Design and operation of an expanded system of quality control.
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Biomedical subjects
Publications and source records attributed to J J Moore.
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We studied the beta-adrenergic system in the human decidua and its effect on prostaglandin E2 and F2a release from dispersed decidual cells in culture. Beta-adrenergic receptors in decidual membranes were partially characterized using (+)[125I]HYP. Specific binding was demonstrated with maximum binding capacity (Bmax) of 70 +/- 10.6 fmol/mg and an affinity (KD) of 20.85 +/- 1.86 pmol. cAMP dependent phosphoproteins in decidual cytosol were also identified. Two phosphoproteins of M(r) 42,000 and 22,000 were seen in all preparations. Three others (M(r) 39,000, 23,000 and 21,000) were identified in only some of the preparations. Phosphoproteins of similar M(r) to those seen in cytosol prepared from decidual homogenates were also identified in cytosol of cultured decidual cells. Phosphorylation of the 42,000 M(r) and 22,000 M(r) proteins was maximal (3.04 +/- 0.35-fold and 5.7 +/- 0.68-fold) with 10(-6) M cAMP. Cultured decidual cells produced prostaglandin E2 and F2a which increased in a dose-dependent manner in response to dbcAMP, forskolin or isoproterenol. The decidua contains an intact beta-adrenergic system that, when activated, is capable of phosphorylating specific proteins and modulating prostaglandin release.
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Traditionally, the literature has described a certain population as at risk for tetanus infection. We reviewed the demographics, clinical presentation, laboratory findings, management, and outcome of all patients who presented to our emergency department (ED) with tetanus in the last 10 years and compared our experience with this classic literature. We performed a retrospective case series review at a large, inner-city medical center; 11 cases of tetanus were identified from 1986 to 1997. Nine male and two female patients were identified with an average age of 45 years. All had an acute injury to the skin, and most (82%) reported having no history of recent immunization. The most common recorded symptoms were trismus and rigidity in the abdomen, neck, back, or extremities. There was only one misdiagnosis in the ED. Three patients died in the hospital, while the other eight were discharged either home or to a rehabilitation facility. In contrast to the classic literature, we found that tetanus in our inner city ED presented in recent immigrants, particularly younger men, over half of whom had received no childhood immunization. Laboratory results and cultures are of little diagnostic value, so timely recognition of the clinical presentation is important.
Apoptosis is a process by which external or developmental factors induce a specific series of events leading to cell death. Recently, apoptotic cells have been described in rat amnion membrane at late gestation, suggesting apoptosis may be involved in membrane rupture. Mechanisms controlling amnion cell apoptosis are unknown. The objective of this study was to investigate whether cyclooxygenase and prostaglandins are integral to apoptosis in amnion, as reported in intestinal epithelial cells and renal mesangial cells. Amnion-derived WISH cells underwent apoptosis in a dose- and time-dependent manner after incubation with actinomycin D, cycloheximide, or staurosporine, as determined by cell viability, DNA fragmentation analysis, and fluorescent in situ fragmentation analysis. Cells cultured with increasing doses of these agents also demonstrated concomitant increases in prostaglandin E2 output. WISH cell coincubation with these agents and the cyclooxygenase inhibitors indomethacin or piroxicam resulted in dose-dependent decreases in both prostaglandin E2 and apoptosis. Cultures incubated with 0.5 microgram/mL actinomycin D showed 80.7% cell apoptosis after 12 hours compared with 1.1% in untreated cultures. After 24 hours incubation with actinomycin D, 0.8% of the original cell number remained attached to the plate. In cultures coincubated with 0.5 microgram/mL actinomycin D and 100 mumol/L indomethacin, only 19.2%, 24.7%, and 39.3% of the cells were found to be apoptotic after 12, 24, and 48 hours in culture, respectively. Similar trends were observed after the use of cycloheximide or staurosporine in combination with indomethacin or prioxicam. These data suggest that cyclooxygenase and/or prostaglandins play a role in programmed cell death of amnion-derived WISH cells in culture.
