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Background The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown. Objective To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma. Methods Stable asthmatics had spirometry, skin prick test, measurement of Fe NO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. Results A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation ( HR 7.6 95% CI: 1.6-35.2, P=.010) as did having Fe NO >25 ppb ( HR 3.4 95% CI: 1.1-10.4, P=.033). Conclusion and Clinical Relevance Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and Fe NO, could be included in the risk assessment of patients with asthma in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Exenatide, a glucagon-like peptide- 1 (GLP-1) analogue, is an effective glucoregulator for treating overweight individuals, not at target HbA 1 c. This prospective study aimed to determine whether estimates of beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) predict response to Exenatide treatment. Methods: Prospective data on 43 type 2 diabetes patients were collected for up to 2.8 years in UK primary care. HOMA-B and HOMA-S were estimated prior to initiating Exenatide, with monitoring of cardio-metabolic risk factors. Results: Mean (SD) age and BMI pre-treatment were 54.1 ± 10.5 years and 35.7 ± 7.5 kg/m² respectively. HbA m1c decreased (mean reduction 0.9 %, p = 0.04; p for trend = 0.01) in 61 % of patients. In univariate analyses, HOMA-S as a measure of insulin sensitivity was inversely (β = - 0.41, p 0.009) related to change in HbA m1c, with no relation for HOMA-B. In a random effects regression model that included age at baseline, weight, LDL-C, HDL-C and triglycerides, change in HbA m1c (β = - 0.14, p < 0.001) and HDL-C (β = - 0.52, p = 0.011) were independently associated with increasing insulin sensitivity (r² = 0.5²). Thus patients with greater measured insulin sensitivity achieved greater reduction in HbA m1c independent of the factors described above. In logistic regression those in the highest tertile of log-HOMA-S were 45 % more likely to have a fall in HbA m1c with an odds ratio (OR) of 0.55 (95 % CI 0.47-0.66) p < 0.0001 (log likelihood ratio for the model χ² = 71.6, p < 0.0001). Discussion: Patients with greater measured insulin sensitivity achieve greater reduction in HbA m1c with Exenatide. Determination of insulin sensitivity may assist in guiding outcome expectation in overweight patients treated with GLP-1 analogues. [ABSTRACT FROM AUTHOR]

This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood-brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF:serum albumin ratio indicative of impairment of the blood-CSF and blood-brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-alpha levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood-brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood-brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-alpha was associated with a good prognosis. [ABSTRACT FROM AUTHOR]

The authors report a case of Leydig cell tumor in a 46-year-old woman who first presented with severe clinical hyperandrogenism and associated complex medical history. Investigations revealed markedly raised serum concentrations of testosterone (28.3 nmol/l) and free androgen index (54.4), whereas sex hormone binding globulin, random cortisol, androstenedione, 17-hydroxyprogesterone and dehydroepiandrosterone sulphate concentrations were all within the normal range. Transabdominal ultrasound and computed tomography scan of the pelvis and abdomen showed a slightly bulky right ovary, but no other abnormalities. An ovarian source of androgens was suspected and surgery was arranged. Following a three-year history of defaulting appointments due to agoraphobia, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and intraoperative selective ovarian venous sampling. Histopathological examination revealed a 2 cm Leydig cell tumor within the right ovary. Successful intraoperative ovarian venous sampling demonstrated significantly elevated testosterone levels (>260 nmol/l) from the right ovarian vein. Hyperandrogenaemia normalized post-operatively. The patient showed significant regression of clinical signs and symptoms, including the anxiety disorder. Clinical presentation, biochemistry and imaging modalities should allow to detect androgen-secreting ovarian tumors, while selective venous sampling should be reserved for patients whom uncertainty remains. The present case confirms that androgen-secreting ovarian tumors represent a diagnostic and therapeutic challenge. They have to be considered in the differential diagnosis of severe hyperandrogenism even in peri-menopausal women. Although selective venous sampling is of diagnostic value, however, its impact on future management should be considered on individual basis. [ABSTRACT FROM AUTHOR]

Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P.aeruginosa was subsequently isolated (492.75 μg/ml vs. 1339.43 μg/ml, p = 0.018). Those with the CD14 -159CC genotype had a significantly increased risk of early infection with P.aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P.aeruginosa. [ABSTRACT FROM AUTHOR]

We have previously reported a relationship between increased airway responsiveness (AR) in infancy and reduced childhood lung function. The current study aimed to determine whether the Arg16Gly polymorphism of the β2 adrenoceptor (β2AR) gene was important to this relationship. A cohort that initially numbered 253 individuals underwent assessments of AR and lung function aged 1 month, 6 and 11 years; genotyping for polymorphisms of the β2AR was performed. At 1 month of age, the genotype homozygous Arg16 ( n=24) was associated with a mean increase in log dose–response slope (AR) of 0.27 [95% confidence interval (CI) 0.07, 0.49] compared with the genotype homozygous Gly16 ( n=58), P=0.01. At 11 years of age, the genotype homozygous Arg16 ( n=35) was associated with a mean reduction in the percentage of forced expiratory volume in 1 s of 5.3% [95% CI 0.3, 10.2] compared with the genotype homozygous Gly16 ( n=65), P=0.03. There was no association between the Arg16Gly polymorphism and atopy or diagnosed asthma. However, nine of 69 individuals with the genotype homozygous Gly16 were admitted to hospital with asthma compared with five out of 111 individuals with the remaining genotypes ( P<0.05). The Arg16Gly polymorphism may be important to the association between increased AR in infancy and reduced lung function in childhood and may also be a determinant of asthma severity in children but not asthma per se. [ABSTRACT FROM AUTHOR]

Abstract Aims To examine the influence of age on glucose homeostasis in a population of healthy, non-diabetic hospital personnel. Methods One hundred and twenty female and 71 male non-diabetic individuals (fasting plasma glucose < 7.0 mmol/l) were fasted overnight prior to blood sampling. Glycated haemoglobin (HbA1c ), fasting plasma glucose (FPG) and fasting plasma insulin (FPI) were measured using a BioRad Diamat automated HPLC, a Hitachi 747 analyser and a sensitive in-house radioimmunoassay, respectively. Mathematical modelling of the fasting glucose and insulin pairs (homeostasis model assessment (HOMA)) generated indices of pancreatic β cell function, HOMA-B and tissue insulin sensitivity HOMA-S. Results Spearman rank correlation analysis showed that in the whole group there was a significant negative correlation between age and HOMA-B (r s = -0.218, P = 0.0022) and a significant positive correlation between age and both HbA1c (r s = 0.307, P = 0.0001) and FPG (r s = 0.26, P = 0.0003). There was no correlation between age and either FPI (r s = -0.08, P = 0.266) or HOMA-S (r s = 0.024, P = 0.75). Analysis by gender showed the above associations to be present in the females (r s = -0.243, P = 0.0076; r s = 0.304, P = 0.0007; r s = 0.32, P = 0.0004 for age vs. HOMA-B, HbA1c , and FPG, respectively). Again there was no correlation of age with FPI or insulin sensitivity. In the males there was a significant correlation of HbA1c with age (r s = 0.35, P = 0.002), but no significant correlation of age with any of the other parameters. Conclusions Glycaemic control deteriorates with age in healthy, non-diabetic individuals. Age-related rises in FPG and haemoglobin A1c result from a small but steady decline in pancreatic β cell function. Diabet. Med. 19, 254–258 (2002). [ABSTRACT FROM AUTHOR]