Frequency of lower respiratory tract infections in relation to adaptive immunity in children with Down syndrome compared to their healthy siblings.

AIM: Children with Down syndrome (DS) experience respiratory tract infections (RTIs) more frequently than healthy children. We investigated whether this is related to different immunological characteristics associated with DS. METHODS: The study group consisted of 22 children with DS and 22 of their healthy, age-range matched siblings. Data were collected on infections and hospitalizations because of lower RTIs. Immunoglobulin and IgG subclass levels in blood, as well as lymphocyte and T cell (subset) counts, were determined. RESULTS: The children with DS had a significantly higher frequency of lower RTIs and related hospitalization than their siblings. We also found significantly reduced IgG2 levels as well as significantly lower counts of total lymphocytes, CD4(+) T lymphocytes, CD4(+) invariant natural killer (iNKT) cells and regulatory T cells in the DS group. CONCLUSION: In children with DS, reduced levels of IgG2, total lymphocytes, T lymphocytes, iNKT cells and regulatory T cells might contribute to their higher susceptibility to lower RTIs.

Loss of heterozygosity at 9p and p53 immunopositivity in surgical margins predict local relapse in head and neck squamous cell carcinoma.

A major problem in head and neck cancer surgery is the high rate of local relapse (LR). In at least 25% of the surgically treated head and neck squamous cell carcinoma (HNSCC) patients, a genetically defined preneoplastic lesion, also known as "field," can be detected in the surgical margins. A remaining field may be an important cause for the development of LR. The aims of our study are (i) to investigate whether HNSCC patients with an unresected field are more likely to develop LR, and (ii) to identify molecular risk factors that predict malignant transformation of field. We retrospectively studied 35 HNSCC patients of whom 16 patients developed LR and 19 patients remained disease-free for at least 4 years. Loss of heterozygosity (LOH) at chromosomes 3p, 9p and 17p, p53 immunostaining, Ki-67 immunostaining and histopathological grading of all available paraffin-embedded surgical margins was performed, and related to LR. Significant associations were determined by Kaplan-Meier analysis and Cox-proportional hazard models. We show that presence of field is significantly associated with LR and that LOH at 9p and p53 immunostaining have the most predictive potential (hazard ratios 3.17 and 3.46, and p values 0.027 and 0.017, respectively). The combination of LOH at 9p and/or a large p53 positive field is most predictive (hazard ratio 7.06 and p = 0.01). Presence and grade of dysplasia was not associated with LR. These data may have major impact for future diagnostic workup of surgically treated HNSCC patients.

Nephrotic syndrome in The Netherlands: a population-based cohort study and a review of the literature.

Nephrotic syndrome (NS) is a clinical diagnosis with proteinuria, hypoalbuminaemia and oedema. NS is rare in children, and its incidence in The Netherlands is unknown. The aim of this study was to estimate the incidence of idiopathic NS in the Netherlands. All paediatric patients (age 0-18 years) with a newly diagnosed NS in the Netherlands were registered by the Dutch Pediatric Surveillance Unit during the years 2003 until 2006, secondary NS was excluded. All paediatricians filled out questionnaires about the first clinical findings of the patients and incidences were calculated. A literature review on incidences of childhood NS was conducted. The incidence of NS in children in the Netherlands in the years 2003 until 2006 was 1.52/ 100, 000 children/ year. The median age at diagnosis was 3.88 years with a mean age of 5.08 years. A significant male:female ratio of 2.04:1 was found. This prospective study of NS in the Netherlands revealed an incidence of 1.52:100, 000 children/year, and is similar to the incidences found all over the world.

Prospective effects of hearing status on loneliness and depression in older persons: identification of subgroups.

