Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Fluorine-18 fluorodeoxyglucose splenic uptake from extramedullary hematopoiesis after granulocyte colony-stimulating factor stimulation

Two patients with sarcoma, one with recurrent osteosarcoma of the spine and the other with metastatic synovial cell sarcoma, were treated with high-dose chemotherapy that produced severe leukopenia. The patients received granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow (480 mg given subcutaneously twice daily for 5 to 7 days); their responses were seen as a marked increase in peripheral leukocyte count with no change in the erythrocyte or platelet counts. The patients had fluorine-18 fluorodeoxyglucose (F-18 FDG) imaging 24 hours after the end of G-CSF treatment. Diffusely increased uptake of F-18 FDG was seen in the bone marrow in both patients. In addition, markedly increased uptake in the spleen was noted in both, indicating that the spleen was the site of extramedullary hematopoiesis. The patients had no evidence of splenic metastases. The first patient had a history of irradiation to the dorsal spine, which was less responsive to G-CSF administration than was the nonirradiated lumbar spine.     

Effect of pediatric advanced life support course on pediatric residents' intubation success

Background: The Pediatric Advanced Life Support Program (PALS) course very important for teaching about intubation, resuscitation, shock, trauma, respiratory failure and rhythm disturbances. The aim of the present study was to evaluate the effect of the PALS course on pediatric residents' intubation success during their rotation, daytime and night‐time practice in the pediatric intensive care unit (PICU). Methods: The study was carried out from 1 March 2005 to 28 February 2007. The study period had two parts, in that the number of attempts and successful intubations performed by pediatric residents, and the pediatric intensivist successful intubation ratio were evaluated in two different periods: before the PALS course, 1 March 2005–28 February 2006, and after the PALS course, 5 March 2006–28 February 2007. The participating residents' pediatric levels (PL) were classed as PL‐1, PL‐2, PL‐3, PL‐4, and all had first experience in the PICU at the PL‐1 level. The PALS instructor was a pediatric emergency or intensive care doctor. We evaluated whether the PALS course influenced intubation success or not. Results: Sixteen residents participated in the study. The proportion of successful intubations was 110 (53.3%) and 104 (65.4%) attempts before and after the PALS course, respectively. The proportion of intubations done by intensivists decreased from 49.1% to 31.7% before and after PALS. The most frequently used endotracheal tube (ETT) internal diameter (ID) was 4.0 mm, and cuffed ETT was used 16% and 21% before and after the course, respectively. Appropriate placing of ETT tip occurred 70.4% and 82.2% of the time before and after the PALS course, respectively. Proportion of successful intubations by residents increased in all levels, except for PL‐1. The most important reason for unsuccessful attempts was inappropriate patient position. Only one patient could not be intubated, and laryngeal mask airway was used in that case. During intubation, complications were broken teeth in two patients before the course, and subglottic stenosis developed in only one patient due to cuffed ETT. Conclusion: Successful intubation is a life‐saving intervention during resuscitation, ETT revision for extubation or obstruction for extubation or obstruction during mechanical ventilation. This skill can be developed in the PALS course and by clinical study in PICU and pediatric emergency services. The PALS course must be given to pediatric residents especially within the first year. Also, cuffed ETT can be used for infants and children.     

Detection of pancreatic metastases by EUS-guided fine-needle aspiration

BACKGROUND: Metastases to the pancreas are usually found incidentally. Tissue diagnosis is imperative because imaging alone is incapable of differentiating them from primary pancreatic tumors. This study tested whether it is possible to differentiate metastases from other focal pancreatic lesions by using EUS-guided fine-needle aspiration (EUS-FNA) for cytodiagnosis. METHODS: One hundred fourteen consecutive patients (mean age 61 years) with focal pancreatic masses, detected on CT, underwent EUS-FNA by using a linear-array echoendoscope and 22-gauge needles. RESULTS: Adequate specimens were obtained from 112 lesions. Carcinomas were identified in 68 cases (60.7%), 56 (50%) of pancreatic origin and 12 (10.7%) from distant primary tumors. The metastases were all located in the head and body of the pancreas and measured 1.8 to 4.0 cm. The echo-texture was heterogeneous or hypoechoic in all cases and resembled that of primary tumors. Six of the 12 patients with metastatic disease had a prior diagnosis of cancer (breast, 3; renal cell, 2; salivary gland, 1), 4 of them with a recurrence and 2 with a second carcinoma metastasizing to the pancreas. Six patients without a prior diagnosis of cancer had metastases from renal cell, colonic, ovarian, and esophageal carcinomas; one metastasis was from an unknown primary and another was from a malignant lymphoma. These findings influenced the therapeutic strategy in 8 patients who underwent nonsurgical palliation. There were no complications. CONCLUSIONS: Pancreatic metastasis is an important cause of focal pancreatic lesions, but the EUS features are not diagnostic. Simultaneous EUS-FNA allows cytodiagnosis and can have a decisive influence on the selection of appropriate therapeutic strategies.