Evolution of Treatment of Fistula in Ano

Background  

Fistula-in-ano is a common medical problem affecting thousands of patients annually. In the past, the options for treatment of fistula-in-ano were limited to fistulotomy and/or seton placement. Current treatment options also include muscle-sparing techniques such as a dermal island flap, endorectal advancement flap, fibrin sealent injection, anal fistula plug, and most recently ligation of the intersphincteric fistula tract (procedure). This study seeks to evaluate types and time trends for treatment of fistula-in-ano.     

Hepatic Resection for Colorectal Metastasis: Impact of Tumour Size

Background Many colorectal liver metastasis patients are denied surgical resection on the basis of tumour size. The aim of this study was to explore the impact of metastasis size on modern liver resection.Methods Using a prospectively collected database, this was a retrospective analysis of 484 consecutive patients who underwent liver resection for colorectal liver metastases between 1993 and 2003. The cohort was divided into two groups: smaller metastases (<8 cm) and larger metastases (≥ 8 cm). Those with larger metastases were then further stratified into big metastases (8–12 cm) and giant metastases (>12 cm). Demographic, pathological, surgical technique and outcome data were compared between the groups.Results There were 88 (18%) patients with metastases measuring 8 cm or larger. There was an association between higher carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels and larger metastases. The actuarial 5-year survival for patients with larger metastases was 38% compared with 42% for smaller metastases (not statistically significant). Patients with giant metastases had poorer overall and disease-free survival (both nonsignificant) compared with those with big metastases: 29% and 28% at 5 years, respectively.Conclusion Patients with colorectal liver metastasis greater than 8 cm and up to 12 cm in size should not be treated differently from those with smaller lesions.     

Evaluation of cytotoxic, oxidative stress, proinflammatory and genotoxic responses of micro- and nano-particles of dolomite on human lung epithelial cells A(549)

Dolomite is a natural mineral of great industrial importance and used worldwide, thus millions of workers are at risk of occupational exposure. Its toxicity is however, meagerly documented. In the present investigation, a dolomite powder obtained from its milling unit was analyzed by some standard methods namely, optical microscopy, transmission electron microscopy and dynamic light scattering. Results showed that dolomite powder contained particles of different shapes and size both microparticles (MPs) and nanoparticles (NPs), suggesting potential occupational exposure of these particles. An attempt was therefore, made to investigate dolomite toxicity in a particle size-dependent manner in human lung epithelial cells A(549). The comparative toxicity evaluation of MPs and NPs was carried out by assessing their effects on cell viability, membrane damage, glutathione, reactive oxygen species (ROS), lipid peroxidation (LPO), micronucleus (MN) and proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). These markers of cytotoxicity, genotoxicity and inflammation were assayed in cells exposed to MPs and NPs in a dose-and time-dependent manner. Invariably, their toxic effects were dose-and time-dependent while NPs in general were significantly more toxic. Notably, NPs caused oxidative stress, genotoxicity and inflammatory responses, as seen by significant induction of ROS, LPO, MN, TNF-α, IL-1β and IL-6. Thus, the study tends to suggest that separate health safety standards would be required for micrometer and nanometer scale particles of dolomite.     

A Rare Association of Left Ventricular Diverticulum and Noncompaction: Continuum of Common Developmental Abnormality?

A previously healthy 16‐year‐old girl presented with history of fever of 3 months duration without any significant clinical finding on examination. Transthoracic echocardiography (TTE) revealed moderate pericardial effusion and later diagnosed as tubercular in etiology. Besides, TTE also showed an incidental finding of large left ventricular (LV) diverticulum in submitral region along the postero‐basal segment and left ventricular noncompaction (LVNC). Nonapical LV diverticulum is a rare variant of this uncommon congenital condition and its association with LVNC has not been reported in literature. Patient was discharged on antitubercular therapy for pericardial effusion and advised for 6 monthly follow‐up for diverticulum.     

