Perilunate injuries: biomechanics, imaging, and classification.

Perilunate injuries are uncommon injuries that are often misdiagnosed. Although conventional radiographs can underestimate the severity of the perilunate injuries, assessment with cross-sectional imaging can be complex, and terminology is inconsistent in the scientific literature. The aim of this paper is to describe the biomechanics, anatomy, and classification of perilunate trauma in order to provide a systematic approach to the description and diagnosis of these injuries.

Paediatric vertebral marrow signal: defining a normal reference range for the marrow-to-disc signal ratio.

AIM: To establish a normal reference range of bone marrow from birth to 16 years of age. MATERIALS AND METHODS: Two independent observers performed region-of-interest measurements of the magnetic resonance imaging (MRI) signal on sagittal non-contrast T1-weighted images of the spine of paediatric patients collected from a 12-year picture archiving and communication system (PACS) archive. The mean signal of the bone marrow and adjacent intervertebral disc were recorded. The mean marrow signal of the L1-L5 vertebrae was expressed as a ratio to the mean signal from the adjacent disc. RESULTS: Two hundred and ninety-seven MRI studies (149 males, 148 females) met inclusion criteria. The ratio of the signal from the vertebral marrow to disc increased with age. The normal reference range was calculated for each of six age groups and defined as two standard deviations above and below the mean. The lower limit of the reference range crossed the isointense line at the age of 2 years. CONCLUSION: The ratio of disc to marrow signal increases until the age of 2 years, after which it remains stable. It can be normal to see a bright disc on T1 below the age of 1 year, but after the age of 2 years a hyperintense disc on T1 is outside the 95% reference range.

[Molecular analysis of childhood B-acute lymphoblastic leukemia: Identification and prognosis of rare breakpoints].

Acute lymphoblastic leukaemia (ALL) is the most common subtype of childhood cancer. Detection of a specific gene rearrangement allows the identification of prognostically relevant subgroups in childhood B-ALL. There are four common gene rearrangements which are widely studied to see prognostical values (TEL-AML1, BCR-ABL, E2A-PBX1, MLL-AF4) in childhood B-ALL. In this study we show the prevalence of these common gene rearrangements and also explain the way to identify some rare breakpoints which also occur in these gene rearrangements. 97 samples received for diagnosis from paediatric B-ALL patients were included in this study. Qualitative reverse transcriptase PCR was used for detection of the TEL-AML1-t(12;21), E2A-PBX1-t(1;19), BCR-ABL1-t(9;22) and MLL-AF4 t(4;11) fusion transcripts. Unusually sized amplicons were confirmed by FISH and DNA sequencing to confirm atypical breakpoints. Amongst the paediatric B-ALL samples t(12;21), was detected in (∼20%), t(9;22), was detected in (∼8%), t(1;19) was detected in (∼9%) and t(4;11) was detected in 2 cases. t(12;21) with intron 1of the AML1 gene was detected as the most common gene rearrangement in paediatric ALL, whereas one rare form of the TEL-AML1 breakpoint in which TEL is fused with intron 2 of AML1 was also observed. In the t(9;22) breakpoints e13a2, e14a2 and e1a2 were detected as the common breakpoints. Two atypical and rare breakpoint of t(9;22) were detected namely e6a2 and e13a3 in paediatric ALL. TEL-AML1 was found to be the most common translocation in Paediatric B-ALL. Identification of the rare breakpoints through RT-PCR technique requires designing of PCR in such a way that it can detect these rare breakpoints also.

Bivalent IAP antagonists, but not monovalent IAP antagonists, inhibit TNF-mediated NF-κB signaling by degrading TRAF2-associated cIAP1 in cancer cells.

