Identification of Factors Affecting Preservative Efficacy and Chemical Stability of Lamivudine Oral Solution Through Statistical Experimental Design

To identify factors affecting the chemical stability and preservative efficacy of lamivudine oral liquid formulations, an optimization study using a central composite design was performed. In this design, five factors, each at three levels, were investigated: pH (4.5, 5.5, and 73, sucrose (5%, 20%. and 50% w/v), propylene glycol (0% 2%, and 5% w/v), glycerin (4% 8%, and 12% w/v). and EDTA (0.100. 0.175, and 0.250 mg/mL). All formulations contained a constant concentration of lamivudine, parabens, and artificial strawberry and banana flavors. All formulations were evaluated for preservative effectiveness against USP and BP standards and for chemical stability at 30°C and 40°C for three months. All formulations were effective against bacteria and yeasts, but indicated reduced preservative effectiveness against the mold Aspergillus niger. Preservative effectiveness improved with increasing pH (4.5 to 7.5) and to a lesser extent with increasing EDTA concentration (0.100 to 0.250 mg/mL). Increasing glycerin concentration (4% to 12% w/v) slightly decreased preservative effectiveness. Over the concentration ranges tested, no change in preservative effectiveness was noted with concentration changes in sucrose or propylene glycol. The pH was the main factor influencing the chemical stability of the drug and preservatives in this study. Lamivudine chemical stability increased with increasing pH from 4.5 to 7.5. Methyl and propylparaben showed extensive degradation at pH 7.5.     

Measurement of photon beam backscatter from collimators to the beam monitor chamber using target-current-pulse-counting and telescope techniques

Backscattered radiation (BSR) arising from field-defining collimators and entering the beam monitor chamber (BMC) may contribute to observed variations in medical linear accelerator photon beam output with collimator setting. Measuring the magnitude of such contributions for particular accelerators under specified operating conditions is therefore important when attempting to understand and model accelerator head scatter. The present work was conducted to confirm some backscatter measurements for collimating jaws reported previously and to extend these to include other accelerators and a multileaf collimator (MLC). BSR reaching the BMC from the jaws of Clinac 600C, 2100C and 2300CD accelerators and from an MLC on the 2300CD was investigated using both target-current-pulse-counting and telescope methods. Our measurements show that for the Clinac 600C BSR-dependent output variations are negligible. However, for the 2100C and 2300CD BSR-dependent relative output increased in an almost linear fashion, by up to 2.4% for 15 and 18 MV beams, and by up to 1.7% for 6 MV beams, as the field size varied from 5 x 5 cm2 to 40 x 40 cm2. The magnitude of BSR dependent upon collimator location in the head, as expected, thereby contributing to the collimator exchange effect. An earlier study at our centre using the telescope method had reported higher BSR levels. This discrepancy was resolved when corrections for telescope block and room scatter, previously assumed negligible, were made.     

Long-term progression in chronic manganism: ten years of follow-up

We studied the long-term clinical course of five patients with chronic manganese intoxication. The mean scores of the King's College Hospital Rating Scale for Parkinson's disease increased from 15.0 +/- 4.2 in 1987 to 28.3 +/- 6.70 in 1991 and then to 38.1 +/- 12.9 in 1995. The deterioration was most prominent in gait, rigidity, speed of foot tapping, and writing. Tissue concentrations of manganese in blood, urine, scalp hair, and pubic hair returned to normal. Follow-up MRIs did not show paramagnetic high-signal intensity on T1-weighted images. The data indicate that clinical progression in patients with manganese parkinsonism continues even 10 years after cessation of exposure.     

Steady-state modeling of resistive-gate MOSFETs

The Pao-Sah model for the long-channel MOSFET is generalized to include MOSFETs with resistive-gate electrodes (RG-MOSFETs). The RG-MOdSFETs current-voltage characteristics are studied using this extended Pao-Sah model. The steady-state operation of the RG-MOSFET can be divided into three regimes, separated by the uniform channel condition and the pinch-off condition, respectively. The regions of operation are discussed, and a simple analytical I-V expression is given for the device     

Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus

We cloned the murine full-length cDNA encoding Ahch, the mouse homologue of DAX1 (DSS-AHC Region on Human X Chromosome, Gene1) which is the gene responsible for human X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH). Sequence analysis revealed that the murine and human cDNAs have 65% aa identity and 75% aa similarity overall. The cysteine residues in the putative DNA binding domain, which may interact with Zn2+ ions to form zinc fingers, are 100% conserved between the two species, indicating that the novel zinc-finger structures in DAX1 may be functional. In addition, mouse interspecific backcrosses show that the Ahch gene is closely linked to the glycerol kinase locus, GyK, on the mouse X chromosome, indicating that the order of the loci is conserved in this syntenic region between mouse and human.     

Breast cancer screening of the medically underserved: results and implications

Socioeconomic status is the most significant factor influencing the decreased survival associated with breast cancer in minority groups in the United States. Barriers to the use of early detection programs by low-income women often result in the detection of breast cancer at stages too advanced to assure optimum outcomes. In an effort to increase accessibility of breast cancer screening among such individuals, the Early Detection Program (EDP) was initiated in 1987. The program provided breast cancer screening to women 40 years of age and older who attended eight primary healthcare centers located in low-income neighborhoods throughout Dade County, Florida. From its inception in October 1987 through December 1993, 23,866 medically underserved women had mammography examinations, with more than 17,000 of these women undergoing baseline mammograms. Since the program's inception, 126 cancers were diagnosed in 123 women. A dramatic shift from later to earlier stage breast cancers was observed. These results warrant a greater inclusion of medically underserved and lower socioeconomic status women in screening programs for the early detection of breast cancer.