Clinical evaluation of cefixime in children

A new beta-lactamase-stable oral cephem antibiotic, cefixime (CFIX), was evaluated for safety, efficacy and pharmacokinetics in children. CFIX was effective in 19 of 20 cases (95%) with bacterial infections. The drug was especially effective against the cases of pneumonia due to beta-lactamase-producing H. influenzae or B. catarrhalis. Pharmacokinetic parameters of CFIX (3 mg/kg) with premeal administration were as follows: Kel 0.328 +/- 0.066 hr-1, T 1/2 2.14 +/- 0.36 hrs, AUC 10.9 +/- 8.7 micrograms X hr/ml, and Vd/F 1.64 +/- 1.42 L/kg. In most of the cases tested, the urinary excretion rate in 12 hours was 5 to 17%. A dose of 3 mg/kg twice daily seems to be adequate for a regular treatment.     

Repetitive firing properties in subpopulations of the chick Edinger Westphal nucleus.

The avian Edinger Westphal nucleus, through the ciliary ganglion, controls accommodation, iris constriction, and blood flow through the choroid. In live brainstem slices, the nucleus is easily identifiable as an olive-shaped cluster of neurons dorsal to the oculomotor nerve and nucleus. Intracellular recordings from neurons in the nucleus identified two classes of responses to sustained (300 to 500 ms) injections of depolarizing current. One set of cells fired action potentials for the duration of the pulse while a second set of cells fired action potentials only transiently, during the first 50 to 100 ms, after which they remained silent regardless of the size of the depolarization. Intracellular recordings followed by injections of the fluorescent dye lucifer yellow revealed that repetitively firing cells were located in the lateral half of the nucleus while non-repetitively or transiently firing cells were located in the medial half. These locations correspond to different Edinger Westphal subdivisions which have distinct inputs and target populations. The varying firing patterns are discussed with reference to the known functions of the subdivisions in which they occur. Replacement of calcium by magnesium in the extracellular medium had no effect on the number of action potentials fired by non-repetitively firing cells, suggesting that a calcium-activated potassium current is not responsible for suppressing repetitive firing in these cells. In contrast, in repetitively firing cells removal of extracellular calcium increased the frequency of action potential discharge and decreased the amplitude of afterhyperpolarizations following single action potentials. Addition of cadmium to the bath medium had similar effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression and growth-promoting effect of adult T-cell leukemia-derived factor. A human thioredoxin homologue in hepatocellular carcinoma.

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin homologue. ADF is detected in many malignant tissues and has a growth-promoting effect on transformed cells. In this study, ADF expression was examined immunohistochemically in human liver cell lines and liver tissues, and its growth-promoting effect was tested on human hepatoma cells. On three liver cell line--PLC/PRF/5, HepG2, and Chang liver cells--ADF stained positively and also was detected by immunoblotting. ADF had strong staining in the fetal liver (n = 8), although it was faint in the normal adult liver (n = 6). In hepatocellular carcinoma (n = 25), ADF expression generally was enhanced and was very strong in 52% (13 of 25) of the cases, although it was moderate in cases of chronic hepatitis or cirrhosis. ADF augmented the growth of PLC/PRF/5 cells and showed an additive effect with epidermal growth factor. These results indicate possible involvement of ADF in cell activation and growth of hepatocytes, as is the case with lymphocytes.     

FIBER TYPE DIFFERENTIATION AND MYOSIN EXPRESSION IN REGENERATING RAT MUSCLES

The relation between fiber type differentiation and the expression of slow and fast myosin isoforms was examined in regenerating rat muscles after injection of a myotoxic agent, bupivacaine. The histochemical myosin ATPase reaction for fiber typing demonstrated that immature type 2C fibers differentiated into type 1, 2A and 2B fibers. Slow and fast myosin isoforms were demonstrated immunohistochemically using antibodies raised against myosins extracted from the slow-twitch soleus and fast-twitch tensor fasciae latae muscles of mature guinea pigs (anti-SOL, anti-TFL). The results showed that immature type 2C fibers destined to differentiate into type 1 fibers first reacted with anti-TFL only, and later reacted with both anti-TFL and anti-SOL, whereas those destined to differentiate into type 2A and 2B fibers reacted with anti-TFL only throughout regeneration. The significance of the myosin isoforms that react with anti-TFL in immature type 2C fibers was discussed. ACTA PATHOL. JPN. 37: 1537-1547, 1987.     

Mediators of induction of augmented expression of plasminogen activator inhibitor type-1 in Hep G2 cells by platelets.

Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. We have shown previously that PAI-1 biosynthesis in cultured cells depends on several factors in serum. Because platelets are richly endowed with specific growth factors and because the release reaction is an integral part of thrombosis, the present study was performed to determine whether platelets augment PAI-1 production and if so, to define mediators responsible. Hep G2 cells were used to determine whether platelet lysates increased PAI-1 synthesis in a dose and time-dependent manner. In cells labeled metabolically with 35S-methionine for 6 h, an increase in labeled PAI-1 was elicited indicative of de novo synthesis as well as increased secretion of PAI-1 mediated by platelet lysates. Steady state levels of both the 3.2 and 2.2 kb forms of PAI-1 mRNA increased after 2 h and peaked in 3-5 h in a dose-dependent fashion as well. Incubation of Hep G2 cells with collagen activated platelets resulted in a similar induction of PAI-1 mRNA. The increase in PAI-1 mRNA occurred with exposure of the cells to platelet lysates for intervals as brief as 15 min and was not inhibited by cycloheximide indicating its independence of new protein synthesis. In order to identify the factors in platelets responsible for the induction of PAI-1 synthesis in the Hep G2 cell model system, neutralizing antibodies were used to inhibit specific platelet associated growth factors. Antibodies to transforming growth factor-beta (TGF-beta) and to the epidermal growth factor (EGF)/transforming growth factor alpha (TGF-alpha) receptor inhibited the platelet lysate-mediated increase in PAI-1 protein by 77%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chromosome analysis of brain tumors in childhood

We performed a chromosome analysis of 26 pediatric brain tumors, including 20 primitive neuroectodermal tumors (PNETs), 5 astrocytomas, and I immature teratoma. Specimens were treated with collagenase, placed in overnight or short-term cultures, and harvested for chromosome analysis. Numerical and/or structural abnormalities were noted in 14 of the 20 PNETs and 4 of the 5 astrocytomas. In 13 PNETs, so-called medulloblastoma in the cerebellum, an i(17q) was the most frequent structural abnormality, accounting for 30% (4/13). Double minute chromosomes (dmin) were observed in one tumor. Near-diploidy was demonstrated in three of these PNETs, hyperdiploidy in three, and near-tetraploidy in three. We could not find any correlation of these cytogenetic findings with the prognosis. In the remaining seven PNETs other than medulloblastoma, the karyotypes of five PNETs demonstrated a variety of numerical and structural abnormalities. As to the astrocytomas, losses of chromosomes 7 and 9 with dmin were observed in two, and structural abnormalities of chromosomes 1 and 17 were also observed in two tumors. In our limited cases, however, we could not find the same chromosome abnormalities that are well known in adult astrocytomas. A congenital immature teratoma showed hyperdiploidy with increased numbers of chromosomes 3, 6, and 12. We conclude that i(17_q) is an important chromosome abnormality in medulloblastomas, and that the oncogenesis of pediatric astrocytomas might be different cytogenetically from that of adult astrocytomas.