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Biomedical subjects

Herbert Riechelmann

Publications and source records attributed to Herbert Riechelmann.

14 recordsLinked to original sources

Effect of nasal antifungal therapy on nasal cell activation markers in chronic rhinosinusitis.

OBJECTIVE: To examine the effect of nasal antifungal treatment on eosinophil cationic protein (ECP) and tryptase levels in samples of nasal lavage fluid from patients with chronic rhinosinusitis and nasal polyps. DESIGN: Prospective double-blind placebo-controlled clinical trial. SETTING: Tertiary surgical center. PATIENTS: Subjects with severe chronic rhinosinusitis and nasal polyps. Of 120 screened patients, 76 were eligible. Six patients withdrew because of minor adverse events, and 10 dropped out for other reasons. In total, 60 patients completed the study according to the study protocol. INTERVENTIONS: Nasal treatment with amphotericin B or saline control for 8 weeks. MAIN OUTCOME MEASURES: Nasal lavages were performed before and after treatment. Fungal elements were assessed by culture and with different polymerase chain reaction assays. Levels of ECP and tryptase were determined by fluorescent enzyme immunoassay. RESULTS: No correlation between cell activation markers and fungus detection was observed before treatment (all P>.20). Nasal amphotericin B treatment had no effect on levels of ECP (P = .17) or tryptase (P = .09) in nasal lavage samples. Moreover, successful fungus eradication, defined as fungus detection before but not after treatment, did not influence nasal ECP or tryptase levels (all P>.40). CONCLUSION: Neither topical amphotericin B therapy nor fungal state before and after treatment had any significant influence on activation markers of nasal inflammatory cells in chronic rhinosinusitis.

Administration, Intranasal↗

Trifunctional bispecific antibody-induced tumor cell lysis of squamous cell carcinomas of the upper aerodigestive tract.

BACKGROUND: The trifunctional bispecific antibody Removab (tbAB) bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune-cell inducing tumor cell lysis. tbAB-induced tumor cytotoxicity was assessed in an autologous human ex vivo system. METHODS: One hundred forty tumor samples and autologous peripheral blood mononuclear cells from a total of 36 patients with head and neck squamous cell carcinomas (HNSCCs) were incubated on a chicken embryo chorioallantois membrane with Removab. Tumor cells coincubated with cisplatin or cell culture medium served as positive and negative controls. Tumor cell lysis was assessed by acridine orange staining or by fluorescence-activated cell sorting of propidium iodide-marked cells after 24 and 48 hours (T24/T48) coincubation. RESULTS: Coincubation of HNSCC cells with tbAB and autologous peripheral blood mononuclear cells resulted in a 49% +/- 6% decrease of viable cells at T24 (p < .005) and in a decrease of 56% +/- 8% at T48 (p < .005) compared with the control. The tumor cytotoxicity was similar to that of cisplatin (49% +/- 7% decrease at T24 and 49% +/- 8% at T48). CONCLUSION: In an autologous human ex vivo system, the tbAB-induced tumor cell lysis was comparable to that by cisplatin.

Antibodies, Bispecific↗

Fungus culture and PCR in nasal lavage samples of patients with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) affects approximately 15 % of the adult population in industrialized countries. Fungi have been recognized as important pathogens in CRS in the immunocompromised host. Recently, fungi have been detected in more than 90 % of nasal lavages (NLs) in immunocompetent patients with CRS. Employing NLs of immunocompetent patients with CRS in the present study, the detection rates for fungi by culture techniques were compared with the results of different fungus-specific PCR assays. Standard fungal cultures were performed on NLs from 77 patients with CRS. NLs were also tested for the presence of fungal DNA by a panfungal assay with and without specific probes for Candida spp. and Aspergillus spp./Penicillium spp., and an Aspergillus-specific nested PCR assay. Nineteen of the 77 samples (25 %) grew fungi. Fungus-specific DNA was detected in 34 of 77 NLs (44 %). Twelve samples were positive for both culture and panfungal PCR, whereas seven specimens grew fungi in culture, but were negative in panfungal PCR, and an additional seven samples were positive in panfungal PCR, but negative in culture. The combination of culture and all employed PCR assays detected fungi in 39 patients (50 %). This study demonstrated that PCR and conventional culture techniques could be complementary diagnostic techniques to detect fungi in nasal specimens from CRS patients.

Adult↗

Nasal cytologies--impact of sampling method, repeated sampling and interobserver variability.

