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.

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 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 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 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.

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.

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.

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.

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.

Early and frequent histological recurrence of Crohn's disease in small intestinal allografts.

BACKGROUND: Recurrence of Crohn's disease in small intestinal allografts, although rarely described, can cause serious morbidity and jeopardize graft survival among transplant recipients with Crohn's disease. However, systematic studies to determine the frequency, predictors, and clinical implications of recurrent Crohn's disease have not been reported METHODS: We analyzed our transplant program's experience with small intestinal allografts in patients with Crohn's disease based on retrospective review of clinical and pathological records and corresponding pathology slides. RESULTS: Of 67 patients undergoing 70 transplantations between 1998 and 2004, six adults (three males, three females; mean age 48.1 years) had Crohn's disease complicated by short gut syndrome and total parenteral nutrition failure. Four survivors surveyed endoscopically for a mean 29 (range, 20-40) months and underwent a mean 37 endoscopic examinations with biopsies (range, 31-44) while on maintenance immunosuppression. Despite absence of any endoscopic or clinical manifestations of Crohn's disease throughout this period, two patients had granulomatous enteritis characteristic of Crohn's disease in multiple biopsies, one patient in 8/44 examinations (18%) ranging from 34 days to 20 months postoperatively and the other in 6/32 examinations (19%) ranging from 20 days to 22 months postoperatively. No comparable changes occurred in 57 other patients without Crohn's disease followed endoscopically under the same protocol CONCLUSIONS: Histological recurrence of Crohn's disease may occur in small intestinal allografts despite the absence of endoscopic and clinical disease manifestations. Such recurrences are probably not rare, may occur as early as 3 weeks after transplantation, and do not necessarily portend early clinical recurrence or mandate aggressive therapy to prevent allograft loss.

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.

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.

In situ and invasive adenocarcinomas of the gallbladder extending into or arising from Rokitansky-Aschoff sinuses: a clinicopathologic study of 49 cases.

We report 49 cases of gallbladder carcinomas that extended into or originated from Rokitansky-Aschoff sinuses (RAS), all of which were resected by laparoscopic cholecystectomy. Twenty-one tumors were in situ carcinomas that extended along RAS; six in situ carcinomas arose in adenomyomatous hyperplasia and 22 were invasive adenocarcinomas with extension into RAS. Thirty-seven patients were women and 12 men. Forty patients had cholelithiasis. The age of the patients ranged from 55 to 84 years (mean 67 years). All in situ carcinomas were incidental microscopic findings in gallbladders removed for cholelithiasis and/or cholecystitis. No patient with in situ carcinoma died as a result of the tumor, including two with in situ carcinoma that originated in adenomyomatous hyperplasia and showed microinvasion. In contrast, of 15 patients with invasive well to moderately differentiated adenocarcinoma extending into RAS and invading the muscle layer or subserosal connective tissue, 8 died 2 to 4 years after surgery. Seven patients survived 1 to 8 years after cholecystectomy. Useful clues to separate RAS with in situ carcinoma from tubular neoplastic invasive glands were the following: connection of the epithelial invaginations to the surface epithelium, recognition of normal biliary epithelium admixed with neoplastic epithelium, presence of inspissated bile in long dilated spaces, and lack of invasion to the smooth muscle bundles. In situ carcinoma spreading along RAS consisted of long tubular often dilated structures extending through the intermuscular connective tissue, whereas neoplastic glands were usually small or of medium size that invaded smooth muscle bundles or intermuscular connective tissue. Perineural invasion was seen only in invasive glands located in the subserosal connective tissue. Two cases of in situ carcinoma that arose in adenomyomatous hyperplasia and three invasive adenocarcinomas that were composed predominantly of tall columnar mucin containing cells similar to gastric foveolar cells with varying degrees of atypia and cells with biliary phenotype bear some resemblance to intraductal papillary mucinous carcinoma of the pancreas or to mucinous cystic pancreatic neoplasm. Metaplastic pyloric glands often seen in the muscle layer and subserosal connective tissue maintain their lobular pattern and should not be confused with invasive glands. Our findings indicate that distinction of in situ carcinoma spreading into RAS from tubular neoplastic glands of invasive adenocarcinomas is crucial to determine prognosis in this group of patients with gallbladder carcinoma.

