Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.     

The psychometric properties of the Evaluation of Daily Activity Questionnaire in seven musculoskeletal conditions

Purpose: The purpose of this study is to psychometrically test the Evaluation of Daily Activity Questionnaire in seven musculoskeletal conditions.

Materials and methods: One thousand and two hundred people with ankylosing spondylitis; osteoarthritis; systemic lupus erythematosus; systemic sclerosis; chronic pain; chronic upper limb disorders; or Primary Sjögren’s syndrome completed the Evaluation of Daily Activity Questionnaire, Health Assessment Questionnaire and Short-Form Health Survey v2. We examined internal construct validity using Rasch analysis, internal consistency, concurrent validity with the Health Assessment Questionnaire and Short-Form Health Survey v2. Participants repeated the Evaluation of Daily Activity Questionnaire to assess test–retest reliability.

Results: The 12 domains satisfied Rasch model expectations for fit, local dependency, unidimensionality and invariance by age and gender, in each musculoskeletal condition. Internal consistency was consistent with individual use (Cronbach’s α?>?0.90); concurrent validity was strong (Health Assessment Questionnaire:?r_s?=?0.60–0.92; Short-Form Health Survey v2 Physical Function:?r_s?=??0.61 to ?0.91) and test–retest reliability excellent (Intra-Class Correlation Coefficient(2,1)?=?0.77–0.96).

Conclusion: The Evaluation of Daily Activity Questionnaire satisfied Rasch model requirements for construct validity and has good reliability and validity in each MSC. The Evaluation of Daily Activity Questionnaire can be used as a measure of everyday activity in practice and research with people with musculoskeletal conditions.

• Implications for rehabilitation

• The Evaluation of Daily Activity Questionnaire evaluates users’ ability to perform common daily activities (in 12 domains) that were identified as problematic by people with seven musculoskeletal conditions (i.e., osteoarthritis, systemic lupus, ankylosing spondylitis, chronic pain, chronic upper limb conditions, systemic sclerosis, Sjogren’s syndrome).

• Most patients considered the Evaluation of Daily Activity Questionnaire was the right length and would be helpful for discussing everyday problems with an occupational therapist.

• The 12 domains have good reliability and validity and can be combined into two components: Self-Care and Mobility.

• The Evaluation of Daily Activity Questionnaire is suitable for use both in clinical practice and research and a User Manual is available for therapists and researchers.

     

Cancer‐like metabolism of the mammalian retina

The retina, like many cancers, produces energy from glycolysis even in the presence of oxygen. This phenomenon is known as aerobic glycolysis and eponymously as the Warburg effect. In recent years, the Warburg effect has become an explosive area of study within the cancer research community. The expanding knowledge about the molecular mechanisms underpinning the Warburg effect in cancer promises to provide a greater understanding of mammalian retinal metabolism and has motivated cancer researchers to target the Warburg effect as a novel treatment strategy for cancer. However, if the molecular mechanisms underlying the Warburg effect are shared by the retina and cancer, treatments targeting the Warburg effect may have serious adverse effects on retinal metabolism. Herein, we provide an updated understanding of the Warburg effect in mammalian retina.     

Dimensions of osteoarthritis self-management

Our aims were to determine whether a taxonomy of self-management strategies for osteoarthritis could be identified, and whether the resultant dimensions of such a taxonomy demonstrate predictable relationships with health status indices. Participants (n = 117) from community-based self-help groups and a general rheumatology outpatient clinic completed a self-management inventory consisting of 11 items, answered for both the past 7 days and a day on which symptoms were worse than usual. Duration of symptoms, level of pain, perceived functional ability and self-rated health were recorded as indicators of health status. Three essentially identical factors were obtained for both past 7 days and worse day items. Resultant scales were labeled passive, complementary and active, respectively. Correlations with health status measures provided modest evidence for the construct validity of these self-management scales. Compared with a simple aggregate score based on the total number of strategies used, the scales provided a clearer understanding of the relationship between self-management and health. The study provided a useful extension to existing research, addressing a number of shortcomings identified by previous researchers. The identified self-management dimensions offered a greater insight into the self-management choices of patients. Suggestions for further improvements to the measurement of self-management are outlined.Abbreviations OA Osteoarthritis