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The follow-up results between Inoue balloon (n = 43, group 1) and double-balloon (n = 43, group 2) mitral valvotomies were compared in a patient-to-patient matched study. Matching was based on patients' age, mitral valve echo score, fluoroscopic calcification, mitral valve area before valvotomy, and follow-up period. The mean follow-up period was 13 +/- 9 months for both groups. At follow-up, 72% of patients were symptom free in each group; 2 (4.7%) patients in group 1 and 1 (2.3%) patient in group 2 underwent mitral valve replacement surgery. Of these 3 patients, 2 died after surgery, 1 from each group. The mitral valve area by Doppler was 1.8 +/- 0.3 cm2 in group 1 and 1.8 +/- 0.4 cm2 in group 2 (p = 0.7); the area by echo planimetry was 1.7 +/- 0.3 cm2 in group 1 and 1.8 +/- 0.3 cm2 in group 2 (p = 0.3) at follow-up. Restenosis occurred in 5 (12%) patients from each group. The cumulative restenosis-free rate was 96% at 1 years, 78% at 2 years, and 58% at 3 years in group 1 and 98%, 76%, and 51%, respectively, in group 2 (p = 0.8). Balloon selection did not appear to influence the clinical outcome at follow-up. We conclude that both the inoue balloon and the double-balloon valvotomies are effective therapies with comparable follow-up results for patients with mitral stenosis.

In a freshly isolated endothelial cell preparation from rabbit aorta, the regulation of the acetylcholine (ACh)-sensitive intracellular Ca2+ store and the effects of the Ca(2+)-induced Ca2+ release agonists ryanodine and caffeine were studied using fura 2 imaging fluorescence microscopy. ACh (10 mumol/L) caused a transient release of Ca2+ from an intracellular store, presumably via an inositol tris-phosphate-sensitive mechanism. This ACh response could be repeated in the presence of extracellular Ca2+ but was obtained only once in Ca(2+)-free bathing solution, which shows that a depleted intracellular Ca2+ store can be rapidly refilled from the extracellular space. Refilling can be prevented by the endoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (10 mumol/L), implying that Ca2+ enters the cytoplasm before accumulation in the endoplasmic reticulum. Ionomycin (10 mumol/L) caused a large Ca2+ release even after the ACh-releasable store had been emptied, indicating the existence of other ACh-insensitive stores, perhaps including the mitochondria. In one third of the cells studied, ACh induced oscillations in [Ca2+]i that were dependent on extracellular Ca2+. Also investigated were the effects of caffeine and ryanodine. In this cell preparation neither caffeine nor ryanodine induced a Ca2+ transient but instead slowly increased [Ca2+]i. It was observed that both caffeine and ryanodine were able to slowly deplete the ACh-sensitive store. These results indicate the presence of functional ryanodine receptors in native endothelial cells and demonstrate overlap between the caffeine and agonist-sensitive Ca2+ stores. We also found that caffeine was able to directly inhibit the process of ACh-induced Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

We assessed immediate and late outcome in 55 patients with significantly calcified valves (group 1) after balloon mitral valvotomy and compared the results with those from 60 patients with noncalcified or minimally calcified valves (group 2). After valvotomy, mitral valve area increased from 1.03 +/- 0.30 cm2 to 1.64 +/- 0.35 cm2 (p = 0.0001) by echo planimetry in group 1 but was significantly smaller than the mitral valve area in group 2 after valvotomy (1.94 +/- 0.38 cm2; p = 0.0001). At a mean follow-up period of 30 months (range 2 to 81 months), 51% of patients in group 1 and 83% in group 2 were symptom free (p = 0.0002). In group 2, 15 (27%) patients and in group 2, 4 (7%) patients had cardiac events (p = 0.003). The risk ratio for cardiac events was 4.3 times greater in group 1 than in group 2. In group 1, the risk ratio for cardiac events was 3.2 times higher in patients age > or = 65 years and in patients with atrial fibrillation. The 6-year cumulative cardiac event-free survival rate was 64% in group 1 and 90% in group 2 (p = 0.005). In 75 (65%) patients who had follow-up echocardiographic study (35 in group 1 and 40 in group 2), mitral valve area decreased to 1.48 +/- 0.42 cm2 at follow-up in group 1 (p < 0.01) and to 1.77 +/- 0.50 cm2 in group 2 (p = 0.3). Restenosis occurred in 16 (46%) of 35 patients in group 1 and 10 (25%) of 40 in group 2 (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

There is a growing interest in using care maps in ICU. So far, the emphasis has been on developing the critical path, problem/outcome, and variance reporting for specific diagnoses. This paper presents a conceptual knowledge-based care protocol system design for the ICU. It is based on the manual care map currently in use for managing myocardial infarction in the ICU of the Sturgeon General Hospital in Alberta. The proposed design uses expert rules, object schemas, case-based reasoning, and quantitative models as sources of its knowledge. Also being developed is a decision model with explicit linkages for outcome-process-measure from the care map. The resulting system is intended as a bedside charting and decision-support tool for caregivers. Proposed usage includes charting by acknowledgment, generation of alerts, and critiques on variances/events recorded, recommendations for planned interventions, and comparison with historical cases. Currently, a prototype is being developed on a PC-based network with Visual Basic, Level-Expert Object, and xBase. A clinical trial is also planned to evaluate whether this knowledge-based care protocol can reduce the length of stay of patients with myocardial infarction in the ICU.

