Equine insect bite hypersensitivity: immunoblot analysis of IgE and IgG subclass responses to Culicoides nubeculosus salivary gland extract

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides and sometimes Simulium spp. The allergens causing IBH are probably salivary gland proteins from these insects, but they have not yet been identified. The aim of our study was to identify the number and molecular weight of salivary gland extract (SGE) proteins derived from Culicoides nubeculosus which are able to bind IgE antibodies (ab) from the sera of IBH-affected horses. Additionally, we sought to investigate the IgG subclass (IgGa, IgGb and IgGT) reactivity to these proteins. Individual IgE and IgG subclass responses to proteins of C. nubeculosus SGE were evaluated by immunoblot in 42 IBH-affected and 26 healthy horses belonging to different groups (Icelandic horses born in Iceland, Icelandic horses and horses from different breeds born in mainland Europe). Additionally, the specific antibody response was studied before exposure to bites of Culicoides spp. and over a period of 3 years in a cohort of 10 Icelandic horses born in Iceland and imported to Switzerland. Ten IgE-binding protein bands with approximate molecular weights of 75, 66, 52, 48, 47, 32, 22/21, 19, 15, 13/12 kDa were found in the SGE. Five of these bands bound IgE from 50% or more of the horse sera. Thirty-nine of the 42 IBH-affected horses but only 2 of the 26 healthy horses showed IgE-binding to the SGE (p<0.000001). Similarly, more IBH-affected than healthy horses had IgGa ab binding to the Culicoides SGE (19/22 and 9/22, respectively, p<0.01). Sera of IBH-affected horses contained IgE, IgGa and IgGT but not IgGb ab against significantly more protein bands than the sera of the healthy horses. The cohort of 10 Icelandic horses confirmed these results and showed that Culicoides SGE specific IgE correlates with onset of IBH. IBH-affected horses that were born in Iceland had IgGa and IgGT ab (p< or =0.01) as well as IgE ab (p=0.06) against a significantly higher number of SGE proteins than IBH-affected horses born in mainland Europe. The present study shows that Culicoides SGE contains at least 10 potential allergens for IBH and that IBH-affected horses show a large variety of IgE-binding patterns in immunoblots. These findings are important for the future development of a specific immunotherapy with recombinant salivary gland allergens.

Use and relevance of a bovine mammary gland explant model to study infection responses in bovine mammary tissue

Our aim was to develop an explant model to define more precisely the early response of bovine mammary epithelial cells to infection. Therefore we investigated the mRNA expression encoding for some soluble immunological factors in lipopolysaccharide (LPS)-treated bovine mammary gland explants. Explants were taken out from the mammary gland of eight lactating cows after slaughter then incubated with LPS (10 mug/ml) for 6 h. The mRNA expression of alpha-lactalbumin (alpha-la), various cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, and two immunoglobulin receptors, the neonatal Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIGR), were assessed with qPCR before and after 3 h and 6 h of LPS challenge. Both immunoglobulin receptors and alpha-la increased at 3 h then recovered their initial level at 6 h whereas IL-1beta, IL-6 and IL-8 increased only after 6 h (P<0.05). Surprisingly, TNF-alpha transcripts did not show any regulation in response to the LPS treatment. We nevertheless concluded that our model was valid to examine the short-term response of mammary epithelial cell challenged with LPS.

Postoperative radiation therapy for T1 and T2 primary parotid carcinoma: is it useful?

OBJECTIVE: The benefit of postoperative radiation for advanced primary parotid carcinoma has been reported previously, whereas studies to evaluate the usefulness of postoperative radiation for T1 and T2 parotid carcinomas have never been performed. STUDY DESIGN AND SETTING: Retrospective analysis on 58 previously untreated patients with T1 and T2 parotid carcinomas. In 34 patients, postoperative radiation was included in the treatment protocol and in 24 patients, no postoperative radiation was applied. RESULTS: A local recurrence was observed in 8 of 24 (33%) patients without and in 1 of 34 (3%) patients with postoperative radiation (P < 0.5). The 5-year actuarial and disease-free survival rate was 83% and 70% for patients without postoperative radiation and 93% and 92% for patients with postoperative radiation. CONCLUSION AND SIGNIFICANCE: Local recurrence was less often observed in patients with postoperative radiation. Nevertheless, prospective randomized studies are needed to confirm the usefulness of postoperative radiation in early carcinomas. EBM rating: B-3b.

