APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput screening identified 34 compounds that inhibit APOBEC3G catalytic activity. 20/34 small molecules contained catechol moieties, which are known to be sulfhydryl reactive following oxidation to the orthoquinone. Located proximal to the active site, C321 was identified as the binding site for the inhibitors by a combination of mutational screening, structural analysis, and mass spectrometry. Bulkier substitutions C321-to-L, F, Y, or W mimicked chemical inhibition. A strong specificity for APOBEC3G was evident, as most compounds failed to inhibit the related APOBEC3A enzyme or the unrelated enzymes E. coli uracil DNA glycosylase, HIV-1 RNase H, or HIV-1 integrase. Partial, but not complete, sensitivity could be conferred to APOBEC3A by introducing the entire C321 loop from APOBEC3G. Thus, a structural model is presented in which the mechanism of inhibition is both specific and competitive, by binding a pocket adjacent to the APOBEC3G active site, reacting with C321, and blocking access substrate DNA cytosines.
Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically-achievable concentration of 2.5μg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.
breast cancer; dietary prevention; reactive oxygen species; ERK; DNA damage
Unsafe injection practices and injection overuse are widespread in developing countries harming the patient and inviting risks to the health care workers. In Nepal, there is a dearth of documented information about injection practices so the present study was carried out: a) to determine whether the selected government health facilities satisfy the conditions for safe injections in terms of staff training, availability of sterile injectable equipment and their proper disposal after use and b) to assess knowledge and attitudes of healthcare workers in these health care facilities with regard to injection safety.
A descriptive cross-sectional mixed type (qualitative and quantitative) survey was carried out from 18th May to 16th June 2012. In-depth interviews with the in-charges were conducted using a semi-structured questionnaire. Observation of the health facilities using a structured observation tool was done. The data were analysed manually by summarizing, tabulating and presenting in various formats.
The in-charges (eight males, two females) who participated in the study ranged in age from 30 to 50 years with a mean age of 37.8 years. Severe infection followed by pain was the most important cause for injection use with injection Gentamicin being most commonly prescribed. New single use (disposable) injections and auto-disable syringes were used to inject curative drugs and vaccines respectively. Sufficient safety boxes were also supplied to dispose the used syringe. All health care workers had received full course of Hepatitis B vaccine and were knowledgeable about at least one pathogen transmitted through unsafe injection practices. Injection safety management policy and waste disposal guideline was not available for viewing in any of the facilities. The office staff who disposed the bio-medical wastes did so without taking any safety measures. Moreover, none of these staff had received any formal training in waste management.
Certain safe injection practices were noticed in the studied health care facilities but there remain a number of grey areas where unsafe practices still persists placing patient and health workers at risk of associated hazards. Training concentrating on injection safety, guidelines to dispose biomedical waste and monitoring of the activity is needed.
Baglung; Health care workers; Needle stick injury; Nepal; Safety; Safe injection practice; Sharp waste
Despite receiving identical reimbursement for treating heart disease patients with bare metal stents (BMS) or drug-eluting stents (DES), cardiologists’ use of the new technology (DES) may have varied by patient payer type as DES diffused. Payer-related factors that differ between hospitals and/or differential treatment inside hospitals might explain any overall differences by payer type.
To assess the association between payer and DES use; and to examine between- and within-hospital variation in DES use over time.
We conducted a retrospective analysis of 4.1 million hospitalizations involving DES or BMS from the 2003–2008 Nationwide Inpatient Sample. We estimated hybrid fixed effects logit models and calculated the adjusted within-quarter, cross-payer differences in DES use.
Coronary stent patients with Medicaid or without insurance were significantly less likely to receive DES than were patients with private insurance throughout the study period. The differences fluctuated over time as the popularity of DES relative to BMS rose and fell. The within-hospital gaps paralleled the overall differences, and were largest in Q3 2003 (Medicaid: 11.9, uninsured: 10.9 percentage points) and Q4 2008 (Medicaid: 12.8, uninsured: 20.7 percentage points), and smallest in Q4 2004 (Medicaid: 1.4, uninsured: 1.1 percentage points). The between-hospital adjusted differences in DES use by payer were small and rarely significant.
We found substantial differences in DES use by payer within hospitals, suggesting physicians selected the new technology for patients in a manner associated with patients’ payer type.
