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Biomedical subjects

G Cooper

Publications and source records attributed to G Cooper.

At least 19 recordsLinked to original sources
PubMed1992

Popliteal embolectomy: does it still have a role?

The failure of a femoral embolectomy presents a difficult problem. The role of popliteal embolectomy in the subsequent management is still not clear. A study of 12 patients who underwent a secondary popliteal embolectomy is reported. Nine of the 12 patients had successful results in terms of limb salvage. The question that has to be addressed is the role of popliteal embolectomy as opposed to thrombolysis. Recent studies tend to favour the latter approach. It is concluded that if an embolectomy catheter will not pass or will not clear the distal segment, the surgeon should consider intraoperative thrombolysis or popliteal embolectomy prior to embarking on a bypass procedure.

Amputation, Surgical↗
PubMed1992

An analysis of errors causing morbidity and mortality in a trauma system: a guide for quality improvement.

The purpose of auditing trauma care is to maintain quality assurance and to guide quality improvement. This study was conducted to identify the incidence, type, and setting of errors leading to morbidity and mortality in trauma patients. Determinations of the Medical Audit Committee of San Diego County were reviewed and classified by the authors for identification of preventable errors leading to morbidity or mortality. Errors were classified by type and categorized by phase of care. Errors were identified in the cases of 4% of all patients admitted for trauma care over a 4-year period. Of all trauma patient deaths, 5.9% were considered preventable or potentially preventable. The most common single error across all phases of care was failure to appropriately evaluate the abdomen. Although errors in the resuscitative and operative phases were more common, critical care errors had the greatest impact on preventable death. The detected error rate of 4% may represent the baseline error rate in a trauma system. While regionalized trauma care has dramatically reduced the incidence of preventable death after injury, efforts to further reduce preventable morbidity and mortality may be guided by an identification of common errors in a trauma system and their relationship to outcome.

California↗
PubMed1992

Left ventricular hypertrophy due to volume overload versus pressure overload.

Left ventricular hemodynamic overload produces an increase in stroke work (SW), which is compensated by the development of left ventricular hypertrophy. However, recent reports question the adequacy of this compensation in mitral regurgitation (MR). Accordingly, we examined the adequacy of compensatory hypertrophy in chronic experimental MR. Six dogs with chronic severe MR were matched according to SW with six dogs that had severe chronic aortic stenosis (ASSW). SW in the two groups was increased identically (40%) compared with normals. However, the hypertrophic response was much greater in the AS group [left ventricular wt (g) to body wt (kg) ratio (LVBW) 4.0 +/- 0.2 normals, 5.0 +/- 0.2 MR, and 7.5 +/- 0.2 ASSW; P < 0.05 MR vs. ASSW]. This differing hypertrophic response increased normalized SW, the area within the stress-volume loop, in MR (90 +/- 5 g) vs. 63 +/- 5 g in ASSW (P < 0.05). Thus in MR, each unit of myocardium had to perform more work than in AS. In a separate comparison, four different dogs with AS (ASHy), which had a similar amount of hypertrophy to the MR dogs (LVBW) (5.0 +/- 0.2 MR, 5.2 +/- 0.2 ASHy) were studied. SW was greater in the MR group, suggesting more SW overload was required to produce similar amounts of hypertrophy in MR vs. AS. Contractile function was depressed in the MR group but not in the AS. These findings indicate that the hypertrophic response to a similar SW demand is less in MR than AS, a response associated with contractile dysfunction in the MR group.

Animals↗
PubMed1992

Endothelin stimulates multiple responses in isolated adult ventricular cardiac myocytes.

We have examined the responses to endothelin (ET) in isolated adult cardiac myocytes from both rodent and feline species to assess whether endothelin may have a role in the induction or mediation of cardiac hypertrophy in the adult animal. We have evidence that ET acts by more than one mechanism to promote cell-signaling events believed important in growth regulation. In isolated adult cardiac ventricular myocytes labeled overnight with [3H]inositol, endothelin (ET) promoted a two- to fourfold increase in the accumulation of inositol polyphosphates in a dose-dependent manner with an half-maximal effective concentration (EC50) of approximately 5 nM. In contrast, picomolar concentrations of ET promoted an increase in both the extent and velocity of sarcomere shortening in electrically stimulated myocytes. Pretreatment of cells with pertussis toxin had no effect on the ET-stimulated phosphoinositide hydrolysis, but blocked the ET-stimulated positive inotropic effect. In addition to these early responses to ET, results obtained by Northern blot analysis demonstrate that exposure of isolated cardiac myocytes to 100 nM ET promoted the expression of c-fos and c-zif in both mammalian species. These data demonstrate that ET stimulates multiple cell-signaling pathways in adult mammalian cardiac myocytes. A paracrine mechanism of regulation of adult myocardium is suggested.

