Tinea Capitis Presenting as Diffuse Hair Loss and Significance of Trichoscopy: Four Case Reports.

Tinea capitis is a common fungal infection in children but is less frequently encountered in adults. Tinea capitis presenting as diffuse hair loss is a rare presentation. When patient presents with a diffuse hair loss, tinea capitis is not commonly thought of as differential diagnosis. Low clinical suspicion can lead to inappropriate empiric treatments that delay diagnosis. Trichoscopy in tinea capitis obviates the need for lengthy and invasive procedure or even KOH examinations in the absence of a side lab for diagnosing this common scalp disorder and also avoids misdiagnosis. Trichoscopy not only differentiates tinea capitis from female patterned hair loss but also aids in differentiating ectothrix from endothrix. Here, we present case reports of tinea capitis masquerading as female pattern hair loss with trichoscopy aiding in diagnosis of endothrix infection.

Spironolactone in adolescent acne vulgaris.

Acne vulgaris (AV) is the most common skin condition affecting adolescents, most likely due to elevated androgen levels during puberty. Androgens stimulate and enlarge the sebaceous glands and keratinocytes, resulting in increased production of sebum and abnormal hyperproliferation of keratinocytes which lead to the formation of acne lesions. Current standard of care for AV includes topical therapies for mild cases and antibiotics or oral retinoids for severe cases. In recent years, spironolactone, an aldosterone antagonist and diuretic, has been applied to the treatment of AV due to its anti-androgen effects. Spironolactone is currently recommended in women who use oral contraceptives, are refractory to or contraindicated for standard treatment, show clinical signs of hyperandrogenism, or present with late-onset or persistent-recurrent AV past the teenage years. It is not prescribed to adolescents due to potential side effects; however, current data studying adults indicate that most side effects are mild, and that potential associations with hyperkalemia and increased risk of cancer are not sufficiently supported. Hence, we believe that spironolactone may be a safe and effective therapy for adolescent AV.

Early Diagnosis and Prompt Treatment Improves Quality of Life in Patients with Frontal Fibrosing Alopecia.

Frontal fibrosing alopecia (FFA) is a slowly progressive cicatricial alopecia. FFA patients typically present with hair loss in the frontal, temporal, or frontotemporal scalp and eyebrows. It can also involve facial and body hair. It has an early inflammatory stage, which slowly progresses to the stage of fibrosis. In this article, we report a case of FFA in the early inflammatory stage who responded well to intralesional steroid.

Mixed adenoneuroendocrine carcinoma of the gallbladder, histopathological features.

An unusual case of mixed adenoneuroendocrine carcinoma is described which posed a diagnostic challenge in view of neuroendocrine component mimicking signet ring cells of adenocarcinoma. Diagnostic criteria for these mixed tumors, their histogenesis and treatment modalities are highlighted.

Malignant rhabdoid tumor of kidney and brain in an infant.

BACKGROUND: Malignant rhabdoid tumors of kidney are associated with atypical teratoid rhabdoid tumors of brain, both being characterized genetically by deletion/ mutation of SMAR CBI/ INI gene. CASE CHARACTERISTICS: 6-month-old male presented with a brain tumor and was subsequently found to have malignant rhabdoid tumor of kidney. INTERVENTIONS: Surgical resection of brain tumor followed by chemotherapy and subsequently resection of renal tumor. OUTCOME: Child died seven months after initial presentation. MESSAGE: Children presenting with embroynal brain tumor, should be investigated for renal tumors and vice versa. MESSAGE: Children presenting with embroynal brain tumor, should be investigated for renal tumors and vice versa.

High frequency of enterovirus serotype circulation in a densely populated area of India.

