Is frequent attendance a persistent characteristic of a patient? Repeat studies of attendance pattern at the family practitioner

OBJECTIVE: To assess the extent of frequent attendance as a persistent characteristic of patients by repeat studies of attendance at a health centre. DESIGN: A follow-up of frequent attenders and compared patients in 1991 among frequent attenders in 1996. SETTING: Mariehem health centre in Ume? in northern Sweden providing care for 10,500 and 12,000 inhabitants in 1991 and 1996, respectively. SUBJECTS: Frequent attenders, defined as patients who had at least 5 consultations with physicians during 1 year at the health centre, compared to attenders who had between 1 and 4 consultations in 1991 and 1996. RESULTS: The proportion of people who lived in the area and consulted a doctor at the health centre at least once during 1 year increased from 40.0% in 1991 to 45.2% in 1996. The number of frequent attenders increased from 179 to 303 and they took 15% and 20% of all consultations in 1991 and 1996, respectively. Twenty-five patients (21 females and 4 males) were identified as frequent attenders in both years. CONCLUSION: With the exception of a small group of patients, mostly females, frequent attendance seems not to be a persistent characteristic of patients.     

Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes

OBJECTIVE: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS: Diazoxide decreased circulating C-peptide concentrations by approximately 50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 +/- 0.22 vs. 0.31 +/- 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (-0.05 +/- 0.24 vs. -0.18 +/- 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 +/- 0.20 and 0.20 +/- 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS: This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.     

A prospective, multicenter, open-label assessment of atomoxetine in non-North American children and adolescents with ADHD

OBJECTIVE: The aim of this study was to study treatment response to atomoxetine in a large, multicenter study of non-North American patients with ADHD. METHODS: A total of 604 children and adolescents with ADHD were enrolled in a 10-week open-label trial with atomoxetine prior to randomization to a double-blind relapse prevention phase at 33 sites in the United Kingdom, continental Europe, Israel, South Africa, and Australia. All patients had ADHD symptom severity at least 1.5 standard deviations above United States age and gender norms for their diagnostic subtype as measured by the investigator-scored ADHD Rating Scale (ADHD RS). Outcomes were assessed by analysis of change in the ADHD RS; functional and psychosocial outcomes were assessed using the Child Health Questionnaire (CHQ). RESULTS: At endpoint, ADHD RS total scores decreased by an average of 56.7%, and 69% of patients were rated as having no or minimal symptoms. Significant improvement was observed in psychosocial and functional outcomes. Discontinuations attributed to adverse events were < 4%. CONCLUSION: These open-label data, gathered in an international setting, add to our knowledge of the value of atomoxetine in treating ADHD symptoms, as well as its safety and tolerability.     

Central migration of neuronal tissue and embryonic stem cells following transplantation along the adult auditory nerve

The regeneration of the auditory nerve remains a challenge in restoring hearing. An interesting approach would be to use a cell replacement therapy with the potential to establish connections from the inner ear to the central auditory system. This hypothesis was tested by xenografted (mouse to rat) implantation of embryonic dorsal root ganglion (DRG) neurons and embryonic stem (ES) cells along the auditory nerve in the adult host. DRG neurons were obtained at embryonic day 13-14 in transgenic animals expressing enhanced green fluorescence protein (EGFP). For embryonic stem cells, a tau-GFP ES cell line was used as a donor. The fibers of the auditory nerve in the adult rat were transected through the modiolus at the first cochlear turn, and the biological implants were transplanted into the transection. The transplanted DRG neurons and ES cells survived for a postoperative survival time ranging from 3 to 9 weeks, verified by EGFP/GFP fluorescence, and neurofilament or TUJ1 immunostaining. At 9 weeks following implantation, the implanted DRG neurons were found to have migrated along the auditory nerve in the internal meatus. At the same postoperative time, the ES cells had migrated into the brain stem close to the ventral cochlear nucleus. The results demonstrate not only the survival and migration of xenografted DRG neurons and stem cells along the adult auditory nerve but also the feasibility of a cell replacement therapy in the degenerated auditory system.     

One hundred males with Asperger syndrome: a clinical study of background and associated factors

The objective of this study was to investigate the background and associated factors in a representative group of young males with Asperger syndrome (AS) presenting at a specialized autism clinic. One hundred males aged 5 years 6 months to 24 years 6 months, with a mean age of 11 years 4 months (SD 3y 10mo), who had a clinical diagnosis of AS were included in the study. An in-depth review of their medical records and neuropsychological test data was performed. There was a high rate (51%) of non-verbal learning disability (defined as Verbal IQ more than 15 points higher than Performance IQ), but otherwise there was little or no support for the notion of right-hemisphere brain dysfunction being at the core of the syndrome. There was a very high rate of close relatives with autism spectrum problems, but also high rates of prenatal and perinatal problems, including prematurity and postmaturity. In comparison with general population data, those with AS very often had a combination of genetic and prenatal and perinatal risk factors. Non-verbal learning disability test results applied in about half the group. There was a subgroup of individuals with AS who had macrocephalus. However, there was no support for an association of AS with low body mass index.     