Animals↗
PubMed1992

Adrenergic effects on the biology of the adult mammalian cardiocyte.

BACKGROUND: To delineate the mechanism(s) of catecholamine-mediated cardiac toxicity, we exposed cultures of adult cardiac muscle cells, or cardiocytes, to a broad range of norepinephrine concentrations. METHODS AND RESULTS: Norepinephrine stimulation resulted in a concentration-dependent decrease in cardiocyte viability, as demonstrated by a significant decrease in viable rod-shaped cells and a significant release of creatine kinase from cells in norepinephrine-treated cultures. Norepinephrine-mediated cell toxicity was attenuated significantly by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, whereas the effects mediated by the alpha-adrenoceptor were relatively less apparent. When norepinephrine stimulation was examined in terms of cardiocyte anabolic activity, there was a concentration-dependent decrease in the incorporation of [3H]phenylalanine and [3H]uridine into cytoplasmic protein and nuclear RNA, respectively. The decrease in cytoplasmic labeling was largely attenuated by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, but alpha-adrenoceptor stimulation resulted in relatively minor decreases in cytoplasmic labeling. The norepinephrine-induced toxic effect appeared to be the result of cyclic AMP-mediated calcium overload of the cell, as suggested by studies in which pharmacological strategies that increased intracellular cyclic AMP led to decreased cell viability, as well as studies that showed that influx of extracellular calcium through the verapamil-sensitive calcium channel was necessary for the induction of cell lethality. Additional time-course studies showed that norepinephrine caused a rapid, fourfold increase in intracellular cyclic AMP, followed by a 3.2-fold increase in intracellular calcium [( Ca2+]i). CONCLUSIONS: These results constitute the initial demonstration at the cellular level that adrenergic stimulation leads to cyclic AMP-mediated calcium overload of the cell, with a resultant decrease in synthetic activity and/or viability.

Animals↗
PubMed1992

Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.

This study was designed to answer two questions. First, does the left ventricular contractile dysfunction resulting from mitral regurgitation (MR) reflect a primary defect in the cardiac muscle cell? Second, what is the basis for any change in cellular contractile function that might be observed? Left ventricular volume overload was produced in 10 dogs by catheter transection of mitral chordae tendineae. Three months later in these and in seven control dogs, left ventricular contractile function was characterized by the end-ejection stress-volume relation (EESVR). Investigators who were blinded to these results then characterized the contractile performance of cardiac muscle cells, or cardiocytes, from these same left ventricles in terms of the viscosity (graded external load)-velocity relation. Finally, the tissue and cellular components of these same left ventricles were analyzed morphometrically. Both the left ventricles from the MR group and their constituent cardiocytes showed marked contractile abnormalities. By matching ventricles with cells from the same MR dogs, ventricular EESVR was correlated with cardiocyte peak sarcomere shortening velocity (SSV). The correlation coefficient between EESVR and SSV was 0.63, but between a size-independent measure of active ventricular stiffness and SSV, it was 0.88. No change in left ventricular interstitial volume fraction was found in MR dogs, but both ventricular and cellular contractile dysfunction strongly correlated with a decreased volume fraction of cardiocyte myofibrils. Last, in an attempt to relate the degree of contractile dysfunction to the hypertrophic response, left ventricular mass in the MR dogs was correlated with both cellular and ventricular contractile indexes; no significant correlation was found. Three conclusions are warranted by these studies. First, chronic left ventricular volume overload from mitral regurgitation leads to contractile defects at both the ventricular and cellular levels, the extent of which correlates well in individual animals. Second, no quantitative interstitial change resulted from MR. Taken together, these two findings strongly suggest that the contractile defect is intrinsic to the cardiocyte. Third, while the contractile abnormality in MR remains undefined, the most basic defects appear to be a combination of myofibrillar loss with the failure of compensatory hypertrophy to occur in response to progressive decrements in cellular and ventricular function.

