Pulsed high intensity focused ultrasound mediated nanoparticle delivery: mechanisms and efficacy in murine muscle.

High intensity focused ultrasound (HIFU) is generally thought to interact with biological tissues in two ways: hyperthermia (heat) and acoustic cavitation. Pulsed mode HIFU has recently been demonstrated to increase the efficacy of a variety of drug therapies. Generally, it is presumed that the treatment acts to temporarily increase the permeability of the tissue to the therapeutic agent, however, the precise mechanism remains in dispute. In this article, we present evidence precluding hyperthermia as a principal mechanism for enhancing delivery, using a quantitative analysis of systemically administered fluorescent nanoparticles delivered to muscle in the calves of mice. Comparisons were carried out on the degree of enhancement between an equivalent heat treatment, delivered without ultrasound, and that of the pulsed-HIFU itself. In the murine calf muscle, Pulsed-HIFU treatment resulted in a significant increase in distribution of 200 nm particles (p < 0.016, n = 6), while the equivalent thermal dose showed no significant increase. Additional studies using this tissue/agent model also demonstrated that the pulsed HIFU enhancing effects persist for more than 24 h, which is longer than that of hyperthermia and acoustic cavitation, and offers the possibility of a novel third mechanism for mediating delivery.

Delivering care to the streets.

St. Francis Hospital's management team has collaborated with other community organizations to respond to the very real needs of the homeless and indigent in Wilmington, DE. St. Francis Hospital has developed two innovative programs: St. Clare Medical Outreach and Tiny Steps. Recognizing that the poor and indigent find transportation, clinic schedules, and intimidating paperwork to be major barriers to healthcare, St. Francis Hospital and its partner in this collaborative ministry, Ministry of Caring, sought a creative approach that would bring healthcare to Wilmington's needy in a nonthreatening way, while also offering continuity of care. St. Clare Medical Outreach van staff began administering much-needed healthcare services on April 27, 1992. For years, St. Francis Hospital has supported a pediatric clinic at West End Neighborhood House, an organization offering a variety of family-related services to the indigent. In September 1992 the hospital collaborated with other community organizations to offer a more comprehensive, holistic healthcare service to those in need. This joint-venture of St. Francis Hospital and 11 other community organizations is designed to lower the infant mortality rate by identifying high-risk pregnancies early on and managing complications during pregnancy and after birth.

Total body potassium in long-term frusemide therapy: is potassium supplementation necessary?

Measurements of total body potassium (T.B.K.) were made by whole-body counting in four groups of patients receiving oral frusemide for one year. Patients in group 1 had essential hypertension and normal renal function and received 40 mg frusemide daily without potassium supplements. Patients in group 2 were similar but received oral potassium supplements for the first four months of treatment. Patients in group 3 had hypertension associated with renal disease and received 120 mg frusemide daily without potassium supplements. Patients in group 4 also had hypertension and renal impairment and in addition to 120 mg frusemide daily they received oral potassium supplements for four months. No evidence of depletion of T.B.K. was found in any of the groups after continuous treatment with frusemide for one year. It is questioned whether potassium supplementation in long term diuretic therapy with frusemide is necessary unless there is evidence of pre-existing potassium depletion or of some other factor such as cardiac failure, cirrhosis of the liver, or the nephrotic syndrome.