Therapeutics and delivery vehicles for local treatment of osteomyelitis

Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long-term, systemic antibiotic administration, which contributes to the development of antibiotic-resistant bacteria and has limited ability to eradicate challenging biofilm-forming pathogens including Staphylococcus aureus—the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm-forming, antibiotic-resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.     

Light exposure required for optimum conversion of light activated resin systems

OBJECTIVE: The aim of this study was to evaluate the relationship between the degree of conversion (DC) of composites and the light intensity using LED-curing units and also to determine the amount of exposure required to achieve optimal curing. METHOD: The light outputs of light-curing units and the depths of cure of composites exposed to these units were determined using the methods outlined in modified ISO standards, ISO/TS10650 and ISO 4049, respectively. The distributions of DC in composites were investigated by IR spectra of microareas obtained at various depths from the irradiated surface of thin specimens cut out from the cured composites. IR spectra were measured using a Fourier transform infrared spectrometer equipped with a microscopic unit. DC was calculated from the changes in the amount of C=C double bonds in the IR spectra. RESULTS: The light intensity at various depths through the cured composite was calculated from the attenuation coefficient of each material, obtained from the linear relationship between the depth of cure and the logarithm of the amount of exposure, which is defined as the product of the irradiance and irradiation time. There was a third or fourth order regression relationship between DC and the logarithm of total light energy at a particular depth. SIGNIFICANCE: The minimum light energy required to produce a saturated DC was about 1000 s mW/cm2.     

Syndrome of inappropriate secretion of arginine vasopressin in patients with cancer of the head and neck.

The syndrome of inappropriate secretion of arginine vasopressin (AVP) known as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is associated with a variety of malignant and nonmalignant diseases. Only 17 cases of SIADH have been reported in the literature in association with cancer isolated to the head and neck. A retrospective review of 1,436 patients with head and neck malignancy excluding skin cancer through The University of Iowa Tumor Registry revealed 60 patients with the diagnosis of either SIADH or hyposmolality. A chart review for each of these patients was then done to establish the diagnosis of SIADH through relevant laboratory values and by excluding other causes of hyposmolality and hyponatremia. In 43 of these patients (3%), SIADH was found to be associated only with the cancer of the head and neck. We conclude that the incidence of SIADH in patients with cancer of the head and neck is much higher than previously recognized. As elevated serum AVP levels may not be clinically apparent unless associated with excessive water ingestation, it is possible that an even higher percentage of patients may have increased serum AVP levels.     

The Domain of Hypertrophic Chondrocytes in Growth Plates Growing at Different Rates

In this study, we tested the hypotheses that (a) both the domain volume (volume of the cell and the matrix it has formed) and matrix volume of juxtametaphyseal hypertrophic chondrocytes in the growth plate is tightly controlled, and that (b) the domain volume of juxtametaphyseal hypertrophic chondrocytes is a strong determinant of the rate of bone length growth. We analyzed the rate of bone length growth (oxytetracycline labeling techniques) and nine stereologic and kinetic parameters related to the juxtametaphyseal chondrocytic domain in the proximal and distal radial and tibial growth plates of 21- and 35-day-old rats. The domain volume increased with increasing growth rates, independent of the location of the growth plate and the age of the animal. Within age groups, the matrix volume per cell increased with increasing growth rates, but an identical growth plate had the same matrix volume per cell in 21- and 35-day-old rats. The most suitable regression model (R ²= 0.992) to describe the rate of bone length growth included the mean volume of juxtametaphyseal hypertrophic chondrocytes and the mean rate of cell loss/cell proliferation. This relationship was independent of the location of the growth plate and the age of the animal. The data suggest that the domain volume of juxtametaphyseal hypertrophic chondrocytes, as well as the matrix volume produced per cell, may be tightly regulated. In addition, the volume of juxtametaphyseal hypertrophic chondrocytes and the rate of cell loss/rate of cell proliferation may play the most important role in the determination of the rate of bone length growth. Received: 2 December 1996 / Accepted: 24 March 1997     

Nursing involvement in euthanasia: how sound is the philosophical support?

Abstract  Preference utilitarians are concerned to maximize the autonomous choices of individuals; for this reason, they argue that nurses ought to advocate for those patients who desire assistance with ending their lives. This approach prompts us to consider, then, the moral validity of nursing involvement in measures intended to end the lives of patients. In this article, the terms of preference utilitarianism are set out and considered in order to determine whether this approach offers sufficient philosophical support for sanctioning a role for nursing in euthanasia. Ultimately, it is found that preference utilitarianism is lacking in this respect, as well as in its fitness for guiding nursing activity in general. In particular, it is found that nurses are required to exchange a handmaiden relationship with the medical profession for an equally undignified relationship with patients. If nursing involvement in measures intended to end the lives of patients is to find sufficient philosophical support, then we need to look elsewhere.     

Ventilation performance using a self-inflating anesthesia bag: effect of operator characteristics

Adequate ventilation is required for successful cardiopulmonary resuscitation (CPR). Operator characteristics that influence ventilation performance are not well defined. This study compared ventilation performance and operator characteristics in 74 medical personnel using a self-inflating anesthesia bag. Ventilation device, operator hand size, ventilation technique, average tidal volume, cumulative minute ventilation, and ventilation pressures were recorded during 3 minutes of ventilation. Ventilation volumes and airway pressures were not correlated with hand size or device type. Techniques that used one hand to squeeze the bag resulted in significantly lower average tidal volume than two-handed techniques, with no significant difference in peak or average airway pressure. There was no difference between emergency department and prehospital personnel in average tidal volume delivered. However, prehospital personnel ventilated at significantly higher airway pressures. Emergency department nurses delivered the greatest average tidal volume (923 cc), while emergency department physicians delivered the least (775 cc). Paramedics recorded the highest airway pressures (average, 53 cm H2O; peak, 72 cm H2O), while respiratory therapists recorded the lowest pressures (average, 34 cm H2O; peak, 54 cm H2O). Ventilation during CPR is a complex, learned skill. Large variation exists among different operators. However, appropriate tidal volumes can be delivered using safe airway pressures. Ongoing assessment and retraining of individuals performing ventilation during CPR are essential.     

Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.