Patients’ knowledge on prescribed medications play a key role in the long term management of cardiac diseases and in determining their outcome. The present study evaluates the knowledge about prescribed medication among cardiac patients and aim to identify factors influencing knowledge.
A descriptive-cross-sectional study was conducted among 200 adult patients attending clinics at the Cardiology Unit of the National Hospital of Sri Lanka. Knowledge assessment focused on four different sections; drug name, dose, frequency and indication. The total score of 60 was calculated by giving each component the following weighted scores; drug name = 20, indication = 20, drug dose = 10 and frequency = 10. A binary logistic regression analysis to evaluate factors associated with ‘good knowledge’ (total score ≥ 40) was performed.
Among 200 participants 56.5% (n = 113) were males. Mean age was 59.7 ± 8.2 years and a majority (n = 170, 85.0%) were older than 50 years of age. Sinhala was the primary language of 91.5% (n = 183) of participants, while English was the primary language in only two of the study participants (1.0%). Eighty four percent of the participants were educated up to secondary education or above, while 2.5% (n = 5) had no formal education. The overall knowledge (total score-60) on prescribed medications among the study population was ‘poor’ (score ≤ 20) in 46%, ‘adequate’ (score 21–40) in 36.5% and ‘good’ (score ≥ 40) in 17.5%. The results of the binary logistic regression analysis indicates that Secondary (OR-1.53) and Tertiary levels (OR-2.79) of education, self-reported perception of illness as being Moderate (OR-1.23) or Severe (OR-1.70) and being educated by a doctor (as reported by patients) (OR-1.69) significantly increased the odds of having a ‘Good Knowledge of Drugs’. Majority of the patients were unable to read and understand the information written in English. The doctor’s contributed towards educating on drug information only in 33.0% of the patients.
In a resource-poor setting in patients with Limited English Proficiency, lower level of education and misperception of illness severity resulted in reduced knowledge on prescribed medications. Furthermore, being educated by a doctor significantly improved knowledge. However the doctors’ contribution at present to deliver quality health information to their patients was at an unsatisfactory level.
Limited English proficiency; Health literacy; Sri Lanka; Cardiac disease
Interleukin-15 (IL-15) is a pleiotropic cytokine with a broad range of biological functions in many diverse cell types. It plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems. This review provides an overview of the mechanisms by which IL-15 modulates the host response to infectious agents and its utility as a cytokine adjuvant in vaccines against infectious pathogens.
IL-15; infectious diseases; vaccines; inflammation; molecular adjuvants
To study influenza viruses in pigs in Sri Lanka,we examined samples from pigs at slaughterhouses. Influenza (H3N2) and A(H1N1)pdm09 viruses were prevalent during 2004–2005 and 2009–2012, respectively. Genetic and epidemiologic analyses of human and swine influenza viruses indicated 2 events of A(H1N1)pdm09 virus spillover from humans to pigs.
swine influenza; Sri Lanka; epidemiology; viruses; spillover; ecology; A(H1N1)pdm09; influenza
Botanical work since 2008 on the Sleeping Giant section of the Kamdebooberge (Sneeuberg mountain complex, Eastern Cape, South Africa) has indicated that these mountains may be of significant conservation value. Accordingly, a precursory, rapid multi-disciplinary biodiversity assessment was undertaken in January 2011, focusing on plants, tetrapod vertebrates and leafhoppers. The botanical results confirm the Kamdebooberge as being of high botanical conservation value, hosting three strict endemics, healthy populations of five other Sneeuberg endemics, and fynbos communities comprising species not found elsewhere in the Sneeuberg. The Kamdebooberge are important for herpetofauna (excluding serpentoids) and mammals, hosting several range-restricted and regional endemics. The expedition uncovered three new leafhopper species, together with several species previously only known from the Cape Floristic Region. Further detailed faunal work may provide further interesting results from these mountains, which show a high conservation value unique to the southern Escarpment.
Electronic supplementary material
The online version of this article (doi:10.1186/2193-1801-1-56) contains supplementary material, which is available to authorized users.
Endemics; Great escarpment; Kamdebooberge; Plants; Invertebrates; Sneeuberg centre of floristic endemism; Vertebrates
To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats.
Materials and Methods:
The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day.