For a variety of reasons, relating the photophysical properties of a copper phenanthroline to a structure in solution is problematic. To elucidate some of the issues involved, in this paper we describe the crystal and molecular structures of a series of Cu(NN)2(+)-containing systems along with spectral data obtained from the solids themselves. The NN ligands investigated are tmp (3,4,7,8-tetramethyl-1,10-phenanthroline), dpdmp (2,9-diphenyl-4,7-dimethyl-1,10-phenanthroline), dptmp (2,9-diphenyl-3,4,7,8-tetramethyl-1,10-phenanthroline), and dipp (2,9-diisopropyl-1,10-phenanthroline). The results show that a flattening distortion can have a large impact on the spectroscopic properties of a Cu(NN)2+ system, whereas a typical rocking distortion has comparatively little effect. The reflectance spectra of orange or orange-red salts that have approximately perpendicular phenanthroline ligands exhibit absorption bands in the neighborhood of 460 nm along with a shoulder at longer wavelength. In the other limit, when a pronounced flattening distortion occurs and the dihedral angle between ligands is 20 degrees or more off perpendicular, the reflectance spectrum exhibits two distinct visible bands with intense absorption occurring at 525 nm or even longer wavelength. If the phenanthroline ligand lacks bulky substituents in the 2,9 positions, the compound may even be purple, depending on the counterion. Cu(NN)2+ complexes that contain phenyl substituents in the 2,9 positions and exhibit long-wavelength absorption in solution probably adopt a flattened structure in the ground electronic state. In most other systems ground-state flattening is a solid-state effect induced by lattice forces. However, a flattening distortion is an intrinsic attribute of the emissive excited state, although intra- or intermolecular forces can inhibit the effect. In the case of the Cu(dptmp)2+ system, intramolecular steric interactions oppose flattening because the methyl groups in the 3,8 positions control the torsion angles of the neighboring phenyl groups. In the case of [Cu(tmp)2]BPh4, packing interactions induce a small flattening in the crystal, but they also constrain the degree of distortion that can occur in the excited state. As a consequence [Cu(tmp)2]BPh4 exhibits a weak photoluminescence in the solid phase (tau = 15 ns). This is the first report of emission from a bis(phenanthroline)copper(I) system that does not have bulky substituents in the 2 and/or 9 positions of the ligand. The [Cu(tmp)2]BPh4 system crystallizes in space group P2(1)/n with a = 17.4883(4) A, b = 9.86860(10) A, c = 26.3747(6) A, alpha = 90 degrees, beta = 97.7021(8) degrees, gamma = 90 degrees, V = 4510.8(3) A3, and Z = 4. For 12,948 unique data with Fo2 > 2 sigma(Fo2), R = 6.5%. The [Cu(dpdmp)2]PF6 system crystallizes in space group P2/n with a = 16.0722(13) A, b = 8.1100(7) A, c = 16.8937(10) A, alpha = 90 degrees, beta = 93.947(5) degrees, gamma = 90 degrees, V = 2196.8(5) A3, and Z = 2. For 2833 unique data with Fo2 > 2 sigma(Fo2), R = 6.0%. The [Cu(dptmp)2]PF6.THF system crystallizes in space group P1 with a = 12.8486(4) A, b = 13.7341(1) A, c = 15.1678(3) A, alpha = 99.5819(14) degrees, beta = 96.7263(13) degrees, gamma = 97.3311(12) degrees, V = 2591.3(2) A3, and Z = 2. For 13,753 unique data with Fo2 > 2 sigma(Fo2), R = 7.4%. Finally, the [Cu(dipp)2]TFPB system crystallizes in space group P1 with a = 14.2523(3) A, b = 16.0496(4) A, c = 17.5801(3) A, alpha = 112.4150(13) degrees, beta = 105.7480(13) degrees, gamma = 99.6078(11) degrees, V = 3408.7(3) A3, and Z = 2. For 8774 unique data with Fo2 > 2 sigma(Fo2), R = 9.3%.
