Effects of Surgical Stress on Early Nonspecific Immune Response in Children

Surgery alters the body’s homeostatic balance and defense mechanisms. In adults transient postoperative cellular and humoral immunosuppression after different degrees of operative stress has been reported. In children the immunologic consequences of operations are not elaborated. This study investigates the effect of minor and major surgery on early nonspecific immune response in terms of neutrophil counts and function. Forty-three children undergoing minor and major elective procedures were studied. Blood samples were collected before, immediately after, and 72 h after surgery. Total white cell count, differential neutrophil count, and neutrophil phagocytic function were studied using nitroblue tetrazolium test. Children were divided into two groups—group 1 underwent minor surgery and group 2 major surgery. In group 1 there was a significant drop in total counts after surgery, but in group 2 total counts were not affected. In both groups, the percentage of neutrophils increased immediately after surgery but fell to near or less than preoperative levels 72 h after surgery. However, the assessment of neutrophil functions by nitroblue tetrazolium test in both unstimulated and stimulated forms revealed it to be unchanged in group 1. In group 2 the unstimulated neutrophil function was elevated 72 h after surgery, whereas stimulated function was elevated immediately after surgery. Minor surgery does not alter the early nonspecific immune response. However, major surgery seems to induce a transient increase in neutrophil phagocytic activity.     

4‐Hydroxy‐α‐Tetralone and its Derivative as Drug Resistance Reversal Agents in Multi Drug Resistant Escherichia coli

The purpose of present investigation was to understand the drug resistance reversal mechanism of 4‐hydroxy‐α‐tetralone ( 1 ) isolated from Ammannia spp. along with its semi‐synthetic derivatives ( 1a – 1e ) using multidrug resistant Escherichia coli (MDREC). The test compounds did not show significant antibacterial activity of their own, but in combination, they reduced the minimum inhibitory concentration (MIC) of tetracycline (TET). In time kill assay, compound 1 and its derivative 1e in combination with TET reduced the cell viability in concentration dependent manner. Compounds 1 and 1e were also able to reduce the mutation prevention concentration of TET. Both compounds showed inhibition of ATP dependent efflux pumps. In real time polymerase chain reaction (RT‐PCR) study, compounds 1 and 1e alone and in combination with TET showed significant down expression of efflux pump gene (yojI) encoding multidrug ATP binding cassettes (ABC) transporter protein. Molecular mechanism was also supported by the in silico docking studies, which revealed significant binding affinity of compounds 1 and 1e with YojI. This study confirms that compound 1 and its derivative 1e are ABC efflux pump inhibitors which may be the basis for development of antibacterial combinations for the management of MDR infections from inexpensive natural product.     

Discordant and heterogeneous clinically relevant genomic alterations in circulating tumor cells vs plasma DNA from men with metastatic castration resistant prostate cancer

Circulating tumor cell (CTC) and cell‐free (cf) DNA‐based genomic alterations are increasingly being used for clinical decision‐making in oncology. However, the concordance and discordance between paired CTC and cfDNA genomic profiles remain largely unknown. We performed comparative genomic hybridization (CGH) on CTCs and cfDNA, and low‐pass whole genome sequencing (lpWGS) on cfDNA to characterize genomic alterations (CNA) and tumor content in two independent prospective studies of 93 men with mCRPC treated with enzalutamide/abiraterone, or radium‐223. Comprehensive analysis of 69 patient CTCs and 72 cfDNA samples from 93 men with mCRPC, including 64 paired samples, identified common concordant gains in FOXA1, AR, and MYC, and losses in BRCA1, PTEN, and RB1 between CTCs and cfDNA. Concordant PTEN loss and discordant BRCA2 gain were associated with significantly worse outcomes in Epic AR‐V7 negative men with mCRPC treated with abiraterone/enzalutamide. We identified and externally validated CTC‐specific genomic alternations that were discordant in paired cfDNA, even in samples with high tumor content. These CTC/cfDNA‐discordant regions included key genomic regulators of lineage plasticity, osteomimicry, and cellular differentiation, including MYCN gain in CTCs (31%) that was rarely detected in cfDNA. CTC MYCN gain was associated with poor clinical outcomes in AR‐V7 negative men and small cell transformation. In conclusion, we demonstrated concordance of multiple genomic alterations across CTC and cfDNA platforms; however, some genomic alterations displayed substantial discordance between CTC DNA and cfDNA despite the use of identical copy number analysis methods, suggesting tumor heterogeneity and divergent evolution associated with poor clinical outcomes.     

Diagnostic utility of urine cytology in detection of decoy cells in renal transplant patients: Report of five cases and review of literature

BK polyoma virus (PV) is one of the commonest post‐transplant viral infections, affecting approximately 15% of renal transplantation recipients, leading to graft failure in more than half of cases. The epithelial cells with polyoma viral inclusions in urine cytology specimens are termed “decoy cells” to caution pathologists not to misdiagnose these cells as cancer cells. The infected cells in urinary sediments are characterized by enlarged nucleus, basophilic intranuclear homogenous inclusions, and ground glass chromatin, which may cause diagnostic error in urine cytology. We report five cases of renal transplant patients, in which urine sample was positive for decoy cells. Routine urine cytology of post renal transplant patients with worsening renal function is a useful screening procedure to rule out PV reactivation, before ascertaining transplant rejection. Its cost‐effectiveness in addition to the short processing time makes it an invaluable tool in the evaluation of transplant recipients with symptoms suggestive of graft rejection.     

