New methods for fast on-site measurement of odorous compounds.

New methods for measurement of odorous gases, especially for aerosol-bound chemical compounds, have been developed in the Department of Measurement Technology (Technical University of Hamburg Harburg--MT-TUHH). Odorous compounds in the waste gases produced by the food industry were analysed based on high-volume aerosol sampling techniques, enrichment on solid phase micro extraction (SPE) cartridges and analytical measurement techniques using thermal desorption gas chromatography-mass spectrometry. The analysis results were compared to classic analytical procedures using adsorbence materials (Tenax) for enrichment. In comparison to aerosol sampling, analysis of Tenax samples was found to be ineffective, especially for analyzing polar semi volatile compounds. In addition, sensor arrays were also used in the study to characterize odors of different waste gases emitted by food production facilities. Measuring the odor units of the waste gas of a fat producing factory, the results of sensor-array-measurements show good correlation with results obtained with olfactometric measurements.

Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma.

BACKGROUND: Two-thirds of patients with squamous cell carcinomas of the head and neck (SCCHN) at diagnosis have advanced disease with projected 5-year survival rates of 30%. In those patients with distant metastatic or previously treated recurrent disease, response rate to the standard regimen of cisplatin and 5-fluorouracil is approximately 30%. The authors investigated the use of paclitaxel and carboplatin in a limited Phase II study in recurrent or metastatic SCCHN to evaluate tumor response, time to progression, survival, and toxicities of this regimen. METHODS: Patients with recurrent or metastatic SCCHN not amenable to further surgical or radiation therapy were treated with 200 mg/m(2) by 3-hour infusion of paclitaxel followed by carboplatin at an area under the concentration time curve of 6 mg/mL/minute via a 20-30-minute infusion every 3 weeks. RESULTS: Thirty-seven patients were enrolled. Ninety-five percent of patients had received prior surgery and postoperative radiotherapy. The overall response rate was 27% (95% confidence interval, 13-41%) with 1 complete and 9 PRs. Median survival of all patients was 4.9 months, and 1-year survival rate was 16%. There was a 43% response rate and 15.7-month median survival rate in patients with only distant metastatic disease and 38% response rate and a 4.5-month median survival in patients with locoregional and metastatic disease. The response rate for patients with only locoregional recurrence was 7% with a median survival of 4.8 months. Grade 3-4 myelotoxicity occurred in 24% of cycles administered. There were two treatment-related deaths due to neutropenic fever and one additional death on study may have been caused by treatment-induced thrombocytopenia. CONCLUSIONS: The combination of paclitaxel and carboplatin is significantly myelotoxic and ineffective in patients with previously treated locoregionally recurrent SCCHN, whereas it deserves further evaluation in those patients with distant metastatic disease alone. In those patients with locoregional disease, other more innovative treatments are needed.

Ototoxicity resulting from combined administration of metronidazole and gentamicin.

HYPOTHESIS: The hypothesis that metronidazole can augment the ototoxicity of gentamicin was tested. BACKGROUND: Metronidazole and gentamicin are antibiotics that are used in combination to provide broad-spectrum antimicrobial coverage. It has been observed clinically that an increased ototoxic effect occurs when these agents are used in combination. METHODS: Groups of guinea pigs were given various doses of gentamicin alone, various doses of gentamicin in combination with metronidazole, or metronidazole alone. Auditory damage was determined electrophysiologically by measurement of the compound action potential. Hair cell damage was quantified by immunofluorescent microscopy. RESULTS: Electrophysiologic data revealed an augmented ototoxic effect when metronidazole was given with both a moderate and a high dose of gentamicin. Thresholds (dB SPLp) for the compound action potential (N1) for animals receiving a medium dose of gentamicin alone (50 mg/kg) were approximately 20-dB SPLp. This threshold increased to approximately 50-dB SPLp when metronidazole (35 mg/kg) was administered along with the medium-dose gentamicin. Additionally, animals receiving high-dose gentamicin (75 mg/kg) alone demonstrated increased N1 thresholds from 85 to 95 when metronidazole (35 mg/kg) was added to the gentamicin regimen. This effect was evident histopathologically by increased cochlear hair cell damage. Outer hair cell loss for animals receiving medium-dose gentamicin alone did not differ from that of controls. When metronidazole (35 mg/kg) was combined, however, outer hair cell loss increased to approximately 50%. CONCLUSIONS: These data support the clinical observation of augmented ototoxicity in patients receiving combined gentamicin and metronidazole. Caution should be used when administering these two agents together. Clinicians should consider other antibiotic strategies whenever possible.

