We recently reported that human blood dendritic cells from allergic subjects have impaired IFN-α production following TLR9-dependent innate immune stimulation. It is not known how subcutaneous allergen immunotherapy (SCIT) affects dendritic cell immune responses.
The aim of this study is to determine how SCIT affects human dendritic cell function.
PBMC and plasmacytoid dendritic cells (pDCs) were isolated from the blood of 7 dust mite allergic subjects at baseline and upon reaching a standard SCIT maintenance dose that included dust mite and other aeroallergens. Cells were stimulated with various adaptive and innate immune receptor stimuli, or media alone for 20hrs with secreted cytokine levels determined by ELISA. A portion of the cells were used to measure intracellular signaling proteins by flow cytometry. Humoral immune responses were measured from plasma.
SCIT resulted in a 3-fold increase in PBMC production of IFN-α in response to CpG at 100 nM (P = 0.015) and at 500 nM (P = 0.015), n = 7. The predominant cell type known to produce IFN-α in response to CpG (CpG ODN-2216) and other TLR9 agonists is the pDC. As expected, a robust innate immune response from isolated pDCs was re-established among allergic subjects undergoing SCIT resulting in a 5-fold increase in IFN-α production in response to CpG at 500 nM (P = 0.046), n = 7. In contrast, IL-6 production was unaffected by SCIT (P = 0.468). Consistent with published reports, IgG4 blocking antibody increased 10-fold with SCIT (P = 0.031), n = 7. There was no significant increase in the frequency of pDCs or the expression of TLR9 that would account for the rise in IFN-α production.
Allergen immunotherapy increases dendritic cell TLR9 mediated innate immune function, which has previously been shown to be impaired at baseline in allergic subjects.
allergy; immunotherapy mechanisms; SCIT; dendritic cell; pDC; IFN-α; TLR9; cytokines
Some studies reported the possible induction of food allergy, caused by neo-sensitization to cross-reacting allergens, during immunotherapy with aeroallergens, while other studies ruled out such possibility.
The aim of this study was to evaluate the development of neo-sensitization to Pen a 1 (tropomyosin) as well as the appearance of reactions after ingestion of foods containing tropomyosin as a consequence of sublingual mite immunization.
Materials and methods
Specific IgE to Tropomyosin (rPen a 1) before and after mite sublingual immunotherapy in 134 subjects were measured. IgE-specific antibodies for mite extract and recombinant allergen Pen a 1 were evaluated using the immunoenzymatic CAP system (Phadia Diagnostics, Milan, Italy).
All patients had rPen a 1 IgE negative results before and after mite SLIT and did not show positive shrimp extract skin reactivity and serological rPen a 1 IgE conversion after treatment. More important, no patient showed systemic reactions to crustacean ingestion.
Patients did not show neo-sensitization to tropomyosin, a component of the extract (namely mite group 10) administered. An assessment of a patient's possible pre-existing sensitisation to tropomyosin by skin test and/or specific IgE prior to start mite extract immunotherapy is recommended.
This trial is registered in EudraCT, with the ID number of 2010-02035531.
Working Purpose: Allergic diseases such as asthma exhibit increased incidence partly due to increased concentration of allergens in the atmosphere. The aeroallergens associated with increased asthma exacerbations and related hospitalizations. Studies show that different weather conditions cause variability in the distribution of allergens in the ground. The purpose of this study was to estimate the concentration of aeroallergens in various altitudes and the investigation of their association with meteorological variables.
Patients and methods
Measurable concentrations of 25 different types of allergens were recorded over the northern outskirts of the city of Thessaloniki with the help of car and light aircraft at altitudes from the surface to 2,000 meters. The counting was done at the main part of the period movement of aeroallergens. Studied differences between concentrations at different heights and correlations with the meteorological data of the region.
Of the 25 different aeroallergens detected, the most populous in the concentration recorded by the aircraft was pine, oak, grasses, plantain and the olive tree, representing over 80% of all measurements. Drive rate>75% were grasses. The concentrations varied at different heights depending on the type of pollen: at higher altitudes higher concentrations were observed for pine and oak and lower for the grasses. The measurement period showed a direct correlation with concentrations in various heights. The observed correlations of pollen with meteorological data led to the development of a predictive model of concentration in the area of interest.
