The mismatch response in normal hearing adults: a performance comparison with stimuli relevant for objective validation of hearing aid fittings.

OBJECTIVE: A long-standing observation is that the Mismatch Response (MMR) has the potential to offer a clinically feasible index of sound discrimination. However, findings that positively identify MMRs at the individual level have been mixed, even for those who are normally hearing and who can discriminate sounds behaviourally. This complicates interpretation when an MMR is not observed. The objective of this study was to determine the reliability of the MMR using an optimised paradigm and a range of stimuli relevant to audiological applications in relation to objective verification of hearing aid fittings. DESIGN: MMRs were measured using an optimised 3-deviant paradigm in response to a range of sounds designed for aided and unaided sound field assessments, including complex tones (CTs) and speech-like signals. STUDY SAMPLE: Seventeen normally hearing adults (18-56 years). RESULTS: The most robust MMRs were recorded in response to CTs; responses were positively identified in 50 out of 51 instances (98%), assessed via objective Hotelling's T2 bias-free statistical analyses. CONCLUSIONS: The results indicate that CTs in conjunction with optimised recording and analysis parameters offer the potential to elicit robust MMRs, supporting future utilisation of MMRs for clinical audiological applications.

Emerging Topics in the Behavioral Neuroscience of Tinnitus.

This volume has highlighted the many recent advances in tinnitus theory, models, diagnostics, therapies, and therapeutics. But tinnitus knowledge is far from complete. In this chapter, contributors to the Behavioral Neuroscience of Tinnitus consider emerging topics and areas of research needed in light of recent findings. New research avenues and methods to explore are discussed. Issues pertaining to current assessment, treatment, and research methods are outlined, along with recommendations on new avenues to explore with research.

Increased auditory cortex neural response amplitude in adults with chronic unilateral conductive hearing impairment.

Animal studies have demonstrated that unilateral hearing loss can induce changes in neural response amplitude of the mature central auditory system (CAS). However, there is limited physiological evidence of these neural gain changes in the auditory cortex of human adults. The present study investigated the impact of chronic, unilateral conductive hearing impairment on cortical auditory evoked potentials (CAEPs) recorded from 15 adults (21-65 years old) in response to a 1 kHz tone (80 ms duration) presented to the impaired ear via a bone conduction transducer. The amplitude and latency of the main CAEP components were compared to those obtained from normal hearing age-matched control participants. Both P1-N1 and N1-P2 amplitudes were significantly larger in the hearing impaired relative to the control participants. Differences between groups in the mean latencies of P1, N1, and P2 were not statistically significant. These results are the first to provide direct evidence of increased neural response amplitude in the adult human auditory cortex in the presence of unilateral conductive hearing loss. Importantly, the study shows that central gain changes are a direct result of deprivation of sound rather than cochlear or neural pathology.

Evaluation and comparison of staining patterns of factor XIIIa (AC-1A1), adipophilin and GATA3 in sebaceous neoplasia.

BACKGROUND: Reliable nuclear immunohistochemical stains for sebaceous neoplasms have not been readily available. Positive nuclear staining has been reported for GATA3 and factor XIIIa (AC-1A1). We sought to determine the diagnostic utility of these nuclear stains by comparing their staining pattern to adipophilin, a consistently positive cytoplasmic stain. METHODS: Cases with the diagnosis of sebaceous hyperplasia, sebaceous adenoma, sebaceous epithelioma/sebaceoma, sebaceous carcinoma, and nonsebaceous neoplasms (basal cell carcinoma and squamous cell carcinoma) were examined. Intensity and extent of staining of the basal cells and mature sebocytes were evaluated for each stain. RESULTS: Factor XIIIa (AC-1A1) was 87.3% sensitive and 95.1% specific for all sebaceous neoplasms sand showed high inter-observer reliability. Adipophilin was 83.2% sensitive and 87.8% specific. GATA3 was the least sensitive (80.9%) and specific (75.6%) marker. When factor XIIIa was compared against composite staining of all three markers its staining was still uniquely significant (P = .0210). CONCLUSION: Factor XIIIa (AC-1A1) is a sensitive and specific nuclear marker for sebaceous differentiation. Its diagnostic utility exceeds that of adipophilin. Factor XIIIa should be included in the expanding group of immunohistochemical and special stains which can be utilized to aid in the diagnosis of sebaceous neoplasms.

