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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↗

Appearance of GFAP-positive cells in adult human brain cultures spontaneously decelerated in growth.

Cell cultures were derived from adult human brain biopsies [from cortical gray (cultures 9-HB-G and 33-HB-G) and white (culture 14-HB-W) and stroke-injured white matter (culture 33-HB-IW)]. The morphology and growth rate of cultured cells were examined and correlated with the presence of vimentin and glial fibrillary acidic protein (GFAP). The cultures from various brain matters differed in cell morphology and rate of growth but not in GFAP and vimentin staining. Cells of primary and rapidly proliferating cultures were GFAP-negative and vimentin-positive. Spontaneous growth deceleration occurred in culture 14-HB-W within passages 5 to 10 and in cultures 9-HB-G, 33-HB-G, and 33-HB-W within passages 17 to 20. This deceleration, as well as the successive complete growth arrest, were accompanied by an appearance of GFAP-positive cells and an elevated intensity for vimentin staining. We propose that GFAP-positive astrocytes originate from glial precursor cells that migrate from the explants and differentiate under prolonged subcultivation.

Adult↗

Deceleration and acceleration in the rate of posterior neuropore closure during neurulation in the curly tail (ct) mouse embryo.

Curly tail (ct) is a mouse mutant producing spinal neural tube defects as a result of delayed closure of the posterior neuropore (PNP). The purpose of the present study was to determine in ct/ct embryos the time of onset of the delay in PNP closure, and the pattern of this closure, as well as to study the possibility that reopening of the neural tube occurs. Normal spinal neurulation was studied in non-mutant Swiss (Sw) embryos. In the latter, the average PNP length diminished steadily between the 7- and 25-somite stages, and then decreased more rapidly, indicating an acceleration of closure rate, until the 30- to 32-somite stage, when all PNPs closed. PNP width decreased steadily between the stages of 7 and 30 somites. In ct/ct embryos the average PNP length showed a slight increase between the stage of 23 to 28 somites, indicating a temporary deceleration of closure rate, and the range of PNP sizes increased markedly. This was followed by a decrease in PNP length until the 37-somite stage, indicating an acceleration of closure rate. From the stage of 32 somites onwards, the proportion of embryos with closed PNPs gradually increased to 90%. The population of ct/ct embryos was subdivided. Embryos with large PNPs showed a marked deceleration of closure rate during a period of 11 somite stages, followed by a brief but very high acceleration of closure rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation.

The effects of two inspiratory flow waveforms (WFs), decelerating and constant have been studied in 14 patients undergoing intermittent positive-pressure ventilation (IPPV). With tidal volume (VT), inspiratory time, inspiratory-expiratory (I/E) ratio and frequency being kept constant, the decelerating waveform produced statistically significant reduction of peak pressure, total respiratory resistance, work of inspiration, ratio of dead space to tidal volume (VD/VT) and alveolar-arterial gradient for oxygen (A-a)PO2. There was significant increase in total static and kinetic compliances and PaO2, with no significant changes in PaCO2, in cardiac output (CO) and in other haemodynamic measurements.

Adult↗

A new dynamometer measuring concentric and eccentric muscle strength in accelerated, decelerated, or isokinetic movements. Validity and reproducibility.

A new computerized dynamometer (the SPARK System) is described. The system can measure concentric and eccentric muscle strength (torque) during linear or nonlinear acceleration or deceleration, isokinetic movements up to 400 degrees.s-1, and isometric torque. Studies were performed to assess: I. validity and reproducibility of torque measurements; II. control of lever arm position; III. control of different velocity patterns; IV. control of velocity during subject testing; and, V. intra-individual reproducibility. No significant difference was found between torque values computed by the system and known torque values (p greater than 0.05). No difference was present between programmed and external measurement of the lever arm position. Accelerating, decelerating and isokinetic velocity patterns were highly reproducible, with differences in elapsed time among 10 trials being never greater than 0.001 s. Velocity during concentric and eccentric isokinetic quadriceps contractions at 30 degrees.s-1, 120 degrees.s-1 and 270 degrees.s-1 never varied by more than 3 degrees.s-1 among subjects (N = 21). Over three days of testing, the overall error for concentric and eccentric quadriceps contraction peak torque values for 5 angular velocities between 30 degrees.s-1 and 270 degrees.s-1 ranged from 5.8% to 9.0% and 5.8% to 9.6% respectively (N = 25). The results indicate that the SPARK System provides valid and reproducible torque measurements and strict control of velocity. In addition, the intra-individual error is in accordance with those reported for other similar devices.