Variations in care; technology; access
Long-term exposure to low doses of environmental carcinogens contributes to sporadic human breast cancers. Epidemiologic and experimental studies indicate that green tea catechins (GTCs) may intervene with breast cancer development. We have been developing a chronically induced breast cell carcinogenesis model wherein we repeatedly expose non-cancerous, human breast epithelial MCF10A cells to bioachievable picomolar concentrations of environmental carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), to progressively induce cellular acquisition of cancer-associated properties, as measurable end points. The model is then used as a target to identify non-cytotoxic preventive agents effective in suppression of cellular carcinogenesis. Here, we demonstrate, for the first time, a two-step strategy that initially used end points that were transiently induced by short-term exposure to NNK and B[a]P as targets to detect GTCs capable of blocking the acquisition of cancer-associated properties and subsequently used end points constantly induced by long-term exposure to carcinogens as targets to verify GTCs capable of suppressing carcinogenesis. We detected that short-term exposure to NNK and B[a]P resulted in elevation of reactive oxygen species (ROS), leading to Raf-independent extracellular signal-regulated kinase (ERK) pathway activation and subsequent induction of cell proliferation and DNA damage. These GTCs, at non-cytotoxic levels, were able to suppress chronically induced cellular carcinogenesis by blocking carcinogen-induced ROS elevation, ERK activation, cell proliferation and DNA damage in each exposure cycle. Our model may help accelerate the identification of preventive agents to intervene in carcinogenesis induced by long-term exposure to environmental carcinogens, thereby safely and effectively reducing the health risk of sporadic breast cancer.
Among African-Americans, genome wide association revealed a strong correlation between the G1 and G2 alleles of APOL1 (apolipoproteinL1, also called trypanolytic factor) and kidney diseases including focal and segmental glomerulosclerosis, HIV-associated nephropathy and hypertensive nephrosclerosis. In the prevailing hypothesis, heterozygous APOL1 G1 and G2 alleles increase resistance against Trypanosoma that cause African sleeping sickness, resulting in positive selection of these alleles, but when homozygous the G1 and G2 alleles predispose to glomerulosclerosis. While efforts are underway to screen patients for G1 and G2 alleles and to better understand “APOL1 glomerulopathy,” no data prove that these APOL1 sequence variants cause glomerulosclerosis. G1 and G2 correlate best with glomerulosclerosis as recessive alleles, which suggests a loss of function mutation for which proof of causality is commonly tested with homozygous null alleles. This test cannot be performed in rodents as the APOL gene cluster evolved only in primates. However, there is a homozygous APOL1 null human being who lives in a village in rural India. This individual and his family offer a unique opportunity to test causality between APOL1 null alleles and glomerulosclerosis.
Methods and Findings
We obtained clinical data, blood and urine from this APOL1 null patient and 50 related villagers. Based on measurements of blood pressure, BUN, creatinine, albuminuria, genotyping and immunoblotting, this APOL1 null individual does not have glomerulosclerosis, nor do his relatives who carry APOL1 null alleles.
This small study cannot provide definitive conclusions but the absence of glomerulosclerosis in this unique population is consistent with the possibility that African-American glomerulosclerosis is caused, not by loss of APOL1 function, but by other mechanisms including a subtle gain of function or by the “genetic hitchhiking” of deleterious mutations in a gene linked to APOL1 G1 and G2.
Seven isolates of bacteria (SRI-156, SRI-158, SRI-178, SRI-211, SRI-229, SRI-305 and SRI-360) were earlier reported by us as having potential for biocontrol of charcoal rot of sorghum and plant growth promotion (PGP) of the plant. In the present study, the seven isolates were characterized for their physiological traits (tolerance to salinity, pH, temperature and resistance to antibiotics and fungicides) and further evaluated in the field for their PGP of rice. All the seven isolates were able to grow at pH values between 5 and 13, in NaCl concentrations of up to 8% (except SRI-156 and SRI-360), temperatures between 20 and 40°C and were resistant to ampicillin (>100 ppm; except SRI-158 and SRI-178) but sensitive (<10 ppm) to chloramphenicol, kanamycin, nalidixic acid, streptomycin (except SRI-156 and SRI-211) and tetracycline. They were tolerant to fungicides benlate and captan, except SRI-158 and SRI-178, bavistin and sensitive to thiram (except SRI-156 and SRI-211) at field application level. In the field, four of the seven isolates (SRI-158, SRI-211, SRI-229 and SRI-360) significantly enhanced the tiller numbers, stover and grain yields, total dry matter, root length, volume and dry weight over the un-inoculated control. In the rhizosphere soil at harvest, all the isolates significantly enhanced microbial biomass carbon (except SRI-156), microbial biomass nitrogen and dehydrogenase activity (up to 33%, 36% and 39%, respectively) and total N, available P and% organic carbon (up to 10%, 38% and 10%, respectively) compared to the control. This investigation further confirms that the SRI isolates have PGP properties.
