Detection of heart disease by open access echocardiography: a retrospective analysis of general practice referrals

Background

Heart disease is difficult to detect clinically and it has been suggested that echocardiography should be available to all patients with possible cardiac symptoms or signs.

Aim

To analyse the results of 2 years of open access echocardiography for the frequency of structural heart disease according to request.

Design and setting

Retrospective database analysis in a teaching hospital open access echocardiography service.

Method

Reports of all open access transthoracic echocardiograms between January 2011 and December 2012 were categorised as normal, having minor abnormalities, or significant abnormalities according to the indication.

Results

There were 2343 open access echocardiograms performed and there were significant abnormalities in 29%, predominantly valve disease (n = 304, 13%), LV systolic dysfunction (n = 179, 8%), aortic dilatation (n = 80, 3%), or pulmonary hypertension (n = 91, 4%). If echocardiography had been targeted at a high-risk group, 267 with valve disease would have been detected (compared to 127 with murmur alone) and 139 with LV systolic dysfunction (compared to 91 with suspected heart failure alone). Most GP practices requested fewer than 10 studies, but 6 practices requested over 70 studies.

Conclusion

Open access echocardiograms are often abnormal but structural disease may not be suspected from the clinical request. Uptake by individual practices is patchy. A targeted expansion of echocardiography in patients with a high likelihood of disease is therefore likely to increase the detection of clinically important pathology.     

Synthesis of 99mTc‐roxithromycin: A novel diagnostic agent to discriminate between septic and aseptic inflammation

Roxithromycin is a second‐generation macrolide antibiotic derived from erythromycin. In the current study, roxithromycin (ROX) was successfully labeled with technetium‐99m for early diagnosis of bacterial infection and discrimination between septic and aseptic inflammation. The highest radiochemical purity of ≥95% was achieved by investigating different labeling parameters such as pH, ligand/reducing agent concentration, temperature, and amount of stabilizing agent. For this purpose, 0.3–0.5 mg ligand, 2–6 μg SnCl₂·2H₂O as a reducing agent at basic pH (8–10 pH) and 2 mg mannitol used as a stabilizing agent, in the end, 370 MBq ^99mTc added into the reaction vials and incubated for a wide range of temperature (?4 to 65°C). The percent radiochemical purity of ^99mTc‐roxithromycin was assessed with the help of the radio‐thin‐layer chromatography technique. The characterization studies were carried out using electrophoresis and Radio‐HPLC techniques as well as saline stability and serum stability studies were also performed. Furthermore, biodistribution study was also performed in an inflamed animal model to discriminate between septic (heat‐killed Staphylococcus aureus) and aseptic (turpentine oil) inflammatory lesions. The results were elaborated that ^99mTc‐roxithromycin (^99mTc‐ROX) was clearly bounded at the septic inflammation site (T/NT ratio of 7.08 ± 1.14) at 30 min postadministration, and maximum accumulation was seen in heart, lungs, liver, stomach, kidneys, and intestine. The results were suggested that ^99mTc‐ROX might be used to discriminate between septic and aseptic inflammatory lesions at an early stage.     

Evaluation of D-methionine as a novel oral radiation protector for prevention of mucositis.