Adult↗

Analysis of causes of velocity spread during initial deceleration in the ascending aorta in children and young adults.

Factors that predict the magnitude of instantaneous systolic velocities within the Doppler sample volume in the ascending aorta have not been elucidated in normal persons. This study determines whether the magnitude of instantaneous velocity spread in the ascending aorta is related to ascending aortic diameter, Reynolds number or other factors. Ascending aortic velocity tracings and diameters were recorded for 77 normal subjects using a 25 degrees off-axis transducer that permitted beam-flow alignment. Percent instantaneous velocity spread at peak modal velocity, which corresponds temporally to initial deceleration, was determined by dividing instantaneous velocity spread by peak modal velocity. Using standard formulations, values were computed in the ascending aorta of each subject for Reynolds number using peak and mean velocity, Womersley's alpha, and critical oscillatory Reynolds number. The highest correlation occurred for percent instantaneous velocity spread and ascending aortic diameter (r = 0.54) (p less than 0.001). The second highest correlation occurred for percent instantaneous velocity spread and critical oscillatory Reynolds number (r = -0.47) (p less than 0.001). A low but significant correlation (r = 0.30) (p less than 0.05) was found between alpha and percent instantaneous velocity spread. No significant correlation was found between percent instantaneous velocity spread and heart rate (r = 0.23), Reynolds number (r = -0.11) or maximal ascending aortic velocity (r = 0.14). This study demonstrates that percent instantaneous velocity spread in the human aorta is most closely related to ascending aortic diameter, an increase of which will cause a higher percent instantaneous velocity spread at initial deceleration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Late decelerations and brain tolerance of the fetal monkey to intrapartum asphyxia.

Eight monkey fetuses near term were subjected to regulated asphyxia during labor by mechanically constricting the maternal abdominal aorta and diminishing blood flow to the uterus. A magnitude of asphyxia was produced and maintained for an initial three hours that was close to but not sufficient to elicit late decelerations. The asphyxia was then augmented during a fourth hour to cause late decelerations of magnitudes of 5 to 15 per cent of the initial heart rate. After termination of the fourth hour of asphyxia, the fetuses were delivered by hysterotomy and provided intensive care. During the three to nine months of survival after birth, all animals were neurologically intact; on necropsy the brains were free of pathologic changes both grossly and microscopically. These results support the thesis that fetal heart rate monitoring during labor exhibits a sensitivity sufficient to diagnose asphyxia of the fetus of clinical significance before it reaches a magnitude that may cause permanent neurological injury. The results are particularly pertinent to those clinical circumstances where the decreases in intervillous space blood flow brought about by uterine contractions are accentuated due to low maternal blood pressure.

Animals↗

Nonstressed antepartum heart rate monitoring: implications of decelerations after spontaneous contractions.

Fetal outcome in 98 patients with spontaneous antepartum late decelerations was studied by combining the data of two obstetric departments. Heart rate variability was used to classify the different patterns into two categories: terminal and decelerative. In 14 of the 47 pregnancies in which a terminal pattern was found, intrauterine death occurred within a week. Of the remaining 33 fetuses, 71% were acidemic at elective cesarean section (CS). In contrast, all of the 51 fetuses with a decelerative cardiotocogram (CTG) survived the antenatal period, and only two of 25 were acidemic at elective CS. Labor was induced in 20 patients with a decelerative CTG, and fetal distress occurred in 12, of whom 10 were eventually delivered by CS. All fetuses with a repetitive decelerative heart rate pattern antepartum developed distress in labor. In contrast, an isolated deceleration, on one occasion only, was not associated with distress during labor, except in growth-retarded fetuses. The clinical implications of these findings are discussed and the results are compared with those of oxytocin contraction stress tests.

Acidosis↗

Neonatal heart rate reactivity following variable decelerations during labor.

The instantaneous heart rate of 65 healthy neonates was continuously monitored during labor and the first 30 minutes of neonatal life. It was found that infants who had moderate or severe variable decelerations in utero had a significantly delayed neonatal heart rate (NHR) reactivity without any evidence of perinatal asphyxia. The NHR pattern of infants with and without variable decelerations is described and possible mechanisms which could explain the delayed NHR reactivity are discussed.

Adult↗

Association of spontaneous fetal heart rate decelerations during antepartum nonstress testing and intrauterine growth retardation.

