Role of FNAC in palpable chest wall lesions in developing country

Palpable chest wall lesions are unusual manifestation of an underlying thoracic pathology and it is difficult to diagnose them with their diverse spectrum ranging from benign to malignant. Considering the exposure of patient to invasive biopsy/excision and the risk of local complications, FNAC is now being increasingly used in the primary assessment of these lesions. Objectives of this study were to report the spectrum of chest wall lesions in the population of a developing country and evaluating the diagnostic role of FNAC. All the patients who presented with palpable cutaneous or subcutaneous chest wall swelling during a period of January 2003 to August 2010 were reviewed retrospectively. May Grunwald Giemsa and Papanicolaou stained aspirates were examined, along with special stains. Seven hundred seventy‐three cases were subjected to chest wall FNAC, of which 726 (93.9%) cases were satisfactory. Age ranged from 1 to 93 years with M:F = 0.92:1. 358 (49.3%) were diagnosed as inflammatory and 368 (50.7%) were neoplastic lesions. Two‐hundred thirty four cases (32.2%) were diagnosed as mycobacterial abscess (likely tuberculous). Of the neoplastic lesions, 153 were malignant with carcinomas being predominant (88.2%). Malignant cases comprised of scar site recurrence in breast carcinoma (73 cases), metastatic carcinomas (62 cases), primary sarcomas (eight cases), hematological neoplasms (six cases), and miscellaneous group (four cases). Overall malignant lesions accounted for 21.1% (153/726) of satisfactory chest wall aspirates. FNAC is very useful and simple investigation for early diagnosis of chest wall abscesses, cutaneous metastases from visceral malignancies, and scar site recurrence in breast carcinoma. Diagn. Cytopathol. 2014;42:653–659. © 2014 Wiley Periodicals, Inc.     

Is liquid heparin comparable to dry balanced heparin for blood gas sampling in intensive care unit?

Introduction:

Blood gas (BG) analysis is required for management of critically ill patients in emergency and intensive care units. BG parameters can be affected by the type of heparin formulations used-liquid heparin (LH) or dry balanced heparin (DBH). This study was conducted to determine whether blood gas, electrolyte, and metabolite estimations performed by using DBH and LH are comparable.

Materials and Methods:

A prospective study was conducted at pediatric intensive care unit (PICU) of a tertiary care hospital. Paired venous samples were collected from 35 consecutive children in commercially prepared DBH syringes and custom-prepared LH syringes. Samples were immediately analyzed by blood gas analyzer and compared for pH, pCO₂, pO₂, HCO₃⁻, Na⁺, K⁺, Cl^-, and lactate. Paired comparisons were done and agreement was assessed by Bland-Altman difference plots. The 95% limits of absolute agreement (LOA) were compared with the specifications for total allowable error (TEa).

Results:

The P values were significant for all measured parameters, with the exception of pCO₂ and K +. Bland-Altman difference plots showed wide LOA for pCO₂, pO₂, HCO₃⁻, Na⁺, K⁺, and Cl⁻ when compared against TEa. For pCO₂, HCO₃⁻, Na⁺, K⁺, and Cl⁻, 40%, 23%, 77%, 34%, and 54% of samples were outside the TEa limits, respectively, with LH.

Conclusion:

Our study showed that there is poor agreement between LH and DBH for the BG parameters pCO2, pO₂, HCO3^-, K⁺, Na⁺, and Cl⁻ and, thus, are not comparable. But for pH and lactate, LH and DBH can be used interchangeably.     

High-fidelity DNA histograms in neoplastic progression in Barrett's esophagus

This study describes the high-fidelity DNA histograms in different stages of neoplastic progression to Barrett's adenocarcinoma (BAC). High-fidelity DNA histograms were obtained with image cytometry on sections, and were classified based on DNA index values of the peaks into diploid, mild aneuploid, moderate aneuploid and severe aneuploid. Heterogeneity index (HI) representing cells with different DNA content and the 5N exceeding cell fraction were determined. One hundred and eighty-seven cases, including 34 normal gastrointestinal mucosa (control), 66 Barrett's-specialized intestinal metaplasia (SIM), 22 low-grade dysplasia (LGD), 22 high-grade dysplasia (HGD) and 43 BAC were investigated. Controls showed sharp diploid peaks with HI values less than 13, and no 5N exceeding nuclei. SIM showed a spectrum of histograms including diploid, mild aneuploid and moderate aneuploid histograms. The frequency and severity of aneuploidy increased with worsening histological grades of dysplasia. All BAC cases were aneuploid, with moderate or severe aneuploidy. Marked elevated HI values (>20) and 5N exceeding fractions (>5%) were found in 5%, 32%, 50% and 88% of cases with SIM, LGD, HGD and BAC, respectively. The high-fidelity DNA histograms suggest that (1) Barrett's SIM may already be dysplastic in nature, and all BAC may be markedly aneuploid; and (2) elevated cellular DNA heterogeneity and 5N fractions may be markers of progressive chromosomal changes and 'unstable aneuploidy' that identifies progressive lesions.     

