Further investigation of the association between gastroesophageal reflux and bronchoconstriction

A double-blind modification of the intraesophageal acid perfusion challenge (Bernstein procedure) was performed in asthmatic subjects with and without gastroesophageal reflux, nonasthmatic subjects with reflux, and normal subjects. Conventional spirometric functions and total respiratory resistance (Rrs) were measured prior to and after the infusion. There were no changes in pulmonary functions except in the asthmatic subjects who had had a positive add challenge. The greatest changes occurred in Rrs, which increased significantly with reflux symptoms (p < 0.01) and decreased toward baseline (p < 0.05) when these symptoms were relieved with antacids. The response was even greater in asthmatic subjects who associated reflux symptoms with attacks of asthma. These results support previous findings that acid reflux symptoms could cause a bronchoconstrictive response in certain asthmatic patients.     

Olfactory and taste sensitivity in children with cystic fibrosis.

Psychophysical experiments measured both olfactory sensitivity to 1-butanol and sodium chloride and taste sensitivity to sodium chloride in normal children and in children with cystic fibrosis. The sensitivity of the children with cystic fibrosis fell within the normal range. These results stand in contrast to those of Henkin and Powell, who found children with cystic fibrosis to be hypersensitive to both olfactory and taste stimuli. Apparent hypersensitivity to taste stimuli could have resulted from the adapting effects of the relatively high level of sodium in the saliva of children with cystic fibrosis. If the contaminating effects of saliva are removed, children with cystic fibrosis yield, on the average, a taste threshold identical to that of normal children. There appears to be no simple explanation for why Henkin and Powell found hypersensitivity to odorants. The present results indicate that, in fact, children with cystic fibrosis display a slight hyposensitivity to odorants.     

The effect of the muscarinic antagonist scopolamine on regional cerebral blood flow during the performance of a memory task

Scopolamine, a muscarinic antagonist, impairs memory performance in both humans and animals. In this study, repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers whilst performing auditory verbal memory tasks, before and after the administration of scopolamine (0.4 mg s.c.) or placebo. Compared to placebo, scopolamine increased blood flow in the lateral occipital cortex bilaterally and the left orbitofrontal region. Scopolamine decreased rCBF in the region of the right thalamus, the precuneus and the right and left lateral premotor areas. Scopolamine attenuated memory-task-induced increases of rCBF in the left and right prefrontal cortex and the right anterior cingulate region. These data suggest that acute blockade of cholinergic neurotransmission affects diverse brain areas, including components of the visual and motor systems, and, in addition, modulates memory task activations at distinct points in a distributed network for memory function.     

Familial insertional translocation of a portion of 3q into 11q resulting in duplication and deletion of region 3q22.1→q24 in different offspring

The use of elongated prophase and prometaphase chromosome preparations has allowed detection of an insertion of a small segment of 3q into 11q in a kindred with 4 balanced carriers and 8 unbalanced offspring. Those with partial 3q deletion have a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome with an appearance suggestive of the Schwartz-Jampel syndrome.     

Advocating healthcare reform

Although sweeping healthcare reforms may be slow in coming, political and public concerns over the inequities in the current system should keep the process moving. As healthcare leaders, you need to stay atop the issues and keep the conversations going.     

Inhibition of DNA repair as a means of increasing the antitumor activity of DNA reactive agents

Chemotherapeutic alkylnitrosoureas (BCNU, CCNU, streptozotocin) and alkyltriazenes (DTIC, temozolomide) produce a cytotoxic lesion at the O(6)-position of guanine. The DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase removes damage from the O(6)-position in a single-step mechanism without co-factors. There is extensive evidence that this protein is one of the most important factors contributing to alkylnitrosourea and alkyltriazene treatment failure. There is an inverse correlation between the level of this protein and the sensitivity of cells to the cytotoxic effects of O(6)-alkylating agents. Attempts have been made to modulate AGT activity using anti-sense technology, methylating agents, O(6)-alkylguanines, and O(6)-benzylguanine analogs. O(6)-Benzylguanine and its analogs are clearly the most potent direct inactivators of the AGT protein. The mechanism involves O(6)-benzylguanine acting as a low-molecular weight substrate with transfer of the benzyl group to the cysteine residue within the active site of the repair protein. Pretreatment of cells with non-toxic doses of O(6)-benzylguanine results in an increase in the sensitivity to O(6)-alkylating agents. Animal studies revealed that the therapeutic index of BCNU increased when administered in combination with O(6)-benzylguanine. This drug is currently in phase I clinical trials. Evidence from animal studies indicates that myelosuppression may be the dose-limiting toxicity, thus, efforts are aimed at improving the therapeutic index by the stable expression of O(6)-benzylguanine-resistant AGT proteins into targeted normal tissue such as bone marrow. The successful modulation of alkyltransferases brings on an exciting new era for alkylnitrosoureas and alkyltriazenes.     

Book review

A Colour Atlas of Haematological Cytology (3rd ed.) F G J Hayhoe & R J Flemans. Wolfe Publishing Ltd., London. 384 pages. Price ￡82.95.