Using family and staff experiences of a botulinum toxin-A service to improve service quality.

BACKGROUND: The decision for families to proceed with botulinum toxin-A (BoNT-A) injections for managing childhood conditions involving hypertonia can be complex. Family-centred care is a service model that facilitates supporting families in this decision-making process. Understanding families' experiences of services is critical to developing family-centred care. The aim of this project was therefore to increase understanding of the experiences of families of children attending a BoNT-A service in order to improve the service and its family-centred approach to care. METHOD: Sixteen staff of a BoNT-A service participated in a patient journey mapping exercise. Nine families of the service participated in in-depth interviews. Interviews were audio-recorded and transcribed verbatim. Data from the staff session and interviews were analysed independently using grounded, hermeneutic thematic analysis. RESULTS: Staff sessions revealed 5 core themes that related to impacting on the family experience. Family interviews revealed 4 core themes, with 7 subthemes and 1 latent theme. CONCLUSIONS: Areas of importance identified by families relating to BoNT-A treatment included acknowledgement of individual needs, care coordination, empowerment of families and patients, consistency in service delivery, and the distressing nature of appointment and decision-making. Comparison of the data from the staff patient journey mapping and family interviews suggested that staff have a good but incomplete understanding of the factors important to families, highlighting the need for consumer engagement in establishing family-centred care. The themes identified can guide the provision of family-centred BoNT-A injection clinics.

Daniel Turner (1667-1741): syphillis and the condum.

Daniel Turner 1667-1741 was the first English medical author to use the term syphillis incidentally, also mentioning early usage of the condom (condum). This paper shows that venereologists in 18th century London wrote on the use of condoms by some men, but who were sceptical about its usage. This paper also describes some of the contemporary spellings of condum and syphillis.

Evaluating paediatric brain injury services in NSW.

BACKGROUND: Rehabilitation professionals strive to provide high-quality evidence-based services for children. Developing systems to measure and monitor the benefits of our services, and health outcomes for children is complex and challenging. The Community Outcome Project aims to introduce systematic outcome measurement across the network of paediatric community-based brain injury services within the New South Wales Brain Injury Rehabilitation Program (BIRP) to support clinical practice and service evaluation. METHODS: A literature review informed the development of the evaluative framework and identified available paediatric outcome measures which may be appropriate. Extensive consultation with clinicians supported project planning and identified clinical priorities that the outcome measures needed to capture. Outcome measures were shortlisted by matching them to identified clinical priorities, and then trialled in clinical practice. Qualitative feedback regarding clinical utility and feasibility was obtained from clinical staff. The process has utilized change management strategies to ensure the success of the project and keep staff engaged. RESULTS: The process identified the three main clinical priorities for outcome measurement - family functioning, school performance and participation. Three outcome measures were chosen for the pilot project that is currently underway. They are Family Burden of Injury Interview, Academic Competence and Evaluation Scales and Child and Adolescent Scale of Participation. Plans for analyses of outcome data within the paediatric BIRP services are discussed. CONCLUSIONS: Extensive preparation is required to optimize staff engagement in a project that systematically introduces outcome measures that are useful to clinicians, clients and service providers. Managing the change required is a key focus of the project. Benefits and costs to clinicians and services will be discussed.

Differential effects of the phosphatidylinositol 4-kinases, PI4KIIα and PI4KIIIß, on Akt activation and apoptosis.