Significance of IFN‐ɤ/IL‐2 Ratio as a Circulating Diagnostic Biomarker in Extrapulmonary Tuberculosis

Extrapulmonary tuberculosis (EPTB) remains a challenging diagnosis both for clinicians and microbiologists. We hypothesized that the profile of IFN‐?/IL‐2 ratio in clinically diagnosed cases of EPTB would be distinct from that of age‐ and sex‐matched healthy controls. Therefore, in our study, we have assessed the ratio of serum levels of IFN‐? and IL‐2 in clinically diagnosed cases of EPTB to assess their potential role as diagnostic biomarkers. Sixty‐nine (69) clinically confirmed EPTB cases and 69 age‐ and sex‐matched healthy controls were included in the study. All the extrapulmonary specimens were subjected to Ziehl–Neelsen staining for acid‐fast bacilli and culture on Lowenstein–Jensen (LJ) medium. Detection of serum levels of IFN‐? and IL‐2 was carried out using commercially available ELISA kits following manufacturers' instructions. The ratio of serum levels of IFN‐? and IFN‐?/IL‐2 was discriminative for the diagnosis of EPTB cases (p < 0.001), although the same was not observed with IL‐2 (p > 0.05). Distribution of all biomarkers significantly differed between culture‐positive and culture‐negative cases (p < 0.05). Among the smear‐positive and smear‐negative ones, only IFN‐? and IFN‐?/IL‐2 ratio could significantly differentiate (p < 0.05). Ratio of IFN‐? and IL‐2 rather than the individual levels was the best discriminatory biomarker with the highest area under the ROC curve. Although IFN‐? and IFN‐?/ IL‐2 ratio could aid in the diagnosis of EPTB, IL‐2 has a limited utility in the diagnosis of EPTB. Further elaborate studies to validate these results are required.     

Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience.

A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n = 2). Donor/recipient HLA matching based on low-/intermediate-resolution molecular typing for HLA-A and -B and high-resolution HLA-DRB1 typing was 5/6 or 6/6 (n = 21) or 4/6 (n = 11). The preparative therapy consisted of busulfan, melphalan, and antithymocyte globulin, with cyclosporine and corticosteroids for graft-versus-host disease (GVHD) prophylaxis. The median age was 1.6 years (range, 0.5-3.9 years), and the median weight was 10.5 kg (range, 5.8-19.5 kg). Cord blood grafts contained a median of 10.7 x 10 7 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 x 10(5) CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/microL) at day 42 was 0.59 (95% confidence interval [CI], 0.44-0.78) at a median of 31 days (range, 23-55 days). The CINC and Kaplan-Meier estimates of platelet engraftment at day 180 were 0.53 (95% CI, 0.34-0.69) and 0.82 (95% CI, 0.61-1.00), respectively. CINC estimates of grade III/IV acute GVHD at day 100 and chronic GVHD at 1 year were 0.25 (95% CI, 0.09-0.41) and 0.26 (95% CI, 0.09-0.44), respectively. The CINC estimate of relapse was 0.31 (95% CI, 0.16-0.47) at 2 years. With a median follow-up of 27.8 months (range, 23.4-46.7 months), the probability of survival at 1 year was 0.47 (95% CI, 0.30-0.64). A preparative regimen containing a busulfan/melphalan/antithymocyte globulin preparative regimen is well tolerated in the setting of unrelated donor cord blood transplantation for childhood leukemia and can serve as a platform preparative regimen for intensifying host immunosuppression and antileukemic therapy to allow for improved engraftment and improved relapse-free survival.     

Large deformation three-dimensional image registration in image-guided radiation therapy

In this paper, we present and validate a framework, based on deformable image registration, for automatic processing of serial three-dimensional CT images used in image-guided radiation therapy. A major assumption in deformable image registration has been that, if two images are being registered, every point of one image corresponds appropriately to some point in the other. For intra-treatment images of the prostate, however, this assumption is violated by the variable presence of bowel gas. The framework presented here explicitly extends previous deformable image registration algorithms to accommodate such regions in the image for which no correspondence exists. We show how to use our registration technique as a tool for organ segmentation, and present a statistical analysis of this segmentation method, validating it by comparison with multiple human raters. We also show how the deformable registration technique can be used to determine the dosimetric effect of a given plan in the presence of non-rigid tissue motion. In addition to dose accumulation, we describe a method for estimating the biological effects of tissue motion using a linear-quadratic model. This work is described in the context of a prostate treatment protocol, but it is of general applicability.     

