A murine femoral ostectomy model with hardware exchange to assess antibiotic-impregnated spacers for implant-associated osteomyelitis.

Implant-associated osteomyelitis is a chronic infection that complicates orthopaedic surgeries. Once infected, 50 % of patients suffer treatment failure, resulting in high healthcare costs. While various small animal models have been developed to investigate the efficacy of prophylactic and therapeutic treatments, the minute scale of murine-model bone and hardware has been prohibitive for evaluating interventions with a complete implant exchange in the setting of an infected critical defect. To address this, the aim of the present study was to develop a murine femur model in which an initial mid-diaphyseal infection was established by surgical implantation of a titanium screw contaminated with bioluminescent Staphylococcus aureus (Xen36). 7 d after the infection was established, an ostectomy was performed to remove the middle segment (3 mm flanking the infected screw hole) and a bone-cement spacer, with or without impregnated gentamicin, was secured with a plate and screws to fix the septic segmental defect. Longitudinal bioluminescent imaging revealed a significant decrease in Xen36 growth following one-stage revision, with the antibiotic-impregnated spacer treated systemically with vancomycin (p < 0.05). This result was corroborated by a significant decrease in colony forming units (CFU) recovered from spacer, bone, soft tissue and hardware 12 d post-operative (p < 0.05). However, ~ 105 CFU/g Xen36 still persisted within the bone despite a clinical therapeutic regimen. Therefore, the model enables the investigation of new therapeutic strategies to improve upon the current standard of care in a mouse model of implant-associated osteomyelitis that employs reconstruction of a critical defect.

Evaluating the quality of research into a single prognostic biomarker: a systematic review and meta-analysis of 83 studies of C-reactive protein in stable coronary artery disease.

BACKGROUND: Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. METHODS AND FINDINGS: We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78-2.17), with substantial heterogeneity (I(2) = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39-1.96), I(2) = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13-1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57-0.66). CONCLUSION: Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research.

Detection of the beta s gene: an evaluation of the solubility test against automated chromatography and haemoglobin electrophoresis.

The solubility test is evaluated against automated high-performance liquid chromatography (HPLC) and haemoglobin (Hb) electrophoresis for its efficacy in screening for the beta s gene in population groups in remote areas. Blood samples taken from 3246 individuals from the tribal populations of the Dhule and Gadchiroli districts of Maharashtra state were analysed by all three methods. The solubility test detected 871 out of 932 individuals positive for the beta s gene by HPLC and Hb electrophoresis, and showed an overall sensitivity of 93.8% and specificity of 100%, with a positive predictive value of 100% and negative predictive value of 97.4%. Both HPLC and Hb electrophoresis are relatively expensive and not available in most laboratories in remote tribal areas, where the frequency of the beta s gene is very high. We conclude that the solubility test could be used for preliminary screening to determine the prevalence of the beta s gene in different population groups, particularly in remote areas where other facilities are not available. Individuals who test positive for the beta s gene by the solubility test require further investigation by either HPLC or Hb electrophoresis.

Splenomegaly in school children in a remote tribal area of Dhole district, Maharashtra.

Sickle-cell gene is known to protect against P. falciparum infection and provides a selective survival advantage in those areas where P. falciparum infection is endemic. This protection is not absolute and many other factors, inherited and acquired also contribute to the immunity against P. falciparum infection. We investigated incidence of splenomegaly and typical history of malaria in the past two years in apparently healthy school children in a tribal area in Dhole district of Maharashtra to see whether the incidence of malaria (splenomegaly and typical history) was different in children having sickle-cell trait to that of those who did not have this trait. A total of 480 school children were clinically examined for splenomegaly and history of typical malaria fever and/or blood slide positivity for malaria in the past two years. About 9.55 per cent of normal population had either splenomegaly or convincing history of malarial infection in the past two years which is not statistically different from the sickle-cell trait patients having evidence of past malaria (8.79 per cent; p > 0.05).

Serum amino acids and genesis of protein energy malnutrition.

Twenty four patients of classical marasmus and kwashiorkor along with equal number of healthy controls were selected for the study. Their serum amino acid patterns analysis revealed a mean ratio of glutamate to alanine in fasting samples of normal individuals to be 0.33, while it as 9.3 in kwashiorkor and 1.6 in marasmus. This differences in controls, kwashiorkor and marasmus was statistically significant. This observation may explain evolution of marasmus and kwashiorkor in children with similar diets. On the basis of the present observation it is postulated that in kwashiorkor, the conversion of pyruvate to alanine in presence of glutamate, an aminogroup donor does not proceed normally, resulting in accumulation of glutamate and low alanine. Thus the development of marasmus and kwashiorkor may not be related to dietary inadequacy alone but also to the transaminase function. This could be genetic in origin.