Ototoxicity resulting from combined administration of cisplatin and gentamicin.

The hypothesis that cisplatin can augment the ototoxicity of gentamicin was tested. Seven groups of 11 guinea pigs each were given a single dose of cisplatin either alone or 14 days before, at the beginning, midway through, or at the end of a course of gentamicin administered daily for 14 days. Blood and perilymph gentamicin and cisplatin concentrations were determined in three of the animals from each group. Auditory damage was determined in the remaining 8 animals electrophysiologically by measuring the compound action potential and alternating-current cochlear potential. Hair cell damage was determined using the surface preparation technique. An augmented ototoxic effect occurred when the cisplatin was given early in the 14-day course of gentamicin and did not occur when it was given at the end of treatment.

Quantitative study of vestibulotoxicity induced by gentamicin or cisplatin in the guinea pig.

Although aminoglycoside vestibulotoxicity is well established, the question of cisplatin vestibulotoxicity is controversial. The goals of this study were 1. to determine whether cisplatin induces vestibulotoxicity as measured histologically, and 2. to compare the vestibulotoxicity between gentamicin and cisplatin. Guinea pigs' vestibular end-organ hair bundles in control, gentamicin, and cisplatin groups were compared. In the lateral cristae of the cisplatin group, hair bundles decreased 21% on the central apex portion. In the gentamicin group, a slight decrease (17%) of hair bundles on the striola from the utricular maculae was observed, as was severe damage on the entire cristae, especially on the central apex (70%). These results indicate that gentamicin and cisplatin may not influence vestibular function of the otolithic membrane. However, gentamicin may severely damage and cisplatin may slightly damage the crista ampullaris hair bundles.

Longitudinal assessment of quality of life in laryngeal cancer patients.

BACKGROUND: Although quality of life (QL) and performance status are important outcomes in head and neck (HN) cancer, there is little systematic inclusion of these parameters in treatment trials. METHODS: Rate and recovery of function were evaluated over a 6-month period in 21 laryngeal cancer patients, 7 in each of 3 treatment groups: total laryngectomy (group 1), hemilaryngectomy (group 2), and radiotherapy only (group 3). Assessment included Performance Status Scale for Head and Neck Cancer Patients (PSS-HN: Diet, Speech, and Eating in Public subscales) and the FACT-HN, a multidimensional QL measure. RESULTS: Groups differed in patterns of performance recovery over time in expected directions. Group 1 recovered most slowly, without achieving normal functioning by 6 months; most of group 2 returned to normal functioning by 3 months; group 3 showed little overall dysfunction. There was no difference in overall QL between groups or over time. Performance status was significantly correlated with the FACT head and neck subscale and somewhat with the Physical subscale. In contrast, ability to eat and/or speak was not associated with overall QL nor with any other specific QL dimension (eg, emotional or social well-being). CONCLUSIONS: Results support the sensitivity and applicability of two site-specific performance/QL measures: PSS-HN and FACT-HN. Findings also emphasize the need to employ multidimensional tools to adequately evaluate the nonmedical outcomes in head and neck patients.

Temporal bone histopathology of cisplatin ototoxicity.

Cisplatin (cis-diamminedichloroplatinum II) is a potent chemotherapeutic agent that is useful in the treatment of a variety of malignancies. Ototoxicity is a well-known adverse side effect of this drug and has been widely described in reports on clinical and animal studies. Few human temporal bone studies, however, have been performed for cisplatin ototoxicity. This report presents four cases of cisplatin ototoxicity in patients from whom temporal bone specimens with minimal post-mortem autolysis were obtained at autopsy. All patients received between 1 and 6 cycles of cisplatin with doses ranging from 100 to 165 mg/M2 per cycle. None of the patients received significant amounts of aminoglycosides or loop diuretics. Histopathologic changes included loss of inner and outer hair cells in the basal turn of the cochlea, degeneration of the stria vascularis, and a significant decrease in spiral ganglion cells predominantly in the upper turns.

Aminoglycoside cochlear ototoxicity.

