Season of birth and risk of atopic disease among children and adolescents.

BACKGROUND: Season of birth (SOB) has been regarded as a risk factor for atopy. The aim of this study was to explore the relationship between season of birth (SOB) and later development of atopic disease in children and adolescents. METHODS: A total of 1,007 randomly selected subjects, 7 to 17 years of age, who were living in urban Copenhagen, Denmark were studied. All participants were interviewed about respiratory symptoms and possible risk factors for atopic disease. Skin test reactivity, serum total immunoglobulin E (IgE), and airway responsiveness were measured using standard techniques. RESULTS: The overall risk of atopy, as judged by skin test reactivity and serum total IgE, was the same regardless of SOB. On the contrary, asthma was more common in subjects born in the autumn compared with subjects born during the remaining part of the year (12.4% vs. 5.6%), OR = 2.40, 95% CI (1.56-3.94), p < 0.001. This was observed both for atopic asthma OR = 2.41, 95% CI (1.25-4.64), p = 0.007, non-atopic asthma, OR = 2.35, 95% CI (1.14-4.83), p = 0.02, and house dust mite (HDM) sensitive airway hyperresponsiveness, OR = 3.00, 95% CI (1.44-6.24), p = 0.002. Rhinitis and pollen allergy were not significantly related to SOB. CONCLUSIONS: Atopy itself is independent of season of birth, whereas asthma is more prevalent among subjects born during the autumn. Regarding asthma, these results suggest that the first months of life enclose a period of particular vulnerability towards environmental risk factors, especially exposure to aeroallergens like HDM.     

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion The relationship between acute otitis media and otitis media with effusion (OME) is uncertain and the aetiology of OME is multifactorial. Otitis media with effusion may be an inflammatory condition; both bacteria and viral infections could play a part in this inflammation. The four bacteria Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus and Branhamella catarrhalis cause 60% of the infections whereas S. pneumoniae accounts for up to 35%. IgA provides the dominant surface response to polysaccharide and lipopolysaccharide antigens, of which IgA₂ is the main subclass. Once the mucosa has been breached, most protection is provided by IgG. IgG₂ acts mainly against bacterial capsular antigens. This study looked at two groups of 50 children with and without OME who were aged between 3 and 10 years. The aims were to determine if, firstly, the levels of the serum immunoglobulins were different in the two groups, secondly whether these children made the appropriate antibody response to the capsular antigen to S. pneumoniae (PCP), and finally if there was a delay in the maturity of the IgA response. The total IgG, IgA and all subclass levels were measured using radial immunodiffusion. Levels of functional IgA and IgG were measured using ELISAs (25 patients in each group). The results were analysed with non‐parametric tests. The immunoglobulin levels were within the normal levels for both groups. There were very good correlations between the IgG total anti‐PCP and the IgG₂ anti‐PCP (R > 0.9, p = 0.001). There was a good correlation between the levels of both IgG total and IgG₂ anti‐PCP against IgA total anti‐PCP in both groups (R > 0.85, p > 0.01). This confirms a normal antibody response between both groups of patients. The ages of the controls and patients (50 samples) were correlated with increasing titres of circulating functional antibodies (P = 0.001). This is highly suggestive of a normal age‐related response. In conclusion, the findings were contradictory to our original hypothesis that there is a subtle difference in surface protection between children with and without OME. We believe that a previous history of recurrent acute otitis media is unrelated to the development of OME after 3 years of age.     

Routine postoperative chest x-ray following laparoscopic nephrectomy.

PURPOSE: To determine whether a routine postoperative chest x-ray is required following uneventful laparoscopic nephrectomy to rule out pneumothorax. METHODS: From June 1999 to May 2003, 308 laparoscopic nephrectomy cases were performed by 5 different surgeons. This consisted of 121 radical nephrectomies, 106 donor nephrectomies, 29 simple nephrectomies, 29 partial nephrectomies, and 23 nephroureterectomies. Of the 308 procedures, 186 postoperative chest x-ray s were obtained in the recovery room: 183 routinely and 3 for known intraoperative diaphragmatic injuries. Routine chest x-rays were not obtained in 122 cases due to the individual surgeon's preference. Of these 122 patients, 15 underwent chest x-ray performed while hospitalized secondary to pulmonary issues or fever. RESULTS: Of the 308 cases, 4 pneumothoraces were identified on chest x-ray. Three were identified in the patients who had intraoperative identification of diaphragmatic injury. The fourth pneumothorax was identified in a patient who did not have a routine postoperative chest x-ray but did have a chest x-ray obtained due to postoperative shoulder pain. The pneumothorax in this patient resolved spontaneously. No incidental findings existed of pneumothorax in any patient who underwent routine postoperative chest x-ray. CONCLUSION: In our series, a pneumothorax was identified either intraoperatively or based on postoperative clinical findings. None of the 183 routine postoperative chest x-rays changed patient management. Routine postoperative chest x-ray is not necessary in uncomplicated laparoscopic nephrectomy.     

Mechanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent

Background BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. Methods and Results Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC₅₀ of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC₅₀ of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%) and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC₅₀ value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t_1/2) uptake was very rapid (approximately 35 seconds), and washout t_1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. Conclusions F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.     

Sequential 99mTc-hydrazinonicotinamide-annexin V imaging for predicting response to chemotherapy.

This study was undertaken to evaluate changes in relative (99m)Tc-hydrazinonicotinamide (HYNIC)-annexin V tumor uptake over time in patients undergoing chemotherapeutic treatment at baseline and at 5-7 h and 40-44 h after treatment initiation. Imaging results are related to clinical outcomes, as assessed with response evaluation criteria in solid tumors (RECIST). METHODS: We prospectively included 20 patients (11 men and 9 women; mean age, 59.8 y; range, 22-75 y) scheduled for chemotherapy (n = 19) or bisphosphonate treatment (n = 1). Curable disease was present in 5 patients. The other patients had metastatic disease and were treated in a palliative setting. Three of the 20 enrolled patients were excluded from analysis: 1 patient ultimately refused the proposed chemotherapy treatment; because of difficulties with the labeling procedure, 1 patient did not receive a pretreatment scan; and 1 patient presented with an allergic reaction (rash and nausea) to the (99m)Tc-HYNIC-annexin V formulation. The remaining 17 patients underwent 3 scintigraphic scans with (99m)Tc-HYNIC-annexin V: before treatment and 5-7 h and 40-44 h after treatment initiation. The tumor response was evaluated with RECIST and related to observed changes in the ratios of tumor activity to background activity for the largest known lesion; values exceeding 25% the baseline value on either the 5- to 7-h scan or the 40- to 44-h scan were considered significant. RESULTS: With the proposed sequential imaging protocol and a 25% change threshold, responders to treatment could be separated from nonresponders with a 94% accuracy (16/17 patients). CONCLUSION: Sequential (99m)Tc-HYNIC-annexin V imaging may allow for assessment of the response to chemotherapy within 3 d after treatment initiation.     

Effect of pregnancy on the pharmacokinetics of metformin.

AIMS: To determine the effects of pregnancy on metformin pharmacokinetics. METHODS: Seven women with Type 2 diabetes mellitus taking metformin throughout pregnancy were studied on two occasions, once at 28-36 weeks gestation and once at least 8 weeks postpartum. Serum metformin concentrations were determined across a dosing interval using high-performance liquid chromatography. The areas under the serum concentration-time curve from 0 to 4 h post-dose (AUC0-4) and 0 to 8 h post-dose (AUC0-8) where possible, were compared in the pregnant and non-pregnant state. RESULTS: Metformin concentrations were lower in pregnancy in six subjects, with a mean (95% CI) AUC0-4 that was 69% (53.6, 84.8) of the postpartum value. The AUC0-4 of one subject was higher in pregnancy at 142% of the postpartum value. Overall, the mean (95% CI) AUC0-4 during pregnancy for all seven subjects was 80% (51.3, 107.8) of the postpartum value (P = 0.053, two-tailed t-test; P = 0.027, one-tailed t-test). CONCLUSION: These results are consistent with our hypothesis that the clearance of metformin increases in pregnancy as a result of enhanced renal elimination. A larger study is required to establish whether metformin dose adjustments are required in late pregnancy to maintain therapeutic effect.     

Tissue-engineered trachea: History, problems and the future.

This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartilage tissue to reepithelialization and revascularization of the prosthesis. In the end we propose a novel concept of 'in vivo bioreactor', defined as the design of a perfusion system inside the scaffold, and explain its potential application in the construction of a tissue-engineered trachea.     

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.