The influence of sampling technique, repeated sampling and the interobserver variability on quantitative analysis of nasal cytologies were explored. Nasal cytologies from 12 healthy and 4 allergic volunteers were repeatedly collected with a total of three different sampling techniques. Cells were demonstrated by May-Grünwald-Giemsa staining and by immunostaining for CD45 and eosinophil peroxidase (EPO). To determine the interobserver variability specimens were evaluated by three observers with various levels of nasal cytology experience. When adjusted for the variability due to sampling method and repeated sampling, the staining index for CD45+ cells was 53.4 +/- 11% (interindividual coefficient of variation: 0.21) with an average intraindividual coefficient of variation of 0.14. For CD45, staining indices differed significantly between the washing techniques and the nasal swabs (p<0.01). Repeated sampling did significantly influence the staining indices of specimens collected with nasal swabs (p<0.05). Subjects with nasal allergy had less CD45+ cells in their nasal cytologies than the non-allergic subjects (p=0.02). A high level of compliance for the quantitative analysis of nasal cytologies between three observers was found (kappa(w) range 0.95-0.98). For studies that require repeated sampling, the lavage will be recommended as best suitable to obtain nasal cytologies.

Adult↗

Three-step reconstruction of complex saddle nose deformities.

OBJECTIVE: To evaluate a reproducible surgical technique for augmentation rhinoplasty of complex saddle nose deformities, which are characterized by substantial loss of nasal structural support and result in multiple nasal abnormalities. DESIGN: Case series and surgical outcome study. SETTING: Tertiary referral center. PATIENTS: A total of 43 patients (32 female and 11 male; mean +/- SD age, 36 +/- 12 years) with complex saddle nose deformities and extensive loss of nasal volume, shape, and support who underwent reconstructive surgery between 1997 and 1999. INTERVENTION: A standardized 3-step surgical procedure using autogenous costal cartilage. MAIN OUTCOME MEASURES: Assessment of additional nasal abnormalities, graft recipient site conditions, postoperative complications, postoperative analgesic consumption, and subjective outcome assessed with a standardized telephone interview 2 years following surgery. RESULTS: Besides nasal abnormalities characteristic of complex saddle nose deformities, several additional nasal abnormalities were frequently encountered. Forty of the 43 patients had undergone previous septorhinoplasty, 26 of whom through multiple procedures. One transplant extrusion was recorded, which required revision surgery. In 8 patients, minor surgical corrections were performed. Nasal airflow was judged satisfactory or good by 30 of the 37 patients who were contacted by telephone and aesthetic appearance was considered good by 17, satisfactory by 10, and unsatisfactory by 10. CONCLUSIONS: Three-step nasal reconstruction with costal cartilage is indicated in severe saddle nose deformities. It is a comparatively reliable surgical procedure yielding satisfying results even in patients with severe deformities and unfavorable recipient site conditions.

Adult↗

Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: a randomized, double-blind clinical trial.

BACKGROUND: Recently, fungal elements were suspected to be the causative agent of chronic rhinosinusitis, and benefits of topical amphotericin B therapy have been reported. OBJECTIVE: The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind, randomized clinical trial. METHODS: Patients with chronic rhinosinusitis were administered 200 microL per nostril amphotericin B (3 mg/mL) or saline nasal spray 4 times daily over a period of 8 weeks. The response rate, defined as a 50% reduction of pretreatment computed tomography score, was the primary outcome variable. Additional outcome variables included a symptom score, a quality of life score, and an endoscopy score. Before and after treatment, nasal lavages were pretreated with dithiothreitol and examined for fungal elements by PCR and standard culture techniques. RESULTS: Seventy-eight patients were included, and 60 patients finished the study per protocol. In the control group, no positive response (0 of 32) was observed, and 2 of 28 patients responded in the amphotericin B group (P>.2). The symptom scores were distinctly worse after amphotericin B therapy (P <.005). The other parameters investigated did not differ remarkably between the treatment groups. CONCLUSION: Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms.

Administration, Topical↗

Genotype and phenotype of glutathione-S-transferase in patients with head and neck carcinoma.

OBJECTIVE: Association of glutathione-S-transferase M1 (GSTM1) polymorphisms and cancer has been demonstrated. Possible underlying mechanisms and genotype-phenotype correlations are not adequately investigated. The aim of this study was to investigate the influence of the GSTM1-null-genotype on the level of GSTM enzyme concentration and on the enzyme activity of GST in patients with head and neck cancer (HNC). METHODS: We investigated in 83 patients and 91 healthy controls the GSTM1 polymorphisms, GSTM1 protein concentration, GSTM1 protein in tumor tissues, and total GST enzyme activity. RESULTS: Total GST enzyme activity was significantly lower in patients with HNC (208 +/- 9 micromol/min*l) than in controls (264 +/- 11 micromol/min*l, P< 0.0001) but did not depend on GSTM1-genotype (P = 0.1). GSTM protein concentration in null-genotype patients (3.6 +/- 2.5 microg/mL, mean +/- SE) was significantly lower than in GSTM1 allele carriers (26.7 +/- 9.6 microg/ml, P< 0.0001); GSTM protein expression did not depend on GSTM1-genotype (P> 0.5). CONCLUSION: GST enzyme activity in patients with HNC is suppressed, indicating impaired detoxification capacity of tobacco-smoke-related carcinogens. This suppression is not correlated with the GSTM1-genotype.

