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Biomedical subjects

Ruby Pawankar

Publications and source records attributed to Ruby Pawankar.

At least 19 recordsLinked to original sources
PubMed2006

Survey on the impact of comorbid allergic rhinitis in patients with asthma.

BACKGROUND: Allergic rhinitis (AR) and asthma are inflammatory conditions of the airways that often occur concomitantly. This global survey was undertaken to understand patient perspectives regarding symptoms, treatments, and the impact on their well-being of comorbid AR and asthma. METHODS: Survey participants were adults with asthma (n = 813) and parents of children with asthma (n = 806) from four countries each in the Asia-Pacific region and Europe. Patients included in the survey also had self-reported, concomitant AR symptoms. Patients and parents were recruited by telephone interview or by direct interview. RESULTS: Most patients (73%) had pre-existing symptoms of AR when their asthma was first diagnosed. Shortness of breath (21%) was the most troublesome symptom for adults, and wheezing (17%) and coughing (17%) the most troublesome for children. Patients used different medications for treating asthma (most commonly short-acting beta-agonists and inhaled corticosteroids) and for treating AR (most commonly oral antihistamines). The concomitant presence of AR and asthma disrupted the ability to get a good night's sleep (79%), to participate in leisure and sports activities (75%), to concentrate at work or school (69% of adults, 73% of children), and to enjoy social activities (57% of adults, 51% of children). Most patients (79%) reported worsening asthma symptoms when AR symptoms flared up. Many (56%) avoided the outdoors during the allergy season because of worsening asthma symptoms. Many (60%) indicated difficulty in effectively treating both conditions, and 72% were concerned about using excessive medication. In general, respondents from the Asia-Pacific region reported more disruption of activities caused by symptoms and more concerns and difficulties with medications than did those from Europe. Differences between the two regions in medication use included more common use of inhaled corticosteroids in Europe and more common use of Chinese herbal remedies in the Asia-Pacific region. CONCLUSION: Results of this survey suggest that comorbid asthma and AR substantially impact patient well-being and that the worsening of AR symptoms in patients with asthma can be associated with worsening asthma symptoms. These findings underscore the need for physicians who treat patients with asthma to evaluate treatment options for improving symptoms of both AR and asthma when present concomitantly.

Adolescent↗
PubMed2006

Increased expression of RANTES, CCR3 and CCR5 in the lesional skin of patients with atopic eczema.

BACKGROUND: Atopic eczema (AE) is a relapsing inflammatory disease based on IgE sensitization and characterized by peripheral blood eosinophilia and eosinophil infiltration into the lesional skin. In the patch test reaction of AE by allergens, an increased infiltration of activated eosinophils has been demonstrated peaking at 24-48 h. Regulated on activation normal T cell expressed and secreted (RANTES/CCL5) is a chemokine that induces eosinophil migration, and CCR3 and CCR5 are the receptors of RANTES. OBJECTIVE: In order to further clarify the pathomechanisms of eosinophil infiltration in ongoing chronic inflammation in the skin of patients with AE and its relation to disease severity, we examined the expression of RANTES and its receptors CCR3 and CCR5 in challenged and unchallenged lesional skin of AE. METHODS: We examined the number of RANTES+ cells, CCR3+ cells, CCR5+cells, activated (EG2+) eosinophils and CD3+ T cells in normal skin of healthy volunteers, and in challenged lesional skin (24 h after mite patch test) as well as unchallenged lesional skin of AE patients by immunohistochemistry. The cellular source of RANTES, CCR3 and CCR5 was analyzed by double immunohistochemistry using specific antibodies to RANTES, CCR3 or CCR5, and antibodies to ECP (EG2) or CD3. RESULTS: The numbers of RANTES+ cells, CCR3+ cells, CCR5+ cells, EG2+ cells and CD3+ cells were all significantly increased in challenged (mite patch-tested) lesional skin of AE patients as compared to those in unchallenged lesional skin and normal skin. The numbers of these cells in unchallenged lesional skin were greater than those in normal skin. The number of EG2+ cells in the unchallenged lesional skin correlated with both the peripheral blood eosinophil count and the SCORAD index. The number of EG2+ cells in challenged lesional skin correlated with the number of CCR5+ cells. Activated eosinophils and T cells expressed RANTES and various proportions of these cells were CCR3+ and CCR5+ in both challenged and unchallenged lesional skin. CONCLUSION: Taken together, these results suggest that RANTES as well as its receptors CCR3 and CCR5 may play important roles in the orchestration of eosinophil infiltration in ongoing chronic inflammation in AE, and also reflect the severity of disease.