Evaluation of Streptococcus mutans adhesion to fluoride varnishes and subsequent change in biofilm accumulation and acidogenicity

Objectives

The aim of this study was to evaluate Streptococcus mutans adhesion to fluoride varnishes and subsequent change in biofilm accumulation and acidogenicity.

Methods

After producing fluoride varnish-coated hydroxyapatite discs using Fluor Protector (FP), Bifluorid 12 (BIF), Cavity Shield (CASH), or Flor-Opal Varnish White (FO), S. mutans biofilms were formed on the discs. To assess S. mutans adhesion to the discs, 4-h-old biofilms were analysed. To investigate the change in biofilm accumulation during subsequent biofilm formation, the biomass, colony forming units (CFU), and water-insoluble extracellular polysaccharides (EP) of 46-, 70-, and 94-h-old biofilms were analysed. To investigate the change in acidogenicity, pH values of the culture medium were determined during the experimental period. The amount of fluoride in the culture medium was also determined during the experimental period.

Results

BIF, CASH, and FO affected S. mutans adhesion (67–98% reduction) and subsequent biofilm accumulation in 46-, 70-, and 94-h-old biofilms. However, the reducing effect of the fluoride varnishes on the biomass, CFU count, water-insoluble EP amount, and acid production rate of the biofilms decreased as the biofilm age increased. These results may be related to the fluoride-release pattern of the fluoride varnishes. Of the fluoride varnishes tested, FO showed the highest reducing effect against the bacterial adhesion and subsequent biofilm accumulation.

Conclusions

Our findings suggest that if the results of these experiments are extrapolable to the in vivo situation, then reduced clinical benefit of using fluoride varnishes may occur with time.

Clinical significance

Fluoride varnish application can affect cariogenic biofilm formation but the anti-biofilm activity may be reduced with time.     

Oral Verrucous Hyperplasia: A Case Report

Oral verrucous hyperplasia is a whitish or pinkinsh elevated pre malignant lesion which occurs rarely. Its is also considered to be an early form of verrucous carcinoma. We have reported a case of verrucous hyperplasia which was diagnosed and treated with buccal fat pad as graft.     

Lipoma of the Floor of the Mouth: Report of an Unusually Large Lesion

Lipomas are among the most common benign tumors affecting the human body. However, they are relatively uncommon in the oral cavity. Oral lipomas are likely to affect cheek, tongue, lips, gingiva and rarely the floor of the mouth. We report a case of huge lipoma of the floor of the mouth, associated with difficulty in speech and mastication in a 72-year-old male. The tumor was completely excised and sent for histopathological examination, which confirmed the tumor to be a simple classical lipoma.     

Development and validation of analytical method for the estimation of nateglinide in rabbit plasma

Nateglinide has been widely used in the treatment of type-2 diabetics as an insulin secretogoga. A reliable, rapid, simple and sensitive reversed-phase high performance liquid chromatography (RP-HPLC) method was developed and validated for determination of nateglinide in rabbit plasma. The method was developed on Hypersil BDSC-18 column (250 mm×4.6 mm, 5 mm) using a mobile phase of 10 mM phosphate buffer (pH 2.5) and acetonitrile (35:65, v/v). The elute was monitored with the UV–vis detector at 210 nm with a flow rate of 1 mL/min. Calibration curve was linear over the concentration range of 25–2000 ng/mL. The retention times of nateglinide and internal standard (gliclazide) were 9.608 min and 11.821 min respectively. The developed RP-HPLC method can be successfully applied to the quantitative pharmacokinetic parameters determination of nateglinide in rabbit model.     

A study on coronal incision for treating zygomatic complex fractures

Objective  To study the value of coronal incisions for treating zygomatic complex fractures and evaluate the advantages, indications and complications associated with it. Method  In this prospective study, 12 patients were randomly selected regardless of age, sex requiring open reduction and internal fixation of communited zygomatic complex fractures with or without other associated fractures of the midface. Patients were all treated by coronal approach for open reduction and internal fixation of fracture of the zygomatic complex. Other local incisions were used if required. Results  In all cases postoperative complications were relatively minor except in one case were the temporal branch of facial nerve weakness persisted at 3 months. Whereas 5 cases reported with slight weakness of the temporal branch of the facial nerve which resolved at the end of 3 months. The time taken for exposure of the fracture site via the coronal incision had a mean of 28.7 minutes. There were no cases of flap infection and just 1 case of stitch abscess reported. The same case later reported with a hypertrophic scar formation of greater than 0.5cm at 3months. In all other cases scar formation was negligible and well hidden within the hairline. There were no reported cases of paraesthesia at the operated site or hollowing of the temporal fossa. Conclusion  The coronal incision provides excellent access to the zygomatic arch and zygomatic complex, aiding in good anatomical reduction and also has the added advantage of the scar hidden in the hairline. It also has disadvantages like long operating time, risk of facial nerve injury, scarring in patients with male pattern baldness, paraesthesia of operated site etc. Therefore the incision should be judiciously used and not overused and indications strictly applied.