Evaluation of chemiluminescence, toluidine blue and histopathology for detection of high risk oral precancerous lesions: A cross-sectional study

Background

Chromogenic in situ hybridization (CISH) is fast becoming a well established technique for easy and sensitive determination of HER2 gene status in breast cancer. However, for the chromogenic method to achieve status as a safe and reliable technique, the method needs to be validated against already known and validated FISH techniques.

Methods

Here it is reported from a comparative study where HER2 gene status obtained by HER2 CISH pharmDx? Kit was compared to HER2 gene status obtained by the FDA approved HER2 FISH pharmDx? Kit and the PathVysion HER-2 DNA probe Kit. The study included 365 formalin fixed and paraffin-embedded invasive breast cancer tissue specimens collected consecutively at a US reference laboratory.

Results

The data obtained revealed an overall HER2 status concordance of approximately 98% for comparisons of HER2 CISH pharmDx? Kit to both HER2 FISH pharmDx? Kit and PathVysion HER-2 DNA Probe Kit.

Conclusions

The concordance between results obtained using the recently FDA approved HER2 CISH pharmDx? Kit with previously FDA approved FISH techniques for HER2 gene status determination indicate that the HER2 CISH pharmDx? Kit is a reliable chromogenic alternative to fluorescence-based methods.     

Photo Essay: Retinal Changes in Type 3 Gaucher Disease

Ocular features of Gaucher disease include gaze abnormalities, corneal clouding, ocular deposits and pigmentary changes in the macula. We report the presence of bilateral fovea sparing macular deposits in a 21-year-old woman with type 3 Gaucher disease. Macular deposits occur due to glucocerebroside accumulation within histiocytes and retinal deposits might correlate with the degree of systemic infiltration.     

Spontaneous bacterial empyema in a noncirrhotic patient: an unusual scenario

Spontaneous bacterial empyema (SBEM) is infection of a preexisting pleural effusion without evidence of pneumonia. It has been reported mostly in patients with hepatic hydrothorax. Only 1 case of SBEM in a noncirrhotic patient has been reported. We present an unusual case of bilateral SBEM from Streptococcus pneumoniae bacteremia in a noncirrhotic patient. A 52-year-old man presented with bilateral pleuritic chest pain and dyspnea for 2 days. His medical history included congestive heart failure, hemodialysis-dependent renal failure and known bilateral pleural effusions. No ascites or hepatosplenomegaly was noticed. Bilateral pleural effusions were again present on physical examination and confirmed by a chest computed tomography scan. Cardiac medical treatment and hemodialysis failed to improve his condition. Bilateral thoracentesis revealed purulent pleural fluid that was culture-positive for Streptococcus pneumonia as were blood cultures. There was no clinical or radiographic evidence of pneumonia. The detailed clinical course, treatment and highlighted points are described.     

Role of red cell distribution width in classifying microcytic hypochromic anaemia

Red cell distribution width (RDW) is an automated laboratory determination of red cell anisocytosis. The aim of the study was to analyse the role of RDW in differentiating iron deficiency anaemia (IDA) from thalassaemia trait. There were 500 patients who were screened for the study. Selection criteria of microcytic anaemia were Hb < 13 g/dl in males, Hb < 12 g/dl in females with mean corpuscular volume (MCV) < 80fl. These cases were subjected to complete iron profile and haemoglobin chromatography for definite diagnosis. The values of RDW were analysed in all these cases to see the utility of RDW in classifying microcytic anaemia; especially differentiating iron deficiency anaemia from thalassaemia minor cases. There were 133 out of 500 cases anaemic; 105/133 cases had microcytic anaemia, of which 53 had iron deficiency anaemia, 39 were thalassaemia traits, 6 were thalassaemia major, and 7 had other haemoglobinopathies. Thirty-six cases (67.92%) out of 53 iron deficiency anaemia had increased RDW, 32.08% (n = 17) had normal RDW; 71.79% (n = 28) of thalassaemia trait had increased RDW, 28.21% (n =11) had normal RDW. Evaluation of RDW as screening test to detect microcytic anaemia had sensitivity of 71.42% and specificity of 40%, Evaluation of RDW as a screening test for IDA had sensitivity of 67.9% and specificity 25%. It was found uniform increase in RDW in all cases of microcytosis. It is concluded that RDW adds useful but limited information in classifying microcytic anaemia.     

A comparative study of insulin resistance for Saudi and Caucasian subjects across a range of glycaemic categories

AimSaudi and Caucasian subjects, matched for adiposity, and of differing glycaemic status were compared using several insulin sensitivity indices and to also to assess insulin, glucose and insulin-like growth factor binding protein-1 (IGFBP-1) responses to intravenous glucose.MethodsSubjects with normal glucose tolerance (NGT; n = 24), impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), and type 2 diabetes (DM; n = 13) were recruited from Saudi (n = 33) and Caucasian (n = 28) populations. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test (FSIVGTT) at a second visit.ResultsSaudis in the NGT and pooled glucose intolerance categories had significantly higher diastolic blood pressure (p < 0.001, p < 0.05 respectively) and HbA1c (p < 0.01, p < 0.05 respectively) compared to Caucasians. Caucasians in the NGT category had significantly higher Si, fasting and 2 h IGFBP-1 (p < 0.01, p < 0.05 and p < 0.01 respectively) compared to Saudis. Two hours following oral or intravenous glucose serum IGFBP-1 decreased to 44% (p < 0.001) and 50% (p < 0.05) of baseline levels respectively.ConclusionsOur data suggest that adult Saudis with normal glucose tolerance appear to be more insulin resistant than Caucasians matched for adiposity. In normal individuals at 2 h the IGFBP-1 level will be about half the baseline level regardless of the route of glucose administration.     