Adult↗
PubMed2006

ARIA update: I--Systematic review of complementary and alternative medicine for rhinitis and asthma.

Complementary-alternative medicines are extensively used in the treatment of allergic rhinitis and asthma, but evidence-based recommendations are lacking. To provide evidence-based recommendations, the literature was searched by using MedLine and the Cochrane Library to March 2005 (Key words: Asthma [OR] Rhinitis, [AND] Complementary [OR] Alternative Medicine, [OR] Herbal, [OR] Acupuncture, [OR] Homeopathy, [OR] Alternative Treatment). Randomized trials, preferably double-blind and published in English, were selected. The articles were evaluated by a panel of experts. Quality of reporting was assessed by using the scale validated by Jadad. The methodology of clinical trials with complementary-alternative medicine was frequently inadequate. Meta-analyses provided no clear evidence for the efficacy of acupuncture in rhinitis and asthma. Some positive results were described with homeopathy in good-quality trials in rhinitis, but a number of negative studies were also found. Therefore it is not possible to provide evidence-based recommendations for homeopathy in the treatment of allergic rhinitis, and further trials are needed. A limited number of studies of herbal remedies showed some efficacy in rhinitis and asthma, but the studies were too few to make recommendations. There are also unresolved safety concerns. Therapeutic efficacy of complementary-alternative treatments for rhinitis and asthma is not supported by currently available evidence.

Acupuncture↗
PubMed2006

Rhinosinusitis: developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗
PubMed2006

Rhinosinusitis: Developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication, "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗
PubMed2005

Increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and matrix metalloproteinase-13 in lesional skin of bullous pemphigoid.

BACKGROUND: Matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 can degrade type IV collagen which is the major component of the basement membrane zone (BMZ). In bullous pemphigoid (BP), the separation occurs within the BMZ. OBJECTIVE: To evaluate the involvement of MMPs in the pathogenesis of BP, we examined the expression of MMP-2, MMP-9 and MMP-13 in the lesional skin of BP patients. METHODS: The expression of MMP-2, MMP-9, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 was analyzed by immunohistochemistry in the lesional skin of BP patients in comparison with that in normal human skin. Next, the cellular sources of MMP-2, MMP-9 and MMP-13 were analyzed by double immunohistochemistry. Finally, the levels of these MMPs in the serum and blister fluid of BP patients were measured by ELISA. RESULTS: The number of cells expressing MMP-2, MMP-9 and MMP-13 were significantly increased in the lesional skin of BP patients as compared to that in normal skin. Although the number of cells expressing TIMP-1 and TIMP-2 were also increased in the lesional skin of BP patients as compared to that in normal skin, the ratio of MMPs to TIMPs in the lesional skin of BP patients was high (2.4:1). T cells comprised the major source of MMP-2, MMP-9 and MMP-13, while a proportion of mast cells and eosinophils also expressed these MMPs. Furthermore, marked expression of MMP-2 was detected in the epidermal keratinocytes. The levels of these MMPs in the blister fluid were significantly greater than those in the serum. CONCLUSION: These results suggest that MMP-2, MMP-9 and MMP-13 may be involved in the mechanism of blister formation in BP and that besides infiltrating inflammatory cells, structural cells like epidermal keratinocytes may also participate in the induction of blister formation in BP.

Aged↗
PubMed2005

Expression of full-length Cochlin p63s is inner ear specific.

OBJECTIVE: The COCH gene mutated in DFNA9, murine an autosomal dominant hereditary hearing impairment, encodes Cochlin. Cochlin is also suggested to be the self-antigen of autoimmune sensorineural hearing loss. We previously reported that Cochlin constitutes 70% of the inner ear proteins and is classified into three types of isoform, p63s, p44s, and p40s. To study the specificity of expression of Cochlin isoforms in various organs, here we have investigated expression of the COCH gene at both the transcriptional and translational level. METHODS: COCH gene expression was studied by RT-PCR and Southern blot analysis. Cochlin isoforms were studied by Western blot analysis using an isoform specific antibody. RESULTS: At the transcriptional level, COCH mRNA was detected only in the inner ear by RT-PCR. Southern blot analysis of RT-PCR products detected a high level of COCH mRNA in the inner ear, lower level in spleen, and very low levels in the cerebrum, cerebellum/brain stem, eye, liver and kidney. At the translational level, Western blot analysis showed that a set of isoform, p63s, p44s, and p40s was detected at high levels only in the inner ear. In contrast, multiple proteins were detected at much lower levels in other organs tested. Notably, full-length Cochlin p63s was detected only in the inner ear. CONCLUSION: Our findings demonstrate that the COCH gene is expressed preferentially in the inner ear and that expression of full-length Cochlin p63s is specific to the inner ear. These results will be central to understanding the function of Cochlin and its role in the pathophysiology of DFNA9.

