Endothelial lipopigment as an indicator of α-tocopherol deficiency in two equine neurodegenerative diseases

Two spontaneous neurodegenerative diseases of the horse, equine motor neuron disease (EMND) and equine degenerative myeloencephalopathy (EDM), have been associated with -tocopherol deficiency, and both were characterized by prominent accumulations of endothelial lipopigment in the small vessels of the spinal cord. These endothelial pigment deposits appear to be reversible. In EMND horses pasture-supplemented for 9 months or more after the progression of weakness and wasting had arrested, there was very little endothelial lipopigment. The origin and the potential effects of these endothelial lipopigment accumulations are discussed.     

Factors affecting total and "respirable" dose delivered by a salbutamol metered dose inhaler.

BACKGROUND--Many factors contribute to the high variability of doses delivered to the lungs of patients using metered dose inhalers (MDIs). Relatively little attention has been paid to the contribution to this variability of the way in which the MDI is handled before the inhalation manoeuvre. Instruction leaflets often recommend procedures at odds with those used for in vitro testing of the device. The standard protocol for in vitro assessment of salbutamol MDIs involves shaking the MDI vigorously for 30 seconds and wasting the first two actuations. Subsequent actuations are introduced into the testing device at five second intervals. Patient instructions do not include a recommendation to waste the first two actuations and recommend a delay of one minute between actuations. A series of experiments was performed to determine whether such differences might be important. METHODS--The total and "respirable" doses delivered by a salbutamol MDI (Ventolin, Allen & Hanburys) under various conditions were assessed with a multistage liquid impinger. The quantity of drug deposited on each stage was measured by an ultraviolet spectrophotometric method. The effect on the delivered dose of not shaking the canister, not wasting the first two doses, waiting 30 seconds between actuations, and using multiple rapid actuations was assessed by comparing the results with those obtained using the standard in vitro testing protocol. RESULTS--Compared with a standard protocol, it was found that not shaking the MDI before use reduced the total and "respirable" dose by 25.5% and 35.7%, respectively. The dose delivered when actuating the MDI at 30 second intervals was no different from that when intervals was no different from that when intervals of five seconds were used. Two actuations separated by one second had no effect on the total dose but reduced the "respirable" dose by 15.8%, while four rapid actuations reduced the total and "respirable" doses by 8.2% and 18.2%, respectively. Storing the MDI stem down reduced the total and "respirable" dose delivered in the first actuation by 25.0% and 23.3% despite shaking the MDI before use. CONCLUSIONS--MDIs containing drug in suspension must be shaken before use to resuspend the drug contained in the MDI, but shaking does not alter the composition of the suspension in the metering chamber and hence the dose in the first actuation remains low. Very rapid actuations can reduce the dose delivered per actuation, but salbutamol MDIs can be actuated immediately after a 10 second breath holding pause without affecting the dose delivered.     

The use of chemical restraint in helicopter transport

Introduction: Helicopter transport of the combative patient is a major safety hazard facing air medical teams. Although physical restraints alone are helpful, the addition of chemical restraint (CR) often is necessary to control these patients while in flight.

Methods: A survey was conducted to determine the current practices of using nonparalyzing CR in air medical transport programs nationwide. The survey consisted of 24 questions on the use of CR during transport. Each U.S. program belonging to the Association of Air Medical Services was contacted by telephone, and a flight nurse or paramedic provided answers based on personal experience and statistics compiled by his or her individual program.

Results: Of the 100 programs responding, benzodiazepines were used most commonly to control agitation with 51% using midazolam. Patients with a head injury required CR more frequently than any other condition (73%). Crews flying larger aircraft reported less need for CR. A physician order was required by only 30% of the programs, but delays infrequently endangered the patient (2%). Only 7% of the responding programs had a patient whose condition deteriorated because of CR.

Conclusion: CR is necessary in air medical transport. Most programs use short-acting benzodiazepines. Crews in smaller aircraft use CR more frequently, and head injury is the most common condition requiring such restraint.     

