Pros and cons of treating murine myasthenia gravis with anti-C1q antibody

To test the feasibility of classical complement pathway manipulation in experimental autoimmune myasthenia gravis (EAMG) treatment, C57BL/6 (B6) and RIIIS/J mice with EAMG were treated with 10 microg or 100 microg of anti-C1q Ab or isotype Ab. Treatment with 10 microg anti-C1q Ab significantly reduced the clinical severity, decreased lymph node cell IL-6 production and T cell populations. Conversely, administration of 100 microg anti-C1q Ab caused harmful side effects such as increased serum anti-acetylcholine receptor antibody, immune complex, C3 and lymph node B cell levels and kidney C3 and IgG deposits, which reduced the treatment efficacy.     

Cannabis use and brain structural alterations in first episode schizophrenia--a region of interest, voxel based morphometric study

Structural alterations of the brain in schizophrenia have been associated with genetic and environmental factors. Among the environmental factors, cannabis use has been associated with increased risk for patients with schizophrenia, but the effect of cannabis on their brain structure is unclear. We examined gray matter alterations in first episode schizophrenia patients (FES) with cannabis use (FES+C; n=15) compared to FES without cannabis use (FES-C; n=24) and 42 healthy controls who did not use cannabis. We conducted a voxel based morphometric analysis of a priori determined regions of interest consisting of the CB1 receptor rich brain regions. We observed a decrease in gray matter density in the right posterior cingulate cortex (PCC) in FES+C when compared with FES-C. The results suggest that cannabis use may be associated with altered brain structure, in particular regions rich in CB1 receptors. These findings need to be confirmed by larger, prospective studies.     

Distraction histiogenesis for treatment of Kienbock's disease: A 2- to 8-year follow-up

Background:

Distraction histiogenesis is known to enhance vascularity and stimulate new tissue formation. Its use in Kienbock''s disease is not reported in the literature, so we proposed to study the outcome after distraction histiogenesis in treating this condition.

Materials and Methods:

This prospective study comprised of six patients (two male and four female) with mean age 18.16 years (range 21-35 years) with clinicoradiologically diagnosed Lichtman stage II (n = 3) and stage III (n = 3) Kienbock''s disease with a mean duration of symptoms 6.67 months. The ulnar variance was neutral in two and was negative in four patients treated with the application of Joshi external stabilization system (JESS) across the wrist. The gradual distraction was done at a rate of 0.5 mm/day. After the distraction of 5-7 mm, the distractors were kept static for 3 weeks. The wrist was mobilized by using hinged distractors for next 3 weeks. Later short cockup splint was used for further 4 weeks. At the end of minimum 2 years, an assessment was done on the basis of relief of symptoms, ability to perform activities of daily living, range of movement at wrist, grip strength, and on radiology (change in the density of bone and C:MC ratio i.e ratio of carpal height to third metacarpal height).

Results:

The mean follow-up was of 4.5 years (range 2-8 years). The average duration of treatment was 5.3 months (range 4.5-6 months), and the duration of distraction (both static and hinged) was 8 weeks. Clinically all the patients were relieved of the symptoms with an increase in the range of wrist movement (ulnar deviation increased from 20.8° to 29.5°, radial deviation from 17.5° to 21°, dorsiflexion from 37.5° to 52.5°, and palmer flexion from 38.3° to 47.5°). At the last follow-up, activities of daily living were not affected, and all the patients were on their previous jobs without any fresh complaints. The average grip strength increased to 73-86% of normal. Radiologically the C:MC ratio (ratio of carpal height to third metacarpal height) did not show any significant improvement, but the density of lunate decreased.

Conclusion:

Distraction histiogenesis when used in Lichtman stage II and III with negative or neutral ulnar variance gives good symptomatic relief, allowing return to normal activities. This study has also shown that reparative process is possible in avascular bone by distraction. The authors recommend further research in this modality of treatment.     

Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community

BACKGROUND: Despite national disease management plans, optimal asthma management remains a challenge in Australia. Community pharmacists are ideally placed to implement new strategies that aim to ensure asthma care meets current standards of best practice. The impact of the Pharmacy Asthma Care Program (PACP) on asthma control was assessed using a multi-site randomised intervention versus control repeated measures study design. METHODS: Fifty Australian pharmacies were randomised into two groups: intervention pharmacies implemented the PACP (an ongoing cycle of assessment, goal setting, monitoring and review) to 191 patients over 6 months, while control pharmacies gave their usual care to 205 control patients. Both groups administered questionnaires and conducted spirometric testing at baseline and 6 months later. The main outcome measure was asthma severity/control status. RESULTS: 186 of 205 control patients (91%) and 165 of 191 intervention patients (86%) completed the study. The intervention resulted in improved asthma control: patients receiving the intervention were 2.7 times more likely to improve from "severe" to "not severe" than control patients (OR 2.68, 95% CI 1.64 to 4.37; p<0.001). The intervention also resulted in improved adherence to preventer medication (OR 1.89, 95% CI 1.08 to 3.30; p = 0.03), decreased mean daily dose of reliever medication (difference -149.11 microg, 95% CI -283.87 to -14.36; p=0.03), a shift in medication profile from reliever only to a combination of preventer, reliever with or without long-acting beta agonist (OR 3.80, 95% CI 1.40 to 10.32; p=0.01) and improved scores on risk of non-adherence (difference -0.44, 95% CI -0.69 to -0.18; p=0.04), quality of life (difference -0.23, 95% CI -0.46 to 0.00; p=0.05), asthma knowledge (difference 1.18, 95% CI 0.73 to 1.63; p<0.01) and perceived control of asthma questionnaires (difference -1.39, 95% CI -2.44 to -0.35; p<0.01). No significant change in spirometric measures occurred in either group. CONCLUSIONS: A pharmacist-delivered asthma care programme based on national guidelines improves asthma control. The sustainability and implementation of the programme within the healthcare system remains to be investigated.     

