Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.     

Ulnar recurrent adipofascial flap for reconstruction of massive defects around the elbow and forearm.

An ulnar recurrent adipofascial flap was raised and turned over to reconstruct massive defects around the elbow and forearm after wide resection of malignant tumours. Compared to the fasciocutaneous flap, the ulnar recurrent adipofascial flap has the following advantages: (1) a larger flap can be harvested without the problem of primary closure of the donor site, (2) the contour and scar of the donor site is reasonably acceptable since no tension is presented, (3) the flap can be turned over to cover a wider area, and (4) debulking of the flap can be performed during the operation if needed. The rotation arc of the ulnar recurrent adipofascial flap reaches a wide region, including the distal one-half of the upper arm, the elbow, and the proximal two-thirds of the forearm. Sensory deficit in the forearm was avoided in our patients because meticulous separation and preservation of the medial cutaneous nerve of the forearm was achieved without jeopardising the blood supply to the flap. The ulnar recurrent adipofascial flap is an easy and reliable option for one-stage reconstruction of massive defects around the elbow.     

The influence of local and systemic preconditioning on oxygenation, metabolism and survival in critically ischaemic skin flaps in pigs.

Stress proteins represent a group of highly conserved intracellular proteins that provide adaptation against cellular stress. The present study aims to elucidate the stress protein-mediated effects of local hyperthermia and systemic administration of monophosphoryl lipid A (MPL) on oxygenation, metabolism and survival in bilateral porcine random pattern buttock flaps. Preconditioning was achieved 24h prior to surgery by applying a heating blanket on the operative site (n = 5), by intravenous administration of MPL at a dosage of 35 microg/kg body weight (n = 5) or by combining the two (n = 5). The flaps were monitored with laser Doppler flowmetry, polarographic microprobes and microdialysis until 5h postoperatively. Semiquantitative immunohistochemistry was performed for heat shock protein 70 (HSP70), heat shock protein 32 (also termed haem oxygenase-1, HO-1), and inducible nitrc oxide synthase (iNOS). The administration of MPL increased the impaired microcirculatory blood flow in the proximal part of the flap and partial oxygen tension in the the distal part by approximately 100% each (both P<0.05), whereas both variables remained virtually unaffected by local heat preconditioning. Lactate/pyruvate (L/P) ratio and glycerol concentration (representing cell membrane disintegration) in the distal part of the flap gradually increased to values of approximately 500 mmol/l and approximately 350 micromol/l, respectively (both P<0.01), which was substantially attenuated by heat application (P<0.01 for L/P ratio and P<0.05 for glycerol) and combined preconditioning (P<0.01 for both variables), whereas the effect of MPL was less marked (not significant). Flap survival was increased from 56% (untreated animals) to 65% after MPL (not significant), 71% after heat application (P<0.05) and 78% after both methods of preconditioning (P<0.01). iNOS and HO-1 were upregulated after each method of preconditioning (P<0.05), whereas augmented HSP70 staining was only observed after heat application (P<0.05). We conclude that local hyperthermia is more effective in preventing flap necrosis than systemic MPL administration because of enhancing the cellular tolerance to hypoxic stress, which is possibly mediated by HSP70, whereas some benefit may be obtained with MPL due to iNOS and HO-1-mediated improvement in tissue oxygenation.     

Complications occurring during conservative management of splenic trauma in children.

AIM: Conservative management of splenic rupture in haemodynamically stable children is now generally accepted. However, during follow-up, many complications can occur. The aim of this study was to describe the complications we observed and to propose a standardised follow-up adapted to them. METHODS: Between March 1992 and December 2002 we managed 65 children (aged between 3 and 15 years old) with accidental splenic rupture. Follow-up and treatment consisted of a 10-day bed rest with sonogram and Doppler controls on the 5th and 10th day and subsequently every month until complete healing. Complications included secondary haemorrhage in 3 cases, cystic evolution in 5 cases, and pseudo-aneurysm in 2 cases. All were treated by renewed bed rest. Three of the cysts resolved spontaneously, the other two underwent cystic resection and epiploplasty by laparotomy (n = 1) or laparoscopy (n = 1) and both pseudo-aneurysms were selectively embolised. There were no splenectomies. CONCLUSIONS: Complications essentially occurred in older children and were not related to gender, type of fracture, or extent of bleeding. Cystic evolution of the sub-capsular haematomas can appear up to 1 month after trauma. Peripheral pseudo-aneurysms which could be responsible for secondary haemorrhages were selectively embolised. We favour the use of the Doppler sonogram for follow-up until total recovery of these patients, even in low-grade traumas. Considering the number of complications encountered we do not believe the American evidence-based guidelines are suitable for our population.     

Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction.

