Brainstem neurons projecting to different levels of the spinal cord of the dogfish Scyliorhinus canicula.

Neurons in the brain that project to different levels of the spinal cord in the dogfish Scyliorhinus canicula have been identified by retrograde labelling with horseradish peroxidase. Injections have been made at four different levels, namely, cervical (segments 3-6), pectoral (segments 16-18), pelvic (segments 34-36) and caudal (segments 60-80). Labelled neurons were located in the diencephalon, mesencephalon and rhombencephalon. Twenty nuclei contained labelled cells following cervical injections. Fourteen of these contained labelled cells following pectoral injections as did nine following pelvic injections and only seven after caudal injections. Of the three diencephalic nuclei projecting to the cord only nucleus thalamus ventralis pars medialis projected further than cervical regions. From the mesencephalon, the tectospinal projection, which arises from tectal and tectotegmental regions, reaches only as far as the cervical cord. The reticulospinal system, arising from cell groups in both the mesencephalon and rhombencephalon, provides the major descending pathway and reaches the most caudal levels. From the octaval region a vestibulospinal pathway arises from nucleus octavus magnocellularis, to reach all levels of the cord, and from nucleus octavus descendens, to project only as far as the pectoral cord. Other rhombencephalic cell groups--the trigeminal nuclei and nuclei B, F and G--project at least as far as the pectoral cord. We conclude that few brainstem nuclei can directly affect the whole spinal cord, whereas many nuclei may have an impact on its most rostral regions; here we have found labelled spinal interneurons with long descending axons that reach the most caudal cord levels.     

Axial tissue diffusion can account for the disparity between current models of hepatic elimination for lipophilic drugs

An assumption of previous models of hepatic elimination is that there is negligible axial diffusion in the liver. We show, by construction of a stochastic model and analysis of published data, that compounds which are readily diffusible and partitioned into hepatocytes may undergo axial tissue diffusion. The compounds most likely to be affected by axial tissue diffusion are the lipophilic drugs for which the cell membranes provide little resistance and which are highly extracted, thereby creating steep concentration gradients along the sinusoid at steady state. This phenomenon greatly modifies the availability of the compound under conditions of altered hepatic blood flow and protein binding. For moderately diffusible compounds, these relationships are similar to those predicted by the simplistic venous-equilibrium model. Hence, the paradoxical ability of the venous-equilibrium model to describe the steady-state kinetics of lipophilic drugs such as lidocaine, meperidine, and propranolol may be finally resolved. The effects of axial tissue diffusion and vascular dispersion on hepatic availability of drugs are compared. Vascular dispersion is of major importance to the availability of poorly diffusible compounds, whereas axial tissue diffusion becomes increasingly dominant for highly diffusive and partitioned substances.This study was supported by the National Health and Medical Research Council of Australia.     

Autoimmune diseases in pregnancy.

Autoimmune diseases are a significant problem in women of reproductive age. This article reviews some of the more common autoimmune disorders and discusses their diagnosis and management during pregnancy. The effects of the autoimmune disorder on pregnancy and the effects of pregnancy on the course of the autoimmune disorder are also discussed with an emphasis on the implications for clinical management.     

Return to training and competition after deep venous calf thrombosis.

A 25-yr-old female triathlete presented with 4 d of increasing left calf pain that started 1 d after an elective termination of pregnancy during the eighth week of gestation. She had been training with running, bicycling, and swimming but did not recall any injury to the calf muscle. Deep venous thrombosis of the calf and popliteal veins was diagnosed, and she was treated with intravenous heparin and oral warfarin anticoagulation. Her major concern was return to training and competition. A protocol was developed based on experience with less active patients and animal studies to allow a progressive return to training activities over 5 wk, followed by running in the sixth week. After release from the hospital, she accelerated the return-to-training protocol and progressed to running within 3 wk. She developed the post-phlebitic syndrome that resolved within 2 yr. The diagnosis and treatment of deep venous thrombosis are reviewed, with specific attention to the needs of athletic patients.     

Maturational changes in retinal excitatory amino acid receptors

The appearance, kinetics and pharmacological properties of receptors for n-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate (KA), L-glutamate (Glu) and L-aspartate (Asp) was investigated using 3H-ligand binding during the development of chick embryo retina. Receptors for AMPA are maximally concentrated at embryonic day 7 (ED 7) and decline 50% in subsequent days; L-Glu receptors are low until ED 11, and the same is true for Asp and NMDA receptors which increase at ED 14 and 18 respectively. All receptors studied underwent an increase in pharmacological specificity, whereas only AMPA-receptors showed an important change in affinity during ontogeny. Results demonstrate that receptors for excitatory amino acids in the retina suffer maturational changes and suggest that while NMDA and aspartate could interact with the same receptor, AMPA and glutamate seem to bind to different sites.     

