Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “cycle threshold value”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1996

Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody.

Although histologically benign, one-third of all pituitary tumors will be invasive of surrounding structures. In this study, the relationship between the proliferative activity in pituitary adenomas and their invasiveness was investigated. Invasion was defined as gross, operatively or radiologically apparent infiltration of dura or bone. Using the recently developed MIB-1 monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas, and 7 primary pituitary carcinomas were determined. All tumors were fully classified by histology, immunohistochemistry, and electron microscopy. The mean Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%, respectively (mean +/- standard error of the mean). An analysis of variance and then individual pairwise comparisons confirmed significant differences in the mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P = 0.03). Establishing a threshold labeling index of 3% served to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and was associated with positive and negative predictive values of 96 and 80%, respectively. Although invasive pituitary tumors exhibited significantly higher growth fractions than did noninvasive tumors, there were individual exceptions, indicating that in a subpopulation of invasive pituitary tumors, factors other than proliferative activity determine invasive potential.

Adult↗
PubMed1997

Stage duration and increase of work load in incremental testing on a cycle ergometer.

Any variation of the test protocol for incremental testing (IT) in cycle ergometry may affect the accuracy of the determination of anaerobic threshold (AnT). For lactate threshold concepts, indicating the maximum lactate steady-state (max Lass), the formation of the quasi-steady-state (QSS=95% of steady-state level) is evident. Previous studies have not specified the time that it takes for blood lactate to stabilize following incremental changes in WL. The purpose of this study was to identify the minimum duration of exercise necessary to establish QSS following various increments in WL (10, 20, 30, 40 and 50 W). Eight male endurance-trained cyclists [relative maximal oxygen consumption = 64.8 (4.2) ml x kg(-1) x min(-1)] performed three different exercise tests on a cycle ergometer: (1) an exhaustive IT with a starting WL of 100 W, followed by 20-W increments every 3 min; (2) a threshold test with 20-W increments every 9 min to determine the MaxLaSS; and (3) five incremental exercise tests (from 100/110 W, with 20-W increments every 3 min) with a final 10-, 20-, 30-, 40- or 50- W increment lasting 10 min, at 10 W below MaxLaSS (T10-T50 experiments). The time constant of lactate kinetics (tau), the time constant of lactate elimination, and the time taken to elicite QSS, defined as 95% of the time taken to reach steady-state level (t95%), were calculated in the T10-T50 experiments. The tau and t95% increased significantly with WL increment size: the correlation was not linear. Smaller WL increments required proportionally longer durations. Mean (SD) t95% values (min:s) were 1:57 (0:27) (T10), 2:58 (0.16) (T20), 4:08 (0:23) (T30), 4:45 (0:45) (T40) and 5:06 (0:43) (T50). The application of these references in IT protocols may lead to an extension of total test duration, particularly with smaller increments. Therefore, lactate threshold modelling, the training status of the athletes and comparability with lactate measurements obtained during training events should be considered. IT protocols not accomplishing QSS criteria may effect an underestimation of WL-related lactate values and an overestimation of lactate thresholds, which indicate MaxLaSS, especially in highly trained athletes. This suggests that the establishment of an increment-size-dependent t95% may reduce protocol-related influences on AnT and standardize the use of the AnT in IT procedures in the training management of elite cyclists.

Adult↗
PubMedDate not supplied

The effect of a submaximal exercise orientation on cardiopulmonary cycle ergometer stress test results in older adults.

