Cell cycle kinetics in hematologic diseases

The cell cycle kinetics in peripheral blood lymphocytes from 30 patients with hematologic diseases, including non-Hodgkin lymphomas [10], acute nonlymphoblastic leukemias [10], and myelodysplastic syndromes [10] were studied. Thirty normal healthy subjects formed the control group. Non-Hodgkin lymphoma patients showed an elongation of the cell cycle time (43% of metaphases in the first cycle), whereas leukemic patients presented a shortening of the cell cycle progression with 46% of cells in the third division. Myelodysplastic syndromes showed most of the metaphases (55%) in the second cycle.     

Experimental Studies on Reproduction with the Lipid-Regulating Agent Gemfibrozil

Experimental Studies on Reproduction with the Lipid-RegulatingAgent Gemfibrozil. FITZGERALD, J. E., PETRERE, J. A., AND DELA IGLESIA, F. A. (1987). Fundam. Appl. Toxicol. 8, 454–464.Gemfibrozil, a new lipid-regulating agent, was evaluated inrats and rabbits for effects on various phases of the reproductionprocess. In teratology studies groups of pregnant rats and rabbitsreceived gemfibrozil at doses up to 200 mg/kg during organogenesis(rat, Days 6–15; rabbit, days 6–18). For peri- andpostnatal studies, groups of pregnant rats were given 92 or3 31 mg/kg from Day 15 of gestation through weaning. In fertilitystudies groups of sexually mature male rats were given 93 or326 mg/kg of gemfibrozil for 61 days and females were given94 or 318 mg/kg for 15 days prior to mating within treatmentgroups. Drug administration continued in females through gestationand weaning of the F₁ offspring. In subsequent fertility experiments,treated male rats were mated with untreated females and treatedfemales were cohabitated with untreated males. Gemfibrozil didnot elicit a teratogenic response in either rats or rabbitsup to doses that resulted in maternal toxicity. Reduced pupweights during the neonatal and weaning periods in the femalefertility study as well as in the perinatal–postnatalstudy were the only apparent drug effect. Treatment of femalerats prior to mating had no significant effects on general reproductiveparameters. Male rats given doses of about 300 mg/kg/day showedinconsistent and equivocal lower rates of fertility relativeto the concurrent controls. No adverse effects were seen inthe reproductive performance of offspring of gemfibrozil-treatedmale rats.     

Acute effects of lamotrigine (BW430C) in persons with epilepsy

Sixteen epileptic patients took single doses of lamotrigine, 120 mg or 240 mg. Six photosensitive patients showed reduction (with abolition in two) in photosensitivity after lamotrigine administration. Five subjects with frequent interictal spikes showed reduction in spike frequency over 24 h after lamotrigine administration. The half-life (t1/2) of lamotrigine in subjects taking sodium valproate was prolonged, whereas the t1/2 in subjects taking carbamazepine and/or phenytoin was reduced. The area under the curve of co-medication plasma levels was not affected by a single dose of lamotrigine. Five patients reported mild and generally transitory side effects; some of which represented exacerbation of preexisting complaints.     

Chequerboard titrations: the influence of the composition of serial dilutions of antibiotics on the fractional inhibitory concentration index and fractional bactericidal concentration index

Chequerboard titrations carried out with modified serial dilutions of antibiotics such that consecutive concentrations in these series were four times smaller than those in two-fold serial dilutions enable MICs and MBCs to be determined with greater accuracy. Interaction indices calculated by this method can differ markedly from those calculated on the basis of two-fold serial dilutions. The differences calculated in this study ranged from -0.30 to +1.06.     

Treatment of febrile episodes in neutropenic children by ceftazidime combined with netilmicin. Results of a multicenter study apropos of 88 cases

Infection is the most important cause of mortality in leucopenic patients. A broad spectrum antibiotic therapy is imperative in febrile and neutropenic patients. In a multicentric study we have used ceftazidime (100 mg/kg/d) and netilmicin (6 mg/kg/d) in 88 children (fever greater than or equal to 38.5 degrees C, neutropenia less than 500/mm3) treated for acute leukemias (59), non Hodgkin lymphomas (13) or solid tumors (16). Median age was 7 years (2 months-16 years). In patients who continued to remain febrile, vancomycin (40 mg/kg/d) was added after 48 hours. The effective treatment was continued until a neutrophil count greater than 1,000/mm3. The first combination (ceftazidime + netilmicin) was effective in 64 children (73%) and the second combination (ceftazidime + netilmicin + vancomycin) in 11 patients. Bacteria were isolated in 39 children: Escherichia coli: 9, Staphylococcus epidermidis: 9, Staphylococcus aureus: 8, Streptococcus: 6, Pseudomonas aeruginosa: 3, Streptococcus pneumoniae: 1, Haemophilus: 1, Klebsiella pneumoniae: 1, Proteus: 1, Serratia: 1, Flavobacterium: 1. In these 39 patients, 30 became apyretic with ceftazidime and netilmicin and 6 after vancomycin. All blood culture were negative after the first combination. The median duration of antibiotic therapy was 14 days (5-9 days: 28, 10-20 days: 43, greater than 20 days: 17). There were no death, no superinfection. Tolerance was good without kidney or liver or biological perturbation. We conclude that the combination ceftazidime and netilmicin is effective in neutropenic children.     

A possible pain control system in a non-mammalian vertebrate (a lizard, Gekko gecko)

In a lizard (Gekko gecko) the anterograde tracer PHA-L was microiontophoretically applied to the predominantly serotonergic nucleus raphes inferior. Extensive spinal projections from the rostral magnocellular part of this nucleus were demonstrated to the superficial layers of the dorsal horn and to the intermediate zone, more sparsely to the ventral horn. But, in addition, retrogradely labeled neurons were found in and just below a periventricular cell group in tegmentum mesencephali, i.e. the laminar nucleus of the torus semicircularis, a cell group which receives spinal afferents and projects to the spinal cord as the mammalian periaqueductal gray. These data suggest the presence of a three-tiered pain control system in a lizard composed of projections from the laminar nucleus of the torus semicircularis to the rostral part of the inferior raphe nucleus which in its turn projects to the superficial layers of the dorsal horn of the spinal cord.     

ELISA tests for dapsone and pyrimethamine and their application in a malaria chemoprophylaxis programme

Enzyme-linked immunosorbent asays (ELISAs) are described for determining levels of dapsone and pyrimethamine in urine. Both assays have a sensitivity of about 20 μg/l and are reproducible, but each produces some false positives. The problem of false positive reactions was partially obviated by requiring positive results in both assays. In a pilot study involving 50 children aged 3 months to 4 years who were given a single dose of Maloprim (pyrimethamine + dapsone), 75% were positive for dapsone 7 days after administration of the drug, while 25% were still positive 15 days after its administration. The corresponding proportions for pyrimethamine were 73% and 30%, respectively. Comparison of the results obtained in a larger chemoprophylaxis trial with those from the pilot study indicated that the assays described could be used to investigate whether antimalarials had been taken.