Circadian rhythm in patients with hydranencephaly.

Circadian rhythm and sleep were studied in three hydranencephalic infants who were diagnosed on the basis of computed tomographic and/or magnetic resonance imaging scans and electrophysiologic findings. In all three cases, although the active sleep cycle was preserved, quiet sleep decreased and indeterminate sleep increased. The sleep-circadian rhythm was disturbed in all three cases. The hormone secretion rhythm was studied in two cases (cases 1 and 3). In both cases, cortisol secretion showed two or three peaks during the day. In one case (case 3), growth hormone secretion did not show sleep enhancement. Prolactin secretion showed an increase during sleep in both cases. The circadian rhythm of body temperature appeared at 6 months of age and disappeared after 1 year of age in case 1. Case 2 did not show a circadian rhythm of body temperature, but case 3 did at 2 years 6 months of age. However, it was thought that the circadian rhythm of body temperature in case 3 was a false one due to severe opisthotonus. Thus, it is suggested that the development of the circadian rhythm may require the rostral brain structure more than the midbrain and that there may be multiple oscillators in humans.     

Multiple hepatosplenic abscesses: successful treatment by continuous intraportal administration of amphotericin B in a case with acute promyelocytic leukemia]

A 40-year-old female was admitted in August 1989 with a diagnosis of acute promyelocytic leukemia (AML; M3). One course of modified-DCMP regimen induced complete remission in September, but she developed spiking fever at a nadir period of WBC after induction chemotherapy. CT revealed multiple hepato-splenic abscesses presumably due to candida infection. She was treated with intravenous administration of amphotericin B (AMPH-B) and other antifungal agents. Despite the hematological remission and prolonged use of these antifungal agents, high fever persisted. A catheter was inserted into the portal vein under ultrasonic-guidance. AMPH-B was administered through the catheter: the initial dose was 3 mg/day and was soon increased to 20 mg/day. Her fever subsided in 1 week, and the sizes of liver abscesses on CT reduced markedly. Chill and hypokalemia were observed during this therapy. The catheter was removed from the portal vein after 29 days. Partial portal vein thrombosis was noted around the catheter tip. This case suggests the usefulness of intraportal administration of AMPH-B in patients with hematological malignancy developing multiple liver abscesses.     

Inhibitory anti-tumor effects of interleukin-4 on Philadelphia chromosome-positive acute lymphocytic leukemia and other hematopoietic malignancies.

IL-4 has been shown to possess a broader spectrum of biological activities. Recently, anti-tumor activities of IL-4 on malignant tumors including hematopoietic tumors has been revealed in vitro or in vivo. We investigated the effect of recombinant human (rhIL-4) on the in vitro growth of human leukemia cells and demonstrated the inhibitory anti-tumor activity of rhIL-4 on Ph1-positive ALL cells in association with the decreased activity of cellular tyrosine kinase. This finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibility for patients with Ph1-positive ALL. In this paper, we presented the IL-4-dependent inhibition of Ph1-positive ALL cells and reviewed implications for mechanism of IL-4-dependent inhibition and anti-tumor activities of IL-4.     

Bovine serum albumin (BSA) nephritis in rats. IV. A sequential evaluation of mononuclear phagocyte system (MPS) function

A clearance kinetic study of intravenously administered 125I-labeled aggregated human IgG (125I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected 125I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was less than 0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of 125I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Antimicrobial-induced release of endotoxin from Pseudomonas aeruginosa: comparison of in vitro and animal models

