Pattern of mismatch repair protein loss and its clinicopathological correlation in colorectal cancer in North India.

BACKGROUND: To determine the mismatch repair (MMR) protein loss in colorectal cancer (CRC) in north Indian patients and its clinicopathological correlation. METHOD: A prospective study on patients with colorectal cancer from a tertiary level hospital conducted between May 2014 and June 2015. MMR protein loss was determined using immunohistochemistry for MLH1, MSH2, PMS2 and MSH6. RESULTS: 52 patients (38 male and 14 females) of CRC, with median age of 52.5 years who underwent resection form the study group. 18 (35%) patients were < 50 years of age. Family history of malignancy was present in 3 (6 %) patients. A total of 15 (29%) patients had loss of MMR protein of which 7 (46%) were < 50 years. Most common MMR loss was combined loss of MSH2 + MSH6 [6 (11.5%)] followed by isolated loss of PMS2 [5 (9.6%)]. MMR protein loss was more frequent in patients with right side colon cancer [12 (42%)] compared to left [3 (13%)] (p = 0.033). MMR protein loss was seen in 11 (34%) out of 32 patients fulfilling the revised Bethesda criteria compared to 4 (20%) out of 20 patients who did not fulfil the criteria (p = 0.352). CONCLUSION: This study demonstrates high frequency of MMR protein loss in colorectal cancer in north Indian patients which was more common in right colon cancer. Many patients having MMR protein loss do not satisfy the revised Bethesda criteria and would have been missed if selective testing was done. Further research and larger studies are required to validate these findings and develop India specific clinical criteria.

Association of heterogenicity of Helicobacter pylori cag pathogenicity island with peptic ulcer diseases and gastric cancer.

OBJECTIVE: To investigate the frequency and integrity of certain cag pathogenicity island genes (cagPAI) in Helicobacter pylori strains and their association with peptic ulcer disease (PUD) and gastric cancer. MATERIAL AND METHODS: We enrolled 240 adult patients [120 with functional dyspepsia (FD), 50 with PUD and 70 with gastric cancer] undergoing upper gastrointestinal endoscopy. H. pylori infection was diagnosed when either culture or any two of the three tests (rapid urease test, histopathology and specific ureA PCR) were positive. DNA extracted from H. pylori isolates and positive gastric tissues were tested by PCR for the presence of different genes of cagPAI using specific primers. RESULTS: A total of 122 (51%) patients were H. pylori positive. Frequencies of cagPAI genes cagA, cagE, cagT and cagM in H. pylori strains from different groups of patients were as follows: functional dyspepsia 73, 83, 76 and 60%, PUD 70, 94, 91, 70% and gastric cancer 75, 95, 90 and 70%, respectively. Risk associated for the presence of PUD and gastric cancer with cagPAI genes cagE, cagT and cagM was 5.0-, 4.6- and 4.1- and 3.0-, 2.8- and 2.5-folds, respectively. Prevalence of intact cagPAI was significantly higher in PUD and gastric cancer compared to functional dyspepsia (PUD vs. functional dyspepsia, 71% vs. 38%, P = 0.01; gastric cancer vs. functional dyspepsia, 75% vs. 38%, P < 0.01). Intact cagPAI was associated with increased risk for the presence of PUD (odds ratio 5.2, 95% CI 2.4-11.3) and for the presence of gastric cancer (odds ratio 4.5, 95% CI 2.3-7.1). CONCLUSIONS: cagPAI integrity and its different genes are linked to different forms of gastric disease and so may have a role in pathogenesis, diagnosis and management.

Ultrasound-guided fine needle aspiration cytology of gallbladder lesions: a study of 596 cases.

