Temporal reproducibility of IgG and IgM autoantibodies in serum from healthy women.

Autoantibodies are present in healthy individuals and altered in chronic diseases. We used repeated samples collected from participants in the NYU Women's Health Study to assess autoantibody reproducibility and repertoire stability over a one-year period using the HuProt array. We included two samples collected one year apart from each of 46 healthy women (92 samples). We also included eight blinded replicate samples to assess laboratory reproducibility. A total of 21,211 IgG and IgM autoantibodies were interrogated. Of those, 86% of IgG (n = 18,303) and 34% of IgM (n = 7,242) autoantibodies showed adequate lab reproducibility (coefficient of variation [CV] < 20%). Intraclass correlation coefficients (ICCs) were estimated to assess temporal reproducibility. A high proportion of both IgG and IgM autoantibodies with CV < 20% (76% and 98%, respectively) showed excellent temporal reproducibility (ICC > 0.8). Temporal reproducibility was lower after using quantile normalization suggesting that batch variability was not an important source of error, and that normalization removed some informative biological information. To our knowledge this study is the largest in terms of sample size and autoantibody numbers to assess autoantibody reproducibility in healthy women. The results suggest that for many autoantibodies a single measurement may be used to rank individuals in studies of autoantibodies as etiologic markers of disease.

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.

BACKGROUND: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful. METHODS: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay. RESULTS: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio. CONCLUSION: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

A prospective study of endogenous estrogens and breast cancer in postmenopausal women.

BACKGROUND: Circumstantial evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue. PURPOSE: Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease. METHODS: The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14,291 New York City women, 35-65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5 1/2 years of study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35,509 person-years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at -80 degrees C since sampling. RESULTS: For increasing quartiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend = .06); the ORs for increasing quartiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend = .06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4, 3.0, and 2.9 (P value for trend < .01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend < .01), thus suggesting a strong protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn 2 or more years before breast cancer diagnosis. CONCLUSIONS: These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer. IMPLICATIONS: Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman's risk of developing breast cancer later in life.

Carcinogenic sulfide salts of nickel and cadmium induce H2O2 formation by human polymorphonuclear leukocytes.

Some derivatives of nickel, cadmium, and cobalt are carcinogenic in humans and/or animals but their mechanisms of action are not known. We show that they are capable of stimulating human polymorphonuclear leukocytes (PMNs), as measured by H2O2 formation, a known tumor promoter. Most effective were the carcinogens nickel subsulfide, which caused a 550% net increase in H2O2 over that formed by resting PMNs, followed by cadmium sulfide, 400%, and nickel disulfide, 200%. Nickel sulfide and cobalt sulfide caused statistically nonsignificant increases of 45 and 20%, respectively. Noncarcinogenic barium and manganese sulfides, and sulfates of nickel, cadmium, and cobalt were inactive. The enhancement of H2O2 formation by CdS and Ni3S2 (1 mumol/2.5 x 10(5) PMNs) was comparable to that mediated by the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate, used at 0.5 and 1 nM, respectively. Concurrent treatment of 12-O-tetradecanoylphorbol-13-acetate-stimulated PMNs with Ni3S2 or NiS caused a decrease in H2O2 accumulation from that expected if the effects were additive. Including catalase in the reaction mixture proved that the oxidant formed by stimulated PMNs was H2O2, whereas adding superoxide dismutase showed that superoxide was also present in PMN samples treated with NiS but not with Ni3S2. Since nickel- and cadmium-containing particulates are deposited in the lungs and cause infiltration of PMNs, the ability to activate those cells and induce H2O2 formation may contribute to their carcinogenicity.

Endogenous estrogens and risk of breast cancer by estrogen receptor status: a prospective study in postmenopausal women.