INTRODUCTION: In the state of Uttar Pradesh in India, enteroviruses are a significant cause of infection presenting in endemic or epidemic forms. The present study aimed to use molecular methods to identify enterovirus serotypes in clinical specimens to determine their circulation in the community. METHODOLOGY: A total of 320 clinical specimens were collected between January 2009 and December 2010 from children younger than 15 year of age in northern India. Reverse- transcription (RT) real time PCR and semi-nested RT PCR targeting the 5'untranslated region and VP1 region was used for the detection and identification of enterovirus serotypes. RESULTS: The enterovirus genome was detected in 79 (24.7%) of 320 clinical specimens by real time PCR. Central nervous system syndrome (CNS) was the most common clinical manifestation (n=32, 62.74%), followed by respiratory tract infection (n=8, 15.69%), acute febrile illness (n=7, 13.73%), and gastrointestinal disease (n=4, 7.84%). A total of 32 different serotypes were identified with the predominance of coxsackievirus B5 and echovirus 6. Phylogenetic analysis of partial VP1 gene sequences from this study showed that many enterovirus serotypes showed good similarity with strains from America and Europe in comparison to neighbouring Asian countries. CONCLUSIONS: To our knowledge this is the first study of enterovirus prevalence from northern India based on unbiased molecular methods which leads to the identification of fifteen different enterovirus serotypes. The high frequency of enterovirus B species serotypes circulation may be an important cause of CNS infection in the children of this region.

Environmental surveillance of enterovirus in Northern India using an integrated shell vial culture with a semi-nested RT PCR and partial sequencing of the VP1 gene.

Enteroviruses have been reported in epidemic form during last 10 years in northern India. Environmental surveillance of sewage is the method of choice in limited resources countries for detection of enterovirus serotypes circulating in the community. Twenty-four sewage samples collected between January, 2009 and December, 2010 were tested for enterovirus by using a new modified integrated shell vial culture (ISVC) with a semi-nested RT-PCR of a partial VP1 gene and virus isolation integrated with semi-nested RT-PCR of a partial VP1 gene. Twenty-one (87.5%) out of 24 samples were positive for enterovirus by the conventional method and all samples (100%) by the ISVC-RT-PCR. The additional positive samples detected by ISVC-RT-PCR was typed as six different enterovirus serotypes (Sabin poliovirus 3, Coxsackievirus B3, Coxsackievirus A13, Coxsackievirus A17, Echovirus 33, and Enterovirus 75). Phylogenetic analysis of a partial VP1 gene of Echovirus 19 showed that one genetic lineage clustered with isolates from Georgia suggesting their importation into northern India. Detection of wild poliovirus in the absence of clinical cases with 16 different co-circulating enterovirus serotypes supports the need of increased molecular surveillance of sewage. Rapid identification and characterization of enterovirus serotypes is necessary to study their transmission and evolution in different geographical regions to prevent future outbreak.

Molecular identification of enteroviruses associated with aseptic meningitis in children from India.

We identified and characterized enteroviruses associated with aseptic meningitis in children between April 2009 and March 2010. Enterovirus RNA was detected in 51 (45.5 %) of 112 CSF samples. Molecular typing by RT-PCR and sequencing of a partial VP1 region revealed the predominance of echovirus (ECV) 32 (n = 20), followed by ECV 11 (n = 10), ECV 13 and ECV 14 (n = 5 each), coxsackievirus (CV) B3 and CV B6 (n = 3 each), CV A2, CV A10 and ECV 30 (n = 1 each). Phylogenetic analysis of ECV 32 showed 0 to 4 % sequence divergence among strains of the present study and 20-23 % from the prototype Puerto Rico strain at the nucleotide level. This is the first report of ECV 32 associated with an aseptic meningitis epidemic and identification of seven different enterovirus serotypes (CV A2, CV A10, CV B3, CV B6, ECV 13, ECV 14 and ECV 32) in meningitis cases from India.

Molecular identification and phylogenetic study of coxsackievirus A24 variant isolated from an outbreak of acute hemorrhagic conjunctivitis in India in 2010.

An outbreak of acute hemorrhagic conjunctivitis (AHC) occured in India between August and October 2010. Molecular typing by RT-PCR and sequencing of a partial VP1 region identified coxsackievirus A24 variant (CV A24v) as the serotype involved in this outbreak. Phylogenetic analysis based on the VP1 and 3C genes revealed that CV A24v strains associated with the 2010 AHC outbreak in India were genetically similar to strains from Central and South America that caused outbreaks of AHC in Cuba between 2008 and 2009 and Brazil in 2009. The result shows that the Indian strain of CV A24v may be responsible for the recent AHC outbreak in Marseille, France, in 2012.

Molecular epidemiological study of enteroviruses associated with encephalitis in children from India.

