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.     

Quality of life among children with sickle cell disease receiving chronic transfusion therapy.

Sickle cell disease (SCD) is a genetic disorder that is most prevalent among those of African American and Mediterranean descent. Hemoglobin SS is the most severe form of SCD and carries an increased risk for stroke. Although the initial treatment for stroke is an exchange transfusion, the use of routine, chronic transfusion therapy (CTT) has been shown to help prevent this neurological injury. The treatment plan is rigorous and time consuming, both of which impact one's quality of life (QoL). The purpose of this study was to explore QoL, from the child's perspective, as it is affected by CTT Semistructured interviews were performed on 10 children undergoing CIT: Five themes emerged from the data: (a) pain, (b) school issues, (c) disease knowledge, (d) transfusion therapy, and (e) having a stroke. Data from this study reveal that CTT does have an impact on QoL. This information is important to share with those making CTT treatment decisions.     

Retroviruses and schizophrenia in Jamaica

Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon called “an epidemic of schizophrenia,” with the inference that a novel virus, likely to be perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Islands, is perinatally transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/ HTLV-I associated myelopathy). We therefore examined inpatients at the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population, indicating that HTLV-I and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics.     

Ontogeny and thymus-dependence of T cell surface antigens in Xenopus : flow cytometric studies on monoclonal antibody-stained thymus and spleen

Recently generated anti-Xenopus T cell monoclonal antibodies (mAbs) to the 120 kDA XTLA-1 determinant and against the putative CD5 and CD8 homologues, together with anti-IgM and anti-MHC class II mAbs, are used in dual colour flow cytometric experiments to characterize cell surface antigenic expression on lymphocytes in thymus and spleen of Xenopus laevis during larval and early adult life and also in metamorphosis-inhibited animals. Histological confirmation of T cell emergence early in larval ontogeny is supplied by cryostat sections stained for CD8. Five-day thymectomy i.e. prior to T-lineage cell differentiation in the thymus, abolishes T cell marker expression in the spleen for up to 1 year. Moreover, late larval (20 days) or early adult (3 months) thymectomy (i.e. removal after peripheralization of T cells has occurred) also leads to severe depletion of mAb-defined T cells in the spleen.     

Effects of age and age-related hearing loss on the neural representation of speech cues.

OBJECTIVE: To examine the effects of aging and age-related hearing loss on the perception and neural representation of a time-varying speech cue. METHODS: P1, N1 and P2 cortical responses were recorded from younger and older normal-hearing adults, as well as older adults with age-related hearing loss. Synthetic speech tokens representing 10 ms increments along a /ba/-/pa/ voice-onset-time (VOT) continuum were used to evoke the responses. Each participant's ability to discriminate the speech tokens was also assessed. RESULTS: Compared with younger participants, older adults with and without hearing loss had more difficulty discriminating 10 ms VOT contrasts. In addition, both older groups elicited abnormal neural response patterns. There were no significant age-related findings for P1 latency; however, N1 latencies were prolonged for both older groups in response to stimuli with increased VOT durations. Also, P2 latencies were delayed for both older groups. The presence of age-related hearing loss resulted in a significant increase in N1 amplitude in response to voiceless stimuli. CONCLUSIONS: Aging and age-related hearing loss alter temporal response properties in the central auditory system. Because both older groups had difficulty discriminating these same speech stimuli, we conclude that some of the perceptual difficulties described by older adults might be due to age-related changes regulating excitatory and inhibitory processes. SIGNIFICANCE: Some of the speech understanding difficulties expressed by elderly adults may be related to impaired temporal precision in the aging auditory system. This might explain why older adults frequently complain that wearing a hearing aid makes speech louder, but does not necessarily improve their ability to understand speech.     

Staphylococcal toxins: screening of burn wound isolates and evidence for alphahaemolysin production in the burn wound

Culture filtrates of Staphylococcus aureus strains isolated from burn patients were examined for cytotoxic activities. A large molecular weight cytotoxin (MW=253000 daltons) that exhibited cytotoxicity for human foreskin cells and haemolytic activity against human and rabbit erythrocytes was identified. The cytotoxic activity could be completely neutralized by antiserum formed against the cytotoxin. Further characterization of the molecule by isoelectric focusing revealed that the cytotoxin was composed of at least two toxic factors of smaller molecular weight. Both factors exhibited cytotoxicity to tissue-culture cells. however, one factor lysed rabbit but not human erythrocytes whereas the other factor had the opposite haemolytic pattern. The cytotoxicity of each factor was neutralized by the antiserum formed against the cytotoxin. A cytotoxic factor that exhibited haemolytic activity for rabbit erythrocytes, and that was neutralized by the cytotoxin antiserum, was identified in burn wound extracts of mice infected with Staph. aureus. On the basis of molecular weight and isoelectric focusing data, we conclude that the large molecular weight cytotoxin was composed of an aggregation of alpha-haemolysin and another presently unidentified toxic molecule, possibly delta-toxin. Alpha-haemolysin appears to be produced in vivo during experimental staphylococcal burn wound infection.