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Clinical genetic research is often regarded as more ethically problematic than other forms of research, and in some countries is subject to specific regulation, requiring researchers to follow specialised guidelines. In this paper, an approach to enhancing the ethical conduct of genetic research is proposed, which is believed to be more effective than simply attempting to follow general guidelines. The potential concerns, likely areas of misunderstanding and negative reactions of the participant group are systematically investigated before starting a study on genetics. This would constitute, in effect, an ethical pilot study, similar to a feasibility pilot study to test equipment, procedures and logistics. The findings of the ethical pilot study would be used to help in designing ethically important aspects of research protocol, such as recruitment procedures, written and other information for potential participants, informed consent processes and reporting of results including ambiguous or uncertain results. doi: 10.1136/jme.2005.013201

Abstract Objective To compare the effect of a behavioural sleep intervention with written information about normal sleep on infant sleep problems and maternal depression. Design Randomised controlled trial. Setting Well [...]

The Eustachian, or auditory, tube forms the connection between the middle ear space and the nasopharynx. The Eustachian tube functions to equalize pressure within the middle ear and to allow mucous produced in the middle ear to drain into the nasopharynx. Blockage of this structure can lead to the accumulation of fluid in the middle ear space or to the development of a partial vacuum within this space; either of these events can lead to an impairment of hearing. In some patients, either for feeding or for removal of secretions from the stomach, a tube is passed into the nose, through the nasopharynx, and down into the esophagus and stomach; this is called a nasogastric tube. This study investigated the effect of using a nasogastric tube on Eustachian tube function in 10 patients undergoing head and neck surgery which required placement of the nasogastric tube. Measurement of the mechanical function of the middle ear cavity and Eustachian tube can be rapidly made with an impedance tympanometer. Tympanometric examinations are very sensitive to irregularities of the nasopharynx and middle ear spaces. Before their surgery, all patients received a comprehensive auditory examination which included a tympanogram. Following the surgery, the patients' auditory function was evaluated with conventional audiograms, examinations and tympanograms. Nine of the 10 patients developed new ear symptoms as a result of the use of nasogastric tubes. These symptoms were confirmed by tympanometry. Fortunately, the symptoms were temporary. Eustachian tube dysfunction caused by a nasogastric tube has not been reported previously. (Consumer Summary produced by Reliance Medical Information, Inc.)

An eight-wave cohort study i conducted with 2,032 students selected from Grade 9 classes in Victoria, Australia, aimed to assess changes in overweight and obesity between adolescence and young adulthood. [...]

The aim of this study was to describe child health and well‐being across the spectrum of cerebral palsy (CP) and to report on psychometric properties of the Child Health Questionnaire (CHQ) in this population. Parents of 80 individuals (45 males, 35 females; mean age 11 years 4 months, SD 3 years 6 months; range 5 to 18 years) attending a CP clinic in Victoria, Australia were surveyed. Measures included the CHQ PF‐50, a 50‐item parent‐reported heath status measure; severity of CP, based on the Gross Motor Function Classification System; and cognitive status and presence of epilepsy. CHQ data were compared with normative data collected in Victoria two years earlier. The CHQ demonstrated good psychometric properties for children with CP. Children with CP had markedly poorer health on every CHQ scale than those in the normative sample. Health status did not vary by cognitive status or epilepsy. Children with severe CP had the poorest physical health, but psychosocial health and emotional impact on parents were similar for mild and severe CP showing that these should not be assumed to be less prevalent when CP is mild.

