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The toxicity of single doses of the anthracycline epirubicin was compared in the rat after either the intravenous (i.v.; 2-6 mg/kg) or intraperitoneal (i.p.; 4-8 mg/kg) administration of the drug. These doses produced comparable acute toxicity that was characterised by a dose-dependent, transient reduction in body weight (less than 15%) in the first 2 weeks after drug administration. Sequential measurements of cardiac output in animals that received i.v. doses of epirubicin showed that the time-related changes in cardiac function were biphasic. There was an initial decline in cardiac output in the first 12 weeks, which was followed by a phase of persistent depression in cardiac output between 12 weeks and 20 weeks. The time-related changes in cardiac function after i.p. doses of the drug were more variable, although the trend of changes, as after i.v. administration, appeared to be dose-dependent. Recovery of cardiac function occurred at 20 weeks after an i.p. dose of 4 mg/kg; however, after 6 mg/kg, cardiac function was significantly depressed after greater than or equal to 16 weeks. For both routes of administration, the likelihood of late cardiac complications was dependent on the level of the reduction in cardiac output at 12 weeks. A study of the impairment of cardiac output and the incidence of cardiac-related mortality demonstrated that epirubicin was more cardiotoxic after i.v. administration. Equivalent cardiotoxic doses of epirubicin after i.v. and i.p. administration were highly linearly correlated (r = 0.998), although there appeared to be a threshold dose of 3.33 mg/kg after i.p. administration of the drug. Thus, the relative cardiotoxicity between the two routes of administration was found to be dependent on the drug dose and, hence, the level of effect. The difference in the effect was less for high drug doses. The LD50 for deaths due to cardiotoxicity at 20 weeks was 4.42 +/- 0.42 mg/kg after i.v. administration, which was significantly lower than the value of 6.28 +/- 0.41 mg/kg obtained after i.p. administration of the drug (P less than 0.01). There was no qualitative difference in the histological lesions induced in the myocardium after the i.v. vs i.p. administration of epirubicin. [ABSTRACT FROM AUTHOR]

Background:Myofibroblasts have an important role in regulating the normal colorectal stem cell niche. While the activation of myofibroblasts in primary colorectal cancers has been previously described, myofibroblast activation in lymph node metastases has not been described before.Methods:Paraffin-embedded lymph node sections from patients with macrometastases, micrometastases and isolated tumour cells were stained to identify myofibroblasts and to characterise the distribution of different cell types in tumour-containing lymph nodes. The extent of myofibroblast presence was quantified and compared with the size of the metastasis and degree of proliferation and differentiation of the cancer cells.Results:We show substantial activation of myofibroblasts in the presence of colorectal metastases in lymph nodes, which is intimately associated with glandular structures, both in micro- and macrometastases. The degree of activation is positively associated with the size of the metastases and the proportion of Ki67+ve cancer cells, and negatively associated with the degree of enterocyte differentiation as measured by CK20 expression.Conclusion:The substantial activation of myofibroblasts in tumour-containing lymph nodes strongly suggests that these metastatic cancer cells are still significantly dependent on their microenvironment. Further understanding of these epithelial-mesenchymal interactions could lead to the development of new therapies in metastatic disease. [ABSTRACT FROM AUTHOR]

Both central obesity and increased carotid intima-media thickness (IMT) are markers of atherosclerosis and associated with cardiovascular diseases (CVD). Information of IMT in Chinese subjects with central obesity is limited. This study was performed to assess the rate of atherosclerosis and abnormal IMT in asymptomatic Chinese subjects with central obesity, and to investigate the association between IMT values and CVD risk factors including hypertension, hyperglycaemia and dyslipidaemia. We studied 122 centrally obese adults who had good past health. IMT measurements on carotid arteries were performed and fasting blood taken for plasma glucose and lipid profiles. Abnormal IMT was defined as > 0.9 mm. Atherosclerosis was defined as the presence of one or more visible plague. Of the 122 subjects, the mean (±SD) age was 59.4 ± 5.8 years (median [range]: 59.0 [45-75] years). The median IMT value was 0.70 mm (range: 0.53-1.19 mm) [men vs. women: 0.74 mm vs. 0.66 mm, P-value: < 0.001]. IMT values and the rate of atherosclerosis increased with age and the number of CVD risk factors ( P-value for trend: < 0.05). Using binary logistic regression to predict the presence of atherosclerosis with the presence of abnormal IMT, age, gender, and other CVD risk factors as independent variables, age (OR [95% CI] = 1.13 [1.03, 1.23], P = 0.009) and abnormal IMT (OR [95% CI] = 4.05 [1.09, 15.03], P = 0.037) were independently associated with atherosclerosis. In conclusion, among Hong Kong Chinese asymptomatic subjects with central obesity, there was a high rate of CVD risk factors. We found that 19% of these subjects had carotid atherosclerotic plaques and 10% of them had abnormal IMT (>0.9 mm). Carotid IMT study may serve as an appropriate screening tool to diagnose atherosclerosis in the centrally obese middle-aged population. [ABSTRACT FROM AUTHOR]

We look forward to the development and distribution of commercially available fluorescence laparoscopes that can detect multiple wavelengths, which will allow more widespread use of methylene blue as a fluorescence dye to identify the position of ureters intra-operatively. In the two studies which were quoted by the review [[2]], we used an in-house fluorescence capable laparoscope that was tuned to the 660 nm wavelength to detect fluorescence from methylene blue. Dear Sir I read with interest the article entitled "Currently available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters: a systematic review" by Slooter et al. [[1]]. [Extracted from the article]

The article discusses the research study conducted which examines the quality of information related to patients of anal fissures and fistulas and its treatment, available on Internet on several search engines including Google, Yahoo and Wikipedia. Topics discussed include information on symptoms, investigations, and treatment option of the diseases, use of DISCERN instrument used to evaluate the quality and reliability of the information available, and variability in quality of information.

