Biomechanical performance of locked intramedullary nail systems in comminuted femoral shaft fractures

The biomechanical properties of commercially available locked nail systems designed for use in comminuted femoral shaft fractures were compared and evaluated. Ender nails as well as three forms of interlocking nails, Brooker-Wills (B-W), Klenm-Schellman (K-S), and Grosse-Kempf (G-K), were implanted in cadaver femora. The femora were tested in torsion, bending, and axial loading to failure. Two fracture models were tested--a 3 cm subtrochanteric defect and an 8 cm midshaft defect. Results of the testing revealed the three interlocking nails to be comparable to each other and superior to Ender nails in bending and torsion. However, the distally bolted locked nails (K-S, G-K) resisted significantly higher loads than either the distally bladed locked nail (B-W) or Ender nails when tested to failure by axial loading.     

Rat small intestinal morphology and tissue regulatory peptides: effects of high dietary fat.

Sprague-Dawley rats (3 weeks old) were fed on isoenergetic diets in which 40% of the total energy was provided as fat either in the form of butter (high saturated fat), olive oil (high monounsaturated fat) or maize oil (high polyunsaturated fat), with one group on low-fat (10% of total energy) standard diet as a control. Animals were killed after 8.4 (se 0.8) weeks by cardiac puncture. Similar pieces of jejunum and ileum were prepared for morphometric studies. Extracts of tissue from the proximal and distal segments of the whole small intestine from four animals per group were assayed using established techniques for enteroglucagon, motilin, neurotensin, somatostatin, substance P and vasoactive intestinal peptide (VIP). We found that maize oil and olive oil increased villus height: crypt depth ratio in both jejunum and ileum. Maize oil increased tissue concentrations of somatostatin (P less than 0.05) and substance P (P less than 0.005) in the proximal segment. Both maize oil and olive oil increased tissue concentrations of neurotensin and substance P (P less than 0.005) in the distal segments. These observations may explain the improvement of intestinal absorption of fluid following supplementation with polyunsaturated fat.     

A general method for characterization of humoral immunity induced by a vaccine or infection

A universal system to diagnose disease, characterize infection or evaluate the response to a vaccine would be useful. Towards this end we introduce a machine-readable platform that we term “Immunosignaturing”. Rather than attempt to identify antibodies one by one, we splay the entire immune response across an array of 10,000 random sequence peptides. This segregates serum antibodies sufficiently to group and characterize responses caused by disease or vaccination. In the present study, we explore in detail the murine immunosignature to influenza A/PR/8/34 immunization and subsequent challenge. Even though the peptides are random sequence, the response to immunization and challenge is quite apparent. We find that the immunosignatures contained information not evident in whole virus ELISA. Antibody recognition of 283 influenza-specific peptides increased upon immunization and remained elevated for 211 days post-challenge. A set of 65 peptides, which overlapped 39 of the peptides that were consistent across time, was capable of distinguishing mice based on infectious dose, while whole virus ELISA could not. These peptide populations are consistently recognized in independent biological replicates of infection and are largely, but not solely, composed of virus reactive antibodies. The immunosignaturing analysis was expanded to analysis of human recipients of the 2006/2007 seasonal influenza vaccine. We find that 30 peptides are significantly recognized by all donors 21 days post-immunization and have the power to distinguish immune from pre-immune samples. Taken together the data suggest that immunosignaturing on a random peptide array can serve as a universal platform to assess antibody status in ways that cannot be replicated by conventional immunological assays.     

The bioavailability and pharmacokinetics of slow release nifedipine during chronic dosing in volunteers.

Eight healthy volunteers received slow release nifedipine 20 mg 12 hourly, for six doses. A nifedipine pharmacokinetic profile was performed after the fifth dosing interval using 12 sampling times over 12 h. A specific high pressure liquid chromatography (h.p.l.c.) nifedipine assay was used. Six of the volunteers subsequently received an i.v. infusion of 3.5 mg of nifedipine after an identical period (five dosing intervals) of chronic oral dosing with slow release nifedipine 20 mg 12 hourly. An identical pharmacokinetic profile was performed after the infusion. Bioavailability, clearance (CL), apparent volume of distribution (V), apparent half life (t1/2) and area under the curve (AUC) were calculated. The geometric mean apparent t1/2 for the slow release preparation was 6.3 +/- 2.0 h. In the six volunteers, the mean bioavailability was 46% (range 29-86%), the mean CL was 588.0 +/- 67.1 ml min-1, the mean apparent V was 160.1 +/- 61.7 l. The pharmacokinetics of slow release nifedipine during chronic dosing appear similar to those derived from single dose studies.     