Phase I: There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P < 0.05). Phase II: Between D0 and D30, the difference in food consumption was shown only in diabetes-induced rats (P < 0.001). Similarly, the significant difference following cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001).
C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats.
Blood glucose; Ceylon cinnamon; Cinnamomum zeylanicum; diabetes mellitus; lipids; Sprague-Dawley rats
Despite the eradication of smallpox, there is heightened concern that it could be reintroduced as a result of intentional release of Variola major virus through an act of bioterrorism. The live vaccine that was pivotal in the eradication of smallpox though considered a gold standard for its efficacy still retains sufficient residual virulence that can cause life-threatening sequelae especially in immune deficient individuals. Therefore, a safer smallpox vaccine that can match the efficacy of first generation vaccines is urgently needed. We previously reported that the integration of human IL-15 cytokine into the genome of Wyeth strain of vaccinia (Wyeth/IL-15), the same strain as the licensed vaccine, generates a vaccine with superior immunogenicity and efficacy in a mouse model. We now demonstrate that Wyeth/IL-15 is non-lethal to athymic nude mice when administered intravenously at a dose of 107 plaque forming units and it undergoes enhanced in vivo clearance in these immune deficient mice. Furthermore, a majority of cynomolgus monkeys vaccinated with vaccinia viruses with integrated IL-15, when challenged 3 years later with a lethal dose of monkeypox virus displayed milder clinical manifestations with complete recovery supporting the utility of Wyeth/IL-15 for contemporary populations as a safer and efficacious smallpox vaccine.
Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation. Transcranial brain targeted dosage design is therefore feasible.
Brain targeted; electroencephalography; emissary veins; diazepam; sesame oil; sleep latency; transcranial
Tuberculosis caused by Mycobacterium tuberculosis is responsible for nearly two million deaths every year globally. A single licensed vaccine derived from Mycobacterium bovis, bacille Calmette-Guerin (BCG) administered perinatally as a prophylactic vaccine has been in use for over 80 years and confers substantial protection against childhood tuberculous meningitis and miliary tuberculosis. However, the BCG vaccine is virtually ineffective against the adult pulmonary form of tuberculosis that is pivotal in the transmission of tuberculosis that has infected almost 33% of the global population. Thus, an effective vaccine to both prevent tuberculosis and reduce its transmission is urgently needed. We have generated a multi-valent, vectored vaccine candidate utilizing the modified virus Ankara (MVA) strain of vaccinia virus to tandemly express five antigens, ESAT6, Ag85A, Ag85B, HSP65 and Mtb39A of Mycobacterium tuberculosis that have been reported to be protective individually in certain animal models together with an immunostimulatory cytokine interleukin 15 (MVA/IL-15/5Mtb). Although, immunological correlates of protection against tuberculosis in humans remain to be established, we demonstrate that our vaccine induced comparable CD4+ T cell and greater CD8+ T cell and antibody responses against Mycobacterium tuberculosis in vaccinated mice in a direct comparison with the BCG vaccine and conferred protection against an aerogenic challenge of M. tuberculosis, thus warranting its further preclinical development.
Tuberculosis; vaccine; IL-15
The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune-stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein, derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing antibodies and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with H5N1 virus of a different clade. In addition to having the potential as a universal influenza vaccine, in the event of an impending pandemic, the Wyeth/IL-15/5Flu is also readily amenable for bulk production to cover the global population. For those individuals for whom the use of Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago.
Viral; Cytokines; vaccination
Most medical schools use simulated patients (SPs) for teaching. In this context the authenticity of role play and quality of feedback provided by SPs is of paramount importance. The available literature on SP training mostly addresses instructor led training where the SPs are given direction on their roles. This study focuses on the use of peer and self evaluation as a tool to train SPs.
SPs at the medical school participated in a staff development and training programme which included a) self-assessment of their performance while observing video-tapes of their role play using a structured guide and b) peer group assessment of their performance under tutor guidance. The pre and post training performance in relation to authenticity of role play and quality of feedback was blindly assessed by students and tutors using a validated instrument and the scores were compared. A focus group discussion and a questionnaire assessed acceptability of the training programme by the SPs.
The post-training performance assessment scores were significantly higher (p < 0.05) than the pre-training scores. The degree of improvement in the quality of feedback provided to students was more when compared to the improvement of role play. The acceptability of the training by the SPs was very satisfactory scoring an average of 7.6 out of 10. The majority of the SPs requested the new method of training to be included in their current training programme as a regular feature.
