Human embryonic zeta-globin chains in adult patients with alpha-thalassemias.

Human embryonic zeta-globin chains are alpha-globin-like chains that are normally present during the first three months of gestation. In this investigation, zeta-globin chains measured by a specific and sensitive radioimmunoassay and by an electrophoretic technique were found to be present in all 7 patients studied with hereditary Hb H disease, and in 8 out of 24 patients with alpha-thalassemia trait. zeta-Globin chains were not detected in 20 other patients with beta-thalassemia trait. These results suggest that the deletion of two alpha-globin genes on the same chromosome is accompanied by the continued expression of embryonic zeta-globin genes in adult individuals.     

Compound heterozygosity for Hb S [β6(A3)Glu→Val] and Hb Kenya (Aγ81Leu-β86Ala) in a Ugandan woman

Hb Kenya is a hemoglobin (Hb) tetramer composed of two normal α- and two non α-globin chains. The latter are the product of a fusion gene in which the 5' end is (A)γ and the 3' end is β. The crossover point is between codon 81 of the (A)γ gene and codon 86 of the β gene. Like the other non α genes, the hybrid protein product ((A)γ81Leu-β86Ala) has 146 amino acids. The purpose of this report is to highlight the laboratory findings of Hb Kenya and to emphasize the pitfalls in misdiagnosis, particularly when associated with another variant such as Hb S [β6(A3)Glu→Val].     

Neuro-cognitive impairment in breast cancer patients: pharmacological considerations

Post-chemotherapy cognitive impairment has been an issue of concern in cancer survivors. While most reviews are focused on patient-related factors, it is proposed that drug-related factors may also be determinants. The objective of this review is to study the relationship between the types and dose intensities of chemotherapy regimens on cognitive impairment in breast cancer patients through a systematic literature search. Eighteen prospective studies were selected. The types, dose intensities and durations of chemotherapy regimens received by subjects were compared against prevalence results obtained in individual studies. It was observed that the duration of impairment varied across different generations of chemotherapy regimens. Concurrent administration of multiple cytotoxic agents can lead to a synergistic decline on cognition. Current clinical evidence is insufficient to evaluate the relationship between the types, dose intensities of chemotherapy regimens and cognitive impairment. More investigation is needed to examine the role of pharmacological factors in chemotherapy-associated cognitive changes.     

IMI Pathologic Myopia

Pathologic myopia is a major cause of visual impairment worldwide. Pathologic myopia is distinctly different from high myopia. High myopia is a high degree of myopic refractive error, whereas pathologic myopia is defined by a presence of typical complications in the fundus (posterior staphyloma or myopic maculopathy equal to or more serious than diffuse choroidal atrophy). Pathologic myopia often occurs in eyes with high myopia, however its complications especially posterior staphyloma can also occur in eyes without high myopia.Owing to a recent advance in ocular imaging, an objective and accurate diagnosis of pathologic myopia has become possible. Especially, optical coherence tomography has revealed novel lesions like dome-shaped macula and myopic traction maculopathy. Wide-field optical coherence tomography has succeeded in visualizing the entire extent of large staphylomas. The effectiveness of new therapies for complications have been shown, such as anti-VEGF therapies for myopic macular neovascularization and vitreoretinal surgery for myopic traction maculopathy.Myopia, especially childhood myopia, has been increasing rapidly in the world. In parallel with an increase in myopia, the prevalence of high myopia has also been increasing. However, it remains unclear whether or not pathologic myopia will increase in parallel with an increase of myopia itself. In addition, it has remained unclear whether genes responsible for pathologic myopia are the same as those for myopia in general, or whether pathologic myopia is genetically different from other myopia.     

Reduced-order parameter optimization for simplifying prostate IMRT planning

Intensity-modulated radiotherapy (IMRT) has become an effective tool for cancer treatment with radiation. However, even expert radiation planners still need to spend a substantial amount of time manually adjusting IMRT optimization parameters such as dose limits and costlet weights in order to obtain a clinically acceptable plan. In this paper, we describe two main advances that simplify the parameter adjustment process for five-field prostate IMRT planning. First, we report the results of a sensitivity analysis that quantifies the effect of each hand-tunable parameter of the IMRT cost function on each clinical objective and the overall quality of the resulting plan. Second, we show that a recursive random search over the six most sensitive parameters as an outer loop in IMRT planning can quickly and automatically determine parameters for the cost function that lead to a plan meeting the clinical requirements. Our experiments on a ten-patient dataset show that for 70% of the cases, we can automatically determine a plan in 10 min (on the average) that is either clinically acceptable or requires only minor adjustment by the planner. The outer-loop optimization can be easily integrated into a traditional IMRT planning system.