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Biomedical subjects

R Rajan

Publications and source records attributed to R Rajan.

At least 19 recordsLinked to original sources
PubMed2006

A novel stimulus system for applying tactile stimuli to the macrovibrissae in electrophysiological experiments.

The rat's vibrissae are a wonderful system for the study of sensory neural encoding in relation to behaviour because the vibrissae are easily identifiable and accessible for manipulation, allowing easy application of a variety of different types of deflections that mimic natural whisking. Here we report the development of a powerful and flexible method for precisely deflecting these vibrissae. Recordings from CNS neurons showed, in response to variations in the parameters of a trapezoid whisker deflection stimulus that mimics the basic unit of whisking, a variety of complex responses as well as complex interactions between different response components. The recordings also included a response that is reported to be found during active whisking (movement under muscle control) and not passive whisker movements and thus to differentiate active from passive whisker deflections. Thus, this system could well be used in anaesthetized animals to apply whisker deflections that well mimic natural active whisking in awake animals, thereby allowing highly detailed study of the neuronal responses and neuronal interactions found with natural whisking behaviour.

Action Potentials↗
PubMed2006

Contextual modulation of cochlear hearing desensitization depends on the type of loud sound trauma.

In ears in which cochlear efferent pathways were cut and with testing done under anaesthetic conditions that preclude middle ear muscle activity (so as to examine the "intrinsic" effects of loud sound on the cochlea without any confounding effect of efferent pathways to the auditory periphery), atraumatic background white noise (WN) increases cochlear hearing loss (temporary threshold shifts, TTSs) induced by a traumatic pure tone but reduces TTSs caused by traumatic 5-kHz wide narrow band (NB) sound. The short-duration moderately intense traumata used in these studies most likely cause TTSs by affecting cochlear mechanics and these WN modulatory effects, exerted directly on the cochlea's intrinsic susceptibility to TTSs, are not predicted by any current description of cochlear mechanics. Here it is demonstrated that background WN reduces trauma-induced TTSs with even a relatively small increase in trauma bandwidth beyond that of a pure tone, discounting the alternative that contextual modulatory effects transition systematically along a continuum as trauma bandwidth increases from a pure tone to a broader bandwidth (albeit 2 kHz-wide NB) trauma. These results have implications for cochlear mechanics as the TTSs due to the traumatic sound of this study are most likely due to changes in cochlear mechanics but are not easily explained by what is currently known of cochlear mechanics.

Acoustic Stimulation↗
PubMed2006

Bandwidth determines modulatory effects of centrifugal pathways on cochlear hearing desensitization caused by loud sound.

Centrifugal olivocochlear (OC) pathways modulate cochlear hearing losses induced in cats by loud sounds varying in bandwidth from tones to clicks and noise bands, in a variety of conditions. The general effect, always to reduce hearing damage, can be a net effect resulting from complex interactions between OC subcomponents (crossed and uncrossed OC pathways). The interactions between these subcomponents vary with type of loud sound, suggesting that sound bandwidth may be important in determining how OC pathways modulate loud sound-induced hearing loss. This dependency was examined and here it is reported that OC pathways do not alter cochlear hearing losses caused by loud noise with a 2-kHz-wide bandwidth intermediate between the loud sounds of previous studies. Increasing stimulus bandwidth even slightly more, to use a loud 3.5-kHz-wide bandwidth noise as the damaging sound, once again revealed OC modulation of cochlear hearing loss. The fact that OC pathways do not modulate cochlear hearing losses induced by loud 2-kHz-wide noise was demonstrated in three very different test conditions in which OC pathways modulate hearing losses caused by narrower or broader bandwidth sounds. This confirmed that the absence of centrifugal modulation of hearing loss to this particular sound was a robust phenomenon not related to test condition. The absence of overall centrifugal effects was also true at the level of subcomponent pathways; neither crossed nor uncrossed OC pathways individually modulated cochlear hearing losses to the loud 2-kHz-wide noise. This surprising frequency dependency has general implications for centrifugal modulation of cochlear responses.

