Is being a victim of bullying or cyberbullying in secondary school associated with subsequent risk-taking behavior in adolescence? A longitudinal study in secondary schools.

INTRODUCTION: Neurobiological and social changes in adolescence can make victims of bullying more susceptible to subsequent impulsive behavior. With the high prevalence of bullying in schools and rise in cyberbullying in the United Kingdom, it is important that the health impacts of bullying victimization, including on risk-taking, are understood. Our study aims to investigate whether bullying/cyberbullying victimization is associated with subsequent health risk-taking behavior in adolescence. Risk-taking behavior includes electronic cigarette and cigarette smoking, alcohol consumption, illicit drug use, early sexual debut, weapon carrying, damaging property, and setting fire. METHODS: A secondary quantitative analysis of data from 3337, English, secondary school students in the control arm of the INCLUSIVE trial, constituting an observational cohort. Bullying victimization was measured at baseline (age 11/12 years) using the gatehouse bullying scale and a separate question on cyberbullying victimization. Logistic regression was used to test for an association between bullying/cyberbullying victimization at baseline and risk-taking behavior at 36 months, adjusting for baseline risk-taking behavior and other potential confounders, and accounting for school clustering. RESULTS: There was strong evidence (p ≤ .02) for a positive dose-responsive association between being bullied at baseline and nearly all risk-taking behavior at follow-up. Although there was no evidence for an association between being bullied at baseline and weapon carrying (p = .102), there was evidence for a positive association between being cyberbullied at baseline and weapon carrying (p = .036). CONCLUSIONS: It is plausible that bullying/cyberbullying victimization increases the likelihood of subsequent risk-taking behavior in adolescence. Policy options should focus on implementing evidence-based antibullying school interventions.

Gastrin antibodies: induction, demonstration, and specificity.

Antibodies to the antral hormone gastrin have been induced in the rabbit and detected by passive hemagglutination. Specificity of the antibody, as determined by three methods, is directed to gastrins I and II, gastrin pentapeptide, and gastrin tetrapeptide, as well as to the stage-1 gastrin used for immunization.

Successful treatment of cepacia syndrome with combination nebulised and intravenous antibiotic therapy.

We report the case of successful treatment of a 31-year-old lady with cystic fibrosis and an en-bloc liver-pancreas transplant, who developed cepacia syndrome on a background of chronic infection with the ET12 epidemic strain of Burkholderia cenocepacia. Combination therapy with nebulised and intravenous meropenem and tobramycin led to clinical improvement with a return to baseline function and complete resolution of the acute chest X-ray changes.

A novel solution for severe urinary incontinence in women with cystic fibrosis.

BACKGROUND: To explore whether Tension-free Vaginal Tape offers a solution for women with cystic fibrosis who suffer from severe stress incontinence. METHODS: Four adults with cystic fibrosis were formally assessed by gynaecological and urological specialists, prior to hospital admission for surgery. RESULTS: The procedure was tolerated well by all patients. In three, leakage ceased completely. The fourth patient experienced considerable improvement in symptoms. CONCLUSIONS: Tension-free Vaginal Tape is a safe, effective and worthwhile solution for stress incontinence in females with cystic fibrosis.

Quantitative measurement of postural sway in mouse models of human neurodegenerative disease.

Detection of motor dysfunction in genetic mouse models of neurodegenerative disease requires reproducible, standardized and sensitive behavioral assays. We have utilized a center of pressure (CoP) assay in mice to quantify postural sway produced by genetic mutations that affect motor control centers of the brain. As a positive control for postural instability, wild type mice were injected with harmaline, a tremorigenic agent, and the average areas of the 95% confidence ellipse, which measures 95% of the CoP trajectory values recorded in a single trial, were measured. Ellipse area significantly increased in mice treated with increasing doses of harmaline and returned to control values after recovery. We also examined postural sway in mice expressing mutations that mimic frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (T-279, P301L or P301L-nitric oxide synthase 2 (NOS2)(-/-) mice) and that demonstrate motor symptoms. These mice were then compared with a mouse model of Alzheimer's disease (APPSwDI mice) that demonstrates cognitive, but not motor deficits. T-279 and P301L-NOS2(-/-) mice demonstrated a significant increase in CoP ellipse area compared with appropriate wild type control mice or to mice expressing the P301L mutation alone. In contrast, postural instability was significantly reduced in APPSwDI mice that have cognitive deficits but do not have associated motor deficits. The CoP assay provides a simple, sensitive and quantitative tool to detect motor deficits resulting from postural abnormalities in mice and may be useful in understanding the underlying mechanisms of disease.

