Psychosocial factors associated with chronic pain in adolescents

A number of psychosocial factors have been associated with the onset, exacerbation and/or maintenance of chronic pain in adolescents. The present study was conducted to evaluate the relative importance of vulnerability, reinforcement, and modeling. We compared 222 adolescents with chronic pain and no documented physiological etiology (headache, back, limb and abdominal pain) with 148 controls and their (respectively 183 vs. 127) parents. Analyses showed that adolescents with chronic pain are more vulnerable in terms of neuroticism, negative fear of failure, and (less) experienced social acceptance. Contrary to our expectations, the chronic pain group experienced less reinforcement for their pain behavior by both parents and peers than the control group. While the number of pain models was higher in the chronic pain group, no differences were found between their parents and those of the adolescents without chronic pain in pain experience, pain parameters, and pain coping. Regression analyses on the contribution of psychosocial factors to chronic pain and its parameters sustained the positive relation between vulnerability, (less) pain reinforcement, pain models and coping with pain. Furthermore, we also found evidence that gender differences have to be taken into account.     

Children referred for specialist care: a nationwide study in Dutch general practice.

BACKGROUND: Insight into referral patterns provides general practitioners (GPs) and specialists with a frame of reference for their own work and enables assessment of the need for secondary care. Only approximate information is available. AIM: To determine how often, to which specialties and for what conditions children in different age groups are referred, as well as how often a condition is referred given the incidence in general practice. METHOD: From data of the Dutch National Survey of Morbidity and Interventions in General Practice, 63,753 new referrals (acute and non-acute) were analysed for children (0-14 years) from 103 participating practices (161 GPs) who registered. Practices were divided into four groups. Each group of practices participated for three consecutive months covering a whole year altogether. We calculated referral rates per 1000 children per year and referability rates per 100 episodes, which quantifies the a priori chance of a condition being referred for specialist care. RESULTS: The referral rate varied by age from 231 for children under 1 year old to 119 for those aged 10-14 years (mean 159). The specialties mainly involved were ENT, paediatrics, surgery, ophthalmology, dermatology and orthopaedics. Referrals in the first year of life were most frequently to paediatricians (123); among older children the referral rate to paediatricians decreased (mean 36). Referrals to ENT specialists were seen particularly in the age groups 1-4 (71) and 5-9 (53). For surgery, the referral rate increased by age from 19 to 34. Differences between boys and girls were small, except for surgery. The highest referral rates were for problems in the International Classification of Primary Care (ICPC) chapters: respiratory (28); musculoskeletal (25); ear (24) and eye (21). Referability rates were, in general, low for conditions referred to paediatrics and dermatology and high for surgery and ophthalmology. The variation in problems presented to each specialty is indicated by the proportion of all referrals constituted by the 10 most frequently referred diagnoses: from 35% for paediatrics to 81% for ENT; for ophthalmology, five diagnoses accounted for 83% of all referrals. CONCLUSIONS: The need for specialist care in childhood is clarified with detailed information for different age categories, specialties involved and variation in morbidity presented to specialists, as well as the proneness of conditions to be referred.     

Skin tests, T cell responses and self-reported symptoms in children with allergic rhinitis and asthma due to house dust mite allergy

Background In allergic responses, a distinction is made between an early-phase response, several minutes after allergen exposure, and a late-phase response after several hours. During the late phase, eosinophils and T cells infiltrate the mucosa and play an important role in inflammation. Objective The aim of this study was to examine the relationship between allergen-induced late-phase skin responses and in vitro T cell reactivity. In addition, the relationship between allergen-induced skin or T cell responses and the severity of self-reported symptoms was studied in children with house dust mite allergy. Methods A total of 59 house dust mite-allergic children (6–18 years) were recruited in general practice. These children or their parents rated their nasal and asthma symptoms on diary cards during 1 month. Allergen skin tests were performed and read after 15 min (early phase) and 6 h (late phase). Allergen-specific T cell proliferation was determined, and Th2 cytokine (IL-5 and IL-13) secretion was analysed. Results The size of the late-phase skin response correlated with in vitro T cell proliferation (r_s=0.38, P=0.003) but not with Th2 cytokine secretion (r_s=0.16, P=0.2 for both IL-5 and IL-13). Moreover, the late-phase skin response and T cell proliferation correlated with asthma symptoms (r_s=0.30, P=0.02 for skin response and r_s=0.28, P=0.03 for T cell proliferation) but not with nasal symptoms (r_s=0.19, P=0.15 for skin response and r_s=0.09, P=0.52 for T cell proliferation). The early-phase skin response correlated with the nasal symptom score (r_s=0.34, P=0.01) but not with asthma symptom scores (r_s<0.005, P=0.97). Conclusion In this study, the late-phase skin test response correlated with in vitro T cell proliferation but not with Th2 cytokine secretion. We found weak or no correlations between late-phase skin responses and symptoms of asthma or rhinitis in children with house dust mite allergy. This suggests that late-phase skin responses reflect certain T cell properties but are of limited value for the evaluation of airway symptoms in atopic children.     