BACKGROUND: Orientation sessions are sometimes used to habituate subjects before exercise stress testing. The extent of habituation in older subjects has not been clearly defined. Additionally, the use of repetitive maximal stress testing as an orientation method may not be necessarily applicable in the aged. METHODS: To determine if the employment of a submaximal orientation session would effect cardiopulmonary cycle ergometer exercise results, 266 older adults (68.6 +/- 5.0 years) male (n = 100) and female (n = 166) subjects participated in this study. One hundred thirty-one subjects received an orientation before stress testing. One hundred thirty-five did not. RESULTS: Analysis of resting values revealed no significant differences. Separate gender analysis was performed at submaximal workloads. Men were examined at 0, 60, and 105 Watts; women at 0, 45, and 75 Watts. Oriented subjects displayed significantly lower heart rates for both males and females at all submaximal workloads. Oxygen uptake was significantly lower for oriented women at 45 Watts (P < or = .05) and men at 60 Watts (P < or = .05). Oriented males displayed significantly lower systolic blood pressure at 0 Watts (P < or = .05), 60 Watts (P < or = .01), and 105 Watts (P < or = .05). The oriented group reached ventilatory threshold (VeT) at a higher workload (P < or = .001), lower heart rate (P < or = .001), and higher VO2 uptake (P < or = .05). Nonoriented subjects obtained a significantly higher maximal heart rate than oriented subjects (147 +/- 15.7 beats per minute (bpm) vs. 140 +/- 17.1 bpm, P < or = .01). Separate gender analysis revealed a significant difference (P < or = .01) in maximal heart rate in males (oriented = 137.4 +/- 18.8 bpm vs. nonoriented = 147.7 +/- 15.7 bpm). Although nonoriented women achieved a higher maximal heart rate, the difference was not significant (146.9 +/- 15.8 bpm vs. 142.6 +/- 16.0 bpm). CONCLUSION: These results indicate that both male and female older subjects display significant modification in physiologic performance from habituation after a single submaximal exercise orientation session. This effect was greater at submaximal than maximal workloads, and appears to be greater than that previously reported in younger subjects.

Aged↗
PubMed1998

K+ currents of encephalitogenic memory T cells decrease with encephalitogenicity while interleukin-2 (IL-2) receptor expression remains stable during IL-2 dependent cell expansion.

Previous studies revealed a linkage between increased K+ current and lymphocyte activation upon non-specific stimulation with mitogenic lectins and antibodies. So far no information is available about the behaviour of K+ currents in specifically autoantigen-stimulated lymphocytes. Therefore, we have investigated K+ currents in encephalitogenic T line cells, specifically stimulated with myelin basic protein, using the whole-cell patch-clamp technique. In parallel, the T cell activation marker interleukin-2 (IL-2) receptor was measured quantitatively by flow cytometry. Outward currents were observed in response to depolarizing voltage steps from a holding potential of -80mV. The peak current density increased with more positive membrane potentials, where the current threshold was about -40mV and the maximum conductance was 1.22nS/pF. This current was characterized by a fast activation and a fast inactivation with half maximal inactivation at -67mV. The sensitivity of the peak current to K+ channel blocking agents was as follows: 4-aminopyridine (4-AP) had a half blocking concentration of 0.4mM and a maximal block of 83.7% at 10mM 4-AP, tetraethyl-ammonium caused a block of 6% at 0.1mM, 15% at 1mM and 40% at 10mM, charybdotoxin blocked 90% at 100nM, whereas iberiotoxin had no effect (all values at a clamped membrane potential of +30mV). The encephalitogenic T cells used in our study reach their highest encephalitogenic potency on day 3 to 4 after the onset of restimulation. Furthermore, K+ currents were measured during the whole course of an in vitro restimulation cycle. The peak currents normalized to cell capacitance reached their maximum on day 2 (326+/- 52.8pA/pF, n = 4) and decreased thereafter as follows: day 3: 139.7 +/- 7.87pA/pF (n = 27), day 4: 85.4 +/- 8.95pA/pF (n = 28) and day 5: 40.9 +/- 7.45pA/pF (n = 17). The activation and inactivation characteristics of the current and its responses to selective blockers were similar at all days after restimulation. In contrast to the K+ current, IL-2 receptor expression was maintained on > 95% of cells until day 6 after restimulation. In conclusion, the K+ currents measured in rat encephalitogenic T cells resemble n-type voltage-gated K+ currents described in mice and man. The comparison of K+ current, IL-2 receptor expression and encephalitogenic potency let us suppose that the observed K+ current represents an early event of specific T cell activation and can serve as a parameter of high functional activity of T cells corresponding to their encephalitogenicity.

