Daily scheduled opioids (DSO) have been employed in some instances to remediate intractable headache. However, long-term studies of effectiveness, sequelae over several years, predictors of long-term ...benefit, comparisons of pain-related outcome measures, and prevalence of problematic drug behavior are not available.
The authors evaluated the results of a treatment program at their institution designed to treat and monitor intractable headache patients administered DSO. Of 160 sequential patients participating in the program, 70 who remained on DSO for at least 3 years qualified for inclusion in an efficacy analysis. Patients completed structured questionnaires at each medical visit as part of routine clinical care. The authors assessed medical records during treatment, and during the 2 years before starting DSO. The primary clinical efficacy variable was percentage improvement in the severe headache index (frequency x severity of severe headaches/week).
Analysis of the medical records found 41 (26%) of the original 160 patients with >50% improvement. Patients reported larger improvements on a visual analog scale (mean improvement = 70%) than shown by the medical record (mean improvement = 46%), p < 0.00001. Problem drug behavior (dose violations, lost prescriptions, multisourcing) occurred in 50% of patients, usually involving dose violations.
For a select group of intractable headache patients, DSO can offer significant benefit. However, 74% of those treated either failed to show significant improvement or were discontinued from the program for clinical reasons. The relatively low percentage of patients with demonstrated efficacy and unexpectedly high prevalence of misuse have clinical relevance.
Monte Carlo simulations are employed to study a fluid vesicle that contains a single worm-like polymer chain. The contour length of the polymer is about five times the circumference of the nominally ...spherical vesicle. We vary the degree of polymer confinement in our simulations by increasing the persistence length of the polymer. The vesicle is represented by a randomly triangulated self-avoiding network that can undergo bending deformations. Upon increasing the persistence length of the polymer beyond the size of the vesicle, we observe a transition of the polymer from an isotropic disordered random conformation to an ordered toroidal coil. Concomitantly, the vesicle adopts an oblate shape to allow for some expansion of the polymer coil inside the vesicle. It is convenient to characterize both polymer and vesicle in terms of the asphericity, a quantity derived from the gyration tensor. At the onset of the polymer's ordering transition, the asphericity passes through a minimum for both polymer and vesicle. The increase in vesicle asphericity for a semi-flexible polymer can be understood in terms of ground state energy calculations, either for a simplified representation of the vesicle shape (we specifically discuss a disk shape with a semi-toroidal rim) or involving a full vesicle shape optimization. The asphericity of the polymer coil results from conformational fluctuations and can be rationalized using Odijk's deflection length of strongly curved semi-flexible polymers.
The conformations of a fluid-like lipid vesicle that encloses a single worm-like polymer are studied using Monte Carlo simulations and phenomenological modeling.
In this population-based study of acute lymphoblastic leukaemia (ALL) diagnosed among children aged under 15 years in England and Wales during 1986-1995, we analysed incidence at census ward level in ...relation to a range of variables from the 1991 census, which could be relevant to theories of infectious aetiology. 'Population-mixing' measures, used as surrogates for quantity and diversity of infections entering the community, were calculated from census data on the origins and destinations of migrants in the year before the census. Incidence at ages 1-4 years tended independently to be higher in rural wards, to increase with the diversity of origin wards from which in-migrants had moved during the year before the census, and to be lower in the most deprived areas as categorised by the Carstairs index. This last association was much weaker when urban/rural status and in-migrants' diversity were allowed for. There was no evidence of association with population mixing or deprivation for ALL diagnosed at ages 0 or 5-14 years. The apparent specificity to the young childhood age group suggests that these associations are particularly marked for precursor B-cell ALL, with the disease more likely to occur when delayed exposure to infection leads to increased immunological stress, as predicted by Greaves. The association with diversity of incomers, especially in rural areas, is also consistent with the higher incidence of leukaemia predicted by Kinlen, where population mixing results in below average herd immunity to an infectious agent.
Microtubules (MTs) have been proposed to act mechanically as compressive struts that resist both actomyosin contractile forces and their own polymerization forces to mechanically stabilize cell ...shape. To identify the origin of MT bending, we directly observed MT bending and F-actin transport dynamics in the periphery of LLC-PK1 epithelial cells. We found that F-actin is nearly stationary in these cells even as MTs are deformed, demonstrating that MT bending is not driven by actomyosin contractility. Furthermore, the inhibition of myosin II activity through the use of blebbistatin results in microtubules that are still dynamically bending. In addition, as determined by fluorescent speckle microscopy, MT polymerization rarely results, if ever, in bending. We suppressed dynamic instability using nocodazole, and we observed no qualitative change in the MT bending dynamics. Bending most often results from anterograde transport of proximal portions of the MT toward a nearly stationary distal tip. Interestingly, we found that in an in vitro kinesin-MT gliding assay, MTs buckle in a similar manner. To make quantitative comparisons, we measured curvature distributions of observed MTs and found that the in vivo and in vitro curvature distributions agree quantitatively. In addition, the measured MT curvature distribution is not Gaussian, as expected for a thermally driven semiflexible polymer, indicating that thermal forces play a minor role in MT bending. We conclude that many of the known mechanisms of MT deformation, such as polymerization and acto-myosin contractility, play an inconsequential role in mediating MT bending in LLC-PK1 cells and that MT-based molecular motors likely generate most of the strain energy stored in the MT lattice. The results argue against models in which MTs play a major mechanical role in LLC-PK1 cells and instead favor a model in which mechanical forces control the spatial distribution of the MT array.
