Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVE: The objective of this study was to identify differentially expressed salivary proteins in bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients that could serve as biomarkers for BRONJ diagnosis. SUBJECTS AND METHODS: Whole saliva obtained from 20 BRONJ patients and 20 controls were pooled within groups. The samples were analyzed using iTRAQ-labeled two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: Overall, 1340 proteins were identified. Of these, biomarker candidates were selected based on P-value (<0.001), changes in protein expression (≥1.5-fold increase or decrease), and unique peptides identified (≥2). Three comparisons made between BRONJ and control patients identified 200 proteins to be differentially expressed in BRONJ patients. A majority of these proteins were predicted to have a role in drug metabolism and immunological and dermatological diseases. Of all the differentially expressed proteins, we selected metalloproteinase-9 and desmoplakin for further validation. Immunoassays confirmed increased expression of metalloproteinase-9 in individual saliva (P = 0.048) and serum samples (P = 0.05) of BRONJ patients. Desmoplakin was undetectable in saliva. However, desmoplakin levels tended to be lower in BRONJ serum than controls (P = 0.157). CONCLUSIONS: Multiple pathological reactions are involved in BRONJ development. One or more proteins identified by this study may prove to be useful biomarkers for BRONJ diagnosis. The role of metalloproteinase-9 and desmoplakin in BRONJ requires further investigation.

Diagnostic and therapeutic management for suspected neonatal herpes simplex virus infection.

BACKGROUND: Neonatal herpes simplex virus (HSV) is a rare disease associated with high mortality and morbidity rates. HSV infection can be subdivided into 3 clinical manifestations: isolated skin, eye and mouth (SEM) disease, central nervous system (CNS) disease and disseminated disease. Consensus guidelines for diagnostic and therapeutic management are not available. OBJECTIVES: To evaluate the diagnostic work-up and therapeutic management in neonates with suspected or proven HSV infection. STUDY DESIGN: Retrospective study of diagnostic and therapeutic management in all neonates with suspected HSV infection admitted to our neonatal nursery between January 2005 and July 2010. RESULTS: A total 53 neonates with suspected HSV infection were included in the study and classified as SEM disease (n=2), CNS disease (n=41) or disseminated disease (n=10). None of the included infants tested positive for HSV infection. Correct and complete diagnostic work-up was performed in only 11% (6/53) of the cases. All neonates were treated with intravenous acyclovir. CONCLUSIONS: None of the neonates with suspected HSV tested positive. Diagnostic management in neonates with suspected HSV infection was often improper and incomplete. Consensus guidelines to identify low-risk infants in whom HSV testing and acyclovir treatment is not warranted, are urgently needed.

Parvovirus B19 infection in pregnancy: new insights and management.

In this article, we review the virology, pathology, epidemiology and clinical spectrum of intrauterine human parvovirus B19 (B19V) infection, including intrauterine fetal death, non-immune hydrops fetalis, thrombocytopenia and neurological manifestations such as pediatric stroke and perivascular calcifications. In addition, we discuss the new insights into the neurodevelopmental outcome of intrauterine B19V infection. Current diagnosis and management of B19V infection is summarized, including a diagnostic and follow-up flowchart for practical clinical use.

Is routine TORCH screening and urine CMV culture warranted in small for gestational age neonates?

BACKGROUND: congenital infections are associated with a wide variety of clinical symptoms, including small for gestational age (SGA). AIMS: to determine the co-occurrence of SGA and congenital TORCH infections, as diagnosed by TORCH serologic tests and/or cytomegalovirus (CMV) urine culture. STUDY DESIGN: we performed a retrospective study of all neonates admitted to our neonatal intensive care unit from January 2004 to February 2010 in whom SGA was diagnosed and TORCH serologic tests and/or CMV urine cultures were performed. RESULTS: TORCH serologic tests (in neonatal or maternal serum) and/or a CMV urine culture were performed in 112 neonates with SGA. None of the neonates tested positive for Toxoplasma gondii, Rubella, and Herpes simplex virus. Positive CMV urine culture was detected in 2% (2/112) of neonates, but their CMV IgM titers were negative. CONCLUSIONS: the co-occurrence of TORCH congenital infection in infants with SGA is rare. Routine TORCH screening in neonates with isolated SGA does not seem warranted and should be limited to CMV urine cultures.

Is routine TORCH screening warranted in neonates with lenticulostriate vasculopathy?

BACKGROUND: Congenital infections are associated with a wide spectrum of clinical symptoms, including lenticulostriate vasculopathy (LSV). OBJECTIVE: To determine the relationship between LSV and congenital infections, as diagnosed by TORCH serology and viral culture for cytomegalovirus (CMV). METHODS: All neonates with LSV admitted to our neonatal intensive-care unit from 2004 to 2008 were included in the study. Results of maternal and neonatal TORCH testing were evaluated. RESULTS: During the study period, cranial ultrasound scans were performed in 2,088 neonates. LSV was detected in 80 (4%) neonates. Maternal and/or neonatal serological TORCH tests were performed in 73% (58/80) of cases. None of the mothers or infants (0 of 58) had positive IgM titres for Toxoplasma, rubella, CMV or herpes simplex virus. Additional urine culture for CMV was performed in 38 neonates. None of the infants (0 of 38) had a positive CMV urine culture test. CONCLUSIONS: Routinely applied efforts to diagnose congenital infections in cases presenting with LSV have a poor yield. Routine TORCH screening in neonates with LSV cases should only be regarded as mandatory once well-designed studies demonstrate a clear diagnostic benefit.

[Infection with human parvovirus B19 ('fifth disease') during pregnancy: potential life-threatening implications for the foetus]. / Infectie met het Humaan parvovirus B19 ('vijfde ziekte') in de zwangerschap: voor de foetus soms levensbedreigend.

Four pregnant women, aged 29, 32, 36 and 36 years, respectively, were diagnosed with Human parvovirus B19 (B19V) infection. Only the first woman had exanthema and fever. In the first three cases, the source of infection appeared to be another child; two of these children were infected during a school outbreak. All four foetuses were infected, but the first foetus was asymptomatic and healthy at birth. The second foetus had anaemia and increased blood flow in the middle cerebral artery; it received an intrauterine transfusion and was healthy at birth. The third foetus was almost immobile and had cardiomegaly and hydrops fetalis; it was dead upon induced birth. In the fourth case, pregnancy was uneventful until two days before parturition, when the mother reported a decrease in foetal movement. The infant was born and developed respiratory insufficiency after 8 hours. Imaging revealed multiple bilateral lesions in frontal, occipital and parietal white matter consistent with infarction. The infant died after 5 days. Infection with B19V is associated with a wide range of clinical presentations and outcomes. Effects may range from an uncomplicated pregnancy to severe hydrops fetalis or intrauterine foetal death. Maternal symptoms may be aspecific, which complicates early diagnosis. When maternal B19V infection is suspected, immediate investigation for recent B19V infection should be performed. Quantitative B19 viral load measurements may provide insight into the stage of infection and may guide foetal monitoring. Referral to a foetal therapy unit is essential for hydrops fetalis or severe foetal anaemia. Intrauterine transfusion with erythrocytes significantly improves foetal outcome. Despite a successful transfusion procedure, long-term neurodevelopment may be affected, and developmental follow up is advised.