Animals↗
PubMed2006

Phasic menstrual cycle effects on the control of breathing in healthy women.

This study examined the effects of menstrual cycle phase on ventilatory control. Fourteen eumenorrheic women were studied in the early follicular (FP; 1-6 days) and mid-luteal (LP; 20-24 days) phase of the menstrual cycle. Blood for the determination of arterial PCO(2) (PaCO(2)) , plasma strong ion difference ([SID]), progesterone ([P(4)]), and 17beta-estradiol ([E(2)]) concentrations were obtained at rest. Subjects performed a CO(2) rebreathing procedure that included prior hyperventilation and maintenance of iso-oxia to evaluate central and peripheral chemoreflex, and nonchemoreflex drives to breathe. Resting PaCO(2) and [SID] were lower; minute ventilation (V (E)), [P(4)] and [E(2)] were higher in the LP versus FP. Within the LP, significant correlations were observed for PaCO(2) with [P(4)], [E(2)] and [SID]. Menstrual cycle phase had no effect on the threshold or sensitivity of the central and/or peripheral ventilatory chemoreflex response to CO(2). Both (V (E)) and the ventilatory response to hypocapnia (representing nonchemoreflex drives to breathe) were approximately 1L/min greater in the LP versus FP accounting for the reduction in PaCO(2) . These data support the hypothesis that phasic menstrual cycle changes in PaCO(2) may be due, at least in part, to the stimulatory effects of [P(4)], [E(2)] and [SID] on ventilatory drive.

Adult↗
PubMed2006

Serial O-(2-[(18)F]fluoroethyl)-L: -tyrosine PET for monitoring the effects of intracavitary radioimmunotherapy in patients with malignant glioma.

PURPOSE: Intracavitary radioimmunotherapy (RIT) offers an effective adjuvant therapeutic approach in patients with malignant gliomas. Since differentiation between recurrence and reactive changes following RIT has a critical impact on patient management, the aim of this study was to analyse the value of serial O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) PET scans in monitoring the effects of this locoregional treatment. METHODS: Following conventional therapy, 24 glioma patients (5 WHO III, 19 WHO IV) underwent one to five RIT cycles with either (131)I-labelled (n=19) or (188)Re-labelled (n=5) anti-tenascin antibodies. Patients were monitored with serial FET PET scans (2-12 scans). For semiquantitative evaluation, maximal tumoural uptake (TU(max)) was evaluated and the ratio to background (BG) was calculated. Results of PET were correlated with histopathological findings (n=9) and long-term clinical follow-up for up to 87 months. RESULTS: In seven tumour-free patients, PET revealed slightly increasing but homogeneous FET uptake surrounding the resection cavity with a peak up to 18 months following RIT (TU(max)/BG 2.07+/-0.25) but stable or decreasing values during further follow-up (last follow-up: TU(max)/BG 1.63+/-0.22). Seventeen patients developed regrowth of residual tumour/tumour recurrence showing additional nodular FET uptake (TU(max)/BG 2.79+/-0.53). A threshold value of 2.4 (TU(max)/BG) allowed best differentiation between recurrence and reactive changes (sensitivity 82%, specificity 100%). CONCLUSION: FET PET is a sensitive tool for monitoring the effects of locoregional RIT. Homogeneous, slightly increasing FET uptake around the tumour cavity with a peak up to 18 months after RIT, followed by stable or decreasing uptake, points to benign, therapy-related changes. In contrast, nodular uptake is a reliable indicator of recurrence.

Adult↗
PubMed2001

Pulmonary function subsequent to expiratory muscle fatigue in healthy humans.