OBJECTIVE: To determine the possible longitudinal relationships between hearing status and depression, and hearing status and loneliness in the older population. DESIGN: Multiple linear regression analyses were used to assess the associations between baseline hearing and 4-year follow-up of depression, social loneliness, and emotional loneliness. Hearing was measured both by self-report and a speech-in-noise test. Each model was corrected for age, gender, hearing aid use, baseline wellbeing, and relevant confounders. Subgroup effects were tested using interaction terms. STUDY SAMPLE: We used data from two waves of the Longitudinal Aging Study Amsterdam (2001-02 and 2005-06, ages 63-93). Sample sizes were 996 (self-report (SR) analyses) and 830 (speech-in-noise test (SNT) analyses). RESULTS: Both hearing measures showed significant adverse associations with both loneliness measures (p < 0.05). However, stratified analyses showed that these effects were restricted to specific subgroups. For instance, effects were significant only for non-hearing aid users (SR-social loneliness model) and men (SR and SNT-emotional loneliness model). No significant effects appeared for depression. CONCLUSIONS: We found significant adverse effects of poor hearing on emotional and social loneliness for specific subgroups of older persons. Future research should confirm the subgroup effects and may contribute to the development of tailored prevention and intervention programs.

Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study.

BACKGROUND: The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only. METHODS/DESIGN: This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis. DISCUSSION: This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous parents of affected children compared to the consanguineous parents of healthy children. If our hypothesis proves to be correct, further studies are needed to obtain different risk figure estimates for the different proportions of DNA identical-by-descent. With more precise information about their risk status, empowerment of couples can be improved when making reproductive decisions.

Evaluation of temporomandibular function after high partial condylectomy because of unilateral condylar hyperactivity.

PURPOSE: The purpose of this study was to assess temporomandibular function after condylectomy because of unilateral condylar hyperactivity (UCH) by means of standardized diagnostic criteria. The results were compared with those obtained in a control group. PATIENTS AND METHODS: In this study, 33 patients with UCH who underwent condylectomy and 31 controls matched for age and gender filled out a history questionnaire and underwent a clinical examination as part of the research diagnostic criteria for temporomandibular disorders. Data analysis was performed by use of the Fisher exact test for 2-by-2 tables. RESULTS: Patients and controls did not differ significantly regarding myofacial pain (P = .131), disc displacement (P = .516), and depression (P = .34). The groups differed significantly concerning arthralgia, osteoarthritis, and osteoarthrosis (P = .003), as well as pain with low disability (P = .022). CONCLUSIONS: In patients with UCH who underwent condylectomy because of progressive mandibular asymmetry, more joint-related temporomandibular problems as well as more postoperative pain developed when compared with age- and gender-matched controls. However, these problems did not lead to more severe disabilities in daily life.

Paratracheal lymph node dissection does not negatively affect thyroid dysfunction in patients undergoing laryngectomy.

The aim of this retrospective study was to evaluate the prognostic significance of paratracheal lymph node dissection including hemithyroidectomy for the development of hypo(para)thyroidism. From 1990 to 2004, 169 patients with a carcinoma of the larynx or hypopharynx who underwent paratracheal lymph node dissection were selected. Data of 137 patients (23 women, 114 men) were analyzed. Hundred patients were tested on thyroid function. Patient, tumor and treatment characteristics were noted including age, gender, site, TNM stage and details of surgery, radiotherapy and chemotherapy. Seventy percent of the tested patients had hypothyroidism (36% clinical, 34% subclinical); 33% had hypoparathyroidism. All patients with hypo(para)thyroidism underwent various lymph node treatment modalities. For the various treatment combinations, no increase of hypo(para)thyroidism was found if a bilateral paratracheal lymph node dissection was performed. The incidence of hypo(para)thyroidism after laryngectomy in combination with hemithyroidectomy, neck dissection and paratracheal lymph node dissection is high. An additional risk of paratracheal dissection for the development of hypo(para)thyroidism could not be shown.

Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib.

