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.     

Autozygome maps dispensable DNA and reveals potential selective bias against nullizygosity

PurposeCopy number variants are an important source of human genome diversity. The widespread distribution of hemizygous copy number variants in the DNA of healthy humans suggests that haploinsufficiency is largely tolerated. However, little is known about the extent to which corresponding nullizygosity (two-copy deletion) is similarly tolerated.MethodsWe analyzed a cohort of first cousin unions to enrich for shared parental hemizygous events and tested their Mendelian inheritance in offspring.ResultsAnalysis of autozygous DNA blocks (autozygome) in the offspring not only proved an efficient method of mapping “dispensable” DNA but also revealed potential selective bias against the occurrence of nullizygous changes. This bias was not restricted to genic copy number variants and was not accounted for by a high rate of miscarriages.ConclusionsThe autozygome is an efficient way to map dispensable segments of DNA and may reveal selective bias against nullizygosity in healthy individuals.Genet Med 2012:14(5):515–519