Anorexic effect of (R)-sibutramine: comparison with (RS)-sibutramine [corrected] and (S)-sibutramine

Sibutramine is one of the very few drugs that are approved for long-term treatment of obesity. Sibutramine is a racemic mixture (RS) containing two equal forms of the R(+) and S(-) enantiomers. In this paper, we have investigated comparative anorexic effect of sibutramine enantiomers and their recemate form in rats. After obtaining two days of baseline results, rats were administered orally either with (RS)-sibutramine or its enantiomers (R)- or (S)-sibutramine at dose levels of 5, 10, 20 mg/kg each for 4 days and body weight, food intake and water intake were measured daily. Locomotor activity score of each rat was also recorded on each day. R-Sibutramine and (RS)-sibutramine produced dose dependant decrease in the body weight and food intake. On the other hand, (S)-sibutramine was shown to increase in these parameters. Neither sibutramine nor it's enantiomers showed any consistent effects on spontaneous motor activity (SMA) scores. In conclusion, (R)-sibutramine is better anorexic than or (RS)-sibutramine or it's (S)-enantiomers.     

Enhanced Oromucosal Delivery of Progesterone Via Hexosomes

Purpose Formulation and characterization of progesterone loaded hexosomes employing a novel method for oromucosal delivery. Method Hexosomes were prepared employing a method in which ethanolic solution of lipid phase (monolein and oleic acid) was vortexed with aqueous phase (surfactant solution) and characterized for particle size, morphology and internal structure. FT-IR and confocal laser scanning microscopy (CLSM) were performed to investigate the possible mechanism and penetration pathway of hexosomes within the mucosa. Results Hexosomes exhibited anisotropy, hexagonal shape and nanometric size (251.2 ± 1.8 nm). Internal structure confirmed by X-ray diffraction peaks with spacing ratio of √1:√3:√4 proved two-dimensional hexagonal arrangements. Entrapment efficiency of system was greater than 95%. In vitro release studies revealed an enhanced transmucosal flux (4.67 ± 0.14 μg cm⁻² h⁻¹) and decreased lag time (1.54 h) across albino rabbit mucosa. FT-IR and CLSM of treated mucosa shows lipid extraction phenomena as well as structural irregularities within intercellular lipids respectively. These irregularities can function as ‘virtual channels’ facilitating hexosome’s penetration. Conclusion Developed hexosomes formulation exhibited high entrapment efficiency, high permeability and better stability on storage, thus proposing itself a novel carrier for enhanced oromucosal delivery of progesterone.     

Measurement of end-expiratory lung volume by oxygen washin–washout in controlled and assisted mechanically ventilated patients

Objective  Assessing limits of agreement with helium dilution and repeatability of a new system (lung funcution, LUFU) that measures end-expiratory lung volume (EELV) in mechanically ventilated patients using the O₂ washin (EELV_Win) and washout (EELV_Wout) technique. LUFU consists of an Evita 4 ventilator, a side-stream oxygen analyzer, and a dedicated PC software. Design and setting  Prospective human study in a general ICU of a University hospital. Patients  Thirty-six mechanically ventilated patients. Interventions  We obtained 36 couples of both EELV_Win and EELV_Wout measurements in each patient (5 with healthy lungs, 9 with ALI, 22 with ARDS). Measurements were obtained with patients ventilated either by assisted (ASB, 16 measurements) or controlled (CMV, 20 measurements) ventilation. In 19 of 20 cases in CMV, we obtained helium dilution measurements (EELV_He). Measurements and results  Bias for agreement with EELV_He was −16 ± 156 and 8 ± 161 ml, respectively, for EELV_Win and EELV_Wout. Bias for agreement between EELV_Win and EELV_Wout was 28 ± 78 and 23 ± 168 ml, respectively, for CMV and ASB. During CMV bias for repeatability were 8 ± 92 and 23 ± 165 ml, respectively, for EELV_Win and EELV_Wout. During ASB bias for repeatability were 32 ± 160 and −15 ± 147 ml, respectively, for EELV_Win and EELV_Wout. Conclusions  The LUFU method showed good agreement with helium, and good repeatability during partial and controlled mechanical ventilation. The technique is simple and safe.