Metastatic malignant melanoma: an unusual case presentation

Secondary involvement of the genitourinary tract with malignant melanoma is a common autopsy finding, but rarely evident clinically. We report a rare case involving a previously asymptomatic patient presenting with gross hematuria and a large renal mass, which was found to be metastatic melanoma. We propose that metastatic melanoma to the kidney, although rare, be considered in the differential diagnosis of disease processes causing hematuria.     

TFF1 gene expression in human medullary thyroid carcinoma

This epidemiological study investigated the reasons why children in Northern Ireland who need orthodontic treatment do not receive treatment even when it is provided free by the state. A total of 1584 15- and 16-year-olds were examined in 23 high schools with the Index of Orthodontic Treatment Need. The characteristics of the adolescents who had received orthodontic treatment were compared with those who had a definite need for treatment and yet did not receive treatment or advice. One in 10 of the adolescents examined had an unmet need for orthodontic treatment. Logistic regression analysis was used to assess the influence of 11 variables including socioeconomic status, religion, and standard of dental health on the uptake of orthodontic care. This analysis revealed that the only significant predictors of whether an adolescent received orthodontic treatment was the dental attendance pattern of the adolescent, the adolescent's dental health, and the dental attendance pattern of the adolescent's mother. Those adolescents who had good dental health, who regularly attended a dentist, and whose mother regularly attended a dentist were more likely to receive orthodontic treatment.     

Stability of posterior spinal instrumentation and its effects on adjacent motion segments in the lumbosacral spine

STUDY DESIGN: An in vitro biomechanical analysis of three anterior instability patterns was performed using calf lumbosacral spines. Stiffness of the constructs was compared, and segmental motion analyses were performed. OBJECTIVES: To clarify the factors that alter the stability of the spinal instrumentation and to evaluate the influence of instrumentation on the residual intact motion segments. SUMMARY OF BACKGROUND DATA: Recently, many adverse effects have been reported in fusion augmented with rigid instrumentation. Only few reports are available regarding biomechanical effects of stability provided by spinal instrumentation and its effects on residual adjacent motion segments in the lumbar-lumbosacral spine. METHODS: Eighteen calf lumbosacral spine specimens were divided into three groups according to instability patterns--one-level, two-level, and three-level disc dissections. Six constructs were cyclically tested in rotation, flexion-extension, and lateral bending of intact spines, of destabilized spine, and of spines with four segmental posterior instrumentation systems used to extend the levels of instability (Cotrel-Dubousset compression hook and three transpedicular screw fixation systems). During each test, stiffness values and segmental displacements were measured. RESULTS: The rigidity of the instrumented construct increased as the fixation range became more extensive. Although application of the instrumentation effectively reduced the segmental motion of the destabilized vertebral level, the motion at the destabilized level tended to increase as the number of unstable vertebral levels increased, and the fixation range of the instrumentation became more extensive. Instrumented constructs produced higher segmental displacement values at the upper residual intact motion segment when compared with those of the intact spine. In contrast, the instrumented constructs decreased their segmental displacement values at the lower residual intact motion segment with higher magnitude of the translational (shear) motion taking place compared with the intact spine in flexion-extension and lateral bending. These changes in the motion pattern became more distinct as the fixation range became more extensive. CONCLUSIONS: As segmental spinal instrumentation progresses from one level to three levels, the overall torsional and flexural rigidity of the system increases. However, segmental displacement at the site of simulated instability becomes more obvious. Application of segmental instrumentation changes the motion pattern of the residual intact motion segments, and the changes in the motion pattern become more distinct as the fixation range becomes more extensive and as the rigidity of the construct increases.     

Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group

PURPOSE: To compare raltitrexed (Tomudex; Zeneca Pharmaceuticals Ltd, Macclesfield, United Kingdom) a direct, specific thymidylate synthase (TS) inhibitor with fluorouracil (5-FU) plus high-dose leucovorin (LV) as first-line treatment for advanced colorectal cancer (ACC). PATIENTS AND METHODS: A total of 495 patients were randomized to raltitrexed (3 mg/m2) once every 3 weeks or 5-FU (400 mg/m2) plus LV (200 mg/m2) daily for 5 days every 4 weeks. RESULTS: The randomized groups were well balanced demographically. With a minimum 17-month follow-up, median survival was comparable between groups (10.9 months raltitrexed v 12.3 months 5-FU/LV; hazards ratio, 1.15; 95% confidence interval [CI], 0.93 to 1.42; P=.197), although time to progression was statistically significantly shorter in the raltitrexed group. Overall objective responses were comparable (19% raltitrexed v 18% 5-FU/LV), with more than 50% of patients in each group having stable disease. Significantly less World Health Organization (WHO) grade 3 and 4 stomatitis (2% v 16%, P < .001) and a reduced incidence of leukopenia (6% v 13%) and diarrhea (10% v 19%) occurred in the raltitrexed group (particularly at cycle 1 ). This resulted in fewer dose reductions at cycle 2 (4% raltitrexed v 28% 5-FU/LV) and early quality-of-life (QoL) benefits for raltitrexed patients. Reversible, clinically insignificant increases in transaminases were reported in 13% of raltitrexed patients. Palliative benefits of weight gain, improved performance status, and reduced disease-related symptoms were evident in both groups. CONCLUSION: Raltitrexed is confirmed as an effective option in the first-line palliative management of ACC, with comparable efficacy to and tolerability advantages (in terms of reduced incidence of stomatitis, diarrhea, and leukopenia) over 5-FU/LV. Raltitrexed has the added convenience of an every 3 weeks dosing schedule.     