A prospective observational study of the pathophysiology of sodium and water disorders in patients with pituitary region tumours after surgical excision was carried out in 20 patients. Serial pre-operative and post-operative fluid and sodium balance, plasma and urine elctrolyte biochemistry and their derived parameters, and circulating hormones associated with fluid balance, atrial natriureic peptide (ANP) and antidiuretic hormone (ADH) were documented to correlate with the patients' clinical conditions. Ten out of these twenty cases developed diabetes insipidus (DI) requiring ADH replacement therapy, although in the majority (6 cases), this way only a transient event. Of the nine patients who developed hyponatraemia, six had symptoms such as impaired consciousness and convulsions. Four patients developed alternating hypoatraemia and hypernatraemia, which constituted a difficult group, where appropriate sodium and fluid management, and ADH replacement therapy were based upon twice daily plasma and urine biochemistry and their derived parameters. Whilst DI in this group of patients was the result of a low circulating ADH level, hyponatraemia was not associated with an exaggerated ADH activity (6.0 ± 2.3 vs 7.4 ± 2.3 pmol/ml, mean ± SEM). Rather, hyponatraemia was strongly associated with an elevated circulating ANP concentration (82.4±10.5 vs 30.0 ±3.1 pmol/ml, mean ± SEM, p < 0.001), resulting in salt wasting and hypovolaemia. [ABSTRACT FROM AUTHOR]

We report the incidence of the chronic lymphoproliferative disorders evolving with leukaemia in Hong Kong. Our findings demonstrate that B cell malignancies are significantly more frequent than mature T cell neoplasms, a picture similar to that seen in Western countries but different from other Eastern countries, eg Japan, where T cell malignancies are more frequent. In contrast to the West, where chronic lymphocytic leukaemia (CLL) is the most common disorder, in Hong Kong there is a clear predominance of B cell lymphomas in leukaemic phase accounting for two-thirds of the cases and particularly those displaying lymphoplasmacytic features or with villous lymphocytes. CLL in Hong Kong has similar clinical and laboratory features to the disease in patients from the West. Distinct disease categories, rare in the West such as the variant form of hairy cell leukaemia and T cell prolymphocytic leukaemia, are also documented. It is unclear whether the differences in prevalence of disease subtypes between Hong Kong and the West relate to different genetic background or environmental factors determinant of the development or progression of the leukaemia. Further studies investigating the genetic/molecular lesions may help to clarify whether the aetiopathogenesis of the lymphoid disorders in Hong Kong is similar to that of Western countries. [ABSTRACT FROM AUTHOR]

The protective activity of the bisdioxopiperazine ICRF-187 against the cardiotoxicity of doxorubicin was evaluated in the rat using both functional and histological assays. Animals that had received a single i.v. dose of doxorubicin (4 mg/kg) alone were compared with those that had been pretreated with a single i.v. injection of saline or ICRF-187 (40 or 60 mg/kg). All rats showed a transient reduction in body weight during the first 3 weeks after drug administration. The greatest reduction (approximately 16%) was observed in animals that had received a combination of ICRF-187 (40 or 60 mg/kg) and doxorubicin. Deaths related to cardiotoxicity were observed only in rats that had received doxorubicin alone and in those treated with saline; most of the deaths occurred at between 8 and 13 weeks after drug administration. Sequential assessments of heart function showed a persistent depression of cardiac output in animals that had received doxorubicin, with or without pretreatment with ICRF-187. The reduction in cardiac output observed in rats that had been pretreated with ICRF-187 (40 or 60 mg/kg) amounted to approximately 15% and approximately 30% after 12 and 20 weeks, respectively, indicating that cardioprotection was only partial. Nevertheless, this represented a marked improvement as compared with the approximately 35% reduction in cardiac output measured at 12 weeks in animals that had received doxorubicin but without pretreatment with ICRF-187. Histological examination of animals that had died during the course of the study and had received doxorubicin after pretreatment with saline revealed severe myocardial lesions typical of doxorubicin-induced damage. In contrast, animals that had been pretreated with ICRF-187 and survived for up to 20 weeks after treatment showed a marked amelioration of these lesions. The present findings may be interpreted as a true cardioprotection or a delay in the onset of the cardiotoxicity of doxorubicin resulting from pretreatment with the bisdioxopiperazine ICRF-187. Although prior and ongoing clinical trials clearly indicate that ICRF-187 protects patients well against doxorubicin-induced heart damage, further investigations are required before high doses of ICRF-187 can be used as a means of increasing the protective activity of this drug against doxorubicin-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg/kg doxorubicin (DOX) given either as free drug or in the form of three N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly-Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg/kg) was significantly lower than that observed in those that received free DOX (4 mg/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg/kg; P less than 0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of approximately 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was approximately 12% lower than that measured in age-matched control rats (P less than 0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P less than 0.05). In addition, no significant histological change was observed in the heart of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) [ABSTRACT FROM AUTHOR]

A correction to the article "Quality of patient information on the internet for the treatment of anal fistula and anal fissure," by F. Scott and colleagues, that was published in a 2014 issue of the periodical is presented.