Immunostimulatory effect of the aqueous leaf extract of Phyllanthus niruri on the specific and nonspecific immune responses of Oreochromis mossambicus Peters.

Plant derived immunostimulants are a promising alternative to chemotherapeutics and also perhaps vaccines. In the present study, we examined the immunostimulating properties of aqueous leaf extract of Phyllanthus niruri, an Indian traditional medicinal herb, on neutrophil activation and antibody response of Oreochromis mossambicus (Peters). Serial ten-fold diluted doses of P. niruri ranging from 0.002 mg to 20 mg were administered to two groups of O. mossambicus (n=8). One group of fishes was administered with sheep red blood cells and the primary and secondary antibody responses were estimated using direct haemagglutination assay. The other group of fishes was administered heat-aggregated BSA to assess the ability of plant extract to elicit neutrophil activation. Our results indicate a significant enhancement of both neutrophil activation and antibody response. Among the various doses tested, fishes administered 20 mg/kg body weight caused the maximal enhancement of both primary and secondary antibody response and 0.002 mg/kg showed higher neutrophil activation compared to that of the control group. This short study indicates that aqueous leaf extract of P. niruri has the potential to be used as an immunostimulant and after confirming its immunostimulatory properties by a battery of tests on other nonspecific and specific parameters and disease-protective property by challenging the fish with virulent fish pathogens, it can be used either as a routine feed supplement to activate the immune system of farmed fishes or as an adjuvant to enhance the efficacy of vaccines.

Enhanced intensity discrimination in the intact ear of adults with unilateral deafness.

Physiological measures of neural activity in the auditory cortex have revealed plasticity following unilateral deafness. Central projections from the remaining ear reorganize to produce a stronger cortical response than normal. However, little is known about the perceptual consequences of this increase. One possibility is improved sound intensity discrimination. Intensity difference limens were measured in 11 individuals with unilateral deafness that were previously shown to exhibit increased cortical activity to sounds heard by the intact ear. Significantly smaller mean difference limens were observed compared with controls. These results provide evidence of the perceptual consequences of plasticity in humans following unilateral deafness.

Evidence for multiple mechanisms of cortical plasticity: a study of humans with late-onset profound unilateral deafness.

OBJECTIVE: To investigate 1: plasticity due to partial unilateral deafness of slow onset and 2: the time course of plasticity following abrupt, profound unilateral deafness in adult humans using cortical auditory evoked potentials. METHODS: Baseline data were measured from six participants with partial unilateral deafness due to an acoustic neuroma and compared with data from six controls. Further measurements were made in the unilaterally deaf group at 1-, 3- and 6-months post surgery for acoustic neuroma removal and consequent profound unilateral deafness. Data were recorded from 30 channels in response to pure tones presented to the intact ear. RESULTS: Baseline data revealed statistically higher amplitudes in unilaterally deaf participants but with normal hemispheric asymmetry. Longitudinal data revealed further increases in P1 amplitudes by 1-month post-surgery, and in N1 and P2 amplitudes by 6-months post-surgery, with statistically different scalp field topographies indicating reduced hemispheric asymmetries. CONCLUSION: Different patterns of plasticity occur following partial and profound unilateral deafness. Plasticity occurs both relatively rapidly and more gradually over at least 6-months post-surgery. SIGNIFICANCE: The different patterns of change over time are consistent with multiple physiological mechanisms of plasticity. Unravelling these mechanisms and their time course in humans may be relevant in understanding and, ultimately, influencing plasticity for therapeutic gain.

Investigation of cortical and subcortical plasticity following short-term unilateral auditory deprivation in normal hearing adults.

There is growing evidence that auditory stimulation or deprivation can induce physiological and perceptual changes in the auditory system of normal hearing adults. The present study investigated cortical (hemispheric asymmetry) and subcortical (acoustic reflex threshold) changes in 11 normal hearing adults after 7 days of continuous unilateral earplug use (around 30 dB of attenuation at the high frequencies). The results revealed: (a) a decrease in high frequency acoustic reflex thresholds of around 7 dB in the ear that had been plugged and (b) no change in hemispheric asymmetry. The change in acoustic reflex is consistent with subcortical plasticity. It is unclear if homoeostatic plasticity preserved the normal hemispheric asymmetry or if this is the result of the experimental paradigm.

