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Introduction: Demand for cosmetic therapy of gingival melanin pigmentation is common. Re-pigmentation after gingival depigmentation is an important point. The aim of this study is to evaluate the effect of surgical scraping and electrosurgery on postoperative pain, healing and recurrence of pigmentation., Materials and Methods: Fifteen patients with esthetic concern related to black gums were selected and treated by surgical scraping with respect to right quadrant and electrosurgery with respect to left quadrant. Patients were recalled post-operatively to evaluate healing and recurrence of pigmentation. Each patient was asked to complete the Visual Analogue Scale (VAS) index cards 2 and 24 hours postoperatively., Results: In the initial post-operative period, VAS index cards showed that the discomfort and pain level associated with electrosurgery was significantly higher than conventional scalpel surgery (P < 0.05). Clinically delayed healing was observed in the electrosurgically treated site. Electrosurgery showed better results as compared to epithelial excision for recurrence of pigments. At the end of 15 months, 7 sites in the scalpel excision group showed recurrence, whereas only 4 site showed recurrence in the electrosurgically treated group., Conclusion: The methods used here produced desired results and above all, the patients were satisfied with the outcome. Increased pain level and clinically delayed healing was associated with electrosurgery as compared to scalpel surgery, whereas repigmentation occurred more frequently in scalpel-treated sites.

Unlabelled: Today's dentistry is dominated by restorative procedures which are carried out to meet the demands of not only function but also aesthetics. Prosthetic and restorative therapies generally require a healthy periodontium as a prerequisite for successful treatment outcome. A mouth with a healthy periodontium may be affected by restorations of poor quality, and restorations of the highest quality may fail in a mouth with periodontal disease. This is the first of two articles that attempt to explain the concept of the complex question of biologic width and the problems that occur after improper margin placement in the periodontium. Initially, the dimensions of biologic width are considered and then margin placement and reasons for restorative procedures are discussed. This article also addresses the interactions between periodontal tissues and restorative procedures., Clinical Relevance: Understanding the impact of restorative procedures on periodontal health in regular dental examination by dentists can help in early diagnosis and treatment of periodontal diseases. This could prevent further progression of disease and reduce the frequency of tooth loss.

Patients with liver cirrhosis were traditionally believed to be protected against development of blood clots. Lately, studies have shown that these patients may probably be at an increased risk of venous thrombotic complications. Although the hemostatic changes in the chronic liver disease patients and the factors that may predict bleeding vs thrombotic complications remains an area of active research, it is believed that the coagulation cascade is delicately balanced in these patients because of parallel reduced hepatic synthesis of pro and anticoagulant factors. Thrombotic state in cirrhotic patients is responsible for not only portal or non-portal thrombosis [deep vein thrombosis (DVT) and pulmonary embolism (PE)]; it has also been associated with progression of liver fibrosis. The use of anticoagulants in cirrhosis patients is a challenging, and often a scary situation. This review summarizes the current literature on the prevalence of venous thrombosis (DVT and PE), risk factors and safety of prophylactic and therapeutic anticoagulation in patients with chronic liver disease.

Transcatheter device closure of atrial septal defect (ASD) in small children less than 15 kg may be associated with increased complications. Complete atrioventricular heart block (CHB) is a rare complication of ASD device closure in such a setting. We report the case of a 2-year-old girl, less than 15 kg, who underwent device closure of ASD with Amplatzer Septal Occluder and subsequently developed CHB 12 h after the procedure which resolved completely with steroid treatment on fifth day. Case report of a similar kind is rarely reported in the literature. Despite adequate postero-inferior margin CHB may still occur in small children as in our case., (Copyright © 2014 Cardiological Society of India. All rights reserved.)

Objective: The objective of the study was to determine the contribution of submucosal fibroids (SMs) to heavy menstrual bleeding (HMB) and anemia among women with HMB., Study Design: Our retrospective study included premenopausal women who presented to a tertiary care center for HMB between January 2007 and October 2011. All women in this cohort underwent flexible office hysteroscopy (n = 1665) and 259 (15.6%) had SMs. We also reviewed the clinical ultrasounds (n = 914) from these women to determine whether SMs (n = 148) or any fibroids (n = 434) were present in the uterus. Clinical evaluation of bleeding included hemoglobin and pictorial blood loss assessment charts., Results: In our cohort, hysteroscopically diagnosed SMs were associated with significantly lower hemoglobin (adjusted difference -0.35 g/dL; 95% confidence interval [CI], -0.56 g/dL to -0.13g/dL) and higher risk of anemia (odds ratio [OR], 1.46; 95% CI, 1.04-2.03). Women with ultrasound-diagnosed SMs had lower hemoglobin and anemia, but results were not significant once adjusted for confounders (hemoglobin: adjusted difference -0.21 g/dL; 95% CI, -0.47g/dL to 0.06 g/dL; and anemia: OR, 1.28; 95% CI, 0.82-1.97). Ultrasound-diagnosed fibroids anywhere in the uterus were not associated with hemoglobin (P = .7) or anemia (P = .8). Self-reported pictorial blood loss assessment charts scores did not differ between women with and without fibroids diagnosed by either hysteroscopy or ultrasound (P = .4 and P = .9, respectively)., Conclusion: SMs were related to lower hemoglobin and higher risk of anemia but not self-reported bleeding scores. Diagnostic modality was important: hysteroscopically diagnosed SMs had lower hemoglobin and more anemia than ultrasound-diagnosed SMs. This may explain the inconsistent results in the literature., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents in the United States. It is strongly associated with childhood obesity, insulin resistance and metabolic syndrome. Although some children with NAFLD may remain asymptomatic, progression to nonalcoholic steatohepatitis (NASH), and to advanced stages of fibrosis and cirrhosis is well recognized. Unfortunately, despite the increase in awareness of this disease, there are still no reliable non-invasive diagnostic tests and liver biopsy remains the gold standard for the diagnosis of NASH and staging of fibrosis. In addition, there are no approved pharmacological treatments currently. Lifestyle modification remains the cornerstone of treatment. Team based multidisciplinary approach involving hepatologists, endocrinologists, exercise physiologist, dieticians, and cardiologists may lead to better outcomes. Recently, the American Association for the Study of Liver Diseases (AASLD) and European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) committees have made recommendations for the diagnosis and management of NAFLD in pediatric patients. This review focuses on current literature on epidemiology, natural history, pathogenesis along with summarizing the recent guidelines on diagnosis and treatment of pediatric NAFLD.