This study was conducted to establish the validity of left-sided cardiac output measurement with a Swan-Ganz catheter and assess its accuracy in estimating mitral valve area (MVA) by the Gorlin formula. The use of right-sided cardiac output after balloon mitral valvotomy (BMV) can give inaccurate measurements for Gorlin-derived MVA because of the atrial septal defect (ASD) created during the procedure. The left-sided cardiac output was measured with a Swan-Ganz catheter (proximal port in the left atrium and then in the left ventricle, and distal port in the ascending aorta) in 10 consecutive patients before and after BMV. Gorlin-derived MVA cardiac output by this method was compared with (1) Gorlin-derived MVA by means of right-sided cardiac output with and without balloon occlusion of the ASD and (2) MVA measured by echocardiography. Before BMV, a close agreement with a good correlation between left-sided and right-sided cardiac output was found (r = 0.83, p = 0.006). Furthermore, Gorlin-derived MVA by cardiac output with either method was comparable with valve area by echo. After BMV, left-sided cardiac output correlated well (r = 0.92, p = 0.0002) and was comparable with right-sided cardiac output with occlusion of the ASD (mean difference 0.17 +/- 0.49 L/min, p = 0.3) but was significantly lower than the value obtained with open ASD (mean difference 0.93 +/- 0.77 L/min, p = 0.004). Comparison of the correspondent MVAs yielded similar results. Gorlin-derived MVA with left-sided cardiac output and MVA by echo were also similar.(ABSTRACT TRUNCATED AT 250 WORDS)

The structure formed by the DNA oligonucleotide d(G3T4G3) has been studied by one- and two-dimensional 1H NMR spectroscopy. In NaCl solution, d(G3T4G3), like d(G4T4G4) (Oxy-1.5), forms a dimeric quadruplex with the thymines in loops across the diagonal of the end quartets. Unlike Oxy-1.5, the dimer is not symmetric, and both monomer strands are observed in NMR spectra. Three quartets are formed from the GGG tracts. Glycosidic conformations of the guanines are 5'-syn-syn-anti-(loop)-syn-anti-anti in one strand and 5'-syn-anti-anti-(loop)-syn-syn-anti in the other strand. Thus, the stacking of the quartets (tail-to-tail, head-to-tail) is unlike all previously described fold-back (tail-to-tail, head-to-head) and parallel-stranded (head-to-tail, head-to-tail) quadruplexes.

This paper describes the development and validation of a decision-support system prototype that can help manage hypovolemic hypotension in the Cardiovascular Intensive Care Unit (CVICU). The prototype uses physiologic pattern-matching, therapeutic protocols, computational drug-dosage response modeling and expert reasoning heuristics in its selection of intervention strategies and choices. As part of model testing, the prototype simulated real-time operation by processing historical physiologic and intervention data on a patient sequentially, generating alerts on questionable data, critiques of interventions instituted and recommendations on preferred interventions. Bench-testing with 399 interventions from 13 historical cases showed therapies for bleeding and fluid replacement proposed by the prototype were significantly more consistent (p < 0.0001) than those instituted by the staff when compared against expert critiques (80% versus 44%). This study has demonstrated the feasibility of formalizing hemodynamic management of CVICU patients in a manner that may be implemented and evaluated in a clinical setting.

Objective: To assess the outcome after attempted percutaneous balloon dilatation of the mitral valve in patients with severe mitral stenosis between February 1986 and June 1992., Design: Clinical state, mitral valve area, and restenosis at follow up were analysed. Mitral valve area as determined by the Gorlin formula, planimetry, and Doppler methods was compared before and after dilatation and at follow up., Setting: University hospital., Patients: 176 patients had serial clinical and Doppler echocardiographic follow up and 44 of them also underwent recatheterisation., Result: At follow up 93% of patients were in New York Heart Association functional class I or class II. Mitral valve area (planimetry) increased from 0.97(0.24) cm2 before to 1.86(0.39) cm2 after dilatation (p = 0.0001) and then decreased to 1.72(0.39) cm2 at follow up (p < 0.001); mitral valve area (Doppler) increased from 1.01 (0.24) to 1.89 (0.42) cm2 (p = 0.0001) and then decreased to 1.78(0.40) cm2 (p < 0.05). The overall restenosis rate was 15% and over 90% of the patients were free from cardiovascular events. Age, valvar calcification, echocardiographic score, and mitral valve area after dilatation were found to be determinant predictors of restenosis. In patients who underwent recatheterisation, mitral valve area by the Gorlin method at follow up was comparable with that by planimetry and Doppler methods whereas a significant discrepancy between the three methods was noted immediately after dilatation., Conclusion: Balloon dilatation of the mitral valve provided sustained anatomical and functional improvement in over 80% of patients at late follow up. Older age, heavy calcification, high echocardiographic score, and suboptimal immediate results are significant predictors of restenosis. Doppler echocardiographic examination is the procedure of choice for follow up evaluation.

