Emerging Patterns in Adolescent Drug Use: The Belfast Youth Development Study 2000-2002

This paper reports the findings from the first 2 years of the Belfast Youth Development Study. The Belfast Youth Development Study is a 5-year longitudinal investigation of the onset and development of adolescent drug using behaviours, the findings of the first 2 years from the study in relation to drug use patterns among the young people participating in the research are reported here. The findings show that while the majority of young people have not yet used an illicit substance, the study has seen a substantial increase in the numbers using such substances between year 1 and year 2. Boys still make up the majority of drug users in this period but there has been a substantial increase in the number of girls using illicit drugs and, more generally, an increase in the frequency of use among all those using such substances during this period.     

Effects of residence and race on burden of travel for care: cross sectional analysis of the 2001 US National Household Travel Survey

Background  

Travel burden is a key element in conceptualizing geographic access to health care. Prior research has shown that both rural and minority populations bear disproportionate travel burdens. However, many studies are limited to specific types of patient or specific locales. The purpose of our study was to quantify geographic and race-based differences in distance traveled and time spent in travel for medical/dental care using representative national data.     

Controlled-release codeine is equivalent to acetaminophen plus codeine for post-cholecystectomy analgesia

PURPOSE: Following ambulatory surgery, long-acting analgesics may provide advantages over short-acting analgesics. This study compared controlled-release codeine (CC) and acetaminophen plus codeine (A/C; 300 mg/30 mg) for pain control in the 48-hr period following laparoscopic cholecystectomy. METHODS: Eligible patients were randomized to CC or A/C in a double-blind, double-dummy parallel group study. Unrelieved pain in hospital was treated with fentanyl i.v. bolus. Pain [100 mm visual analogue scale (VAS)] was assessed before the first dose of medication; at 0.5, one, two, three, and four hours post-dose; at discharge; and three times a day for 48 hr. Adverse events were recorded and measures of patient satisfaction were assessed at the end of the study. RESULTS: Eighty-four patients were enrolled in the study; 42 patients in each group. There were no statistically significant differences between CC and A/C treatment. Mean VAS baseline pain was similar in both groups (P = 0.49) and there was no significant difference in the time to onset of analgesia (P = 0.17). At 0.5 hr, the mean VAS pain score was significantly reduced from baseline in both groups (P = 0.0001). The VAS pain scores at discharge were reduced 59% and 56% from baseline, respectively (P = 0.61). There was no difference between treatments in the incidence of adverse events and patients reported similar levels of satisfaction. CONCLUSIONS: Controlled-release codeine provides an equivalent onset of analgesia, reduction in postoperative pain, and level of patient satisfaction, to acetaminophen plus codeine, over 48 hr following cholecystectomy, with the advantage of less frequent dosing.     

Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and occludin in synovial sarcoma: an immunohistochemical study with ultrastructural correlation.

Synovial sarcoma demonstrates epithelial differentiation, either by light microscopy (biphasic synovial sarcoma) or by immunohistochemical/ultrastructural methods only (monophasic) and poorly differentiated synovial sarcoma. Although the glands of synovial sarcoma are known to have tight junction-like structures, far less is known about junction formation in the spindled component of synovial sarcomas. Additionally, it is unknown whether the tight junctions of synovial sarcoma are normally constituted. The tight junction is a multiprotein complex consisting of numerous proteins that include ZO-1, claudin-1 and occludin. A total of 35 cases of synovial sarcoma (13 biphasic, 14 monophasic and eight poorly differentiated) were immunostained for ZO-1, claudin-1 and occludin using commercially available antibodies, heat-induced epitope retrieval and standard avidin-biotin technique. When available, corresponding electron micrographs were reviewed. For five cases, the presence of either an SYT-SSX1 (three cases) or SYT-SSX2 (two cases) gene fusion was known. Positive cases showed particulate membrane staining. The glands of biphasic synovial sarcomas expressed ZO-1 (13/13), claudin-1 (12/13) and occludin (11/13) in a manner identical to normal glandular epithelia, at the apical portion of the lateral membrane. The spindle cells of biphasic synovial sarcomas showed abnormal circumferential membranous expression of ZO-1 (12/13), claudin-1 (6/13) and occludin (3/13). Monophasic synovial sarcomas expressed ZO-1 in a circumferential pattern (13/14) but less often claudin-1 (4/14) or occludin (3/14). Poorly differentiated synovial sarcomas expressed ZO-1 (8/8) and claudin-1 (6/8) but only rarely occludin (2/8). By electron microscopy, recognizable tight junctions were seen only in glands. No correlation was seen between histologic subtype or fusion type and expression of tight junction proteins. We conclude that the glands of biphasic synovial sarcomas show well-organized, true epithelial tight junctions. In contrast, the spindled cells of all synovial sarcomas show significant abnormalities in the expression and localization of tight junction proteins, suggesting partial and/or aberrant epithelial differentiation.     

Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. We carried out two randomized, double-blind, placebo-controlled, multi-centre, multi-national studies with xaliproden (a drug with neurotrophic effect) to assess drug efficacy and safety at two doses. Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1 (n=867); or to the same regimen with addition of riluzole 50 mg bid background therapy in Study 2 (n=1210 patients). The two primary endpoints were defined as: 1. Time to death, tracheostomy, or permanent assisted ventilation (DTP), and 2. Time to vital capacity (VC)<50% or DTP before (log-rank test) and after adjustment using a Cox proportional hazard model for prespecified prognostic factors. Secondary endpoints were rates of change of various functional measures. In Study 1, primary outcome measures did not reach statistical significance. For the 2 mg group, for time to VC<50% analysis (without DTP) a significant 30% RRR was obtained (95% confidence interval [CI]: 8.46, P=0.009). In Study 2, no significant results were obtained. However, there was a trend in favour of add-on 1 mg dose xaliproden vs. placebo (RRR 15% [-6.31, ns] for time to VC<50%; RRR 12% [CI: -6.27, ns] for time to VC<50% or DTP). Adjusted RR ratios were consistently more favourable for the xaliproden groups. Tolerability was good, and dose-dependent side effects were largely associated with the serotonergic properties of xaliproden. An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.     

L-Dopa-responsive Parkinson's syndrome in association with phenylketonuria: In vivo dopamine transporter and D2 receptor findings.

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.     

Characterization and opioid modulation of inflammatory temporomandibular joint pain in the rat.

PURPOSE: Experimental inflammation of the rat temporomandibular joint (TMJ) is commonly used to study trigeminal nociceptive processing. This study describes spontaneous pain-related behaviors following TMJ inflammation in the rat. The ability of preemptive systemic morphine to attenuate behaviors as well as immediate-early gene expression in the trigeminal nucleus is described. MATERIALS AND METHODS: Adult male Sprague-Dawley rats received an intra-articular injection of mustard oil (0% to 20%, 50 microL) and were observed for behavioral changes. Morphine sulfate (0 to 10 mg/kg SC) was given 30 minutes before mustard oil; this was reversed in one group with naltrexone hydrochloride (5 mg/kg SC). Two hours after injection rats were killed and perfused. Immunohistochemistry for the protein product of the immediate-early gene c-fos was performed, and brain stem sections including the trigeminal subnucleus caudalis were examined for positive nuclei. RESULTS: Mustard oil inflammation of the rat TMJ induces dose-dependent, morphine-sensitive behaviors. Behaviors observed included excessive grooming of the region, a chewing-like behavior, and head shaking. Fos expression in the trigeminal subnucleus caudalis parallels changes in behaviors. Morphine dose dependently attenuates the number of behaviors, as well as Fos expression; this effect is reversed by the micro-opioid receptor antagonist naltrexone. CONCLUSIONS: Mustard oil inflammation of the rat TMJ causes reliable behavioral changes, which may be quantified and, together with Fos expression, used to assess various experimental TMJ treatment modalities.