Improved aero-anaerobe recovery from infected prosthetic joint samples taken from 72 patients and collected intraoperatively in Rosenow's broth

INTRODUCTION: Recovery of the bacteria responsible for prosthetic joint infections is a major problem, which is due in part to the alteration of their ability to grow by storage during transportation to the laboratory. METHODS: In this prospective study, we assessed the benefit of inoculating an enriched liquid medium (Rosenow's broth) with intraoperative samples from 72 patients with prosthetic joint revision due to infection. We compared the results of culture of specimens collected in a standard receptacle with the results for specimens collected in Rosenow's broth. RESULTS AND INTERPRETATION: 144 samples were taken by each of the 2 collection methods for subsequent culture. Concordance between standard and Rosenow samples was observed for 52 of the 58 strains cultured on agar and for 42 of the 97 strains (p < 0.001) which grew only in liquid medium. Infection would not have been diagnosed in 26 patients (almost one-third of all patients) without combining sample collection in Rosenow's broth with standard collection. The bacteria that were not recovered from standard samples but which were recovered from those collected in Rosenow's broth included not only strict anaerobes, in particular Propionibacterium acnes, but also coagulase-negative staphylococci and streptococci.     

Local control of embryonal rhabdomyosarcoma in children by radiation therapy when combined with chemotherapy

Between August 1970 and March 1978, 58 patients with embryonal rhabdomyosarcoma (ERMS) were treated at the Radiation Therapy and Pediatric Departments of MSKCC. Chemotherapy was given according to T2 protocol (sequential administration of dactinomycin, vincristine, adriamycin and cyclophosphamide) or the T6 protocol (simultaneous administration of the previous drugs plus bleomycin, methotrexate and BCNU), which was introduced in 1975. The primary tumor or regional metastases were completely or partially removed in 43 patients, while biopsy was the only surgical procedure in 15. There were 41 boys and 17 girls, between 4 months and 19 years old. Eight had stage I-B disease, (microscopic residual), 16 stage II, (gross residual), 24 stage III, (node metastases), and 10 patients stage IV (disseminated tumors). Thirty-five patients were treated with T2 protocol, twenty-three with T6 protocol. Sixteen patients received more than 5000 rad, 21 had between 4000 and 5000 rad and 21 had less than 4000 rad. Forty-four patients are alive, 38 of them disease free. Local tumor control was not achieved in 14 patients, 10 of them were treated with T2 and 4 with T6. There were no local failures in patients treated for microscopic disease with doses between 3000 and 4000 rad. In patients treated for bulky tumors with 4000–5000 rad there were 3 failures out of 11 tumors and 3 out of 17 in those treated with higher doses. Radiation doses 3000–4000 rad were sufficient for local control of microscopic disease and 4000–5000 rad were as effective for control of bulky tumors as higher doses.     

Anterior segment parameters in Indian young adults using the Pentacam

To evaluate Pentacam-Scheimpflug imaging of anterior segment parameters in young Indian adults. In this prospective study 120 eyes of 60 normal Indian subjects with a mean age of 25.93 ± 6.58 years (range 17–39 years) were assessed by Pentacam. Main outcome measures were central corneal thickness (CCT), thinnest corneal thickness (TCT), apex corneal thickness (apex CT), peripheral corneal thickness at 2, 4, 6 and 8 mm from the thinnest point, location of the thinnest pachymetry, corneal volume (CV), anterior chamber depth (ACD), anterior chamber volume (ACV) and anterior chamber angle (ACA). Independent samples t test, dependent samples t test, ANOVA and Pearson correlation test were used for statistical analysis. The mean CCT, TCT, Apex CT and CV were 544.95 ± 35.42, 542 ± 35.19, 545.43 ± 35.45 and 61.64 ± 4.17 μm, respectively. There was a gradual increase in CT from the thinnest point to the periphery. The mean ACD was 3.14 ± 0.33 mm, mean ACV was 177.77 ± 29.02 mm³, and mean ACA was 39.36° ± 5.42°. There was no significant difference between CCT, TCT and Apex CT. A significant positive correlation was found between CCT and peripheral CT and also between anterior chamber parameters. TCT was mainly located in the inferotemporal and superotemporal zone. No significant difference was found in parameters between the right and left eyes and also between genders. This study provided information about a wide range of parameters in the anterior segment of healthy Indian eyes. These results could be helpful in assessment of patients with corneal diseases, glaucoma and screening for refractive surgeries.     

Mortality in individuals without known coronary artery disease but with discordance between the Framingham risk score and coronary artery calcium

A risk-management approach based on the Framingham risk score (FRS), although useful in preventing future coronary artery disease (CAD) events, is unable to identify a considerable portion of patients with CAD who need aggressive medical management. Coronary artery calcium (CAC), an anatomic marker of atherosclerosis, correlates well with presence and extent of CAD. This study investigated mortality risk associated with CAC score and FRS in subjects classified as "low risk" versus "high risk" based on FRS. In total 730 veterans without known CAD (61 ± 10 years old, 12.8% women) underwent measurement of their FRS and CAC. Subjects were classified as "discordant low risk" (DLR) if their FRS was <10% and CAC score was ≥ 100 (n = 108, 14.8%) or "discordant high risk" (DHR) if their FRS was ≥ 20% and CAC score was 0 (n = 104, 14.2%). Survival analysis was used to compare mortality rates associated with FRS and CAC in DLR versus DHR subjects. Mortality rate during the mean 48-month follow-up was 7.3% (n = 53) including 18.5% (n = 20) in the DLR group and 7.7% (n = 8) in the DHR group, respectively. Adjusted relative risks of mortality were 5.46 (95% confidence interval [CI] 2.44 to 12.20, p = 0.0001) in subjects with CAC score ≥ 100 compared to CAC score 0 and 1.35 (95% CI 1.01 to 4.32, p = 0.04) in subjects with FRS ≥ 20% compared to FRS <10%. Adjusted relative risk of mortality was 3.6 (95% CI 1.57 to 8.34, p = 0.003) for DLR compared to DHR. Areas under the receiver operator curve to predict mortality were 0.72 for FRS, 0.82 for CAC score, and 0.92 for the combination. In conclusion, the prognostic value of CAC to predict future mortality is superior to the FRS. Addition of CAC score to FRS significantly improves the identification and prognostication of patients without known CAD.     

Comparison of the effect of topiramate and sodium valporate in migraine prevention: a randomized blinded crossover study

BACKGROUND: Topiramate and sodium valporate are anticonvulsants, demonstrated to be effective as monotherapy for migraine prevention in placebo-controlled trials. OBJECTIVES: To compare the relative efficacy of topiramate and sodium valporate in the prevention of migraine. PATIENTS AND METHODS: A 24-week, randomized, double-blind, crossover, clinical trial was conducted from October 2003 to September 2004. A total of 64 patients with migraine headache, aged 14 to 57 years, were randomly allocated to the 2 treatment groups. The first group received topiramate (25 mg daily increment over 1 week to 50 mg) for a total of 2 months. The second group received sodium valporate (200 mg daily increment over 1 week to 400 mg) for 2 months. Response to treatment was assessed at 0, 1, 8, 16, and 24 weeks after start of therapy. RESULTS: Topiramate appeared to be equivalent in efficacy and safety to sodium valporate. A significant decrease in duration, monthly frequency, and intensity of headache occurred in both groups. Of the 32 patients treated with sodium valporate, the mean standard deviation (SD) of monthly migraine frequency decreased from 5.4 (2.5) to 4.0 (2.8) episode per month, headache intensity from 7.7 (1.2) to 5.8 (1.7) by visual analog scale (VAS), and headache duration from 21.3 (14.6) to 12.3 (10.7) hours (P < .001). Correspondingly, in the 32 patients treated with topiramate, the mean SD of monthly headache frequency decreased from 5.4 (2.0) to 3.2 (1.9) per month, headache intensity from 6.9 (1.2) to 3.7 (1.3), and headache duration from 17.3 (8.4) to 3.9 (2.7) hours (P < .001). CONCLUSION: This study demonstrates that treatment with topiramate and sodium valporate both significantly reduce migraine headache. This effect of topiramate and sodium valporate has previously been shown to reduce migraine headache, and we postulate that treatment with topiramate and sodium valporate may have a similar benefit.     

A haplotype framework for cystic fibrosis mutations in Iran

This is the first comprehensive profile of cystic fibrosis transmembrane conductance regulator (CFTR) mutations and their corresponding haplotypes in the Iranian population. All of the 27 CFTR exons of 60 unrelated Iranian CF patients were sequenced to identify disease-causing mutations. Eleven core haplotypes of CFTR were identified by genotyping six high-frequency simple nucleotide polymorphisms. The carrier frequency of 2.5 in 100 (1 in 40) was estimated from the frequency of heterozygous patients and suggests that contrary to popular belief, cystic fibrosis may be a common, under-diagnosed disease in Iran. A heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were identified on 64 (53%) of the 120 chromosomes. The five most common Iranian mutations together represented 37% of the expected mutated alleles. The most frequent mutation, DeltaF508 (p.F508del), represented only 16% of the expected mutated alleles. The next most frequent mutations were c.1677del2 (p.515fs) at 7.5%, c.4041C>G (p.N1303K) at 5.6%, c.2183AA>G (p.684fs) at 5%, and c.3661A>T (p.K1177X) at 2.5%. Three of the five most frequent Iranian mutations are not included in a commonly used panel of CF mutations, underscoring the importance of identifying geographic-specific mutations in this population.     

