Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty?

OBJECTIVES: We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. METHODS: For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood. RESULTS: A CoCr JFR > 1 showed a specificity of 83% (77% to 88%) and sensitivity of 63% (55% to 70%) for the detection of severe ALVAL and/or SOTP. In patients with CoCr JFRs > 1, the median blood Cr to serum Cr ratio was 0.99, compared with 0.71 in patients with CoCr JFRs < 1 (p < 0.001). Regression analysis demonstrated that the blood Cr to serum Cr value was positively associated with the JF Co concentration (p = 0.011) and inversely related to the JF Cr concentration (p < 0.001). CONCLUSION: Elevations in CoCr JFRs are associated with adverse biological (severe ALVAL) or tribocorrosive processes (SOTP). Comparison of serum Cr with blood Cr concentrations may be a useful additional clinical tool to help to identify these conditions.Cite this article: D. J. Langton, S. Natu, C. F. Harrington, J. G. Bowsher, A. V. F. Nargol. Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty? Bone Joint Res 2019;8:146-155. DOI: 10.1302/2046-3758.83.BJR-2018-0049.R1.

Diagnostic guidelines for the histological particle algorithm in the periprosthetic neo-synovial tissue.

BACKGROUND: The identification of implant wear particles and non-implant related particles and the characterization of the inflammatory responses in the periprosthetic neo-synovial membrane, bone, and the synovial-like interface membrane (SLIM) play an important role for the evaluation of clinical outcome, correlation with radiological and implant retrieval studies, and understanding of the biological pathways contributing to implant failures in joint arthroplasty. The purpose of this study is to present a comprehensive histological particle algorithm (HPA) as a practical guide to particle identification at routine light microscopy examination. METHODS: The cases used for particle analysis were selected retrospectively from the archives of two institutions and were representative of the implant wear and non-implant related particle spectrum. All particle categories were described according to their size, shape, colour and properties observed at light microscopy, under polarized light, and after histochemical stains when necessary. A unified range of particle size, defined as a measure of length only, is proposed for the wear particles with five classes for polyethylene (PE) particles and four classes for conventional and corrosion metallic particles and ceramic particles. RESULTS: All implant wear and non-implant related particles were described and illustrated in detail by category. A particle scoring system for the periprosthetic tissue/SLIM is proposed as follows: 1) Wear particle identification at light microscopy with a two-step analysis at low (× 25, × 40, and × 100) and high magnification (× 200 and × 400); 2) Identification of the predominant wear particle type with size determination; 3) The presence of non-implant related endogenous and/or foreign particles. A guide for a comprehensive pathology report is also provided with sections for macroscopic and microscopic description, and diagnosis. CONCLUSIONS: The HPA should be considered a standard for the histological analysis of periprosthetic neo-synovial membrane, bone, and SLIM. It provides a basic, standardized tool for the identification of implant wear and non-implant related particles at routine light microscopy examination and aims at reducing intra-observer and inter-observer variability to provide a common platform for multicentric implant retrieval/radiological/histological studies and valuable data for the risk assessment of implant performance for regional and national implant registries and government agencies.

Aseptic lymphocyte-dominated vasculitis-associated lesions are related to changes in metal ion handling in the joint capsules of metal-on-metal hip arthroplasties.

OBJECTIVES: We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL). PATIENTS AND METHODS: We examined the influence of the ALVAL grade on synovial fluid Co and Cr concentrations following adjustment for patient and device variables, including volumetric wear rates. Initially restricting the analysis to include only patients with one MoM hip resurfacing device, we performed multiple regression analyses of prospectively collected data. We then repeated the same statistical approach using results from a larger cohort with different MoM designs, including total hip arthroplasties. RESULTS: In the resurfacing cohort (n = 76), the statistical modelling indicated that the presence of severe ALVAL and a large fluid collection were associated with greater joint fluid Co concentrations after adjustment for volumetric wear rates (p = 0.005). These findings were replicated in the mixed implant group (n = 178), where the presence of severe ALVAL and a large fluid collection were significantly associated with greater fluid Co concentrations (p < 0.001). CONCLUSION: The development of severe ALVAL is associated with elevations in metal ion concentrations far beyond those expected from the volumetric loss from the prosthetic surfaces. This finding may aid the understanding of the sequence of events leading to soft-tissue reactions following MoM hip arthroplasties.Cite this article: D. J. Langton, R. P. Sidaginamale, T. J. Joyce, J. G. Bowsher, J. P. Holland, D. Deehan, A. V. F. Nargol, S. Natu. Aseptic lymphocyte-dominated vasculitis-associated lesions are related to changes in metal ion handling in the joint capsules of metal-on-metal hip arthroplasties. Bone Joint Res 2018;7:388-396. DOI: 10.1302/2046-3758.76.BJR-2018-0037.

