Enamel defects and salivary methylmalonate in methylmalonic acidemia

Introduction and objective:  To characterize enamel defects in patients with methylmalonic acidemia (MMA) and cobalamin (cbl) metabolic disorders and to examine salivary methylmalonate levels in MMA.
Subjects and methods:  Teeth from patients ( n  = 32) were evaluated for enamel defects and compared with age- and gender-matched controls ( n  = 55). Complementation class ( mut , cblA , cblB and cblC ) and serum methylmalonate levels were examined. Primary teeth from two patients were examined by light and scanning electron microscopy and salivary methylmalonate levels from two patients were analyzed.
Results:  Enamel defects were significantly more prevalent per tooth in the affected group than the control group, across complementation types ( P  <   0.0001). The mut MMA subgroup had a significantly higher prevalence per individual of severe enamel defects than controls ( P  =   0.021), and those with enamel defects exhibited higher serum methylmalonate levels than those without ( P  = 0.017). Salivary methylmalonate levels were extremely elevated and were significantly higher than controls ( P  =   0.002). Primary teeth were free of enamel defects except for two cblC patients who exhibited severe enamel hypoplasia. One primary tooth from a cblC patient manifested markedly altered crystal microstructure.
Conclusion:  Enamel anomalies represent a phenotypic manifestation of MMA and cbl metabolic disorders. These findings suggest an association between enamel developmental pathology and disordered metabolism.     

Associations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: the Hvidoere Study Group on Childhood Diabetes

Background: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by differences in demographic, medical, or treatment variables. Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers. Methods: An observational cross‐sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants. Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory. All individuals with diabetes aged 11–18 yr (49.4% female), with duration of diabetes of at least 1 yr, were invited to participate. Individuals completed a self‐reported measure of quality of life (Diabetes Quality of Life ‐ Short Form [DQOL‐SF]), with well‐being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project. Results: Older participants (p < 0.001) and females (p < 0.001) reported less physical activity. Physical activity was associated with positive health perception (p < 0.001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis. The more time spent on the computer (r = 0.06; p < 0.05) and less time spent doing school homework (r = ?0.09; p < 0.001) were associated with higher HbA1c. Between centers, there were significant differences in reported physical activity (p < 0.001) and sedentary behavior (p < 0.001), but these differences did not account for center differences in metabolic control. Conclusions: Physical activity is strongly associated with psychological well‐being but has weak associations with metabolic control. Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences.     

Pharmacokinetics of recombinant activated factor VII in trauma patients with severe bleeding

Introduction  

Recombinant activated factor VII (rFVIIa) has been used as adjunctive therapy in trauma patients with severe bleeding. However, its pharmacokinetics profile remains unknown.     

Positional precautions in needle aspiration lung biopsy

The authors performed 308 needle aspiration biopsies of parenchymal lung masses. The patients were then placed with the puncture site down for a period of at least 1 hour or until air leakage stopped. Coughing, talking, and activity were restricted. Complications included pneumothorax, at a rate of 25.0%, and chest tube placement, at a rate of 1.6%. In a subgroup of 262 patients who required only one pleural puncture at biopsy, a pneumothorax rate of 17.9% and a chest tube placement rate of 0.4% were encountered. When compared with a similar series of 143 control patients, significant reductions in both pneumothorax rate (P = .0004) and chest tube placement rate (P = .0001) were demonstrated.     

p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.     

Predictors of general complications after video-assisted thoracoscopic surgical procedures

Background The video-assisted thoracoscopic approach has become the preferred method for many procedures due to the reduced trauma, complication rate and morbidity. The aim of this study was a risk evaluation of patients undergoing video-assisted thoracoscopic surgery (VATS) procedures. Methods Between 1991 and 2004, 1,008 patients were included in this single-center retrospective analysis. Risk assessment was performed using univariate and multivariate analysis. Results Multivariate analysis revealed that patient age (p = 0.003), the duration of the VATS procedure (p = 0.008), redo-VATS (p < 0.001) and conversion to open thoracotomy (p < 0.001) correlated significantly with the incidence of complications. Patients with immune deficiency following organ transplantation had the highest complication rate at 31.7%, which was significantly higher than for patients with either benign disease (p = 0.010) or malignant disease (p = 0.019). Conclusions VATS is a safe procedure, but extra caution is recommended for patients with a higher risk profile (age, redo-VATS, immune deficiency). Hauke Winter, Georgios Meimarakis authors contributed equally to the work     