A positive association between postmenopausal serum levels of total estradiol, percentage of free estradiol, and percentage of estradiol not bound to sex hormone-binding globulin (SHBG) and breast cancer risk was recently reported by the New York University Women's Health Study (P. Toniolo et al., J. Natl. Cancer Inst., 87: 190-197, 1995). Data from this prospective study are used to assess whether the observed associations differ according to estrogen receptor (ER) status of the tumor. Between 1985 and 1991, 7063 postmenopausal women donated blood and completed questionnaires at a large breast cancer screening clinic in New York City. Before 1991, 130 cases of first primary breast cancer were identified by active follow-up of the cohort. For each case, two controls were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees since sampling. ER information was abstracted from pathology reports. Separate statistical analyses were conducted of ER-positive, ER-negative, and ER-unknown groups (53, 23, and 54 matched sets, respectively). In each of the 3 groups, the mean estradiol and the mean percentage of free estradiol were greater (21-28% and 6-7%, respectively) in cases than in controls. Conversely, the mean percentage of estradiol bound to SHBG was 9-12% lower in cases than in controls. The logistic regression coefficients measuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the ER-positive, ER-negative, and ER-unknown groups. These data suggest that in postmenopausal women, the association of endogenous estrogens with breast cancer risk is independent of the ER status of the tumor. This result is more compatible with the hypothesis of a progression from ER-positive to ER negative tumors than with the hypothesis that ER status identifies two distinct types of breast cancer.

Reliability of measurements of total, protein-bound, and unbound estradiol in serum.

Estradiol (E2) circulates in the blood in three states: unbound (U-E2), bound to sex-hormone binding globulin (SHBG-E2), and bound to albumin. There is evidence to support the concept that only U-E2 and albumin-bound E2, are bioavailable (i.e., rapidly extracted by tissues). A case-control study nested within a large cohort of women, in which we are examining the effect of estrogens on breast cancer risk, offered the opportunity to assess the reliability of measurements of E2, the percentage of SHBG-E2, and the percentage of U-E2 based on multiple annual serum specimens. Long-term (1-2 year) reliability, as estimated by the intraclass correlation coefficient, was assessed in a subgroup of 71 premenopausal and 77 postmenopausal controls for whom two or three serum specimens were assayed. In postmenopausal women the intraclass correlation coefficient for a single measurement of total E2 was only 0.51. As for the percentage of SHBG-E2, intraclass correlation coefficients were 0.83 and 0.94, and for U-E2, 0.72 and 0.77 in the premenopausal and postmenopausal groups, respectively. These data suggest that, whereas single determinations of total E2 are insufficient to reliably estimate a woman's true mean level, a single measurement of the percentage of SHBG-E2 or U-E2 is adequate to assess bioavailability of E2 in an epidemiological study, irrespective of day of the menstrual cycle.

Reliability of serum prolactin measurements in women.

Prolactin, a hormone indispensable for milk secretion, has been shown to enhance the development and growth of mammary tumors in rodents; however, its importance in human breast cancer is uncertain. Serum prolactin levels are known to fluctuate considerably under normal conditions, and lack of precision in the hormone measurements may have contributed to the largely negative findings in humans to date. The purpose of this study was to investigate the reliability of prolactin measurements in women using stored serum from an ongoing prospective study of breast cancer. Separate groups of postmenopausal and premenopausal women who donated multiple blood samples at approximately 1-year intervals were studied. The reliability of a single log prolactin determination, as measured by the intraclass correlation coefficient, was 0.76 for the postmenopausal women (95% confidence interval, 0.66-0.85) and 0.48 for the premenopausal women (95% confidence interval, 0.31-0.62). These findings suggest that a single measurement is sufficient to characterize the serum prolactin level of postmenopausal women for epidemiological research. For premenopausal women, however, multiple samples are desirable. Controlling for phase of the menstrual cycle does not appear to substantially improve the reliability of premenopausal measurements.

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.

OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

Prospective study of factors influencing the onset of natural menopause.

Late or early menopause has been implicated in risk of several chronic diseases in women. To study factors influencing the onset of natural menopause, the authors analyzed the follow-up data of 4694 premenopausal women who enrolled in the New York University Women Study at ages 34-61. In an average of 5.4 years of observation, there were 2035 incidences of menopause, with the median age of 51.3 years. Current smokers experienced menopause 0.75 years earlier than never-smokers. Those who smoked more than 10 cigarettes per day had a 40% increase in risk of earlier menopause. In contrast, women who had three or more children experienced menopause 0.86 years later than nulliparous women, and Jewish women, 0.66 years later than Catholic women. There was also a modest increase in the age at menopause with increasing body mass index. This prospective study provides solid epidemiologic evidence that several factors other than cigarette smoking have impact on the onset of natural menopause.