The clinical implications of metal debris release from the taper junctions and bearing surfaces of metal-on-metal hip arthroplasty: joint fluid and blood metal ion concentrations.

AIMS: We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on-metal (MoM) hip arthroplasty. Some reports have suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces. PATIENTS AND METHODS: We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions. RESULTS: The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces. CONCLUSION: The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925-33.

Immunoprotective effect of lentinan in combination with miltefosine on Leishmania-infected J-774A.1 macrophages.

Rejuvenation of deteriorated host immune functions is imperative for successful annihilation of Leishmania parasites. The use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. We herein investigated the immunostimulatory potency of a ß-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on Leishmania-infected J-774A.1 macrophages. Our study shows that infected macrophages when stimulated with 2.5 µg/mL and above concentrations of lentinan secreted significant amount of host-protective molecules. The in vitro interaction between lentinan and miltefosine showed some synergy (mean sum of fractional inhibitory concentration [mean ∑FIC] 0.87) at IC50 level. Lentinan (2.5 µg/mL) plus low-dose miltefosine (2 µM) displayed heightened level of pro-inflammatory cytokines, IL-12 (13.6-fold) and TNF-α (6.8-fold) along with nitric oxide (7.2-fold higher) when compared with infected control. In combination group, we also observed remarkably (P<.001) suppressed levels of anti-inflammatory cytokines, IL-10 and TGF-ß, than that of untreated macrophages. Additionally, in comparison with infected group, we observed significant induction in phagocytic activity of macrophages in combination with treated group. Collectively, these findings emphasize the immunostimulatory effect of lentinan alone and in combination with low dose of miltefosine against Leishmania donovani.

Prediction of Poor Ovarian response by Biochemical and Biophysical Markers: A Logistic Regression Model.

OBJECTIVES: To study correlation between ovarian reserve with biophysical markers (antral follicle count and ovarian volume) and biochemical markers (S. FSH, S. Inhibin B, and S. AMH) and use these markers to predict poor ovarian response to ovarian induction. METHODS: This is a prospective observational study. One hundred infertile women attending the Obst & Gynae Dept, KGMU were recruited. Blood samples were collected on day 2/day 3 for assessment of S. FSH, S. Inhibin B, and S. AMH and TVS were done for antral follicle count and ovarian volume. Clomephene citrate 100 mg 1OD was given from day 2 to 6, and patients were followed up with serial USG measurements. The numbers of dominant follicles (> or = 14 mm) at the time of hCG administration were counted. Patients with <3 follicles in the 1st cycle were subjected to the 2nd cycle of clomephene 100 mg 1OD from day 2 to day 6 with Inj HMG 150 IU given i.m. starting from day 8 and every alternate day until at least one leading follicle attained ≥18 mm. Development of <3 follicles at end of the 2nd cycle was considered as poor response. RESULTS: Univariate analyses showed that s. inhibin B presented the highest (ROCAUC = 0.862) discriminating potential for predicting poor ovarian response, In multivariate logistic regression model, the variables age, FSH, AMH, INHIBIN B, and AFC remained significant, and the resulting model showed a predicted accuracy of 84.4 %. CONCLUSION: A derived multimarker computation by a logistic regression model for predicting poor ovarian response was obtained through this study. Thus, potential poor responders could be identified easily, and appropriate ovarian stimulation protocol could be devised for such pts.

Tentpole technique for bone regeneration in vertically deficient alveolar ridges: A review.

BACKGROUND AND OBJECTIVES: Vertical augmentation is necessary in cases of extensive resorption of alveolar ridge for dental implants placement and esthetic prosthetic rehabilitation. Several surgical techniques have been used to increase bone height including distraction osteogenesis, and particulate or block bone graft. This study was done to describe the evolution of "tentpole technique" and to review the literature related to this technique and thus evaluate its effectiveness to augment large vertical alveolar ridge defects for implant placement. MATERIAL AND METHODS: The evidence was obtained by PubMed and Google search using key words: tentpole technique, ridge resorption, and alveolar ridge augmentation . The years of search included from 2002 till 2013. RESULTS: The technique was described as effective on review of outcome of existing studies. It was found that considerable and stable increase in alveolar ridge height was achieved using tentpole technique. CONCLUSIONS: Tenting of periosteum and soft tissue matrix maintains space and enhances the effectiveness of bone graft. This technique offers predictable functional and esthetic reconstruction of large vertical alveolar defects.