Adult↗

Cumulative lifelong alcohol consumption alters auditory brainstem potentials.

BACKGROUND: Alcohol is one of the most widely abused substances in the United States and Europe. It is believed that alcohol causes brain damage that may influence the central auditory tracts. Brainstem auditory evoked potentials (BAEPs) are a common method for measuring central auditory pathways. Therefore, the influence of cumulative lifelong alcohol consumption on BAEPs in subjects with normal hearing was investigated both qualitatively and quantitatively. METHODS: BAEPs were measured in 38 male subjects, 19 of whom were head and neck tumor patients with an ECOG (Eastern Cooperative Oncology Group) scale of zero and 19 plastic surgery patients. A self-report questionnaire on alcohol and nicotine consumption together with blood tests and pure tone audiometry were obtained for all subjects before the BAEP measurement. RESULTS: The alcohol consumption of the head and neck tumor patients corresponded to high-risk, dangerous, and risky alcohol consumption behavior, whereas that of the plastic surgery patients corresponded to risky and low-risk consumption behavior. In this way, a wide spectrum of alcohol consumption was covered. The latency I-V of the high-risk, dangerous, and risky drinkers was found to be significantly delayed compared with low-risk drinkers. A logarithmic relationship between BAEP latencies and cumulative lifelong alcohol consumption was obtained. CONCLUSION: Alcohol consumption leads to damage in the brainstem. The logarithmic behavior between BAEP latencies and cumulative lifelong alcohol consumption reveals that even alcohol consumption within the range of low-risk drinkers may alter auditory evoked brainstem potentials significantly.

Adult↗

Short-term exposure to urban dust alters the mediator release of human nasal mucosa.

LEARNING OBJECTIVES: Identify any changes in cytokine (mediator) concentrations in nasal secretions after healthy individuals were experimentally exposed to urban dust. Recall what connection there was, if any, between post-exposure cytokine levels in nasal secretions on the one hand, and, on the other, counts of inflammatory cells and nasal symptoms. Report the investigators' conclusions as to whether exposure to urban dust is a cause of persistent inflammation and chronic airway disease. ABSTRACT: Thirty healthy volunteers were nasally exposed to control air and urban dust (SRM 1649a) in concentrations of 150 and 500 microg/m3 for 3 hours. Thirty minutes, 8 hours, and 24 hours after exposure, nasal cytologies were obtained, and nasal secretion levels of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha, epithelial neutrophil activating protein-78, monocyte chemoattractant protein-1, and substance P were determined. Twenty-four hours after exposure to 500 microg/m3, nasal secretion levels of IL-1beta increased 72.3% (0-150.2%, P=0.002), levels of IL-6 increased 42.2% (-28-161.9%,P=0.01), and levels of IL-8 increased 19.7% (-20.3-60.5%, P=0.03; median and 95% confidence interval). These cytokines correlated closely with nasal inflammatory cell counts. No exposure-related changes of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, epithelial neutrophil activating protein-78, and substance P levels were observed. These results provide experimental support for recent epidemiological observations that short-term increase of outdoor particulate matter concentration increases the frequency of upper respiratory diseases.

Adult↗

Effects of low-toxicity particulate matter on human nasal function.

Chronic nasal and paranasal sinus problems affect approximately 15% of the population in industrialized countries. Recent studies suggest that particulate matter might contribute to this condition. The effects of acute exposure to low-toxicity particulate matter on human nasal airflow, mucociliary transport, and nasal discomfort should be assessed. Thirty-two healthy volunteers were exposed to 0 (control), 500, 1000, and 5000 micrograms/m3 calcium carbonate dust for 3 hours and nasal saccharin transport time (STT), rhinomanometry, and visual analog scales (VAS) on nasal discomfort were obtained. A dose dependent decrease of STT (P = 0.02) and nasal patency (P = 0.04), and increased sensation of nasal obstruction (P = 0.002) and dryness (P = 0.03) was observed. The results indicate that acute exposure to low-toxicity particulate matter in concentrations frequently encountered in western agglomeration areas may affect nasal functions and cause nasal symptoms.

Adult↗

Comparison of conjunctival and nasal provocation test in allergic rhinitis to house dust mite.

