Cost-effectiveness in establishing hemophilia carrier detection and prenatal diagnosis services in a developing country with limited health resources

The cost-effectiveness of carrier detection and prenatal diagnosis for hemophilia at the International Hemophilia Training Center, Bangkok, Thailand was studied. From 1991 to 2002, 209 females from 124 families with hemophilia A and B were included. There were 180 hemophilia A carriers and 29 hemophilia B carriers which could be classified into 78 obligate and 131 possible carriers. The phenotypic analysis for possible carriers involved the determination of levels of factor VIII or IX clotting activity (FVIII:C, FIX:C) and the ratio of FVIII:C and von Willebrand factor antigen. The result revealed that 49 females (37.4%) were diagnosed as carriers, 65 females (49.6%) were normal and 17 females (13%) were undetermined. Additional genotypic analysis was provided to 46 families with 74 females with obligate, proven or undetermined carriers within the reproductive life. The polymorphisms associated with factor VIII and IX genes were used including Bcl I for the factor VIII gene and combined use of Mse I, Sal I, Nru I, Hha I and Dde I for the factor IX gene. The informative rate was 59.4% (44/74). Consequently, 12 prenatal diagnoses for fetus at risk were performed. Sex determination was initially determined and followed by the diagnosis of hemophilia through informative gene tracking and/or the measurement of fetal levels of FVIII:C or FIX:C. The result revealed that 3 male fetuses were affected. The total cost of carrier detection and prenatal diagnosis that the families had to pay in the government hospital was 238,600 Baht (US dollars 5,965). It was compared to the estimated cost of minimal replacement therapy using lyophilized cryoprecipitate for the survival time of 30 years in one patient with hemophilia of 1,012,500 Baht (US dollars 25,312.5). The cost of prevention was much less than the replacement therapy. In conclusion, it is cost-effective to establish the service for carrier detection and prenatal diagnosis for hemophilia especially in developing countries with limited health resources.     

Lipid peroxidation,glutathione, vitamin E,and antioxidant enzymes in synovial fluid from patients with osteoarthritis

Aim: To compare levels of lipid peroxidation and antioxidants in synovial fluid from primary knee osteoarthritis (OA) patients with severe cartilage damage undergoing total knee replacement with those in the synovial fluid from injured knee joint patients with intact cartilage undergoing knee arthroscopy. Methods: Thirty‐two OA patients and 10 injured knee joint patients were recruited. Lipid peroxidation (thiobarbituric acid reactive substances [TBARs]), iron and glutathione (GSH) were measured using a colorimetric method. Vitamin E was measured with high‐performance liquid chromatography (HPLC). Activities of antioxidant enzymes (glutathione peroxidase [GPx], superoxide dismutase [SOD]) were analyzed with the use of a kinetic method. Results: TBARs, iron and GSH levels in synovial fluid were not significantly different between OA patients and injured knee joint patients. Antioxidant enzymes such as GPx and SOD activities also indicated no significant difference. Only vitamin E level was significantly lower in the synovial fluid of OA patients than in that of the injured knee joint patients. Conclusions: Oxidative stress may have a role in pathogenesis of knee osteoarthritis. Vitamin E supplementation may have a role in the management of patients.     

Genotypes and phenotypes of protein S deficiency in Thai children with thromboembolism

The prevalence of protein S (PS) deficiency in Asian patients with venous thromboembolism is around 8–30%, higher than that in Caucasian populations. The present study reports the genotypes (including one novel mutation) and phenotypes of children with PS deficiency at a tertiary care institute. A total of six patients were included, three with arterial ischemic stroke, two with cerebral venous sinus thrombosis, and one with deep vein thrombosis. PS mutations were identified in four patients: p.R355C, p.G336D, p.E67A, and p.N188KfsX9. p.N188KfsX9 is a novel mutation with less than 20% PS activity noted in heterozygotes.     