Leptin augments protective immune responses in murine macrophages and enhances potential of miltefosine against experimental visceral leishmaniasis.

Adverse side effects and drug resistance issues are the two most important drawbacks which influence the widespread use of existing antileishmanial drugs. Use of immune stimulating agent with standard antileishmanial might be helpful to minimize the toxic effect of drug, shorten the dose regimen and delay the emergence of resistance. In the present study, we explored the in vitro immunomodulatory potential of an immunomodulator, leptin with lower concentration of standard drug, miltefosine. The level of Th1/Th2 cytokines, production of nitric oxide and reactive oxygen species and phagocytic activity was assessed by ELISA, Griess reaction and flow cytometric analysis, respectively. Leptin at a concentration of 15µg/mL showed heightened level of Th1 cytokines and nitric oxide generation from murine macrophages (J-774A.1 cells). Leptin (15µg/mL) also reduces the effective concentration of miltefosine by 2-folds from 7.5µM to 3.7µM. When given in conjunction with lower concentration of miltefosine (4µM), leptin (15µg/mL) significantly (***p<0.001) elevated the level of IL-12 (7.7 fold), TNF-α (8.1 fold) and nitric oxide (6.6 fold) along with markedly (***p<0.001) suppressed level of IL-10 and TGF-ß when compared with untreated infected macrophages. Leptin plus miltefosine also induces the phagocytic ability (**p<0.01) of macrophages in comparison to leptin alone and miltefosine alone treated groups. These finding illustrate that leptin activates host macrophages to generate protective immune response for the successful elimination of Leishmania parasite at lower concentration of miltefosine and has potential for further exploration in experimental animal model of visceral leishmaniasis (VL).

Elucidation of dietary risk factors in osteoarthritis knee­a case-control study.

BACKGROUND AND OBJECTIVE: Nutritional imbalance, combined with endocrine abnormalities, may be involved in the pathogenesis of osteoarthritis (OA). This study was conducted to determine the association of OA with dietary factors, such as quantity and quality of nutrient intake. METHODS: This case-control study enrolled 180 knee osteoarthritis (KOA) subjects who met the American College of Rheumatology definition of KOA, with an equal number of matched controls. Outcome measures, such as dietary nutrient intake and its frequency, were recorded using a food frequency questionnaire. RESULTS: Compared to controls, cases were older individuals with a higher body mass index (BMI). Physical activity scores were lower in female cases compared to male cases and controls. A significantly higher intake of phosphorus and fat was observed in overall cases (fat in females only). A significantly lower intake of vitamin C and vitamin D was observed in overall cases and the significance of vitamin D persisted on gender-wise bifurcation. On multiple logistic regression analysis, the intake of vitamin D (odds ratio [OR] = 0.79) and vitamin C (OR = 0.97) was inversely associated with the presence of KOA in the observation group, especially in females. Generally, the intake of food servings/day, green leafy vegetables (GLVs), and fats/oils was higher, whereas the intake of fruits, milk/milk products, and meat/poultry was lower in cases compared to controls. CONCLUSION: Low intake of vitamin D and vitamin C is a possible risk factor for KOA. Certain food groups, such as fruits, milk/milk products, and meat/poultry are beneficial for KOA. Further studies are needed to elucidate the associations between diet and KOA.

Revised histopathological consensus classification of joint implant related pathology.

This extended classification of joint implant related pathology is a practical histopathologic classification based on defined morphological criteria covering the complete spectrum of pathohistologic changes in periprosthetic tissues. These changes may occur as a consequence of endoprosthetic replacement of large joints and may lead to a reduction in the prosthesis survival rate. We describe the established consensus classification of the periprosthetic membrane, in which aseptic and septic prosthetic loosening can be subdivided into four histological types, as well as histopathological criteria for additional significant pathologies including endoprosthetic-associated arthrofibrosis, particle-induced immunological, inflammatory and toxic mechanisms (adverse reactions), and bone tissue pathologies. These characteristic tissue alterations and their relationships are summarized in the extended classification. Since particle heterogeneity in periprosthetic tissue is high and particle identification is a necessary part of diagnosis, the identification of different types of particles is described in the histopathological particle algorithm. The morphological qualities of prosthetic material particles and the demarcation between abrasion and non-abrasion endogenous particles are also summarized. This feasible classification which is based on low cost standard tissue processing and examination and on well-defined diagnostic criteria is a solid platform for the histological diagnosis of implant associated pathologies providing a stable and reproducible tool for the surgical pathologist. Since this classification is suitable for standardized histopathological diagnostics, it might also provide a useful data set for joint arthroplasty registers, particularly for registers based on so-called routine data.