OBJECTIVE: Fine needle aspiration (FNA) is not a commonly performed procedure for gallbladder lesions for fear of causing biliary peritonitis; hence data on gallbladder cytology is scarce. The aims of the present study were to evaluate the diagnostic application of ultrasound-guided (US) FNA cytology in the pre-operative diagnosis of neoplastic as well as non-neoplastic lesions of the gallbladder and to review the cytomorphological spectrum of gallbladder lesions encountered along with various diagnostic difficulties that can arise during reporting. METHODS: The study was carried out on 596 patients with gallbladder lesions in whom US-guided FNA was performed over a 5-year period. In 130 cases, simultaneous aspirations from other organs were done. The histological correlation was available in 32 cases. No major complications such as haemorrhage, peritonitis, etc. were encountered related to the procedure. RESULTS: The majority were mass lesions whereas in 73 cases (12.2%) only focal or diffuse gallbladder wall thickening was present. Cytological examination of 596 cases revealed malignancy in 462 (77.6%), 26 (4.4%) suspicious of malignancy, 23 (3.8%) inflammatory lesion, 29 negative (4.8%) and 56 cases showed necrosis only or were inadequate for any definite opinion. The lesions diagnosed on FNA cytology included carcinoma (predominantly adenocarcinoma), xanthogranulomatous cholecystitis (XGC), acute suppurative inflammation and tuberculosis. Of 26 with adequate cytology, 24 were accurate with respect to malignant (including one suspicious FNA) versus benign: one false positive and one false negative both involved xanthogranulomatous change. CONCLUSION: The present study is the largest series evaluating the role of US-guided FNA in the diagnosis of gallbladder lesions. It is a safe, rapid, reliable, cost-effective and reasonably accurate method for diagnosing gallbladder lesions. FNA should always be attempted in cases with a mass lesion.

Cure for immune-tolerant hepatitis B in children: is it an achievable target with sequential combo therapy with lamivudine and interferon?

We prospectively studied the HBsAg seroconversion with sequential combination therapy of lamivudine (LAM) and interferon (IFN) in hitherto untreatable 'immune-tolerant' chronic hepatitis B in children. In this case-control study, 28 children with immune-tolerant hepatitis B [HBsAg positive for >6 months with near normal aminotransferase level, minimal/no inflammation in liver histology and high viral load (HBV DNA>10(7) copies/mL)] were treated with LAM alone at 3 mg/kg/day for 8 weeks followed by LAM plus IFN alpha (5 MU/m(2) three times a week) for another 44 weeks. They were compared with 34 untreated children. HBV markers (HBsAg, HBeAg, anti-HBe, quantitative HBV DNA) were carried out at baseline, at the end of therapy and 6 monthly thereafter. The mean age was 5.9 ± 3.2 years and 24 were boys. End therapy response: HBe seroconversion was achieved in 11, and of these, five had complete response (HBsAg clearance), 11 did not respond and six had virologic response (DNA undetectable but no HBe seroconversion). Six months after therapy, 10 of the 11 (91%) originally seroconverted children remained seroconverted while one seroreverted. Six of the 28 (21.4%) children lost HBsAg and they remained HBsAg negative and anti-HBs positive on follow-up. After a mean follow-up of 21.1 ± 11.9 months, the status remained same in the responders but one of the nonresponders HBe seroconverted (39.3%). There were no serious side effects of therapy. It is possible to achieve a cure in more than one-fifth of immune-tolerant children with hepatitis B with the sequential combination of LAM and IFN.

Expression profile of latent and lytic transcripts of epstein-barr virus in patients with gastroduodenal diseases: a study from northern India.

Epstein-Barr virus (EBV) has been shown to be associated with gastric cancer. However, inconsistent findings have been reported regarding the EBV reactivation in gastric cancer and non-carcinomatous gastric epithelium. Therefore, the aim of the study was to investigate the effect of clinicopathological findings on the expression of different transcripts of EBV in patients with gastric cancer, peptic ulcer, and dyspepsia. A total of 200 adult patients (dyspepsia [120], peptic ulcer [30], gastric cancer [50]) undergoing upper gastrointestinal endoscopy were enrolled. EBV infection was diagnosed with non-polymorphic Epstein-Barr nuclear antigen1 (EBNA1) gene based PCR and confirmed by real-time PCR. The transcripts of EBV were detected by real-time RT-PCR. In patients with gastric cancer and peptic ulcer, EBV DNA was detected more often than in those with dyspepsia (P < 0.05). EBNA1 transcript was detected in all EBV positive cases and its expression was neither associated with disease nor with histopathological findings. The expression of BZLF1 was significantly associated with gastric cancer and peptic ulcer compared to dyspepsia (P < 0.01). BZLF1 expression was also found to be higher in Helicobacter pylori infected patients (P = 0.058). Expression of BARF1 and BcLF1 were significantly higher in gastric epithelium of patients having severe grade chronic inflammation (P = 0.05) and gastric atrophy (P = 0.02), respectively. In conclusion, increased expression of lytic transcripts in patients with gastric cancer, peptic ulcer, gastric atrophy, chronic inflammation and H. pylori infection suggests the association of these factors with EBV reactivation.

