Functional differences between human cutaneous mast cells and basophils: a comparison of morphine-induced histamine release

Intravenous administration of morphine sulfate often produces urticarial and hypotensive reactions associated with elevations in plasma histamine. The source of this histamine and mechanisms controlling its release are poorly understood. Previous studies of morphine-induced histamine release compared human leukocytes to rat peritoneal mast cells. The effects of morphine on human cutaneous mast cells has not been examined. We studiedin vitro histamine release from human basophils and human skin preparations containing cutaneous mast cells to evaluate their relative, contribution to the pharmacologic effects of morphine.Human skin mast cell preparations showed dosedependent histamine release over a morphine concentration range of 1.5×10^–5 to 4.5×10^–3 M, with peak release occurring at 5×10^–4 M, with peak release occurring at 5×10^–4 M. Clinically, morphine sulfate is usually injected as a 1.5×10^–2 M solution. Histamine release was calcium dependent and equivalent to that obtained with 3 and 10 mM strontium. Morphologic examination revealed degranulation and exocytosis occurring in morphine-stimulated tissue but not in specimens exposed to buffer alone. Lactate dehydrogenase levels did not increase following morphine incubation, thus supporting a noncytolytic mechanism of histamine release.Basophils, in contrast, showed no significant histamine release from exposure to morphine up to 10^–2 M. Concanavalin A, as a positive control in these same preparations, produced a mean histamine release of 21.0%.Our studies indicate distinct functional differences between human skin mast cell and human blood basophil responses to morphine sulfate. We conclude that the cutaneous and systemic reactions to morphine sulfate probably result from the release of histamine from mast cells rather than from basophils.This study was supported by: National Institutes of Health Grants 2-T32 AMO7153, 5-RO1 AI18615, AI 15557, HL 25831, American Society of Anesthesiologists Starter Grant 1283, and a grant from the Bramble Foundation.     

Additive cytotoxicity of adriamycin and a naturally occurring growth inhibitor extracted from bovine aorta

A factor of nominal molecular weight 6K–10K Daltons, isolated from bovine aorta, has previously been shown to inhibit neovascularization and tumor growth in vivo and the growth of some tumor cells as well as endothelial cells in culture. This factor, termed A-10, was tested alone and in combination with Adriamycin against TA3Ha mammary adenocarcinoma cells in tissue culture. It was found to have cytotoxicity additive to that of Adriamycin in inhibiting the growth of these cells. In vitro and animal studies show that the sequence of Adriamycin A-10 is superior to either agent alone in delaying the appearance of palpable tumors after subcutaneous injection of 10⁵ pre-treated tumor cells in the tail of strain A mice. While the growth rate of the primary tumor was not affected by such treatment, survival was prolonged to a greater degree by the this sequence than by either of these agents used alone. A-10 treatment reduced the number of metastases to the adrenal gland but not to lung, liver, or lymph nodes. It did, however, reduce the size of metastases to para-aortic lymph nodes.     

A Randomized Pilot Study of DASH Patterned Groceries on Serum Urate in Individuals with Gout

The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU); however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks; crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: −0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by −0.48 mg/dL (95% CI: −0.98, 0.01) compared to DDG by −0.05 mg/dL (95% CI: −0.48, 0.38; P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day; 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: −34.0, −8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.     

Relative Validity of MijnEetmeter: A Food Diary App for Self-Monitoring of Dietary Intake

This study aimed to evaluate the relative validity of intake of energy, nutrients and food groups assessed with MijnEetmeter food diary as compared to 24-h dietary recalls, and if this differed between experienced and new users. One hundred men and women aged 18–70 y participated, of whom 47 had prior experience with the tool. Participants kept MijnEetmeter on three days. Trained dietitians called them three times for a 24-h dietary recall interview, once recalling food consumption on the same day as the food recording in MijnEetmeter. Systematic differences and correlations were assessed, and Bland–Altman plots were created; both for 3-day mean intakes and for intakes on the same day. Relative to 24-h dietary recalls, MijnEetmeter underestimated consumption of drinks, added fat, cereal products, and potatoes. Relative underestimation was observed for energy intake (6%) and about half of the nutrients. Experienced MijnEetmeter users underestimated intake the least. For intake of energy and six key nutrients, correlations between 3-day mean intakes were above 0.7 except for sodium intake. In conclusion, MijnEetmeter moderately underestimates intakes of energy and some nutrients and food groups. To improve the self-monitoring of dietary intake, it is recommended that the users record food consumption for several days and that the apps probes for easily forgotten foods and drinks.     

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness,research, and response

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely – and at times uniquely – affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy – in consultation with a variety of external experts and stakeholders.     