PURPOSE: Oral mucositis is a common acute morbidity associated with radiation and/or chemotherapy treatment for cancer. D-Methionine (D-Met), the dextro-isomer of the common amino acid l-methionine, has been documented to protect normal tissues from a diverse array of oxidative insults. EXPERIMENTAL DESIGN: We evaluated if D-Met could selectively prevent radiation-induced oral mucositis using in vitro cell culture models as well as an in vivo model of radiation injury to the oral mucosa in C3H mice. RESULTS: Unlike free-radical scavengers, which protected both normal and transformed tumor cells in vitro from radiation-induced cell death, treatment with d-Met in culture protected nontransformed primary human cells from radiation-induced cell death (protective factor between 1.2 and 1.6; P<0.05) whereas it did not confer a similar protection on transformed tumor cells. D-Met treatment also provided significant protection to normal human fibroblasts, but not to tumor cell lines, from radiation-induced loss of clonogenicity (protection factor, 1.6+/-0.15). D-Met treatment did not alter DNA damage (as measured by histone phosphorylation) following irradiation but seemed to selectively mitigate the loss of mitochondrial membrane potential in nontransformed cells, whereas it did not provide a similar protection to tumor cells. Tumor control of implanted xenografts treated with radiation or concurrent cisplatin and radiation was not altered by D-Met treatment. Pharmacokinetics following administration of a liquid suspension of D-Met in rats showed 68% bioavailability relative to i.v. administration. Finally, in a murine model of mucositis, a dose-dependent increase in protection was observed with the protective factor increasing from 1.6 to 2.6 over a range of oral D-Met doses between 200 and 500 mg/kg (P<0.0003). CONCLUSIONS: D-Met protected normal tissues, but not tumor cells, in culture from radiation-induced cell death; it also protected normal cells from radiation-induced mucosal injury in a murine model but did not alter tumor response to therapy. Further studies on the use of D-Met to protect from oral mucositis are warranted.     

Malnutrition and liver disease in a developing country

Malnutrition is a highly prevalent and under recognized condition in developing countries of South Asia. The presence of malnutrition causes a severe impact on patients with liver cirrhosis. The etiology of cirrhosis differs in the South Asian region compared to the West, with hepatitis B and C still being the leading causes and the prevalence of nonalcoholic fatty liver disease increasing over time. Comorbid malnutrition worsens outcomes for cirrhosis patients. Urgent attention to address malnutrition is needed to improve patient outcomes. The etiology and pathophysiology of malnutrition in liver diseases is multifactorial, as reduction in liver function affects both macronutrients and micronutrients. A need for nutritional status assessment for liver disease patients exists in all parts of the world. There are many widely studied tools in use to perform a thorough nutritional assessment, of which some tools are low cost and do not require extensive training. These tools can be studied and evaluated for use in the resource limited setting of a country like Pakistan. Treatment guidelines for proper nutrition maintenance in chronic liver disease exist for all parts of the world, but the knowledge and practice of nutritional counseling in Pakistan is poor, both amongst patients and physicians. Emphasis on assessment for nutritional status at the initial visit with recording of vital signs is needed. Simultaneously, treating physicians need to be made aware of the misconceptions surrounding nutritional restrictions in cirrhosis so that patient education is done correctly based on proper scientific evidence.     

Evaluation of micronucleus frequencies and DNA damage in glass workers exposed to arsenic

Arsenic (As) is a known human carcinogen; however, very little is known about the health consequences of occupational exposure to As. In the present study, we assessed the genotoxic damage in the blood cells and in the buccal cells of south Indian glass factory workers who are occupationally exposed to As. The As content in the whole blood of 200 workers and 165 controls was evaluated with inductively coupled plasma mass spectrometry. Blood leukocytes from the subjects were monitored for the level of DNA damage using the Comet assay (mean comet tail length); buccal cells were used to determine the frequency of micronuclei (MN). The mean As concentration was significantly higher in the workers (56.76 microg/L) than in the controls (11.74 microg/L) (P < 0.001). The workers also had increased frequencies of MN in the buccal cells and increased levels of DNA damage in leukocytes compared to the controls (P < 0.001). There were significant correlations between the genotoxicity endpoints that were evaluated and blood As concentration, smoking, age, and the duration of working in the factory. Also, a significant correlation was observed between the frequency of MN and comet tail-length for the worker samples. Our findings indicate that chronic occupational exposure to As is genotoxic and that the Comet assay and micronucleus test are useful assays for evaluating genotoxicity in humans occupationally exposed to As.     

In vivo genotoxic effect of nickel chloride in mice leukocytes using comet assay.