Enteroviruses have been reported in encephalitis cases. However, clinical and epidemiological characteristics of enteroviruses in encephalitis are not fully established. We prospectively investigated 204 children with encephalitis over a period of 2 years (2009 to 2010) for enterovirus. Enterovirus was detected in 45 specimens (22.1%); of these, 40 were typed by seminested reverse transcription-PCR (RT-PCR) and sequencing of the VP1 gene. Molecular typing of enterovirus revealed the predominance of echovirus 21 associated with an epidemic during the rainy seasons of 2010 and the circulation of echovirus 1, coxsackievirus B1, enterovirus 75, enterovirus 76, coxsackievirus B5, and echovirus 19. The nucleotide divergence among echovirus 21 strains was 0 to 2% at the nucleotide level. This study suggests that enterovirus is an important cause of encephalitis in children from India. To our knowledge, this is the first report of echovirus 21 in encephalitis cases worldwide.

An epidemic of encephalitis associated with human enterovirus B in Uttar Pradesh, India, 2008.

BACKGROUND: Human enteroviruses (HEVs) are a rare cause of encephalitis, presenting in endemic or epidemic form. OBJECTIVES: The aim of the study is to identify and characterise the causative agent of the encephalitis epidemic, which occurred in Uttar Pradesh, India during the summer of 2008. STUDY DESIGN: A total of 90 cerebrospinal fluid (CSF) specimens were collected between June and October 2008 from children with symptoms of encephalitis admitted to Chhatrapati Shahuji Maharaj Medical University and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Conventional and molecular methods were used to identify and characterise the viral agent associated with the epidemic. RESULTS: Enterovirus RNA was detected in 37 (41.11%) of 90 CSF samples by real-time polymerase chain reaction (PCR). Seroneutralisation, amplification and sequencing of the 3'-end of the VP1 region of EV isolates revealed coxsackievirus B5 (CBV) and echovirus 19 (ECV) as the main serotypes causing this epidemic. Phylogenetic analysis showed that sequence divergence among the same serotypes was 0-4% at the nucleotide level. CONCLUSIONS: This is the first report suggesting that CBV 5 and ECV 19 may be responsible for an epidemic of encephalitis in India. These serotypes were variant and evolved within the studied area.

Haplotype diversity and linkage disequilibrium at DRD2 locus--a study on four population groups of Andhra Pradesh, India.

Dopamine receptor D2 (DRD2) is expressed in the central nervous system and has a high affinity for many antipsychotic drugs. Besides several epidemiological investigations on association of DRD2 locus polymorphism(s) with neuropsychiatric problems and addictive behavior, a few polymorphisms in this locus have also been used to understand genomic diversity and population migratory histories globally. The present study attempts to understand the genomic diversity/affinity among four endogamous groups of Andhra Pradesh (India) against the backdrop of diversity studies from other parts of India and the rest of the world, with special reference to DRD2 locus. The four population groups from Adilabad District of Andhra Pradesh, namely, Brahmin (n=50), Nayakpod (n=49), Thoti (n=52), and Kolam (n=53), were included in the study. The DRD2 markers typed for the present study are three biallelic restriction fragments, that is, TaqI A (rs1800497), TaqI B (rs1079597), and TaqI D (rs1800498). Scoring of DRD2 haplotypes with respect to the three TaqI sites shows that five out of eight possible haplotypes are shared by the four populations. Ancestral haplotype B2D2A1 is most frequent among Thotis (0.359). The results of the present study indicate a differential gene flow into South India followed by certain important demographic events resulting in diversified peopling of India.

Endothelial caveolin-1 regulates pathologic angiogenesis in a mouse model of colitis.

BACKGROUND & AIMS: Increased vascular density has been associated with progression of human inflammatory bowel diseases (IBDs) and animal models of colitis. Pathologic angiogenesis in chronically inflamed tissues is mediated by several factors that are regulated at specialized lipid rafts known as caveolae. Caveolin-1 (Cav-1), the major structural protein of caveolae in endothelial cells, is involved in the regulation of angiogenesis, so we investigated its role in experimental colitis. METHODS: Colitis was induced by administration of dextran sodium sulfate to wild-type and Cav-1(-/-) mice, as well as Cav-1(-/-) mice that overexpress Cav-1 only in the endothelium. Colon tissues were analyzed by histologic analyses. Leukocyte recruitment was analyzed by intravital microscopy; angiogenesis was evaluated by immunohistochemistry and in vivo disk assays. RESULTS: Cav-1 protein levels increased after the induction of colitis in wild-type mice. In Cav-1(-/-) mice or mice given a Cav-1 inhibitory peptide, the colitis histopathology scores, vascular densities, and levels of inflammatory infiltrates decreased significantly compared with controls. Lower levels of leukocyte and platelet rolling and adhesion colitis also were observed in Cav-1(-/-) mice and mice given a Cav-1 inhibitory peptide, compared with controls. Cav-1(-/-) mice that received transplants of wild-type bone marrow had a lower colitis score than wild-type mice. Data from mice that overexpress Cav-1 only in the endothelium indicated that endothelial Cav-1 is the critical regulator of colitis. Genetic deletion or pharmacologic inhibition of endothelial Cav-1 also significantly decreased vascular densities and angiogenesis scores, compared with controls. CONCLUSIONS: Endothelial Cav-1 mediates angiogenesis in experimental colitis. Modulation of Cav-1 could provide a novel therapeutic target for IBD.