Alchemical molecular dynamics simulations are performed to determine the difference in the free energy of binding of the tyrosine substrate between the wild type of tyrosyl-tRNA synthetase (TyrRS) from Bacillus stearothermophilus and the mutant Tyr169-->Phe. The results are of general interest because the Tyr169 hydroxyl group interacts with the ammonium group of the substrate in a manner corresponding to that found in other amino acid binding proteins (e.g. the Asp receptor of the chemotactic bacterium Salmonella typhimurium and class I major histocompatibility complex molecules). The calculated free-energy change due to the Tyr169-->Phe mutation is 3.4 kcal/mol (the statistical error is +/- 0.5 kcal/mol) in satisfactory agreement with the experimental value of 3(+/- 0.5) kcal/mol. By use of thermodynamic integration, the contribution of the different terms to the free energy change are estimated. The path dependence of such a decomposition is discussed and it is suggested that the alchemical choice is of primary interest for understanding the interactions involved. There are large protein contributions to the alchemical free energy difference of the bound and free enzyme that cancel in the overall result. Due to this cancellation, the essential interactions contributing to the free-energy change are those between the OH group of Tyr169 and water in the free enzyme and those between the OH group of Tyr169 and the ammonium group of the substrate in the bound system. The results thus support simple models based on a balance of hydrogen bonding interactions.

The recent introduction of the Management Information System (MIS) guidelines has sparked much interest among health care institutions across Canada regarding proper approaches to the recording and interpretation of various financial and workload indicators. While the benefits of the MIS guidelines are widely acknowledged, much less attention has been directed to how departmental managers can analyze and make use of the vast amount of information generated. In this paper we attempt to review some of the computer-based decision-support tools that may be useful to the manager of the rehabilitation services department in analyzing the various MIS data that are collected. The data are assumed to be available through a computerized rehabilitation information system which includes workload measures. The quantitative models reviewed in this paper include basic descriptive statistics, deviation, trend and what-if-analysis and graph-plotting. Although the use of such tools can assist the rehabilitation manager in the routine decision-making process, it is very important that we ask the right questions and employ the proper model to make the most rational and best decision. In this respect, ongoing training in general problem-solving skills, decision-making processes, and use of computer-based decision-support tools may be very beneficial.

The massive volume of hemodynamic data routinely available within the Cardiovascular Intensive Care Unit (CVICU) can adversely affect the quality, relevance, and timing of hemodynamic management decisions on patients after cardiac surgery. Yet, at the same time, the lack of appropriate treatment-outcome data and access to prior CV case histories deprives the clinician of any opportunity to improve personal decision-making skill and assess the effectiveness of various treatment methods. This paper presents a formalized decision-support model for CVICU that incorporates expert and quantitative knowledge, as well as prior outcome and case experience to augment the clinician's decision-making capability. This includes the use of optimal hemodynamic patterns derived from outcome analysis as therapy goals, expert rules and trend analysis to interpret incoming data, standardized protocols based on predefined hemodynamic patterns from clinical cases, and access to the database for similar case comparison. Most importantly, the model suggests an integrated approach where the clinical database not only is a documentation source for the patient, but also can serve as an outcome research database where clinical experience can be formalized and combined with expert knowledge to influence future therapy decisions. At present, a prototype is being developed at the CVICU of the University of Alberta Hospitals on a Unix platform using ART-IM, C and Ingres. Once implemented, the prototype will be evaluated on a small group of CV patients for its effectiveness and acceptability to clinicians.