Evaluation of MC4R [rs17782313, rs17700633], AGRP [rs3412352] and POMC [rs1042571] Polymorphisms with Obesity in Northern India.

OBJECTIVE: Genetic variants of the melanocortin-4 receptor gene (MC4R), agouti related protein (AGRP) and proopiomelanocortin (POMC) are reported to be associated with obesity. Therefore, the aim of this study is to examine MC4R rs17782313, MC4R rs17700633, AGRP rs3412352 and POMCrs1042571 for any association with obesity in North Indian subjects. METHODS: The variants were investigated for association in 300 individuals with BMI ≥30 kg/m(2) and 300 healthy non-obese individuals BMI <30 kg/m(2.) The genotyping were analyzed by Taqman probes. The statistical analysis was performed by the SPSS software, ver.19 and p≤0.05 was considered statistically significant. RESULTS: The genotypes of MC4R rs17782313 and POMC rs1042571 were significantly associated with obesity (C), (p=0.02; OR=1.7 and p=0.01; OR=1.6, respectively); however, MC4Rrs17700633 (p=0.001; OR=0.55) was associated with low risk. In addition, AGRPrs3412352 (p=0.93; OR=0.96) showed no association with obesity (BMI ≥30 kg/m(2)) in North Indian subjects. CONCLUSION: This study provides the report about the significant association of MC4R (rs17782313) and POMC (rs1042571) with morbid obesity (BMI ≥30 kg/m(2)), but MC4R (rs17700633) and AGRP (rs34123523) did not show any association with obesity in the studied North Indian population.

Factors affecting response to medical management in patients of filarial chyluria: A prospective study.

INTRODUCTION: Filarial chyluria is a common problem in filarial endemic countries. Its management begins with medical therapy but some patients progress to require surgery. The present study aimed to determine factors affecting response to medical management in patients of filarial chyluria. MATERIALS AND METHODS: This prospective study conducted between August 2008 and November 2012, included conservatively managed patients of chyluria. Demographic profile, clinical presentation, treatment history and urinary triglycerides (TGs) and cholesterol levels at baseline were compared between the responders and non-responders. Apart from the clinical grade of chyluria, hematuria was evaluated as an independent risk factor. RESULTS: Out of the 222 patients (mean age, 37.99 ± 13.29 years, 129 males), 31 patients failed to respond while 35 had a recurrence after initial response; the overall success rate being 70.3% at a mean follow-up of 25 months. No difference was observed in demographics, clinical presentation, presence of hematuria, disease duration and mean urinary TGs loss between responders and non-responders. On multivariate analysis, patients with treatment failure were found to have a higher-grade disease (14.3% Grade-I, 36.6% Grades-II and 60% Grade-III), higher number of pretreatment courses (1.59 ± 1.08 vs. 1.02 ± 0.79) and heavier cholesterol (26.54 ± 23.46 vs. 8.81 ± 8.55 mg/dl) loss at baseline compared with responders (P < 0.05). CONCLUSION: Conservative management has a success rate in excess of 70%, not affected by the disease chronicity, previous episodes and recurrent nature. However, higher-grade disease, extensive pre-treatment with drugs and higher urinary cholesterol loss at baseline are the predictors of poor response. Hematuria is not an independent poor risk factor for conservative management.

Initial drug resistance pattern among pulmonary tuberculosis patients.