Source analysis reveals plasticity in the auditory cortex: evidence for reduced hemispheric asymmetries following unilateral deafness.

OBJECTIVE: To investigate the effect of acquired unilateral deafness on hemispheric asymmetries in adult humans using cortical auditory evoked potentials. METHODS: N1 cortical auditory evoked potentials were measured from 30 channels in 18 unilateral profoundly-deaf participants (6 right-sided and 12 left-sided deafness) and 18 audiogram-matched controls. Stimuli were 0.5-kHz and 4-kHz tones presented monaurally, and the data were analysed using global field power and dipole source analysis. RESULTS: There was a statistically significant difference in dipole source strength and orientation between the two groups. Similar changes (increased dipole strength and more medial orientation) were apparent after profound unilateral deafness of either ear and for both stimuli. CONCLUSIONS: The results reveal evidence of central auditory system plasticity that is consistent with animal models having experimentally induced unilateral deafness. SIGNIFICANCE: The trend towards reduced hemispheric asymmetries was reflected in the dipole source model by changes in dipole strength, location and orientation. These findings may explain the inconsistencies reported in previous studies involving dipole source analysis where location and orientation have not always been considered.

Uterine pleomorphic rhabdomyosarcoma: a case report and review of literature.

Primary pleomorphic rhabdomyosarcoma of the uterus is a very rare neoplasm. We describe a 65-year old female with this diagnosis, who underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy and lymph node dissection. Also included is a discussion on the different types of rhabdomyosarcoma with reviews of their histological features, epidemiology and common sites of origin.

A rare case of synchronous invasive ductal carcinoma of the breast and follicular lymphoma.

Synchronous presentation of breast cancer and lymphoma is extremely rare. Few cases are reported in the literature. We describe a case of invasive ductal carcinoma of the breast with micrometastasis to a non-sentinel lymph node and subsequent incidental finding of a low-grade follicular lymphoma in an axillary node of a 52-year-old woman. The characteristic immunohistochemical profile of the lymphoma is described.

Immune response and disease resistance of Oreochromis mossambicus to Aeromonas hydrophila after exposure to hexavalent chromium.

The objective of this study was to investigate the effect of chronic exposure to sublethal concentrations of hexavalent chromium (K2Cr2O7) on the immune response and disease resistance of Oreochromis mossambicus (Peters) to bacterial Aeromonas hydrophila infection. Fish (45 to 50 g) were exposed to 0.005, 0.05, 0.5, and 5 mg l(-1) [0.01, 0.1, 1, and 10% LC50, respectively] of hexavalent chromium Cr (VI) for 28 d. The specific immune response was assessed by antibody response to A. hydrophila by bacterial agglutination assay, and to sheep red blood cells (SRBC) by plaque forming cell (PFC) assay. In addition, nonspecific immune mechanisms were assessed by serum lysozyme activity and reactive nitrogen intermediates, the latter in terms of nitric oxide (NO) production by peripheral blood leucocytes. Overall immunity was assessed by disease resistance against live virulent A. hydrophila. The study clearly indicated that chronic exposure of fish to 0.5 and 5 mg l(-1) of chromium (VI) decreased both nonspecific and specific parameters of the immune system, which resulted in a lower disease resistance to A. hydrophila. Interestingly, 0.05 mg l(-1) of Cr (VI) enhanced disease resistance and both nonspecific and specific immune responses to A. hydrophila. Our study revealed a concentration-dependent modulation of the immune system by chromium (VI), as demonstrated by suppressive or stimulatory effects on lymphocytes, lysozyme, phagocytic killing mechanisms, and disease resistance in O. mossambicus.

Report of unusual clinical appearance in bacteraemia with nonhaemolytic M-type 58 Streptococcus pyogenes.

