Comparison of clinical characteristics of influenza and respiratory syncytial virus infection in hospitalised children and adolescents

While significant morbidity due to respiratory syncytial virus (RSV) infection in the paediatric population has been well acknowledged, little is known about the burden of influenza in primarily healthy children in Europe. In our institution, a University Childrens Hospital in Switzerland, medical staff were encouraged to take nasopharyngeal specimens for multiplex polymerase chain reaction assays for influenza A and B, RSV and several other pathogens from patients hospitalised with respiratory symptoms. We took advantage of this strategy and performed a retrospective study to compare specific characteristics of influenza virus infections with those of RSV during two consecutive winter seasons. Overall, 126 patients were positive for RSV and 60 patients were positive for influenza (type A: 45; type B: 15). The median age of children with RSV, influenza A, and influenza B infection was 4 months; 2 years and 4 months; and 6 years and 2 months, respectively (P<0.001). Fever and cough predominated in children with influenza infection whereas cough, rhinorrhoea, feeding difficulties and dyspnoea were the major symptoms in children with RSV infection. Of patients with influenza, 41% suffered from lower respiratory tract infection compared to 91% of those with RSV infection (P<0.001). Of 60 patients hospitalised with influenza, 12 (20%) experienced febrile convulsions. None of the patients with influenza had been immunised in the respective winter season, although 27% of them had at least one underlying medical condition that would have counted as an indication for immunisation in Switzerland. Conclusion: influenza virus infections, like respiratory syncytial virus infections, are a major cause of hospitalisation in children with respiratory illness during the winter season. Since it is impossible to make an aetiological diagnosis on clinical grounds, it is important to apply specific diagnostic tools in children hospitalised with respiratory illness in order to better characterise the relative burden of disease caused by the respective agents.Abbreviations LRTI lower respiratory tract infection - NPS nasopharyngeal specimens - RAT rapid antigen test - RSV respiratory syncytial virusThis work forms the medical thesis of Susanne Meury at the Medical Faculty, University of Basel, Switzerland.     

Cervical immunoglobulin A and altered vaginal flora in pregnant women with threatened preterm delivery

The aim of our study was to investigate the cervical immunoglobulin A concentration in women with threatened preterm delivery. Immunoglobulin A concentration in the cervical mucus of 80 women with symptoms of preterm delivery was measured using radial immunodiffusion. The results were compared with those of 60 healthy pregnant women. Concentrations of immunoglobulins in maternal serum were also measured. There was no significant difference of cervical immunoglobulin A (IgA) concentration between women with threatened preterm delivery and controls: 53.98 (0.0-189.7) mg/l vs. 61.7 (1.4-400.9; p<0.4) mg/l (median, range). The median of cervical IgA levels in the group of threatened preterm delivery did not differ significantly between patients delivered preterm (n=34) or at term (n=46): 38.3 (0.0-187.9) vs. 65.7 (1.4-189.7; p<0.2) mg/l. Women with a normal vaginal flora showed a significantly higher cervical IgA concentration than those with a pathological colonization: 72.7 (0.0-187.9) vs. 42.5 (0.0-189.7) mg/l. Patients with a pathological vaginal smear and preterm delivery had the lowest IgA levels (35.0; 0.0-187.9 mg/l). Measurement of cervical IgA concentration does not differentiate between women who deliver before or at term.     

Severe ADAMTS-13 deficiency in childhood

Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic disorder with high morbidity and significant mortality. The primary form of TTP is caused by severe deficiency, acquired or hereditary, of the von Willebrand factor cleaving protease (VWF-CP), ADAMTS-13. Because TTP occurs less frequently in children, general pediatricians are not well informed about the spectrum of clinical symptoms and altered laboratory values, increasing the risk of nondiagnosis and possible fatal outcome. If renal involvement is present, the condition can easily be misdiagnosed as hemolytic-uremic syndrome (HUS). We present a case series of children with severe VWF-CP deficiency with emphasis on the clinical heterogeneity responsible for misdiagnosis and inappropriate treatment. The inherited form may involve onset of symptoms ranging from isolated thrombocytopenia to the full clinical picture characteristic of classical TTP. The most common assumed diagnoses of oligosymptomatic forms are immune thrombocytopenia (ITP) and Evans syndrome, respectively. Accordingly, this article is directed towards pediatricians on neonatal and intensive care units, as well as their colleagues specializing in nephrology, hematology, and neurology.     