Two hundred one patients with high-risk pregnancy and 66 patients with term uncomplicated pregnancy underwent a nonstress test 7 days or less prior to delivery. The incidence of spontaneous fetal heart rate decelerations in the high-risk group was 5.5%. None of the fetuses in the normal group showed this finding. Among those infants presenting with spontaneous decelerations, there was an 18.2% mortality. Disturbances of intrauterine growth were found in 63.6% of cases. The possible metabolic mechanisms and clinical implications underlying this finding are discussed.

Electrocardiography↗

Effects of reduced uterine blood flow on accelerations and decelerations in heart rate of fetal sheep.

Experiments were conducted in unanesthetized fetal sheep during the last third of gestation to examine the effects of prolonged reversible reductions in uterine blood flow on mean fetal heart rate, accelerations and decelerations in fetal heart rate, and fetal arterial pressure. With use of a Teflon vascular clamp placed around the maternal common internal iliac artery, uterine blood flow was reduced, leading to a reduction in fetal arterial oxygen saturation from 60% to 30% for 2 hours. This was associated with an initial transient fetal bradycardia and hypertension followed by tachycardia. Mean fetal heart rate remained significantly elevated for 2 hours following the release of the vascular clamp. There was no change in the number, amplitude, or duration of accelerations, but there was a significant increase in both the number and amplitude of decelerations during the period of reduced uterine blood flow.

Animals↗

Deceleration in cumulative food intake curves, changes in body temperature and diet-induced thermogenesis.

In order to assess the relationship between the shape of the cumulative food intake curve and a reflection of internal processes, eating behaviour, postprandial thermogenesis, and skin and core temperature of normal weight restrained and unrestrained eating women and of obese restrained eating women were recorded during four-course solid food lunches, eaten in a laboratory setting (respiration chamber) at a constant ambient temperature of 22 degrees C. The skin temperature (upper arm, upper leg, liver proximity) and core temperature were measured constantly from one hour prior to until two hours after the lunch. Normal weight unrestrained eaters displayed decelerated cumulative food intake curves and an increase in the liver temperature data of 0.8-1.5 degrees C, from the beginning of the meal onwards, remaining high until 60-90 minutes after the meal was consumed. The postprandial thermogenesis of normal weight unrestrained eaters was on average 8.1 +/- 1.3%, calculated over two and a half hours from the beginning of the meal. Overweight and normal weight restrained eaters displayed linear cumulative food intake curves, almost no changes in skin and core temperatures and a postprandial thermogenesis of 4.2 +/- 0.3% and 4.8 +/- 0.7%, calculated over two and a half hours from the beginning of the meal onwards. In conclusion, deceleration in cumulative food intake curves is positively correlated with a temperature increase in the skin in the proximity of the liver, and with postprandial thermogenesis.

Adult↗

Cardiac deceleration and E-wave brain potential components in young, middle-aged and elderly adults.

Event-related potentials (ERPs), heart rate, and behavioral data were recorded from young, middle-aged, and elderly adults during an S1-S2 recognition memory paradigm. Anticipatory and evoked cardiac decelerations decreased significantly with age, as did the accuracy of recognition memory. The E-wave prior to S2 did not differ with age, however, and was not correlated with heart rate deceleration in any age group. Correlations between physiological measures and performance were weak in all groups. Taken together, the data provide little support for the hypothesis that the poorer recognition memory of older adults is related to an increasing uncoupling of E-wave and anticipatory heart rate with age.

Adult↗

The impact of two different reinforcers on conditioned operant heart-rate acceleration and deceleration.

The effects of two types of reinforcers on operant heart-rate acceleration and deceleration conditioning were examined over a number of sessions. The initial use of monetary reinforcement facilitated discriminative pre-trial to trial heart-rate acceleration during sessions utilizing both monetary reinforcement and visual feedback. The initial use of visual feedback did not produce such discriminative control, but the subsequent use of monetary reinforcement resulted in increases in pre-trial and trial heart rate over sessions. No effects due to type of reinforcement were noted for heart-rate deceleration. Increases and decreases in cardiovascular functioning were imposed upon a background of increased skin responding. The cardiovascular responses that developed over sessions appeared to be relatively independent of changes in skin response.

Conditioning, Operant↗

Deceleration of age-specific mortality rates in chromosomal homozygotes and heterozygotes of Drosophila melanogaster.