OBJECTIVE: To investigate whether pathological changes in the umbilical artery (UA), ductus venosus (DV) and short-term fetal heart variation are related to perinatal outcome in severe, early intrauterine growth restriction (IUGR). METHODS: This multicenter, prospective, longitudinal, observational study was carried out in the Departments of Fetal Medicine and Obstetrics in Hamburg, Amsterdam, Utrecht and London. In 70 singleton pregnancies with IUGR fetuses, delivered at 26-33 weeks of gestation because of antepartum fetal distress, short-term variation (STV) of fetal heart rate, pulsatility index of the fetal UA (UA PI) and DV pulsatility index for veins (DV PIV) were assessed at least weekly. The final measurement was performed within 24 h of delivery. Standard cut-off levels (2 SD or 3 SD, absent flow or reversed flow) were used and new cut-off levels were calculated by means of receiver-operating characteristics analysis. Adverse outcome was defined as perinatal death, cerebral hemorrhage (> or = Grade II) or bronchopulmonary dysplasia before discharge. The predictive value for adverse outcome was calculated for different cut-off levels of the monitoring parameters, adjusted for gestational age (GA), by multivariate logistic regression analysis. Data were analyzed separately for three different time blocks, namely 8-14, 2-7 and 0-1 days before delivery. RESULTS: Adverse perinatal outcome occurred in 18/70 (26%) infants. During the last 24 h before delivery DV PIV and UA PI were significantly higher and STV lower in the adverse outcome group, while 2-7 days before delivery only DV PIV was significantly higher. Adverse perinatal outcome could be predicted at 0-1 days before delivery by DV PIV at a cut-off of three multiples of the SD (odds ratio (OR) 11.3; 95% CI 2.3-57) and GA (OR 0.4; 95% CI 0.3-0.8), at 2-7 days by DV PIV at 2 SD (OR 3.0; 95% CI 0.8-12) and GA (OR 0.5; 95% CI 0.3-0.8) and at 8-14 days by DV PIV at 2 SD (OR 3.9; 95% CI 0.8-20) and GA (OR 0.5; 95% CI 0.3-0.8). Other parameters did not contribute to the multivariate model. CONCLUSIONS: DV PIV measurement is the best predictor of perinatal outcome. This measurement may be useful in timing the delivery of early IUGR fetuses and in improving perinatal outcome, even when delivery may be indicated at an earlier GA. However, as GA was also an important factor influencing outcome, with poorer outcome at earlier gestation at delivery, this hypothesis needs to be tested in a multicenter, prospective, randomized trial.     

Significance of malperfusion syndromes prior to contemporary surgical repair for acute type A dissection: outcomes and need for additional revascularizations.

OBJECTIVE: The aim of this study was to assess the significance of malperfusion syndromes in patients with acute type A aortic dissection following a contemporary surgical management algorithm and the effects on morbidity, hospital mortality, and long-term survival. We believe that obliteration of the primary tear site with restoration of flow in the true aortic lumen results in decreased need for revascularization of malperfused organ systems. METHODS: Our operative approach aims at replacing the entire ascending aorta, resuspension of the aortic valve with repair or replacement of the sinus segment, and routine open replacement of the arch under hypothermic circulatory arrest with retrograde cerebral perfusion with obliteration of false lumen at the distal arch/proximal descending thoracic aorta, thus reestablishing normal flow in the descending thoracic true lumen. From January 1993 to December 2004, 221 consecutive patients underwent repair of acute type A aortic dissection at our institution. Data were collected retrospectively and prospectively. Various types of malperfusion syndromes were present in 26.7% of patients. The organ systems with malperfusion were as follows: cardiac, 7.2%; cerebral, 7.2%; ileofemoral, 12.7%; renal, 4.1%; mesenteric, 1.4%; innominate, 5.4%; and spine, 2.2%. RESULTS: Coronary malperfusion required coronary revascularization in 62.5% of cases. Distal revascularization was needed in 42.9% of patients with ileofemoral malperfusion. Patients with malperfusion were more likely to suffer perioperative myocardial infarction (p<0.001), postoperative coma (p=0.012), delirium (p=0.011), sepsis (p=0.006), acute renal failure (p=0.017), dialysis (p=0.018), and acute limb ischemia (p<0.001). The in-hospital mortality was 30.5% in patients presenting with any malperfusion syndrome while only 6.2% in patients without malperfusion syndrome (p<0.001). Both cardiac (p=0.020) and cerebral malperfusions (p<0.001) were risk factors for in-hospital mortality. The actuarial long-term survival in patients with malperfusion syndrome was estimated by Kaplan-Meier methods to be 67.8%+/-6.1% at 1 year, 54.0%+/-7.0% at 5 years, and 43.1%+/-8.0% at 10 years and for patient without malperfusion 82.7%+/-3.0% at 1 year, 66.3%+/-3.9% at 5 years, and 46.1%+/-6.7% at 10 years (log rank 2.55, p=0.110). Cerebral malperfusion was a significant risk factor for decreased long-term survival (p=0.0002). CONCLUSIONS: The occurrence of malperfusion in patients with acute type A dissection is associated with significant increased risk of in-hospital mortality and complications. Additional revascularization is generally needed in patients with coronary malperfusion and ileofemoral malperfusion. Patients presenting with cardiac and cerebral malperfusions have a high hospital mortality and preoperative cerebral malperfusion is associated with dismal long-term survival.     

The influence of aging on the prognostic value of the revised cardiac risk index for postoperative cardiac complications in vascular surgery patients.

OBJECTIVE: The Lee-risk index [Lee-index] was developed to predict major adverse cardiac events [MACE]. However, age is not included as a risk factor. The aim was to assess the value of the Lee-index in vascular surgery patients among different age categories. METHODS: Of 2642 patients cardiovascular risk factors were noted to calculate the Lee-index. Patients were divided into four age categories; < or = 55 (n=396), 56-65 (n=650), 66-75 (n=1058) and > 75 years (n=538). Outcome measures were postoperative MACE (cardiac death, MI, coronary revascularization and heart failure). The performance of the Lee-index was determined using C-statistics within the four age groups. RESULTS: The incidence of MACE was 10.9%, for Lee-index 1, 2 and > or = 3; 6%, 13% and 20%, respectively. However, the prognostic value differed among age groups. The predictive value for MACE was highest among patients under 55 year (0.76 vs 0.62 of patients aged > 75). The prediction of MACE improved in elderly (aged > 75) after adjusting the Lee-index with age, revised risk of operation (low, low-intermediate, high-intermediate and high-risk procedures) and hypertension (0.62 to 0.69). CONCLUSION: The prognostic value of the Lee-index is reduced in elderly vascular surgery patients, adjustment with age, risk of surgical procedure, and hypertension improves the Lee-index significantly.