Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases.

BACKGROUND: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era. METHODS: In our individual-level analysis of 712 patients (2000-2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism. The study outcomes were new or recurrent venous thromboembolism or peripheral septic lesions, major bleeding, all-cause death and clinical sequelae. RESULTS: The median age was 21 (Q1-Q3: 17-33) years, and 295 (41%) were female. At diagnosis, acute thrombosis of head/neck veins was detected in 597 (84%) patients, septic embolism in 582 (82%) and both in 468 (80%). After diagnosis and during in-hospital follow-up, new venous thromboembolism occurred in 34 (5.2%, 95% CI 3.8-7.2%) patients, new peripheral septic lesions became evident in 76 (11.7%; 9.4-14.3%). The rate of either was lower in patients who received anticoagulation (OR: 0.59; 0.36-0.94), higher in those with initial intracranial involvement (OR: 2.35; 1.45-3.80). Major bleeding occurred in 19 patients (2.9%; 1.9-4.5%), and 26 died (4.0%; 2.7-5.8%). Clinical sequelae were reported in 65 (10.4%, 8.2-13.0%) individuals, often consisting of cranial nerve palsy (n = 24) and orthopaedic limitations (n = 19). CONCLUSIONS: Patients with Lemierre syndrome were characterized by a substantial risk of new thromboembolic complications and death. This risk was higher in the presence of initial intracranial involvement. One-tenth of survivors suffered major clinical sequelae.

Value of fine-needle aspiration cytology of parotid gland masses.

OBJECTIVE: To evaluate the usefulness and accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses. STUDY DESIGN: Retrospective chart review of patients undergoing FNAC. METHODS: Between January 1990 and December 1998, 410 parotid glands were resected at the Department of Otorhinolaryngology-Head and Neck Surgery at the University of Berne, Inselpital (Berne, Switzerland). Included in the study were 228 cases with preoperative FNAC. In a retrospective study the results of FNAC were analyzed and compared with the corresponding histopathological diagnosis. RESULTS: Histological evaluation revealed 65 malignant tumors and 163 benign lesions (150 neoplasms and 13 nonneoplastic lesions). The cytological findings were nondiagnostic in 13 (5.7%), true-negative in 146 (64%), true-positive in 39 (17%), false-negative in 22 (9.8%) and false-positive in 8 (4.5%) cases in detecting malignant tumors. Nineteen of 39 (49%) malignant tumors (true-positive) and 123 of 146 (84%) benign lesions (true-negative) were classified accurately. The accuracy, sensitivity, and specificity were 86%, 64%, and 95% respectively. CONCLUSIONS: Fine-needle aspiration cytology is a valuable adjunct to preoperative assessment of parotid masses. Preoperative recognition of malignant tumors may help prepare both the surgeon and patient for an appropriate surgical procedure.

[Results of voice rehabilitation with Provox prostheses]. / Ergebnisse der Stimmrehabilitation mit Provox-Prothesen.

From 1992 to 1998, 105 patients of the Department of Otorhinolaryngology, Head and Neck Surgery in Berne underwent laryngectomy with primary implantation of a Provox prosthesis. These patients were followed up in an open prospective study and evaluated by the HRS scale, based on speaking ability and quality as well as on prosthesis care. 46 patients (44%) attained successful rehabilitation of the voice, defined as 12-15 points according to the HRS scale. Age, tumour stage and postoperative irradiation did not influence the results. Compared to the patient group with less than 12 HRS points, frequent replacements or short in situ lifetime of the prosthesis improve the results of rehabilitation. Patient compliance is an important factor in achieving success with the Provox prosthesis.

[Epiglottitis--a pediatric disease?]. / Die Epiglottitis--eine Erkrankung im Kindesalter?

Epiglottitis, commonly described as a paediatric disease, also occurs in adults. Early diagnosis and immediate treatment are crucial because of the rapid and possibly lethal course of upper airway obstruction due to swelling. Initial treatment consists in securing the upper airway and in antibiotic treatment. Streptococci and, especially in children, Haemophilus influenzae b are the most common bacteria. Our study focused on clinical and epidemiological changes since children started to be vaccinated against Haemophilus influenzae b in Switzerland (1992). We reviewed patient histories of 31 adults and 88 children who were hospitalised with epiglottitis at the University Hospital of Berne between 1989 and 1999. Our findings show that the incidence of epiglottitis in children, a clinically, epidemiologically and bacteriologically homogeneous disease, has dramatically decreased. Epiglottitis in adults presents as a more heterogeneous disease without change since the beginning of the vaccination programme. Due to the variety of germs it is impossible to recommend vaccination for adults against Haemophilus influenzae b.

