Pharmacotherapeutic strategies for critical asthma syndrome: a look at the state of the art

ABSTRACT

Introduction

‘Critical Asthma Syndrome’ (CAS) is an umbrella term proposed to include several forms of asthma, responsible for acute and life-threatening exacerbations. CAS requires urgent and adequate supportive and pharmacological treatments to prevent serious outcomes.     

Switch From Twice-daily Tacrolimus to Once-daily,Prolonged-release Tacrolimus in Kidney Transplantation: Long-term Outcome

Background

One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety.

Faecal occult blood test‐based screening programme with high compliance for colonoscopy has a strong clinical impact on colorectal cancer

Background:

The results of a pilot colorectal cancer screening programme by biennial immunochemical faecal occult blood test (FOBT) are reported.

Methods:

All residents aged between 50 and 69 years in the Italian province of Lecco were invited to have a FOBT. Those with a positive result were offered colonoscopy. FOBT uptake and compliance with colonoscopy were assessed. Detection rate and positive predictive value (PPV) for cancer and adenoma were calculated. Tumour stages were compared between screen‐detected cancers and other colorectal cancers diagnosed within the target age group.

Results:

Some 38 693 (49·6 per cent) of 78 083 individuals had a FOBT and 2392 (6·2 per cent) had a positive result. Colorectal cancer was diagnosed in 4·6 per cent and advanced adenoma in 32·7 per cent. PPVs were 4·0 per cent for cancer, 28·1 per cent for advanced adenoma and 36·6 per cent for any adenoma. There was a significant difference in incidence of stage III/IV disease between screened and non‐screened cohorts. Compliance for colonoscopy was 92·0 per cent. Major determinants of compliance were age less than 59 years, female sex, high education level and non‐manual work.

Conclusion:

These results justify extension of colorectal cancer screening to other regions of Italy. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

An overview of erdosteine antioxidant activity in experimental research.

Erdosteine was introduced in the market as a mucolytic agent for chronic pulmonary diseases more than 10 years ago. The drug contains two blocked sulphydryl groups one of which, after hepatic metabolization and opening of the thiolactone ring, becomes available both for the mucolytic and free radical scavenging and antioxidant activity too. There are several experimental evidences which support the protective effect of erdosteine in acute injury induced by a variety of pharmacological or noxious agents, mediated by products of oxidative stress. Experimental data in animal assigned to receive the noxious agent evidence that co-treatment with erdosteine increases the tissue antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase, compared with the toxic agent alone; meanwhile erdosteine decreases the tissue level of nitric oxide, xanthine oxidase, which catalyze oxygen-free radical production. In summary, erdosteine prevents the accumulation of free oxygen radicals when their production is accelerated and increases antioxidant cellular protective mechanisms. The final result is a protective effect on tissues which reduces lipid peroxidation, neutrophil infiltration or cell apoptosis mediated by noxious agents. Recent positive clinical trials in humans seem to fulfill the impressive promises that theory and experimental research have put forward.     

Septic arthritis of the temporomandibular joint successfully treated with arthroscopic lysis and lavage: case report and review of the literature.

Septic arthritis of the temporomandibular joint (TMJ) is infrequently reported. We present a case of septic arthritis of the TMJ following the extraction of the left upper second molar that occurred 1 week before beginning of symptoms. No evident predisposing factors were detected. Arthroscopic diagnosis of septic arthritis, lysis and lavage, and capsular stretch were performed. Cultures taken from the TMJ space grew Streptococcus sp. After 1 month of antimicrobial therapy the patient was asymptomatic and mandibular function was normal. Literature related to septic arthritis of TMJ and its treatment was reviewed. Different surgical procedures are available to treat this condition. Arthroscopy should be preferred as initial treatment on account of the possibility of drainage and accurate lavage under direct visualization of joint space, at the same time allowing confirmation of diagnostic hypotheses. Improving joint mobility with lysis of adhesions and capsular stretch in an early stage of disease may be helpful in stopping the fibrosis process.     

Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.     

Sources of cortical rhythms change as a function of cognitive impairment in pathological aging: a multicenter study.

OBJECTIVE: The present study tested the hypothesis that cortical electroencephalographic (EEG) rhythms. change across normal elderly (Nold), mild cognitive impairment (MCI), and Alzheimer's disease (AD) subjects as a function of the global cognitive level. METHODS: Resting eyes-closed EEG data were recorded in 155 MCI, 193 mild AD, and 126 age-matched Nold subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. RESULTS: Occipital delta and alpha 1 sources in parietal, occipital, temporal, and 'limbic' areas had an intermediate magnitude in MCI subjects compared to mild AD and Nold subjects. These five EEG sources presented both linear and nonlinear (linear, exponential, logarithmic, and power) correlations with the global cognitive level (as revealed by mini mental state examination score) across all subjects. CONCLUSIONS: Cortical EEG rhythms change in pathological aging as a function of the global cognitive level. SIGNIFICANCE: The present functional data on large populations support the 'transitional hypothesis' of a shadow zone across normality, pre-clinical stage of dementia (MCI), and AD.