Fibronectin binding to thrombin-stimulated platelets: evidence for fibrin(ogen) independent and dependent pathways

Plasma fibronectin binds in a specific and saturable manner to thrombin- stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin- stimulated cells. Second, formaldehyde-fixed cells with surface- associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.     

Dental caries and erosion status of 12-year-old Hong Kong children

Background

We examined the association of alcohol use disorders (AUD) with adherence to and health-related quality of life (HRQOL) outcomes of antiretroviral treatment (ART) for HIV/AIDS patients.

Methods

A cross-sectional multi-site survey was conducted in 468 drug users and 648 non-drug users (age: 35.4 ± 7.0 years; 63.8% male) in 3 epicentres of Vietnam. AUD, ART adherence, and HRQOL were measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), the self-reported Visual Analogue Scale (VAS), and the World Health Organization Quality of Life instrument (WHOQOL-HIV BREF).

Results

35.0% of drug users were hazardous drinkers, compared to 25.9% of non-drug users. 22.3% of drug users engaged in binge drinking, and 25.9% reported suboptimal ART adherence. Adjusting for propensity scores of AUD, patients who had either at-risk or binge drinking behaviour were about twice as likely to be treatment non-adherent as those who did not have AUD. Hazardous drinkers reported small to medium decrements in the Performance, Physical, Social, Spirituality, and Environment quality of life domains. Binge drinkers had a slightly higher score in Social dimension.

Conclusion

AUD is prevalent and negatively affecting adherence to and HRQOL outcomes of ART services in injection-driven HIV epidemics. Screening and intervention are recommended for AUD, especially during the stable periods of ART. Other social and psychological interventions might also enhance patients’ responses to and outcomes of ART in Vietnam.     

Neurological symptoms in children with intussusception

Aim:  The classical combination of abdominal pain, vomiting, rectal blood loss and a palpable abdominal mass is only present in a minority of children with intussusception. Neurological signs and symptoms have been described, but are not a well understood phenomenon. We performed a retrospective study to ascertain the frequency and nature of these symptoms and to describe the characteristics of the patients presenting in this atypical way.
Methods:  The records of 58 children presenting with intussusception from 2003 to 2008 were reviewed for abdominal and neurological signs and symptoms, duration of symptoms and effectiveness of treatment.
Results:  In 10 out of 58 patients (17%), one or more neurological symptoms were recorded at presentation, with lethargy being the most frequent, followed by hypotonia and fluctuating consciousness. The patients with neurological abnormalities were significantly younger and presented with a shorter duration of symptoms. Therapy was more invasive, although not statistically significant, in this patient category.
Conclusion:  Intussusception should be considered in the differential diagnosis in young children presenting with lethargy, hypotonia and/or sudden alterations of consciousness even in the absence of the classical symptoms of intussusception.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

Comment on ‘Predicting recurrence in axillary node negative breast cancer patients’, by Rosner and Lane

on behalf of the Nottingham Breast Unit     

Neural and musculoskeletal contributions to the development of stance balance control in typical children and in children with cerebral palsy

Studies on the development of automatic postural responses in both typically developing children and children with cerebral palsy were performed. With the appearance of "pull-to-stand" behavior, typically developing children first began to show muscle responses to platform movements in mainly the ankle muscles. With increased development, additional agonist muscles were added to the response pattern and a consistent distal to proximal sequence began to emerge. Well-organized responses were seen with the onset of independent stance and walking, along with the reduction of antagonist muscle co-activation. The older children with cerebral palsy who were pre-walkers had immature muscle activation patterns like those seen in the typically developing children at the pull-to- stand stage of development. These included disorganized muscle responses and increased frequency of coactivation of both proximal–distal and agonist–antagonist muscles. In order to determine if musculoskeletal constraints contributed to these response patterns, normal children were asked to stand in a crouched posture similar to that of children with CP. This caused postural muscle response patterns to more closely approximate those of children with spastic diplegia.