Intracranial germ cell tumors at unusual locations.

Germ cell tumor (GCT) is relatively uncommon in intracranial locations. They constitute ~ 0.3-0.6% of intracranial neoplasms and encompass a wide pathologic range. The majority occurs in young adults and occupies the midline locations like pineal gland followed by suprasellar compartment. These tumors are rare in the cerebral hemisphere, basal ganglia, thalamus and ventricles. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histological confirmation. Germ cell tumors can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs). Their proper identification as well as histopathological typing is important as treatment and prognosis vary greatly between different groups. Germinomas have a superior prognosis and are more radiosensitive as compared to non-germinomatous germ cell tumors. Standard management is still controversial. In this case series we are presenting three cases of intracranial germ cell tumors arising in two unusual locations, that is intraventricular and thalamic region. Apart from the clinical, radiological, histopathological and surgical details we also discuss the various aspects of intracranial germ cell tumors.

Intraoperative squash cytology: accuracy and impact on immediate surgical management of central nervous system tumours.

OBJECTIVE: To assess the diagnostic accuracy of squash cytology, reasons for deferment, disagreement and partial agreement, and assess its impact on immediate surgical management of central nervous system tumours. STUDY DESIGN: All cases of squash cytology received from January 2007 to July 2010 were reviewed and correlated with final histopathological diagnoses. Deferments, disagreements and partial disagreements were reviewed to look for possible reasons. The impact of disagreements and partial agreements on immediate surgical management was evaluated in consultation with neurosurgeons. RESULTS: Overall accuracy (including complete and partial agreement) for squash smear diagnosis of 334 cases was 94.9% while complete agreement was 79.9%, excluding deferred cases. Disagreement was seen in 17 cases and 31 cases were deferred for final histopathology diagnosis. Good correlation was seen in astrocytoma, meningioma, schwannoma, medulloblastoma, pituitary adenoma and metastatic carcinoma, whereas poor correlation was seen in oligodendroglioma, ependymoma and lymphoma. Among 17 cases with disagreement and 50 cases with partial agreement, an adverse impact on immediate surgical management was found in six (35.3%) cases and one (2.0%) case, respectively. The sensitivity and specificity of squash for diagnosis of neoplastic lesions were 98.7% and 87.5%, respectively. CONCLUSION: Squash cytology is a rapid, reliable, simple technique for intraoperative consultation in neurosurgical practice with high overall accuracy. Causes causing an adverse impact on surgical management were rare and potential avoidable reasons for them were identified.

Quantitation of Helicobacter pylori ureC gene and its comparison with different diagnostic techniques and gastric histopathology.

Numerous diagnostic assays for Helicobacter pylori detection are available. However, these techniques have their own advantages as well as limitations. Here we tried to develop a real-time quantitative (Q) PCR assay to measure ureC copy number to detect H. pylori, based on the fact that there is only one copy of the ureC gene per bacterium. We enrolled 120 adult patients [non-ulcer dyspepsia (NUD) 60, peptic ulcer disease (PUD) 20, gastric cancer (GC) 40] undergoing upper gastrointestinal endoscopies. During each endoscopic examination, antral biopsies from normal region of the antrum were obtained and subjected to the following tests: RUT, culture, histopathology, H. pylori-specific ureC PCR and ureC Q-PCR. Calculation of H. pylori copy number was based on the standard curve generated using 10-fold dilutions of DNA extracted from the H. pylori control strain varying from 10(5) to 10(1) copies. The prevalence of H. pylori infection in our study population was 54% with no significant difference among disease and control population. The sensitivity of Q-PCR was found to be 100% which was highest among all diagnostic tests. The established Q-PCR is around 10 times more sensitive than the conventional PCR method. The copy number of H. pylori DNA was significantly increased when overall gastritis, H. pylori density, chronic inflammation and intestinal metaplasia were present. In summary, we developed a rapid and sensitive Q-PCR method for detecting H. pylori. This technique offers a significant improvement over other available methods for detecting H. pylori in clinical and research samples.

p53, carcinoembryonic antigen and carbohydrate antigen 19.9 expression in gall bladder cancer, precursor epithelial lesions and xanthogranulomatous cholecystitis.