Characterization of beta-adrenoceptor mediated smooth muscle relaxation and the detection of mRNA for beta1-, beta2- and beta3-adrenoceptors in rat ileum.

1. Functional and molecular approaches were used to characterize the beta-AR subtypes mediating relaxation of rat ileal smooth muscle. 2. In functional studies, (-)-isoprenaline relaxation was unchanged by CGP20712A (beta1-AR antagonist) or ICI118551 (beta2-AR antagonist) but shifted by propranolol (pKB=6.69). (+/-)-Cyanopindolol, CGP12177 and ICID7114 did not cause relaxation but antagonized (-)-isoprenaline relaxation. 3. BRL37344 (beta3-AR agonist) caused biphasic relaxation. The high affinity component was shifted with low affinity by propranolol, (+/-)-cyanopindolol, tertatolol and alprenolol. CL316243 (beta3-AR agonist) relaxation was unaffected by CGP20712A or ICI118551 but blocked by SR58894A (beta3-AR antagonist; pA2 = 7.80). Enhanced relaxation after exposure to forskolin and pertussis toxin showed that beta3-AR relaxation can be altered by manipulation of components of the adenylate cyclase signalling pathway. 4. The beta-AR agonist RO363 relaxed the ileum (pEC50=6.18) and was blocked by CGP20712A. Relaxation by the beta2-AR agonist zinterol (pEC50=5.71) was blocked by SR58894A but not by ICI118551. 5. In rat ileum, beta1-, beta2- and beta3-AR mRNA was detected. Comparison of tissues showed that beta3-AR mRNA expression was greatest in WAT>colon=ileum >cerebral cortex>soleus; beta1-AR mRNA was most abundant in cerebral cortex > WAT > ileum = colon > soleus; beta2-AR mRNA was expressed in soleus > WAT > ileum = colon > cerebral cortex. 6. These results show that beta3-ARs are the predominant beta-AR subtype mediating rat ileal relaxation while beta1-ARs may produce a small relaxation. The beta2-AR agonist zinterol produces relaxation through beta3-ARs and there was no evidence for the involvement of beta2-ARs in relaxation despite the detection of beta2-AR mRNA.     

Chronic (−)-isoprenaline infusion down-regulates β1- and β2-adrenoceptors but does not transregulate muscarinic cholinoceptors in rat heart

