Dermatopathology for the surgical pathologist: a pattern based approach to the diagnosis of inflammatory skin disorders (part I)

The accurate diagnosis of inflammatory conditions in dermatopathology requires integrating the histopathologic findings with the clinical features. This can be difficult when skin biopsies are seen infrequently and the terminology is unfamiliar, as in a general surgical pathology practice. This 2-part review of inflammatory cutaneous conditions presents a pattern-based approach to the diagnosis of dermatologic disorders and reviews the salient clinical and histologic features. Part I will focus on the spongiotic, psoriasiform, interface, and bullous patterns, whereas Part II will review the perivascular, vasculitis, panniculitis, and nodular and diffuse patterns.     

Thyroid-associated ophthalmopathy in Iranian patients

We determined the frequency of clinical thyroid ophthalmopathy in Iranian patients. This cross-sectional study was performed at the Endocrinology Institute of Tehran University of Medical Sciences. All patients with documented thyroid disorders from September 2003 to July 2005 were recruited. Eye examinations included evaluation of soft tissue changes, measurement of proptosis, lid width, lagophthalmos, evaluation of eye muscle function, and determination of visual acuity. The activity of ophthalmopathy was scored according to the NOSPECS scale. Among 851 visited patients, 303 cases had thyroid eye disease (TED). The nature of the ophthalmopathy breaks down as follows: 53.4% were hypothyroid (9.3% Hashimoto disease), 5.5% euthyroid and 41.1% had Graves' disease. The prevalence of TED in males was 60% which was nearly 2 times the prevalence of TED in females. There was a significant relationship between presentation of TED and active smoking of the patients (P<0.0001) while no significant relationship with passive smoking was obtained (P=0.181). The most common clinical sign of TED in descending order respectively were proptosis with 63.4%, soft tissue involvement (40.9%), extraocular muscle involvement (22.1%), corneal involvement (12.9%) and optic nerve dysfunction (6.3%). Myasthenia gravis occurred in only 2 patients. In the logistic regression, occurrence of TED was influenced by cardiovascular disease (OR=5.346), Graves' disease (OR=47.507), radioiodine therapy (OR=2.590), and anti-thyroid medications (OR=0.650). Thyroid ophtalmopathy (orbitopathy) is a matter of important health concern among patients with thyroid disorder. Since TED occurred with a high prevalence in all thyroid states, a close collaboration between endocrinologists and ophthalmologists along with timely referrals of patients with any eye complaint is deemed necessary. Also smoking was the most important risk factor for developing TED. Therefore, it is advisable to raise awareness and to strongly encourage smokers with thyroid disorders to quit smoking.     

Chronic allergen challenge induces pulmonary extramedullary hematopoiesis

Allergic inflammation is associated with increased generation and trafficking of inflammatory cells, especially eosinophils, to sites of inflammation. The effect of acute versus chronic airway allergen challenge on hematopoietic activity in the bone marrow (BM) and lungs was investigated using murine models of allergic airway inflammation. Acute allergen challenge induced proliferation of BM cells and significantly increased generation of eosinophil, but not multipotent, granulocyte-macrophage (GM), or B-lymphocyte progenitor cells. However, no hematopoietic activity was observed in the lungs. With chronic challenge, BM cells failed to proliferate, but exhibited increased capacity to generate multipotent as well as eosinophil, GM, and B-lymphocyte progenitors. In addition, increased generation of eosinophil- and GM-specific progenitors was observed in the lungs. Although no differences were observed in their ability to roll on BM endothelium in vitro or in vivo, CD34-enriched hematopoietic/stem progenitor cells (HSPCs) from chronic-, but not acute-, challenged mice demonstrated reduced migration across BM endothelial cells associated with decreased CXCR4 expression. Overall, these studies demonstrate that chronic allergen exposure can alter BM homing due to decreased transendothelial migration enabling noninteracting HSPCs to egress out of the BM and recruit to sites of inflammation such as the airways, resulting in extramedullary hematopoiesis.     

The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.     

Volatile organic compound detection as a potential means of diagnosing cutaneous wound infections

Chronic cutaneous wound infections and surgical site infections (SSIs) present a huge burden on the healthcare system and can lead to increased morbidity and mortality. Current diagnostic methods of identifying and confirming infection involve culture‐based and molecular methods. Both techniques are time‐consuming and delays commonly lead to untargeted empirical treatment. An ideal diagnostic method would be noninvasive and highly sensitive and detect pathogenic organisms with a high degree of accuracy to allow targeted treatment. Volatile organic compounds (VOCs) are a diverse group of carbon‐based molecules produced and released by humans and microorganisms. VOC detection has the potential in aiding cutaneous wound infection diagnostics using noninvasive and time‐efficient methods. This review provides a comprehensive update on VOCs produced and emitted by bacteria commonly associated with chronic wounds and SSIs. VOC sampling has the advantage of being painless, time‐efficient, noninvasive, and reproducible. VOCs emitted by these organisms are diverse. In vitro studies have identified potential signature volatile profiles, which can be used in detecting these microorganisms. Combining these profiles with volatile profiles emitted from acute, chronic and surgical wounds in vivo could potentially allow identification of bacterial‐specific VOCs. VOC detection has the potential for a relatively inexpensive, portable, noninvasive, and reliable clinical diagnostic tool, which could be used in detecting cutaneous wound infections and guiding their optimal management.     

