Characterization of bone and soft-tissue tumors with in vivo 1H MR spectroscopy: initial results

PURPOSE: To determine if in vivo detection of choline by using hydrogen 1 (1H) magnetic resonance (MR) spectroscopy with dynamic contrast material-enhanced MR imaging can help differentiate between benign and malignant musculoskeletal tumors. MATERIALS AND METHODS: MR imaging was performed in 36 consecutive patients with bone and soft-tissue tumors larger than 1.5 cm in diameter. Examinations were performed at 1.5 T with a surface coil appropriate for the location of the lesions. Single-voxel 1H MR spectroscopy was performed by using a point-resolved spectroscopic sequence with echo times of 40, 135, and 270 msec. The volume of interest within lesions was positioned on the areas of early enhancement (<8 seconds after arterial enhancement) according to the findings of dynamic contrast-enhanced MR imaging with subtraction. The criterion for determining whether choline was present in a lesion was a clearly identifiable peak at 3.2 ppm in at least two of the three spectra acquired at echo times. MR spectroscopic results and histopathologic findings were determined in blinded fashion and compared with kappa statistics. P <.001 was considered to indicate a significant difference. RESULTS: Choline was detected in 18 of 19 patients with malignant tumors and in three of 17 patients with benign lesions. The three benign lesions included one perineurioma, one giant cell tumor, and one abscess. Choline was not detected in 14 patients with benign lesions nor in one patient with a densely ossifying low-grade parosteal osteosarcoma. In vivo 1H MR spectroscopy characterized bone and soft-tissue tumors, resulting in a sensitivity of 95%, specificity of 82%, and accuracy of 89% (P <.001). CONCLUSION: Choline can be reliably detected in large malignant bone and soft-tissue tumors by using a multiecho point-resolved spectroscopic protocol. 1H MR spectroscopy can help differentiate malignant from benign musculoskeletal tumors by revealing the presence or absence of water-soluble choline metabolites.     

A hematology surveillance study of petrochemical workers exposed to benzene

Historically, complete blood counts (CBCs) have been recognized as an easy and readily available screen for hematotoxicity following occupational exposure to benzene. The purpose of this study is to evaluate hematology data from employees who have ever participated in the Shell Benzene Medical Surveillance Program (BMSP) compared to employees who have not participated and to examine the sensitivity of CBCs to detect hematological changes in a low-exposure occupational setting. This large study included 1200 employees who participated in the BMSP, with mean benzene exposure (TWA-8) of 0.60 ppm from 1977 to 1988 and 0.14 ppm since 1988, and 3227 comparison employees. The comparison group included employees not enrolled in either the benzene or butadiene surveillance programs. Abnormality of six CBC parameters and the adjusted mean values of these parameters in the exposed group were compared with that of the comparison group. We found no increased abnormality for any hematology parameter among exposed employees. The adjusted mean values (adjusted for age, sex, race, length of time between first and last exam, and current smoking status) of the exposed employees were similar to those in the comparison group. At current occupational exposure levels for benzene, no evidence of adverse hematological effects was observed in this study. These results raise the question of whether annual CBC surveillance for benzene-exposed workers has adequate sensitivity to detect meaningful hematological changes due to low-level exposures.     

Development and validation of an HPLC method for AG331 bulk drug substance and lyophilized powder for injection

AG331 is a water soluble glucuronate salt of a novel antitumor compound synthesized by protein structure based drug design. A lyophilized powder for injection was developed for clinical studies. During HPLC assay development, AG331 showed an inherent tailing problem due to an amino group in the structure. An optimized reverse-phase gradient HPLC method was developed to minimize the tailing and separate AG331 from its synthetic intermediates (I-1, I-2, I-3, I-4, I-5, I-6, I-8), other impurities and degradation compounds. The method was shown to be linear, precise, accurate, rugged and stability-indicating.     

Optimization of sustained-release propranolol dosage form using factorial design and response surface methodology

The purpose of this study was to develop propranolol extended release formulations containing hydroxypropylmethylcellulose (HPMC). The results indicate that the drug release from the tablet form containing a high amount of HPMC was incomplete, and avicel addition could increase the release percent at a later stage. In order to readily obtain an optimal formulation, response surface methodology and multiple response optimization utilizing a quadratic polynomial equation was used. The model formulations were prepared according to a factorial design. The effects of causal factors including the HPMC/drug ratio (X1) and avicel level (X2), on drug release were also measured. The drug release percentage at 1.5, 4, 8, 14 and 24 h were the target response and were restricted to not more than 25%, 35-50%, 55-70%, 75-90%, and 95-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrices tablets followed quasi-Fickian diffusion.     

