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Biomedical subjects

R Rajan

Publications and source records attributed to R Rajan.

At least 19 recordsLinked to original sources
PubMed1998

Absence of plasticity of the frequency map in dorsal cochlear nucleus of adult cats after unilateral partial cochlear lesions.

In adult animals, lesions to parts of the auditory receptor organ, the cochlea, can produce plasticity of the topographic (cochleotopic) frequency map in primary auditory cortex and a restricted or patchy plasticity in the auditory midbrain. This effect is similar to the plasticity of topographic maps of the sensory surface seen in visual and somatosensory cortices after restricted damage to the appropriate receptor surface in these sensory systems. There is dispute about the extent to which subcortical effects contribute to cortical plasticity. Here, we have examined whether topographic map plasticity similar to that seen in the auditory cortex and the midbrain is observed in the adult auditory brainstem. When partial cochlear lesions were produced in the same manner as those that were produced in the cortex and midbrain studies, we found no plasticity of the frequency map in the dorsal cochlear nucleus (DCN). Small regions of the DCN that were deprived of their normal, most sensitive frequency (characteristic frequency; CF) input by the cochlear lesion appeared to have acquired new CFs at frequencies at or near the edge of the cochlear lesion. However, examination of thresholds at the new CFs established that the changes simply reflected the residue of prelesion input to those sites: The patterns of CF thresholds were very well predicted by simple calculations of the patterns that were expected from such residual input. The results of this study suggest that the DCN does not exhibit the type of plasticity that has been found in the auditory cortex and midbrain; therefore, it does not account for the changes in responsiveness observed in the higher level structures under similar experimental conditions.

Age Factors↗
PubMed1998

The occurrence of subsequent malignancy in patients presenting with deep vein thrombosis: results from a historical cohort study.

BACKGROUND: Several studies have reported that patients who present with idiopathic deep vein thrombosis (DVT) have an increased risk of subsequently developing cancer. A clinical trial had previously been conducted examining the optimal duration of oral anticoagulant therapy following initial heparin treatment in patients with proximal DVT. METHODS: A historical cohort study was performed on patients enrolled in the duration of anticoagulant trial. Patients known to have cancer at the time of entry into the trial were excluded. The qualifying DVTs were classified as idiopathic (no known associated risk factors) or secondary without knowledge of subsequent recurrent venous thrombosis or cancer. The patients were then followed for the development of cancer. RESULTS: Thirteen (8.6%) of the 152 patients in the idiopathic cohort subsequently developed cancer compared to eight (7.1%) of 112 patients in the secondary cohort, P = 0.86. Two (5.4%) of 37 patients with recurrent venous thromboembolism and 19 (8.4%) of 227 patients without recurrent thromboembolism developed cancer, P = 0.7. CONCLUSION: Our study did not detect an increased risk of subsequent cancer in patients presenting with idiopathic DVT compared to secondary DVT; nor did we detect an increased incidence of cancer in patients with recurrent venous thromboembolism. Further studies are required prior to pursuing a policy of aggressive screening for cancer in patients with idiopathic venous thromboembolism.

Administration, Oral↗
PubMed1997

Auditory response areas altered by intermodulation distortion products from background tones.

Response areas (RAs) of sensory neurones are dynamically modified by attention, denervation of specific afferent input, blocking inhibition, and by prolonged conditioning with extra-RA stimuli. Here we demonstrate in auditory neurones that the RA is also critically influenced by the background to stimuli. When RAs are measured in the presence of non-excitatory extra-RA tones, new RAs arise at frequencies otherwise not excitatory, as a consequence of non-linear receptor organ transduction. The new RAs can become more sensitive than the RA in quiet conditions such that neurones are then effectively tuned to a new frequency. Thus, even in a modestly complex environment, auditory neurones do not signal a fixed range of sounds but effectively code sounds to which they are otherwise unresponsive.

Acoustic Stimulation↗
PubMed1997

Effects of lithium chloride as a potential radioprotective agent on radiation response of DNA synthesis in mouse germinal cells.

Mouse spermatogonial germ cells are highly sensitive to ionizing radiation. Lithium salts are reported to stimulate the postirradiation recovery of hematopoietic marrow cells. We have, therefore, examined whether administered lithium chloride (LiCl) would also be able to protect the mouse germinal cells against radiation injury. Taking DNA synthesis as an endpoint, our results show that the testicular DNA-specific activity in irradiated mice was higher by 61% on average when they had been pretreated with LiCl both 24 h and 1 h prior to gamma-irradiation (2.0 Gy). It was also observed that the DNA synthetic activity in the germinal cells fully recovered after LiCl pretreatment at doses of 40 mg per kg body weight prior to total body irradiation of 0.05-0.25 Gy, whereas at doses of 0.5-6.0 Gy, following the same procedure of LiCl pretreatment, only an incomplete recovery was observed. The dose reduction factor for LiCl is 1.84. The current findings indicate that pretreatment with LiCl provides considerable protection against radiation damage in mouse spermatogonia.

