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.     

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.     

Aldicarb Immunotoxicity: Functional Analysis of Cell-Mediated Immunity and Quantitation of Lymphocyte Subpopulations

Aldicarb Immunotoxicity: Functional Analysis of Cell-MediatedImmunity and Quantitation of Lymphocyte Subpopulations. THOMAS,P., RATAJCZAK, H., DEMETRAL, D., HAGEN, K., AND BARON, R. (1990).Fundam. Appl. Toxicol. 15, 221–230. Adult female B6C3F1mice received distilled water only or water containing 1.0,10, or 100 ppb of aldicarb daily for 34 days. The target concentrationof aldicarb present in the 100 ppb dosing solution was analyticallyverified. To further develop an immune profile of this compound,following aldicarb exposure, the ability of splenic naturalkiller cells and specifically sensitized cytotoxic T-lymphocytesto lyse YAC-1 lymphoma and P815 tumor cells, respectively, wasevaluated. To supplement the functional assays, the impact ofaldicarb exposure on the percentages and absolute numbers oftotal T-cells, T-suppressor, T-helper, and B-cells was evaluated.The absence of statistically significant effects on any of theseparameters supports earlier reports that aldicarb does not resultin adverse effects on the immune system of mice.     

A JOINT PROBLEM DRINKING CLINIC: THE KING'S COLLEGE AND MAUDSLEY HOSPITALS INITIATIVE

We describe the establishment of a joint alcohol misuse clinic,staffed by both a psychiatrist and a physician, in a LondonTeaching Hospital providing general as well as specialist medicalservices. The demographic and medicopsychiatric problems ofthe first 100 referrals (60% attendance rate) are described.The clinic provides an assessment and re-education role formost patients referred with alcohol misuse problems: the needfor specialist alcohol treatment facilities, especially forin-patients, remains essential. In addition, the clinic providesa valuable training and research resource.     

AN EVALUATION OF REBREATHING WITH THE BAIN SYSTEM DURING ANAESTHESIA WITH SPONTANEOUS VENTILATION

Data from 12 anaesthetized patients breathing spontaneouslyfrom the Bain system were used to calculate the degree of rebreathingoccurring when the fresh gas flowrate(F) was equal to 2,1 and 0.7 times the estimated normalminute ventilation (_tot)- Measurementsof the expired minute volume (E) and end-tidal carbon dioxide tension (PE'_CO2) were made to determinethe effects of this rebreathing. No rebreathing occurred whenF was equal to twice tot. When F was equal to tot rebreathing was usually small in amount and produced no changes in E or PE'_CO2. Changes attributable torebreathing occurred in only two patients when F was reduced to 0.7 _tot.These results are explained by the presence of anaesthesia-inducedventilatory depression and favourable changes occurring in therespiratory wave forms in the majority of patients studied.In some patients, greater values of E and rebreathing occurred in response to strong surgical stimulation.The net result of increased ventilation in these patients wasa decrease in PE'_CO2-,. It is concluded that during anaesthesia,when the Bain system is used with F equal to _tot, any increasein PE'_CO2 which may result from rebreathing is likely to besmall and seldom of clinical importance.     

The Noninvasive Mouse Ear Swelling Assay: II. Testing the Contact Sensitizing Potency of Fragrances

The Noninvasive Mouse Ear Swelling Assay. I. Refinements forDetecting Weak Contact Sensitizers. THORNE, P. S., HAWK, C,KAUSZEWSKI, S. D., AND GUINEY, P. D. (1991). Fundam. Appl. Toxicol.17, 790–806. The noninvasive mouse ear swelling assay(MESA) is a model for delayed-type hypersensitivity that holdspromise as a testing protocol for allergic contact dermatitis(ACD). The MESA employs only topical sensitization on the abdomenand does not use injections, adjuvants, anesthesia, occlusion,or disruption of the stratum comeum. Five days after induction,the ears are challenged topically and ear swelling measurementstaken at 24,48, and 72 hr indicate the extent of ACD. In thisstudy, refinements of the assay were explored in BALB/cBy miceusing dinitrofluorobenzene (DNFB) and dinitrochlorobenzene (DNCB).A complete dose-response curve was developed for DNFB and thedose which sensitized half the mice in a group (SD50, 0.001%,w/v) was used to test noninvasive enhancement protocols. Severaltriple-dose protocols tested produced no increase in responsivenessand daily dosing showed a trend toward tolerance induction yielding20% positive responses. Dietary vitamin A supplementation produceda dramatic enhancement of the responses: ear thickness increasewas doubled and the SD50 sensitized 94 to 100% of the mice inthe vitamin A groups. We conclude that the MESA allowed identificationof ACD potency for known sensitizers at very low concentrationswhich do not produce ACD with other techniques. The importanceof dose-response studies for avoiding the high-dose reduced-responseregion was also shown. Based on the observation that the vitaminA-augmented MESA was considerably more sensitive than with regularfeed, a companion study (P. S. THORNE, C. HAWK, S. D. KALISZEWSKI,P. D. GUINEY, Fundam. Appl. Tox. 17, 807–820, 1991) presentstests of the enhancements to the MESA developed in this work,using weak sensitizers and complex mixtures.     

A TEN-YEAR HOSPITAL SURVEY OF EYELID CANCER

Two hundred and four cases of malignant eyelid tumours, managed at the Concord Hospital, were reviewed. These cases spanned a ten-year period between 1973 and 1982 and all were treated surgically. The nature of each tumour was confirmed by histopathological examination. Included in this review were the site of the tumour, the tumour pathology, the surgical management, the type of surgeon involved, the ocular complications, the management of recurrences and any mortality. The importance of preventing recurrences by adequate initial surgery with frozen section control is emphasized.