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AIM: We report findings from a large single centre paediatric renal biopsy cohort in South Asia. METHODS: We analyzed all renal biopsies performed on children aged ≤18 years between 1996 and 2015 at our centre. The clinical characteristics and histological diagnosis pertaining to each case, distribution of renal diseases in children with various clinical presentations, and changes in the pattern of kidney disease during the study period were analyzed. RESULTS: A total of 1740 paediatric kidney biopsies were performed during the study period. The mean age was 12.8 ± 4.9 years (8 months to 18 years) and the male: female ratio was 1.5:1. The most common indication for renal biopsy was nephrotic syndrome (63.2%) followed by acute nephritic syndrome (13%). Minimal change disease was the most common cause of nephrotic syndrome while endocapillary proliferative glomerulonephritis (65.7% infection related), remained the commonest cause of acute nephritic syndrome. IgA nephropathy was the commonest cause of chronic kidney disease. Contrary to trends in European paediatric cohorts, the frequency of lupus nephritis increased over the two decades of the study, while that of endocapillary proliferative glomerulonephritis did not show any appreciable decline. CONCLUSION: This study provides the largest data on biopsy proven renal disease in children from South Asia published till date and highlights important differences in the spectrum and trends of kidney disease compared to data from other regions.
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Biópsia , Nefropatias/patologia , Rim/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Sistema de Registros , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Self-directed learning (SDL) is defined as learning on one's own initiative, with the learner having primary responsibility for planning, implementing, and evaluating the effort. Medical education institutions promote SDL, since physicians need to be self-directed learners to maintain lifelong learning in the ever-changing world of medicine and to obtain essential knowledge for professional growth. The purpose of the study was to measure the self-directed learning readiness of medical students across the training years, to determine the perceptions of students and faculty on factors that promote and deter SDL and to identify the role of culture and curriculum on SDL at the Christian Medical College, Vellore, India. METHODS: Guglielmino's SDL Readiness Scale (SDLRS) was administered in 2015 to six student cohorts (452 students) at admission, end of 1st, 2nd, 3rd and 4th year of training, and at the beginning of internship in the undergraduate medicine (MBBS) program. Analysis of variance (ANOVA) was used to compare SDL scores between years of training. 5 student focus groups and 7 interviews with instructors captured perceptions of self-direction. Transcripts were coded and analyzed thematically. RESULTS: The overall mean SDLRS score was 212.91. There was no significant effect of gender and age on SDLR scores. There was a significant drop in SDLRS scores on comparing students at admission with students at subsequent years of training. Qualitative analysis showed the prominent role of culture and curriculum on SDL readiness. CONCLUSIONS: Given the importance of SDL in medicine, the current curriculum may require an increase in learning activities that promote SDL. Strategies to change the learning environment that facilitates SDL have to be considered.
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Características Culturais , Educação de Graduação em Medicina/métodos , Docentes de Medicina/psicologia , Autoaprendizagem como Assunto , Estudantes de Medicina/psicologia , Adolescente , Análise de Variância , Estudos Transversais , Currículo , Avaliação Educacional/normas , Feminino , Grupos Focais , Humanos , Índia , Masculino , Pesquisa Qualitativa , Faculdades de Medicina , Adulto JovemRESUMO
This editorial is an analysis the review article by Nabi et al recently published in this journal. Achalasia Cardia is a disease whose pathophysiology is still unclear. It is known that there is inflammation of unknown aetiology leading to loss of ganglion cells in the muscularis propria. The end result is lower oesophageal sphincter spasm, loss of receptive relaxation, decreased oesophageal peristalsis, all leading on to varying degrees of dysphagia. The treatment of this condition is palliative in nature, performed by myotomy of the lower oesophagus either surgically or endoscopically. Gastroesophageal reflux disease (GERD) has been associated with the myotomy performed, particularly with the Peroral Endoscopic Myotomy (POEM) procedure. Nabi et al have provided an excellent overview of the latest developments in predicting, preventing, evaluating, and managing GERD subsequent to POEM. Based on this theme, this review article explores the concept of using histology of the oesophageal muscle layer, to grade the disease and thereby help tailoring the length/type of myotomy performed during the POEM procedure. In the future, will a histology based algorithm available preoperatively, help modify the POEM procedure, thereby decreasing the incidence of GERD associated with POEM?