Acoustic Stimulation↗
PubMed2005

An international cohort study of cancer in systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. METHODS: We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. RESULTS: The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). CONCLUSION: These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.

Adult↗
PubMed2005

Non-Hodgkin's lymphoma in systemic lupus erythematosus.

BACKGROUND: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). OBJECTIVES: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. METHODS: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. RESULTS: 42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. CONCLUSIONS: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.

Adult↗
PubMed2005

Contextual modulation of olivocochlear pathway effects on loud sound-induced cochlear hearing desensitization.

This study shows that the cochlear hearing losses [temporary threshold shifts (TTSs)] induced by traumatic sound and the effect of olivocochlear (OC) pathways to the cochlea on these hearing losses depend on the context of the sound. Background atraumatic white noise (WN) has been shown to 1) exacerbate loud-pure-tone-induced TTSs, and 2) promote the modulation of TTSs by the uncrossed OC (UOC) pathways additional to the action on TTSs, elicited by binaural loud tones themselves, by the crossed OC (COC) pathway. Here the same atraumatic WN reduced TTSs caused by loud narrow band sound. It also reduced TTS modulation by OC pathways. The UOC no longer exerted any effects on TTSs, and COC effects were significantly reduced in two discrete frequency bands: low frequencies within the narrow band ("within-band" frequencies) and high frequencies outside the band ("high-side" frequencies). COC effects were unchanged at high frequencies within the band. Despite these reductions in OC effects, because the WN itself reduced TTSs, the total effect of OC pathways and background WN now produced larger TTS reductions, especially at higher frequencies. Thus the modulatory effects of the OC pathways on TTSs depend on how background WN modulates cochlear state. It is postulated that the WN background and the OC pathways both modulate TTSs by acting on the outer hair cells, in a way that promotes the reduction of TTSs caused by the narrow band sound trauma. This joint promotion of a protective end-effect on TTSs to narrow band sound trauma contrasts against the effects seen with pure tone trauma where the same background WN exacerbated TTSs at high-side frequencies.

Acoustic Stimulation↗
PubMed2005

Colonization of mycoplasma in the upper respiratory tract of AIDS patients with pulmonary symptoms in Chennai, India.

BACKGROUND & OBJECTIVE: Mycoplasmas have been implicated in causing minor to severe respiratory infections in man. Mycoplasmas are considered to act as cofactors in patients with AIDS. A preliminary study was conducted to isolate mycoplasmas from sputum specimens of AIDS patients and non-HIV patients with underlying pulmonary symptoms and signs. METHODS: A total of 130 sputum samples (100 from AIDS patients and 30 from non-HIV) were cultured on standard pleuropneumonia-like organisms (PPLO) glucose agar up to 3 wk. The plates were examined for the presence of fried-egg colonies characteristic of Mycoplasma. Subsequently the plates were stained using Diene's stain. Sputum specimens from the AIDS patients were also screened for other bacterial pathogens. RESULTS: Mycoplasmas were detected from 36 (36%) of the AIDS patients and only 5 (16.6%) of the non HIV control individuals with underlying pulmonary symptoms. Data on the detection rates of other microorganisms from the AIDS cases were also analysed. INTERPRETATION & CONCLUSION: This preliminary study provided supportive evidence that mycoplasma colonized in upper respiratory tract of individuals with AIDS to a larger extent than that of the non HIV subjects with pulmonary symptoms. Further studies need to be done to characterize mycoplasma isolates to species level.

AIDS-Related Opportunistic Infections↗
PubMed2004

Factors associated with abnormal Pap results in systemic lupus erythematosus.