OBJECTIVE: This study was designed to determine the effect of dexamethasone treatment on peripheral blood lymphocyte counts and subpopulations in premature infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Peripheral blood lymphocyte subpopulations in 12 premature infants with BPD were analyzed before treatment with a 6-week course of dexamethasone (day 0), on days 3 and 10 of treatment, and 2 weeks after discontinuing dexamethasone therapy (day 56). Lymphocyte immunophenotypes were determined using direct two-color immunofluorescent staining followed by flow cytometry. RESULTS: The percentage of lymphocytes was significantly lower on days 3 (17.55 +/- 2.55) and 10 (20 +/- 11.8) of dexamethasone therapy compared with before (30.36 +/- 6.41) or after treatment. The percentage of T cells was significantly lower on days 3 and 10 of dexamethasone therapy (mean +/- SEM; 58.09 +/- 1.93 and 60.09 +/- 2.47, respectively) compared with before (67.09 +/- 4.24) or after treatment. The absolute number of T cells was significantly lower on day 10 of therapy. The percentage of CD4+ cells was significantly lower on days 3 (38.91 +/- 2.49) and 10 (40.45 +/- 2.24) of therapy, and this decrease persisted after dexamethasone was stopped (36.73 +/- 3.41). The absolute number of CD4 cells was significantly lower on day 10 (1328 +/- 216) of therapy and reached a nadir on day 56 (1143 +/- 106). Similarly, the CD4/CD8 ratio was also significantly lower on days 3 and 10 of treatment (1.56 +/- 0.18 and 1.64 +/- 0.14, respectively) and reached a nadir on day 56 (1.04 +/- 0.13). CONCLUSION: Dexamethasone significantly reduced the percentage and absolute number of lymphocytes, T cells, and CD4 cells, as well as the CD4/CD8 ratio. A reduction in CD4 cells and in the CD4/CD8 ratio persisted 2 weeks after dexamethasone therapy was stopped. In contrast, the absolute number of B cells increased transiently, and CD8 cells were unaffected by dexamethasone. This alteration in lymphocyte subpopulations may help account for the clinically beneficial anti-inflammatory effect of dexamethasone in the treatment of BPD complicated by respiratory failure. The dexamethasone-induced decrease in CD4 cells may also increase the susceptibility of these infants to infection.
OBJECTIVE: To evaluate the effect of weekly telephone contact with families in enhancing the use of home apnea monitors. STUDY DESIGN: This was a prospective, randomized, single-blinded study of 65 infants who were prescribed home apnea monitoring at the time of initial discharge from the hospital. Exclusion criteria included participation in any other study involving home monitoring or nonavailability of home telephone. Infants were randomized either to the "standard" or "telephone" group by a stratified balanced block technique. All families were instructed to use the monitor during the first 4-week period at all times except during bathing and during the second 4-week period at all unattended times and at night. The families in the telephone group were contacted weekly for 8 weeks. The telephone interview reviewed the events of the previous week but did not include specific encouragement to use the monitor. Both groups received routine pediatric care and follow-up at our high-risk premature clinic. The primary outcome measure was compliance measured as the percentage of time as well as the hours per day that the infant spent on the monitor as recorded by the documented monitor. RESULTS: The telephone (n = 30) and standard (n = 32) groups were similar (p > 0.10) with respect to birth weight (1567 +/- 778 versus 1710 +/- 777 gm), gestational age (30.9 +/- 4.2 versus 31.1 +/- 4.6 weeks), maternal age (24.9 +/- 6.0 versus 25.3 +/- 5.4 years), and commercial insurance (46.7% versus 46.9%), a marker of higher socioeconomic status. Compliance of the telephone versus the standard group was similar during the first 4-week period (74.7 +/- 24.9 versus 75 +/- 27.8%, p = 0.85) (17.9 +/- 5.9 versus 18.2 +/- 6.6 hours/day), the second 4 week period (63.4 +/- 29.1 versus 58.9 +/- 30.9%, p = 0.59) (15.2 +/- 7.0 versus 14.1 +/- 7.4 hours/day) and the entire 8-week period (69.3 +/- 24.7 versus 67.7 +/- 26.2%, p = 0.82, Mann-Whitney U-test) (16.7 +/- 6.0 versus 16.1 +/- 6.5 hours/day), respectively. An abnormal pneumocardiogram at the time of discharge was the only identified factor that improved the compliance for the entire 8-week period (73.1 +/- 22 versus 52.1 +/- 28.5%, p = 0.02) (17.5 +/- 5.2 versus 12.5 +/- 6.8 hours/day) and the first 4-week period of monitoring (81.7 +/- 22.9 versus 59.5 +/- 31.3%, p = 0.01) (19.6 +/- 5.5 versus 14.2 +/- 7.5 hours/day). CONCLUSION: Weekly telephone contact, without specific encouragement to use the monitor, did not improve compliance. Compliance was greater in subjects who had abnormal pneumocardiogram results at the time of discharge from hospital regardless of their telephone/standard group assignment. We speculate that in this already compliant population, more targeted advice is necessary to increase compliance.