Use of structured self-reflective and peer-interactive, practice based methods of SP training is recommended to improve SP performance. More studies on these methods of training may further refine SP training and lead to improvement of SP performance which in turn may positively impact medical education.
The prevalence of macrovascular disease and hyperlipidaemia was examined in 500 patients with non-insulin-dependent diabetes mellitus attending a diabetic clinic in a Sri Lankan teaching hospital and 250 controls matched for age and gender. Macrovascular disease was assessed using a modified World Health Organisation questionnaire and modified Minnesota coding of electrocardiogram recordings. Twenty-one per cent of diabetic patients and 14.3% of controls had hypercholesterolaemia (P < 0.05). Macrovascular disease was present in 13.4% of diabetic patients and 8.2% of controls. Significant differences were seen in the prevalence of hypertension (15.6% vs 4.8%, P < 0.05), obesity (16.2% vs 9.7%, P < 0.05), peripheral vascular disease (5.6% vs 2%, P < 0.05) and electrocardiographic abnormalities (12% vs 6%, P < 0.05) in diabetic patients when compared to controls. Hyperlipidaemia and macrovascular disease is common in non-insulin-dependent diabetic patients in Sri Lanka and accounts for significant morbidity.
To determine whether fear avoidance beliefs (FAB) in older adults with chronic low back pain (CLBP) is significantly associated with gait speed and/or self-report (Roland Morris Questionnaire, RMQ)
Academic Medical Center (single site)
Two-hundred English-speaking participants aged 65 and older with CLBP every day or almost every day of ≥ moderate intensity for ≥3 months.
The physical activity portion of the FAB questionnaire assessed fear avoidance beliefs. Disability was measured with gait speed and the RMQ. Covariates measured included age, gender, BMI, chronic disease (Cumulative Illness Rating Scale-CIRS), depression (Geriatric Depression Scale-GDS), and pain (McGill Pain Questionnaire short form-MPQ.)
Fear avoidance beliefs were significantly associated with the RMQ (p<.0001) and gait speed (p=.002) after controlling for all covariates.
Fear avoidance beliefs related to physical activity in older adults with CLBP were significantly associated with both self-reported and performance-based disability after controlling for known confounders. Previous studies have reported similar associations between self-reported measures of disabling back pain and fear avoidance beliefs. Ours is the first study to examine the relationship between FAB and gait speed, a powerful predictor of morbidity and mortality. Future work should examine whether targeting fear avoidance in addition to other psychosocial measures in older adults with CLBP improves gait speed and functional independence.
EPR and 1H ENDOR spectroscopies have been used to analyze intermediate states formed during the hydroxylation of (1R)-camphor [H2-camphor] and (1R)-5,5-dideuterocamphor [D2-camphor] as induced by cryoreduction (77 K)/annealing of the ternary ferrous cytochrome P450cam-O2-substrate complex. Hydroxylation of H2-camphor produced a primary product state in which 5-exo-hydroxycamphor is coordinated with Fe(III). ENDOR spectra contained signals derived from two protons [Fe(III)-bound C5-OHexo and C5-Hendo] from camphor. When D2-camphor was hydroxylated under the same condition in H2O or D2O buffer, both ENDOR Hexo and Hendo signals are absent. For D2-camphor in H2O buffer, H/D exchange causes the C5-OHexo signal to reappear during relaxation upon annealing to 230 K; for H2-camphor in D2O, the C5-OHexo signal decreases through H/D exchange. These observations clearly show that Cpd I is the reactive species in the hydroxylation of camphor in P450cam.
