Altered gene expression with abnormal patterning of the telencephalon in embryos of diabetic Albino Swiss mice.

AIMS/HYPOTHESIS: Several studies have shown that maternal diabetes increases the risk of congenital malformations in various organ systems including the neural tube. The present study analysed molecular and morphological changes in the forebrain of embryos from diabetic Albino Swiss mice. METHODS: Maternal diabetes-induced morphological changes in the forebrain were examined histologically. Cell proliferation index was assayed by BrdU labelling. In situ hybridisation and quantitative real-time PCR were used to analyse the expression of genes coding for sonic hedgehog ( Shh), Nkx2.1, brain factor-1 ( BF-1) and bone morphogenetic protein-4 ( Bmp4) that control forebrain patterning. RESULTS: There were no distinguishable abnormalities in the forebrain of embryos from diabetic pregnancies on embryonic day 0.5. At embryonic day 11.5, embryos of diabetic pregnancies displayed a fusion and thickening of the ventral telencephalic neuroepithelium and a partial absence of the dorsal telencephalon, indicating a severe patterning defect in the dorsoventral axis of the telencephalon. The cell proliferation index was also higher in the ventral telencephalon of these embryos. Molecular analyses indicated that expression of Shh, Nkx2.1 and BF-1 was increased and their expression domains expanded dorsally in the ventral telencephalon in embryos of diabetic mice at embryonic day 11.5. The expression of Bmp4 was reduced in the dorsal forebrain of these embryos. At embryonic day 8.5, only Shh expression was increased. CONCLUSIONS/INTERPRETATION: Altered expression of various genes involved in dorsoventral patterning of the forebrain is associated with forebrain malformations in embryos of diabetic mice.

Transjugular liver biopsy: comparison with percutaneous liver biopsy.

A transjugular liver biopsy was performed on 60 patients. Specimens were successfully obtained from 57 (95%) patients. Specimens obtained from cirrhotic patients were frequently small-sized/fragmented. The wedge hepatic venous pressure and hepatic venous pressure gradient were higher in patients with small-sized/fragmented specimens than those with non-fragmented specimens (16.3 +/- 6.4 vs 12.3 +/- 4.9 and 10.9 +/- 6.2 vs 7.3 +/- 3.4 mmHg, P < 0.05, respectively). During the same period of time, percutaneous liver biopsies were consecutively performed on 277 patients. The liver specimens by transjugular method were generally smaller (0.63 +/- 0.58 vs 1.50 +/- 0.86 cm, P < 0.001) and more fragmented (63% vs 16%, P < 0.01) than those obtained by percutaneous method. Biopsy specimens obtained for diagnosis by the former method were inadequate from 6 (10%) patients and by the latter route were inadequate from 7 (2%) patients. Subcapsular haematoma in one patient was associated with the transjugular liver biopsy. Minor complications occurred in three patients: neck haematoma in two and paroxysmal supraventricular tachycardia during the procedure in one. In comparison, percutaneous liver biopsy was followed by minor complications in 20 patients and major complications in four patients. It is concluded that transjugular liver biopsy is a safe, valuable and alternative procedure to obtain liver specimens, especially in patients who were contraindicated for percutaneous liver biopsy.

Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis.

The relationship between the severity of cirrhosis and systemic and hepatic haemodynamic values was evaluated in 193 patients with cirrhosis, most of whom were diagnosed with post-necrotic cirrhosis. It was found that the hepatic venous pressure gradient and cardiac output in Pugh's A patients (13.6 +/- 4.8 mmHg and 6.2 +/- 1.6 L/min, mean +/- s.d.) were significantly lower than in both Pugh's B (16.8 +/- 4.3 mmHg and 7.3 +/- 2.1 L/min) and Pugh's C (18.8 +/- 5.5 mmHg and 7.4 +/- 2.3 L/min) patients (P < 0.01), respectively. In contrast, the systemic vascular resistance in Pugh's A patients (1232 +/- 369 dyn/s per cm5) was significantly higher than in both Pugh's B (1016 +/- 345 dyn/s per cm5) and Pugh's C (935 +/- 234 dyn/s per cm5) patients (P < 0.01), respectively. Additionally, not only was there a positive correlation found between Pugh's score and cardiac output and hepatic venous pressure gradient, but a negative correlation was found between Pugh's score and systemic vascular resistance. It was also confirmed that the degree of portal hypertension and the hyperdynamic circulation were more severe in patients with ascites than in those without ascites. However, there were no statistically significant differences in hepatic venous pressure gradient among patients with F1, F2 and F3 esophageal varices (15.7 +/- 4.0, 17.0 +/- 4.8 and 18.0 +/- 4.8 mmHg, respectively). It is concluded that in those patients with cirrhosis, the severity of cirrhosis is closely related to the degree of the hyperkinetic circulatory state and portal hypertension.