Pharmacokinetic/pharmacodynamic models for the depletion of Vbeta5.2/5.3 T cells by the monoclonal antibody ATM-027 in patients with multiple sclerosis, as measured by FACS

AIMS: (i) To model the effects of the monoclonal antibody ATM-027 on the number of target cells and on the receptor density on the cell surface as measured by Fluorescence Activated Cell Sorter analysis, (ii) to investigate the effects of categorizing a continuous scale, and (iii) to simulate a phase II trial from phase I data in order to evaluate the predictive performance of the model by comparison with the actual trial results. METHODS: Based on the data from one phase I and one phase II study in multiple sclerosis (MS) patients, models were developed to characterize the pharmacokinetics and pharmacodynamics of the monoclonal antibody ATM-027 and its effects on Vbeta5.2/5.3+ T cells. The pharmacodynamic variables were the number of target T cells and the expression of its receptor. The latter was modelled in both a categorical and continuous way. The modelling was performed with a nonlinear mixed effects approach using the software NONMEM. The joint continuous models were used to simulate the phase II trial from the phase I data. RESULTS: The pharmacokinetics of ATM-027 were characterized by a two-compartment model with a total volume of distribution of 5.9 litres and a terminal half-life of 22.3 days (phase II parameter estimates) in the typical patient. Continuous receptor expression was modelled using an inhibitory sigmoidal Emax-model. Similar results from the phase I and phase II data were obtained, and EC50 was estimated to be 138 and 148 microg litre(-1), respectively. Categorical receptor expression was modelled using a proportional odds model, and the EC50 values obtained were highly correlated with those from the continuous model. The numbers of target T cells were also modelled and treatment with ATM-027 decreased the number of cells to 25.7% and 28.9% of their baseline values in the phase I and II trials, respectively. EC50s for the decrease in the number of T cells were 83 microg litre(-1) and 307 microg litre(-1), respectively. Simulations of the phase II trial from the phase I models gave good predictions of the dosing regimens administered in the phase II study. CONCLUSION: All aspects of effects of the monoclonal antibody ATM-027 on Vbeta5.2/5.3+ T cells were modelled and the phase II trial was simulated from phase I data. The effects of categorizing a continuous scale were also evaluated.     

Receptive field properties of human periodontal afferents responding to loading of premolar and molar teeth

Impulses in 45 single mechanoreceptive afferents were recorded from the human inferior alveolar nerve with permucosally inserted tungsten microelectrodes. All afferents responded to mechanical stimulation of one or more premolar or molar teeth and most likely innervated their periodontal ligaments. For each afferent, isolated "ramp-and-hold" shaped force profiles of similar magnitudes (252 +/- 24 mN; mean +/- SD) were applied to the lower first premolar, the second premolar, and the first molar on the recording side. The tooth loads were applied in six directions: lingual, facial, mesial, and distal in the horizontal plane and up and down in the vertical direction of the tooth. The afferents response during the static phase of the stimulus was analyzed. All afferents were slowly adapting, discharging continuously in response to static forces in at least one stimulation direction. Twenty-nine afferents (64%) were spontaneously active, exhibiting an ongoing discharge in the absence of external stimulation. Stimulation of a single tooth was found to excite each afferent most strongly. The most sensitive tooth (MST) was the first premolar for 23, the second premolar for 13, and the first molar for 9 afferents. About half of the afferent population also responded to loading of one or two more teeth. The response profiles of these afferents indicated that the multiple-teeth receptive fields were due to mechanical coupling between the teeth rather than branching of single afferents to innervate several teeth. The afferent responses to loading the mesial and distal halves of the first molars were very similar. Thus both intensive and directional aspects of the afferent response when loading one side of the tooth was preserved to a great extent when loading the other side. When loading the MST, the afferents typically showed excitatory responses in two to four of the six stimulation directions, i.e., the afferents were broadly tuned to direction of tooth loading. In the horizontal plane, the afferent populations at the premolar teeth expressed no clear directional preferences. The afferents at the molar, however, showed a strong directional bias in the distal-lingual direction. In the vertical plane, there was a preference for downward-directed forces with a gradually decreasing sensitivity distally along the dental arch. The present results demonstrate that human periodontal afferents supplying anterior and posterior teeth differ in their capacity to signal horizontal and vertical forces, respectively.