Cathepsin S as an early biomarker for cardiovascular disease in chronic kidney disease patients / Catepsina S como um biomarcador precoce para doença cardiovascular em pacientes com doença renal crônica

Abstract Introduction: A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. Objective: To investigate cathepsin S as an early biomarker for CVD in patients with CKD. Methods: A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. Results: The level of serum Cat S was increased in CKD patients with CVD (p <0.05) as well as in later stages of CKD (p <0.05). CVD was also more common in patients in early stage CKD. In early stages CKD, Cat S and CVD were positively correlated. Conclusion: These findings suggest that serum Cat S might be useful as an early biomarker for CVD in CKD patients.

Resumo Introdução: Uma alta incidência de eventos de doença cardiovascular (DCV) e mortalidade prematura é observada em pacientes com doença renal crônica (DRC). Assim, novos biomarcadores que podem ajudar a prever o desenvolvimento de DCV nos estágios iniciais da DRC estão sendo investigados juntamente com outros fatores de risco tradicionais. Objetivo: Investigar a catepsina S como um biomarcador precoce para DCV em pacientes com DRC. Métodos: Um total de 64 pacientes com DRC foram incluídos e classificados em 2 grupos: pacientes com DRC com DCV estabelecida e pacientes com DRC com DCV não estabelecida. Todos os pacientes foram submetidos a investigações de rotina incluindo hemograma completo, glicemia aleatória, hemoglobina glicada (HbA1C), eletrólitos séricos, ureia, creatinina, proteína total, albumina total, cálcio total, fósforo, ácido úrico, vitamina D, paratormônio, perfil lipídico, teste de função hepática, medição da catepsina S sérica (Cat S), e Eco 2D do coração. Resultados: O nível de Cat S sérica esteve aumentado em pacientes com DRC com DCV (p <0,05), bem como em estágios posteriores da DRC (p <0,05). A DCV também foi mais comum em pacientes com DRC em estágio inicial. Em estágios iniciais da DRC, a Cat S e a DCV foram positivamente correlacionadas. Conclusão: Estes achados sugerem que a Cat S sérica pode ser útil como um biomarcador precoce para DCV em pacientes com DRC.

Differential diagnosis of non-small cell lung carcinoma by circulating microRNA

Introduction: More than 70% of lung cancer comprises nonsmall-cell lung carcinoma and is associated with poor survival outcome owing to late diagnosis. Identification of lung cancer in early stages when no clinical signs or symptoms are evident, can drastically improve the prognosis. To this end, we aimed to evaluate the changes occurring at tissue level by assessing the expression of six microRNAs (miRNAs) in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). Materials and Methods: Peripheral blood of histopathologically proven cases of lung AC and SCC was collected and processed for the isolation of miRNAs using commercially available kit. Primers against mir-2114, mir-2115, mir-2116, mir-2117, mir-449c, and mir-548q with loading control Caenorhabditis elegans were used. Screening was carried out in thirty cases of both AC and SCC, whereas twenty healthy controls were included. Results:Real-time polymerase chain reaction data revealed that the expression of mir-2114 and mir-449c in AC and mir-2115 in SCC was significantly upregulated. The expression of these miRNAs was also confirmed in lung AC cell line. The differential pattern of expression of these miRNAs can be used for precise diagnosis of lung carcinoma Conclusions: We have used a noninvasive technique to identify the subtype of lung cancer based on molecular genetic signatures. The results suggest that through molecular profiling of miRNA, we can screen high-risk cases for cancer interception

Estimation of bone mineral density and its correlations with homocysteine, and various other biochemical bone markers in postmenopausal women

