Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

AIMS: Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. METHODS: Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. RESULTS: During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. CONCLUSIONS: Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.     

Insulin inhibition of endothelial prostacyclin production

Graft thrombosis is a common cause of early graft failure in pancreatic transplantation, even in the absence of rejection. Altered endothelial cell (EC) production of thromboactive substances may play a primary role in this and other settings of thrombosis where intraluminal insulin concentrations are high. We therefore investigated the effect of insulin on EC production of prostacyclin (PGI2), a potent endogenous antagonist of platelet aggregation and vasodilator. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated for 15 min in Hanks'/Hepes buffer containing 0, 50, 250, or 500 microU/ml of human insulin or 0, 500, 1000, or 2000 microU/ml of porcine insulin. PGI2 production was assessed by exposing the monolayers to either 20 microM arachidonic acid (stimulated) or arachidonic acid vehicle (basal) for an additional 15 min. Test buffers were then assayed by RIA for 6-keto-PGF1 alpha, the stable metabolite of PGI2. The results of these experiments indicate that human insulin inhibits both basal and arachidonic acid-stimulated production of PGI2 from HUVEC in a dose-dependent manner. Inhibition of stimulated production was significant at concentrations of 250-500 microU/ml. Porcine insulin also inhibited arachidonic acid-stimulated production of PGI2 from HUVEC in a dose-dependent manner. However, HUVEC were less sensitive to porcine insulin than to human insulin and a concentration of 2000 microU/ml was required for significant inhibition. We therefore conclude that insulin, in locally high concentrations, inhibits endothelial PGI2 production in vitro. The ability of insulin to alter the production of thromboresistant substances from endothelium may facilitate thrombosis in circumstances where counterregulatory mechanisms are disturbed by injury or transplantation.     

Major fragment of soluble peptidoglycan released from growing Bordetella pertussis is tracheal cytotoxin.

Bordetella pertussis is known to release a factor which promotes the loss of ciliated respiratory epithelium and copurifies with a soluble peptidoglycan (PG) fragment termed tracheal cytotoxin (TCT). The objective of this study was to determine whether pertussis organisms turn over and release PG derivatives in addition to TCT. B. pertussis Tohama (phase III) was grown in liquid Stainer-Scholte medium containing [3H]diaminopimelic acid (DAP) to label PG specifically, washed to remove free label, and suspended in fresh medium without [3H]DAP. Molecular sieve chromatography of supernatants obtained from such cultures revealed a single included peak of 3H, the elution volume of which corresponded roughly to a disaccharide peptide monomer standard (ca. 10(3) daltons). This material (i) contained [3H]DAP in acid-hydrolyzable linkage, (ii) comigrated with 1,6-anhydro-N-acetylmuramic acid-containing disaccharide peptides on paper chromatography, (iii) was resistant to degradation by mild alkali, and (iv) was indistinguishable from authentic TCT by high-voltage paper electrophoresis and two reversed-phase high-performance liquid chromatography systems. Together, the data suggest that B. pertussis releases a markedly homogeneous set of PG fragments, consisting principally of TCT, and that TCT is possibly a nonreducing, anhydromuramic acid-containing fragment or a cyclic PG derivative.     

In vitro effects of Nd:YAG laser radiation on blood: A quantitative and morphologic analysis

Use of the Neodymium: yttrium -aluminum -garnet (Nd:YAG) laser to recanalize stenosed arteries may require delivery of the beam through blood. To assess the degree of hemolysis and debris formation, 54 samples of citrated whole blood were exposed to Nd:YAG laser radiation of varying powers (10, 20 and 30 watts) and duration (1, 2.5 and 5 seconds). Compared to control samples which were not subjected to laser light, there was no significant decrease in hematocrit (41 to 40.5 +/- 5%), hemoglobin concentration (13.8 to 13.8 +/- .06 g/1OO ml), or increase in "free" hemoglobin concentration. Debris weight (from .45 +/- .002 to .45 +/- .002 mg), as well as the white blood cell count, was also not significantly changed (from 5,400 to 5,200 +/- 240 WBC/cm). Light microscopy examination of debris from samples of whole blood, washed erythrocytes, and platelet-rich plasma subjected to the laser at 30 watts for five seconds failed to demonstrate the presence of membrane denaturation of blood elements, as compared with the morphologic changes observed in whole blood samples exposed to a "hot tip" rather than Nd:YAG laser radiation. Nd:YAG laser can be used intravascularly without fear of hemolysis or debris "micro-embolization" up to a power of 30 watts for five seconds.     

Epidemiological findings of seasonal changes in mood and behavior. A telephone survey of Montgomery County, Maryland

Patterns of seasonal changes in mood and behavior in Montgomery County, Maryland, were evaluated in randomly selected household samples by lay interviewers using a telephone version of the Seasonal Pattern Assessment Questionnaire. The method for selecting the sample unit was random-digit dialing. We found that 92% of the survey subjects noticed seasonal changes of mood and behavior to varying degrees. For 27% of the sample seasonal changes were a problem and 4.3% to 10% of subjects, depending on the case-finding definition, rated a degree of seasonal impairment equivalent to that of patients with seasonal affective disorder. The seasonal pattern of "feeling worst" exhibited a bimodal distribution with a greater winter and a substantially lower summer peak (ratio, 4.5:1). Younger women who have a problem with seasonal changes and who feel worse on short days tended to exhibit the highest seasonality scores. It is apparent from our study that seasonal affective disorder represents the extreme end of the spectrum of seasonality that affects a large percentage of the general population. The influence of environmental factors on mood disorders and mood changes in the general population might provide valuable insight into pathogenesis, treatment, and prevention of affective illness.     

Massive pulmonary embolism: triple-armed therapy

Many patients who suffer a massive pulmonary embolus die despite emergent therapy. In these desperately ill patients an aggressive, combined method of management was initiated to improve their chances and quality of survival. During a 5-year period 10 patients were treated with (1) low-dose topical, intrapulmonary thrombolytic therapy to dissolve thrombus, (streptokinase or urokinase); (2) anticoagulation to prevent thrombus propagation (heparin); and (3) the simultaneous insertion of a Greenfield filter to prevent the early, recurrent, and therefore potentially fatal pulmonary embolus--"triple-armed therapy." Thrombolytic therapy was administered through a Swan-Ganz catheter wedged against the pulmonary embolus. During the same interval 10 other patients also sustained massive pulmonary emboli but were treated only with systemic heparin. Serial pulmonary arteriography was performed daily. The patients treated by triple-armed therapy responded favorably with a rapid (less than 6 hours), significant improvement in PaO2, pulmonary artery pressure, cardiac output, pulmonary vascular resistance, and blood pressure, compared with patients treated with continuous heparin alone. Nine patients in the triple-armed therapy group survived whereas only six in the heparin group survived. Two additional patients were treated by triple-armed therapy and had thrombolysis with triple-armed therapy with tissue plasminogen activator; these patients demonstrated the most rapid improvement in cardiorespiratory dynamics and arteriographic clearance of emboli. This management protocol shows promise for patients who sustain a massive pulmonary embolus, because it reduces the morbidity associated with pulmonary embolectomy while avoiding the hazards associated with systemic thrombolytic therapy.