Pharmacokinetics and pharmacodynamics of two oral forms of cefuroxime axetil

Summary— Cefuroxime axetil is a cefuroxime ester that can be administered by mouth. Two dosage forms (tablets and granules) have been developed for oral administration. We evaluated the pharmacokinetics and pharmacodynamics of these forms in an open cross-over study involving 12 healthy volunteers receiving single doses of 250 mg. The bioavailability of the two forms was different, the observed peak concentration and time-concentration curve values of the tablet form being, respectively, 39 and 27% higher than those of the granule form. However, ex vivo studies of serum bactericidal activity against Streptococcus pneumoniae showed no significant differences between the two formulations. This is in keeping with the fact that the bactericidal activity of samples from only six subjects gave evaluable data for Haemophilus influenzae ; although small differences were found between the two formulations, further investigations are required. The pharmacodynamic approach is becoming an essential element in determining the equivalence of antibiotic dosage forms.     

Practical aspects of managing diabetes in adolescents

In 1988 and 1990 screening for HbA_1c and albumin excretion rate in diabetic children was carried out throughout Denmark. Each study included approximately 1000 diabetic patients. Raised levels of HbA_1c (9.5-10%) were found despite 60% of these young people receivin6g three or more insulin injections daily. The prevalence of persistent microalbuminuria was 4.3%, which was associated only with age and diastolic blood pressure. A recent international survey of HbA _1c and insulin treatment involving 2873 children found an average HbA_1c of 8.6%± 1.7%, which varied significantly ( p < 0. 0001) between centres. Severe hypoglycaemia was related to a young age (0-8 y) and low HbA _1c. There were no significant differences in glycaemic control between adolescents treated with two, three, four or more insulin injections daily. Adolescents on four or more injections received significantly ( p < 0:001) more insulin. Girls receiving four or more injections had a significantly ( p < 0:01) higher body mass index than girls on twice-daily insulin. Preadolescent children on premixed insulin showed similar HbA _1c levels to those on a combination of short- and long-acting insulin, whereas in adolescents, significantly better HbA _1c values were achieved with individual combinations. Despite intensive diabetes management, particularly in adolescence, near normoglycaemia is achieved only in a few individuals.     

Expression of p53 in human leukemia and lymphoma

Analysis of fresh human tumors have indicated that patients with B type lymphoproliferative diseases and the majority of patients with acute lymphoblastic leukemia (ALL) express elevated levels of p53 production. It is suggested that in these human malignancies, p53 may provide a novel tool for monitoring cancer activity. Conversely, p53 is not expressed in acute myeloid leukemias, myeloproliferative diseases, or myeloid leukemic cell lines. Analysis of the p53 gene structure indicated the existence of similar patterns of p53 restriction fragments in producer and nonproducer cells, which suggests that the p53 gene is not altered in the latter. However, in one case of acute promyelocytic leukemia (APL), we have observed a rearrangement in the p53 gene. Karyotype analysis has indicated that these APL cells do not contain the typical 15;17 translocation. In other APL patients who exhibit a 15;17 translocation, we found no genomic changes of the p53, suggesting that the p53 gene, which was recently mapped to the short arm of chromosome 17 in the human, is not structurally related to the typical chromosomal break point found in the long arm of chromosome 17 of APL patients.     

Why women resist screening mammography: patient-related barriers

Mammography utilization remains below the level needed to achieve the National Cancer Institute's year-2000 goals for reducing breast cancer mortality by 50%. Previous research has identified both patient and physician barriers. The authors interviewed 600 randomly selected women who were offered a free mammographic examination. Interviews were conducted by professional interviewers using a brief, structured questionnaire. Data were analyzed with chi 2 Wilcoxon and Kruskal-Wallis rank-sum statistics and discriminant analysis. Noncompliant subjects reported more barriers than compliant subjects. The former were more likely to believe that mammography is unnecessary in the absence of symptoms and that it is inconvenient. In both the bivariate and multivariate analyses, the woman's belief that her doctor believes in regular mammography was an important predictor of compliance.     

The relative numbers of oligodendroglia in different brain regions of normal and postnatally undernourished rats

The relative numbers of oligodendroglia were compared in representative brain regions of 21 day old undernourished and control rats. As a result of postnatal undernutrition which produced half normal body weights and a 10-15 percent reduction in brain weight, the relative numbers of oligodendroglia were slightly increased in photomicrographs of corticospinal tract (a motor tract), medial lemniscus (a sensory tract), red nucleus (a motor nucleus) and somatosensory cortex. Relative numbers were reduced in the corpus callosum, and the thickness of the corpus callosum was significantly reduced. Cell sizes of oligodendroglia were essentially normal throughout the brain, although some reductions of 5 to 6 percent were observed. Areas of brain structures in cross section were essentially unchanged. We have previously hypothesized that nutritionally induced brain hypomyelination results from a reduction in the specific numbers of oligodendroglia and consequently a lasting reduction in the brain myelin concentration. The present results are inconsistent with this hypothesis, as both the density of oligodendroglia and sizes of brain regions are essentially normal. We know from prior work using the same model of nutritional deprivation that myelin synthesis is greatly reduced. Consequently an important depressant effect of undernourishment on oligodendroglia in the developing brain involves either the communication between axons and oligodendroglia leading to myelin induction or the synthetic capacity to make myelin.