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Acalasia Esofágica , Esfíncter Esofágico Inferior , Refluxo Gastroesofágico , Cirurgia Endoscópica por Orifício Natural , Humanos , Acalasia Esofágica/cirurgia , Acalasia Esofágica/fisiopatologia , Acalasia Esofágica/diagnóstico , Esfíncter Esofágico Inferior/cirurgia , Esfíncter Esofágico Inferior/fisiopatologia , Esofagoscopia/métodos , Esofagoscopia/efeitos adversos , Refluxo Gastroesofágico/cirurgia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/diagnóstico , Miotomia/métodos , Miotomia/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodos , Piloromiotomia/efeitos adversos , Piloromiotomia/métodos , Resultado do TratamentoRESUMO
Crohn's disease (CD) usually affects younger individuals but delayed-onset disease is not uncommon. We studied the epidemiology, demographic profile, and clinical characteristics of patients with delayed-onset CD (disease onset >50 years) and compared them with CD in younger individuals (disease onset 20-40 years) in a tertiary care center in India. The presenting symptoms, site of involvement, and treatment profile were similar, except for weight loss, which was more often noted in young-onset CD. However, granulomatous inflammation on mucosal biopsy was twice as common in young-onset compared to delayed-onset CD. As it is thus seen less often in delayed-onset CD, this may lead to a potential delay in diagnosis and treatment.
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Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Biópsia , Inflamação/diagnóstico , Inflamação/epidemiologia , Índia/epidemiologiaRESUMO
BACKGROUND: Colorectal cancer is one of the alarming health problems worldwide. Prognostic biomarkers are the key for risk stratification in patients with colon cancer and the decision to recommend adjuvant chemotherapy. It has been difficult to identify a single prognostic biomarker for colon cancer. Currently, tumor stage, tumor grade, and microsatellite instability remain the most important prognostic variables that aid in the treatment of patients with colon cancer. Some studies highlighted that CDX2 immunohistochemistry negativity is an independent prognostic factor and indicates a worse survival rate. Our aim was to study the prevalence of CDX2 biomarker expression in patients diagnosed with primary adenocarcinoma and to correlate this with the clinical profile and pathological features. METHODS: Endoscopic mucosal biopsies and resection specimens of 148 patients diagnosed with colonic adenocarcinoma were analyzed. CDX2 immunohistochemistry was performed, and the result was correlated with clinicopathological features. The results were presented as mean, frequencies, and percentages. Pearson's Chi-square test was used to assess the associations between clinicopathological parameters and CDX2 immunohistochemistry negativity. RESULTS: The prevalence of CDX2 expression by immunohistochemistry in colon cancer was found to be 92%. CDX2 biomarker negativity was found to be higher in left-sided colon cancers, poorly differentiated adenocarcinoma, mucinous carcinoma, and higher TNM stages. CONCLUSION: CDX2-negative tumors are often associated with several adverse prognostic variables (e.g., advanced stage, poor differentiation, and metastasis). Thus, sub-classification of colon cancer based on the CDX2 biomarker aids to separate them into prognostically relevant categories.
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To study the association of Helicobacter pylori (H. pylori) in patients with laryngeal pathologies. Study design: prospective observational study. Tertiary care teaching hospital. One hundred consecutive patients with laryngeal lesions scheduled for microlaryngoscopy were enrolled in the study. Laryngopharyngeal reflux was assessed using the reflux symptom index and reflux finding score. Tissue samples from the laryngeal lesions were taken under general anaesthesia and were screened for the presence of H. pylori using real time polymerase chain reaction (PCR) for ureA genes and histopathological examination. Of the 100 patients, 14 had a significant reflux symptom index score and 35 had significant reflux finding score. The lesions in the study subjects included both benign and malignant laryngeal pathologies. Vocal cord polyps formed more than half of the laryngeal pathology (57%) studied. Our study could not detect H. pylori in any laryngeal lesions by PCR analysis and histopathological examination. H. pylori may not be associated with laryngeal pathologies.
