Despite the widespread use of proteasome inhibitors in the treatment of multiple myeloma, the mechanisms of the anti-myeloma activity and the molecular pathways that execute the tumor cell killing are still unknown. In the present work we compared gene expression profile changes in response to bortezomib treatment of cultured bone marrow samples from patients with bortezomib-sensitive versus bortezomib-resistant myeloma. The results showed a pronounced induction of>70 genes including>30 heat shock protein transcripts in both patient groups and therefore debate the anti-tumor action, attributed to the unfolded protein response. In contrast, a subset of 7 genes (MMP12, IL7R, MGST1, C3, CYP27A1, MIR148A and CXXC4) changed only in the samples from the bortezomib-sensitive cases and therefore these tumor-associated genes might serve as predictors of the treatment efficacy, as well as for making of further insights onto the mechanism of action of proteasome inhibitors. In summary, we identified a subset of 7 genes which distinguished in our small series betweensensitive versus resistant tumor cells to bortezomib, which requires further assessment in a larger cohort of patients.
Rationale: Mutations in Transient Receptor Potential Channel 6 (TRPC6) gene are associated with autosomal dominant focal and segmental glomerulosclerosis (FSGS). The majority of the identified mutations affect the ion channel function. Since calcium channels are promising candidate drug targets, there is an an urgent need for a mouse model to assess new therapeutic drugs and to help delineate the pathogenic process leading to FSGS. We have previously reported the generation of three independent transgenic mouse lines carrying different Trpc6 mutations that display a glomerular disease comparable to the phenotype presented by individuals with FSGS. However, the utility of these models for drug testing is dampened by the late-onset of the presentation and the mild phenotypic manifestations. Methodology: In order to obtain a time-effective mouse model for Trpc6-associated FSGS we generated a new transgenic mutant Trpc6 mouse model emulating the amino acid change carried by the first pediatric patient of FSGS associated with a TRPC6 mutation: M132T. Results: Mice carrying the orthologous Trpc6 M131T transgene showed early onset proteinuria and early signs of FSGS. When exploring molecular consequences of the overexpression of this mutated form of Trpc6 in podocytes, differences in expression levels of Axin2 and β-catenin were found in glomeruli from transgenic Trpc6 M131T mice. These data supports the proposed molecular mechanisms related to the activation of calcineurin-NFAT/Wnt signaling, as outcome of the increased calcium influx caused by the mutated form of Trpc6. Conclusion: Given that the Trpc6 M131T mouse develops an early onset of FSGS-like phenotypes it represents a promising model for studying the pathogenesis of FSGS caused by TRPC6, facilitating the assessment of new drugs as treatments and allowing further studies to understand underlying molecular pathways involved in the development of the TRPC6 mediated disease.
Background: Understanding prescribing pattern of antimicrobials in postoperative period will provide data pertaining to efficacy of prophylaxis during post surgical period and economic burden faced by patients. This data will help local authorities formulate practical guidelines to ensure their rational prescription. Our aim was to evaluate the type and dosage schedule of antimicrobials used in post-operative patients and to estimate the cost of antimicrobials in these patients. Materials and Methods: This is a prospective observational study conducted by the Department of Pharmacology at R.L. Jalappa Hospital and Research Centre attached to Sri Devaraj Urs Medical College between April and September 2013. All patients above the age of 18 years undergoing surgical procedures in the departments of Orthopedics, Surgery and ENT and hospitalised were included. Results: There were 500 patients, 351 males and 149 females. The mean age and duration of stay was 43.15±16.8 years and 6.7±3.1 days respectively. Types of surgeries were, fracture fixation (31.8%), head and neck (18.2%), soft tissue - extremities (18.0%), abdominal (9.4%) and others (22.6%). All patients received antimicrobials prophylactically. 72% of the patients received anti-microbials for more than 24 hours. Commonly prescribed antimicrobials were cephalosporins (54.6%) and aminoglycosides (22.3%). The daily defined dose (DDD) /1000 patient days) was highest for aminoglycoside - amikacin (296.96±63.5). Conclusion: All patients received prophylactic antimicrobials and more than seventy percent were continued with the antimicrobials in the post operative period to prevent surgical site infection. However use of third generation cephalosporins was extensive, which may result in the development of resistance to these agents in the near future.
