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Biomedical subjects

J A Spratt

Publications and source records attributed to J A Spratt.

At least 37 records · Page 2Linked to original sources
PubMed1994

Pulmonary mucormycosis: results of medical and surgical therapy.

Mucormycosis is an opportunistic fungal infection that commonly begins by invading the respiratory tract. The purpose of the present study was to define the clinical presentation of pulmonary mucormycosis and to evaluate current treatment regimens. Thirty patients treated at our institution and 225 cases reported in the literature were reviewed. For the combined groups, the mean age at presentation was 41 +/- 21 years and associated medical conditions included leukemia or lymphoma (37%), diabetes mellitus (32%), chronic renal failure (18%), history of organ transplantation (7.6%), or a known solid tumor (5.6%). The in-hospital mortality was 65% for patients with isolated pulmonary mucormycosis, 96% for those with disseminated disease, and 80% overall. The mortality in patients treated surgically was 11%, significantly lower than the 68% mortality in those treated medically (p = 0.0004). The most common causes of death were fungal sepsis (42%), respiratory insufficiency (27%), and hemoptysis (13%). Pulmonary mucormycosis has a high mortality; however, antifungal agents appear to improve survival. In addition, surgical resection may provide additional benefit to patients with pulmonary mucormycosis confined to one lung.

Adolescent↗
PubMed1994

[Growth rate of breast cancer, implication for early detection and therapeutic effects].

Numerous trials have shown, that breast cancer have highly variable rates of growth. It is assumed, that the rates (relative growth rates) decelerate with increasing tumour size. The Universities of Heidelberg and Louisville carried out a retrospective statistical analysis of the mammographically measured growth rates of 448 screening patients until breast cancer diagnosis. The analysis did not include fast-growing carcinomas appearing between mammograms for which only one mammogram was available or some cancer, where growth was not detectable by mammography. Generalized logistic curves provided the best fit to the data on the increase in tumour size, as observed in mammograms. Large variations in individual tumour doubling times were found, from extremely fast-growing to extremely slow-growing tumours. The results are relevant for patient prognosis, for the evaluation of therapy, and for screening strategies.

Adolescent↗
PubMed1993

Decelerating growth and human breast cancer.

BACKGROUND: Improved understanding of human breast cancer growth rates may have many clinical applications. Previous reports have used small numbers of patients and assumed an exponential growth rate. METHODS: The exponential equation and the most commonly used decelerating growth equations, the Gompertz equation and seven generalized forms of the logistic equation, were fitted to mammographic measurements of primary breast cancer using the least squares method. An average of 3.4 observations was made in 113 patients, whereas two measurements were made in another 335 patients. Tumors were assumed to originate as a single cell with the lethal tumor volume assumed to be 2(40) cells. RESULTS: All decelerating equations tested provided a better fit than the exponential, whereas a form of the logistic equation provided the best fit to the data. Limitations in the number of tumor measurements, the assumption of maximal tumor size, and biases inherent in the method of data collection are reviewed. These observations suggest families of curves that characterize breast cancer growth during the early period of clinical observation. CONCLUSIONS: Breast cancer growth in the early clinical period was modeled by a form of the logistic equation. The exponential equation fit the data least well.

Breast Neoplasms↗
PubMed1993

Mammographic assessment of human breast cancer growth and duration.

BACKGROUND: Accumulating data from numerous sources have confirmed that breast cancers have highly variable rates of growth. Contemporary thought supports that collectively the gross rates should decelerate with increasing tumor mass. METHODS: Using composite data derived from mammographically measured growth of breast cancers observed at the Universities of Heidelberg and Louisville, the growth curve providing the best fit to the observed data, and the variance occurring around this curve has been calculated. RESULTS: A generalized logistic equation provided the best fit, with a natural variance ranging from extremely rapidly growing to slowly growing cancer. These data do not cover the entire range of growth rates because cancers appearing acutely between mammograms were observed only once, and some breast cancers never grew. CONCLUSIONS: The highly variable decelerating growth rates of breast cancers are better but incompletely defined, and these rates are of value in considering screening strategies and prognosis.

Adolescent↗
PubMed1990

The effects of dopamine on myocardial functional recovery after reversible ischemic injury.

