Efficacy of phototherapy in non-haemolytic hyperbilirubinaemia

Clinical experience of phototherapy for non-haemolytic hyperbilirubinaemia in 3999 infants in Kandang Kerbau Hospital, Singapore, is documented. Phototherapy was most effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1500 g) and least effective in full term infants with very low birth weight (gestation greater than or equal to 37 weeks, birth weight less than or equal to 1500 g) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2270 g). Overall, phototherapy was effective in almost all the infants, with a failure rate of only 2.00/1000 infants. No characteristic features common to all the failures could be detected. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1000), with the response to the second exposure comparable to that to the first. No infant required a third exposure. All the infants tolerated phototherapy well, none developing any illness that could be attributed to the treatment. This clinical experience shows that phototherapy for the treatment of nonhaemolytic hyperbilirubinaemia is effective and safe.     

Proximal gastric vagotomy. The preferred operation for perforations in acute duodenal ulcer.

Simple closure, the conventional operation for perforated acute duodenal ulcers, is associated with symptomatic relapse in a large proportion of patients. In order to assess the role of immediate definitive surgery, 78 fit patients with perforated acute ulcers were prospectively randomized to undergo either closure alone or proximal gastric vagotomy with closure (PGV). Patients taking potentially ulcerogenic drugs or who had severe stress were excluded from the study. Both groups were comparable with respect to age, sex, general medical health, duration of perforation, length of ulcer history, and presence of duodenal scarring. There was no hospital mortality. Minor complications occurred in 7.3% after closure and 10.8% after PGV. At 3 years follow-up, the cumulative recurrence rates were 36.6% and 10.6% after closure and PGV, respectively (p = 0.001). Eighty-five per cent of recurrences after closure were symptomatic, and half of them required reoperation. Duodenal scarring itself did not appear to influence the outcome after closure. PGV was not associated with dumping, diarrhea or other unwanted side effects. Although less than that in chronic ulcers, there is a substantial risk of symptomatic relapse after closure of perforated acute duodenal ulcers. With judicious patient selection, PGV effectively reduces this risk without incurring disabling side effects associated with other ulcer operations.     

Interleukin-4 is a neutrophil activator

We investigated the ability of the lymphokine, interleukin-4 (IL-4), to function as a neutrophil (PMN) activator. IL-4 enhanced PMN-mediated killing of opsonized bacteria (by up to 91.6% at 3 units of IL-4; p less than 0.05). IL-4 was a weak secondary granule secretagogue and did not by itself generate a respiratory burst. However, IL-4 did increase in a dose-dependent fashion the respiratory burst mediated by the peptide formyl-methionyl-leucyl-phenylalanine (10(-7) mol/L). Maximal potentiation of PMN activity occurred at 100 units of IL-4 (6.3 nmol superoxide produced without IL-4 to 9.8 nmol at 100 units; p less than 0.01). Enhancement of the respiratory burst was not a generalized phenomenon, since IL-4 did not potentiate the respiratory burst mediated by either phorbol myristate acetate, calcium ionophore A23187, or zymosan-treated serum. Similarly, IL-4 potentiated the formyl-methionyl-leucyl-phenylalanine-stimulated secretion of both lysozyme (40.2%) and beta-glucuronidase (108.2%). Finally, IL-4 was demonstrated to enhance the ability of PMN to phagocytose sheep erythrocytes opsonized with rabbit IgG (by up to 94.2% at 30 units of IL-4). This increased phagocytosis correlated with the recruitment of a population of PMNs that did not phagocytose targets in the absence of IL-4. In conclusion, IL-4 enhanced neutrophil-mediated bactericidal activity. This increase may have occurred secondary to the stimulation of phagocytosis by IL-4 or by potentiation of degranulation and the respiratory burst.     

Wall effects in sucrose density gradient centrifugation of viruses

Summary The depletion of sedimenting particles to be expected from wall effects in the course of sucrose gradient centrifugation, was computed for various types of swing-out rotors on the assumption that particles hitting the tube wall are lost from the gradient.This assumption was roughly verified for heat-denatured, but not for native poliovirus. Tween 20 reduced the depletion, and prevented tight sticking of heat-denatured virus particles to tube walls.     

A simple quantitative protein A micro-immunoprecipitation method; assay of antibodies to the N and H antigens of poliovirus

Staphylococcus aureus (Cowan strain I) was used to absorb immune complexes from antiserum to poliovirus to which labeled N or H poliovirus antigens had been added, and the radioactivity in the pelleted organisms and in the supernatant was measured. Excellent agreement was obtained between values calculated separately from the pellet and supernatant readings, validating the use of supernatant measurements from a microtitration plate method.     

Antithrombin III in systemic lupus erythematosus

Plasma antithrombin III (AT III) was studied in 39 patients with systemic lupus erythematosus (SLE) and in 12 patients with other connective tissue disorders. AT III was measured immunologically by the Mancini method as well as by functional assay using thrombin and the chromogenic substrate, chromozyn TH (Boehringer). Reduced AT III activity was found in 17 patients; 8 had thrombosis. In 6 patients low AT III correlated with disease exacerbations and 2 had systemic vasculitis. No significant correlation could be demonstrated between low AT III levels and thromboembolic disease. A marked variation of functional AT III activity was observed in 30 patients in whom the presence of the lupus anticoagulant was demonstrated. The significance of this association is discussed.     

Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical obesity in mice

Objective

Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy homeostasis. Single NPY or dynorphin deletion reduces food intake or increases fat loss. Future developments of obesity therapeutics involve targeting multiple pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis independently, thus double NPY and dynorphin ablation would result in greater weight and/or fat loss than the absence of NPY or dynorphin alone.

Design and methods

We generated single and double NPY and dynorphin knockout mice (NPYΔ, DYNΔ, NPYDYNΔ) and compared body weight, adiposity, feeding behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP-1) expression to wildtype counterparts.

Results

Body weight and adiposity were significantly increased in NPYDYNΔ, but not in NPYΔ or DYNΔ. This was not due to increased food intake or altered UCP-1 expression, which were not significantly altered in double knockouts. NPYDYNΔ mice demonstrated increased body weight loss after a 24-h fast, with no effect on serum glucose levels after glucose injection.

Conclusions

Contrary to the predicted phenotype delineated from single knockouts, double NPY and dynorphin deletion resulted in heavier mice, with increased adiposity, despite no significant changes in food intake or UCP-1 activity. This indicates that combining long-term opioid antagonism with blockade of NPY-ergic systems may not produce anti-obesity effects.