Guidance for development of chemopreventive agents.
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Biomedical subjects
Publications and source records attributed to G Burke.
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The timely distinction between infants with necrotizing enterocolitis (NEC) who need surgery and those who are likely to recover with medical management is important, but it may be difficult clinically. Because pneumoperitoneum is not always present, additional markers of bowel gangrene are needed. Among 73 babies managed for NEC over the study period, 49 (67%) met the study criteria of Bell's stage > 1, and their records were reviewed to determine the usefulness of common laboratory tests in predicting outcome. The patients were divided into three groups based on management. Group 1 (7 patients) required surgery at the time of initial presentation because of pneumoperitoneum. The remaining 42 patients were initially managed medically, 19 of whom (group 2) recovered successfully; the other 23 (group 3) required surgery. The combination of certain laboratory tests, ie, white blood cell count (WBC), immature:total neutrophil ratio (I:T), platelet count (PLT), and base excess (BE), was of significance in distinguishing between infants who would need surgery and those who would recover with medical therapy (group 3 v group 2) 4 to 12 hours or 12 to 24 hours after the diagnosis of NEC was established. A scoring scale was developed, with a point for each of the following: WBC < 9,000/mm3, I:T > .5, PLT < 200,000/mm3, and BE < or = -2. A score of > or = 3 during 4 to 12 hours after diagnosis of NEC strongly predicted the presence of surgical disease (positive predictive value, 100%; negative predictive value, 76%; specificity, 100%; sensitivity, 64%).(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Both the Centers for Disease Control and Prevention and the American Academy of Pediatrics have recommended influenza immunizations for neonatal intensive care unit staff. Compliance rates for influenza immunization among neonatal intensive care unit staff have not yet been reported. METHODS: To determine both the rates and the associated factors for compliance between 1990 and 1993 among neonatal intensive care unit nursing staff, interviews were conducted at three Hartford area hospitals by means of a structured questionnaire. RESULTS: Compliance rates at the three hospitals were 15% in 1990 to 1991, 20% in 1991 to 1992, and 17% in 1992 to 1993 (89% sampling of all nurses with direct patient care). Sixty-three percent were not immunized between 1991 and 1993, 26% were vaccinated once, 9% were vaccinated twice, and 2% were vaccinated three times within the 3-year period. Convictions regarding vaccine safety and effectiveness, concern about getting influenza, and awareness of national recommendations for annual influenza immunization were shown to be associated with vaccination compliance. Concern over exposing neonates, peer influence, pain from injection, and previous adverse reaction were not statistically significant factors differentiating compliers from noncompliers. CONCLUSIONS: There is a poor acceptance of the influenza vaccine among our neonatal intensive care unit nursing staff. Educational and research efforts directed toward influenza risks among neonates and vaccine safety and effectiveness, along with incentives to comply, may improve compliance rates.
Neutrophil (PMN) chemotaxis and chemokinesis were longitudinally studied in a group of 17 neonates with birthweights between 750 and 1250 g. Five of the 17 neonates were treated with prenatal betamethasone to attempt to prevent hyaline membrane disease, six received postnatal dexamethasone in an effort to reduce bronchopulmonary dysplasia, three received both, and three were not treated with corticosteroids. The group of 17 neonates were tested on four separate occasions: (1-2, 3-4, 7-8, and 10-14 postnatal days). PMN chemotaxis and chemokinesis were determined using a standard micropore filter assay. A group of 36 adults was used as additional controls. There were no significant differences noted in PMN chemotaxis or chemokinesis for the corticosteroid vs the noncorticosteroid-treated groups. In the total group of 17 neonates, there was depression in PMN chemotaxis compared with adult values, which lasted at least through postnatal day 8. By day 13 to 14, PMN chemotactic values were similar to those of adults. In contrast, chemokinesis, was depressed during the initial 14 days (except for the first 2 postnatal days). These data suggest that perinatal corticosteroid administration does not affect PMN motility in newborn infants.
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A case of chronic gastric organoaxial volvulus, gastroesophageal reflux, esophagitis, and chronic anemia is presented. Reflux esophagitis and chronic anemia have not been reported previously as clinical signs associated with gastric volvulus in a child. A Meckel's scan is used to diagnose the displaced stomach.