Animals↗
PubMed1997

Injury-induced reorganization of frequency maps in adult auditory cortex: the role of unmasking of normally-inhibited inputs.

Restricted cochlear lesions in adult animals, causing partial deafness, result in a reorganization of primary auditory cortex (AI) such that the region deprived of its normal input by the lesion is occupied by an expanded representation of peri-lesion cochlear regions, and hence of peri-lesion frequencies. One possible mechanism underlying the change in frequency responsiveness involved in such reorganization is that inputs to the cortical neurons at frequencies at and near their "new" post-lesion characteristic frequencies (CFs) are normally present but suppressed by inhibition, and are "unmasked" by the effects of the lesion. Evidence in support of this explanation is provided by two-tone forward-masking experiments which reveal that many AI neurons receive surround inhibitory input. When input to such neurons at their CF is reduced by an intense temporary-threshold-shift (TTS)-inducing stimulus, the response areas of some neurons expand into the region of their inhibitory surrounds, the effect that would be expected if unmasking were involved in cortical reorganization. In other neurons, however, response areas contracted after the TTS-inducing stimulation. Although unmasking of normally-inhibited inputs is likely to contribute to auditory cortical reorganization, the immediate unmasking that is seen in visual and somatosensory systems is unlikely to play a major role in auditory cortical reorganization, as no evidence of immediate unmasking was seen following acute cochlear lesions in guinea pigs.

Animals↗
PubMed1996

Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor cell line, and EGF immunoreactive proteins are present at sites of metastasis in the stroma of lymph nodes and medullary bone.

Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at a frequency in excess of that which would be predicted by random tumor cell dissemination. In order to determine whether chemoattractants in these organs promote organ-specific metastasis, we utilized human cell lines derived from and/or related to these organs as sources of potential chemoattractants. Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1 (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1 prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition, secretory proteins from a human prostatic stromal cell line (hPS) and from the TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites represent organs of hematopoietic/lymphoid proliferation and activation, we undertook identification of specific cytokines present at these sites which may promote the chemomigration of prostate tumor cells. In this context, the cytokines interleukin-1 alpha, interleukin-2, interleukin-6, tumor necrosis factor-beta, transforming growth factor-beta, interferon alpha 2-a, and granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells through the Boyden chambers in a dose-dependent manner. Western blot analysis of secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1 identified EGF-immunoreactive proteins in all cases. In addition, EGF immunoreactivity was localized to the stroma of the human prostate, the osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line, and that EGF within the stroma of pelvic lymph nodes and medullary bone may act as a chemoattractant for prostate tumor cells, thereby facilitating the preferential formation of metastatic foci within these organs.

Bone Neoplasms↗
PubMed1996

A model for the interaction of trifluoroethanol with peptides and proteins.

The structural stabilizing property of 2,2,2-trifluoroethanol (TFE) in peptides has been widely demonstrated. More recently, TFE has been shown to enhance secondary structure content in globular proteins, and to influence quaternary interactions in protein multimers. The molecular mechanisms by which TFE exerts its influence on peptide and protein structures remain poorly understood. The present analysis integrates the known physical properties of TFE with a variety of experimental observations on the interaction of TFE with peptides and proteins and on the properties of fluorocarbons. Two features of TFE, namely the hydrophobicity of the trifluoromethyl group and the hydrogen bonding character (strong donor and poor acceptor), emerge as the most important factors for rationalising the observed effects of TFE. A model is proposed for TFE interaction with peptides which involves an initial replacement of the hydration shell by fluoroalcohol molecules, a process driven by apolar interactions and favourable entropy of dehydration. Subsequent bifurcated hydrogen-bond formation with peptide carbonyl groups, which leave intramolecular interactions unaffected, promotes secondary structure formations.

Entropy↗
PubMed1996

Alkalinisation of lignocaine to reduce the pain of digital nerve blockade.

OBJECTIVE: To see if the alkalinisation of lignocaine caused a reduction in the pain of injection for digital nerve blockade. METHODS: The study was a prospective randomised double blind study with each patient acting as their own control. During the study period, all patients aged 16 years and over presenting to the accident and emergency department with a condition requiring digital nerve blockade were considered for inclusion in the study. Each patient received an injection of both alkalinised and non-alkalinised lignocaine. The pain of each injection was then assessed on a visual analogue scale. RESULTS: 98 patients were entered in the study. The mean difference in pain scores between the non-alkalinised and alkalinised injections was 0.739, P < 0.001, 95% confidence interval 0.47 to 1.01. CONCLUSIONS: Alkalinisation of lignocaine reduces the pain of injection for digital nerve blockade.