QTc dispersion on the baseline ECG predicts arrhythmias during electroconvulsive therapy.

OBJECTIVE: Our objective in this study was to test the hypothesis that prolonged QTc dispersion predisposes to arrhythmias in electroconvulsive therapy (ECT). METHODS AND RESULTS: We measured QTc dispersion on ECT patients' baseline ECG and also measured PVCs and PACs during and for two minutes after ECT seizures. Using Poisson regression analysis, we found that baseline QTc dispersion was positively associated with ictal and post ictal PVCs and with post ictal PACs. CONCLUSIONS: We conclude that QTc dispersion appears to be a valid predictor of arrhythmias.

Synovial chondromatosis of the temporomandibular joint with extension into the middle cranial fossa and internal carotid canal.

This report presents the case of an extensive synovial chondromatosis of the temporomandibular joint (TMJ), with extension into the middle cranial fossa, middle ear, and carotid canal. Synovial chondromatosis of the TMJ is rare, particularly when associated with intracranial involvement. This case is unique owing to its size and the involvement with the internal carotid artery. The importance of a multidisciplinary approach in the surgical management of such a rare and complex form of this condition is highlighted.

Evaluation of dye exclusion and colony inhibition techniques for detection of polyoma-specific, cell-mediated immunity.

Cellular immunity directed against polyoma virus-induced antigen was observed with C3H/HeJ splenic lymphoid cells from mice sensitized by a short-term immunization schedule with syngeneic polyoma 4198 and 4198V tumor cells. Polyoma specificity of the response was shown by demonstration that splenic cells from DBA/2J animals with polyoma virus-induced tumors were cytotoxic for the C3H 4198 and 4198V cells, but not for the L-M cell, another cell line of C3H origin. The polyoma-specific response in the syngeneic system was detectable with the dye exclusion assay but not with the colony inhibition procedure. Colony inhibition with the L-M cell was observed with sensitized lymphoid cells in both allogeneic and syngeneic systems.

The minimal leak test technique for endotracheal cuff maintenance.

Endotracheal tube (ETT) cuff pressure management is an essential part of airway management in intubated and mechanically ventilated patients. Both under- and over-inflation of the ETT cuff can lead to patient complications, with an ideal pressure range of 20-30 cmH2O defined. A range of techniques are employed to ensure adequate ETT cuff inflation, with little comparative data. We performed an observational cross-sectional study in a tertiary metropolitan ICU, assessing the relationship between the minimal leak test and cuff manometry. Forty-five mechanically ventilated patients, over a three-month period, had ETT cuff manometry performed at the same time as their routine cuff maintenance (minimal leak test). Bedside nurse measurements were compared with investigator measurements. At the endpoint of cuff inflation, 20 of 45 patients (44%) had cuff pressures between 20 and 30 cmH2O; 11 of 45 patients (24%) had cuff pressures <20 cmH2O; 14 of 45 patients (31%) had cuff pressures ≥30 cmH2O. Univariate analysis demonstrated an association between both patient obesity and female gender requiring less ETT cuff volume (P=0.008 and P <0.001 respectively), though this association was lost on multivariate analysis. No association was demonstrated between any measured variables and cuff pressures. Inter-operator reliability in performing the minimal leak test showed no evidence of bias between nurse and investigators (Pearson coefficient = 0.897). We conclude the minimal leak test for maintenance of ETT cuffs leads to both over- and under-inflation, and alternative techniques, such as cuff manometry, should be employed.

Regulation of protein kinase D during differentiation and proliferation of primary mouse keratinocytes.

Diseased skin often exhibits a deregulated program of the keratinocyte maturation necessary for epidermal stratification and function. Protein kinase D (PKD), a serine/threonine kinase, is expressed in proliferating keratinocytes, and PKD activation occurs in response to mitogen stimulation in other cell types. We have proposed that PKD functions as a pro-proliferative and/or anti-differentiative signal in keratinocytes and hypothesized that differentiation inducers will downmodulate PKD to allow differentiation to proceed. Thus, changes in PKD levels, autophosphorylation, and activity were analyzed upon stimulation of differentiation and proliferation in primary mouse keratinocytes. Elevated extracellular calcium and acute 12-O-tetradecanoylphorbol-13-acetate (TPA) treatments induced differentiation and triggered a downmodulation of PKD levels, autophosphorylation at serine 916, and activity. Chronic TPA treatment stimulated proliferation and resulted in a recovery of PKD levels, autophosphorylation, and activity. Immunohistochemical analysis demonstrated PKD localization predominantly in the proliferative basal layer of mouse epidermis. Co-expression studies revealed a pro-proliferative, anti-differentiative effect of PKD on keratinocyte maturation as monitored by increased and decreased promoter activities of keratin 5, a proliferative marker, and involucrin, a differentiative marker, respectively. This work describes the inverse regulation of PKD during keratinocyte differentiation and proliferation and the pro-proliferative/anti-differentiative effects of PKD co-expression on keratinocyte maturation.