The collection and study, but also to predict the concentration of allergens in different heights in the atmosphere is technically feasible. The aeroallergens fly at higher altitudes than was thought until now. Rain as potential allergens should be taken seriously for genesis of allergic reactions even from such heights. The detection of pollen at high altitudes and keeping them even in extreme weather raises questions about secure environment free of allergens and morbidity that accompanies allergic individuals.
Peripheral nerve palsies of the upper extremities presenting at birth can be distressing for families and care providers. It is therefore important to be able to identify patients whose diagnosis is compatible with full recovery so that their families can be reassured.
We conducted a retrospective review of all infants presenting with weakness of the upper extremity to our clinic between July 1995 and September 2009. We also conducted a review of the current literature.
During the study period, 953 infants presented to our clinic. Of these patients, 25 were identified as having isolated radial nerve palsy (i.e., a radial nerve palsy in isolation with good shoulder function and intact flexion of the elbow). Seventeen infants (68.0%) had a subcutaneous nodule representing fat necrosis in the inferior posterolateral portion of the affected arm. Full recovery occurred in all patients within a range of one week to six months, and 72.0% of the patients (18/25) had fully recovered by the time they were two months old.
Although the outcome of obstetrical brachial plexus palsy is highly variable, isolated radial nerve palsy in the newborn carries a uniformly favourable prognosis.
Objective: Although the anterior approach is normally used for elective laparoscopic splenectomy (LS), the posterolateral approach may be superior. We have retrospectively compared the effectiveness and safety of these approaches in patients with non-severe splenomegaly scheduled for elective total LS.
Methods: Patients with surgical spleen disorders scheduled for elective LS between March 2005 and June 2011 underwent laparoscopic splenic mobilization via the posterolateral or anterior approach. Main outcome measures included operation time, intraoperative blood loss, frequency of postoperative pancreatic leakage, and length of hospital stay.
Results: During the study period, 203 patients underwent LS, 58 (28.6%) via the posterolateral and 145 (71.4%) via the anterior approach. Three patients (1.5%) required conversion to laparotomy due to extensive perisplenic adhesions. The posterolateral approach was associated with significantly shorter operation time (65.0 ± 12.3 min vs. 95.0 ± 21.3 min, P < 0.01), reduced intraoperative blood loss (200.0 ± 23.4 mL vs. 350.0 ± 45.2 mL, P < 0.01), and shorter hospital stay (5.0 ± 2.0 d vs. 9.0 ± 3.0 d, P < 0.01) than the anterior approach. The frequency of pancreatic leakage was slightly lower in patients undergoing LS via the posterolateral than the anterior approach (0.0% vs. 3.4%, P > 0.05)
Conclusions: The posterolateral approach is more effective and safer than the anterior approach in patients without severe splenomegaly (< 30 cm).
Laparoscopic splenectomy; Posterolateral approach; Anterior approach; Comparative study.
Case report of a complete arcuate foramen in a human atlas vertebra inhibiting the placement of lateral mass screw instrumentation at C1.
Our objective is to report the presentation of the case, the operative considerations, and the management for this anatomic variation.
The groove for the vertebral artery on the posterolateral surface of the atlas (C1) varies in size and depth from a slight impression to a clear sulcus. With anomalous ossification the sulcus can be bridged which results in a posterolateral tunnel within the posterior arch of the atlas. With increasing rates of screw fixation instrumentation that include the atlas, it is of paramount importance to know the location and course of the vertebral artery in relation to the planned route of instrumentation.
The patient underwent a posterolateral fusion from C1 to C4 using autogenous iliac crest bone graft. Internal fixation from C2 to C4 was obtained using lateral mass screw instrumentation. After the vertebral artery was identified passing through the posterior arch of C1, sublaminar wires were utilized for fixation from C1 to C2. The patient responded well to surgical intervention without complications.
Abnormal vertebral artery coursing through a posterolateral tunnel in the posterior arch of C1 has been described and its incidence has a range from 1.14% to 18%. When this variant is present, lateral mass screw fixation at C1 may be contraindicated. We recommend close scrutiny of preoperative radiographs to avoid the possibility of endangering the vertebral artery when this situation exists.