BACKGROUND & OBJECTIVES: The occurrence of haemolytic colonies on blood agar often provides the starting point for the laboratory diagnosis of pyogenic streptococci, while non-haemolytic variants could pass unrecognised, leading to a failure of diagnosis. We report the details of two epidemiologically unrelated patients with bacteraemia featuring M-type 58 Streptococcus pyogenes, a seemingly rare cause of human infection in the UK, and briefly review previous reports of infection with non-haemolytic strains of this species. METHODS: Case notes of the two patients were reviewed. Isolates obtained from clinical specimens were recovered and identified and cultured on horse blood agar to observe pattern of haemolysis. RESULTS: In the first case, of a 75 year-old man with leukaemia and a retropharyngeal abscess, the isolate was consistently non-haemolytic, probably due to a failure to produce streptolysin S as has been described before in a small number of reports involving various M-types. In the second case, of an 84 year-old woman with dermatitis and septicaemia, the organism was principally beta-haemolytic but with no haemolysis on aerobic culture where the colonies were well spaced, a phenomenon thought to be associated with abundant production of serum opacity factor (OF). INTERPRETATION & CONCLUSION: These cases are a reminder that misleading cultural appearances can occur with S. pyogenes and that OF positive strains can produce poor haemolysis on aerobic culture, or fail even to do so at all.

Changing incidence of detected streptococcal bacteraemia in North Yorkshire, England.

BACKGROUND & OBJECTIVES: Streptococcal bacteraemia remains a major and challenging clinical problem throughout the world. The epidemiology of these infections appears to be changing. In the present study we analysed the data collected over a period of 20 yr (1978-1999) to throw light on this. METHODS: Laboratory records of all patients yielding clinically significant, non-pneumococcal, nonenterococcal streptococcal bacteraemia were reviewed for the decades 1978-1988 and 1990-1999 in the two districts (combined population 260,000). RESULTS: From a total of 3134 patients with detected bacteraemia 338 (10.8%) yielded streptococci. The organisms comprised: in the beta-haemolytic group (n=169), GAS (32%), GBS (34%), GCS (5%), GGS (28%), GRS (1%); in the non-haemolytic/Streptococcus milleri group (n=160): S. milleri (21%), S. bovis (10%), S. sanguis (30%), S.mitis (10%), S. oralis (8%) and other 'viridans' streptococci (20%); nine isolates were of anaerobic streptococci. There was a steady increase in the number of blood cultures submitted for investigation during the period and streptococcal isolations of all species rose in proportion (approximately x 2.5) in the second decade compared with the first. Complementary data on the occurrence of necrotising fasciitis and toxic shock syndrome in these districts suggested a real increase in the occurrence of serious forms of GAS infection. INTERPRETATION & CONCLUSION: An increase in the level of detected streptococcal bacteraemia was seen in this part of England over 20 yr, involving a wide variety of different streptococcal species. This represented both improved ascertainment of infection and an increase in the burden of disease in the population.

Streptococcus milleri group bacteraemia in North Yorkshire, England (1989-2000).

BACKGROUND & OBJECTIVES: Though carriage and local infection with organisms of the Streptococcus milleri group (SMG) are regular in clinical practice, bacteraemia is infrequent in man. The objective of the present study was to give an account of our experience with the SMG bacteraemia over a period of 12 yr in North Yorkshire. METHODS: The laboratory and clinical records of all clinically significant cases of SMG bacteraemia in our district general hospital catchment (combined population 260,000) were reviewed for the 12 yr period from 1989 to 2000. Viable isolates were recovered, species identified, and minimum inhibitory concentration (MIC) determined. RESULTS: Twenty nine episodes of infection gave an annual incidence of 0.93 cases per 100,000 population. Infections included abscess, pneumonia, septic arthritis, genital and urinary tract infections, endocarditis and diffuse septicaemia. Patient ages ranged from 18 to 90 yr but most patients were elderly, 82 per cent had evident predisposing conditions and mortality rate was 10 per cent. Species determination of the 22 isolates showed S. anginosus (64%), S. constellatus (27%) and S. intermedius (9%). Nearly all isolates were non-haemolytic and Lancefield grouping showed carriage of the F antigen (in 41%), C (14%) and no detected group (45%). Most of the isolates were susceptible to the antimicrobials tested. INTERPRETATION & CONCLUSION: Bacteraemia with SMG organisms was infrequent, often opportunistic and featured a low overall mortality rate. Intra-abdominal sepsis was the local feature in 16 (55%) of the patients and 9 (31%) of the total patient group showed abscess or empyema. There was a low rate of antibiotic resistance in these organisms from bloodstream infection.

Head kidney neutrophils of carp (Cyprinus carpio L.) are functionally modulated by the haemoflagellateTrypanoplasma borreli.