Biocontrol; Plant growth promotion (PGP); Rice; Field evaluation; Rhizosphere bacteria
To compare maternal and neonatal outcomes of vacuum versus forceps application in assisted vaginal delivery.
Material and Method
Women in labor with vertex presentation were delivered by vacuum and forceps. A total of 120 cases were included in this prospective study. Maternal and neonatal morbidity were compared in terms of perineal lacerations, episiotomy extension, post-partum hemorrhage, Apgar score, instrumental injuries, NICU admissions PNM etc. χ2 test was used to analyze the data.
Maternal morbidity viz. episiotomy extension as well as first and second degree perineal tear were significant in the forceps group (P = 0.0001 and P = 0.02, respectively). With regards to neonatal morbidity, no statistically significant difference was noted.
Vacuum and forceps should remain appropriate tools in the armamentarium of the modern obstetrician. However, ventouse may be chosen first (if there is no fetal distress) as it is significantly less likely to injure the mother.
Vacuum extraction; Forceps; Maternal morbidity; Neonatal outcome
A sufficient cardiology workforce is necessary to ensure access to cardiovascular care. Specifically, access to cardiologists is important in the management and treatment of chronic cardiovascular disease. Previous workforce analyses focused narrowly on the total numbers necessary to care for the entire population and not the geographic distribution of the workforce. To examine the supply and distribution of the cardiologist workforce, we mapped the ratios of cardiologists, primary care physicians, and total physicians to the population aged 65 years or older within different Hospital Referral Regions from the years 1995 and 2007. We found within the 12-year span of our study growth in the cardiology workforce was modest compared to the primary care physician and total physician workforces. Also we found a persistent geographic misdistribution of cardiologists associated with socioeconomic population characteristics. Our results suggest that large segments of our population, specifically in rural areas, continue to have decreased access to cardiologists despite a modest growth in the overall workforce. Policy initiatives focused upon increasing the cardiologist workforces in these areas in necessary to provide adequate cardiovascular care.
Workforce Issues; Access to Care; Physicians
There are conflicting data on the relationship between the level of secreted NS1 (sNS1), viremia, and disease severity upon dengue virus (DENV) infection in the clinical setting, and therefore, we examined this relationship in the widely accepted AG129 mouse model. Because of the failure of a routinely used NS1 detection kit to detect sNS1 of the mouse-adapted DENV2 strain, we screened 15 previously undescribed NS1 monoclonal antibodies and developed a robust capture enzyme-linked immunosorbent assay (ELISA) with detection sensitivity at the low nanogram level (0.2 ng/ml) using recombinant baculovirus-expressed sNS1 as well as sNS1 that was immunoaffinity purified from the various DENV2 strains employed in this study. Using this test, we demonstrated that increased viremia paralleled severe pathologies; however, sNS1 level did not correlate with viremia or severity. Furthermore, among the DENV2 strains that were tested, the level of NS1 secretion did not correspond to virus replication rate in vitro, at the cellular level. Together, our data indicate that the magnitude of NS1 secretion appears to be strain dependent and does not correlate with viral virulence in the AG129 mouse model.
Little is known about the association between financial stress and health care outcomes. Our objective was to examine the association between self-reported financial stress during initial hospitalization and long-term outcomes after acute myocardial infarction (AMI).
Materials and Methods
We used Prospective Registry Evaluating Myocardial Infarction: Event and Recovery (PREMIER) data, an observational, multicenter US study of AMI patients discharged between January 2003 and June 2004. Primary outcomes were disease-specific and generic health status outcomes at 1 year (symptoms, function, and quality of life (QoL)), assessed by the Seattle Angina Questionnaire [SAQ] and Short Form [SF]-12. Secondary outcomes included 1-year rehospitalization and 4-year mortality. Hierarchical regression models accounted for patient socio-demographic, clinical, and quality of care characteristics, and access and barriers to care.