BACKGROUND: Gallbladder cancer (GBC) is the commonest gastrointestinal cancer in women of north India. Precursor epithelial lesions in GBC are known; however, the role of xanthogranulomatous (XG) inflammation in the pathogenesis of GBC is unknown. AIMS: To analyze the role of precursor lesions in the pathogenesis of GBC we studied the immunohistochemical (IHC) expression of p53, carcino-embryonic antigen (CEA) and carbohydrate antigen 19.9 (CA-19.9) in GBC, chronic cholecystitis (CC), XG cholecystitis (XGC) and precursor lesions. MATERIALS AND METHODS: The study included 51 GBC, 68 CC, 42 XGC and 10 normal gallbladders. All cases were evaluated for presence of precursor lesions and IHC was performed. RESULTS: p53 immunoreactivity was found in 55% GBC, 32% of dysplasia with malignancy and in 14% of dysplasia with CC. Sixteen percent GBC had associated XG inflammation. Normal and metaplastic epithelium in CC and in XGC did not express p53. CEA expression was apical in normal and inflammatory GBs (CC, XGC), while cytoplasmic focal to diffuse positivity was seen in 82% GBC. CA-19.9 expression was seen in all cases of normal and inflammatory GBs; however, foci of antral metaplasia were negative. Seventy-five percent of GBC expressed CA-19.9; all negative cases were high-grade on histology. CONCLUSIONS: Altered CEA expression is seen in GBC as compared to normal and inflammatory gallbladders. Loss of expression of CA19.9 in antral metaplasia and poorly differentiated GBC may indicate that it is a marker of biliary differentiation. p53 over-expression seen in GBC and in dysplasia associated with malignancy and with CC suggests that p53 mutation and dysplasia are early events in the evolution of GBC. Epithelial metaplasia and XG inflammation are often associated with GBC but do not appear to play a role in its pathogenesis through the p53 pathway.

Dilemmas in cytodiagnosis of subcutaneous swellings: mimics and look-alikes of cysticercosis.

BACKGROUND: Fine needle aspiration (FNA) is the modality of choice in the initial characterisation of subcutaneous swellings. The site, distribution, number and clinical association of such swellings determines to a large extent the clinical diagnoses rendered in these cases. AIMS AND METHODS: 15 unusual cases of subcutaneous cysticercosis, diagnosed by FNA, which clinically simulated diverse aetiologies, are reported. RESULTS: Three cases occurred in patients with known malignancies which were thought to be metastatic deposits. In another nine cases the clinical diagnoses included lymphoma, squamous cell carcinoma, neurofibroma and lipoma. Two cases strongly mimicked tubercular lymphadenitis, while one case occurred in a renal transplant recipient. CONCLUSIONS: FNA may help diagnosis of a parasitic aetiology in cases where malignancy or tuberculosis is a clinical probability. Cysticercosis should be an integral part of the differential diagnosis of all subcutaneous swellings, regardless of the clinical setting. Helpful cytological clues are discussed.

Role of E-cadherin gene in gall bladder cancer and its precursor lesions.

The aim was to investigate the genomic instability in the E-cadherin (CDH1) gene and to correlate it with its protein expression in gall bladder cancer (GBC) and in other gall bladder (GB) diseases viz. chronic cholecystitis (CC), xantho-granulomatous cholecystitis (XGC), and normal GB to explicate its role in GBC tumorigenesis. Microsatellite instability (MSI) and loss of heterozygosity (LOH) in CDH1 were studied using D16S421, D16S496, D16S503, D16S512, D16S2624, and D16S3021 microsatellite markers and D2S123 (2p16), D2S382 (2q24), D6S292 (6q21-23), D7S480 (7q31), and D17S796 (17p13.1-3) were used to investigate genomic instability at 2p, 2q, 6q, 7q, and 17p loci in 40 GBC, 50 CC, 34 XGC, and 15 normal GB cases. Immunohistochemistry was carried out to analyze the E-cadherin and p53 protein expression. Overall LOH in CDH1 and other markers was high in GBC and XGC as compared to CC; however, it did not correlate with its protein expression in GBC cases. Loss of E-cadherin expression was high in GBC (67%), while majority of the CC (94%) and XGC (91%) cases retained positive E-cadherin expression. Overexpression of p53 was high in GBC (43%) whereas CC, XGC, normal GB cases were negative for p53 overexpression. None of the normal GB cases showed genomic instability at any of the markers. High LOH in CDH1 and other chromosomal loci in GBC indicated that the genomic instability followed a GBC>XGC>CC trend during the process of neoplastic transformation in GB, highlighting the fact that CC might act as a precursor lesion of GBC.

