Weaning Index Research Articles

Reproductive and developmental toxicity study of a new antineoplastic agent, S-1 (IV)--Perinatal and postnatal study in rats by oral administration

S-1 is a newly developed antineoplastic agent consisting in a molar ratio of 1:0.4:1 mixture of tegafur (FT), 5-chloro-2, 4, dihydroxypyridine (CDHP) and potassium oxonate (Oxo) was administered orally to SD rats at doses of 0, 1, 4 and 7 mg/kg/day (as a dose of FT) during the perinatal and postnatal periods to examine its effect on dams and postnatal growth of the offspring. A group as the control was treated only with medium (0.5% hydroxypropyl methylcellulose) solution. The administration of 7 mg/kg/day to dams caused suppression in body weight gains and in food consumption during the treatment period. No adverse effects of S-1 on the length of gestation, gestation index, delivery and nursing ability were found. The administration of 4 and 7 mg/kg/day caused suppression in body weight gains in offspring of both sexes. Significant decrease in kidney weights were observed in females of the 4 mg/kg/day group and in both sexes of the 7 mg/kg/day group. No adverse effects of S-1 were found in number of live offspring at birth, sex ratio of live offspring, number of dead offspring at birth, birth index, viability index, weaning index, incidence of external anomalies, general conditions, postnatal development, reflex responses, motor coordination, emotional behavior, learning ability, skeletons, necropsy findings or reproductive functions. No adverse effects of S-1 on F2 offspring were found in any treatment groups. Under the conditions of the present study, the non-observed effect dose levels of S-1 was 4 mg/kg/day for general toxicology of dams, 7 mg/kg/day for reproductive ability of dams, 1 mg/kg/day for postnatal growth in F1 offspring and 7 mg/kg/day for postnatal growth in F2 offspring.

Occlusion Pressure and Its Ratio to Maximum Inspiratory Pressure Are Useful Predictors for Successful Extubation Following T-Piece Weaning Trial

In most weaning studies, failure group patients are reventilated prior to extubation, thus compromising the evaluation of the applied weaning indices' predictive values. This study determines the usefulness of both standard and recent indices in predicting successful extubation following prolonged mechanical ventilation. Following a successful 20-min T-piece trial, ten traditional weaning criteria, as well as airway occlusion pressure (PO.1), maximal inspiratory pressure (MIP), PO.1/MIP ratio, and shallow breathing (F/VT) were determined in unselected patients undergoing prolonged mechanical ventilation. Having satisfied 8 of 10 classic weaning criteria, 67 patients were extubated after an additional 40 min of successful spontaneous T-piece breathing, and included in the study. After extubation, the tracheal tube resistive pressure (RP) values were measured. Twelve (18%) patients failed extubation. The failure group's average age was significantly greater (69.43 vs 48.43 years). The PO.1, PO.1/MIP, and F/VT values of the success (3.62 +/- 1.35 cm H2O, 0.05 +/- 0.04, and 50 +/- 23 b.min-1.L-1) and failure (7.38 +/- 2.67 cm H2O, 0.14 +/- 0.04, and 69 +/- 25 b.min-1.L-1) groups were significantly different (p < 0.005). The diagnostic accuracies of these indices were, respectively, 88%, 98%, and 73%. The spirometric, gas exchange, and tracheal tube RP values of the two groups showed no significant differences. PO.1 and PO.1/MIP ratio provide the best means of predicting extubation success, and they are not influenced by tracheal tube resistance.

