Large Meningioma Complicating Pregnancy

EDITORIAL COMMENT: This case report was accepted for publication because of the clinical lesson it delivers, namely that intracranial tumours, although rare in pregnancy, may as the authors state 'produce a wide variety of symptoms that are difficult to distinguish from the more common symptoms of pregnancy, including nausea, vomiting and headache'. This case suggests that examination of the optic fundi is essential in patients with neurological symptoms even when/especially when there is a history of psychiatric illness.     

Preterm labour. The present and future of tocolysis

This chapter discusses the tocolytic agents currently in use for the treatment of preterm labour and considers them in light of the evidence base. These agents are the beta2 sympathomimetic agonists, magnesium sulphate (MgSO(4)), indomethacin, nifedipine and atosiban. The available evidence for these agents shows that the beta2 agents are effective but have significant maternal side effects and no effect on perinatal outcome. MgSO(4) and glyceryl trinitrate are clearly ineffective. Nifedipine is effective with a low maternal side effect profile and is associated with improved perinatal outcomes. Meta-analyses of the several randomized controlled trials of atosiban show that it is no more effective than other tocolytic therapies. Possible directions for the future will be discussed.     

A simple model for potential use with a misclassified binary outcome in epidemiology

STUDY OBJECTIVE: Error in determination of disease outcome occurs in epidemiology, but such error is not usually corrected for in statistical analysis. A method of correction of risk estimates for misclassification of a binary disease outcome is developed here. METHODS: The method is a simple, closed form correction to the logistic regression estimate. A closed form variance estimate is also developed. SETTING: The method is illustrated in two studies, a cross sectional survey of cervicitis in Iran in 1996-97, as determined by inflammation on cervical smear specimens, and a case-cohort study of benign proliferative epithelial disease of the breast, in Canada 1980-88. MAIN RESULTS: The method provides corrected odds ratio estimates and corrects the spurious precision conferred by misclassification. CONCLUSIONS: The method is easy to apply and potentially useful, although potential failures of the assumptions involved should be borne in mind. It is necessary to give careful consideration to the plausibility or otherwise of the assumptions in the context of the individual study. Correction for misclassification of disease outcome may become more common with the development of readily applicable methods.     

Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections

Purpose

The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders.

Method

A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1?=?60:20:20 and F2?=?40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed.

Results

A significant titer loss (~2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1?=?13.1?±?1.7?×?10⁴ pfu and SD-F2?=?11.0?±?1.4?×?10⁴ pfu) than from their counterpart SFD formulations (SFD-F1?=?8.3?±?1.8?×?10⁴ pfu and SFD-F2?=?2.1?±?0.3?×?10⁴ pfu).

Conclusion

Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.

     

Pre-weaning carvedilol treatment in spontaneously hypertensive rats

Hypertension in spontaneously hypertensive rats (SHR) has been permanently abolished by aggressive treatment regimens targeted against the sympathetic nervous system and adrenal medulla, initiated during the pre-weaning period (guanethidine and nerve growth factor antiserum combined with either adrenal demedullation or prazosin treatment). To investigate the components of the sympatho-adrenal system involved, we treated pre-weaning SHR with the combined alpha(1)- and beta-adrenoceptor antagonist carvedilol (60 mg/kg/day s.c.; postnatal days 1-21). Carvedilol treatment significantly blocked adrenoceptors during the treatment period, delayed development (eye opening), reduced growth, and reduced arterial pressure and heart rate. However, there was only modest attenuation of the subsequent development of hypertension at 10 weeks of age (mean arterial pressure 129.5+/-1.8 versus 136.1+/-1.6 mm Hg in vehicle-treated littermates; P<0.05). Thus pre-weaning carvedilol treatment slightly but significantly attenuated the development of SHR hypertension at 10 weeks, suggesting that the profound antihypertensive effects of pre-weaning sympatho-adrenal ablation are attributable to factors other than alpha(1)- and beta-adrenoceptor-mediated effects of catecholamines during this period.     