The inhibitor of apoptosis (IAP) proteins have pivotal roles in cell proliferation and differentiation, and antagonizing IAPs in certain cancer cell lines results in induction of cell death. A variety of IAP antagonist compounds targeting the baculovirus IAP protein repeat 3 (BIR3) domain of cIAP1have advanced into clinical trials. Here we sought to compare and contrast the biochemical activities of selected monovalent and bivalent IAP antagonists with the intent of identifying functional differences between these two classes of IAP antagonist drug candidates. The anti-cellular IAP1 (cIAP1) and pro-apoptotic activities of monovalent IAP antagonists were increased by using a single covalent bond to combine the monovalent moieties at the P4 position. In addition, regardless of drug concentration, treatment with monovalent compounds resulted in consistently higher levels of residual cIAP1 compared with that seen following bivalent compound treatment. We found that the remaining residual cIAP1 following monovalent compound treatment was predominantly tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2)-associated cIAP1. As a consequence, bivalent compounds were more effective at inhibiting TNF-induced activation of p65/NF-κB compared with monovalent compounds. Moreover, extension of the linker chain at the P4 position of bivalent compounds resulted in a decreased ability to degrade TRAF2-associated cIAP1 in a manner similar to monovalent compounds. This result implied that specific bivalent IAP antagonists but not monovalent compounds were capable of inducing formation of a cIAP1 E3 ubiquitin ligase complex with the capacity to effectively degrade TRAF2-associated cIAP1. These results further suggested that only certain bivalent IAP antagonists are preferred for the targeting of TNF-dependent signaling for the treatment of cancer or infectious diseases.

Safety and Efficacy of Sodium Bicarbonate versus Hyaluronidase in Peribulbar Anaesthesia.

BACKGROUND: 400 cases undergoing surgery for cataract under local anaesthesia were studied. Peribulbar anaesthesia involves injecting a mixture of 2% lignocaine, bupivicaine 0.5% and hyaluronidase into the peripheral space of the orbit through a single infero-lateral point. Sodium bicarbonate has been shown to reduce the time of onset of anaesthesia and pain perception when mixed with local anaesthetics. METHODS: This study compared two groups of patients (200 each), one receiving hyaluronidase mixed anaesthetic and the other sodium bicarbonate buffered anaesthetic. The groups were compared for effectiveness of the anaesthesia, its onset, duration and the final visual outcome. RESULTS AND CONCLUSION: Sodium bicarbonate was shown to reduce the time of onset and increase the successful block rate without any adverse affects.

A genetic analysis of HIV-1 from Punjab, India reveals the presence of multiple variants.

OBJECTIVE: To determine the extent of HIV-1 genetic variation in Indian patients. DESIGN: To avoid any bias in selecting viral variants, HIV-1 DNA was amplified directly from the peripheral blood mononuclear cells of patients and sequenced. Genetic similarity between Indian sequences and other geographic isolates was analysed by phylogenetic analysis algorithms. METHODS: A fragment encompassing the C2/V3-V5 regions of HIV-1 gp120 was amplified from the lymphocyte DNA of 12 Indian patients. Multiple clones from each patient were sequenced. Nucleotide sequences encompassing about 650 base pairs were aligned for the Indian and other geographically distinct isolates. Inter-isolate relationships were analysed by means of distance, parsimony and neighbour-joining algorithms. RESULTS: Nucleotide sequence comparisons showed low interpatient variation. Amino-acid comparisons revealed a high degree of homology between Indian sequences in this study and those studied earlier. On distance and parsimony trees, most of the Indian sequences clustered together as subtype C. However, sequences from three patients also showed significant homologies and phylogenetic clustering outside of subtype C. CONCLUSIONS: The predominant strain of HIV-1 in India belongs to subtype C and little interpatient nucleotide sequence divergence in the majority of cases suggests recent spread of HIV-1 in this region. This study also presents the first evidence for non-C subtypes in the Indian population with two epidemiologically linked samples remaining unclassified for any existing env subtype. The presence of variant subtypes in Indian patients sheds light on the transmission routes of HIV-1 to India and emphasizes the need to include these sequences in vaccine development strategies.

PIP: Health workers collected blood samples from 12 persons infected with HIV living in the Punjab in India to obtain peripheral blood mononuclear cells so researchers could determine the extent of HIV-1 genetic variation. They prepared multiple clones of the C2/V3-V5 regions of HIV-1 gp120 from the lymphocyte DNA of each patient. They used distance, parsimony, and neighbor-joining algorithms to analyze the inter-isolate relationships. They aligned nucleotide sequences of about 650 base pairs for the Indian and other geographically distinct isolates. All but two cases were males. The two females acquired HIV from their husbands. Based on the nucleotide sequence comparisons, there was low interpatient variation. Amino acid comparisons found a high degree of homology between Indian sequences in this study and those studied previously. Most Indian sequences clustered together as subtype C on the distant and parsimony trees. Three patients had significant homologies and phylogenetic clustering outside of subtype C. One patient had env gene homology to subtype B sequences prevalent in Europe and the Americas. The two others had env gene sequences that clustered away from all presently known subtypes of HIV-1. These three cases were the first sequences divergent from subtype C in India. All of these patients and one that clustered marginally with subtype C had possible contacts outside India. Variant subtypes in Indian patients provide clues on the transmission routes of HIV-1 to India. They also underscore the need for researchers to include these sequences as they develop an HIV/AIDS vaccine. Since the leading HIV-1 strain in India conforms to subtype C and there was limited nucleotide sequence variation in most cases, these findings indicate recent spread of HIV-1 in the Punjab.