Introduction- Omocysteine (HCY) prevents collagen cross-linking and activates osteoclast function within the bones. Bone mineral density (BMD) may be affected by Hyperhomocysteinemia via Cathepsin K. Aim- To find the correlation of BMD with biochemical bone markers. Methods- BMD was investigated by the DXA scan with the help of the Hologic QDR1000 system. As per WHO guidelines, subjects were divided into three different subsets with; normal bone mass, osteopenia, and osteoporosis. Every subject underwent routine biochemical laboratory investigations, HCY, Vitamin B12, and folic acid levels. Results-Among 355 postmenopausal women, 69% (245) had osteoporosis while 11.27% (40) had normal BMD (mean age, 53 ± 8.35 years) and 19.72% (70) had osteopenia (mean age 52.86 ± 7.93 years). The mean age in the osteoporotic group was 56.49 ± 6.65 years. The mean levels of HCY in the three groups were 15.58± 7.92 μmol/L, 16.13± 7.34μmol/L and 17.05± 5.13μmol/L, respectively. Hip BMD showed a strong inverse correlation with age (r=-0.360, p=0.002), while no significant correlations were found between weight and BMI. PTH was consistently seen to be negatively correlated with BMD at Spine (r=-0.0339, p=0.004), Forearm (r=-0.267, p=0.027), and Hip (r=-0.224, p=0.064). Conclusion- Low BMD is an important problem in postmenopausal female patients. Age and duration of menopause are independent risk predictors for the development of osteoporosis. Vitamin D levels do not predict low BMD in postmenopausal females. Weight is protective for osteoporosis especially at spine and forearm BMD. Vitamin B12 and Hcy levels did not correlate with low BMD.

In vitro susceptibility of dermatophytes to oral antifungal drugs and amphotericin B in Uttar Pradesh, India

Background: Dermatophytosis is a major public health problem in our country. Although resistance to conventional oral and topical antifungal agents is being increasingly encountered, the sensitivity pattern of dermatophytes has not been systematically analysed. Aims: We aimed to determine the sensitivity pattern of dermatophyte isolates to amphotericin B and six oral antifungal drugs. Materials and Methods: Patients with dermatophytosis attending the outpatient department of dermatology were enrolled in the study. Samples were collected for mycological examination and in vitro antifungal sensitivity testing was done by broth microdilution as per the Clinical and Laboratory Standard Institute M38-A standards. Results: A total of 804 patients were enrolled. Specimens from 185 patients (23%) were both KOH and culture positive, and 44 of these isolates (41 Trichophyton mentagrophytes and 3 Trichophyton rubrum) were subjected to sensitivity testing. Minimum inhibitory concentrations (MIC) of itraconazole, ketoconazole, voriconazole and amphotericin B were comparable. The median MIC to fluconazole was higher than the other tested drugs. Dermatophytes were most susceptible to ketoconazole and voriconazole, followed by itraconazole, amphotericin B, fluconazole and griseofulvin. A high incidence of resistance was found to terbinafine and the difference was statistically significant in comparison to fluconazole, itraconazole, voriconazole, ketoconazole (P = 0.001) and griseofulvin (P = 0.003). The strains were more sensitive to amphotericin B as compared to griseofulvin (P = 0.02) and terbinafine (P < 0.001). Limitations: This was a hospital-based study and may not reflect the true pattern in the community. Only a few of the isolates were selected for study. The clinical response of patients, whose isolates were studied for in vitro sensitivity of the antifungals, was not studied. Conclusions: The sensitivity pattern of dermatophytes to various antifungals including amphotericin B, ketoconazole, voriconazole and itraconazole were determined. The studied isolates were least susceptible to terbinafine.

Association of GLUT-1 (XbaI) Gene Polymorphism in Diabetes and Diabetes Nephropathy Patients of North Indian Population

Diabetic nephropathy (DN) is a chronic complication of both type 1 and type 2 diabetes. However, there is still inadequate understanding of the exact mechanism related to progressive diabetic renal disease. The GLUT-1 XbaI gene polymorphism in the glucose transporter has been suggested in the development of DN. However, its association with T2DM and DN is controversial and has not been established in different ethnic populations. To enhance the understanding of GLUT-1 XbaI gene polymorphism in the context of T2DM and DN. We investigated the possible genetic association of GLUT-1 XbaI polymorphism with T2DM and DN in North Indian population. 100 T2DM patients and 100 patients of DN with 100 healthy controls were included in the study. GLUT-1 XbaI polymorphism was determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). The obtained data showed no significant association between GLUT-1 XbaI gene polymorphism with T2DM and DN leading us to conclude that GLUT-1 XbaI gene polymorphism may not have major effects on T2DM and DN in North Indian population.

