Blood loss and contributing factors in femoral fracture surgery

Background

Substantial blood losses frequently accompany orthopedic procedures.

Methods

We prospectively noted peri-operative hemoglobin changes in 93 patients undergoing surgery for femoral fracture with an aim of establishing blood loss and related factors.

Results

The mean total blood loss assessed 72 hours after the surgical procedure was 3.31 (SD 1.56) units of whole blood. A multiple regression analysis revealed diathermy use and a simple fracture pattern as significant factors in reducing blood loss (p<0.01).

Conclusions

Open intramedullary fixation of femur fractures leads to considerable peri-operative blood loss. This is can be reduced by use of diathermy during surgery.     

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator ( AIRE ) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1–7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.     

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.      

Protective effect of aminoguanidine against cardiovascular toxicity of chronic doxorubicin treatment in rats

The cardiotoxicity-induced by chronic treatment of doxorubicin have recently be attributed to free radical formation and/or release of nitric oxide. In the present study, an already established rat model of doxorubicin -induced cardiotoxicity was used. Doxorubicin in a total cumulative dose of 15 mgkg(-1) I.P. given in six equal injections over two week period was administered. After three weeks of doxorubicin administration, the blood pressure, serum lactate dehydrogenase, lipid peroxides, asites fluid and mortality rate were significantly increased. Doxorubicin-induced cardiotoxicity was further confirmed by examining the histopathology of heart sections. Myocardial fibres necrosis with prominent acute inflammatory cells were observed in rats hearts treated with doxorubicin. Aminoguanidine, an inhibitor of nitric oxide synthase, 100 mgkg(-1) injected every other day for two week was given concurrently with doxorubicin. Aminoguanidine given concurrently with doxorubicin return blood pressure, lactate dehydrogenase and lipid peroxides to normal control values. Furthermore, aminoguanidine reduces the mortality rate, ascites fluid formation- induced by doxorubicin and improved the histopathology of rats hearts treated with doxorubicin. In conclusion, inhibition of nitric oxide formation may be beneficial in protecting rat hearts against doxorubicin- induced cardiotoxicity.     

The uncemented isoelastic/isotitan total hip arthroplasty. A 10-15 years follow-up with bone mineral density evaluation

The present study analyses the long-term outcome of isoelastic hip prostheses and their influence on the extent of periprosthetic bone remodeling. Ninety-two patients (102 hips) with Isoelastic/Isotitan uncemented total hip arthroplasty were evaluated after an average of 13.4 years. The average age of patients at surgery was 42.5 years. The clinical outcome was assessed based on the Harris hip score, complications and thigh pain. Bone mineral density (BMD) of the proximal femur in the seven Gruen zones was evaluated by dual-energy X-ray absorptiometry (DEXA) scans with the contralateral hip serving as a control. The average Harris hip score at the most recent follow-up was 72 points, with 72 hips (70%) rating completely pain free. Eight stems required revision whereas none of the cups showed any evidence of loosening. The change in the mean BMD values between the femora on the operated side and the contralateral femora averaged 15% for all zones Although the isoelastic stems are no longer used owing to their high loosening rate, it appears that this prosthesis preserved periprosthetic bone better than reported for cemented or uncemented metallic implants. Besides, the provision of a titanium coating on the isoelastic stem, comparable to that on the RM cup, would presumably have improved its long-term fixation by encouraging bony ongrowth.