Recent studies have demonstrated that statins reduce cell viability and induce apoptosis in various types of cancer cells. The molecular mechanisms underlying these effects are poorly understood. The JAK/STAT pathway plays an important role in the regulation of proliferation and apoptosis in many tissues, and its deregulation is believed to be involved in tumorigenesis and cancer. The physiological activation of STAT proteins by GH is rapid but transient in nature and its inactivation is regulated mainly by the expression of SOCS proteins. UMR-106 osteosarcoma cells express a GH-responsive JAK2/STAT5 signaling pathway, providing an experimental model to study the influence of statins on this system. In this study we investigated the actions of simvastatin on cell proliferation, migration, and invasion on UMR-106 cells and examined whether alterations in GH-stimulated JAK/STAT/SOCS signaling may be observed. Results showed that treatment of osteosarcoma cells with simvastatin at 3 to 10 µM doses decreases cell proliferation, migration, and invasion in a time- and dose-dependent manner. At the molecular level, although the mechanisms used by simvastatin are not entirely clear, the effect of the statin on the reduction of JAK2 and STAT5 phosphorylation levels may partially explain the decrease in the GH-stimulated STAT5 transcriptional activity. This effect correlated with a time- and dose-dependent increase of SOCS-3 expression levels in cells treated with simvastatin, a regulatory role that has not been previously described. Furthermore, the finding that simvastatin is capable of inducing SOCS-3 and CIS genes expression shows the potential of the JAK/STAT pathway as a therapeutic target, reinforcing the efficacy of simvastatin as chemotherapeutic drug for the treatment of osteosarcoma.
Prenatal exposure to chlorpyrifos (CPF), an organophosphorus insecticide, has long been associated with delayed neurocognitive development and most recently with decrements in working memory at age 7. In the current paper, we expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. We evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7 years. We did not observe a remediating effect of a high quality home environment (either parental nurturance or environmental stimulation) on the adverse effects of prenatal CPF exposure on working memory. However, we detected a borderline significant interaction between prenatal exposure to CPF and child sex (B (95% CI) for interaction term = −1.714 (−3.753 to 0.326)) suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, we detected a borderline interaction between parental nurturance and child sex (B (95% CI) for interaction term = 1.490 (−0.518 to 3.499)) suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. To our knowledge, this is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure.
chlorpyrifos; neurodevelopment; working memory; HOME inventory; sex-specific
Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use.
Protein kinases are essential enzymes for cellular signalling, and are often regulated by participation in protein complexes. The mitogen-activated protein kinase (MAPK) p38 is involved in multiple pathways, and its regulation depends on its interactions with other signalling proteins. However, the identification of p38 interacting proteins is challenging. For this reason, we have developed label transfer reagents (LTRs) which allow labelling of p38 signalling complexes. These LTRs leverage the potency and selectivity of known p38 inhibitors to place a photo-crosslinker and tag in the vicinity of p38 and its binding partners. Upon UV irradiation, proteins that are in close proximity to p38 are covalently crosslinked, and labelled proteins are detected and/or purified through an orthogonal chemical handle. Here we demonstrate that p38-selective LTRs selectively label a diversity of p38 binding partners, including substrates, activators, and inactivators. Furthermore, these LTRs can be used in immunoprecipitations to provide low-resolution structural information on p38-containing complexes.
protein-protein interactions; signal transduction; p38 MAPK; crosslinking; chemical biology
Recent research has shown facial adiposity (apparent weight in the face) to be a significant predictor of both attractiveness and health, thus making it an important determinant of mate selection. Studies looking at the relationship between attractiveness and health have shown that individuals differentiate between the two by preferring a lower weight for attractiveness than for health in female faces. However, these studies have either been correlational studies, or have investigated weight perceived from only the face. These differences have been discussed with regard to sociocultural factors such as pressure from parents, peers and also media, which has been seen to have the highest influence. While exposure to media images has been shown to influence women’s own-body image, no study has yet directly tested the influence of these factors on people’s preferred weight in other women’s bodies. Here we examine how a short exposure to images of models influences men’s and women’s judgments of the most healthy looking and attractive BMI in Malaysian Chinese women’s bodies by comparing differences in preferences (for attractiveness and health) between groups exposed to images of models of varying attractiveness and body weight. Results indicated that participants preferred a lower weight for attractiveness than for health. Further, women’s but not men’s preferred BMI for attractiveness, but not health, was influenced by the type of media images to which they were exposed, suggesting that short term exposure to model images affect women’s perceptions of attractiveness but not health.