Among 2344 AMI patients, 1241 (52.9%) reported no financial stress, 735 (31.4%) reported low financial stress, and 368 (15.7%) reported high financial stress. When comparing individuals reporting low financial stress to no financial stress, there were no significant differences in post-AMI outcomes. In contrast, individuals reporting high financial stress were more likely to have worse physical health (SF-12 PCS mean difference −3.24, 95% Confidence Interval [CI]: −4.82, −1.66), mental health (SF-12 MCS mean difference: −2.44, 95% CI: −3.83, −1.05), disease-specific QoL (SAQ QoL mean difference: −6.99, 95% CI: −9.59, −4.40), and be experiencing angina (SAQ Angina Relative Risk = 1.66, 95%CI: 1.19, 2.32) at 1 year post-AMI. While 1-year readmission rates were increased (Hazard Ratio = 1.50; 95%CI: 1.20, 1.86), 4-year mortality was no different.
High financial stress is common and an important risk factor for worse long-term outcomes post-AMI, independent of access and barriers to care.
Rosai-Dorfman disease (RDD) is a rare benign disorder of histiocytic proliferation that usually presents with bilateral cervical lymphadenopathy in children. We describe the case of a 50-year-old lady suffering from this disease who presented with generalized lymphadenopathy and a left sided chest wall lump. Fine needle aspiration cytology (FNAC) from all the lesions showed abundant benign histiocytes with lymphophagocytosis which was compatible with the diagnosis of RDD. This case is being reported for its rarity in presentation in an elderly female with both generalized nodal as well as extranodal manifestations.
Background. Methicillin-resistant Staphylococcus aureus (MRSA) infection incidence has increased in healthy US children. Our objective was to evaluate MRSA incidence and correlates in HIV-infected youth. Methods. The CDC-sponsored LEGACY study is a US multicenter chart abstraction study of HIV-infected youth. We identified MRSA infections among participants with ≥1 visit during 2006. We used bivariate and multivariable analyses to compare sociodemographic and HIV clinical factors between MRSA cases and noncases. Results. Fourteen MRSA infections (1 invasive, 12 soft tissue, 1 indeterminate) occurred among 1,813 subjects (11.1 infections/1,000 patient-years (PY), 95% CI: 11.06–11.14). Most (86%) isolates were clindamycin susceptible. Compared with noncases, MRSA cases were more likely older (17 versus 14 years), black (100% versus 69%), behaviorally HIV infected (43% versus 17%), and in Maryland (43% versus 7%) and had viral loads (VL) >1000 copies/mL (86% versus 51%) and lower mean CD4% (18% versus 27%) (all P < 0.05). In multivariate analysis, independent risk factors were Maryland care site (adjusted odds ratio (aOR) = 9.0), VL >1000 copies/mL (aOR = 5.9), and black race (aOR undefined). Conclusions. MRSA occurred at a rate of 11.1 infections/1,000 PY in HIV-infected youth but invasive disease was uncommon. Geographic location, black race, and increased VL, but not immunosuppression, were independently associated with MRSA risk.
Intravenous fluid is recommended in international guidelines to improve patient post-operative symptoms, particularly nausea and vomiting. The optimum fluid regimen has not been established. This prospective, randomized, blinded study was designed to determine if administration of equivolumes of a colloid (hydroxyethyl starch 130/0.4) reduced post operative nausea and vomiting in healthy volunteers undergoing ambulatory gynecologic laparoscopy surgery compared to a crystalloid solution (Hartmann’s Solution).
120 patients were randomized to receive intravenous colloid (N = 60) or crystalloid (N = 60) intra-operatively. The volume of fluid administered was calculated at 1.5 ml.kg-1 per hour of fasting. Patients were interviewed to assess nausea, vomiting, anti-emetic use, dizziness, sore throat, headache and subjective general well being at 30 minutes and 2, 24 and 48 hours post operatively. Pulmonary function testing was performed on a subgroup.
At 2 hours the proportion of patients experiencing nausea (38.2 % vs 17.9%, P = 0.03) and the mean nausea score were increased in the colloid compared to crystalloid group respectively (1.49 ± 0.3 vs 0.68 ± 0.2, P = 0.028). The incidence of vomiting and anti-emetic usage was low and did not differ between the groups. Sore throat, dizziness, headache and general well being were not different between the groups. A comparable reduction on post-operative FVC and FEV-1 and PEFR was observed in both groups.