In this study, we investigated the role of PI4P synthesis by the phosphatidylinositol 4-kinases, PI4KIIα and PI4KIIIß, in epidermal growth factor (EGF)-stimulated phosphoinositide signaling and cell survival. In COS-7 cells, knockdown of either isozyme by RNA interference reduced basal levels of PI4P and PI(4,5)P(2), without affecting receptor activation. Only knockdown of PI4KIIα inhibited EGF-stimulated Akt phosphorylation, indicating that decreased PI(4,5)P(2) synthesis observed by loss of either isoform could not account for this PI4KIIα-specific effect. Phospholipase Cγ activation was also differentially affected by knockdown of either PI4K isozyme. Overexpression of kinase-inactive PI4KIIα, which induces defective endosomal trafficking without reducing PI(4,5)P(2) levels, also reduced Akt activation. Furthermore, PI4KIIα knockdown profoundly inhibited cell proliferation and induced apoptosis as evidenced by the cleavage of caspase-3 and its substrate poly(ADP-ribose) polymerase. However, in MDA-MB-231 breast cancer cells, apoptosis was observed subsequent to knockdown of either PI4KIIα or PI4KIIIß and this correlated with enhanced proapoptotic Akt phosphorylation. The differential effects of phosphatidylinositol 4-kinase knockdown in the two cell lines lead to the conclusion that phosphoinositide turnover is inhibited through PI4P substrate depletion, whereas impaired antiapoptotic Akt signaling is an indirect consequence of dysfunctional endosomal trafficking.

Use of three-dimensional kinematic analysis following upper limb botulinum toxin A for children with hemiplegia.

BACKGROUND AND PURPOSE: To examine whether three-dimensional (3-D) kinematic analysis can detect changes in upper limb tasks (reach and hand-to-mouth) in children with hemiplegia, following upper limb botulinum toxin A injections. METHODS: Ten children with hemiplegic cerebral palsy (7 males, 3 females, aged 9-17 years). Subjects received botulinum toxin A (Botox) injections into elbow forearm muscles combined with 6 weeks of occupational therapy. Participants completed a 3-D kinematic analysis of two upper limb tasks, Melbourne Assessment of Unilateral Upper Limb Function and modified Ashworth scores measured at baseline, 2, 6 and 12 weeks post-injection. RESULTS: Post-injections, elbow flexor muscle tone was reduced for 12 weeks (p < 0.05). Group differences in active range of motion during 3-D analysis tasks could not be demonstrated at any time post-intervention. However, individual analyses found that at 2 weeks post-injection, three subjects had >15 degrees increases in active elbow extension and six subjects showed an increase of >25 degrees in forearm supination during performance of the reach and hand-to-mouth tasks, respectively. CONCLUSIONS: 3-D kinematics can detect changes in active movements during functional tasks following botulinum toxin A injections, suggesting this could be a potential objective outcome measure in a clinical trial.

Autografting followed by rituximab for chemosensitive mantle cell lymphoma: a pilot study and literature review.

Mantle cell lymphoma (MCL) is rarely cured with either conventional-dose chemotherapy or autografting. Recent evidence suggests that anti-CD20 monoclonal antibody therapy (rituximab) in combination with chemotherapy may improve the response rate. We report a pilot study of autografting using busulfan-melphalan conditioning followed by rituximab in 9 patients (median age 52 years) with chemosensitive MCL. Rituximab was given for 4 doses of 375 mg/m(2) between 4 and 10 weeks post-transplant. Three of 5 patients autografted after induction therapy remain alive in clinical and molecular complete remission at 33-50 months post-transplant. Only 1 of 4 patients autografted after relapse remains in complete remission. Two of the 3 patients with persistent marrow molecular positivity post-autograft became negative after rituximab therapy. Molecular negativity was first observed in 2 patients only after rituximab therapy. Overall, 2 patients have relapsed and the remaining 3 died of late-onset respiratory failure, probably reflecting infection and/or aggressive conditioning in an older patient population. These preliminary results, together with a review of the literature, suggest that the combination of autografting and rituximab may lead to durable molecular remissions in patients with chemosensitive MCL. Further studies are required to clarify whether the administration of rituximab: (1) is optimal pre- or post-autograft and (2) impacts on the incidence of infection and idiopathic pneumonitis in this context.

Oral Kaposi's sarcoma in a non-HIV homosexual White male.

This paper reports the exceedingly rare occurrence of oral Kaposi's sarcoma in a non-HIV Caucasian White male. The lesion presented as a 8 mm vascular nodule on the buccal mucosa on the left. He was homosexual. The lesion was removed and histological examination confirmed Kaposi's sarcoma. The patient has been tested on 10 occasions for HIV from December 1998 to March 2004 and has been negative. The patient remains alive and well with no evidence of recurrence.

