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   2017| November  | Volume 146 | Issue 8  
    Online since March 26, 2018

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Spectrum of hyperosmolar hyperglycaemic state in neurology practice
UK Misra, J Kalita, SK Bhoi, D Dubey
November 2017, 146(8):1-7
DOI:10.4103/ijmr.IJMR_57_15  PMID:29578188
Background & objectives: Hyperosmolar hyperglycaemic state (HHS) is a medical emergency, but there is a paucity of studies reporting the spectrum of neurological manifestations of HHS. We, therefore, report the neurological spectrum, triggering factors and outcome of HHS in general neurology practice. Methods: The records of the patients with HHS were extracted from computerized hospital information system and those managed currently were prospectively included. The demographic, clinical manifestations, duration of diabetes and precipitating events such as infection, stress and stroke were noted. Patients with HHS were categorized into seizure, movement disorder and encephalopathy groups. Their electroencephalography, magnetic resonance imaging (MRI) findings and outcome were noted. Results: There were 17 patients with HHS (age range 40 and 75 yr) and seven were females. Seven patients were diabetic for five years, one for four years, one for one year and four were diagnosed after the occurrence of HHS. Four patients had epilepsia partialis continua persisting for 72-360 h, one patient had focal seizures and his MRI revealed T2 hyperintensity in frontal region in one patient and cerebellar vermian hyperintensity in another. All the five patients improved, but two had neurological deficits on discharge. Nine patients had encephalopathy which was precipitated by stroke in six patients, urinary infections in two and meningitis in one. Three females had hemichorea-hemiballismus syndrome, which was triggered by infections. Abnormal movements lasted 5-10 days and responded to correction of hyperosmolarity. Nine out of 17 patients improved completely whereas the remaining eight had partial recovery, these patients had stroke, ventilator-related complications or meningoencephalitis. Interpretation & conclusions: The most common presentation of HHS was encephalopathy (9) followed by seizure (5) and hemichorea-hemiballismus syndrome (3) which responded to the correction of hyperosmolar state.
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Effect of multilevel lower-limb botulinum injections & intensive physical therapy on children with cerebral palsy
Monica Juneja, Rahul Jain, Ankita Gautam, Ritu Khanna, Kamia Narang
November 2017, 146(8):8-14
DOI:10.4103/ijmr.IJMR_1223_15  PMID:29578189
Background & objectives: Botulinum toxin is considered as an effective treatment for spasticity in children with cerebral palsy (CP). However, there are only a few long-term studies, and the effects on motor function have been inconclusive. Moreover, due to its high cost and need for intensive post-injection therapy, utility in context of developing nations has not been established. This retrospective study was undertaken to assess the long term effects of botulinum toxin-A with physical therapy in children with CP. Methods: This retrospective study was conducted at a tertiary care centre in India, where a limited supply of botulinum toxin was introduced in the year 2009. It was used in a selective group of patients with CP along with intensive physical therapies. All children who received lower-limb botulinum injections over a 42-month period were analyzed. For evaluation of treatment effect, the measurement at 1st pre-injection assessment and the last measurements, i.e. 12 wk after last injection received by that child were compared. Results: Twenty nine patients (20 males, median age 51 months) received 69 sessions of botulinum toxin injections in the lower limbs over a 42-month period. Thirteen patients were diplegic, 10 were quadriplegic, five were triplegic and one was hemiplegic. There was a significant improvement in pre- and post-injection scores on Observational Gait Scale (right side 7.1±3.6 to 10.7±3.7, left side 6.7±3.5 to 9.9±3.4), Gross Motor Function Measure Scale (47.9±17.7 to 67.6±17.2), Modified Ashworth Scale, passive range of motion and Gross Motor Function Classification System. Most of the patients showed gain in motor milestones as well. Interpretation & conclusions: Our results showed that judicious use of botulinum injections along with intensive physio/occupational therapies could yield good results in children with CP.