Dopamine frequently is used to improve cardiac performance after acute myocardial ischemia. Inotropic agents, however, increase myocardial oxygen demand and could potentially delay recovery from ischemic injury. To evaluate this problem, we studied eight chronically instrumented dogs in the conscious state and performed two 15-minute coronary occlusions 48 hours apart. After one of the occlusions, either dopamine (15 micrograms/kg/min) or saline placebo was administered intravenously from 1.0 to 1.5 hours of reperfusion. The alternative infusion was given during the second study. Preload recruitable work area, the area beneath the stroke work versus end-diastolic length relationship, was used to assess intrinsic myocardial performance. Ischemia decreased preload recruitable work area to 13% of control after both occlusions. After reperfusion, a 30-minute dopamine infusion acutely increased myocardial function nearly threefold as compared with placebo. Myocardial performance after dopamine administration, however, was significantly depressed compared with placebo throughout the remaining 24 hours of reperfusion (p less than 0.01). These data indicate that dopamine may impair functional recovery after ischemic myocardial injury and suggest that inotropic interventions should be used in this setting only when absolutely indicated.

Animals↗
PubMed1988

Quantification of regional myocardial dysfunction after acute ischemic injury.

Quantification of myocardial performance after regional ischemic injury is difficult because available performance indexes are markedly dependent on concurrent load changes. To develop a more load-insensitive index of myocardial function during ischemia, eight conscious dogs were instrumented to measure left ventricular pressure with micromanometers and myocardial segment length with ultrasonic dimension transducers. Preload was varied by transient vena caval occlusion during control conditions, after 15 min of coronary occlusion, and at intervals during 24 h of reperfusion. Acute ischemia shifted the linear relationship between segmental stroke work (SW) and end-diastolic segment length (EDL) rightward, diminishing the slope and increasing the chi-intercept. Preload recruitable work area (PRWA), defined as the area under the SW-EDL curve, reflected changes in both slope and intercept. During acute ischemia, conventional performance indexes and PRWA decreased significantly and required up to 24 h of reperfusion to return to control values. Of all parameters examined, PRWA was most responsive to prolonged ischemic dysfunction after reperfusion and was insensitive to concurrent load changes. Thus PRWA provides improved precision in quantifying of myocardial dysfunction after regional ischemic injury. This parameter should be especially useful in assessing the subtle effects of acute interventions designed to modify functional recovery.

Algorithms↗
PubMed1988

Physiologic determinants of coronary blood flow during external cardiac massage.

Adequate coronary blood flow is a major determinant for successful resuscitation from cardiopulmonary arrest. To develop compression techniques that optimize coronary blood flow, we implanted in eight dogs electromagnetic flow probes that measured circumflex coronary blood flow and ascending aortic blood flow. Micromanometers measured left ventricular and aortic pressures. Each dog was anesthetized and intubated, and the heart was fibrillated electrically. High-impulse manual chest compressions were performed with the dog in the supine position, and compression rate was varied from 60/min to 150/min. Antegrade coronary blood flow occurred primarily during artificial diastole, and there was a brief period of retrograde coronary blood flow with compression during artificial systole. Cardiac output and diastolic aortic pressure increased with compression rate, significantly augmenting peak coronary blood flow velocity. However, diastolic perfusion time decreased linearly with compression rate and limited coronary perfusion at rates greater than 120/min. As a result, net coronary blood flow during high-impulse manual chest compression was determined primarily by diastolic aortic pressure and diastolic perfusion time. Coronary blood flow was optimized in this model at a compression rate of 120/min.

Animals↗
PubMed1988

A physiologic comparison of external cardiac massage techniques.

