Molecular analysis of genomic DNA allows rapid, and accurate, prenatal diagnosis of peroxisomal D-bifunctional protein deficiency.

Prenatal diagnosis was requested for a couple with a previous child affected by the peroxisomal disorder D-bifunctional protein deficiency. Prior analysis of the D-bifunctional protein cDNA sequence from the propositus had shown that it was missing 22 bp. This was subsequently attributed to a point mutation in the intron 5 donor site (IVS5 + 1G>C) of the D-bifunctional protein gene. Consistent with parental consanguinity, the patient was shown to be homozygous for this mutation, which is associated with loss of a Hph 1 restriction site in the genomic sequence. Prenatal testing of the fetus using genomic DNA isolated from uncultured amniocytes indicated that both alleles of the D-bifunctional protein had the IVS5 + 1G>C substitution. The peroxisomal defect was later confirmed biochemically using cultured amniocytes, which were found to have elevated levels of very long chain fatty acids (VLCFA). This is the first report of prenatal diagnosis of D-bifunctional protein deficiency using molecular analysis of genomic DNA.     

Parent influences in the transmission of eating and weight related values and behaviors

Early adolescent boys (n = 587) and girls (n = 619) and a parent completed questionnaires, that assessed child dieting behaviors, body dissatisfaction and tendency to overeat, child's current and ideal size, mother and father dieting, and encouragement of the child to diet.     

Difficult tracheal intubation induced by maxillary distraction devices in craniosynostosis syndromes

BACKGROUND: Difficult intubation occurred during anaesthesia for removal of maxillary distraction devices in five of seven children with syndromal craniosynostoses (four with Apert, two with Pfeiffer and one with Crouzon syndrome). METHODS: Intubation was assessed in terms of laryngeal view and an established intubation difficulty score and had been straightforward before device insertion. Difficulty was induced by trismus due to device insertion and by increased maxillary prominence. This was compounded by preexisting mandibular hypoplasia. Cephalometric analysis, with each child acting as their own control, demonstrated anterior displacement of the maxilla and increased maxillary vertical height, as well as increased protuberance of the maxillary incisors. RESULTS: All five difficult tracheal intubations were associated with preoperative Mallampati scores of 3 or 4 and the nine straightforward intubations with scores of 1 or 2. Maximal interincisor distance was less than the lower 95% confidence limit for age in all five children who were difficult to intubate at the time of device removal. No child had a failed intubation, but all had significantly increased intubation difficulty. CONCLUSIONS: In view of the risks of trauma, hypoxia and aspiration associated with difficult direct laryngoscopy, we recommend elective fibreoptic intubation at anaesthesia for removal of maxillary distraction osteogenesis devices in these children.     

Surgical Strategy for Cystic Diseases of the Liver in a Western Hepatobiliary Center

The aim of this study was to define the indications and evaluate the results of various management options in patients with cystic liver disease. Between 1992 and 1999 we managed 60 consecutive patients with cystic liver disease. Diagnoses included a simple cyst (solitary 12, multiple 10), adult polycystic liver disease (APLD 17), Caroli’s disease (8), hydatid cysts (4), and neoplastic cysts (9). Half of the patients with simple cysts had mild or no symptoms and required no treatment. Percutaneous drainage in eight patients (simple cyst 4, APLD 4) was followed by symptomatic recurrence in three. Laparoscopic deroofing in three patients (multiple simple cysts 2, APLD 1) was followed by symptomatic enlargement of the remaining cysts that required further intervention (laparoscopic deroofing 2, transplantation 1). Laparoscopic hepatectomy was successful in three patients with solitary simple cysts. Of 18 patients who underwent open hepatic resection (neoplastic 8, Caroli’s 4, simple cysts 3, hydatid cysts 2, APLD 1), 2 patients with Caroli’s disease required liver transplantation for disease progression. Nine patients (Caroli’s 5, APLD 4) underwent liver transplantation, and three had a concomitant renal transplant. Seven patients developed complications, and three died (5%). Cholangiocarcinoma developed in three patients with bilateral Caroli’s disease, and all died. Radiologic treatment has a limited role in the management of patients with simple cysts or APLD. Laparoscopic deroofing of simple cysts may have to be repeated, whereas resection minimizes cyst recurrence. Unilobar Caroli’s disease may be resected, whereas bilateral disease requires early liver transplantation owing to the high risk of malignancy. Transplantation is a reserved option in patients with extensive APLD.     

Susceptibility of thermally injured mice to cytomegalovirus infection

Thermally injured patients are very susceptible to infection with cytomegaloviruses. In this study a role of burn-associated type 2 T cell responses on the cytomegalovirus infection was examined in a mouse model of thermal injury. A predominance of type 2 T cell responses in splenic lymphocytes of thermally injured mice has been previously demonstrated. SCID mice inoculated with splenic T cells from thermally injured mice were susceptible to infection with a small amount (5 PFU/mouse) of murine cytomegalovirus (MCMV). Conversely, SCID mice inoculated with splenic T cells from normal mice were resistant to the same infection. High levels of IL-4 and IL-10, but not IFN-gamma and IL-2, were detected in sera of thermally injured mice (TI-mice) infected with MCMV when those were compared with sera of normal mice infected with MCMV. IL-4 and IL-10 (type 2 cytokines) were produced by splenic T cells from MCMV-infected TI-mice, when they were stimulated in vitro with anti-CD3 mAb. Type 1 cytokines (IFN-gamma and IL-2), however, were not produced by these T cells after the same stimulation. In contrast, splenic T cells from MCMV-infected normal mice produced type 1 cytokines by the stimulation with anti-CD3 mAb. These results suggest that the susceptibility of mice to MCMV infection is markedly influenced by burn-associated type 2 T cell responses.