The Italian external quality assessment scheme in classical cytogenetics: four years of activity.

BACKGROUND: The Italian external quality assessment scheme in classical cytogenetics was started in 2001 as an activity funded by the National Health System and coordinated by the Italian Public Institute of Health. OBJECTIVES: The aim of our work is to present data from the first 4 years of activity, 2001-2004. METHODS: Italian cytogenetics public laboratories were enrolled on a voluntary basis, and this nationwide program covered prenatal, postnatal and oncological diagnosis. The scheme is annual and retrospective; a panel of experts reviewed the quality of images and reports in order to assess technical, analytical and interpretative performance. RESULTS: Over the 4-year period, the number of participating laboratories increased: from 36 in 2001, 46 in 2002, 49 in 2003 to 51 in 2004. The overall technical performance was satisfactory. Inadequacy or lack of information in reporting was the most frequent analytical inaccuracy identified in all parts of the scheme. However, the percentage of complete reports increased significantly during the period: by 36% in postnatal diagnosis between 2001 and 2004 (p < 0.001) and by 42% in oncological diagnosis between 2002 and 2004 (p = 0.003). CONCLUSIONS: Our experience reveals that participation in external quality assessment programs has significant advantages, helping to standardize and to assure quality in cytogenetic testing.

Gastrointestinal damage induced by celecoxib and rofecoxib in rats.

Five experimental models were developed in different groups of Wistar rats (N = 15) to study selective COX-2-inhibitor NSAIDs such as celecoxib and rofecoxib, as follows: (1) dose-dependent oral Celecoxib and Rofecoxib for 5 days, and 24 hr after oral indomethacin; (2) Same as 1 but subcutaneously; (3) gastric ulcer induced by glacial acetic acid; (4) duodenal ulcer induced by cysteamine; and (5) stress by immobilization and immersion in water at 15 degrees C for 6 hr. Celecoxib and Rofecoxib, either orally or subcutaneously, did not produce necrotic lesions in healthy gastrointestinal mucosa (0%), showing normal histology. In contrast, previously indomethacin-induced lesions were aggravated (90%, P < 0.001). Total necrosis in the small intestine as well as increased ulcers and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also aggravation of the necrotic gastric area in stress (60-90%, P < 0.05). Celecoxib and rofecoxib showed neutrophilia (5000/mm3) similar to that with indomethacin. In contrast, there was no leukocyte infiltration in the gastric múcosa; thus, we can consider it a selective COX-2 NSAID. In conclusion, celecoxib and rofecoxib at doses causing COX-2 but not COX-1 inhibition did not produce toxic lesions in healthy gastrointestinal mucosa, yielding a broad therapeutic margin. In contrast, when administered in altered gastrointestinal mucosa, they aggravated and complicated gastric ulcers as well as necrosis in the small intestine, consequently restricting their clinical use.

[Gastrointestinal damage induced by celecoxib and rofecoxib in rats]. / Daño gastrointestinal inducido por celecoxib y rofecoxib, en ratas.

UNLABELLED: Five experimental models were carried out in different groups of Wistar rats (n = 15) in order to study selective (cyclo-oxygenase) COX-2 non-steroid antiinflammatory inhibitors, such as celecoxib and rofecoxib, as follows: 1) Dose-dependent oral celecoxib and rofecoxib for 5 days, and 24 hours after oral indomethacin. 2) Same as 1, but subcutaneously. 3) Gastric ulcer induced by means of glacial acetic acid. 4) Duodenal ulcer induced by means of cysteamine. 5) Stress due to being kept under restraint and immersion in water at 15 degrees C for 6 hours. Celecoxib and rofecoxib, either orally or subcutaneously, did not produce necrotic injuries in healthy gastrointestinal mucosa (0%), showing normal histology. On the other hand, the injuries previously induced by indomethacin worsened (90%, p < 0.001). Total necrosis of small intestine as well as increased ulcer and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also worsening of gastric necrotic area with stress (60-90%, p < 0.05). Celecoxib and rofecoxib showed neutrophilia (5,000/mm3) similar to that presented by indomethacin, but there was no leukocyte infiltration in the gastric mucosa; thus we can consider it a COX-2 selective NSAID (non-steroidal anti-inflammatory drug). CONCLUSION: Dose-dependent administration of celecoxib and rofecoxib as COX-2 inhibitors and non-COX-1 inhibitors, respectively, did not produce toxic injuries on healthy gastrointestinal mucosa, thus providing a broad therapeutic spectre. On the other hand, when administered in presence of altered gastrointestinal mucosa, they worsened and complicated gastric ulcers, and also induced necrosis in the small intestine, thereby restricting their clinical use.

Daño gastrointestinal inducido por celecoxib y rofecoxib, en ratas / Gastrointestinal damage induced by celecoxib and rofecoxib in rats

En diferentes grupos de ratas Wistar (n=15), se estudiaron AINEs inhibidores selectivos de la COX-2, como delecoxib y refecoxib, en cinco modelos experimentales: 1) Celecoxib y rofecoxib por vía oral y dosis dependiente durante 5 días y 24 hs. Después de indometacina oral. 2) Similar a 1, pero subcutáneo. 3) Ulcera gástrica inducida por ácido acético glacial. 4) Ulcera duodenal por cisteamina. 5) Estrés por inmovilización e inmersión en agua a 15 grados Celsius durante 6 horas. Celecoxib y rofecoxib por vía oral o SC en mucosa gastrointestinal sana no provaron lesiones necróticas en una superficie del 0 grados Celsius, presentanto histología normal; en cambio, agravaron y complicaron lesiones inducidas en forma previa por indometacina en más del 90 por ciento (p<0,001), con necrosis masiva del intestino delgado, así como ampliaron y causaron perforaciones en las úlceras gástricas y duodenales inducidas por ácido acético y cisteamina. Se produjo asimismo agravación de la zona necrótica gástrica por estrés en un 60-90 por ciento (p<0,05). Celecoxib y rofecoxib condujeron a una neutrofilia de 5000/mm3, similar a la inducida por la indometacina; en cambio, no produjeron infiltración leucocitaria en mucosa gástrica (MPO), siendo un marcador de AINE selectivo COX-2. Se concluyó que celecoxib y rofecoxib, administrados en dosis dependiente como inhibidores de COX-2 y no COX-1, no provocaron en mucosa gastrointestinal sana ninguna lesión por toxicidad, observándose un amplio margen terapéutico. En cambio, suministrados en mucosa gastrointestinal dañada agravaron y complicaron las lesiones ulcerosas gástricas y necróticas intestinales, limitando su uso en clínica.

Prenatal diagnosis of 30 fetuses at risk for fragile X syndrome.

The results of 30 prenatal diagnoses for fragile X syndrome are reported. Amniotic fluid cells were examined in 1 case, fetal blood in 4, and chorionic villi samples in the others. Of the 5 fetuses analyzed by cytogenetic methods, 1 had showed 4% of fraXq27.3 expression sites and the pregnancy was terminated. For 1 diagnosis, linkage analysis was used: the female fetus turned out to be normal. In 24 fetuses, the direct analysis of the mutation by StB12.3 probe was performed: 6 female and 3 male fetuses were found to carry a full mutation and 1 female fetus was found to carry a premutation. In 3 cases, the diagnoses were verified on fetal blood samples. Several tissues of 2 aborted male fetuses were analyzed for the fragile X mutation. The results are reported and discussed.