OBJECTIVE: To compare the effect of a behavioural sleep intervention with written information about normal sleep on infant sleep problems and maternal depression. DESIGN: Randomised controlled trial. SETTING: Well child clinics, Melbourne, Australia. PARTICIPANTS: 156 mothers of infants aged 6-12 months with severe sleep problems according to the parents. MAIN OUTCOME MEASURES: Maternal report of infant sleep problem; scores on Edinburgh postnatal depression scale at two and four months. INTERVENTION: Discussion on behavioural infant sleep intervention (controlled crying) delivered over three consultations. RESULTS: At two months more sleep problems had resolved in the intervention group than in the control group (53/76 v 36/76, P=0.005). Overall depression scores fell further in the intervention group than in the control group (mean change -3.7, 95% confidence interval -4.7 to -2.7, v -2.5, -1.7 to -3.4, P=0.06). For the subgroup of mothers with depression scores of 10 and over more sleep problems had resolved in the intervention group than in the control group (26/33 v 13/33, P=0.001). In this subgroup depression scores also fell further for intervention mothers than control mothers at two months (-6.0, -7.5 to -4.0, v -3.7, -4.9 to -2.6, P=0.01) and at four months (-6.5, -7.9 to 5.1 v -4.2, -5.9 to -2.5, P=0.04). By four months, changes in sleep problems and depression scores were similar. CONCLUSIONS: Behavioural intervention significantly reduces infant sleep problems at two but not four months. Maternal report of symptoms of depression decreased significantly at two months, and this was sustained at four months for mothers with high depression scores.

Aim To examine the relation between a child's height and grade progression in primary school. Methods Height was measured in a representative cross sectional sample of children from 24 primary schools in Victoria in late 1997. Height measurements were transformed to standardised scores using Cole's "LMS" method to allow for comparison across ages and genders. Children within each grade were divided into three equal groups based on age (youngest third, middle third, oldest third), again to allow for cross age comparison. Results A total of 2848 children aged 5-12 years (51% male) were included, with approximately 400 children in each of the seven grades from preparatory to grade 6. Analysis of variance showed a significant relation overall between age and height, with a sequential decrease in height from the youngest to the oldest third. When genders were considered separately, the relation remained significant for boys but not for girls. A total of 133 children (66% male) repeated a grade in primary school. When this group of grade repeaters was removed from the sample, analysis of variance showed no significant relation between standardised height score and age tertile for boys. Although birth weight category and maternal education were independent predictors of height scores overall, they did not appear to influence decisions to retain pupils in grades. Conclusions Older boys within grades, notably those who have repeated a grade, are shorter than their peers. Decisions to retain pupils, particularly boys who are experiencing school difficulties, may be influenced by their height.

The methods and results of measurement of more than 100 Energy Doubler magnets are described. Training, quenchbehavior, ac loss, integral field, longitudinal homogeneity DC and AC multipole content, and vertical-plane angle measurements are described.

In the management of craniosynostosis, there is a need for quantitative assessment of treatment methods and outcome. Radiology and pressure studies are well documented, but so far little attention has been given to cerebral blood flow changes and their possible relevance. This paper reports our initial experience using transcranial Doppler sonography to calculate the cerebrovascular resistance and cerebral blood velocities in the major basal vessels before and after surgery for craniosynostosis. Ten patients were studied using the Scimed 2-MHz probe through the temporal and frontal “windows” of the skull. Measurements were taken under standard physiological conditions before, during and after surgery. Preliminary results suggest that this non-invasive technique may be helpful in predicting and assessing the outcome following surgery for craniosynostosis.

In 1984, two young infants with unusual “clover-leaf” patterns of skull deformity were treated by posterior skull-releasing surgery that dramatically improved their overall skull shape, to the extent that further operative intervention was not required. This focused our attention on the posterior skull and its role in craniosynostosis. In cases of multi-suture craniosynostosis and craniofacial syndromes severely raised intracranial pressure is frequent, demanding early surgery. One of the problems identified with such surgery undertaken before 6 months of age is recurrent craniosynostosis needing later re-operation. This occurred in 15 (5%) of 275 patients treated between 1978 and 1994. Since 1986, in the presence of significantly raised intracranial pressure it has been our policy to do an initial posterior skull release or decompression. This takes the pressure of the growing brain away from the orbits, allowing us to defer fronto-orbital advancement until the age of 12 months or later. Three patients managed in this way completely avoided anterior surgery, while in another 9 patients re-operation for recurrent anterior deformity has not been required. The exception to this policy has been the presence of severe exorbitism posing a threat to vision. Under these circumstances early fronto-orbital advancement is mandatory, and an additional posterior skull release may be helpful later. Debate continues especially on the management of unilateral lambdoid synostosis. The recent increase in positional posterior plagiocephaly, possibly related to supine nursing of newborns, has emphasised the need to differentiate between a fixed deformity, which might require surgical correction, and positional moulding of the occiput, which improves spontaneously. This paper reports our experience with 22 patients treated by posterior skull surgery, either alone or as an additional procedure, which we believe has a definitive role in the management of craniosynostosis.

