Glomerular parietal epithelial expression of CD44 in minimal change nephrotic syndrome and primary focal segmental glomerulosclerosis: A clinico-pathological study

Introduction: Minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) are the two common causes of nephrotic syndrome (NS) in both children and adults with overlapping clinical features, but with distinct prognostic and therapeutic implications. The distinction between these relies entirely on histopathology, which can sometimes be difficult. CD44 is expressed by activated parietal epithelial cells, plays a role in matrix deposition and thus in the pathogenesis of FSGS. Aims: To assess the expression of CD44 in MCNS and FSGS and to evaluate its association with the known clinical and histopathological prognostic factors. Materials and Methods: Thirty cases each of MCNS and FSGS were studied. The clinical, laboratory, histopathological, and CD 44 immunohistochemical data were recorded. The findings were analyzed and correlated. A P value of < 0.05 was considered statistically significant. Results: Statistical association was noted between CD44 positivity and serum creatinine (p = 0.031), estimated glomerular filtration rate (p = 0.040), segmental sclerosis (p < 0.001), tubular atrophy (p = 0.027), interstitial fibrosis (p = 0.027), and histological diagnosis (p < 0.001). The sensitivity, specificity, positive predictive, and negative predictive values were 90%, 76.67%, 79.41% and 88.46%, respectively. Conclusions: CD44 immunostain can effectively distinguish MCNS from FSGS. The congruent results of CD44 positivity with known prognostic factors support the possibility of using the CD44 marker as a predictive tool in selecting high-risk patients and offering appropriate therapeutic measures.

Report on Death of Dwarf Sperm Whale, Kogia sima (Order: Cetacea: Family: Kogiidae) in Vedalai Shore of Mandapam, Gulf of Mannar

Aims: Present study aims to highlight an accidental death of a male Dwarf Sperm Whale scientifically known as Kogia sima which found to be as Least Concern (LC) as per IUCN Red List data. Kogia sima represents important higher trophics of marine ecosystem which faced the several threats and conservation need in Gulf of Mannar, India. Study Design: The study undertaken during extensive coral reef monitoring survey was carried out in Gulf of Mannar under the CRAM Project of National Centre for Coastal Research (NCCR). The present report emphasize the Morphometric observation of the dead Kogia sima and try to find out possible cause of death by examining in situ investigation. Place and Duration of Study: The field study was taken in Vedalai Sea shore (N09�.626�, E79�.977�) under the Mandapam Union of Ramnathapuram District of Tamil Nadu. The male whale specimen was found on 5th May, 2019 lying dead on the sandy seashore. Methodology: Animal was photographed and morphological attributes were measured to identify the specimen. Several injuries have been highlighted in the paper which helps in investigating the cause of death. Results: The Dwarf Sperm Whale was infant and has mild damage on the mouth parts including scuff off skin from the body and severe blood clotting at major part of the right side near to pectoral fin. Death of this infant is not clear but it is assumed that the male infant has lost from his parents and came to the inshore area of Mandapam where it gets stuck with running boat or boulder rocks as this immature whale limits its diving capabilities. The necessary morphological characters and measures have been listed in Table 1. Conclusion: This unfortunate death clearly indicated that acute information on ecological behavior of Dwarf Sperm Whale is still under data collection stage in India and that previous conservation efforts in country must be reviewed in terms of role of local authorities, live stranded cetaceans and hunting or incidental killing which in future can build a road map for effective action plans to save this marine mammal.

Clinical Evaluation of a Patient With Symptoms of Colonic or Anorectal Motility Disorders

Constipation, irritable bowel syndrome, fecal incontinence, abdominal pain, and anorectal pain are problems that affect 40% of the population. They commonly present with overlapping symptoms indicating that their pathophysiology affects multiple segments of the gut as well as brain and gut interactions. Clinically, although some conditions are readily recognized, dyssynergic defecation, fecal incontinence, and anorectal pain are often missed or misdiagnosed. Consequently, the assessment of lower gastrointestinal symptoms in patients with suspected colonic or anorectal motility disorder(s) remains challenging for most clinicians. A detailed history, use of the Bristol stool form scale, prospective stool diaries, ideally through a phone App, digital rectal examination, and judicious use of complementary diagnostic tests are essential. Additionally, it is important to evaluate the impact of these problems on quality of life and psychosocial issues, because they are intricately linked with these disorders. The Rome IV diagnostic questionnaire for functional gastrointestinal disorders can provide additional information often missed during history taking. Here, we discuss a systematic approach for the clinical evaluation of patients with suspected lower gastrointestinal problems, grouped under 4 common diagnostic categories. We describe how to take a detailed history, perform meticulous digital rectal examination, and use validated tools to supplement clinical evaluation, including assessments of quality of life and scoring systems for disease severity and digital Apps. These tools could facilitate a comprehensive plan for clinical management including diagnostic tests, and translate the patients’ complaints into definable, diagnostic categories.

