Recent advances in diagnostic and therapeutic guidelines for primary and secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterized by excessive activation of macrophages and T cells resulting from defective cytotoxicity. It is potentially life threatening due to the large amounts of cytokines released by the activated macrophages and lymphocytes secondary to a hyperinflammatory response. It has a high fatality in children with an incidence of approximately 1.2cases/million per year. METHOD: The literature was extensively searched in PubMed, MEDLINE and Google scholar. RESULTS: A variable and nonspecific symptomatology can delay the diagnosis and hence requires a high index of suspicion in both primary and secondary HLH.

N-acetyl-L-cysteine modulates multiple signaling pathways to rescue male germ cells from apoptosis induced by chronic hCG administration to rats.

The present study was aimed to investigate the beneficial effects of N-acetyl-L: -cysteine (NAC, 150 mg/kg bw twice/week) against testicular germ cell apoptosis in rats induced by chronic hCG administration (100 IU/rat/day for 30 days). NAC co-treatment improved serum testosterone, prevented rise in lipid peroxidation, intracellular H(2)O(2) and the activities of antioxidant enzymes in germ cells. Replenishment of intracellular GSH and total antioxidant capacity was seen. There was a marked reduction in TUNEL positive germ cells and expression of caspase-3 (p < 0.01) and PARP cleavage. Pro-apoptotic markers Fas, FasL, caspase-8 were also significantly downregulated. While Bcl-2 was fully restored, rise in Bax, caspase-9, phospho-JNK/JNK and phospho-c-Jun/c-Jun expression was significantly arrested. Anti-apoptotic phospho-Akt/Akt and NF-κB were otherwise found upregulated. Taken together, the above findings demonstrate that NAC intervention rescued the testicular germ cells from demise following chronic hCG treatment through regulation of multiple signaling mechanisms of metazoan apoptosis.

Multifunctional Ribbond--a versatile tool.

Pediatric dentists come across a variety of cases in their day to day practice that requires quick intervention in order to enhance or restore children's smile and functions in the oral cavity. Ribbond is one such material, which has occupied an important place in the dentist's repertoire. Ribbond can be used as an alternative to conventional treatment in pediatric dentistry. This case report demonstrates usage of Ribbond as a space maintainer a fixed partial denture with an acrylic tooth pontic, an endodontic post and a splint material in children. Ribbond combines high-strength fibers with enhanced bondability and patented crosslink lock-stitch leno weave. Ribbond's strength, esthetics, and bondability make it useful for multiple applications in clinical pediatric dentistry.

Ultrasound diagnosis of syndromic cases with vascular malformations and soft tissue overgrowth: A rare case of CLOVES syndrome.

Introduction: Syndromes associated with vascular malformation and soft tissue overgrowth in the paediatric population present with multiple soft tissue swellings. Ultrasound is the initial investigation of choice for paediatric soft tissue swellings. Ultrasound evaluation can accurately assess the nature of vascular malformations and pattern of lipomatous hypertrophy in areas of soft tissue overgrowth to facilitate early diagnosis of such syndromes. Case Report: Here, we report a case of CLOVES (congenital lipomatous overgrowth (CLO), vascular malformations (V), epidermal nevi (E), and spinal/skeletal anomalies/scoliosis (S)) syndrome in a 6-year-old girl referred for evaluation of soft tissue swellings. CLOVES syndrome is a rare overgrowth syndrome in the paediatric population which presents with multiple soft tissue swellings. The ultrasound and clinical features of the syndrome have been illustrated to help radiologists accurately diagnose this rare syndrome based on detailed ultrasound and clinical evaluation. Discussion: Radiological features of CLOVES syndrome and differentiating ultrasound features of other such syndromes have been described in detail. A systematic stepwise approach to diagnosing complex syndromic associations of vascular malformations with lipomatous overgrowth has been proposed. Role of ultrasound in the management, Wilms tumour screening and follow-up of CLOVES syndrome have also been discussed. Conclusion: Ultrasound plays a crucial role in the early diagnosis and management of complex syndromes presenting with soft tissue swelling in the paediatric population. It also aids in the differentiation of such syndromes, tumour screening, guided sclerotherapy and follow-up of vascular lesions encountered in such syndromes.

N-acetyl-L-cysteine counteracts oxidative stress and prevents H2O2 induced germ cell apoptosis through down-regulation of caspase-9 and JNK/c-Jun.