Age-specific mortality trajectories were estimated in mixed-sex cohorts of D. melanogaster. We studied 22,000 flies that were either second-chromosome homozygotes or heterozygotes with a randomized genetic background. Broad-sense heritabilities for longevity were estimated to be 6% for males and 9% for females. Heterozygotes lived longer than homozygotes on average, but there were exceptions to the usual heterotic pattern; in several crosses parental homozygotes had average life spans as long as that of their F1 heterozygotes. Estimated age-specific mortality rates were found to decelerate at advanced ages in both homozygotes and heterozygotes. The mortality models that best fit the data are the logistic model and the two-stage Gompertz model, both of which produce mortality trajectories that level off at advanced ages. Old-age mortality deceleration is not peculiar to inbred Drosophila.

Animals↗

Consequences of increasing heart rate on deceleration time, the velocity-time integral, and E/A.

The ascendancy of diastolic heart failure to "epidemic" proportions has increased the use of and reliance on Doppler echocardiography as a source for diagnosis and as the preferred method for determining indexes of diastolic function (DF). Current indexes are primarily derived from shape-based features of Doppler E and A waves, such as their amplitudes, slopes, durations, and areas. Load dependence and pathologic correlates of these indexes have been considered, but DF indexes are not routinely corrected for heart rate (HR). To determine the dependence of selected Doppler-derived indexes of DF on HR, transmitral Doppler flow velocities and electrocardiograms were simultaneously recorded during supine bicycle exercise in 21 young, healthy volunteers. Standard E- and A-wave shape-based indexes (acceleration time, deceleration time [DT], peak E, peak A) were measured using triangle approximation. Velocity-time integrals (VTIs) were calculated by trapezoidal and triangular approximations. A-wave peak velocity (A) was measured conventionally, relative to baseline, and also using 2 alternative methods: A*, measured relative to the E@A velocity, and Ac, relative to the E-wave deceleration value at peak A-wave velocity. E/A was calculated conventionally and by using A* and Ac. The results showed that DF indexes derived from individual E waves are essentially HR independent. DT showed a mere 20% decrease for a 100% increase in HR. A triangular approximation for the E-wave VTI and the corrected E/Ac were found to be nearly HR independent. In conclusion, on the basis of the established continuity of cardiac output as a function of increasing HR and the observed data, Doppler-derived indexes of DF (DT, VTIs, E/Ac) can be treated as essentially HR independent only if the VTI and A-wave peak are corrected for HR as described.

Adult↗

Rate of head growth decelerates and symptoms worsen in the second year of life in autism.

BACKGROUND: Longitudinal studies of head circumference growth in infants later diagnosed with autism are needed to understand the accelerated head growth in this disorder. METHODS: We analyzed longitudinal head circumference data from birth to 3 years in 28 children later diagnosed with autism spectrum disorder on the basis of individual growth curve analyses using hierarchical linear models. RESULTS: Head circumference Z scores relative to norms significantly increased in the autism sample from birth to 12 months, but this pattern did not persist beyond 12 months. Rather, the rate of change in head circumference from 12 to 36 months was not different from the normative sample. CONCLUSIONS: These results suggest that a period of exceptionally rapid head growth occurs during the first year of life in autism; after 12 months of age, the rate of head circumference growth decelerates relative to the rate during the first year of life. Studies of behavioral development in infants later diagnosed with autism suggest that the period of acceleration of head growth precedes and overlaps with the onset of behavioral symptoms, and the period of deceleration coincides with a period of worsening of symptoms in the second year of life.

Age Factors↗

Vinburnine decelerates [3H]N-methylscopolamine binding to recombinant human muscarinic M1-M4 acetylcholine receptors.

The kinetics of [3H]N-methylscopolamine binding to membranes of Chinese hamster ovary (CHO) cells expressing muscarinic M(1)-M(4) acetylcholine receptors was studied. [3H]N-methylscopolamine dissociation was used for the "single-point" analysis of allosteric modulation by vinburnine (L-eburnamonine). [3H]N-methylscopolamine dissociation was decelerated by vinburnine with EC(50) values of 29.5, 4.1, 9.5 and 15.0 microM for muscarinic M(1)-M(4) receptors, respectively. Acetylcholine doubled the EC(50) of vinburnine for muscarinic M(3) receptors. These kinetic EC(50) values correlated with equilibrium binding constants, supporting the ternary allosteric model. Vinburnine also decelerated the association of [3H]N-methylscopolamine binding, resulting in opposite cooperativity for muscarinic M(1) and M(2) receptors.

Allosteric Regulation↗