Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome.

Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy. INTRODUCTION: Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD. MATERIALS AND METHODS: One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed. RESULTS: Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr. CONCLUSIONS: The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.     

Generating a model of epileptic stigma: the role of qualitative analysis

This paper uses an account of the goals, methods and results of a British community study of coping with epilepsy to consider the nature and range of the contributions qualitative analyses can make to theory formation. Different functions and contexts of qualitative analyses are described, and illustrations given of ways in which these helped generate and inform a particular model of the impact of the stigma of epilepsy on day-to-day life.     

Serum IgG and IgM levels in new and regular long-term plasmapheresis donors.

This Australian study monitored the effects of monthly plasmapheresis on donor serum IgG and IgM levels in 127 new and 124 established plasma donors who donated 1014 units over a five-month period. Of the 251 donors, 3% had reduced total serum protein (TSP) levels, 7% had low IgG levels and 12% had low IgM levels prior to donation on at least one occasion over the study period. Statistical analysis showed that the TSP, IgG and IgM levels of new donors who had donated plasma on less than 10 occasions were no more likely to fall below normal than those of old donors. However, new and old donors whose IgG or IgM levels fell below normal at any time during the study had significantly lower levels of the relevant parameter on entry to the study. Followed longitudinally, IgG and IgM levels in old and new donors tended to fall, although levels fluctuated throughout the study. Statistical analysis failed to show any correlation between TSP levels and IgG or IgM levels. These parameters did not correlate significantly with the number of previous plasmaphereses, donor weight, volume collected or history of infection. This study highlighted the need for regular, specific quantitation of IgG and IgM levels as well as TSP in regular plasmapheresis donors. The frequency of testing is yet to be determined, in view of the high materials and labour costs of such a programme.     

Axillary artery aneurysm as an occult source of emboli to the upper extremity

Reported here is a case of axillary artery aneurysm secondary to crutch trauma as a source of emboli to the upper extremity. This patient along with several reported in the literature was initially diagnosed and treated for brachial artery embolism. It is believed that awareness of this entity as a cause of forearm and hand ischemia is important in planning the appropriate surgical therapy.     

Acute ischemic stroke review.

More than 700,000 people have a stroke each year in the United States. A diagnosis of stroke formerly elicited a nihilistic approach, but this has substantially changed in the last decade. Currently, time is brain, and it is important for all disciplines to work together to initiate acute stroke protocols in the emergency department and identify patients within the therapeutic time window for thrombolytic and neuroprotective therapies. Evolving protocols, management, and nursing care all have important implications during the acute phase of ischemic stroke. Patient and family education on risk reduction must also be addressed by the entire healthcare team.     

Mediators of induction of augmented expression of plasminogen activator inhibitor type-1 in Hep G2 cells by platelets.

Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. We have shown previously that PAI-1 biosynthesis in cultured cells depends on several factors in serum. Because platelets are richly endowed with specific growth factors and because the release reaction is an integral part of thrombosis, the present study was performed to determine whether platelets augment PAI-1 production and if so, to define mediators responsible. Hep G2 cells were used to determine whether platelet lysates increased PAI-1 synthesis in a dose and time-dependent manner. In cells labeled metabolically with 35S-methionine for 6 h, an increase in labeled PAI-1 was elicited indicative of de novo synthesis as well as increased secretion of PAI-1 mediated by platelet lysates. Steady state levels of both the 3.2 and 2.2 kb forms of PAI-1 mRNA increased after 2 h and peaked in 3-5 h in a dose-dependent fashion as well. Incubation of Hep G2 cells with collagen activated platelets resulted in a similar induction of PAI-1 mRNA. The increase in PAI-1 mRNA occurred with exposure of the cells to platelet lysates for intervals as brief as 15 min and was not inhibited by cycloheximide indicating its independence of new protein synthesis. In order to identify the factors in platelets responsible for the induction of PAI-1 synthesis in the Hep G2 cell model system, neutralizing antibodies were used to inhibit specific platelet associated growth factors. Antibodies to transforming growth factor-beta (TGF-beta) and to the epidermal growth factor (EGF)/transforming growth factor alpha (TGF-alpha) receptor inhibited the platelet lysate-mediated increase in PAI-1 protein by 77%.(ABSTRACT TRUNCATED AT 250 WORDS)