One of the mechanisms proposed to explain the decrement in pulmonary function often seen after exercise is fatigue of the expiratory muscles. To test the hypothesis that expiratory muscle fatigue alters lung function, several indices of pulmonary function were measured before and after expiratory muscle fatigue was induced by expiratory loaded breathing. Eight subjects completed a fatigue trial (EF) in which expiratory threshold loaded breathing was performed at an initial resistance equal to 80 % of their maximal expiratory pressure (MEP), at a respiratory rate of 13 bpm, and a duty cycle (T(I)/T(Tot)) of 0.33. MEP was taken at predefined intervals throughout the loaded breathing protocol, and loaded breathing was discontinued when MEP was less than 80 % of each subject's pre EF trial MEP (T(Lim)). FVC, FEV(1.0), FEF(25 %), FEF(25-75 %), and maximal inspiratory and expiratory pressures (MIP and MEP) were taken prior to, immediately after, and at 5, 10, and 15 min post fatigue. On a separate day a control trial (CON) was performed that was identical to each subjects EF trial with the exception that no expiratory load was utilized. At T(Lim) MEP was significantly reduced (p < 0.001) by 23.5 % from the pre-expiratory loaded breathing value (183.1 +/- 39.56 to 140.13 +/- 30.45 mmHg), whereas it remained unchanged during the CON trial (191.06 +/- 44.18 to 188.06 +/- 43.50 mmHg). FVC measured prior to and immediately after T(Lim) remained unchanged following both the EF (5349.45 +/- 1130.8 to 5387.43 +/- 1139.92 mL) and CON trials (5287.75 +/- 1220.29 and 5352.78 +/- 1191.30 mL). These results suggest that any expiratory muscle fatigue developed during exercise by itself does not result in altered pulmonary function. However, any interactions between expiratory muscle fatigue and other consequences of exercise that may alter lung function cannot be ruled out.

Adult↗
PubMed1977

Automatic measurement of sister chromatid exchange frequency.

An automatic system for detecting and counting sister chromatid exchanges in human chromosomes has been developed. Metaphase chromosomes from lymphocytes which had incorporated 5-bromodeoxyuridine for two replication cycles were treated with the dye 33258 Hoechst and photodegraded so that the sister chromatids exhibited differential Giemsa staining. A computer-controlled television-microscope system was used to acquire digitized metaphase spread images by direct scanning of microscope slides. Individual objects in the images were identified by a thresholding procedure. The probability that each object was a single, separate chromosome was estimated from size and shape measurements. An analysis of the spatial relationships of the dark-chromatid regions of each object yielded a set of possible exchange locations and estimated probabilities that such locations corresponded to sister chromatid exchanges. A normalized estimate of the sister chromatid exchange frequency was obtained by summing the joint probabilities that a location contained an exchange within a single, separate chromosome over the set of chromosomes from one or more cells and dividing by the expected value of the total chromosome area analyzed. Comparison with manual scoring of exchanges showed satisfactory agreement up to levels of approximately 30 sister chromatid exchanges/cell, or slightly more than twice control levels. The processing time for this automated sister chromatid exchange detection system was comparable to that of manual scoring.

Autoanalysis↗
PubMed1990

Are obese children truly unfit? Minimizing the confounding effect of body size on the exercise response.