Aims: Bovine tuberculosis (bTB) is a chronic infectious and contagious zoonotic disease of domestic, wild animals and humans. The disease occurs in a wide range of mammalian species and therefore, poses a public health threat. It also results in considerable economic losses in livestock production and carcass condemnation of infected cattle during meat inspection. This study was aimed at determining the prevalence of zoonotic bovine tuberculosis in slaughtered cattle, based on Post-Mortem (PM) meat inspection, Ziehl-Neelsen staining (ZN) and Polymerase Chain Reaction (PCR) techniques in abattoir and slaughter houses in Bauchi State, Nigeria. Place and Duration of study: A cross-sectional abattoir based-study was conducted on 800 slaughtered cattle in the Northern, Central and Southern Zonal abattoirs of Bauchi State, Nigeria. This work was carried out between June-September, 2013. Study Design: Experimental. Methodology: One hundred and twenty (120) tissue samples from different organs were suspected to have bTB lesions at PM 15% (120/800). Out of the samples examined 35 (29.2%) were Acid-Fast Bacilli (AFB) positive; 10 (8.3%) of which were confirmed positive for M. bovis by the confirmatory Polymerase Chain Reaction (PCR). Results: The present study found the prevalence rates of 3.33% (4/120) and 5.00% (6/120) for males and females, respectively. This gave an overall prevalence of 8.33% for bTB (M. bovis) based on PCR. Bovine TB sex-specific rates were 10.00% (4/40) and 7.50% (6/80) by PCR, in males and females respectively. Female cattle also had a higher prevalence than male cattle but there was no statistically significant association (p>0.05, x2 = 0.218) between the presence of bTB in the tissues sampled and the sex of the cattle. There was a statistically significant association (p<0.05, x2 =7.002, OR=3.363) between detection of bTB in suspected tissues and the age of cattle. Using ZN, cattle aged six (6) years and above had the highest number of positive bTB cases 67.9% (31), while cattle aged 3-5 years old had the lowest 14.81% (4/27). PCR technique, revealed age-specific prevalence rate in cattle aged 6-8 and 9-11 years were 17.07% and 5.77%, respectively. Bauchi zonal abattoir had the highest number of suspected bTB cases (62.5%), followed by Katagum (26.7%) and Misau (10.8%). Conclusion: High infection rate of bTB was found among cattle sampled in the study area, with a significant prevalence in Bauchi metropolitan abattoir than the other two (2) slaughter houses (Katagum and Misau). This showed that the prevalence of bTB was higher in Bauchi metropolitan abattoir which supplies larger population of the state with beef. These findings also demonstrated that, there is urgent need for public health authorities in the state to intervene.
Aims: Inheritance of polycystic ovary syndrome (PCOS) is still a controversy. Our study aims to analyze the family history of PCOS features and related metabolic disturbances including the male members to determine the mode of their inheritance. Study Design: A cross sectional study with convenient sampling. Place and Duration of Study: Department of Medicine, Kasturba Medical College, Mangalore between 2009 and 2012. Methodology: Demographic data such as body weight and age was recorded. Menstrual, obstetric and medical history of 85 PCOS females was collected. Presence of metabolic syndrome (MetS) was confirmed. Blood pressure and waist circumference were measured. Biochemical and hormonal estimations were done. Relevant information required for the study of 604 members of first and second generation relatives was collected. SPSS (version 17.0) was used to analyze the data. Results: Seventy eight percent of the PCOS patients were either overweight or obese and 98% of them had hirsutism. Approximately, 33% of them had MetS which was higher in the first generation (62%) of PCOS relatives. An equal transmission of MetS characteristics from the paternal and maternal side indicated that it was not X- linked inheritance. Segregation analysis of nine families PCOS of patients suggested that MetS inheritance was autosomal dominant although PCOS inheritance was not. Conclusion: PCOS daughters come from families of MetS suggesting that parental MetS features may be related to the occurrence of PCOS in their off-springs.