Aim: THE AIM OF THE PRESENT STUDY IS TO EVALUATE AND TO COMPARE THE ACCURACY OF TWO ELECTRONIC APEX LOCATORS (EALS): DentaPort ZX and iPex, at a position 0.5 mm short of the apical foramen., Materials and Methods: Thirty single-rooted, mandibular premolar teeth were selected. Standard access cavities were prepared and the actual length (AL) was calculated. The samples were then embedded in alginate and the electronic measurements were determined and recorded., Results: The results obtained showed that in determining the root canal length with a tolerance level of ±0.5 mm, i.e., AL ± 0.5 mm, DentaPort ZX was accurate in 93.3% of the samples and iPex was accurate in 90% of the samples at a position 0.5 mm short of the apical foramen., Conclusion: A strong correlation was seen between the two electronic methods and AL and also in between the two EALs, showing the possibility of their use to measure the root canal length. No statistically significant difference was found between both the apex locators.

Background and Aims: The psychological stress associated with type 1 diabetes (T1D) may be higher in children from developing world due to limited health resources. The aims of the study were to assess the quality of life (QoL), emotional well-being, behavioral, and cognitive profile of children/adolescents with T1D diagnosed at least 6 months prior., Materials and Methods: Forty-nine children with T1D, aged 6-18 years were assessed using DAWN Youth QoL questionnaire, WHO-5 Well-Being Index, Child Behavior Checklist (CBCL), and Malin's Intelligence Scale for Indian children (MISIC). The association of the scores was studied with age, gender, socioeconomic status (SES), frequency of hypoglycemia, HbA1c, and age of onset and duration of T1D., Results: The mean (standard deviation (SD)) for DAWN QoL, WHO-5, CBCL, and MISIC scores was 24.7 (16.7), 74.6 (19.4), 52.6 (8.8), and 96.0 (11.2), respectively. The significant associations noted were: Elevated HbA1c with poorer emotional well-being; higher negative impact on 'symptoms of disease' and 'future prospects' sub-areas of QoL; shorter duration of disease with more behavioral issues; lower maternal education with more 'withdrawn/depressed' behaviors and 'worry about future prospects'; and lower SES with lower MISIC scores. Earlier onset (age <5 years) was associated with fewer behavioral problems and less negative impact on QoL., Conclusion: Children with recent diagnosis, older age at onset, lower maternal educational level, elevated HbA1c, or belonging to lower SES were identified to have higher prevalence of various psychological and cognitive problems. In resource-limited settings, these children should be prioritized for behavioral and cognitive evaluation.

Background: The aim of the present study was to evaluate and compare the clinical and microbiological effectiveness of Periochip™ as an adjunct to scaling and root planing (SRP) with SRP alone in patients with chronic periodontitis., Materials and Methods: This randomized, split mouth, 3-month clinical and microbiological trial included 30 sites in 15 patients aged 30-50 years diagnosed with chronic periodontitis. In each patient, two bilateral pockets probing 5-7 mm were randomly assigned to test and control groups. The test group received SRP plus Periochip™, whereas the control group received SRP alone. Clinical indices and anaerobic culture analysis was done at baseline, 1 month, and 3 months interval. Total bacterial count and analysis of four major periodontopathogenic bacteria Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Fusobacterium nucleatum (Fn) was done., Results: Significant improvement was obtained in all clinical variables in the test group as compared to the control group over the study period. Total colony counts were significantly reduced in the test group as compared to control over the period of time. At baseline Aa was recovered from 4 test group sites and 5 control group sites, Pg from 15 test group and 14 control group sites, Pi from 5 test group and 2 control group sites, Fn from 7 test and 7 control group sites. At 3 months, Aa was recovered from 1 test group and 4 control group sites, Pg from 4 test group and 8 control group sites, Pi from 1 test group and 1 control group site, Fn from 3 test and 4 control group sites., Conclusion: Periochip™ placement as an adjunct to SRP, showed promising results, when compared to SRP alone. Healthy microflora can be maintained for a longer period of time and delay in the repopulation by periodontopathic microorganisms was observed.

Objectives: Oxidative stress has been implicated in the development of nonalcoholic fatty liver disease (NAFLD) and progression to the more severe form, nonalcoholic steatohepatitis (NASH), in children. We aimed to study the clinical correlation between bilirubin, a potent endogenous antioxidant with cytoprotective properties, and histopathological findings in pediatric patients with NAFLD., Methods: We included consecutive children with biopsy-proven NAFLD and obtained demographic, clinical, and histopathological data. We performed logistic regression analysis to assess the clinical factors associated with the histological features of NASH or fibrosis., Results: From a total of 302 biopsies, 67% (203) had evidence of NASH, whereas 64.2% had some degree of fibrosis (stage 1 in 51%, stage 2 in 6.3%, and stage 3 in 6.6%). Mean total bilirubin was significantly lower in the NASH group compared with the non-NASH group (0.65 ± 0.24 vs 0.73 ± 0.22 mg/dL, P = 0.007). Higher total bilirubin levels were negatively correlated with the presence of steatosis and the NAFLD activity score (P < 0.05), whereas a trend in that direction was observed for presence of fibrosis and inflammation (P = 0.051). On multivariable analysis, higher bilirubin levels were significantly associated with a decreased likelihood of a histological diagnosis of NASH on biopsy (odds ratio 0.29, 95% CI 0.10-0.85, P = 0.024)., Conclusions: In children with NAFLD, there is an inverse relation between serum bilirubin levels and the presence of NASH on biopsy. This may be secondary to the antioxidant effect of bilirubin.

Cavernous hemangiomas occur frequently in the intracranial structures but they are rare in the spine, with an incidence of 0.22 cases/million/year, which account for 5 - 12% of the spinal vascular lesions, 51% of which are extradural. Most of the epidural hemangiomas are secondary extensions from the vertebral lesions. The spinal cavernous hemangiomas which do not involve the vertebrae are referred to as "pure" types. The pure epidural hemangiomas are rare, which account for only 4% of all the epidural lesions. A case of a Pure spinal epidural cavernous hemangioma in a 50 year old male, with the clinical picture of a slowly progressive compressive myelopathy, has been presented here. The imaging studies showed a well-defined, enhancing epidural lesion at the T7 - T8 level, with dorsal cordedema and myelomalacic changes. A radiological diagnosis of a meningioma was considered. Histopathologically, the lesion was diagnosed as a hemangioma. The patient improved dramatically after the excision of the lesion.