Comparison of five clinical weaning indices

Despite extensive data acquired in the area of weaning, clinicians still struggle with the questions of how and when to begin the process. Clinical weaning indices, designed to predict weaning potential, are often difficult to use. They provide an answer at a specific time; extrapolation to the weaning process is rarely possible. No single index has proven to be superior. To test the efficacy of five clinical weaning indices (Burns Weaning Assessment Program; Weaning Index; frequency tidal volume ratio; compliance, resistance, oxygenation and pressure index; and negative inspiratory pressure) at regular intervals during withdrawal of ventilatory support and to determine threshold levels for the program. A prospective convenience sample consisted of 37 adult critical care patients requiring mechanical ventilation for at least 7 days and identified as stable and ready to wean. Data were collected on all weaning indices every other day until the patient was weaned. With the exception of the Burns Weaning Assessment Program, weaning indices did not change significantly from preweaning scores. Furthermore, the results failed to demonstrate that any of the five clinical weaning indices have strong predictive power related to weaning trial outcomes, although all the indices had negative predictive values that may be helpful in predicting unsuccessful weaning trials. The results of this study suggest that the process of weaning may be enhanced by comprehensive, systematic approaches and that clinical weaning indices like the Burns Weaning Assessment Program might best serve as tools to track trends in progress, keep care planning on target, and prevent unsuccessful weaning trials.

Reproductive and developmental toxicity studies of lactitol (NS-4) (2)--Teratogenicity study in rats by oral administration

A teratogenicity study of lactitol, a hepatic encephalopathy drug, was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 7 to day 17 of pregnancy. Twenty-two female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and thirteen pregnant rats per dose level were allowed to deliver naturally for postnatal examination of their offspring. The high dose of lactitol caused diarrhea or soft stool in pregnant rats. The food consumption of female rats decreased in the intermediate and high dose groups. The water consumption of female rats increased in the high dose group. The drug failed to alter the body weight of female rats. The weights of cecum of dams increased in the intermediate and high dose group. The high dose caused enlargement of cecum in dams. The drug failed to alter the numbers of corpora lutea and implantations, fetal mortality, the number of live fetuses, body weight of live fetus, sex ratio, and external, visceral and skeletal development of fetuses. Lactitol did not affect the delivery of dams, the number of live newborns, birth index, external development, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 10 g/kg for reproductive function in mother animals and their offspring.

Reproductive and developmental toxicity studies of paclitaxel. (III)--Intravenous administration to rats during the perinatal and lactation periods

Paclitaxel, an antineoplastic agent, was administered intravenously to pregnant Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.1, 0.3 and 1.0 mg/kg from day 17 of gestation to postpartum day 21. Results were as follows: 1. The vehicle-treated group had no effect in any of the parameters that were measured in this study when compared to the saline-treated group. 2. 1.0 mg/kg paclitaxel caused suppression of the body weight gains associated with the decreased food consumption in F0 dams during the lactation period. 3. Thymic, heart and uterine weights were reduced in 1.0 mg/kg F0 dams at completion of the lactation period. In addition, thymic atrophy was observed for 1.0 mg/kg F0 dams macroscopically. 4. Paclitaxel did not alter the delivery status of F0 dams or birth, viability and weaning indices in F1 pups. 5. The days required for presence of hair, incisor eruption and testicular descent were statistically delayed in 1.0 mg/kg F1 rats. 6. The latency time for olfactory orientation was prolonged in 1.0 mg/kg F1 rats on postnatal day 15. Further, the positive response rates for air righting were reduced in 1.0 mg/kg F1 rats from postnatal day 17 to day 20. 7. 1.0 mg/kg paclitaxel caused suppression of the body weight gains in male F1 rats from postnatal week 1 to week 12. Though body weight gains were decreased in 1.0 mg/kg female F1 rats from postnatal week 1 to week 7, there were no significant differences between dosed animals and saline-treated animals regarding the body weight gains and food consumption during the gestation period. 8. Paclitaxel did not affect the learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 9. The reproductive performance in both male and female F1 rats were not affected by paclitaxel. 10. Splenic weights were reduced in 1.0 mg/kg male and female F1 rats at weaning. Furthermore, liver weights were decreased in 1.0 mg/kg male F1 rats after mating. 11. No influence on prenatal development was observed for F2 fetuses even at the highest dose level of paclitaxel. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 1.0 mg/kg/day and 0.3 mg/kg/day for dams (F0) and their offspring (F1), respectively.