Aim: The study was conducted to assess the knowledge and perception of probiotics among medical science students and practitioners in Lagos state. Study Design: This is a questionnaire based survey. Place and Duration of Study: The study was conducted in Lagos state which is located in the south-western part of Nigeria. The questionnaires were distributed from March to August, 2013. Methodology: Predesigned pilot tested questionnaires were randomly administered to 270 medical science students and professionals from various health institutes in Lagos state. The knowledge level was scored 0-3 as poor, 4-6 as fair and 7-9 as good and analyzed using Epi info version 3.5.3. Results: Of the 270 questionnaires distributed, 265(98.1%) were returned by 164 medical science students and 101 practitioners. The knowledge score of medical science students and practitioners was low (Mean±SD of 3.62±2.7). Ninety-four (57.3%) students disclosed that they have never heard of probiotics before and 139(84.8%) indicated interest in knowing more. Seventy (69.3%) practitioners were familiar with the term probiotics but 42(41.6%) had poor knowledge. Seventy three percent were not aware of any proven probiotic product in Nigeria and none has prescribed probiotic products for any medical condition. All indicated interest in knowing more about probiotics. The comparison of knowledge result across the various groups was statistically significant (P<0.05). Conclusion: There is limited knowledge and poor perception on benefits of probiotic use among medical science students and professionals in Lagos state. The result of this study indicates a need for education on the availability, sources and benefits of probiotics.
Introduction: Male births occur slightly in excess of female births. In man, the ratio of male divided by total live births (M/F) is expected to approximate 0.515. Warfare has been shown to exert significant effects on M/F. This study was carried out in order to identify any such effects on M/F in belligerent countries in recent conflicts. Methods: Births were obtained from a World Health Organisation Mortality database. Recent wars (post Second World War) were identified. Chi-square tests were used throughout. Male and female births in belligerent countries were compared to the aggregate of the previous and following years. Countries included were those with available data for periods spanning identified wars. Results: This study analysed 260747284 live births. M/F in the United States increased significantly during the Korean (p=0.011) and Vietnam (p=0.011) conflicts but decreased during the Gulf War (p=0.02) and there were no changes during the invasion of Iraq. There was no significant shift in M/F in Greece during the invasion of Cyprus, in England and Argentina in the Falkland war and in the Balkans during the Yugoslavian wars. The South Ossetia and Abkhazia Wars were associated in rises in M/F in the Southern Caucasus (Armenia, Azerbaijan, Georgia) only after the wars, and then serially to the end of the 20th century (probably due to sex-selective terminations of pregnancy in favour of male births). The Portuguese Colonial War lowered Portugal’s M/F during the last year of conflict (1974, p=0.0001). Discussion: This study confirms the observation that M/F rises during lengthy periods of warfare, and may fluctuate even during short periods of conflict. The former has been attributed to increased coital rates which increase conception rates early in the menstrual cycle, skewing M/F in favour of male conceptions. The latter may be due to the known M/F lowering effect of stress.
Aim: To study the prevalence of Down syndrome by conventional chromosome analysis and G-banded karyotyping. Materials and Methods: A retrospective analysis was performed on the case records of2750 paediatrics patients, of which 682 cases of confirmed Down syndrome was recorded by G-banding karyotyping. Results: Non-disjunction was the most common type of abnormality followed by Robertsonian translocation and lastly mosaic in ratio of 92.2:7.0:0.73 respectively. Conclusion: Results suggest that advanced maternal age is classic risk factor attributed to the incidences of Down syndrome.