We describe a preterm infant with marked motor automatism and skin manifestations after being exposed to fluoxetine in utero. The fluoxetine level drawn at 96 hours of age was 92 ng/ml, which was in adult therapeutic range. The neurologic symptoms resolved by 7 days and follow-up at 4 months revealed normal neurodevelopmental examination.
Foetal membrane rupture is thought to follow from gene-controlled tissue remodelling and apoptosis. We reported previously that staurosporine, cycloheximide, actinomycin D, as well as more physiological apoptotic agents (lactosylceramide, 15d-PGJ(2)) increase prostaglandin release in parallel with induction of apoptosis in WISH and amnion epithelial cells. Also, inhibition of prostaglandin release by cyclooxygenase inhibitors or PKA activators is accompanied by a parallel decrease in apoptosis. We hypothesize that amnion prostaglandin metabolism is linked with apoptosis in amnion epithelial cells and thus to membrane rupture. Amnion mesenchymal cells are also critical for membrane integrity. Their susceptibility to apoptotic agents is unknown and is the subject of this report. In amnion epithelial cells, lactosylceramide (125 microM) induced 6.5-fold, 20-fold increases in PGE(2) and NMP production (apoptosis), respectively. Conversely, in mesenchymal cells, lactosylceramide doses up to 200 microM had no effect on PGE(2) or NMP release. In both cell types, incubation with 15d-PGJ(2) (5-100 microM) demonstrated dose and time dependent increases in PGE(2) and NMP. PKA activators inhibited 15d-PGJ(2) induced PGE(2) release and apoptotis in epithelial cells, but not in mesenchymal cells, however. Major amnion cell types have different sensitivities to physiological apoptotic agents. Prostaglandin release occurs coincident with apoptosis in both amnion epithelial and mesenchymal cells.
Aggressive feeding practices are thought to increase the incidence of necrotizing enterocolitis (NEC). Detailed feeding histories of the 39 cases occurring between January 1, 1984 and May 31, 1985 were compared with matched controls. The study period included a cluster (epidemic) of 11 cases diagnosed within 1 month. Data were analyzed collectively and separately for endemic and epidemic cases. Collectively, cases had greater average daily intake volume, maximum daily intake volume, intake volume on the day prior to diagnosis, and maximum daily caloric intake (all p less than 0.05) than controls. The only recorded parameter that differed in endemic cases vs controls was intake the day prior to diagnosis. In contrast, epidemic cases were fed significantly more volume, more calories, and faster than controls: average intake volume (62.5 +/- 27.2 vs 37.4 +/- 18.0 ml/kg/day); maximum intake volume (118.5 +/- 33.5 vs 76.4 +/- 38.8 ml/kg/day); intake day prior to diagnosis (109.8 +/- 30.9 vs 63.8 +/- 43.1 ml/kg/day); maximum daily increment (42.6 +/- 16.7 vs 26.7 +/- 16.4 ml/kg); maximum caloric intake (126.1 +/- 44.6 vs 77.3 +/- 50.0) (all p less than 0.01). Five of the feeding parameters were significantly less for the epidemic controls than the endemic controls, suggesting a general slowing of feeding during the NEC epidemic. In summary, the data suggest feeding patterns may have an impact on NEC especially during epidemic periods.
The enactment of a new drug law in Italy, brinaing with it special requirements for reporting on distribution of many controlled substances, provides an opportunity for the construction of an information system that can greatly assist in planning drug-related programmes. The Author summarizes the various types of drug information that can be collected from various points in the reporting network and suggests this system could be operated at relatively low cost of it were implemented in Italy in the very near future.