Posterolateral rotatory instability of elbow is considered to be due to the disruption of the ulnar part of the lateral collateral ligament (LUCL). This instability pattern may also be induced by a fracture of components of the lateral column.
We present the case of a 16-year-old boy who fell on his left outstretched arm as he attempted to jump over a tennis net. On initial physical examination, the elbow had instability found on varus stress and the radial head could be felt posteriorly. With attempted valgus and supination force combined with axial loading, the elbow gapped open and the patient had a sense of increased instability. X-rays showed a fracture of the lateral humeral epicondyle and posterolateral subluxation of the elbow. In the operating room, the patient was found to have reproducible posterolateral instability of the elbow. The lateral epicondyle was found to be fractured off the humerus with the LUCL still attached to the fragment. The elbow was reduced, and the injury was stabilized with small screws and suture anchors. At 6-month follow-up, the patient was pain-free, and physical examination revealed 170° of flexion, full extension, 90° of pronation, and 65° of supination. X-rays showed healing of the fracture with concentric reduction of the elbow joint.
In lateral epicondyle fractures, the affected elbow should be assessed for any signs of associated instability. If signs of clear instability are seen that would prohibit proper postinjury rehabilitation, then surgical reduction and fixation of the epicondyle with reinforcement of the LUCL is an effective method of treatment.
Elbow; Rotatory; Instability; Ulnar collateral ligament
Prostaglandin E2 (PGE2), experimentally administered to asthma patients or assayed in murine models, improves allergen-driven airway inflammation. The mechanisms are unknown, but fluctuations of the endogenous cyclooxygenase (COX)-2/prostaglandin/E prostanoid (EP) receptor pathway activity likely contribute to the clinical outcome. We analyzed the activity of the pathway in mice sensitized to aeroallergens, and then studied its modulation under exogenous PGE2.
Mice were exposed to house dust mite (HDM) aeroallergens, a model that enable us to mimic the development of allergic asthma in humans, and were then treated with either subcutaneous PGE2 or the selective EP1/3 receptor agonist sulprostone. Simultaneously with airway responsiveness and inflammation, lung COX-2 and EP receptor mRNA expression were assessed. Levels of PGE2, PGI2, PGD2 were also determined in bronchoalveolar lavage fluid.
HDM-induced airway hyperreactivity and inflammation were accompanied by increased COX-2 mRNA production. In parallel, airway PGE2 and PGI2, but not PGD2, were upregulated, and the EP2 receptor showed overexpression. Subcutaneous PGE2 attenuated aeroallergen-driven airway eosinophilic inflammation and reduced endogenous PGE2 and PGI2 production. Sulprostone had neither an effect on airway responsiveness or inflammation nor diminished allergen-induced COX-2 and PGE2 overexpression. Finally, lung EP2 receptor levels remained high in mice treated with PGE2, but not in those treated with sulprostone.
The lung COX-2/PGE2/EP2 receptor pathway is upregulated in HDM-exposed mice, possibly as an effort to attenuate allergen-induced airway inflammation. Exogenous PGE2 downregulates its endogenous counterpart but maintains EP2 overexpression, a phenomenon that might be required for administered PGE2 to exert its protective effect.
The MRI findings in a case of decubital ischemic fasciitis located posterolateral to the right greater trochanter, in a 72-year-old woman, are presented. Decubital ischemic fasciitis is an uncommon entity encountered mostly in debilitated, elderly patients, in the deep subcutaneous tissue, at pressure points or bony prominences. It can simulate soft-tissue sarcomas. Recognition of this lesion radiologically is important to prevent unnecessary interventions.