On the basis of recent investigation, controversy has arisen regarding which of several cardiopulmonary resuscitation methods optimizes hemodynamics. The present study was designed to compare five recently described chest compression techniques: high-impulse manual chest compression at 150/min, mechanical compression at 60/min with simultaneous ventilation, mechanical compression at 60/min with simultaneous ventilation and either systolic or diastolic abdominal compression, and pneumatic vest compression at 60/min. Eight dogs were chronically instrumented with electromagnetic flow probes in the ascending and descending aorta while matched micromanometers measured aortic, left ventricular, and pleural pressures. At study, each dog was anesthetized with morphine, intubated, and the heart was fibrillated by rapid ventricular pacing. The five cardiopulmonary resuscitation methods were performed randomly in each preparation within 7 to 10 minutes of arrest. In four dogs, brachiocephalic blood flow was computed as total cardiac output minus descending aortic blood flow, and in all dogs coronary perfusion pressure was calculated as mean diastolic aortic pressure minus mean diastolic left ventricular pressure. Average cardiac output for seven studies was 662 +/- 61 ml/min with high-impulse manual compression, 340 +/- 46 ml/min with mechanical compression and simultaneous ventilation, 336 +/- 45 ml/min with mechanical compression and simultaneous ventilation with systolic abdominal compression, 366 +/- 52 ml/min with mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 196 +/- 29 ml/min with vest resuscitation (high-impulse manual compression significantly greater than other techniques by multivariate analysis, p less than 0.05). Brachiocephalic blood flow generally followed cardiac output and was statistically the greatest with high-impulse manual compression at 273 +/- 47 ml/min (p less than 0.05). Finally, high-impulse manual compression provided the highest coronary perfusion pressure of 31 +/- 4 mm Hg (p less than 0.05) compared to 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation, 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation with systolic abdominal compression, 23 +/- 3 mm Hg for mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 11 +/- 2 mm Hg for vest resuscitation. These data demonstrate that high-impulse manual compression generated physiologically and statistically superior hemodynamics when compared with other methods in this model of cardiopulmonary resuscitation.

Animals↗
PubMed1987

Dissociation between early recovery of regional function and purine nucleotide content in postischaemic myocardium in the conscious dog.

Since abnormalities in regional myocardial function and nucleotide metabolism persist for a prolonged period after a brief coronary occlusion the temporal relation between the resolution of myocardial dysfunction and repletion of nucleotide pools in postischaemic myocardium was studied in conscious mildly sedated animals. In a second experiment 5-amino-4-imidazolecarboxamide riboside (AICAriboside) was infused in an attempt to influence myocardial function by altering the rate of adenine nucleotide synthesis. Conscious dogs mildly sedated with morphine underwent coronary occlusion for 15 min followed by reperfusion for 30 min or 12 h, at which time a myocardial sample was obtained for nucleotide analysis. Segment shortening averaged 62% of control values at 15 min of reperfusion and increased to 81% of control by 12 h of reperfusion (p less than 0.05). Adenine nucleotide content was 75(5)% of control after 30 min of reperfusion and did not change significantly over the next 12 h of reperfusion. Thus the early return of systolic function was not accompanied by a detectable increase in total adenine nucleotide content. In the second experiment a pronounced stimulation of the proximal purine nucleotide synthetic pathway occurred as evidenced by a 13-fold to 25-fold increase in inosine monophosphate content. One branch of the distal purine pathway was also stimulated as evidenced by complete repletion of guanine nucleotide pools, but the product of the other branch (adenine nucleotides) did not increase significantly. These results indicate a selective limitation of the distal adenine nucleotide synthetic pathway in postischaemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoimidazole Carboxamide↗
PubMed1987

The end-systolic pressure-volume relationship in conscious dogs.

The end-systolic pressure-volume relationship (ESPVR) has been shown to be an afterload-insensitive descriptor of ventricular inotropic state in the isolated heart. The purpose of this study was to examine the effects of changes in afterload, heart rate, intravascular volume, autonomic tone, and inotropic state on the ESPVR in conscious dogs. In 30 dogs, left ventricular and pleural pressures were measured with micromanometers, and left ventricular volume was assessed with global ultrasonic crystals. The ESPVR was obtained during vena caval occlusions in each dog during pharmacologic afterload interventions at control and after autonomic blockade. Analysis of variance techniques were used to compare the slopes (Emax) and intercepts (Vd) of ESPVR regression lines in a given study. All estimates of the ESPVR in conscious dogs involved large extrapolations to obtain estimates of Vd. Repeat determinations of Emax at control in the unblocked state were significantly different in six of eight dogs (p less than .05). After autonomic blockade, these differences were significant in only one of eight dogs. Changes in heart rate and volume loading had minimal effects on the ESPVR. In the absence of autonomic blockade, increases in inotropic state with either calcium or dobutamine tended to cause parallel shifts in the ESPVR. After autonomic blockade, Emax increased with augmentation of inotropic state, while Vd was unchanged. ESPVRs obtained at different afterloads showed statistically significant differences in Emax and in Vd in 12 of 14 dogs. However, no statistically significant relationship of Emax to afterload was observed. Thus, the ESPVR is probably valid in conscious dogs, but measurement with an intact cardiovascular system is hampered by statistically significant variability in Emax and Vd with changes in afterload. Baseline variability is magnified by the autonomic nervous system, probably mediated through sympathetic reflexes.

