Dopamine activates NF-κB and primes the NLRP3 inflammasome in primary human macrophages.

Induction of innate immune genes in the brain is thought to be a major factor in the development of addiction to substances of abuse. As the major component of the innate immune system in the brain, aberrant activation of myeloid cells such as macrophages and microglia due to substance use may mediate neuroinflammation and contribute to the development of addiction. All addictive drugs modulate the dopaminergic system and our previous studies have identified dopamine as a pro-inflammatory modulator of macrophage function. However, the mechanism that mediates this effect is currently unknown. Inflammatory activation of macrophages and induction of cytokine production is often mediated by the transcription factor NF-κB, and prior studies have shown that dopamine can modulate NF-κB activity in T-cells and other non-immune cell lines. Here we demonstrated that dopamine can activate NF-κB in primary human macrophages, resulting in the induction of its downstream targets including the NLRP3 inflammasome and the inflammatory cytokine IL-1ß. These data also indicate that dopamine primes but does not activate the NLRP3 inflammasome in human macrophages. Activation of NF-κB was required for dopamine-mediated increases in IL-1ß, as an inhibitor of NF-κB was able to abrogate the effects of dopamine on production of these cytokines. Connecting an increase in extracellular dopamine to NF-κB activation and inflammation suggests specific intracellular targets that could be used to ameliorate the inflammatory impact of dopamine in neuroinflammatory conditions associated with myeloid cell activation such as addiction.

Antibody-associated lymphotoxin in acute infection.

Five pediatric patients who were known to be previously healthy acutely developed lymphopenia during various viral or mycoplasma infections. In one case, fatal generalized varicella occurred and in another, severe toxic epidermal necrolysis ensued. To further investigate this phenomenon, a study was done to determine the incidence of and elucidate the pathogenesis of lymphopenia occurring during the acute phase of viral or mycoplasma infections. Acute and convalescent sera from patients with viral or mycoplasma infection and children immunized with live measles virus were screened for lymphocytotoxic activity against normal lymphocytes by the microcytotoxicity method of Terasaki and McClelland (1). Sera with lymphocytotoxic activity were found in 15 of 48 cases of viral infections, 4 of 22 mycoplasma infections, and 1 of 11 measles virus immunized persons. All those who had sera which were cytotoxic to lymphocytes in vitro had lymphopenia. The lymphocytotoxic activity resided in 19S fractions in 8 of 11 positive sera while the remaining 3 had activity both in 19S and 7S fractions and could be completely removed by absorption with antilight chain antiserum. The cytotoxic activities were all complement-dependent and were greater at 37 degrees C than at 4 degrees C. The significance of acute acquired immunologic deficiency due to the development of antibody-associated lymphotoxin (AbAL) during acute infections is discussed and five cases having more severe clinical manifestations are presented (Appendix).

Pediatric clinical faculty structure and teaching hospital function.

An organization of clinical faculty has been formed at Rainbow Babies and Childrens Hospital, Cleveland, Ohio, to help coordinate the mutual goals but sometimes conflicting needs of practicing pediatricians and a teaching hospital. The organization has been active in developing and conducting educational experiences for students, house officers, and practitioners. It has contributed to efforts to improve ambulatory and inpatient care. Collaborative clinical research projects involving practitioners and academicians are planned. We know of no other existing similar organization. We propose that other institutions with similar needs consider this mechanism to help improve their academic and patient care programs.

Feeding patterns of urban black infants.

Feeding patterns of 116 urban black infants were studied from 3 weeks to 6 months of age. Dietary data were collected using a diet history and a food frequency checklist completed by trained interviewers at each well child clinic visit at 3 weeks and at 2, 4, and 6 months of age. At 3 weeks, 20% of the infants were solely breast fed, 58% were formula fed, and 22% were partially breast fed. Twenty percent of 3-week-old infants were receiving baby foods. This increased to 48% at 2 months, and to 72% at 4 months. By 6 months of age, 98% of infants received baby foods. Nursing mothers tended to introduce baby foods later than formula-feeding mothers. This is consistent with other studies. Commercially prepared baby foods were used much more commonly than were foods prepared at home. Infant cereal was most often introduced first, followed by strained juices, strained fruits, strained vegetables, combination dinners, desserts, and plain meats, in that order. Table foods contributed very little to caloric intakes of infants less than 4 months of age. Liberal amounts of water and sugar water were given to infants in this cultural group.

Predicting low birthweight and complicated labor in urban black women: a biopsychosocial perspective.

This study explored demographic, biomedical and psychosocial factors as predictors of two adverse pregnancy outcomes: intrapartum complications and low birthweight, in 140 urban black pregnant women. The intrapartum complication rate was 18%. A four factor equation (low family functioning, advanced maternal age, working during pregnancy, and short stature) predicted intrapartum complications (80% sensitivity, 67% specificity and 35% positive predictive value). The low birthweight rate was 14%. Four factors (low family functioning, stressful events, Quetelet's Index, and cigarette smoking) predicted low birthweight (65% sensitivity, 84% specificity and 42% positive predictive value). Family functioning, alone, predicted low birthweight with 65% sensitivity, 64% specificity and 31% positive predictive value. Family functioning, was the only predictor for both outcomes. Family functioning and other psychosocial risk factors may potentially improve identification of high risk pregnant urban black women.

Education of residents in the pediatric office.