Prevalence of Disaccharidase Deficiency in Adults With Unexplained Gastrointestinal Symptoms

Background/Aims@#Disaccharidase assay is used for assessing carbohydrate intolerance in children, but its usefulness in adults is not known. The aim of this study is to assess the prevalence of disaccharidase deficiency in patients with unexplained gastrointestinal symptoms. @*Methods@#A retrospective review of adults with chronic (> 1 year) abdominal symptoms and negative imaging and endoscopy/colonoscopy and who completed bowel symptom questionnaire and duodenal biopsy for lactase, maltase, sucrase, and palatinase was performed. A subset also underwent 25 g lactose breath test (LBT). @*Results@#One hundred twenty patients (females = 83) were evaluated, of whom 48 also underwent LBT. Fifty-six (46.7%) patients had enzyme deficiency; 44 (36.7%) had single (either lactase or maltase), 1 had 3 enzyme deficiencies, 11 (9.2 %) had all 4 disaccharidase enzyme (pan-disaccharidase) deficiency, and 64 (53.0%) had normal enzyme levels. Baseline prevalence and severity of 11 gastrointestinal symptoms were similar between normal and single enzyme deficiency groups. The sensitivity and specificity of LBT was 78.3% and 72.0%, respectively and overall agreement with lactase deficiency was 75.0%. @*Conclusions@#Isolated disaccharidase deficiency occurs in adults, usually lactase and rarely maltase, and pan-disaccharidase deficiency is rare. Baseline symptoms or its severity did not predict enzyme deficiency.

Expression and serological application of recombinant epitope-repeat protein carrying an immunodominant epitope of Newcastle disease virus nucleoprotein

PURPOSE: The aim of the present study was to develop a serodiagnostic test for differentiation infected from vaccinated animal (DIVA) strategy accompanying the marker vaccine lacking an immunodominant epitope (IDE) of nucleoprotein of Newcastle disease virus (NDV). MATERIALS AND METHODS: Recombinant epitope-repeat protein (rERP) gene encoding eight repeats of the IDE sequence (ETQFLDLMRAVANSMR) by tetra-glycine linker was synthesized. Recombinant baculovirus carrying the rERP gene was generated to express the rERP in insect cells. Specificity and sensitivity of an indirect enzyme-linked immunosorbent assay (ELISA) employing the rERP was evaluated. RESULTS: The rERP with molecular weight of 20 kDa was successfully expressed by the recombinant baculovirus in an insect-baculovirus system. The rERP was antigenically functional as demonstrated by Western blotting. An indirect ELISA employing the rERP was developed and its specificity and sensitivity was determined. The ELISA test allowed discrimination of NDV infected sera from epitope deletion virus vaccinated sera. CONCLUSION: The preliminary results represent rERP ELISA as a promising DIVA diagnostic tool.

Anorectal Manometry in Defecatory Disorders: A Comparative Analysis of High-resolution Pressure Topography and Waveform Manometry

BACKGROUND/AIMS: Whether high-resolution anorectal pressure topography (HRPT), having better fidelity and spatio-temporal resolution is comparable to waveform manometry (WM) in the diagnosis and characterization of defecatory disorders (DD) is not known. METHODS: Patients with chronic constipation (Rome III) were evaluated for DD with HRPT and WM during bearing-down “on-bed” without inflated rectal balloon and “on-commode (toilet)” with 60-mL inflated rectal balloon. Eleven healthy volunteers were also evaluated. RESULTS: Ninety-three of 117 screened participants (F/M = 77/16) were included. Balloon expulsion time was abnormal (> 60 seconds) in 56% (mean 214.4 seconds). A modest correlation between HRPT and WM was observed for sphincter length (R = 0.4) and likewise agreement between dyssynergic subtypes (κ = 0.4). During bearing down, 2 or more anal pressure-segments (distal and proximal) could be appreciated and their expansion measured with HRPT but not WM. In constipated vs healthy participants, the proximal segment was more expanded (2.0 cm vs 1.0 cm, P = 0.003) and of greater pressure (94.8 mmHg vs 54.0 mmHg, P = 0.010) during bearing down on-commode but not on-bed. CONCLUSIONS: Because of its better resolution, HRPT may identify more structural and functional abnormalities including puborectal dysfunction (proximal expansion) than WM. Bearing down on-commode with an inflated rectal balloon may provide additional dimension in characterizing DD.