Background & Objectives: Human papillomavirus (HPV) is the necessary cause of cervical cancer and Chlamydia trachomatis (CT) is considered a potential cofactor in the development of cervical intraepithelial neoplasia (CIN). The objective of this pilot study was to determine the association of CT infection with HPV, other risk factors for cervical cancer, and CIN in symptomatic women., Methods: A total of 600 consecutively selected women aged 30-74 yr with persistent vaginal discharge, intermenstrual/postcoital bleeding or unhealthy cervix underwent conventional Pap smear, Hybrid Capture 2 (HC2) testing for HPV and CT DNA and colposcopy, with directed biopsy of all lesions., Results: HPV DNA was positive in 108 (18.0%) women, CT DNA in 29 (4.8%) women. HPV/CT co-infection was observed in only four (0.7%) women. Of the 127 (21.2%) women with Pap >ASCUS, 60 (47.2%) were HPV positive and four (3.1%) were CT positive. Of the 41 women with CIN1 lesions, 11 (26.8%) were HPV positive, while two were CT positive. Of the 46 women with CIN2+ on histopathology, 41 (89.1%) were HPV positive, two (4.3%) were CT positive and one was positive for both. The risk of CIN2+ disease was significantly increased (P<0.05) by the following factors: age <18 yr at first coitus, HPV infection and a positive Pap smear. Older age (>35 yr), higher parity, use of oral contraceptives or smoking did not show any significant association with HPV or abnormal histopathology. Parity >5 was the only risk factor positivity associated with CT infection (P<0.05)., Interpretation & Conclusions: Our findings showed that CT infection was not significantly associated with CIN, and most of its risk factors, including HPV infection, in symptomatic women. Longitudinal studies with carefully selected study sample would be able to answer these questions.

Objective: To determine the etiology, course and predictors of outcome in children with crescentic glomerulonephritis (GN)., Study Design: Retrospective, descriptive study., Setting: Pediatric Nephrology Clinic at a referral center in Northern India., Methods: Clinic records of patients aged <18 year with crescentic GN diagnosed from 2001 - 2010 and followed at least 12 months were reviewed. Crescentic GN, defined as crescents in ≥50% glomeruli, was classified based on immunofluorescence findings and serology. Risk factors for renal loss (chronic kidney disease stage 4-5) were determined., Results: Of 36 patients, (median age 10 yr) 17 had immune complex GN and 19 had pauci-immune crescentic GN. The etiologies of the former were lupus nephritis (n=4), postinfectious GN (3), and IgA nephropathy, Henoch Schonlein purpura and membranoproliferative GN type II (2 each). Three patients with pauciimmune GN showed antineutrophil cytoplasmic antibodies (ANCA). Rapidly progressive GN was present in 33 patients, and required dialysis in 12. At median 34 (19-72) months, 2 patients with immune complex GN and 8 with pauciimmune GN showed renal loss. Renal survival was 94.1% at 3 yr, and 75.3% at 8 yr in immune complex GN; in pauciimmune GN survival was 63.2% and 54.1%, respectively (P=0.054). Risk factors for renal loss were oliguria at presentation (hazards ratio, HR 10.50; P=0.037) and need for dialysis (HR 6.33; P=0.024); there was inverse association with proportion of normal glomeruli (HR 0.91; P=0.042)., Conclusions: Pauci-immune GN constitutes one-half of patients with crescentic GN at this center. Patients with pauciimmune GN, chiefly ANCA negative, show higher risk of disease progression. Renal loss is related to severity of initial presentation and extent of glomerular involvement.

Symmetrical peripheral gangrene (SPG) is an extremely rare complication of malaria that has been well described in multiple case reports of Plasmodium falciparum and mixed infection. We present a case of malaria with isolated Pl. vivax infection complicated by SPG. This index case is the first reported case of peripheral gangrene involving bilateral hands and feet in Pl. vivax infection in an adult.

Introduction: Hodgkin lymphoma (HL) is a highly curable lymphoma with cure rates of over 80% and even higher with limited stage disease. Computerized tomography (CT) scan is currently the recommended modality in staging and assessment of response to therapy in patients with HL. However, CT has its limitations. This study describes our experience with patients of HL where fluorodeoxyglucose positron emission tomography (FDG-PET)-CT scan helped decide further management, after completion of chemotherapy., Methodology: This is a retrospective review of the records of children diagnosed with HL at our center. Patients with post-treatment CT scan showing evidence of residual disease, who underwent FDG-PET-CT for deciding further management, were included in the study., Results: Thirty one patients were diagnosed with HL during this period. Nine patients were eligible and underwent PET-CT. In 8 out of 9 patients, PET-CT showed no scan evidence of active disease. In one patient, FDG-PET-CT carried out after completion of chemotherapy showed evidence of active disease and was given radiotherapy., Conclusion: FDG-PET-CT is a promising modality in deciding further management when there is discordance between the post-treatment CT scan and clinical condition of the patient with HL thus avoiding unnecessary chemotherapy/radiotherapy.