Mature circulating endothelial cell (CEC) as well as endothelial progenitor populations may reflect the activity of anti-angiogenic agents on tumor neovasculature or even constitute a target for anti-angiogenic therapy. We investigated the behavior of CECs in parallel with hematopoietic progenitor cells (HPCs) in the blood of renal cell cancer patients during sunitinib treatment. We analyzed the kinetics of a specific population of small VEGFR2-expressing CECs (CD45(neg)/CD34(bright)), HPCs (CD45(dim)/CD34(bright)), and monocytes in the blood of 24 renal cell cancer (RCC) patients receiving 50 mg/day of the multitargeted VEGF inhibitor sunitinib, on a 4-week-on/2-week-off schedule. Blood was taken before treatment (C1D1), on C1D14, C1D28, and on C2D1 before the start of cycle 2. Also plasma VEGF and erythropoietin (EPO) were determined. Remarkably, while CD34(bright) HPCs and monocytes decreased during treatment, CD34(bright) CECs increased from 69 cells/ml (C1D1) to 180 cells/ml (C1D14; P = 0.001) and remained high on C1D28. All cell populations recovered to near pre-treatment levels on C2D1. Plasma VEGF and EPO levels were increased on C1D14 and partly normalized to pre-treatment levels on C2D1. In conclusion, opposite kinetics of two circulating CD34(bright) cell populations, HPCs and small CECs, were observed in sunitinib-treated RCC patients. The increase in CECs is likely caused by sunitinib targeting of immature tumor vessels.

Shoulder morbidity after non-surgical treatment of the neck.

BACKGROUND AND PURPOSE: Reports on shoulder function after non-surgical treatment are not available. In the present study shoulder morbidity after surgical and non-surgical treatment of the neck is determined and compared. MATERIALS AND METHODS: In 100 head and neck cancer patients 174 neck sides were treated by surgery (n=51) or (chemo)radiation (n=123). Abduction, anteflexion, endorotation and exorotation were assessed. Subjective measurements were performed using the Visual Analogue Scale for pain, the Shoulder Disability Questionnaire (SDQ) and stiffness reporting. RESULTS: Predictive factors for SDQ-score>0 (n=54) were VAS pain score, stiffness, abduction, anteflexion, physiotherapy, low shoulder position and surgical treatment. The SDQ, stiffness and pain scores were significantly higher in the surgically treated group than in the non-surgical group (p<0.01). Anteflexion, abduction and exorotation were less impaired in the non-surgically treated group than in the surgically treated group (p<0.01). No differences between neck dissection and neck dissection with post-operative radiotherapy, and radiotherapy and chemoradiation were found for these movements. CONCLUSIONS: Shoulder morbidity is often present after non-surgical treatment of the neck, but to a lesser extent compared to surgical treatment. Radiotherapy adds no morbidity to neck dissection and chemotherapy does not add extra morbidity to primary radiation.

Do 'cinnamon-sensitive' patients react to cinnamate UV filters?

BACKGROUND: Use of sunscreens has increased dramatically worldwide, and some sunscreen chemicals may be allergens. Ultraviolet (UV) filters are added to various cosmetic products. Cinnamate UV filters are structurally related to cinnamon-related fragrances. OBJECTIVE: The purpose of this study was to determine if 'cinnamon-sensitive' patients show positive photopatch tests to cinnamate UV filters and, therefore, should avoid these UV filters. METHOD: We photopatch tested cinnamon-sensitive patients (n = 18) with cinnamon, cinnamon-related fragrances, Myroxylon pereirae, and two cinnamate UV filters. RESULTS: No positive photopatch test to cinnamate UV filters was found (95% confidence interval 0-13%). DISCUSSION: The risk of developing unwanted allergic contact dermatitis because of cinnamate UV filters in cinnamon-sensitive patients seems to be low, but our study population was small. Therefore, we recommend cinnamon-sensitive patients to perform a use test, for example the repeated open application test, before using cosmetic products containing cinnamate UV filters. In addition, physicians and patients should be aware that many sunscreens contain (cinnamon-related) fragrances and could, therefore, elicit allergic contact dermatitis in cinnamon-sensitive patients, independently from other potential sensitizing components of the sunscreen.

Hearing status, need for recovery after work, and psychosocial work characteristics: results from an internet-based national survey on hearing.