Although it is widely recognized that many proteins contain discrete functional domains, it is less certain whether smaller, less obviously discrete, units of structure will retain their specific function when transplanted into a different context. The observation that the potent inflammatory cytokine human interleukin 1 beta has the same overall structure as soybean trypsin inhibitor (STI) (Kunitz) prompted us to replace a tight turn in the cytokine sequence with the large loop in soybean trypsin inhibitor that binds to the active site of trypsin. Wild-type interleukin 1 beta (IL-1 beta) is highly resistant to proteolysis, but the chimeric STI/IL is specifically cleaved by trypsin, apparently in the inserted loop. Other chimeric interleukins have also been constructed, by replacing the same tight turn with inhibitory loops from other protein protease inhibitors: turkey ovomucoid inhibitor (TOI), a chymotrypsin inhibitor, and alpha 1-antitrypsin (AT), an elastase inhibitor. Although these loops come from proteins not related structurally to interleukin 1, they confer specific protease sensitivity or inhibition on the chimeric cytokine. The cytokine properties of these chimeric interleukins have also been evaluated. The chimeras formed from human IL-1 beta and all inhibitory loops tested bind to the interleukin 1 receptor with reasonable affinity. The typical cellular effects of IL-1, however, are not observed with all the recombinant proteins, thus confirming that receptor binding and signal transduction can be uncoupled. When these results are taken together with the results of site-directed mutagenesis of IL-1, reported in this paper and elsewhere, they allow the receptor and intracellular transduction sites on the protein to be mapped in detail.

This study compared the efficacy and safety of lomefloxacin with that of trimethoprim/sulfamethoxazole (TMP/SMX) in the treatment of adult patients with acute diarrhea of bacterial etiology. Two centers enrolled a total of 133 patients; 99 (74%) presented with severe symptoms. The patients were randomized to receive either lomefloxacin 400 mg once daily (n=68) or TMP/SMX 160/800 mg twice daily (n=65) for five days. Bacteriologic success was achieved in 89.5% of evaluation lomefloxacin-treated patients and in 97.5% of patients treated with TMP/SMX. Clinical success was achieved in 100% and 97.5% of patients in the two treatment groups, respectively. The predominant organisms isolated in both groups at baseline, i.e. Shigella flexneri, Vibrio parahaemolyticus, and Salmonella Group D, were eradicated in all patients. Campylobacter jejuni was isolated at baseline in four patients in the lomefloxacin group but in none randomized to receive TMP/SMX; this organism persisted in three patients. Adverse events were experienced by 14 (23%) of the lomefloxacin-treated patients and by 18 (30%) of the TMP/SMX-treated patients. All adverse events reported were mild or moderate in severity and their distribution was similar in both groups. The results of this study show that lomefloxacin 400 mg once daily is as effective as TMP/SMX 160/800 mg twice daily and suggest that lomefloxacin is a promising new quinolone for the treatment of bacterial diarrhea.

Resurgence of the transseptal procedure in the last decade has occurred coincident with the advent of therapeutic catheterizations and in particular mitral balloon vavuloplasty. As larger numbers of these procedures have been performed, experience shows that the position of intended septal puncture varies for each anticipated procedure and need not lie at the fossa ovalis, which is frequently displaced or inaccessible. Recognizing the dynamic alterations in septal and atrial anatomy that accompany the various combinations of valvular heart disease, the experienced interventionalist will use precatheterization echo and radiological techniques to enable precise and localized transseptal puncture. Using these techniques in 597 patients for valvular heart disease, we have had no deaths and a morbidity of 1.8% with the transseptal puncture.

The results of percutaneous mitral valvotomy by means of the Inoue single-balloon (N = 85, group 1) and the double-balloon (N = 322, group 2) techniques were compared in a nonrandomized study. The groups were not significantly different with regard to age, sex, calcification, or hemodynamic values before percutaneous mitral valvotomy. After percutaneous mitral valvotomy, patients in both groups had significant hemodynamic and clinical improvement. The increases in mitral valve area and cardiac output and the decreases in mitral valve gradient, mean pulmonary artery pressure, and mean left atrial pressure were greater in group 2. Mitral valve area determined by the Gorlin method increased 191% in group 2 and 106% in group 1; Doppler-determined mitral valve area increased 133% in group 2 and 98% in group 1. Optimal results were achieved in 93% of the patients in group 2 and 76% in group 1 (p less than or equal to 0.0001). In group 1, 6% of patients had a left-to-right shunt as shown by angiography versus 14% in group 2 (p less than or equal to 0.05). In group 2, 46% of patients had at least a 1+ increase in mitral regurgitation versus 52% in group 1. Among the patients who had an increase in mitral regurgitation, 36% of those in group 1 versus 9% in group 2 had a 2+ or more increase (p less than or equal to 0.001). The mean balloon diameter to anulus ratio was larger in group 2, and the larger the balloon diameter to anulus ratio, the greater the increase in mitral valve area.(ABSTRACT TRUNCATED AT 250 WORDS)

This is a 43-yr-old female presenting with recurrent atrial septal defect, closed surgically, 10 years prior, severe aortic and mitral stenosis, and severe tricuspid regurgitation. She was considered inoperable because of the severe pulmonary hypertension and the complexity of the disease. A percutaneous umbrella closure of the atrial septal defect in conjunction with mitral and aortic balloon valvotomies could be safely and successfully performed. After significant clinical and hemodynamic improvement, surgery was judged feasible, but was refused by the patient who suddenly expired 8 weeks later. The usefulness of percutaneous therapy as a rescue procedure and the management of patients with Eisenmenger's physiology are discussed.

