Scintigraphic diagnosis of tricuspid regurgitation

The authors describe a simple technique for diagnosis of tricuspid regurgitation. Red blood cells were labeled in vivo with 99mTc and 22 patients were studied with ECG-gated blood-pool imaging of the liver. A single region of interest was manually drawn around the liver and a time-activity curve obtained. The per cent change in liver counts during the cardiac cycle was found to be significantly higher in the 12 patients with tricuspid regurgitation (Group I) (mean, 4.04 +/- 1.6%; range, 1.3-21.4%) compared with the 10 controls (Group II) (mean, 0.35 +/- 0.16%; range, 0.013-1.3%) (p less than 0.05). Using a 1% change in liver counts as the criterion of a positive study, all 12 cases in Group I were diagnosed correctly, but there was one false positive in Group II; thus the sensitivity was 100% and the specificity 90%.     

Effect of sulphinpyrazone and aspirin on latelet adhesion to activated charcoal and dialysis membranes in vitro.

Charcoal haemoperfusion is used in the treatment of severe drug overdosage, and is potentially useful in fulminant hepatic failure and chronic uraemia. Haemo-compatibility of early devices has improved, but platelet loss and occasional associated haemorrhage still occur. During a double blind cross-over study, in 8 healthy male volunteers, aspirin 600 mg/day, sulphinpyrazone 800 mg/day, or a combination of both or placebo were administered for 2 days at 14 day or longer intervals. The effects of these agents were measured with reference to 1) forearm bleeding times using a spring loaded device, 2) platelet adsorption during 2 hrs haemoperfusion of heparinized blood through 2% acrylic hydrogel coated or uncoated activated charcoal in vitro, and 3) platelet retention from citrated blood on PT₁₅₀ and PT₂₅₀ cuprophan dialysis membranes in vitro. Aspirin and aspirin in combination with sulphinpyrazone prolonged bleeding time, but sulphinpyrazone alone had no significant effect on bleeding time. Aspirin alone, sulphinpyrazone alone, and their combination reduced platelet adsorption on coated activated charcoal, and platelet retention on cuprophan membranes. Aspirin, and aspirin in combination with sulphinpyrazone, reduce platelet adsorption on uncoated charcoal, while sulphinpyrazone alone had no significant effect. The results indicate that 2 days treatment with sulphinpyrazone or aspirin produce significant antiplatelet action and that the effects of sulphinpyrazone on platelet function should be explored in relation to clinical haemoperfusion and haemodialysis.     

Molecular defects in Sanfilippo syndrome type B (mucopolysaccharidosis IIIB)

Summary Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is an autosomal recessive disease that is caused by the deficiency of the lysosomal enzyme α-N-acetylglucosaminidase (NAGLU). NAGLU is involved in the degradation of the glycosaminoglycan (GAG) heparan sulphate, and a deficiency results in the accumulation of partially degraded GAGs inside lysosomes. Early clinical symptoms include hyperactivity, aggressiveness and delayed development, followed by progressive mental deterioration, although there are a small number of late-onset attenuated cases. The gene for NAGLU has been fully characterized and we report the molecular analysis of 18 Sanfilippo B families. In total, 34 of the 36 mutant alleles were characterized in this study and 20 different mutations were identified including 8 novel changes (R38W, V77G, 407–410del4, 703delT, A246P, Y335C, 1487delT, E639X). The four novel missense mutations were transiently expressed in Chinese hamster ovary cells and all were shown to decrease the NAGLU activity markedly, although A246P did produce 12.7% residual enzyme activity.     

Monitoring the clinical and biochemical response to enzyme replacement therapy in three children with Fabry disease

Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme -galactosidase A. This leads to the progressive accumulation of glycosphingolipids in lysosomes of most visceral tissues and in body fluids. Following successful clinical trials in adults, two recombinant enzyme preparations of -galactosidase have recently been licensed in Europe for the treatment of Fabry disease and treatment in children has commenced. We now report the clinical findings and the levels of globotriaosylceramide in plasma and urine in three boys who have been treated with enzyme replacement therapy (agalsidase beta, Fabrazyme), 1 mg/kg for 2 years. In one boy there was a rapid improvement in all the clinical and biochemical parameters measured. This has been maintained. In the other two boys, who are siblings, there was no measurable clinical improvement after 1 year and the levels of globotriaosylceramide in plasma and urine, although lower than before treatment, were still considerably elevated. There was no evidence of blocking or neutralising antibodies so the dose of enzyme was increased to 2 mg/kg at 74 weeks of therapy. At 2 years their pain scores had improved but this was not accompanied by any reduction in the plasma or urine globotriaosylceramide levels. Conclusion:measurement of globotriaosylceramide in plasma and urine may not be the most appropriate marker to monitor the progression of treatment by enzyme replacement therapy in all patients. Certainly the subjective clinical improvement in the two brothers in this report outweighed the objective biochemical findings.Abbreviations CTH globotriasosylceramide - ERT enzyme replacement therapy - FA fatty acid - LCB sphingosine - MS/MS tandem mass spectrometry     

Community-acquired pneumonia mortality: a potential link to antibiotic prescribing trends in general practice

BACKGROUND: Community prescribing of antibiotics has decreased substantially in the UK in recent years. We examine the association between pneumonia mortality and recent changes in community-based antibiotic prescribing for lower respiratory tract infections (LRTI). METHODS: Retrospective analysis of aggregated data for pneumonia mortality, influenza incidence, and antibiotic prescribing for LRTI in England and Wales during 12-week winter periods between 1993/94 and 1999/2000. RESULTS: Winter antibiotic prescribing for LRTI showed a 30.0% decline since 1995/96. Over the same period, there was a 50.6% increase in winter excess pneumonia mortality adjusted for influenza incidence. Negative binomial regression analysis showed that the incidence of influenza alone had a significant association with winter pneumonia mortality (P<0.001). The analysis also showed the reduction in antibiotic prescribing had a small but significant association with mortality (P<0.001), when simultaneously modelling for influenza incidence. CONCLUSIONS: Our findings suggest an association between recent reductions in antibiotic prescribing for LRTI in general practice and an increase in pneumonia mortality in England and Wales. This retrospective study of aggregate data represents the first attempt to assess the effect of limiting antibiotic prescribing on patient outcomes, and highlights the need to identify which patients benefit from antibiotic treatment for LRTI.