Methamphetamine self-administration causes persistent striatal dopaminergic alterations and mitigates the deficits caused by a subsequent methamphetamine exposure

Preclinical studies have demonstrated that repeated methamphetamine (METH) injections (referred to herein as a "binge" treatment) cause persistent dopaminergic deficits. A few studies have also examined the persistent neurochemical impact of METH self-administration in rats, but with variable results. These latter studies are important because: 1) they have relevance to the study of METH abuse; and 2) the effects of noncontingent METH treatment do not necessarily predict effects of contingent exposure. Accordingly, the present study investigated the impact of METH self-administration on dopaminergic neuronal function. Results revealed that self-administration of METH, given according to a regimen that produces brain METH levels comparable with those reported postmortem in human METH abusers (0.06 mg/infusion; 8-h sessions for 7 days), decreased striatal dopamine transporter (DAT) uptake and/or immunoreactivity as assessed 8 or 30 days after the last self-administration session. Increasing the METH dose per infusion did not exacerbate these deficits. These deficits were similar in magnitude to decreases in DAT densities reported in imaging studies of abstinent METH abusers. It is noteworthy that METH self-administration mitigated the persistent deficits in dopaminergic neuronal function, as well as the increases in glial fibrillary acidic protein immunoreactivity, caused by a subsequent binge METH exposure. This protection was independent of alterations in METH pharmacokinetics, but may have been attributable (at least in part) to a pretreatment-induced attenuation of binge-induced hyperthermia. Taken together, these results may provide insight into the neurochemical deficits reported in human METH abusers.     

Fetal body ratios in second trimester: a useful tool for identifying chromosomal abnormalities?

This study was carried out to determine if second trimester fetal body ratios are useful in detecting chromosomally abnormal fetuses. As a reference population, normative data for five fetal body ratios (femur length/biparietal diameter, biparietal diameter/fetal length, femur length/head circumference, head circumference/abdominal circumference, and femur length/abdominal circumference) were derived using regression analysis from a population of chromosomally normal fetuses (n = 1770) who underwent genetic amniocentesis at our institution between 14 and 21 menstrual weeks. During the same time period, 37 chromosomally abnormal fetuses were identified by amniocentesis. In comparing the two groups using the 10th and 90th percentiles as cutoffs between normal and abnormal, approximately 25% of chromosomally abnormal fetuses were identified, whereas approximately 20% of the normal fetuses were incorrectly classified as abnormal. Moreover, the use of 1.5 standard deviations above the mean for BPD/FL identified only 19% of Down syndrome fetuses. Our data, and those from a comprehensive review of the literature, suggest that the sensitivity of these ratios in detecting chromosomally abnormal fetuses is too low to recommend them for routine screening.     

Effects of aspirin and low-dose heparin in head and neck reconstruction using microvascular free flaps

Objective: The success of microvascular free‐tissue transfer to the head and neck has been greatly increased secondary to increased experience, yet postoperative anticoagulation continues to be routinely used to prevent pedicle thrombosis. However, there is currently no consensus as to what the ideal regimen, if any, is recommended for postoperative anticoagulation. This study reviews the outcome and incidence of perioperative complications in patients undergoing free flaps for head and neck reconstruction, using a simple postoperative anticoagulation regimen of aspirin and subcutaneous heparin (SQH). Design: Retrospective chart review. Methods: With institutional review board approval, the charts of 261 patients undergoing free flap reconstruction from January 2000 to January 2004 were retrospectively reviewed. Patients who received a standard postoperative anticoagulation regimen of SQH (5000 U SC bid) and aspirin (325 mg PO qd) were included in the study (216 patients). Charts were reviewed for postoperative complications, specifically for free flap failure, vascular compromise (arterial insufficiency/venous congestion), and hematoma. Results: There were six flap failures (2.8%), resulting in an overall free flap survival rate of 97.2%. There were six patients with venous congestion of the flap that required neck exploration (2.8%), and 12 patients with postoperative hematoma (5.6%), requiring surgical intervention. Conclusion: The free flap survival rate in patients undergoing head and neck reconstruction using this simple anticoagulation regimen of aspirin and SQH appears to be equivalent to the free flap survival rate in patients using other anticoagulation agents. In addition, aspirin and SQH do not increase the incidence of postoperative hematoma when compared with the other anticoagulation agents. Therefore, aspirin and SQH appear to be reliable postoperative anticoagulation agents for patients undergoing head and neck reconstruction using free flaps.     

