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Biomedical subjects

B Duncan

Publications and source records attributed to B Duncan.

At least 55 records · Page 3Linked to original sources

Office laboratory procedures, economics of practice, patient and parent education, and urinary tract infection.

This review highlights recent advances in four major areas that are relevant to office practice: office laboratory procedures, economics of practice, adolescent risk-taking behavior in terms of sexually transmitted diseases, and urinary tract infections. Who should be screened for diseases and where these screening tests should be done are addressed, keeping the practicing pediatrician in mind. Next we review current office economics, including whether professional courtesy should be continued, how our practices are going to be increasingly influenced by guidelines developed by the American Academy of Pediatrics, the Clinical Laboratory Improvement Amendments, and the new Clinton Health Plan if it survives Congress, and finally how all of these issues will affect our expected income in the years ahead. As pediatricians strive to retain adolescent patients in their practices, they will need to find appropriate ways of counseling these patients concerning risk behaviors that could result in sexually transmitted diseases or HIV infections. Should we leave the comfortable confines of our offices to participate in these counseling programs for adolescents, and are there lessons from existing successful International Health Programs that we can use? Finally, urinary tract infections (UTIs) continue to be a common cause of childhood infections with possible serious long-term sequelae. Can we do a better job of diagnosing UTIs, has improved treatment become available, and is prevention of recurrences possible? Once the diagnosis has been made, how can we best evaluate these children with UTIs for underlying urologic abnormalities? It is our hope that the practicing pediatrician will be better prepared to face these issues having read this review.

Adolescent↗

Human Ig production and isotype switching in severe combined immunodeficient-human mice.

Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cell is a prerequisite for in vivo isotypes switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus.

Animals↗

Regulation of prolyl hydroxylase by ascorbic acid is mediated by polyADP-ribose synthesis.

While it is well known that cellular prolyl hydroxylase activity is increased in the presence of ascorbic acid, the mechanism of this modulation is not fully understood. Ascorbic acid is known to generate reactive oxygen radicals which are involved in the regulation of gene expression through mechanisms involving the synthesis of polyADP-ribose in the nucleus. We examined a possible role for this mechanism in modulating prolyl hydroxylase activity in cultures of human fetal (20 week) and neonatal (foreskin) dermal fibroblasts and IMR-90 fibroblasts. The activity of prolyl hydroxylase in these cells increased in the presence of ascorbate. Ascorbate markedly increased the levels of polyADP-ribose synthetase. The increase in prolyl hydroxylase activity was abolished or decreased by inhibitors of polyADP-ribose synthesis. Our studies suggest that ascorbate may regulate the cellular activity of prolyl hydroxylase by activating epigenetic control mechanisms involving polyADP-ribose.

Ascorbic Acid↗

Exclusive breast-feeding for at least 4 months protects against otitis media.

OBJECTIVE: This study was designed to assess the relation of exclusive breast-feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life. METHODS: Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children's Respiratory Study were reviewed. Detailed prospective information about the duration and exclusiveness of breast-feeding was obtained, as was information relative to potential risk factors (socioeconomic status, gender, number of siblings, use of day care, maternal smoking, and family history of allergy). Acute otitis media and recurrent otitis media, defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months, were the outcome variables. RESULTS: Of the 1013 infants followed for their entire first year, 476 (47%) had at least one episode of otitis and 169 (17%) had recurrent otitis media. Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. This protection was independent of the risk factors considered. CONCLUSION: These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media.

Acute Disease↗

Human fetal liver-derived CD7+CD2lowCD3-CD56- clones that express CD3 gamma, delta, and epsilon and proliferate in response to interleukin-2 (IL-2), IL-3, IL-4, or IL-7: implications for the relationship between T and natural killer cells.