Regulation of -adrenoceptor (-ar) subtypes and transregulation of muscarinic cholinoceptors (mAchr) was examined in regions of rat heart after chronic infusion of (–)-isoprenaline (450 /kg per hour) for 14 days. Following (–)-isoprenaline infusion systolic blood pressure was reduced for 10 days but then gradually returned to control levels, whereas heart rate was increased for 7 days before declining to a level significantly above control. Heart weight to body weight ratio was increased in (–)-isoprenaline treated rats. -ar subtype densities were measured by quantitative autoradiography with [¹²⁵I]-cyanopindolol (CYP) in sinoatrial node (SA), atrioventricular node (AV), bundle of His (BH), left (LB) and right (RB) bundle branches, interventricular (IVS) and interatrial (IAS) septa, right atria (RA), apex (AX) and mitral valve (MV). ₁-ars were reduced by 59.1–74.2% in the AV conducting regions, 53.4% in the SA node and 43.3–53.4% in myocardial areas. ₂-ars were markedly reduced in myocardial regions (93.2–98.5%) and in pacemaker and conducting regions (87.7–97.8%). No changes in mAchr densities measured using [³H]-N-methyl scopolamine (NMS) occurred in the AV node, BH, LB, RB, IVS and IAS following (–)-isoprenaline infusion.Densities of ₁- and ₂-ars and mAchrs were also measured in ventricular homogenates from control and (–)-isoprenaline treated animals. -ar levels were significantly reduced (P < 0.05) in treated animals and the ratio of ₁- to ₂-ars increased after treatment. mAchr density in ventricular homogenates measured using either [³H]-NMS or [³H]-quinuclidinyl [phenyl-4-³H]benzilate (QNB) was unchanged. Homogenates of left and right ventricle also showed no change using [³H]-NMS.Organ bath studies were used to investigate the effect of (–)-isoprenaline infusion on negative inotropic and chronotropic effects of the non-selective muscarinic receptor agonist bethanechol in left and right atria, respectively. Lower concentrations of bethanechol (3 × 10^–10 to 10^–6 M) produced a negative inotropic response in isolated electrically driven left atria from (–)-isoprenaline treated rats, but not from control rats, with the slope of the curves being significantly different between groups (ANCOVA, P = 0.037). At concentrations of bethanechol from 10^–6 to 3 × 10^–4 M the negative inotropic response was not changed between (–)-isoprenaline treated and control animals. Bethanechol also produced a negative chronotropic response at lower concentrations (10^–10 to 10^–6 M) in (–)-isoprenaline treated rats, but not in controls. A second, steeper phase of the negative chronotropic response occurred at concentrations of bethanechol greater than 10^–6 M and was also seen in control rats.Expression of M₂ (cardiac) mAchrs (m₂Achr) in left and right ventricular tissues measured using a quantitative non-competitive polymerase chain reaction (PCR) assay showed a significant (P = 0.001) 28.5% increase in expression in left ventricle and a significant (P = 0.003) 21.5% decrease in expression in right ventricle after (–)-isoprenaline treatment, compared to controls. There was no significant difference in total ventricular m₂Achr expression between the two groups of rats. The results suggest that chronic -ar stimulation down-regulates both ₁- and ₂-ars, and appears to differentially transregulate m₂Achr expression, but not mAchr protein. Following (–)-isoprenaline infusion, muscarinic receptor mediated responses were sensitised, with no change in receptor densities, suggesting changes occur in the cell signalling system beyond the level of the receptor.     

Is the phakic eye normal in monocular pediatric aphakia?

This retrospective review of 97 pediatric patients who underwent monocular surgery for congenital or developmental cataracts studied the incidence of abnormalities in the contralateral phakic eye. Fifty-nine percent of patients had a normal phakic eye. However, 40 patients showed at least one abnormality in the phakic eye: reduced vision (21%), nystagmus (19%), cataract (15%), iris heterochromia (9%), myopia (6%), microphthalmos (6%), pupillary miosis (2%), congenital glaucoma (2%), optic nerve abnormality (2%), aniridia (1%), and corneal opacity (1%). Not all abnormalities were detected at the time of diagnosis of the contralateral cataract. The more significant findings of reduced vision and nystagmus in the phakic eye were usually detected postoperatively, often several months after the optimum time for treatment of pediatric cataracts. We suggest that monocular cataract surgery not be delayed. This will allow the best vision to be obtained for the aphakic eye, as the "sound eye" may not always be normal in monocular pediatric aphakia.     

Pregnancy outcome in patients with repeat visits to the labor observation area near term

Patients whose pregnancies are near term and who repeatedly visit the labor observation area but are found not to be in labor and have no clear diagnosis for their complaints remain a source of concern for the obstetrician. In order to determine whether this is a population with special perinatal risks, such cases were reviewed over a 4-month period at Charity Hospital in New Orleans. Seventy-one patients were identified who had repeatedly visited the labor observation area near term. Compared with those in the general obstetrics population, these patients had a significantly increased risk of cesarean section for "failure to progress." Repeat visitors to the labor observation area should be viewed as having a high risk for later abnormalities of active labor. Careful management of labor abnormalities in such patients could theoretically lower their need for cesarean section.     

Beyond dirty linen: linen use management as an innovative asset

Because linen is an item used by virtually every inpatient in the hospital, hospital administrators will find that if they provide laundry managers an appropriate data base, they can motivate them to a larger role of linen use managers.