Targeting of doxorubicin to the urinary bladder of the rat shows increased cytotoxicity in the bladder urine combined with an absence of renal toxicity

Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein lysozyme via the acid-sensitive cis-aconityl linker. All free amino groups of the lysozyme were used for drug attachment to achieve intact excretion of the doxorubicin-aconityl-lysozyme conjugate into the bladder. In the bladder, the cytotoxic drug should be regenerated through acidification of the urine. First, the doxorubicin-aconityl-lysozyme conjugate was tested in rats for its target specificity and general toxicity. Wistar rats were injected intravenously with 2 mg/kg free doxorubicin or 10 mg/kg lysozyme-conjugated doxorubicin. Total urinary excretion of doxorubicin was about 10 times higher if the drug was coupled to lysozyme (39 +/- 3% versus 4.4 +/- 0.4%). Free doxorubicin had no detectable toxic effects on heart, liver and lung but caused severe renal damage (proteinuria, N-acetylglucosaminidase excretion and glomerulosclerosis). None of the rats injected with doxorubicin-lysozyme conjugate showed such renal toxicity. Second, we tested whether doxorubicin could be released from the conjugate in the bladder through acidification of the urine and if the released doxorubicin could still exert a cytotoxic effect. Doxorubicin-aconityl-lysozyme (2 mg/kg conjugated doxorubicin, i.v.) was administered in rats with acidified urine (pH 6.1 +/- 0.1) and in rats with a high urinary pH (8.2 +/- 0.4). Ten times more doxorubicin was released from the conjugate in the group with acidified urine (15 +/- 7% versus 1.7 +/- 0.1%). In agreement with this, cytotoxicity was also higher in the low pH group (IC50 of 255 +/- 47 nM versus 684 +/- 84 nM doxorubicin). In conclusion, a specific delivery of doxorubicin to the urinary bladder combined with a reduced toxicity of doxorubicin in the kidneys can be achieved by coupling this anti-tumor drug to the low-molecular weight protein lysozyme via an acid-labile linker. A release of cytotoxic doxorubicin in the urinary bladder can be achieved by acidification of the urine. This technology, after further optimization, may provide an interesting tool for the treatment of bladder carcinoma.     

Review article: nitroimidazole resistance in Helicobacter pylori

The efficacy of a nitroimidazole-containing regimen for the treatment of Helicobacter pylori infection is decreased by nitroimidazole resistance. Nitroimidazoles are meta- bolized by H. pylori by several nitro-reductases of which an oxygen-insensitive NADPH nitroreductase encoded by the rdxA gene is the most important. Null mutations in this gene are associated with resistance.
Susceptibility testing to nitroimidazoles may give variable results. This is not only related to the slow growth under specific conditions, but also to variability in the activity of the other nitroreductases and the ability to deactivate toxic metabolites of an NI and to repair DNA damage. Moreover, co-infections with resistant and susceptible bacteria are frequently found. The presence of nitroimidazole resistance is related to the previous use of this drug. The prevalence of resistance is rising and nowadays 10–50% of the isolates are resistant.
Resistance reduces the efficacy of a treatment regimen to a variable degree. This is related to efficacy of the other components of the regimen and the treatment duration. Whether a nitroimidazole is still effective in resistant strains remains unresolved.
When nitroimidazole resistance is present, a nitro-imidazole-containing regimen should be avoided or a regimen with other highly effective components should be used.     

Chronic pain and its impact on quality of life in adolescents and their families

OBJECTIVE: To study chronic pain not caused by somatic disease in adolescents and the effect of pain on the quality of life of the adolescents and their families. METHODS: One hundred twenty-eight youngsters (12-18 years) who had reported chronic pain kept a 3-week diary of their pain and completed a questionnaire on quality of life. Their mothers completed a questionnaire on the impact of their youngster's pain on the family. RESULTS: The most prevalent pains were limb pain, headache, abdominal, and back pain. The pain increased during the day, with the highest frequency around dinner time and the highest intensity around bedtime. Girls reported more intense and more frequent pain than boys. The higher the intensity and frequency of the pain, the lower the self-reported quality of life of the female or male adolescent, especially regarding psychological functioning (e.g. feeling less at ease), physical status (a greater incidence of other somatic complaints), and functional status (more impediments to leisure and daily activities). Chronic pain also had a negative impact on family life. The mothers reported restrictions, particularly in social life, and problems dealing with the stress of the adolescent's pain. CONCLUSIONS: Chronic pain, not caused by somatic disease, was present to a higher degree in girls; the pain increased during the day and had a negative impact on quality of life of the adolescents and the family. There is a need for future research aimed at identifying risk factors for chronic pain and pain-associated quality of life in children and adolescents.