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PURPOSE: Assessment of disease activity in Crohn's helps predict important clinical outcomes. Among the various modalities available to assess disease activity, magnetic resonance enterography (MRE) is considered a safe and reliable imaging option. Various MRE-based scoring systems have been developed to measure disease activity, one of which being the MRE global score (MEGS). We aimed to correlate MEGS with some of the important indices of Crohn's disease activity. METHODOLOGY: Crohn's disease patients referred for MRE were included in the study. Along with demographic profile and relevant investigations, MRE parameters related to MEGS were also assessed. RESULT: A total of 47 patients were recruited for the study. Their median age was 34 years (range 18-68 years), and male:female ratio was 16:31. There was modest positive correlation between MEGS and faecal calprotectin (r = 0.3, p = 0.04), CRP level (r = 0.34, p = 0.02) and Harvey Bradshaw index (r = 0.3, p = 0.043), respectively. However, there was strong correlation between segmental MEGS and Simple Endoscopic Score in those with terminal ileal disease (r = 0.81, p < 0.001). Mural thickness was the only MRE parameter that correlated with active disease (OR - 1.35, 95% CI 1.01, 1.81, p = 0.041) on multivariate analysis. There was moderate inter-observer agreement (Lin's r = 0.78, p < 0.001). CONCLUSION: MEGS showed modest correlation with indices of Crohn's disease activity which corroborates the complementary role of MRE in management of such patients.
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Doença de Crohn , Adolescente , Adulto , Idoso , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Feminino , Humanos , Íleo , Complexo Antígeno L1 Leucocitário , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Multiple genetic risk factors for Crohn's disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries. AIM: To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population. METHODS: We conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences. RESULTS: A total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD. CONCLUSION: Unlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.
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BACKGROUND: Fundic gland polyps (FGP) of stomach are benign, while some hyperplastic polyps (HP) may harbor dysplasia or malignancy. Conventional white light endoscopy (WLE) cannot reliably distinguish FGP from HP. We investigated the role of image-enhanced endoscopy in differentiating FGP from HP. METHODS: Patients with gastric polyps were recruited prospectively. The characteristics of the polyps were assessed using WLE and magnification narrow band imaging (mNBI). The microsurface, intervening space (IS), and microvascular (V) features of polyps were evaluated on mNBI. The pattern characteristic of FGP and HP were determined. Histopathology of polyps was the gold standard for diagnosis. Finally, in the validation phase, five endoscopists applied the characteristic features identified in this study to predict the type of gastric polyp and their performance was assessed. RESULTS: Forty-five patients with a total of 70 gastric polyps (HP-46, FGP-24) were included in this study. On mNBI, the pattern characteristic of HP included peripheral curved type of white structures forming large circular/villous loops (microsurface), enlarged intervening space, and microvessels appearing as dark patches in the intervening space (p<0.001 vs. FGP). These were noted in 95.7% HP. In contrast, 95.8% FGP had a pattern characterized by dotted/elliptical/tubular white structures (microsurface), normal width of intervening space, and microvessels surrounding the white structures in a network pattern. This IS-V pattern classification had an accuracy of >90% in the validation phase with intra-class correlation coefficient of 0.95. The accuracy of mNBI was higher than WLE (97.1% vs. 67%) in predicting the type of gastric polyp. CONCLUSIONS: Image-enhanced endoscopy with mNBI (IS-V pattern) performs very well in differentiating HP from FGP.