Successful myoblast transplantation in rat tongue reconstruction

BACKGROUND: Controversy exists regarding the success of myoblast transplantation. The purpose of this study was to determine the survival of transplanted myoblasts in a rat tongue reconstruction model by using fluorescently labeled myoblasts and surgical stains to mark the location of the pocket into which transplanted cells were delivered. We evaluated tongue histology after myoblast transplantation under the hypothesis that myoblast transplantation will promote muscle regeneration and result in minimal scar tissue formation. METHODS: Sterile solutions of 1:10 India ink, 1% methylene blue, and 1% crystal violet were applied to the inner lining of a left-sided mucosa-sparing hemiglossectomy pocket. After air-drying, the hemiglossectomy defect was filled with collagen gel and closed. The tongues were evaluated histologically at 6 weeks. Next, myoblasts were cultured and labeled with three commercially available fluorescent dyes, 5-chloromethyl-fluorescein diacetate (CMFDA), chloromethylbenzamido (CM-DiI), and fluorescently labeled microspheres (FLMs), to determine which would optimally label myoblasts in a tongue reconstruction model. Next, Lewis rats underwent left hemiglossectomy, and the created pockets were coated with 1:10 India ink. Control animals received collagen gel alone, whereas experimental animals received labeled myoblast/collagen constructs into the tongue defect. Tongues were harvested at intervals to determine the presence of labeled fluorescent cells, the relative numbers of viable myoblasts, and the degree of scarring. RESULTS: India ink coating of the hemiglossectomy pocket caused minimal inflammation and lasted longer than the other tested dyes. CMFDA and FLMs both successfully label myoblasts for transplantation. In vivo, donor cells were observed in all specimens at week 0 with increasing numbers of cells and muscle formation, determined by desmin immunofluorescence, after 6 weeks. There was less scar tissue contracture in the experimental group and a significant increase in the amount of desmin-stained muscle in the surgical defect. CONCLUSIONS: India ink is an appropriate vehicle for intra-operative marking of a hemiglossectomy cavity. The introduction of myoblast/collagen constructs into the rat hemiglossectomy defect increases the amount of regenerated muscle, results in less scar contracture, and may increase meaningful tongue function.     

Enhanced specificity of truncated transmembrane protein for serologic confirmation of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by western blot (immunoblot) assay containing recombinant envelope glycoproteins.

Immunoassays based on the highly immunogenic transmembrane protein of human T-cell lymphotropic virus type 1 (HTLV-1) (protein 21c) are capable of detecting antibodies in all individuals infected with HTLV-1 and HTLV-2. However, because of antigenic mimicry with other cellular and viral proteins, such assays also have a large proportion of false-positive reactions. We have recently identified an immunodominant epitope, designated GD21-I located within amino acids 361 to 404 of the transmembrane protein, that appears to eliminate such false positivity. This recombinant GD21-I protein was used in conjunction with additional recombinant HTLV type-specific proteins and a whole virus lysate to develop a modified Western blot (immunoblot) assay (HTLV WB 2.4). The sensitivity and specificity of this assay were evaluated with 352 specimens whose infection status was determined by PCR assay for the presence or absence of HTLV-1/2 proviral sequences. All HTLV-1-positive (n = 102) and HTLV-2-positive (n = 107) specimens reacted with GD21-1 in the HTLV WB 2.4 assay, yielding a test sensitivity of 100%. Furthermore, all specimens derived from individuals infected with different viral subtypes of HTLV-1 (Cosmopolitan, Japanese, and Melanesian) and HTLV-2 (IIa0, a3, a4, IIb1, b4, and b5) reacted with GD21-I in the HTLV WB 2.4 assay. More importantly, HTLV WB 2.4 analysis of 81 PCR-negative specimens, all of which reacted to recombinant protein 21e in the presence or absence of p24 and p19 reactivity in the standard WB assay, showed that only two specimens retained reactivity to GD21-I, yielding an improved test specificity for the transmembrane protein of 97.5%. None of 41 specimens with gag reactivity only or 21 HTLV-negative specimens demonstrated reactivity to GD21-I. In an analysis of additional specimens (n = 169) from different geographic areas for which PCR results were not available, a substantial increase in the specificity of GD21-I detection was demonstrated, with no effect on the sensitivity of GD21-I detection among specimens from seropositive donors. Thus, the highly sensitive, GD21-I-based HTLV WB 2.4 assay eliminates the majority of false-positive transmembrane results, thereby increasing the specificity for serologic confirmation of HTLV-1 and HTLV-2 infections.     

