Understanding the polarity of ionic liquids.

The polarities of a wide range of ionic liquids have been determined using the Kamlet-Taft empirical polarity scales α, ß and π*, with the dye set Reichardt's Dye, N,N-diethyl-4-nitroaniline and 4-nitroaniline. These have been compared to measurements of these parameters with different dye sets and to different polarity scales. The results emphasise the importance of recognising the role that the nature of the solute plays in determining these scales. It is particularly noted that polarity scales based upon charged solutes can give very different values for the polarity of ionic liquids compared to those based upon neutral probes. Finally, the effects of commonplace impurities in ionic liquids are reported.

Otosclerosis and measles virus - association or causation?

Otosclerosis is a frequent condition which occurs exclusively in the human temporal bone. This peculiar disease affects mainly Caucasians and Indians and may cause conductive, mixed conductive-sensorineural or occasionally merely sensorineural hearing loss. Morphological investigations of the otosclerotic focus show all three phases of a chronic inflammation with bone resorption, formation of new bone and finally eburnation. Various hypotheses about the cause of inflammation were proposed in the past. Immunological reactivity to collagen, the existence of otosclerosis genes (OTSC 1-5) including mutations of the collagen gene 1A1 and 1A2 or a measles virus (MV) infection were suggested. The existence of the MV proteins and RNA within the otosclerotic tissue has been shown by several authors. However, due to mainly technical problems, no further progress to elucidate the role of the virus could be made. Epidemiological studies revealed a dramatic decrease of measles and related diseases such as the subacute sclerosing panencephalitis since the introduction of MV vaccination programs in USA and Europe. Indeed, some surgeons reported decreasing numbers of stapes surgery and a shift towards elder patients. Our epidemiological survey of all patients hospitalized with otosclerosis in Germany between 1993 and 2004 demonstrates a highly significant decrease in otosclerosis among the population vaccinated against the MV. The strong correlation makes it most plausible that the MV is at least one triggering factor for the development of otosclerosis.

Nontumorous Enlargement of the Internal Auditory Canal: A Risk Factor for Sensorineural Hearing Loss? A High Resolution CT-Study.

PURPOSE: First aim of the study was to define normal shape and diameter of the internal auditory canal (IAC). In the second part the clinical relevance of IAC-enlargement was analyzed, considering also lesions of the subtle structures at the fundus of the internal auditory canal. MATERIALS AND METHODS: 440 high resolution CT-scans of the temporal bone were used for retrospective analysis of the internal auditory canal and its fundus region. RESULTS: The mean value of the IAC diameter in axial and coronal plane was determined. In 20 of 440 patients IAC enlargement was found. In the group with pronounced enlargement (3fold SD) nearly all patients suffered from hearing impairment. In some of them we found structural abnormalities near the IAC fundus in the CSF/perilymph border zone. CONCLUSION: A new CT-based definition of normal shape and diameter of the internal auditory canal is presented. There is some evidence that a pathologic transmission of CSF-pressure in case of IAC-enlargement and/or abnormal fistulous communications could play an important role in the pathophysilogy of hearing loss. KEY POINTS: • New CT-based definition of normal internal auditory canal.• Nearly all patients showing pronounced IAC-enlargement suffer from hearing impairment.• Possible pathomechanism: Transmission of CSF-pressure on the inner ear.

Substance P modulates lymphokine activities in supernatants of cultured human duodenal biopsies.

A duodenal biopsy culture technique was used to investigate the effect of substance P on lymphokine secretion by the human gut associated lymphoid tissue. Duodenal biopsies of 7 healthy volunteers were cultured in 1 ml medium each with Pokeweed mitogen (1 microgram/ml) for 4 days at 37 degrees C. Substance P (SP) was added in concentrations ranging from 10(-12) M to 10(-6) M. Media were changed every day. Interleukin (IL)-1 beta, IL-2 and IL-2-receptor activities were determined by means of specific ELISAs. Values were referred to 5 mg biopsy weight and expressed as per cent change of basal Pokeweed mitogen-pulsed supernatant activities. 10(-8) M and 10(-6) M SP led to a decrease of IL-1 beta activity (78 +/- 13.9% and 62.8 +/- 17.1%, respectively, alpha = 0.01 each). In contrast, 10(-8) and 10(-10) M SP showed an increase in IL-2 activity up to 182.9 +/- 94.5% and 295.6 +/- 144.7%, respectively. 10(-6) M and 10(-8) M SP enhanced IL-2 receptor activities by 81.5 +/- 70% and 40.9 +/- 11.8%, respectively (alpha = 0.05). The present data demonstrate for the first time distinct SP-mediated effects on lymphokine activities in supernatants of cultured human duodenal biopsies.