Subtype‐specific peripheral blood gene expression profiles in recent‐onset juvenile idiopathic arthritis

Objective

To identify differences in peripheral blood gene expression between patients with different subclasses of juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent‐onset JIA prior to treatment with disease‐modifying antirheumatic drugs (DMARDs) or biologic agents.

Methods

Peripheral blood mononuclear cells (PBMCs) from 59 healthy children and 136 patients with JIA (28 with enthesitis‐related arthritis [ERA], 42 with persistent oligoarthritis, 45 with rheumatoid factor [RF]–negative polyarthritis, and 21 with systemic disease) were isolated from whole blood. Poly(A) RNA was labeled using a commercial RNA amplification and labeling system (NuGEN Ovation), and gene expression profiles were obtained using commercial expression microarrays (Affymetrix HG‐U133 Plus 2.0).

Results

A total of 9,501 differentially expressed probe sets were identified among the JIA subtypes and controls (by analysis of variance; false discovery rate 5%). Specifically, 193, 1,036, 873, and 7,595 probe sets were different in PBMCs from the controls compared with those from the ERA, persistent oligoarthritis, RF‐negative polyarthritis, and systemic JIA patients, respectively. In patients with persistent oligoarthritis, RF‐negative polyarthritis, and systemic JIA subtypes, up‐regulation of genes associated with interleukin‐10 (IL‐10) signaling was prominent. A hemoglobin cluster was identified that was underexpressed in ERA patients but overexpressed in systemic JIA patients. The influence of JAK/STAT, ERK/MAPK, IL‐2, and B cell receptor signaling pathways was evident in patients with persistent oligoarthritis. In systemic JIA, up‐regulation of innate immune pathways, including IL‐6, Toll‐like receptor/IL‐1 receptor, and peroxisome proliferator–activated receptor signaling, were noted, along with down‐regulation of gene networks related to natural killer cells and T cells. Complement and coagulation pathways were up‐regulated in systemic JIA, with a subset of these genes being differentially expressed in other subtypes as well.

Conclusion

Expression analysis identified differentially expressed genes in PBMCs obtained early in the disease from patients with different subtypes of JIA and in healthy controls, providing evidence of immunobiologic differences between these forms of childhood arthritis.

     

Association of microsomal epoxide hydrolase exon 3 Tyr113His and exon 4 His139Arg polymorphisms with gastric cancer in India

Background

Microsomal epoxide hydrolase, an important phase II xenobiotic enzyme, exhibits polymorphisms at exon 3 (Tyr113His [T/C]) and exon 4 (His139Arg [A/G]), which modulate enzyme activity; this may affect susceptibility to cancers. We studied association between these polymorphisms and gastric cancer (GC).

Methods

In a prospective study, 77 patients with GC, 50 with peptic ulcer, and 160 healthy controls (HC) were genotyped for exon 3 (PCR-RFLP followed by sequencing) and exon 4 (PCR-RFLP). Helicobacter pylori was considered to be present if two of three tests (histology, rapid urease test, and IgG antibody) were positive.

Results

Tyr113His and His139Arg genotypes and haplotypes were comparable among groups. 113His carriers were commoner among H. pylori-negative patients with GC than HC (p-value?=?0.019, odds ratio (OR)?=?2.5, 95 % confidence interval (CI)?=?1.2–5.4). Haplotype combination of exons 3 and 4 113Tyr-139Arg (TA) were associated with higher and reduced risk in patients with GC than HC in presence and absence of H. pylori (25 % vs. 11 %; p-value?=?0.033, OR?=?2.61, 95 % CI?=?1.08–6.3 and 11.6 % vs. 28.7 %; p-value?=?0.004, OR?=?0.33, 95 % CI?=?0.15–0.7, respectively).

Conclusions

Though 113Tyr-139Arg was associated with GC in presence of H. pylori, in its absence, it appeared to be protective. Exon 3, 113His, however, was associated with GC even in absence of H. pylori infection.     

Combinatorial antimicrobial effect of curcumin with selected phytochemicals on Staphylococcus epidermidis

Staphylococcus epidermidis is reported to be the main causative agent of nosocomial infections. It has become increasingly difficult to treat this micro-organism because of the emergence of new antibiotic-resistant strains and its ability to form biofilm on medical associated devices. Phytochemicals acting in synergy are effective in killing the micro-organisms by lowering the doses, and synergistic compounds evade the development of resistance due to different mechanism of action. This study aims to determine the synergistic antimicrobial potential of curcumin with cinnamaldehyde, eugenol, and ellagic acid against S. epidermidis. Curcumin with ellagic acid as well as eugenol were found to have additive antimicrobial effect, whereas, in combination, curcumin and cinnamaldehyde were found to have synergistic effect against S. epidermidis (fractional inhibitory concentration index (FICI) = 0.5). Synergy between curcumin and cinnamaldehyde was established by time–kill kinetics and was further evaluated for antibiofilm activity. The dose required to inhibit biofilm formation was reduced to half than that needed to inhibit its planktonic culture (minimal inhibitory concentration (MIC) of curcumin = 3.12 μg/ml; MIC of cinnamaldehyde = 15.62 μg/ml; FICI = 0.248). Both curcumin and cinnamaldehyde disrupted the bacterial membrane for killing the bacteria as determined by permeability studies on Escherichia coli ML-35p.