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.     

Successful tracheal autotransplantation with a vascularized omental flap.

A major problem in tracheal transplantation is the restoration of an adequate vascular supply to the transplanted trachea. In 12 piglets, a segment (6 rings) of thoracic trachea was removed and the excised segment was then sutured back in place. In 9 animals (group A), a vascularized omental flap was wrapped around the autotransplanted trachea. In the other 3 pigs (group B), the omentum was not used. Eight of 9 group A pigs were killed, 1 or 2 months later, having had no signs of airway obstruction; the 9th pig was killed after 14 days because of airway obstruction. The 3 pigs in group B were killed after 11 to 13 days because of progressive respiratory obstruction. In the 8 asymptomatic pigs in group A, the omental flap was viable and tracheal growth was normal with no differences in diameter between normal and autotransplanted trachea. Histologically intact cartilage was lined with respiratory epithelium. In the one group A pig who was killed early, the omental flap was necrotic. In this pig and in the 3 group B animals, extensive tracheal necrosis and nonviable cartilage were observed. These findings indicate that in the pig, a 6-ring segment of trachea can be transplanted with vascularization provided by an omental flap.     

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.     

Bending and torsion fractures in long bones (a mechanical and radiologic assessment of clinical cases).

Long bone injuries in clinical cases are studied by comparison of roentgenograms with a rational mechanical analysis of the injuries. Fractures produced by torsional loads have a spiral shape with a smooth and even surface. Fractures induced by bending loads have uneven and rugged fracture surfaces perpendicular to the bone axis. Long bones are weak in torsion but strong in tensile stress produced by bending. This result corresponds to the clinical fact that a large direct external force is needed to produce a transverse fracture while a spiral fracture is produced by a relatively small torque.     

Analysis of reticulocyte counts using various methods.

The precision and accuracy of manual reticulocyte counts using the Miller disc reticle, other ruled reticle and no reticle are compared with the reticulocyte results from the automated Hematrak 590 instrument. Two slides of each of 50 patient blood specimens were sent to the hematology laboratories of each of six participating hospitals. In addition to between-method comparison (precision), the manual method results using the three different counting techniques were each compared with the Hematrak results to determine if there were significant differences in reported results (accuracy). Statistical analysis revealed that the Miller disc method was the most precise and accurate manual method as compared with the Hematrak. Methods without a Miller disc reported significantly higher reticulocyte counts. Imprecision was also higher among non-Miller manual methods. By using the Miller disc, the accuracy and precision of manual methods may be increased to that of the automated Hematrak method.     

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.