[Assessment of outer hair cell function recovery by means of the DPOAE threshold]. / Die Erfassung von Regenerationsvorgängen äusserer Haarzellen mit Hilfe der DPOAE-Schwelle.

Distortion product otoacoustic emissions (DPOAE) originate from nonlinear mechanical sound processing in the inner ear, mainly due to normal outer hair cell function. Outer hair cell impairment can be detected by means of DPOAE. With a special primary tone level paradigm which optimises the primary tone level difference over a wide stimulus level range (L1 = 0.4 L2 + 39 dB, L2 = 20 to 65 dB SPL, f2 = 0.5 to 8 kHz, f2/f1 = 1.2), DPOAE can be measured at levels close to the psychophysical hearing threshold. From the DPOAE growth functions, which are constructed from measurements at different stimulus levels, a DPOAE threshold can be defined (Boege et al., 1998), which can be interpreted as a threshold of mechanical processing by the outer hair cells. In this study, DPOAE thresholds were examined in 9 patients with reversible cochlear hearing loss, i.e. sudden deafness or noise trauma. With increasing hearing loss, low primary tone level DPOAE in particular decreased, and thus the DPOAE threshold increased. The DPOAE threshold makes it possible to detect mechanical sensitivity losses in a frequency-specific manner. Thus, loss of mechanical amplification may be differentiated from a non-mechanical cause of hearing loss.

Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects.

AIMS: Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in six healthy volunteers in a randomized, double-blind, three-way cross-over study. METHODS: Acoustically evoked short (SLP) and middle (MLP) latency potentials, transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra were analysed after short i. v. injections of placebo, or 0.15 mg kg-1 midazolam, or alpha-hydroxy-midazolam, respectively. RESULTS: All subjects fell asleep during the 4 min infusion of active drug. SLP showed a significant transient increase of Jewett wave V 10 min after injection for midazolam and alpha-hydroxy-midazolam while the latency of wave I was unchanged. Both benzodiazepines induced a marked and long-lasting MLP amplitude decrease for 240 min with slow recovery over the following 360 min. No changes of TEOAE were observed. In agreement with earlier reports, increases in EEG beta activity and decreases in alpha activity were observed after administration of either drug. CONCLUSIONS: Systemically administered benzodiazepines modulate the auditory pathway above the level of the cochlea. While SLP changes were closely associated with sedation and high plasma benzodiazepine concentrations, MLP effects persisted for hours after sedation even at low benzodiazepine plasma levels. Evoked potentials may therefore be more sensitive than EEG as a tool to monitor benzodiazepine effects.

Biomechanical properties of sterilized human auditory ossicles.

Bone allograft material is treated with sterilization methods to prevent the transmission of diseases from the donor to the recipient. The effect of some of these treatments on the integrity of the bone is unknown. This study was performed to evaluate the effect of several sterilization methods on the mechanical behaviour of human middle ear bones. Due to the size and composition of the bones (approximately 1.5 mm diameter by 4 mm long), mechanical testing options were limited to the traditional platens compression test. Experiments were first performed with synthetic bone to evaluate the precision of this test applied to small specimens. Following this, fresh frozen human ossicles were thawed and sterilized with (i) 1 N NaOH (n = 12); (ii) 0.9% LpH, a phenolic solution (n = 12); or (iii) steam at 134 degrees C (n = 18). A group of 26 control specimens did not receive any sterilization treatment. Material and structural properties were determined from axial compression testing. Results from the synthetic bone showed that the test was reproducible, with standard deviations less than 20% of the means. Significant differences occurred in stiffness and ultimate force values between NaOH-treated and autoclaved bones when compared to normals (p<0.05), but not for LpH-treated bones. LpH is not approved for medical use, so NaOH is the most appropriate of the treatments studied for the sterilization of ossicle allografts.

Extramedullary solitary plasmacytoma of the head and neck. A clinicopathological study.