Intra-operative administration of colloid increased the incidence of early postoperative nausea and has no advantage over crystalloid for symptom control after gynaecological laparoscopic surgery.
Fluid therapy; Colloid; Crystalloid solutions; Nausea; Vomiting
Lipid-based innovations have achieved new heights during the last few years as an essential component of drug development. The current challenge of drug delivery is liberation of drug agents at the right time in a safe and reproducible manner to a specific target site. A number of novel drug delivery systems has emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery. Microparticulate lipoidal vesicular system represents a unique technology platform suitable for the oral and systemic administration of a wide variety of molecules with important therapeutic biological activities, including drugs, genes, and vaccine antigens. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. Also, novel lipid carrier-mediated vesicular systems are originated. This paper has focused on the lipid-based supramolecular vesicular carriers that are used in various drug delivery and drug targeting systems.
The Tiger (Panthera tigris) population in India has undergone a sharp decline during the last few years. Of the number of factors attributed to this decline, habitat fragmentation has been the most worrisome. Wildlife corridors have long been a subject of discussion amongst wildlife biologists and conservationists with contrasting schools of thought arguing their merits and demerits. However, it is largely believed that wildlife corridors can help minimize genetic isolation, offset fragmentation problems, improve animal dispersal, restore ecological processes and reduce man animal conflict. This study attempted to evaluate the possibilities of identifying a suitable wildlife corridor between two very important wildlife areas of central India – the Kanha National Park and the Pench National Park – with tiger as the focal species. Geographic Information System (GIS) centric Least Cost Path modeling was used to identify likely routes for movement of tigers. Habitat suitability, perennial water bodies, road density, railway tracks, human settlement density and total forest edge were considered as key variables influencing tiger movement across the Kanha-Pench landscape. Each of these variables was weighted in terms of relative importance through an expert consultation process. Using different importance scenarios, three alternate corridor routes were generated of which one was identified as the most promising for tiger dispersal. Weak links – where cover and habitat conditions are currently sub-optimal – were flagged on the corridor route. Interventions aimed at augmenting the identified corridor route have been suggested using accepted wildlife corridor design principles. The involvement of local communities through initiatives such as ecotourism has been stressed as a crucial long term strategy for conservation of the Kanha-Pench wildlife corridor. The results of the study indicate that restoration of the identified wildlife corridors between the two protected areas is technically feasible.
Pigeonpea (Cajanus cajan L.) is an important food legume crop of rainfed agriculture. Owing to exposure of the crop to a number of biotic and abiotic stresses, the crop productivity has remained stagnant for almost last five decades at ca. 750 kg/ha. The availability of a cytoplasmic male sterility (CMS) system has facilitated the development and release of hybrids which are expected to enhance the productivity of pigeonpea. Recent advances in genomics and molecular breeding such as marker-assisted selection (MAS) offer the possibility to accelerate hybrid breeding. Molecular markers and genetic maps are pre-requisites for deploying MAS in breeding. However, in the case of pigeonpea, only one inter- and two intra-specific genetic maps are available so far. Here, four new intra-specific genetic maps comprising 59–140 simple sequence repeat (SSR) loci with map lengths ranging from 586.9 to 881.6 cM have been constructed. Using these four genetic maps together with two recently published intra-specific genetic maps, a consensus map was constructed, comprising of 339 SSR loci spanning a distance of 1,059 cM. Furthermore, quantitative trait loci (QTL) analysis for fertility restoration (Rf) conducted in three mapping populations identified four major QTLs explaining phenotypic variances up to 24 %. To the best of our knowledge, this is the first report on construction of a consensus genetic map in pigeonpea and on the identification of QTLs for fertility restoration. The developed consensus genetic map should serve as a reference for developing new genetic maps as well as correlating with the physical map in pigeonpea to be developed in near future. The availability of more informative markers in the bins harbouring QTLs for sterility mosaic disease (SMD) and Rf will facilitate the selection of the most suitable markers for genetic analysis and molecular breeding applications in pigeonpea.
Electronic supplementary material
The online version of this article (doi:10.1007/s00122-012-1916-5) contains supplementary material, which is available to authorized users.
