Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.     

Disorders of language, communication, and behavior in mentally retarded children. Some ideas on their co-occurrence

The thesis of this article is that deficits in language and communication contribute to behavior problems in childhood. Mentally retarded children show a range of deficits in language and communication compared with normals; they are also at increased risk for behavior problems. The evidence suggests that these deficits are quantitative rather than qualitative. In addition, these linguistic deficits may contribute independently to the development of behavior disorders insofar as the linguistic deficit interferes with the child's ability to make himself understood or to understand others.     

Glycine potentiation of anticonvulsant drugs in pentylenetetrazol seizures in rats

This study evaluates the glycine potentiation of anticonvulsant drugs in subcutaneous pentylenetetrazol seizures in rats. Administered alone, glycine (30 or 40 mM/kg, PO) induced no anticonvulsant effect or neurological deficit. Coadministered with anticonvulsants, glycine significantly enhanced the anticonvulsant potency of diazepam and sodium valproate without affecting the neurological deficit induced by the anticonvulsants. Glycine did not significantly alter the anticonvulsant activity of ethosuximide or phenobarbital. These findings indicate a possible glycine-sensitive component in the mechanism of action of diazepam and sodium divalproate in subcutaneous pentylenetetrazol seizures. With the possible exception of sodium valproate, the present study provides little support for a glycine and gamma-aminobutyric acid (GABA) interaction as a mechanism of anticonvulsant activity in SC PTZ seizures. Further studies are required to determine the role of strychnine-sensitive and strychnine-insensitive glycine receptors in this experimental model of absence epilepsy.     

The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in nod mice

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.     

Physeal injuries of the distal humerus.

Physeal injuries of the distal humerus comprise approximately 10% of all physeal injuries. Diagnosis of these injuries at a young age before the ossification centers have ossified and become visible radiographically is difficult. Poor outcome of distal humeral physeal injuries is not uncommon and can be best prevented by knowledge of anatomy and the use of all appropriate imaging techniques. The focus of this article is to correlate anatomy at different ages with the occurrence of specific injuries.     

Nonvoluntary sexual activity among adolescents

Data from the 1987 round of the National Survey of Children indicate that seven percent of Americans aged 18-22 have experienced at least one episode of nonvoluntary sexual intercourse. Women were more likely than men to report having had such an experience, with just under half of all nonvoluntary experiences among women occurring before the age of 14. Multiple classification analysis reveals that white women who had lived apart from their parents before age 16, those who had been brought up in poverty, those who had had a physical, emotional or mental limitation when they were young, those whose parents had been heavy drinkers, those whose parents had used illegal drugs and those whose parents had smoked cigarettes when they themselves were teenagers were at significantly greater risk for experiencing sexual abuse. Six percent of young white women with no risk factors, nine percent of those with one, 26 percent of those with two, and 68 percent of those with three or more had been sexually abused before or during adolescence.     

Glutathione trapping to measure microsomal oxidation of furan to cis-2-butene-1,4-dial.

Furan is a liver carcinogen and toxicant. Furan is oxidized to the reactive dialdehyde, cis-2-butene-1,4-dial, by microsomal enzymes. This reactive metabolite readily reacts with glutathione nonenzymatically to form conjugates. A high-performance liquid chromatography-electrochemical method for the detection of cis-2-butene-1,4-dial-glutathione (GSH) conjugates in microsomal preparations was developed to measure the extent of furan metabolism to cis-2-butene-1,4-dial in vitro. Previously unobserved mono-GSH reaction products of cis-2-butene-1,4-dial were detected in addition to the already characterized bis-GSH conjugates. Chemical characterization of these compounds indicated that the alpha-amino group of glutathione had reacted with cis-2-butene-1,4-dial to form a thiol-substituted pyrrole adduct. The analytical method was used to estimate the extent of furan oxidation in rat liver microsomes from untreated or acetone-pretreated F344 rats as well as in human P450 2E1 Supersomes. Our results confirm that cytochrome P450 2E1 can catalyze the oxidation of furan to cis-2-butene-1,4-dial. However, the data are also consistent with the involvement of other P450 enzymes in the oxidation of furan in untreated animals. This assay will be a valuable tool to explore tissue and species differences in rates of furan oxidation.