Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation.

To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.     

Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.     

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.     

Prediction of remission in Graves' disease after thionamide therapy by technetium-99m early uptake]

In the clinical management of Graves' thyrotoxicosis, one of the most important subject is when to stop antithyroid drugs after achieving an euthyroid state. T3 suppression test and other methods have been used to forecast the outcome after drug cessation, but the results were not always satisfactory. We have attempted to predict remission of Graves' disease by single measurement of early technetium uptake without administration of triiodothyronine. Drugs were discontinued in the seventy-five patients with Graves' disease on maintenance doses of either methimazole or propylthiouracil who showed normalized uptake (4.0% or less). Of 64 patients evaluable after twelve months, 55 (86%) remained euthyroid, 8 relapsed, and 1 became hypothyroid. With its accuracy in prediction of short-term remission comparable or superior to T3 suppression test, this rapid and simple method seemed suitable for routine use in clinical practice.     

Noradrenergic activation of immediate early genes in rat cerebral cortex.

Previous studies have shown that stimulation of adrenergic receptors in the brain increases the expression of the immediate early gene (IEG), c-fos, in vivo (Mol. Brain Res., 6(1989) 39-45). The present study was undertaken to determine whether this also holds for other IEGs which have been shown to be activated in brain cell culture by adrenergic agonists. Both yohimbine injection and stressful stimulation, two treatments causing brain norepinephrine (NE) release, were found to cause a parallel, transient activation of at least 5 IEGs (c-fos, nur77, tis-7, zif-268 and tis-21) in the rat cortex. Genes that are not immediate early (beta-actin, NGF and HSP70) were found not to be affected in the interval used (6 h). The responses were mediated predominantly by beta-adrenoceptors with some contribution from alpha 1 receptors. The parallel activation of multiple genes by noradrenergic receptors may enable the coding of different biochemical responses to the activation of different receptors.     

Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation.

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.     

A negative correlation between the induction of long-term potentiation and activation of immediate early genes.

In the present study we examined the relationship between the induction of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats and activation of immediate early genes (IEGs; c-fos and zif/268) using several different high-frequency stimulation paradigms. Stimulation parameters that effectively induced LTP were not associated with IEG activation. Conversely, stimulation parameters that failed to induce LTP consistently resulted in IEG activation. These results suggest that there is a negative correlation between IEG activation and LTP, and that activation of IEGs is neither necessary nor sufficient for the induction of LTP.     

Cytokeratin expression in a congenital multipotential primitive neuroectodermal tumor

A case of an uncommon congenital primitive neuroectodermal cerebellar tumor (PNET) in a 5-month-old child is reported. After subtotal surgical resection, the residual tumor did not respond to radiation and chemotherapy. Histologically, the tumor was composed of small, round, undifferentiated cells and several other patterns like astrocytomatous, oligodendrogliomatous, and ependymomatous structures. Immunostaining was positive for most of the cells for vimentin and S 100, fewer were positive for glial fibrillary acid protein (GFAP) and neuron-specific enolase, and only a few for synaptophysin. Surprisingly, the tumor showed strong expression of several monoclonal cytokeratins (CK) with different molecular weights, together with epithelial membrane antigen. Furthermore, we found a coexpression of the tumor cells for CK and vimentin, while CK-GFAP and CK-S 100 were negative. Ultrastructurally, intracyto-plasmic intermediate filaments could be observed corresponding to immunohistochemical CK expression. The very strong CK and vimentin expression in this case was interpreted as a sign of the embryonic nature of the tumor.