BACKGROUND: Drug resistant tuberculosis (DRTB) is an emerging problem that adversely affects treatment outcomes and public health in the developing world. OBJECTIVE: To determine the initial drug resistance pattern among pulmonary tuberculosis patients registered under the Revised National Tuberculosis Control Programme. STUDY DESIGN: A cross-sectional study design. SETTING: Two urban Directly Observed Treatment Supervised (DOTS) centres in Lucknow District of Uttar Pradesh. METHODS: The present study consisted of newly diagnosed sputum smear-positive for acid-fast bacilli (AFB) cases at the time of registration under the tuberculosis control programme. All sputum smear positive cases were subjected to culture and drug-susceptibility testing by 1% proportion method on Lowenstein-Jensen (LJ) medium. RESULTS: A total of 185 newly diagnosed sputum smear positive for AFB i n pulmonary tuberculosis patients weresubjected to culture and drug sensitivity test. Among 185 isolates, 170 (91.4%) isolates were culture positive. Of these 170 isolates, 169 (99.4%) were M. tuberculosis and one (0.5%) was Mycobacterium other than tuberculosis (MOTT). Out of 99.4% M. tuberculosis positive isolates, 21.3% were resistant to at least one drug. Resistance pattern of 21.3% strains of M. tuberculosis showing resistance to single, double, triple, and quadruple drugs were 5.9%, 10.7%, 2.4% and 2.4% respectively. Multi-drug resistance (MDR) was observed in 4.7% isolates. CONCLUSION: The present study highlights the high rate of drug resistance pattern among the new sputum smear positive pulmonary tuberculosis patients and also high MDR tuberculosis. Routine surveillance of drug resistance profile of patients provides useful information for adopting new strategies of effective treatment within National Tuberculosis Control Programmes in order to combat the threat of MDR-TB in the general population.

Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial.

BACKGROUND: Animal, epidemiologic, and human clinical studies suggest a putative role for vitamin D in osteoarthritis (OA). Inadequate sunlight exposure and lower serum levels of 25(OH)D appear in some reports to be associated with an increased risk for progression of knee OA. QUESTIONS/PURPOSES: We asked whether treatment with vitamin D would (1) reduce knee pain (WOMAC and VAS), (2) improve function (WOMAC), and (3) change levels of relevant biochemical markers in patients with knee OA with vitamin D insufficiency. METHODS: This randomized controlled pilot trial prospectively enrolled 107 patients with knee OA with vitamin D insufficiency (25(OH)D ≤ 50 nmol/L) to receive oral vitamin D or placebo. The primary outcome measures were pain and function, and the secondary were biochemical markers. At baseline, the two groups were comparable. The patients were followed for 1 year. RESULTS: At 12 months, knee pain had decreased in the vitamin D group by mean -0.26 (95% CI, -2.82 to -1.43) on VAS and -0.55 (95% CI, -0.07 to 1.02) on the WOMAC, whereas in the placebo group, it increased by mean 0.13 (95% CI, -0.03 to 0.29) on the VAS and 1.16 (95% CI, 0.82 to 1.49) on the WOMAC (effect size = 0.37 and 0.78). Likewise knee function improved in the vitamin D group by mean -1.36 (95% CI, -1.87 to -0.85) over the placebo group which had a mean 0.69 (95% CI, -0.03 to 1.41; effect size = 0.06). There were significant biochemical changes in serum total calcium, 25(OH)D and alkaline phosphatase. CONCLUSIONS: The results above suggest there is a small but statistically significant clinical benefit to vitamin D treatment in patients with knee OA, although we recommend a long-term study to determine whether these changes are clinically important and whether they will be sustained with time. Further studies with long-term radiologic evaluations are needed.

Significance of obesity markers and adipocytokines in high grade and high stage prostate cancer in North Indian men - a cross-sectional study.

BACKGROUND: Prostate cancer (CaP) in India is the 10th most common malignancy affecting men. CaP incidence in India is low, but rising like other countries. The reasons for this racial disparity are uncertain. The foremost reasons that may underlie regional/ethnic differences are genetic polymorphisms, altered hormonal status, socioeconomic status, and obesity. This study aimed at investigating the role of adipocytokines in stimulating the promotion and progression of CaP. METHODS: A cross-sectional study on histopathologically proven prostate cancer (N=95) and benign prostatic hyperplasia (N=95) patients was undertaken. CaP patients were classified into high-grade (N=62) and low-grade (N=33), and high stage (N=31) and low stage (N=64) groups. The level of body mass index (BMI), waste to hip ratio (WHR), interleukin-6 (IL-6), leptin, and adiponectin were compared between BPH and CaP groups and between grades and stages of prostate cancer. RESULTS: The level of BMI was significantly (p<0.001) higher in CaP patients (26.58±4.76) in comparison to BPH (22.15±2.90). Similarly, WHR was significantly (p<0.0001) higher in the CaP patients (1.08±0.37) in comparison to BPH (0.86±0.15). Leptin (BPH: 25.60, CaP: 56.00) and II-6 levels (BPH: 9.90, CaP: 32.30) were significantly higher, but adiponectin was significantly lower in CaP patients as compared to BPH. High grade CaP patients had significantly higher BMI and WHR in comparison to low grade, and WHR was also higher in high stage CaP. Leptin and IL-6 level were higher in high stage and high grade, but adiponectin was low in high stage and high grade groups in comparison to low stage and low grade groups. CONCLUSIONS: Higher BMI and WHR correlate with prostate cancer independently, suggesting obesity to be a promoter of poor prostate health. Leptin and IL-6 appear to have stimulating effect on prostate cancer cells inducing the promotion and progression of CaP, but adiponectin appears to be protective against prostate cancer.