Practicing pediatricians can contribute a much-needed dimension to the education of those primary care physicians who will care for children by teaching medical students and residents in their offices. This article is intended to help the prospective pediatrician-teacher plan, conduct, and evaluate productive educational experiences in his office. Approaches to planning primary care educational experiences are discussed. Considerations for developing an efficient practice into an effective educational setting are also presented. Effective teaching strategies based upon principles of adult learning are suggested. The importance of a systematic approach to education, which entails defining objectives and evaluating the students' learning ', is emphasized.

Family function, respiratory illness, and otitis media in urban black infants.

Associations between maternal perceptions of family functioning and rates of infant presentation for respiratory illness and otitis media were analyzed using data collected prospectively in a sample of 114 urban black mother-infant pairs. Family functioning was evaluated using the Family APGAR, truncated versions of Olson's FACES II cohesion and adaptability subscales, and a shortened version of Hudson's Index of Family Relationships. Lower maternal scores of family function were significantly associated with higher rates of physician visits for infant respiratory illness and otitis media during the first 15 months of life. This correlation persisted when controlled for breast feeding. Maternal perceptions of family function, including those tested antenatally, may be useful in identifying infants in similar populations who are at risk for increased frequency of visits to the family physician for respiratory illness and otitis media.

A clinical trial to reduce the rate of low birth weight in an inner-city black population.

BACKGROUND: The goal of our study was to measure the effectiveness of a home-based intervention for prevention of low birth weight with 154 high-risk, low-income black women attending a prenatal clinic in Cleveland. METHODS: Based on previous research, risk was defined by clinic registration between the 17th and 28th weeks of gestation, low family functioning score, and experience of at least one stressful life event prior to registration. Optional factors included being a smoker, a low maternal weight-height ratio, being age 27 or older, and a previous premature birth. A 21-item family function screen previously validated in a similar population was the primary determinant of psychosocial risk. Low birth weight was defined as weight less than 2,500 g regardless of gestational age. RESULTS: There was no decrease in the rate of low birth weight for women who received four home visits focusing on smoking, drug and nutrition education, support, and links with community services, compared to women who received no visits. The number of prenatal visits was significantly higher in the intervention group, but an increased number of prenatal visits did not correlate with a reduced rate of low birth weight. Despite previous research, the family function screen was not an effective predictor of low birth weight in our study. A revised equation involving a history of previous premature birth, smoking, and a low maternal weight-height ratio did predict low birth weight. CONCLUSIONS: These findings question the utility of short-term psychosocial interventions for influencing low birth-weight rates in low-income black clinic populations. The family function screen was not cross validated. Integration of any psychosocial intervention with the routine prenatal care occurring in the obstetrical clinic is suggested for future research.

Clinical hypothesis testing in family practice: a biopsychosocial perspective.

Recent studies of the clinical problem-solving process have demonstrated the importance of hypothesis generation and testing in shaping the nature of information gathering, differential diagnosis, and therapeutic decision making. Family physicians and other primary care physicians are often faced with complex and undifferentiated illness problems that require them to go beyond the traditional biomedical model and entertain an expanded range of psychosocial hypotheses. In this paper the authors draw upon clinically relevant behavioral and social science research and propose several biopsychosocial hypotheses that have proven useful in the management of family practice patients. Seven illustrative case studies are presented, and some implications of this biopsychosocial paradigm for practice, research, and teaching are discussed.

Development of an instrument to identify attitudes of family practice and other physicians: a pilot study.

Research has shown that characteristic attitudes can be attributed to certain medical specialties and can affect specialty selection. The purpose of this study was to develop an attitude scale that would discriminate between family practice and other physician groups on current health care issues. From a sample of 490 randomly selected physicians, 40 percent (N = 193) responded to the study instrument, a 44-item, five-point Likert scale in which physicians were asked their level of agreement on various statements. One-way analyses of variance were performed on responses to each item by family centered nature of practice and specialty. Ten statements were found to significantly differentiate physicians who were family centered from physicians who were not family centered. Statements showed that family centered practitioners were confident in their competence and in their role as an essential medical practitioner. They also expressed more awareness of a patient's response and total well-being. Responses also suggest that there is acknowledgement of supposed family medicine issues by all physicians.

Defining family in family medicine: perceived family vs household structure in an urban black population.

This paper explores two hypotheses: first, that household structure, the people who live in one's household, and perceived family, the people one considers members of one's family, are different entities among urban black pregnant women; and second, that the perceived family is a stronger predictor of social, psychological, and health outcomes than is household structure. The study data are from the first interview of a prospective study of a consecutive sample of 140 black pregnant women patients of a Cleveland, Ohio, university hospital family practice center. The study hypotheses are supported: household structure and perceived family differ in their size and the inclusion or exclusion of members of the family of origin and the father of the baby. Household structure is strongly correlated with demographic variables such as age, socioeconomic status, and household income, whereas perceived family is less strongly associated with these measures. Perceived family, but not household structure, is associated with family functioning, measures of psychological status, worries about household change, and better family and parental relationships during the woman's childhood.

Postgraduate training in ambulatory pediatrics. Program evaluation.

Ambulatory pediatric, adolescent medicine, and child development fellowship programs listed in the Ambulatory Pediatric Association (APA) newsletter were surveyed to gather information about the programs for prospective fellows, to develop a descriptive summary, and to determine the extent to which programs adhere to APA guidelines. Number and types of positions offered, criteria for admission to programs, program educational objectives and activities, and career choice of graduates were examined for the 73 programs offering 132 fellowship positions in 1976 to 1977. In general, APA guidelines were followed. Programs emphasized patient care experience in contrast to health care administration, research, and teaching.