Correspondence between theoretical models and dual energy X-ray absorptiometry measurements of femoral cross-sectional growth during adolescence

We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9–26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.     

The effect of oral anticoagulant therapy on aptt results from a bedside coagulation monitor

Objective. The Ciba Corning 512 coagulation monitor (CC512) can be used to monitor heparin therapy by performing an activated partial thromboplastin time (APTT) at the patient’s bedside. This study was designed to compare the CC512 results to results using the laboratory system. The relative sensitivities of both systems to the effect of oral anticoagulant therapy also was investigated.Methods. Activated partial thromboplastin times were performed with both the CC512 and laboratory system on 74 specimens from patients receiving IV heparin therapy, and on 14 specimens from patients on warfarin only. Heparin assays were performed on 43 of the specimens from the heparinized patients.Results. When a patient was receiving heparin only, the APTT results of the CC512 proved to be similar to existing laboratory methods. The CC512 APTT results of patients on warfarin only were markedly prolonged, whereas the laboratory APTTs were only slightly affected.Conclusion. The CC512 results were comparable to the laboratory system. However, the CC512 APTT was more sensitive to the effect of warfarin than the laboratory APTT system used in this study. CC512 APTT results on a patient receiving both oral and intravenous anticoagulation could be misleading. The authors wish to thank D.M. O’Brien and the nursing staff of the Coronary Care Unit for providing CC512 data and laboratory specimens, and I. Smith for the preparation of graphics. We also wish to thank Australian Diagnostics Corporation, which provided consumables.     

A high performance liquid chromatography method for the detection of brodifacoum in serum

A procedure for the detection of brodifacoum (BDF) in serum was developed. Extraction of BDF was achieved by acidification of 2 ml of serum with 1 ml of 1.5% acetic acid followed by dual extractions with 10 ml diethyl ether and ether: acetonitrile [1:1]. In spiking experiments, 68 +/- 3, 61 +/- 4 and 65 +/- 5% of added BDF was recovered from serum containing 1000, 100 and 25 ng BDF/ml, respectively. Two high performance liquid chromatography solvent systems were used for chromatographic separation (A: 1.5% acetic acid, pH 4.5: acetonitrile [1:2] with 1% dibutylamine; and B:O.2 M tris(hydroxymethyl)aminomethane, pH 7.5:acetonitrile [1:3]). Detection limits were 75 and 3 ng BDF/ml of serum using ultraviolet absorption (254 nm) and fluorescence measurement (313 nm excitation, 375 nm emission), respectively. This method has been used successfully to monitor serum concentrations of BDF in experimental and field cases of exposure.     

Cardiac Surgery in Nonagenarians

A bstract Objectives and Background : The purpose of this study was to document our initial experience with patients 90 years of age and older and to determine whether cardiac surgery is justified in this age group. Cardiac surgery in octogenarians has proven to be a successful and worthwhile procedure. A small group of nonagenarians with severe coronary artery disease (CAD) and aortic valve disease refractory to medical therapy have been considered for surgery. Methods : Fourteen patients aged 90 or more underwent cardiac surgery for symptomatic CAD or aortic valvular disease refractory to medical therapy. Eight patients underwent isolated coronary artery bypass grafting (CABG) and six patients underwent aortic valve replacement (AVR). All patients were in NYHA Class IV preoperatively. Results : Hospital mortality occurred in one patient (7%). Hospital morbidity occurred in 10 patients (71%) and included 7 cardiac, 5 neurological, 1 gastrointestinal, 1 infectious, and 1 pulmonary event. All survivors left the hospital symptomatically improved. The mean length of stay was 26 days. Four CABG patients went on to die at a mean of 2 years and 2 months, and 3 remain alive at a mean of 2 years and 4 months. Three AVR patients expired at a mean of 3 years and 4 months, and 3 remain alive at 4 years and 1 month. Conclusions : Cardiac surgery in carefully selected nonagenarians is justified and can be performed with acceptable results.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.