Two murine monoclonal antibodies specific for IFN-gamma, ADI-1, and ADI-23 (both IgG1 kappa), were generated in BALB/c mice. The ADI-1 exhibited a higher avidity for canine rIFN-gamma than for nIFN-gamma and human rIFN-gamma. In contrast, the ADI-23 showed equal avidity for the three IFN-gamma preparations. The anti-canine IFN-gamma mAb did not bind to mouse and rat rIFN-gamma. The ADI-1, and ADI-23 mAb were also tested for binding to human rTFN-alpha and, contrary to our expectations, it was found that ADI-23 showed significant binding to human rTFN-alpha and rIFN-gamma, in contrast to ADI-1. Both anti-canine IFN-gamma mAb stained 48-h PHA-induced dog lymphoblasts. A two-site mAb ELISA was developed, which was linear in the range of 7-500 ng of canine rIFN-gamma, which indicated that the two mAb detected non-overlapping epitopes on the canine rIFN-gamma molecule. We studied the effect of ADI-1 on the prolongation of canine renal allografts. Recipients of kidney allografts, that were treated with ADI-1 by continuous arterial infusion, were prolonged to 22 and 25 days, compared to 9 and 13 days for animals given the IgG1 isotype control.
OBJECTIVE: To study platelet function in normotensive and hypertensive intrauterine growth retardation (IUGR). DESIGN: ADP and collagen induced whole blood platelet aggregation, beta-thromboglobulin release and platelet count were measured in the IUGR groups at a mean gestational age of 36 weeks (28-40), and at 1, 24, 48 h and six weeks post delivery. The normal pregnancy group were studied serially at 12, 20, 28, 32 and 36 weeks of gestation and at 1, 24, 48 h and six weeks post delivery. SETTING: Trinity College Medical School, St. James's Hospital, Dublin. SUBJECTS: Twenty-nine women with a fetus with diagnosed IUGR were recruited for the study. Of these, 15 were normotensive throughout their pregnancy and the remaining 14 pregnancies were complicated by both hypertension and proteinuria. Twenty healthy primigravida acted as controls. RESULTS: In the hypertensive IUGR group, levels of collagen and ADP induced aggregation were almost 50% lower before delivery than in normal pregnancy. Platelet count in the hypertensive group was decreased by 30% compared with normal pregnancy. Levels of beta-thromboglobulin were 40 to 50% higher in both the normotensive and hypertensive IUGR groups compared with normal pregnancy. Unlike the hypertensive IUGR group, the normotensive IUGR group showed similar levels of platelet count and ADP and collagen induced aggregation to those found at 36 weeks of normal pregnancy. In the early puerperium of hypertensive pregnancies, the platelet parameters measured returned gradually to normal. The normotensive IUGR group had increased levels of ADP induced aggregation in the first 24 to 48 h post delivery. The platelet count in the normotensive but not the hypertensive group correlated with birthweight. CONCLUSIONS: Normotensive and hypertensive IUGR are accompanied by platelet activation. In normotensive IUGR, this activation appears to be confined to the uteroplacental circulation. In hypertensive IUGR, the results suggest that platelet activation also extends into the peripheral circulation resulting in a reduced platelet responsiveness and a lower platelet count. Release of vasoactive amines from activated platelets in the peripheral circulation may be responsible for the clinical syndrome of hypertension and proteinuria present in pregnancies complicated by pre-eclampsia and IUGR but absent in normotensive IUGR.
Data from police accident reports involving pedestrians less than 20 years of age in Hartford, Conn, during 1988 through 1990 were abstracted and entered into a geographic information system. Two high-frequency collision areas were identified and compared. There were 374 child pedestrians involved in collisions (a rate of 28 per 10,000). Two high-occurrence areas accounted for 30% of collisions. Collisions in one of these areas were more likely to involve younger children (8.1 vs 10.2 years of age) and to occur in the late afternoon, and occurred closer to the child's residence, than collisions in the other area. The geographic information system is a useful tool in the study of child pedestrian collisions.
OBJECTIVE: Impaired neutrophil (PMN) function, due in part to release of immature PMNs into the circulation, contributes to the increased rate of infection observed in adults suffering blunt trauma. The objective of this study was to determine whether similar events occur in children. METHODS: We assessed PMN chemotaxis and PMN maturation in 25 children (7 young children and 18 adolescents) and 25 adults 1 to 9 days after suffering blunt trauma, and in healthy adult control subjects. PMN chemotaxis was determined using a standard micropore filter assay, whereas PMN maturation was determined with 31D8, a novel monoclonal antibody that binds to mature PMNs more avidly than immature PMNs and band forms. RESULTS: In patients suffering blunt trauma, mean PMN chemotactic values were similar among children (44.6 +/- 2.3 microns) and adults (41.3 +/- 2.1 microns) and both were significantly less than among healthy adults (53.5 +/- 2.4 microns, P < .0005). PMN chemotactic values increased significantly in the 9 days after trauma for both children and adults (F = 13.8, df = 1, P < .0002). Mean PMN 31D8 binding among children with trauma (92.5 +/- 5.2) was significantly less than among healthy adults (117.6 +/- 5.4, P < .0009). CONCLUSIONS: Impairment in PMN chemotaxis occurs in children after blunt trauma and is due in part to release of immature PMNs into the circulation.