Status dystonicus and Hallervorden-Spatz disease: treatment with intrathecal baclofen and pallidotomy.

Severe dystonia or status dystonicus is a life threatening disorder that develops in patients with both primary and secondary dystonia. We present the case of a 9-year-old boy with Hallervorden-Spatz disease (HVS) who developed status dystonicus, failing to respond to high dose oral therapy with multiple antidystonic agents. High dose intravenous sedating agents combined with endotracheal intubation and mechanical ventilation were required to control the spasms. Alleviation of the spasms was achieved by a combination of temporary intrathecal baclofen infusions and bilateral pallidotomy. Although it could be argued this is a situation where only palliative measures should be used, we believe a relatively aggressive approach was justified. It relieved the intense pain associated with the spasms and allowed the child to be discharged home without the prolonged stay in intensive care, morbidity and mortality, which characterize status dystonicus.

Taxanes synergize with the bispecific antibody MDXH447 to enhance antibody-dependent cell-mediated cytotoxicity.

The interaction between antibody based therapy and cytotoxic chemotherapy is complex. To explore these interactions we investigated, in vitro, the effects of IC20 growth inhibitory concentrations of taxanes on bispecific antibody-mediated tumor cell cytotoxicity. MDXH447 is a bispecific antibody with specificity for the high affinity IgG receptor (CD64) and the type I epidermal growth factor receptor type (EGF-R). A431 cells, an epidermoid carcinoma cell line that over expresses EGF-R, were exposed to a range of IC20 growth inhibitory concentrations of paclitaxel or docetaxel. Interferon gamma activated monocytes were armed with MDXH447 and a standard chromium release antibody-dependent cell-mediated cytotoxicity (ADCC) assay was performed. Using the Chou and Talalay median effect analysis, we found that MDXH447-mediated ADCC was enhanced when A431 target cells were pretreated with paclitaxel or docetaxel. Median effect analysis of these interactions supported a synergistic interaction (CI < 1). Pretreatment of A431 cells with taxanes did not increase EGF-R expression compared to untreated controls. A431 epidermoid carcinoma cells pretreated with IC20 growth inhibitory concentrations of taxanes enhanced interferon gamma activated monocyte mediated ADCC killing through MDXH447.

Prevalence of asymptomatic chlamydial urethritis in military recruits in the Celje region, Slovenia.

The aim of this research was to evaluate the prevalence of asymptomatic chlamydial urethritis in military recruits in the Celje region (population 300,000), Slovenia. A first-void urine specimen was tested for Chlamydia trachomatis using the polymerase chain reaction assay. The research was supported by a questionnaire to obtain information on sexual behaviour of the participants. In the cross-sectional study from 1999 to 2001, 1272 asymptomatic recruits were included. None had received antibiotics in the previous two weeks. The mean age was 19.9 years. At the time of their first sexual experience the mean age was 16.6 years, whereas the age of their female sexual partners was 17.1 years. During their first sexual intercourse 77% of recruits used contraception (condom, diaphragm, contraceptive pill), most of those a condom (86%). The prevalence of asymptomatic chlamydial urethritis was 2.6% (95% confidence interval: 1.7 to 3.5). The mean age of those infected was 19.8 years. At the time of their first sexual experience the mean age was 16.2 years, whereas the age of their female sexual partners was 16.9 years. During their first sexual intercourse 57% of infected subjects used protection, half of which was a condom. Those who never or only occasionally used condoms were at a greater risk of being infected with C. trachomatis (adjusted odds ratio 2.04).

Reproductive Potential of Monosporascus cannonballus.