Update on the Pathophysiology and Management of Anorectal Disorders

Anorectal disorders are common and present with overlapping symptoms. They include several disorders with both structural and functional dysfunction(s). Because symptoms alone are poor predictors of the underlying pathophysiology, a diagnosis should only be made after evaluating symptoms and physiologic and structural abnormalities. A detailed history, a thorough physical and digital rectal examination and a systematic evaluation with high resolution and/or high definition three-dimensional (3D) anorectal manometry, 3D anal ultrasonography, magnetic resonance defecography and neurophysiology tests are essential to correctly identify these conditions. These physiological and imaging tests play a key role in facilitating a precise diagnosis and in providing a better understanding of the pathophysiology and functional anatomy. In turn, this leads to better and more comprehensive management using medical, behavioral and surgical approaches. For example, patients presenting with difficult defecation may demonstrate dyssynergic defecation and will benefit from biofeedback therapy before considering surgical treatment of coexisting anomalies such as rectoceles or intussusception. Similarly, patients with significant rectal prolapse and pelvic floor dysfunction or patients with complex enteroceles and pelvic organ prolapse may benefit from combined behavioral and surgical approaches, including an open, laparoscopic, transabdominal or transanal, and/or robotic-assisted surgery. Here, we provide an update on the pathophysiology, diagnosis, and management of selected common anorectal disorders.

Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer.

Background & objectives: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD. Methods: Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues. Results: Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC (P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression. Interpretation & conclusions: The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future.

Diagnosis and Treatment of Dyssynergic Defecation

Dyssynergic defecation is common and affects up to one half of patients with chronic constipation. This acquired behavioral problem is due to the inability to coordinate the abdominal and pelvic floor muscles to evacuate stools. A detailed history, prospective stool diaries, and a careful digital rectal examination will not only identify the nature of bowel dysfunction, but also raise the index of suspicion for this evacuation disorder. Anorectal physiology tests and balloon expulsion test are essential for a diagnosis. Newer techniques such as high-resolution manometry and magnetic resonance defecography can provide mechanistic insights. Recently, randomized controlled trials have shown that biofeedback therapy is more effective than laxatives and other modalities, both in the short term and long term, without side effects. Also, symptom improvements correlated with changes in underlying pathophysiology. Biofeedback therapy has been recommended as the first-line of treatment for dyssynergic defecation. Here, we provide an overview of the burden of illness and pathophysiology of dyssynergic defecation, and how to diagnose and treat this condition with biofeedback therapy.

How to Perform and Assess Colonic Manometry and Barostat Study in Chronic Constipation

Management of chronic constipation with refractory symptoms can be challenging. Although new drugs and behavioral treatments have improved outcome, when they fail, there is little guidance on what to do next. At this juncture, typically most doctors may refer for surgical intervention although total colectomy is associated with morbidity including complications such as recurrent bacterial overgrowth. Recently, colonic manometry with sensory/tone/compliance assessment with a barostat study has been shown to be useful. Technical challenges aside, adequate preparation, and appropriate equipment and knowledge of colonic physiology are keys for a successful procedure. The test itself appears to be safe with little complications. Currently, colonic manometry is usually performed with a 6-8 solid state or water-perfused sensor probe, although high-resolution fiber-optic colonic manometry with better spatiotemporal resolutions may become available in the near future. For a test that has evolved over 3 decades, normal physiology and abnormal findings for common phenotypes of chronic constipation, especially slow transit constipation, have been well characterized only recently largely through the advent of prolonged 24-hour ambulatory colonic manometry studies. Even though the test has been largely restricted to specialized laboratories at the moment, emerging new technologies and indications may facilitate its wider use in the near future.

Optimal Testing for Diagnosis of Fructose Intolerance: Over-dosage Leads to False Positive Intolerance Test

No abstract available.