Background: Cervical cancer screening using cytology is expensive and requires repeat testing with loss to follow-up for triage. Adjunctive testing using two tests in a parallel or sequential combination can improve diagnostic accuracy, decrease costs and minimise referral rates., Aim: To evaluate the performance of visual inspection with acetic acid (VIA), human papillomavirus (HPV) DNA and cervical cytology in sequential and parallel combinations, to determine the optimum screening strategy., Methods: A total of 548 symptomatic women presenting to a gynaecology clinic were screened using conventional cytology; HPV testing of self- and physician-collected samples using HC2 assay; and VIA. All women underwent colposcopy with biopsy from all lesions as the reference standard. Test characteristics were calculated individually, and then applied jointly in parallel and sequential combinations., Results: Biopsy-proven CIN2+ was present in 40 (7.8%) women. The sensitivity and specificity, respectively, of the various tests were as follows - VIA 82.5, 66.9%, Pap (≥ASCUS) 77.5, 86.8%, HPV-Physician (HPV(P)) 90.0, 91.5%, HPV-Self (HPV(S)) 80.0, 88.1%. Among the adjunctive testing scenarios, sequential testing performed better than parallel. VIA followed by HPV test had the highest specificity (90.4%) and diagnostic accuracy (90.5%), comparable to HPV-P followed by Pap., Conclusions: Sequential testing combination of VIA and HPV, followed by colposcopy and directed biopsy for diagnosis, combines economic viability with high scientific fidelity. The high specificity and negative predictive value reduce referral and treatment rates, as well as number of visits required for diagnosis. HPV (P) followed by reflex Pap is a suitable option for high resource situations with access to liquid-based cytology., (© 2012 The Authors Australian and New Zealand Journal of Obstetrics and Gynaecology © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Juvenile myelomonocytic leukemia (JMML) is a rare mixed myeloproliferative and myelodysplastic disorder of early childhood, characterized by excessive proliferation of monocytic and granulocytic cells, along with myelodysplastic features. There are reports of viral infections mimicking JMML, with all clinical and hematological parameters normalizing on resolution of infection. The authors describe a 1- year- old boy with concomitant JMML and CMV infection. The diagnostic dilemma, the significance of distinguishing it from a mimicking viral infection, as well as potential synergistic effect of concomitant infections on the presentation or actual disease severity of underlying JMML will be discussed.

Background: Subcutaneous panniculitis-like T-cell lymphoma is as yet a poorly characterized subtype of cutaneous T-cell lymphomas. It is difficult to diagnose and lacks a standard treatment protocol., Materials and Methods: We report our experience with five such cases in patients with age ranging from 13 to 45 years, wherein we reviewed their clinical presentations, histopathological findings, treatment and clinical outcome., Results: Three out of the five cases are alive of which two are in complete remission. Our series stresses on the need to be aware of this uncommon entity in a dermatology clinic. Facial and upper extremity skin nodules with involvement of the lower dermis on light microscopical examination and suggestive immunohistochemical findings were frequently observed in our patients in contrast to previously described cases.

Phosphoinositide 3-kinases (PI3Ks) contribute to the pathogenesis of asthma by regulating the activation of inflammatory mediators, inflammatory cell recruitment and immune cell function. Recent findings have indicated that PI3Ks also regulate the expression of interleukin (IL)-17, which has been recognised as an important cytokine involved in airway inflammation. In the present study, we investigated a role of PI3Kδ in the regulation of IL-17 expression in allergic airway disease using a murine model of asthma. After ovalbumin inhalation, administration of a selective p110δ inhibitor, IC87114, significantly attenuated airway infiltration of total cells, lymphocytes, neutrophils and eosinophils, as well as airway hyperresponsiveness, and attenuated the increase in IL-17 protein and mRNA expression. Moreover, IC87114 reduced levels of IL-4, -5 and -13, expression of keratinocyte chemoattractant protein and mRNA, and nuclear factor (NF)-κB activity. In addition, a NF-κB inhibitor, BAY 11-7085 substantially reduced the increase in IL-17 protein levels. Our results also showed that inhibition of IL-17 activity with an anti-IL-17 antibody remarkably reduced airway inflammation and hyperresponsiveness. These findings suggest that inhibition of the p110δ signalling pathway suppresses IL-17 expression through regulation of NF-κB activity and, thus, has therapeutic potential in asthma.

Dilatation and oesophageal body aperistalsis in achalasia can lead to stasis which in turn can induce repeated microaspiration. It is therefore conceivable that patients with achalasia may also have abnormalities in lungs secondary to repeated episodes of microaspiration. There is a lack of systematic study on involvement of lungs in patients with achalasia. Thirty patients with achalasia underwent pulmonary function tests (spirometry, and carbon mono-oxide diffusion capacity) and high resolution computerized tomography (HRCT) of the chest. The mean age of patients and mean duration of disease were 33.5 +/- 10.9 years and 28.1 +/- 27.3 months respectively. Regurgitation was present in 22 (73.3%) of them. Respiratory symptoms in them were dry cough in 17 (56.6%), and chest pain in 18 (60%). The oesophagus was dilated in 26 (86.6%) and 13 (43.3%) had residue in oesophagus. Sixteen (53.3%) patients had either anatomical changes as seen on HRCT or functional changes as observed on pulmonary function tests. Of those with functional abnormalities, five (16.6%) and one (3.3%) had restrictive and obstructive airways disease respectively. While evidence of tracheo-bronchial compression by dilated oesophagus was present in eight (26.6%), 10 (33.3%) patients had parenchymal lung disease [nodular opacities in five (16.6%), ground glass appearance six (20%), patchy pulmonary fibrosis five (16.6%), air trapping two (6.6%), consolidation and bronchiectasis one (3.3%) each]. There was a significant association between presence of regurgitation and dilatation of oesophagus (P = 0.032). More than half (53.3%) of patients with achalasia have structural and/or functional abnormalities in lungs.

The Declaration of Helsinki (DoH) was adopted by the World Medical Association (WMA) in 1964, as a statement of ethical principles, to provide guidance to physicians and other participants in medical research involving human subjects. Having undergone several amendments, the most recent version was approved on 18 October 2008, by the WMA General Assembly at Seoul, South Korea, replacing all previous versions. This version highlights issues such as, participant safety, the need to include participants from otherwise underrepresented groups, clinical trial registration, post-study access, usage of data and human tissues, compensating participants with research-related injury, and usage of placebo. In this article, we discuss the major aspects of the 2008 version, including the impact of this version on all stakeholders in research, including, investigators, ethics committee members, sponsors, authors, editors, and reviewers.