OBJECTIVE: Previous studies have suggested that women with systemic lupus erythematosus (SLE) are at greater risk for cervical dysplasia than are women in the general population. However, the factors associated with abnormal Pap test results in SLE have not been well studied. We therefore aimed to determine the factors associated with lifetime occurrence of an abnormal Pap test in women with SLE, and the influence of immunosuppressive exposure on the odds of abnormal Pap test results occurring after diagnosis of SLE. METHODS: Data were pooled from SLE cohorts from three centres. Self-report data were available on smoking, reproductive history, use of oral contraceptives (OC), history of sexually transmitted diseases (STDs) and whether the subjects had had cervical dysplasia on Pap testing. Logistic regression was used to examine the effect of these variables on the lifetime odds of cervical dysplasia. We then generated the adjusted odds ratio (OR) for the effect of immunosuppressive exposure on cervical dysplasia occurring after diagnosis of SLE. RESULTS: History of STDs and use of OCs were positively associated with reports of cervical dysplasia in adjusted analyses. The ORs for the effect of immunosuppressives on abnormal Pap test occurrence (adjusted for race, age, smoking, nulliparity, OC use and history of STDs) after diagnosis of SLE was 1.6 (95% CI 1.0, 2.7). CONCLUSIONS: A history of STDs and use of OCs were associated with abnormal Pap reports in this SLE sample. Immunosuppressive exposure may confer further risk to women with SLE.

Adult↗
PubMed2004

Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus.

OBJECTIVES: To determine if breast cancer risk in women with SLE is modified by a history of exposure to hormone replacement therapy (HRT) or oral contraceptives (OC), after adjusting for other risk factors. METHODS: Data were pooled from SLE cohorts at three centres. For each female cohort member (n = 871), the probability of developing breast cancer was estimated from factors (age, parity, age at first live birth, age of menarche, personal history of benign breast disease, family history) in the Gail model, an established tool for predicting breast cancer risk. From these probabilities, the expected number of breast cancers for the cohort was estimated. Actual occurrence of cases was determined by linkage with regional cancer registries. Standardized incidence ratios (SIRs; ratio of cancers observed to expected) were calculated, with subgroup analyses according to HRT and OC exposure. RESULTS: In the cohort, 15 breast cancers occurred vs 7.2 predicted [SIR 2.1, 95% confidence interval (CI) 1.1, 3.5]. When controlling for Gail model risk factors, estimates were similar for women never exposed to HRT vs those exposed to HRT. Adjusted SIR estimates appeared similar also for women exposed or not exposed to OC. CONCLUSIONS: Although not definitive, the data suggest that the breast cancer experience in this sample is not completely explained by factors such as reproductive and family history, or by exogenous hormonal exposures. Other determinants, including medication exposures or genetic factors (possibly related to oestrogen receptors or metabolism) may be important. Variations in these factors might explain why an elevated risk of breast cancer has not been apparent in all SLE populations.

Adult↗
PubMed2002

Performance of power assisted respirators during simulated asbestos removal.

Protection factors were measured on full face mask power assisted respirators when worn by experienced asbestos removal operatives under simulated asbestos removal work conditions. The sulfur hexafluoride test method as defined in European Standards was employed to determine the leakage into the respirators. Protection factors were measured on a total of 21 test volunteers. The test method allowed protection factors to be related to wearer activities and practices. Poor fitting techniques and simulated reduction in the respirator's performance resulted in a reduction in the protection factor. Visual inspection of the RPE usually worn by the volunteers identified inadequate maintenance. This study re-emphasises that careful selection, facepiece fit testing and correct use and maintenance of RPE are essential to ensure optimum protection to the wearer.

Asbestos↗
PubMed2001

Correlations to predict droplet size in ultrasonic atomisation.