Diversified genomic contribution among south Indian populations--a study on four endogamous groups of Andhra Pradesh.

BACKGROUND: The present study examines genomic variation among three tribal (Nayakpod, Thoti and Kolam) and a caste (Niyogi Brahmin) population groups of Andhra Pradesh, south India. AIM: The present study examined the genomic diversity of the populations in relation to other population groups of India using 20 autosomal loci. SUBJECTS AND METHODS: A total of 204 blood samples from the population groups described above were collected and analysis was carried out following standard protocols. RESULTS: All markers were found to be polymorphic in these groups except AluCD4 among Thotis. High average heterozygosity values (0.3927 among Thotis to 0.4268 among Brahmins) are comparable with the available autosomal (Alu and restriction site polymorphisms) data for the Nilgiri hill tribes of Tamil Nadu, south India. The gene differentiation value (Gst) was found to be 4.2. The principal coordinate analysis (PCO) based on data from the 20 markers presents a smaller cluster of presently studied populations than that of the Nilgiri hill tribes of Tamil Nadu, south India. CONCLUSION: Although the presently studied populations of Andhra Pradesh have heterozygosity similar to that of Nilgiri hill populations, the former are more closely placed on the PCO plot than the latter, who are more scattered. Also the gene differentiation (Gst) of the former is much lower than that of the latter, indicating considerable regional variation in the inflow of genes from diverse ethnic groups within south India.

In-stent stenosis: potential role of increased oxidative stress and glutathione-linked detoxification mechanisms.

This study was designed to determine whether red-cell oxidative stress status and antioxidant enzyme levels can serve as markers in patients predisposed to in-stent stenosis. Blood was collected from patient groups undergoing coronary angiography for chest pain evaluation, namely, group A (without coronary artery disease), group B (previous coronary stents without in-stent stenosis), and group C (previous coronary stents with in-stent stenosis). Thiobarbituric acid reactive substances (measure of lipid peroxidation), glutathione-linked detoxification enzymes, catalase, and superoxide dismutase were determined. Compared with group A, patients in group C showed increased lipid peroxidation products and glutathione-S-transferase but decreased glutathione peroxidase and glutathione reductase activities. Results in group B patients were intermediate between those of groups A and C with significant decreases in glutathione peroxidase versus controls. In-stent stenosis is associated with significant increase in lipid peroxidation and attenuated glutathione-linked detoxification enzymes, consistent with oxidative stress.

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues.

Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed.

T cell-associated CD18 but not CD62L, ICAM-1, or PSGL-1 is required for the induction of chronic colitis.

The induction and perpetuation of chronic colitis are thought to involve a complex set of adhesive interactions between T cells and endothelial cells located on the vasculature within secondary lymphoid tissue and the intestine. The objective of this study was to assess the roles of T cell-associated CD18, CD62L (L-selectin), ICAM-1, and P-selectin glycoprotein ligand-1 (PSGL-1) in the induction of chronic colitis in mice. CD4(+)CD25(-) T cells derived from either wild-type (WT), CD18-deficient [CD18 knockout (KO)], CD62L KO, ICAM-1 KO, or PSGL-1 KO mice were adoptively transferred into recombinase activating gene-1 (RAG-1)-deficient mice (RAG KO mice) to assess the potential of these T cells to induce chronic colitis. At 8-10 wk following T cell transfer, we observed moderate to severe colitis as assessed by increases in colon weight-to-length ratios and by blinded histopathological analysis. In contrast, we found that transfer of CD18 KO T cells into RAG KO recipients resulted in the significant attenuation of colonic inflammation in these mice. Furthermore, we observed fewer infiltrating CD4(+) T cells in the colonic lamina propria in the CD18 KO-->RAG KO group compared with the WT-->RAG KO group. Finally, message levels of colonic TNF-alpha, IL-1beta, and IFN-gamma were significantly reduced in CD18 KO-->RAG KO mice compared with colitic control animals. We conclude that T cell-associated CD18, but not CD62L, ICAM-1, or PSGL-1, is required for the development of chronic colitis.