Adolescent↗
PubMed1996

Sensitivity to interaural intensity differences of neurons in primary auditory cortex of the cat. I. types of sensitivity and effects of variations in sound pressure level.

1. Interaural intensity differences (IIDs) provide the major cue to the azimuthal location of high-frequency narrowband sounds. In recent studies of the azimuthal sensitivity of high-frequency neurons in the primary auditory cortex (field AI) of the cat, a number of different types of azimuthal sensitivity have been described and the azimuthal sensitivity of many neurons was found to vary as a function of changes in stimulus intensity. The extent to which the shape and the intensity dependence of the azimuthal sensitivity of AI neurons reflects features of their IID sensitivity was investigated by obtaining data on IID sensitivity from a large sample of neurons with a characteristic frequency (CF) > 5.5 kHz in AI of anesthetized cats. IID sensitivity functions were classified in a manner that facilitated comparison with previously obtained data on azimuthal sensitivity, and the effects of changes in the base intensity at which IIDs were introduced were examined. 2. IID sensitivity functions for CF tonal stimuli were obtained at one or more intensities for a total of 294 neurons, in most cases by a method of generating IIDs that kept the average binaural intensity (ABI) of the stimuli at the two ears constant. In the standard ABI range at which a function was obtained for each unit, five types of IID sensitivity were distinguished. Contra-max neurons (50% of the sample) had maximum response (a peak or a plateau) at IIDs corresponding to contralateral azimuths, whereas ipsi-max neurons (17%) had the mirror-image form of sensitivity. Near-zero-max neurons (18%) had a clearly defined maximum response (peak) in the range of +/- 10 dB IID, whereas a small group of tough neurons (2%) had a restricted range of minimal responsiveness with near-maximal responses at IIDs on either side. A final 18% of AI neurons were classified as insensitive to IIDs. The proportions of neurons exhibiting the various types of sensitivity corresponded closely to the proportions found to exhibit corresponding types of azimuthal sensitivity in a previous study. 3. There was a strong correlation between a neuron's binaural interaction characteristics and the form of its IID sensitivity function. Thus, neurons excited by monaural stimulation of only one ear but with either inhibitory, facilitatory, or mixed facilitatory-inhibitory effects of stimulation of the other ear had predominantly contra-max IID sensitivity (if contralateral monaural stimulation was excitatory) or ipsi-max sensitivity (if ipsilateral monaural stimulation was excitatory). Neurons driven weakly or not at all by monaural stimulation but facilitated binaurally almost all exhibited near-zero-max IID sensitivity. The exception to this tight association between binaural input and IID sensitivity was provided by neurons excited by monaural stimulation of either ear (EE neurons). Although EE neurons have frequently been considered to be insensitive to IIDs, our data were in agreement with two recent reports indicating that they can exhibit various forms of IID sensitivity: only 23 of 75 EE neurons were classified as insensitive and the remainder exhibited diverse types of sensitivity. 4. IID sensitivity was examined at two or more intensities (3-5 in most cases) for 84 neurons. The form of the IID sensitivity function (defined in terms of both shape and position along the IID axis) was invariant with changes in ABI for only a small proportion of IID-sensitive neurons (approximately 15% if a strict criterion of invariance was employed), and for many of these neurons the spike counts associated with a given IID varied with ABI, particularly at near-threshold levels. When the patterns of variation in the form of IID sensitivity produced by changes in ABI were classified in a manner equivalent to that used previously to classify the effects of intensity on azimuthal sensitivity, there was a close correspondence between the effects of intensity on corresponding types of azimuthal and IID sensitivity

Animals↗
PubMed1996

Additivity of loud-sound--induced threshold losses in the cat under conditions of active or inactive cochlear efferent-mediated protection.