In conventional two fluid nozzles, the high velocity air imparts its energy to the liquid and disrupts the liquid sheet into droplets. If the energy for liquid sheet fragmentation can be supplied by the use of ultrasonic energy, finer droplets with high sphericity and uniform size distribution can be achieved. The other advantage of ultrasound induced atomisation process is the lower momentum associated with ejected droplets compared to the momentum carried by the droplets formed using conventional nozzles. This has advantage in coating and granulation processes. An ultrasonic probe sonicator was designed with a facility for liquid feed arrangement and was used to atomise the liquid into droplets. An ingenious method of droplet measurement was attempted by capturing the droplets on a filter paper (size variation with regard to wicking was uniform in all cases) and these are subjected to image analysis to obtain the droplet sizes. This procedure was evaluated by high-speed photography of droplets ejected at one particular experimental condition and these were image analysed. The correlations proposed in the literature to predict droplet sizes using ultrasound do not take into account all the relevant parameters. In this work, a truly universal correlation is proposed which accounts for the effects of physico-chemical properties of the liquid (flow rate, viscosity, density and surface tension), and ultrasonic properties like amplitude, frequency and the area of vibrating surface. The significant contribution of this work is to define dimensionless numbers incorporating ultrasonic parameters, taking cue from the conventional numbers that define the significance of different forces involved in droplet formation. The universal correlations proposed are robust and can be used for designing ultrasonic atomisers for different applications. Among the correlations proposed here, those ones that are based on the dimensionless numbers and Davies approach predict droplet sizes within acceptable limits of deviation. Also, an empirical correlation from experimental data has been proposed in this work.

Humans↗
PubMed2001

Cortical reorganization in patients with high frequency cochlear hearing loss.

Animal research has shown that tonotopic representation in the auditory cortex is not statically fixed in the adult organism but can be altered after deafferentation. The present study examines the plasticity of the human auditory cortex in patients with high frequency cochlear hearing loss by means of magnetoencephalographic measurements. The data show that the cortical map can reorganize such that cortical neurons deprived of their usual most sensitive afferent input now respond to tone frequencies adjacent to the frequency range of the partial hearing loss. The results suggest that deafferentation due to cochlear damage in adults may lead to functional reorganization of auditory cortical structures.

Acoustic Stimulation↗
PubMed2001

Clinical and sensorimotor gating effects of ketamine in normals.

The clinical similarities between PCP psychosis and schizophrenia have contributed importantly to the development of the glutamate hypothesis of schizophrenia. Sensory gating, as measured by prepulse inhibition of the acoustic startle reflex (PPI), is impaired in patients with schizophrenia. In animals, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia. The purpose of this work is to investigate the modulation of sensory gating in humans by subanaesthetic doses of ketamine. 16 healthy male subjects received a 60-min infusion of ketamine (0.5 mg/kg) or normal saline on two separate days in a randomized double-blind crossover design. Clinical ratings and PPI were done during the infusion on both days. Ketamine produced robust clinical effects. Dissociative symptoms as measured by the CADSS increased from 0 +/- 0.0 to 29.3 +/- 14.3; negative symptoms (Affect Rating Scale) increased from 17.2 +/- 0.8 to 24.8 +/- 3.1; and total BPRS scores increased from 18.3 +/- 0.8 to 26.4 +/- 5.1. ANOVAs for these ratings were all significant at the p <.000 level, although BPRS increases were not in the range seen in decompensated schizophrenic patients. The amplitudes of the startle responses to pulse-alone stimuli were not significantly different on ketamine and placebo days. Ketamine did not cause disruption in PPI as expected. On the contrary, in the first block of the PPI session ketamine significantly enhanced PPI (ANOVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in normal controls.

Adult↗
PubMed2001

Plasticity of excitation and inhibition in the receptive field of primary auditory cortical neurons after limited receptor organ damage.

Permanent receptor organ damage can cause plasticity of topographic cortical maps of that receptor surface while temporary receptor organ damage, and conditions mimicking such damage, can unmask new excitatory inputs in central sensory neurons receiving input from that receptor surface. Cortical plasticity is associated with an anatomically or pharmacologically defined decrease in inhibition in cortex. It is therefore widely proposed that a reduction incentral inhibition underlies cortical neural plasticity. Here I demonstrate that small receptor organ damage results, in primary auditory cortical (A1) neurons, in loss of one component of functionally defined afferent inhibition but unmasking of another component of afferent inhibition along with new excitatory responses. Overall, there did not appear to be any change in the strength of afferent inhibition or in the strength of excitation. Thus, auditory receptor organ damage can unmask new excitatory inputs as well as inhibitory inputs from within the receptive field of the neurons.