Liver cancer is one of the most frequent solid cancers. The major risk factor associated with the development of hepatocellular carcinoma (HCC) is cirrhosis caused by hepatitis B, hepatitis C virus or chronic alcohol consumption. The overall prognosis of patients with HCC is very poor and this is mainly due to the advanced stages of cancer at presentation and also because of underlying cirrhosis. When HCC is diagnosed at early stages, prognosis is better with five-year disease free survival of around 50% with resection, or local ablative treatments such as radio-frequency ablation or percutaneous ethanol injection, and 70-80% with liver transplantation. Therefore, systematic screening of all the high-risk patients is the key to an early diagnosis of small HCC and the use of an appropriate treatment modality. The currently available tools for the screening, surveillance and diagnosis of HCC in the presence of cirrhosis remain sub-optimal. The advancements made in the past 10 years, however, have made HCC a potentially curable disease in a highly selected group of patients. This review will briefly discuss the current guidelines for surveillance and diagnosis of HCC in high-risk subjects and then review the potential role of endoscopic ultrasound and fine needle aspiration for the diagnosis of small HCC.

Background: Patients with inflammatory bowel disease (IBD) have low bone mineral density (BMD). Dietary calcium is important for them in the prevention of osteopenia and osteoporosis. There are no reports on the status of BMD in Indian patients with IBD., Methods: Dietary calcium intake and cumulative steroid and immunosuppressive drug use was noted in 46 randomly selected patients (mean [SD] age 40.5 [14.7] years; 28 men) with IBD (ulcerative colitis 22, Crohn's disease 24). To compare values of BMD for patients, data from 46 age- and sex-matched healthy controls (age 40.5 [14.6] years; 28 men) were selected from an existing database of healthy Indian volunteers whose BMD had been measured in a community-based survey carried out among people residing in Delhi (unpublished data). BMD was measured using DXA (Hologic QDR 4500). Osteopenia and osteoporosis were defined as per the standard WHO criteria., Results: The mean duration of disease was 87.7 (78.3) months. The mean calcium intake by 41 patients (89.1%) was <200 mg/day, by 2 patients (4.3%) 200-400 mg/day and by 3 patients (6.4%)>400 mg/day. Significantly lower values of BMD at the spine and hip regions were seen in patients with both ulcerative colitis and Crohn's disease as compared with Indian healthy controls. In comparison to age- and sex-matched healthy controls, 29 (63%) and 21 (45.6%) patients had either osteopenia or osteoporosis at the spine and hip region, respectively. Of them, 4 and 7 patients had osteoporosis at the spine and hip region, respectively. There was no correlation between values of BMD and the age of patient, duration of disease, and cumulative steroid dose., Conclusions: Two thirds of Indian patients with IBD have low BMD. Since the intake of dietary calcium is inadequate in a majority of these patients, they should be advised to increase the intake of dairy products.

Linear porokeratosis is a rare variant. It can be present at birth or can develop in adult life. Lesions of linear porokeratosis are grouped and linearly arranged along the lines of Blaschko. On the extremities it affects the distal portion more than the proximal areas. On the trunk these can be zosteriform in distribution. Lesions of linear porokeratosis probably result from an abnormal clone of epidermal precursors. A 20 year old male presented with annular plaques in linear pattern following the lines of Blaschko over the left upper limb extending up to the axilla present since childhood. The lesions had atrophic centre and raised hyperkeratotic borders. The lesions were more proximal than distal. Few scattered lesions were present on left side of trunk. There was no family history of such lesions. Systemic examination of patient was normal. On histopathological examination there was hyperkeratosis and parakeratosis. A coronoid lamella was present. At the base of coronoid lamella thinned out granular layer and necrotic keratinocytes were also seen. In the dermis pigment incontinence and perivascular lymphocytic infiltrate were present. This case is being reported because of its rarity. It is an atypical presentation because the lesions were disposed more over proximal than distal area of upper limb. Linear porokeratosis is associated with an increased risk of malignant transformation.

PI3K plays key roles in cell growth, differentiation, and survival by generating the second messenger phosphatidylinositol-(3,4,5)-trisphosphate (PIP3). PIP3 activates numerous enzymes, in part by recruiting them from the cytosol to the plasma membrane. We find that in immature B lymphocytes carrying a nonautoreactive Ag receptor, PI3K signaling suppresses RAG expression and promotes developmental progression. Inhibitors of PI3K signaling abrogate this positive selection. Furthermore, immature primary B cells from mice lacking the p85alpha regulatory subunit of PI3K suppress poorly RAG expression, undergo an exaggerated receptor editing response, and, as in BCR-ligated cells, fail to progress into the G1 phase of cell cycle. Moreover, immature B cells carrying an innocuous receptor have sustained elevation of PIP3 levels and activation of the downstream effectors phospholipase C (PLC)gamma2, Akt, and Bruton's tyrosine kinase. Of these, PLCgamma2 appears to play the most significant role in down-regulating RAG expression. It therefore appears that when the BCR of an immature B cell is ligated, PIP3 levels are reduced, PLCgamma2 activation is diminished, and receptor editing is promoted by sustained RAG expression. Taken together, our results provide evidence that PI3K signaling is an important cue required for fostering development of B cells carrying a useful BCR.

Class 1 phosphoinositide 3-kinases (PI3Ks), consisting of PI3Kalpha, beta, gamma, and delta, are a family of intracellular signaling molecules that play important roles in cell-mediated immune responses. In thymocytes, however, their role is less clear, although PI3Kgamma is postulated to partially contribute to pre-TCR-dependent differentiation. We now report that PI3Kdelta, in conjunction with PI3Kgamma, is required for thymocyte survival and ultimately for T-cell production. Surprisingly, genetic deletion of the p110delta and p110gamma catalytic subunits resulted in a dramatic reduction in thymus size, cellularity, and lack of corticomedullary differentiation. Total thymocyte counts in these animals were 27-fold lower than in wild-type (WT) controls because of a diminished number of CD4+ CD8+ double-positive (DP) cells and were associated with T-cell depletion in blood and in secondary lymphoid organs. Moreover, this alteration in the DP population was intrinsic to thymocytes, because the reconstitution of p110gammadelta-/- animals with WT fetal liver cells restored the proportions of all thymocyte populations to those in WT controls. The observed defects were related to massive apoptosis in the DP population; TCRB expression, pre-TCR selection, and generation of DP cells appeared relatively unperturbed. Thus, class 1 PI3Ks work in concert to protect developing thymocytes from apoptosis.