Animals↗
PubMed1991

An empirical analysis of likelihood-weighting simulation on a large, multiply connected medical belief network.

We are developing a probabilistic reformulation of the Quick Medical Reference (QMR) system. Our current probabilistic model of the QMR knowledge base of internal medicine consists of a two-level, multiply connected, belief network. Because of the size and connectivity of this belief network, most exact algorithms for calculating the posterior marginal probabilities of diseases are not applicable. In this paper, we analyze the convergence properties of an approximation algorithm, called likelihood-weighting simulation, on the QMR-DT belief network. Specifically, on two difficult diagnostic cases, we examine the effects of Markov blanket scoring, importance sampling, and self-importance sampling, demonstrating that the Markov blanket scoring and self-importance sampling significantly improve the convergence of the simulation on our model.

Algorithms↗
PubMed1991

Signals for cardiac muscle hypertrophy in hypertension.

Hypertension is associated with a rise in arterial pressure and a compensatory increase in cardiac mass, which if not treated effectively, progresses to decompensated congestive heart failure. This decompensation of an initially compensatory hypertrophy has intensified interest in the factors that initiate and maintain the development of cardiac hypertrophy. The potential signals that induce the development of cardiac hypertrophy are grouped as hemodynamic, growth-promoting hormonal, vasoconstriction-promoting hormonal, and genetic factors. Growth-promoting hormones such as insulin and thyroxine appear to play a permissive, but essential, role in the development and maintenance of cardiac hypertrophy. However, changes in cardiac load, both above and below normal, result in parallel changes in cardiac mass, which will return to normal when a normal load is restored. This adaptive response of the myocardium in direct response to elevated and depressed loads demonstrates that cardiac structure, composition, and function are not fixed postneonatal cardiac properties, but instead are regulated dynamically by the cardiocyte loading environment. This adaptive response is subject to modulation by vasoconstriction-promoting hormones and genetic factors. The current thrust in this research area is to elucidate the cellular signals that transduce the physical stimulus for hypertrophy into biochemical events underlying hypertrophic cardiac growth. To remove complex systemic interactions in vivo from the experimental paradigm, several in vitro models have been used to examine three general, but distinct, cellular pathways involving protein kinase C activation, cyclic AMP formation, and increased ion fluxes. Each pathway demonstrated a stimulatory effect on general protein synthesis, which is necessary for growth in all cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cellular versus myocardial basis for the contractile dysfunction of hypertrophied myocardium.

Contractile dysfunction has been demonstrated in many previous studies of experimental right ventricular pressure-overload hypertrophy; however, given the complex changes that occur both in the cardiac muscle cell and in the multiple components of the cardiac interstitium, it is not clear whether the contractile dysfunction observed is an intrinsic property of the cardiac muscle cell or whether it is the result of a mechanically normal cardiac muscle cell contracting within an abnormal interstitial environment. The purpose of the present study was to examine the contractile behavior of cardiac muscle cells, or cardiocytes, isolated from seven cat right ventricles that were pressure-overloaded by banding the pulmonary artery; right ventricular cardiocytes from seven sham-operated cats served as controls. Cardiocytes were obtained from these cats via standard cell isolation procedures; contractile function of the cardiocytes in response to graded viscous external loads was defined by laser diffraction. The cells were stimulated to contract at a frequency of 0.25 Hz, using 100-microA direct current pulses of alternating polarity. Hypertrophied right ventricular cardiocytes obtained from banded cats showed marked systolic contractile abnormalities in comparison with right ventricular cardiocytes from sham-operated cats. The peak velocity of sarcomere shortening for the control and hypertrophied cardiocytes in 1-cp superfusate was 3.6 +/- 0.2 and 2.1 +/- 0.1 microns/sec, respectively (p less than 0.001); the maximum extent of sarcomere shortening for the control and hypertrophied cardiocytes was 0.21 +/- 0.01 and 0.14 +/- 0.01 microns, respectively (p less than 0.001). Further, the time to peak shortening in the 1-cp superfusate was significantly longer for the hypertrophied cardiocytes (150.1 +/- 3.3 versus 160.4 +/- 3.7 msec; p less than 0.04). When the relengthening properties of the cells were examined in the 1-cp superfusate, there were significant differences between cardiocyte groups. The peak rate of sarcomere relengthening was 3.5 +/- 0.2 microns/sec in the control cardiocytes and 2.2 +/- 0.17 microns/sec in the hypertrophied cardiocytes (p less than 0.001). Similarly, the time to peak velocity of sarcomere relengthening (48.8 +/- 1.8 versus 57.9 +/- 2.9 msec) and the time to 50% maximal sarcomere relengthening (57.1 +/- 3.1 versus 67.1 +/- 3.1 msec) were both significantly prolonged for the hypertrophied cardiocytes (p less than 0.02). This study shows for the first time that the contractile defect in this model of right ventricular pressure-overload hypertrophy is intrinsic to the cardiac muscle cell itself. This finding provides a basis for further, more focused investigations designed to determine the mechanisms responsible for the contractile dysfunction observed in this form of experimental cardiac hypertrophy.