The massive volume of hemodynamic data routinely available within the Cardiovascular Intensive Care Unit (CVICU) can adversely affect the quality, relevance and timing of hemodynamic management decisions on patients after cardiac surgery. Yet, at the same time, the lack of appropriate treatment-outcome data and access to prior CV case histories deprives the clinician of any opportunity to improve personal decision-making skill and assess the effectiveness of various treatment methods. This paper presents a formalized decision-support model for CVICU that incorporates expert and quantitative knowledge, as well as prior outcome and case experience to augment the clinician's decision-making capability. This includes the proposed use of optimal hemodynamic patterns derived from outcome analysis as therapy goals, expert rules and trend analysis to interpret incoming data, standardized protocols based on predefined hemodynamic patterns from clinical cases, and access to the database for similar case comparison. Most importantly, the model suggests an integrated approach where the clinical database is not only a documentation source for the patient, but can also serve as an outcome research database where clinical experience can be formalized and combined with expert knowledge to influence future therapy decisions. At present, a prototype is being developed at the CVICU of the University of Alberta Hospitals on a Unix platform using ART-IM, C and Ingres. Once implemented, the prototype will be evaluated on a small group of CV patients for its effectiveness and acceptability to clinicians.

This paper describes the conceptual framework and preliminary results of an outcome-oriented decision-support system prototype for the cardiovascular intensive care unit (CVICU). The major characteristics of this design include: (1) its problem-based approach to solving clinical problems; (2) an integrated structure with the hospital information system in terms of its data, model and knowledge bases; (3) proposed alternative modes of interaction that include monitoring and critiquing; (4) and research modules that design, manage, and analyze outcome-based clinical studies. At present, an initial prototype has been implemented on a PC as a set of modules accessible from a main menu. The structural framework of the overall system is fairly well defined but only limited quantitative, statistical and expert knowledge has been captured. The second phase of the project involves porting the prototype to a Unix workstation environment, refining and adding models to the model base, expanding its knowledge bases, reasoning capability, and testing the prototype with actual clinical cases in a real-time fashion.

A patient with progressive disabling angina was found to have a single right coronary artery with atresia of the left main coronary artery, and absence of any obstructive coronary disease. The patient required aortocoronary by-pass surgical reconstruction of a left main coronary artery to control her angina. Possible mechanisms for the development of her anginal pain are briefly discussed.

The protease-binding sequence EAIPMSIPPE from alpha 1-antitrypsin has been inserted into the cytokine interleukin-1 beta, replacing residues 50-53. The resulting mutant protein was cleaved specifically at a single site by elastase and chymotrypsin, but not by trypsin. The cleavage by elastase was shown to be between Met and Ser of the inserted loop. In contrast, wild-type interleukin is not susceptible to cleavage by any of these enzymes. The mutant protein acts as an inhibitor of elastase, with a KI of approximately 30 microM. The wild type displays no such inhibitory activity. The overall structure of the mutant, as demonstrated by CD, appears to be indistinguishable from that of the wild type. These results indicate that the protease-binding region of alpha 1-antitrypsin can be recognized and is active even within the context of an entirely different protein structure. Given that interleukin-1 beta binds to, and is internalized by, many types of cells, this hybrid protein also demonstrates the feasibility of using interleukin-1 beta as a delivery system for useful therapeutic agents.

Two-dimensional nuclear magnetic resonance spectroscopy has been used to study the bacterial ribonuclease barnase (MW 12,382). Resonance assignments have been made for protons in all of the 110 residues. Analysis of medium- and long-range contacts in NOESY spectra has demonstrated that the major elements of secondary structure in barnase in solution are essentially identical with those found in the crystal structure.

Percutaneous double balloon valvotomy for severe rheumatic mitral stenosis was successfully performed in 281 of 285 consecutive patients. The changes evoked were a decrease of the mean transvalvular gradient from 16 +/- 7 to 5 +/- 3 mm Hg, an increase in cardiac output from 3.8 +/- 1.0 liters/min to 5.4 +/- 1.5 liters/min and an increase in mitral valve area from 0.86 +/- 0.24 cm2 to 2.41 +/- 0.54 cm2. The mean pulmonary artery pressure decreased from 37 +/- 13 mm Hg to 27 +/- 12 mm Hg and the pulmonary vascular resistance decreased from 307 +/- 181 to 238 +/- 122 dynes/s/cm-5. Symptomatic improvement occurred in 272 of the 285 (95%) patients. There were 3 procedure-related deaths (1%). Postdilatation mitral regurgitation was not significant in most patients. Therefore, this procedure can be performed at a low risk with effective results and a fast recovery.