Resistance to anti leprosy drugs in multi-bacillary leprosy: A cross sectional study from a tertiary care centre in eastern Uttar Pradesh, India

Background: WHO MDT is the main drug regimen for treating leprosy and has been used for more than three decades. Many cases of relapse of leprosy have been reported, which points towards the emergence of drug resistance with the antileprotic drugs. Objectives: To find the resistance with the antileprotic drugs by detecting the mutations in drug resistance determining region of the rpoB, folP1 and gyrA genes of Mycobacterium leprae. Methods: Leprosy patients with bacterial index ≥2 were included in the study. The slides were further processed to extract genomic DNA, and polymerase chain reactions were performed to amplify the drug resistance determining region (DRDR) of rpoB, folP1 and gyrA genes. The samples in which genes could be amplified were subjected to DNA sequencing to detect mutations. Results: Out of 78 samples rpoB gene was amplified in 39 (50%), folP1 in 32 (41%) and gyrA in 45 (57.7%). In 20 (25.6%) samples no gene was amplified. Only 32 samples of rpoB, 25 samples of folP1 and 38 samples of gyrA gene were included in the study, rest were excluded due to sequencing error. No mutation was seen in rpoB gene and in folP1 gene. In gyrA gene samples mutations were seen in 8 (21%) samples, and were present at codon 91 GCA → GTA (Alanine → Valine). Limitations: Small sample size and less efficient method to detect resistance. Conclusion: Resistance is not a problem with conventional drugs in MDT. It is more common with quinolones.

Disseminated cutaneous fusariosis in human immunodeficiency virus-infected patient and dramatic response with oral itraconazole

Fusarium species are known to cause disseminated cutaneous lesions in immunocompromised patients. Some cases of fusariosis are reported in patients infected with the human immunodeficiency virus. There are two reports in such patients with systemic comorbidities like lymphoma, neutropenia and infective port-a-catheter. Another reported patient had systemic fusariosis, without skin involvement. Diagnosis and treatment of cutaneous fusariosis is difficult and resistance to antifungals is a problem. Our patient was at an advanced human immunodeficiency virus infection stage with disseminated cutaneous fusariosis, without any systemic involvement, who responded completely to oral itraconazole.

Co-infections and sero-prevalence of HIV, syphilis, hepatitis B and c infections in sexually transmitted infections clinic attendees of tertiary care hospital in north India

Background: HIV, syphilis, hepatitis B and C [HBV and HCV] infections modify the epidemiology and presentation of each other. This study aimed to estimate the seroprevalence of these infections and their co-infections in sexually transmitted infections ]STI] clinic attendees in New Delhi, India

Methods: A retrospective study including 220 patients was conducted during May 2014 through December 2014. Serodiagnosis of HIV was performed as per Strategy III of NACO guidelines; syphilis by VDRL followed by TPHA; HBV and HCV by rapid immuno-chromatographic test followed by ELISA

Results: Male subjects were slightly more in number as compared to females [56.36% vs. 43.63%]. Twelve [5.45%], 14 [6.36%], three [1.36 %] and one [0.45%] were reactive for HIV, VDRL, HBV and HCV, respectively. Three were both HIV and syphilis positive and one was both HIV and HBV positive; no co-infections of HBV/HCV, HIV/HBV/HCV and HIV/HBV/HCV/syphilis coexisted

Conclusions: High prevalence of HIV, HBV, HCV and syphilis in STI clinic attendees mandate routine screening to detect co-infections and follow prompt therapy in order to minimize their sequelae

The reservoir effect of topical steroids in vitiliginous skin: A cross-sectional study.