Background and Introduction: The incidence of Obesity and overweight appears to be on the increase in resource poor nations that previously had to battle infectious disease and under-nutrition only. Obesity is a cause of life threatening diseases and a leading cause of death in the developed world. The most effective way of tackling obesity and overweight is by helping the population understand its dangers and have an attitude that allows for healthy trim people. Since family history reflects genetic susceptibility and environmental exposures shared by close relatives, this study assessed the perception of and attitude to obesity among mothers in a tertiary center in a Nigerian city. This is on the background knowledge that children of obese parents who also have poor perception of obesity are at a higher risk for obesity and associated diseases. Methods: The study was a cross sectional study of Nigerian mothers attending the immunization and child welfare clinic at the Institute of Child Health, University of Nigeria Teaching Hospital Enugu. Participants were enrolled consecutively after the research team had obtained ethical clearance from the hospital’s Health Research Ethics Committee. Questionnaires were administered on 322 consecutive consenting Mothers attending the immunization Clinic. Their perception and attitude were measured from a well-structured questionnaire alongside their body mass index (BMI) obtained from height (meters) and weight (Kg) measurement. Results: The mean (standard deviation) and median weights were 71Kg (±13.4) and 69Kg respectively; while the mean (standard deviation) and median heights were 1.6m (0.1) and 1.6m respectively (Table 1). Two hundred and four (63%) of mothers were overweight/obese (112, 36% overweight, 87, 27% obese) while 118 (37%) had normal BMI. The median BMI was 26.9 and the median BMI class was the overweight class. Fifty nine (18%) and 65 (20%) mothers had not heard of overweight and obesity respectively. Eighteen percent and 16% of respondents correctly defined overweight and obesity in lay terms while 48% and 39% had no idea respectively (Fig. 2). Forty eight (24%) of the 204 overweight and obese respondents knew they were obese or overweight. Twenty six participants (8%) perceived obesity as a sign of good living while 264 (84%) perceived it as not being good. Ninety four (29%) believed that nothing could be done about obesity since it is inherited. Forty seven (14.6%) subjects perceived their parents to be obese and 97% of these perceived obese parents were mothers. Of the 15 participants whose children were perceived to be obese, 86% had one affected child while 14% had 2 affected children. Conclusion: Awareness of overweight/obesity and prevention is low in the studied population and the incidence of obesity is high. A good proportion of mothers also had perceived obese parents and children. There is poor perception of body size among the obese/overweight participants. Intensive and sustained media campaign should be carried out by both government and non-government agencies to enlighten the general public on the dangers and complications including death that arise from obesity and overweight. Also, appropriate policy action and implementation will likely help to address obesity in the country of study.
Background: Gastrointestinal stromal tumors (GISTs) are rare tumors, but comprise the most common mesenchymal neoplasms of the gastrointestinal (GI) tract. We report a clinical series of abdominal GIST and discuss the diagnosis and management in Indian patients. Case Series: The data on demographic profile, clinical presentation and management of 12 cases of GIST from a single surgical unit in the last seven years were studied retrospectively. Preoperatively, ultrasonographic and computerized tomographic scans of the abdomen were the main investigations used for evaluation; the others being upper gastrointestinal endoscopy and X-ray of the chest. Histopathological examination and immunohistochemical evaluation were used to confirm the diagnosis. Results: The mean age at presentation was 47.9 years (range 35 – 70 years). Mean duration of symptoms was of 5 months (range 10 days–2 years). While all 12 patients presented with abdominal pain, 10 complained of abdominal lump. Two patients complained of vomiting and 1 of upper GI bleed. All patients were operated. In 7 cases, the GIST was arising from the ileum, 3 from the stomach and 2 from the mesentery. Nine cases had low grade benign tumors and 3 had malignancy. Conclusion: Abdominal pain and lump are the most common clinical symptoms of abdominal GIST. Vomiting, upper GI bleeding and weight loss are among the other important symptoms. Most of the tumors are benign and surgical resection remains the mainstay of treatment.
Background: It is uncertain whether the Sjogren Syndrome (SS) associated with Rheumatoid Arthritis (RA) represents a clinical entity similar to primary SS (pSS) or merely a manifestation in the clinical spectrum of RA. In the present study, we sought to determine the clinic and serologic features of SS associated with RA in comparison to the RA features using well defined SS classification criteria. Methods: RA patients successively referred for a biologic infusion were questioned on oral and ocular dryness. Schirmer’s test and unstimulated salivary flow were performed in each patient. Patients with subjective oral or ocular dryness and/or 1 abnormal objective test underwent a minor salivary gland biopsy. The diagnosis of secondary SS was based on the criteria of European-American consensus group criteria for SS. Clinical and biological parameters of SS and RA (with measure of disease activity and health status of RA, search for Raynaud’s phenomenon, anti-CCP, RF anti-SSA-positivity and beta2-microglobulin level) were then compared between patients with/without sSS. Results: Among the 76 patients prospectively assessed, 11(14.1%) fulfilled the European-American consensus group criteria for secondary SS. Median age and RA disease duration were similar in patients with sSS as in patients with RA only (63.0 v 59.2, p=0;33; 18.2 vs 13.9, p= 0.12). Median DAS28-ESR and HAQ were not significantly different between patients with sSS and patient with RA only (4.0 vs 4.1, p= 0.8; 0.84 vs 0.81, p=0.7). Patients with sSS had more frequently a Raynaud’s phenomenon (27.2 vs 1.5%, p=0.01). RF and anti-CCP-positivity were similar in the 2 groups. The prevalence of anti-SSA antibodies was comparable in the 2 groups (p=1). Median beta2-microglobulin levels were higher in sSS than RA only (2.4 vs 1.9 mg/l, p= 0.02). Conclusion: 14% of patients with RA had secondary SS in the present study. Conversely to previous reports, secondary SS did not modify the clinical and biologic pattern of RA.