Decubital ischemic fasciitis; hip; MRI; soft-tissue tumor
The house dust mite is a major cause of respiratory allergy worldwide. The management of mite allergy is based on avoidance measures, drug treatment, and allergen immunotherapy, but only allergen immunotherapy is able to modify the natural history of the disease. Injectable subcutaneous immunotherapy was introduced a century ago, while sublingual immunotherapy was proposed in the 1980s and emerged in the ensuing years as an effective and safe option to subcutaneous immunotherapy. However, the quality of the extracts to be used in allergen immunotherapy is crucial for the success of treatment. The mite extract for sublingual immunotherapy known as Staloral 300 was developed to offer optimal characteristics concerning the mite culture medium, standardization, and allergen dose. Double-blind, placebo-controlled trials with Staloral 300 have provided a substantial part of the clinical evidence analyzed in a meta-analysis of the efficacy of allergen immunotherapy in mite-induced rhinitis and asthma. Safety and tolerability are very good, mild local reactions in the mouth being the most common side effect. This makes it feasible to carry out sublingual immunotherapy for the 3–5-year duration needed to achieve long-lasting tolerance to the specific allergen. The performance of Staloral 300 may provide optimal conditions for an effective and safe sublingual immunotherapy in patients with mite-induced respiratory allergy.
house dust mite; rhinitis; asthma; allergen extracts; sublingual immunotherapy
The association between sensitizations and severity of allergic diseases is controversial.
This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China.
A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens.
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to Artemisia vulgaris and Ambrosia artemisifolia (p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE.
Artemisia vulgaris and Ambrosia artemisifolia sensitizations are associated with the severity of intermittent rhinitis and D. pteronyssinus and D. farinae sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.
sensitization; aeroallergens; disease severity; allergic rhinitis; asthma; association.
The associations between sensitizations and severity of allergic diseases are controversial. This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitivity in allergic patients in China.
A cross-sectional survey was performed in 6,304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire related to the respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. 2,268 of them were taken blood for serum specific IgE (sIgE) measurements for 16 common aeroallergens.
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was related to skin wheal size and sIgE to Artemisia vulgaris and Ambrosia artemisifolia (P < 0.001). Moderate-severe asthma was associated with increasing in skin and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (P < 0.001). Moderate-severe rhinitis and asthma were also associated with increasing in number of skin and sIgE sensitized allergens.
Outdoor allergen sensitizations are significantly associated with severity of intermittent rhinitis and indoor allergen sensitizations are significantly associated with severity of asthma in patients in China. Number of allergen sensitization is also related to severity of rhinitis and asthma.
The diagnosis of allergic rhinitis (AR) is based on clinical manifestations and supported by a positive result for skin prick test (SPT) or serum specific immunoglobulin E (sIgE) antibodies to aeroallergens. Our objective was to investigate the frequency of patients with clinical manifestations of AR without evidence of specific IgE sensitization.
We evaluated patients with clinical manifestations suggestive of AR, other causes of rhinitis excluded, aged >5 years and who had total serum IgE and SPT or sIgE to aeroallergens measured. Skin tests were performed with extracts of Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis and Aspergillus fumigatus (FDA Allergenic) and total serum IgE and sIgE, for the same allergens, by ImmunoCAP (Phadia). Patients were subdivided into groups according to the results profile, and comparatively analyzed for association with asthma, severity of rhinitis and age.
We evaluated 116 patients (64% female) aged between 5 and 79 years, including 34 children (29%) and 63 (54%) with bronchial asthma. The observed profiles and frequencies were: high IgE levels and positivity in the SPT or sIgE –55%; normal IgE levels and SPT or sIgE positivity –9%; high IgE levels and SPT and sIgE negativity –3 %; normal IgE levels and negativity in the SPT and sIgE –23%. Among patients with normal levels of total serum IgE and no evidence of specific IgE sensitization, 14% had asthma, while in the remainder the prevalence of asthma was 34% (P = 0.0009). There was no statistical significance in the influence of the rhinitis severity and age in the absence of markers of atopy and allergen sensitization.
We observed a significant number of patients with clinical manifestations of AR, without evidence of systemic atopy and specific IgE sensitization, indicating the importance of careful research of local allergic rhinitis, as well as other causes of chronic rhinitis. Local allergic rhinitis appears to be less frequent in patients with rhinitis and asthma. The observation of 13% of patients with elevated levels of total IgE without specific sensitization implies the possibility of sensitization to aeroallergens which were not investigated, such as occupational allergens.
