Double germline mutations in the RET Proto-oncogene in MEN 2A and MEN 2B kindreds.

Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all thyroid malignancies. It occurs mostly as a sporadic tumor or in association with autosomal dominant inherited cancer syndromes--multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in exons 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene are found in most of the familial cases. There are only a few published data reporting multiple germline mutations in the RET proto-oncogene. We have detected double germline mutations in 2 different exons on the same RET allele in two MEN 2 families. In the MEN 2A family, double germline mutation in exons 10 (Cys620Phe) and 13 (Tyr791Phe) was detected. In the MEN 2B family, beside the classical germline mutation in exon 16 (Met918Thr) a second germline mutation in exon 13 (Tyr791Phe) was found. This study revealed that MEN 2 syndromes can also be caused by double germline mutations in the RET proto-oncogene and these families can be added to small worldwide cohort of families with multiple germline mutations.     

Penicillium piceum infection: diagnosis and successful treatment in chronic granulomatous disease.

Infections due to Penicillium species other than P.marneffei are rare. We identified a boy with X-linked chronic granulomatous disease (X-CGD) with a pulmonary nodule and adjacent rib osteomyelitis caused by Penicillium piceum. The only sign of infection was an elevated sedimentation rate. P. piceum was isolated by fine needle aspirate and from excised infected tissues. Surgical removal and one year of voriconazole treatment were very well tolerated and led to complete recovery. Microbiological, microscopic and molecular studies support the fungal diagnosis. P. piceum should be considered as a relevant pathogen in immunocompromised patients.     

Women's Evaluations of Their Experience in a Multicenter Randomized Controlled Trial of Intrapartum Fetal Pulse Oximetry (The FOREMOST Trial)

Abstract: Background: Fetal pulse oximetry improves the assessment of fetal well‐being during labor. The objective of this study was to evaluate women's satisfaction with their experience with this additional technology. Methods: We surveyed women participating in the FOREMOST trial, a randomized controlled trial comparing the addition of fetal pulse oximetry (FPO) to conventional cardiotocograph (CTG) monitoring (intervention group), versus CTG‐only (control group), in the presence of nonreassuring fetal status during labor. Our survey evaluated 3 aspects of women's experience: labor, fetal monitoring, and participation in the research. The survey was administered within a few days of giving birth and repeated 3 months later. Results: No differences were found between the intervention and control groups for women's evaluations of their labor, fetal monitoring, research, or overall experiences when surveyed on both occasions. Within each study group, a small but statistically significant decline occurred in women's scores for their experience of labor and overall experience from the initial survey close to the time of giving birth, to 3 months later. The magnitude of differences in responses over time was similar for the both groups. Women were more satisfied after a spontaneous or assisted vaginal birth than after cesarean section. Length of time the research midwife was present had a significant positive effect on women's ratings of their experience several days after giving birth (p = 0.006), but no effect at 3 months. Conclusions: The addition of fetal pulse oximetry for the assessment of fetal well‐being during labor did not affect childbearing women's perceptions of fetal monitoring or their labor. Women evaluated their experience in the research process positively overall. Small changes occurred in women's perception of their satisfaction over time. (BIRTH 33:2 June 2006)     

Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation.

OBJECTIVE: To establish reference intervals for the fetal right, left and total lung volumes and heart volume between 12 and 32 weeks of gestation. METHODS: Fetal lung and heart volumes were measured using three-dimensional (3D) ultrasound in 650 normal singleton pregnancies at 12-32 weeks. The VOCAL (Virtual Organ Computer-aided AnaLysis) technique was used to obtain a sequence of six sections of each lung and the heart around a fixed axis, each after a 30 degrees rotation from the previous one. The rotation axis for the lungs extended from the apex to the upper limit of the diaphragm dome, and the rotation axis for the heart extended from its apex to its connection to the great vessels. The contour of each of these organs was drawn manually in the six different rotation planes to obtain the 3D volume measurement. In 60 cases the fetal lungs and heart volumes were measured by the same sonographer twice and also by a second sonographer once in order to compare the measurements and calculate intra- and interobserver agreement. RESULTS: The total lung volume and heart volume increased with gestation, from respective mean values of 1.6 and 0.6 mL at 12 weeks to 10.9 and 4.3 mL at 20 weeks and 49.3 and 26.6 mL at 32 weeks. The right to left lung volume ratio did not change significantly with gestation (median, 0.7), whereas the heart to total lung volume ratio increased with gestation from about 0.3 at 12 weeks to 0.5 at 32 weeks. In the Bland-Altman plot, the difference between paired measurements by two sonographers was, in 95% of the cases, less than 0.05, 0.5 and 1.9 mL for each lung at 12-13, 19-22 and 29-32 weeks, respectively, and the corresponding values for the heart volumes were 0.04, 0.4 and 2.3 mL. CONCLUSIONS: In normal fetuses the lung and heart volumes increase between 12 and 32 weeks of gestation. The extent to which in pathological pregnancies possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined.     

Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene

Background Familial partial lipodystrophy (FPLD) is a monogenic form of diabetes characterised by a dominantly inherited disorder of adipose tissue associated with the loss of subcutaneous fat from the limbs and trunk, with excess fat deposited around the face and neck. The lipodystrophy causes severe insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia, and increased risk of cardiovascular disease. Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome. Case report We report a 24-year-old patient with FPLD caused by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone. Subcutaneous fat increased following rosiglitazone treatment as demonstrated by a 29% generalised increase in skin-fold thickness. Leptin levels increased from 5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2–31.6) but no change in glycaemic control. The lipid profile worsened during the follow-up period. Conclusion This initial case suggests that, for modification of cardiovascular risk factors, there are no clear advantages in treating patients with FPLD with rosiglitazone despite increases in subcutaneous adipose tissue. Larger series will be needed to identify moderate beneficial effects and treatment may be more effective in patients with generalised forms of lipodystrophy.