The purpose of this study was to determine incidence of vaginal discharge in pregnant and non-pregnant sexually active females of age group 20-40 years presenting with the chief complaint of vaginal discharge. One hundred sexually active females in the age group of 20-40 years, with vaginal discharge, were selected for this study at random. A detailed clinical history and a thorough examination of all the cases were done. After making the clinical diagnosis, appropriate tests for diagnosing candidiasis, trichomoniasis, gonorrhoea and bacterial vaginosis were done. It was observed that out of 100 cases, 13 (13%) patients were pregnant and 87 (87%) were non-pregnant.

The present study was undertaken to know incidence of various causes of vaginal discharge in sexually active females of age group 20-40 years. One hundred sexually active females in the age group of 20-40 years, with vaginal discharge, were selected for this study at random. A detailed clinical history and a thorough examination of all the cases was done. After making the clinical diagnosis, appropriate tests for diagnosing candidiasis, trichomoniasis, gonorrhoea and bacterial vaginosis were done. The present study showed 45% incidence of bacterial vaginosis, 31% vulvovaginal candidiasis, 2% trichomoniasis, 3% gonorrhoea, 5% non-specific urogenital causes, and 14% with other causes.

A 23-day-old male infant had hairy 'bathing trunk' naevus covering, neck and upper trunk along with multiple congenital melanocytic naevi scattered all over the body.

Neurturin (NTN) is a recently identified homologue of glial-cell-line-derived neurotrophic factor. Both factors promote the survival of dopaminergic (DA) neurons. We investigated the biological activity of mammalian-cell-produced NTN versus purified Escherichia coli-produced NTN. Baby hamster kidney cells were engineered to stably secrete mature human NTN. Mammalian-cell-derived NTN enhanced the activity of embryonic DA neurons in vitro, with greater potency (maximum effect achieved in the picogram range) than purified E. coli-produced NTN. Cell-based delivery of NTN (less than 10 ng/day) was also shown to be biologically active in vivo. These results suggest that mammalian-cell-derived NTN, synthesized de novo and delivered in small quantities to the parenchyma at the target site, may be as active as much larger quantities of purified, E. coli-produced NTN, delivered by other means., (Copyright 2000 Academic Press.)

The kinetics of rolling and transient adhesions through selectins may depend on the kinetics and mechanical properties of the selectin:ligand bond, as well as on cellular properties including receptor-anchoring to the cell membrane and cytoskeleton. Kinetics are known to depend on the selectin and may also be ligand dependent. Here, we study the kinetics of transient and rolling interactions of leukocytes with L-selectin immobilized on a substrate. Remarkably, all properties examined are similar to those seen when the sidedness is opposite, i.e., when the L-selectin ligand is on the substrate and when the ligand is isolated from HEV rather than present on leukocytes. The similar properties include rolling velocity, a threshold shear stress above 0.4 dyn/cm2 required to support rolling, a k degreesoff of 7.0 to 6.8 s-1 for the L-selectin tether bond, and a mechanical bond length of 0.24 to 0.20 A. Our results argue against a model in which L-selectin shedding mediates rolling. Furthermore, the fast and force-resistant kinetic properties suggest that L-selectin is specialized dynamically for tethering leukocytes to vessel walls and adherent leukocytes.

Interactions between adhesion molecules on two different cells differ from interactions between receptors and soluble ligands in that the adhesion molecule interaction (bond) is often subjected to force. It is widely assumed by cell biologists that the 'strength' of a bond is a simple function of the affinity of one adhesion molecule for the other, whereas biophysicists suggest that bonds have 'mechanical properties' that affect their strength. Mechanical properties are a function of the shape of the energy landscape related to bond formation and dissociation, whereas affinity is related only to the net energy change. Mechanical properties determine the amount by which the kinetics and affinity of bonds are altered by applied force. To date there has been no experimental manipulation of an adhesion molecule that has been shown to affect mechanical properties. L-selectin is an adhesion molecule that mediates lymphocyte binding to, and rolling on, high endothelial venules; these are prerequisites for the emigration of lymphocytes from the bloodstream into lymph nodes. Here we report a selective and reversible chemical modification of a mucin-like ligand that alters the mechanical properties of its bond with L-selectin. The effect of force on the rate of bond dissociation, that is, on a mechanical property, is altered, whereas there is little or no effect of the modification on the rate of bond dissociation in the absence of force. Moreover, the puzzling requirement for hydrodynamic shear flow above a threshold level for L-selectin interactions is dramatically altered.

The structure of basic Winged Bean Agglutinin (WBAI) with two dimeric molecules complexed with methyl-alpha-D-galactopyranoside in the asymmetric unit, has been determined by the molecular replacement method and refined with 2.5 A X-ray intensity data. The polypeptide chain of each monomer has the characteristic legume lectin tertiary fold. The structure clearly defines the lectin-carbohydrate interactions. It reveals how the unusually long variable loop in the binding region endows the lectin with its characteristic sugar specificity. The lectin forms non-canonical dimers of the type found in Erythrina corallodendron lectin (EcorL) even though glycosylation, unlike in EcorL, does not prevent the formation of canonical dimers. The structure thus further demonstrates that the mode of dimerisation of legume lectins is not necessarily determined by the covalently bound carbohydrate but is governed by features intrinsic to the protein. The present analysis and our earlier work on peanut lectin (PNA), show that legume lectins are a family of proteins in which small alterations in essentially the same tertiary structure lead to wide variations in quaternary association. A relationship among the non-canonical modes of dimeric association in legume lectins is presented., (Copyright 1998 Academic Press Limited.)

Two mechanisms have been proposed for regulating rolling velocities on selectins. These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive compliance, i.e., the susceptibility of the bond dissociation reaction to applied force. To determine which of these mechanisms explains the 7.5-11.5-fold faster rolling of leukocytes on L-selectin than on E- and P-selectins, we have compared the three selectins by examining the dissociation of transient tethers. We find that the intrinsic kinetics for tether bond dissociation are 7-10-fold more rapid for L-selectin than for E- and P-selectins, and are proportional to the rolling velocities through these selectins. The durations of pauses during rolling correspond to the duration of transient tethers on low density substrates. Moreover, applied force increases dissociation kinetics less for L-selectin than for E- and P-selectins, demonstrating that reactive compliance is not responsible for the faster rolling through L-selectin. Further measurements provide a biochemical and biophysical framework for understanding the molecular basis of rolling. Displacements of tethered cells during flow reversal, and measurements of the distance between successive pauses during rolling provide estimates of the length of a tether and the length of the adhesive contact zone, and suggest that rolling occurs with as few as two tethers per contact zone. Tether bond lifetime is an exponential function of the force on the bond, and the upper limit for the tether bond spring constant is of the same order of magnitude as the estimated elastic spring constant of the lectin-EGF unit. Shear uniquely enhances the rate of L-selectin transient tether formation, and conversion of tethers to rolling adhesions, providing further understanding of the shear threshold requirement for rolling through L-selectin.

