Oral hypoglycemic agents. Pyrimido[1,2-a]indoles and related compounds.

A series of pyrimido[1,2-a]indoles were synthesized and studied for their hypoglycemic activity following oral administration at a standard dose of 100 mg/kg to fed rats. The effect of 10-alkoxyalkyl, 10-alkyl, 10-aryl, and 3,3-dialkyl substitution on the activity of 10-hydroxypyrimido[1,2-a]indoles was investigated. Relative potencies of a number of the most active compounds were defined by three-point dose-response studies. The most potent compounds were those with either 3,3-dimethyl substituents, compounds 21, 22, and 38, or 3,3-spirocyclohexane substituents, compounds 39 and 49. 10-Aminopyrimido[1,2-a]indoles were in general less active than the 10-hydroxy analogues, and potency was further decreased by derivatizing the 10-amino group. The most potent 10-amino derivatives were 57 and 58.     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.     

Expression of CD44V2 in transitional cell carcinoma of the urinary bladder and in urine

CD44 is the principal cell surface receptor for hyaluronate. Variant forms of the receptor, produced by alternative splicing, have been found to be associated with tumor progression in a variety of cancers. Based on investigations at the RNA level, it has recently been proposed that expression of CD44 variant V2 was present in urothelial cancer but not in normal urothelium. Since a distinctive marker for urothelial cancer would be extremely useful, frozen sections of normal urothelium and urothelial cancer were examined for expression of standard CD44 and CD44V2. Frozen sections of specimens of 35 patients with transitional cell carcinoma of the bladder, 16 specimens of normal bladder and 5 ureters were examined. Immunohistochemical staining was performed using a polyclonal antibody to CD44V2 (PAB CD44V2), a monoclonal antibody to CD44V2 (MAB CD44V2) and a monoclonal antibody to CD44S (MAB CD44S). CD44V2 and CD44S were also measured in lysates of urine sediments from 21 patients by enzyme-linked immunoabsorbent assay (ELISA). All investigated transitional cell carcinomas expressed CD44V2. There was no differentiation between invasive and noninvasive carcinoma. CD44V2 was also expressed in normal urothelium. Standard CD44 was expressed by the transitional cell carcinoma, normal urothelium, musculature and interstitial tissue. The amount of CD44V2 and CD44S in lysates of urine sediments is not correlated to diagnosis. In contrast to investigations at the RNA level, CD44V2 on the protein level seems not to be a distinctive marker for urothelial cancer. Therefore, CD44V2 will not be a useful diagnostic marker for detection of transitional cell carcinoma.     

Diffuse liver disease: MRI with Gd-DTPA versus CT and ultrasound

Twenty-nine patients with diffuse liver disease were examined by ultrasound, CT and MRI. MRI was performed using T1- and T2-weighted spin-echo sequences as well as fast gradient-echo-sequences. The paramagnetic contrast agent Gd-DTPA was applied intravenously (0.1 mmol/kg). in patients with hepatitis, MRI could be used in guiding liver biopsies as inflammatory changes were clearly delineated. CT and ultrasound were superior to MRI in the detection of focal or diffuse fatty degeneration. On the other hand MRI was more helpful in differentiating fatty changes and neoplasm. In liver cirrhosis, fibrotic changes were most clearly demonstrated by MRI. In patients suffering from hemochromatosis MRI offers advantages over CT and ultrasound in the diagnosis and follow up due to the paramagnetic properties of iron, resulting in a reduction in signal intensity. In patients with Wilson's disease a characteristic pattern of parenchymal changes was seen. Administration of Gd- DTPA contributes additional information about perfusion conditions in the liver parenchyma, however this information was not of diagnostic relevance in the cases we studied. Correspondence to: T.J. Vogl     

Fulminant subacute sclerosing panencephalitis in association with pregnancy

Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.     

Audiotaped versus written administration of the Situational Competency Test

The Situational Competency Test (SCT) is an audiotaped, verbal role-play measure of coping responses to eight drinking and eight non-drinking situations. The present investigation evaluated the comparability of response scores to audiotaped versus written administrations of the SCT in two samples of alcohol clients. The written administration of the SCT yielded significantly shorter durations of response in both clinical samples, but there were no other significant differences between the administration methods on the other scoring dimensions. Correlations of the audiotaped and written summary scores revealed no consistently significant or meaningful associations. Given the differences in duration, the generally poor correlations between summary scores, and the loss of the latency measure in the written format, we recommend retention of the audiotaped administration for use in research.