Cells from fetal liver or fetal and adult bone marrow that are membrane (m)CD3 negative and have not rearranged TCR genes but express CD3 proteins in their cytoplasm are considered to be committed T-cell progenitors. Recent findings question whether CD3 is T-cell specific because fetal natural killer (NK) cells have been shown to express cCD3 delta and epsilon proteins. To further examine the relationship between T and NK cells, we generated mCD3-cCD3+ clones from fetal liver. Two stable clones, FL412 and FL508, isolated from different donors, were selected on the basis of absence of the NK cell marker CD56. These clones shared a common phenotype of CD7+CD2lowCD3-CD4-CD8-CD5-CD6-CD11b+CD16-CD56 -. Like fetal NK clones, these clones expressed cytoplasmic CD3 delta and epsilon transcripts and proteins. However, the clones exhibited no or very low levels of cytotoxic activity against K562, JY, or Daudi, which were lysed efficiently by fetal NK clones. TCR beta, gamma, and delta genes in these clones were in germline configuration. Furthermore, both FL412 and FL508 responded not only to interleukin-2 (IL-2), IL-4, or IL-7, but also to IL-3 with proliferation. These results suggest that FL412 and FL508 retained some characteristics of a putative T or NK precursor in the fetal liver and may be useful for analyses of this poorly defined cell type.

Antigens, CD↗

Maternal mortality in the Thyolo District of southern Malawi.

The Sisterhood Method, a community-based survey technique, was used to estimate the Life Time Risk of a woman dying a maternal death in Southern Malawi. With this figure, the maternal mortality ratio for that area was calculated to be 409 deaths per 100,000 live births. The 4124 adults interviewed reported 150 maternal deaths in sisters. An in-depth questionnaire was then used to determine that 56% of these deaths occurred outside a health facility, largely due to lack of transportation or poor access to fixed health care facilities; 25% died from excessive hemorrhage; 20% from obstructed labour; 18% from abortion; 13% from sepsis; while eclampsia accounted for only 4% of the maternal deaths. This field experience with the Sisterhood Method technique combined with an in-depth questionnaire for determining causes of maternal deaths has provided useful information in a simple and cost-effective manner for use in planning intervention strategies designed to decrease maternal mortality.

Adolescent↗

Treatment of infants with acute diarrhea: what's recommended and what's practiced.

In 1985, the American Academy of Pediatrics (AAP) published a policy statement on the treatment of infants with acute diarrhea complicated by mild to moderate dehydration. To determine how closely physicians in the United States follow the AAP's treatment guidelines, a questionnaire was sent to 457 pediatricians and 360 family practitioners. The questionnaire presented a hypothetical infant with acute diarrhea complicated by mild to moderate dehydration and included questions regarding the number of such patients seen yearly, length of time used to rehydrate the infant, and how formula or solids are introduced following rehydration. Complete responses were received from 53% of pediatricians and 40% of family practitioners. The number of patients with acute diarrhea seen per year did not affect physician's treatment. Pediatricians and family practitioners responded similarly to most questions. Contrary to the AAP's guidelines to rehydrate in 4 to 6 hours, 62% of responding physicians extend the rehydration period to 12 to 24 hours. Also contrary to the AAP's recommendations, 62% of pediatricians and family practitioners use a lactose-free formula. The majority of responding physicians do follow the AAP's treatment guidelines to initiate feedings with diluted formula. Significantly more pediatricians than family practitioners advance to a full-strength formula within 1 day (P = .011). Fewer than 50% of physicians polled started solids within 24 hours as suggested by the AAP. Overall, the findings suggest that very few pediatricians and family practitioners follow all aspects of the AAP's treatment guidelines for infants with acute diarrhea complicated by mild to moderate dehydration.

Acute Disease↗

The neonatal immune response to washed and irradiated red cells: lack of evidence of lymphocyte activation.

A total of 21 neonatal infants (11 males and 10 females) were evaluated for lymphocyte subpopulation changes and cellular activation following the receipt of washed and gamma-irradiated red cells. The mean donor exposure was 2 +/- 1.5 donors, and the mean white cell concentration of each 10-mL-per-kg transfusion was 2 x 10(7) cells. A total of 2800 rad (28 Gy) was delivered to each red cell unit prior to washing. The lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3+/CD25+, CD3+/HLA-DR, CD4+/CD45RA, CD4+/CDw29, and CD4+/ICHL-1 were analyzed, as were plasma gamma-interferon and neopterin levels, before and after blood transfusion. Posttransfusion samples were obtained from 3 to 12 days after the last blood transfusion. There were no posttransfusion changes in the percentage of lymphocyte subsets analyzed. Furthermore, overlay-histogram analysis of pretransfusion and posttransfusion CD45RA-, CDw29-, and UCHL-1-positive helper T cells failed to reveal a shift in mean channel fluorescence intensity, which is indicative of a lack of cellular activation. Gamma-interferon levels remained unchanged after transfusion (range, 90 +/- 5.9 to 95.5 +/- 5.3 pg/mL), as did neopterin levels (range, 3.7 +/- 1.5 to 4.6 +/- 1.5 ng/mL). This study could not find any evidence, by either cellular or humoral markers, of the activation of neonatal lymphocytes by transfusion. It is hypothesized that this failure to observe lymphocyte activation is due to the low number of donor white cells present in washed, irradiated red cells and/or to a lack of recipient recognition of transfused, allogeneic, donor white cells.