Prevalence of RET/PTC expression in papillary thyroid carcinoma and its correlation with prognostic factors in a north Indian population.

CONTEXT: The prevalence of Rearranged during Transfection/Papillary Thyroid Carcinoma (RET/PTC) rearrangement in papillary thyroid carcinoma (PTC) varies in different geographic regions and its prognostic significance remains unclear. AIM: The aim of this study was to recognize the prevalence of RET/PTC expression in PTC from the endemically iodine-deficient region in Northern India and to correlate the expression with the clinicopathologic prognostic factors. SETTINGS AND DESIGN: Retrospective. Archival tissue used. MATERIALS AND METHODS: Immunohistochemistry was performed to look for activated RET protein expression in 50 cases of PTC. No patient had any history of prior irradiation. STATISTICAL ANALYSIS USED: Chi-square method, Student t test, and binary regression method. A P value of <.05 was considered significant for all the tests. RESULTS: The prevalence of RET expression was 44%. Twenty-six (52%) cases showed RET immunoreactivity in histiocytes. Immunoreactivity was the highest in the classic variant of PTC (47.5%), followed by tumors with poorly differentiated areas (25%) and follicular variant (16.7%). RET expression was more prevalent in young patients (45.5 vs. 35.3%), females (43.3 vs. 40.0%), small tumors (33.3 vs. 26.7%), multicentric tumors (36.8 vs. 33.3%), tumors with extrathyroidal invasion (38.9 vs. 32.4%), and regional lymphadenopathy (55.2 vs. 22.2%), while it was less in cases with distant metastases (20 vs. 43.9%). There was no significant correlation of immunoreactivity with any prognostic factor. However, when the cases having immunoreactivity within histiocytes (n=26) and histiocytes + tumor tissue (n=28) were considered, then the expression was significantly more in cases with lymphadenopathy (P values=.009, in both instances). However, the exact clinical significance of RET/PTC positive histiocytes remained unexplained. CONCLUSIONS: Prevalence of RET/PTC in our study was consistent with the reported prevalence from other geographic areas. There was no significant correlation with the clinicopathologic factors. However, uniform techniques of detection and large international collaborative studies could clear the uncertainties regarding the prognostic importance of RET/PTC.

Characterization of tumefactive demyelinating lesions using MR imaging and in-vivo proton MR spectroscopy.

BACKGROUND AND OBJECTIVES: Diagnosis of tumefactive demyelinating lesions (TDLs) is challenging to both clinicians and radiologists. Our objective in this study was to analyze and characterize these lesions clinically, biochemically, electrophysiologically, and on imaging. METHODS: A retrospective analysis with prospective follow-up of 18 cases of TDLs was performed. Imaging included T2-, T1-weighted, fluid-attenuated inversion recovery (FLAIR), post-contrast T1-weighted, diffusion weighted imaging (DWI), and proton magnetic resonance spectroscopy (PMRS). RESULTS: All the lesions appeared hyperintense on T2 and FLAIR images. Increased Apparent diffusion coefficient (ADC) (0.93-2.21 x 10(-3) mm(2)/s) in centre of the lesion was seen in 14/18 cases; however, peripheral restriction (ADC values 0.55-0.64 x 10(-3) mm(2)/s) was noted in 11/18 cases. In all, 13/18 cases showed contrast enhancement with open ring (n = 5), complete ring (n = 1), minimal (n = 4), and infiltrative (n = 3) pattern of enhancement. Nine of these 13 cases also showed venular enhancement. On PMRS, nine showed glutamate/glutamine (Glx) at 2.4 ppm. CONCLUSION: Clinical features along with several MRI characteristics such as open ring enhancement, peripheral restriction on DWI, venular enhancement, and presence of Glx on spectroscopy may be rewarding in differentiating TDLs from neoplastic lesions.

Primary central nervous system lymphoma: prognostication as per international extranodal lymphoma study group score and reactive CD3 collar.