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Comparison of Disease Activity Score in 28 joints with ESR (DAS28), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) & Routine Assessment of Patient Index Data with 3 measures (RAPID3) for assessing disease activity in patients with rheumatoid arthritis at initial presentation
B Siddhartha Kumar, P Suneetha, Alladi Mohan, D Prabath Kumar, K V. S Sarma
November 2017, 146(8):57-62
DOI:10.4103/ijmr.IJMR_701_15  PMID:29578196
Background & objectives: In patients with rheumatoid arthritis (RA), disease severity assessment is done using Disease Activity Score in 28 joints with ESR (DAS28). Computing DAS28 is time-consuming, requires laboratory testing and an online calculator. There is a need to validate rapid methods of disease severity assessment for routine daily use. This study was conducted to compare DAS28, Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) and Routine Assessment of Patient Index Data with 3 measures (RAPID3) to assess the disease activity in patients with RA. Methods: We prospectively studied the utility of CDAI, HAQ-DI and RAPID3 scoring in 100 consecutive newly diagnosed, disease modifying antirheumatic drugs (DMARDs) naïve adult patients with RA seen during January 2013 and June 2014 at a tertiary care teaching hospital in south India. Results: The mean age of the patients was 42.1±11.6 yr, there were 82 females. The median [interquartile range (IQR)] symptom duration was 6 (range 4-12) months. The median (IQR) DAS28, CDAI, HAQ-DI and RAPID3 scores at presentation were 7 (6-7), 36 (28-43), 2 (1-2) and 17 (13-19), respectively. A significant positive correlation was observed between DAS28 and CDAI (r=0.568; P<0.001); DAS28 and HAQ-DI (r=0.304; P=0.002) and DAS28 and RAPID3 (r=0.404; P<0.001). A 'slight-to-fair' agreement was observed in between DAS28 and CDAI (kappa-statistic=0.296). The agreement between DAS28 and HAQ-DI (kappa-statistic=0.007) and RAPID3 (kappa-statistic=0.072) was less robust. Interpretation & conclusions: In adult patients with RA, in the setting where illiteracy is high, CDAI emerged as the preferred choice for rapid assessment of severity of disease at the time of initial presentation.
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Assessment of osteoporotic fracture risk in urban Indian population using quantitative ultrasonography & FRAX tool
Raju Vaishya, Vipul Vijay, Amit K Agarwal, Prashant Maheshwari
November 2017, 146(8):51-56
DOI:10.4103/ijmr.IJMR_1220_15  PMID:29578195
Background & objectives: There have been studies around the world on the prevalence of osteoporosis and its related risk factors, but there have been limited studies on risk factors and osteoporosis in the Indian population. In this study, the incidence of osteoporosis and the associated clinical risk factors (CRFs) were studied in the urban Indian population. Methods: Bone mineral density of 445 individuals >38 yr of age using qualitative ultrasound (QUS) was assessed. The patients were also questioned regarding the presence of the various CRFs as per the FRAX tool. The patients were categorized into normal, osteopenia and osteoporosis groups on the basis of T-score from QUS. Results: There were 223 males and 222 females in this study. Sex was significantly associated with T-score (P<0.001). Forty (8.99%) patients were osteoporotic, 265 (59.55%) were osteopenic and the remaining 140 (31.46%) were normal. A significant association of T-score was found with parent history of fracture (P<0.05), rheumatoid arthritis (P<0.05) and secondary osteoporosis (P<0.05). Previous history of fracture's association was not found to be significant. Smoking, alcohol intake and steroid intake were not found to be significantly associated with T-scores. Interpretation & conclusions: The incidence of osteoporosis was found to be high in the urban Indian population. More care and attention should be targeted towards elderly, especially the ones with the risk factors to prevent osteoporosis in future.