An association between allergic disease and depression has been consistently reported, but whether the key mediating ingredients are predominantly biological, psychological, or mere artifacts remains unknown. In the current study, we examine the hypothesized relationship between allergen-specific immunoglobulin E (IgE) status and changes in allergy symptoms with worsening in depression scores in depressed sensitized individuals.
In patients with recurrent mood disorders, we individually coupled sensitization to specific seasonal aeroallergens (as assessed by allergen-specific IgE) with temporal windows of exposure to aeroallergens (low versus high tree or ragweed pollen counts measured according to the National Allergy Bureau guidelines). We compared Structured Interview Guide for the Hamilton Depression Rating Scale–Seasonal Affective Disorder Version (SIGH-SAD) depression score changes in 41 patients with mood disorders [25 with major depression and 16 with bipolar I disorder, diagnosed by Structured Clinical Interview for DSM (SCID)] seropositive for tree or ragweed pollen-specific IgE antibody versus 53 patients with mood disorders (30 with major depression and 23 with bipolar I disorder) seronegative for aeroallergen-specific IgE.
Worsening in total depressive scores from low to high pollen exposure was greater in allergen-specific IgE positive patients as compared to allergen-specific IgE antibody negative patients (p = 0.01). When stratified by polarity, the association was significant only in patients with bipolar I disorder (p = 0.004). This relationship was resilient to adjustment for changes in allergy symptom scores.
To our knowledge, this is the first report of coupling a molecular marker of vulnerability (allergen-specific IgE) with a specific an environmental trigger (airborne allergens) leading to exacerbation of depression in patients with bipolar I disorder.
allergen; allergen-specific IgE antibody; allergy; bipolar disorder; depression; ragweed pollen; tree pollen
Specific immunotherapy via the subcutaneous or oral route is associated with local and, in some cases, systemic side effects and suffers from low patient compliance. Due to its unique immunological features, the skin represents a promising target tissue for effective and painless treatment of type I allergy. The current study was performed to compare the efficacy of transcutaneous immunotherapy via laser-generated micropores to subcutaneous injection.
BALB/c mice were sensitized by intraperitoneal injection of recombinant grass pollen allergen Phl p 5 together with alum. Subsequently, lung inflammation was induced by repeated intranasal challenge. During the treatment phase, adjuvant-free Phl p 5 was applied in solution to microporated skin or was subcutaneously injected. Lung function and cellular infiltration; Phl p 5–specific serum levels of IgG1, IgG2a, and IgE; and cytokine levels in bronchoalveolar lavage fluids as well as in supernatants of splenocyte cultures were assessed.
Both therapeutic approaches reduced airway hyperresponsiveness and leukocyte infiltration into the lungs. Whereas subcutaneous immunotherapy induced a systemic increase in Th2-associated cytokine secretion, transcutaneous application revealed a general downregulation of Th1/Th2/Th17 responses. Successful therapy was associated with induction of IgG2a and an increase in FOXP3+ CD4+ T cells.
Transcutaneous immunotherapy via laser microporation is equally efficient compared with conventional subcutaneous treatment but avoids therapy-associated boosting of systemic Th2 immunity. Immunotherapy via laser-microporated skin combines a painless application route with the high efficacy known from subcutaneous injections and therefore represents a promising alternative to established forms of immunotherapy.
allergy; immunotherapy; laser; micropores; transcutaneous
This study used multi-frequency bioimpedance spectroscopy (BIS) of the arm and whole body to estimate muscle mass (MM) and subcutaneous adipose tissue (SAT) in 31 hemodialysis (HD) patients comparing these results with magnetic resonance imaging (MRI) and body potassium (40K) as gold standards. Total body and arm MM (MMMRI) and SAT (SATMRI) were measured by MRI. All measurements were made before dialysis treatment. Regression models with the arm (aBIS) and whole body (wBIS) resistances were established. Correlations between gold standards and the BIS model were high for the arm SAT (r2 = 0.93, standard error of estimate (SEE) = 3.6 kg), and whole body SAT (r2 = 0.92, SEE = 3.5 kg), and for arm MM (r2 = 0.84, SEE = 2.28 kg) and whole body MM (r2 = 0.86, SEE = 2.28 kg). Total body MM and SAT can be accurately predicted by arm BIS models with advantages of convenience and portability, and it should be useful to assess nutritional status in HD patients.