The influence of medical conditions associated with hormones on the risk of breast cancer.

Medical conditions related to hormonal abnormalities were investigated in a case-control study of breast cancer among women who attended a screening centre. Information was obtained by telephone interview regarding physician-diagnosed medical conditions such as thyroid or liver diseases, diabetes, and hypertension, as well as hirsutism, acne, galactorrhoea, and reproductive, menstrual, and gynaecological factors. Results are presented for 354 cases and 747 controls. Women with fertility problems who never succeeded in becoming pregnant were at significantly increased breast cancer risk (adjusted odds ratio [OR] = 3.5; 95% confidence interval [CI]:1.1-10.9). An elevated cancer risk was also associated with having excess body hair (OR = 1.5; 95% CI:1.0-2.3), or having excess body hair in addition to persistent adult acne (OR = 6.8; 95% CI:1.7-27.1). Recurrent amenorrhea (OR = 3.5; 95% CI:1.1-11.5), and a treated hyperthyroid condition (OR = 2.2; 95% CI:1.1-4.4) were significantly associated with risk. A non-significant elevation of risk was present for endometrial hyperplasia (OR = 1.8; 95% CI: 0.8-4.0). There was a suggestion of an association between a history of galactorrhoea and breast cancer risk (OR = 2.0; 95% CI:0.8-4.9) among premenopausal women. No associations were found with other medical or gynaecological factors. The possibility that some of these findings are due to chance cannot be excluded because of the problem of multiple comparisons.

Diet, smoking and anthropometric indices and postmenopausal bone fractures: a prospective study.

OBJECTIVE: Bone fractures are an important cause of morbidity and mortality among the elderly in the US. The present study assesses the possible role of a number of risk factors for postmenopausal bone fractures. METHODS: We analysed the relationships of anthropometric, demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospective cohort study, the New York University Women's Health Study. RESULTS: After an average of 7.6 years of follow-up, 1025 new incident bone fractures were reported, including 34 hip and 159 wrist fractures (incidence rates; 71.6 and 334.7 per 105 woman-years, respectively). The risk of fracture increased with increasing age, body height and total fat intake, while it was significantly lower among obese and African American women. The relative risk among African Americans was 0.45 (95% CI: 0.32-0.63) compared with non-African Americans. Women taller than 170 cm had a 64% increase in risk of fractures, as compared with those under 155 cm. These associations were generally more pronounced when fractures were limited to those at the hip and wrist. CONCLUSIONS: The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity, short stature and African American ethnicity.

Body fat distribution and obesity in pre- and postmenopausal breast cancer.

BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight.

The low carcinogenicity of electron radiation relative to argon ions in rat skin.

The carcinogenicity of electron radiation relative to argon ions in rat skin was examined, specifically investigating whether the linear-quadratic model is useful for predicting cancer yield for one type of radiation based on yields observed for a different type. Three experiments were conducted to obtain information on the relationship between cancer yield and the dose of electron radiation: (1) a conventional dose-response protocol where the number of rats per group was based on the expected tumor yield; (2) a multiple-fraction protocol designed to take advantage of yield additivity as a way to estimate carcinogenicity at lower doses; and (3) a protocol to examine the effect of age at the time of irradiation on the dose-response relationship for cancer induction. Published data on the induction of skin cancer in rats irradiated with electrons were reanalyzed and combined with results of the new experiments. Skin cancer yield versus dose for argon ions was consistent with the linear-quadratic model, but the cancer yield for electrons was considerably lower (by a factor of 6.7 at 10 Gy) than the prediction based on the linear-quadratic model. The cancer yield for electron radiation was better fitted by a dose-cubed power function than a linear-quadratic function. The results indicate a substantially lower carcinogenic effectiveness for electron radiation, especially at lower doses, in comparison to argon ions and suggest that electrons may cause cancer by a three-event pathway instead of the two-event pathway that is consistent with the results for argon ions.