Leptospirosis is known to be an important cause of weather disaster-related infectious disease epidemics. In 2011, an outbreak of leptospirosis occurred in the relatively dry district of Anuradhapura, Sri Lanka where diagnosis was resisted by local practitioners because leptospirosis was not known in the area and the clinical presentation was considered atypical. To identify the causative Leptospira associated with this outbreak, we carried out a cross-sectional study. Consecutive clinically suspected cases in this district were studied during a two-and-a-half-month period. Of 96 clinically suspected cases, 32 (33.3%) were confirmed by qPCR, of which the etiological cause in 26 cases was identified using 16S rDNA sequencing to the species level. Median bacterial load was 4.1×102/mL (inter-quartile range 3.1–6.1×102/mL). In contrast to a 2008 Sri Lankan leptospirosis outbreak in the districts of Kegalle, Kandy, and Matale, in which a predominance of Leptospira interrogans serovars Lai and Geyaweera was found, most cases in the 2011 outbreak were caused by Leptospira kirschneri. Seven (21.9%) confirmed cases had acute renal failure; five (15.6%) had myocarditis; severe thrombocytopenia (<20,000/uL) was seen in five (15.6%) cases. This outbreak of leptospirosis in the relatively dry zone of Sri Lanka due primarily to L. kirschneri was characterized by markedly different clinical presentations and low leptospiremia. These observations and data demonstrate the public health relevance of molecular diagnostics in such settings, possibly related to the microgeographic variations of different Leptospira species, but of particular value to public health intervention in what appears to have been a regionally neglected tropical disease.
Leptospirosis outbreaks occur predictably in Sri Lanka after seasonal rains and flooding in the endemic wet zone. Molecular investigations with quantification of a post-flood leptospirosis outbreak in the non-endemic dry zone of Sri Lanka in 2011 suggest variation of biological, clinical, and molecular characteristics compared to previous reported leptospirosis outbreaks in the endemic areas, probably showing a micro-geographic variation of leptospirosis. This work demonstrates the direct clinical and public health relevance of modern molecular diagnostic technologies to identifying an endemic neglected tropical disease where previously not suspected, especially in the resource-poor setting.
A broadly based investigation of the effects of a diverse array of substituents on the photochemical rearrangement of p-hydroxyphenacyl esters has demonstrated that common substituents such as F, MeO, CN, CO2R, CONH2, and CH3 have little effect on the rate and quantum efficiencies for the photo-Favorskii rearrangement and the release of the acid leaving group or on the lifetimes of the reactive triplet state. A decrease in the quantum yields across all substituents was observed for the release and rearrangement when the photolyses were carried out in buffered aqueous media at pHs that exceeded the ground-state pKa of the chromophore where the conjugate base is the predominant form. Otherwise, substituents have only a very modest effect on the photoreaction of these robust chromophores.
substituent; pH; pKa; solvent effects; photorelease
Although osteoporosis affects women of all ages, the impact is most pronounced in frail residents in long term care. Nevertheless, few interventional trials have been performed in this population and few data on therapeutic alternatives are available in this cohort.
We describe the challenges and lessons learned in developing and carrying out a trial in frail long term care residents.
The ZEST (Zoledronic acid in frail Elders to STrengthen bone) study was designed to examine the safety and efficacy of a single-dose therapy for osteoporosis in frail residents in long term care in the Pittsburgh area. Women with osteoporosis who were 65 years of age and older and currently not on therapy, were randomized in a blinded fashion to intravenous zoledronic acid or placebo. Follow-up of each participant was planned for 2 years. All participants received appropriate calcium and vitamin D supplementation.
Seven hundred and thirty-three contacts were made with long term care residents of 9 participating facilities. Of 252 women screened, 181 women were eligible, enrolled, and were randomized. Multiple barriers to research in long term care facilities were encountered but overcome with direct communication, information sessions, in-service trainings and social events. Lessons learned included designing the study in a manner that avoided placing an additional burden on an already overcommitted facility staff, a two-stage consent process to separate screening from randomization, and a flexible examination schedule to accommodate residents while obtaining the necessary outcome measurements. Furthermore, a mobile unit accessible to participants containing state-of-the-art dual x-ray absorptiometry, assessment for vertebral fractures, and phlebotomy equipment allows all assessments to be performed on-site at each facility. Serious adverse events are collected from affiliated hospitals in real time with a novel electronic surveillance system.
The major limitation is selection of outcomes that can be assessed at participating facilities and do not require transport of participants to hospitals or clinics.
Clinical research for osteoporosis can be successfully and safely performed with frail residents in long term care facilities. Lessons learned from this study may inform future investigations among frail elderly residents of these facilities.
osteoporosis; long term care; frail elderly
In addition to bone mineral density (BMD), trabecular microstructure contributes to skeletal strength. Our goal was to examine changes in trabecular microstructure in women on therapy.