A patient with a continuous murmur due to flow through an internal mammary-to-pulmonary artery fistula is described. Previously reported cases have been thought to be congenital in origin. A history of an anteriorly placed chest tube suggests an acquired etiology for this malformation.

The results of this investigation reveal that 39 per cent of patients in a study group of 46 patients with heart valve prostheses had gallstones if they survived 18 months or longer following valve replacement. In contrast, the prevalence of gallstones in a general population of autopsied rheumatic heart disease patients, including those who had been operated for severe valvular heart disease and had not survived for more than one month, was only 12 per cent. These findings suggest that gallstones are a frequent late complication of heart valve replacement.

The step from coronary angiography to surgery is taken primarily on the basis of the ejection fraction (EF) and number of diseased vessels (NV), taken jointly as coronary status (CS). This study reviewed (1) how well EF, NV and CS are estimated from clinical data, (2) how much improvement is gained by adding noninvasive data, (3) how good this model is when applied to a larger cohort and (4) whether the decision to angiography can be made on the basis of CS estimated from clinical data alone. A quantitative definition of CS was established as a principal component of EF and NV. Estimates of EF, NV and CS were made from clinical data of 60 patients. Correlations with the actual values were EF 87%, NV 93% and CS 93%. When noninvasive data were added to this model, the correlations increased to EF 95%, NV 99% and CS 98%. When the clinical data model was applied to 169 patients, the correlations decreased to EF 77%, NV 71% and CS 74%. CS estimated from clinical data alone was set up as a test for angiography for 169 patients. This test had a sensitivity of 98% and a specificity of 63%, demonstrating the feasibility of using clinical data alone in deciding angiography.

Four amphipathic drugs, primaquine, propranolol, chlorpromazine and tetracaine, were used to cause endocytosis in glucose-depleted red cells, and the relative reduction of membrane surfaces was measured by the toluidine blue (TB) method. The TB measurements correlated well with the observed electron microscopic alterations. In vitro blood storage studies indicated loss of cell membrane during storage correlated with decreasing uptake of TB by the red cells. Regeneration of cellular ATP with adenosine did not always restore TB uptake by the cells. Loss of red blood cell membrane either by exocytosis or endocytosis may occur during normal in vivo or in vitro ageing, and may be increased in pathological states or by the action of drugs.

Frank lead ECG's from infants were studied for frequency content by introducing low-pass filters of 50, 75, 100, and 150 150 Hz bandwidths before obtaining computer measurements. Results indicated that a minimum bandwidth of 100 Hz is required to avoid amplitude error of 10 per cent or greater. This bandwidth requierement is essentially the same as that required for adult ECG's despite the fact that infant QRS durations are usually about half those of adults. Although the average infant ECG spectrum is likely to contain higher frequencies than the average adult ECG spectrum, duration values for Q, R, and S waves overlap in these populations to such an extent that bandwidth requirements are practically identical.

The percentage of increase in total and MB creatine phosphokinase (CPK) after treadmill exercise was determined in 29 patients--ten patients with ST segment depression greater than 1 mm (group 1) and 19 patients with no ST segment depression (group 2). Values were determined pretest and 6, 12, and 24 hours after exercise. The mean exercise duration was 8 min, 18 sec. Total CPK increased within the normal range 12 hours after exercise in group 1 patients exercising less than 8 min, 18 sec, and in all patients exercising longer. The MB CPK remained unchanged after exercise in all patients. These data suggest that while normal range variation of total CPK occurs after treadmill exercise testing, the myocardium does not release MB CPK, regardless of the level of treadmill exercise our patients performed or the development of presumed ischemic ST segment responses. Abnormal elevation of MB CPK suggests myocardial damage.

Frank vectorcardiograms (VCGs) were collected on magnetic tape for 666 normal newborn infants at 1, 6, 12, 24, 36, 48, 60, and 72 hours after birth and analyzed by computers. The final total included 1,337 VCGs for white babies and 413 for blacks. No previous report has been made for the normal neonate with such a large sample, and no previous substantiation exists of possible age or sex differences at this early age. This study establishes a statistically significant change in vectorcardiographic patterns over the first three days, specifically in the measurements P duration, QRS duration, maximal spatial QRS amplitude, S in lead x, and T in lead z, as well as for several time-normalized QRS vectors. (P less than or equal to .005.) Racial differences were significant for T waves in lead z. This study supports the use of vectorcardiographic standards sensitive to the age of the newborn as well as to race.

A simple, noninvasive technique for continuous cardiovascular monitoring in obstetrics using R--pulse wave timing is described. This preliminary study suggests that different maternal heart rate/R pulse patterns are found in different clinical circumstances. A significant decrease in the R pulse interval occurred in the third trimester in both normal and diabetic women in the left lateral position when compared to the supine position. The R pulse intervals were all prolonged in the standing position in both gravid and nongravid women. During labor R pulse interval usually shortened during uterine contraction. Prolongation of R pulse interval was observed during thiopental injection, hypotension, and excessive bleeding at cesarean section. Exercise testing in healthy male subjects suggested that the change in R pulse interval becomes constant when the oxygen consumption rate reaches a plateau at 100% maximal work load. Further extensive clinical study appears worthwhile since it may add another dimension to cardiovascular monitoring and give an early indication of cardiovascular reserve.

