Comparative vaccination of cattle against Boophilus microplus with recombinant antigen Bm86 alone or in combination with recombinant Bm91

Cattle were vaccinated either with a single recombinant tick antigen, Bm86 or with a combination of two recombinant antigens, Bm86 and Bm91 from the tick Boophilus microplus . In three experiments, the responses of cattle to subsequent challenge with the tick were assessed. The addition of the Bm91 antigen enhanced the efficacy of the vaccination over that with Bm86 alone to a statistically significant degree. Moreover, co-vaccination with two antigens did not impair the response of cattle to the Bm86 antigen. Finally, responses of individual cattle to the two antigens were independent. All of these results may be relevant to the increase in efficacy expected from a dual antigen vaccine.     

ACEA-1328, AN NMDA RECEPTOR ANTAGONIST, INCREASES THE POTENCY OF MORPHINE AND U50,488H IN THE TAIL FLICK TEST IN MICE

The effect of 5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), a competitive and systemically bioavailable NMDA receptor/glycine site antagonist, was examined on opioid-induced antinociception in the tail flick test. Swiss Webster mice were injected with ACEA-1328 either alone or in combination with morphine or (±)-trans-U-50488 methanesulfonate (U50,488H), a μ- and a κ-opioid receptor agonist, respectively, and tested for antinociception. Systemic administration of ACEA-1328 alone increased the tail flick latencies with an ED₅₀of approximately 45 mg kg⁻¹. Concurrent administration of ACEA-1328 with morphine, or U50,488H, at doses that did not affect tail flick latencies, potentiated the antinociceptive effect of the opioid analgesics and vice versa. Naloxone, an opioid receptor antagonist, while not modifying the effect of ACEA-1328, did block the augmentation, suggesting that opioid receptors might be involved in the latter effect. 5-Aza-7-chloro-4-hydroxy-3-(m-phenoxyphenyl)quinoline-2(1H)-one (ACEA-0762), a selective NMDA receptor/glycine site antagonist, also showed enhancement of the antinociceptive effect of morphine and U50,488H. However, concurrent administration of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), a selective non-NMDA receptor antagonist, with morphine did not alter the antinociceptive potency of the opioid analgesic. Overall, the data suggest that ACEA-1328 may increase the potency of the opioid analgesics by antagonising the glycine site associated with the NMDA receptor.     

A New Low Threshold Platinized Epicardial Pacing Electrode: Comparative Evaluation in Immature Canines

A prospective comparison of pacing and sensing capabilities between the conventional Medtronic Model 4951 platinum-iridium epicardial pacing electrode and a new modified "platinized" version of the same electrode was performed in immature canines to determine if the new electrode design improves pacing in the immature myocardium. The conventional electrode was modified by electroplating platinum black particles onto the surface to increase the effective or true microscopic surface area, yet essentially maintain the same overall geometric electrode size. Both epicardial electrodes were inserted into the right ventricular myocardium with the lead pad sutured to the epicardium, and externalized to the scruff in five puppies (age 3 months). An additional left ventricular lead was implanted to permit chronic pacing following epicardially-induced atrioventricular block. Acute and chronic sensing and pacing capabilities of each externalized electrode were performed at implant and weekly up to 4 months. Histologic examination of each electrode implant site was performed at the end of the study period. At implant, both electrodes exhibited comparable values for sensed R waves, lead impedances, and pacing thresholds. During the study, the platinized electrode exhibited lower pacing thresholds. Analysis of all postimplant data demonstrated this threshold difference to be significantly lower (P less than .01) for the platinized version. Lead impedance and sensing capabilities remained comparable between the two designs. Histologic study demonstrated less fibrotic infiltration at the platinized electrode site. This preliminary evaluation indicates that for the duration of the postimplant study period, the platinized epicardial electrode design was associated with significantly lower thresholds and less fibrosis as a function of time compared to the conventional smooth electrode surface design. The new platinized electrode limits exit block in the developing immature myocardium and permits safe pacing at lower pulse widths and voltages to increase battery life.     

CLINICAL EVALUATION OF THE AUGMENTED DELTA QUOTIENT MONITOR FOR INTRAOPERATIVE ELECTROENCEPHALOGRAPHIC MONITORING OF CHILDREN DURING SURGERY AND CARDIOPULMONARY BYPASS FOR REPAIR OF CONGENITAL CARDIAC DEFECTS