To test the hypothesis that obese children are unfit (i.e., have abnormal responses to exercise testing consistent with reduced levels of habitual physical activity), we used new analytic strategies in studies of 18 obese children performing cycle ergometry. The subject's weight (mean +/- SD) was 168 +/- 24% that predicted by height, and the age range was 9 to 17 years. Size-independent measures of exercise (e.g., the ratio of oxygen uptake (VO2) to work rate during progressive exercise and the temporal response of VO2, carbon dioxide output (VCO2), and minute ventilation (VE) at the onset of exercise) were used. The ability to perform external mechanical work was corrected for VO2 at unloaded pedaling (change in maximum oxygen uptake (delta VO2max) and in anaerobic threshold (delta AT). On average, obese children's responses were in the normal range: delta VO2max, 104 +/- 41% (+/- SD) predicted (by age); delta AT, 85 +/- 51%; ratio of change in VE to change in VCO2, 111 +/- 21% and ratio of change in VO2 to change in work rate, 100 +/- 24%, but six of the obese children had values of delta VO2max or delta AT that were more than 2 SD below normal. In addition, obese children did not have increased delta VO2max or delta AT with age as observed in nonobese children. Although the response time of VO2 was normal (99 +/- 32% of predicted), those for both VCO2 and VE were prolonged. We conclude that the finding of obesity in a child is not a reliable indicator of poor fitness but that testing cardiorespiratory responses to exercise can be used to identify subjects with serious impairment and to individualize therapy.

Adolescent↗
PubMed2003

Are there threshold numbers for protected forests?

Maintenance of forests biodiversity is intimately related on the one hand to the species and community-related ecological needs of flora and fauna living in the forest and on the other hand the disturbance regimes of the specific forest type. Populations of plants and animals need minimum biotopes for their ontogeny; for assuring their survival they depend on a minimum of connected suitable areas. Specific traits of forest types are based upon different disturbance regimes, ranging from small-scale internal processes (e.g. regeneration, growth, senescence, mortality, gap dynamics) generating normal forest cycles (i.e. regular sequences, e.g. regeneration, optimum, decay phases) to potentially chaotic and large-scale, frequently external, disturbances, e.g. fire, landslides, or beetle attacks. Forest protection may meet the needs of these very different demands by varied protected area networks going from small (>100 ha), medium (1000 ha) to large-scale reserves (National Parks, several thousands of ha). According to this triple protection concept not only graduated threshold numbers, but also threshold sizes and threshold areas for forest protection must be defined. To realize this concept the regional and local conditions (forest area, forest cover percentage, forest composition, socio-economic targets) must always be taken in consideration.

Animals↗
PubMed1997

Reliability of using the D-max method to define physiological responses to incremental exercise testing.

The purpose of this study was to examine the reliability of using a mathematical method, D-max, to define blood lactate kinetics in response to an incremental exercise test, and to compare the physiological responses corresponding to the workload at D-max with those at the traditional 4 mmol l-1 lactate threshold and ventilatory thresholds. Ten male endurance trained athletes, with an average (+/- SD) age of 25.6 +/- 8.2 years and maximal oxygen consumption of 64.0 +/- 1.7 ml kg-1 min-1, performed an incremental cycling test on two occasions separated by four weeks. The expired gas was analysed on-line and plasma lactate concentration was analysed for each workload and at exhaustion. The lactate response to exercise was represented by a third-order polynomial regression curve. The D-max was defined as the point on the regression curve that yields the maximal distance to the straight line formed by the two end points of the curve. The results demonstrated a high test-retest reliability (intraclass correlation coefficients 0.77-0.93, p < 0.01) in oxygen consumption, heart rate and exercise intensity at both D-max point and exhaustion. No significant differences were found in the mean values of the variables between the two tests. It is concluded that the D-max appears to be a reliable method for defining the individual physiological responses to exercise tests, with the advantage of objectivity. However, there is no evidence to support the theory that the exercise intensity defined by the D-max method is superior to that defined by other methods to prescribe training intensity or predict aerobic performance for athletes. Further investigations are warranted to examine the validity of using this method in exercise prescription.

Adolescent↗
PubMed2003

Effects of short-term training using powercranks on cardiovascular fitness and cycling efficiency.

