Detection of MDM2 alterations in cultured human hepatocytes treated with 17beta-estradiol or 17alpha-ethinylestradiol

BACKGROUND: Preneoplastic and neoplastic lesions of the liver are suspected to arise as a result of estrogen treatment. Here we present the first report on the modulational effects of the steroids 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) on oncogene MDM2 in human hepatocytes. MATERIALS AND METHODS: Collagen-embedded cultures of hepatocytes stimulated with different E2/EE2 concentrations were analyzed by immunocytochemistry, RT-PCR and sequencing for MDM2 protein/mRNA expression, MDM2 mRNA splicing and MDM2 gene mutation. RESULTS: The hepatocytes responded to stimulation with steroid E2/EE2 concentrations from 1-100 nmol/l with the overexpression of MDM2 protein while non-stimulated cells were negative. Stimulation with 1 nmol/l E2 and 10-100 nmol/l EE2 induced MDM2 splicing variants. Hepatocytes treated with 100 nmol/l E2 contained full-length MDM2 mRNA carrying a new type of MDM2 gene mutation. Unstimulated hepatocytes revealed neither mRNA splicing nor alteration of the MDM2 genes. CONCLUSION: The data show that steroid hormones are involved in the induction of MDM2 alterations in benign human hepatocytes. We speculate that some of the alterations may influence MDM2 function, thus possibly favouring genesis of liver changes.     

Transcranial duplex sonography in the detection of patent foramen ovale

PURPOSE: To determine the sensitivity of contrast material-enhanced transcranial color-coded sonography (c-TCCS) compared with that of contrast-enhanced transesophageal echocardiography (c-TEE) for detection of cardiac right-to-left shunt. MATERIALS AND METHODS: Forty consecutive patients with stroke or transient ischemic attack were admitted to the hospital and were examined by using c-TCCS and c-TEE. High-intensity transient signals (HITS) were counted for 25 seconds after the end of the Valsalva maneuver, and the numbers of HITS were classified in one of four categories (zero HITS, one to 10 HITS, >10 HITS without curtain, and curtain). A statistically significant difference was calculated with the Fisher exact test. RESULTS: HITS were counted in 21 (52%) patients by using c-TCCS and c-TEE. With both tests, no HITS were counted in 15 (38%) patients. In two (5%) patients, no HITS were counted with c-TEE but three HITS in one patient and five HITS in the other were counted with c-TCCS. In two (5%) patients, no HITS were counted with c-TCCS, but a small patent foramen ovale (PFO) was seen at c-TEE. With c-TCCS, the sensitivity was 91% (21 of 23) and the specificity was 88% (15 of 17). In 23 patients examined with c-TCCS, 14 (61%) patients had category 1 PFO; seven (30%) patients, category 2 PFO; and two (9%) patients, category 3 PFO. Mean HITS count in patients with category 1 PFO was 4.4 and that for those with category 2 PFO was 27.6. CONCLUSION: c-TCCS is a sensitive noninvasive method for detecting cardiac right-to-left shunt and is as sensitive as c-TEE.     

Intervertebral Disc Calcification in Childhood – A Case Report and Review of the Literature

Summary  The authors report the case of a 10-year-old girl with intervertebral disc calcifications from the levels C6/C7 to Th1/Th2, presenting with a herniated calcified intervertebral disc at the C7/Th1 level, causing spinal cord compression with subsequent progressive paresis and sensory loss of her left leg. After anterior cervical discectomy and fusion the neurological deficits completely resolved within 2 weeks. It can be concluded that calcification of an intervertebral disc is a rare syndrome in childhood, causing progressive neurological deficit only in a few reported cases. Although the treatment of choice is conservative, surgery is required in patients who develop progressive neurological deficit.     

Radiation exposure during chest X-ray examinations in a premature intensive care unit: phantom studies

Background. There are few reports on the radiation dose received by infants, their family and radiographers exposed to scatter radiation in a premature baby intensive care unit. Objective. To evaluate the degree of radiation exposure from diagnostic X-ray examinations with mobile X-ray machines in a premature intensive care unit. Materials and methods. The radiation exposure of an adjacent newborn, the radiographer and other persons in the room was simulated using phantoms during X-ray examination of the chest using vertical and horizontal beams. Results. Most of the measured doses were below the registration limit of the measuring apparatus and had to be extrapolated by multiple exposures. Without exception, the maximal doses were significantly lower than the permitted limit for persons not professionally exposed to X-rays. Conclusions. Recommendations to avoid unnecessary radiation exposure are given. Received: 29 September 1997 Accepted: 24 September 1998     

Phenobarbital-induced drug metabolism in man

Phenobarbital and antipyrine half-lives were measured in 31 subjects. A high correlation (r = 0.87) was found for the plasma elimination rates of the two drugs, suggesting the same or a similar route or a common regulatory control of their metabolism. The half-lives of phenobarbital and antipyrine also correlated highly with the aryl hydrocarbon hydroxylase (AHH) inducibilities in mitogen-stimulated lymphocytes of the same individuals. In the second part of the study, plasma antipyrine half-lives were measured in 22 subjects after a single oral dose of 18 mg/kg, and the AHH inducibilities were determined in their cultured lymphocytes. After 7 days on phenobarbital at aryl hydrocarbon hydroxylase inducibilityadjusted doses ranging between 1.0 and 2.0 mg/kg daily, the antipyrine half-lives were measured again and the percentage of decrease between the initial and second antipyrine half-lives was determined. Shortening of the plasma half-lives occurred in all subjects to various degrees, ranging between 13.3 and 30.6%. However, under our experimental conditions in which the dose of phenobarbital was adjusted to the individual rates of metabolism of the inducing agent, no relationship could be found between the initial antipyrine half-life and the percentage of shortening of its plasma half-life, such as had been reported by several authors.