To assess the augmented delta quotient (ADQ) monitor as a monitorof cerebral function during cardiac surgery, we monitored duringoperation the electroencephalograms of 48 young subjects (aged2 weeks to 19 yr). We found ADQ patterns produced by cardiopulmonarybypass, hypothermia and general anaesthetic agents correlatedwith those obtained from a compressed spectral array (CSA) monitorand could be differentiated from changes caused by cerebralischaemia, except in the youngest group of patients ( 18 months)undergoing deep hypothermia (19.4 (SD 0.8) °C nasopharyngeal).In all other age groups the ADQ proved to be a simple monitorof the adequacy of cerebral perfusion. Neurological deficitoccurred only if the ADQ was abnormal during hypotension fora period exceeding 7 min. ADQ evaluation of cerebral functionwas limited by events which produced artificially normal ADQreadings such as low amplitude EEG activity and the describedisoflurane effect that was demonstrated to occur in some cardiacpatients. The results obtained by the ADQ were comparable tothose obtained by compressed spectral array and the ADQ waseasier to use and interpret. ^*Present address: Department of Anaesthesia and Intensive Care,Basingstoke District Hospital, Basingstoke, Hants.     

LONGEVITY AMONG ETHNIC GROUPS IN ALCOHOLIC LIVER DISEASE

As part of a multicenter V.A. Cooperative Study, 437 male veteranswith varying stages of alcoholic liver injury were followedover a 4.5 year period. Their ethnic distribution consistedof 256 Caucasians, 109 black Afro-Americans, 63 Puerto RicanHispanics, and 9 Native American Indians. Survival analysesrevealed significant differences between groups (P = 0.0002):66% of Afro-Americans were still living at 42 months; Caucasianswere intermediate with 40% survival; and only 28% of Hispanicswere alive. The number of Native American Indians enrolled wastoo small to draw conclusions but none of those enrolled survivedbeyond 24 months. Survival regression analysis of 30 clinical,laboratory, histologic and nutritional parameters, revealedthe following significant risk factors: clinical severity (P< 0.0001), histologic severity (P < 0.0001), race (P =0.001), age (P = 0.002), BUN (P = 0.01) and ALT (P = 0.02).These analyses indicated that ethnicity, independent of othervariables, is significantly associated with outcome from thedisease.     

Invasive electrophysiological evaluation of patients with sleep apnoea-associated ventricular asystole—methods and preliminary results

SUMMARY  Twelve patients (aged 48 ± 12 y) with ventricular asystole of >3s due to complete atrioventricular (AV) block ( n = 8), sinoatrial (SA) block or sinus node arrest ( n = 3) or both ( n = 1) associated with obstructive sleep apnoea underwent invasive electrophysiological evaluation of sinus node function and AV conduction properties before and after administration of atropine (0.02 mg kg^-1). Ventricular asystole lasted for 5.9 ± 2.8 s (range 3.1–13 s). Sinus node function was assessed by measurement of sinus node recovery time, sinoatrial conduction time, and the response of sinus rate to atropine. Parameters of AV-conduction assessment included AH- and HV-intervals, AV- and VA-Wenckebach periods, and effective refractory period of the AV node before and after atropine. Sinus node function was normal in 11 of the 12 study patients and moderately abnormal in 1 patient. AV-nodal function was normal in 8 patients and moderately abnormal in 4 patients. A slightly prolonged HV-interval (59–63 ms) was present in 6 patients. Intra- or infra His block was not observed in any patient. In conclusion, normal or only moderately abnormal electrophysiological findings in patients with sleep apnoea-associated ventricular asystole suggest that a neurally mediated cardioinhibitory reflex may cause ventricular asystole in these patients. This sleep apnoea-triggered 'vasovagal' reflex may unmask pre-existing mild to moderate structural abnormalities of the AV conduction system.     

Transplantation Antigens and Malignant Lymphomas in Man: Follicular Lymphoma, Reticulum Cell Sarcoma and Lymphosarcoma

134 patients with malignant lymphoma (follicular lymphoma, 56 patients; lymphosarcoma, 50 patients; reticulum cell sarcoma, 28 patients) have been typed for eight well-defined antigens of the HL—A system, the major histocompatibility system in man. A significant association exists between HL—A12 and this disease group. This is most marked for the patients with follicular lymphoma. The significance of this finding is discussed.     

Risk-taking and adolescent development: The functions of smoking and alcohol consumption in adolescence and its consequences for prevention

