Beta-2-adrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man

Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS) — an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with ^113mIn. Ten patients with ARDS exhibiting increased PPA indices (>1.0x10^-3/min) were given an intravenous infusion of terbutaline (7 g/kg) over 30 min. Of the four patients in whom the post-drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0x10^-3/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n=5) and non-survivor (n=5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p<0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implication for beta-2-agonists in ARDS.     

Use of refractometry to identify opioid-containing solutions

The purpose of this laboratory study was to assess the value of refractometry in identifying the contents of a variety of opioid-containing solutions. A hand-held refractometer was used to document the refraction produced by the undiluted contents of alfentanil, fentanyl, morphine, sufentanil ampoules and by solutions of Ringer’s lactate, 0.9% saline, 3.3% dextrose in 0.3% saline, and distilled water. Each opioid was then serially diluted in serial 1:2, 1:4, and 1:8 dilutions in each of these solutions and the refractions of each determined. Based on this information, blinded identification of various diluted opioid solutions was attempted. Refractometer values for undiluted fentanyl and sufentanil were identical with those for distilled water. Those for undiluted alfentanil and morphine were almost identical with each other and with 1:2 and 1:4 dilutions of either drug in Ringer’s lactate or 0.9% saline. We conclude that refractometry is an unreliable screening method to detect tampering with opioid solutions.     

Original article: Effects of Raised Extracellular Magnesium on Platelet Reactivity

The inhibitory effects on platelet reactivity of increased extracellular magnesium were investigated. Wherever possible, experiments were performed in hirudinized whole blood. Concentration dependent inhibition of platelet aggregation and dense granule release were observed with MgSO(4). Antiaggregatory effects were identical with MgCl(2), indicating that the effects are due to the Mg(2+) ion. Antiaggregatory effects of CaCl(2), differed from those of MgCl(2), indicating that this is not a non-specific divalent cation effect. MgSO(4) also caused concentration-dependent inhibition of platelet thromboxane production. Experiments in the presence of apyrase and indomethacin showed that complex formation with ADP and inhibition of cyclo-oxygenase do not entirely account for the inhibitory effect of magnesium on platelet activation. Studies with an anti-GPIIb/IIIa antibody showed that the inhibitory effects on the release reaction and thromboxane synthesis are independent of those on aggregation. The results are consistent with magnesium modifying an intracellular signal transduction pathway common to several agonists, rather than the effects of magnesium being specific for one agonist. This study also shows that MgSO(4) inhibits agonist-induced increases in intracellular free calcium. Increasing the extracellular concentration of magnesium up to 10 mM had no effect on agonist-induced increments in intraplatelet free Mg(2+) concentration.     

Practice effects with the NIMH AIDS abbreviated neuropsychological battery.

The degree of practice effects with the Brief NIMH Neuropsychological Battery for HIV Infection and AIDS is reported using a 7-10 day test-retest interval. The patient groups were asymptomatic and symptomatic of HIV while the control group was made up of "at risk" volunteers. Statistically significant practice effects were obtained on the California Verbal Learning Test, the Paced Auditory Serial Addition Task and the Visual Search Test among the infected individuals. The controls subjects demonstrated statistically significant practice effects on all of the neuropsychological tests. The implications of these findings in prospective studies are discussed.     

The early operation for acute severe cholecystitis: the Riedel paper; an introduction and translation

BACKGROUND: For acute cholecystitis in the latter 19th century and early 20th century, the diagnosis was difficult and the management not defined. METHODS AND RESULTS: Bernhard Riedel of Jena in Germany documented his patients, analysed his results, and described his method of cholecystectomy. CONCLUSIONS: Riedel advocated early operation for acute cholecystitis when the conditions were favourable, as for acute appendicitis. He stressed the importance of good lighting, an experienced surgeon and trained assistants. He advocated conservative treatment for minor cholecystitis (biliary colic) until the diagnosis was certain, followed by elective cholecystectomy to reduce the risk of subsequent acute cholecystitis or bile duct stones. Caution was advised when analysing previous statistics, to ensure appropriate patient comparison.     

Depression and somatic diseases. On one retrospective study of 210 patients with major depression hospitalized in a psychiatric hospital

Associations between depression and somatic disorders are common and little studied. We present the results of a retrospective study including 210 psychiatric inpatients, suffering from a major depressive episodes (MDE-DSM III-R criteria). The purpose of this study was: first, to access the prevalence of comorbid MDEs with somatic illness, second to describe the clinical, therapeutic and evolutionary characteristics of MDEs secondary to a physical trouble, comparatively with primary depressions and depressions secondary to another psychiatric disorder. A somatic comorbidity was found in 55% of patients (n = 116), the physical illness being, in 6% of cases, causal regarding MDEs. MDEs with a somatic comorbidity (n = 55) are significantly different from primary MDEs (n = 36) and MDEs secondary to another psychiatric disorder (n = 58), regarding an older age at hospitalization and at first affective episode. Moreover, they are different from MDEs secondary to another psychiatric disorder through fewer past suicide attempts, more episodes with melancholic or psychotic characteristics and a lower frequency of tricyclic antidepressant use. Despite methodologically limited, these results confirm the frequency of physical comorbidity in depressed patients hospitalized in general hospitals, especially in elderly subjects. They also reflect the heterogeneity of the group of secondary depressions, MDEs associated with a somatic illness being closer to MDEs secondary to another psychiatric disorder than to primary MDEs.     

Mouse oligospheres: from pre-progenitors to functional oligodendrocytes

To study the biology and repair capacities of mouse oligodendroglial cells, we established cultures of cells purified from neonatal wild-type and 9.6-kb MBP-LacZ transgenic newborn mice cerebral hemispheres as free-floating aggregates in the continuous presence of neuroblastoma conditioned medium (N1-B104). In vitro analysis indicated that the initial cell preparations were enriched in oligodendrocyte pre-progenitors that expressed PSA-NCAM and GAP-43 but not GD3, O4, NF68 or glial fibrillary acidic protein (GFAP) markers. These pre-progenitors required increased concentrations of insulin and progesterone to allow their survival in vitro. With time in culture, spheres composed of oligodendrocyte pre-progenitors became oligospheres enriched in oligodendrocyte progenitors expressing GAP-43 and GD3. As well as conserving bipotentiality in vitro, these spheres were able to form myelin in vivo after transplantation into the neonatal shiverer mouse brain. Thus, the oligosphere strategy is a powerful method for generating large populations of mouse oligodendrocyte pre-progenitors and progenitors. The ability to generate oligospheres from transgenic mice will be instrumental in the further dissection of the molecular and cellular mechanisms of myelination and remyelination of the central nervous system.