BACKGROUND: Primary central nervous system (CNS) lymphoma is being increasingly recognized in immunosuppressed as well as immunocompetent individuals. It has a poor prognosis and the majority of these have diffuse large B-cell type of morphology. AIM: To categorize cases of primary CNS lymphoma according to the International Extranodal Lymphoma Study Group (IELSG) score and to correlate the score with reactive CD3 collar around blood vessels and necrosis. MATERIALS AND METHODS: We reviewed the clinico-pathological, morphological and immuno-histochemical features of 30 cases of primary CNS lymphoma reported at our institute in the last nine years and categorized them according to the score given by IELSG. RESULTS: All our cases were HIV-negative and had diffuse large cell histology. Twenty-seven of the 30 cases were associated with poor prognostic factors of intermediate to high risk according to the IELSG score. Reactive CD3 collar around the blood vessels was seen in seven cases which had low to intermediate IELSG score. However, no significant statistical difference of perivascular reactive CD3 collar and necrosis was seen with IELSG score. CONCLUSION: Approximately 90% (27 cases) were associated with poor prognostic factors in the present study according to the IELSG score. Perivascular reactive CD3 collar was seen in cases with low to intermediate IELSG score. A larger study is required to further validate that the presence of reactive perivascular CD3 collar is associated with good prognosis. This histological marker could be supplemented with IELSG score to stratify the patients of primary CNS lymphoma according to their aggressiveness.

A case of collapsing glomerulopathy associated with febrile illness.

Collapsing glomerulopathy (CG) is a distinct clinicopathological entity characterized by high levels of nephrotic range proteinuria, rapidly progressive renal failure, marked parenchymal injury, and poor response to present therapeutic regimens. Growing awareness has led to the identification of associated conditions other than human immunodeficiency virus (HIV) and idiopathic. We report a case of CG from India in a HIV-negative young female, presenting with heavy proteinuria and rapidly progressing renal failure preceded by a febrile illness.

Progression of chronic pulmonary tuberculosis in mice intravenously infected with ethambutol resistant Mycobacterium tuberculosis.

PURPOSE: Ethambutol (EMB) is an important first line drug, however little information on its molecular mechanism of resistance and pathogenicity of resistant isolates is available. Present work was designed to study virulence of the EMB resistant M. tuberculosis strains and the host responses in-vivo on infection of EMB resistant M. tuberculosis using Balb/c mouse model of infection. METHODS: Three groups of Balb/c mice (female, age 4-6 wk; 21 mice in each group) were infected intravenously with 106 CFU of M. tuberculosis H37Rv and two EMB resistant clinical isolates. Age and sex matched control animals were mock inoculated with Middlebrook 7H9 broth alone. At 10, 20, 30, 40, 50, 60, and 70 days post-infection three animals from each group were sacrificed by cervical dislocation and lung tissue was collected for further analysis. RESULTS: Infection with EMB resistant M. tuberculosis led to progressive and chronic disease with significantly high bacillary load (p=0.02). Massive infiltration and exacerbated lung pathology with increased expression of IFN-gamma and TNF-alpha was observed in lungs of mice infected with EMB resistant strains. The present study suggests that infection with EMB resistant M. tuberculosis leads to chronic infection with subsequent loss of lung function, bacterial persistence with elevated expression of TNF-alpha resulting in increased lung pathology. CONCLUSION: These findings highlight that EMB resistant M. tuberculosis regulates host immune response differentially and its pathogenicity is different from drug sensitive strains of M. tuberculosis.

Post-mortem examination of prenatally diagnosed fatal renal malformation.

OBJECTIVE: Renal malformations can be associated with genetic syndromes and chromosomal disorders. Fetal autopsy including histopathological examination of kidney is important to arrive at definite diagnosis. The objective was to assess importance of fetal autopsy and histopathology. STUDY DESIGN: Retrospective analysis of cases with fetal renal malformations was done. All fetuses terminated were examined with whole body radiograph, external and internal examination and histopathological examination. RESULT: A total of 21 cases with renal malformations were studied. Of all 3 were of bilateral renal agenesis, 4 showed autosomal recessive polycystic kidney disease and 13 showed features of multicystic kidney. Three of these had hyperplasic-enlarged bladder and autopsy confirmed urorectal septum malformations in two cases and posterior urethral valve in one case. One case had associated malformations like encephalocele that suggested diagnosis of Meckel-Gruber syndrome and another had associated lateral body wall defect. In five cases kidney was hypoplastic suggestive of Potter type IIa. CONCLUSION: Ultrasound is an effective diagnostic modality; however fetal autopsy after termination of pregnancy is important to arrive at a definitive diagnosis. It's important to distinguish between autosomal recessive polycystic kidney disease (ARPKD) and cystic dysplastic kidney as recurrence risk is 3% in case of cystic renal dysplasia in contrast to 25% in case of ARPKD. Gross examination may point toward syndromic diagnosis like Meckel-Gruber syndrome; hence mode of prenatal diagnosis may vary in subsequent pregnancies.