The inner ears of representatives of all six gymnophionan families, as well as an ontogenetic series of one species, were studied in order to understand the origin and changes of the amphibian and basilar papillae. The amphibian papilla is in close proximity to the papilla neglecta in some adult gymnophionans. During ontogeny, both epithelia are adherent before they are separated by the formation of the utriculosaccular foramen. The nerve fibers to both epithelia run together, and both epithelia show a comparable variation in size and position among amphibians (amphibian papilla) and among vertebrates (papilla neglecta). Based on these arguments we propose that the amphibian papilla is a translocation of a part of the papilla neglecta specific to amphibians. Present in all primitive gymnophionans, the basilar papilla is lost in all derived gymnophionans. In contrast to anurans, but similar to some urodeles, amniotes, and Latimeria, the basilar papilla rests partly on a basilar membrane. Because of similarities in structure, topology, and innervation, the basilar papilla is suggested to be homologous in Latimeria and tetrapods. The structural differences of most amphibian basilar papillae, compared to those of amniotes and Latimeria, may be due to the different course of the periotic system and the formation of a basilar papillar recess rather than to a separate evolution of this epithelium. In addition to loss of the basilar papilla, some derived gymnophionans have lost the lagena, presumably independently, and the amphibian papilla is extremely reduced in the only genus without a stapes (Scolecomorphus). The papilla neglecta is, for unknown functional reasons, relatively large in aquatic gymnophionans, whereas it is almost lost in some thoroughly terrestrial gymnophionans. The regressive changes in the inner ear are not reflected in obvious changes in the pattern of eighth nerve projection. However, there is a rearrangement of cell masses in the rhombencephalic alar plate of derived gymnophionans, which may be related to the partial or complete loss of lateral line afferents. We propose that the presence of a basilar papilla is a synapomorphy of tetrapods and Latimeria, that the translocation of the papilla neglecta is related to the unique course of the amphibian periotic canal, and that regressive changes in the inner ear are related to the primitive absence of a tympanic ear.

Abstract: Craniosynostosis, the premature fusion of one or multiple cranial sutures, can be complicated by visual failure resulting from raised intracranial pressure (ICP). Of the 290 children operated on at the Birmingham Children's Hospital between 1978 and 1995 for craniosynostosis, 9 were found to have defective visual acuity attributable to raised ICP. Mean age at presentation was 3.11 years (range: 1–6 years) and mean follow-up, 7.33 years (range: 1.5–16 years). All these patients presented significantly later than usual, and 5 of them developed recurrent craniosynostosis. At the initial examination bilateral papillo-edema was seen in 4 patients, unilateral disc oedema in 1 patient, bilateral optic atrophy in 3 patients and unilateral optic atrophy in 1 patient. Following decompressive craniofacial surgery, the visual outcome was good in 4 out of 5 patients with papilloedema and poor in all patients with optic atrophy. Visual failure resulting from raised ICP in craniosynostosis is a devastating complication, which appears to be associated with late presentation and recurrent craniosynostosis.

The feasibility of developing biodegradable polymer scaffolds to engineer tissues was investigated by studying the effects of pore size on the dynamics of fibrovascular tissue ingrowth. Tissue advanced into amorphous poly(l-lactic acid) porous substrates faster as the pore diameter increased. Porous cylindrical devices of 13.5 mm diameter, 5 mm thickness, and approximately 500 μm pore size were filled completely by tissue 5 days postimplantation. Although prevascularized devices possessed minimal void volume for cell seeding to regenerate metabolic organs, they hold promise in the regeneration of tubular tissues by relying on the epithelization of prevascularized grafts.