Antigen expression and polymerase chain reaction amplification of mantle cell lymphomas

Flow immunophenotyping, DNA content analysis, and polymerase chain reaction (PCR) amplification for t(11;14) and t(14;18) were performed on 11 cases of typical mantle cell lymphoma (MCL), 5 cases of apparent MCL with proliferation centers (MCL-PC), and 5 cases of small lymphocytic lymphoma (SLL). Immunophenotyping showed IgM (P < .001), Ig light (P < .001), and CD20 (P < .001) expression to be more intense in MCL than in SLL. In MCL-PC, the mean intensity of IgM, Ig light chain, and CD20 expression was intermediate to the intensities observed in MCL and SLL. Furthermore, in contrast to SLL, all MCL and 4 of 5 MCL-PC cases exhibited stronger CD20 than CD19 expression. CD10 expression was not observed in any case and CD5 expression was present in all SLL and MCL-PC cases and in 9 of 11 MCL cases. DNA content analysis showed an S- phase fraction of less than 3% in all cases studied and, except for 1 MCL case, all lymphomas were DNA diploid. The t(11;14) breakpoint junctions involving the bcl-1 major translocation cluster were amplified by PCR in 4 of 11 (36%) MCL cases and in none of the MCL-PC or SLL cases. The t(14;18) involving the bcl-2 major breakpoint region was not identified by PCR in any case. We conclude that the level of expression of surface antigens and the rapid detection of t(11;14) by PCR are potentially useful for distinguishing MCL and SLL in the clinical setting. Further investigations as to the biologic relationship between MCL, MCL-PC, and SLL, and the utility of t(11;14) PCR in these lymphomas are warranted.     

Prophylactic Thyroidectomy in 75 Children and Adolescents with Hereditary Medullary Thyroid Carcinoma: German and Austrian Experience

RET proto-oncogene were found in 1993 to account for hereditary medullary thyroid carcinoma (MTC), surgeons obtained the opportunity to operate on patients prophylactically (i.e., at a clinically asymptomatic stage). Whether this approach is justified, and, if so, when and to which extent surgery should be performed remained to be clarified. A questionnaire was sent to all surgical departments in Germany and Austria. All of the patients who fulfilled the following criteria were enrolled: (1) preoperatively proved RET mutation; (2) age ≤ 20 years, (3) clinically asymptomatic thyroid C cell disease; and (4) TNM classification pT0–1/pNX/pN0–1/M0. Seventy-five patients were identified, and fifteen mutations were detected in six codons. Two adolescents had unilateral pheochromocytomas as part of the multiple endocrine neoplasia II (MEN-II) syndrome. No hyperparathyroidism was noted. All patients underwent total thyroidectomy, and 57 patients went on to have lymph node dissection. Parathyroid glands were removed in 34 patients and autografted in 11. Histopathology revealed MTC in 46 patients (61%, youngest 4 years); C cell hyperplasia (CCH) only was detected in the other 29 patients. Three patients had lymph node metastases (LNMs) the youngest being age 14 years. Calcitonin levels were not useful for differentiating between CCH and MTC, but in all patients with LNMs at least the stimulated calcitonin levels were assayed. After surgery, five patients (6.7%) sustained permanent hypoparathyroidism, and one patient (1.3%) had a permanent unilateral recurrent nerve palsy. All but three patients (96%) were biochemically cured. In conclusion, prophylactic total thyroidectomy can be performed safely in experienced centers. We recommend prophylactic total thyroidectomy at age 6. Cervicocentral lymph node dissection should be included when calcitonin levels are elevated or if patients are older than 10 years. Bilateral lymph node dissection should be performed if LNMs are suspected or when patients with elevated calcitonin are older than 15 years.