Animals↗
PubMed1990

Interpreting chromosomal abnormalities using Prolog.

This paper describes an expert system for interpreting the standard notation used to represent human chromosomal abnormalities, namely, the International System for Human Cytogenetic Nomenclature. Written in Prolog, this program is very powerful, easy to maintain, and portable. The system can be used as a front end to any database that employs cytogenetic notation, such as a patient registry.

Chromosome Aberrations↗
PubMed1990

Load and length regulation of cardiac energetics.

Crossbridge cycling and consequent energy utilization during contraction are subject to physiologic regulation by load and length; the length effect on the sensitivity of troponin C to a given [Ca2+]i is an important, newly defined mechanism for this length regulation in cardiac muscle. Further, energy utilization persists throughout the cardiac contraction, demonstrably for isometric contractions initiated at optimal length, and is continuously modulated by length changes during variably loaded twitch contractions. The extent, rate, and time of load-induced length changes during myocardial contraction appear to be the primary variables affecting crossbridge activity and energetics. Load and length regulation of the properties of the heart represents a remarkably simple and direct biological response to the physiologic input and role in this organ. This mechanism is utilized by the heart in response to its dynamic loading environment both for long-term adaptation of cardiac mass to chronic load alterations, as discussed here recently (23), and for short-term adaptation of cardiac mechanics and energetics to instantaneous load alterations, as discussed above. It is probably no coincidence, given their central physiologic importance, that both of these most basic adaptive responses of the heart are simultaneously coming to be understood at the molecular level.

Animals↗
PubMed1989

Neurohumoral activation in congestive heart failure: a double-edged sword?

The search for the basic mechanism(s) responsible for the progressive and frequently irreversible deterioration of left ventricular pump function in congestive heart failure has been quite extensive; nonetheless, no single explanation has been forthcoming. Indeed, given the complexity of this disease process, it is becoming increasingly unlikely that a single pathogenetic mechanism will ever be uncovered for congestive heart failure. This review will examine recent experimental and clinical evidence which suggests that excessive adrenergic stimulation of the heart is double-edged. That is, while increased adrenergic input to the heart may initially enable the failing myocardium to function adequately for a period of months to years, continued excessive adrenergic stimulation of the heart through both local neural and circulating catecholamines may lead to frank myopathic effects on the heart, with resultant worsening of left ventricular function and the development of intractable congestive heart failure. While we do not mean to suggest that excessive sympathetic stimulation of the heart is the only, or even the major mechanism responsible for the development of irreversible congestive heart failure, the data reviewed herein do suggest that adrenergic stimulation may play a primary role in the pathogenesis of congestive heart failure.

Adrenergic beta-Antagonists↗
PubMed1989

Load induction of cardiac hypertrophy.

We have shown in surgical animal models that increased and decreased cardiac loading results in myocardial hypertrophy and atrophy, respectively. These changes, which are readily reversible upon the restoration of a normal cardiac load, occur without any requirement for neural or circulating intermediary factors. In our current studies we have focused first on an unequivocal demonstration of these same phenomena in a much simpler model consisting of isolated quiescent cardiocytes maintained in serum-free medium and second on an elucidation in isolated papillary muscles of the means by which a change in cardiac load is transduced into a change in cardiac mass. Adherent isolated adult cardiocytes held at their rest length exhibit only a very gradual loss of their differentiated features. In contrast, unloaded cardiocytes in suspension culture immediately cease nuclear RNA synthesis and rapidly come to resemble unloaded cardiac muscle--a cardiocyte cellular analog of cardiac tissue atrophy, while loaded adherent cardiocytes stretched past their rest length respond in terms of synthetic activity characteristic of growth initiation--a cardiocyte cellular analog of cardiac tissue hypertrophy. Both quiescent and contracting papillary muscles exhibit increased synthesis of cardiocyte structural proteins in direct relation to active and/or passive muscle tension. This load-dependent protein synthesis appears to require initial sodium influx through deformation-dependent sarcolemmal cation channels, in a manner analogous to the dependence of mitogen-stimulated growth initiation in a variety of other cell types on initial sodium entry, albeit by a different mechanism. Thus, load variation functions as an independent regulator of cardiac growth in the adult, and sarcolemmal deformation with consequent sodium entry may be an initial direct link between load and growth in the heart.