Late repair of simultaneous bilateral distal biceps brachii tendon avulsion with fascia lata graft

A 50 year old rock climber sustained a bilateral rupture of the distal biceps brachii tendons. He retained some flexion power in both arms but minimal supination, being weaker on the non-dominant right side. As the patient presented late, with retraction and shortening of the biceps muscle bellies, reconstruction was carried out using fascia lata grafts on both sides. Because of residual weakness on the left (dominant) side, three further surgical procedures had to be carried out to correct for elongation of the graft. A functionally satisfactory outcome, comparable with that on the right side, was eventually obtained. In summary, bilateral fascia lata grafts to bridge the gap between the retracted biceps bellies and the radial tuberosities were successful in restoring function and flexion power to the elbow. Despite being the stronger side, the dominant arm did not respond as well to the initial surgery. This may be due to overuse of this arm after the operation.     

A facile and efficient route to one-pot synthesis of new cyclophanes using vinamidinium salts

In this study, an efficient method for the synthesis of new cyclophanes (5a–f, 6a–g) through the condensation of 1,4-phenylenedimethanamine (3) or 2,3,5,6-tetramethylbenzene-1,4-diamine (4) with 2-substituted vinamidiniums (2a–g) is described. The cyclophane derivatives are obtained in good to excellent yields in the presence of acetic acid in refluxing acetonitrile after 15 h. The structure of new compounds was validated based on their spectral data (¹H NMR, ¹³C NMR, IR) and elemental analysis.

New cyclophane derivatives are synthesized from the reaction of γ-substituted vinamidinium salts with 1,4-phenylenedimethanamine and 2,3,5,6-tetramethylbenzene-1,4-diamine in the presence of acetic acid and acetonitrile as solvent.     

Regenerating heavily biofouled dissolved oxygen sensors using bacterial viruses

Bacterial biofilms are aggregates of bacterial cells embedded in a self-produced extracellular polymeric matrix. Biofilm formation has always been considered a major challenge for sensors used in underwater measurements, and is a primary source of measurement error, especially when it comes to long-term in situ monitoring. We demonstrate the utility of lytic bacteriophages (bacterial viruses) as a non-invasive strategy for removing bacterial biofilms formed on the gas permeable membrane of electrochemical dissolved oxygen sensors. Our results show that a 4 day Pseudomonas aeruginosa biofilm with a fully developed matrix significantly affected the sensor signal and response time, decreasing the signal by 32% and increasing the response time by 94%. In addition, measurements with the biofouled membrane had a very low signal to nose ratio compared to a clean sensor membrane. A single dose of overnight phage treatment effectively removed the biofilm (as indicated by scanning electron micrographs and fluorescence images of the membrane), without the need for repeated treatments. Furthermore, the sensor signal that had plummeted by 32% for a fully biofouled membrane, was returned to the original value (7.96 ± 0.27 mg L⁻¹) after phage treatment and the signal to noise ratio (calculated as the ratio of mean to standard deviation) increased 8 folds for a phage-treated membrane compared to a biofouled membrane. Our data indicate near complete regeneration and signal recovery for the dissolved oxygen sensor, making the biofouled sensor reusable without the use of harsh chemicals that could destroy the fragile sensor membrane.

Lytic bacteriophages can be utilized as a non-invasive method for removing bacterial biofilms formed on the surface of gas permeable membranes of dissolved oxygen sensors.     

Characterizing a Cohort of α-Thalassemia Couples Collected During Screening for Hemoglobinopathies: 14 Years of an Iranian Experience

Our study aimed to determine the number of couples with normal hemoglobin (Hb) electrophoresis and low-borderline hematological values, which may come up with a clinically critical status in their offspring. The number of couples at risk for severe α-thalassemia (α-thal) needed to be estimated before recommending genetic counseling and prenatal diagnosis (PND). During the past 14 years, from at least 7000 referrals, 754 couples were investigated for α-thal by direct mutation detection methods followed by reverse strip assay and α-globin gene sequencing for inconclusive cases. Detection of silent β-thalassemia (β-thal) mutations was done in suspected cases by complete β-globin gene sequencing. We were able to provide a molecular diagnosis in 87.3% (658/754) of couples. A total of 9.1% (60/658) may have a clinically significant hemoglobinopathy in their offspring. Significant conditions included hydrops fetalis (20.0%; 12/60), certain Hb H (β4) genotypes (78.3%; 47/60) and β-thal intermedia (β-TI) (1.7%; 1/60). The diagnostic flowchart for couples with microcytic hypochromic anemia in countries with a high prevalence of hemoglobinopathies should include α and β gene sequencing. As our results indicate, every nine out of 100 of these couples will face significant hemoglobinopathies and every two out of 100 can carry Hb Bart’s (γ4) hydrops fetalis in their pregnancies. For such cases, PND should be utilized to allow the carrier couples to decide whether or not to abort the fetus.