  1,736 311 1
Uromodulin rs4293393 T>C variation is associated with kidney disease in patients with type 2 diabetes
Vinod Kumar, Ashok Kumar Yadav, Vivek Kumar, Anil Bhansali, Vivekanand Jha
November 2017, 146(8):15-21
DOI:10.4103/ijmr.IJMR_919_16  PMID:29578190
Background & objectives: Uromodulin, a UMOD gene encoded glycoprotein is synthesized exclusively in renal tubular cells and released into urine. Mutations lead to uromodulin misfolding and retention in the kidney, where it might stimulate cells of immune system to cause inflammation and progression of kidney disease. Genome-wide association studies (GWAS) have identified UMOD locus to be associated with hypertension and diabetic nephropathy (DN). In this study, we investigated the association between rs4293393 variation in UMOD gene and susceptibility to kidney disease in individuals with type 2 diabetes mellitus (T2DM). Methods: A total of 646 individuals, 208 with T2DM without evidence of kidney disease (DM), 221 with DN and 217 healthy controls (HC) were genotyped for UMOD variant rs4293393T>C by restriction fragment length polymorphism. Serum uromodulin levels were quantified by enzyme-linked immunosorbent assay. Results: A significant difference was found in genotype and allelic frequency among DM, DN and HC. TC+CC genotype and C allele were found more frequently in DN compared to HC (33.9 vs 23.0%, P=0.011 and 20.1 vs 12.9%, P=0.004, respectively). Compared to DM, C allele was found to be more frequent in individuals with DN (20.1 vs 14.7%, P=0.034). Those with DN had higher serum uromodulin levels compared to those with DM (P=0.001). Serum uromodulin levels showed a positive correlation with serum creatinine (r=0.431; P<0.001) and negative correlation with estimated glomerular filtration rate (r=−0.423; P<0.001). Interpretation & conclusions: The frequency of UMOD rs4293393 variant with C allele was significantly higher in individuals with DN. UMOD rs4293393 T>C variation might have a bearing on susceptibility to nephropathy in north Indian individuals with type 2 diabetes.
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Initial treatment dropout in patients with substance use disorders attending a tertiary care de-addiction centre in north India
Debasish Basu, Abhishek Ghosh, Siddharth Sarkar, Bichitra Nanda Patra, BN Subodh, Surendra Kumar Mattoo
November 2017, 146(8):77-84
DOI:10.4103/ijmr.IJMR_1309_15  PMID:29578199
Background & objectives: Dropout from substance use disorders treatment is associated with poor outcomes. Although many factors have been associated with an early dropout of patients, the reasons for dropping out of treatment prematurely remain poorly understood particularly in the Indian context. This study was aimed to study socio-demographic and clinical variables predicting initial dropout of patients attending a tertiary care de-addiction treatment centre in north India. Methods: Information was extracted from the records of consecutive newly registered patients from January 2011 to December 2014. The patients who did not come for follow up within 30 days of the first contact were defined as initial dropouts. Results: Data of 7991 patients could be retrieved. Majority of the sample consisted of male, married and employed individuals. Of them, 4907 patients (61.3%) were considered initial dropouts. Multivariate analysis revealed that after controlling for other factors, greater age, being employed, lower educational status, lesser duration of substance use, use of alcohol, opiate, tobacco, cannabis or sedative-hypnotic use but the absence of multi-substance use predicted initial drop out. Interpretation & conclusions: This study identified some socio-demographic and clinical variables which might predict treatment attrition in substance use disorders. Clinician's awareness towards these factors and tailor-made intervention might improve initial treatment retention. Future research could be directed to find the validity of this assumption.
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Unenhanced renal magnetic resonance angiography in patients with chronic kidney disease & suspected renovascular hypertension: Can it affect patient management?
J Yamuna, Anupama Chandrasekharan, Rajeswaran Rangasami, S Ramalakshmi, Santhosh Joseph
November 2017, 146(8):22-29
DOI:10.4103/ijmr.IJMR_1613_15  PMID:29578191
Background & objectives: Renal artery stenosis (RAS) is an important cause of severe hypertension in patients with chronic kidney disease (CKD). It is important to detect RAS early as it can reverse hypertension and stop rapid deterioration of renal function. The potential drawbacks of various imaging modalities used to detect RAS including contrast-related adverse effects associated with diagnostic angiography have led to increasing interest in unenhanced magnetic resonance (MR) renal angiography. The aim of this study was to detect and grade RAS in patients with CKD and suspected renovascular hypertension using unenhanced MR angiography (UMRA) and to identify patients with significant RAS (>70%) who would subsequently require further investigation and revascularization. Methods: Thirty five CKD patients with suspected RAS were subjected to UMRA using non-contrast MR angiography of ArTery and VEins 3D True fast imaging with steady state precession technique over a three year period. Patients with RAS >70 per cent on UMRA were subjected to digital subtraction angiography (DSA) with intervention if indicated. Results: In all, 76 renal arteries were evaluated using UMRA in 35 patients, of which 18 arteries showed stenosis and 11 were haemodynamically significant (eight patients). Seven patients (10 renal arteries) underwent DSA. Interpretation & conclusions: An association between UMRA and DSA findings was obtained in six patients (nine renal arteries), and these patients were stented. Post-procedure follow up showed good improvement in blood pressure and renal function. UMRA was found to be a useful non-invasive imaging modality to detect RAS in CKD patients. It can identify patients who require further invasive angiography and revascularization.