Segmental bioimpedance; Magnetic resonance imaging; Skeletal muscle mass; Subcutaneous adipose tissue
Tissue oxygenation is the primary determinant of wound infection risk. Mild hypercapnia markedly improves cutaneous, subcutaneous, and muscular tissue oxygenation in volunteers and patients. However, relative contributions of increased cardiac output and peripheral vasodilation to this response remains unknown. We thus tested the hypothesis that increased cardiac output is the dominant mechanism.
We recruited 10 ASA III patients, aged 40–65 years, undergoing cardiopulmonary bypass for this crossover trial. After induction of anaesthesia, a Silastic tonometer was inserted subcutaneously in the upper arm. Subcutaneous tissue oxygen tension was measured with both polarographic electrode and fluorescence-based systems. Oximeter probes were placed bilaterally on the forehead to monitor cerebral oxygenation. After initiation of cardiopulmonary bypass, in random order patients were exposed to two arterial CO2 partial pressures for 30 minutes each: 35 (normocapnia) or 50 mmHg (hypercapnia). Bypass pump flow was kept constant throughout the measurement periods.
Hypercapnia during bypass had essentially no effect on PaO2, mean arterial pressure, or tissue temperature. PaCO2 and pH differed significantly. Subcutaneous tissue oxygenation was virtually identical during the two PaCO2 periods (139 [50,163] vs. 145 [38,158], P=0.335) (median [range]). In contrast, cerebral oxygen saturation (our positive control measurement) was significantly less during normocapnia (57 [28,67]%) than hypercapnia (64 [37,89]%, P=0.025).
Mild hypercapnia, which normally markedly increases tissue oxygenation, did not do so during cardiopulmonary bypass with fixed pump output. This suggests that hypercapnia normally increases tissue oxygenation by increasing cardiac output rather than direct dilation of peripheral vessels.
Carbon Dioxide; Hypercapnia; Hypercarbia; Acidosis; Respiratory; Oxygenation; Oxygen; Tissue; Cutaneous; Subcutaneous; Cerebral; Perfusion; Cerebrovascular; Cardiac Output
Rationale: Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood.
Objective: To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing.
Methods: A total of 285 children at high risk for allergic disease and asthma were followed prospectively from birth. The timing and etiology of viral respiratory wheezing illnesses were determined, and aeroallergen sensitization was assessed annually for the first 6 years of life. The relationships between these events were assessed using a longitudinal multistate Markov model.
Measurements and Main Results: Children who were sensitized to aeroallergens had greater risk of developing viral wheeze than nonsensitized children (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.2–3.1). Allergic sensitization led to an increased risk of wheezing illnesses caused by human rhinovirus (HRV) but not respiratory syncytial virus. The absolute risk of sensitized children developing viral wheeze was greatest at 1 year of age; however, the relative risk was consistently increased at every age assessed. In contrast, viral wheeze did not lead to increased risk of subsequent allergic sensitization (HR, 0.76; 95% CI, 0.50–1.1).
Conclusions: Prospective, repeated characterization of a birth cohort demonstrated that allergic sensitization precedes HRV wheezing and that the converse is not true. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to more severe HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway. Therefore, therapeutics aimed at preventing allergic sensitization may modify virus-induced wheezing and the development of asthma.
virus; wheezing; allergic sensitization; RSV; human rhinovirus
Introduction. Aeroallergen sensitization occurs at an earlier age than previously noted. The purpose of this paper was to identify which pollens cause early sensitization in young children presenting with rhinitis symptoms. Methods. This paper was a retrospective analysis of skin test results from 2- to 8-year-old patients presenting with a history consistent with allergic rhinitis. Patients were tested to aeroallergens common to the Great Basin along with a histamine and saline control. Pollen counts were obtained from a Reno, NV-certified counting station. Results. 123 children less than 8 years of age were identified. Over 50% of these children were sensitized to at least one aeroallergen. Chemopodaciae, timothy, alfalfa, black walnut, olive, mountain cedar and willow were predominating sensitizing aeroallergens of the Great Basin Region. Pollen counts were notable for a early spring peak for the tree season, grass season in May and weed season in August. Pollen levels continued to November at low levels. Discussion. Aeroallergens causing early sensitization differed from those which had predominately been reported in other regions of the United States. Pediatric allergists should consider performing a local review of sensitizing aeroallergens in their region to assist with identification and management of allergic rhinitis in their youngest patients. Please make style changes as appropriate.
