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.     

Impact of Nutrients on Cellular Lipid Peroxidation and Antioxidant Defense System

A symposium entitled Impact of Nutrients on Cellular Lipid Peroxidationand Antioxidant Defense System was held at the 33rd Annual Meetingof the Society of Toxicology (SOT) at the Loews Anatole Hotelin Dallas, Texas. The symposium was sponsored by the Food SafetySpecialty Section and focused on the role of particular nutrientsin cellular lipid peroxidation and antioxidant defense system.Emphasis was placed on defining underlying mechanisms for damageand protection, as well as potential ramification in human healthissues. The following are extractions of some of the highlightsfrom each presentation.     

An action research investigation into the feasibility of experienced registered sick children's nurses (RSCNs) becoming children's emergency nurse practitioners (ENPs)

• ? Emergency nurse practitioners (ENPs) formally developed in accident and emergency (A & E) departments as a direct response to waiting times for the walking wounded, the need to reduce junior doctors hours and changes in nursing practice.
• ? ENPs existed informally for many years in minor injuries units and specialist ophthalmic departments.
• ? This study aimed to examine whether or not the role of ENP could be applied to the specialist service of a paediatric casualty department.
• ? The results showed that 3% of patients could be seen and treated to conclusion by a children's ENP, and some patients could have their care accelerated by a children's ENP.
• ? The introduction of children's ENPs would have an impact on waiting times, junior doctors work-load and the quality of patient care.

     

Potency of a Complex Mixture of Polychlorinated Dibenzo-p-dioxin, Dibenzofuran, and Biphenyl Congeners Compared to 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Causing Fish Early Life Stage Mortality

Use of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity equivalentsconcentration (TEC) assumes that polychlorinated di benzo-p-dioxins(PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) act additivelyand via a common mechanism to cause toxicity. To test theseassumptions, 11 TCDD-like congeners and three non-TCDD-likecongeners were combined at ratios typically found in Lake Michiganlake trout. The potency of the mixture, expressed as TEC basedon fish-specific toxic equivalency factors, was compared toTCDD for producing lake trout and rainbow trout early life stagemortality. Signs of toxicity following exposure of newly fertilizedeggs to the mixture or to TCDD were indistinguishable; sac frymortality associated with blue-sac disease, and slopes of thedose-response curves for percentage sac fry mortality versusegg TEC or versus egg TCDD were parallel. However, the mixturedose-response curves were significantly shifted to the rightof the TCDD dose-response curves by 1.3- to 1.8-fold as illustratedby LD₅₀ values. Following exposure to the mixture or TCDD, LD₅₀sfor lake trout early life stage mortality were 97 (89–110)pg TE/g egg and 74 (70–80) pg TCDD/g (LD₅₀, 95% fiduciallimits) and for rainbow trout were 362 (312–406) pg TE/gegg and 200 (148–237) pg TCDD/g egg. These data suggestthat TCDD-like congeners act via a common mechanism to causetoxicity during trout early development, but may not act strictlyadditively when combined in a mixture of TCDD- and non-TCDD-likecongeners at ratios found in Great Lakes fish. The deviationfrom additivity, however, is less than current safety factorsof 10-fold commonly applied in ecological risk assessments,providing support for the continued use of a TE additivity modelfor assessing risk posed by complex mixtures of PCDDs, PCDFs,and PCBs to fish.     

Tumors of the Bladder, Kidney, and Intestine of F344 Rats and Liver of B6C3F1 Mice Administered o-Nitroanisole in Feed