Prediction of perinatal outcome in preeclampsia using middle cerebral artery and umbilical artery pulsatility and resistance indices

Objective: In preeclampsia, changes in fetal hemodynamics can be detected 2–3 weeks earlier than any changes in cardiotocogram. Thus, these Doppler changes can be used to predict perinatal outcome. The present study is planned to assess the accuracy of the middle cerebral artery to umbilical artery (UA) pulsatility index (PI) and resistance index (RI) in predicting adverse perinatal outcome in pregnancies complicated by preeclampsia. Methods: Total of 115 and 108 pregnant women were included in preeclampsia and control group, respectively. Weekly Doppler study was done in both groups starting from 30 weeks till 36 weeks or delivery, whichever is later. Results: Mean gestational age at delivery was 250 ± 13 and 273 ± 8 days, respectively, in preeclampsia and control group (p < 0.01). Thirty-four babies in preeclampsia group had been admitted to nursery; out of which three died (p < 0.01). On receiver operating characteristic analysis, MCA /UmA PI ratio and MCA /UmA RI ratio had sensitivity of 9% and 9.7% and specificity of 98% and 96.6%, respectively, for predicting adverse perinatal outcome. Conclusion: Doppler indices of MCA and Um A are significantly abnormal in preeclampsia. But on diagnostic statistical analysis they have good specificity but low sensitivity for detecting adverse perinatal outcome.     

Impedance of a goat eye lens

The complex electrical impedance of a goat eye lens is studied in the frequency range 10mHz−10Hz at room temperature, using a computer-controlled AC impedance system. AC impedance software (model 368, version 2.2) is employed to determine the total impedance and capacitance of the eye lens at various frequencies. A Cole-Cole plot of the eye lens material is drawn between the real component of impedance Z′ and the imaginary component Z″ for each excitation frequency that shows a perfect arc of a semicircle, with its centre lying below the abscissa at an angle of 35°. The half-angle ϕ between R₀ and R_∞ is found to be 55°, which mathematically demonstrates the selective permeability of the eye lens. Using graphical analysis of the Cole-Cole plot, characteristic frequency f_c and distribution factor α are observed to be 1Hz and 0.77, respectively. At characteristic frequency, capacitance and total impedance are found to be 1.14μF and 9.08kΩ. The effect of electrode polarisation on capacitance is corrected, based on Fricke's power function. The observed electrical parameters are then used to explain the multiple current path through various tissue compartments. Further, an attempt is made to explain the results on the basis of a possible dipolar model.     

Inverted terminal repeat sequences of adeno-associated virus enhance the antibody and CD8(+) responses to a HIV-1 p55Gag/LAMP DNA vaccine chimera

The immune responses to an HIV-1 p55Gag vaccine encoded as a DNA chimera with the lysosomal associated membrane protein-1 (LAMP) have been examined for the effect of the addition of the inverted terminal repeat (ITR) sequences of the adeno-associated virus (AAV) to the DNA plasmid construct, and of packaging the LAMP/gag gene as a recombinant AAV vector (rAAV). DNA plasmids encoding Gag and the LAMP/Gag protein chimera were constructed in two vectors, the pcDNA3.1 and a corresponding plasmid containing the ITR sequences (pITR) flanking the expression elements of the plasmid, and the pITR LAMP/gag DNA plasmid was encapsidated in the rAAV vector. Human 293 cells transfected in vitro with LAMP/gag plasmids either in pcDNA3.1 or pITR produced much Gag protein in cell extracts (1.6 and 2.2 ng of Gag/mg of protein, respectively). The immune responses of mice to immunization with these constructs were examined under three protocols: DNA prime/DNA boost, DNA prime/rAAV boost, and a single rAAV immunization. The results demonstrated that under DNA prime/DNA boost protocol, the "naked" DNA vaccines encoding the LAMP/gag chimera, either as pcDNA3.1 or pITR DNA plasmid constructs, elicited strong CD4(+) T cell responses. In contrast, significantly higher levels of CD8(+) and antibody responses were observed with the pITR-DNA constructs. Immunization with the rAAV vector under the DNA prime/rAAV boost protocol resulted in sustained T cell responses and a markedly increased antibody response, predominantly of the IgG(1) isotype resulting from the activation of the Th2 subset of CD4(+) T cells, that was sustained for at least 5 months after immunization.