Vine decline of melons caused by Monosporascus cannonballus is a destructive disease worldwide. Ascospores, the only spore stage produced by this soilborne fungus, serve as the primary inoculum. Ascospore production on roots occurs primarily at the end of the cropping season, and high soil temperatures (25 to 30°C) govern, in part, the rate of reproduction of the pathogen. In vitro studies confirm that the optimal temperature for reproduction ranged from 25 to 30°C. Additionally, the root system of a single mature cantaloupe plant is capable of supporting the production of approximately 400,000 ascospores. The latter population, if incorporated uniformly into 0.03 m3 (1 ft3) of soil, would be equivalent to 10 ascospores per gram of soil. Known problem fields contain as few as 2 ascospores per gram of soil. These results offer a possible explanation for field observations that economically significant disease problems can occur after only two consecutive melon crops if environmental conditions are conducive to pathogen reproduction, and they suggest that strategies to inhibit reproduction would be instrumental in disease management.

Application of Preplant Fumigants via Drip Irrigation Systems for the Management of Root Rot of Melons Caused by Monosporascus cannonballus.

Root rot and vine decline, caused by Monosporascus cannonballus, is a destructive disease of melons in the desert production regions of southern California. In 1998, we initiated studies on the use of preplant fumigation to reduce resident pathogen populations in soil. Preplant fumigation with methyl iodide injected as a hot gas at 448.4 kg/ha through drip irrigation tape in preformed, tarped beds consistently provided significant (P < 0.05) reductions in the percentage of roots infected compared with the nonfumigated controls; these reductions were equal to or better than those achieved with an equivalent rate (448.4 kg/ha) of methyl bromide. Chloropicrin applied in water at 249.0 kg/ha through buried drip irrigation tape to either tarped or nontarped beds significantly (P < 0.05) reduced the percentages of both roots infected and roots on which perithecia were produced compared with nonfumigated controls.

EGF receptors as transcription factors: ridiculous or sublime?

The notion that a transmembrane receptor at the cell surface can somehow reappear as a transcription factor in the nucleus is bound to be controversial. However, there are two reported examples of this. If this hypothesis can withstand the inevitable and necessary battery of additional empirical tests, then our understanding of signal transduction needs to move in a new direction.

Signalling and non-caveolar rafts.

Rafts are small membrane domains containing discrete subsets of lipids and proteins. Although microscopic raft structures termed 'caveolae' were described nearly 50 years ago, the importance of rafts, particularly signalling within rafts, is only beginning to be understood. Our studies focus on receptor-dependent phosphoinositide signalling. Using their characteristic buoyancy in density gradients, we and others found that the epidermal growth factor (EGF) receptor, phosphatidylinositol 4-kinase and phosphoinositides are localized within a caveolin-rich fraction of A431 carcinoma cells. We subsequently found that membrane fragments containing the EGF receptor and most cellular phosphoinositides can be separated from caveolae. Consequently, components of EGF-dependent phosphoinositide signalling localize to one or more novel types of raft, the composition of which we are currently determining. A key component is the type II phosphatidylinositol 4-kinase, which, for many years, has proven difficult to purify and clone. We describe our recent purification from rafts and cloning of this elusive enzyme, and discuss how the structure sheds light on the rafting of this enzyme.

Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel lipid kinase family.

Phosphoinositide lipids regulate numerous cellular processes in all eukaryotes. The versatility of this phospholipid is provided by combinations of phosphorylation on the 3', 4', and 5' positions of the inositol head group. Two distinct structural families of phosphoinositide (PI) kinases have so far been identified and named after their prototypic members, the PI 3-kinase and phosphatidylinositol (PtdIns) phosphate kinase families, both of which have been found to contain structural homologues possessing PI 4-kinase activity. Nevertheless, the prevalent PtdIns 4-kinase activity in many mammalian cell types is conferred by the widespread type II PtdIns 4-kinase, which has so far resisted molecular characterization. We have partially purified the human type II isoform from plasma membrane rafts of human A431 epidermoid carcinoma cells and obtained peptide mass and sequence data. The results allowed the cDNA containing the full open reading frame to be cloned. The predicted amino acid sequence revealed that the type II enzyme is the prototypic member of a novel, third family of PI kinases. We have named the purified protein type IIalpha and a second human isoform, type IIbeta. The type IIalpha mRNA appears to be expressed ubiquitously in human tissues, and homologues appear to be expressed in all eukaryotes.