MATERIALS and METHODS
We followed 10 postmenopausal women receiving a bisphosphonate, risedronate (35 mg once weekly), over 12 months and examined trabecular microarchitecture with high resolution wrist MR images (hr-MRI). MRI parameters included bone volume/total volume (BV/TV), surface density (representing plates), curve density (representing rods), surface-to-curve ratio and erosion index (depicting deterioration). We assessed BMD of the spine, hip and radius and markers of bone turnover.
Women had been receiving bisphosphonate therapy for 43 ± 9 months (mean ± SD) prior to the first MRI. Indices of hr-MRI demonstrated improvement in surface-to-curve ratio (13.0 %) and a decrease in erosion index (12.1 %) consistent with less deterioration (both p<0.05). BMD of the spine, hip and radius and markers of bone turnover remained stable. Parameters of hr-MRI were associated with 1/3 distal radius BMD (correlation coefficient 0.71 to 0.86, p<0.05).
We conclude hr-MRI of the radius demonstrates improvements in trabecular microstructure not appreciated by conventional BMD and provides additional information on parameters that contribute to structural integrity in patients on antiresorptive therapy.
trabecular microarchitecture; high resolution MRI; bisphosphonate therapy; osteoporosis
Androgen deprivation therapy (ADT), a treatment for prostate cancer, is associated with bone loss and fractures. Dual energy x-ray absorptiometry (DXA) measured bone mineral density does not assess vertebral fractures (VF). High resolution microMRI (HR-MRI) assesses bone microarchitecture and provides structural information.
To determine if VF identification increased the diagnosis of osteoporosis beyond DXA and if HR-MRI demonstrated skeletal deterioration in men with VF, we cross-sectionally studied 137 men ≥ 60 years with nonmetastatic prostate cancer on ADT for ≥6 months. Vertebral fracture assessment (VFA) by DXA was confirmed with x-rays. HR-MRI of the wrist included bone volume to total volume (BV/TV), surface density (trabecular plates), surface/curve ratio (plates/rods) and erosion index (higher depicts deterioration).
VF were found in 37% of men; the majority were unknown. 7% of participants were classified as osteoporotic by hip or spine DXA. 37% of men without osteoporosis by DXA had VF identified, suggesting that 90% of patients with clinical osteoporosis would have been misclassified by DXA alone. By ANOVA comparison across VF grades, the BV/TV, surface density and spine, hip and wrist DXA were lower, and erosion index was higher in men with moderate-severe VF compared to lesser grades (all p<0.05). By unadjusted ROC analysis, the addition of HR-MRI to DXA at the spine, hip and femoral neck, added substantially (AUC increased 0.831 to 0.902, p<0.05) to prediction of moderate-severe vertebral fracture. HR-MRI indices were associated with spine, hip and wrist DXA measures (p< 0.01). Longer duration of ADT was associated with lower BV/TV, surface density and surface/curve ratio (p<0.05).
ADT for men with prostate cancer is associated with silent VF. DXA alone leads to misclassifications of osteoporosis which can be avoided by VF assessment. HR-MRI provides a novel technique to assess deterioration of structural integrity in men with VF and adds microstructural information.
prostate cancer; osteoporosis; bone densitometry; radiology
Constrictive pericarditis is a rare complication in the post–renal transplant period. It poses a diagnostic dilemma even in the modern era. Its incidence is not known and tuberculosis is implicated in some of the cases.
A 54-year-old Sri Lankan man, in the sixth year of transplant presented with resistant ascites, shortness of breath and elevated creatinine from the baseline. Pre-transplant he was empirically treated for tuberculosis pericarditis and was on isoniazid prophylaxis for 1 year following transplantation. Two-dimensional echocardiography and cardiac catheterization confirmed the diagnosis, and pericardiectomy was performed, which resulted in full resolution of the symptoms as well as the graft function. The histology or bacteriology failed to demonstrate features suggestive of tuberculosis in the surgical specimen.
In constrictive pericarditis, a causative factor is difficult to find. Isoniazid prophylaxis shows benefit in preventing tuberculosis-associated constrictive pericarditis.
Constrictive pericarditis; Isoniazid prophylaxis; Renal transplant; Tuberculosis