We report a case of very large ossifying fibroma of the maxilla in a 22-year-old male. It is a bony tumour of the maxilla of possibly odontogenic origin with aggressive behavior and high tendency for recurrence.
Cemento-ossifying fibroma; Maxilla
Coumarinic oral-anticoagulants (COAs) are commonly used for treatment of thromboembolic events. However, these medications have a narrow therapeutic range and there are large inter-individual variations in drug response. This is especially important in the initial phases of oral-anticoagulant therapy. Recent advancements in pharmacogenetics have established that clinical outcomes in oral-anticoagulant therapy are affected by genetic factors. The allelic variants of genes like cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are closely associated with maintenance dose of oral anti-coagulants. In addition, GGCX (Gamma-glutamyl carboxylase) polymorphism at position 12970 (rs11676382), CYP4F2 (rs2108622; V433M; 1347 C > T) and Apolipoprotein E (APOE) variants have been shown to explain a small but significant influence on dose requirements. There are large differences in the frequencies of these polymorphisms between different world populations which are also related to the requirements of oral anticoagulants. However, the final drug dosage in an individual is determined by complex sets of genetic and environmental factors and several dosing algorithms which combine clinical and genetic parameters to predict therapeutic COA doses have also been developed. The algorithm based dose prediction shows the importance of pharmacogenetic testing in patients undergoing oral anticoagulant therapies.
Coumarinic oral anticoagulants; Pharmacogenetics; Vitamin K cycle; Drug metabolism; Polymorphism; Dosing algorithm
The survival of transplant recipients is significantly lower than age-matched controls in the general population. The aim of this study was to analyze the trends in mortality of renal allograft recipients at our centre. We retrospectively analyzed data from all patients who were transplanted between October 1988 and June 2010 and were followed at our center. Patients were considered to have death with graft function (DWGF) if death was not preceded by return to dialysis or re-transplantation. The study included 98 renal allograft recipients (male : female – 7.99 : 1). The mean recipient and donor ages were 35.06 ± 11.84 (range: 15–69) and 41.17 ± 10.44 (range: 22–60) years, respectively. Basic kidney diseases were CGN (chronic glomerulonephritis) (60.20%), CIN (chronic interstitial nephritis) (15.31%), DN (diabetic nephropathy) (8.16%), ADPKD (autosomal dominant polycystic kidney disease) (2.04%) and others (14.29%). They were followed up for a mean 79.91 ± 60.05 patient-months. Mortality occurred in 25 (25.51%) patients (male : female – 4 : 1). Causes of death were sepsis/infection (36%), coronary artery disease (28%), CVA (8%), failed graft (4%), and rest unknown (24%). DWGF was 88% of total death and contributed to 78.57% of total graft loss. Overall patient survival at 1, 5, 10, and 15 years were 90.8%, 80.2%, 65.6%, and 59.1%, respectively (Kaplan–Meier analysis). Those who died exhibited significant differences in recipient's age (median 40 years vs 31 years, P=0.007), pretransplantation hypertension (HTN) (100% vs 65.75%, P<0.001), post-transplant infection (76% vs 42.47%, P=0.005), coronary artery disease (28% vs 1.37%, P<0.001), and serum creatinine at last follow up (median 2.3mg/dL vs 1.56mg/dL, P=0.003). Cardiovascular disease, in addition to infection, is an important cause of death during the first 15 years following renal transplantation even in nondiabetic recipients. Death with functioning graft is of concern.
CVD; death with graft function; infection; mortality; renal transplantation
Anemia is common among patients hospitalized with acute myocardial infarction (AMI), and is associated with poor outcomes. Less is known about the incidence, correlates, and prognostic implications of acute, hospital-acquired anemia (HAA).
Methods and Results
We identified 2909 patients with AMI who had normal hemoglobin (Hgb) on admission in the multi-center TRIUMPH registry. We used hierarchical Poisson regression to identify independent correlates of HAA, and multivariable proportional hazards regression to identify the association of HAA with mortality and health status. At discharge, 1321 (45.4%) patients had HAA, of whom 348 (26.3%) developed moderate-severe anemia (Hgb 9.1–11). The incidence of HAA varied substantially across hospitals (range: 33.3% to 69.2%, median rate ratio for HAA development 1.13 (95% CI 1.07–1.23) controlling for patient characteristics). Although documented bleeding was more frequent with more severe HAA, fewer than half of patients with moderate-severe HAA had any documented bleeding. Independent correlates of HAA included age, female gender, white race, chronic kidney disease, ST segment elevation MI, acute renal failure, use of glycoprotein IIb/IIIa inhibitors, in-hospital complications (cardiogenic shock, bleeding and bleeding severity), and length of stay. After adjustment for GRACE score and bleeding, patients with moderate-severe HAA had higher mortality (HR 1.82 (95% CI 1.11–2.98) vs. no HAA), as well as poorer health status at 1-year.