The mechanism of H(2)O(2) induced oxidative stress leading to male germ cell apoptosis was earlier reported from our laboratory. In the present study, we investigated the mechanisms by which N-acetyl-L-cysteine (NAC, which is highly cell specific with strong antioxidant and anti-genotoxic properties), stimulated cell survival under such conditions. Co-incubation with 5 mM NAC significantly (P<0.001) reduced the germ cell apoptosis induced by 10 µM H(2)O(2). Lipid peroxidation was brought down with significant restoration of activities of antioxidant enzymes, SOD, GST, and catalase. Expression of pro-apoptotic marker, Bax up-regulated following H(2)O(2) exposure, was reversed back to control levels. In contrast, expression of anti-apoptotic Bcl-2 and phospho-Akt revealed a completely opposite trend. While caspase-8 activity remained unaffected, NAC successfully attenuated the increased activities of caspase-3 and -9 in the H(2) O(2) treated cells. Simultaneously, the increased expression of caspase-9, phospho-JNK, and phospho-c-Jun after H(2)O(2) treatment was down-regulated by NAC. The above findings indicate that the mechanism of inhibition of H(2)O(2) induced male germ cell apoptosis by NAC is mediated through regulation of caspase-9 and JNK.

N-acetylcysteine counteracts oxidative stress and prevents hCG-induced apoptosis in rat Leydig cells through down regulation of caspase-8 and JNK.

We have earlier reported that following persistent stimulation with hCG, oxidative stress-induced apoptosis in rat Leydig cells was mainly achieved through the extrinsic pathway. In the present study, the role of N-acetylcysteine (NAC) in counteracting the oxidative stress and the mechanisms of inhibition of apoptosis under such conditions were investigated. NAC (1 mM) intervention with repeated hCG stimulation (50 ng/ml, four times, each with 30 min challenge) prevented the decline in Leydig cell viability and the rise in lipid peroxidation and reactive oxygen species. Simultaneously, the activities of the enzymes glutathione-S-transferase, catalase, superoxide dismutase and the intracellular glutathione and antioxidant capacity of the treated cells improved significantly. Apoptotic markers Fas, FasL, and caspase-8, up-regulated following repeated hCG exposure, were significantly down-regulated following NAC co-incubation. While Bcl-2 expression was fully restored, Bax and caspase-9 remained unchanged. NAC treatment induced down-regulation of upstream JNK/pJNK and down-stream caspase-3 in the target cells. Taken together, the above findings indicate that NAC counteracted the oxidative stress in Leydig cells induced as a result of repeated hCG stimulation, and inhibited apoptosis by mainly regulating the extrinsic and JNK pathways of metazoan apoptosis.

Demographic and clinicopathological profile of patients of gastrointestinal stromal tumor from a tertiary care center of North India: An observational study.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal system. This study was aimed to analyze the demographic and clinicopathological data of the patient with a primary diagnosis of GIST, who were treated at our center. MATERIALS AND METHODOLOGY: Patients of GIST registered at our center from September 1, 2008, to August 31, 2016, were enrolled for this study. Patient's demographic and clinicopathological data were collected from clinical records. The data were represented as absolute number, percentage, and median (range: minimum to maximum), whichever applicable. RESULTS AND OBSERVATIONS: The analysis of 27 patients revealed that pain was the most common clinical feature. The stomach was the most common primary site. Most of the patients underwent upfront radical surgery (92.6%) followed by adjuvant imatinib. Histopathological data revealed that most tumors were >10 cm in size, 51.8% of patients had low mitotic index, and all these patients were either immunohistochemical positive for cluster differentiation 117 or KIT. The median duration of tyrosine kinase inhibitors therapy (imatinib) in our study individual was 2.5 years with a range of 4.8 months-3 years. Response assessment revealed 74.1% complete remission, 11.1% stable disease, and 3.7% progressive disease. Median overall survival in study individuals was 2.63 years (range: 0.1-8.6 years). Patient- and tumor-related factors were analyzed for prognostic significance using univariate survival analysis; however, none was found to have a significant prognostic correlation. CONCLUSIONS: Patients who underwent upfront surgery followed by adjuvant imatinib has shown good response to the treatment. However, the limitation of the small sample size and short follow-up in this study may not be a true data representation of the entire population.

Adverse effects associated with persistent stimulation of Leydig cells with hCG in vitro.

The detrimental effects of persistent stimulation with hCG were investigated in rat Leydig cells in vitro. Significant rise in lipid peroxidation and reactive oxygen species (ROS) with concomitant attenuation in the activities of antioxidant enzymes: superoxide dismutase, catalase, and glutathione-S-transferase was observed. Transcripts for catalase and superoxide dismutase were also depleted. Subsequent to each hCG challenge, the total antioxidant capacity in the target cells also declined significantly (P < 0.05). There was an increase in cell apoptosis (23%), which was associated with a rise in caspase-3 activity, PARP cleavage, and Fas, FasL, caspase-8 expression. While Bax and Caspase-9 expression remained unchanged, Bcl-2 demonstrated a marked decline. Taken together, the above data indicate that persistent hCG stimulation of Leydig cells induced adverse effects leading to oxidative stress and apoptosis which was channeled primarily through the extrinsic pathway.