Reproductive and developmental toxicity studies of lactitol (NS-4) (4)--Perinatal and postnatal study in rats by oral administration

A perinatal and postnatal study of lactitol, a hepatic encephalopathy drug was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats per level were allowed to deliver naturally for postnatal examination of their offspring. The high dose caused diarrhea or soft stool in dams. The high dose suppressed the body weight of dams during the perinatal period. The food consumption of dams decreased in the intermediate and high dose groups. The water consumption of dams increased in the high dose group. The high dose caused enlargement of cecum and increase of weights of cecum in dams. The drug failed to affect the delivery of dams and gestation index. However, high dose caused prolongation of gestation period. Two dams in the high dose group failed to nurse their all newborns during early lactation. The drug did not affect the number of live newborns, birth index, external appearance, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that the no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 2.65 g/kg for reproductive function in mother animals, and 10 g/kg for their offspring.

Reproductive and developmental toxicity studies of paclitaxel. (II)--Intravenous administration to rats during the fetal organogenesis

Paclitaxel, an antineoplastic agent, was administered intravenously to pregnant Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.15, 0.3 and 0.6 mg/kg from day 7 to day 17 of gestation. Results were as follows: 1. The ossification of hyoid bodies was retarded in F1 fetuses by the vehicle. However, the vehicle-treated group had no effect in the other parameters that were measured in this study when compared to the saline-treated group. 2. Body weight gains and food consumption in F0 dams were not affected by paclitaxel during the gestation and lactation periods. 3. Paclitaxel failed to affect the organ weights in F0 dams. 4. Paclitaxel did not alter the prenatal development in F1 fetuses. 5. External, internal and skeletal malformations were not induced by paclitaxel. Further, paclitaxel did not affect the skeletal variations and ossification processes. 6. Paclitaxel did not alter the delivery status of F0 dams or viability and weaning indices in F1 pups. 7. The day required for presence of hair was significantly delayed in 0.6 mg/kg F1 pups at paclitaxel. However, the days required for pinnae detachment, incisor eruption, eye opening, testicular descent and vaginal opening were not affected by paclitaxel. 8. No effects on body weight gains or food consumption were observed in both male and female F1 rats. 9. Paclitaxel did not alter the developmental behavior, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 10. The reproductive performance in both male and female F1 rats were not affected by paclitaxel. 11. Paclitaxel did not alter the organ weights in both male and female F1 rats. 12. No influence on prenatal development was observed for F2 fetuses even at the highest dose level of paclitaxel. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 0.6 mg/kg/day and 0.3 mg/kg/day for dams (F0) and their offspring (F1), respectively.

Evaluation of a New Weaning Index Based on Ventilatory Endurance and the Efficiency of Gas Exchange

We hypothesized that the ventilatory capacity needed to wean from mechanical ventilation (mv) depends on two variables: ventilatory endurance and the efficiency of gas exchange. We also hypothesized that these variables could be assessed from data readily available at the bedside, including tidal volume (VT) on mv and during spontaneous breathing (sb), ventilator peak inspiratory pressure (Ppk), and patient negative inspiratory pressure (NIP). Ventilatory endurance was evaluated using a modified pressure-time index: PTI = TI/Ttot x Pbreath/NIP, where Pbreath = Ppk x VTsb/VTmv. Defining VE40 as the minute ventilation needed to bring PaCO2 to 40 mm Hg, the efficiency of gas exchange was evaluated by calculating VE40/VTsb = (VE x PaCO2)mv/VTsb x 40. Because high levels of inspiratory effort might cause patients to reduce VTsb and thereby compromise CO2 elimination, we devised a weaning index (WI) that combines ventilatory endurance and the efficiency of gas exchange: WI = PTI x (VE40/VTsb). The study population comprised 38 patients with chronic obstructive pulmonary disease, adult respiratory distress syndrome, pneumonia, neuromuscular disease, and miscellaneous other conditions. They had been mechanically ventilated more than 3 days and were considered by clinical criteria to be ready for weaning. Of 46 weaning trials, 19 were successful, 2 were partially successful, and 25 failed. PTI and VE40/VTsb were higher in patients who failed (p less than 0.05), but neither variable alone had sufficient sensitivity or specificity to predict the outcome of weaning trials accurately.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic analysis of absolute growth measurements, relative growth rate and restricted selection indices in red Angus cattle.