Propylene oxide mutagenesis at template cytosine residues.

Propylene oxide (PO) is a widely used industrial reagent which is mutagenic and carcinogenic. We have recently shown that a variety of aliphatic epoxides, including propylene oxide, can react with DNA to form hydroxyalkyl adducts at N-3 of cytosine which rapidly undergo hydrolytic deamination to produce uracil adducts. These 3-hydroxyalkyl uracil adducts are stable in DNA and are postulated to be an important class of potentially mutagenic lesions. Mutagenesis at cytosine residues due to PO modification of single-stranded M13mp2/C141 DNA was studied by transfection of modified DNA into SOS and non-SOS induced E. coli host cells. Mutations of the proline (CCC) codon at C141 which result in reversion of the lacZ phenotype (blue plaques) were scored. It was found that PO treatment of single-stranded DNA results in dose-dependent mutagenesis that is highly SOS dependent. The spectrum of base-substitution mutations found at this site differed when PO-modified DNA was transfected into E. coli with different DNA repair backgrounds. These results indicate that propylene oxide induced DNA adducts at template cytosine residues are mutagenic in E. coli and that this mutagenesis is greatly increased by SOS processing. They also show that these lesions may be repaired by one or more mechanisms.

Chromatic and luminance systems deficits in glaucoma.

The purpose of this study was to compare the effects of glaucoma, at different stages of the disease process, on the two color-opponent system and on the luminance system. Discrimination thresholds were measured along the two equiluminant cardinal color axes (RG and YV) and along an achromatic luminance axis (LD) in 27 patients with open-angle glaucoma (OAG) and in 13 glaucoma suspects. Patients with OAG showed increased thresholds along all three axes. The threshold increases correlated significantly with the level of visual field loss. For glaucoma suspects, thresholds were also increased along all three axes. A subgroup of patients with OAG, those with pigmentary glaucoma, showed minimal increases in threshold along the RG axis. To further investigate this finding an additional 15 patients, seven with primary OAG and eight with pigmentary glaucoma were run in a two-alternative forced-choice experiment. For patients with pigmentary glaucoma, thresholds were increased less along the RG axis. The results of the study for OAG patients and glaucoma suspects are consistent with deficits in the two color-opponent systems, and in the luminance system.

Disaster nomenclature--a functional impact approach: the PICE system.

A standard nomenclature that concisely describes any disaster is currently lacking. This article describes a model taxonomy system. Instead of the term "disaster," a root word "PICE," "potential injury-creating event," is used. Descriptive modifiers to account for all possible scenarios surround this root word, as illustrated. [table: see text] A modifier is chosen from each column and a stage is assigned to each PICE. Column A describes the potential for additional casualties. Column B describes whether resources are overwhelmed and, if so, whether they must simply be augmented (disruptive) or they must first be reconstituted (paralytic). Column C describes the extent of geographic involvement. "Stage" refers strictly to the likelihood that outside medical assistance will be needed. Stage 0 means there is little chance, stage I means there is a small chance (place outside help on "alert"), stage II means there is a moderate chance (place on "standby"), and stage III means local medical resources are clearly overwhelmed (immediately dispatch outside resources, commit personnel, prepare remote hospitals). For example, a multiple vehicle crash in a large city would be a "static, controlled, local PICE, stage 0." In conclusion, a new nomenclature for describing disasters is reported. A short phrase describes the incident and communicates the need for outside assistance. The model may be useful for disaster planning, management, and research.

Ketorolac vs meperidine for the management of pain in the emergency department.

