The cerebellar bioenergetic state predicts treatment response in COQ8A-related ataxia.

INTRODUCTION: Primary coenzyme Q10 (CoQ10) deficiency, a recessive disorder associated with various defects of CoQ10 biosynthesis and widely varying clinical presentation, is customarily managed by oral Q10 supplementation but the benefit is debated. METHODS: To address this question, we mapped individual responses in two patients with COQ8A-related ataxia following coenzyme Q10 supplementation using noninvasive imaging. Metabolic 31phosphorus magnetic resonance spectroscopy imaging (31P-MRSI) and volumetric cerebellar neuroimaging were performed to quantify the individual treatment response in two patients with COQ8A-related ataxia, each compared with eight age- and gender-matched healthy control subjects. RESULTS: Post-treatment change in energy metabolite levels differed in the two patients, with higher energy levels and improved dysarthria and leg coordination in one, and decreased energy levels without clinical benefit in the other. CONCLUSIONS: Our results suggest that the cerebellar bioenergetic state may predict treatment response in COQ8A-related ataxia and highlight the potential of pathophysiology-orientated neuroimaging evidence to inform treatment decisions.

Thermodynamics of rapid solidification and crystal growth kinetics in glass-forming alloys.

Thermodynamic driving forces and growth rates in rapid solidification are analysed. Taking into account the relaxation time of the solute diffusion flux in the model equations, the present theory uses, in a first case, the deviation from local chemical equilibrium, and ergodicity breaking. The second case of ergodicity breaking may exist in crystal growth kinetics of rapidly solidifying glass-forming metals and alloys. In this case, a theoretical analysis of dendritic solidification is given for congruently melting alloys in which chemical segregation does not occur. Within this theory, a deviation from thermodynamic equilibrium is introduced for high undercoolings via gradient flow relaxation of the phase field. A comparison of the present derivations with previously verified theoretical predictions and experimental data is given. This article is part of the theme issue 'Heterogeneous materials: metastable and non- ergodic internal structures'.

Kinetic transition in the order-disorder transformation at a solid/liquid interface.

Phase-field analysis for the kinetic transition in an ordered crystal structure growing from an undercooled liquid is carried out. The results are interpreted on the basis of analytical and numerical solutions of equations describing the dynamics of the phase field, the long-range order parameter as well as the atomic diffusion within the crystal/liquid interface and in the bulk crystal. As an example, the growth of a binary A50B50 crystal is described, and critical undercoolings at characteristic changes of growth velocity and the long-range order parameter are defined. For rapidly growing crystals, analogies and qualitative differences are found in comparison with known non-equilibrium effects, particularly solute trapping and disorder trapping. The results and model predictions are compared qualitatively with results of the theory of kinetic phase transitions (Chernov 1968 Sov. Phys. JETP26, 1182-1190) and with experimental data obtained for rapid dendritic solidification of congruently melting alloy with order-disorder transition (Hartmann et al. 2009 Europhys. Lett.87, 40007 (doi:10.1209/0295-5075/87/40007)).This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'.

First Report of Foliar Infection of Rosa gymnocarpa by Phytophthora ramorum.

In May 2003, Phytophthora ramorum S. Werres & A.W.A.M. de Cock was isolated from leaflets of wood rose (Rosa gymnocarpa Nutt.), a native, low shrub of the Rosaceae family, at the Jack London State Park in Sonoma County, California. Affected leaflets had cream-to-brown lesions or spots, sometimes delimited by a chlorotic zone. Lesions coalesced with time and spread into the petiole and rachis. Lesions on the stems were not observed. Isolates were typical of P. ramorum with large chlamydospores and caduceus, semipapillate sporangia, and the sequence (GenBank Accession No. AY526571) of the internal transcribed spacer (ITS) region of the rDNA matched those published previously (4). The site was a mixed forest containing some confirmed P. ramorum-infected trees of coast redwood (Sequoia sempervirens), bay laurel (Umbellularia californica), and tanoak (Lithocarpus densiflorus) (3,4). These sites also contained California rose (R. californica Cham. & Schldl.); however, no symptoms were observed on this species. A terminal leaflet of asymptomatic, pesticide-free, potted-plants of California rose and wood rose (four plants each) was inoculated with zoospores of a P. ramorum isolate (American Type Culture Collection, Manassas, VA, ATCC MYA-3281; Centraal Bureau voor Schimmelcultures, Baarn, the Netherlands, CBS 114390) obtained from infected wood rose (2). A control leaflet of each plant was dipped in sterile deionized water. Branches containing the inoculated and control leaflets were placed in moist plastic bags, and plants were maintained at 21 to 22°C in the laboratory for 6 days. The inoculation experiment was repeated. In both inoculations, brown lesions (extending up to 8 mm from the leaflet tip) were observed on leaflets of both species 2 days after inoculation with P. ramorum. At 6 days after inoculation, lesions starting from the leaflet tip averaged 12.2 mm in length (range 10 to 16 mm) for wood rose and 9.6 mm (range 3 to 20 mm) for California rose. Some lesions extended into the petiole in both rose species. Sporangia were observed in washings of the lesions from four plants of California rose and one plant of wood rose, and P. ramorum was reisolated on Phytophthora-selective agar medium modified with 25 mg of pentachloronitrobenzene (PCNB) (4) from all lesions. Control leaflets had no lesions, and P. ramorum was not reisolated. To our knowledge, this is the first report of a species of Rosa as a natural host for P. ramorum, although R. sempervirens was identified as being susceptible in artificial inoculations of detached leaves (E. Moralejo and L. Hernández, personal communication). Toyon (Heteromeles arbutifolia) in California and salmon berry (Rubus spectabilis) in Oregon are the other known hosts from the family Rosaceae (1). Wood rose is popular in the horticultural industry and is readily available from native plant nurseries in California, Oregon, Washington, and British Columbia, Canada. California rose is also popular, primarily in California. The pathogen could be disseminated on these plants, especially since sporangia were obtained from inoculated leaflets of these two species. References: (1) J. M. Davidson et al. On-line publication. doi:10.1094/PHP-2003-0707-01-DG. Plant Health Progress, 2003. (2) D. Hüberli et al. Plant Dis. 87:599, 2003. (3) P. E. Maloney et al. Plant Dis. 86:1274, 2002. (4) D. M. Rizzo et al. Plant Dis. 86:205, 2002.

