Blue rubber-bleb naevus syndrome: report of a case with consumption coagulopathy complicated by manifest thrombosis

Abstract Blue rubber-bleb naevus (BRBN) syndrome is a rare disorder characterized by subcutaneous and gastrointestinal haemangiomas. The latter may lead to bleeding complications. A case is reported in which a process of chronic intravascular coagulation resulted in serious thrombotic complications. In the presence of a chronic consumption coagulopathy, it remains uncertain whether antiplatelet drugs are of prophylactic antithrombotic value

The cystic fibrosis defect approached from different angles - New perspectives on the gene, the chloride channel, diagnosis and therapy

Abstract The search for the basic defect in cystic fibrosis (CF) has reached a decisive stage since the recent identification of the responsible gene. Electrophysiological and biochemical research had defined the CF defect as a dysregulation of epithelial chloride channels. The putative protein product of the now identified gene shares properties with other known transport proteins, but it is not necessarily itself a chloride channel protein. Elucidation of the primary cellular defect will certainly have important aetiological and hopefully therapeutic implications. The identification of the major gene mutation already has significant consequences for genetic counselling and prenatal diagnosis. Heterozygote detection at the population level awaits identification of the probably heterogenous mutations on about 30% of the CF chromosomes. At present, about 50% of CF patients are homozygous for the recently identified major CF mutation

Bile Acid Malabsorption in Cystic Fibrosis; Membrane Vesicles, a Tool for Revealing the Role of the Ileal Brush Border Membrane

ABSTRACT. Increased fecal bile acid loss in cystic fibrosis (CF) may result from ileal dysfunction. A method to quantitate in vitro Na+‐dependent taurocholate uptake into brush border membrane vesicles prepared from frozen ileum and ileal biopsy specimen is described. This transport across the ileal brush border membrane can be measured selectively, in contrast to in vivo measurements which represent a complex overall process. Preliminary results obtained with ileal specimen of 2 CF patients, suggest that in vitro bile acid uptake is low but not abnormal. Copyrigh

Changes in globus pallidus with (pre)term kernicterus

OBJECTIVE: We report serial magnetic resonance (MR) and sonographic behavior of globus pallidus in 5 preterm and 3 term infants with kernicterus and describe the clinical context in very low birth weight preterm infants. On the basis of this information, we suggest means of diagnosis and prevention. METHODS: Charts and MR and ultrasound images of 5 preterm infants and 3 term infants with suspected bilirubin-associated brain damage were reviewed. Included were preterm infants with severe hearing loss, quadriplegic hypertonia, and abnormal hypersignal of globus pallidus on T2-weighted MR imaging (MRI). In 1 infant who died on day 150, the diagnosis was confirmed during the neonatal period. The others were picked up as outpatients and scanned at 12 or 22 months' corrected age. Three instances of term kernicterus were included for comparison of serial MRI in the neonatal period and early infancy: they were caused by glucose-6-phosphate dehydrogenase deficiency, urosepsis, and dehydration plus fructose 1-6 biphosphatase deficiency. RESULTS: Five preterm infants of 25 to 29 weeks' gestational age presented with total serum bilirubin (TSB) levels below exchange transfusion thresholds commonly advised. Mixed acidosis was present in 3 infants around the TSB peak. The bilirubin/albumin molar ratio was >0.5 in all, in the absence of displacing drugs. All failed to pass bedside hearing screen tests and had severe hearing loss on auditory brain response testing. Symmetrical homogeneous hyperechogenicity of globus pallidus was the alerting feature in 1 infant. Globus pallidus was hyperintense on T1-weighted MR images in this child. The other infants presented with severe developmental delay as a result of dyskinetic quadriplegia and hearing loss. Globus pallidus was normal on T1- but hyperintense on T2-weighted MR images at 12

Regulation of chloride transport in cultured normal and cystic fibrobis keratinocytes

Abstract Cultured normal (N) and cystic fibrosis (CF) keratinocytes were evaluated for their Cl−-transport properties by patch-clamp-, Ussing chamber- and isotopic efflux-measurements. Special attention was paid to a 32 pS outwardly rectifying Cl− channel which has been reported to be activated upon activation of cAMP-dependent pathways in N, but not in CF cells. This depolarization-induced Cl− channel was found with a similar incidence in N and CF apical keratininocyte membranes. However, activation of this channel in excised patches by protein kinase (PK)-A or PK-C was not successfull in either N or CF keratinocytes. Forskolin was not able to activate Cl− channels in N and CF cell-attached patches. The Ca2+-ionophore A23187 activated in cell-attached patches a linear 17 pS Cl− channel in both N and CF cells. This channel inactivated upon excision. No relationship between the cell-attached 17 pS and the excised 32 pS channel could be demonstrated. Returning to the measurement of Cl− transport at the macroscopic level, we found that a drastic rise in intracellular cAMP induced by forskolin did in N as well as CF cells not result in a change in the short-circuit current (Isc) or the fractional efflux rates of 36Cl− and 125I−. In contrast, addition of A23187 resulted in an increase of the Isc and in the isotopic anion efflux rates in N and CF cells. We conclude that Cl−-transport in cultured human keratinocytes can be activated by Ca2+, but not by cAMP-dependent pathways

Benign recurrent intrahepatic cholestasis (BRIC): Evidence of genetic heterogeneity and delimitation of the BRIC locus to a 7-cM interval between D18S69 and D18S64

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disease characterized by multiple episodes of cholestasis without progression to chronic liver disease. The gene was previously assigned to chromosome 18q21, using a shared segment analysis in three families from the Netherlands. In the present study we report the linkage analysis of an expanded sample of 14 BRIC families, using 15 microsatellite markers from the 18q21 region. Obligate recombinants in two families place the gene in a 7-cM interval, between markers D18S69 and D18S64. All intervening markers had significant LOD scores in two-point linkage analysis. More over, we identified one family in which the BRIC gene seems to be unlinked to the 18q21 region, or that represents incomplete penetrance of the BRIC genotype