Dose-dependent activation of Ca2+-activated K+ channels by ethanol contributes to improved endothelial cell functions

BACKGROUND: Regular moderate alcohol (EtOH) intake seems to protect against both coronary artery disease and ischemic stroke, whereas the risk increases with heavy EtOH consumption. Effects of EtOH on endothelial cell function may be relevant to these disparate effects. Potassium channels play an important role in the regulation of endothelial cell functions. Therefore, we investigated whether Ca-activated K channels (BKCa) are modulated by EtOH. Furthermore, we examined whether EtOH-induced changes of endothelial nitric oxide (NO) formation and cell proliferation are due to BKCa activation. METHODS: The patch-clamp technique was used to investigate BKCa activity in cultured human umbilical vein endothelial cells (HUVEC). NO formation was analyzed by using the fluorescence dye 4,5-diaminofluorescein. Endothelial proliferation was examined by using cell counts and measuring [H]thymidine incorporation. RESULTS: EtOH dose-dependently (10-150 mmol/liter) modulated BKCa-activity, with the highest increase of open-state probability at a concentration of 50 mmol/liter (n = 13; p < 0.05). Inside-out recordings revealed that this effect was due to direct BKCa activation, whereas open-state probability was not changed in cell-attached recordings after pertussis toxin preincubation. EtOH (10 and 50 mmol/liter) caused a significant increase of NO levels, which was blocked by the highly selective BKCa inhibitor iberiotoxin (100 nmol/l; n = 30; p < 0.05). Higher concentrations of EtOH (100 and 150 mmol/liter) significantly reduced NO synthesis (n = 30; p < 0.05). Both methods revealed a significant increase of HUVEC proliferation, which was inhibited by iberiotoxin (n = 30; p < 0.05). At a concentration of 150 mmol/liter, EtOH caused a significant reduction of endothelial proliferation. CONCLUSIONS: EtOH directly activates BKCa in HUVEC, leading to an increase of endothelial proliferation and production of NO. These results indicate a possible beneficial effect of low-dose EtOH on endothelial function, whereas higher concentrations must be considered as harmful.     

Risk factors for complications after pancreatic head resection

BACKGROUND: Postoperative morbidity is high after pancreatic head resections. Data about risk factors are controversial. The aim of this study was to evaluate risk factors for complications after pancreatic head resection and to assess whether the complication rate changed during the study period. METHODS: Data of 301 patients undergoing pancreatic head resection were recorded prospectively. Risk factors were assessed by multivariate analysis. The first and second part of the study period were compared. RESULTS: Mortality was 3%. Overall and surgery-related complications occurred in 42% and 28%, respectively. Independent risk factors for postoperative morbidity were impaired renal function (odds ratio [OR] 2.7), absence of preoperative biliary drainage (OR 1.9), and resection of other organs (OR 3.2). Complication rate, duration of surgery, amount of blood transfused, and length of hospital stay decreased during the study period. CONCLUSIONS: Increasing hospital experience decreased complication rates. Patients with risk factors should be considered for transferal to specialized centers.     

Impact of neoadjuvant therapy of perioperative morbidity in patients with esophageal cancer