How to Assess Regional and Whole Gut Transit Time With Wireless Motility Capsule

Assessment of transit through the gastrointestinal tract provides useful information regarding gut physiology and pathophysiology. Although several methods are available, each has distinct advantages and limitations. Recently, an ingestible wireless motility capsule (WMC), similar to capsule video endoscopy, has become available that offers a less-invasive, standardized, radiation-free and office-based test. The capsule has 3 sensors for measurement of pH, pressure and temperature, and collectively the information provided by these sensors is used to measure gastric emptying time, small bowel transit time, colonic transit time and whole gut transit time. Current approved indications for the test include the evaluation of gastric emptying in gastroparesis, colonic transit in constipation and evaluation of generalised dysmotility. Rare capsule retention and malfunction are known limitations and some patients may experience difficulty with swallowing the capsule. The use of WMC has been validated for the assessment of gastrointestinal transit. The normal range for transit time includes the following: gastric emptying (2-5 hours), small bowel transit (2-6 hours), colonic transit (10-59 hours) and whole gut transit (10-73 hours). Besides avoiding the use of multiple endoscopic, radiologic and functional gastrointestinal tests, WMC can provide new diagnoses, leads to a change in management decision and help to direct further focused work-ups in patients with suspected disordered motility. In conclusion, WMC represents a significant advance in the assessment of segmental and whole gut transit and motility, and could prove to be an indispensable diagnostic tool for gastrointestinal physicians worldwide.

Analysis of autosomal dominant spinocerebellar ataxia type 1 in an extended family of central India.

Background: Spinocerebeller ataxia type 1 (SCA1) is a specific type of ataxia among a group of inherited diseases of the central nervous system. In SCA1, genetic defects lead to impairment of specific nerve fibers carrying messages to and from the brain, resulting in the degeneration of the cerebellum, the coordination center of the brain. We investigated 24 members of an extended family in Gwalior city, India, some of which were earlier clinically diagnosed to be suffering from yet unconfirmed type of SCA neurodegenerative disorder. Materials and Methods: All the family members from each age group were screened clinically and the characteristics of those resembling with ataxia were recorded for diagnosis by MRI. The confirmed patients of the family were genetically tested by PCR based molecular testing to identify the type of SCA (i.e., SCA 1, 2, 3, 4, 6 or 7). Family tree of the disease inheritance was constructed by pedigree based method. Result and Conclusion: We found the clinical (symptoms and MRI) and genetic (Pedigree and PCR) results to be correlated. The PCR result revealed the disease to be of SCA 1 type being inherited in the family.

Cross-cultural standardization of the South Texas Assessment of Neurocognition in India.

Background & objectives: Despite the central role of cognition for mental disorders most studies have been conducted in western countries. Similar research from other parts of the world, particularly India, is very limited. As a first step in closing this gap this cross-cultural comparability study of the South Texas Assessment of Neurocognition (STAN) battery was conducted between USA and India. Methods: One hundred healthy adults from Kerala, India, were administered six language independent subtests of the Java Neuropsychological Test (JANET) version of the STAN, assessing aspects of general intellectual ability (Matrix Reasoning), attention (Identical Pairs Continuous Performance, 3 Symbol Version Test; IPCPTS), working memory (Spatial Capacity Delayed Response Test; SCAP), response inhibition (Stop Signal Reaction Time; SSRT), Emotional Recognition and Risk taking (Balloon Analogue Risk Task; BART). Test results were compared to a demographically matched US sample. Results: Overall test performance in the Kerala sample was comparable to that of the US sample and commensurate to that generally described in studies from western countries. Interpretation & conclusions: Our results support the metric equivalence of currently available cognitive test batteries developed in western countries for use in India. However, the sample was restricted to individuals who were literate and had completed basic primary and secondary education.

Unusual Canal Morphology In Mandibular Second Molar - A Case Report.

A case of unusual root morphology is presented to demonstrate anatomic variations in mandibular second molars. The most common configuration of mandibular second molar is to have two roots with three root canals; however mandibular molars may have many different combinations. Endodontic therapy was performed in a mandibular second molar with three separate roots one located mesially and two distally. Radiographically all 3 root canals terminated with individual foramina. Three orifices or 3 independent canals were found in the three separate roots, indicating a rare anatomic configuration. Looking for additional roots, canals and unusual morphology is an important part of successful endodontics, as the knowledge of their existence occasionally enable clinicians to treat a case that otherwise might have ended in failure.

Utility of QuantiFERON TB gold test in a south Indian patient population of ocular inflammation.