Tissue engineering in facial plastic and reconstructive surgery

Current biomaterials technology meets some of the needs of the facial plastic and reconstructive surgeon. However, there is a genuine need for improvement in the area of tissue replacement. The principle of tissue engineering provides a natural way to generate needed tissue using the patient's own cells as building blocks, coupled with biodegradable polymers which have been used safely in [figure: see text] patients for decades. This technology enables the creation of complex structures which ultimately have no immunogenicity. Current obstacles to human clinical trials for auricular repair are being pursued for resolution, and the number of new tissues which it may be possible to generate in this fashion continues to expand. Through continued experimentation and collaboration among surgeons, chemical engineers, and materials scientists, we are certain that the barriers to widespread clinical use for this emerging technology will be overcome.     

Multimodality approach to management of the paralyzed face

OBJECTIVES: Despite the ability of facial reanimation techniques to introduce meaningful movement to the paralyzed face, dynamic methods do not address all zones of the face. Our objective was to retrospectively review outcomes after multimodality management of the patient with facial paralysis, to describe several novel surgical methods that introduce subtle improvements in static facial balance, and to present an algorithm for comprehensive management of the paralyzed face. METHODS/RESULTS: Three hundred thirty-seven patients with facial paralysis were seen and treated in a busy facial nerve center setting over a 3-year period using a range of standard muscle transfers, physical therapy, chemodenervation with botulinum toxin, and static surgical techniques. Three adjunct techniques emerged as novel and useful procedures that more fully addressed facial balance issues than existing techniques. Of patients proceeding with physical therapy, greater than 80% of patients experienced a benefit, and 97% of those who proceeded with botulinum toxin therapy experienced a benefit. CONCLUSIONS: Facial paralysis is best managed using a multimodality approach that includes surgical interventions, physical therapy, and chemodeneveration. We describe three adjunctive surgical techniques for management of the paralyzed face and present a comprehensive algorithm for management of the paralyzed face. That may provide improved function and cosmesis in all zones of the paralyzed face.     

The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis.

Hepatitis C virus (HCV) infection is associated with extrahepatic B-cell lymphoproliferative disorders. To determine whether a viral antigen drives this B-cell expansion, the B-cell receptors were cloned from HCV-associated lymphomas and were expressed as soluble immunoglobulins. The rescued immunoglobulins were then tested for their ability to bind the HCV-E2 envelope glycoprotein, an antigen that was previously implicated in the pathogenesis of HCV-associated B-cell diseases. One of 2 lymphoma immunoglobulin test cases bound the E2 protein in a manner identical to a bona fide human anti-E2 antibody. Moreover, it bound E2 from multiple viral genotypes, suggesting reactivity with a conserved E2 epitope. These findings support the hypothesis that some HCV-associated lymphomas originate from B cells that were initially activated by the HCV-E2 protein and might explain the association between HCV infection and some B-cell lymphoproliferative disorders.