Intraductal tubular adenoma, pyloric type, of the pancreas: additional observations on a new type of pancreatic neoplasm.

Three cases of a distinctive intraductal tubular adenoma, pyloric type, of the main pancreatic duct are reported. The patients, two women and a man, whose ages ranged from 63 to 70 years, complained of abdominal pain attributed to chronic pancreatitis in two patients. The patient with the largest tumor also had symptoms of gastric outlet obstruction. The tumors, two of which arose in the head and one in the tail of the pancreas, led to occlusion and cystic dilatation of the main pancreatic duct. Two adenomas were sessile and one was attached to the wall of the pancreatic duct by a thin fibrous stalk. Microscopically, they were composed of lobules of closely packed tubular glands similar to pyloric glands. In one tumor, nearly all glands were lined by columnar mucin-secreting cells with abundant clear cytoplasm and basally oriented nuclei. In addition to pyloric glands, two adenomas contained glands lined by cells with little or no mucin as well as by pink oncocytic cells. Focal intestinal differentiation was identified in one tumor. Both intracellular and extracellular mucin was detected with the mucicarmine, periodic acid-Schiff, and alcian blue stains. All three adenomas were CK7 positive and CK20 negative. Focal carcinoembryonic antigen linear reactivity along the apical cytoplasm was seen in many cells, but few cells expressed cytoplasmic carcinoembryonic antigen. All three adenomas showed low proliferative activity as measured by the MIB-1 labeling index. The three adenomas were p53 negative and showed loss of DPC4 expression. No endocrine cells were identified in any of the tumors. All patients are alive and symptom free from 4 months to 5 years following surgical treatment.

Gamma knife surgery in the management of brain metastases from lung carcinoma: a retrospective analysis of survival, local tumor control, and freedom from new brain metastasis.

OBJECT: The objective of this retrospective study was to analyze the results of stereotactic radiosurgery performed using a gamma knife in the treatment of 44 consecutive patients with brain metastases from lung carcinoma. METHODS: Forty-four patients with lung carcinoma were treated for metastatic brain tumors by performing radiosurgery with a Leksell Gamma Knife. Twenty-one patients (47.7%) were women and 23 were men. The mean age of the patients was 56 years (range 35-77 years). Twenty-two patients (50%) had solitary tumors and the rest had multiple tumors (two-six lesions). Eighteen patients (40.9%) presented with a recurrent and/or progressive brain disease that previously had been treated with other modalities (surgery, external-beam radiotherapy, or both). Fifteen patients had controlled lung disease and 19 patients had systemic metastases (in lymph nodes, liver, and/or bones) at the time of radiosurgery. The median follow-up period was 18.25 months. All patients were followed up for three different end points: 1) death caused by the disease; 2) clinical and/or radiological evidence of progression of the tumor that had been treated with radiosurgery; and 3) appearance of new lesions. At the last follow-up review, 17 patients (38.6%) were alive and 27 (61.4%) had died. Ten patients (22.7%) died as a result of brain disease (failure of local control or new metastases). Controlled primary disease at the time of detection of metastases and the ability to achieve local tumor control after radiosurgery significantly improved the patient survival (p < 0.01). Control of the treated tumor(s) was achieved in 32 of 44 patients (72 tumors) and 10 patients experienced treatment failure. In addition to the 44 patients comprising the study population, two other patients were treated, but died of lung disease too early in the follow-up period to have been assessed. As of the last follow-up review, no new brain metastasis had occurred in 36 patients (81.8% [includes surviving and nonsurviving patients]). The median duration of overall survival was 7 months, the median period of controlled brain disease was 21 months, and the median period of freedom from new brain metastases was 17 months (95% confidence interval 13-19 months). CONCLUSIONS: Gamma knife surgery has significantly reduced the incidence of mortality from brain disease by effectively accomplishing local tumor control in patients with metastatic lung cancer. Local control and freedom from new brain metastases is not influenced by prior external-beam radiotherapy.

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.

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.