The Effects of Magnetic Resonance Imaging on Implantable Pulse Generators

The effects of magnetic resonance imaging were assessed on four dual chamber and two single chamber pulse generators. The tests were performed with a resistive, water-cooled magnet operating at 0.15 T. The 6.4-MHz radiofrequency (RF) field was operated at a maximum power of 1,000 watts with a period adjusted from 130 to 500 ms. Reed switch closure occurred in all six pulse generators tested when placed near the entrance of the magnetic resonance imaging scanner, and the generators reverted to asynchronous operation unless programmed to the "magnet off" mode. None of the pulse generators exhibited any alterations in programmed parameters or in the ability to be reprogrammed after RF pulsing. When the RF field was turned on, there was no change in the asynchronous paced cycle length in four pulse generators; however, during RF scanning there was rapid cardiac stimulation at the RF pulse period in one single chamber and one dual chamber pulse generator.     

Design of Animal Carcinogenicity Studies for Goodness-of-Fit of Multistage Models

Design of Animal Carrinogenkity Studies for Goodness-of-Fitof Multistage Models. PORTIER, C. J., AND HOEL, D. G. (1984).Fundam. Appl. Toxicol. 4, 949–959. The effect of bioassaydesign changes on the variability of risk estimates in the experimentaldose region is investigated. Three-dose designs with a controlgroup and other "usual" designs utilizing 200 animals are studiedin detail. Constraints on the minimum power of the linear trendtest in proportions are used to eliminate designs with unacceptablepower. An acceptable design region is compared to designs aimedat improving the low dose extrapolation. A group of designsacceptable for a range of objectives is proposed.     

MODULATION OF ALCOHOL PREFERENCE BY NMDA ANTAGONISTS IN MALE RATS

Chronic alcoholization by alcohol inhalation was used to studythe properties of magnesium, a non-competitive NMDA receptorantagonist, and CGP 39551, a competitive NMDA receptor antagonist,on behavioural dependence as estimated by the free-choice paradigm[alcohol 10% (v/v) vs. water], on the hypermotility after alcoholwithdrawal, and finally on the cortical vascularization. Thefirst experimental group received the drugs per os during thewhole alcoholization period. Magnesium (20 mg/kg/day) decreasedthe alcohol dependence while CGP 39551 (5 and 10 mg/kg/day)increased, in a dose-dependent manner, the dependence to alcohol.A second group of animals received the same drugs at the samedosages, not simultaneously during chronic alcoholization, butimmediately after alcoholization in one shot i.p. injection.In this case, rats receiving 5 mg/kg CGP 39551 never showedany dependence towards alcohol, while 10 mg/kg CGP 39551 or20 mg/kg magnesium prolonged the number of days of alcohol dependence.These results thus indicate the close interaction between NMDAreceptor function and dependence for alcohol. Magnesium hadno effects on hypermotility, while CGP 39551-treated animalspresented a decrease in the hypermotility observed after alcoholwithdrawal. Neither drug affected the hypervasculanzation accompanyingthe chronic alcoholization.     

FLUMAZENIL IN ALCOHOL WITHDRAWAL: A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY

The purpose of the present study was to study -aminobutyricacid (GABA)-A receptor function in alcohol-dependent subjectsduring withdrawal, using the benzodiazepine antagonist flumazenil.In particular, we wanted to examine the hypotheses that an endogenousinverse agonist ligand at the GABA-A benzodiazepine receptor(GBzR) is active during withdrawal (in which case flumazenilshould be anxiolytic), or whether chronic alcohol intake resultsin a shift in sensitivity of the receptor in the inverse agonistdirection (in which case flumazenil should be anxiogenic). Resultsfrom 15 alcohol-dependent subjects in a double-blind placebo-controlledcross-over study showed that flumazenil was neither anxiolyticnor anxiogenic, although withdrawal scores were reduced duringthe course of the study. The fact that flumazenil was not anxiogenic,as it is in panic disorder, suggests that the GBzR is functioningdifferently in these two clinically similar conditions.     

Immunomodulation by Metals

A symposium entitled Immunomodulation by Metals was held atthe 32nd Annual Meeting of the Society of Toxicology (SOT) inNew Orleans, Louisiana. The symposium was cosponsored by theImmunotoxicology and Metals Specialty Sections of SOT and wasdesigned to describe the types of adverse immunological reactionswhich occur in response to environmental and/or occupationalexposure to metals. Epidemiological evidence and underlyingmechanisms responsible for the observed alterations were alsodiscussed. The following is a summary of each of the individualpresentations.     

Immunotoxicological Profile of Morphine Sulfate in B6C3F1 Female Mice

This study was undertaken to investigate a number of immuneparameters which may be compromised with exposure to morphinesulfate. Mice were implanted subcutaneously with 8-, 25-, or75-mg morphine sulfate pellets. Placebo pellets of identicalmakeup to the 75-mg morphine pellet (without morphine of course)were used as a control. Twenty-four hours after implantationof a 75-mg morphine pellet, blood levels reached a peak of 1610ng/ml. Corticosterone increased in parallel with morphine andreached a peak level of 966 ng/ml 24 hr after implantation.The dose response of morphine to increase corticosterone, however,was fiat. The weight of the lymphoid organs, spleen and thymus,and the liver were significantly reduced in the morphine-treatedgroups. Morphine treatment was associated with an increase inserum albumin, SGPT, BUN, and alkaline phosphatase indicativeof hepatic damage. In contrast to increased serum proteins,the C3 component of complement was reduced in a dose-dependentmanner. Leukocyte number in the peripheral blood was significantlyreduced, while erythro-cyte number and hematocrit were bothincreased. The number of B cells and T cells was decreased inmorphine-treated animals. However, the percentage of T cellsrelative to B cells was increased. The primary IgM antibodyresponse to the T-depen-dent antigen, sheep red blood cells,was decreased. Natural killer cell activity was reduced in responseto morphine, as was the phagocytic capacity of Kupffer cells.Host-resistance models of Listeria monocytogenes or Streptococcuspneumoniae showed an increased resistance following administrationof morphine. This increased host resistance, however, was notdue to an increase in antimicrobial action of sera obtainedfrom mice treated with morphine. The majority of morphine'seffects on the immune system exhibited a flat dose response,suggesting that these effects may be mediated secondarily throughcorticosterone.     

