Positive effects of allosteric modulators on the binding properties and the function of muscarinic acetylcholine receptors

Data are reviewed indicating that allosteric modulators can enhance the affinities of muscarinic receptors for their antagonists and agonists, that the enhancement of the affinity for agonists is relevant functionally, and that the allosterically induced conformational change also affects the interaction between the receptors and the G proteins.     

MR of the heart under pharmacologic stress

Magnetic resonance imaging is one method for assessing cardiac function and perfusion at rest and under stress conditions. In this article, the potential of stress magnetic resonance imaging for evaluating ischemic heart disease is reviewed, and technical aspects of some developments that may contribute to comprehensive magnetic resonance imaging assessment of heart disease under rest and stress are discussed.     

Physiological analysis of stress-induced changes in the suppressor activity of mouse T-lymphocytes

BACKGROUND: Despite their potential therapeutic benefit, the effects of cholinergic agents on anal function have been poorly investigated. AIM: To analyse the effects of neostigmine and atropine on anorectal responses to rectal isobaric distension. METHODS: This was a placebo-controlled, randomized, double-blind crossover study, performed in 12 healthy volunteers who received intravenously, on 3 separate days, neostigmine, atropine or the placebo. During each day of the experiment, seven pressure steps (ranging from 1 to 31 mmHg) in three different protocols of rectal isobaric distension (phasic, stepwise and tonic) were applied using an electronic barostat. Manometric responses of the anal canal, adaptative volumes and perception scores of the rectum were recorded. RESULTS: During stepwise distension, a significant drug effect was encountered at the anal level. No drug effect was observed on the other investigated parameters (rectal volumes and rectal perception scores) or for the other modes of distension. Compared to placebo, neostigmine significantly decreased pressures at the upper level of the anal canal for both recto anal inhibitory reflex and mean resting pressures. In contrast, atropine significantly increased pressures at the lower part of the anal canal but did not modify upper anal pressures. CONCLUSION: The present study suggests that cholinergic effects result more from an indirect action on intermediate neurotransmitters and rectal myenteric neurons, than from a direct action on anal targets.     

Starvation injury after gastric reduction for obesity

Gastric reduction operations are designed to control body weight by establishing a small, meal-size juxtaesophageal, gastric pouch that empties into the jejunum (gastric bypass) or the larger portion of the stomach (gastroplasty). If the outlet of the pouch is too small, a patient may be limited to ingesting clear liquids. Vomiting then occurs if heavier liquids or normal foods are taken. An occasional patient has difficulty eating properly and vomits even though the pouch volume and outlet are of optimum size. For a patient who reports vomiting, a distinction must be made between episodic improper eating and uncontrolled starvation. Three types of starvation injury are described: (1) sudden death from protein malnutrition; (2) refeeding syndrome; and (3) Wernicke-Korsakoff syndrome. The mechanisms of the development, manifestations, prevention, and treatment of these complications are explained. Surgeons who treat severe obesity should be aware of these complications and be prepared to manage patients who have uncontrolled vomiting so that such complications either do not develop or are recognized and treated as early as possible before serious and irreversible injury occurs.     

Tumors of childhood in Ibadan, Nigeria (1973-1990)

Childhood neoplasms provide a fertile field for epidemiological research and afford a unique opportunity for studying possible mechanisms of carcinogenesis. The present study reviews 1881 malignant childhood neoplasms in children less than 15 years of age seen in the University College Hospital, Ibadan during an 18-year period. The male-to-female ratio was 1.4:1 and modal age of occurrence was 10 years. The most common childhood neoplasms were lymphomas (45.4%), retinoblastomas (9.7%), and malignant renal neoplasms (8.5%). Burkitt's lymphoma constituted 92% of all lymphomas and 37% of all childhood tumors. Comparison of two clinicopathological studies of childhood cancer in Ibadan between 1960-1972 and 1973-1990 revealed a dramatic upsurge in the relative frequencies of intracranial neoplasms, leukemias, renal neoplasms, and retinoblastomas, with a decline in the relative frequencies of bone neoplasms and Burkitt's lymphoma during the latter period. Whether these changes reflect actual changes in the distribution of childhood cancer in the local population will require further study.