The aminoglycoside antibiotics streptomycin, kanamycin, neomycin, gentamicin, tobramycin, amikacin, and netilmicin are discussed in this article on cochlear toxicity of aminoglycosides. Topics discussed include pharmacokinetics, comparative studies on toxicity, toxicity in neonates and children, histopathology, and aminoglycoside monitoring.

Is fine needle aspiration biopsy of salivary gland masses really necessary?

The use of fine needle aspirate biopsies (FNAB's) in the outpatient setting has progressively escalated, particularly in the area of head and neck pathology. An increasing percentage of these are for salivary gland masses. We present our experience with salivary gland FNAB's at our institution for four years, from 1988-1992. One thousand and twenty-two (1,022) FNAB's of superficial masses were performed by two pathologists. One hundred sixty-three (15.9%) were salivary gland biopsies. Of these 163 cases, 21 (12.9%) were normal tissue, 77 (47.2%) were inflammatory processes, 50 (30.7%) were benign tumors, and 15 (9.2%) were malignant tumors. None of the aspirates were unsatisfactory. Tissue correlation was possible in 47 (28.8%) cases. Two false negative cases (4.3%) were identified; these were a Warthin's tumor diagnosed as chronic sialoadenitis by FNAB; and a poorly differentiated squamous cell carcinoma diagnosed as adenocarcinoma by FNAB. There were no false positive cases. Overall sensitivity was 95.7% and specificity was 100%. Our experience indicates that FNAB of salivary glands is an effective screening procedure in evaluating salivary gland masses. The cytologic diagnosis may assist the clinician in allaying patients' anxieties, as well as in further collateral workup prior to definitive therapy.

Facial nerve monitoring in otologic surgery: clinical indications and intraoperative technique.

While identification of the intratemporal portion of the facial nerve is mandatory in most otologic surgical procedures, inadvertent instrumentation, traction, or thermal injury may still result from inaccurate delineation, purposeful avoidance, or false protection of this critical structure. Improved functional preservation of the facial nerve has been achieved in acoustic neuroma surgery through the monitoring of evoked facial electromyographic activity. This technique may also be used during otologic procedures in which facial nerve manipulation is anticipated in the management of recurrent cholesteatoma, temporal bone trauma, congenital deformity, or purposeful access for cochlear implantation. Potential indications for using facial nerve monitoring in contemporary otologic surgery are detailed through illustrative case presentations, and necessary instrumentation and techniques are briefly reviewed. Intraoperative monitoring can assist the surgeon in isolating the facial nerve when chronic inflammation, traumatic injury, or anomalous development has resulted in distortion or absence of microanatomic landmarks.

The incisor absent rat: an animal model for the study of otosclerosis.

The incisor absent (ia) rat is introduced as an animal model for the study of otosclerosis. Previous animal models have failed to accurately reflect the dynamic nature of this disease. Auditory brainstem response testing suggested a conductive hearing loss in the incisor absent rat as compared to age-matched normal controls. The hearing loss, which was manifested during puberty, was progressive in nature up to 18 weeks of age. Microscopic dissection of the middle ear revealed bony abnormalities of the ossicles and oval window in the incisor absent rat. Scanning electron microscopy of the ossicles demonstrated bony lesions at the incudostapedial joint and stapes footplate. Histologic examination demonstrated thickened spongiotic bone involving the otic capsule and ossicles. The incisor absent rat model possesses an inheritable defect of the otic capsule and ossicles that results in a progressive conductive hearing loss. The genetically transmitted lesion appears histologically similar to otospongiosis. The bony pathology in the incisor absent rat is caused by defective osteoclasts and transplantation of bone marrow cells from normal rats to the incisor absent rats corrects the cellular abnormality. The incisor absent rat may represent the best animal model to date for the study of otosclerosis, its cause, and clinical treatment.

Clinical perspectives on ototoxic drugs.

Ototoxic drugs such as salicylates, the aminoglycoside antibiotics, loop diuretics, cisplatin, erythromycin, and vancomycin are widely used in clinical practice. The most commonly used are aspirin and the aminoglycoside antibiotics. This chapter briefly discusses the pharmacology of the commonly prescribed ototoxic drugs and the doses that may result in ototoxicity. An outline for the monitoring of ototoxic drugs is presented. The role of topical ear drops as a possible cause of ototoxicity is reviewed.

Indirect videolaryngoscopy versus direct endoscopy for larynx and pharynx cancer staging. Toward elimination of preliminary direct laryngoscopy.