Amanitins↗
PubMed1989

Supernormal ejection performance is isolated to the ipsilateral congenitally pressure-overloaded ventricle.

Congenital left ventricular pressure overload is associated with "excessive" hypertrophy that leads to subnormal afterload (wall stress), permitting enhanced ventricular ejection performance. Whether congenital right ventricular pressure overload is associated with a similar phenomenon is uncertain. It is also unknown whether supranormal ejection performance affects only the overloaded ventricle or is a general process affecting both ventricles. Conflicting data exist about whether the hypertrophic process associated with pressure overload is induced primarily by local loading conditions or by neuroendocrine influences. If the former postulate is true, the hypertrophic response should be confined to the overloaded ventricle; if the latter is true, one might predict that both ventricles would be affected by a less specific response to circulating catecholamines. To help resolve these issues, both right and left ventricular performance was examined in seven patients with isolated congenital pulmonary stenosis (average pulmonary pressure gradient 78 +/- 13 mm Hg), six patients with isolated congenital aortic stenosis (average gradient 80 +/- 10 mm Hg) and six normal subjects. Right ventricular ejection fraction was increased in patients with pulmonary stenosis (61 +/- 2%) compared with the value in normal subjects (53 +/- 2%, p less than 0.01) and in patients with aortic stenosis (50 +/- 3%, p = 0.007). Left ventricular ejection fraction was increased in patients with congenital aortic stenosis (84 +/- 4%) compared with the value in normal subjects (70 +/- 4%, p less than 0.01) and in patients with congenital pulmonary stenosis (65 +/- 2%, p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Stenosis↗
PubMed1989

Ectopic prostate tissue at the bladder dome.

A 71-year-old white man with asymptomatic microscopic hematuria had a sessile tumor at the dome of the bladder containing benign prostatic glandular tissue. Benign prostatic polyps occur commonly in the prostatic urethra and bladder neck as vestigial remains of embryonic prostatic elements. Ectopic prostatic tissue elsewhere is rare and has not been described previously arising at the bladder dome. The origin of prostate glands in this unlikely location is unclear. The clinical course of ectopic prostatic polyps at any location is benign, although local recurrence has been reported.

Aged↗
PubMed1989

Contractile function of isolated feline cardiocytes in response to viscous loading.

The classical force-velocity relationship is a standard measure of the contractile function of isolated linear cardiac muscle, but no such simple index of contractile function exists for the isolated mammalian cardiocyte. Therefore, this study established an analogous viscosity-velocity relationship for the characterization of cardiocyte contractile function. For this purpose, force was imposed on unfettered adult feline cardiocytes as a series of defined viscous loads, which provided resistance to cardiocyte shape changes during contraction. This was done by increasing the viscosity of the Krebs superfusate (37 degrees C, pH 7.4) in graded, reproducible steps from 1 to 500 centipoise by the addition of methylcellulose. Sarcomere motion within each contracting cardiocyte was measured as movement of the diffraction pattern cast onto a photodiode array by a laser beam passing through the cell. Both the rate and extent of sarcomere shortening varied inversely with increasing viscosity, whereas neither resting sarcomere length nor osmolarity was altered. Further, increased inotropism effected by paired-pulse stimulation of cardiocytes caused an upward shift of the entire viscosity-velocity relationship. Thus the cardiocyte viscosity-velocity relationship is analogous in form to the force-velocity relationship of isolated linear cardiac muscle and provides a simple reproducible method for characterizing the contractile performance of relatively large numbers of cardiocytes isolated from a single specimen of myocardium.

Animals↗