The main aim of the study is to address the relationship between hearing status and need for recovery. In addition, the role of hearing status in the relationship between psychosocial work characteristics (i.e. job demands and job control) and need for recovery was assessed. The sample comprised 925 normally-hearing and hearing-impaired working adults (aged 18-65 years) participating in the National Longitudinal Study on Hearing. Hearing status was determined using the national hearing (speech-in-noise) test over the internet. Psychosocial work characteristics and need for recovery were assessed using the job content questionnaire and the Dutch questionnaire on the experience and assessment of work. Regression models revealed a significant association between hearing status and need for recovery after work, poorer hearing leading to an increasing need for recovery. Additionally, poorer hearing led to a higher odds for risky levels of need for recovery. Hearing status did not influence the significant relationship between psychosocial work characteristics (i.e. job demand and job control) and need for recovery after work. Implications for clinical practice, such as the necessity of having adequate enablement programs for this specific group of patients, are discussed.

Objective acoustic-phonetic speech analysis in patients treated for oral or oropharyngeal cancer.

OBJECTIVE: Speech impairment often occurs in patients after treatment for head and neck cancer. New treatment modalities such as surgical reconstruction or (chemo)radiation techniques aim at sparing anatomical structures that are correlated with speech and swallowing. In randomized trials investigating efficacy of various treatment modalities or speech rehabilitation, objective speech analysis techniques may add to improve speech outcome assessment. The goal of the present study is to investigate the role of objective acoustic-phonetic analyses in a multidimensional speech assessment protocol. PATIENTS AND METHODS: Speech recordings of 51 patients (6 months after reconstructive surgery and postoperative radiotherapy for oral or oropharyngeal cancer) and of 18 control speakers were subjectively evaluated regarding intelligibility, nasal resonance, articulation, and patient-reported speech outcome (speech subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 module). Acoustic-phonetic analyses were performed to calculate formant values of the vowels /a, i, u/, vowel space, air pressure release of /k/ and spectral slope of /x/. RESULTS: Intelligibility, articulation, and nasal resonance were best predicted by vowel space and /k/. Within patients, /k/ and /x/ differentiated tumor site and stage. Various objective speech parameters were related to speech problems as reported by patients. CONCLUSION: Objective acoustic-phonetic analysis of speech of patients is feasible and contributes to further development of a speech assessment protocol.

Screening for distant metastases in head and neck cancer patients by chest CT or whole body FDG-PET: a prospective multicenter trial.

BACKGROUND AND PURPOSE: The aim of the study was to define the added value of whole body FDG-PET in screening for distant metastases in patients with head and neck squamous cell carcinoma and risk factors. MATERIALS AND METHODS: In a multi-center prospective study between 1998 and 2003, 145 consecutive HNSCC patients with risk factors for distant metastases underwent chest CT and whole body FDG-PET for screening of distant metastases. The data of 92 evaluable patients who developed distant metastases or who had a follow-up of at least 12 months were analyzed. Besides their performance in clinical practice, the operational characteristics of PET and CT using ROC analyses were investigated. RESULTS: Pretreatment screening identified distant metastases in 19 patients (21%). FDG-PET had a higher sensitivity (53% vs. 37%) and positive predictive value (80% vs. 75%) than CT. The combination of CT and FDG-PET had the highest sensitivity (63%). The ROC analyses of the five point ordinal scales revealed that the "area under the curve" (AUC) of FDG-PET was significantly higher as compared to CT. CONCLUSION: In HNSCC patients with risk factors, pretreatment screening for distant metastases by chest CT is improved by FDG-PET.

Colonic lavage with two polyethylene glycol solutions prior to colonoscopy makes no difference: a prospective randomized controlled trial.