Powercranks use a specially designed clutch to promote independent pedal work by each leg during cycling. We examined the effects of 6 wk of training on cyclists using Powercranks (n=6) or normal cranks (n=6) on maximal oxygen consumption (VO2max) and anaerobic threshold (AT) during a graded exercise test (GXT), and heart rate (HR), oxygen consumption (VO2), respiratory exchange ration (RER), and gross efficiency (GE) during a 1-hour submaximal ride at a constant load. Subjects trained at 70% of VO2max for 1 h.d(-1), 3 d.wk(-1), for 6 weeks. The GXT and 1-hour submaximal ride were performed using normal cranks pretraining and posttraining. The 1-hour submaximal ride was performed at an intensity equal to approximately 69% of pretraining VO2max with VO2, RER, GE, and HR determined at 15-minute intervals during the ride. No differences were observed between or within groups for VO2max or AT during the GXT. The Powercranks group had significantly higher GE values than the normal cranks group (23.6 +/- 1.3% versus 21.3 +/- 1.7%, and 23.9 +/- 1.4% versus 21.0 +/- 1.9% at 45 and 60 min, respectively), and significantly lower HR at 30, 45, and 60 minutes and VO2 at 45 and 60 minutes during the 1-hour submaximal ride posttraining. It appears that 6 weeks of training with Powercranks induced physiological adaptations that reduced energy expenditure during a 1-hour submaximal ride.

Adult↗
PubMed2004

Reproducibility of internal atrial defibrillation threshold in paroxysmal and persistent atrial fibrillation.

BACKGROUND: Several pharmacological or technical factors may affect atrial defibrillation threshold (ADFT) for internal cardioversion (ICV) in the treatment of atrial fibrillation (AF). METHODS: We evaluated the reproducibility of ADFT in lone paroxysmal (electrically induced AF, 10 pts, 51+/-4 years) or persistent AF (15 pts, 64+/-7 years). The AF pattern (F-F interval) was characterised before each ICV attempt. A first step-up synchronised ICV test (ICV1, biphasic shock waveform 6 ms/6 ms) with increasing energy levels from 0.2 to 20 J was performed by a dual-lead defibrillation system (right atrium-coronary sinus configuration) connected to an external cardioverter defibrillator. After 30 min of stable sinus rhythm, a new sustained AF was induced (>20 min duration) and ICV protocol was repeated (ICV2). The AF cycle length was recorded for 30 s from the lateral wall of right atrium in basal condition and before each cardioversion attempt. RESULTS: The mean values of AF cycle length before a successful shock were similar in both AF populations (paroxysmal AF: pre-ICV1 175+/-21 ms vs pre-ICV2 181+/-20 ms (p=NS); persistent AF pre-ICV1 194+/-25 ms vs pre-ICV2 202+/-15 ms (p=NS)). No significant differences were observed between the two successful ICV tests concerning intensity, energy and impedance levels. The value of ADFT energy was reproducible in paroxysmal AF population (SD differences 1.2, coefficient of variability 9.6%). In persistent AF group only the impedance was reproducible (SD differences 2.6 Omega, coefficient of variability 4.5%), but not the energy requirements (SD differences 9.6, coefficient of variability 44.3%). CONCLUSIONS: ADFT is reproducible in paroxysmal AF patients, while a high coefficient of variability is present in persistent AF, possibly related to different patterns of re-entrant circuits in the reinduced AF. This observation is important in order to evaluate factors influencing ICV-ADFT correctly in AF patients.

Aged↗
PubMed1988

Brain state and plasticity: an integration of the reciprocal interaction model of sleep cycle oscillation with attentional models of hippocampal function.