Aim: The aim was to evaluate self-assessed foot health status and working efficiency of healthcare workers when using composite insoles to treat foot problems. Introduction: Foot pain and fatigue are two of the most common problems facing healthcare workers owing to many hours of walking and standing per day. Many choices of conservative treatment are available such as the use of insoles and orthotic support. Commercially prefabricated insoles are one of the most widely used treatments for foot pain and fatigue as they are easily accessible at reasonable prices. However, there is limited evidence supporting the effectiveness of these treatments. Methodology: Test subjects included 49 volunteers from Tung Song Hospital screened by an orthopedist and physical therapist to meet predetermined criteria. Data collected included demographic data, validated foot function score of a Foot Health Status Questionnaire (FHSQ), and a synthetic working efficiency score generated using the Thai Questionnaire of Working Efficiency for Healthcare workers. A self-evaluation form was designed to record the efficacy of using Smile feet™ insoles before and after one month of treatment. Statistical analysis was performed using the Wilcoxon signed rank test. Results: Responses to the Foot Heath Status Questionnaire showed a statistically significant change in several foot health metrics (p-value < 0.01) after using the composite insoles for 1 month: Improvement greater than the minimal important difference was achieved by 75.5% in foot pain, 44.9% in foot function, 89.8% in foot wear, and a 57.1% in general foot health. Respondents to the Thai Working Efficiency questionnaire reported improvement in sections of working, reducing muscle soreness and fatigue in 30 of the 49 volunteers (61.2%). Among those that experienced improvement, [self-reported] work productivity increased by 73%. Conclusion: Healthcare workers reported improvements after using a commercially available composite insole in all criteria on a self assessment questionnaire, including muscle soreness, working efficiency, work productivity, fatigue, foot pain, foot function, foot wear, and general foot health. Level of Evidence: Level IV, therapeutic case series.
Purpose: The aim of the present study was to define the very first score enabling discrimination between benign and malignant solitary fibrous tumors of the pleura (SFTPs), on the basis of reliable preoperative CT features. Methods: Between December 2004 and November 2012, 56 patients underwent complete resection for SFTP at six institutes. CT scans were reviewed retrospectively, and a diagnostic scoring system for predicting malignant SFTP preoperatively was designed. Results: Univariate analysis revealed seven significant predictors of malignant SFTP: tumor size ≥ 10 cm (p=0.002), tumor heterogeneity spontaneously (p=0.019) or after contrast medium injection (p=0.029), existence of intratumoral fluid density areas (p=0.011), a pleural effusion (p=0.01), measurable (diameter >1 mm) intratumoral vessels (p=0.019), a hypervascular character (visible intratumoral vessels and/or intense enhancement) (p=0.001). A scoring system based on these seven CT features, each assigned 1 point, and with a cut-off of 4 points, could predict malignant SFTP with a specificity of 85% and a sensitivity of 48%. Conclusion: Our scoring system using seven CT features (tumor size ≥ 10 cm, tumor heterogeneity with or without contrast injection, intratumoral fluid density areas, pleural effusion, measurable intratumoral vessels, and a hypervascular character of the tumor) may be helpful for predicting histological malignancy of solitary fibrous tumors of the pleura.