Analysis of Pro12Ala PPAR gamma polymorphism and Helicobacter pylori infection in gastric adenocarcinoma and peptic ulcer disease.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor involved in various disease processes including inflammation and carcinogenesis. We investigated the association of Pro12Ala PPARgamma polymorphism and Helicobacter pylori infection with gastric cancer and peptic ulcer disease (PUD). PATIENTS AND METHODS: In total, 348 adult patients [62 gastric adenocarcinoma, 45 PUD and 241 nonulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. PPARgamma polymorphism was analyzed by PCR-based restriction fragment length polymorphism. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. RESULTS: PPARgamma G carrier had significant association with gastric adenocarcinoma [P = 0.023, odds ratio (OR) = 2.136, 95% CI = 1.112-4.104] and PUD (P = 0.028, OR = 2.165, 95% CI = 1.008-4.306) when compared with NUD. Combination of G carrier and H. pylori infection further increased the risk of gastric adenocarcinoma (OR = 3.054, 95% CI = 1.195-7.807) and PUD (OR = 11.161, 95% CI = 3.495-35.644). PPARgamma polymorphism did not increase the risk of gastric adenocarcinoma and PUD in H. pylori-negative subjects. CONCLUSIONS: The study suggests that Pro12Ala PPARgamma polymorphism is associated with gastric adenocarcinoma and PUD, and is a potential marker for genetic susceptibility to these two diseases in the presence of H. pylori infection.

An insufficient anti-inflammatory cytokine response in mouse brain is associated with increased tissue pathology and viral load during Japanese encephalitis virus infection.

Infection of the central nervous system with Japanese encephalitis virus (JEV) results in fatal encephalitis in humans. No reports exist describing the sequence of pathological changes and their correlation to the immune response in the brain following infection with JEV. In this report, we analyzed inducible nitric oxide synthase (iNOS) mRNA, proinflammatory (IFN-gamma, TNF-alpha) and anti-inflammatory (IL-4, IL-10) cytokine expression, viral load, and the correlation of these factors with the major histopathological changes in brain of JEV challenged mice at different time points during infection. We report for the first time that in JE, there is a progressive decline in the level of IL-4. The extent of progressive decrease in IL-4 and IL-10 level following viral infection is inversely correlated to the increased level of proinflammatory cytokines and histopathological changes with negative consequences following viral infection. In contrast, proinflammatory mediators like IFN-gamma and TNF-alpha were significantly upregulated (P < 0.05). A negative correlation between IFN-gamma and iNOS indicates their independent actions during JEV infection. To conclude, an insufficient anti-inflammatory cytokine response indicated by IL-4 and IL-10 in the brain is associated with increased tissue pathology and viral load, which regulates inflammatory responses driven by IFN-gamma in concert with TNF-alpha to cause brain tissue damage.

Arthritis as presenting manifestation of pure neuritic leprosy--a rheumatologist's dilemma.

OBJECTIVES: Leprosy classically presents with cutaneous and neurological manifestations. In diagnosed cases of leprosy, rheumatological involvement varies from 1% to 70%. A primary articular presentation without cutaneous manifestations is not yet known. Herein, we present our experience of five cases of leprosy that presented with predominant articular involvement in the absence of cutaneous manifestations. METHODS: The study was conducted in the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences located in the state of Uttar Pradesh, one of the nine endemic states in India. Case records of patients with a definite diagnosis of leprosy were screened for the presenting manifestations, pattern of articular involvement, tenosynovitis, neurological signs and symptoms. Reports of nerve conduction study (NCS), nerve and synovial biopsy and other diagnostic tests were retrieved from laboratory records. Available radiographs were examined for evidence of juxta-articular osteopenia and erosions. RESULTS: Case records of 11,740 patients were screened, of which 28 had a diagnosis of leprosy. Twenty patients had presented with rheumatological complaints primarily. Five of the patients who presented with inflammatory arthritis with/without tenosynovitis (n = 4) and tenosynovitis alone (n = 1) had pure neuritic leprosy. All of these patients had thickened peripheral nerves and abnormal NCS. Sural nerve biopsy confirmed the diagnosis of leprosy in all these cases. CONCLUSION: A combination of tenosynovitis and thickened nerves in association with symmetric polyarthritis should raise a suspicion of leprosy even in the absence of cutaneous features.