Partial Removal of Orbital Tumor in Rosai-Dorfman Disease

Background Rosai-Dorfman disease is a rare idiopathic histiocytic proliferation disorder that typically presents with painless cervical lymphadenopathy. We report our experience with the management of a case of Rosai-Dorfman disease with compressive optic neuropathy.Case Rosai-Dorfman disease involving the bilateral orbital and paranasal sinuses was diagnosed in a 14-year-old boy. Diagnosis was based on the characteristic histopathologic features of sinus histiocytosis, composed of large, round S-100 protein-positive histiocytes with striking emperipolesis. The boy received chemotherapy to resolve the bilateral proptosis and compressive optic neuropathy in the right eye, but this treatment failed. Orbital debulking surgery using the Lynch approach was performed.Observations Corneal exposure was resolved and visual acuity recovered from 14/20 to 20/20 after partial removal of the tumor mass. There were no complications after surgery. During the 22 months of follow-up, orbital tumor masses redeveloped to cause lagophthalmos again, but did not cause visual impairment.Conclusions Rosai-Dorfman disease is a rare disorder, especially in Asia. The disease is usually chronic with spontaneous remission and is refractory to treatment. Partial removal of tumor masses is a workable way to improve visual acuity and correct corneal exposure. Before carrying out this procedure, we discussed with the parents of the patient the potential complications that might follow surgery and secured their permission before proceeding further. Jpn J Ophthalmol 2004;48:154–157 © Japanese Ophthalmological Society 2004     

Prevalence and causes of visual impairment in an elderly Chinese population in Taiwan: the Shihpai Eye Study

OBJECTIVE: Few population-based data on the prevalence and causes of visual impairment are available from East Asia. The purpose of this study was to determine the prevalence and causes of visual impairment in an elderly Chinese population in Taiwan. DESIGN: Population-based cross-sectional study. PARTICIPANTS: The Shihpai Eye Study was a survey of vision and ocular disease among an elderly Chinese population 65 years of age or older residing in Shihpai, Taiwan. A random sample of 2045 elderly residents was identified and selected from the household registration databank. Among them, 1361 (66.6%) underwent a detailed ophthalmic examination. METHODS: The ophthalmic examination included best-corrected visual acuity measurements using standardized protocols. Visual acuity was assessed with a Snellen E chart. The major cause of visual loss was identified for all participants who were visually impaired. MAIN OUTCOME MEASURES: Low vision and blindness were defined as a best-corrected visual acuity in the eye with better vision worse than 20/60 to a lower limit of 20/400 and worse than 20/400, respectively, according to World Health Organization categories of visual impairment. RESULTS: The mean age of the participants was 72.2 (range, 65-91) years old. A total of 40 participants met the World Health Organization criteria of low vision, and 8 were diagnosed as blind. The rate of blindness and low vision was estimated to be 0.59% (95% confidence interval, 0.25%, 1.16%) and 2.94% (95% confidence interval, 2.11%, 3.99%), respectively. There was a significant increase in the rate of low vision (P<0.001) from 0.83% at 65 to 69 years of age to 8.33% at age 80 years or older. There was no gender difference in the prevalence of blindness or low vision. The leading cause of visual impairment was cataract (41.7%), followed by myopic macular degeneration (12.5%) and age-related macular degeneration (10.4%). CONCLUSIONS: The rate of blindness and low vision is close to that reported for other developed countries. The high frequency of myopic macular degeneration as a major cause of visual loss, however, is not observed in European-derived populations. Specific prevention or low-vision rehabilitation programs should be developed for the elderly Chinese population.     