Calla positive acute lymphoblastic leukemia after etoposide-based therapy for Ewing's sarcoma.

This is an unusual and interesting case report concerning a 10 year old boy with an initial diagnosis of Ewing's sarcoma of the right tibia. He was successfully treated with a chemotherapy regimen consisting of vincristine, cyclophosphamide (cumulative dose 7200 mg/m2), doxorubicin, etoposide (cumulative dose 2700 mg/m2) and cisplatin and local radiotherapy to the tibia. After an interval of 37 months he developed CALLA positive acute lymphoblastic leukemia with 11q23 chromosomal abnormality. The possible roles of etoposide and cyclophosphamide are discussed.

Triceps skinfold thickness in adolescents.

The triceps skinfold thickness (TSF) was measured in 1000 healthy adolescents aged 11 to 18 yr. Measurements were made with the Standard Harpenden skinfold caliper. Females at all ages studied had thicker skinfolds than their male counterparts. Significant differences in skinfold fat were observed between the high and low socio-economic groups, in both sexes. TSF thickness among girls showed a steady gain throughout adolescence. In boys however, there was a dip in TSF followed by a slow rise, the final thickness being somewhat lower than the prepubertal value. TSF was found to have no correlation with height but good positive correlation with weight and wt/ht2 (body mass index). Hence it may be regarded as a reliable indicator of obesity in this age group, where variable pubertal growth makes nutritional assessment difficult.

Secondary ANLL with t(11;19)(q23;p13) following etoposide and cisplatin for ovarian germ cell tumor.

This is a case report of a ten year old girl with ovarian germ cell tumor who was successfully treated with BEP chemotherapy. She developed acute myloid leukemia, AML-M5 with t(11;19)(q23;p13), 29 months after being off therapy. She received a cumulative dose of 2000 mg/m2 of etoposide and 400 mg/m2 of cisplatin. The association of etoposide and therapy related leukemia is reviewed.

Brush cytology: an adjunct to diagnostic upper GI endoscopy.

Endoscopic brush cytology (EBC) was performed in antral and duodenal brushings of children subjected to upper GI endoscopy for the detection of H. pylori (Hp) and trophozoites of Giardia lamblia (Glt) in addition to routine endoscopic grasp biopsy (EGB). It was hospital based prospective study. EBC was performed in children subjected to upper GI endoscopy with a sheathed cytology brush. Mucosal brushings were collected from antrum, body of the stomach and second or third part of duodenum by gently rubbing the surface of the brush with the mucosal wall in all the directions, brush withdrawn and brushings performed on a glass slide. The smears were placed in 95% ethyl alcohol and later examined for Glt and Hp using Giemsa and Hematoxylin & Eosin stain. EGB was taken from antrum, body of the stomach and duodenum from sites other than those used for brushings. One hundred and seventy children between 1-13 years (median age = 5 years) were subjected to upper GI endoscopy for malabsorption (n = 94), recurrent abdominal pain (n = 49), failure to thrive (n = 16) and recurrent vomiting/regurgitation (n = 11) and EBC was performed in addition to routine EGB. Thirty five children (20.4%) were colonized by Hp, 14 (8.2%) were detected to have Glt and in 6 cases (3.5%) both Hp as well as Glt were detected. Out of 41 cases colonized by Hp, 24 cases (58.5%) were detected by EGB and 27 cases (65.8%) were detected by EBC. Out of 20 children in whom Glt were detected from their duodenum, the detection was by EBG in 12 cases (60%) and by EBC in as many as 19 cases (95%). Comparison of EGB and EBC suggested that detection rates with EBC were higher than EGB. Detection by EBC was significantly higher for Glt than Hp. There were no complications attributed to EBC and procedure time for endoscopy was not significantly prolonged. On the contrary, detection of Hp and particularly Glt in higher proportion of cases with the help of EBC was helpful in their appropriate management. Our results suggest that EBC is a safe and useful tool to enhance the value of diagnostic endoscopic procedure when used in combination with routine EGB.

