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The pharmacokinetics of ceftriaxone was studied in the plasma, urine, and cerebrospinal fluid of seven neonates and seven infants with meningitis. In addition, plasma and urine data were obtained in five neonates and one infant receiving ceftriaxone for other serious infections. All neonates younger than 14 days received daily doses of 50 mg/kg ceftriaxone; all other patients but two received 100 mg/kg. The average weight-corrected values for total body clearance (ClT), volume of distribution (Vdss), and biologic half-life (t 1/2) were 0.37 ml/min/kg, 0.45 L/kg, and 16.2 hours in neonates younger than 1 week; 0.77 ml/min/kg, 0.48 L/kg, and 9.2 hours in neonates older than 1 week; and 1.03 ml/min/kg, 0.39 L/kg, and 7.1 hours in older infants, respectively. There was a significant difference in ClT and t 1/2 between the neonates younger and both neonates older than 1 week, and infants. The Vdss was not significantly different among the three age groups. The average renal clearance in neonates younger than 1 week (0.28 ml/min/kg was 70%, in neonates older than 1 week (0.54 ml/min/kg) was 77%, and in older infants (0.49 ml/min/kg) was 47% of ClT, indicating that nonrenal elimination was less developed in neonates. The quantitation of CSF diffusion of ceftriaxone was assessed by comparison of the areas under the CSF and plasma concentration-time curve. The mean ceftriaxone penetration into the CSF in neonates and infants with bacterial meningitis was 17%. On the other hand, penetration in patients with aseptic meningitis amounted to only 4%. Mean ceftriaxone concentrations in the CSF in patients with bacterial meningitis were 2.8 mg/L after 24 hours, exceeding by many times the minimum inhibitory concentration of the common meningitis pathogens at this time.

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A prospective study of the histology and ultrastructure of liver biopsies and analysis of liver tissue for retinoid was performed in twenty psoriasis patients treated with etretinate for 6 months. Nonspecific ultrastructural changes were noted in several liver specimens. Etretinate was detected in all samples. We find no significant hepatotoxicity after a 6 month course of etretinate. Body fat is probably a more important site than the liver for storage of etretinate.

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An analytical method for the determination of two aromatic retinoids in human plasma (etretinate and its main metabolite) is described, using normal-phase high-performance liquid chromatography. The method is highly sensitive (4 ng/ml) and selective, and allows good separation of isomerization products. Both compounds are well extracted (95%) from plasma in the practically important concentration range (10--1000 ng/ml). After chromatographing the compounds together with an internal standard, they are quantified by spectrophotometry.

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A good tumoricidal activity of vindesine (VDS) has been reported in a variety of animal tumors and in human leukemias and lymphomas. We treated 22 patients who had received no prior chemotherapy and were suffering from a variety of malignant neoplasms with 0.5 mg/m2 to 3.0 mg/m2 VDS i. v. once or three times at weekly intervals and recorded the clinical, hematologic, and especially, neurological side effects. Clinically we observed fatigue in nine patients, paresthesias in seven, myalgias in three, vertigo and diarrhea in two, and skin pains, tinnitus, gastric pains, alopecia, and tremor in one patient each. There was no obvious dose-action relationship. Paravenous injection caused cellulitis similar to that seen with vincristine. No side effects were apparent in liver (SGPT) and renal (creatinine) function tests. Hematologically there was a clear trend toward leukopenia with higher doses of DVA and a mean increase in the thrombocyte count by 51 X 10(3)/mm3 was found (sign test: P greater than 0.05). The hemoglobin level did not change. Clinical neurological examination and monitoring by electroneurography revealed no changes in tensiometer performance, motor and sensory nerve conduction velocity, motor or sensory nerve action potential amplitudes, or H-reflex responses. There was dose-related diminution of the proprioceptive reflexes, especially in the lower extremities. Even with as little as 2.0 mg/m2 VDS i. v. at weekly intervals for 3 weeks Achilles and patellar tendon reflexes were diminished or absent in all patients.

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Previous studies have shown that nerve growth factor (NGF) produces a selective induction of tyrosine hydroxylase (TH) in peripheral adrenergic neurons and that NGF is transported retrogradely with a high selectivity from the adrenergic nerve terminals to the perikaryon. In order to investigate the biological importance of retrograde NGF transport, the following experiments have been performed; (a) effect of NGF on TH activity in superior cervical ganglia (SCG) after unilateral injection into the anterior eye chamber and the submaxillary gland; and (b) effect of systemic injection of NGF on TH activity in SCG after blockage of retrograde axonal transport by axotomy. After unilateral injection of NGF into the anterior eye chamber and submaxillary gland of both 8-10-day-old rats and adult mice, the increase in TH activity in the SCG was considerably larger on the injected than on the non-injected side although the adrenergic neurons supplying the two organs do not account for more than 25% of the total number of adrenergic neurons in the SCG. A direct diffusion mechanism could be excluded by the fact that unilateral local injection of [125 I] produced no significant side difference in the accumulation of radioactivity in the SCG 2 after injection whereas after 14 h there was a several-fold difference between the injected and non-injected side. Moreover, the nodose ganglia which are located very close to the SCG exhibited no statistically significant difference in the accumulation of radioactivity at any time. Forty-eight hours after subcutaneous injections of 10 mg/kg of NGF the increase in TH activity of the SCG amounted to 154% on the intact side and to 92% on the axotomized side. However, these experiments do not permit decisions about the extent the axotomy, as such, impaired the response to NGF. It is concluded that the biological effect of NGF results to a considerable extent, from the moiety which reaches the cell body by retrograde transport from the nerve terminals.

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