Tumors of the Bladder, Kidney, and Intestine of F344 Rats andLiver of B6C3F₁ Mice Administered o-Nitroanisole in Feed. IRWIN,R. D., CHHABRA, R., EUSTIS, S., PINTER, A., AND PREJEAN, J.D. 1996). Fundam. Appl. Toxicol. 30, 1–12. o-Nitroanisole, a mutagenic intermediate used in the manufactureof azo dyes, was administered in feed for 2 years at concentrationsof 0, 222, 666, or 2000 ppm to groups of 60 male and 60 femaleF344 rats. No significant increase in neoplasms occurred inthese groups of rats. Additional (stop exposure) groups of 60male and 60 female F344 rats received diets containing 0, 6000,or 18,000 ppm for 27 weeks followed by maintenance on controldiets for up to an additional 77 weeks. Survival of the stopexposure groups was reduced because of the development of chemicalrelated neoplasms of the urinary bladder. After 13, 28, 40,and 65 weeks on study, 10 rats per group were necropsied andevaluated for the presence of chemical associated lesions. Hyperplasiaof the epithelium of the urinary bladder was significantly increasedat all interim evaluations. A transitional cell carcinoma wasobserved at the 13-week evaluation in one male rat that received18,000 ppm and thereafter transitional cell neoplasms of thebladder were present in male and female rats at each interimevaluation. Adeno matous polyps of the large intestine weresignificantly increased in groups that received 6000 or 18,000ppm. In addition carcino mas of the large intestine were presentin four males and two females that received 18,000 ppm. Hyperplasiaof the transitional epithelium of the renal pelvis was significantlyincreased in groups of rats that received 6000 or 18,000 ppmand transitional cell papillomas were observed in three malesand one female that received 18,000 ppm. Transitional cell carcinomasof the kidney occurred in one male that received 6000 ppm andsix males and one female that received 18,000. Groups of 60male and 60 female B6C3F₁, mice received dietary concentrationsof 0, 666, 2000, or 6000 ppm o-nitroanisole for 2 years. Nostop exposure study was conducted with mice. The only neoplasticresponse observed in mice was in the liver of males; hepatocellularadenomas or carcino mas were increased in groups of male micethat received 2000 or 6000 ppm. No increase in neoplasms associatedwith chemical exposure occurred in female mice.     

Pulmonary Immunotoxicity of Inhaled Ammonium Metavanadate in Fisher 344 Rats

Male Fisher 344 rats were exposed to 2 mg vanadium(V)/m³ (asammonium metavanadate NH⁴VO³, 0.32 µm MMD) atmospheresfor 8 hr/day for 4 days in a nose-only exposure system. In exposedrats, lung V burdens increased in a time-dependent fashion.Analysis of lung cells and lavage fluid 24 hr after the finalexposure suggested that tissue damage and a strong inflammatoryresponse was elicited; numbers of neutrophil and small macrophages(M), as well as levels of lavageable protein and lactate dehydrogenase,were significantly elevated as compared with levels observedwith air-exposed rats. Vanadium also affected pulmonary alveolarM (PAM) capacities to produce and respond to immunoregulatingcytokines. Inducible PAM production of tumor necrosis factor-awas significantly inhibited, as was the ability to increasecell surface Class II/I-A molecule expression in response tointerferon- (rFN-). PAM from V-exposed hosts were also inhibitedin their ability to be primed by EFN- to produce superorideanion and hydrogen peroxide in response to stimulation withopsonized zy-mosan. These studies indicate that short-term repeatedexposure of rats to atmospheric V, at levels encountered inan occupational setting, can alter host pulmonary immunomocompetence,with one major effect occurring at the level of cytokine-relatedfunctions. These alterations may be underlying mechanisms forthe well-documented increases in bronchopulmonary infectionsand cancers in workers chronically exposed to V-containing atmospheres.     

Retinoid-Induced Hypertriglyceridemia in Rats Is Mediated by Retinoic Acid Receptors

Retinoids in clinical use today are known to induce hypertriglyceridemiaas one of their major side effects. The purpose of the presentstudy was to determine, in an appropriate animal model, if retinoid-inducedhypertriglyceridemia is mediated by retinoic acid receptors(RARs) and/or by retinoid X receptors (RXRs). Oral gavage ofmale Fischer rats with 13-cis-retinoic acid for 6 days causeda rapid and sustained increase in serum triglycerides that wasreversible within 4 days posttreatment In subsequent experiments,rats were treated by gavage once daily for 3 days with variousretinoids, and serum triglyceride levels were determined 24hr after the last treatment without fasting. All-trans-and 13-cis-retinoicacid, which can be converted to both RAR and RXR agonists, and9-cis-retinoic acid, an RAR/RXR pan-agonist, caused dose-dependentincreases in serum triglycerides at doses that did not causeweight loss or mucocutaneous toxicity. Ro 13–6298 andAGN 190121, two RAR-specific agonists, caused dose-dependentincreases in serum triglycerides, although Ro 13–6298only induced hypertriglyceridemia at weight-suppressive doses.Two RXR-selective agonists, LG100268 and AGN 191701, failedto induce hypertriglyceridemia or weight loss up to the highestdoses tested. A structural isomer of AGN 190121 that does notactivate RARs or RXRs, AGN 190727, did not induce hypertriglyceridemia.Hypertriglyceridemia induced by AGN 190121 was significantlyinhibited by co-treatment with an RAR-selective antagonist,AGN 193109. Taken together, these data provide strong evidencethat retinoid-induced hypertriglyceridemia is mediated, at leastin part, by RARs. These data also suggest that RXR-specificagonists may have reduced potential to induce hypertriglyceridemiarelative to RAR-active retinoids.     

