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.     

The ability of the SCORE high-risk model to predict 10-year cardiovascular disease mortality in Norway.

AIMS: To evaluate the predictive accuracy of the Systematic Coronary Risk Evaluation (SCORE) project high-risk function in Norway. METHODS AND RESULTS: We included 57 229 individuals screened in 1985-1992 from two population-based surveys in Norway (age groups 40-49, 50-59, and 60-69 years). The data have been linked to the Norwegian Cause of Death Registry. The SCORE high-risk algorithm for the prediction of 10-year cardiovascular disease (CVD) mortality was applied, and the risk factors entered into the model were age, sex, total cholesterol, systolic blood pressure, and smoking (yes/no). The number of expected events estimated by the SCORE model (E) was compared with the observed numbers (O). The SCORE low-risk algorithm was studied for comparison. In men, the observed number of CVD deaths was 718, compared with 1464 estimated by the SCORE high-risk function (O/E ratios 0.53, 0.53 and 0.45, for age groups 40-49, 50-59 and 60-69, respectively). In women, the observed and expected numbers were 226 and 547. The O/E ratios decreased with age (ratios 0.60, 0.45 and 0.37, respectively), i.e. the overestimation increased with age. The low-risk function predicted reasonably well for men (ratios 0.85, 0.92 and 0.79, respectively), whereas an overestimation was found for women aged 50-59 and 60-69 years (ratios 0.69 and 0.56, respectively). CONCLUSION: The SCORE high-risk model overestimated the number of CVD deaths in Norway. Before implementation in clinical practice, proper adjustments to national levels are required.     

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.     

Comparison of dynamic and step-and-shoot intensity-modulated radiation therapy planning and delivery.

Intensity-modulated radiation therapy (IMRT) is commonly delivered using the dynamic or segmental mode of multileaf collimators (DMLC or SMLC). Both methods are designed to deliver intensity-modulated beams as determined by inverse planning software. In this study, we have used the Helios IMRT planning system to generate ideal treatment plans for 10 cases of 2 common treatment sites (prostate and head and neck) and have investigated the actual treatment fluence distributions generated for each of the MLC leaf motion choices. The 2 dose delivery techniques were dosimetrically compared to each other and to the treatment plans. For each technique, point doses were measured in a water phantom using ionization chambers. Also for each technique, 2-dimensional dose distributions at a selected depth in a plastic phantom were obtained, using extended range film. The total delivery time and the number of monitor units (MU) delivered by each method were also compared. Our results indicate that the 2 delivery methods produce comparable results dosimetrically. For the cases reviewed, the delivery time was an average of 15% longer for SMLC deliveries, while the number of MUs (beam-on time) required by SMLC was an average of 15% fewer, than that for the DMLC. In the interest of simplicity, lower beam-on time, and potentially fewer mechanically-related problems, we think that the SMLC delivery technique may be the better choice when Helios is used for planning and Varian linear accelerators are used for delivery.     

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.