Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice.
Five electronic databases were searched between 2007 and 2009 to look for agreement studies. A total of 3,260 titles were initially identified. Only 412 titles were potentially related, and finally 210 fitted the inclusion criteria. The Bland-Altman method is the most popular method with 178 (85%) studies having used this method, followed by the correlation coefficient (27%) and means comparison (18%). Some of the inappropriate methods highlighted by Altman and Bland since the 1980s are still in use.
This study finds that the Bland-Altman method is the most popular method used in agreement research. There are still inappropriate applications of statistical methods in some studies. It is important for a clinician or medical researcher to be aware of this issue because misleading conclusions from inappropriate analyses will jeopardize the quality of the evidence, which in turn will influence quality of care given to patients in the future.
Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins, including CBX4, have been shown to accumulate at sites of DNA damage. However, it remains unclear whether or not CBX4 or its E3 sumo ligase activity is directly involved in the DNA damage response (DDR). Here we define a novel role for CBX4 as an early DDR protein that mediates SUMO conjugation at sites of DNA lesions. DNA damage stimulates sumoylation of BMI1 by CBX4 at lysine 88, which is required for the accumulation of BMI1 at DNA damage sites. Moreover, we establish that CBX4 recruitment to the sites of laser micro-irradiation-induced DNA damage requires PARP activity but does not require H2AX, RNF8, BMI1 nor PI-3-related kinases. The importance of CBX4 in the DDR was confirmed by the depletion of CBX4, which resulted in decreased cellular resistance to ionizing radiation. Our results reveal a direct role for CBX4 in the DDR pathway.
The neuroprotective and antioxidative effects of germinated brown rice (GBR), brown rice (BR) and commercially available γ-aminobutyric acid (GABA) against cell death induced by hydrogen peroxide (H2O2) in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H2O2-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP) and prevented phosphatidylserine (PS) translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.
germinated brown rice; γ-aminobutyric acid; hydrogen peroxide; neuroprotective; SH-SY5Y cell death
The polycomb repressor complex ubiquitylates γ-H2AX and other components of the DNA damage response pathway to facilitate genomic repair.
Polycomb group (PcG) proteins are major determinants of cell identity, stem cell pluripotency, and epigenetic gene silencing during development. The polycomb repressive complex 1, which contains BMI1, RING1, and RING2, functions as an E3-ubuiquitin ligase. We found that BMI1 and RING2 are recruited to sites of DNA double-strand breaks (DSBs) where they contribute to the ubiquitylation of γ-H2AX. In the absence of BMI1, several proteins dependent on ubiquitin signaling, including 53BP1, BRCA1, and RAP80, are impaired in recruitment to DSBs. Loss of BMI1 sensitizes cells to ionizing radiation to the same extent as loss of RNF8. The simultaneous depletion of both proteins revealed an additive increase in radiation sensitivity. These data uncover an unexpected link between the polycomb and the DNA damage response pathways, and suggest a novel function for BMI1 in maintaining genomic stability.
Adenomatous colorectal polyps (ACPs) are known to be the precursor lesions for colorectal cancer. The aim of the study was to determine the prevalence, endoscopic and pathological features of ACPs in patients referred for colonoscopy.
Patients and Methods:
The endoscopic and histological reports of adult patients who underwent complete colonoscopy in the gastroenterology unit of a regional Kuwaiti hospital between January 2008 and December 2008 were retrospectively studied. The specimens of polyps were reviewed by an experienced pathologist who was blinded to the clinical or endoscopic information. Non-neoplastic polyps were not included in the analysis.
Of 530 eligible patients (mean age, 45 years; male-female ratio, 2:1), 54 (10%) had 103 ACPs. Of the patients with ACPs (mean age, 57 years), 43 (80%) were males and 36 (67%) were Kuwaitis. Histopathological examination of the most significant polyp in each patient revealed that 40 (74%) polyps were tubular adenomas (TAs); 11 (20%), tubulovillous (TV) adenomas; and 3 (6%), villous adenomas. High-grade dysplasia was noticed in 4 (10%) adenomas. Fifteen (2.8%) of the 530 patients had advanced ACPs. Logistic regression analysis of some variables and their association with ACPs found that age (P<0.001; OR, 1.9; CI, 1.5-2.3), history of adenoma (P=0.001; OR, 6.4; CI, .2.1-19.4) and being Kuwaitis (P=0.029; OR, 2.1; CI, 1.1-4.1) to be independently associated with ACPs.