A Rifapentine-Containing Inhaled Triple Antibiotic Formulation for Rapid Treatment of Tubercular Infection

Purpose

The potential for rifapentine-containing oral therapeutic regimens to significantly shorten the current six-month anti-tubercular treatment regimen is confounded by high plasma protein binding of rifapentine. Inhaled aerosol delivery of rifapentine, a more potent anti-tubercular antibiotic drug, in combination with other first-line antibiotics may overcome this limitation to deliver a high drug dose at the pulmonary site of infection.

Methods

A formulation consisting of rifapentine, moxifloxacin and pyrazinamide, with and without leucine, was prepared by spray-drying. This formulation was assessed for its physico-chemical properties, in vitro aerosol performance and antimicrobial activity.

Results

The antibiotic powders, with and without leucine, had similar median aerodynamic diameters of 2.58?±?0.08 μm and 2.51?±?0.06 μm, with a relatively high fine particle fraction of 55.5?±?1.9% and 63.6?±?2.0%, respectively. Although the powders were mostly amorphous, some crystalline peaks associated with the δ polymorph for the spray-dried crystalline pyrazinamide were identified.

Conclusions

Stabilisation of the powder with 10% w/w leucine and protection from moisture ingress was found to be necessary to prevent overt crystallisation of pyrazinamide after long-term storage. In vitro biological assays indicated antimicrobial activity was retained after spray-drying. Murine pharmacokinetic studies are currently underway.     

Mycobacterium ulcerans-specific immune response after immunisation with bacillus Calmette-Guérin (BCG) vaccine

BackgroundBacillus Calmette–Guérin (BCG) vaccine provides partial protection against Buruli ulcer caused by Mycobacterium ulcerans in epidemiological studies. This study aimed to quantify M. ulcerans-specific immune responses induced by BCG immunisation.MethodsIntracellular cytokine analysis of in-vitro experiments done 10 weeks after BCG immunisation in 130 Australian infants randomised to one of three BCG vaccine strains given either at birth (BCG-Denmark, BCG-Japan, or BCG-Russia) or at two months of age (BCG-Denmark).ResultsProportions of polyfunctional CD4⁺ T-cells were higher in M. ulcerans-stimulated compared to unstimulated control samples. These proportions were not influenced by the vaccine strain or timing of the immunisation. The M. ulcerans-specific immune responses showed similar patterns to those observed in M. tuberculosis-stimulated samples, although they were of lower magnitude.ConclusionsOur data show that BCG immunisation induces M. ulcerans-specific immune responses in infants, likely explaining the cross-protective effect observed in epidemiological studies. (ACTRN12608000227392)     

Renal preglomerular arterial-venous O2 shunting is a structural anti-oxidant defence mechanism of the renal cortex

1. High blood flow to the kidney facilitates a high glomerular filtration rate, but total renal O2 delivery greatly exceeds renal metabolic requirements. However, tissue Po2 in much of the renal cortex is lower than may be expected, being similar to that of other organs in which perfusion is closely matched to metabolic demand. 2. The lower than expected renal cortical Po2 is now attributed largely to diffusional shunting of as much as 50% of inflowing O2 from blood within preglomerular arterial vessels to post-glomerular venous vessels. However, the functional significance of this O2 shunting remains unclear. Indeed, this mechanism may appear maladaptive, given the kidney's susceptibility to hypoxic insults. 3. We hypothesize that renal preglomerular arterial-venous O2 shunting acts to protect the kidney from the potentially damaging consequences of tissue hyperoxia. The diffusion of O2 from arteries to veins within the kidney acts to reduce the O2 content of the blood before it is distributed to the renal microcirculation. Because high tissue Po2 may increase the production of reactive oxygen species, we suggest that renal arterial-venous O2 shunting may provide a physiological benefit to the organism by limiting O2 delivery to renal tissue, thereby reducing the risk of cellular oxidation.