Repeated bladder distension by the Cystomat in the treatment of detrusor instability.

Treatment of idiopathic detrusor instability with drugs and prolonged distension of the bladder is often unsatisfactory. Some amelioration of symptoms has previously been described by using the Cystomat. The present study showed that 1 week's treatment with the Cystomat produced convincing subjective improvement as well as an increase in bladder capacity. The improvements were statistically significant and persisted for 3 months. Although the mechanism by which bladder distension exerts its effect is poorly understood, the technique of repeated distension offers an alternative in the treatment of patients with idiopathic detrusor instability.

Alpha-adrenergic blockade in the diagnosis of detrusor instability secondary to infravesical obstruction.

Detrusor instability secondary to infravesical obstruction is probably caused by overactive stretch receptors in the bladder wall. Since recent studies have shown that alpha-adrenergic blockade with phenoxybenzamine reduces the intravesical pressure under micturition, we undertook this investigation in order to see if phenoxybenzamine has an effect on detrusor instability caused by infravesical obstruction. We found that the detrusor instability was abolished by phenoxybenzamine, which supports the 'stretch receptor theory'. Further, phenoxybenzamine is probably a good test in the diagnosis of detrusor instability secondary to infravesical obstruction.

Acute retention of urine due to benign prostatic obstruction treated with alpha-adrenergic blockers.

Bladder catheterisation is the usual treatment in patients with acute retention of urine due to prostatic hypertrophy. The interference is not without complications why medical treatment would be a progress. The prostatic gland has been found to contain alpha-adrenergic receptors, and it has been argued that some cases of acute retention of urine is caused by over-stimulation of the alpha-adrenergic receptors. In the present study we have investigated the effect of intravenously administered phentolamine ( Regitin ) in patients with acute retention of urine, due to prostatic hypertrophy, and find that the treatment is an alternative to conventional bladder catheterisation.

Lignocaine test and detrusor instability.

Detrusor instability in infravesical obstruction is well recognised and often resolves after surgery. The aetiology is not clearly understood but is probably due to increased vesical sensory input. Since intravesical lignocaine has been proved to have an effect (although shortlived) on detrusor instability in some patients, we have used it in order to differentiate between idiopathic detrusor instability and detrusor instability caused by infravesical obstruction. Our study showed that in patients with a positive lignocaine test pre-operatively, the detrusor instability and micturition disorder disappeared after operation, and in patients with a negative lignocaine test, it persisted. The differences were statistically significant (P less than 0.5).

Improvement of detrusor instability following repeated bladder distension with cystomat. A case report.

Treatment of idiopathic detrusor instability with drugs and prolonged distension of the bladder is often unsatisfactory. Some amelioration of symptoms was previously described after 24-hour bladder distension with use of the cystomat. A case is presented in which detrusor instability was successfully treated with continuous infusion via the cystomat, and thereby repeated bladder distension, for one week. The symptoms subsided, the cystometric bladder capacity was increased and there was no side effects. The improvement has persisted for six months. Though the mechanism by which the bladder distension exerts its effect is poorly understood, the technique of repeated distension offers an alternative in the treatment of patients with idiopathic detrusor instability.

A comparison between the combination emepronium bromide/flavoxate and emepronium bromide in the treatment of detrusor instability.

Emepronium bromide and flavoxate have both and separately been used with success in the treatment of detrusor instability. In this study we have combined the two drugs emepronium bromide and flavoxate and compared the results with emepronium bromide. 20 consecutive patients with an uninhibited bladder, 12 men and 8 women, were randomly allocated to treatment with either emepronium bromide/flavoxate or emepronium bromide. In this trial we found that treatment with the combination is significantly better than treatment with emepronium bromide only.

Ruptured achilles tendons treated surgically under local anaesthesia.

Twenty-two patients with rupture of the Achilles tendon were successfully treated by simple end-to-end suture under local anaesthesia. The results are discussed in the light of previous literature on surgical versus conservative treatment and the advantages of surgery under local anaesthesia are pointed out.

Visualization of chicken red blood cells in capillaries by immunofluorescence.

Chicken red blood cells labelled with specific rabbit antiserum were used for the demonstration of cortical distribution of blood in the dog kidney by means of direct immunofluorescence. Immunization and labelling techniques are described.