Clinical features in a family with an R460H mutation in transforming growth factor beta receptor 2 gene.

OBJECTIVES: To describe the clinical findings and natural history in 22 carriers of an R460H mutation in the transforming growth factor beta receptor 2 gene (TGFbetaR2) from a five-generation kindred ascertained by familial aortic dissection. METHODS: 13 of the confirmed carriers were interviewed and examined, and information about the remaining carrier was obtained from medical records. Clinical information about deceased individuals was obtained, when possible, from postmortem reports, death certificates and medical records. RESULTS: There have been eight sudden deaths; the cause of death was aortic dissection in all six cases in which a postmortem examination was performed. Three individuals had undergone aortic replacement surgery. Dissection had occurred throughout the aorta, and in one case in the absence of aortic root dilatation. Subarachnoid haemorrhage, due to a ruptured berry aneurysm, had occurred in two individuals. Four gene carriers and one deceased family member who were investigated had tortuous cerebral blood vessels. One had tortuous vertebral arteries, two had tortuous carotid arteries and one a tortuous abdominal aorta. Two individuals were found to have a brachiocephalic artery aneurysm and a subclavian artery aneurysm, respectively. CONCLUSIONS: Despite the predisposition to aortic dilatation and dissection, individuals did not frequently manifest the skeletal features of Marfan syndrome, with the exception of joint hypermobility. No one individual had ocular lens dislocation. Striae and herniae were common. There was some overlap with Ehlers-Danlos syndrome type 4, OMIM 130050, with soft translucent skin, which is easily bruised. Other features were arthralgia, migraine and a tendency to fatigue easily, varicose veins and prominent skin striae. This family provides further evidence that mutations in TGFbetaR2 cause a distinct syndrome that needs to be distinguished from Marfan syndrome to direct investigation and management of patients and shows the natural history, spectrum of clinical features and variable penetrance of this newly recognised condition.

Mechanism of basic fibroblast growth factor-induced cell death.

Basic fibroblast growth factor (bFGF) is a potent mitogen for a number of different cell types. Its over-expression has been implicated in transformation and malignant progression. The use of bFGF to treat malignancy is therefore counterintuitive. However, recent studies have shown bFGF-induces cell death in some tumour types. This mini review will summarise the most recent findings on bFGF-induced cell death and discuss its potential mechanism of action.

Multi-presenter mental health patients in emergency departments--a review of models of care.

Only a small proportion of the treatment of mental illness occurs in an institution or hospital. By far the most significant treatment happens in the community and in the patient's own social and family environment. However, de-institutionalisation of mental health services has brought increasing numbers of patients to the emergency department in need of psychiatric assistance. The traditional service model of emergency departments, focusing on physical illness and injury, is being challenged. The literature review identified numerous psychiatric service models in place but dramatically highlighted the lack of a specific service model addressing psychiatric patients who present on multiple occasions [multi-presenters] in emergency departments. At present, accurate data on the effects of multi-presentation of psychiatric disorders are not available. Recent international and local research into models of service delivery management and best practice is examined.

Induction of cell death by basic fibroblast growth factor in Ewing's sarcoma.

Ewing's sarcoma is thought to arise after developmental arrest of primitive neural cells during embryogenesis. Because basic fibroblast growth factor (bFGF) has a critical role in the regulation of cell survival, proliferation, and differentiation during embryogenesis, we have tested the hypothesis that bFGF and FGF receptors may contribute to the development of Ewing's sarcoma and may provide a mechanism for the modulation of their behavior. All four of the Ewing's sarcoma cell lines examined expressed bFGF and FGF receptors, which were detected by immunofluorescence and Western blotting. bFGF-induced a significant dose-dependent decrease in Ewing's sarcoma cell proliferation on plastic and reduced anchorage-independent growth in soft agar. Unexpectedly, this decrease in cell number reflected bFGF-induced apoptosis and necrosis, as demonstrated by electron microscopy, binding of annexin V, and staining with acridine orange. Induction of cell death was dependent on dosage of, and period of exposure to, bFGF. bFGF did not induce differentiation of Ewing's sarcoma cells in either the presence or the absence of serum or nerve growth factor. Treatment of NuNu mice with bFGF decreased growth of the highly tumorigenic Ewing's sarcoma cell lines. Histologically tumors grown in the NuNu mice treated with bFGF were less cellular than those in control mice, and showed an increased level of apoptotic nuclei. This is in contrast to the mitogenic effect bFGF has in most other cancer cells. In summary, bFGF decreases Ewing's sarcoma growth in vitro and in vivo by the induction of cell death. This novel observation may provide a new therapeutic strategy for Ewing's sarcomas.

