Novel approaches for the design, delivery and administration of vaccine technologies.

It is easy to argue that vaccine development represents humankind's most important and successful endeavour, such is the impact that vaccination has had on human morbidity and mortality over the last 200 years. During this time the original method of Jenner and Pasteur, i.e. that of injecting live-attenuated or inactivated pathogens, has been developed and supplemented with a wide range of alternative approaches which are now in clinical use or under development. These next-generation technologies have been designed to produce a vaccine that has the effectiveness of the original live-attenuated and inactivated vaccines, but without the associated risks and limitations. Indeed, the method of development has undoubtedly moved away from Pasteur's three Is paradigm (isolate, inactivate, inject) towards an approach of rational design, made possible by improved knowledge of the pathogen-host interaction and the mechanisms of the immune system. These novel vaccines have explored methods for targeted delivery of antigenic material, as well as for the control of release profiles, so that dosing regimens can be matched to the time-lines of immune system stimulation and the realities of health-care delivery in dispersed populations. The methods by which vaccines are administered are also the subject of intense research in the hope that needle and syringe dosing, with all its associated issues regarding risk of injury, cross-infection and patient compliance, can be replaced. This review provides a detailed overview of new vaccine vectors as well as information pertaining to the novel delivery platforms under development.

Peripheral joint laxity increases in pregnancy but does not correlate with serum relaxin levels.

OBJECTIVE: Our purpose was to evaluate peripheral joint laxity during pregnancy and to determine whether serum relaxin levels are associated with increased joint laxity. STUDY DESIGN: A prospective observational study was performed. RESULTS: A significant increase in joint laxity was found in five of seven peripheral joints over the course of the pregnancy and post partum. There was no correlation with serum relaxin levels. There were no significant differences in joint laxity on the basis of parity, age, or prepregnancy exercise levels. CONCLUSIONS: Peripheral joint laxity is noted to increase as pregnancy progresses. The cause of this change is undetermined.

Chronic exertional compartment syndrome: correlation of compartment pressure and muscle ischemia utilizing 31P-NMR spectroscopy.

In the past 5 years, a great deal of time and effort has been expended in an effort to better define clinical, anatomic, and laboratory parameters of CECS. It is now a well-recognized entity and one that can be readily resolved with fasciotomy. But the reasons for predisposition and the pathophysiologic mechanisms remain obscure. It appears, however, that basing the decisions for fasciotomy on clinical characteristics alone leads to overdiagnosis and excessive surgery. In this series, almost 50% of the referred subjects failed to demonstrate adequate laboratory criterion for the diagnosis of CECS. Fasciotomy in these patients may have effected a cure, but the reasons may be unrelated to increased intracompartmental pressure. Furthermore, in the laboratory diagnosis of CECS, the rate of return to resting compartment pressure following exercise seems more accurate than reliance on resting pressure alone. 31P-NMR has proved valuable in the dynamic assessment of muscle ischemia as reflected by relative PCr concentrations. Finally, although a mechanism explaining the source of pain has not been established by this study, it appears that ischemia is not a significant factor.

Compartment syndrome: a quantitative study of high-energy phosphorus compounds using 31P-magnetic resonance spectroscopy.

The purpose of this study was to quantitate the intracellular high-energy phosphate compounds during 6 hours of tissue ischemia in the anterior tibial compartment of beagles subjected to an induced traumatized compartment syndrome. The goal of this work was to provide clinicians with objective criteria to augment clinical judgment regarding surgical intervention in the impending compartment syndrome. A beagle model was utilized in which the Delta pressure (difference between the mean arterial pressure and compartment pressure) could be controlled. The model, in conjunction with 31P-magnetic resonance spectroscopy (MRS), allowed a measure of high-energy phosphate compounds and pH in the compartment at various Delta pressures. The extent of ischemic metabolic insult in the compartment was then quantitated. Our data suggest the following: 1) lower Delta pressures result in a proportionally greater drop in the intracellular phosphocreatine ratio and pH; 2) at lower Delta pressures, there is proportionally greater decline in the percentage recovery post-fasciotomy; 3) blood pressure is extremely important and periods of hypotension may result in increased muscle damage at lower compartment pressures.

The compartment syndrome. An experimental and clinical study of muscular energy metabolism using phosphorus nuclear magnetic resonance spectroscopy.

In an experimental ischemic compartment syndrome in dogs, phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy was used to determine the tissue pressure threshold at which resting skeletal muscle begins to use anaerobic energy sources due to insufficient cellular oxygen delivery. The interactive effects of systemic perfusion pressure and moderate muscle trauma on this anaerobic threshold were also evaluated. The severity of cell injury produced by various degrees of compartment pressurization over an eight-hour period was concomitantly studied using muscle biopsy and electron microscopy. Clinical correlation of a preliminary patient series studied using 31P-NMR demonstrated that the threshold for cellular metabolic derangement in skeletal muscle subjected to increased tissue pressure was more closely associated with the difference between mean arterial blood pressure (MABP) and compartment pressure than with the absolute compartment pressure alone. The difference is termed MABP-compartment pressure, or delta P. The lowest delta P at which a normal cellular metabolic state can be maintained is approximately 30 mmHg in normal muscle and 40 mmHg in moderately traumatized muscle. It is imperative to interpret compartment pressure measurements in light of the degree of soft tissue trauma sustained and the patient's blood pressure, as well as the clinical signs and symptoms.

Electrical stimulation of human muscle studied using 31P-nuclear magnetic resonance spectroscopy.

This study used phosphorous nuclear magnetic resonance (31P-NMR) spectroscopy to examine the metabolic demand resulting from electrical muscle stimulation (EMS) applied to human skeletal muscle. For each of six subjects, the forearm flexor muscle group was monitored with 31P-NMR during both maximum voluntary and 6-s EMS-induced contractions. A simple protocol using a tourniquet was added in one subject to assess the role of blood flow in this model. Eight hertz (nontetanic) EMS showed less (p less than 0.025) depletion of phosphocreatine (36%) than did tetanic 70-Hz EMS (60%), voluntary isometric (66%), and voluntary isokinetic (68%). The results of the tourniquet studies suggested that the nontetanic EMS allowed relatively increased muscle blood flow and oxygen supply during contraction. Tetanic EMS provided a similar metabolic demand to that of conventional resistive exercise, as measured by 31P-NMR spectroscopy.

Rocket UV flash spectra from the solar eclipse of March 7, 1970.

Flash spectra of the total solar eclipse throughout all its phases have been obtained in the extreme ultraviolet for the first time.