Association between lactate levels in vaginal fluid and time of spontaneous onset of labor in suspected cases of prelabor rupture of membranes.

PURPOSE: To assess correlation between lactate levels in vaginal fluid and onset of labor in suspected PROM. METHOD: A prospective observational study conducted at the Dept. of Obstetrics and Gynecology and Pathology from 2008 to 2009. 118 women with complaints of leaking per vaginum underwent a sterile speculum examination and vaginal fluid was taken to estimate lactate level. Then, women were followed till the spontaneous onset of labor. The association was presented as Odds ratio with 95 %CI. RESULTS: The median time of onset of spontaneous labor and examination was 12 h in patients with lactate levels >5.0 mmol/L and 76 h in patients with lactate levels <5.0 mmol/L. Among 62 women with lactate levels >5.0 mmol/L, 67.7 % of women (n = 42) had spontaneous onset of labor within 24 h and 83.87 % women of (n = 52) within 48 h. CONCLUSION: A lactate level >5.0 mmol/L is significantly associated with the spontaneous onset of labor within 24 and 48 h in suspected cases of PROM.

Diabetes mellitus with pulmonary tuberculosis--a double trouble.

Diabetic patients are often at a higher risk for developing several types of infections and infection does alter the handling of glucose by tissues. Pulmonary infections in diabetics are characterised by alteration in host defence, in entire body and in the lung locally as well as in the function of respiratory epithelium and ciliary motility. Association between diabetes mellitus and pulmonary tuberculosis is well established, while the prevalence of tuberculosis is increased 4-5 times more among diabetics. Impairment of host defence plays an important role for changing the clinical, radiological and bacteriological presentation in diabetic patients. It is also reported by the various studies that hyperglycaemia favours the growth of tuberculosis bacilli. So the severity of tuberculosis appears more cirtical with the degree of hyperglycaemia and host defence activity. This overlap between the diabetic and tuberculosis epidemics could adversely affect global tuberculosis control efforts.

Association of PPAR-γ gene polymorphisms with obesity and obesity-associated phenotypes in North Indian population.

OBJECTIVES: The worldwide increasing prevalence of obesity is considered as a major health problem. Peroxisome proliferator-activated receptor gamma (PPAR-γ) controls adipocyte differentiation and regulates a number of genes associated with energy homeostasis. In this study, we investigated the association of PPAR-γ gene Pro12Ala (rs1801282) and C1431T (rs3856806) polymorphisms with morbid obesity and related phenotypes, in north Indian population. METHODS: A total of 6,42 subjects, 309, obese and 333 nonobese individuals were included in this case-control study. Insulin, adiponectin, glucose, and lipid levels were estimated using standard protocols. All subjects were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The ProAla+AlaAla genotypes of PPAR-γ Pro12Ala were significantly associated with higher risk of obesity while C1431T polymorphism did not show any significant association. None of the haplotypes showed association with morbid obesity. However, a strong association of variant genotypes was observed with higher levels of insulin, HOMA-IR, and lower serum adiponectin concentrations. CONCLUSION: PPAR-γ gene polymorphisms influence obesity and obesity phenotype in a complex manner, probably involving insulin resistance in north Indian population.

Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women.

BACKGROUND: Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels. METHODS: The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91±6.05) and 272 healthy females without metabolic syndrome (age 30.96±7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion. RESULTS: Homozygous mutant genotype (AA) (p=<0.001: OR=3.24: 95% CI=2.15-4.89) and mutant allele (A) (p=<0.001: OR=3.04: 95% CI=2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors. CONCLUSIONS: Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.