The present paper relates the reciprocal interaction model for sleep cycle oscillation (McCarley and Hobson, ref. 29) to an attentional model of hippocampal function (Schmajuk and Moore, ref. 44). We consider mechanisms by which the interaction between gigantocellular tegmental field (FTG) cells and locus coeruleus (LC) activity proposed by the sleep cycle model may differentially modulate the information processing carried out in the hippocampus as described by the attentional model. Our fundamental assumption is that learning about the relevancy of different stimuli is proportional to the level of LC activation. If the environment becomes unpredictable during waking, the FTG and LC are activated and the LC facilitates hippocampal learning about stimulus relevancy. In a predictable situation during waking, FTG cells discharge rarely because no novelty is detected, and LC neurons are moderately active. If the predictable situation lasts, LC cells also decrease their activity, and a sleep period might start. At sleep onset, LC inhibition decreases and FTG activity is low leading to slow sleep. As FTG activity increases and LC activity reaches its low point, REM sleep starts. Because LC activity is low during REM sleep, values of stimulus relevancy remain unchanged. Since during sleep the threshold for external stimuli is high, only internally generated novel stimuli (subjectively perceived as dream mentation) may activate the LC. LC renewed inhibitory influence on the FTG ends REM sleep.

Animals↗
PubMed2000

A phase I clinical and pharmacokinetic study of the dolastatin analogue cemadotin administered as a 5-day continuous intravenous infusion.

PURPOSE: The dolastatins are a class of naturally occurring cytotoxic peptides which function by inhibiting microtubule assembly and tubulin polymerization. Cemadotin is a synthetic analogue of dolastatin 15 with potent antiproliferative and preclinical antitumor activity. This report describes a phase I study to evaluate the administration of cemadotin to adult cancer patients by a 5-day continuous intravenous (CIV) infusion. METHODS: All patients had histologically confirmed refractory solid tumors. The dose was escalated from an initial level of 2.5 mg/m2 (0.5 mg/m2 daily) according to a modified Fibonacci algorithm. A minimum of three patients was evaluated at each dose level until the maximum tolerated dose (MTD) was established. Treatment was repeated every 21 days until patients were removed from the study due to toxicity or disease progression. Drug-related toxicities were evaluated and graded by the U.S. National Cancer Institute's Common Toxicity Criteria. A radioimmunoassay (RIA) that detected both the parent drug and its metabolites with an intact N-terminal region of the molecule was used for pharmacokinetic studies. RESULTS: Twenty heavily pretreated patients received a total of 40 courses of cemadotin over five dose levels ranging from 2.5 to 17.5 mg/m2. Reversible dose-related neutropenia was the principal dose-limiting toxicity and 12.5 mg/m2 was established as the MTD. Nonhematologic toxicities attributed to the drug were moderate, and there was no evidence of the cardiovascular toxicity noted in the prior phase I studies of cemadotin given IV as a 5-min injection or 24-h infusion. There were no objective antitumor responses. Time courses of the cemadotin RIA equivalent concentration in whole blood were defined in 14 patients during the first cycle of therapy. The RIA-detectable species exhibited apparent first-order pharmacokinetics across the entire range of doses. The mean +/- SD of the observed steady-state blood concentration at the 12.5 mg/m2 MTD was 282 +/- 7 nM (n = 3). Blood levels decayed monoexponentially following the end of the infusion, with a mean half-life of 13.2 +/- 4.3 h (n = 14) in all patients. Mean values (n = 14) of the total blood clearance and apparent volume of distribution at steady state were 0.52 +/- 0.09 lh/m2 and 9.9 +/- 3.3 l/m2, respectively. CONCLUSIONS: The cardiotoxic effects of cemadotin were completely avoided by administering it as a 120-h CIV infusion. Thus. cardiovascular toxicity appears to be associated with the magnitude of the peak blood levels of the parent drug or its metabolites, whereas myelotoxicity is related to the duration of time that blood levels exceed a threshold concentration. Nevertheless, the data acquired during the extensive clinical experience with cemadotin requires careful examination to assess whether advancing this compound into disease-oriented efficacy studies is merited.

Adult↗
PubMed1992

Exercise training at and above the lactate threshold in previously untrained women.