Circulating lymphocytes gain access to lymph nodes owing to their ability to initiate rolling along specialized high endothelial venules (HEVs). One mechanism of rolling involves L-selectin binding to peripheral node addressin (PNAd) on HEVs. Activated platelets are shown to bind to circulating lymphocytes and to mediate rolling in HEVs, in vivo, through another molecule, P-selectin, which also interacts with PNAd. In vitro, activated platelets enhanced tethering of lymphocytes to PNAd and sustained lymphocyte rolling, even in the absence of functional L-selectin. Thus, a platelet pathway operating through P-selectin provides a second mechanism for lymphocyte delivery to HEVs.

Selectins are cell adhesion molecules that bind carbohydrate ligands and promote interaction between leukocytes and the vessel wall in vascular shear flow. Selectin-ligand bonds have high mechanical strength, allowing initial tethering to the vessel wall through one or few bonds, and have fast on and off rates, permitting rolling in response to hydrodynamic drag. The L-selectin molecule on leukocytes binds to peripheral node addressin on high endothelial venules of lymph nodes to mediate leukocyte rolling and binds to a ligand on neutrophils to mediate rolling of leukocytes over one another. Here we describe a surprising mechanism for regulation of these interactions, both in vitro and in vivo. Shear above a critical threshold is required to promote and maintain rolling interactions through L-selectin, but not through E-selectin, P-selectin or VCAM-1. The shear threshold requirement for L-selectin may be physiologically important in low shear to prevent inappropriate aggregation of leukocytes and interaction with the vessel wall.

The complete amino acid sequence of a cytotoxin-like basic protein (CLBP) from the venom of Naja naja naja (Indian Cobra) was determined by manual degradation using a 4-dimethylaminoazobenzene-4'-isothiocyanate double-coupling method. Peptide fragments obtained by chemical cleavage with cyanogen bromide and enzymic cleavages with trypsin and Staphylococcus aureus proteases for sequence analysis were purified by reversed-phase chromatography. The total number of amino acid residues was 61, with leucine as the C-terminal residue.

The binding of winged bean basic agglutinin (WBA I) to 4-methylumbelliferyl (MeUmb) galactosides was examined by extrinsic fluorescence titration and stopped-flow spectrofluorimetry. Upon binding to WBA I, MeUmb alpha-galactosides show quenching in fluorescence intensity, decrease in UV absorbance with a concomitant blue shift, and decrease in fluorescence excited-state lifetimes. However, their beta-analogues show enhancement in fluorescence intensity, increase in UV absorbance with a red shift, and an increase in fluorescence excited-state lifetimes. This implies that the umbelliferyl groups of alpha- and beta-galactosides experience non-polar and polar microenvironments, respectively, upon binding to WBA I. Replacement of the anomeric hydroxyl group of galactose by 4-methylumbelliferyl moiety increases the affinity of resulting saccharides. Substitution of C-2 hydroxyl of galactose by an acetamido group leads to increased affinity due to a favorable entropy change. This suggests that acetamido group of MeUmb-alpha/beta-GalNAc binds to a relatively non-polar subsite of WBA I. Most interestingly, this substitution also reduces the association rate constants dramatically. Inspection of the activation parameters reveals that the enthalpy of activation is the limiting factor for the differences in the forward rate constants for these saccharides and the entropic contribution to the activation energy is small.

Titration calorimetry measurements of the binding of methyl alpha-D-mannopyranoside (Me alpha Man), D-mannopyranoside (Man), methyl alpha-D-glucopyranoside (Me alpha Glu), and D-glucopyranoside (Glu) to concanavalin A (Con A), pea lectin, and lentil lectin were performed at 281 and 292 K in 0.01 M dimethylglutaric acid-NaOH buffer (pH 6.9) containing 0.15 M NaCl and Mn+2 and Ca+2 ions. The site binding enthalpies, delta H, are the same at both temperatures and range from -28.4 +/- 0.9 (Me alpha Man) to -16.6 +/- 0.5 kJ mol-1 (Glu) for Con A, from -26.2 +/- 1.1 (Me alpha Man) to -12.8 +/- 0.4 kJ mol-1 (Me alpha Glu) for pea lectin, and from -16.6 +/- 0.7 (Me alpha Man) to -8.0 +/- 0.2 kJ mol-1 (Me alpha Glu) for lentil lectin. The site binding constants range from 17 +/- 1 x 10(3) M-1 (Me alpha Man to Con A at 281.2 K) to 230 +/- 20 M-1 (Glu to lentil lectin at 292.6 K) and exhibit high specificity for Con A where they are in the Me alpha Man:Man:Me alpha Glu:Glu ratio of 21:4:5:1, while the corresponding ratio is 5:2:1.5:1 for pea lectin and 4:2:2:1 for lentil lectin. The higher specificity for Con A indicates more interactions between the amino acid residues at the binding site and the carbohydrate ligand than for the pea and lentil lectin-carbohydrate complexes. The carbohydrate-lectin binding results exhibit enthalpy-entropy compensation in that delta Hb (kJ mol-1) = -1.67 +/- 0.06 x 10(4) + (1.30 +/- 0.12)T(K) delta Sb (J mol-1K-1). Differential scanning calorimetry measurements on the thermal denaturation of the lectins and their carbohydrate complexes show that the Con A tetramer dissociates into monomers, while the pea and lentil lectin dimers dissociate into two submonomer fragments. At the denaturation temperature, one carbohydrate binds to each monomer of Con A and the pea and lentil lectins. Complexation with the carbohydrate increases the denaturation temperature of the lectin and the magnitude of the increases yield binding constants in agreement with the determinations from titration calorimetry.