  1,137 293 1
Epigallocatechin gallate & curcumin prevent transforming growth factor beta 1-induced epithelial to mesenchymal transition in ARPE-19 cells
Sivasankar Shanmuganathan, Venil N Sumantran, Narayanasamy Angayarkanni
November 2017, 146(8):85-96
DOI:10.4103/ijmr.IJMR_1583_15  PMID:29578200
Background & objectives: Proliferative vitreoretinopathy (PVR) is characterized by the presence of epiretinal membrane (ERM), which exerts traction and detaches the retina. Epithelial to mesenchymal transition (EMT) of the retinal pigment epithelial (RPE) cells underlies ERM formation. Adjuvant therapies aimed at preventing recurrence of PVR after surgery mostly failed in clinical trials. This study was aimed to evaluate the anti-EMT properties of bio-active compounds epigallocatechin gallate (EGCG), curcumin and lycopene as inhibitors of EMT induced by transforming growth factor beta 1 (TGF-β1) in cultured ARPE-19 cells. Methods: ARPE-19 cells were treated with TGF-β1 alone or co-treated with EGCG (1-50 μM), lycopene (1-10 μM) and curcumin (1-10 μM). The mRNA and protein expression of EMT markers, alpha-smooth muscle actin, vimentin, zonula occludens-1 and matrix metalloproteinase-2 (MMP-2), were assessed by reverse transcription polymerase chain reaction/quantitative polymerase chain reaction and immunofluorescence/enzyme linked immunosorbent assay. Activity of MMP-2 was assessed by zymography. Functional implications of EMT were assessed by proliferation assay (MTT assay) and migration assay (scratch assay). Western-blot for phosphorylated Smad-3 and total Smad-3 was done to delineate the mechanism. Results: EGCG and curcumin at 10 μM concentration reversed EMT, inhibited proliferation and migration through Smad-3 phosphorylation, when induced by TGF-β1 in ARPE-19 cells. Lycopene did not prevent EMT in ARPE-19 cells. Interpretation & conclusions: EGCG and curcumin are potent in preventing EMT induced by TGF-β1 in ARPE-19 cells and therefore, proposed as potential molecules for further pre-clinical evaluation in PVR management.
  1,080 282 1
Interlink between cholesterol & cell cycle in prostate carcinoma
Govind Singh, Shrimanjunath Sankanagoudar, Premnath Dogra, Nimai Chand Chandra
November 2017, 146(8):38-44
DOI:10.4103/ijmr.IJMR_1639_15  PMID:29578193
Background & objectives: Earlier reports have shown hypocholesterolaemia in cancer patients and high number of lipid rafts in cancer cells. The primary objective of this study was to compare the intracellular cholesterol turnover in non-cancerous (benign) prostatic hyperplasia (BPH) and carcinoma prostate (CAP) with normal prostate cells obtained from patients undergoing radical cystectomy for carcinoma bladder (sham control). Methods: ELISA-based estimation of prostate-specific antigen (PSA), evaluation of expression of low-density lipoprotein receptor (LDLR), peripheral-type benzodiazepine receptor (PBR) and cyclin E, immunohistochemistry and confocal microscopy, measurement of integrated optical density of the diaminobenzidine (DAB)-stained immunohistograms, isolation of nucleus and cell cytoplasm from prostate tissue by ultracentrifugation followed by estimation of cholesterol spectrophotometrically in isolated nuclear and cytoplasmic fractions were performed. Results: Seventy five individuals, 25 for each group (BPH n=25; CAP n=25 and sham control n=25), were included in the study. Cholesterol was increased in the cytoplasm and nucleus of the prostate cancer cells along with elevated expression of LDLR. Increased cholesterol concentration in the cell nucleus was found comparable with the increased expression of cholesterol transporter viz. PBR in the prostate tumour tissues as compared to its expression in normal prostate cells obtained from individuals undergoing radical cystectomy for carcinoma bladder. Cell cycle protein cyclin E was also highly expressed in cancer tissues. Interpretation & conclusions: The present findings along with increased expression of cell cycle protein cyclin E in the cell nucleus of the tumour tissue suggested the possibility of an intriguing role of cholesterol in the mechanism of cell cycle process of prostate cell proliferation.