Nutritional disorders in adolescent girls.

Four hundred and fifty four adolescent girls (11-18 years) were screened for nutritional disorders by anthropometry (weight, height and triceps skinfold measurements), clinical examination and hemoglobin estimation. Of these, 56% belonged to high socio-economic groups (Group A) and the rest (44%) to lower middle class (Group B). A large number of girls from Group B were undernourished (35.5% had weight/height2 less than the fifth percentile of reference standard) stressing the need for nutritional screening, nutrition and health education. Obesity was prevalent in 3.1% of Group A adolescents. Goitre grade I or more was observed in a high proportion of Group B girls, stressing the need for continued consumption of iodized salt in Delhi. Anemia appears to be a major health problem in adolescent girls in both groups (47, 56% in Groups A and B, respectively) underlying the ned for iron supplementation along with health education.

Low incidence of CNS relapse with cranial radiotherapy and intrathecal methotrexate in acute lymphoblastic leukemia.

OBJECTIVES: To assess the incidence of isolated central nervous system (CNS) relapses in patients of acute lymphoblastic leukemia (ALL) treated with a protocol containing cranial irradiation and intrathecal methotrexate as CNS directed therapy. DESIGN: Prospective non randomized study. SETTING: Department of Medical Oncology, Tata Memorial Hospital. SUBJECTS: 623 children of ALL on MCP 841. METHODS: CNS relapse was diagnosed, if upon examination of the CSF, more than 50 cells/microliter were observed, or a count of 5 cells which were unequivocally lymphoblasts. RESULTS: The incidence of isolated CNS relapse was 1.75% with the use of this treatment. Age, sex, white blood cell count, platelet count, lactic dehydrogenase and immunophenotyping were not significantly related to isolated CNS relapse. CONCLUSION: A low incidence of isolated CNS relapse demonstrates the adequacy of the presymptomatic CNS therapy.

Epidemiology of bacterial isolates among pediatric cancer patients from a tertiary care oncology center in North India.

BACKGROUND: Infections are a major cause of morbidity and mortality in pediatric oncology. Resistance pattern of bacterial isolates determine empiric antibiotic therapy and influence outcome. AIMS: This study was planned to determine profile of bacterial isolates and their antibiotic resistance pattern among pediatric cancer patients. DESIGN: It was a retrospective, single institutional study. MATERIALS AND METHODS: The study was carried out in the department of pediatric hematology-oncology of a tertiary care cancer centre in north India over a period of 24 months (2012-2014). Microbiological data pertaining to pediatric cancer patients, less than 18 yrs of age was analysed. RESULTS: Hence, 238 bacterial isolates were cultured from among 1757 blood, urine and other specimens. Gram negative bacteria were the most common (74%) pathogens identified and E. coli and Klebsiella comprised 80% of them. A high incidence of extended spectrum beta lactamase producing organisms (84%), beta-lactam beta-lactamase inhibitor (78%) and carbapenem resistance was observed (29%). Blood stream infection with multi-drug resistant Klebsiella was associated with high mortality. The gram positive bacteria isolated were predominantly staphylococcus aureus and were antibiotic sensitive. Reduction in the number of culture positive isolates in the second year of our study was probably due to rigorous implementation of infection control measures. CONCLUSION: These results on microbiologic profile and antibiotic sensitivity pattern of the isolates will be extremely helpful in revision of antibiotic guidelines for our patients and in developing strategies for coping with high prevalence of multi-drug resistance. Antibiotic stewardship and strict implementation of infection control practices will be important components of this effort.

Differentiation between oligodendroglioma genotypes using dynamic susceptibility contrast perfusion-weighted imaging and proton MR spectroscopy.