OBJECTIVE: To reevaluate the timing and level of rise in breath hydrogen (H2) excretion following oral lactose challenge in children with respect to the subsequent development of symptoms consistent with lactose intolerance. METHODS: Breath hydrogen test (BHT) data from 581 individuals < 19 yr of age (mean age 7.4 yr), all of whom had a fasting baseline breath H2 concentration of < 20 ppm, were reviewed. All subjects ingested 2 g/kg lactose (maximum 50 g) and had breath H2 analysis at 30-min intervals for 3 h. Symptoms of abdominal pain, bloating, gas, and diarrhea were monitored. RESULTS: Seventeen percent of subjects had no H2 detectable in their breath at any time, 41% had a rise < 10 ppm from baseline, 6% increased 10-19 ppm, and 36% had a rise > or = 20 ppm. Symptom development (gas, bloating, abdominal pain, diarrhea) was similar in the non-H2 excretors, the delta < 10 ppm, and the delta 10-19 ppm groups. Compared to the < 10 ppm or < 20 ppm groups, subjects with a rise of > or = 20 ppm were more likely to develop diarrhea (p < 0.0001), gas (p < 0.0001), bloating (p < 0.0001), and abdominal pain (p < 0.0001). Symptoms were more common in the > or = 20 ppm group than in the delta 10-19 ppm group (p < 0.02 for diarrhea, p < 0.0001 for gas, bloating, and abdominal pain). Fifty-three percent of subjects with a rise in breath H2 < 20 ppm reported symptoms during or after the BHT, and 9% of those with a rise > or = 20 ppm were asymptomatic. CONCLUSION: A rise of breath H2 concentration of > or = 20 ppm over baseline appears to correlate better with subsequent symptom development than does > or = 10 ppm. However, the frequently poor association between symptoms of lactose intolerance and breath H2 excretion suggest caution in the interpretation of the clinical significance of the BHT.
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We have developed a rapid (24 hours) quantitative PCR assay to measure the direct effect of cyclosporine on IL-2 mRNA production by activated PBMC cultures from renal transplant patients. The PBMCs were purified from normal laboratory volunteers (group A, n = 26), CsA-treated renal transplant patients with good renal function, tested between 3 and 8 weeks (group B, n = 14) or between 2 and 8 years (group C, n = 15) after surgery, and stimulated with PHA in media supplemented with either patient serum or pooled commercially obtained AB serum. The mRNA was then isolated and, using semiquantitative PCR or quantitative PCR with a competitive inhibitor, the relative levels or exact levels of IL-2 mRNA (in attomoles) could be measured. A 3-day confirmatory lymphoproliferation assay of [3H]thymidine incorporation was also performed on the samples. Kinetic analysis of the data from group A showed that the peak level of IL-2 transcription into mRNA occurred at 6 hours after mitogen stimulation. Increasing in vitro concentrations of CsA in this group resulted in lower IL-2 mRNA levels and a shift in the peak time to 12-24 hours. In the transplant recipients, there was no correlation between individual CsA blood levels and proliferation responses. However, some correlation was found between CsA blood levels and IL-2 mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
The Cardiovascular Health Study (CHS) is a longitudinal population-based study of coronary heart disease and stroke in men and women 65 years and older. The initial CHS cohort consisted of 5201 men and women recruited from a random sample of the Health Care Financing Administration (HCFA) Medicare eligibility lists in four communities in the United States. Extensive historical, physical, and laboratory evaluations were performed at the baseline examination in 1989 to 1990 to identify risk factors and subclinical disease. Periodic contacts are carried out to ascertain and verify incident cardiac and stroke events and their sequelae. Since only a short time has passed since entry of all the patients into the study, data are not available on time trends in the mortality rate of stroke, but we expect to contribute in this area in the years ahead. This article then is a description of the CHS, of methods of assessing stroke in the CHS cohort, and of prevalence of stroke and transient ischemic attacks at the initial examination.
A case of a strangulated omental hernia detected by a scrotal scan is presented. This may be the first report in which the scrotal scan showed diffuse increased isotope accumulation throughout the hemiscrotum.