Vital exhaustion, extent of atherosclerosis, and the clinical course after successful percutaneous transluminal coronary angioplasty

It has been observed that vital exhaustion, a state characterizedby unusual tiredness, increased irritability and feelings ofdemoralization not uncommonly precedes myocardial infarctionin apparently healthy individuals. This observation raised thequestion as to whether vital exhaustion is a marker of subclinicalcoronary disease. To answer that question the condition wasassessed in 105 male patients (mean age 54·8 year) beforeand 2 weeks after successful percutaneous transluminal coronaryangioplasty (PTCA) by the Maastricht questionnaire. Vital exhaustionwas found to be significantly correlated with the number ofdiseased vessels before PTCA and to decrease significantly afterPTCA. However, the association was rather modest (R²=0·08)and most patients remained exhausted after PTCA. During a follow-upperiod of 1·5 years, 32 patients (30%) experienced anew cardiac event (cardiac death, myocardial infarction, coronaryartery bypass grafting, repeat PTCA, a new coronary lesion orrecurrent angina with documented ischaemia). Univariate andmultivariate analyses showed that the number of diseased vessels,hypercholesterolaemia, and vital exhaustion were independentlyassociated with future events. The odds ratios were 3·74(P=0·02), 3·08 (P=0·08) and 3·07(P=0·04), respectively. It is concluded that the tirednesspreceding a cardiac event is only modestly associated with theextent of coronary artery disease and that a state of exhaustionafter PTCA increases the risk for a new cardiac event.     

Dietary Changes Favorably Affect Bone Remodeling in Older Adults

OBJECTIVE: To determine whether dietary counseling to increase milk intake could produce useful changes in the calcium economy and what, if any, other nutrition-related changes might be produced. DESIGN: Randomized, open trial. SUBJECTS/SETTING: Two hundred four healthy men and women, aged 55 to 85 years, who habitually consumed fewer than 1.5 servings of dairy foods per day. Six academic health centers in the United States. INTERVENTION: Subjects were instructed to consume 3 servings per day of nonfat milk or 1% milk as a part of their daily diets, or to maintain their usual diets, for a 12-week intervention period, which followed 4 weeks of baseline observations. MAIN OUTCOME MEASURES: Energy and nutrient intake assessed from milk intake logs and 3-day food records; serum calciotrophic hormone levels at baseline and at 8 and 12 weeks; urinary excretion of calcium and N-telopeptide at 12 weeks. STATISTICAL ANALYSES: Repeated-measures analysis of variance. RESULTS: In the milk-supplemented group, calcium intake increased by 729 +/- 45 mg/day (mean +/- standard error), serum parathyroid hormone level decreased by approximately 9%, and urinary excretion of N-telopeptide, a bone resorption marker, decreased by 13%. Urine calcium excretion increased in milk-supplemented subjects by 21 +/- 7.6 mg/day (mean +/- standard error), less than half the amount predicted to be absorbed from the increment in calcium intake. All of these changes were significantly different from baseline values in the milk group and from the corresponding changes in the control group. Bone-specific alkaline phosphatase level (a bone formation marker) fell by approximately 9% in both groups. Serum level of insulin-like growth factor-1 (IGF-1) rose by 10% in the milk group (P < .001), and the level of insulin-like growth factor binding protein-4 (IGFBP-4) fell slightly (1.9%) in the milk group and rose significantly (7.9%) in the control group (P < .05). APPLICATIONS/CONCLUSIONS: The changes observed in the calcium economy through consumption of food sources of calcium are similar in kind and extent to those reported previously for calcium supplement tablets. The increase in IGF-1 level and the decrease in IBFBP-4 level are new observations that are beneficial for bone health. Important improvements in skeletal metabolism can feasibly occur in older adults by consumption of food sources of calcium. Dietitians can be confident that food works, and that desired calcium intakes can be achieved using food sources.     

Coping with rheumatoid arthritis. How can specialist nurses influence it and promote better outcomes?

• ? Psychological stressors are said to be an important influence on the outcome of chronic illnesses such as rheumatoid arthritis (Engel, 1977).
• ? Helping patients to cope with stressors is identified as a central concept in the delivery of nursing care (Khan et al., 1994). It is thus reasonable to suggest that rheumatology nurses may be key players in the process of coping with rheumatoid arthritis.
• ? But in order for rheumatology nurses to be effective players in this process, they need to discourage coping behaviour(s) linked to poor outcomes, and/or promote an overall behaviour pattern linked to a better outcome. Literature showing the link between different coping behaviours and outcome is examined, and cognitive restructuring is emphasized as one method nurses could use.
• ? Having identified coping behaviour which is optimal in terms of future outcome, further study of different forms of coping-based educational intervention is suggested, to reveal how such patterns of behaviour can be taught by nurses in the most effective way