Three-in-one femoral nerve block as analgesia for fractured neck of femur in the emergency department: a randomized, controlled trial.

STUDY OBJECTIVE: We determine whether 3-in-1 femoral nerve block is effective as analgesia for fractured neck of femur when administered by emergency physicians. METHODS: This was a prospective, randomized controlled trial with blinded assessors conducted in a district general hospital emergency department in the United Kingdom. Over a 6-month period, all patients with fractured neck of femur were considered for study. Patients were randomly assigned to receive 3-in-1 nerve block with bupivacaine plus intravenous morphine or intravenous morphine. An accreditation package for all ED medical staff was devised to ensure competence in the technique of 3-in-1 nerve block. Pain scores were recorded on arrival and at intervals up to 24 hours after admission. Morphine consumption in the first 24 hours was recorded. RESULTS: Ninety-four patients sustained fractured neck of femur during the study period; 50 were studied. Of 44 not studied, 42 were confused, 1 did not consent, and 1 was overlooked. Patients receiving 3-in-1 nerve blocks recorded a faster time to reach the lowest pain score: 2.88 hours for patients with nerve block and 5.81 hours for control patients (mean difference -2.93 h; 95% confidence interval [CI] -5.48 to -0.38 h). Nerve block recipients required significantly less morphine per hour than control patients (mean of 0.49 mg/h versus 1.17 mg/h; mean difference -0.68 mg/h; 95% CI -1.23 to -0.12 mg/h). CONCLUSION: Three-in-one femoral nerve block is an effective method of providing analgesia to patients with fractured neck of femur in the ED. All grades of medical staff were able to apply and consolidate this skill.

Affirmative action and the allocation of health care.

The justifications of affirmative action, the compensatory, corrective and redistributive, have been widely recognized in legal thinking. They have been applied, principally, to employment practices. They can also be applied to health care. Arguments for affirmative action in health care allocation shift the burden of proof to those who deny that racism is the root cause of differential morbidity and mortality experienced by, for example, African Americans. At the very least, these arguments mandate much needed research into the causes of minorities' poor health. Without such research, racism remains the presumptive cause of, and affirmative action the appropriate remedy for, the health care problems minorities face.

Advance directives in Utah. Information from death certificates and informants.

BACKGROUND: Advance directives have been studied in different patient populations and institutions. Most reports have shown limited use and little medically observable effect. To our knowledge, no previous study has focused on the use of advance directives by individuals who have died or how their family members perceived the documents' effect. METHODS: We contacted informants listed on Utah Death Certificates from 1992 to estimate the prevalence and effect of advance directives. Eighty-two percent of 1398 informants we contacted agreed to our telephone interview. RESULTS: More than 50% of decedents reportedly completed an advance directive. Individuals older than 65 years (57.3%), women (58.1%), nursing home residents (63.4%), and hospice users (75.2%) were most likely to have had advance directives. Education, religion, religiosity, and location had no effect on prevalence. Most informants stated that advance directives had no effect on the decedent's care, but a minority felt they helped to limit treatment. Do-not-resuscitate orders were written more often for patients with advance directives. Feeding tubes were removed more often from decedents with living wills than from other decedents. Mechanical ventilatory support was not less frequent in patients with advance directives. CONCLUSIONS: Our study confirms others that found little evidence that advance directives affect life-sustaining treatments. In the infrequent situations when they apply, they may be more persuasive than family members in convincing physicians to limit treatment. We observed that survivors had 2 perceptions about advance directives, not emphasized in previous reports, that they seemed to limit treatment and to ease their burden of decision making.

Patients' understanding and use of advance directives.

The Patient Self-Determination Act was implemented in December 1991. Before and after its implementation, we used a structured interview of 302 randomly selected patients to determine their awareness, understanding, and use of advance directives. Implementation of the Act did not have a major effect on these. Although more than 90% of patients were aware of the living will, only about a third selected the correct definition or the correct circumstances in which it applied, and less than 20% of patients had completed one. About a third of patients were aware of a Durable Power of Attorney for Health Care and chose the correct definition, and about half identified the correct circumstances in which it applies; less than 10% had completed such a document. Surprisingly, patients who said they had completed advance directives did not demonstrate better understanding of these documents. Our results indicate that many patients, including some who have completed advance directives, do not fully understand them. It may be unwise to regard these documents as carefully considered, compelling statements of patients' preferences. Appropriate responses to our findings include increased public education, revising state statutes to bring them into congruence with public perception, and expanding the dialogue between physicians and patients.

Advance directives for voluntary euthanasia: a volatile combination?

Defenders of patient autonomy have successfully supported the legal adoption of advance directives. More recently, some defenders of patient autonomy have also supported the legalization of voluntary active euthanasia. This paper explores the wisdom of combining both practices. If euthanasia were to become legal, should it be permitted by advance directives? The paper juxtaposes the most significant doubts about advance directives, with the most significant doubts about euthanasia. It argues that the doubts together raise more concern about the combined practices than about either euthanasia or advance directives separately. Not all cases of voluntary euthanasia by advance directive are equally problematic, however. Advance directives can help in the defense of euthanasia for patients who make the request in advance and reaffirm it under circumstances of severe suffering.