HAA develops in nearly half of AMI hospitalizations, commonly in the absence of documented bleeding, and is associated with worse mortality and health status. Better understanding of how HAA can be prevented, and whether its prevention can improve patient outcomes is needed.
myocardial infarction; anemia; hemoglobin; outcomes
A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of aceclofenac (ACF), paracetamol (PCM) and tramadol hydrochloride (TRM) in pharmaceutical dosage form. The chromatographic separation was achieved on a HiQ-Sil™ HS C18 column (250×4.6 mm i.d., 5 μm particle size), kromatek analytical column at ambient temperature. The mobile phase consisted of 40: 60 (v/v); phosphate buffer (pH 6.0): methanol. The flow rate was set to 1.0 mL min−1 and UV detection was carried out at 270 nm. The retention time (tR) for ACF, PCM and TRM were found to be 14.567 ± 0.02, 3.133 ± 0.01 and 7.858 ± 0.02 min, respectively. The validation of the proposed method was carried out for linearity, precision, robustness, limit of detection, limit of quantitation, speci city, accuracy and system suitability. The linear dynamic ranges were from 40–160 μg mL−1 for ACF, 130–520 μg mL−1 for PCM and 15–60 μg mL−1 for TRM. The developed method can be used for routine quality control analysis of titled drugs in pharmaceutical dosage form.
Aceclofenac; Paracetamol; Tramadol hydrochloride; Method development; Validation; HPLC
To develop a population specific pharmacogenetic acenocoumarol dosing algorithm for north Indian patients and show its efficiency in dosage prediction.
Multiple and linear stepwise regression analyses were used to include age, sex, height, weight, body surface area, smoking status, VKORC1 -1639 G>A, CYP4F2 1347 G>A, CYP2C9*2,*3 and GGCX 12970 C>G polymorphisms as variables to generate dosing algorithms. The new dosing models were compared with already reported algorithms and also with the clinical data for various performance measures. Odds ratios for association of genotypes with drug sensitive and resistant groups were calculated.
The pharmacogenetic dosing algorithm generated by multiple regression analysis explains 41.4% (p-value <0.001) of dosage variation. Validation of the new algorithm showed its predictive ability to be better than the already established algorithms based on similar variables. Its validity in our population is reflected by increased sensitivity, specificity, accuracy and decreased rates of over- and under- estimation in comparison to clinical data. The VKORC1-1639 G>A polymorphism was found to be strongly associated with acenocoumarol sensitivity according to recessive model.
We have proposed an efficient north India specific pharmacogenetic acenocoumarol dosing algorithm which might become a baseline for personalised medicine approach for treatment of patients in future.
Amalgam has been used in dentistry since about 150 years and is still being used due to its low cost, ease of application, strength, durability, and bacteriostatic effect. When aesthetics is not a concern it can be used in individuals of all ages, in stress bearing areas, foundation for cast-metal and ceramic restorations and poor oral hygiene conditions. Besides all, it has other advantages like if placed under ideal conditions, it is more durable and long lasting and least technique sensitive of all restorative materials, but, concern has been raised that amalgam causes mercury toxicity. Mercury is found in the earth's crust and is ubiquitous in the environment, so even without amalgam restorations everyone is exposed to small but measurable amount of mercury in blood and urine. Dental amalgam restorations may raise these levels slightly, but this has no practical or clinical significance. The main exposure to mercury from dental amalgam occurs during placement or removal of restoration in the tooth. Once the reaction is complete less amount of mercury is released, and that is far below the current health standard. Though amalgam is capable of producing delayed hypersensitivity reactions in some individuals, if the recommended mercury hygiene procedures are followed the risks of adverse health effects could be minimized. For this review the electronic databases and PubMed were used as data sources and have been evaluated to produce the facts regarding amalgam's safety and toxicity.
Amalgam; mercury; myth; restoration; safety; tooth; toxicity