Subject(s)
Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Hysterectomy/methods , Lymph Nodes/pathology , Neoplasm Staging , Radiotherapy Dosage , Survival Analysis , Time Factors , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathologyABSTRACT
Urinary pyridinoline and deoxypyridinoline crosslinks (crosslink) are excreted when bone is resorbed. The aims of this study in healthy infants were to determine whether crosslinks a) could predict growth velocity, b) are variable due to circadian rhythm, and c) differ in infants who were either breast-fed or formula-fed. In 78 healthy infants (48 male; 30 female) urine samples were collected and anthropometric measurements were taken at 2, 3, 4, 5, 6, 8, 10 and 12 months of age. In addition, a total of 25 samples were collected during the day (0700-2000) in 5 of the infants to determine circadian rhythm of crosslink excretion. Crosslink excretion decreased (p < 0.001) with age between 2 and 12 months. Pyridinoline excretion showed a significant, but weak correlation (r > or = 0.21; p < 0.05) with linear growth velocity and weight velocity in the subsequent month until 6 months of age, and no correlation thereafter. Infants studied for circadian rhythm showed a 63% greater (p < 0.05) rate of pyridinoline excretion after a nap as compared to the 13-hour mean value. In a subset of infants whose energy intake was exclusively from breast milk (BF, n = 23) or formula (FF, n = 10), crosslink excretion was greater in BF infants at 3 months of age (p < 0.05). The correlations between crosslink excretion and growth parameters indicate that crosslinks may be useful as a marker of growth in infant populations. However sources of variation in crosslink excretion, such as circadian rhythm and diet may limit their utility to predict growth in an individual infant. These factors should be considered in future studies examining markers of bone turnover in infants.
Subject(s)
Pyridinium Compounds/urine , Age Factors , Amino Acids/urine , Animals , Anthropometry , Biomarkers/urine , Birth Weight , Body Height , Breast Feeding , Circadian Rhythm/physiology , Cross-Linking Reagents/metabolism , Female , Food, Formulated , Growth , Humans , Infant , Longitudinal Studies , Male , Pregnancy , Sleep/physiology , Time FactorsABSTRACT
A structured mathematical model describing the dynamics of hybridoma growth and monoclonal antibody (mAb) production in suspension cultures is presented. The model fits well to experimental data obtained from batch, fed-batch, and continuous cultures with hybridoma cells. Applications of the model for process control are demonstrated. 1. An extended Kalman filter (EKF) was designed to estimate the state of the process. The oxygen consumption rate of the cell culture is monitored on-line and is used as the only measurement information for the EKF. This EKF is able to provide good estimates for living and dead cell densities and the medium composition. 2. The mathematical model can be applied for the optimization of fed-batch cultures.
Subject(s)
Antibodies, Monoclonal/biosynthesis , Immunoglobulin G/biosynthesis , Amino Acids, Essential/metabolism , Animals , Cell Survival , Culture Techniques/methods , Glucose/metabolism , Glutamine/metabolism , Hybridomas/cytology , Hybridomas/immunology , Hybridomas/metabolism , Kinetics , Mathematics , Mice , Models, Biological , Oxygen ConsumptionABSTRACT
The infant mortality rate (IMR) in the Jewish and Arab populations in the Western Galilee was studied during the 2-year period 1985-86, and compared with those of previous surveys conducted since 1964-65. The IMR declined steadily during the two decades, from 33.6 to 8.5/1,000 in the Jewish population and from 49.2 to 18.2/1,000 in the Arab population. The decline was noted in both neonatal and postneonatal periods. Analysis of the causes of death showed that enteric and respiratory infections ranked high in the first and second surveys (1964-65 and 1970) and decreased to a low level in both population groups in recent years, but were still relatively high among Arab infants living in villages. The decrease in the IMR seems to be the result of an improvement in the general living conditions of the population and the efficiency of the health services.
Subject(s)
Infant Mortality , Ethnicity , Humans , Infant , Infant, Newborn , Israel , Jews , Rural Population , Urban PopulationABSTRACT
The pharmacodynamic parameters of 1-beta-D-arabinofuranosylcytosine (ara-C) in patient plasma and its active anabolite 1-beta-D-arabinofuranosylcytosine-5-triphosphate (ara-CTP) in circulating and bone marrow blast cells were studied in 20 pediatric patients with acute leukemia. ara-C (3 g/m2) was administered as a short-term infusion over 3 h every 12 h for a total of eight doses. The peak plasma concentration of ara-C ranged from 0.02 to 5.6 microM after the first dose of ara-C. The area under the concentration-time curve (AUC) of ara-C in plasma ranged from 302 to 20,298 microMh after the first dose of ara-C. The half-life of elimination (t1/2,el) of ara-C from plasma was 2.4 +/- 1.5 h in three patients with acute nonlymphoblastic leukemia (ANLL) and 4.78 +/- 4.1 h in 9 patients with acute lymphoblastic leukemia (ALL). The intracellular peak concentration of ara-CTP in circulating blast cells averaged 432.2 +/- 14.5 microM and 544.3 +/- 330 microM in patients with ANLL and ALL, respectively. The elimination kinetics of ara-CTP was monoexponential with t1/2,el of 3.30 +/- 0.8 h and 6.9 +/- 2.8 h in patients with ANLL and ALL. DNA synthetic capacity (DSC) of the blast cells was inhibited to between 24 and 64% of control after the first dose of ara-C and it declined further to between 1 and 32% after four doses of ara-C. The AUC of ara-CTP in leukemic cells ranged from 1,073 to 14,751 microMh and it was not related to the AUC of ara-C in plasma. The pharmacodynamic parameters of ara-CTP in circulating blast cells were more homogeneous in patients with ANLL than in patients with ALL. Four of six patients (67%) with ANLL and six of 14 patients (43%) with ALL achieved either complete remission or partial remission with high dose ara-C. We conclude that treatment of pediatric patients with leukemia in relapse with high dose ara-C is tolerable and moderately successful. Inhibition of DSC is positively correlated with the probability of having zero nadir peripheral blast cells. In turn there is a trend for a zero nadir peripheral blast cell count to be related to achievement of a response to therapy. This latter result is consistent with the results of larger studies in adults with leukemia.
Subject(s)
Cytarabine/pharmacokinetics , Leukemia/drug therapy , Arabinofuranosylcytosine Triphosphate/blood , Child , Cytarabine/administration & dosage , Cytarabine/adverse effects , Half-Life , Humans , Leukemia/blood , Leukemia, Lymphoid/blood , Leukemia, Lymphoid/drug therapy , Neutropenia/chemically inducedSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asparaginase/administration & dosage , Cytarabine/administration & dosage , Leukemia, Lymphoid/drug therapy , Leukemia/drug therapy , Acute Disease , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asparaginase/adverse effects , Bacterial Infections/etiology , Child , Child, Preschool , Cytarabine/adverse effects , Female , Humans , Infant , Leukemia/pathology , Leukemia, Lymphoid/pathology , Male , Neutropenia/chemically induced , Recurrence , Thrombocytopenia/chemically inducedABSTRACT
Five acute schizophrenic patients were given a standard thioridazine dose (4 mg/kg/day po). Their plasma concentrations of thioridazine and its metabolites were determined by GLC, and their ECG's were recorded routinely. In four of the five patients, abnormal ECG's (malformation of the T-wave or lengthening of the repolarization time) were found whenever plasma concentrations of the thioridazine ring sulfoxide were elevated. No relationship could be detected between the appearance of ECG abnormalities and the concentrations of thioridazine and its other metabolites.