1. An additivity model for the accretion of cochlear sensorineural hearing losses has been described from studies in the guinea pig cochlea. Among other aspects, the model allows determination of how residual hearing losses after an initial exposure (E1) affect hearing losses to be expected to a subsequent second exposure (E2). In the present study, the model was applied to temporary hearing losses produced in the cat cochlea by loud pure tones at a frequency from 3 to 15 kHz, affecting regions from 2 to 28 kHz. Successive identical exposures, generally with an interexposure interval of approximately equal to 35 min, were used to produce compound action potential (CAP) threshold losses. Total losses after E2 were compared with those predicted by the model. Testing was carried out under conditions where olivocochlear bundle (OCB)-mediated protection was or was not activated. (As shown elsewhere, OCB-mediated protection is activated by particular binaural exposures, but not monaural exposure, and reduces threshold losses in the binaural condition with intact OCB compared with losses in either the monaural condition, or the binaural condition where the OCB was cut before loud sound.) 2. The additivity model was a very good predictor of total losses under a variety of conditions; different exposure frequencies, monaural and binaural exposures, and with intact or cut OCB pathways. In these exposures, the model's application could be generalized so that as long as residual losses just pre-E2 were well specified in an animal, total losses could be as well predicted using normative data bases of a single exposure with the same parameters. 3. The model also allowed determination of whether OCB-mediated protection was exercised during E2 in dual identical exposures. Expression of protection for E2 depended on whether E1 elicited protection. When tested with monaural (at 7 or 15 kHz) or binaural exposures (at kHz) for which E1 did not elicit protection, neither did E2. However, when tested with a binaural E1 (at 7, 11, or 15 kHz), which activated protection, E2 also elicited protection. In the latter case, for 7- and 11-kHz exposures, the amount of E2 protection increased with total hearing loss, a relationship similar to that seen for single exposures in cat and guinea pig. For 15-kHz exposure, the amount of E2 protection was constant across test frequencies. 4. Finally, a critical observation with 11-kHz exposure was that a binaural E1 eliciting protection was able to "prime" the OCB so that protection could be elicited by a subsequent monaural E2, which, by itself as a singel exposure, does not evoke protection. This result has important implications in terms of the physiology of the protective OCB pathways and clinically in terms of the manner in which loud-sound-induced hearing loss accumulated.

Action Potentials↗
PubMed1995

Involvement of cochlear efferent pathways in protective effects elicited with binaural loud sound exposure in cats.

1. Studies in guinea pigs have shown that the crossed olivocochlear efferent [crossed olivocochlear bundle (OCB)] pathways can reduce the cochlear neural desensitization caused by loud sounds. In one experimental paradigm, binaural loud sound exposure produced less damage than did monaural exposure, and various tests confirmed that this could be attributed to the OCB. In contrast, a study in cats has shown no such protection from the OCB for binaural exposures. There are some methodological differences between the cat and guinea pig studies that could account for the difference. The present study was carried out to determine whether two factors, namely anesthetic or exposure frequency, could account for the difference. Experiments were carried out in cats using barbiturate anesthesia, as in the guinea pig experiments. 2. Using a unilateral middle ear muscle (MEM) tenotomy, it was confirmed that under Nembutal anesthesia the MEM did not affect the threshold losses to monaural or binaural exposure. However, comparing results for monaural versus binaural 11-kHz exposures, there were significantly less threshold losses to the binaural exposure, independent of the presence of the MEM. No such difference between monaural and binaural exposures was seen for 3-kHz exposures. 3. By employing unilateral surgical strategies such as MEM tenotomy and/or various brain stem incisions, it was confirmed that the protection with binaural compared with monaural 11-kHz exposure was due specifically to the OCB. In unilaterally deefferented animals, binaural 11-kHz exposure always produced lower threshold losses on the OCB-intact side than on the OCB-cut side, regardless of the status of the MEM. Brain stem cuts that affected other rostrally or laterally located structures but not the OCB produced similar threshold losses bilaterally after binaural exposure, and the losses were comparable with the protected levels seen in other cases with intact OCB and binaural exposure. These data confirmed that when using an exposure frequency very similar to that used in the guinea pig experiments, a protective OCB effect could be demonstrated in cats, as previously seen in guinea pigs. The MEMs appeared to be inactive in barbiturate-anesthetized animals and were not activated by 3-, 7-, or 11-kHz exposures at 100 dB SPL for 10 min. The companion manuscript demonstrates this same effect across a wider range of exposures.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1995

Frequency and loss dependence of the protective effects of the olivocochlear pathways in cats.