Structure-activity relationship observations oftrans-trimedlure enantiomers

tert-Butyl 4- (and 5-) chloro-trans-2-methylcyclohexane-1-carboxylate (TML), a mixture of four majortrans and four minorcis isomers, is used as an attractant for detecting and monitoring the male Mediterranean fruit fly (medfly),Ceratitis capitata (Wiedemann). The eight isomers (racemic mixtures) were isolated by HPLC, and their relative attractiveness in the field was determined. A quantitative structure-activity relationship (QSAR) was proposed that related a molecular measurement (ų) of the TML structure to male medfly captures. More recently, thetrans-TML enantiomers were synthesized in sufficient quantities for field testing. This paper reports the computer-aided molecular modeling, via Chem-X, of thetrans-TML enantiomers and the staggered and superimposed fitting with the most attractive isomer, (1S,2S,4R)-TML-C, to determine common volumes and surface areas from Van der Waals (VdW) maps. Observations of structure-activity relationships (SAR) are reported for the staggered fittings.     

DNA adducts of 2,3-epoxy-4-hydroxynonanal: detection of 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine and 1,N6-ethenoadenine by gas chromatography/negative ion chemical ionization/mass spectrometry

2,3-Epoxy-4-hydroxynonanal (EH) is a bifunctional aldehyde formed by epoxidation of trans-4-hydroxy-2-nonenal, a peroxidation product of omega-6 polyunsaturated fatty acids. EH is mutagenic and tumorigenic and capable of modifying DNA bases forming etheno adducts in vitro. Recent studies showed that etheno adducts are present in tissue DNA of humans and untreated rodents, suggesting a potential endogenous role of EH in their formation. A sensitive assay is needed so we can determine whether EH is involved in etheno adduct formation in vivo and study the biological significance of the etheno adducts in DNA. In this study, we developed a gas chromatography/negative ion chemical ionization/mass spectrometry assay for the analysis of 1, N6-ethenoadenine (epsilonAde) and 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine (DHH-epsilonAde) in DNA; both are products from the reaction of adenine with EH. The assay entails the following sequence of steps: (1) addition of [15N5]epsilonAde and [15N5]DHH-epsilonAde to DNA as internal standards, (2) acid hydrolysis of DNA, (3) adduct enrichment by C18 solid phase extraction (SPE), (4) derivatization by pentafluorobenzylation (PFB), (5) separation of PFB-epsilonAde and PFB-DHH-epsilonAde on a Si SPE column, (6) acetonide (ACT) formation of PFB-DHH-epsilonAde, and (7) GC/MS analysis with selective ion monitoring (SIM). The limit of detection by on-column injection for PFB-epsilonAde monitoring of the (M - PFB)- ion at m/z 158 was 30 amol and for ACT-PFB-DHH-epsilonAde monitoring of the (M - PFB)- ion at m/z 328 was 0.4 fmol; the detection limits for the entire assay were 6.3 fmol for epsilonAde and 36 fmol for DHH-epsilonAde. In calf thymus DNA modified with EH at 37 degreesC for 50 h, both epsilonAde and DHH-epsilonAde were detected at high levels by this method, 4.5 +/- 0.7 and 90.8 +/- 8.7 adducts/10(3) adenine, respectively. These levels were also verified by HPLC fluorescence analysis, indicating that EH extensively reacts with adenine in DNA, forming etheno adducts. The high sensitivity of the assay suggests that it may be used in the analysis of ethenoadenine adducts in vivo.     

mu-Opioid agonist-stimulated [35S]GTPgammaS binding in guinea pig hypothalamus: effects of estrogen

The distribution of growth associated protein-43 (GAP-43) immunoreactive (IR) neurons were studied in human neocortical areas, using immunofluorescence and confocal microscopy. The GAP-43-IR cells were generally localised close to blood vessels, and contained fewer lipofuscin granules than GAP-43 negative cells. Quantification of the relative number of GAP-43-IR cells in control cases showed that the highest number of GAP-43-IR cells were present in layers III and V in the motor and visual cortices, fewer in the temporal cortex, and the lowest number in the frontal cortex. After general ischemia, GAP-43-IR cells were significantly reduced at various survival times, with the counts being lowest in the 1 week surviving case, and higher, but still subcontrol, in the 1 year post-ischemic case.