OBJECTIVE: It is suggested that bowel preparations for colonoscopy are easier to tolerate when a smaller volume of solution with a more pleasant taste is used. The aim of this study was to establish equivalence between a 3-l sulphate-free polyethylene glycol solution (SF-PEG) and a 4-l PEG solution in effectiveness, patients' acceptability and tolerability. MATERIAL AND METHODS: The study comprised 110 patients scheduled for elective colonoscopy and randomized to receive either SF-PEG or PEG. Before colonoscopy, the patients completed a questionnaire on stool frequency, medication, concomitant diseases, the amount of solution ingested, willingness to re-take it, volume of other fluid taken and tolerance of bowel preparation, taste of the laxative and occurrence of abdominal cramps. Three experienced endoscopists, blinded to the type of preparation, assigned bowel-cleansing scores using a validated 5-point scale to assess cleansing effect. RESULTS: Data were available for 102 patients (44 M (40%), mean age 53 years, range 23-83 years). No significant differences were found in cleansing the rectosigmoid (p = 0.71) or complete colon (p = 0.79). Diverticulosis, constipation, gender and body mass index (BMI) did not influence cleansing. There was no significant difference in compliance between the two groups (p = 0.61). No differences were found for tolerance, taste and abdominal cramps. Patients who received SF-PEG had a preference for the same preparation next time in comparison with patients who had PEG cleansing (17 (33%) versus 4 (8%), respectively) (p = 0.03). CONCLUSIONS: Both preparations are comparable in their cleansing effect and toleration. However, patients prefer cleansing with a smaller volume of solution. Improving the acceptability of colonic preparation could improve willingness to undergo colonoscopies in the future.

Comparative evaluation of genetic assays to identify oral pre-cancerous fields.

BACKGROUND: Oral squamous cell carcinomas often develop in a pre-cancerous field, defined as mucosal epithelium with cancer-related genetic alterations, and which may appear as a clinically visible lesion. The test characteristics of three genetic assays that were developed to detect pre-cancerous fields were investigated and compared to histology. METHODS: In total, 10 pre-cancerous fields that were not visible at clinical inspection and gave rise to malignant transformation based on an identical TP53 mutation in tumor and mucosal epithelium in the surgical margin, as well as 10 normal oral mucosa specimens were analyzed for numerical chromosomal changes with multiplex ligation-dependent probe amplification (MLPA), for loss of heterozygosity (LOH), with microsatellite PCR and for DNA index alterations with DNA image analysis. RESULTS: No alterations were detected in normal tissue by either of the assays. Both MLPA and LOH assays detected all pre-cancerous fields. DNA cytometry identified aneuploidy in four of 10 pre-cancerous fields, while the corresponding tumors that developed in these fields were shown to be aneuploid. CONCLUSIONS: Both the MLPA and LOH assay seem suitable for screening pre-cancerous fields in subjects at high risk for oral cancer even in the absence of clinically abnormal appearing oral mucosa. Measurements of DNA index might be valuable to determine the time to progression.

A randomized trial of PET scanning to improve diagnostic yield of direct laryngoscopy in patients with suspicion of recurrent laryngeal carcinoma after radiotherapy.

The RELAPS study (REcurrent LAryngeal carcinoma PET Study) was designed to determine whether FDG-PET is of value in the selection of patients for direct laryngoscopy under general anesthesia in patients with suspicion of recurrent laryngeal carcinoma after radiotherapy. In a randomized controlled clinical trial the current diagnostic practice, i.e. all patients undergo direct laryngoscopy, will be compared to a strategy in which FDG-PET selects the patients for laryngoscopy. All eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group NWHHT will participate in this multicenter trial. The study population consists of patients with clinical suspicion of recurrent T2-T4 laryngeal carcinoma after radiotherapy (without obvious signs of tumor) in whom a direct laryngoscopy under general anesthesia with taking of biopsies is indicated by the local physician. The primary efficacy endpoint is the difference in the number of futile indications for direct laryngoscopy between the conventional diagnostic arm and the FDG-PET based diagnostic arm. An indication for laryngoscopy is classified as futile if this laryngoscopy was negative and no recurrence was diagnosed within 6 months follow-up (gold standard). The FDG-PET based strategy may increase the risk of missing recurrent tumor compared to current practice. Safety endpoints include survival and morbidity due to laryngoscopy with taking of biopsies. Survival rates of both groups will have to be collected outside the time frame of the funded trial. Resectability of recurrent tumor and tumor negative surgical margins after total laryngectomy will be used as proxy endpoints. The trial will also compare quality of life and direct medical costs between both arms.

