Colopathy associated with the systemic use of nonsteroidal antiinflammatory medications. An underestimated entity

BACKGROUND/AIMS: Adverse effects of NSAIDs (nonsteroidal antiinflammatory drugs) on the upper gastrointestinal tract and small intestine are well described. Evidence is also accumulating that implicate NSAIDs in inducing and exacerbating damage in the distal gastrointestinal tract. In this article we describe eight cases of colonic inflammation associated with nonsteroidal antiinflammatory drug administration; our aim is to stress the importance of an underestimated entity by clinicians. METHODOLOGY: Over a five-year period at two clinics, eight cases of NSAID-colopathy have been diagnosed. Crohn's disease, ulcerative and infections colitis have been excluded from this analysis. In all these subjects a careful drug history has been taken in a prospective manner and colonic inflammation appeared to be directly related to NSAID administration. There was a time interval (mean: 20 months) between initiation of treatment with NSAID and presentation with diarrhea, rectal hemorrhage and tenesmus. RESULTS: A correct diagnosis of colopathy associated with NSAIDs administration was made on careful drug history, pathological findings, stool cultures and biochemical changes which were insignificant, in contrast to the protracted troublesome symptoms. Resolution of symptoms was observed on discontinuation of NSAID medication. CONCLUSIONS: Our report is further evidence that NSAIDs administration is associated with significant mucosal injury in the distal gastrointestinal tract, despite is underestimated by most physicians.     

Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy

Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.     

Synthesis and antifungal and antioxidant properties of some new 5-substituted-4-amino(or aryl)-3-mercapto-4(H)-1,2,4-triazoles

The synthesis and antifungal and antimicrobial evaluation of some new 5-substituted-4-amino(or aryl)-3-mercapto-4(H)-1,2,4-triazoles is reported. The involvement of the new compounds in free radical processes is also investigated and their lipophilicity is calculated and related to the determined antioxidant activity. Compounds 7a, 7b and 7c exhibited interesting antioxidant properties at concentration 0.01 mmol/l, expressed by their capacity to inhibit Fe2+/ascorbate induced hepatic microsomal lipid peroxidation, to scavenge OH.and to interact with nitrogen centered radicals such as 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH). Moreover, compound 6a showed activity against Aspergillus versicolor, possessing a MIC of 82 micrograms/ml.     

Synthesis and antiviral activity evaluation of some new 6-substituted 3-(1-adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles

A number of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives, containing the adamantyl moiety, were synthesized and examined in various viral test systems. No antiviral effects were noted with any of the compounds at subtoxic concentrations in cell culture.     

Diet in relation to endometrial cancer risk: a case-control study in Greece

The risk of endometrial cancer is positively associated with obesity, but the role of specific nutrients remains unclear. Given the distinct characteristics of the Greek diet and the low incidence of this form of cancer among Greek women, we undertook a case-control study to investigate the association of endometrial cancer with food groups and micronutrients. Cases were 84 women with histologically confirmed endometrial cancer and controls were 84 women with intact uterus admitted to the same teaching hospital in Athens, Greece. Consumption of pulses, nuts, and seeds was significantly inversely related to the risk for endometrial cancer. No other significant association with food groups was detected, although a protective effect of added lipids, which in the Greek diet are primarily represented by olive oil, was highly suggestive. Retinol, nicotinic acid, vitamin B- 6, and riboflavin were inversely associated with the disease. These findings need to be replicated, because this was a relatively small study with the statistical power to detect only strong associations between cases and controls; they appear, however, to support a role of diet in the etiology of endometrial cancer.     

Acute comitant esotropia after cataract surgery

A 52-year-old woman developed comitant esotropia after cataract surgery. The ocular history was significant for accommodative esotropia; preoperatively, she manifested peripheral fusion with central suppression. Immediately postoperatively, the patient was diplopic with comitant esotropia and was treated with extraocular muscle surgery. The appearance of horizontal strabismus after cataract surgery in patients with a history of accommodative esotropia, especially those with subnormal binocularity, is a possible complication that should be discussed with the patient.     

The origin of α-fetoprotein in first-trimester anembryonic pregnancies

OBJECTIVE: Our purpose was to evaluate the origin of α-fetoprotein in the maternal circulation and coelomic fluid of pregnancies with an empty gestational sac on first-trimester ultrasonographic examinatin.STUDY DESIGN: The α-fetoprotein level and the affinity of α-fetoprotein for concanavalin A Sepharose was measured between 8 and 11 weeks of gestation in the maternal serum and coelomic fluid of nine pregnancies complicated by an empty gestational sac and of 27 normal pregnancies.RESULTS: The maternal serum α-fetoprotein level in patients with an empty gestational sac was high in seven cases and normal in two cases. In these cases the median level was significantly (p < 0.01) higher in the serum and lower in the coelomic fluid compared with normal pregnancies. In eight cases of the nine pregnancies with an empty sac, >50% of α-fetoprotein molecules in the coelomic fluid were of the concanavalin A nonreactive fraction, whereas in one case the coelomic fluid sample contained <5% of this fraction. A similar distribution was found in the corresponding serum samples.CONCLUSION: Normal or high maternal serum AFP levels and α-fetoprotein molecules predominantly of yolk sac origin in the coelomic fluid of pregnancies with an empty gestational sac on ultrasonography provide further evidence that the most likely explanation for this feature is the early death of the embryo with persistence of the placental tissue.     

Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1 transcriptional control over hCdt1

Replication licensing ensures once per cell cycle replication and is essential for genome stability. Overexpression of two key licensing factors, Cdc6 and Cdt1, leads to overreplication and chromosomal instability (CIN) in lower eukaryotes and recently in human cell lines. In this report, we analyzed hCdt1, hCdc6, and hGeminin, the hCdt1 inhibitor expression, in a series of non-small-cell lung carcinomas, and investigated for putative relations with G(1)/S phase regulators, tumor kinetics, and ploidy. This is the first study of these fundamental licensing elements in primary human lung carcinomas. We herein demonstrate elevated levels (more than fourfold) of hCdt1 and hCdc6 in 43% and 50% of neoplasms, respectively, whereas aberrant expression of hGeminin was observed in 49% of cases (underexpression, 12%; overexpression, 37%). hCdt1 expression positively correlated with hCdc6 and E2F-1 levels (P = 0.001 and P = 0.048, respectively). Supportive of the observed link between E2F-1 and hCdt1, we provide evidence that E2F-1 up-regulates the hCdt1 promoter in cultured mammalian cells. Interestingly, hGeminin overexpression was statistically related to increased hCdt1 levels (P = 0.025). Regarding the kinetic and ploidy status of hCdt1- and/or hCdc6-overexpressing tumors, p53-mutant cases exhibited significantly increased tumor growth values (Growth Index; GI) and aneuploidy/CIN compared to those bearing intact p53 (P = 0.008 for GI, P = 0.001 for CIN). The significance of these results was underscored by the fact that the latter parameters were independent of p53 within the hCdt1-hCdc6 normally expressing cases. Cumulatively, the above suggest a synergistic effect between hCdt1-hCdc6 overexpression and mutant-p53 over tumor growth and CIN in non-small-cell lung carcinomas.