The most common histological type of ACPs was tubular adenoma. Advancing age, being Kuwaiti nationals and prior removal of ACPs were significantly associated with the occurrence of ACPs.
Colonoscopy; colorectal polyps; Kuwait
The aim of the study is to investigate whether standard doses of rosiglitazone (4 mg/daily) and ramipril (5 mg/daily) can reverse pre-clinical macrovasculopathy in newly diagnosed never treated type 2 diabetes (T2DM) patients.
In this randomized, double-blind, placebo-controlled study, 33 T2DM patients were randomized to rosiglitazone (4 mg/daily) or ramipril (5 mg/daily) or placebo for 1 year. Hemodynamic variables were measured at 3 treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.
In diabetic patients, PWV (P = 0.037) and AI (P = 0.005) with ramipril and AI (P < 0.001) with rosiglitazone were significantly reduced during overall treatment period from the baseline; however, these differences were not significant in comparison to placebo.
Discussion and conclusion
The present study showed that treatment with standard doses of rosiglitazone and ramipril are not adequate to reverse pre-clinical vasculopathy in T2DM. The lack of benefit in newly diagnosed T2DM may be because of the relatively short-term intervention and/or the use of lower doses of rosiglitazone/ramipril. Further trials are needed for a longer period of time, possibly with higher doses, to show whether rosiglitazone/ramipril can reverse pre-clinical vasculopathy in T2DM (ClinicalTrials.gov number, NCT00489229).
rosiglitazone; ramipril; diabetic vasculopathy
Stump appendicitis is a rare complication of appendectomy due to recurrent inflammation of the residual appendix. The diagnosis is often delayed due to low index of suspicious, which may result in serious complications.
We describe a case of stump appendicitis occurred 12 months after appendectomy in 25 years old man. Despite past medical history of appendectomy the diagnosis was made by means of ultrasound scan and an high degree of clinical suspicion.
Stump appendicitis is a rare but important complication of appendectomy, often misdiagnosed. Prompt recognition is important to avoid serious complications. This pathologic entity should always be kept in mind on case of right lower quadrant pain.
Tooth wear is the non-carious loss of tooth tissue, which results from three processes namely attrition, erosion and abrasion. These can occur in isolation or simultaneously. Very mild tooth wear is a physiological effect of aging. This study aims to estimate the prevalence of tooth wear among 16-year old Malay school children and determine a feasible sample size for further study. Fifty-five subjects were examined clinically, followed by the completion of self-administered questionnaires. Questionnaires consisted of socio-demographic and associated variables for tooth wear obtained from the literature. The Smith and Knight tooth wear index was used to chart tooth wear. Other oral findings were recorded using the WHO criteria. A software programme was used to determine pathological tooth wear. About equal ratio of male to female were involved. It was found that 18.2% of subjects have no tooth wear, 63.6% had very mild tooth wear, 10.9% mild tooth wear, 5.5% moderate tooth wear and 1.8 % severe tooth wear. In conclusion 18.2% of subjects were deemed to have pathological tooth wear (mild, moderate & severe). Exploration with all associated variables gave a sample size ranging from 560 – 1715. The final sample size for further study greatly depends on available time and resources.
pilot study; tooth wear; prevalence and sample size determination
A variety of apheresis devices are now available on the market for plateletapheresis. We compared two apheresis instruments (Fenwal Amicus and Fresenius COM.TEC) with regard to processing time, platelet (PLT) yield and efficiency, and white blood cell (WBC) content.
Material and Methods
Donors undergoing plateletpheresis were randomly separated into two groups (either the Amicus or the COM.TEC cell separator).
In the pre-apheresis setting, 32 plateletpheresis procedures performed with each instrument revealed no significant differences in donors’ sex, age, weight, height and total blood volume between the two groups. However, the pre-apheresis PLT count was higher with the COM.TEC than with the Amicus (198 × 103/μl vs. 223 × 103/μl; p = 0.035). The blood volume processed to reach a target PLT yield of ≥3.3 × 1011 was higher in the COM.TEC compared to the Amicus (3,481 vs. 2,850 ml; p < 0.001). The median separation time was also significantly longer in the COM.TEC than in the Amicus (61 vs. 44 min; p < 0.001). 91 and 88% of the PLT products collected with the Amicus and the COM.TEC, respectively, had a PLT count of >3.3 × 1011 (p = 0.325). All products obtained with both instruments had WBC counts lower than 5 ↔ 106, as required. There was no statistical difference with regard to collection efficiency between the devices (55 ± 15 vs. 57 ± 15%; p = 0.477). However, the collection rate was significantly higher with the Amicus compared to the COM.TEC instrument (0.077 ± 0.012 × 1011 vs. 0.057 ± 0.008 × 1011 PLT/min; p < 0.001).