Distress in spouses and patients after treatment for head and neck cancer.

BACKGROUND: The objective of this study is to obtain insight into distress in spouses and patients treated for head and neck cancer. METHODS: Forty-one patient-spouse pairs completed the Hospital Anxiety and Depression Scale (HADS). Inclusion criteria included curative treatment for head and neck cancer. Exclusion criteria were visiting the clinic without a spouse, bad news at the routine follow-up examination, diseases causing cognitive dysfunction, and poor understanding of the Dutch language. Next to the HADS, the assessment protocol included age, gender, health status, coping strategy, time since cancer treatment, tumor stage and site, treatment modality, functional and social impairment, and caregiving burden. RESULTS: A clinical level of distress was noted in 20% of the spouses and in 27% of the patients. Distress in spouses was related to the presence of a feeding tube in patients, a passive coping style, less vitality, and a disrupted daily life schedule resulting from caregiving. Distress in patients was related to the presence of a feeding tube, speech and swallowing problems, less social contacts, a passive style of coping, and nonexpression of emotions. CONCLUSION: Distress is often present in spouses and patients treated for head and neck cancer. Routine screening for psychologic distress is recommended.

The prevalence of hypothyroidism after treatment for laryngeal and hypopharyngeal carcinomas: are autoantibodies of influence?

CONCLUSIONS: The incidence rate of hypothyroidism after treatment for laryngeal and hypopharyngeal cancer is high, especially after combination treatment. An association between hypothyroidism and autoantibodies was found. OBJECTIVES: The incidences of hypothyroidism and autoantibodies were assessed retrospectively in 156 patients with laryngeal and hypopharyngeal carcinoma who were treated with surgery and/or radiotherapy between 1977 and 2002. PATIENTS AND METHODS: Patients treated for T2-T4 carcinoma or a recurrence after T1 who visited the outpatient clinic for their regular follow-up visit were included. All patients were evaluated for the development of hypothyroidism, defined as increased thyroid-stimulating hormone level (>4.5 mU/L) and the presence of autoantibodies. A questionnaire regarding symptoms was administered. RESULTS: The prevalence of undiagnosed hypothyroidism following treatment of laryngeal carcinoma was 28.2%: 18.6% subclinical hypothyroidism and 9.6% clinical hypothyroidism. The prevalence of circulating antithyroid antibodies (anti-thyreoperoxidase and/or anti-thyreoglobulin) was 10.5%. Univariate analysis showed that patients with laryngectomy, hemithyroidectomy, ipsilateral neck dissection and autoantibodies had a higher risk of hypothyroidism. The combination of surgery and radiotherapy increased the risk. Symptoms such as weight gain and cold intolerance were significantly associated with hypothyroidism. Multivariate analysis showed hemithyroidectomy, autoantibodies, weight gain and cold intolerance to be prognostic factors for the development of hypothyroidism.

Prognostic factors in adult soft tissue sarcomas of the head and neck: a single-centre experience.

Adult soft tissue sarcomas of the head and neck are rare and consist of a variety of histopathological subtypes and sites. The purpose of this study was to review patients treated for adult soft tissue sarcomas of the head and neck at our institute. The medical records of 41 adult patients treated for head and neck soft tissue sarcomas between 1983 and 2004 were reviewed. Thirty-six tumours were histologically reviewed. Histopathological revision showed that 7% of the original sarcomas were found not to be sarcomas and 39% of the sarcoma subtypes changed. Multivariate analysis showed that surgical margin status and lymph node metastases are the most important prognostic factors. Review of histopathological examination of tumours showed a change in subtype in a substantial number of head and neck sarcomas. Negative surgical margins are an important prognostic factor, but are difficult to obtain in head and neck sarcomas.