Monoclonal extramedullary plasmacytoma (EMP) is a rare, low-grade lymphoma found predominantly in the head and neck region. Only since the introduction of immunophenotyping techniques 2 decades ago has it been possible to differentiate EMP from benign polyclonal plasma cell proliferation. The purpose of this study was to trace the evolutionary profile of the disease under consideration of monoclonality assessment. The records of 24 patients with morphologically diagnosed EMP treated in a single institution underwent clinical and pathological review. Only 14 patients had true monoclonal plasmacytoma. No EMP-related deaths occurred. Two patients had local recurrence, and 2 patients developed multiple myeloma. Review of the literature confirms the low-grade malignancy of EMP. Diagnostic procedures must exclude benign polyclonal plasmacytoma, multiple myeloma, and solitary bone plasmacytoma. The slow natural progression of the disease and the rarity of secondary multiple myeloma favor nonmutilating local surgery whenever possible to avoid the long-term sequelae of radiotherapy.

Spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in locally advanced head and neck cancer.

BACKGROUND: Apoptotic cell death plays a key role in the pathogenesis, aggressiveness, and therapy responsiveness of cancer. The suicidal machinery of apoptosis is genetically controlled. Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. OBJECTIVE: To assess the rate of spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in locally advanced squamous cell carcinomas of the head and neck. DESIGN: Twenty-six patients with locally advanced squamous cell carcinoma of the head and neck were included in the study. The expression of p53, Bcl-2, Mcl-1, Bax, and Bak was assessed by immunohistochemical analysis. The terminal deoxytransferase-mediated deoxyuridine nick end-labeling assay was used to quantify apoptosis by flow cytometry. RESULTS: Tumor cells containing immunostaining for the antiapoptotic proteins Bcl-2 and Mcl-1 were present in 4 (15%) and 24 (92%) of the cases evaluated, respectively, whereas immunopositivity for the proapoptotic proteins Bax and Bak was found in 9 (35%) and 24 (92%) of the samples. Immunoreactivity to p53 was detected in 20 (77%) of the samples. There was a positive correlation between the expression of Bcl-2 and Bax and between Mcl-1 and Bak. A low fraction of apoptotic cells (<2.5%) in the pretreatment tumor samples was significantly correlated with increased 2-year survival in these patients. CONCLUSIONS: Our results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl-1, Bax, and Bak in locally advanced head and neck cancer. In addition, this study suggests that the apoptotic fraction in pretreatment tumor samples might be of prognostic importance for the outcome in these patients.

Expression of apoptosis regulatory proteins of the Bcl-2 family and p53 in primary resected non-small-cell lung cancer.

Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. Alterations in the expression of these proteins can contribute to the formation of cancer, as well as influence tumour response to chemo- and radiotherapy. We used antibodies specific for the human Bcl-2, Mcl-1, Bax, Bak and p53 proteins to examine the expression of these apoptosis-regulating genes in 49 archival specimens of patients with radically resected non-small-cell lung cancer (NSCLC). Tumour cells containing immunostaining for the antiapoptotic proteins Bcl-2 and Mcl-1 were present in 31% and 58% of the cases evaluated, respectively, whereas immunopositivity for the proapoptotic proteins Bax and Bak was found in 47% and 58% of the samples. p53 immunopositivity was detected in 61% of the samples. The expression of Bcl-2 and p53 and the expression of Mcl-1 and Bax showed a positive association (P = 0.02 and P = 0.06 respectively), whereas the expression of Bax was inversely related to p53 (P = 0.008). The expression of Bcl-2 had a negative influence on relapse-free survival in this population of primary resected NSCLC patients (P = 0.02). The expression of p53 and Bcl-2 was significantly associated with metastasis-free survival (P < 0.01). Only patients with p53-positive tumours developed metastases during the follow-up period. Our results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl-1, Bax and Bak in NSCLC. It can be expected that Bcl-2 family members have no straightforward impact on clinical outcome in this disease because their interactions in the regulation of apoptosis are complex.

Radiologic and mechanical properties of inactivated ossicle homografts.