DNA damage induced by nickel chloride (NiCl2) in leucocytes of Swiss albino mice has been studied in vivo. The comet assay or the alkaline single cell gel electrophoresis (SCGE) assay was used to measure the DNA damage. The mice were administered orally with acute doses of 3.4, 6.8, 13.6, 27.2, 54.4 and 108.8 mg/kg body weight (b.wt.) NiCl2. Samples of whole blood were collected at 24, 48 and 72 h, first week and second week post-treatment for alkaline SCGE assay to study single/double strand breaks in DNA. A significant increase in mean comet tail length indicating DNA damage was observed with NiCl2 at 24, 48 and 72 h post-treatment (P<0.05). A gradual decrease in the mean tail length was observed at 72 h post-treatment indicating repair of the damaged DNA. The mean tail length showed a dose-related increase and time dependent decrease after treatment with NiCl2 when compared to controls. The study also confirms that the comet assay is a sensitive and rapid method to detect DNA damage caused by heavy metals like nickel (Ni).     

Breast Cancer Screening in Malaysia: A Policy Review

Background: Breast cancer is the leading cause of cancer among Malaysian women. The implementation of prevention measures including screening has the potential to reduce the burden of breast cancer which caused by late presentation. Aims: This paper aimed to review the public health policy relating to breast cancer screening in Malaysia that was undertaken in order to contribute to policy development regarding cancer prevention, detection and the improvement of services for Malaysian women. Methods: The policy review strategy included a specific search of the website of the Ministry of Health in Malaysia for relevant policies. In addition, we searched Google and Pubmed for breast cancer screening programmes, policies, and guidelines for women in Malaysia. In addition, experts and stakeholders provided additional resources, published in Malay language. Relevant guidelines in the Malay language were translated into English and included the document review. Results: The policy analysis indicated that although it is known that screening, early detection and diagnosis improve survival rates, delayed diagnosis remains a significant issue.  The Ministry of Health policy stipulates the provision of opportunistic mammography screening. However, the uptake is varied, and implementation is challenging due to a lack of awareness about screening and difficulties related to accessing services, especially in rural areas. The establishment and implementation of referral guidelines is essential to receive timely treatment for breast cancer patients. There is a need to enhance the cancer reporting by the doctors to the national cancer registry, in collaboration with government services and the private cancer-care sector to improve the monitoring and evaluation of cancer control policies and programmes. Conclusion: A focus on raising awareness, increasing the accessibility of screening facilities and improving referral processes and the overall connectivity of the cancer care system are key steps to down-staging breast cancer in Malaysia.     

In vivo genotoxic effect of potassium dichromate in mice leukocytes using comet assay.

Hexavalent chromium is a well-known mutagen and carcinogen. In the present investigation, single-/double-stranded DNA breaks by potassium dichromate (K2Cr2O7) in mice, a sensitive model for genotoxic effects, have been studied in vivo using alkaline single-cell gel electrophoresis (SCGE)/comet assay. Mice were administered orally with a range of doses starting from 0.59 to 76.0 mg/kg body weight of K2Cr2O7 and samples of whole blood were collected at 24, 48, 72, 96 h, week 1 and week 2 post-treatment for alkaline SCGE assay to study DNA damage. The rationale for using leukocytes was to reflect biomarker analysis in humans. Significant increase in mean comet tail length (5.7-24.25 microM) indicating DNA damage was observed at all the doses with K2Cr2O7 when compared with controls (3.26 microM). Maximum increase in mean comet tail length was observed at 9.5 mg/kg body weight at 48 h post-treatment (24.25 microM). The mean comet tail length showed a clear dose-dependent increase from 0.59 to 9.5 mg/kg body weight and a dose-dependent decrease in higher doses (19.0-76.0 mg/kg body weight). A gradual decrease in the tail lengths from 72 h post-treatment was observed by the second week, and values had returned to control levels at all doses, indicating repair of the damaged DNA and/or loss of heavily damaged cells. The study also reveals that comet assay is a sensitive and rapid method for detecting DNA damage caused by heavy metals such as chromium (Cr).