The taking of health risks among adolescents–especiallyin the form of tobacco and alcohol consumption–remainsone of the outstanding problems facing health education aimedat the young. The majority of adolescents react to preventivemeasures and statements about health with either refractorinessor non-compliance, blaming adults for alleged "hypocrisy" anddouble-standards over health matters. An important–buthitherto scarcely discussed–part of the background tothis problem would seem to lie in the "blindness" of healthresearchers and educators to the multiple developmental functionsof the health risk-taking process for the adolescents themselves. In this article, health risk-taking is analysed in its functionalaspect, therefore, by focusing on possible developmental benefits.It can be shown that different stages of development and the‘tasks’ inherent in them correspond closely to theinitiation, stabilisation and habitualisation processes of healthrisk-taking practices. How adolescents cope with developmentaldemands includes learning how to deal with such intoxicantsas tobacco and alcohol; the acquiring of risk-related expertiseand competence can be defined and assessed in terms of a peculiar"developmental task" of this period. In developed societies, furthermore, the young conceive healthin a frame of reference and with priorities different from thoseof epidemiologists and health experts. Professional neglectof such factors has led to the failure of many preventive measurestargeted at this group. In a functional perspective of healthrisk-taking, an innovative concept such as the "health promotionapproach" (aiming at lifestyle-formation rather than asceticismin isolated behavioural sectors) seems well suited to take upyoung people's needs and ensure their participation. The principalaim of prevention should therefore be the establishment of "abuseawareness" through the acquisition of comprehensive life skills.     

Nancy Milio's work and its importance for the development of health promotion

This review considers Nancy Milio's books and papers from theperspective of health promotion in general, and in particular,from the perspective of inter-sectoral policy, the promotionof health by the collaboration of the health-service sectorwith sectors outside health (such as agriculture and energy)to develop and implement health-enhancing rather than health-damagingpolicies in those other sectors. Milio's substantial conceptualand empirical contributions are discussed and her significantaffirmations of healthy values are noted. With the aim of allowingMilio to speak for herself, extensive quotations are used toindicate her concept of health, social perspectives and approachto health promotion through the development of healthenhancingpublic policy. Milio's concept of health as a sustainable balance or adaptationof the individual to the environment might seem to imply a passiveor reactive attitude. But her approach to health policy is reminiscentof the dynamism of the public-health academics and campaignersof the nineteenth century in tackling the hostile environment.The "environment" is taken by Milio to encompass not only thebiological, chemical and physical environments but also thesociocultural, political and economic environments. The range and character of Milio's approach to advancing people'shealth is discussed principally in relation to her seminal bookPromoting Health through Public Policy but her approach is alsoillustrated by reference to her detailed studies of tobaccopolicy and Norwegian farmfood policy. The basic tools Miliosees as being needed to help the health sector promote health-enhancingpolicies in other sectors include the development of socialepidemiology, new kinds of health education and health economics,and the study of information technology. Finally, a paper in which Milio discussed love and power asneglected issues in health care is used both to illustrate thebreadth and sensitivity of Milio's perceptions and to suggestthat, though she begins to raise questions about fundamentaleconomic concepts (of efficiency and productivity), her otherwiseecologically orientated perspective stops short of confrontingbasic economic concepts relevant to health.     

Delayed Enhancement of Acetaminophen Hepatotoxicity by General Anesthesia Using Diethyl Ether or Halothane

Delayed Enhancement of Acetaminophen Hepatotoxicity by GeneralAnesthesia Using Diethyl Ether or Halothane. WELLS, P. G., RAMJI,P., AND KU, M. S. W. (1986). Fundam. App. Toxicol 6, 299–306.Acetaminophen (Tylenol) is a widely used analgesic/antipyreticdrug which is enzymatically bioactivated, or toxified, by thecytochromes P-450 to a hepatotoxic reactive intermediary metabolite.Brief general anesthesia with diethyl ether has been shown toinhibit both the toxifying cytochromes P-450 and enzymatic glucuronidation,the latter constituting up to 60% of acetaminophen eliminationvia a nontoxifying pathway. Thus ether potentially could producea temporally differentiated inhibition of bioactivating and"detoxifying" pathways, resulting in an enhancement of acetaminophenhepatotoxicity if the balance favored bioactivation. To evaluatethis possibility, separate groups of male NIH strain mice weretreated with acetaminophen at different times after 5 min ofanesthesia with ether. Ether produced a 40-fold enhancementin acetaminophen hepatotoxicity as determined by plasma glutamic-pyruvictransaminase (GPT) concentrations. This toxicologic enhancementwas observed only if acetaminophen administration was delayed,with a maximal enhancement when acetaminophen was given 6 hrafter ether, and no effect with a delay of 16 hr. Similar studiesin male CD-1 mice were carried out using halothane (Fluothane)as the general anesthetic given either over 5 min or over 1hr. While halothane given over 5 min had no effect, a 1 hr anestheticduration produced a 10-fold increase in acetaminophen hepatotoxicityas determined by peak GPT concentration, with no observed hepatotoxicityin the halothane controls. Toxicologic enhancement occurredonly with delayed administration of acetaminophen; however,the maximal enhancement observed with a 6-hr delay was stillevident with a 12-hr delay. Conversely, inhibition of acetaminophenhepatotoxicity was observed if acetaminophen was given either2 hr or 18 hr after halothane. These observations may have clinicalrelevance, and they indicate potential complications in theinterpretation of results obtained from animals subjected togeneral anesthesia.