BACKGROUND: Conflicting results of preoperative radiochemotherapy in patients with esophageal cancer have been obtained; only patients with a complete pathological response seem to benefit from this therapy. However, there is evidence that preoperative radiochemotherapy leads to considerable postoperative morbidity. Therefore, postoperative morbidity was retrospectively investigated in 82 patients with an esophageal cancer who received preoperative radiochemotherapy. METHODS: One hundred twenty-two consecutively operated on patients were included (1991 to 2001). Preoperative radiochemotherapy was initiated in 1994 for cT >1, cNx, cM0 regardless of histology (n = 82); 36 Gy was applied (1.8 Gy daily, days 1 to 5, weeks 1 to 4), concurrently 5-fluorouracil (500 mg/m(2) days 1 to 5, weeks 1 to 4), and cisplatin (20 mg/m(2) days 1 to 5, weeks 1 and 4). Postoperative morbidity was categorized as surgery- and nonsurgery-related morbidity. Survival was calculated by the Kaplan-Meier method. Results were stratified into histology and compared with patients who were operated on only (n = 40). RESULTS: Complete pathological response after preoperative radiochemotherapy was achieved in 22%. An increase in surgery-related morbidity was observed after preoperative radiochemotherapy due to lesion of recurrent nerve (38% versus 12.5%, P = 0.009), as well as a marked difference in pulmonary morbidity (57% versus 37.5%, P = 0.05). The proportion of combined morbidity was increased after preoperative radiochemotherapy (49.4% versus 15%, P = 0.02), which led to a considerable prolongation of postoperative hospital stay (33 versus 21 days median, P = 0.0022). Patients with a longer postoperative hospital stay (>30 days; 43.2%) lived significantly shorter than patients with a shorter postoperative hospital stay (56.8%, P = 0.001). There was no statistical survival benefit in the neoadjuvant treated group. However, calculation of long-term survival revealed a significant survival advantage in patients with squamous cell cancer and a complete pathological response compared with patients without response (median 642 days versus 302, P = 0.026). CONCLUSIONS: Perioperative morbidity was significantly increased after preoperative radiochemotherapy. Long-term survival was clearly affected by the length of postoperative stay. Therefore, we need better patient selection for application of preoperative radiochemotherapy.     

Application of Bispectral Index and Narcotrend index to the measurement of the electroencephalographic effects of isoflurane with and without burst suppression

BACKGROUND: The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) has recently been introduced as an intraoperative monitor of anesthetic state, based on a classification scheme originally developed for visual assessment of the electroencephalogram. The authors compared the performance of the Narcotrend index (software version 4.0) to the Bispectral Index (BIS, version XP; Aspect Medical Systems, Natick, MA) as electroencephalographic measures of isoflurane drug effect during general anesthesia. METHODS: The authors observed 15 adult patients scheduled to undergo radical prostatectomy with a combined epidural-isoflurane general anesthesia technique. At least 45 min after induction of general anesthesia, during a phase of constant surgical stimulation, end-tidal isoflurane concentrations were varied between 0.5 and 2.0 multiples of minimum alveolar concentration, and the BIS and the Narcotrend index were recorded. The prediction probability (PK) was calculated for the BIS and the Narcotrend index to predict isoflurane effect compartment concentration for each measure. The correlation analysis of the BIS and the Narcotrend index with the isoflurane effect compartment concentration was obtained by pharmacodynamic modeling based on two sigmoidal curves to account for the discontinuity in both indices with the onset of burst suppression. RESULTS: The prediction probabilities were indistinguishable (BIS PK = 0.72 +/- 0.07 (mean +/- SD); range, 0.61-0.84; Narcotrend index PK = 0.72 +/- 0.10; range, 0.51-0.87), as were the correlations between the electroencephalographic measures and isoflurane effect compartment concentrations (BIS R = 0.82 +/- 0.12; Narcotrend index R = 0.85 +/- 0.09). The pharmacodynamic models for the BIS and the Narcotrend index yielded nearly identical results. CONCLUSIONS: The BIS and the Narcotrend index detected the electroencephalographic effects of isoflurane equally. Combining two fractional sigmoid Emax models adequately described the data before and after the onset of burst suppression.     

PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study

The aim of this study was to evaluate the use of [¹⁸F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2–T4) were studied by FLT-PET. For comparison, [¹⁸F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUV_mean=3.4±1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUV_mean=2.4±1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUV_FLT: 3.2 vs SUV_FDG: 4.7 in primary tumours and SUV_FLT: 2.9 vs SUV_FDG: 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG (P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum.