Laboratory diagnosis and molecular epidemiology of an outbreak of hepatitis C virus infection among recipients of human intravenous immunoglobulin in Spain

BACKGROUND: Passive transfer of antibody to hepatitis C virus (HCV) has been thought to occur after infusion of human intravenous immunoglobulin (IVIG), as anti-HCV and/or HCV RNA was commonly found in that product. Recently, however, HCV RNA was detected in the serum of recipients of IVIG. Establishment of a causal relationship between IVIG therapy and HCV infection in recipients was attempted. STUDY DESIGN AND METHODS: Anti-HCV and HCV RNA sequences were investigated in serum samples from 39 persons who received a human IVIG product in seven different hospitals in Spain. HCV RNA was also investigated in two batches of the IVIG shared by some recipients. All the viral RNA detected were characterized with a line probe assay, restriction fragment length polymorphism analysis of the 5'-noncoding and core regions, and sequencing of the nonstructural 5 region. RESULTS: On the basis of both clinical and laboratory data, a relationship could be established between the IVIG therapy and the acquisition of the HCV infection by the recipients. Several HCV strains were detected among the recipients, with most of the recipients coming from the same hospital presenting with closely related strains. Moreover, an HCV strain almost identical to the main strain detected among the recipients was found in one batch of the IVIG that probably was shared by most of them. Follow-up studies and evaluation of low-avidity anti- HCV IgG suggested that both acute primary infections and reinfections were produced. In one case, direct evidence of reinfection by a different HCV strain was obtained. CONCLUSION: The results did not exclude the possibility that a second HCV strain associated with a further, unidentified batch of the IVIG could have contributed to this outbreak.     

Osteomyelitis in the neonate. Clinical aspects and the role of radiography and scintigraphy in diagnosis and management

Based on experience with 22 cases of neonatal osteomyelitis in 10 years, the authors suggest these patients can be divided into two groups depending on severity of disease. Premature infants requiring umbilical catheterization and severely ill full-term infants constitute a high-risk group; signs are more overt, multifocal infection and joint involvement more frequent, and severe skeletal deformities more common. The patients in the low-risk group had much milder disease but also presented more difficulty in diagnosis because of the vagueness of the presenting signs. Radiographic examination is essential for diagnosis and follow-up of osteomyelitis, particularly limb deformities. Bone scans should be reserved for situations in which the clinical and radiographic findings are equivocal.     

Autonomic alcoholic polyneuropathy

Measurement of heart rate variability was performed in a group of 106 healthy volunteers and 31 alcoholics. The mean momentary arrhythmia of normal individuals shows an exponential decrease with growing age. In 5 of 31 alcoholics a cardiac autonomic neuropathy was found with this parameter. The withdrawing alcoholics had a significant increase of heart rate and decrease of heart rate variability compared to later measurements, what is in agreement with the concept of hyperexcitability in early withdrawal.     

Monocytes enhance the bidirectional release of type I plasminogen activator inhibitor by endothelial cells

Human umbilical vein endothelial cells cultured on a collagen lattice were used to study the effects of the interaction between human monocytes and endothelial cells on the production of type 1 plasminogen activator inhibitor (PAI-1) by endothelial cells. The effects of adherence and transendothelial migration of monocytes on endothelial PAI-1 release were compared with those of other leukocytes, conditioned media from monocytes, and interleukin-1 beta (IL-1 beta). Because the cell culture system used allows simultaneous analysis of the lumenal and the subendothelial compartment of endothelial cell monolayers, we also studied into which direction PAI-1 is released by endothelial cells. Under quiescent conditions, the net amount of PAI-1 accumulated at the lumenal side was twofold higher than that accumulated at the subendothelial side (about 2.0 micrograms PAI-1/10(6) cells and 1.1 microgram PAI-1/10(6) cells, respectively, in 24 hours), as analyzed by a quantitative immunoradiometric assay (IRMA). Direct cell-cell contact between highly purified monocytes and endothelial cells strongly enhanced the PAI-1 release by endothelial cells in a dose-dependent way, whereas lymphocytes and neutrophils did not affect endothelial PAI- 1 production. The monocyte-mediated increase was first detected after 12 hours of incubation and lasted for at least 48 hours. In the presence of two monocytes per endothelial cell, the increases of PAI-1 at the lumenal side and at the subendothelial side were 87% and 32% in 24 hours, respectively. The effect of IL-1 beta on PAI-1 release by endothelial cells closely resembled that observed for monocytes. Monocyte-conditioned medium contained heat-labile product(s) which also, although to a much lesser extent than intact monocytes, enhanced endothelial PAI-1 release. Similarly, monocytes cultured on top endothelial cell separated by a microporous filter enhanced the release of PAI-1 to a lesser extent. Thus, these findings indicate that monocytes enhance endothelial PAI-1 release by mechanisms that are, at least in part, dependent on cell-cell contact.     

Incidence of type I diabetes mellitus in Navarre, Spain (1975–91)

The aim of this study was to ascertain the incidence of Type 1 diabetes mellitus in Navarre, an autonomous community in northern Spain. Subjects were patients who presented with diabetes between 1975 and 1991, age range 0–16 years, resident in Navarre at the onset of symptoms. Endocrinologists in outpatient centres and hospitals (both public and private) in Navarre were the primary source of data, while secondary sources were: independent general practitioners, health centre paediatricians and the Child-Youth Diabetics Parents' Association of Navarre. The degree of ascertainment was 97.8%. Average annual incidence of diabetes detected was 9.54/100 000 (95% CI 8.2–11.1) in the 0–14 year-old group. The least incidence was observed in 1976 and highest in 1990. The incidence in males (9.71/100 000) was higher than in females (7.83/100 000). The highest incidence was observed in the 10–14 year-old group (13.70/100 000) when analysed by groups. No seasonal variation in the onset of diabetes was observed. These results suggest a significant increase in the incidence of type 1 diabetes between 1975 and 1991.