Unbiased Combinatorial Screening Identifies a Bispecific IgG1 that Potently Inhibits HER3 Signaling via HER2-Guided Ligand Blockade

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Psychosocial risk factors for cardiovascular disease in women: The role of social support

Lack of social support is becoming increasingly important as a psychosocial risk factor in the study of coronary heart disease (CHD). There may also be an association between vital exhaustion and lack of social support. Because most research has focused on men, we decided to explore the associations between structural and functional social support and first myocardial infarction (MI) in women. Subjects were 79 women hospitalized with a First MI (mean age 59.3; SD = 9.3) and 90 women hospitalized with an acute surgical event (mean age 57.4: SD = 9 1). MI cases reported more vital exhaustion than did controls (p < ,040), and exhausted women reported less structural (p < .001) and functional support (p < .000). After controlling for age, hypertension, diabetes, menopausal status, smoking, nonanginal pain, and vital exhaustion, multiple logistic regression analysis showed that poor structural support was associated with an increased risk for MI. These results suggest that social support is associated with vital exhaustion, which is a well-known risk factor for CHD. Furthermore, it is suggested that women with only a few confidants are more at risk for MI even after adjustment for well-known risk factors for CHD.     

Discordant fetal growth in multiple pregnancy: intervention should be based on chorionicity]

In three women, aged 28, 35, and 38 years, with multiple pregnancies and discordant foetal growth, the question arose what to do in case of (threatening) intrauterine death of one twin. In one monochorionic pregnancy with single foetal death the survivor suffered irreversible neurological damage and died at the age of five months, in one monochorionic pregnancy the survivor was born healthy and in one dichorionic pregnancy both twins were born healthy although one twin showed severe intrauterine growth retardation. The problem concerning single foetal death in a monochorionic pregnancy is whether to terminate the pregnancy and accept the risk of premature birth to the surviving twin, or to continue the pregnancy and accept the risk of damage to the survivor. In a dichorionic pregnancy foetal death of one twin does not entail any great risk of damage to the survivor; in such a pregnancy single foetal death in a premature phase may be accepted and the pregnancy may be continued. Sonographic determination of the chorionicity in multiple pregnancy at an early stage is essential because it also determines the policy if foetal problems occur.     

Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II: Multi-Institutional Propensity Score Matched Analysis

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Moving from physician-centered care towards patient-centered care for Parkinson's disease patients

Today's society is changing rapidly and individuals increasingly favor an active role in designing their own lives. Contemporary patients are no exception, but the present health care system–which is organized primarily from the provider's perspective–is not yet prepared for this development. Here, we argue that an alternative way to organize health care, namely more from the patient's perspective, may help to contain costs, while improving the quality, safety and access to care. This involves a redefinition of the patient–doctor relationship, such that patients are no longer regarded as passive objects, but rather as active subjects who work as partners with health care professionals to optimize health (‘participatory medicine’). The opportunities that come with such a collaborative and patient-centered care model are reviewed within the context of patients with Parkinson's disease. We also discuss societal and Parkinson-specific barriers that could impede implementation of this alternative care model to the management of Parkinson's disease and other chronic conditions.     

Quantitative analysis of fetal general movements: methodological considerations.

OBJECTIVES: We studied the effects of gestational age and various smoothing procedures on four incidence parameters of fetal general movement, to evaluate reported variation in previous studies and to establish the optimal way of smoothing. SUBJECTS AND METHODS: General movements were studied longitudinally between 24 and 40 weeks of gestation in 29 healthy fetuses. The number of movement bursts per hour, burst duration, onset-onset interval between successive bursts (OOI) and the percentage incidence were analysed in detail. RESULTS: Advancing gestation was characterised by a proportional increase in OOI's lasting > 60 s and a decreased number of bursts, whereas burst duration remained relatively stable (unsmoothed data). Smoothing resulted in an exaggerated decrease in the number of bursts and in increases in burst duration, OOI and percentage incidence. These changes occurred in a gestational age specific manner and could largely explain the variation in results between previous studies. CONCLUSIONS: The temporal patterning of fetal general movements undergoes developmental change, as shown by differential effects of smoothing between mid and late pregnancy. A smoothing procedure is to be preferred which includes short intervals (1-3 s) between the elements composing a burst, since small changes in movement generation can still be recognised this way.     

Posttransfusion purpura following bone marrow transplantation

BACKGROUND : Thrombocytopenia is a major cause of morbidity and hospital expense following bone marrow transplantation. Platelet transfusions in these patients are frequently complicated by the recipient's development of antibodies to HLA class I antigens. When these patients become refractory to the transfusion of HLA-matched platelets, the recipient's platelet antigen phenotype must be determined, to ensure that donor platelets will be phenotypically compatible. Cases of alloimmunization to HPA-1a and HPA-1b resulting in refractoriness to transfused platelets and the subsequent development of a posttransfusion purpura-like syndrome are reported. CASE REPORTS: In the first case, a 43-year-old woman with Stage IV infiltrating ductal breast cancer presented to the hospital for a transplant of autologous peripheral blood stem cells. After the transplant, her platelet count remained less than 10 × 10⁹ per L, despite daily platelet transfusions, including HLA-matched platelets. Fourteen days following the transplant, her serum was found to contain anti-HPA-1a. Initially, the patient was refractory to the transfusion of HPA-1a-negative platelets, but after treatment with intravenous immunoglobulin, she had transient increases in posttransfusion platelet counts. She was also treated with a staphylococcal protein A immunoadsorption column and has not had any such subsequent refractoriness. Her genotype has been found, by use of allele-specific oligonucleotide hybridization with white cell DNA, to be HPA-1b/1b. The second case involved a 32-year-old woman with chronic myelogenous leukemia who received an unrelated-donor marrow transplant. Three years later, her CML recurred, and she was treated with interferon-alpha. Four months afterward, she experienced interferon-alpha-induced thrombocytopenia and the interferon therapy was discontinued. She received 12 platelet transfusions in 20 days, but none was effective. Antibodies specific for HLA antigens and HPA-1b were detected, and three HLA-matched, HPA-1b-negative apheresis platelet components were given, but without effect. Two days after treatment with methylprednisolone (1 g intravenously) and prednisone (2 mg/kg/day orally), her platelet count was 26 × 10⁹ per L, and after 8 more days, it was 102 × 10⁹ per L, without further transfusions. She was found to be homozygous for HPA-1a (HPA-1a/1a). CONCLUSION : Anti-HPA- 1a and anti-HPA-1b can cause refractoriness to platelet transfusions in bone marrow transplant patients. Testing for platelet-specific antibodies should be considered in all patients who are refractory to HLA-matched platelets.