A total of 46 patients who survived aortic valve replacement with the present model Smeloff-Cutter prosthesis between 1968 and 1973 were followed up postoperatively. All patients received oral anticoagulant therapy. The average age at implantation was 44 +/- 13 (mean +/- standard deviation) years; 36 patients were male and 10 were female. The valve damage was caused by rheumatic disease in 19 (41 percent), infective endocarditis in 14 (30 percent), congenital heart disease in 7 (15 percent) and other factors in 6 (13 percent). Late death occurred in eight patients (17 percent). All available patients were followed up until December 1976. During the 8 years of follow-up study, seven patients, including four heroin addicts, had postoperative endocarditis (15 percent); five of the seven had cerebral involvement, possibly from septic emboli. Four patients were reoperated on; three had active endocarditis and one had a high transvalve pressure gradient. The mean follow-up time was 4.9 years per patient. Of the 38 living patients, 33 have functional improvement and are still being followed up. Only one patient had a bland embolism to a systemic artery. No ball variance or other types of material failure have been detected. Although the chronic aspects of valve disease remain after prosthetic valve replacement, the Smeloff-Cutter aortic prosthesis deserves strong consideration when selecting a rigid prosthesis for aortic valve replacement.

A systematic study by site-directed mutagenesis has been conducted on the effector site of phosphofructokinase from Escherichia coli to delineate the role of side chains in binding the allosteric activator, GDP, and inhibitor, PEP, and to search for key residues in the allosteric transtion. Target residues were identified from the crystal structure of the enzyme-nucleoside diphosphate complex. It is found that both activator and inhibitor bind to the same set of amino acid side chains. Deletion of positively charged groups (Arg21, Arg25, Arg54, Arg154, and Lys213 mutated to alanine) weakens binding of both effectors by 2-3 kcal/mol, consistent with the disruption of charged hydrogen bonds. Residue Glu187, which is known from the crystal structure to bind the coordinated Mg2+ ion of GDP, is found to have a unique behavior on mutation and appears to be crucial in triggering the allosteric transition. All other residues mutated simply weaken binding of both PEP and GDP in a parallel manner. However, mutation of Glu----Ala187 reverses the roles of GDP and PEP, causing GDP to become an allosteric inhibitor and PEP an activator. Mutation of Glu----Gln187 has only a small effect on the binding of PEP, and both PEP and GDP are inhibitors. Studies are described in which mutations in different subunits of a tetrameric complex complement each other. The effector site is composed of residues from two subunits. In particular, Arg21 and Lys213 in each site are from different subunits. Mutations of either one of these residues abolishes activation by GDP of the homotetramer.(ABSTRACT TRUNCATED AT 250 WORDS)

A low incidence rate of thromboembolism has been reported in mitral porcine valve recipients. In contrast, 5 of 22 single mitral porcine valve recipients (23 percent) followed up in our clinic for a mean of 16 months had thromboembolic events. All patients but one were receiving long-term anticoagulant therapy. One thromboembolic event resulted in death, three in permanent neurologic deficits and one in a peripheral arterial occlusion. All five patients with emboli had atrial fibrillation and left atrial enlargement. Three had thromboembolic events before porcine heart valve implantation. In addition, five mitral porcine valve recipients who were not receiving anticoagulant therapy were examined at autopsy. Thrombus was identified in the left atrium in three patients, at the tissue-valve interface (sewing ring) in two, on the porcine valve cusps in one and in the right atrium in one. Factors influencing thrombus formation such as left atrial enlargement, atrial fibrillation and a prosthetic device are present after mitral porcine valve implantation and are indications for long-term anticoagulation therapy.

Some personal views on the selection of an ideal laboratory computer system are presented in this paper. Topics discussed include a review of some of the essential requirements for the ideal system; a survey of some of the commercial turn-key laboratory computer systems that are available; typical future trends that should be noted; and lastly, some criteria that may be used in the evaluation and selection of the ultimate system.

A simple method using a cationic dye, toluidine blue (TB), to quantify changes of red cell membrane area has been developed and tested for its validity. After incubating a glucose-depleted red cell suspension with a fixed quantity of TB at 37 degrees C for 10 min, the remaining TB was measured spectrophotometrically at 640 nm. Using this technique, we were able to show differences in TB uptake by populations of young and old red cells. The exact mechanism for TB uptake by the red cells is not clear. Treatment of the cells with bromelin, papain and trypsin reduced the uptake of TB, but neuraminidase and ficin had little or no effect. No inhibition of TB removal by red cells was observed using heparin, D-glucose, glucuronic acid, or N-acetylglucosamine.