Randomized controlled study comparing simultaneous modulated accelerated radiotherapy versus simultaneous integrated boost intensity modulated radiotherapy in the treatment of locally advanced head and neck cancer.

OBJECTIVES: Comparison of two fractionation schedules of intensity modulated radiotherapy (IMRT) for locally advanced head and neck cancer - simultaneous integrated boost (SIB-IMRT) and simultaneous modulated accelerated radiotherapy (SMART) boost in terms of toxicity and survival end-point measures. PATIENTS AND METHODS: Sixty patients with locally advanced head and neck cancer were randomized in two treatment arms (SIB-IMRT [control arm] and SMART boost arm [study arm]). In the control arm, patients received 70, 63 and 56 Gy in 35 fractions to clinical target volumes (CTV) 1, 2 and 3, respectively. In the study arm, patients received 60 and 50 Gy to CTV 1 and CTV 3, respectively. Toxicities, progression free survival (PFS) and overall survival (OS) were compared between both arms. RESULTS: Baseline patient-related characteristics were comparable between the arms except for primary site of tumour. No significant differences were noted in acute toxicities between the arms except for fatigue which was statistically higher for control arm. No significant differences in 2-year late toxicities were observed. The median follow-up duration was 25.5 (range, 1.8-39.9) months. The 2-year PFS was 53.3% and 80.0% (p = 0.028) for control and study arm, respectively. The 2-year OS was 60.0% and 86.7% (p = 0.020) in control and study arms, respectively. Multivariate analysis showed clinical stage and site to be significant predictors for OS and PFS, respectively. CONCLUSIONS: The SMART boost technique can be a feasible alternative fractionation schedule that reduces the overall treatment time, maintaining comparable toxicity and survival compared with SIB-IMRT.

The use of adaptive intensity-modulated radiotherapy in the treatment of small-cell carcinoma lung refractory to chemotherapy in a patient with preexisting interstitial lung disease.

This is a case report of a 60-year-old diabetic, hypertensive male with a good performance status and a history of bilateral interstitial lung disease with a left upper lobe lung mass diagnosed to be a Stage IIB mixed small-cell/squamous cell carcinoma which was refractory to carboplatin- and etoposide-based chemotherapy. The patient was then taken up for adaptive intensity-modulated radiotherapy with tighter margin under image guidance with a mid-treatment replanning done at 25#. Acute toxicities were assessed weekly and showed no Grade 3 or more reactions. Pulmonary function test showed no detrimental changes during or after radiation. Response assessment at 12 and 20 weeks showed a partial response with decrease in metabolic activity on serial scans.

Platelet functions and coagulation changes in Indian children with nephrotic syndrome.

INTRODUCTION: Only little is known on the effect of the platelet function in the paediatric nephrotic syndrome. The earlier studies which had been done on hypercoagulability have mainly featured the secondary forms of the nephrotic syndrome and the data on the minimal change type of disease is limited. We therefore, made an effort to study the platelet functions and the coagulation profile in children with the nephrotic syndrome,to find the relationship between the steroid response and the coagulation profile, and to look for the correlation between thromboembolism and the hypercoagulable states. METHODOLOGY: Twenty nine children with the steroid responsive nephrotic syndromewere studied to see the platelet aggregation and the coagulation parameters and their response to the steroid therapy. Doppler studies were done for the renal vein and the inferior vena cava (IVC) thrombus. RESULTS: It was seen that an increased aggregability of the platelets occurred with Adenosine diphosphate (ADP) and collagen (out of the four agonists, ADP, Collagen, Ristocetin and Arachidonic acid) which were used as agonists for the assay. We also observed that the Partial thromboplastin time (PTT) had become prolonged and a significant decline in the high values of the procoagulant proteins (Protein C and Protein S) was seen after the steroid therapy and when the children went into remission. These findings were suggestive of a reversibility of the changes in the steroid responsive nephrotic syndrome with the steroid therapy. One child was found to have thrombosis of the inferior vena cava (IVC) on Doppler studies, which resolved with treatment subsequently. CONCLUSIONS: An increased platelet aggregability contributes to the hypercoagulable states, that may increase the incidence of thrombosis in such patients. Although the incidence of such complications is very low, in a given child with the hypercoagulable states, Doppler may be used to look for any evidence of a latent thrombus and, an early intervention could be instituted. A change in the coagulation parameters points to the reversibility of the changes which are produced in a diseased state.