Pharmacokinetics of baicalin in rats and its interactions with cyclosporin A, quinidine and SKF-525A: a microdialysis study

Baicalin, a flavone glucuronide derived mainly from the root of Scutellaria baicalensis, has been used in traditional Chinese medicine as an anti-inflammatory and anti-viral agent. To explore whether the disposition of baicalin is related to multidrug resistance P-glycoprotein (P-gp), baicalin (3, 10 and 30 mg kg(-1); i. v.) was injected to rats for a pharmacokinetic study using microdialysis coupled with HPLC. The results indicate that baicalin goes through hepatobiliary excretion against a concentration gradient based on the blood-to-bile distribution ratio (AUCbile/AUCblood), but that AUCblood or AUCbile did not show any dose-related increase in the range from 3 to 30 mg kg(-1). Coadministration of cyclosporin A (CsA) or quinidine (both are P-gp inhibitors) was used to delineate the role of P-gp on baicalin disposition, while SKF-525A (a cytochrome P450 inhibitor) could specifically inhibit the cytochrome P450 catalysis of baicalin without crossing with P-gp function. Both CsA and quinidine promoted the active transport of baicalin into bile and reduced its level in blood, and this result was the same as that obtained by treating with SKF-525A. Hence, the association of the involvement of P-gp in active baicalin efflux into bile seems to be excluded since CsA and quinidine are also cytochrome P450 inhibitors. In addition, baicalin was not detected in the brain striatum after treating with baicalin alone in the present study. Also, neither CsA nor quinidine co-administered with baicalin is able to induce measurable levels of baicalin in rat brain, which suggests that baicalin might not be able to pass through the blood-brain barrier (BBB).     

Quantification of O-acetyl, N-acetyl and phosphate groups and determination of the extent of O-acetylation in bacterial vaccine polysaccharides by high-performance anion-exchange chromatography with conductivity detection (HPAEC-CD)

The O-acetyl groups in meningococcal A and typhoid Vi polysaccharides (PSs) are functional immunogenic epitopes in humans. To quantify and determine the extent of O-acetylation in these and other bacterial vaccine PSs, anion-exchange HPLC methods have been developed for quantification of O-acetyl, N-acetyl, and phosphate groups in the PSs after these groups were hydrolyzed into anions. The O-acetylation in meningococcal A, C, Y and W-135, pneumococcal 9 V and 18C and typhoid Vi PSs were analyzed. The O-acetyl group was selectively released from a PS as acetate by mild alkaline hydrolysis in 10 or 20 mM NaOH at 37 degrees C until maximum release. The acetate in the hydrolysate was then quantified by high-performance anion-exchange chromatography with conductivity detection (HPAEC-CD) after removal of the PS by filtration with a 10,000 molecular-weight-cut-off membrane. Since the extent of O-acetylation on the PSs depends on bacterial species, strains and growth conditions, the N-acetyl group of amino-sugars, phosphate or monosaccharide components of the PSs were also quantified using HPAEC with conductivity or amperometry detection to determine the molar ratios of the O-acetyl group to these components. The average numbers of O-acetyl molecules in one PS repeating unit of the PSs were obtained from the molar ratios. Besides the O-acetyl determination, the pyruvate component in non-O-acetylated pneumococcal type 4 PS was analyzed by the HPAEC method. The HPAEC method can quantify the O-acetyl content in 0.2 microg of the meningococcal C PS and has a sensitivity at least 10 times higher than that of the colorimetric Hestrin assay. The method can be used for routine analysis of O-acetylation of PSs for quality control of vaccine PSs.     

Prevalence and risk factors of occupational hand dermatoses in electronics workers

The electronics industry is becoming an important mainstream in the workforce in some developed countries and in Taiwan. Among patients with occupational hand dermatitis in northern Taiwan, workers from electronics industries were one of the most important groups. We conducted a field investigation to determine the prevalence, patterns and risk factors of occupational hand dermatoses among electronics workers. The survey was conducted in five electronics plants using a self-administered questionnaire on skin symptoms and risk factors. Skin examination and patch testing were followed for those with symptoms compatible with hand dermatitis. A total of 3070 workers completed the questionnaire. Among them, 302 (9.8%) reported to have symptoms (itching and with either redness/scaling) compatible with contact dermatitis on hands. Hand dermatitis was associated with working in the fabrication unit and personal history of atopy and metal allergy, as well as the following job titles: wafer bonding, cutting, printing/photomasking, softening/degluing, impregnation and tin plating. Among those with reported hand dermatitis, 183 completed skin examination and patch testing, 65/183 (35.5%) were diagnosed as having irritant contact dermatitis (ICD) and 7/183 (3.8%) allergic contact dermatitis. The most important allergens were nickel, cobalt and phenylenediamine. In conclusion, Taiwanese electronics workers have a high risk of having hand dermatitis, especially ICD. Preventive efforts should be focused on the workers with risk factors or at certain worksites.