  911 221 4
Comparison of radiofrequency ablation alone & in combination with percutaneous ethanol injection for management of hepatocellular carcinoma
Naveen Kalra, Mandeep Kang, Ajay K Duseja, Anmol Bhatia, Virendra Singh, Radha K Dhiman, Arvind Rajwanshi, Yogesh K Chawla, Niranjan Khandelwal
November 2017, 146(8):30-37
DOI:10.4103/ijmr.IJMR_1812_15  PMID:29578192
Background & objective: It has been shown that the combined use of alcohol before radiofrequency ablation (RFA) helps to augment the therapeutic advantage of RFA. The present study was conducted to compare the outcome of treatment with RFA alone and RFA with alcohol as ablative technique in patients with small hepatocellular carcinomas (HCCs), who were not candidates for surgery. Methods: Fifty patients with chronic liver disease and concurrent HCC were enrolled in this prospective study. The patients were treated with either RFA alone (n=25) or RFA combined with alcohol (n=25). Patient outcome was evaluated, and the tumour recurrence and survival of the patients were assessed in the two groups. Results: The survival rates at six months in patients who completed at least six months of follow up were 84 and 80 per cent in patients treated with RFA alone and combination therapy, respectively. During the follow up period, 11 and four patients treated with RFA alone showed local and distant intrahepatic tumour recurrence, respectively. All local recurrences were at one to 18 months of the follow up period. The distant recurrences occurred at 6-36 months of the follow up period. During the follow up period, eight and six patients treated with combination therapy showed local and distant intrahepatic tumour recurrence, respectively. All local recurrences were at 1.5-15 months during the follow up period. The distant intrahepatic recurrences occurred at 6-72 months during the follow up period. Interpretation & conclusions: No significant difference was seen between the survival time of the patients treated with RFA alone and RFA with alcohol as well as in the local recurrences and distant intrahepatic recurrences in RFA compared to RFA and alcohol group patients. Combined use of RFA and alcohol did not improve the local tumour control and survival in patients with HCC compared to RFA alone.
  768 256 2
Effect of bone bank processing on bone mineral density, histomorphometry & biomechanical strength of retrieved femoral head
OP Lakhwani, M Jindal, Omkar Kaur, RK Chandoke, SK Kapoor
November 2017, 146(8):45-50
DOI:10.4103/ijmr.IJMR_739_15  PMID:29578194
Background & objectives: Standard processing of the bone grafts involves deep-freezing and sterilization with gamma irradiation which may alter mechanical properties of the bone graft. This study was aimed at measuring the effect of bone bank processing on the mechanical properties of bone allograft and its correlation with bone mineral density [BMD, dual-energy X-ray absorptiometry (DEXA Scan)] and histomorphometric indices. Methods: Femoral heads retrieved from patients undergoing hip replacement surgeries were used as the material. Twenty femoral heads were under taken in the study. Each femoral head was cut into two equal cubes. One cube was subjected to BMD measurement using DEXA Scan followed by unilateral compression test. Histomorphometric indices such as trabecular number (Tb. N.), trabecular separation (Tb. S.), trabecular thickness (Tb. T.) and bone volume (B.V.) were calculated on the same specimen by a computer software. The other cube was kept in deep freezer (−76°C) for a minimum of three weeks, followed by gamma irradiation and subjected to similar tests. Results: Results were compared in pre- and post-processed bone specimens. A significant loss of biomechanical strength (P<0.001) with mean a loss of 18.90 per cent was found in post-processed samples in uniaxial compression tests. Similarly, BMD (mean decrease by 13.8%, P<0.01) and histomorphometric indices such as Tb. T. (mean decrease by 12.37%, P<0.01), Tb. S. (mean increase by 12.60%, P<0.001) and B.V. (mean decrease by 20.84%, P<0.01) were found. However, Tb. N. was not significantly affected. Interpretation & conclusions: The current method of processing of bone allografts i.e. deep-freezing and gamma irradiation appeared to cause a significant reduction in the biomechanical strength of allogenic bone which was more suitable to be use in the morselized form. Appropriate consideration for decreased strength needs to be given when using allogenic bone graft as a structural graft.