Real ear to coupler differences in children having otitis media with effusion.

The aim of this study was to investigate the effects of otitis media with effusion (OME) on the 'real ear to coupler difference' (RECD) in children. RECDs are important in the procedures used for selection of appropriate amplification characteristics for children with permanent (usually sensorineural) hearing impairment. Subjects were 28 children aged between 4.6 and 7.6 years, 14 of whom had OME. There was no evidence of middle ear pathology in the remaining 14 who comprised the control group. All real-ear and coupler measures showed good test-retest repeatability at 4.0 kHz and below. The mean RECDs in frequency range 0.2-3.0 kHz were found to be up to 3.5 dB greater for the children having OME than for those without OME, although when statistically analysed only the differences in RECD at 1.0 kHz and 1.5 kHz were significant. Due to low correlation between the root mean square (RMS) sound pressure level (SPL) in the ear canal and ear canal volume, and low correlation between the subject's maximum RECD and ear canal volume, neither of these other variables could be used to predict an individual's RECD in this study. Large inter-subject variability was found, with a maximum standard deviation of 5.6 dB at 0.2 kHz, so this study greatly supports the need for individual RECD measurements to be made whenever possible, rather than using averaged transformation figures, particularly if the individual has OME.

Probe-tube microphone measures with very young infants: real ear to coupler differences and longitudinal changes in real ear unaided response.

OBJECTIVE: The feasibility and practicalities of performing probe-tube microphone measures with infants is addressed, as well as two aspects of acoustic functioning of infant ears: the real ear unaided response (REUR) and the real ear to coupler difference (RECD). DESIGN: Part 1 is a longitudinal study involving 12 infants. Serial measures of REUR were obtained over an 18-mo period. Infants were < or = 3 mo for the first test and < or = 21 mo at the last test visit. Practicalities of probe-tube microphone testing of unsedated infants and changes in the position (i.e., frequency) of the primary REUR peak were addressed. For part 2 of the project, 33 infants under 12 mo of age took part. A comparison of real ear hearing aid gain versus coupler gain was made. Test-retest differences for real ear aided response were estimated. RESULTS: Part 1 results indicate that probe-tube microphone measures in unsedated infants are feasible and show good within-subject repeatability. REUR measures for the more alert and mobile older subjects, as for the younger infants, showed an acceptably small degree of intersubject variability. The frequency of the primary REUR peak decreased during the first year of life, with a group mean of 2932 Hz reached at the end of the first year. However, thereafter, instead of stabilizing at around this value there was considerable fluctuation in the frequency of REUR peak. For Part 2, results a) confirmed the large RECD value for infants in the first year of life and b) showed a high degree of intersubject variability. Test retest measures of real ear aided response (REAR) gave values small enough to indicate the clear potential of probe-microphone use with infants during the hearing aid selection and fitting process. CONCLUSION: These findings should encourage attempts to carry out individual probe-tube microphone measurements with very young infants. They point to the need for infant hearing aid fitting procedures which involve such measurements to secure appropriate amplification.

Probe-tube microphone measurements with very young infants.

The practicalities of performing probe-tube microphone measurements in a clinical environment with unsedated infants were examined. External ear resonance curves (unaided response) were obtained for both ears of a group of infants aged 0-6 months and an adult comparison group. A repeat measure (with probe-tube repositioning) was made to estimate the test-retest reliability of these measures. Results showed that the mean infant resonance frequency (4200 Hz) occurred at a significantly (P less than 0.005) higher frequency than the mean adult resonance frequency (2950 Hz). Infants test-retest differences for resonance frequency (mean = 286 Hz, s.d. = 404 Hz) and size of peak (mean = 2.2 dB, s.d. = 2.6 dB) showed acceptable stability for the measurements. Size of resonance peak was found to vary positively with ear canal volume; however, estimation of ear canal volume from tympanometry did not provide a useful indicator of the size of the peak. The probe-microphone measurements were found to be feasible, repeatable and practical with these infants.