Conventional and experimental drug therapy in myelofibrosis with myeloid metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (ie, BCR-ABL-negative) myeloproliferative disorder characterized by anemia, multiorgan extramedullary hematopoiesis, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Stem cell transplantation can be curative, but many patients either are not appropriate candidates or do not choose to accept the significant risks associated with transplantation. Current pharmacologic therapy has been beneficial mainly in terms of palliating disease-associated cytopenias, constitutional symptoms, splenomegaly, and other organ damage from excess myeloproliferation. Novel treatment strategies are under investigation, including targeted inhibition of JAK2^V617F, the activating tyrosine kinase point mutation present in about half of patients with MMM. In this article, we review both the old and new pharmacologic options for MMM.     

Angiotensinogen gene polymorphism as a risk factor for ischemic stroke.

While gene polymorphism for angiotensinogen (AGT) is reported to contribute to the regulation of blood pressure and salt sensitivity, its effect on the risk of ischemic stroke remains controversial. We hypothesized that polymorphism of the AGT gene could be a risk factor for ischemic stroke. Major clinical risk factors and the AGT gene M235T polymorphism were examined in 147 consecutive stroke patients and 133 healthy age-matched controls. All patients were categorized into four stroke types (single lacuna, multiple lacunae, large-artery atherosclerosis and branch atheromatous disease in brainstem) and two vascular groups (large and perforating arterial lesions). The AGT gene M allele significantly increased the risk of single lacuna, multiple lacunae and small arterial lesions, in male patients (p=0.029, 0.031 and 0.026, respectively). Synergistic effects of the AGT gene polymorphism and clinical risks were not observed. In conclusion, AGT M allele may present a risk of lacunar infarctions in Japanese men, independent of hypertension.     

Evaluation of clinical outcomes in anterior cruciate ligament surgery

Clinical outcomes data can be used to facilitate patient management decisions, assess clinician and organizational performance, and to provide evidence for the effectiveness of surgery and rehabilitation. The validity of the inferences made from outcomes data are dependent on the validity of the outcomes measures themselves and the circumstances under which the data were collected, analyzed, and interpreted. Clinical outcomes may include measures of impairment of body structure and function, activity limitation, and participation restriction. However, because the relationship between impairment and the resulting activity limitation and participation restriction is not direct, and because activity limitations and participation restrictions are of the utmost concern to the athlete, the primary clinical outcome should be measures of activity limitation and participation restriction. Activity limitation and participation restriction may be measured either through direct observation of performance or by general or specific measures of health related quality of life. Clinical outcomes data must be collected systematically to ensure valid inferences from the data.     

Predictors of oral health quality of life in older adults

There is limited information regarding oral health status and other predictors of oral health‐related quality of life. An association between oral health status and perceived oral health‐related quality of life (OHQOL) might help clinicians motivate patients to prevent oral diseases and improve the outcome of some dental public health programs. This study evaluated the relationship between older persons' OHQOL and their functional dentition, caries, periodontal status, chronic diseases, and some demographic characteristics. A group of 733 low‐income elders (mean age 72.7 ISD=4.71, 55.6% women, 55.1% members of ethnic minority groups in the U.S. and Canada) enrolled in the TEETH clinical trial were interviewed and examined as part of their fifth annual visit for the trial. OHQOL was measured by the Geriatric Oral Health Assessment Index (GOHAI); oral health and occlusal status by clinical exams and the Eichner Index; and demographics via interviews. Elders who completed the four‐year assessment had an average of 21.5 teeth (SD=6.9). with 8.5 occluding pairs (SD=4.6), and 32% with occlusal contacts in all four occluding zones. Stepwise multiple regressions were conducted to predict total GOHAI and its subscores (Physical, Social, and Worry). Functional dentition was a less significant predictor than ethnicity and being foreign‐bom. These variables, together with gender, years since immigrating, number of carious roots, and periodontal status, could predict 32% of the variance in total GOHAI, 24% in Physical, 27% in Social, and 21 % in the Worry subscales. These findings suggest that functional dentition and caries influence older adults' OHQOL, but that ethnicity and immigrant status play a larger role.