Thirty-nine patients with cancer of the larynx and pharynx (33 untreated and six previously treated patients) underwent tumor mapping by both direct laryngoscopy (DL) and indirect videolaryngoscopy (IVL). The examiner in each case was unaware of the findings of the other evaluation method. After definitive treatment had been carried out so that pathologic and operative information was also available, comparisons of the accuracies of the two methods of staging were made. In 32 cases, IVL provided information equal to or better than that provided by DL, and a tissue sample also could be obtained during IVL. On the basis of these findings, we conclude that aggressive, office-based IVL can guide initial treatment planning (partial or total laryngectomy versus irradiation) and patient counseling. A confirmatory DL can be performed without surprises at the time of definitive surgery, rather than as a separate procedure - a cost-effective modification of standard practice.

Comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin.

Fifty-four patients treated with gentamicin and 52 patients treated with amikacin were evaluated for nephrotoxicity and ototoxicity in a prospective, randomized, blinded comparative trail. According to our definition of nephrotoxicity (an increase in serum creatinine levels to at least 50 percent and 0.5 mg/dl above the baseline value), nephrotoxicity occurred in eight (15 percent) of the patients who were treated with gentamicin and none of the patients who were treated with amikacin (p = 0.006). Using several other definitions of nephrotoxicity, the differences in incidence between the treatment arms were not significant. Nephrotoxicity appeared to be associated with impaired baseline renal function, greater age, and the presence of bacteremia. Ototoxicity occurred in six (11 percent) of the 54 gentamicin-treated patients; auditory toxicity occurred in three patients, and toxic changes were observed in three of the 33 patients who could also be evaluated for vestibular toxicity. Similarly, ototoxicity was observed in seven (13 percent) of the 52 amikacin-treated patients; auditory toxicity occurred in four patients, and of the 34 patients who could also be evaluated for vestibular toxicity, three exhibited vestibular toxicity without auditory toxicity are one experienced vestibular effects in addition to those affecting the cochlea. We observed a modest association of ototoxicity with nephrotoxicity and with an elevated mean trough aminoglycoside serum level. The results of this study indicate that amikacin may be less nephrotoxic than gentamicin in humans; however, the broad applicability of this finding to other patient populations is uncertain.

Aminoglycoside ototoxicity.

The author participated in two prospective studies of patients receiving aminoglycoside antibiotics. In the first study, 54 patients received amikacin, and 54 received gentamicin. In the second study, 61 patients received gentamicin, 50 received netilmicin, and 52 received tobramycin. The studies were randomized and the investigator was blinded when evaluating auditory and vestibular toxicity and nephrotoxicity. All patients had pure tone audiometric evaluations, and two thirds of the patients had vestibular function tests consisting of an electronystagmogram performed with 30 degrees C and 44 degrees C water. Nephrotoxicity was measured by changes in serum creatinine levels. The incidence of gentamicin toxicity in the first study was 11 per cent, and it was 18 per cent in the second study. Amikacin was ototoxic 12.9 per cent of the time, whereas the incidence of tobramycin ototoxicity was 11.5 per cent, and the incidence of netilmicin ototoxicity was 2 per cent. Cases of unilateral, delayed-onset, and reversible auditory and vestibular toxicities were seen in all drug treatment groups. Nephrotoxicity was rare with amikacin usage. Gentamicin, on the other hand, produced a 18.6 per cent, tobramycin a 25 per cent, and netilmicin a 21.3 per cent rate of nephrotoxicity.

Oenocyte differentiation correlated with the formation of ectodermal coating in the embryo of a cockroach.

The first signs of 'embryonic membrane' deposition could be observed at the 11th/12th stage of the embryonic development, while serosal apolysis occurs, and the first signs of oenocyte differentiation could be detected at the 15th stage. When pleuropodial cuticle deposition occurs, at the 16th stage, there is a rapid increase in the number of differentiating oenocytes. At the 19th stage there are some fully differentiated oenocytics, whereas, just before the cuticulin layer of the embryonic cuticle is laid down, another wave of oenocyte differentiation could be observed. The differentiation process of oenocytes and of vertebrate cells with a rapid cell membrane biogenesis (steroid secreting cells and hepatocytes) are compared. The correlation of oenocyte differentiation with ectodermal coating deposition, with molting hormone titer and with prothoracic gland differentiation is discussed.