Lack of adherence with the analgesic regimen: a significant barrier to effective cancer pain management.

PURPOSE: To evaluate oncology outpatients' level of adherence to their analgesic regimen during a 5-week period. PATIENTS AND METHODS: A random sample of 65 adult oncology outpatients with a Karnofsky performance status score of >or= 50, an average pain intensity score of >or= 2.5, and radiographic evidence of bone metastasis were recruited for this longitudinal study from seven outpatient settings. On a daily basis, patients rated their level of pain intensity and recorded pain medication intake. Adherence rates for opioid analgesics prescribed on an around-the-clock (ATC) and on an as-needed (PRN) basis were calculated on a weekly basis. RESULTS: Overall adherence rates for ATC opioid analgesics ranged from 84.5% to 90.8% and, for PRN analgesics, from 22.2% to 26.6%. No significant differences over time were found in either of these adherence rates. CONCLUSION: One factor that seems to contribute to ineffective cancer pain management is poor adherence to the analgesic regimen.

Pathological gambling caused by drugs used to treat Parkinson disease.

BACKGROUND: Pathological gambling is a rare potential complication related to treatment of Parkinson disease (PD). However, the etiology of this behavior is poorly understood. OBJECTIVE: To examine the relationship between medical therapy for PD and pathological gambling. METHODS: In our routine movement disorders practice (2002-2004), we encountered 11 patients with idiopathic PD who had recently developed pathological gambling. We assessed the relationship to their medical therapy and compared them with cases identified by systematic review of the existing literature on pathological gambling and PD. RESULTS: All 11 patients with PD and pathological gambling were taking therapeutic doses of a dopamine agonist; 3 of these patients were not treated with levodopa. In 7 patients, pathological gambling developed within 3 months of starting to take or escalating the dose of the agonist; in the other 4 with a longer latency, gambling resolved after the agonist use was discontinued. Pramipexole dihydrochloride was the agonist in 9 of 11 cases in our series and 10 of 17 in the literature (68% in total). CONCLUSIONS: Dopamine agonist therapy was associated with potentially reversible pathological gambling, and pramipexole was the medication predominantly implicated. This may relate to disproportionate stimulation of dopamine D(3) receptors, which are primarily localized to the limbic system.

Determinants of species richness in the Park Grass Experiment.

The Park Grass Experiment at Rothamsted in southeast England was started in 1856, making it the longest-running experiment in plant ecology anywhere in the world. Experimental inputs include a range of fertilizers (nitrogen, phosphorus, potassium, and organic manures) applied annually, with lime applied occasionally, and these have led to an increase in biomass and, where nitrogen was applied in the form of ammonium sulfate, to substantial decreases in soil pH. The number of species per plot varies from three to 44 per 200 m(2), affording a unique opportunity to study the determinants of plant species richness and to estimate the effect sizes attributable to different factors. The response of species richness to biomass depends on the amount and type of nitrogen applied; richness declined monotonically with increasing biomass on plots receiving no nitrogen or receiving nitrogen in the form of sodium nitrate, but there was no relationship between species richness and biomass on plots acidified by ammonium sulfate application. The response to lime also depended on the type of nitrogen applied; there was no relationship between lime treatment and species richness, except in plots receiving nitrogen in the form of ammonium sulfate, where species richness increased sharply with increasing soil pH. The addition of phosphorus reduced species richness, and application of potassium along with phosphorus reduced species richness further, but the biggest negative effects were when nitrogen and phosphorus were applied together. The analysis demonstrates how multiple factors contribute to the observed diversity patterns and how environmental regulation of species pools can operate at the same spatial and temporal scale as biomass effects.

Clinical and economic choices in the treatment of respiratory infections in cystic fibrosis: comparing hospital and home care.

BACKGROUND: A cost-effectiveness evaluation comparing home-based and hospital-based treatment with intravenous antibiotics for respiratory exacerbations in adults with cystic fibrosis (CF) has not been previously undertaken. METHODS: The study was conducted in a UK adult CF centre from a health service perspective. Clinical outcome and resource use data were obtained from a retrospective one-year study and combined with unit cost data in an incremental economic analysis. The primary outcome measure was percentage change in FEV(1); "effectiveness" was defined as maintenance of baseline average FEV(1) over the one-year study period. RESULTS: 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year, there had been a mean percentage decline in FEV(1) compared with baseline average for home-treated patients but an improvement for hospital-treated patients (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). Treatment was deemed "effective" in more hospital (58.8%) than home (42.6%) patients. The cost of hospital treatment was higher than home treatment (mean difference 9,005 pounds, 95% CI 3,507 to 14,700, p<0.001). The mean ICER was 46,098 pounds (2.5th and 97.5th percentiles -374,044 and 362,472). CONCLUSIONS: Hospital treatment was more effective but more expensive than home treatment. Potential methods to improve outcome at home should be considered but these may have resource implications.