BACKGROUND: Nasal allergen provocation tests (NPTs) are useful in confirming the diagnosis of allergic rhinitis, if data obtained by clinical history, skin tests and specific IgE determinations are not conclusive. Since NPTs are laborious, conjunctival provocation tests (CPTs) appear as an attractive alternative. The concordance of CPTs and NPTs with house dust mite allergen extract in sensitized and nonsensitized subjects should be evaluated. METHODS: 50 otherwise healthy subjects with self-reported house dust mite allergy and positive skin prick tests and serum specific IgE to Dermatophagoides pteronyssinus and 45 sex- and age-matched healthy controls without allergic symptoms were included. For NPTs, 100 microl allergen extract [10,000 allergy units (AU/ml)] were applied to the less congested nasal cavity. A clinical symptom score and active anterior rhinomanometry were employed to assess the response. For CPTs, 50 microl low-concentrated D. pteronyssinus extract (1,000 AU/ml), and if negative, 50 microl normally concentrated extract (10,000 AU/ml) were applied to the lower conjunctival sac. The response was assessed employing clinical symptom scores. RESULTS: NPTs and CPTs yielded concordant results in 90% of the subjects successfully tested (Cohen's kappa = 0.78, p < 0.0001). The diagnostic efficacy of the CPT, with the NPT as the reference method, was 89%, whether or not conjunctival symptoms had been reported in addition to rhinitis symptoms. Both techniques were judged almost equally uncomfortable. CONCLUSION: CPTs are an acceptable alternative to NPTs in patients with allergic rhinitis to house dust mite, even if they have no conjunctival symptoms.

Adult↗

Nasal allergen provocation with Dermatophagoides pteronyssinus in patients with chronic rhinitis referred to a rhinologic surgical center.

BACKGROUND: Skin tests and specific immunoglobulin (Ig)E determinations identify the presence of some immune response to allergens, but frequently do not correlate to allergic disease in vivo. OBJECTIVE: To compare clinical history, skin tests and specific IgE determinations with the results of nasal provocation tests (NPT) to confirm clinically relevant allergy to Dermatophagoides pteronyssinus (DP) in patients with chronic rhinitis referred to a rhinologic surgical center. METHODS: Clinical data of 2,194 patients with chronic nasal disorders treated at two rhinologic referral centers between 1992 and 1998 were evaluated. Clinical allergy work-up was routinely performed corresponding to German and European guidelines providing consistent data in both centers. RESULTS: Of chronic rhinitis patients, 752 of 2,194 (34%) had at least one positive skin reaction to a perennial allergen common in Central Europe. Three hundred seventy-three patients had a positive skin test to DP and were paradigmatically evaluated in detail. In 235 patients, a complete dataset including structured allergic history, skin test, specific IgE determinations, and NPT was available. Quality and severity of symptoms, clinical history, skin tests, and allergen-specific IgE-determinations were unreliable predictors of the outcome of NPT with DP. CONCLUSION: In patients referred for surgical treatment of chronic rhinitis, diagnosis of perennial allergy is unreliable unless confirmed with NPT.

Adolescent↗

Nasal toxicity of benzalkonium chloride.

BACKGROUND: Benzalkonium chloride (BAC) is added to nasal preparations to prevent microbial contamination. Adverse effects of BAC on human nasal mucosa should be evaluated. METHODS: The ciliotoxicity of BAC was assessed in isolated human nasal epithelia from 15 donors. The effects of nasal BAC 0.05% (4 x 200 microL/day for 8 days) on nasal saccharin transport time, inflammatory cells and cytokine levels in nasal secretions, and nasal symptom scores were assessed in a randomized, double-blind crossover trial in 16 healthy volunteers. RESULTS: In vitro, BAC was ciliotoxic (p < 0.0001). In vivo, BAC did not alter saccharin transport time in healthy individuals (p > 0.8). No BAC-associated proinflammatory effects were observed. The staining index for myeloperoxidase was 4.8% in the placebo period and 6.3% (p = 0.42) in the BAC period. Also, nasal secretion levels of cytokines and the neuropeptide substance P revealed no BAC-associated differences. Concentrations for interleukin (IL)-6 in the placebo period were 41.5 pg/mL (0.9-91.7 pg/mL) and in the BAC period were 17.6 pg/mL (3.2-65.9 pg/mL; p = 0.46), and concentrations for substance P were 119 pg/mL (58-293 pg/mL) and 131 pg/mL (80-330 pg/mL; p = 0.31), respectively. Immediately after application, BAC caused nasal irritation (p = 0.001), a burning sensation (p = 0.0003), and hypersecretion (p = 0.006). Moreover, BAC caused a persistent sensation of nasal irritation (p < 0.01). CONCLUSION: BAC in concentrations used in nasal preparations is ciliotoxic. In healthy individuals, the ciliotoxic effect of BAC is neutralized, probably by components of nasal secretions. No BAC-related proinflammatory effects have been observed. At higher doses than normally used therapeutically, BAC caused significant nasal irritation.

Adult↗