Complex medical history of a patient with a compound heterozygous mutation in C1QC.

INTRODUCTION: C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation. MATERIAL AND METHODS: Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes. RESULTS: The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes. DISCUSSION: The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.

[Coma in a child after treatment with the 'magic salve' lidocaine-prilocaine cream]. / Coma bij een peuter na behandeling met de 'toverzalf' lidocaine-prilocaïnecrème.

A 2-year-old girl lost consciousness after the topical application of lidocaine-prilocaine cream (EMLA) in preparation for the removal of multiple mollusca contagiosa. Both the area on which cream was applied (80% of body surface) and the total amount of cream (90 g) exceeded the maximum dosage. Lidocaine-prilocaine cream is a widely used local anaesthetic with few side effects when used properly. Intoxication with a lidocaine-prilocaine preparation may have serious consequences, such as changes in intracardiac conduction, excitation or depression of the central nervous system and methaemoglobinaemia. In our patient both methaemoglobinaemia and depression of the central nervous system occurred, resulting in loss of consciousness. She was treated with 100% oxygen and fully recovered.

Exercise-induced asthma and cardiovascular fitness in asthmatic children.

BACKGROUND: The role of physical training in the management of children with exercise-induced asthma is controversial. A study was undertaken to determine whether a relationship could be found between the occurrence of exercise-induced asthma and the degree of cardiovascular fitness in asthmatic children. METHODS: Twenty eight children aged 6-13 with mild to moderate asthma and dyspnoea during or after physical exercise were tested. All patients had a basal forced expiratory volume in one second (FEV1) of > 80% predicted. Twelve patients were taking corticosteroid maintenance medication by inhalation and 16 were not. Two exercise tests were performed on a treadmill to assess peak oxygen consumption rate (VO2max) and the percentage decrease in FEV1 after exercise. RESULTS: There was no correlation between the VO2max and the percentage decrease in FEV1. Patients not taking steroids showed a greater fall in FEV1 than those receiving corticosteroid medication (mean fall in FEV1 28.7% versus 6.6%). Four of the 12 children treated with steroids and two of the 16 children not taking steroids had a level of cardiovascular fitness lower than the 5th percentile for healthy Dutch children. CONCLUSION: Normal cardiovascular fitness does not prevent exercise-induced asthma.

Quantitative aspects of the parenchyma-stroma relationship in experimentally induced cholestasis.

In order to quantify changes of the parenchyma/stroma relations in the progression of experimentally induced biliary fibrosis in the rat, localisation of lactate dehydrogenase activity and Sirius Red staining were used as criteria to detect parenchymal cells and collagen fibers, respectively. Blood levels of bilirubin, alkaline phosphatase, anti-thrombin III activity, alpha 2-antiplasmin, factor II and factor X were related to the data obtained by histomorphometric measurements in sections gathered 1, 2, 4 and 6 weeks after the onset of cholestasis in three animals and after 8 weeks in one animal. Histophotometry showed a reduction in volume density of the parenchymal cell mass of 96%, 78%, 76%, 62% and 59% of the control values, respectively. During the same period, the collagen increased 5-fold in 4 weeks time, levelling off afterwards. Newly formed collagen appeared in the portal areas in close association with proliferating ductules, invading with the latter into the parenchymal mass. After 6 weeks, regressive changes were observed in the ductule complexes formed, manifested by a lowering of the epithelium in which extensive apoptotic cell death was observed with the electron microscope. Of the blood parameters analyzed, the clotting factor X showed the best inverse correlation with the Sirius Red readings (rs = -0.84), i.e. the volume density of collagenous fibers.