Cochlear implants: 100 pediatric case conversions from the body worn to the nucleus esprit 22 ear level speech processor.

OBJECTIVE: To assess performance of Nucleus 22 mini system pediatric users converted from the Spectra 22 body-worn to the ESPrit 22 ear-level speech processor using aided thresholds and speech discrimination measures before and after the conversion. STUDY DESIGN: Spectra 22 body-worn speech processor users were chosen using preselection criteria (stable map, ability to report on the quality of the signal, no device problems). The subjects underwent tuning, map conversion, fitting of the ESPrit 22, and aided soundfield threshold and speech discrimination testing. SUBJECTS: The first 100 consecutive conversions are analyzed in this study. Fifty children (50%) were female, and 50 (50%) were male. The average age at implantation was 4.6 years (median 4.3 years, range 1.7 to 11 years). The average age of fitting the ear level speech processor was 11.1 years (median 11 years, range 6.2 to 18.2 years). SETTING: Tertiary referral pediatric cochlear implant center in the United Kingdom. RESULTS: Of the 100 fittings attempted, all Spectra 22 maps could to be converted for use in the ESPrit 22. Of these 100 fittings, 44 were straightforward with no adjustment to map parameters being required, and 56 needed rate reductions and other map adjustments to achieve the conversion. The difference of the mean thresholds before and after the conversion did not exceed 2 dB across the frequencies studied (0.5-4 kHz). In 95% of the cases, the differences were less than 9 dB(A). With regard to speech discrimination testing, the mean threshold before the conversion was 53.4 dB and after the conversion 52.7 dB. Of the 100 conversions, only five children stopped using the ESPrit 22 despite fitting being achieved. CONCLUSION: Conversion from the Spectra 22 body worn to the ESPrit 22 ear level speech processor was found to be feasible in all the 100 cases studied. Only a minority (5%) of children chose not to use the ear level speech processor suggesting that children and parents were satisfied from the conversion.

Amlodipine monotherapy, angiotensin-converting enzyme inhibition, and combination therapy with pacing-induced heart failure.

In patients with congestive heart failure (CHF) receiving therapy with angiotensin-converting enzyme (ACE) inhibition, institution of calcium channel antagonism with amlodipine provided favorable effects. The goal of the present study was to define potential mechanisms for these effects by measuring left ventricular function, hemodynamics, and neurohormonal system activity in a model of CHF in which amlodipine treatment had been instituted either as a monotherapy or in combination with ACE inhibition. Thirty-two pigs were instrumented to allow measurement of cardiac index, total systemic resistance index, and neurohormonal activity in the conscious state and assigned to one of four groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n = 8), (2) amlodipine (1.5 mg x kg(-1) x d[-1]) and pacing (n = 8), (3) ACE inhibition (fosinopril 1.0 mg/kg BID) and pacing (n = 8), and (4) amlodipine and ACE inhibition (1.0 mg x kg(-1) x d(-1) and 1.0 mg/kg BID, respectively) and pacing (n = 8). Measurements were obtained in the normal control state and after the completion of the treatment protocols. With rapid pacing, basal resting cardiac index was reduced compared with control values (2.7+/-0.2 versus 4.7+/-0.1 L x min(-1) x m(-2), respectively, P<.05) and increased from rapid pacing-only values with either amlodipine or combination therapy (3.7+/-0.3 and 4.4+/-0.5 L x min(-1) x m(-2), respectively, P<.05). Basal resting total systemic resistance index was higher in the rapid pacing-only group compared with control values (2731+/-263 versus 1721+/-53 dyne x s x cm(-5) x m2, respectively, P<.05), was reduced with either amlodipine treatment or ACE inhibition (2125+/-226 and 2379+/-222 dyne x s x cm(-5) x m2, respectively, P<.05), and was normalized with combination therapy. Plasma catecholamines, renin activity, and endothelin levels were increased threefold with rapid pacing. Amlodipine, either as a monotherapy or in combination with ACE inhibition, did not result in increased plasma catecholamines and renin activity compared with the rapid pacing-only group. Furthermore, combination therapy reduced steady state norepinephrine and normalized epinephrine levels. The results of the present study demonstrated that monotherapy with either amlodipine or ACE inhibition provides beneficial effects in this pacing model of CHF. Combined amlodipine and ACE inhibition provided greater benefit with respect to vascular resistance properties and neurohormonal system activity compared with either monotherapy.