A study of the provision of health checks and health-promotion clinics in 18 general practices

Summary

• ? The objective of this study was to describe the variation in provision of health checks and health-promotion clinics operating under the regulations of the 1990 Contract for general practice in the UK.
• ? Eighteen group practices in three Family Health Service Authority (FHSA) areas of England (two in the South West Thames region and one in the Yorkshire region) were selected for the study. The nurses, largely responsible for the implementation of the health checks at these practices, were interviewed using semi-structured interview schedules. They were asked about age-groups targeted, means of recruiting patients for clinics, duration of clinic appointments, and procedures carried out in clinics.
• ? All practices offered health checks, and 55% had started doing so before introduction of the 1990 Contract. Recruitment for health checks took place in a number of ways: self-referral (83% of practices); opportunistically in those with coronary heart disease risk factors (78%); opportunistically during attendance for cervical smears (62%); screening in at least one patient group (78%). Blood pressure, height, weight, urinalysis and life-style advice were included by all practices. Stress management and quit smoking strategies were offered only by a minority of practices. Duration of first health-check appointment ranged between 15 and 30 minutes.
• ? The basic content of health checks, and life-style advice given appeared consistent between the widely varying practices. However, the resources available for intervention and follow up showed more variation.

     

Evaluating the effectiveness of the coronary care nurses' role in smoking cessation

Summary

• ? The aim of this small-scale study was to assess the feasibility and impact of an individualized smoking cessation intervention among clients admitted to a coronary care unit with severe angina or a first time myocardial infarction.
• ? The intervention involved in-depth nursing assessment interviews related to client beliefs, motivation and experiences of smoking, culminating in an individualized cessation plan. Participants were offered follow up support during the first year post-intervention.
• ? The findings are highly encouraging with a 77% smoking cessation rate for surviving clients within the intervention group at the end of the first year, and with 75% continued successful smoking cessation amongst surviving clients 2 years post-intervention.

     

COGNITIVE IMPAIRMENT AND AUTOANTLBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS

Nervous system involvement in systemic lupus erythematosus (SLE)includes a wide array of manifestations some of which have beenassociated with specific autoantibodies. These include reactivityto surface neuronal and lymphocyte antigens, ribosomal P andcardiolipin. The aim of the present study was to examine theassociation between cognitive abnormalities and these autoantibodiesin an unselected female population of SLE patients. Using abattery of standardized neuropsychological tests, cognitiveimpairment was identified in 15/70 (21%) SLE patients comparedto 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%)healthy subjects (P=0.04). Circulating antineuronal antibodieswere measured by indirect immunofluorescence using human neuroblastomacell lines IMR-6 and SK-N-SH. Lyrnphocytotoxic antibodies weremeasured by microcytotoxicity. Antibodies to ribosomal P andcardiolipin were measured by ELISA. Antineuronal antibodieswere detected in 34%, lymphocytotoxic antibodies in 47%, anti-Pantibodies in 17% and anticardiolipin antibodies in 24% of patients.In the cognitively impaired and unimpaired SLE patients therewas no significant difference in the prevalence of antineuronalantibodies (33 vs 35%), lymphocytotoxic antibodies (40 vs 50%),anti-P antibodies (20 vs 17%) or anticardiolipin antibodies(7 vs 29%). The titre and isotype of autoantibodies were alsosimilar in both groups. These results suggest that autoantibodieswhich have previously been associated with nervous system manifestationsof SLE are not likely to be directly involved in the pathogenesisof cognitive dysfunction. KEY WORDS: Cognitive impairment, Autoantibodies, Lupus