Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H- RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.     

Biological evaluation of intervertebral disc cells in different formulations of gellan gum‐based hydrogels

Gellan gum (GG)‐based hydrogels are advantageous in tissue engineering not only due to their ability to retain large quantities of water and provide a similar environment to that of natural extracellular matrix (ECM), but also because they can gelify in situ in seconds. Their mechanical properties can be fine‐tuned to mimic natural tissues such as the nucleus pulposus (NP). This study produced different formulations of GG hydrogels by mixing varying amounts of methacrylated (GG‐MA) and high‐acyl gellan gums (HA‐GG) for applications as acellular and cellular NP substitutes. The hydrogels were physicochemically characterized by dynamic mechanical analysis. Degradation and swelling abilities were assessed by soaking in a phosphate buffered saline solution for up to 170 h. Results showed that as HA‐GG content increased, the modulus of the hydrogels decreased. Moreover, increases in HA‐GG content induced greater weight loss in the GG‐MA/HA‐GG formulation compared to GG‐MA hydrogel. Potential cytotoxicity of the hydrogel was assessed by culturing rabbit NP cells up to 7 days. An MTS assay was performed by seeding rabbit NP cells onto the surface of 3D hydrogel disc formulations. Viability of rabbit NP cells encapsulated within the different hydrogel formulations was also evaluated by Calcein‐AM and ATP assays. Results showed that tunable GG‐MA/HA‐GG hydrogels were non‐cytotoxic and supported viability of rabbit NP cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Increase in minimum inhibitory concentration to quinolones and ceftriaxone in salmonellae causing enteric fever

Multidrug resistance among Salmonella typhi is well known. Reports of treatment failure in enteric fever with Ciprofloxacin made us undertake this study to determine the antibiotic susceptibility pattern of S. typhi and S. paratyphi A isolated from typhoid bacteremia cases, by disc diffusion and MIC by broth dilution method. A total of 50 strains were tested, 48 of Salmonella typhi and 2 of S. paratyphi A. The disc diffusion method was done using ampicillin, chloramphenicol, cotrimoxazole, tetracycline, ciprofloxacin, ofloxacin, cefuroxime and ceftriaxone as antibiotics. The MIC was performed using ciproloxacin, ofloxacin and ceftriaxone based on standard procedure. ACCOT resistance as determined by disc diffusion method was seen in 68% of isolates. All the strains remained susceptible to flouroquinolones cephalosporins and aminoglycosides. The MIC of ciprofloxacin, ofloxacin and ceftriaxone were in the recommended range of susceptibility as given by NCCLS, 14 (28%) strains had MIC of ciprofloxacin greater than 0.5 ug/ml with 4 strains having an MIC of 1.56 ug/ml; 25 (50%) strains had MIC of ofloxacin greater than 0.5 ug/ml and 20 (40%) strains had MIC of ceftriaxone greater than 0.5 ug/ml. The high levels of MIC of ciprofloxacin may account for treatment failure cases. The rising levels of MIC of ofloxacin and ceftriaxone in S. typhi and S. paratyphi is also of concern. We document here the emergence of high levels of MIC not only to ciprofloxacin, but also ofloxacin and ceftriaxone in S. typhi and S. paratyphi A. We recommend that MIC levels of ofloxacin and ceftriaxone should be monitored along with ciprofloxacin in treatment failure cases of enteric fever.     

Juvenile Ossifying Fibroma of the Maxilla: A Case Report

Ossifying fibroma is a benign neoplasm of the bone, usually involving the posterior tooth bearing area of the mandible, predominantly seen in females in 2nd–4th decade of life with 5:1 prediliction. Fibro-osseous lesions other than FD seem to arise from the periodontal membrane. These lesions are usually asymptomatic, well defined clinically and radiologically amenable for enucleation. Fibro-osseous lesions of the jaws, including Juvenile Ossifying Fibroma (JOF), pose diagnostic and therapeutic difficulties due to their clinical, radiological and histological variability. Ossifying fibromas which appear as fast growing mass between 5 and 15 years of age, radiologically well bordered, and consistent with ossifying fibroma histologically, are referred as juvenile (aggressive) ossifying fibroma. We report a case of JOF of left side of the maxilla in an 11 year old girl which is an uncommon site of occurrence.     