Analysis of Variance↗
PubMed1987

Relation between reversal of diastolic creep and recovery of systolic function after ischemic myocardial injury in conscious dogs.

Although prolonged functional abnormalities after transient myocardial ischemia have been well described, the interrelationship between postischemic systolic and diastolic alterations remains controversial. Therefore, 24 chronically instrumented conscious dogs were studied with left ventricular and pleural micromanometers, ultrasonic dimension transducers in the left anterior descending (LAD) coronary distribution, and vena caval and coronary artery occluders. The LAD was occluded for 15 minutes and reperfused for 24 hours while vena caval occlusions were performed at intervals to measure myocardial segment length at 0 mm Hg transmural diastolic left ventricular pressure (L0). Coronary occlusion produced an immediate fall in systolic function as assessed by ejection shortening and stroke work and also induced a 16 +/- 4% increase in L0, which was termed diastolic creep. Throughout reperfusion, reversal of diastolic abnormalities correlated strongly with recovery of segmental shortening and stroke work (p less than 0.001). Correlation between systolic dysfunction and diastolic creep was also observed during alteration of inotropic state by dopamine, during initial reperfusion hyperfunction, and during pharmacologic manipulation of afterload. In 5 additional dog hearts fixed in diastole by rapid glutaraldehyde infusion after coronary occlusion, myocardial creep measured by the segment length transducers paralleled sarcomere elongation measured by electron microscopy. Thus, the direct correlation between diastolic creep and systolic dysfunction throughout reperfusion and during hemodynamic alterations suggests that diastolic properties of postischemic myocardium may not be entirely passive and that systolic and diastolic dysfunction induced by ischemia may have a common basis at the cellular level.

Animals↗
PubMed1986

The influence of manual chest compression rate on hemodynamic support during cardiac arrest: high-impulse cardiopulmonary resuscitation.

Considerable effort has been expended in recent years by a number of laboratories to improve methods of cardiopulmonary resuscitation. This article briefly summarizes 5 years of investigation by our group on hemodynamic support during external cardiac massage. In most studies, long-term canine preparations were used, and implanted transducers allowed precise hemodynamic measurements. Although cardiac output was depressed with all CPR methods, manual chest compressions of high velocity, moderate force, and brief duration at a rate of 120/min seemed to optimize systemic and coronary blood flow. This method was termed high-impulse CPR. High-impulse techniques now have been applied extensively in the clinical setting, and preliminary observations also support their efficacy in man. Based on this experience, it is suggested that the American Heart Association guidelines be changed to recommend a manual chest compression rate of 120/min during closed-chest cardiac massage.

Animals↗
PubMed1985

What is breast cancer doing before we can detect it?

Breast cancer is a cellular disease and the cellular kinetic events in the predetectable period are of great clinical significance. Such events include rate of replication, angiogenesis with distant metastasis, rate of cell death, and the number of cells needed to produce a detectable and later a symptomatic mass of neoplasm. A consideration of these events and their interrelatedness is reported using data from The Breast Cancer Detection and Demonstration Projects and significant reports in the literature. Growth rates in the predetectable period are estimated to be much faster than those that occur with grossly measurable breast cancers in keeping with the prediction of Gompertzian growth.

Breast Neoplasms↗
PubMed1985

Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work.