The nature of binding of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-colcemid (NBD-colcemid), an environment-sensitive fluorescent analogue of colchicine, to tubulin was tested. This article reports the first fluorometric study where two types of binding site of a colchicine analogue on tubulin were detected. Binding of NBD-colcemid to one of these sites equilibrates slowly. NBD-colcemid competes with colchicine for this site. Binding of NBD-colcemid to this site also causes inhibition of tubulin self-assembly. In contrast, NBD-colcemid binding to the other site is characterised by rapid equilibration and lack of competition with colchicine. Nevertheless, binding to this site is highly specific for the colchicine nucleus, as alkyl-NBD analogues have no significant binding activity. Fast-reaction-kinetic studies gave 1.76 x 10(5) M-1 s-1 for the association and 0.79 s-1 for the dissociation rate constants for the binding of NBD-colcemid to the fast site of tubulin. The association rate constants for the two phases of the slow site are 444.4 M-1 s-1 and 11.67 M-1 s-1 [corrected], respectively. These two sites may be related to the two sites of colchicine reported earlier, with binding characteristics altered by the increased hydrophobic nature of NBD-colcemid.

The basic lectin from winged bean (Psophocarpus tetragonolobus) could be crystallized using polyethyleneglycol (PEG) 4000 (I), PEG 8000 (II) and 2-methylpentane-2,4-diol (MPD) (III) as precipitants. Crystal forms I and II grew in the presence of methyl-alpha-D-galactopyranoside or N-acetylgalactosamine while III grew in the absence of sugar. The three forms have the same space group (P2(1)2(1)2) and similar unit cell dimensions with two dimeric molecules in the asymmetric unit. The unit cell dimensions are a = 156.8 A, b = 89.0 A, c = 73.3 A for I, a = 155.5 A, b = 92.3 A, c = 72.5 A for II and a = 148.3 A, b = 90.7 A, c = 73.8 A for III. The crystals, particularly those grown using PEG 8000, are suitable for high resolution X-ray analysis, which is in progress.

2-Dansylamino-2-deoxy-D-galactose (GalNDns) is a useful fluorescent probe to study the interaction of non-fluorescent sugars with the B4 lectin from Vicia villosa seeds (VVLB4). Binding of the lectin to GalNDns leads to a 5.2-fold increase in Dansyl fluorescence with a concomitant 10 nm blue shift in its emission maximum. The strong binding of GalNDns (Ka = 7.33 x 10(4) M-1 at 20 degrees C) is due to a favourable entropic contribution to the association process. Among the other sugars studied, GalNAc alpha 1-O-Ser followed by Me alpha GalNAc are the best ligands. 2-Deoxygalactose, galactosamine and galactose are 2013, 469 and 130 times weaker ligands, respectively, as compared to GalNAc, whereas GalNDns is about 2.44 times more potent than GalNAc, indicating that substitutions at the C-2 position of GalNAc have a considerable influence on the binding affinities. Equatorial orientation of the hydroxyl group at C-3 and axial orientation at C-4 as in galactose are important for the interaction with VVLB4. The C-6 hydroxyl group is not indispensable. The binding site of the lectin is directed exclusively towards monosaccharides alone. Interestingly enough, despite its preference for Me alpha GalNAc over Me beta GalNAc, in oligosaccharides, the lectin prefers terminal beta-linked GalNAc as compared to the alpha-linked one.

The binding of Artocarpus integrifolia lectin (jacalin) to 4-methylumbelliferyl (Meumb)-glycosides, Gal alpha Meumb, Gal beta Meumb, GalNAc alpha Meumb, GalNAc beta-Meumb, and Gal beta 3GalNAc beta Meumb was examined by extrinsic fluorescence quenching titration and stopped flow spectrofluorimetry. The binding was characterized by 100% quenching of fluorescence of Meumb-glycosides. Their association constants range from 2.0 x 10(4) to 1.58 x 10(6) M-1 at 15 degrees C. Entropic contribution is the major stabilizing force for avid binding of Meumb-glycosides indicating the existence of a hydrophobic site that is complementary to their methylumbelliferyl group. The second order association rate constants for interaction of these sugars with lectin at 15 degrees C vary from 8.8 x 10(5) to 3.24 x 10(6) M-1 S-1, at pH 7.2. The first order dissociation rate constants range from 2.30 to 43.0 S-1 at 15 degrees C. Despite the differences in their association rate constants, the overall values of association constants for these saccharides are determined by their dissociation rate constants. The second order rate constant for the association of Meumb-glycosides follows a pattern consistent with the magnitude of the activation energies involved therin. Activation parameters for association of all ligands illustrate that the origin of the barrier between binding of jacalin to Meumb-glycosides is entropic, and the enthalpic contribution is small. A correlation between these parameters and the structure of the ligands on the association rates underscores the importance of steric factors in determining protein saccharide recognitions.

DiflucortolonevalerateO.1percentand hydrocortisone acetate 1.0 percent were compared in a randomized double blind contralateral, intra individual trial in fifty-two patients. Duration of treatment was three weeks. Both the drugs showed significant response after the first second and the third weeks of treatment. At all periods the reduction in pre-treatment signs and symptoms was greater for diflucortolone as compared to hydrocortisone. Response to therapy in eczema was very good in 89.1 percent cases and good 10.9 per cent. Patients having psoriasis and chronic DIE showed very good response in 33.3 per cent and good in 66.6 per cent cases. There were no side effects.

This paper attempts to analyze retrospectively the functional outcome of 75 patients with severe head injury treated consecutively on an inpatient Physical Medicine and Rehabilitation Service. In terms of the outcome relative to regained skills of self-care and ambulation, the results provide evidence that early rehabilitation intervention is medically and therapeutically desirable. However, the potential of this group of patients for a socially and vocationally functional life is indeed limited. This does not conform to the experience of others who indicate a 50-90% rate of return to work.

Depending on the severity of the clinical problem, three categories of treatment--home, outpatient and hospital--were utilized in 82 patients whose conditions met the strict criteria for cervical radiculitis. Details of the clinical picture, laboratory findings, electromyographic examinations, category and results of treatment are detailed. The follow-up results in 59 patients contacted one to two years after the initial treatment are also included. Eighty percent of the patients had good to excellent results when treated with conservative therapy during the initial episode whereas 71% continued to have good to excellent results after one to two years. Seventeen percent of those patients who were followed required a laminectomy.