The significance of crystallographic texture of titanium alloy substrates on pre-osteoblast responses

The aim of this study is to investigate the effects of grain orientation in polycrystalline materials on cell-substrate interactions. Samples are prepared from rods and sheets of Ti-6Al-4V substrates with predominately two distinct crystallographic orientations. X-ray diffraction analysis indicates that 36% of the surfaces of rod samples consist of (1010) plane, while the predominant orientation in the surface of the sheet samples is (1120) plane (29%). Morphological studies and cell biological experiments including cell attachment, proliferation and differentiation are conducted using MC3T3 pre-osteoblast cells cultured on these two different samples. The number of attached cells on the rod Ti-(1010) samples (70% after 1 h and 50% after 2 h) is higher than on the sheet Ti-(1120) samples. Cell proliferation after 3 days is also significantly higher on the Ti-(1010) samples. Alkaline phosphatase activity, however, shows no significant difference between the two samples. Scanning electron microscopy (SEM) analysis of MC3T3 cells grown on samples with different crystallographic texture demonstrate significant differences in morphology with respect to attachment and growth pattern. This study shows that crystal orientation of the substrate can influence cell responses and, therefore, substrate engineering can be used to improve and control cell-substrate interactions.     

Dexamethasone mimics the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia and compensates for morphine induced changes in G proteins gene expression

It is previously reported that the HPA axis plays role in the inhibitory effect of pain on tolerance development to analgesic effect of opioids. The present study was designed to investigate whether the chronic co-administration of dexamethasone as a glucocorticoid is also able to prevent or reverse analgesic tolerance to morphine and to compare the expression of G(alphai/o) and G(beta) subunits of G proteins in the context of chronic dexamethasone, development of morphine tolerance and their combination. Analgesic tolerance to morphine was induced by chronic intraperitoneally (i.p.) administration of morphine 20 mg/kg to male Wistar rats weighing 200-240 g within 4 consecutive days and analgesia was assessed using tail-flick test. Chronic dexamethasone was applied using 4 daily i.p. injections. Lumbar spinal tissues were assayed for the expression of G(alphai/o) and G(beta) proteins using "semiquantitative PCR" normalized to beta-actin gene expression. Results showed that chronic administration of dexamethasone could reduce and reverse the development of tolerance in rats that received chronic i.p. injections of morphine. Chronic administration of dexamethasone significantly increased the expression of G(alphai/o), while chronic administration of morphine did not change its expression. The expression of G(beta), however, was increased after the chronic administration of morphine, but did not change after the administration of chronic dexamethasone. None of these increases were observed when morphine and dexamethasone were co-administered. We conclude that the development of tolerance to analgesic effect of morphine could be prevented and reversed by dexamethasone co-administration. The increase in G(alphai/o) genes expression produced by chronic dexamethasone may facilitate the opioid signaling pathway and compensate for morphine-induced tolerance.     

Establishment of the cumulative margin of exposure for a group of polychlorinated biphenyl (PCB) congeners using an improved approach that accounts for both variability and uncertainty

In this study, the cumulative margin of exposure (MOE) was estimated for a group of polychlorinated biphenyls (PCBs) based on reduction of hepatic retinoids as a mode-of-action relevant toxicological endpoint. The MOE was defined as the ratio between a reference dose, derived using the benchmark dose (BMD) approach, and the estimated human dietary PCB exposure. A distribution for the cumulative MOE was established, taking into account inter- and intra-individual variability as well as uncertainty in data measurements. The cumulative MOE reflected mainly the MOE for PCB 126; other PCB congeners had little contribution to the cumulative exposure and MOE. The median of the 0.1st percentile for the cumulative MOE was about 20 for women; depending on the percentile, cumulative MOE was 2–4 times higher for men compared to women. Furthermore, a relative potency factor (RPF) based approach was compared to an RPF-free approach for estimating the cumulative MOE. The RPF-free approach more completely accounts for variability and uncertainty but is more data intensive than the RPF-based approach, which can be more easily implemented in practice and allows for a use of historical data on RPFs. Consideration of the discussed approaches may contribute to improving cumulative health risk assessments.     

Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers

Substantial variation exists in response to standard doses of codeine ranging from poor analgesia to life-threatening central nervous system (CNS) depression. We aimed to discover the genetic markers predictive of codeine toxicity by evaluating the associations between polymorphisms in cytochrome P450 2D6 (CYP2D6), UDP-glucuronosyltransferase 2B7 (UGT2B7), P-glycoprotein (ABCB1), mu-opioid receptor (OPRM1), and catechol O-methyltransferase (COMT) genes, which are involved in the codeine pathway, and the symptoms of CNS depression in 111 breastfeeding mothers using codeine and their infants. A genetic model combining the maternal risk genotypes in CYP2D6 and ABCB1 was significantly associated with the adverse outcomes in infants (odds ratio (OR) 2.68; 95% confidence interval (CI) 1.61-4.48; P(trend) = 0.0002) and their mothers (OR 2.74; 95% CI 1.55-4.84; P(trend) = 0.0005). A novel combination of the genetic and clinical factors predicted 87% of the infant and maternal CNS depression cases with a sensitivity of 80% and a specificity of 87%. Genetic markers can be used to improve the outcome of codeine therapy and are also probably important for other opioids sharing common biotransformation pathways.