BACKGROUND AND PURPOSE: Oligodendrogliomas with 1p/19q chromosome LOH are more sensitive to chemoradiation therapy than those with intact alleles. The usefulness of dynamic susceptibility contrast-PWI-guided ¹H-MRS in differentiating these 2 genotypes was tested in this study. MATERIALS AND METHODS: Forty patients with oligodendrogliomas, 1p/19q LOH (n = 23) and intact alleles (n = 17), underwent MR imaging and 2D-¹H-MRS. ¹H-MRS VOI was overlaid on FLAIR images to encompass the hyperintense abnormality on the largest cross-section of the neoplasm and then overlaid on CBV maps to coregister CBV maps with ¹H-MRS VOI. rCBVmax values were obtained by measuring the CBV from each of the selected ¹H-MRS voxels in the neoplasm and were normalized with respect to contralateral white matter. Metabolite ratios with respect to ipsilateral Cr were computed from the voxel corresponding to the rCBVmax value. Logistic regression and receiver operating characteristic analyses were performed to ascertain the best model to discriminate the 2 genotypes of oligodendrogliomas. Qualitative evaluation of conventional MR imaging characteristics (patterns of tumor border, signal intensity, contrast enhancement, and paramagnetic susceptibility effect) was also performed to distinguish the 2 groups of oligodendrogliomas. RESULTS: The incorporation of rCBVmax value and metabolite ratios (NAA/Cr, Cho/Cr, Glx/Cr, myo-inositol/Cr, and lipid + lactate/Cr) into the multivariate logistic regression model provided the best discriminatory classification with sensitivity (82.6%), specificity (64.7%), and accuracy (72%) in distinguishing 2 oligodendroglioma genotypes. Oligodendrogliomas with 1p/19q LOH were also more associated with paramagnetic susceptibility effect (P < .05). CONCLUSIONS: Our preliminary results indicate the potential of combing PWI and ¹H-MRS to distinguish oligodendroglial genotypes.

Plasmodium berghei induces apoptotic changes in splenic and peripheral blood cells.

Intracellular parasites manipulate host cell apoptosis in different ways either to increase their life span within infected cells or to spread infection. The present data provided information on the cellular changes taking place in spleen and peripheral blood during Plasmodium berghei-infection and indicated apoptosis mediated host immune response during infection. Our results suggested a significant change in cellular composition and absolute number of white blood cells in spleen and peripheral blood of P. berghei-infected Balb/c mice. Plasmodium berghei-infection was associated with marked increase in percentage of apoptotic mononuclear cells compared to polymorphonuclear white blood cells.

SIRPalpha1 receptors interfere with the EGFRvIII signalosome to inhibit glioblastoma cell transformation and migration.

EGFRvIII, a frequent genetic alteration of the epidermal growth factor receptor (EGFR), has been shown to increase the migratory potential of tumor cells and normal fibroblasts. Previously, we showed that signal regulatory protein alpha1 (SIRPalpha1) receptors interact with SHP-2 to inhibit wild-type (wt) EGFR-mediated tumor migration, survival and cell transformation. However, the effects of SIRPalpha1 inhibitory receptors on EGFRvIII-mediated phenotypes are unclear. The aim of this study was to investigate the effect of SIRPalpha1 receptor on the EGFRvIII signalosome and phenotypes. Overexpression of SIRPalpha1 in U87MG.EGFRvIII cells inhibited transformation and migration in a MAPK-dependent manner, and is independent of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. We observed reduced EGFRvIII/SHP-2/Gab1/Grb2/Sos-1 interaction and enhanced SIRP/SHP-2 association in U87MG.EGFRvIII/SIRPalpha1 cells when compared with empty vector control cells. Interestingly, SIRPalpha1 overexpression differentially modulated SHP-2 phosphorylation at tyrosyl 542 and 580 residues, which may regulate Erk1/2 activity and the EGFRvIII phenotype. In addition, SIRPalpha1-expressing cells exhibited reduced focal adhesion kinase (FAK) phosphorylation and its recruitment to the EGFRvIII/Grb2/Sos-1/Gab1/SHP-2 complex. Collectively, our data indicate that SIRPalpha1 specifically affects the SHP-2/FAK/Grb2/Sos-1/MAPK activation loop to downmodulate EGFRvIII-mediated migration and transformation. Further understanding of the molecular interactions between the SIRPalpha1 inhibitory receptor and the EGFRvIII signalosome may facilitate the identification of novel targets to inhibit the EGFRvIII glioblastoma phenotype.