Animals↗
PubMed2001

Unilateral hearing losses alter loud sound-induced temporary threshold shifts and efferent effects in the normal-hearing ear.

In animals with bilaterally normal hearing, olivocochlear pathways can protect the cochlea from the temporary shifts in hearing sensitivity (temporary threshold shifts; TTSs) caused by short-duration intense loud sounds. The crossed olivocochlear pathway provides protection during binaural loud sound, and uncrossed pathways protect when monaural or binaural loud sounds occur in noise backgrounds. Here I demonstrate that when there is a chronic unilateral hearing loss, effects of loud sounds, and efferent effects on loud sound, in the normal-hearing ear differ markedly from normal. Three categories of test animals with unilateral hearing loss were tested for effects at the normal-hearing ear. In all categories a monaural loud tone to the normal-hearing ear produced lower-than-normal TTSs, apparently because of a tonic re-setting of that ear's susceptibility to loud sound. Second, in the two test categories in which the hearing-loss ear was only partly damaged, binaural loud sound exacerbated TTSs in the normal-hearing ear because it caused threshold shifts that were a combination of "pure" TTSs and uncrossed efferent suppression of cochlear sensitivity. (In normal cats, this binaural tone results in crossed olivocochlear protection that reduces TTS.) Binaural loud sound did not produce such uncrossed efferent effects in the test category in which the nontest ear had suffered total hearing loss, suggesting that this uncrossed efferent effect required binaural input to the CNS. It is noteworthy that, in the absence of this uncrossed efferent suppression, the pure loud sound-alone induced TTSs after binaural exposure were low. Thus in the absence of any efferent effect, the normal-hearing cochlea had a reduced susceptibility to loud tone-induced damage. Finally, the results suggest that, with respect to cochlear actions at high sound levels, uncrossed and crossed efferent pathways may exert different effects at the one type of receptor cell.

Animals↗
PubMed2001

Noise priming and the effects of different cochlear centrifugal pathways on loud-sound-induced hearing loss.

Priming/conditioning the cochlea with moderately loud sound can reduce damage caused by subsequent loud sound. This study examined immediate effects of short-term priming with monaural broadband noise on temporary threshold shifts (TTSs) in hearing caused by a subsequent loud high-frequency tone and the role of centrifugal olivocochlear pathways. Priming caused delay-dependent changes in tone-induced TTSs, particularly or only at frequencies higher than the peak tone-affected frequency, through two general effects: a short-lasting increase in cochlear susceptibility to loud sound and longer-lasting complex end effects of centrifugal pathways. The results indicated the following points. Priming noise had "pure" cochlear effects, outlasting its presentation and declining with delay, that exacerbated tone-induced TTSs at frequencies higher than the peak tone-affected frequency. The centrifugal uncrossed medial olivocochlear system (UMOCS) could prevent this noise exacerbation and as this noise effect declined, could even reduce tone-induced TTSs below those to the unprimed tone. For longer delays, when priming noise no longer had any exacerbative "pure" cochlear effects on TTSs, UMOCS exacerbated TTSs above those to the unprimed tone. The crossed medial olivocochlear system (CMOCS) appeared to show a gradual "build-up" of effects postpriming. A parallel study showed it exercised no end effect on TTSs when noise and tone were concurrent. With priming, CMOCS effects were observed. For the shortest priming delay, the CMOCS blocked a UMOCS effect preventing noise exacerbation of tone-induced TTSs. For longer delays, CMOCS end effects, when present, reduced tone-induced TTSs below those to the unprimed tone. The CMOCS may oscillate between producing these effects and exerting no end-effect. With increasing delay CMOCS protection occurred in a greater proportion of animals. Finally, with a delay of 600 s between primer and loud tone, all these systems appeared to have reset to normal so that TTSs were similar to those in the unprimed condition. Thus the effects of short-term priming are not simple and do not suggest that centrifugal pathways act automatically as a protective system during such priming.

Adaptation, Physiological↗