DNA-based vaccines: new possibilities for disease prevention and treatment.

Ottawa researcher Dr. Heather L. Davis has become a pioneer in the development of DNA-based vaccines. With her collaborators in France and Germany Davis found that introducing the DNA code for the envelope protein of the hepatitis B virus into the muscle tissue of mice prompted a strong and sustained immune response. She believes that DNA-based vaccines could prove to offer many advantages over conventional vaccines, not least of which are greater safety and effectiveness and reduced cost. She has also begun to explore the potential of DNA-based vaccines for use in the treatment of disease. In recent experiments Davis and colleagues in France have successfully used DNA vaccination to cure transgenic mice of a chronic hepatitis B carrier state.     

Successful Treatment of Kasabach-Merritt Syndrome with Prednisone and Epsilon-Aminocaproic Acid

The Kasabach-Merritt syndrome is characterized by thrombocytopenia and localized coagulopathy associated with a hemangioma. Most techniques applied to eradicate the tumor or accelerate its involution (surgery, radiation therapy, embolization) are invasive and require transfusion of large amounts of blood products. In some cases, medical treatment is the only alternative. Efficacy of steroids and antifibronolytic agents has already been described, but even this approach is associated with the administration of blood products. We report two cases of infants with Kasabach-Merritt syndrome associated with cardiac and hepatic hemangiomas. At admission, both had signs of cardiac failure. They were successfully treated with prednisone and epsilon-aminocaproic acid (EACA). Blood products were not required once the diagnosis was made. These observations have important implications for the management of patients with Kasabach-Merritt syndrome because they show that even in severe cases blood transfusions can be avoided by the use of prednisone and EACA.     

Selective inhibition of T cell proliferation but not expression of effector function by human alveolar macrophages

BACKGROUND: Alveolar macrophages are thought to play an important part in regulating lung immune responses. While it is clear that human alveolar macrophages suppress T cell proliferation in vitro, the mechanisms by which this is achieved are not clear, nor is it known whether alveolar macrophages also inhibit other aspects of T cell function. METHODS: Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin or house dust mite allergen, and cultured with variable numbers of autologous alveolar macrophages obtained by bronchoalveolar lavage from 20 normal subjects. RESULTS: Alveolar macrophages induced a reversible inhibition of T cell proliferation in response to both mitogen and allergen stimulation, with the latter being considerably more susceptible to inhibition. This was achieved via heterogenous mechanisms, involving both soluble factors derived from alveolar macrophages and cell-cell contact. Despite inhibiting proliferation, alveolar macrophages had little or no effect on T cell calcium flux, the characteristic changes in CD3, CD2, CD28 and interleukin-2 (IL-2) receptor expression which accompany normal T cell activation, and IL-2 and interferon gamma secretion. In contrast, alveolar macrophages inhibited the tyrosine phosphorylation of proteins which may be involved in IL-2 receptor-associated signal transduction. CONCLUSIONS: The immunoregulatory properties of alveolar macrophages are relatively selective, allowing T cell activation and cytokine secretion while inhibiting T cell proliferation within the lung.


     

A district urinary catheter policy. Why have one?

A catheter audit was performed at the Central Manchester Trust, which found that there was excessive ordering, inappropriate catheter selection by size, materials, balloon size and poor guidelines on catheter storage. From these findings and from the available literature, we have proposed guidelines on catheter selection with the aim of offering the best patient care and to provide cost efficiency which may be of benefit to other hospitals.     

Prevalence of mental illness and its impact on the use of home care and nursing homes: a population-based study of older adults in Manitoba.

OBJECTIVES: To determine the prevalence of mental illness in older adults and its effect on home care and personal care home (PCH) use. METHODS: Using nonidentifying administrative records (fiscal years 1997-1998 to 2001-2002) from the Population Health Research Data Repository housed at the Manitoba Centre for Health Policy, we determined the 5-year period prevalence for individuals aged 55 years and over (119 539 men and 145 752 women) for 3 mental illness categories: cumulative mental disorders (those having a diagnosis of depression, anxiety disorder, personality disorder, schizophrenia, and [or] substance abuse), any mental illness, and dementia. We calculated age-specific and age-adjusted rates of home care and PCH use and the prevalence of mental illness in PCH residents. RESULTS: From the group aged 55 to 59 years to the group aged 90 years or older, the prevalence of mental illness increased with the population's age. The prevalence of any mental illness rose from 32.4% to 45.0% in men and from 42.6% to 51.9% in women, and dementia prevalence rose from 2.0% to 33.6% in men and from 1.3% to 40.3% in women. The age-adjusted annual rates of open home care cases per 1000 population aged 55 and older varied by mental illness grouping (no mental disorder, 57 for men and 91 for women; cumulative mental disorders, 162 for men and 191 for women; dementia, 300 for men and 338 for women). The age-adjusted rates of PCH use per 1000 population aged 75 years and older also varied by mental illness grouping (no mental disorder, 53 for men and 78 for women; cumulative mental disorders, 305 for men and 373 for women; dementia, 542 for men and 669 for women). Among patients admitted to (or resident in) a PCH in 2002-2003, 74.6% (87.1%) had a mental illness, and 46.0% (69.0%) had dementia. CONCLUSIONS: Mental illness affects the use of home care and nursing homes profoundly. Individuals with dementia used home care at 3 times the rate of those having no mental illness diagnosis, and they used PCHs at 8 times the rate.     

Development and evaluation of a presurgical preparation program

Three presurgical preparation programs were developed and evaluated in an Australian hospital utilizing an additive component design. The component basic to all three preparation programs was modeling. This technique was compared with the additional components of teaching child coping skills and parent coping skills via videotape. Subjects were 28 children between the ages of 4 and 13 years who were scheduled for elective surgery. Anxiety of both the children and parents was assessed by self-report and behavior observation. Results indicated that there was no further anxiety reduction by the addition of child and parent coping skills. Results are discussed in terms of the viability of teaching coping skills via videotape particularly to parents. Methodological difficulties associated with research in this area are examined.     

The effects of norepinephrine transporter inactivation on locomotor activity in mice.

BACKGROUND: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. METHODS: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. RESULTS: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. CONCLUSIONS: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.