Both instruments collected platelets efficiently. Additionally, consistent leukoreduction was obtained with both instruments; however, compared with the COM.TEC instrument, the Amicus reached the PLT target yield more quickly.
Plateletpheresis; Apheresis; Amicus; COM.TEC; Cell separator
To determine the prevalence of oral mucosal lesions and dentition status among non smoking diabetes patients attending the Diabetic Clinic at Hospital Universiti Sains Malaysia (HUSM).
Patients and Method:
This cross sectional case-control study involved 300 diabetic case and 300 non-diabetic control subjects. Data was collected from November 2007 till March 2008. Demographic information, duration and type of diabetes, glycosylated hemoglobin values (HbAc), medical complications, history and current use of medication was obtained from medical records. Detail oral examination of the oral cavity was done based on international criteria and WHO codes. The number of remaining teeth and presence of dentures were also noted.
There were more females in cases (67.7%) and controls (57.7%). Mean age in both groups was comparable. A higher percentage of subjects were in the 40–59 years age group. Most had type II diabetes (94.3%). About 42.3% had diabetes within the last five years followed by 35.5% who had diabetes between 5–10 years duration and 22.3% had diabetes for more than ten years. Most diabetic subjects were on oral treatment (64.3%) and had poor metabolic control (41.7%). About 10.7% had some form of diabetes complications. The most prevalent oral lesions among diabetics were fissured tongue (29%), denture stomatitis (13.7%), geographic tongue (3.3%) and frictional keratosis (3.0%). About one third of subjects in both groups use dentures. Diabetics have significantly higher prevalence of geographic tongue (p=0.050) and denture stomatitis (p= 0.026). They have a lower mean number of remaining teeth compared to non-diabetics (p<0.001).
Discussion and Conclusion:
Having less mean number of remaining teeth and a higher prevalence of oral lesions among diabetics is a worrying outcome. Thus diabetic patients need intensive dental care and attention to minimize the disease burden.
Phosphorylation of histone H2AX on serine 139 (gamma-H2AX, γH2AX) occurs at sites flanking DNA double-strand breaks (DSBs) and can provide a measure of the number of DSBs within a cell. Here we describe a rapid and simple flow-cytometry-based method, optimized to measure gamma-H2AX in non-fixed peripheral blood cells. No DSB induced signal was observed in H2AX−/− cells indicating that our FACS method specifically recognized gamma-H2AX accumulation. The gamma-H2AX assay was capable of detecting DNA damage at levels 100-fold below the detection limit of the alkaline comet assay. The gamma-H2AX signal was quantitative with a linear increase of the gamma-H2AX signal over two orders of magnitude. We found that all nucleated blood cell types examined, including the short-lived neutrophils induce gamma-H2AX in response to DSBs. Interindividual difference in the gamma-H2AX signal in response to ionizing radiation and the DSB-inducing drug calicheamicin was almost 2-fold in blood cells from patients, indicating that the amount of gamma-H2AX produced in response to a given dose of radiation varies significantly in the human population. This simple method could be used to monitor response to radiation or DNA-damaging drugs.
The aim of this study was to determine mean values for selected linear measurements on the face of children and adolescents to demonstrate gender differences in the measurements. Cross-sectional data from 262 school children (158 male, 104 female) aged between 6 and 15 years were taken by measuring certain identified facial landmarks using a sliding caliper. The landmarks were first located by careful inspection and/or palpation of the face and a mark created on the cutaneous surface, with the subject sitting in habitual occlusion in an upright position. A sliding caliper was used to measure the distances between the points. The data was analysed using SPSS version 10.0 to determine mean values, standard deviation and gender differences in the measurements. Upper facial heights, total facial height, inter-canthal distance and eye length measurements were significantly higher in male than in female for 15-year-old group (p<0.0001). The measurement between the highest and the lowest point of attachment of external ear to the head was significantly larger in male than in female for 11 year old age group.
facial growth; soft tissue facial morphometry
Tooth wear is a common finding in oral examinations. Pathological tooth wear (PTW) is the amount of wear that exceeds the normal phenomena of ageing or the normal threshold value of wear. The objective of this study was to determine the associated factors of PTW among 16-year-old secondary school children.