Background: Prolonged and frequent use of topical steroids may lead to decrease in effi cacy as well as many local adverse effects. Stratum corneum has a unique property of reservoir effect. Aims: To study the reservoir effect of topical steroids in a steroid-responsive condition which may enable a decrease in the dosing frequency of topical steroids. Methods: A cross-sectional study design was used. Patients with at least three vitiliginous patches of more than 2 cm2 present over the trunk or limbs were included. Exclusion criteria were topical or systemic corticosteroid use within the previous 4 weeks, antihistamine use within the previous 7 days, history of any allergy in the past and immunosuppression. Clobetasol propionate cream was applied on the fi rst vitiliginous area (site A) and fl uticasone propionate ointment was applied on the second vitiliginous area (site B). The third vitiliginous area, site C (control site) was left without applying any medication. Histamine-induced wheal suppression test was performed on each site, at the same time of the day, on every consecutive day following steroid application, until the values obtained at sites A and B approached those obtained at site C. SPSS software for Windows, version 16.0 was used for statistical analysis. The mean and standard deviation of the various studied parameters were calculated for various treatment groups and compared using analysis of variance (ANOVA) test. Results: Forty patients were included in the study. The average wheal volumes and average erythema sizes at sites A and B were signifi cantly smaller than the corresponding values at site C for up to 5 days after applying medication (P < 0.001). Limitations: The presence of a cutaneous reservoir of topical steroid was confi rmed based on its suppressive effect on the wheal and fl are response to histamine. It is not certain that the concentration that suppresses histamine-induced wheal and fl are is suffi cient for therapeutic effi cacy in vitiligo. Conclusion: The reservoir effect of topical clobetasol propionate and fl uticasone propionate persisted for 5 days in vitiliginous skin. Hence, it may be possible to reduce the frequency of topical steroid application in vitiligo.

Relapse in psoriasis with two different tapering regimens of methotrexate: A randomized open-label controlled study.

Background: Systemic therapy with methotrexate is a very useful modality in psoriasis, but relapses can occur soon after stopping it. Aim: To compare the relapse rates in psoriasis with two different tapering regimens of methotrexate after control is achieved. Methods: This was a randomized open-label controlled study, and patients of chronic plaque psoriasis with psoriasis area and severity index (PASI) >10 were included. Methotrexate 0.3 mg/kg weekly was given and the PASI calculated every 2 weeks. After achieving a 75% reduction in the PASI (PASI-75), patients were assigned randomly in to one of three groups. In the half-dose group, the dose of methotrexate was reduced to half and given weekly; in the 2-weekly group, the same dose was given at 2-week intervals; in the control group, methotrexate was stopped. Patients were followed up for 12 weeks. Results: Out of 141 registered patients, 81 were included: 27 in the half-dose group, 28 in the 2-weekly group, and 26 in the control group. After further exclusions due to adverse effects and loss to follow-up, the results were analysed for 16, 17 and 19 patients respectively in the 3 groups. There was statistically a highly signifi cant difference in relapse rates between the half-dose and control groups (P < 0.001), and a signifi cant difference between the 2-weekly and control groups (P = 0.001). Relapse rates in the half-dose and 2-weekly groups did not show a signifi cant difference (P = 0.680). Limitation: Many (35.8%) patients were excluded and only 52 (64.2%) completed the study. Conclusion: There appears to be no signifi cant difference in the frequency of relapse in psoriasis whether methotrexate is tapered by halving the weekly dose or by doubling the interval between two doses, and both methods led to fewer relapses than abrupt cessation of the drug.

Prevalence of pruritus in psoriatic skin lesions and its relations to different variables

To examine the prevalence of itching in psoriatic skin lesions and its relation with different variables. A simple questionnaire and a verbal four point intensity scale were used. Severity of disease was calculated by using Psoriasis Area Severity Index [PASI]. Six hundred and fourteen patients of psoriasis were examined in which majority were chronic plaque type. Pruritus was present in 79% of the patients, and was severe in 34%; moderate in 15% and mild in 29%. Pruritus was common in chronic plaque psoriasis. It was more severe in more severe type of psoriasis and was more common in females in comparison to males. But there is no difference between pediatric and adult psoriasis.

Metastatic testicular cancer in a patient with arsenical keratosis

Arsenicosis is a multisystem disorder, with many cutaneous features. The cutaneous manifestations take the form of pigmentary changes, hyperkeratosis, and skin cancers [Bowen's disease, squamous cell carcinoma, and basal cell carcinoma]. It is a known carcinogen and there is association between chronic arsenic exposure and malignancy of bladder, lung, liver, kidney and other visceral malignancies. Our patient came from an endemic area where levels of arsenic are high in drinking water and had features of arsenical keratosis for past fifteen years along with metastatic testicular cancer at the time of presentation. Arsenic exposure may increase the risk of testicular cancer