Blood Transfusion↗

The influence of preschool pertussis immunization on an epidemic of pertussis.

Between 1988 and 1989 there were 896 reported cases of pertussis in Arizona. Of the 781 investigated cases 55 were identified in children younger than 5 years of age. Thirty-five percent of children between 6 months and 5 years of age were not fully immunized; 3 infants died. Approximately 50% of infected children between 5 and 14 years of age had not received 5 doses of pertussis vaccine. Of the 413 physician respondents to a questionnaire, fully 10% do not administer pertussis vaccine to preschool children because of parental, personal or other reasons. We hypothesize that the reservoir of pertussis-susceptible older children and young adults is augmented by this omission of the fifth diphtheria-tetanus toxoids-pertussis vaccine. Newer educational and vaccine strategies are necessary to prevent epidemics of pertussis.

Adolescent↗

Complete heart block in fetal lambs. I. Technique and acute physiological response.

Prenatally diagnosed complete heart block (CHB), without associated cardiac anomalies, is often refractory to attempts to increase heart rate and cardiac output by medical therapy, and results in fetal death. We developed a model of CHB in fetal lambs in order to evaluate the acute physiological consequences of CHB and to assess the feasibility of fetal cardiac ventricular (V) and atrioventricular (AV) pacing. After hysterotomy and fetal sternotomy AV-sequential pacing leads were placed on the right atrium and ventricle (RV). Electromagnetic flow transducers were placed around the pulmonary artery and the ascending aorta to measure combined ventricular output (CVO) in normal sinus rhythm (NSR), CHB, AV, and V pacing. CHB block was successfully induced in 19 of 21 (90%) fetal lambs at 100 to 110 days' gestation by injection of formalin into the interventricular septum. Two fetuses were refractory to CHB despite multiple injections. The mean ventricular escape rate was 52 +/- 3 (+/- SEM) beats/min (range, 45 to 60 beats/min). CHB lasted for the period of study (1 to 8 hours), and spontaneously reverted to NSR in one fetus after 3 hours. Combined ventricular output in NSR was 470 +/- 31 mL/min (+/- SEM), which fell to 213 +/- 13 mL/min in CHB, 45% of normal CVO (P less than .0001). CVO during AV-sequential and V pacing was 77% (P = .02) and 62% (P less than .001), respectively, of combined ventricular output in NSR. Both RV (27%) and left ventricles (LV) (37%) showed compensatory increase in stroke volume during CHB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Obesity and mortality in the Lipid Research Clinics Program Follow-up Study.

Using data from the Lipid Research Clinics Program for 1972-1983, the study presented here examined weight history and two indices of obesity: the body mass index (BMI) and the triceps skinfold (TSF) thickness. Cox regression analyses with and without adjustment for cardiovascular disease risk factors revealed a significant (p less than 0.05) quadratic association between BMI and all-causes mortality among men, but not women, after an average 8.4 years of follow-up; mortality was relatively high at both extremes of the BMI distribution. The association was stronger among smokers compared with nonsmokers, and it was apparent among male normotensives, but not hypertensives. All TSF-mortality associations and BMI associations with cancer and coronary heart disease mortality were weak and nonsignificant. Among men, per cent weight change in adulthood showed a significant inverse association with all-causes and cancer mortality. Because BMI and weight history were significantly associated with mortality after adjustment for other risk factors, they appear to be independent predictors of mortality among men.

Adult↗