OBJECTIVE: This study examined the effects of old and new inactivation (sterilization) techniques on the radiologic and mechanical properties of ossicle homografts. MATERIALS AND METHODS: Ninety normal incuses and malleuses received either treatment with 1) 5% formaldehyde/cialit, 2) 1N NaOH, 3) 0.9% LpH, or 4) autoclaving at 134'C, or no treatment. All ossicles were assessed radiologically by high-resolution computed tomography. After imaging, all ossicles underwent mechanical testing by destructive axial compression in a mechanical testing machine measuring force and displacement. RESULTS: Ossicles treated with cialit, NaOH, or autoclaving showed a significant decrease of ultimate force and stiffness compared with controls. LpH treatment caused no such changes in these structural properties. Material properties of yield strength, ultimate strength, and elastic modulus were also altered by cialit, NaOH, and autoclaving, but were much more difficult to assess because of uncertainty in parameter estimates. There was a significant increase in radiologic density in autoclaved ossicles, a reduction in cialit- and LpH-treated ossicles, and no change in NaOH-treated ossicles. CONCLUSIONS: All tested inactivation procedures changed the biomechanical and/or radiologic properties of ossicle homografts. However, the new procedures used to inactivate infectious agents produced changes similar to the older treatments with formaldehyde/cialit. Human allografts are able to withstand harsh but safe sterilization procedures. The NaOH treatment seems to be the most suitable method for the future. The biologic (osteogenic) potentials of ossicle homografts treated with these new preservation/inactivation methods are still unknown. Further investigations are necessary to re-evaluate the clinical use of ossicle homografts in middle ear reconstructive surgery.

[Münchhausen syndrome in otorhinolaryngology]. / Das Münchhausen-Syndrom in der Hals-Nasen-Ohren-Heilkunde.

The case of a 22-year-old nurse with Münchausen syndrome is described. Faked symptoms included sudden hearing loss and fever. In addition to the definition and classification, clues for diagnosis of faked disease are given. Early diagnosis avoids unnecessary diagnostic and therapeutic procedures. The prognosis of Münchhausen's syndrome depends on the ability to establish an effective doctor-patient relationship, even though the nature of disease renders any treatment difficult.

Type of inducing signal regulates transactivation by p53.

The tumor suppressor gene p53 is expressed in the contrasting cell fates apoptosis and proliferation. We examined whether the transactivation of the p53 target genes, waf1 and mdm2, is dependent on the cause of p53 induction in human peripheral blood mononuclear cells (PBMC). Both apoptosis triggered by the purine analog 2-chlorodeoxyadenosine (CdA) and growth stimulation by the mitogen phytohemagglutinin (PHA) induced a comparable level and time course of p53 mRNA expression. Both stimuli led also to an increase of p53 protein levels. The cytotoxic agent, but not the mitogen, led to transactivation of waf1 and mdm2 within 18 h. Transactivation was followed by apoptosis of 89% of the PBMC within 48 h. The c-myc oncogene and poly(ADP-ribose)polymerase (PARP), which also have a dual function in proliferation and apoptosis, showed an early induction by both CdA and PHA. These results add further evidence that growth stimulation and DNA damage-induced apoptosis share early gene activation pathways in normal cells. However, since p53 does selectively translate into transactivation of target genes depending on the cause of induction, this function of p53 seems to be regulated by additional factors, which are closely related to the ultimate fate of the cell.

Similarity of apoptosis induction by 2-chlorodeoxyadenosine and cisplatin in human mononuclear blood cells.

The purine analogue 2-chlorodeoxyadenosine (CdA) is unique compared with traditional antimetabolite drugs, as it has shown equal activity in dividing and resting lymphocytes. Poly(ADP-ribose)polymerase (PARP) activation and consecutive NAD+ consumption have been associated with the induction of apoptosis in resting cells. The potential of CdA to induce the p53-dependent DNA damage response was assessed in resting and phytohaemagglutinine (PHA)-activated peripheral blood mononuclear cells (PBMCs) and compared with cisplatin (DDP), a cell cycle-dependent and DNA-damaging agent that is mainly used in the treatment of solid tumours. Both drugs induced transactivation of the p53 target genes waf1 and mdm2, NAD+ consumption and apoptotic death. The expression pattern of p53 and waf1 suggests a partly p53-independent induction of waf1. The expression of c-myc and PARP, which both have a dual role in proliferation and apoptosis, was selectively induced by CdA. Cell cycle stimulation increased the cytotoxic activity of both drugs. These data show that DDP is also a potent inducer of apoptosis in resting and proliferating peripheral blood mononuclear cells. Activation of the p53-dependent DNA damage response seems to be an important component of the toxic effect of CdA.