Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.      

Therapeutic drug monitoring of gentamicin: a 6‐year follow‐up audit

Background and objective : In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic. In this study we report on a 6‐year follow‐up audit since our first assessment of the service. Method : Records of 733 requests for gentamicin monitoring were reviewed. Results : Of the 592 patients involved, 39% were neonates and 42% were adults. Peak gentamicin concentrations were within the therapeutic range in 65% of the patients at first monitoring and 79% of the corresponding trough concentrations were within the non‐toxic range. After dosage adjustment, 81% of the peak concentrations were within the therapeutic range and trough concentrations rose to levels regarded as toxic in 7% of patients. In patients with therapeutic peak concentrations at the first monitoring point, the average duration of gentamicin therapy was statistically shorter than in those patients who failed to achieve a therapeutic peak concentration. The distribution of gentamicin peak and trough concentrations in terms of therapeutic ranges were also better than those found in 1990. Conclusion : TDM for gentamicin is well accepted in HUSM and its application has contributed to improved gentamicin administration. Furthermore, our physicians are now able to choose more appropriate dosage regimens for their patients because the majority of gentamicin concentrations attained even at the first monitoring were within the therapeutic range.