One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.
Aims To examine depth of subcutaneous fat at gluteal intramuscular injection sites.
Design Retrospective study.
Setting General hospital.
Participants 100 consecutive adults who had computed tomography of the pelvis.
Main outcome measures Minimum distance between the surface of the skin and the nearest edge of muscle at intramuscular injection sites.
Results 12 patients had a ventrogluteal site depth of more than 35 mm, the maximum depth of a green needle, and 26 had a ventrogluteal depth of more than 25 mm, the maximum depth of a blue needle. 43 patients had a dorsogluteal site depth of more than 35 mm, and 72 had a dorsogluteal depth of more than 25 mm. The intramuscular site was likely to be deeper in women.
Conclusion Standard green and blue needles do not reach the gluteal muscles in a considerable number of patients.
The safety of accelerated schedules of allergen immunotherapy (ASAI) in patients with bronchial asthma (BA) has been reported but there are little data on the safety of ASAI for patients with atopic dermatitis (AD). In this study, we investigated the safety of ASAI in patients with AD. Sixty patients with AD and 18 patients with BA sensitized to house dust mites (HDM) were studied. A maximum maintenance dose of HDM extract, adsorbed to aluminum hydroxide, was administered to patients by subcutaneous injection with either a 3-day protocol (rush immunotherapy) or 1-day protocol (ultra-rush immunotherapy). Systemic reactions were observed 4 of 15 patients (26.7%) with AD during rush immunotherapy, 13 of 45 patients (28.9%) with AD during ultra-rush immunotherapy, and 4 of 18 patients (22.2%) with BA during rush immunotherapy (P > 0.05). No severe or near fatal systemic reactions occurred in 78 subjects of this study. Systemic reactions developed within 4 hr after administration of the maximum allergen dose in 20 of 21 patients (95.2%) with AD and BA who showed systemic reactions during rush or ultra-rush immunotherapy. In conclusion, ASAI was safe and well tolerated in patients with AD. ASAI can be a useful therapeutic option for AD.
Allergens; Desensitization; Dermatitis, Atopic; Bronchial Asthma; Adverse Effects; Dermatophagoides; Pyroglyphidae
Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM).
Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (RL) and dynamic compliance (Cdyn). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05) the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05) the increase in baseline RL and the decrease in baseline Cdyn caused by chronic exposure to inhaled HDM.
These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.
Open exposure of the posterolateral corner of the knee is challenged by limitations of posterolateral ligamentous tissues and posterior neurovascular structures. We have used a modification of a lateral femoral epicondyle osteotomy, described historically for surgical management of posterolateral rotatory instability, as an approach to the posterolateral intraarticular structures. The historic technique for ligamentous reconstruction has been abandoned because its nonanatomic fixation does not restore ligamentous isometry. In this report, osteotomy of a bone block from the lateral femoral epicondyle is used to access the joint space. The lateral collateral ligament is reflected distally and posteriorly through traction on the block. Once the intraarticular disorder has been addressed, the lateral femoral epicondyle is secured in its native, anatomic position, thereby restoring isometry and normal joint mechanics after surgery. This technique has been used successfully to address posterolateral articular disorders on femoral and tibial sides. Postoperative magnetic resonance imaging verified restoration of lateral collateral ligament anatomy. Physical examination at 0° and 30° knee flexion showed clinical stability at all postoperative evaluations through 6 and 10 months followup. Using this technique, intraarticular disorders at the posterolateral corner may be addressed in an open manner with anatomic reduction and preserved postoperative function of the lateral collateral ligament.
Level of Evidence: Level V, expert opinion. See the Guidelines for Authors for a complete description of levels of evidence.
To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity.
Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement.
Two hundred seventy (66.3%) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively).
The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.
Intima-media thickness; Carotid artery; Protocol; Atherosclerosis; Duplex scan