1. In the previous manuscript I suggested a frequency dependency to olivocochlear bundle (OCB)-mediated protection from loud sound by showing protection for binaural compared with monaural 11-kHz exposures but not 3-kHz exposures of the same intensity and duration. To determine whether this was the case, experiments were carried out in barbiturate-anesthetized cats using the paradigm of a unilateral brain stem incision to deefferent one cochlea in each animal before presentation of a binaural loud sound exposure. With equal-intensity, equal-duration binaural exposures, in different groups protection in OCB-intact compared with OCB-cut ears was seen only for exposures at 11, 15, or 20 kHz, but not at 3 or 7 kHz, suggesting that OCB-mediated protection was found only for higher-frequency exposures. This would be consistent with the OCB-mediated protection in guinea pig studies where 10-kHz exposures were used and its absence in a study in cats where 6-kHz exposures were used. However, this conclusion had to be qualified by the fact that the lower-frequency exposures resulted in smaller threshold losses than did the higher-frequency exposures. 2. To determine whether OCB-mediated protection could be obtained for lower-frequency exposures that were made as damaging as or more damaging than the high-frequency exposures, longer-duration, lower-frequency exposures were used. OCB-mediated protection could then be obtained for exposure at 7 kHz, 100 dB SPL for 15 min but not at 3 or 5 kHz, 100 dB SPL for 20 min or at 3 kHz, 100 dB SPL for 40 min or 106 dB SPL for 20 min. Finally, when large threshold losses were produced with exposure at 3 kHz, 106 dB SPL for 40 min, OCB-mediated protection could be obtained for this low-frequency exposure too. These effects suggested that there were different "activation threshold" for OCB-mediated protection as a function of exposure frequency. To determine whether this also applied for the higher-frequency exposures (11, 15, and 20 kHz), all of which had elicited OCB-mediated protection when presented at 100 dB SPL for 10 min, these exposure frequencies were presented at 100 dB SPL for 7 min to produce low threshold losses. Now protection was found for the 11- and 15-kHz exposures but not for the 20-kHz exposure. 3. Thus the activation threshold for OCB-mediated protection varied in a frequency-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1995

Very low-dose warfarin prophylaxis to prevent thromboembolism in women with metastatic breast cancer receiving chemotherapy: an economic evaluation.

PURPOSE: A recent double-blind, randomized trial demonstrated that very low-dose warfarin (VLDW) reduced the incidence of venous thromboembolism (VTE) without increasing the rate of bleeding in women with metastatic breast cancer receiving chemotherapy. We have evaluated the economic impact on the health care system of using VLDW in such patients. METHODS: The records of patients entered onto the trial and a simultaneous, fully allocated, costing model for a tertiary care hospital in Hamilton, Canada were used to determine the difference in costs associated with the care of patients with and without VLDW. RESULTS: The cost of providing VLDW was $ 21,854 (Canadian dollars) per 100 patients. This therapy led to a reduction in costs of $ 24,297 per 100 patients, thus saving the health care system $ 2,443 per 100 patients. In the sensitivity analysis, VLDW prophylaxis still did not increase health care costs unless the cost of VLDW was greatly increased, the cost of treating thromboembolic episodes was markedly reduced, or the incidence of either VTE or bleeding with VLDW was increased above the rates observed in the trial. CONCLUSION: We conclude that for women receiving chemotherapy for metastatic breast cancer, the benefits of VLDW can be realized without increased health care costs.

Breast Neoplasms↗
PubMed1994

Topographic representation of tone intensity along the isofrequency axis of cat primary auditory cortex.

The sound pressure level (SPL), henceforth termed intensity, of acoustic signals is encoded in the central auditory system by neurons with different forms of intensity sensitivity. However, knowledge about the topographic organization of neurons with these different properties and hence about the spatial representation of intensity, especially at higher levels of the auditory pathway, is limited. Here we show that in the tonotopically organized primary auditory cortex (AI) of the cat there are orderly topographic organizations, along the isofrequency axis, of several neuronal properties related to the coding of the intensity of tones, viz. minimum threshold, dynamic range, best SPL, and non-monotonicity of spike count--intensity functions to tones of characteristic frequency (CF). Minimum threshold, dynamic range, and best SPL are correlated and alter periodically along isofrequency strips. The steepness of the high-intensity descending slope of spike count--intensity functions also varies systematically, with steepest slopes occurring in the regions along an isofrequency strip where low thresholds, narrow dynamic ranges and low best SPLs are found. As a consequence, CF-tones of various intensities are represented by orderly and, for most intensities, periodic, spatial patterns of distributed neuronal activity along an isofrequency strip. For low--to--moderate intensities, the mean relative activity along the entire isofrequency strip increases rapidly with intensity, with the spatial pattern of activity remaining quite constant along the strip. At higher intensities, however, the mean relative activity along the strip remains fairly constant with changes in intensity, but the spatial patterns change markedly. As a consequence of these effects, low- and high-intensity tones are represented by complementary distributions of activity alternating along an isofrequency strip. We conclude that in AI tone intensity is represented by two complementary modes, viz. discharge rate and place. Furthermore, the magnitude of the overall changes in the representation of tone intensity in AI appears to be closely related to psychophysical measures of loudness and of intensity discrimination.

Acoustic Stimulation↗