This case-control study involved 576 participants randomly selected from eight government secondary schools. The Smith and Knight Tooth Wear Index and WHO criteria were used for charting of tooth wear and dental caries respectively. Data were analyzed using a simplified Microsoft Excel program developed based on the index, to quantify PTW. Controls were subjects with no PTW indicated by zero scores on all tooth surfaces. Cases were subjects with PTW having at least one surface scoring 1 for tooth wear. Consequently, responses were obtained from self-administered questionnaire containing socio-demographic profile of the family, general questions, oral hygiene and food and drinks practices and other associated variables for tooth wear, which was previously developed based on expert opinions.
About 40% and 57% were males were in controls and cases respectively. On performing multivariable analysis, sex, monthly household income, carbonated drinks, duration of intake of orange juices, caries experience and swimming were significantly associated with PTW.
In conclusion the factors associated with PTW were no different from those encountered in Western societies. Realizing that some significant variables were modifiable, oral health promotion should emphasize on this information. The erosive potential of some foods and drinks require further investigation.
Intravenous glucose tolerance testing (IVGTT) is a common test of β-cell function in which a glucose load is administered and insulin and/or C-peptide responses are monitored.
Since the first IVGTT may be more stressful and stress may alter β-cell secretion or hepatic insulin extraction, we asked whether there was a first test effect.
Insulin and C-peptide responses were compared from two sequential IVGTTs performed within 6 months during staging for the Diabetes Prevention Trial – Type 1 (DPT-1) in 368 people at high risk for type 1 diabetes. 1+3 minutes (min) insulin data were used because the first phase insulin response (and peak insulin concentration) occurs within this time frame. Areas under the curve (AUC) calculations represent early insulin or C-peptide responses from 0 through 10 min post-glucose challenge.
More than half of all subjects were found to have first test values lower than the second. This was true for all measures of both insulin and C-peptide but the frequency was significantly different only for insulin measures corrected for basal and for insulin AUC (p<0.05). However, for subjects (n=99) whose 1+3min insulin response was < 10th percentile on the first test, there was a significant increase on the second test (p<0.05). The C-peptide: insulin ratio did not change significantly between tests, indicating that differences are due to changes in β-cell secretion rather than hepatic insulin uptake.
A statistically significant first test effect occurs during the IVGTT attributable to variations in insulin secretion rather than hepatic uptake.
An azobenzene-containing surfactant was synthesized for the phase transfer of α-cyclodextrin (α-CD)-capped gold nanoparticles between water and toluene phases by host–guest chemistry. With the use of the photoisomerization of azobenzene, the reversible phase transfer of gold nanoparticles was realized by irradiation with UV and visible light. Furthermore, the phase transfer scheme was applied for the quenching of a reaction catalyzed by gold nanoparticles, as well as the recovery and recycling of the gold nanoparticles from aqueous solutions. This work will have significant impact on materials transfer and recovery in catalysis and biotechnological applications.
azobenzene; cyclodextrin; host−guest systems; phase transfer; photoresponsive systems
Screening for colorectal cancer (CRC) has been associated with a decreased incidence and mortality from CRC. However, patient adherence to screening is less than desirable and resources are limited even in developed countries. Better identification of individuals at a higher risk could result in improved screening efforts. Over the past few years, formulas have been developed to predict the likelihood of developing advanced colonic neoplasia in susceptible individuals but have yet to be utilized in mass screening practices. These models use a number of clinical factors that have been associated with colonic neoplasia including the body mass index (BMI). Advances in our understanding of the mechanisms by which obesity contributes to colonic neoplasia as well as clinical studies on this subject have proven the association between BMI and colonic neoplasia. However, there are still controversies on this subject as some studies have arrived at different conclusions on the influence of BMI by gender. Future studies should aim at resolving these discrepancies in order to improve the efficiency of screening strategies.
Body mass index; Colorectal cancer; Colon cancer screening; Adenomas; Adipokines; Obesity
The Jatropha curcas plant or locally known as “Pokok Jarak” has been widely used in traditional medical applications. This plant is used to treat various conditions such as arthritis, gout, jaundice, wound and inflammation. However, the nature of compounds involved has not been well documented. Hence, this study was conducted to investigate the anti-inflammatory activity of different parts of J. curcas plant and to identify the active compounds involved.