Aim: To study the utility of interferon-γ release assays (QuantiFERON TB gold test) in a south Indian patient population of intraocular inflammation. Design: Evaluation of a diagnostic test- a pilot study from January 2007 to October 2008. Materials and Methods: QuantiFERON TB gold test was performed on the following groups of patients following an informed consent. Group A included healthy volunteers without any exposure to tuberculosis (TB) or past history of TB (n=22). Group B included patients with active systemic TB diagnosed by the demonstration of acid-fast bacilli or by the histopathology finding of caseation with granuloma formation from the sputum, lymph node, skin or intestinal biopsies (n=26). Group C included patients with uveitis of known etiologies other than intraocular TB without any history of exposure to active TB (n=21). Group D included patients with a diagnosis of presumed intraocular TB, who responded to antitubercular therapy by decreased or no recurrences following treatment and with a minimum of nine months follow-up following initiation of antitubercular therapy (n=39). Results: The sensitivity and specificity of the QuantiFERON TB gold test to pick up active systemic TB was 58% and 77% respectively. The sensitivity and specificity of the QuantiFERON TB gold test to pickup intraocular TB was 82% and 76% respectively. Conclusions: QuantiFERON TB gold test alone may not be specific for intraocular TB. The significance of this test in a case scenario needs to be interpreted with clinical presentation and other evidences for intraocular TB.

Effects of tegaserod and erythromycin in upper gut dysmotility: a comparative study.

Objectives Tegaserod may enhance upper gut transit, but, its prokinetic effects on antral/small bowel motility and how this compares with erythromycin is unknown. We prospectively assessed and compared the effects of tegaserod and erythromycin on upper gut motility. Methods In an open label, non-crossover study, 22 patients (M/F=4/18; mean age=37 years) with symptoms of upper gut dysmotility underwent 24-hour ambulatory antroduodenojejunal manometry with a six-sensor solid state probe. The effects of 12 mg oral tegaserod were compared with 125 mg intravenous erythromycin by quantifying pressure wave activity and assessing motor patterns. Results Motor activity increased (p<0.05) in antrum, duodenum and jejunum with both drugs when compared to baseline period. The motor response with tegaserod was higher (p<0.05) in jejunum and occurred during the second or third hours, whereas with erythromycin, it was higher (p<0.05) in antrum and occurred within 30 minutes. After tegaserod, a ‘fed-response’ like pattern was seen whereas after erythromycin, large amplitude (>100 mmHg) antral contractions at 3 cycles per minute were seen. Following tegaserod and erythromycin, phase III MMCs occurred in 12 (55%) and 8 (36%) patients respectively (p>0.05). Conclusions Both drugs increase upper gut motility and induce MMC’s, but exert a differential response. Tegaserod produces a more sustained prokinetic effect in the duodenum/ jejunum, whereas erythromycin predominantly increases antral motor activity.

Bone marrow cells for myocardial repair-a new therapeutic concept.

AIM: To assess the safety and feasibility of transfusing autologous bone marrow stem cells (ABMSC) into the culprit coronary artery after an acute anterior wall myocardial infarction (MI) and further to see the ability of ABMSC to promote improvement in Left Ventricular lsqb;LV] function at follow-up. METHODS: In an ongoing phase I clinical trial, twenty-seven patients of uncomplicated acute anterior wall MI treated as per the current practicing guidelines have been included. Among these, seventeen patients received intra-coronary unfractionated ABMSCs from 77ndash;15 days after acute MI (ABMSC group) and ten patients acted as controls. RESULTS: All the procedures carried out were without any complications. After 6 months, cardiac function analysis of ten patients from the ABMSC group by LV angiography and Cardiac Magnetic Resonance Imaging (MRI) demonstrated a significant rise of 12.74% (p = 0.001) and 7.1% (p = 0.001), respectively in the LV ejection fraction [LVEF]. There was an improvement in the LV systolic function wherein LV end systolic volume (LVESV) decreased significanty to 28.75% (p = 0.010) and 16.49% (p = 0.022) by LV angiography and cardiac MRI, respectively. LV end diastolic volume (LVEDV) decreased marginally by LV angiography (p = 0.548) and by cardiac MRI (p = 0.514). Five patients of the control group by LV angiography demonstrated non-significant rise of 1.0% (p = 0.706) in LVEF, 12.79% (p = 0.332) in LVEDV and 22.56% (p = 0.308) in LVESV. By cardiac MRI controls demonstrated significant rise in EF of 3.2% (p = 0.0367rpar; but non-significant fall of only 2.32% (p = 0.812) in LVEDV and 6.47% (p 7equals; 0.508) in LVESV. CONCLUSION: This study shows that intracoronary infusion of ABMSC is safe and feasible after acute MI and shows a favourable trend towards the improvement of LV function and prevention of ventricular remodeling which determines long-term survival.