Influence of Epstein-Barr virus genomes on patient survival in Hodgkin's disease.

In previous studies, Epstein-Barr virus was considered a possible etiologic factor in Hodgkin's disease. Two hundred twenty-nine cases of Hodgkin's disease were investigated for the presence of Epstein-Barr virus DNA using the polymerase chain reaction technique on formalin-fixed, paraffin-embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. In 42 cases (18.3%), genomic DNA was not amplifiable. The remaining 187 cases included the following subtypes: lymphocyte-predominant type (n = 13), nodular sclerosis type (n = 98), mixed cellularity type (n = 68), and lymphocyte-depleted type (n = 8). Sixty-six cases (35.2%) were positive for Epstein-Barr virus DNA. In the statistical analysis of available follow-up data from 130 patients, no influence of a positive Epstein-Barr virus DNA finding on length of survival time was revealed. This was true within the cohort of all patients and within the histologically defined subtypes of Hodgkin's disease. In this investigation, detection of Epstein-Barr virus DNA by polymerase chain reaction showed no prognostic relevance for patients with Hodgkin's disease.

Detection of Epstein-Barr virus genome in primary cutaneous T and B cell lymphomas and pseudolymphomas.

The Epstein-Barr virus (EBV) genome has recently been identified in Hodgkin's disease (HD) and nodal non-Hodgkin's lymphomas (NHL). In order to elucidate the possible aetiopathogenetic role of EBV in benign and malignant lymphoproliferative disorders we investigated skin specimens from 24 patients with a primary cutaneous lymphoproliferative disorders (10 T-cell lymphomas 6 B-cell lymphomas and 8 pseudolymphomas) and from 22 normal individuals for the presence of EBV DNA using the polymerase chain reaction (PCR) technique and in situ hybridization (ISH) on formalin-fixed paraffin-embedded tissue sections. EBV DNA was identified by PCR in one of two cases of mycosis fungoides, in one of seven cases of pleomorphic T-cell lymphomas, in one case of centroblastic (CB) lymphoma of six B-cell lymphomas, and in three of eight pseudolymphomas. The EBV genome was also found in 2 of 22 specimens of normal skin. The small EBV-encoded nuclear RNAs, EBERs, were not detected in any PCR-positive sample by ISH. Based on our PCR and ISH findings, EBV does not seem to play a significant role in the development of cutaneous lymphomas.

Herpes simplex virus antibodies in the perilymph of patients with Menière disease.

OBJECTIVE: To evaluate the presence of IgG antibodies directed to herpes simplex virus (HSV) in the perilymph of patients with Menière disease. DESIGN: Antibodies to HSV, Epstein-Barr virus, cytomegalovirus, and measles virus were analyzed in serum and perilymph samples by enzyme-linked immunosorbent assay. Total IgG and albumin in serum and perilymph samples were measured by nephelometer analysis. The relation of specific antivirus IgG in the perilymph vs the serum was expressed as an index. PATIENTS: Perilymph and serum samples from 7 patients with long-standing, disabling Menière disease were collected during therapeutic vestibulotomy. Perilymph and serum samples from 7 patients with otosclerosis and 2 recipients of cochlear implants were used as controls. RESULTS: Compared with the corresponding serum sample, the perilymph from the patients with Menière disease disclosed a higher level of specific anti-HSV IgG. An elevated level of specific anti-measles virus IgG in the perilymph was detected in patients with otosclerosis. Patients of all groups showed no variation of specific anti-Epstein Barr virus IgG and anti-cytomegalovirus IgG in the serum or in the perilymph. CONCLUSIONS: Our results show the presence of HSV IgG in the perilymph of patients with Menière disease and support the hypothesis that HSV may play an important role in the etiopathogenesis of Menière disease.

Persistent measles virus infection and otosclerosis.

The cause of otosclerosis is still unknown. Recently, measles virus involvement has been implicated. The aim of this study was to analyze the presence of measles virus RNA within the otosclerotic focus and to evaluate the perilymphatic antibody pattern. Bone and perilymph specimens from 40 patients with the spontaneous form of otosclerosis and from control patients were investigated by reverse transcription polymerase chain reaction (RT-PCR), Western blot techniques, and cell culture. By the use of RT-PCR, measles virus RNA could be detected in 32 patients, but not in controls. Analysis of perilymph revealed the presence of antibodies to N, F1, and M measles virus proteins in all cases, and antibodies against H protein in 2 additional cases. In preosteoblasts cultured from otosclerotic bone chips, no measles virus RNA could be amplified. We conclude that the spontaneous form of otosclerosis is, in the vast majority of cases, a measles virus-associated disease of the otic capsule.