In this study, methanol (80%) extraction of four different parts (leaves, fruits, stem and root) of J. curcas plant was carried out. Phenolic content of each part was determined by using Folin-Ciocalteau reagent. Gallic acid was used as the phenol standard. Each plant part was screened for anti-inflammatory activity using cultured macrophage RAW 264.7 cells. The active plant part was then partitioned with hexane, chloroform, ethyl acetate and water. Each partition was again screened for anti-inflammatory activity. The active partition was then fractionated using an open column chromatography system. Single spots isolated from column chromatography were assayed for anti-inflammatory and cytotoxicity activities. Spots that showed activity were subjected to gas chromatography mass spectrophotometry (GC-MS) analysis for identification of active metabolites.
The hexane partition from root extract showed the highest anti-inflammatory activity. However, it also showed high cytotoxicity towards RAW 264.7 cells at 1 mg/mL. Fractionation process using column chromatography showed five spots. Two spots labeled as H-4 and H-5 possessed anti-inflammatory activity, without cytotoxicity activity. Analysis of both spots by GC-MS showed the presence of hexadecanoic acid methyl ester, octadecanoic acid methyl ester and octadecanoic acid.
This finding suggests that hexadecanoic acid methyl ester, octadecanoic acid methyl ester and octadecanoic acid could be responsible for the anti-inflammatory activity of the J. curcas root extract.
Plant parts; Hexane extract; Hexadecanoic acid methyl ester; Octadecanoic acid methyl ester; Octadecanoic acid
Radiofrequency catheter ablation of the slow pathway is considered to be the treatment of choice for patients with atrioventricular nodal reentrant tachycardia. We report a 34-year-old female with mirror image dextrocardia due to unilateral pulmonary agenesis who underwent successful slow pathway ablation for typical atrioventricular nodal reentrant tachycardia. Using contrast injection, cardiac anatomy was identified in a short time and successfully ablated.
dextrocardia; AVNRT; ablation; pulmonary agenesis
African sleeping sickness is a neglected tropical disease transmitted by tsetse flies. New and better drugs are still needed especially for its second stage, which is fatal if untreated. 28DAP010, a dipyridylbenzene analogue of DB829, is the second simple diamidine found to cure mice with central nervous system infections by a parenteral route of administration. 28DAP010 showed efficacy similar to that of DB829 in dose-response studies in mouse models of first- and second-stage African sleeping sickness. The in vitro time to kill, determined by microcalorimetry, and the parasite clearance time in mice were shorter for 28DAP010 than for DB829. No cross-resistance was observed between 28DAP010 and pentamidine on the tested Trypanosoma brucei gambiense isolates from melarsoprol-refractory patients. 28DAP010 is the second promising preclinical candidate among the diamidines for the treatment of second-stage African sleeping sickness.
Consumption of a glass of bottle gourd juice is thought to work as a health “tonic” and part of traditional healthy living practices in India. The juice may in certain circumstances turn bitter with increased levels of the cytotoxic compound called Cucurbitacins. If the bitter juice is consumed it causes a toxic reaction in the gut, leading to abdominal discomfort/pain, vomiting, hematemesis, and hypotension which may be rarely fatal, especially in persons with pre-existing illness. In the absence of clear cut history regarding the consumption of the bitter bottle gourd juice and the initiation of symptoms, the differential diagnosis for the above symptoms will include diseases causing gastrointestinal bleed with hypotension and/or shock.
We report a case of bitter bottle gourd poisoning presenting with abdominal symptoms, hematemesis and shock and with an initial differential diagnosis of septicemia with septic shock and multi-organ involvement. We conduct a literature review and ponder the various differential diagnoses of this clinical scenario.
Bottle gourd; Cucurbitacins; Food-borne illness
Primary malignant liver tumours account for more than 1% of all paediatric malignancies, with the most common form being hepatoblastomas (HB). Such malignancies among Arab populations have rarely been addressed in the literature. Using data from Oman’s sole national referral centre for childhood solid malignancies, this study aimed to present the nationwide Omani experience with HB over the past 21 years.
This retrospective study reviewed the medical records of all children with HB who were managed in the Royal Hospital, Muscat, Oman, between January 1991 and April 2012. Clinical, radiological and laboratory characteristics were examined as well as treatments and outcomes.
During the study period, 15 patients with HB were treated. Of these, 10 have survived to date. Nine of the survivors were no longer receiving treatment and one patient still had the disease but was in a stable condition. Of the remaining five patients, three did not survive and two were lost to follow-up. The survival rate among patients who completed therapy was 91%.
HB has an excellent prognosis in Oman. The main obstacle to improving outcomes among Omani patients is non-compliance with therapy.
Hepatoblastoma; Neoadjuvant Therapy; Hepatic Cancer; Oman