NADPH oxidase but not myeloperoxidase protects lymphopenic mice from spontaneous infections.

The adaptive immune system plays an important role in host defense against invading micro-organisms. Yet, mice deficient in T- and B-cells are surprisingly healthy and develop few spontaneous infections when raised under specific pathogen-free conditions (SPF). The objective of this study was to ascertain what role phagocyte-associated NADPH oxidase or myeloperoxidase (MPO) plays in host defense in mice lacking both T- and B-cells. To do this, we generated lymphopenic mice deficient in either NADPH oxidase or MPO by crossing gp91(phox)-deficient (gp91 ko) or MPO ko mice with mice deficient in recombinase activating gene-1 (RAG ko). We found that neither gp91 ko, MPO ko mice nor lymphocyte-deficient RAG ko mice developed spontaneous infections when raised under SPF conditions and all mice had life spans similar to wild-type (WT) animals. In contrast, gp91xRAG double-deficient (DKO) but not MPOxRAG DKO mice developed spontaneous multi-organ bacterial and fungal infections early in life and lived only a few months. Infections in the gp91xRAG DKO mice were characterized by granulomatous inflammation of the skin, liver, heart, brain, kidney, and lung. Addition of antibiotics to the drinking water attenuated the spontaneous infections and increased survival of the mice. Oyster glycogen-elicited polymorphonuclear neutrophils (PMNs) and macrophages obtained from gp91 ko and gp91xRAG DKO mice had no detectable NADPH oxidase activity whereas WT, RAG ko, and MPOxRAG DKO PMNs and macrophages produced large and similar amounts of superoxide in response to phorbol myristate acetate. The enhanced mortality of the gp91xRAG DKO mice was not due to defects in inflammatory cell recruitment or NO synthase activity (iNOS) as total numbers of elicited PMNs and macrophages as well as PMN- and macrophage-derived production of nitric oxide-derived metabolites in these mice were similar and not reduced when compared to that of WT mice. Taken together, our data suggest that that NADPH oxidase but not MPO (nor iNOS) is required for host defense in lymphopenic mice and that lymphocytes and NADPH oxidase may compensate for each other's deficiency in providing resistance to spontaneous bacterial infections.

Murine norovirus 1 infection is associated with histopathological changes in immunocompetent hosts, but clinical disease is prevented by STAT1-dependent interferon responses.

Human noroviruses are the major cause of nonbacterial epidemic gastroenteritis worldwide. However, little is known regarding their pathogenesis or the immune responses that control them because until recently there has been no small animal model or cell culture system of norovirus infection. We recently reported the discovery of the first murine norovirus, murine norovirus 1 (MNV-1), and its cultivation in macrophages and dendritic cells in vitro. We further defined interferon receptors and the STAT-1 molecule as critical in both resistance to MNV-1-induced disease in vivo and control of virus growth in vitro. To date, neither histopathological changes upon infection nor viral replication in wild-type mice has been shown. Here we extend our studies to demonstrate that MNV-1 replicates and rapidly disseminates to various tissues in immunocompetent mice and that infection is restricted by STAT1-dependent interferon responses at the levels of viral replication and virus dissemination. Infection of wild-type mice is associated with histopathological alterations in the intestine (mild inflammation) and the spleen (red pulp hypertrophy and white pulp activation); viral dissemination to the spleen, liver, lung, and lymph nodes; and low-level persistent infection in the spleen. STAT-1 inhibits viral replication in the intestine, prevents virus-induced apoptosis of intestinal cells and splenocytes, and limits viral dissemination to peripheral tissues. These findings demonstrate that murine norovirus infection of wild-type mice is associated with initial enteric seeding and subsequent extraintestinal spread, and they provide mechanistic evidence of the role of STAT-1 in controlling clinical norovirus-induced disease.