Incidence of hepatitis B (Australia) antigen among three communities in malarial Western Maharashtra, India.

The incidence of hepatitis B surface antigen (HBs Ag, Australia antigen) has been determined in three communities residing in an endemic malarial region in Western Maharashtra. A high incidence (5.92%) is found in the Marathas, a socially well-placed community, as compared to Nava-Buddhas (2.62%) and scheduled castes (1.63%) which are socially low-placed communities. A higher incidence (8.91%) among the Maratha females is a surprising observation as the males have been shown to be predominant among HBs Ag carriers in most world populations. A positive association of HBs Ag and the anthropometric traits, skinfold thickness of biceps and triceps, has been observed in the present study. The results demonstrate that other factor(s) (e.g. immunological) besides malarial infection may be involved in the maintenance of a high HBs Ag frequency in Western Maharashtra.

Red cell enzyme polymorphism: gene differentiation in three populations of Maharashtra, India.

Blood samples of 1,266 individuals were collected from three caste populations; Nava Budha (Mahar), Maratha, and a mixed group of Scheduled castes from each of three districts of Maharashtra, Nagpur, Akola, and Thane. The samples were tested for 12 enzyme systems, viz., AcPh, AK, CA-I, CA-II, Est-D, LDH, MDH, Oxidase, PGM-1, PGM-2, 6-PGD, and PHI. The gene frequencies of these loci are within the ranges observed among the Indian populations so far studied. The total differences in gene frequencies for each polymorphic locus was partitioned into three components, i.e., the differences between caste populations, the differences between regions, and the differences due to interaction between caste populations and regions. The results show that besides caste variation for two loci, Est-D and PGM-1, the gene frequencies for AK, Est-D, and G-6PD loci have different geographical distributions.

Effects of Hb types and G-6-PD deficiency on height, weight and skinfolds: a study on Indian population.

In this paper the effect of age, Hb types and G-6-PD deficiency on height, weight and skinfold thickness among 1720 subjects belonging to Nava-Budha, Maratha and a mixed Scheduled caste of Maharashtra, India, have been examined using two models of analysis of variance. In the first model the factors used for explaining the variation are communities, age, sex, Hb types based on the total sample. In the second model another factor, G-6-PD deficiency, was introduced and only the male sample (n = 852) was considered. The age groups (assessed), sex and communities contribute highly significantly to the variation in weight. Variation in communities, age and sex is highly significant for variations in height and the three skinfold measurements. The effect of variation in Hb types is more than random for height and significant for biceps and triceps thicknesses. G-6-PD deficiency causes significant variation in height and the three skinfold measurements.

Red cell glucose-6-phosphate dehydrogenase deficiency and haemoglobin variants among ten endogamous groups of Maharshtra and West Bengal.

Over 900 individuals from ten endogamous groups in the Indian states of Maharashtra and West Bengal were studied for G-6-PD deficiency and haemoglobin variants. The incidence of G-6-PD varied from nil to 17.3%, while that of Hb-S varied from nil to 22.3%. In general, the tribal populations of Maharashtra are characterized by the presence of a high incidence of both Hb-S and G-6-PD deficiency. The caste Hindus showed an absence of Hb-S and rather low G-6-PD deficiency. Immigrant Parsis possessed the highest incidence of G-6-PD deficiency (17.3%).

Placental enzyme polymorphism among Maharashtrians: alkaline phosphatase and lactate dehydrogenase.

The distribution of placental alkaline phosphatase and lactate dehydrogenase types in 635 placentas from various endogamous groups of Maharashtra have been studied by starch gel electrophoresis. In the case of alkaline phosphatase, 6 common phenotypes and 6 rare phenotypes (F2I1, S1S2, S2S3, I1S2, F1S2, F1I2) are encountered. The highest frequency of Pls1 allele (0.7394) and lowest frequency of Pli1 allele (0.0246) have been found in the Nava-Budha. 6 cases of Cal-1 and 5 cases of Cal-2 types of LDH variants have been observed in the total samples, and Muslims possess the highest frequency of Cal-1 types (3.64%). Population groups are compared with respect to Pl alleles.