The kinetics and mechanism of the hydrolysis of cyclopentolate hydrochloride in alkaline solutions

Cyclopentolate hydrochloride (Cy · HC1) is an ester of a substituted benzeneacetic acid, having N,N-dimethyl-aminoethanol as the alcohol moiety. A reversed-phase HPLC assay was employed to investigate the kinetics of degradation of Cy · HCI. The influence of pH, buffers, and temperature was studied in alkaline solutions. The degradation follows (pseudo) first-order kinetics at 50°C. Results indicate that it degrades very rapidly at higher pH values. Phenylacetic acid and a-(1-hydroxycyclopentyl)benzeneacetic acid were isolated and identified as the degradation products. The reaction mechanism appears to follow a parallel scheme where phenylacetic acid and a-(1-hydroxycyclopentyl)benzeneacetic acid are formed simultaneously. It is proposed that -(1-hydroxycyclopentyl)benzeneacetic acid is formed by normal ester hydrolysis. Phenylacetic acid is formed via a six-membered transition state and its formation requires the assistance of the hydroxyl group from the adjacent cyclopentanol moiety.     

Auditory dysfunction in traumatic brain injury

Effective communication is essential for successful rehabilitation, especially in patients with traumatic brain injury (TBI). The authors examined the prevalence and characteristics of auditory dysfunction in patients with TBI who were admitted to a Department of Veterans Affairs TBI inpatient unit before and after the onset of Operation Iraqi Freedom (OIF). In order to delineate the characteristics of the auditory manifestations of patients who had sustained blast-related (BR) TBI, we reviewed the medical records of 252 patients with TBI and categorized them according to admission date, either before (Group I, n = 102) or after (Group II, n = 150) the onset of OIF. We subdivided Group II into non-blast-related (NBR) and BR TBI; no subjects in Group I had BR TBI. We found that admissions for TBI have increased 47% since the onset of OIF. In Group I, 28% of patients with TBI complained of hearing loss and 11% reported tinnitus. In Group II-NBR (n = 108), 44% complained of hearing loss and 18% reported tinnitus. In Group II-BR (n = 42), 62% complained of hearing loss and 38% reported tinnitus. Sensorineural loss was the most prevalent type of hearing loss in Group II-BR patients. In light of the high prevalence of hearing loss and tinnitus in this growing population of returning soldiers, we need to develop and implement strategies for diagnosis and management of these conditions.     

Modified LSA2-L2 treatment in 53 children with E-rosette-positive T- cell leukemia: results and prognostic factors (a Pediatric Oncology Group Study)

In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24-49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC.     

Plasmic degradation of crosslinked fibrin. I. Structural analysis of the particulate clot and identification of new macromolecular-soluble complexes

Plasmic degradation of crosslinked fibrin has been studied to identify the proteolytic cleavages that convert the clot into a soluble lysate and also to identify the derivatives that are likely to circulate during clot dissolution. Initial polypeptide chain cleavages do not disrupt the solid clot matrix. With continued exposure to plasmin, high molecular weight derivatives are produced that remain attached to the clot by noncovalent forces. Further degradation then results in the liberation into solution of several large, noncovalently bound complexes. Progressive degradation of the largest, initially liberated complexes to the terminal derivatives, DD/E, DD, and E, occurs in solution after their release from the clot. As the fibrin clot is exposed to plasmin for longer intervals, progressive dissolution occurs, but the structure of the covalently bound insoluble fibrin core, the noncovalently attached derivatives, and the liberated complexes remains constant. Since much of the initially liberated protein is in complexes larger than DD/E, these derivatives probably represent the more prevalent plasmic degradation products of crosslinked fibrin in vivo.     

The effect of cycling deflection on the injection-molded thermoplastic denture base resins

Objective. The aim of this study was to evaluate the effect of cycling deflection on the flexural behavior of injection-molded thermoplastic resins. Materials and methods. Six injection-molded thermoplastic resins (two polyamides, two polyesters, one polycarbonate, one polymethyl methacrylate) and, as a control, a conventional heat-polymerized denture based polymer of polymethyl methacrylate (PMMA) were used in this study. The cyclic constant magnitude (1.0 mm) of 5000 cycles was applied using a universal testing machine to demonstrate plasticization of the polymer. Loading was carried out in water at 23ºC with eight specimens per group (n = 8). Cycling load (N) and deformation (mm) were measured. Results. Force required to deflect the specimens during the first loading cycle and final loading cycle was statistically significantly different (p < 0.05) with one polyamide based polymer (Valplast) and PMMA based polymers (Acrytone and Acron). The other polyamide based polymer (LucitoneFRS), polyester based polymers (EstheShot and EstheShotBright) and polycarbonate based polymer (ReigningN) did not show significant differences (p > 0.05). None of the materials fractured during the loading test. One polyamide based polymer (Valplast) displayed the highest deformation and PMMA based polymers (Acrytone and Acron) exhibited the second highest deformation among the denture base materials. Conclusion. It can be concluded that there were considerable differences in the flexural behavior of denture base polymers. This may contribute to the fatigue resistance of the materials.     

Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix

Because there is no consensus regarding the precise distribution of induced endothelial tissue factor (TF), we studied TF activity in and on tumor necrosis factor alpha-stimulated cultured human umbilical vein endothelial cells (ECs) and their underlying matrix. TF was mainly expressed on the cell surface. Only small traces were found on the apical surface suggesting that TF is predominantly located on the basolateral side of the cell membrane. The presence of TF on the cell surface was confirmed by flow cytometry. Subendothelial TF activity appeared to be dependent upon the procedure used to remove the stimulated EC monolayer. Whereas ammonium hydroxide or hypotonic lysis resulted in relatively high levels of matrix-associated TF, virtually no TF was found on the matrix after mild enzymatic detachment of stimulated ECs. Cell removal with EDTA resulted in intermediate levels of matrix-associated TF. Neither the enzymatic treatment nor EDTA degraded or removed this TF activity. Similar patterns were observed for matrix-associated TF antigen and EC surface markers. Electron microscopic analysis showed cell fragments on the matrix after monolayer lysis. The findings strongly suggest that induced endothelial TF associated with the subendothelial matrix actually represents TF on EC remnants.     

Age Effects in Implicit Memory: The Role of Response Competition Induced by Relative Word Frequency

Background/Study Context: This study examined the effect of age and response competition on implicit memory performance.

Methods: Younger and older adults studied high- and low-frequency words and took a word stem completion test that could be completed with multiple solutions. To manipulate response competition, the test list consisted of word stems that could be completed with target low-frequency words, as well as multiple other solutions with higher frequencies than the target (the high response competition condition) and word stems that could be completed with target high-frequency words, as well as multiple other solutions with lower frequencies than the target (the low response competition condition).

Results: Relative to younger adults, older adults showed reduced levels of priming only under conditions of high response competition (low-frequency targets with high-frequency competitors).

Conclusion: In support of a response competition mechanism, older adults were more likely to complete stems with nonstudied high-frequency solutions than were younger adults. Results demonstrate that older adults have reduced priming compared with younger adults under some conditions of high response competition.     

Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.