Prostaglandin E2 Promotes UV Radiation-Induced Immune Suppression through DNA Hypermethylation

Exposure of mice to UV radiation results in suppression of the contact hypersensitivity (CHS) response. Here, we report that the UV-induced suppression of CHS is associated with increases in the levels of cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂), and PGE₂ receptors in the exposed skin. UV radiation-induced suppression of CHS was inhibited by topical treatment of the skin with celecoxib or indomethacin (inhibitors of COX-2) or AH6809 (an EP2 antagonist). Moreover, mice deficient in COX-2 were found to be resistant to UV-induced suppression of CHS. The exposure of wild-typemice to UVB radiation resulted in DNA hypermethylation, increased DNA methyltransferase (Dnmt) activity, and elevated levels of Dnmt1, Dnmt3a, and Dnmt3b proteins in the skin, and these responses were downregulated on topical treatment of the site of exposure after irradiation with indomethacin or EP2 antagonist. Topical treatment of UVB-exposed COX-2-deficient mice with PGE₂ enhanced the UVB-induced suppression of CHS as well as global DNA methylation and elevated the levels of Dnmt activity and Dnmt proteins in the skin. Intraperitoneal injection of 5-aza-2′-deoxycytidine (5-Aza-dc), a DNA demethylating agent, restored the CHS response to 2,4-dinitrofluorobenzene in UVB-exposed skin and this was associated with the reduction in global DNA methylation and Dnmt activity and reduced levels of Dnmt proteins. Furthermore, treatment with 5-Aza-dc reversed the effect of PGE₂ on UV-induced suppression of CHS in COX-2-deficient mice. These findings reveal a previously unrecognized role for PGE₂ in the promotion of UVB-induced immunosuppression and indicate that it is mediated through PGE₂ regulation of DNA methylation.     

Diagnosis of Paroxysmal Nocturnal Hemoglobinuria: Recent Advances

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder with its protean clinical manifestations. This is due to partial or complete absence of ‘glycophosphatidyl-inositol-anchor proteins’ (GPI-AP). The main aim of this review is to highlight various diagnostic modalities available, basic principle of each test and recent advances in the diagnosis of PNH. Recently among various tests available, the flow cytometry has become ‘the gold standard’ for PNH testing. In order to overcome the difficulties encountered by the testing and research laboratories throughout the world, International Clinical Cytometry Society has come up with guidelines regarding the indications for testing, protocol for sample collection, processing, panel of antibodies as well as gating strategies to be used, how to interpret the test and reporting format to be used. It is essential to test at least two GPI-linked markers on at least two different lineages particularly on red cells and granulocytes/monocytes. The fluorescent aerolysin combined with other monoclonal antibodies in multicolour flow cytometry offered an improved assay not only for diagnosis but also for monitoring of PNH clones. It is equally important to diagnose this rare entity with high index of suspicion.     

Promising Pharmaceuticals： edited by Purusotam Basnet

The better understanding of human biology and disease pathology has been a comer stone of the rapid advancements in the field of pharmaceutical science, including drug discovery, manufacturing and treatment procedures. Building on these important achievements, Purusotam Basnet, the editor of, and a contributing author to the book entitled Promising Pharmaceuticals （its information is shown in Table 1; cover paper is shown in Figure 1）,     

Zinc deficiency in head and neck cancer patients.

Although a great deal of attention has been given to protein and calorie malnutrition in patients with head and neck cancer, zinc status has not been assessed properly in such patients in the past.

In this study we characterized zinc status by cellular zinc criteria and assessed several measures of protein and calorie malnutrition in patients with head and neck cancer. We determined prognostic nutritional index (PNI) based on serum albumin, serum transferrin, triceps skin fold measures, and delayed hypersensitivity, as proposed by Buzby et al. In this study, the baseline zinc status and PNI of 60 head and neck cancer patients were correlated with the tumor size and overall stage of the disease.

Our results showed that the tumor size and overall stage correlated significantly to zinc status whereas no correlation was seen with PNI, alcohol intake, or smoking in our study subjects.

We conclude that zinc status is a better indicator of tumor burden and stage of the disease in head and neck cancer patients than the patients' overall nutritional status.