Otosclerosis: a measles virus associated inflammatory disease.

The etiology of otosclerosis is still unknown. Immunohistochemical studies have revealed the characteristics of chronic inflammation in the otospongiotic area. Paramyxoviral structures have been identified by electron microscopy and the expression of measles virus antigen has been observed by immunohistochemistry in active otosclerotic tissue. By use of the polymerase chain reaction, measles virus related sequences have been detected in otosclerotic bone tissue but not in control specimens. The aim of our study was i) to detect measles virus genome in affected patients using a more sensitive PCR system and ii) to search for anti-measles virus IgG in the perilymph. In 13 out of 14 specimens of bone fragments from surgically removed stapedes of patients suffering from otosclerosis, measles virus RNA sequences could be detected while other tissues from the same patients and from a negative control group lacked such sequences. Furthermore, IgG anti-measles virus antibodies were detected in the perilymph of 6 patients. Our results support our previously stated hypothesis that otosclerosis is a measles virus associated disease which provokes a local immune response within the inner ear.

Measles virus in otosclerosis and the specific immune response of the inner ear.

Histologic and immunohistochemical studies of otosclerotic lesions have shown that there is a chronic inflammatory reaction of the otic capsule with bone resorption resulting from vascular invasion accompanied by inflammatory cells. During the active lytic stage of otosclerosis, paramyxoviral structures have been identified by electron microscopy and measles virus antigen expression by immunohistochemistry. Recently, measles virus related sequences have been detected in tissue of otosclerotic lesions. Because the otosclerotic focus has a close relation to the perilymphatic space, the expression of measles virus antigens within it should represent an immunologic challenge to the immune system of the endolymphatic sac. In this study, measles virus specific antibodies were detected in all of the perilymph samples from 19 patients suffering from otosclerosis, and the relative amount of these IgG antibodies was much higher than in serum samples of the same patients or in perilymph of control patients. These findings support the hypothesis that measles viruses play an crucial role in the pathogenesis of otosclerosis.

Shift of the distribution of age in patients with otosclerosis.

Morphological and biochemical investigations have shown evidence of an association between measles virus and otosclerosis. Epidemiological analysis of age and gender distributions in the 1960s and 1970s revealed a higher incidence of otosclerosis in women, the average age of onset of clinical disturbances and need for surgery being between 15 and 40 years. In the late 1960s and early 1970s a campaign to vaccinate children against measles was started in Germany. The aim of our study was to evaluate whether this campaign has had any influence on the distributions of the age and gender of patients affected by otosclerosis over the past 20 years. The study included patients suffering from clinical otosclerosis who had undergone stapedectomy between 1978 and 1999 and whose clinical data were complete (n = 1351). Statistical analysis during the recruitment period indicated a significant increase in the average age of the otosclerosis patients (p = 0.012). With regard to the gender distribution it was found that the increase of otosclerosis in women compared to men was statistically insignificant (p = 0.418). These data strongly support the hypothesis of a measles virus involvement in otosclerosis and may reflect a decreased incidence of otosclerosis in the generation of patients vaccinated against measles virus.

Persistent measles virus infection as a possible cause of otosclerosis: state of the art.

The etiopathogenesis of otosclerosis is still largely unexplained and remains controversial. Morphologic examinations have shown the presence of a chronic inflammation in otosclerotic tissue. Among the proposed explanations for this inflammation are an immunologic reaction against collagen, mutations of collagen gene 1A1, and a viral infection. In this paper, we focus on the role of measles virus in otosclerosis, and we review the current literature, devoting particular attention to a suspected paramyxoviral etiopathogenesis in Paget's disease. Our examination of footplate fragments by reverse transcription polymerase chain reaction testing in 95 patients with otosclerosis revealed the presence of measles virus RNA in 83% of cases. Quantification of measles virus immunoglobulin G (IgG) in otosclerosis patients indicated that the ratio of antimeasles virus IgG in total IgG was higher in perilymph than in serum. Furthermore, an almost identical incidence of otosclerosis and measles virus-caused mortality in women suggests that women are more susceptible to measles virus infection. Finally, since the introduction of the measles virus vaccination program in Europe, there has been a decline in the incidence of otosclerosis. Moreover, the average age of patients at diagnosis and surgery at our hospital has increased to 54 years. Our findings, when they are considered along with findings regarding the presence of paramyxoviral RNA in Paget's disease, support the hypothesis that measles virus is involved in the etiopathogenesis of otosclerosis.