Performance records on 41,184 Red Angus cattle were analyzed and estimates of parameters calculated for absolute growth rate, relative growth rate and restricted selection indices. Heritability estimates for birth weight, 205-d weight, 365-d weight and postweaning gain were .46 +/- .02, .39 +/- .02, .40 +/- .02 and .36 +/- .02, respectively. Heritability estimates for preweaning, postweaning and postnatal relative growth rates were identical (.33 +/- .02). Heritability estimates for restricted selection indices were .31 +/- .02, .33 +/- .02 and .31 +/- .02 for weaning index, yearling index and postweaning index, respectively. The genetic correlation between preweaning and postweaning absolute growth rate was .15. The genetic correlation between consecutive measurements of relative growth rate (RGR) was -.33. Genetic correlations of birth weight with preweaning RGR and postnatal RGR were -.68 and -.71, respectively. Correlations among measures of relative growth rate using simulated data were similar to correlations of actual data, indicating that these relationships are the result of numerator/denominator relationships and not biological causes. The genetic correlation between weaning and postweaning indices was near zero. Small genetic coefficients of variation for preweaning and postnatal relative growth rates indicate further problems with the expression of growth in this manner. Restricted selection indices exhibited much larger genetic coefficients of variation than measurements of RGR. Genetic standard deviations were 7.8%, 7.2% and 13.7% of the means for weaning, yearling and postweaning indices, respectively.

Multigeneration reproduction and carcinogenicity studies in Sprague-Dawley rats exposed topically to oxidative hair-colouring formulations containing p- phenylenediamine and other aromatic amines

Two-generation reproduction and chronic toxicity-carcinogenicity studies were conducted in Sprague-Dawley rats receiving topical applications of six oxidative hair-colouring formulations. These formulations were prepared as prototypes of permanent hair colourings using the base ingredients and primary intermediates and couplers most often used in this kind of product. Among the dyes included in the various formulations were p-phenylenediamine, p-toluenediamine, p-aminophenol, resorcinol, m-aminophenol, 1-naphthol, 2-amino-4-nitrophenol, 4-chlororesorcinol, p-aminodiphenylamine hydrochloride and N-methyl- p-aminophenol sulphate. The dye solutions were mixed with an equal volume of 6% hydrogen peroxide prior to application. In the reproduction study the samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F 0 parents to the weaning of the F 1a and F 2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated for the six treatment groups and these were compared with the values for the three concurrent control groups. Weanlings selected from the F 1a litters were the subjects for the lifetime carcinogenesis study. For 24 months they received twice-weekly topical applications of the same dyes as were administered to their parents. Clinical chemistry, haematological and urinalysis studies were performed at months 3, 12, 18 and 24, and five animals/sex/group were killed at month 12 and autopsied for histological examination of the rat tissues. All animals in the chronic study were evaluated for incidence of neoplastic and non-neoplastic lesions. In the reproduction phase the application of hair dyes had no adverse effect on the fertility of the males or females, or on gestation, lactation and weaning indices. The average number weaned per litter and the mean body weights of the weanlings were comparable among the treated and control groups. No treatment-related gross lesions were observed in any animals necropsied at month 12 or at study termination, or in any rats that died during the course of the carcinogenicity study. Comparison of the tumour incidences among the six treated and three control groups showed some significant variations among those tumours occurring most frequently in this strain of rats, and pituitary adenomas were also increased significantly ( P < 0.05) in the females of one of the treated groups. The incidence of this tumour is known to be high and variable in untreated female Sprague-Dawley rats. The fact that no pituitary carcinomas occurred in this group suggests that the distribution of these tumours was not related to the experimental treatments. None of the increases of pituitary tumours reported in this study were found to be consistently significant using P < 0.01; the value deemed necessary by statisticians at the National Toxicology Program to avoid false positive results. On the basis of the results of the studies reported here we conclude that the frequent topical application of oxidative hair dyes containing p-phenylenediamine and other commonly used intermediates and couplers has no adverse effects on reproduction and it does not increase the risk of developing cancer.

Mechanical factors in distribution of pulmonary ventilation.

Mechanical factors in distribution of pulmonary ventilation.