Anti-Pseudomonas aeruginosa antibodies and lung disease in cystic fibrosis

The aim of our study was to diagnose and to control three aspects of the evolution of lung disease in CF: the absence of infection, the intermittent colonization and chronic infection by Pseudomonas aeruginosa. Therefore a study of anti-pseudomonas antibodies (Ab) (anti-protease, anti-elastin and antihexo-toxin A) for diagnosis and follow-up of CF patients was considered. Moreover, we related the presence of Ab to the sputum culture, to FEV1, to patient age and to genotype. Tbe Ab were dosed in 121 patients by quantitative ELISA method. Values < 1: 500 were considered negative, values> 1: 500 and < 1:1250 borderline, and > 1:1250 positive. 16.5% of patients did not have Ab, 17% had borderline values and 69.5% had positive values. All the patients with negative Ab had negative sputum culture; 47% of patients with borderline values had at least one positive culture while 53% were negative. 87% of patients with positive values had chronic colonization, 13% intermittent colonization. The increase in the Ab rate is statistically related to a more severe lung disease (p < 0.013). The presence of a severe mutation (?F 508) is related to positive values of Ab. Evaluation of anti-Pseudomonas aeruginosa is an important tool for diagnosis and follow-up of CF lung disease     

Comparison of 0.125% bupivacaine and 0.2% ropivacaine in obstetric analgesia

This comparative study of low doses of ropivacaine was conducted in order to identify the most effective form of analgesia during labour with the aid of supplementary low doses of fentanyl and clonidine. 60 ASA I and II parturient primipares who had asked for epidural analgesia were randomly assigned to two groups. Group R was given 5-7 ml 0.2% ropivacaine and Group B 0.125% bupivacaine with both groups receiving 75 ng clonidine and 50 ng fentanyl with their first bolus of local anaesthetic. The parameters measured included the speed and spread of the sensory blockade and the scale of any motor blockade. The material haemodynamics and VAS pain relief scores were also measured at 30-minute intervals during labour and all side-effects (nausea, vomiting, localised or generalised itching, headache etc) were also monitored. Apgar anaesthetics and other drugs was decided on the basis of the VAS score (a further dose was given to women with a VAS of > 3-4). The study was completed by a telephone interview 6 months after delivery and the data were analysed using the Student's t-test and the chi 2 test. The analgesic effect was satisfactory in both groups and no statistically significant differences were found between the two groups under most of the headings analysed, apart from the top-up doses needed to maintain adequate analgesia. The average time between the first VAS to parturition was 292 mns in Group B and 267 mns in Groups R. Top-up doses of local anaesthetic (2.35 vs 5.05) came on average to 15.8 ml in Group B compared to 24.1 ml in Group R. There were 20% Caesarian sections in Group R and 13.8% in Group B. Optimum analgesia was achieved in Group R, the level of analgesia was insufficient or barely sufficient in 3.3% of cases. There was no Apgar score < 7 in either group. It was therefore concluded that both bupivacaine and ropivacaine offer excellent analgesia during labour and have no significant side effects on mothers or babies.     

Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity.

Monoclonal antibody (mAb) 806 is a novel epidermal growth factor receptor (EGFR) antibody with significant antitumor activity that recognizes a mutant EGFR commonly expressed in glioma known as delta2-7 EGFR (de2-7 EGFR or EGFRvIII) and a subset of the wild-type (wt) EGFR found in cells that overexpress the receptor. We have used two human xenograft mouse models to examine the efficacy of mAb 806 in combination with mAb 528, a prototypical anti-EGFR antibody with similar specificity to cetuximab. Treatment of nude mice, bearing s.c. or i.c. tumor human xenografts expressing the wt or de2-7 EGFR, with mAbs 806 and 528 in combination resulted in additive and in some cases synergistic, antitumor activity. Interestingly, mAb 528 was also effective against xenografts expressing the ligand independent de2-7 EGFR when used as a single agent, showing that its antitumor activity is not merely mediated through inhibition of ligand binding. When used as single agents, neither mAbs 806 or 528 induced down-regulation of the de2-7 EGFR either in vitro or in vivo. In contrast, the combination of antibodies produced a rapid and dramatic decrease in the total cell surface de2-7 EGFR both in vitro and in xenografts. Consistent with this decrease in total cell surface de2-7 EGFR, we observed up-regulation of the cell cycle inhibitor p27(KIP1) and a decrease in tumor cell proliferation as measured by Ki-67 immunostaining when the antibodies were used in combination in vivo. Thus, mAb 806 can synergize with other EGFR-specific antibodies thereby providing a rationale for its translation into the clinic.     

Gastric and masticatory performances in full‐arch immediate loading rehabilitated patients

Full‐arch immediate loading implant rehabilitations provide patients with compromised dentition an effective treatment to improve their aesthetic and function. Aim of this prospective cohort study was to investigate the correlation between masticatory ability and gastric emptying rates among these patients. Ten subjects (five men and five women) with compromised dentition were tested in two occasions: before treatment and 30 days after the immediate loading rehabilitation. Masticatory ability was evaluated using the sieves test, and the gastric half emptying time (T_1/2) was assessed by means of the ¹³C‐octanoic acid breath test. A statistically significant increment (P < 0·005) in masticatory ability was found only in reference to the particles smaller than or equal to 4·75 mm, whereas the gastric emptying rate showed a statistically significant reduction between pre‐ and post‐treatment (P = 0·003). A moderate negative correlation (rho = 0·64, P = 0·048) between the percentage change in masticatory ability and the percentage change in gastric emptying rate was evidenced. Patients with compromised dentition rehabilitated with full‐arch immediate implant prostheses present a significant improvement of the gastric process.     

Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study

We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation.     

Treatment of early stage chronic hepatitis C virus infection

Introduction: Treatment of Hepatitis C Virus (HCV) with direct acting antivirals (DAAs) is able to achieve the cure of infection in almost the totality of patients, independently of the characteristics of the individual and the virus, using short treatment schedules, and without the need of ribavirin. The high cost of DAAs is the main limiting factor for universal treatment of HCV. However, there is a strong evidence that treatment of infection at the early stage of disease may be the most rewarding approach.

Areas covered: This review evaluates the aspects underlying the benefit of treating chronic HCV infection at the early stage of disease. It outlines the considerations that have to be taken into account when planning treatment in patients with HCV and minimal liver disease, assessing the positive reflex of viral eradication on several HCV-associated extra-hepatic conditions such as the risk of lymphoma, insulin-resistance and glycaemic control, and renal function. Lastly, it also covers the improvement of patients’ quality of life and the pharmaco-economic aspects associated with early treatment.

Expert commentary: Treatment of patients with HCV and minimal liver disease is associated with a beneficial, pleiotropic effect of viral eradication that goes beyond the simplistic consideration of the improvement in liver disease-related outcomes.