Aim: This study was undertaken to determine the effect of HEV on liver function enzymes. HEV is endemic in most developing countries, where the prevalence of HEV IgG antibody can be as high as 50%. Acute HEV infection is known to be a cause of decompensated liver cirrhosis. Several studies have suggested that elevated serum ALT and AST may be markers of hepatitis E virus (HEV) infection. Study Design: Cross sectional epidemiological survey. Place and Duration: The study was carried out in three geographical zones of Plateau State, over a six month period from July to December, 2012. Methodology: A total of 426 human subjects were recruited for the study; categorized into 4 groups: apparently healthy (190), pregnant women (108), HIV positive patients (80), and animal handlers (48). Blood samples were collected and analyzed for HEV antibodies (IgG and IgM) using ELISA technique. HEV seropositive samples were then subjected to measurement of liver enzymes (ALT and AST), using Randox kits (Randox USA). Results obtained were analyzed using SPSS version 17.0 statistical software. Results: Elevated ALT and AST levels of up to 1.5 folds to 3 folds above normal in seropositive subjects were found. HIV positive subjects and animal handlers recorded the highest elevated ALT level up to twice (2 folds) the upper limit of normal, (21.0±0.0 I.U/L and 19.0±0.0 I.U/L respectively), while apparently healthy subjects had the least elevated ALT level 1.5 folds the upper limit of normal (14.0±0.0 I.U/L). With regards to AST, pregnant women had the highest level of up to 3 folds of the upper limit of normal with mean of 47.7±45.5 I.U/L, followed by apparently healthy subjects with a mean of 36.2±14.2 I.U/L, but least among animal handlers that recorded a mean of 35.0±0.0 I.U/L. Conclusion: Hepatitis E Virus infection is associated with elevated ALT & AST values. However, this association needs further evaluation by researchers.
Gibson B. Kagaruki, Godfather D. Kimaro, Clement N. Mweya, Andrew M. Kilale, Ray M. Mrisho, Amani F. Shao, Akili K. Kalinga, Amos M. Kahwa, Esther S. Ngadaya, Godlisten S. Materu, Sayoki G. Mfinanga, Mary T. Mayige
Aim: To estimate the prevalence and risk factors for metabolic syndrome (MetS) among HIV positive patients on antiretroviral therapy (ART) in Tanzania. Study Design: A cross sectional study was conducted among adults aged ≥18years living with HIV-infection and receiving ART. Place and Duration of Study: The study participants were recruited from 12 care and treatment clinics in Dar es Salaam (urban) and Mbeya (rural) regions between October 2011 and February 2012. Methodology: The prevalence of MetS was assessed using International Diabetes Federation’s criteria. Biochemical assays, anthropometric measurements, demographic characteristics and lifestyle behavioural data were collected. Results: Study response rate was 351/377(93.1%) and 177 (50.4%) recruited participants were from urban settings and 238 (67.8%) were females. The prevalence of MetS was 25.6% and was higher among participants from urban than those from rural areas (35.6% vs 15.5%, p<.001). The components of MetS including raised triglyceride (43.5% vs 21.3%, p<.001), low high density lipoprotein (85.9% vs 28.2%, p<.001) and raised blood fasting glucose (10.2% vs 5.2%, p=.04) were more common among participants from urban than those from rural settings. MetS Risk factors including; consumption of fruits/vegetables <5 days/week (77.0% vs 59.3%, p<.001), not participating on vigorous intensity activities (65.5% vs 29.4% p<.001) and consuming mixed cooking oil (animal/vegetable) (15.5% vs 8.5%, p=.03) were higher among participants from rural than those from urban areas. In rural, only consumption of vegetables/fruits <5 days/week (AOR=5.50, 95%CI 1.21-24.95, p=.005) predicted the prevalence of MetS. In urban; sex (female) (AOR=3.01, 95%C 1.31-6.85, p=.002), having primary/no formal education (AOR=0.32, 95%CI 0.12-0.89, p=.04) and ex- or current alcohol drinker (AOR=2.43, 95%CI 1.17-5.06, p=.02) were significant predictors of MetS. Conclusion: Prevalence, components and predictors of MetS prevailed more in urban than in rural settings. Interventions targeting prevention of MetS to reduce diabetes and cardiovascular diseases should consider settings diversification.