This study was designed to compare the amount of lipopolysaccharide (LPS) induced following exposure to doripenem, imipenem/cilastatin, meropenem and ceftazidime in an in vitro computerized-simulation system (simulating the drug concentration pattern in human plasma after administration of a drug), with that induced by exposure to a drug at a constant concentration. When Pseudomonas aeruginosa was exposed to the test drugs at constant concentrations of 0.1 x, 1 x and 10 x MIC, differential relative induction of LPS was observed as follows: ceftazidime > meropenem, doripenem > imipenem/cilastatin. In the computerized-simulation system, however, the amount of LPS induced by treatment with ceftazidime (1 g) was similar to that by doripenem (250 mg), imipenem/cilastatin (500 mg) and meropenem (500 mg). In a rat model of P. aeruginosa bacteraemia, rates of eradication of bacteria from the blood were similar for carbapenems and ceftazidime except for 1 h post-administration of ceftazidime. Serum LPS levels induced by treatment with doripenem (30 mg/kg), imipenem/cilastatin (30 mg/kg), meropenem/cilastatin (30 mg/kg) and ceftazidime (50 mg/kg) were almost the same at 3 h after administration of each drug. Data obtained from computerized-simulation systems might be more applicable than those obtained from organisms exposed to constant drug concentrations for estimating the amount of LPS in the plasma of human patients infected with Gram-negative bacteria.     

Strut protrusion and shape impact on endothelial shear stress: insights from pre-clinical study comparing Mirage and Absorb bioresorbable scaffolds

Protrusion of scaffold struts is related with local coronary flow dynamics that can promote scaffold restenosis and thrombosis. That fact has prompted us to investigate in vivo the protrusion status of different types of scaffolds and their relationship with endothelial shear stress (ESS) distributions. Six Absorb everolimus-eluting Bioresorbable Vascular Scaffolds (Absorb, Abbott Vascular) and 11 Mirage sirolimus-eluting Bioresorbable Microfiber Scaffolds (Mirage, Manli Cardiology) were implanted in coronaries of eight mini pigs. Optical coherence tomography (OCT) was performed post-scaffold implantation and obtained images were fused with angiographic data to reconstruct the three dimensional coronary anatomy. Blood flow simulation was performed and ESS distribution was estimated for each scaffold. Protrusion distance was estimated using a dedicated software. Correlation between OCT-derived protrusion and ESS distribution was assessed for both scaffold groups. A significant difference was observed in the protrusion distances (156?±?137 µm for Absorb, 139?±?153 µm for Mirage; p?=?0.035), whereas difference remained after adjusting the protrusion distances according to the luminal areas. Strut protrusion of Absorb is inversely correlated with ESS (r?=??0.369, p?<?0.0001), whereas in Mirage protrusion was positively correlated with EES (r?=?0.192, p?<?0.0001). Protrusion distance was higher in Absorb than in Mirage. The protrusion of the thick quadratic struts of Absorb has a tendency to lower shear stress in the close vicinity of struts. However, circular shape of the less thick struts of Mirage didn’t show this trend in creating zone of recirculation around the struts. Strut geometry has different effect on the relationship between protrusion and shear stress in Absorb and Mirage scaffolds.     

Effect of a platelet activating factor antagonist and antithrombin III on septicemia and endotoxemia in rats

Disseminated intravascular coagulation (DIC) or renal damage associated with septicemia was induced in rats by ligating the cecum or by injecting endotoxin. In the septicemia model, the number of E. coli and Bacteroides spp in the blood increased concomitantly with an increase of endotoxin. In this model the development of hypercoagulability with mild fibrinolysis was observed. Histopathologic findings in the kidneys, including the formation of microthrombi in the glomeruli and the vacuolization and dilatation of renal tubular cells, suggest the development of mild DIC. In the endotoxin-induced DIC model, both remarkable state of hypercoagulability and fibrinolysis were observed with fibrin thrombi in glomeruli. The administration of the platelet-activating factor antagonist, CV-6209, or of human antithrombin III, ameliorated DIC significantly by limiting the increases in prothrombin time, activated partial thromboplastin time and fibrin degradation products. These agents significantly reduced the deposition of fibrin in the glomeruli and significantly prolonged the survival time of the endotoxin injected rats. These observations suggest that the PAF antagonist CV-6209 and ATIII merit clinical evaluation in the management of DIC caused by septisemia.