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Pólipos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Pólipos/diagnóstico , Endoscopia Gastrointestinal , HiperplasiaRESUMO
BACKGROUND AND AIMS: Retinoids are important mediators of cellular differentiation and proliferation in various epithelia of the body including the small intestine. Though alterations in intestinal epithelial cell proliferation have been noted in liver cirrhosis, mechanisms involved in the process are not well understood. This study examined the levels of various retinoids and retinoid-metabolizing enzymes in the small intestine during development of liver cirrhosis. METHODS: Four groups of animals were used (control, phenobarbitone control, thioacetamide and carbon tetrachloride treatment). Twice-weekly intragastric or i.p. administration of carbon tetrachloride or thioacetamide, respectively, produced liver cirrhosis after 3 months, which was confirmed through histology and serum markers. Retinoid levels were measured by high-performance liquid chromatography. RESULTS: A decrease in the levels of retinal, retinoic acid and retinol was evident in the intestine by 3 months, when cirrhosis was evident histologically, and these remained low until 6 months. A decrease in the activities of retinaldehyde oxidase, retinaldehyde reductase and retinol dehydrogenase was also seen in intestine from cirrhotic rats. CONCLUSION: These results suggest that altered retinoid metabolism in the intestine of cirrhotic rats might have an influence on changes in intestinal epithelial cell differentiation, seen in liver cirrhosis.
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Enterócitos/metabolismo , Intestino Delgado/metabolismo , Cirrose Hepática Experimental/metabolismo , Retinoides/metabolismo , Oxirredutases do Álcool/metabolismo , Animais , Biomarcadores/sangue , Tetracloreto de Carbono , Cromatografia Líquida de Alta Pressão , Progressão da Doença , Regulação para Baixo , Enterócitos/enzimologia , Feminino , Intestino Delgado/enzimologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Masculino , Ratos , Retinaldeído/metabolismo , Tioacetamida , Fatores de Tempo , Tretinoína/metabolismo , Vitamina A/metabolismoRESUMO
CONTEXT: The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). AIMS: To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. SUBJECTS AND METHODS: Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers - BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. RESULTS: Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). CONCLUSION: The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects.
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Adenocarcinoma Mucinoso/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Marcadores Genéticos/genética , Repetições de Microssatélites/genética , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Adulto , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Patologia Molecular , Adulto JovemRESUMO
Tuberculosis and Crohn disease are granulomatous disorders affecting the intestinal tract with similar clinical manifestations and pathologic features. We evaluated the use of in situ polymerase chain reaction (PCR) using Mycobacterium tuberculosis complex-specific primers for IS 6110 to differentiate these 2 disorders in archival mucosal biopsy specimens. In situ PCR was positive in 6 of 20 tuberculosis biopsy specimens and 1 of 20 Crohn disease biopsy specimens. Staining was localized to a site of granulomatous inflammation in 3 of the tuberculosis specimens and in the Crohn disease specimen. In the other tuberculosis biopsy specimens, positive staining was localized to inflammatory granulation tissue and to a focus of intact mucosa without granulomatous inflammation. The presence of M tuberculosis DNA in Crohn disease could be due to coexisting latent tuberculosis or indicate a role for these bacteria in triggering an abnormal immune response. Therefore, in situ PCR is potentially useful to differentiate intestinal tuberculosis from Crohn disease, if the sensitivity is improved.
