of acute rheumatism of the leaflets and the papillary muscles. In these patients clinical symptoms and blood tests were negative for rheumatic disease. Mitral incompetence, possibly due to papillary muscle dysfunction, was the prevalent lesion (61.5%). A total of 181 patients (14.05%) with pure mitral incompetence underwent surgery. In 84 patients (46.4%), the floppy mitral valve was the most frequent cause of valve dysfunction, 72 (39.8%) had rheumatic disease, 19 (10.5%) infective endocarditis, and 6 (3.4%) ischemic heart disease. In the group with floppy mitral valve, males were more prevalent than females (51:33). The mean age of the 4 patients with Marfan's syndrome and non-Marfan patients was noticeably different (17 vs 49 yr). Moreover leaflet deformation, tendinous cord elongation and annulus dilatation were the most common causes of valve incompetence. Floppy mitral valve and infective endocarditis were the cause of cordal rupture in 43.5% of the cases. This was a severe complication which always required emergency surgery.