Distribution of nortriptyline in human blood: effects of temperature, pH, and drug concentration

An in vitro study of putative factors causing postvenipuncture redistribution of the tricyclic antidepressant nortriptyline (NT) in blood was carried out in blood samples from a single subject. The influence of varying temperature, pH, and drug concentration on the protein binding of NT was assessed by equilibrium dialysis. The influence of the same variables on the distribution of NT in whole blood was measured by calculating the cell/plasma (C/P) drug concentration ratios after centrifugation of blood samples. Variation in temperature did influence the distribution of NT in blood considerably. From 4 to 37 degrees C, the C/P ratio was found to increase from 1.0 +/- 0.1 to 1.7 +/- 0.2, and protein binding expressed as unbound fraction from 2.9 +/- 0.2 to 7.0 +/- 1.1% (mean +/- SD). Neither pH variations within the 7.0-7.6 range, nor variations in drug concentration, were found to alter NT distribution at 37 degrees C. The observed effect of temperature on NT distribution shows that handling of blood samples from patients taking NT should be standardized in order to avoid errors of interpretation.     

7-Hydroxymethotrexate concentrations in serum and cerebrospinal fluid of children with acute lymphoblastic leukemia

Summary Concentrations of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) were determinded by HPLC in the serum and cerebrospinal fluid (CSF) of 29 children with acute lymphoblastic leukemia. CSF and serum samples were obtained at the end of 104 infusions of MTX given in a dose range of 0.5–8.0 g/m². Concentrations, distribution ratios in serum and CSF for MTX and 7-OH-MTX, and the metabolic index were analyzed with regard to the MTX dose, age and clinical state of the patients. A wide inter-patient (2- to 12-fold) but narrower (1,1- to 3,5-fold) intra-patient variability of the concentrations was observed. A dose-proportional increase in the metabolite concentration was found in serum. On the other hand, the elevation of the level of metabolite in CSF was less than porportional to the dose. The CSF/serum distribution data suggest the existence of a saturable carrier system for MTX and 7-OH-MTX between serum and CSF that has lower affinity for 7-OH-MTX. No correlation was found between concentrations of MTX and 7-OH-MTX in the serum of patients receiving the same dose of MTX. No significant difference was observed in the values for metabolic index between relapsed patients and those who were in continuous complete remission. A significant correlation was found between age and metabolic index: the younger the patient, the higher the metabolite concentration measured in serum.     

Computed tomographic imaging of the airways: relationship to structure and function.

Alterations in the structure of the airways, collectively termed airway remodelling, contribute to airflow obstruction in a variety of chronic lung diseases. While histology has provided valuable insights into the structure of airway wall remodelling, this technique is invasive and does not allow the longitudinal analysis of airway wall dimensions. Technical advances in computed tomography allow the assessment of airway wall dimensions, and are ideally suited for the noninvasive investigation of the pathogenesis of airway wall remodelling and the evaluation of new therapeutic interventions. The aim of this article is to review the use of computed tomography in the investigation of airway structure and function in health and disease.     

Neuronal activity of identified posterior hypothalamic neurons projecting to the brainstem peribrachial area of the cat

Following horseradish peroxidase injections in the brainstem peribrachial (PB) area, massive retrograde labeling was found in the posterior hypothalamic region. Single-unit recordings posterior hypothalamic neurons with antidromically identified projections to the PB area revealed that these neurons have higher firing rates in waking than in slow-wave sleep and dissimilar discharge patterns as compared with intralaminar thalamic neurons. The results are discussed in the context of reciprocal hypothalamo-brainstem circuits.     

Magnetic resonance imaging of hydrostatic pulmonary edema in isolated dog lungs: comparison with computed tomography

Magnetic resonance imaging (MRI) is considered inferior to computed tomography (CT) in the assessment of lung parenchyma, being hampered by low proton density, magnetic susceptibility effects, flow, and cardiac and respiratory motion. In this study the authors assessed the potential usefulness of MRI by comparing it with corresponding CT images of the lung in the absence of motion. They studied eight excised normal canine lung lobes inflated with oxygen before and after induction of pulmonary edema produced by intravascular infusion of saline at 30 cm H2O. T1, T2 and proton density weighted, 5-mm thick, gapped, multislice sequences were performed at 1.5 T. Magnetic resonance images were compared with corresponding 5-mm collimation CT scans at identical levels both before and after the induction of pulmonary edema. The MR and CT scans were assessed independently by two chest radiologists. In normal lung, there was equivalent visualization of vessels down to 1 mm and bronchi to 2 mm in diameter. T1 and proton density scans demonstrated lower spatial resolution but greater contrast than the corresponding CT images. In pulmonary edema both T1 and proton density sequences demonstrated peribronchial edema with greater contrast than CT. Air-space filling was equally well demonstrated by either technique. The authors conclude that, in motionless lung, MRI has lower spatial but greater contrast resolution than CT. It is potentially superior to CT in assessing focal and diffuse lung disease if cardiac and respiratory motion artifacts can be minimized or suppressed.     

Partial meniscectomy via arthroscope in patients over 50 years old

Between July 1983 and July 1986 115 patients, aged 50 years and older, suffering from 122 meniscal tears, were treated by arthroscopic surgery. Of these, 109 patients with 116 meniscectomy could be seen for a follow-up examination 2 years postoperatively. Patients of 50 years and older are known to need a long hospitalisation and a long rehabilitation period after an open meniscectomy. A quarter of all patients had a knee accident in their past as the cause of their complaints. Their main complaints are pain and swelling. As could be expected we found degenerative changes in 78% of the knees. After arthroscopic surgery the hospital stay is short, 75% is back home within 2 days. Half of the patients needed physiotherapy afterwards, 80% of all arthroscopically treated patients were satisfied. The group of patients aged 70 years and older scored worse, 50% of this group was satisfied. Two patients with severe degenerative changes on the X-rays did well. There is a positive correlation between the changes found arthroscopically and the final result.