Effects of chronic exposure to arsenate on the cardiovascular function of rats.

Cardiovascular function was studied in anaesthetised male rats which received 50 micrograms/ml of arsenic (as sodium arsenate) in deionised drinking water for 320 days. High urinary excretion of arsenic was found at the end of treatment and the metal accumulated considerably in the kidneys and liver, which both presented slight alterations. No histopathological modifications were evident in other organs. Base line blood pressure, cardiac inotropism, and chronotropism and cardiovascular reactivity to noradrenaline, acetylcholine, angiotensin II, bradykinin, histamine, and serotonin did not differ in exposed or in control animals. In the exposed group, however, there was potentiation of the effects of vascular beta-adrenoceptor stimulation and a reduction in the vascular responsiveness to angiotensin I. Chronic arsenic exposure did not affect the baroreflex sensitivity but was able to induce sympathetic hyperactivity or hypersensitivity, or both, possibly associated with an antivagal action. Our results might help to explain the cardiovascular alterations seen in people chronically exposed to high concentrations of arsenic.     

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.     

Prokinetic benzamides stimulate peristaltic activity in the isolated guinea pig ileum by activation of 5-HT4 receptors.

Substituted benzamides such as metoclopramide, cisapride, zacopride, renzapride or BRL 20627, stimulate intestinal motility in various species. As they are antagonists at 5-HT3 and agonists at 5-HT4 receptors and as both mechanisms could potentially contribute to their gastrointestinal prokinetic effect, the underlying mechanism is unclear. To clarify this, the effect of some substituted benzamides on gut motility was investigated in the isolated guinea pig ileum using the Trendelenburg technique, in which pressure-induced peristaltic contractions are measured. All benzamides stimulated the peristaltic reflex with the rank order of potency: renzapride greater than cisapride greater than BRL 20627 greater than (+/-)-zacopride greater than metoclopramide. ICS 205-930, granisetron and 2-methyl-5-HT did not change the peristaltic response. 5-HT and 5-methoxytryptamine potently mimicked the effect of the benzamides. The effect of 5-HT was not blocked by ICS 205-930 (10(-7) M). These results indicate that the Trendelenburg preparation is suitable for the investigation of intestinal prokinetic effects of the substituted benzamides. Furthermore, the results suggest that the intestinal effect of benzamides results from activation of 5-HT4 receptors rather than from blockade of 5-HT3 receptors.     

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.     

Papilliferous keratoameloblastoma

A case of papilliferous keratoameloblastoma is reported which is only the second ever documented. The patient was a 76-yr-old black woman with a large expansile multilocular radiolucency of the body, angle and ramus of the mandible. Histologically the lesion consisted of sheets of cystic follicles filled with necrotic debris and sometimes parakeratin. The vast majority of the follicles were lined by a papilliferous epithelium consisting of large rounded cells with centrally placed nuclei. True papillary projections with cores of connective tissue were also present. The remainder of the follicles were lined by a thin parakeratinising stratified squamous epithelium. Histological features characteristic of ameloblastoma were absent. Final classification of these lesions will have to await the reporting of further cases.     

Calcium, network activity, and the role of NMDA channels in synaptic plasticity in vitro.

Functionally effective neuronal circuits are constructed through a competitive process that requires patterned neuronal activity elicited by structured input from the environment. To explore the mechanisms of this activity-dependent synaptic restructuring, we have developed an in vitro preparation of mouse spinal cord neurons maintained in a 3-chambered cell-culture system. Sensory afferents that received chronic electrical stimulation for 3-5 d developed stronger synaptic connections than unstimulated afferents converging onto the same postsynaptic spinal cord neuron. Exposure to 100 microM DL-2-amino-5-phosphonovaleric acid (APV), an antagonist of the NMDA channel, during the stimulation period prevented the competitive advantage associated with electric stimulation. However, when APV was applied with a higher concentration of calcium (3 mM), activity-dependent synaptic plasticity was no longer inhibited by the NMDA receptor antagonist. This reversal of APV block of the plasticity was not impaired by reducing transmitter release with 3 mM magnesium (in addition to 3 mM calcium and APV). A suppressant effect of APV on spontaneous activity was observed, which was attributed to loss of the NMDA component of the EPSP. Activity-dependent plasticity was also blocked if spontaneous activity was suppressed with dilute tetrodotoxin (TTX; 5-10 nM), a dosage that reduces excitability of neurons but is insufficient to block sodium-dependent action potentials. These experiments bring into question how NMDA channel activation is involved in the processes of synaptic remodeling during development. The data suggest that postsynaptic activity is required for synaptic remodeling, but this activity need not involve NMDA receptor activation specifically for activity-evoked synaptic plasticity. Instead, the mechanism for plasticity appears to operate through calcium-dependent processes in general.