Identification of natural antibodies to interleukin-18 in the sera of normal humans and three nonhuman primate species

Natural antibodies to cytokines can be found in the sera of normal healthy individuals in the absence of specific immunostimulation. However, the function, impact, and purpose of natural antibody development have yet to be fully elucidated. Interleukin (IL)-18 is a cytokine that exerts proinflammatory activities and induces natural killer (NK) cell activity. Recombinant human IL-18 (rHuIL-18) is currently in development as a cancer immunotherapy. In this study, the presence of natural antibodies to IL-18 in the sera of normal humans and three nonhuman primate species was evaluated by electrochemiluminescence immunoassay (ECLIA). Of the human sera tested, 6 of 47 samples were positive for natural antibodies to IL-18. Of the nonhuman primate sera tested, 22 of 80 cynomolgus monkey samples, 4 of 31 rhesus monkey samples, and 2 of 20 chimpanzee samples were positive for natural antibodies to IL-18. Natural anti-IL-18 antibodies were neutralizing in 5 of 22 cynomolgus and 2 of 4 rhesus sera. None of the chimpanzee or human sera were able to neutralize IL-18 induction of interferon (IFN)-gamma in vitro. In vivo activity of rHuIL-18 was compared in IL-18 natural antibody-positive and -negative cynomolgus monkeys. The presence of natural antibodies to IL-18 did not alter rHuIL-18 systemic exposure levels, induction of neopterin, or induction of treatment-induced antibodies following intravenous administration of rHuIL-18. In conclusion, our data indicate that, as has been found with other cytokines, natural anti-IL-18 antibodies are relatively common. Moreover, natural anti-IL-18 antibodies do not appear to influence rHuIL-18 activity in vivo and are not predictive of a heightened immune response, suggesting that natural anti-IL-18 antibodies do not impact IL-18 therapy. Finally, our data suggest that the ability to detect natural anti-cytokine antibodies may be a useful measure of the adequacy of an assay for deployment in clinical trials.     

Stigmatization, self-esteem, and coping among the adolescent children of lesbian mothers

Purpose: To examine perceived stigma, coping, disclosure, and self-esteem among adolescents with lesbian mothers.

Method: Interviews were conducted with 76 adolescents ages 11–18 years. Standardized measures of self-esteem and coping skills were used. A measure of stigma was adapted for this study and a measure of disclosure was developed. The relationship between perceived stigma and self-esteem was examined. General coping skills and level of disclosure about the adolescents’ mothers’ sexual orientation were assessed as potential moderators of the relationship between perceived stigma and self-esteem.

Results: Adolescents who perceived more stigma had lower self-esteem in five of seven self-esteem areas, compared to those who perceived less stigma. In addition, coping skills moderated the effect of stigma on self-esteem in three self-esteem areas. However, only one subtype of coping skills, that of decision-making coping, was found to moderate the relationship of perceived stigma and self-esteem in such a way that adolescents using more decision-making coping had higher self-esteem in the face of high perceived stigma. For social support coping, in the face of high perceived stigma, the adolescents with more effective coping skills had lower self-esteem. In the face of high perceived stigma, adolescents who disclosed more about their mother’s sexual orientation had higher self-esteem in the subscale of close friendship than those who disclosed less.

Conclusions: Results suggest that stigma is related to self-esteem among the adolescent children of lesbian mothers. The results indicate that this relationship is moderated by coping skills. These results have implications for intervention and prevention of stigmatization by the establishment of effective coping skills as well as through educational efforts to eradicate stigmatizing attitudes.     

On the road to collaborative treatment planning: Consumer and provider perspectives

Although consumers have made significant gains in having their voices heard in several areas within mental health, they have made less progress in being able to collaborate with their own treaters in setting treatment goals. On the basis of several years of groundwork by staff at the Connecticut Mental Health Center (CMHC), the Patient Care Committee conducted a needs assessment of providers and consumers to assess both groups' current involvement, interest in, and attitudes toward collaborative treatment planning. The results indicate that providers tend to place much of the responsibility for the difficulties in implementing collaborative treatment planning on consumers. Also, providers tend to underestimate consumers' interest in participating in this process. Implications of these findings for the development of an agency-wide training to enhance the collaborative nature of treatment planning are discussed.     

University Students'' Knowledge and Awareness of HPV

BACKGROUND: The purpose of this study was to evaluate the knowledge, attitudes, and behaviors of university students regarding the human papillomavirus (HPV). METHODS: A random sample of 500 university students was mailed a self-administered questionnaire that elicited their knowledge and awareness about HPV and compared their knowledge and attitudes with those of other sexually transmitted diseases (STDs). Among the 480 deliverable addresses, 289 students responded (response rate 60%). RESULTS: Only 37% of respondents had ever heard of HPV, and the median score on a 13-item knowledge scale was only 3. Of seven STDs assessed, respondents indicated they knew the least about HPV and perceived that this STD has received the least educational effort. In multivariate analyses, predictors of lower knowledge and awareness about HPV were male gender and sexual behavior (having multiple partners, not using condoms). CONCLUSIONS: Despite the high prevalence of HPV among young adults, most students knew very little about this infection. Implementing HPV educational programs and measuring their effectiveness should be a priority.