Animals↗
PubMed2005

Mast cells in allergic airway disease and chronic rhinosinusitis.

Conventional knowledge tells us that mast cells are only important in the acute IgE-mediated reactions as seen in anaphylaxis, asthma and rhinitis. Yet, in recent years, much evidence has accumulated on the versatile role of mast cells in allergic inflammation. Here, we describe the novel and potential roles of mast cells in the late phase allergic reaction as well as in chronic allergic inflammation. Mast cells in patients with allergic rhinitis and asthma produce Th2 type cytokines, induce IgE synthesis in B cells and can autoactivate itself via the mast cell-IgE-FcepsilonRI cascade. In addition, mast cells upregulate the production of a variety of cytokines/chemokines in epithelial cells and fibroblasts and induce the recruitment of basophils, T cells and eosinophils into sites of allergic inflammation as well as their own intraepithelial accumulation. Furthermore, mast cells express MMPs and interact with extracellular matrix proteins and ASM and may play a role in nasal and bronchial hyperresponsiveness as well as tissue remodelling. In chronic rhinosinusitis with nasal polyps, the potential role of mast cells not only in orchestrating eosinophilic inflammation but also in the genesis and perpetuation of nasal polyp formation via FcepsilonRI and TLR mediated activation is also of growing interest.

Asthma↗
PubMed2005

Expression of cochlin in the vestibular organ of rats.

The COCH gene mutated in autosomal dominant sensorineural deafness (DFNA9) encodes cochlin, a major constituent of the inner ear extracellular matrix. Cochlin constitutes 70% of the inner ear protein and cochlin isoforms can be classified into three subgroups, p63s, p44s and p40s. Symptoms of some DFNA9 patients are consistent with those of Ménière's disease. Here, we report the expression of cochlin in the vestibular organ of rats using isoform-specific antibodies that recognize all three isoforms. Cochlin is highly expressed in the stromata of the maculae of otolithic organs and cristae of semicircular canals, and in the channels in the bony labyrinth that transmit the dendritic innervation to the cristae and maculae. Cochlin cannot be detected in the sensory cells, dark cells, nor in the acellular structures, otolithic membrane or in the cupula. These findings support the theory that deposition of acidophilic substance in the inner ear caused by mutation of cochlin can induce a secondary retrograde dendritic degeneration of the vestibular nerves.

Animals↗
PubMed2005

Quality of life assessment in Thai patients with allergic rhinoconjunctivitis using the SF-36 questionnaire (Thai version).

The health related quality of life (QOL) of patients with allergic rhinitis and/or conjunctivitis (ARc) as measured by the SF-36 questionnaire, has been shown to be impaired in a similar way to that of asthmatic patients in France and several other countries. We used the SF-36 questionnaire (Thai version) to evaluate the QOL of Thai ARc patients compared to healthy subjects. The SF-36 questionnaire (Thai version) consists of 36 items covering 8 dimensions and one health transition report question. Higher scores indicated better QOL. The internal consistency reliability of the questionnaire was analysed using Cronbach's alpha-coefficient. A total of 705 healthy persons and 900 ARc patients were included in this study. The mean difference of the scores between healthy and ARc groups in each dimension showed higher scores in the healthy group. This difference was statistically significant (p < 0.05 and p < 0.001) for all dimensions, except for the Social Functioning dimension. The internal reliability of the SF-36 questionnaire was confirmed by Cronbach's alpha-coefficient which was above 0.7 for seven of the dimensions; the exception was the Social Functioning dimension. Men were shown to have higher scores than women in several dimensions. In conclusion, this study has confirmed that the SF-36 questionnaire is sensitive enough to discriminate ARc patients from healthy persons with high reliability. QOL of ARc patients was significantly more impaired than healthy persons and hypertensive patients in several dimensions. These findings were similar to reports from other countries using the same instruments. Therefore the SF-36 questionnaire (Thai version) can be a useful tool in evaluating the impact of ARc on a patient's QOL and the improvement in QOL after therapeutic intervention in Thai patients.