We have investigated and quantified the degree of fibrovascular tissue ingrowth in cylindrical poly(vinyl alcohol) (PVA) foams of 12.5 mm diameter, 5 mm thickness, and 71% porosity implanted in the mesentery of rats over a period of 25 days. Fibrovascular tissue penetrated the center of PVA foams 5 days postimplantation yet the void fraction available for cell seeding was 55% and the volume average pore diameter was 190 (±39) μm. By 10 days postimplantation the void fraction had decreased to 32% and the volume average pore diameter was 121 (±20) μm. As time elapsed fibrovascular tissue continued to expand and fill the remaining pore space. At 15 days postimplantation the void space was impractical for cell seeding and continued to decrease through the remainder of the study. Our data suggest that hydrogel foams with a polydispersed pore morphology can be prevascularized with adequate space for cell seeding as the volume of tissue penetrating the foam is limited by the smaller pores in the foam structure; however, available void space for cell seeding decreases with time.

Carboplatin (cis-Diammine-l, l-cyclobutane dicarboxylate platinum II; CBDCA) is a second generation platinum analog with less nephrotoxicity and cochlear ototoxicity than cisplatin, the first generation platinum chemotherapeutic agent. Studies in many animal species have indicated that carboplatin ototoxicity is expressed as damage to cochlear outer hair cells. The lesion is similar, though less severe, than that resulting from cisplatin intoxication. Recent investigations by our laboratory have demonstrated a species-specific ototoxicity of carboplatin in the chinchilla cochlea. Contrary to other animal models, the inner hair cells are the focus of damage; the outer hair cells often sustain little or no damage. Clinical evidence points to vestibular dysfunction in some patients treated with platinum-containing anti-tumoural agents. However, no morphological studies have shown degeneration of the sensory cells in the vestibular labyrinth resulting from carboplatin treatment. The objective of the present study was to determine whether, in view of its unique toxicity in the chinchilla, carboplatin has any toxic effect on the vestibular end organs. Preliminary investigations of the vestibule by light and scanning electron microscopy indicate that sensory cell cilia became exfoliated or deformed in the crista, utricle and in one instance in the saccule. In general the pattern of damage is similar to that caused by other known ototoxic agents including aminoglycosides and cisplatin.

The emerging field of tissue engineering is yielding a variety of new strategies for bone replacement. In vivo assessment of candidate bone substitutes to demonstrate biocompatibility, degradability, and the ability to produce meaningful quantities of bone is essential prior to clinical use. We present results of a large animal model using formed plastic chambers implanted adjacent to the rib periosteum in sheep to fabricate vascularized bone flaps of different shapes. Chambers packed with morcellized corticocancellous bone graft, representing the most favorable natural circumstances for bone formation, were compared to empty chambers, representing the least favorable. Implants containing bone chips yielded formed blocks of vascularized bone after 6 weeks with evidence of remodeling after 13 weeks. Histomorphometric analysis demonstrated that there was full bone penetration into shallow (5 mm) chambers and 8.8 mm (±0.6) penetration into deep (10 mm) implants after 6 weeks. Molded bone segments failed to grow in empty chambers. This model presents a quantifiable range of bone forming potential to which different bone substitutes may be compared for usefulness in creating tissue engineered bone flaps for reconstructive surgery.

A 10T superconducting NbTi/Cu window frame dipole magnet, cooled in a horizontal pressurized helium II bath, was constructed and successfully tested. The dipole magnet coil and clamping structure, trained three times at 4.2K, was cooled down to 1.8K. In the first excitation at this temperature, the central dipole field induction reached to 9.3T, corresponding a maximum field in the coil of 10.4T. This is a record maximum field in this kind of dipole magnets.

Typhlonectes compressicaudahas a diploid number of 28. Its karyotype, when compared to that of other caecilians, suggests some discordance in the hypothesized model of chromosome reduction in the evolution of amphibian lineages.