In the present work responses of carp (Cyprinus carpio) head kidney-derived neutrophils to the blood parasite T. borreli, and the consequences of these responses for parasite survival and other host response mechanisms, were studied. In co-cultures of head kidney leucocytes (HKL) with viable and lysed T. borreli a prominent shape change of neutrophilic granulocytes towards increased size and complexity was observed. In addition, the longevity of neutrophils in vitro was prolonged in the presence of T. borreli antigens. In these cultures, neutrophils also exhibited an increased phagocytosis activity. An up regulation of the production of nitric oxide (NO) and reactive oxygen species (ROS) was observed in T. borreli- and mitogen-stimulated HKL cultures. However, addition of live, fluorescence-labelledT. borreli to previously stimulated HKL cultures, revealed neither killing nor phagocytosis of the parasite by activated neutrophils. Moreover, viable T. borreli, when added to HKL cultures of infected carp, reduced their phagocytosis activity and NO production. Supernatants of co-cultures between T. borreli and HKL also contained mediators, which suppressed a mitogen-induced proliferative response of peripheral blood leucocytes (PBL) in vitro. Thus, while T. borreli itself appeared not to be sensitive to responses of activated neutrophils, the flagellates interferes with the production of immunomodulatory signals of these cells, probably resulting in a partial immunosuppression, which may favour the parasite development in vivo.

The haemoflagellate Trypanoplasma borreli induces the production of nitric oxide, which is associated with modulation of carp (Cyprinus carpio L.) leucocyte functions.

In an attempt to characterise the role of nitric oxide (NO) in immune responses of carp, carp leucocytes obtained during an acute T. borreli infection were examined, for their capacity to generate NO. In a second set of experiments the impact NO on viability of the parasite and on the modulation of functional carp leucocyte responses were tested in vitro. Both in carp head-kidneys and in the peripheral blood, the fractions of lymphoblasts among separated leucocytes were increased. However, the relative proportions of granulocytes among head-kidney leucocytes (HKL) significantly decreased during infection, whereas granulocytes appeared among peripheral blood leucocytes (PBL). The cellular dynamics of HKL and PBL of infected carp were paralleled by an enhanced spontaneous NO release in vitro. NO production was further increased after addition of viable parasites to these cultures. The hypothesis that NO had a possible role in granulocyte activation and lymphocyte proliferation in carp was supported by the reduction of mitogen-induced proliferative responses of PBL from healthy carp in the presence of NO donor substances. The negative effects of NO on lymphocyte proliferation were contrasted by enhancing effects on granulocyte functions: the inhibition of NO generation in T. borreli-stimulated HKL cultures by the l-arginine analogue L-NMMA reduced the viability of granulocytes and their phagocytic activity. Even massive amounts of nitric oxide produced by donor substances (up to 600 micromol l(-1) NO(-)(2)) caused no reduction in the numbers of viable T. borreli flagellates in vitro. Thus, in carp, T. borreli seems to induce high amounts of NO in vivo which are apparently not harmful for the parasite but which may interfere with co-ordinated interactions of activated cells aiming at the defence of the parasite.

Surface characters and extracellular toxins involved in the pathogenesis of Aeromonas hydrophila.

A small number of serotypically distinct strains of A. hydrophila obtained from diseased freshwater fish were examined for their pathogenic properties comprising of cell surface characteristics and extracellular toxins. Test strains exhibited homogeneity in their cell surface characteristics despite being serologically heterogeneous. Studies on extracellular biological activities revealed qualitative and quantitative differences in production of toxins, probably explaining their antigenic diversity. Three distinct proteases, namely heat stable metallo protease, heat labile serine protease and heat labile metallo protease were identified from the strains.

Partial characterization of serum immunoglobulins of Oreochromis mossambicus.

Serum immunoglobulins of O. mossambicus were purified using chromatography methods--CM affinity gel blue chromatography followed by two step purification involving a combination of ion-exchange and gel filtration chromatography. Studies revealed that O. mossambicus produces only one class of high molecular weight macroglobulin as determined by molecular sieving by Sepharose CL 6-B. Immunoelectrophoresis of purified O. mossambicus serum against rabbit anti O. mossambicus serum gave only a single precipitin line. Further analysis of the immunoglobulin by SDS-PAGE showed that the IgM macroglobulin weighs about 900,000 Da, composed of mu-like heavy chain weighing about 90 kDa each and light chains weighing about 30 kDa each.