Activities of Daily Living↗
PubMed2004

Identification of a novel Cochlin isoform in the perilymph: insights to Cochlin function and the pathogenesis of DFNA9.

The COCH gene mutated in DFNA9, an autosomal dominant hereditary sensorineural hearing loss and vestibular disorder, encodes Cochlin. Previously, we reported three bovine Cochlin isoforms, p63s, p44s, and p40s, which exhibit significant molecular heterogeneity in vivo. Here we have characterized Cochlin isoforms by generating four isoform-specific anti-Cochlin antibodies. The same three Cochlin isoforms, p63s, p44s, and p40s, were detected in human and cow inner ear tissue; however, p44s and p40s were not detected in perilymph. We identified a novel short 16kDa isoform in human perilymph and a 18-23kDa isoform in cow perilymph, named Cochlin-tomoprotein (CTP), corresponding to the N-terminus of full-length Cochlin (p63s) and the LCCL domain. Notably, CTP contains all of the known mutation sites associated with DFNA9. The pathogenesis of DFNA9 is not fully clarified as yet, and this novel perilymph-associated CTP isoform might provide mechanistic clues to how mutations in the COCH gene damage the inner ear function.

Amino Acid Sequence↗
PubMed2004

Subjective evaluation of post-tympanoplasty hearing in relation to the pure tone threshold.

OBJECTIVE: In the year 2000, the Otological Society of Japan proposed a new criteria to assess the levels of hearing known as Criteria 2000. However, these criteria are intended to assess pure tone threshold after tympanoplasty and the results do not necessarily reflect the hearing condition from the patient's perspective. Thus, it is essential to study the relationship between the subjective evaluation of post-operative hearing based on the patient's own assessment and the objective assessment by audiometry. METHODS: The present study is a questionnaire-based survey on the levels of post-operative hearing in 460 patients whose degree of satisfaction with their levels of hearing was assessed by visual analogue scale (VAS). The hearing level was assessed based on the Criteria 2000 established by the Otological Society of Japan. RESULTS: The post-operative results indicated a success rate of 78.7%. According to the questionnaire-based survey, 64.4% patients considered their hearing as "improved". The average VAS score was the highest in the "improved" group and gradually decreased when in the "deteriorated" group. The highest success rate was obtained in patients who assessed their hearing as "improved" and the lowest rate was seen in those who assessed their hearing as "deteriorated". On the other hand, the success rate in the three groups, "slightly improved", "unchanged", and "slightly deteriorated", was almost similar and did not relate to the objective audiometry findings. Therefore, except for the "improved" and deteriorated" groups, there is no relation between the subjective self-assessment and the objective post-operative hearing. CONCLUSION: A bi-directional approach, one from an audiological (objective) and one from the patient's perspective (subjective), especially using VAS, is quite useful for the post-operative assessment of hearing.

Adolescent↗
PubMed2004

Interferon-gamma expression in the inner ear of rats following secondary immune reaction in the endolymphatic sac.

Recently, we demonstrated increased intercellular adhesion molecule-1 (ICAM-1) expression in the inner ear of systemically pre-sensitized rats after antigen [keyhole limpet hemocyanin (KLH)] challenge into the endolymphatic sac (ES), in good correlation with the cellular infiltration. Interferon-gamma (IFN-gamma) is an important cytokine that upregulates the expression of ICAM-1. Here, we report upregulation of IFN-gamma expression in the inner ear of systemically pre-sensitized rats after antigen (KLH) challenge into the ES. Immunoreactivity for IFN-gamma was detected in the spiral ligament, suprastrial region, spiral modiolar veins, spiral collecting venules, surface membrane of the perilymphatic compartment and perilymphatic space of immunized, but not control, rats. IFN-gamma expression was detected at 1.5 h post-challenge, peaked at 6 h and gradually returned to baseline levels after 7 days. Interestingly, the time kinetics of IFN-gamma expression were in good correlation with those of ICAM-1. These observations demonstrate that antigen challenge into the ES induces IFN-gamma expression, which can then upregulate ICAM-1 expression and induce cell infiltration, suggesting that IFN-gamma may play a crucial role in immune-mediated inner ear diseases.

Animals↗