The radiopacity of ingested medications

We investigated prospectively the radiopacity of 312 pills found on a university hospital formulary by first radiographing them through 15 and 25 cm of water to duplicate the radiodensity of the human body. The pills that were radiodense through water were studied in a human cadaver model, and their densities were quantified by computed tomography (CT). Thirty-five of 312 pills were radiopaque in 15 cm or more of water, and 23 of these pills were radiopaque on a plain radiograph when placed in the stomach of a cadaver. Common mnemonics used to identify radiopaque pills were found to be incomplete and inadequate. Chloral hydrate, iron-containing preparations, calcium carbonate, iodinated compounds, acetazolamide, busulfan, and potassium preparations were consistently radiopaque. Antihistamines, phenothiazines, and tricyclic antidepressants demonstrated varying radiopacity. There was varying radiopacity among the same medications made by different manufacturers. The presence of an enteric coating did not assure that the pill would be radiopaque. Merely radiographing a pill that has been placed on a standard radiograph cassette will make pills that are actually radiolucent in the body appear radiopaque. This test cannot be used to predict radiopacity in vivo. Visibility when radiographed through 15 cm or more of water and a CT radiodensity of more than 1,300 Hounsfield units are predictors of the radiopacity of a pill in the stomach of a cadaver model on a standard KUB radiograph. Variables, such as the size of the patient, the arrangement of pills in the stomach, air contrasting a pill, and the specific composition of the enteric coating or the pillmatrix, affect the radiodensity of pills.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined thoracic aortic dissection and abdominal aortic fusiform aneurysm.

Certain clinical and autopsy findings are described in 13 patients who had both aortic dissection (AD) and fusiform abdominal aortic aneurysm (AAA). All 13 patients had severe and extensive aortic atherosclerosis. The AAA was diagnosed clinically in 9 patients, and 5 had the AAA resected. The AD was diagnosed clinically in 5 patients, and 2 underwent attempted operative repair. Two patients who had the AAA resected because of suspected rupture were found later to have ruptured a more proximal AD. Thus, AD occurs occasionally in patients who have AAA. In older persons with suspected rupture of an AAA, a more proximal rupture of an AD should be ruled out. When both AAA and AD are present in the same patient, the AD is more likely the cause of cardiovascular collapse than is rupture of the AAA.     

Gender differences in the effect of age on adrenergic neurotransmission in the heart.

In male rats, there is an age-associated decline in the capacity of cardiac sympathetic nerves to release norepinephrine. To investigate whether this phenomenon also occurs in female rats, we examined adrenergic neurochemical transmission in the hearts of female and male Fischer 344 rats. Rats aged 6, 12, and 24 months were employed. Hearts with the right cardiac sympathetic nerve intact were isolated and perfused with Krebs-Ringer solution. Stimulations were performed following the administration of cocaine or metanephrine separately and in combination or following the combination of cocaine, metanephrine, and yohimbine. Cocaine (1 microM) was used to block uptake 1, metanephrine (1 x 10(-5) M) to block uptake 2, and yohimbine (3 microM) to block alpha 2 receptor presynaptically. The nerve was stimulated with frequencies of 2, 6, and 12 Hz, and norepinephrine amount in the effluent was determined by high performance liquid chromatography/electrochemical detection methods. Neither norepinephrine release nor the effects of yohimbine, cocaine, or metanephrine were found to be affected in older female rats (24 month). This suggests that age-related changes in adrenergic neurochemical transmission in the heart of female rats differ from those seen in older male rats.     

Patterns of CD16 and CD56 expression in persistent expansions of CD3+NKa+ lymphocytes are predictive for clonal T-cell receptor gene rearrangements

Phenotypic characteristics, and correlations between the expression of membrane NK-associated (NKa) determinants (CD11b, CD16, CD56 and CD57) and T cell receptor (TCR) genotypic patterns, were examined in 25 patients with persistent (greater than 6 months) expansions of CD3+WT31+NKa+ (CD8+ and CD8dim+) lymphocytes. These studies showed that distinct NKa phenotypic profiles were restricted to cases with rearranged TCR configurations and that clonal CD3+NKa+ components could be predicted in most cases by assessing relationships between membrane CD16 and CD56 expression. For all normal NKa subpopulations, there was a high correlation (P less than 0.0001; n = 31) between the expression of these two membrane determinants. Markedly increased CD16 expression by CD3+NKa+ cells, in relation to CD56 (i.e. a high CD16:CD56 ratio), was found exclusively in cases with rearranged TCR (13/16 cases); 2/3 of the remaining cases showing significantly reduced CD16:CD56 ratios and high (greater than 2.0) CD3+CD56+ absolute numbers. In contrast, 7/9 of the germline TCR cases had a normal CD16:CD56 ratio and 2/9 a decreased ratio with low (less than 1.0) CD3+CD56+ absolute numbers. A high ratio of CD16:CD56 expression by CD3+NKa+ lymphocytes was therefore informative for 82% of TCR rearrangements in this series; and analysis of CD16 and CD56 expression was predictive for germline and rearranged TCR configurations in 24/25 persistent CD3+NKa+ expansions.