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Doença de Crohn/microbiologia , DNA Bacteriano/análise , Mycobacterium tuberculosis/genética , Tuberculose Gastrointestinal/microbiologia , Biópsia , Doença de Crohn/diagnóstico , Diagnóstico Diferencial , Granuloma/microbiologia , Granuloma/patologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Tuberculose Gastrointestinal/diagnósticoRESUMO
BACKGROUND: Myeloperoxidase (MPO) and interleukin-6 (IL-6) are often used as markers of inflammation. The aim of this study was to ascertain whether MPO activity is as reliable as IL-6 as an indicator of inflammation. METHODS: Inflammation was induced in mice, using either turpentine or indomethacin. Duodenal tissue was removed from these animals at various time periods ranging from 6 h to 7 days later. Concentrations of IL-6 and MPO activity were estimated in the tissue. Histopathological examination was also carried out at some of the time periods to determine the presence of neutrophil infiltration in turpentine-treated mice. RESULTS: Concentrations of IL-6 and MPO activity were significantly higher in tissue that had been treated with the agents used, at all the time periods studied, when compared with corresponding control tissue. Fold-increases in MPO activity were higher than fold-increases in IL-6. Concentrations of the 2 parameters showed significant positive correlation. Histopathological examination did not show significantly higher numbers of neutrophils infiltrating the tissue in response to turpentine, at the time periods studied. CONCLUSIONS: Estimation of MPO activity is a reliable indicator of inflammation, being more sensitive than histopathological examination of tissue and as good as measurement of IL-6 concentrations.
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Peroxidase/metabolismo , Animais , Indometacina/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Interleucina-6/metabolismo , Masculino , Camundongos , Terebintina/uso terapêuticoRESUMO
BACKGROUND AND AIM: Macrophages and dendritic cells are closely related mononuclear phagocytic cells. Little is known about their in vivo role in acute intestinal bacterial infections in humans. We undertook to evaluate these cells in rectal mucosal biopsies of patients with acute colitis. METHODS: All mucosal mononuclear phagocytic cells in rectal biopsies of patients with acute Campylobacter colitis (n = 5), shigellosis (n = 5), and cholera (n = 10) were evaluated ultrastructurally and compared with those in controls (n = 5). RESULTS: Mononuclear phagocytic cells in the superficial rectal mucosa showed a higher prevalence of ultrastructural features of activation in Campylobacter colitis and cholera than in controls. A lower prevalence of features of activation with increased monocytes was seen in shigellosis. Cells with the ultrastructural morphology of activated dendritic cells constituted 41% and 45% of all mononuclear phagocytic cells in two of five patients with Campylobacter colitis and 4-22% of cells in four of 10 patients with cholera. Their presence in patients with Campylobacter colitis was associated with significant surface epithelial damage and prominent acute inflammatory changes in the mucosa. CONCLUSIONS: This is the first ultrastructural study to show activated macrophages and dendritic cells in vivo in acute Campylobacter colitis and cholera. Dendritic cell activation occurred early in the clinical course of these infections. Surface epithelial damage may play a role in the activation of dendritic cells.
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Infecções por Campylobacter/imunologia , Cólera/microbiologia , Colite/microbiologia , Células Dendríticas/fisiologia , Mucosa Intestinal/citologia , Macrófagos/fisiologia , Doença Aguda , HumanosRESUMO
Alterations in tissue zinc levels have been documented in patients with gastrointestinal tract malignancies and more frequently, in those with colonic cancer. However, the precise role of tissue zinc in carcinogenesis is not well elucidated. This study, using a well-established colon cancer model in rats, was designed to investigate the relationship of tissue zinc to the carcinogenic process. The aim was to examine tissue zinc levels in the preneoplastic tissues and to study the changes that occur during transition of mucosa from normal to preneoplastic state. Six-week old rats were given a single dose subcutaneous injection of azoxymethane (AOM) (30mg/kg body weight) and sacrificed after 1, 2, 5, and 9 months of the treatment. Plasma zinc levels showed a significant decrease (p<0.05) at 9 months compared with controls. Tissue zinc levels showed a significant decrease in the large intestine at 1 and 2 months (p<0.05) and at 5 and 9 months (p<0.01), in the small intestine at 2, 5, and 9 months (p<0.05), and in the stomach at 5 and 9 months (p<0.05). The maximum percent decrease (45%) in tissue zinc was observed in the large intestine at 9 months. Tissue copper zinc super oxide dismutase (CuZnSOD) activity was assessed in the body of the stomach, small intestine, and large intestine and compared with the control group. There was a significant fall in CuZnSOD levels in the small intestine at 9 months (p<0.05) and in the large intestine at 5 and 9 months (p<0.01). Two of these six rats showed histological evidence of precancerous lesions in the mucosa of the colon. This study suggests that the decrease in plasma zinc, tissue zinc and activity of CuZnSOD is associated with development of preneoplastic lesions in the colonic mucosa.