We examined the effects of training at and above the lactate threshold in previously untrained women. Twenty-four untrained eumenorrheic women (age = 31.3 +/- 4.0 yrs, wt = 66.2 +/- 7.6 kg, ht = 166.4 +/- 5.8 cm) were assessed at baseline [during days 1-3 of the menstrual cycle (MC)] and every 4 MC after that (for 1 year) for VO2 and velocity (V) at LT, fixed blood lactate concentrations (FBLC) of 2.0, 2.5, and 4.0 mM, and Max. Subjects were assigned to control (C, n = 7), at LT/LT, trained 6 days/week at the velocity associated with LT, (n = 9) or above LT (greater than LT, trained 3 days/week at the velocity midway between V LT and V Max and 3 days/week at V LT, n = 8) groups. Exercise prescriptions were adjusted after each assessment and each group progressed similarly in weekly mileage. No between group differences were observed before training. After training the greater than LT group had significantly higher values than the C and /LT groups for LT (p less than 0.05). For FBLC of 2.0, 2.5, and 4.0 mM and Max, the greater than LT group values were greater than the C group (p less than 0.05). No differences were observed after training between the /LT and C groups. Although the greater than LT group had higher VO2 and V Max values than the /LT group after training, these differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Sperm morphologic features as a prognostic factor in in vitro fertilization.

To determine whether there is a prognostic value in the percentage normal sperm morphologic features in a human in vitro fertilization (IVF) program, the authors conducted a prospective study in women with bilateral tubal damage. Based on the percentage of morphologically normal spermatozoa, the patients were divided into four groups: group I, normal morphologic features between 0% and 14%; group II, 15% to 30%; group III, 31% to 45%; and group IV, 46% to 60%. One hundred ninety successful laparoscopic cycles were evaluated. In group I, 104 oocytes were obtained, of which 37% fertilized, but no pregnancy resulted; in group II, 81% of 324 oocytes were fertilized, with a pregnancy rate per embryo transfer (ET) of 22%; in group III, 82% of 309 oocytes were fertilized, with a 31% pregnancy rate; and in group IV, 91% of 69 oocytes were fertilized, with a pregnancy rate of 12%. Probability models indicated that there was a clear threshold in normal sperm morphologic features at 14%, with high fertilization and pregnancy rate in the groups with normal sperm morphologic features greater than 14%.

Embryo Transfer↗
PubMed2000

Solubility of lead, zinc and copper added to mineral soils.

Elevated levels of heavy metals in soils are a result of industrial activities, atmospheric deposition, and the land application of sewage sludges and industrial by-products. Their persistence in the soil environment has created interest in the possible changes in solubility. In this study, total dissolved concentrations of Pb, Zn, and Cu were monitored in seven metal-amended soils (a calcareous and six acid mineral soils). Single metal solutions were added to soils and equilibrated (aged) for 40 days. During the 40 days the soil was allowed to air-dry and was rewetted in cycles of about 5 days. At the end of this reaction period, metal solubility was measured (by atomic absorption spectrometry and direct current plasma spectrometry) at the initial soil pH and at decreased pH values which were induced by addition of small aliquots of acid. As expected, solubility of added Pb, Zn, and Cu increased with a decrease in pH. Furthermore, the results showed that the solubility relationship with pH was similar in all non-calcareous soils. This suggests that metal solubility may be controlled by similar soil components, presumably involving soil characteristics such as pH, organic matter content, and soil mineralogy. For each metal, an approximate pH value was found at which solubility deviated from the solubility of metals when they occur in soils at typical (natural) values. This pH was about (pH+/-0.2): 5.2 for Pb, 6.2 for Zn, and 5.5 for Cu. Thus, pH values below these thresholds may enhance metal mobility, biological availability and toxicity in soils. Metals dissolved at higher pH in the calcareous soil (18.8 g kg(-1) inorganic carbon, initial pH 8.2). In a calcareous soil, a significant fraction of these metals react with carbonates, and decreased pH results in much higher metal dissolution. Yet, metal solubility in soils is not determined by the formation and dissolution of single metal compounds.

Journal Article↗