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.     

Diagnostic delay after dimenhydrinate use in vomiting children.

OBJECTIVE: To determine whether the use of dimenhydrinate was associated with delay in the diagnosis and management of treatable illnesses or with direct adverse effects in children with vomiting presenting to an emergency department. DESIGN: Questionnaire survey and review of drug reaction and telephone inquiry records. SETTING: The emergency department of a tertiary care children's hospital and a provincial poison information centre. PATIENTS: The parents of 148 children who presented with vomiting completed the questionnaire. The database at the poison information centre included 474 reports of adverse drug reactions over an 8-year period and 105 reports of telephone inquiries over a 4-year period. MAIN RESULTS: Twenty-one (14%) of 148 children had received dimenhydrinate before arrival at the emergency department. The patients who had received dimenhydrinate were more likely than the others to present more than 12 hours after the onset of vomiting (14 [67%] of 21 v. 43 [34%] of 127, p less than 0.01). The discharge diagnoses for those who had received dimenhydrinate included asthma, pelvic inflammatory disease and urinary tract infection. No clinically important direct adverse reactions to dimenhydrinate were documented. CONCLUSIONS: The use of dimenhydrinate in children with vomiting is associated with a risk of delay in the diagnosis of treatable medical conditions.     

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.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.