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Neoplasias do Colo/química , Trato Gastrointestinal/química , Lesões Pré-Cancerosas/química , Zinco/análise , Animais , Azoximetano/toxicidade , Carcinógenos/toxicidade , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Trato Gastrointestinal/patologia , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Wistar , Superóxido Dismutase/análiseRESUMO
Very few animal studies have used 1,1-dimethyl hydrazine (unsymmetrical dimethyl hydrazine - UDMH) as a carcinogen. This study was designed to investigate the carcinogenicity of UDMH in the gastrointestinal tract in a rat model. We wanted to observe if there were any changes in tissue zinc levels and tissue copper zinc superoxide dismutase (CuZnSOD) enzyme activity during the carcinogenic process, and to compare these values with those of control rats in the medium- and long-term. Six-week-old Wistar rats were given a subcutaneous injection of UDMH (30mg/kg body wt) twice a week for 20 weeks, and sacrificed after 5 and 9 months of treatment. Tissue zinc levels showed a significant decrease (p<0.05) in the large intestine at 9 months, whereas in the stomach and small intestine there were no significant changes at 5 and 9 months. Tissue CuZnSOD enzyme activity in the stomach, small intestine and large intestine showed no significant decrease at 5 and 9 months as compared to controls. Histologically, the large intestine was normal at 9 months. This study suggests that UDMH administered at the above dosage was not carcinogenic in this model.
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1,2-Dimetilidrazina/química , Dimetilidrazinas/toxicidade , Neoplasias Gastrointestinais/induzido quimicamente , Animais , Testes de Carcinogenicidade , Dimetilidrazinas/química , Mucosa Gástrica/metabolismo , Neoplasias Gastrointestinais/enzimologia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Intestino Grosso/enzimologia , Intestino Grosso/metabolismo , Intestino Grosso/patologia , Intestino Delgado/enzimologia , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Isomerismo , Ratos , Ratos Wistar , Estômago/enzimologia , Estômago/patologia , Superóxido Dismutase/metabolismo , Zinco/metabolismoRESUMO
Highly active anti retroviral therapy (HAART) has dramatically improved life expectancy of human immunodeficiency virus (HIV) infected patients, converting HIV infection into a chronic illness with associated changes in its attendant renal complications. The past two decades have witnessed a decrease in the prevalence of HIV associated nephropathy (HIVAN), traditionally considered to be the hall mark of renal involvement in HIV infection. Simultaneously a host of other glomerular and tubulo-interstitial diseases have emerged, expanding the spectrum of HIV associated renal diseases, predominant among which is HIV associated immune complex mediated kidney diseases (HIVICK). Of the diverse glomerular diseases constituting HIVICK, fibrillary glomerulonephritis (FGN) remains a rarity, with only two existing reports to date, confined to patients co-infected with Hepatitis C virus (HCV). The pathogenetic role of HIV in these patients remains under a cloud because of previously well established association of HCV infection and FGN. We report a case of FGN in a HIV seropositive, HCV negative Indian patient, highlighting the diagnostic electron microscopy (EM) findings of FGN and strengthening the causal association of HIV with FGN. In view of increasing heterogeneity of renal complications in HIV infection, the diagnostic utility of a comprehensive renal biopsy evaluation inclusive of EM is emphasized for appropriate selection of treatment modalities.