OBJECTIVE: To compare the pain relief, sedation, and common side effect profiles of ketorolac tromethamine and meperidine for the management of acute pain in the emergency department (ED). METHODS: A prospective, double-blind, randomized clinical trial was conducted over a 12-month period using consecutive adult patients presenting to a university teaching hospital ED (annual census: 32,000), who required IM analgesia for acute pain. Adult patients with acute pain of various etiologies were randomly assigned to receive a single fixed IM dose of ketorolac (60 mg) or meperidine (100 mg). RESULTS: Ninety-three patients were enrolled in the study; 46 were randomized to meperidine and 47 to ketorolac. Using a visual analog scale, there was no difference in pain relief between the ketorolac and meperidine groups even after adjusting for baseline pain level. Ketorolac caused significantly (p < 0.005) less sedation than did meperidine at one hour. Rescue analgesia was required for seven of the 46 (15.2%) patients receiving meperidine and five of the 47 (10.6%) patients receiving ketorolac (p = NS). Seventeen of 45 (38%) patients receiving meperidine experienced side effects compared with eight of the 47 (17%) patients receiving ketorolac (p = 0.0452). CONCLUSIONS: When used to treat patients who had acute pain states, 60 mg of IM ketorolac produced analgesia similar to that produced by 100 mg of IM meperidine; however, the ketorolac produced fewer subjective side effects and less sedation than did the meperidine.

Out-of-hospital intravenous cannulation: the perspective of patients treated by London Ambulance Service paramedics.

OBJECTIVES: Previous research has highlighted concern about infection rates in field-placed intravenous (IV) cannulae. In a study of IV placement by London Ambulance Service (LAS) paramedics, 17% of placements were judged to be inappropriate. Large variations in rates of IV placement between LAS paramedics were found. The authors' hypothesis was that placement of an IV carries disadvantages-pain, discomfort, distress, and infection-which may be unacceptable to patients. METHODS: This was a survey of all patients having an IV placed by LAS paramedics and transported to one of three London emergency departments (EDs) over a three-week period in December 1996. Patients were excluded if they had a self-inflicted injury/illness, were less than 14 years old, had no known address, or were visitors to the UK, or if their family doctor suggested it was not appropriate to contact the patient. Pain, discomfort, and distress; infection; satisfaction; understanding of the reason for cannulation; and out-of-hospital cannula use were all ascertained and analyzed with chi-square analysis. RESULTS: Thirty-nine percent of the respondents experienced some discomfort, 39% some pain, and 17% some distress. No patient reported an infection. Distress was more likely to be reported if there was no understanding of why the IV cannula was placed (chi2 [1] 6.1; p < 0.05). Further unstructured information revealed satisfaction with the IV cannulation and with general care. CONCLUSIONS: Despite the disadvantages of IV placement being reported by some respondents, overall levels of satisfaction were high, suggesting that these disadvantages were not unacceptable to patients. However, in the context of the 24,000 patients cannulated each year by LAS paramedics, "costs" to the patient are considerable.

Code blue: what's new?

In October 1992, lengthy new guidelines for cardiopulmonary resuscitation and emergency cardiac care were published by the Emergency Cardiac Care Committee and Subcommittees of the American Heart Association. These guidelines represent the efforts of the world's experts in emergency cardiac care. Yet they may be difficult for the busy clinician to digest in a timely fashion. In this article we summarize the changes in the guidelines from the 1986 version. It is not intended as a substitute for the original document but rather as an adjunct to help the clinician assimilate this new information.

Do-not-resuscitate orders. Where are they in the prehospital setting?

Without a well-functioning, prehospital, do-not-resuscitate (DNR) system in place, emergency medical service (EMS) providers must resuscitate all patients who access the system, regardless of the patients' wishes and regardless of what makes ethical or economic sense. In lieu of valid documentation, it is not appropriate to withhold resuscitative measures in this critical, time-dependent situation. In order to help EMS systems implement functional prehospital DNR protocols, this paper reviews the state-of-the-art of prehospital DNR including the issues to consider when designing such a system and a discussion of the features of some of the existing systems. This review includes: 1) the basis and requirements of a DNR system; 2) legal and physical forms for DNR orders; 3) eligibility for DNR status; 4) reversal of DNR orders; and 5) inappropriate use of EMS systems for DNR patients. Finally, a more general discussion of overall resource utilization in prehospital resuscitations is presented to emphasize that implementing prehospital DNR systems is only one piece of a larger issue.