Lipoprotein(a) and the risk of thromboembolism in Thai children

High lipoprotein(a) [Lp(a)] level was identified as a risk factor of both venous and arterial thromboembolism (TE), especially in Caucasian children. The Lp(a) level is affected by apo(a) gene. The genetic polymorphisms that associated with Lp(a) level are the size of apo(a) gene, pentanucleotide repeat (TTTTA )_n and + 93 C/T at promoter region. The increasing size of apo(a) gene, more than 8 pentanucleotide repeats and + 93 C > T polymorphisms are associated with low level of Lp(a) in African and Caucasian populations. This cross - sectional, case control study, aims to identify the association of Lp(a) level and the risk for TE in Thai children. Forty-nine patients and 116 healthy children were enrolled. Mean ± SD for age of patients and controls were 7.6 ± 4.7 and 11.2 ± 1.7 years, with female:male ratios of 1:1.2 and 1.8:1, respectively. The median Lp(a) levels in patients was 8.2 (0-87.3) mg/dL and 7.9 (0-74.9) mg/dL in controls, which were not statistically different, P = 0.65. The frequencies of 8 pentanucleotide repeats and + 93 C/T were different compared to Caucasian and African populations but similar to Chinese population. However, both polymorphisms did not affect the level of Lp(a).     

Quantifying the natural history of biofilm formation in vivo during the establishment of chronic implant‐associated Staphylococcus aureus osteomyelitis in mice to identify critical pathogen and host factors

While it is well known that Staphylococcus aureus establishes chronic implant‐associated osteomyelitis by generating and persisting in biofilm, research to elucidate pathogen, and host specific factors controlling this process has been limited due to the absence of a quantitative in vivo model. To address this, we developed a murine tibia implant model with ex vivo region of interest (ROI) imaging analysis by scanning electron microscopy (SEM). Implants were coated with Staphylococcus aureus strains (SH1000, UAMS‐1, USA300LAC) with distinct in vitro biofilm phenotypes, were used to infect C57BL/6 or Balb/c mice. In contrast to their in vitro biofilm phenotype, results from all bacteria strains in vivo were similar, and demonstrated that biofilm on the implant is established within the first day, followed by a robust proliferation phase peaking on Day 3 in Balb/c mice, and persisting until Day 7 in C57BL/6 mice, as detected by SEM and bioluminescent imaging. Biofilm formation peaked at Day 14, covering ～40% of the ROI coincident with massive agr‐dependent bacterial emigration, as evidenced by large numbers of empty lacunae with few residual bacteria, which were largely culture negative (80%) and PCR positive (87.5%), supporting the clinical relevance of this implant model. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1311–1319, 2015.     

Atlantoaxial transarticular screw fixation and posterior fusion using polyester cable: a 10-year experience

Purpose

To retrospective review the clinical outcomes of the modified operative technique using a polyester suture material (Ethibond* Excel) for atlantoaxial transarticular screw fixation and posterior fusion.

Methods

The retrospective reviews were conducted from 2002 to 2012. The patient’s medical record reviews included demographic data, cause of atlantoaxial instability, orthopedic and surgical history, clinical presentation, radiographic finding including plain radiography, complications, operative detail, and outcome of treatment. Fusion of C1–C2 was defined as either graft consolidation or absence of C1–C2 movement on lateral flexion–extension radiograph.

Results

Twenty-three patients demonstrated clinical and radiographic evidence of atlantoaxial instability (13 men and 10 women, with a mean age of 42 years). Majority of atlantoaxial instability was caused by trauma. Most common clinical symptom was neck pain with or without cervical myelopathy. Bilateral screws were placed in 18 of the 23 patients. Five patients underwent placement of unilateral screws. The 13 patients were inserted by screws with diameter 4.0 mm. The means screw length was 40.33 mm. The means of operative time and estimated blood loss were 3.6 h and 234 ml, respectively. The mean of follow-up duration was 18 months. All 41 screws were positioned satisfactorily in C1 lateral mass. All 23 patients achieved fusion (100 % fusion rate). After a period of follow-up, 9 of the 10 neurological deficit patients had completely recovered.

Conclusions

We concluded that the atlantoaxial transarticular screw fixation and posterior fusion using polyester cable can be used for C1–2 fusion with a high fusion rate and less complications in various cases.