Effect of phorbol ester on vagal stimulation and acetylcholine-evoked exocrine pancreatic secretion and cytosolic free calcium in the rat.

In anaesthetized rats, interaction between either vagal stimulation or acetylcholine (ACh) and the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA) and staurosporine on pancreatic juice secretion have been investigated in vivo. In vitro, rat cytosolic free calcium concentration (Ca2+)i in pancreatic acini loaded with the fluorescent dye, Fura-2 acetoxymethyl ester (AM) have been analysed after the same modifications. In vivo, vagotomy caused a marked reduction in the rate of pancreatic juice flow, total protein output and amylase secretion compared to basal secretory parameters. Furthermore, bolus injection of either saline, TPA (10(-8) mol/kg b wt), staurosporine (10(-8) mol/kg b wt) or a combination of TPA and staurosporine (all 10(-8) mol/kg b wt) had no statistically significant effect on pancreatic juice flow, protein output and amylase secretion compared to vagotomy values. Electrical stimulation (E.S.) of vagues nerves resulted in marked and statistically significant (P < 0.05) increases in the rate of pancreatic juice flow, total protein output and amylase secretion in rats injected with either saline or staurosporine, compared to control values. In contrast, E.S. of the vagus nerves failed to enhance all secretory parameters in the presence of either TPA or a combination of TPA and staurosporine. In vitro, on isolated acini, ACh evoked dose dependent increases in (Ca2+)i. Pretreatment these acini with either TPA, staurosporine or a combination of TPA and staurosporine had no significant effect on the ACh-induced (Ca2+)i. These results indicate that TPA can decrease the secretory responses evoked by E.S. of the vagus nerves in the anaesthetized rat. This attenuation is not associated with either protein kinase C inhibition or the mobilization of the second messenger Ca2+ but possibly through activation of protein kinase C by TPA.

Effects of phorbol ester on cholecystokinin octapeptide-evoked exocrine pancreatic secretion in the rat.

1. A comparative study was made of the effect of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) on cholecystokinin octapeptide-evoked exocrine pancreatic secretion in the anaesthetized rat and isolated permeabilized pancreatic acinar cells. 2. Cholecystokinin octapeptide (CCK8; 0.10-6.40 nmol (kg body weight)-1) induced dose-dependent increases in pancreatic juice flow, total protein output and amylase release in the anaesthetized rat. 3. Administration of TPA (10(-8) mol (kg body weight)-1) in combination with CCK8 resulted in marked attenuation of the CCK8-evoked secretory response. 4. Simultaneous injection of polymyxin B (10(-8) mol (kg body weight)-1), an inhibitor of protein kinase C, with TPA and CCK8 reversed the inhibitory effect of the phorbol ester on CCK8-induced pancreatic juice flow, total protein output and amylase release. 5. In permeabilized rat pancreatic acini CCK8 (10(-13)-10(-9) M) elicited dose-dependent increases in [3H]leucine-labelled protein secretion (3H-labelled protein release). Combining TPA (10(-8) M) with CCK8 resulted in an inhibition of the CCK8-induced 3H-labelled protein release especially at lower concentrations of CCK8. At higher concentrations of CCK8, TPA was unable to inhibit the CCK8-evoked 3H-labelled protein release. Again, polymyxin B reversed the TPA-induced inhibition of CCK8-evoked 3H-labelled protein output. 6. The results indicate that protein kinase C activation may play an important physiological role in modulating the CCK8-evoked secretory response in rat pancreas in vivo and in vitro.

Mechanism of action of magnesium on acetylcholine-evoked secretory responses in isolated rat pancreas.

This study investigates the effects of magnesium (Mg2+) on acetylcholine (ACh)-evoked secretory responses and calcium (Ca2+) mobilization in the isolated rat pancreas. ACh induced marked dose-dependent increases in total protein output and amylase release from superfused pancreatic segments in zero, normal (1 x 1 mM) and elevated (10 mM) extracellular Mg2+. Elevated Mg2+ attenuated the ACh-evoked secretory responses compared to zero and normal Mg2+. In the absence of extracellular Ca2+, but presence of 1 mM-EGTA (ethylene glycol bis(beta-aminoethylether)-N,N,N',N''-tetraacetic acid), ACh elicited a small transient release of protein from pancreatic segments compared to a larger and more sustained secretion in the absence of both Ca2+ and Mg2+. Incubation of pancreatic segments with 45Ca2+ resulted in time-dependent uptake with maximum influx of 45Ca2+ occurring after 20 min of incubation period. ACh stimulated markedly the 45Ca2+ uptake compared to control tissues. In elevated extracellular Mg2+ the ACh-induced 45Ca2+ influx was significantly (P less than 0.001) reduced compared to zero and normal Mg2+. ACh also evoked dose-dependent increases in cytosolic free Ca2+ concentrations ([Ca2+]i) in pancreatic acinar cells loaded with the fluorescent dye Fura-2 AM. In elevated Mg2+ the ACh-induced cytosolic [Ca2+]i was significantly (P less than 0.001) reduced compared to zero and normal Mg2+. These results indicate that Mg2+ can influence ACh-evoked secretory responses possibly by controlling both Ca2+ influx and release in pancreatic acinar cells.

