Diversity of putative Tn5253-like elements in Streptococcus pneumoniae.

Pneumococcal resistance to tetracycline, chloramphenicol, erythromycin and clindamycin is often attributed to carriage of conjugative transposons of the Tn916 family. The less well studied conjugative transposon Tn5253 is a composite transposon consisting of a Tn916-like element inserted within the unrelated Tn5252 element, which has also been associated with chloramphenicol and tetracycline resistance. Here, carriage of the Tn5252 integrase (int(5252)), Tn5252-encoded umuC and umuD homologues and Tn916 integrase (int(916)) was examined among 55 clinical isolates of Streptococcus pneumoniae resistant to one or more of the above mentioned antibiotics. Tn5253-associated genes were common among the antibiotic-resistant S. pneumoniae examined, including members of international clones, although the spectrum of genes and resistances carried was diverse. Analysis of five isolates demonstrated insertion of a Tn5253-related element at the same chromosomal locus but sequence and restriction site diversity. This study shows for the first time a high degree of variability of Tn5253-related elements within clinical isolates of pneumococci. The fact that these elements are prevalent among internationally recognised pandemic clones warrants a more intensive investigation.

Managing peritoneal dialysis (PD)--factors that influence patients' modification of their recommended dialysis regimen. A European study of 376 patients.

OBJECTIVES: The purpose of the study was to assess the prevalence and extent of missed peritoneal dialysis (PD) exchanges and to identify possible predictors for regimen modification. DESIGN: The study was a cross sectional postal survey of PD patients. Patients were asked to complete a single questionnaire looking at factors that influenced their management of the prescribed regimen. PATIENTS: 551 patients were invited to participate in the study from 17 centres across three European countries; 10 centres from Belgium, 5 from Italy and 2 from the UK. Patients on continuous ambulatory peritoneal dialysis (CAPD), CAPD and Quantum, or automated peritoneal dialysis (APD) for more than three months and at least 18 years old were included in the study. 376 out of 551 questionnaires were completed; a response rate of 68%. RESULTS: 20% (n=67) of those who responded to the questionnaire admitted to modifying their treatment in the previous month. Those who were more likely to modify their treatment were younger, employed, had greater contact with the PD team, were on APD 10 hours or longer and were less satisfied with their APD treatment. CONCLUSION: Many of the patients self-reported modifying their dialysis regimen and possible predictors were highlighted from this study. By trying to identifying individual patients who do modify treatment healthcare professionals can target information that can support the patient in making safer treatment modification choices.

The burden of disease and injury in Australia.

An overview of the results of the Australian Burden of Disease (ABD) study is presented. The ABD study was the first to use methodology developed for the Global Burden of Disease study to measure the burden of disease and injury in a developed country. In 1996, mental disorders were the main causes of disability burden, responsible for nearly 30% of total years of life lost to disability (YLD), with depression accounting for 8% of the total YLD. Ischaemic heart disease and stroke were the main contributors to the disease burden disability-adjusted life years (DALYs), together causing nearly 18% of the total disease burden. Risk factors such as smoking, alcohol consumption, physical inactivity, hypertension, high blood cholesterol, obesity and inadequate fruit and vegetable consumption were responsible for much of the overall disease burden in Australia. The lessons learnt from the ABD study are discussed, together with methodological issues that require further attention.

The burden of mental disorders in Victoria, 1996.

BACKGROUND: Between 1998 and 1999, a burden of disease assessment was carried out in Victoria, Australia applying and improving on the methods of the Global Burden of Disease Study. This paper describes the methods and results of the calculations of the burden due to 22 mental disorders, adding 14 conditions not included in previous burden of disease estimates. METHODS: The National Survey of Mental Health and Wellbeing provided recent data on the occurrence of the major adult mental disorders in Australia. Data from international studies and expert advice further contributed to the construction of disease models, describing each condition in terms of incidence, average duration and level of severity, with adjustments for comorbidity with other mental disorders. Disability weights for the time spent in different states of mental ill health were borrowed mainly from a study in the Netherlands, supplemented by weights derived in a local extrapolation exercise. RESULTS: Mental disorders were the third largest group of conditions contributing to the burden of disease in Victoria, ranking behind cancers and cardiovascular diseases. Depression was the greatest cause of disability in both men and women. Eight other mental disorders in men and seven in women ranked among the top twenty causes of disability. CONCLUSIONS: Insufficient information on the natural history of many of the mental disorders, the limited information on the validity of mental disorder diagnoses in community surveys and considerable differences between ICD-10 and DSM-IV defined diagnoses were the main concerns about the accuracy of the estimates. Similar and often greater concerns have been raised in relation to the estimation of the burden from common non-fatal physical conditions such as asthma, diabetes and osteoarthritis. In comparison, psychiatric epidemiology can boast greater scientific rigour in setting standards for population surveys.