[Radiotherapy of the prostate gland--old wine in a new bottle?]

The outcome and morbidity in the treatment of prostate cancer by radiation therapy depends on the balance between tumour control and normal tissue damage. Recent technological advances have allowed to reduce the amount of normal tissue included in target treatment volumes. This diminishes morbidity and provides an opportunity for dose escalation, increasing tumour control rates. The new application techniques are discussed along with their integration in treatment concepts. Although there are no randomised studies to provide evidence of increased survival, the available evidence supports the hypothesis that the introduction of novel radiation techniques leads to survival rates equivalent to surgical series with sufficient safety.

Imaging of salivary gland tumours

Imaging of salivary gland tumours is a major challenge for radiologists due to the great variety of differential diagnoses. This article gives a short overview on the anatomy of the salivary glands, the epidemiology of salivary gland tumours as well as the clinical presentation and the different imaging modalities including new magnetic resonance techniques such as diffusion-weighted magnetic resonance imaging, dynamic contrast-enhanced magnetic resonance imaging and magnetic resonance spectroscopy applied in the work-up of salivary gland masses. The imaging features of different tumour types and their differential diagnoses are also discussed. Finally, staging classification and treatment options are presented.

Adrenal gland development and defects

The network regulating human adrenal development is complex. Studies of patients with adrenal insufficiency due to gene mutations established a central role for transcription factors GLI3, SF1 and DAX1 in the initial steps of adrenal formation. Adrenal differentiation seems to depend on adrenocorticotropic hormone (ACTH) stimulation and signalling, including biosynthesis and action of POMC, PC1, TPIT, MC2R, MRAP and ALADIN, all of which cause adrenocortical hypoplasia when mutated in humans. Studies of knockout mice revealed many more factors involved in adrenal development; however, in contrast to rodents, in humans several of those factors had no adrenal phenotype when mutated (e.g. WT1, WNT4) or, alternatively, human mutations have not (yet) been identified. Tissue profiling of fetal and adult adrenals suggested 69 genes involved in adrenal development. Among them were genes coding for steroidogenic enzymes, transcription and growth factors, signalling molecules, regulators of cell cycle and angiogenesis, and extracellular matrix proteins; however, the exact role of most of them remains to be elucidated.

Associations with multiple pituitary hormone deficiency in patients with an ectopic posterior pituitary gland

INTRODUCTION: The presence of an ectopic posterior pituitary gland (EPP) on magnetic resonance imaging (MRI) is associated with hypopituitarism with one or more hormone deficiencies. We aimed to identify risk factors for having multiple pituitary hormone deficiency (MPHD) compared to isolated growth hormone deficiency (IGHD) in patients with an EPP. METHODS: In 67 patients (45 male) with an EPP on MRI, the site (hypothalamic vs. stalk) and surface area (SA) [ x (maximum diameter/2) x (maximum height/2), mm(2)] of the EPP were recorded and compared in patients with IGHD and MPHD in relation to clinical characteristics. RESULTS: In MPHD (n = 32) compared to IGHD (n = 35) patients: age of presentation was younger (1.4 [0.1-10.7]vs. 4.0 [0.1-11.3] years, P = 0.005), major incidents during pregnancy were increased (47%vs. 20%, P = 0.02) as were admissions to a neonatal intensive care unit (NICU) (60%vs. 26%, P = 0.04), whilst EPP SA was lower (12.3 [2.4-34.6]vs. 25.7 [6.9-48.2] mm(2), P < 0.001). In patients with a hypothalamic (n = 56) compared to a stalk sited EPP (n = 11): prevalence of MPHD was greater (55%vs. 9%,P = 0.05) and EPP surface area was smaller (17.3 [2.4-48.2]vs. 25.3 [11.8-38.5] mm(2), P < 0.001). In regression analysis, after adjusting for age, presence of MPHD was associated with: major incidents during pregnancy (RR 6.8 [95%CI 1.2-37.7]), hypothalamic EPP site (RR 10.9 [1.0-123.9]) and small EPP SA (RR 2.5 [1.0-5.0] for tertiles of SA). CONCLUSION: In patients with an EPP, adverse antenatal events, size (small) and position (hypothalamic) of the posterior pituitary gland on MRI were associated with MPHD. These findings suggest that adverse factors during pregnancy may be important for the development of an EPP.

Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study

BACKGROUND: To use amifostine concurrently with radiochemotherapy (CT-RT) or radiotherapy (RT) alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. METHODS: Five patients (2 males, 3 females) with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma) involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc). Single RT fraction dose, total dose and treatment duration were individually adjusted to the patient's need. Acute and late adverse effects were recorded using the RTOG score. Subjective and objective dry eye assessment was performed for the post-treatment control of lacrimal gland function. RESULTS: All patients have completed CT-RT or RT as indicated. The median total duration of RT was 29 days (range, 23 - 39 days) and the median total RT dose was 40 Gy (range, 36 - 60 Gy). Median lacrimal gland exposure was 35.9 Gy (range, 16.8 - 42.6 Gy). Very good partial or complete tumor remission was achieved in all patients. The treatment was well tolerated without major toxic reactions. Post-treatment control did not reveal in any patient either subjective or objective signs of a dry eye syndrome. CONCLUSION: The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome.

Long-term follow-up after complete resection of well-differentiated cancer confined to the thyroid gland

BACKGROUND: Papillary or follicular thyroid carcinomas exhibit a relatively benign course. Hence, long-term follow-up studies with well-defined disease stages and treatment details are needed to evaluate treatment strategies. METHODS: Patients who underwent complete resection of well-differentiated thyroid carcinoma (WDTC) confined to the thyroid gland between 1972 and 1990 identified from a prospective database were assessed. Follow-up was performed by interview, review of patient charts, and analysis of the Death Registry. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). Review of histology was performed and extent of thyroid resection, postoperative therapy, and recognized prognostic factors but not lymphadenectomy were evaluated. RESULTS: Of 2,867 patients, 213 had complete resection of WDTC confined to the thyroid gland. Follow-up was completed in 166 patients with median age 54.2 (range, 20-85) years, and median follow-up of 27.2 (range, 15.6-34.5) years. The 10- and 20-year OS was 71 and 55%, respectively. DSS at 10 and 20 years was 81 and 69%, respectively, and correlated with age, histology, tumor size, radio-iodide ablation (RIA), and external beam irradiation (EBR) treatment. No patient died of WDTC more than 18 years after resection. Total or near-total thyroidectomy without lymphadenectomy was not superior to partial thyroidectomy. In multivariate analysis for DSS, age was the dominant factor, which correlated with histology. CONCLUSION: After a median follow-up of 27 years, about one-third of patients died of WDTC. Age, histology and postoperative therapy but not extent of thyroid resection determined DSS.

Canalicular adenoma of a minor salivary gland on the palate: a case presentation

Canalicular adenomas are uncommon, benign epithelial neoplasms of the salivary glands that usually involve the upper lip and buccal mucosa of elderly people. Differential diagnosis of the canalicular adenoma versus adenocarcinoma is important, as it may result in unjustified radiotherapy or extensive and aggressive surgery. Despite the benign nature of canalicular adenomas, complete surgical removal and a regular clinical follow-up are recommended. The present article describes the diagnostic procedures, surgical management, and follow-up of a canalicular adenoma involving the palate of a 71-year-old man.

Apocrine papillary cystadenoma of a minor salivary gland on the lower lip: case presentation

Cystadenomas are a rare, painless, and slow-growing benign epithelial tumor of the salivary gland. This article describes the case of a papillary cystadenoma in the lower lip of a 46-year-old man. The lesion was removed using a carbon dioxide laser, and there were no signs of recurrence 1 year postoperatively.

Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of alpha-lactalbumin

Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human alpha-lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.