A brief review of the history of development of Chinese pharmacognosy and its application to gynecology and obstetrics is presented. An evaluation system is introduced for short-listing some potentially useful and anti-fertility plants. Twenty such plants are listed in order of priority according to our evaluation system. Brief descriptions of the botany, phytochemistry and reputed biological effects are provided. It is hoped that this article may provide an impetus for the development of new antifertility agents.

The clinical diagnostic features of right ventricular myxoma are described in a recent patient and related to the 15 cases previously reported. The presence of a pulmonic systolic ejection murmur with a delayed (120 to 140 msec.) and accentuated pulmonic second sound, or calcification in the region of the right ventricular outflow tract should suggest this lesion. Cardiac catheterization with angiocardiography in diagnostic. Ga scanning may assist in the diagnosis and followup after surgical removal of the myxoma. Early surgical removal will avoid the possibility of sudden death.

A new vector for the expression of phosphofructokinase (pfk-1) was constructed with pEMBL, which allows reliable, inducible, high-expression, and facile mutagenesis of the gene. Two mutants in the effector site of the enzyme were produced by site-specific mutagenesis of residue Tyr-55 to assess the role of its side chain in binding an allosteric inhibitor, phosphoenolpyruvate (PEP), and an activator, guanosine 5'-diphosphate (GDP): Tyr-55----Phe-55 and Try-55----Gly-55. The dissociation constant of PEP from the T state is unaffected by the mutations. Mutation of Tyr-55----Phe-55 only slightly increases the dissociation constant of GDP from the R state, indicating a minimal involvement of the hydroxyl group in binding. A 5.5-fold increase in the dissociation constant of GDP on the mutation of Tyr-55----Gly-55 suggests a small hydrophobic interaction of the aromatic ring of the tyrosine residue with guanine of GDP.

Echocardiography is an established method for the diagnosis of pericardial effusion. Echographic findings in fibroadhesive disease have also been described. The interpretation of a changing serial echogram during the clinical course of pericardial disease has not been established. Sixteen patients with echographic evidence of pericardial effusion were followed with serial echographic studies. In seven, surgical or autopsy correlation was obtained. Because of the serial changes noted we undertook a study in dogs to clarify the problem of variability in intensity of sound reflected from the pericardial space. Three open-chested dogs were studied with rapid sequence surface echograms as blood introduced into the pericardial space was converted from the unclotted to the clotted state. In all three dogs blood clooting increased the intensity or sound reflected from the pericardial space. Our study of two patients with fibroadhesive pericardial disease documents serial changes in echoes from the pericardium and pericardial space accompanying the clinical evolution of the disease process, and suggests a method for avoiding the commonly encountered difficulty in proper identification of the pericardial and epicardial echoes. Our preliminary studies suggest that serial echograms should play an important role in the management of patients with pericardial effusion; further surgical/pathological correlations are required.

The mechanisms of increased aldosterone and cortisol metabolic clearance rates (MCR) following ACTH or cortisol administration were studied in 13 subjects undergoing cardiac catheterization and in 9 healthy controls. In control subjects, the MCR (plasma) of both steroids increased by 29% (aldosterone: from 936 +/- 57 to 1204 +/- 55 l/day/m2, cortisol: from 205 +/- 12 to 264 +/- 17 l/day/m2 +/- SE) after ACTH (12 units/h) for 1 to 4 h, and by 20 and 32%, respectively, after cortisol (12 mg/h) for 1 to 2 h. In contrast, aldosterone MCR (whole blood) did not change with ACTH or cortisol administration (from 1276 +/- 57 to 1330 +/- 59 l/day/m2), indicating that the plasma MCR increase results from a redistribution of aldosterone from plasma to red cells. Aldosterone splanchnic extraction was 92 +/- 1% (n = 12) with normal morning cortisol levels, and extraction was unchanged after ACTH administration. For cortisol, however, the splanchnic extraction increased from 8 +/- 0.8% to 17.8 +/- 5.0%, and the MCR (whole blood) likewise increased by 15 to 31% (from 295 +/- 23 to 357 +/- 30 l/day/m2), after ACTH or cortisol administration. In vivo and in vitro measurements (at 37 C) of tracer aldosterone concentration in plasma and in red cells showed an increase in distribution to red cells with increasing cortisol concentrations. The results suggest that a fraction of aldosterone is bound in plasma and displaced by cortisol into red cells. There is an increased aldosterone plasma MCR, but unaltered whole blood MCR, since the liver extracts aldosterone almost completely from both plasma and red cells. The increase in cortisol MCR (plasma) results from both an increased splanchnic extraction as plasma binding sites approach saturation and a redistribution into red cells.