Effects of phorbol ester and related compounds on acetylcholine-evoked [3H]leucine-labelled protein secretion in permeabilized rat pancreatic acini.

The effects of the phorbol ester, 12-tetradecanoyl-phorbol-13-acetate (TPA) and related compounds on acetylcholine (ACh)-evoked [3H]leucine-labelled protein release (secretion) were tested in isolated permeabilized rat pancreatic acini. The aim was to determine whether the diacylglycerol-like compounds can still potentiate the actions of ACh during unfluctuating supramaximal elevation of cytosolic free calcium (Ca2+) levels. TPA and R59022, an inhibitor of diacylglycerol kinase, evoked marked biphasic dose-dependent increases in 3H-labelled protein secretion from permeabilized rat pancreatic acini. Synthetic diacylglycerol (OAG) and 8-bromo cyclic GMP elicited small increases in 3H-labelled protein release while an inactive phorbol ester (4 alpha-phorbol-12,13-didecanoate; 4 alpha-PDD) and polymyxin B, an inhibitor of protein kinase C, were unable to stimulate secretion. Combining polymyxin B with TPA resulted in an inhibition of 3H-labelled protein secretion. Acetylcholine also induced a dose-dependent increase in 3H-labelled protein output, but when TPA or R59022 was combined with ACh, there was a marked potentiation of the ACh-evoked secretory response, particularly at higher concentrations of ACh. This synergism was unaffected by the protein kinase C inhibitor, polymyxin B. The results show that cytosolic free Ca2+ and protein kinase C may not be the only mediators of ACh-evoked secretion. Moreover, they indicate that protein kinase C may not be involved in the potentiation by TPA of ACh-evoked 3H-labelled protein release.

Cimetidine increases the pancreatic response to histamine.

The effects of histamine alone and histamine plus cimetidine on basal pancreatic exocrine secretion were determined in anaesthetized rabbits with an acute pancreatic cannula. Intravenous histamine administration (0.2-0.8 n mol/kg/min) increased pancreatic enzyme secretion. A much greater stimulative effect on pancreatic secretion was observed when histamine was administered against a constant background of H2 antagonist (cimetidine 4 mumol/kg/min). The results indicate that in the rabbit pancreas the stimulatory effect of histamine is mediated by H1 receptors.

Effects of phorbol esters and secretin on pancreatic juice secretion in the anaesthetized rat.

1. An investigation was made of the effects of phorbol esters, 12-O-tetradecanoylphorbol acetate (TPA) and secretin on pancreatic juice secretion in the anaesthetized rat. TPA (10(-12)-10(-8) mol/kg body wt) evoked marked dose-dependent increases in secretory rate and total protein output. 2. An inactive phorbol ester (4 alpha-phorbol-12-13-didecanoate; 4 alpha PDD) had no effect on the secretory rate but increased total protein output compared to saline control animals. 3. When TPA was administered in combination with the protein kinase C inhibitor, Polymyxin B (10(-8) mol/kg body wt) both secretory rate and protein output were significantly reduced (P less than 0.001) compared to TPA alone. 4. Secretin (50-1600 pmol/kg body wt) increased both pancreatic juice flow and total protein output in a dose-dependent manner. 5. Simultaneous administration of secretin (50-1600 pmol/kg body wt) and TPA (10(-10) mol/kg body wt) resulted in a marked attenuation in the secretin-induced secretory rate while secretin-evoked protein output was unaffected. 6. The results indicate that protein kinase C activation is associated with pancreatic juice secretion and it may also modulate secretin-induced pancreatic juice flow in the anaesthetized rat.

Extracellular magnesium regulates acetylcholine-evoked amylase secretion and calcium mobilization in rat pancreatic acinar cells.

Application of ACh (10(-6) M) to the isolated rat pancreas elicited large increases in amylase secretion, radiolabelled 45Ca influx and cytosolic free Ca2+ levels in zero and normal (1.1 mM) extracellular magnesium (Mg2+). Elevated (10 mM) Mg2+ significantly (P less than 0.001) reduced the ACh-induced amylase output and Ca2+ mobilization. Similarly, ACh (10(-5) M) caused a transient increase in 45Ca efflux from pre-loaded pancreatic segments in normal Mg2+ compared with the much reduced effect in elevated Mg2+. The results suggest that a modification in Mg2+ influences ACh-evoked amylase secretion by regulating Ca2+ mobilization.