Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.     

Combining Vaccines with Conventional Therapies for Cancer

Preclinical and clinical investigations currently underway are employing novel strategies for combining vaccines with conventional and experimental anticancer therapies. To date, the FDA has not approved a therapeutic cancer vaccine. However, the results of recent investigations suggest an increasing role for vaccines in new models of combination therapy for many types of cancer. This article reviews and discusses therapeutic cancer strategies that employ vaccines in combination with local radiation, chemotherapy, hormone therapy, and anti-CTLA-4 mAb. Preclinical studies have shown that certain anticancer agents have immune modulatory effects that result in up-regulation of surface expression of MHC molecules, tumor-associated antigens, or Fas on malignant cells, rendering them more susceptible to immune destruction. Preliminary results of clinical studies using combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and improved overall survival. Several larger randomized trials are ongoing, and more are required to support these findings.     

Predicting outcome in severe heart failure. Who will benefit from device therapy (CRT)?

Dyssynchronous ventricular contraction in severe heart failurecontributes to low cardiac output, worsening symptoms, and poorprognosis. Recognition of the effect of dyssynchrony in heartfailure, and the possibility of manipulating the sequence ofelectrical cardiac activation to improve the efficiency of mechanicalevents, led Cazeau et al. to attempt four-chamber pacing in1994.¹ This early system could stimulate both atria and bothventricles extrinsically, and could dictate the temporal relationshipbetween atrial systole and ventricular systole, and the ventriculo-ventricularrelationship. Modern cardiac resynchronization therapy (CRT),involving pacing of the right and left ventricles, with rightatrial pacing to optimize atrio-ventricular delay, has evolvedrapidly from this beginning. Left bundle branch block (LBBB) on the surface electrocardiogram(ECG) has been considered a marker of mechanical dyssynchronyas it represents a delay in conduction of depolarization tothe left ventricle, with the greatest delay usually being in     

Levetiracetam in the treatment of childhood epilepsy

Epilepsy is a common pediatric neurologic disorder that is difficult to manage in a substantial portion of children. Levetiracetam (LEV) is a novel antiepileptic drug (AED) that has recently been approved as add-on treatment for various seizure types in epilepsy populations that include children: for refractory partial seizures in epilepsy patients ≥4 years old, for myoclonic seizures in juvenile myoclonic epilepsy patients ≥12 years old, and for primary generalized tonic-clonic seizures in idiopathic generalized epilepsy patients (≥6 years old with FDA approval; ≥12 years old with EMEA approval). A review of published pediatric studies indicates that the efficacy of LEV is best established for partial seizures; however, results from recent double-blind and open-label trials indicate that adjunctive LEV also controls generalized seizures – particularly myoclonic and generalized tonic-clonic – in children and adolescents with primary generalized epilepsy. LEV was well-tolerated in pediatric studies. The most common adverse events (AEs) reported were sedation related. Behavioral AEs were among the most commonly reported events in some trials; conversely, improvements in behavior and cognition were also frequently reported. LEV appears to be a safe and effective AED with unique characteristics that benefit the treatment of children with epilepsy.     

Perceptions and attitudes of Canadian orthodontists regarding digital and electronic technology.

INTRODUCTION: To plan for future acceptance and implementation of computer-related technology, it is necessary to understand orthodontists' current perceptions and attitudes toward emerging technologies. METHODS: An anonymous, self-administered, mail-out survey of Canadian orthodontists was conducted. The response rate was 45.6% (304/667). RESULTS: Most orthodontists indicated that computer technology could improve current practice efficiency and quality of patient care. Only 15% reported that digital models are quite or very useful; 73.6%, 69.1%, 55%, and 37.4% agreed or strongly agreed with using digital and electronic technology to consult with other dental specialists, other orthodontists, general dentists, and the public, respectively. Cost of the technology was reported as a significant or insurmountable obstacle by 54% of the respondents. Interprovincial legislation, unclear consultation remuneration guidelines, and lack of comfort with the technology were not perceived as significant obstacles. Only 36% reported security or privacy issues as a significant or insurmountable obstacle. CONCLUSIONS: Canadian orthodontists seem to view digital and electronic technology as useful and capable of improving their offices' efficiency and production. Although they are sensitive to some potential obstacles, they are willing to overcome these and incorporate the technology into their practices.     

Use of the risk-rescue rating scale with adolescent suicide attempters: A cautionary note

The assessment of the medical lethality and intent of suicide attempts has been considered an important area of research for those interested in suicide. The current study examined the usefulness of the Risk-Rescue Rating Scale with 109 adolescent suicide attempters and found a restricted range of variability, which, in turn, resulted in poor interrater reliability on a number of items. Results suggest that the Risk-Rescue Rating Scale is of limited usefulness with adolescents, and alternative approaches to assessing lethality and suicidal intent with this age group are discussed.     

Co-operative mineralization and protein self-assembly in amelogenesis: silica mineralization and assembly of recombinant amelogenins in vitro

An amorphous silica mineralization technique was used to produce inorganic/protein composites to elucidate the structure and mechanism of formation of amelogenin assemblies, which may play an important role in regulating enamel structure during the initial stages of amelogenesis. Full-length recombinant amelogenins from mouse (rM179) and pig (rP172) were investigated along with key degradation products (rM166 and native P148) lacking the hydrophilic C terminus found in parent molecules. The resulting products were examined using transmission electron microscopy and/or small-angle X-ray scattering. Using protein concentrations of 0.1–3 mg ml⁻¹, large monodisperse spheres of remarkably similar mean diameters were observed using rM179 (124 ± 4 nm) and rP172 (126 ± 7 nm). These spheres also exhibited 'internal structure', comprising nearly spherical monodisperse particles of ≈ 20 nm in diameter. In the presence of rM166, P148, and bovine serum albumin (control), large unstructured and randomly shaped particles (250–1000 nm) were observed. Without added protein, large dense spherical particles of silica (mean ≈ 500 nm) lacking internal structure were produced. These findings demonstrate that full-length amelogenins have the ability to form higher-order structures, whereas amelogenins that lack the hydrophilic C terminus do not. The results also suggest that full-length amelogenin can guide the formation of organized mineralized structures through co-operative interactions between assembling protein and forming mineral.