Doppler echocardiographic assessment of time to peak velocity in the aorta and pulmonary artery of small for gestational age fetuses

Summary. The time to peak velocity was measured at the level of the ascending aorta and pulmonary artery by Doppler echocardiography in 38 small-for-gestational age (SGA) fetuses before and during maternal hyperoxygenation. The values were compared to a reference range derived from the study of 142 appropriate-for-gestational age (AGA) fetuses. In the SGA fetuses the time to peak velocity at the level of pulmonary artery was significantly lower and at the level of the aorta significantly higher than in AGA fetuses. During maternal hyperoxygenation the aortic time to peak velocity decreased towards normal range but there was no significant change at the level of the pulmonary artery. These results may indicate variations of aortic and pulmonary pressures in SGA fetuses that can be partially modified by maternal hyperoxygenation and which may be associated with changes in the peripheral resistance of the cerebral circulation.     

THE FATE OF PATIENTS WITH LOCALLY ADVANCED BLADDER CANCER TREATED CONSERVATIVELY WITH NEOADJUVANT CHEMOTHERAPY, EXTENSIVE TRANSURETHRAL RESECTION AND RADIOTHERAPY: 10-YEAR EXPERIENCE

Purpose

We asses the results of bladder preservation for infiltrating cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma.

Materials and Methods

From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease.

Results

Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases.

Conclusions

Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Linkage disequilibrium between intra-locus variants in the aminopeptidase n gene and test of their association with coeliac disease

Coeliac disease (CD) is a multigenic and multifactorial enteropathy triggered by gluten-composing proteins. A possible involvement of the intestinal Aminopeptidase N (APN) was investigated by an association analysis. SSCP analysis detected four variants at position 281, 378, 956 and 2957 (referred to no. g178535, GenBank) that were studied in 193 Italian CD families. The haplotypic combinations were determined from family segregation and pairwise linkage disequilibria (D'= D/D_max) between the polymorphic sites were calculated. Significant D' values ranged between 0.78 and 0.31. Association with CD was tested by TDT (Transmission Disequilibrium Test) utilizing as markers the nucleotide substitutions and their haplotypic combinations. No statistically significant transmission distortion to the probands or to their clinically silent sibs was observed. Our data exclude an involvement in CD of the tested markers and of further undetected variation in strong linkage disequilibrium (D'≅ 1) with them. The power of the test was not adequate to detect an association with an unknown polymorphism which is not in complete linkage disequilibrium with those analysed.     

CYCLOLEUCINE ENCEPHALOPATHY

Greco C. M., Powell H. C, Garrett R. S. & Lampert P. W. (1980) Neuropathology and Applied Neurobiology 6,349–360
Cycloleucine encephalopathy
Cycloleucine, a non-metabolizable amino acid analogue produces status spongiosus in cerebral white matter of rats and mice as well as a distinctive lesion of astrocytes. Its mechanisms of action include competition with natural amino acids from transport across the blood-brain barrier leading to inhibition of entry of circulating amino acids into brain, interference with ribosomal RNA maturation, and blockage of transmethylation reactions, including the conversion of homocystine to methionine. Cycloleucine also affects the kidney, producing aminoaciduria. Electron microscopy of cerebral white matter reveals spongiform changes of myelin sheaths caused by separation of myelin lamellae along intraperiod lines and accumulation of whorls of filaments in astrocytes. The myelinopathy is dose related and its toxicity is cumulative due to its long half-life in animals. The findings are discussed with reference to other spongiform myelinopathies, including status spongiosus observed in homocystinuria and other aminoacidurias.