Recorded incidence of childhood acute lymphoblastic leukaemia tends to be lower in poorer communities. A 'preemptive infection hypothesis' proposes that some children with leukaemia die from ...infection without diagnosis of leukaemia. Various different blood abnormalities can occur in untreated leukaemia.
Logistic regression was used to compare pre-treatment blood counts among children aged 1-13 years at recruitment to national clinical trials for acute lymphoblastic leukaemia during 1980-2002 (N=5601), grouped by address at diagnosis within Great Britain into quintiles of the 1991 Carstairs deprivation index. Children combining severe neutropenia (risk of serious infection) with relatively normal haemoglobin and platelet counts (lack of pallor and bleeding) were postulated to be at risk of dying from infection without leukaemia being suspected. A deficit of these children among diagnosed patients from poorer communities was predicted.
As predicted, there was a deficit of children at risk of non-diagnosis (two-sided P(trend)=0.004; N=2009), and an excess of children with pallor (P(trend)=0.045; N=5535) and bleeding (P(trend)=0.036; N=5541), among cases from poorer communities.
Under-diagnosis in poorer communities may have contributed to socioeconomic variation in recorded childhood acute lymphoblastic leukaemia incidence within Great Britain, and elsewhere. Implications for clinical practice and epidemiological studies should be considered.
Introduction
Electronic control with the CEW (conducted electrical weapon) has gained widespread acceptance as the preferred force option due to its significant injury reduction. However, a CEW ...application does stress the human body. In the case of the CEW, the human body response is similar to the challenge of physical exercise combined with emotional stress over a very short time interval. There has been concern whether the tension of the skeletal-muscle system together with the emotional stress of being exposed to the effects of a CEW, can lead to severe metabolic dysfunction.
Methods
A systematic and careful search of the MedLine database was performed to find publications describing pathophysiological effects of CEWs. Additional publications were collected through a manual search of reference lists in retrieved articles. After preliminary exclusions, we carefully reviewed the remaining publications and found 24 papers reporting prospective human clinical research data on adrenergic, ventilation, or metabolic effects. Where there were multiple studies on the same endpoints, we performed meta-analyses.
Results
A CEW exposure provides a clinically insignificant increase in heart rate (7.5 BPM) and a drop in both systolic and diastolic blood pressure. Alpha-amylase goes down but cortisol levels increase—both epinephrine and norepinephrine levels are increased by levels similar to mild exercise. A CEW exposure increases ventilation but does not appear to interfere with gas exchange. Lactate is increased slightly while the pH is decreased slightly with changes equivalent to mild exercise. The lactate and pH changes appear quickly and do not appear to be affected by increasing the exposure duration from 5 to 30 s.
Conclusions
Thorough review and meta-analyses show that electrical weapon exposures have mixed and mild adrenergic effects. Ventilation is increased and there are metabolic changes similar to mild exercise.
The trigger initiating an autoimmune response against melanocytes in vitiligo remains unclear. Patients frequently experience stress to the skin prior to depigmentation. 4-tertiary butyl phenol ...(4-TBP) was used as a model compound to study the effects of stress on melanocytes. Heat shock protein (HSP)70 generated and secreted in response to 4-TBP was quantified. The protective potential of stress proteins generated following 4-TBP exposure was examined. It was studied whether HSP70 favors dendritic cell (DC) effector functions as well. Melanocytes were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in response to 4-TBP exposure was partially released into the medium by immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70 in turn induced membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and activation of DC effector functions towards stressed melanocytes. Melanocytes exposed to 4-TBP demonstrated elevated TRAIL death receptor expression. DC effector functions were partially inhibited by blocking antibodies to TRAIL. TRAIL expression and infiltration by CD11c+ cells was abundant in perilesional vitiligo skin. Stressed melanocytes may mediate DC activation through release of HSP70, and DC effector functions appear to play a previously unappreciated role in progressive vitiligo.
Functional magnetic resonance imaging was used to investigate the neural correlates of passive listening, habitual speech and two modified speech patterns (simulated stuttering and prolonged speech) ...in stuttering and nonstuttering adults. Within-group comparisons revealed increased right hemisphere biased activation of speech-related regions during the simulated stuttered and prolonged speech tasks, relative to the habitual speech task, in the stuttering group. No significant activation differences were observed within the nonstuttering participants during these speech conditions. Between-group comparisons revealed less left superior temporal gyrus activation in stutterers during habitual speech and increased right inferior frontal gyrus activation during simulated stuttering relative to nonstutterers. Stutterers were also found to have increased activation in the left middle and superior temporal gyri and right insula, primary motor cortex and supplementary motor cortex during the passive listening condition relative to nonstutterers. The results provide further evidence for the presence of functional deficiencies underlying auditory processing, motor planning and execution in people who stutter, with these differences being affected by speech manner.
A guest on a cruise ship must be disembarked during the voyage due to a probable malignant pleural effusion recurring after puncture and draining part of the fluid. As in this case, patients are ...often advised by their general practitioners or specialists to take part in an already planned cruise, although complications of existing underlying diseases cannot always be well treated in the on-board hospital. The diagnostic and therapeutic possibilities in the on-board hospital are clearly limited in many aspects compared to hospitals ashore and disembarkation is not desirable everywhere.
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