Evaluation of serum interleukin 6 and tumour necrosis factor alpha levels, and their association with various non-immunological parameters in renal transplant recipients

<p><b>INTRODUCTION</b>Renal transplant rejection involves both immunological and non-immunological factors. The objective of the present study was to investigate the association between immunological factors, such as serum interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α), and non-immunological parameters, such as age, serum creatinine (SCr), creatinine clearance (CrCl) and dyslipidaemia, in renal transplant recipients (RTRs).</p><p><b>METHODS</b>This study included 90 RTRs and 90 healthy controls. Biochemical parameters, including serum IL-6 and TNF-α, were estimated using standard protocols. CrCl was calculated using the Cockroft-Gault equation, and the type of rejection was confirmed on biopsy. Student's t-test and univariate and multivariate analyses were performed using the Statistical Package for the Social Sciences for Windows version 15.</p><p><b>RESULTS</b>The mean levels of serum IL-6 and TNF-αwere significantly higher in RTRs than in the control group (p < 0.001). These parameters were also found to be significantly different between the transplant rejection (TR) and transplant stable (TS) groups (p < 0.001). CrCl was significantly decreased in the TR group when compared to the TS group (p < 0.001). The two cytokines, IL-6 and TNF-α, correlated significantly with all metabolic parameters, such as SCr, CrCl and dyslipidaemia. Multiple regression analysis showed that TNF-α and CrCl were the strongest predictors of IL-6.</p><p><b>CONCLUSION</b>We conclude that immunological factors, as well as non-immunological factors such as CrCl, SCr and dyslipidaemia, play important roles in the pathogenesis of graft rejection and renal graft dysfunction.</p>

Experience with anterior petrosal approach for aneurysms of mid-basilar artery

Anterior petrosal approach [Kawase's approach] is an established technique for the management of basilar artery aneurysms arising near the origin of anterior inferior cerebellar artery [Ba-AICA], however the extent of petrosectomy may vary from patient to patient. Authors report their experience with Kawase's approach for the management of these aneurysms in 5 patients. During the last 10 years, anterior petrosal approach was used to clip aneurysms of Ba-AICA junction in five patients, who were not suitable for endovascular therapy. Both ruptured and unruptured aneurysms were included in this series. Successful clipping could be achieved in all but one patient. In this patient with a large aneurysm and complex morphology, residual filling was noted in the postoperative angiogram. Postoperatively one patient developed hemiparesis and transient sixth nerve palsy. There was no operative mortality in this series. For patients with small Ba-AICA shoulder aneurysms, where clipping is preferred method of treatment, sufficient exposure is achieved through Kawase approach, however minor variation may be required while resecting the petrous bone

Acute appendicitis: a quality assurance study.

The parameters that indicate the quality of patient care in acute appendicits (AA) were evaluated. One hundred sixty-four patients, who underwent emergency appendectomy (EA) at the B.P. Koirala Institute of Health Sciences, Dharan, Nepal were studied prospectively. The mean duration of the symptoms was 42.2 +/- 69.5 hours (range 2-720 hours, median 24 hours). The mean waiting period in the hospital was as 12.7 +/- 21.8 hours (range 1-188 hours, median 7 hours). Special investigations' such ultrasonography, computed tomography or laparoscopy, were not used for diagnosis. The perforation rate was 39%. The histopathology report of 79% of the patients was available. Diagnostic accuracy in histologically evaluated patients was 91.5%. One patient (0.6%) died. The mean hospital stay was 3.2 +/- 2.0 days (range 1-17 days). Patients who had to wait in hospital for < 24 hours before surgery had a longer duration of symptoms, underwent exploratory laparotomy through a mid-line incision more frequently, had a higher incidence of perforated/gangrenous appendix and longer hospital stay. The mean medical expenditure for patients treated in the general ward was Nepali Rupees (NR) 2485 +/- 504 (range NR 1372-4500). The majority of patients/guardians (88%-97%) were satisfied with the medical expenditure incurred, promptness of service, behaviour of the hospital staff and the facilities available in the hospital. The diagnostic accuracy and cost of treatment were favourable. The longer duration of symptoms, non-utilization of special investigations for diagnosis, high perforation rate and less than cent-per cent biopsy rate are the aspects that require attention to improve the quality of surgical care.