Spinal arteriovenous malformation presenting at birth: case report

A newborn with paraplegia and evidence of a subarachnoid hemorrhage was found to have a spinal arteriovenous malformation. The arteriovenous malformation was managed by direct surgical obliteration. This patient is the youngest ever reported to have this disorder and the youngest so treated.     

In vitro characterization and pharmacokinetics in mice following pulmonary delivery of itraconazole as cyclodextrin solubilized solution

This study aims to make a 2-hydroxypropyl-β-cyclodextrin (HPβCD) solubilized itraconazole (ITZ) solution (i.e., HPβCD-ITZ) suitable for pulmonary delivery by nebulization, and compare pharmacokinetics of inhaled nebulized aerosols of HPβCD-ITZ versus a colloidal dispersion of ITZ nanoparticulate formulation (i.e., URF-ITZ). Solid state characterizations of lyophilized HPβCD-ITZ by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated the formation of dynamic inclusion complexes between ITZ and HPβCD. Nebulized aerosols of both HPβCD-ITZ and colloidal dispersion of URF-ITZ were confirmed suitable for deep lung delivery. Single doses of the nebulized aerosols (equivalent to 5.3 mg ITZ/mL in 5 mL) in mice produced similar ITZ lung depositions and pharmacokinetic profiles, with ITZ lung levels of approximately 4 μg/g wet lung weight upon completion of nebulization and remained above 0.5 μg/g at 24 h. HPβCD-ITZ demonstrated faster systemic absorption of ITZ across lung epithelium than URF-ITZ, with t_max values of 1.5 and 3.0 h, and AUC_0–∞ of 2513 and 3717 ng h/mL, respectively. The fast absorption of solubilized ITZ across lung mucosal surface may be due in part to the elimination of the phase-to-phase transition.     

Vasopressin receptor antagonism — a therapeutic option in heart failure and hypertension

The precise role of vasopressin in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is important for several reasons. Firstly, circulating concentrations of vasopressin are elevated in heart failure and some forms of hypertension. Secondly, there is evidence that vasopressin is synthesized not only in the hypophysial-pituitary axis but also in peripheral tissues including the heart where it acts as a paracrine hormone. Thirdly, vasopressin has vasoconstrictor, mitogenic, hyperplastic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Finally, the availability of orally active non-peptide vasopressin receptor antagonists allows vasopressin receptor antagonism to be considered as a therapeutic option in cardiovascular disease.     

The adoption of chronic fatigue syndrome/myalgic encephalomyelitis case definitions to assess prevalence: a systematic review

PurposePrevalence estimates have been based on several case definitions of chronic fatigue syndrome (CFS). The purpose of this work is to provide a rigorous overview of their application in prevalence research.MethodsA systematic review of primary studies reporting the prevalence of CFS since 1990 was conducted. Studies were summarized according to study design, prevalence estimates, and case definition used to ascertain cases.ResultsThirty-one studies were retrieved, and eight different case definitions were found. Early estimates of CFS prevalence were based on the 1988 Centers for Disease Control and Prevention, Australian, and Oxford. The 1994 Centers for Disease Control and Prevention, however, has been adopted internationally, as a general standard. Only one study has reported prevalence according to the more recent, Canadian Consensus Criteria. Additional estimates were also found according to definitions by Ho-Yen, the 2005 Centers for Disease Control and Prevention empirical definition, and an epidemiological case definition.ConclusionsAdvances in clinical case definitions during the past 10 years such as the Canadian Consensus Criteria have received little attention in prevalence research. Future assessments of prevalence should consider adopting more recent developments, such as the newly available International Consensus Criteria. This move could improve the surveillance of more specific cases found within CFS.     

Theory and generalization of Monte Carlo models of the BOLD signal source

The dependency of the blood oxygenation level dependent (BOLD) signal on underlying hemodynamics is not well understood. Building a forward biophysical model of this relationship is important for the quantitative estimation of the hemodynamic changes and neural activity underlying functional magnetic resonance imaging (fMRI) signals. We have developed a general model of the BOLD signal which can model both intra- and extravascular signals for an arbitrary tissue model across a wide range of imaging parameters. The model of the BOLD signal was instantiated as a look-up-table (LuT), and was verified against concurrent fMRI and optical imaging measurements of activation induced hemodynamics.