The Australian Burden of Disease Study: measuring the loss of health from diseases, injuries and risk factors.

This is an overview of the first burden of disease and injury studies carried out in Australia. Methods developed for the World Bank and World Health Organization Global Burden of Disease Study were adapted and applied to Australian population health data. Depression was found to be the top-ranking cause of non-fatal disease burden in Australia, causing 8% of the total years lost due to disability in 1996. Mental disorders overall were responsible for nearly 30% of the non-fatal disease burden. The leading causes of total disease burden (disability-adjusted life years [DALYs]) were ischaemic heart disease and stroke, together causing nearly 18% of the total disease burden. Depression was the fourth leading cause of disease burden, accounting for 3.7% of the total burden. Of the 10 major risk factors to which the disease burden can be attributed, tobacco smoking causes an estimated 10% of the total disease burden in Australia, followed by physical inactivity (7%).

Fifty-two-week oral toxicity study of the new cognition-enhancing agent nefiracetam in dogs.

A 52-week toxicity study by oral administration (capsule) was performed in beagle dogs with nefiracetam (N-(2,6-dimethylphenyl)-2-(2- oxo-1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7), a new cognition-enhancing agent, as a part of a safety evaluation program. Dosages of 0 (control), 10, 30 and 90 mg/kg/d were selected for this study. Treatment-related findings were confined to the 90 mg/kg/d level and indicated the kidney and the testis as the main target organs for toxicity. Signs of systemic toxicity, as indicated by the laboratory investigations, were not apparent until the second half of the study and included the principal findings of higher urea nitrogen, and creatinine, with higher urinary volumes and corresponding lower specific gravity, osmolarity and protein values. The microscopic pathology examination showed various changes at the renal papilla, collecting ducts, and medullary and cortical scarring. This examination also revealed decreased spermatogenesis in the testes, with associated decreased numbers/absence of spermatozoa in the epididymides. At the 30 mg/kg/d level, the minor microscopic pathology changes seen in the kidneys of one male animal were considered to be of equivocal toxicological importance. There were no treatment-related findings at the low dosage level (10 mg/kg/d) and, therefore, this level was considered as the non-toxic effect level of nefiracetam.

Delayed hematopoietic development in osteopetrotic (op/op) mice.

Changes in structure, cellularity, hematopoietic progenitor cell and macrophage content, and osteoclast activity were investigated in the hematopoietic organs of the colony-stimulating factor 1(CSF-1)-less osteopetrotic (op/op) mouse. The data indicated that op/op mice undergo an age-related hematopoietic recovery and resolution of osteopetrosis, suggesting that the hematopoietic system has the capacity to use alternative mechanisms to compensate for the absence of an important multifunctional growth factor, CSF-1. In young animals, op/op femurs were heavily infiltrated with bone, and marrow cellularity was significantly reduced. After 6 wk of age, there was an increase in the marrow space available for hematopoiesis. The femoral cavity of op/op mice progressively enlarged, and by 22 wk of age its appearance and marrow cellularity was comparable to that of controls. The percentage of op/op mononuclear phagocytes, defined by F4/80 antigen expression, progressively increased to normal levels by 35 wk of age. There was no difference in the incidence of both primitive and mononuclear phagocyte-committed, CSF-1-responsive progenitor cells in op/op marrow, but their femoral content was significantly reduced in young mice. During the period of reduced hematopoiesis in the marrow of young op/op mice, splenic hematopoietic activity was elevated. This mutant mouse represents a system for the study of the CSF-1-independent regulatory mechanisms involved in hematopoietic regulation.

Hepatic triglyceride accumulation and the ethanol physical withdrawal syndrome in mice.

Physical dependence on ethanol was induced in TO strain mice by chronic administration of ethanol by inhalation. The severity of the behavioral syndrome of withdrawal from ethanol was quantified by a subjective scoring method. During the chronic administration of ethanol, triglycerides accumulated in livers of male or female mice with a time course similar to that of the induction of physical dependence. When ethanol was withdrawn from adult or weaning dependent mice, a relationship was observed between the decline of triglyceride concentrations in liver and the duration of the ethanol withdrawal syndrome. The addition of DL-carnitine (7% w/w) to diet during the administration of ethanol markedly inhibited the accumulation of triglycerides, and significantly reduced the intensity of the ethanol withdrawal syndrome. Administration of carbon tetrachloride ((1.3 ml/kg i.p.), however, although augmenting hepatic triglyceride accumulation, had no significant effect on the withdrawal syndrome. The results are interpreted as suggesting either that ethanol-induced liver dysfunction plays a part in dependence, or, more likely, that triglyceride accumulation reflects an ethanol-induced metabolic disorder which is itself related to the induction of dependence.