The Frank-Starling relationship generally has been examined with filling pressure as the index of preload, resulting in a curvilinear function that plateaus at higher filling pressures. To investigate this relationship further in the intact heart, 32 dogs were chronically instrumented with left ventricular and pleural micromanometers and with regional (10 dogs) or global (22 dogs) ultrasonic dimension transducers. Seven days after implantation, left ventricular pressure and regional or global dimensions were recorded in the conscious state. After autonomic blockade, preload was varied by vena caval occlusion. Myocardial function was assessed by calculating regional or global stroke work, and preload was measured as end-diastolic segment length or chamber volume. The relationship between stroke work and either end-diastolic segment length or chamber volume (termed the preload recruitable stroke work relationship) was highly linear in every study (mean r = .97) and could be quantified by a slope (MW) and x-intercept (LW). Previous nonlinear relationships between stroke work and filling pressure seemed to reflect the exponential diastolic pressure-volume curve. Over the physiologic range of systolic arterial pressures produced by infusion of nitroprusside or phenylephrine, no significant change was observed in MW or LW in the normal dog. Calcium infusion increased both regional and global MW by 71 +/- 19% and 65 +/- 9%, respectively (p less than .02), with no significant change in LW. To normalize for ventricular geometry and heart rate, stroke work was computed from circumferential stress-strain data and converted to myocardial power output, which was then plotted against end-diastolic circumferential strain. This relationship also was highly linear, and the slope, Mmp (mW/cm3 of myocardium), is proposed as a potential measure of intrinsic myocardial performance independent of loading, geometry, and heart rate.

Animals↗
PubMed1985

Growth rates of benign and malignant neoplasms of the colon.

In summary, there is a wide, natural variance in rates of growth of benign and malignant neoplasms of the lower bowel. There is a crude correlation between growth rate and histopathology. The difference between DT(act) and DT(pot) is manifold. Primary surface desquamating cancers probably grow much slower than their metastases. These factors are of importance in understanding neoplastic behavior and in designing detection and treatment protocols. The gap in knowledge is for in vivo growth rates and mathematical patterns of growth in the period before a neoplasm reaches the threshold size permitting observation. The rates of growth are very relevant to screening and diagnostic strategies.

Cell Division↗
PubMed1984

A hermetically sealed cardiac dimension transducer for long-term animal implantation.

Pulse transit sonomicrometry is a well-accepted method for assessing cardiac dimensions and function in research animals. Unfortunately, this technique has been hampered in chronic applications by a significant incidence of transducer failure secondary to leakage of corrosive biological fluids into the piezoelectric material. The fluid leakage generally occurred at the interface between the encapsulating epoxy and the bioelectric cable and resulted in progressive functional deterioration with time. In this paper, a new hemispheric ultrasonic dimension transducer is described with a mechanical hermetic seal at the bioelectric cable-transducer interface. The hermetically sealed transducers withstood 400 psi compressed air without leakage, while conventional transducers routinely leaked at 60 psi. The performance characteristics of the new transducers were similar to those previously reported with omnidirectional designs, and no failures have occurred during 3 yr of experience with repeated transducer implantations.

Animals↗
PubMed1983

Dynamic ventricular interaction in the conscious dog.

In nine conscious, chronically instrumented dogs, ultrasonic dimension transducers measured left ventricular anterior-posterior and septal-free wall minor axis and major axis diameters. Matched micromanometers measured right and left ventricular transmural and transeptal pressures. Ventricular pressures and volumes were varied by inflation of implanted vena caval and pulmonary artery occluders, and the functional significance of the two types of ventricular interaction, i.e., direct and series, was determined. The left ventricle was represented by a modified ellipsoidal geometry. Left ventricular stroke volume calculated from the dimension data correlated well with that measured directly from ascending aortic electromagnetic flow probes during all interventions (r greater than or equal to 0.96). Partial pulmonary artery occlusion significantly increased right ventricular diastolic and systolic pressures as compared to values obtained during control and venal caval occlusion. During pulmonary artery occlusion, latitudinal septal eccentricity was increased throughout the cardiac cycle compared to control and vena caval occlusion (P less than 0.05), indicating leftward interventricular septal shifting and significant alteration of left ventricular shape. The normalized diastolic pressure-volume curve was shifted to the left with pulmonary artery occlusion compared to control and indicated a decrease in left ventricular chamber compliance. However, when selected cardiac cycles with similar end-diastolic volumes from vena caval and pulmonary artery occlusions were compared, parameters of left ventricular systolic function (stroke volume, percent systolic shortening, peak aortic blood flow, peak left ventricular pressure, and its first derivative) remained relatively constant. These data suggest that mean myocardial fiber length is the major preload determinant of left ventricular systolic function independent of chamber pressure and shape, and that direct ventricular interaction mediated by interventricular septal shifting has minimal effects on systolic myocardial performance in this model. Thus, series ventricular interaction during acute imbalances in biventricular loading, where the output of the right ventricle determines the input of the left, seems to be far more important than direct interaction to the regulation of overall cardiac function.

Animals↗