Review of recent experience in the treatment of carcinoma of the anal canal

A retrospective study was conducted for evaluation for the therapeutic efficacy of the various modalities for treatment of carcinoma of the anal canal. Thirty-seven patients were reviewed. Patients commonly presented in their sixth decade of life and a four-fold predominance of women was noted. Tumor histopathology was of little relevance in determining prognosis. Surgery alone was performed on 15 patients, consisting of either abdominoperineal resection or wide excision. Multidisciplinary therapy as described by Nigro et al., 10-12 which included preoperative chemotherapy and radiation followed by surgery within a period of 4-6 weeks, was used to treat 13 patients. Radiation alone or in combination with surgery was used to treat six patients. One patient refused further treatment following radiation and chemotherapy, and the remaining two patients refused treatment from the onset. There was no difference in survival in Stages O and I patients when treated by surgery alone or with the Nigro protocol. However, Stages II and III patients had a more favorable outcome when treated by the Nigro protocol than by any other regimen. Thirteen of 21 patients treated by surgery and/or radiation therapy developed recurrence, resulting in seven deaths. Three out of 13 patients treated by the Nigro protocol developed recurrence, all of whom are alive and well following salvage treatment. Despite its infrequent use, a favorable trend is noted as a result of utilizing the multimodality protocol, particularly in patients with invasive disease.     

Chloroquinolines block antibiotic efflux pumps in antibiotic-resistant Enterobacter aerogenes isolates

Efflux mechanisms protect bacterial cells by pumping out toxic compounds and actively contribute to bacterial multidrug resistance. Agents inhibiting efflux pumps are of interest for the control of multidrug-resistant bacterial infections. Herein we report the effects of new chloroquinoline derivatives that render resistant Enterobacter aerogenes isolates noticeably more susceptible to structurally unrelated antibiotics. In addition, some of these chloroquinolines increase the intracellular concentration of chloramphenicol. Some of the molecules tested in this work are able to inhibit the main efflux pump (AcrAB-TolC), which is involved in E. aerogenes antibiotic resistance.     

Renal amyloidosis and schistosomiasis

A retrospective study of 60 renal biopsies obtained from nephrotic subjects with schistosomiasis showed amyloid deposits in 10 cases. Distribution was usually segmental, mainly mesangial and overlapped with the conventional mesangio-proliferative lesions of schistosomiasis. The invariable clinical presentation was proteinuria with generalized oedema of insidious onset and a slowly progressive or intermittent course. Differences from conventional schistosomal nephropathy are described. Response to anti-schistosomal treatment was very poor. Repeat renal biopsies showed no regression of the lesions. The possible links between schistosomiasis and amyloidosis are discussed and causes of amyloid deposition suggested.     

Steroidogenic factor-1 and endometriosis

Endometriosis is a common and chronic disease characterized by persistent pelvic pain and infertility. Estradiol is essential for growth and inflammation in endometriotic tissue. The complete cascade of steroidogenic proteins/enzymes including aromatase is present in endometriosis leading to de novo estradiol synthesis. PGE₂ induces the expression of the genes that encode these enzymes. Upon PGE₂ treatment, coordinate recruitment of the nuclear receptor SF-1 to the promoters of these steroidogenic genes is the key event for estradiol synthesis. SF-1 is the key factor determining that an endometriotic cell will respond to PGE₂ by increased estradiol formation. The presence of SF-1 in endometriosis and its absence in endometrium is determined primarily by the methylation of its promoter. The key steroidogenic enzyme in endometriosis is aromatase encoded by a single gene because its inhibition blocks all estradiol biosynthesis. Aromatase inhibitors diminish endometriotic implants and associated pain refractory to existing treatments in affected women.     

IL-23 Gene Expression in PBMCs of Patients with Coronary Artery Disease

Objective: Both adaptive and innate immune systems are involved in coronary artery disease (CAD). The aim of this study was to evaluate TH17 cytokines expression profiles in un-stimulated peripheral blood lymphocytes (PBMCs) of patients with coronary artery disease. Methods: Expression profiles of IL-17, IL-23, and TGF-β1 were determined in individuals with and without CAD using Real-time PCR. Results: A significant decrease in IL-23 gene expression in un-stimulated PBMCs of patients with CAD compared to those without CAD was found (p=0.003, OR=0.045, 95% CI: 0.006–0.355). Conclusion: Our data reinforce the potential role of the IL-23 as a critical regulatory molecule that bridges the innate and adaptive arms of the immune system in the complex mechanisms associated with the development of atherosclerosis.