Differential modulation of apoptotic gene expression by N-acetyl-L-cysteine in Leydig cells stimulated persistently with hCG in vivo.

The present study was designed to investigate the molecular mechanisms of NAC (150 mg/kg bw twice/week) action in vivo under repeated hCG (100 IU/rat/day) stimulation to adult rats. Leydig cell refractoriness led to a significant decline in serum testosterone and intracellular cAMP by day 30 of chronic hCG intervention which improved significantly following NAC co-administration. It inhibited the rise in lipid peroxidation, improved the activity of antioxidant enzymes along with intracellular glutathione and total antioxidant capacity in the target cells. Leydig cell apoptosis declined significantly (P<0.001) with down-regulation of upstream, Fas, FasL, caspase-8, Bax and caspase-9, JNK/pJNK and downstream caspase-3 and PARP. On the other hand, anti-apoptotic Bcl2, NF-kß, and Akt were up-regulated. Taken together, the above findings indicate that the specificity of NAC action was not restricted to regulating marker proteins in the extrinsic and JNK pathways as seen in vitro but extended to include intrinsic pathway of metazoan apoptosis as well.

Comparative Evaluation of Oral Candida albicans Carriage in Children with and without Dental Caries: A Microbiological in vivo Study.

AIM: The aim of this study was to examine the presence of Candida albicans in extensive carious lesions before and after treatment of the carious lesions and to evaluate the carriage of Candida albicans in children with and without caries. MATERIALS AND METHODS: The study was conducted on 60 childrens who were divided into two groups: Experimental group (group 1) and controlled group (group 2). Each group was further divided into 3 subgroups according to the dentition as: Group A (Deciduous), group B (Mixed) and group C (Permanent). Swab samples for mycological studies were collected from the dorsum of the tongue, vestibular sulcus and peak of the palatal vault. All samples were cultured directly on SDA plate (Sabouraud's dextrose agar). Number of Candida colonies was determined by counting colony forming unit on SDA plates. Further identification of Candida albicans was done by germ-tube test and corn-meal agar. RESULT: Overall prevalence of Candida albicans carriage was significantly higher and mean value of Candida albicans CFU (colony forming unit) was remarkably higher in group 1 (experimental group) as compare to group 2 (control group). Significant reduction in the frequency and mean value of Candida albicans CFU/plate was seen in children after treatment of carious lesions. CONCLUSION: This study supports the active role of Candida species in dental caries. Hence, Candida albicans may play an important role as a risk factor for dental caries. It was also seen that the oral environment stabilization procedures were able to reduce Candida albicans counts. Thus, these procedures can be considered efficient in the reduction of caries risk. How to cite this article: Srivastava B, Bhatia HP, Chaudhary V, Aggarwal A, Singh AK, Gupta N. Comparative Evaluation of Oral Candida albicans Carriage in Children with and without Dental Caries: A Microbiological in vivo Study. Int J Clin Pediatr Dent 2012;5(2):108-112.

Intramedullary spinal cord abscess masquerading as spinal tumor.

We report a 5-year-old girl who presented with acute onset paraparesis with differential loss of sensation. Magnetic resonance imaging of spine revealed exophytic intramedullary mass lesion from T12 to L1. Peroperatively, the diagnosis was confirmed as abscess. The patient recovered following decompression and antibiotic treatment.

Pathways involved in testicular germ cell apoptosis induced by H2O2 in vitro.

H(2)O(2) induces apoptosis in variety of cells; however, the sensitivities of testicular germ cells to H(2)O(2) are not known. In the present study, H(2)O(2), at concentrations in the range 1-10 microM, was found to induce apoptosis in testicular germ cells in vitro. Following 1 h of treatment with 10 microM H(2)O(2), a 10-fold rise in the percentage of apoptotic cells was observed. Induction of germ cell apoptosis was directly associated with a significant (P < 0.01) increase in lipid peroxidation and a concomitant decrease in superoxide dismutase and catalase activity. Examination of apoptotic signalling pathways revealed an increased expression of extrinsic (Fas, FasL and caspase-8) and intrinsic (Bid, Bak, Bad, Bax and caspase-9) markers, as well as p53, along with a simultaneous decrease in the Bcl-2 protein at the highest concentration of H(2)O(2) exposure. Both, c-jun N-terminal kinase and p38 phosphorylated forms were found to be up-regulated. Interestingly, up-regulation of the nuclear transcription factor kappa B was also observed. The respective transcripts for many of the above proteins followed an identical trend. Caspase-3 activity was also estimated to be 30-fold higher. Taken together, the above data indicate that testicular germ cells are prone to apoptosis at very low concentrations of H(2)O(2), the mechanism of which involves extrinsic and intrinsic as well other regulatory pathways.