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Impact of attendance in a daycare centre on depression among elderly in rural Puducherry: A pre- & post-intervention study
Sonali Sarkar, Shivanand Kattimani, KC Premarajan, Gautam Roy
November 2017, 146(8):68-76
DOI:10.4103/ijmr.IJMR_857_15  PMID:29578198
Background & objectives: Depression is higher in the elderly and in the rural areas in India. There is a need for interventions to reduce depression among the elderly and improve their quality of life (QOL). This study was conducted to assess the impact of attendance at a community-based daycare centre in rural Puducherry, India, on depression, cognitive impairment (CI) and QOL of the elderly. Methods: This was a before and after intervention study with a daycare centre set up in the village Thondamanatham in Puducherry, India, between January 2013 and January 2014. Socializing activities were held at the centre with psychological counselling. Depression was measured using Geriatric Depression Scale (GDS, short form), CI using the Hindi Mini-Mental Status Examination and QOL using WHO QOL BREF. Results: There were 99 males and 164 females; of whom 42.2 per cent attended the daycare centre at least once a month. Significantly higher proportions of elderly had depression among those with lower frequency of attendance at the daycare centre. Irrespective of the pre-intervention status, attendance at the daycare centre reduced the probability of depression by about 51 per cent. There was an improvement in the WHO QOL scores in the social domain among those who attended more than once a month. Interpretation & conclusions: GDS scores decreased and WHO QOL scores increased with increasing attendance at the daycare centre. Thus, the intervention was found to be effective in reducing depression and improving QOL of the elderly.
  620 188 1
Immunohistochemical expression of hypoxia-inducible factor-1α in stromal cells of vaginal tissue in post-menopausal women with pelvic organ prolapse
Ivana Alujević Jakus, Dora Jakus, Nađa Aračić, Ivica Stipić, Katarina Vilović
November 2017, 146(8):63-67
DOI:10.4103/ijmr.IJMR_388_16  PMID:29578197
Background & objectives: Pelvic organ prolapse (POP) is a common medical condition that affects adult women of different ages. The support of a normal pelvic floor is the result of complex interactions between ligaments, muscles, connective tissue and vaginal walls. Hypoxia and oxidative stress can reduce protein synthesis in the pelvic muscles that may contribute to muscular atrophy. Hypoxia-inducible factor-1α (HIF-1α) is a transcriptional activator which, expressed in response to hypoxia, activates a number of genes involved in cellular response to hypoxia. However, a potential role of hypoxia and oxidative stress in pathogenesis of POP is not known. This study was aimed to compare the level of HIF-1α immunohistochemical expression in the vaginal stromal cells of postmenopausal women with and without POP. Methods: Samples of the vaginal tissue from 120 menopausal women were obtained during surgery, and immunohistochemical expression of HIF-1α was assessed. There were 60 women with POP while 60 women in the control group were without prolapse but with benign gynaecological diseases. Results: In post-menopausal women with prolapse, significant differences were observed in the number of HIF-1α-positive stromal cells in the vaginal tissue compared to the control group. There was a significant increase in the number of HIF-1α in the stromal cells of the vaginal tissue in women with prolapse. Interpretation & conclusions: Difference in expression of HIF-1α in stromal cells of the vaginal tissue in the post-menopausal women with and without POP suggests that prolonged hypoxia probably has an important role in the aetiopathogenesis of POP.
  600 181 1