Transcatheter Aortic Valve Implantation: Bahrain Experience

BACKGROUNDTranscatheter aortic valve implantation (TAVI) is a minimally invasive procedure that is considered a good alternative to surgical aortic valve replacement (sAVR) in selected patients. Our aim is to determine the baseline, procedural characteristics and one-year clinical outcomes of our TAVI registry.METHODSThis study is a retrospective observational analysis of a prospectively designed cohort comprising 81 consecutive patients treated at Mohammed bin Khalifa Cardiac Centre (MKCC) who were enrolled in Bahrain TAVI registry from February 2014 to February 2019. The clinical endpoints were defined according to the updated Valve Academic Research Consortium-2 (VARC-2) consensus document.RESULTSOut of the 81 patients included in our study, there were 37 (45.7%) males. The mean age was 76.4 ± 8.9 years with a mean Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE II) of 4.1 ± 2.5 and a mean Society of Thoracic Surgery (STS) Risk Score of 4.2 ± 3.5. Evolute-R valve was used for 36 (44.4%) patients, Edward Sapien for 26 patients (32.1%), and Core valve for 19 patients (23.5%). At one year follow up, all-cause death was reported in three (3.7%) patients; none of them was cardiovascular mortality. As per VARC-II criteria, no cases fulfilled the criteria of valve dysfunction but TAVI-related complications (i.e., TAV-in-TAV deployment) were reported in four (4.9%) cases. One (1.2%) case of major bleeding was encountered but no patient experienced life-threatening bleeding. Major vascular complications were documented in two patients (2.5%) only. Significant Acute Kidney Injury (AKI) occurred in two (2.5%) patients, both classified as stage-2 but no one deteriorated to stage-3 or hemodialysis. Seven (8.6%) patients required permanent pacemakers, and all were implanted during the index admission for TAVI. One patient (1.2%) had stroke and all survivors completed one-year follow up.CONCLUSIONThe TAVI program in Bahrain is encouraging and corresponds to the finest international centers outcomes in terms of procedural success and complications rate.     

CDC Kerala 13: Antenatal,Natal and Postnatal Factors Among Children (2–6 y) with Autism – A Case Control Study

Objectives

To compare antenatal, natal and postnatal factors among children between 2–6 y of age with autism and a control group of normal children.

Methods

One hundred and forty three confirmed cases of 2–6 y-old children with autism, attending autism clinic of Child Development Centre, who had a CARS score of ≥?30 were included in the study. Two hundred normal children in the same age group were recruited from the well-baby/immunization clinic of SAT Hospital, Thiruvananthapuram. Data was collected using a structured pre-piloted questionnaire consisting of 21 antenatal, 8 natal and 6 postnatal risk factors.

Results

The multivariate analysis on antenatal, natal and postnatal possible risk factors for autism showed statistically significant high odds ratios for (i) excess fetal movement (OR?=?11.44; 95 % CI: 2.85 – 45.98); (ii) maternal respiratory infection/asthma (OR?=?6.11; 95 % CI: 1.56–24.02; (iii) maternal vaginal infection (OR?=?5.20; 95 % CI: 1.72 – 15.73); (iv) maternal hypothyroidism (OR?=?4.25; 95 % CI: 1.38–13.07) and (v) family history of neuro-developmental disorders (OR?=?2.90; 95 % CI: 1.72 – 4.88).

Conclusions

This case control study involving 143 children between 2 and 6 y with autism as per CARS criteria and a control group of 200 normal children has shown that excess fetal movement, maternal respiratory infection/asthma, maternal vaginal infection, maternal hypothyroidism and family history of neuro-developmental disorders are possible risk factors for autism.

     

Unusual Complication of Toxic Megacolon in Typhoid Colitis

Colitis is a rare manifestation of enteric fever in children. Toxic megacolon complicating typhoid colitis is even rarer and requires early recognition and aggressive management due to the high mortality associated with this condition. The authors report a rare case of Toxic megacolon secondary to typhoid colitis in a seven-year-old girl.