Comparison of effects of anti-IL-3, IL-5 and GM-CSF treatments on eosinophilopoiesis and airway eosinophilia induced by allergen

Allergic inflammation is dominated by eosinophils. IL-3, IL-5, and GM-CSF are involved in production and activation of eosinophils. IL-5 has been reported to be crucial for the induction of airway eosinophilia. However, the contribution of IL-3 and GM-CSF to allergic airway inflammation remains to be determined. To address this issue, ovalbumin-sensitized Balb/c mice were repeatedly exposed to allergen via airway route. Animals were pretreated intraperitoneally with neutralising anti-IL-3, anti-IL-5 and/or anti-GM-CSF antibodies. Newly produced inflammatory cells were pulse-labelled with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), which is incorporated into DNA during the cell mitosis. BAL and bone marrow cells were collected 24 h after the last allergen exposure, and differential cell counts and immunocytochemical detection of BrdU-labelled cells were performed. Anti-IL-5 strongly reduced both BAL and bone marrow eosinophilia, as well as the number of BrdU-positive BAL-granulocytes. In contrast, anti-IL-3 and anti-GM-CSF alone had little and no inhibitory effect on these responses, respectively. Even the combined treatment with anti-IL-3 and anti-GM-CSF showed only a non-significant tendency to attenuate these responses. These data suggest that the efficacy of treatments with anti-IL-3 and anti-GM-CSF is much weaker than that with anti-IL-5. IL-5 may be the preferred target to block eosinophilia in allergic diseases.     

Prevalence,diagnosis, and disease course of pertussis in adults with acute cough: a prospective,observational study in primary care

Background

Most cases of adult pertussis probably remain undiagnosed.

Aim

To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough.

Design and setting

Prospective observational study between 2007 and 2010 in primary care in 12 European countries.

Method

Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days.

Results

Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation.

Conclusion

Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation.     

Complications of type 2 diabetes mellitus in Ramallah and al-Bireh: The Palestinian Diabetes Complications and Control Study (PDCCS)

Background

Type 2 diabetes mellitus (T2DM) is a growing pandemic that will lead, if not managed and controlled, to frequent complications, poor quality of life, and high rates of disability and death. Little is known about T2DM complications in Palestine. The aim of this study is to estimate the prevalence of T2DM complications in Ramallah and al-Bireh governorate of Palestine.

A method for heart rate-corrected estimation of baroreflex sensitivity

OBJECTIVE: The relationship between the prevailing heart rate (HR) and the baroreflex sensitivity (BRS) is described in the present study together with a method for individual HR-corrected estimations of BRS. DESIGN: HR and BRS, determined with the sequence method, were measured in ten young healthy subjects during rest, stress, standing and bicycle exercise, i.e. at a wide range of HRs. RESULTS: BRS decreased exponentially with increasing HR. The relationship between the natural logarithm of BRS and HR was linear in each individual and could be described by the equation of a straight line. The equation describing the individual BRS-HR relationship could be derived either from BRS and HR measured during steady-state conditions or from the slope and average HR of the individual sequences occurring throughout the experimental protocol. The latter method was preferable since it did not require recordings during steady-state conditions. In order to eliminate the influence of differences in HR on BRS when comparing BRS between subjects, the equation describing the individual BRS-HR relationship was used to calculate BRS at a HR of 60 bpm, BRS(60), which ranged from 9.5 to 30.1 ms/mmHg for the 10 subjects. CONCLUSIONS: Considering the dramatic effect of a small difference in HR on BRS, especially at lower HRs, BRS should be estimated at a wide range of HRs in order to determine the HR-corrected BRS from the individual HR-BRS relationship. Otherwise, comparisons of BRS between different individuals, study groups or following drug treatment or other interventions would be highly dependent on differences in HR and thereby easily misinterpreted.     

The understanding of core pharmacological concepts among health care students in their final semester

Background

The overall aim of the study was to explore health care students´ understanding of core concepts in pharmacology.

Method

An interview study was conducted among twelve students in their final semester of the medical program (n?=?4), the nursing program (n?=?4), and the specialist nursing program in primary health care (n?=?4) from two Swedish universities. The participants were individually presented with two pharmacological clinically relevant written patient cases, which they were to analyze and propose a solution to. Participants were allowed to use the Swedish national drug formulary. Immediately thereafter the students were interviewed about their assessments. The interviews were audio-recorded and transcribed verbatim. A thematic analysis was used to identify units of meaning in each interview. The units were organized into three clusters: pharmacodynamics, pharmacokinetics, and drug interactions. Subsequent procedure consisted of scoring the quality of students´ understanding of core concepts. Non-parametric statistics were employed.

Results

The study participants were in general able to define pharmacological concepts, but showed less ability to discuss the meaning of the concepts in depth and to implement these in a clinical context. The participants found it easier to grasp concepts related to pharmacodynamics than pharmacokinetics and drug interactions.

Conclusion

These results indicate that education aiming to prepare future health care professionals for understanding of more complex pharmacological reasoning and decision-making needs to be more focused and effective.

     

Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial

BACKGROUND: The efficacy and safety of adding an angiotensin receptor blocker (ARB) in heart failure (HF) patients already taking an angiotensin-converting enzyme-inhibitor (ACE-I) plus an aldosterone antagonist is uncertain (especially if taking a beta blocker as well). The CHARM-Added trial describes the largest experience of using multiple inhibitors of the renin-angiotensin-aldosterone system (RAAS) together. METHODS AND RESULTS: 2548 HF patients, taking an ACE-I (936 no spironolactone/no beta blocker; 1175 no spironolactone/beta blocker; 199 spironolactone/no beta blocker; 238 sprionolactone/beta blocker), were randomized to placebo or candesartan and followed for 41 months (median). The primary outcome was cardiovascular death or HF hospitalization. In patients taking both a beta blocker and spironolactone (in addition to an ACE-I) at baseline, the candesartan:placebo hazard ratio was 0.85(95% CI 0.56, 1.29), compared to 0.85(95% CI 0.75, 0.96) in all randomized patients (interaction p value 0.49). The relative risk of discontinuation of candesartan (compared to placebo) because of hypotension, increased serum creatinine or hyperkalemia was not increased in patients taking spironolactone at baseline. CONCLUSIONS: An ARB may provide added benefit, at acceptable risk, in HF patients already taking spironolactone as well as an ACE-I and beta blocker. These findings must be confirmed in a prospective randomized trial before this approach can be recommended, routinely.     

Influence of Age, Sex and Blood Groups on 15 Blood Coagulation Laboratory Variables in a Reference Material Composed of 80 Blood Donors

Abstract. 15 blood coagulation and fibrinolysis variables were determined in 80 healthy blood donors. Males were shown to have significantly higher levels of factor VII and factor X, and in subjects with blood group O significantly lower levels of VIIIR:AG were observed. In individuals with blood group O a skewed distribution of VIIIR:AG suggested a mixed population of this antigenic determinant. No significant correlation (r<0.36) was found between age and any of the laboratory variables.