Systemic inflammatory mediators and cystic fibrosis genotype

Abstract. Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (F508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4±2.1 pg/ml vs. 5±0.9 pg/ml and 157±16 pg/ml vs. 88.8±16.4 pg/ml, respectively) (P<0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r=-0.37, P<0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P<0.01). No relationship was found between measured chemokines and age, sweat chloride levels, and pancreatic and nutritional status. Our study demonstrates an association between interleukin- 8, forced expiratory volume, and cystic fibrosis genotype. Hence, elevated interleukin-8 serum levels could serve as an indicator of an early inflammatory process and encourage the initiation of anti-inflammatory treatment.     

Adenosine bronchial provocation with computerized wheeze detection in young infants with prolonged cough: correlation with long-term follow-up

BACKGROUND: Chronic cough in babies is often associated with bronchial hyperreactivity (BHR). The objective documentation of BHR in babies is difficult, and acoustic methods have been described (provocative concentration of a substance causing wheeze) for conducting bronchial provocation tests (BPTs). We conducted a study to evaluate automatic computerized wheeze detection (CWD) in determining BHR in young infants with prolonged cough, and its correlation with the subsequent development of wheezing. METHODS: Infants aged < 24 months with prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response determined by CWD and auscultation by a physician. Telephone interviews with parents were conducted after 1 month and yearly for the next 3 years. RESULTS: A total of 28 infants who were 4 to 24 months old with prolonged cough were included in the study. Twenty of these infants (71.4%) had BHR as determined by a positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier, and in 9 tests it occurred at the same step as auscultation by a physician. Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing and shortness of breath, and 3 were well. Six of the eight adenosine-negative patients completed 3 years of follow-up and had no symptoms of BHR. CONCLUSIONS: Acoustic BPT is a technically feasible test for the detection of BHR in young infants. CWD provides an earlier detection of wheeze than stethoscope auscultation. In our group of infants, a positive acoustic BPT result had high correlation with symptoms compatible with BHR over the next 3 years.     

Is Pain Assessment of Community-Dwelling Persons With Advanced Dementia by Family and Paid Care Workers Feasible?

ContextThe experience of pain is aggravated among older persons with advanced dementia (OPAD). It is often undetected and therefore untreated because of their limited capacity to identify and report their symptoms. Therefore, it is crucial to improve the pain identification skills of those who know and live with them.ObjectivesTo compare the identification of pain among OPAD between family members and paid care workers and to compare the detection of pain through the use of two common assessment tools.MethodsThis study is a cross-sectional comparison conducted between 82 dyads of informants: the family member of OPAD and the paid care worker, a total of 164 individuals.MeasurementsThe study used two previously validated pain assessment tools for persons suffering from dementia: the Pain Assessment in Noncommunicative Elderly persons tool (PAINE) and Pain Assessment in Advanced Dementia tool (PAINAD), and a general impression question.ResultsBoth family members and paid care workers were able to successfully use both tools. The correlation between family members' ratings and paid care workers' ratings was statistically significant for all the assessments. The correlations between raters were higher when family members lived with the OPAD. The correlations between PAINE and PAINAD scores were moderate and significant, both among family members and paid care workers.ConclusionThis study shows that it is feasible to improve the assessment and identification of pain among OPAD, through the use of validated tools by family members and paid care workers, suggesting the potential to improve quality of care and quality of life of OPAD.     

The contribution of comprehensive geriatric assessment to primary care physicians

Background

To provide quality care to the growing number of older patients, primary care physicians (PCPs) will require support from geriatric specialists. Multidisciplinary comprehensive geriatric assessment (CGA) has been found to improve outcomes in older people. This study explored the contribution of CGA to the management of older patients by their PCPs; PCP attitudes to CGA; and PCP satisfaction with CGA.

Methods

Two hundred PCPs in an Israeli Preferred Provider Organization were interviewed as part of an evaluative study of the contribution of a national outpatient CGA program to older patients, their families and physicians.

Results

The main reasons for referral to CGA were cognitive impairment and rapid functional decline. Three domains described the contribution of CGA to PCPs: medical treatment, support in counseling patients, and treatment of cognitive impairment. About 69% of PCPs definitely agreed that CGA more fully addressed the physical, mental and social needs of patients than other consultative clinics. About half were very satisfied with the CGA staff’s attitudes to patients, their families and to the PCP.

Conclusions

CGA contributed significantly to the care provided to older patients by PCPs. The expansion of CGA services deserves consideration.

     

Carbamate poisoning: treatment recommendations in the setting of a mass casualties event

The threat of using chemical compounds by terrorists as weapons of mass casualties has been a rising concern in recent years. Carbamates, a group of reversible acetylcholinesterase inhibitors, could be potentially involved in such toxic mass casualty events because they can cause cholinergic crisis that could lead to fatality, similar to that of organophosphate poisoning. The medical management of carbamate poisoning consists of supportive measures and specific antidotal treatment, that is, the anticholinergic compound atropine. The administration of oximes, acetylcholinesterase reactivators, in carbamate poisoning is controversial because of the potential toxicity of oximes in conjunction with carbamate especially in the case of the carbamate—“carbaryl” poisoning. However, recent data suggest that this concern may be unwarranted. In this article, we review the current data regarding the pros and cons of using oximes against carbamates poisoning in a mass casualties event scenario. We also propose a new decision-making algorithm for the medical first responders in a mass casualties event suspected to be caused by a cholinergic substance (organophosphate or carbamate). According to this algorithm, treatment should consist of atropine and oxime regardless of the exact toxic compound involved. We speculate that in a mass casualties event, the benefits of using oximes outweigh the low level of potential risk.     

Clinical-physiologic correlations in acute asthma of childhood

Seventy-one patients who presented to the emergency room with acute asthma were evaluated to determine the relationship between common clinical signs and spirometric and transcutaneous arterial oxygen saturation (SaO2) measurements. Prior to treatment, a physical examination was performed, a clinical score assigned, and pulmonary function and SaO2 were measured. Although forced expiratory volume in 1 second (FEV1) and SaO2 had strong correlation with the overall clinical score (r2 = .47, .49 respectively), many patients with low clinical scores and apparent mild clinical disease had low FEV1 values (as low as 20% predicted). Of the individual components of the clinical score (ie, heart rate, respiratory rate, pulsus paradoxus, accessory muscle use, dyspnea, and wheezing), the degree of accessory muscle use correlated most closely with lung function followed by the degree of dyspnea and wheezing. Similarly, the degree of accessory muscle use correlated most closely with SaO2 followed by dyspnea and respiratory rate. Significant correlation (r2 = .59) was found between SaO2 and FEV1, although the range of SaO2 value for a given FEV1 was wide and some patients with low FEV1 values had normal SaO2 values. These results show that although clinically apparent severe disease and hypoxemia were always associated with low FEV1, their absence does not exclude the presence of airflow obstruction. It is concluded that for the optimal evaluation of acute asthma in children in the emergency room, clinical evaluation should be used in conjunction with objective laboratory measurements.