Regional cerebral blood flow imaging: a quantitative comparison of technetium-99m-HMPAO SPECT with C15O2 PET.

The aim of this study was to compare technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) with regional cerebral blood flow (rCBF) imaging using positron emission tomography (PET). As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data were compared quantitatively with three versions of the SPECT data. These were, first, data normalized to the SPECT cerebellar uptake, second, data linearly corrected using the PET cerebellar value and, finally, data Lassen corrected for washout from the high flow areas. Both the linearly-corrected (r = 0.81) and the Lassen-corrected (r = 0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the normalized HMPAO SPECT data and the PET data was nonlinear. It is not yet possible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.

Pharmacologic profile of amlodipine.

Amlodipine is a potent calcium antagonist, inhibiting Ca2+-induced contractions of depolarized rat aorta with an IC50 of 1.9 nM. Unlike nifedipine, it displayed very slow association and dissociation with the calcium channel. The ability of amlodipine to inhibit Ca2+-induced contractions was strongly dependent on the K+ concentration present before the contraction, suggesting marked voltage dependence of action. Radioligand-binding studies in cardiac membrane preparations suggested that amlodipine may interact directly with both 1,4-dihydropyridine and diltiazem-binding sites on the calcium channel. Hemodynamic studies in anesthetized and conscious dogs showed that amlodipine is a coronary and peripheral vasodilator with a slow onset and long duration of effect, even when given by intravenous injection; the reflex stimulation of cardiac output, heart rate and myocardial contractility induced by amlodipine was attenuated by propranolol, but no marked negative inotropic or dromotropic effects were observed. Amlodipine was an effective oral antihypertensive agent in rat and dog models of hypertension, and its 24-hour duration of action in hypertensive dogs correlated well with its long plasma half-life in this species. The natriuretic properties displayed by amlodipine may contribute to its use as a first-line drug for the treatment of hypertension.

Amlodipine therapy in congestive heart failure: hemodynamic and neurohormonal effects at rest and after treadmill exercise.

This study examined the acute effects of amlodipine treatment on left ventricular pump function, systemic hemodynamics, neurohormonal status, and regional blood flow distribution in an animal model of congestive heart failure (CHF), both at rest and with treadmill exercise. A total of 14 pigs were studied under control conditions and after the development of pacing-induced CHF (240 beats per minute, 3 weeks, n = 7) or with CHF and acute amlodipine treatment for the last 3 days of pacing (1.5 mg/kg per day, n = 7). Under resting conditions, left ventricular stroke volume (mL) was reduced with CHF compared with the normal state (15+/-2 vs. 31+/-1, p<0.05) and increased with amlodipine treatment (23+/-4, p<0.05). At rest, systemic vascular resistance increased with CHF compared with the normal state (3,078+/-295 vs. 2,131+/-120 dyne x s cm(-5), p<0.05) and was reduced after amlodipine treatment (2,472+/-355 dyne x s cm(-5), p<0.05). With exercise, left ventricular stroke volume remained lower and systemic vascular resistance higher in the CHF group, but was normalized with amlodipine treatment. With exercise, left ventricular myocardial blood flow increased from resting values, but was reduced from the normal state with CHF (normal: 1.69+/-0.12 to 7.62+/-0.74 mL/min per gram vs. CHF: 1.26+/-0.12 to 4.77+/-0.45 mL/min per gram, both p<0.05) and was normalized with acute amlodipine treatment (1.99+/-0.35 to 6.29+/-1.23 mL/min per gram). Resting plasma norepinephrine was increased by >5-fold in the CHF group at rest and was not affected by amlodipine treatment. However, with exercise, amlodipine treatment blunted the increase in plasma norepinephrine by >50% when compared with untreated CHF values. Resting plasma endothelin levels increased with CHF compared with the normal state (10.9+/-0.9 vs. 2.8+/-0.4 fmol/mL, p<0.05) and was reduced with amlodipine treatment (7.5+/-1.5 fmol/mL, p<0.5). In other vascular beds, acute amlodipine treatment with CHF improved pulmonary and renal blood flow both at rest and with exercise; however, there were no effects observed on skeletal muscle blood flow. With the development of CHF, acute amlodipine treatment does not negatively influence left ventricular pump function, but rather may provide favorable hemodynamic and neurohormonal effects.