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Nefropatia Associada a AIDS/patologia , Glomerulonefrite/patologia , Nefropatia Associada a AIDS/diagnóstico , Biópsia , Glomerulonefrite/diagnóstico , Humanos , Rim/ultraestrutura , Masculino , Microscopia Eletrônica , Pessoa de Meia-IdadeRESUMO
A patient on treatment for multibacillary leprosy for the past three years, presented with episodes of abdominal pain. Since the patient improved with conservative management, clofazimine induced enteropathy was considered as a remote possibility. A review of the mucosal biopsies showed macrophages with crystal-storing spaces consistent with clofazimine deposition in the duodenum. This case highlights the need to consider and investigate drug-induced disease as part of the differential diagnosis.
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Clofazimina/efeitos adversos , Duodenopatias/induzido quimicamente , Hansenostáticos/efeitos adversos , Duodenopatias/diagnóstico , Gastrite Atrófica/induzido quimicamente , Humanos , Hanseníase Virchowiana/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: No studies so far have examined enteric infections in patients undergoing bone marrow transplantation (BMT) in developing countries where asymptomatic carriage and colonization with enteric pathogens is frequent. METHODS: A prospective study followed 65 patients who underwent BMT in South India between 1995 and 1998. Patients were screened for enteric pathogens before transplantation, weekly during the first 4 weeks after transplantation, and during all episodes of diarrhea. RESULTS: Enteric pathogens were found in 60% of patients before or after transplantation. Pretransplantation screening revealed asymptomatic excretion of enteric pathogens in 29% (19/65). Forty-eight percent of patients undergoing BMT developed diarrhea. Diarrhea was mainly of noninfectious origin in the first 20 days after transplantation. More than 20 days after transplantation, the major causes of diarrhea were graft-versus-host disease and infection. Parasitic infections other than Cryptosporidium did not contribute significantly to morbidity in the pre- and posttransplantation period. Rotavirus and adenoviruses were found in approximately 12% and 5% of subjects, respectively. Bacterial infections in the posttransplantation period were found to be more common in India than in developed countries. Clostridium difficile-associated diarrhea was seen in the posttransplantation period but not before transplantation. Enterotoxigenic and enterohemorrhagic Escherichia coli caused symptomatic infections in the posttransplantation period, but the association of other classes of diarrheogenic E. coli with diarrhea was doubtful. CONCLUSIONS: There was significantly higher mortality (P<0.01) in patients with symptomatic or asymptomatic gastrointestinal infections caused by bacteria than in patients with parasitic or viral infections or without enteric infections.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Diarreia/etiologia , Complicações Pós-Operatórias/fisiopatologia , Adulto , Animais , Infecções Bacterianas/epidemiologia , Diarreia/epidemiologia , Feminino , Doença Enxerto-Hospedeiro , Humanos , Índia , Masculino , Parasitos/classificação , Doenças Parasitárias/epidemiologia , Complicações Pós-Operatórias/classificação , Estudos Retrospectivos , Transplante HomólogoRESUMO
Nonsteroidal anti-inflammatory drugs are used extensively in clinical medicine. In spite of their therapeutic utility, however, they are known to cause significant gastrointestinal and renal toxicities, circumstances that limit their use. The side effects produced in these organs have been attributed mainly to the inhibitory effect of these drugs on the activity of cyclooxygenase, a key enzyme in prostaglandin synthesis. In addition to this, in the small intestine it is known that reactive oxygen species also contribute to the enteropathy seen in response to these drugs. In the kidney, however, there is little information whether other mechanisms contribute to the renal toxicity. This study was designed to look at the possible biochemical mechanisms involved in indomethacin-induced renal damage. Rats fasted overnight were dosed with indomethacin (20 mg/kg) by gavage and sacrificed 24 hr later. Histology of the kidney showed abnormalities in the mitochondria in the proximal tubules. Evidence of oxidative stress was found in the kidney associated with mitochondrial dysfunction and neutrophil infiltration. The lipid composition in the mitochondria was also altered. Such effects were abolished by the prior administration of arginine, a donor of nitric oxide. This study, thus, suggests that one of the mechanisms by which nonsteroidal anti-inflammatory drugs induce renal damage is through oxygen free radicals possibly generated by activated neutrophils and mitochondrial dysfunction.