The effects of formoterol on plasma exudation produced by a localized acute inflammatory response to bradykinin in the tracheal mucosa of rats in vivo.

1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein exudation and microvascular permeability induced by topical, i.e. applied onto the tracheal mucosal surface, bradykinin (10 nmol; 20 microM, 5 min, 0.1 ml min-1) were studied in a perfused segment of trachea prepared in situ in anaesthetized rats. 2. Bradykinin increased the amount of plasma (fluorimetric assay for protein) in the perfusate (response; 10.98 +/- 0.357 microliters, n = 69; total increase in plasma over basal during 45 min after start of bradykinin application) and 2 responses at a 90 min interval were reproducible. Carbon labelling was seen in tracheal sections from animals that received i.v. colloidal carbon, indicating that bradykinin caused tracheal microvessels to leak (increase in microvascular permeability). 3. Five minutes after topical formoterol, 5 or 30 nmol (10 or 60 microM perfused for 5 min), the bradykinin response was significantly reduced. The effects of formoterol were not dose-related, i.e. were maximal at 5 nmol. The bradykinin response was at control levels 30 min after 5 nmol formoterol. After 30 nmol formoterol, the response was still reduced 120 min later. The bradykinin response was significantly reduced 60 min after systemic formoterol (i.p., 0.029 to 870 nmol kg-1) and, for 290 nmol kg-1 i.p. formoterol, this reduction was shown to last at least 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

A model for the prediction of osmolalities of modular formulas

A model is proposed for evaluation of osmolality of multicomponent formulas composed of modular ingredients. Nonlinear curve-fitting techniques applied to empirical data result in prediction of the osmolality of ingredients for any concentration desired. Osmolality of a multicomponent formula can be obtained by adding osmolalities of ingredients. Data handling is made possible by the use of simple microcomputer programs. The model is tested with products available for construction of amino acid-restricted diets.     

Infarction of the conus medullaris

We describe 5 patients who presented with an acute cauda equina syndrome, which we believe was due to infarction of the conus medullaris. In 3 patients, the onset was spontaneous, and in 2 patients it was secondary to temporary occlusion of the distal aorta during medical manipulation. Pain in the buttocks and posterior thighs was a prominent initial symptom in the 3 patients with unprovoked attacks. The main clinical features were profound impairment of bowel and bladder function and of perianal and perineal sensation (S3 to S5 segments). There was sensory and motor impairment in the legs of variable extent, most marked in the S1 and S2 segments, but extending as high as L4 in 2 patients. In 1 patient, ischemic changes in the conus medullaris were confirmed post mortem. Ischemia confined to the caudal tip of the spinal cord is rare, and an underlying anomaly of the pattern of arterial supply is a likely predisposing factor. Four patients had partial return of function over a period of weeks.     

Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.     

Estradiol and tryptophan depletion interact to modulate cognition in menopausal women.

Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.     

Neuro-ophthalmic manifestations of the syndrome of ophthalmoplegia, ataxia and areflexia Observations on 20 patients

The neuro-ophthalmological manifestations of 20 patients with the syndrome of ophthalmoplegia, ataxia and areflexia are described. The symmetrical nature of the ophthalmoplegia and the associated cerebellar ataxia point to centrally placed lesions. Several supranuclear, nuclear and internuclear ophthalmological signs are identified. Some of these, like partial sparing of the levator palpebrae and normal downgaze in the presence of severe ophthalmoplegia are noted too frequently to be just unusual signs of peripheral oculomotor dysfunction. Other identified features included upper lid retraction on attempted upgaze and preserved Bell's phenomenon in the presence of paralysis of the latter, as well as several other central ophthalmological signs. These findings contrast with those seen in the Guillain-Barré syndrome and, thus, the syndrome of ophthalmoplegia, ataxia and areflexia is not a mere variant of it.     

Mitral incompetence associated with lipoma infiltrating the mitral valve

A 54 year old man presented with presyncopal symptoms. Echocardiography and subsequently computed tomography showed a mass in the posterior mitral annulus causing incompetence of the valve. At operation a lipoma was found which could not be resected. Mitral incompetence was the result of chordal rupture where the lipoma had engulfed the papillary muscle. The valve was replaced and the patient made an uneventful recovery. This case report shows a potential danger of an otherwise benign lesion.     

The bright pituitary gland--a normal MR appearance in infancy

Signal intensities of the pituitary gland were measured on T1-weighted sagittal MR images of 25 patients younger than 20 years old. We found that the signal intensities in the eight patients who were 8 weeks old or younger were higher (shorter T1) than those in the 17 older patients. We also noted a difference in the signal intensities across the pituitary gland, the signal being higher in the posterior part of the gland than in the anterior part. We attribute the high signal intensities to the rapid intrauterine pituitary growth, so that at term pituitary protein synthetic activity is at a maximum. Possibly, an increase in the bound fraction of the water molecules of the gland may also be present in the neonatal pituitary as compared with the older gland, but this remains to be proved. The higher signal in the posterior pituitary gland may be due to lipid in the pituicyte cells of the posterior pituitary gland.