Search PubMed⌕ Search

Biomedical subjects

S Ward

Publications and source records attributed to S Ward.

At least 37 records · Page 2Linked to original sources

Iron metabolism in monochorionic twin pregnancies in relation to twin--twin transfusion syndrome.

Fetal iron metabolism was investigated in monochorionic (MC) twin pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal blood samples were obtained both in utero and at birth from MC twins with TTTS (n = 23) and without TTTS (n = 18). In a second group of 30 twin pairs (15 with and 15 without TTTS), liver iron content was assessed by using archived paraffin wax-embedded blocks. Serum ferritin was determined by radioimmunoassay and values are given as gestation independent Z-scores and expressed as mean with 95% confidence intervals. Ferritin concentrations in the recipients were higher than in the donors both in utero (P < 0.01) and at birth (P < 0.01). Fetal serum ferritin in non-TTTS twins were similar to the recipient twins but higher than the donor twins (P < 0.05). A significant association was found between ferritin concentrations, the total red blood cell count and haemoglobin in the TTTS twin pairs (P < 0.01) and the non-TTTS twins as a group (P < 0.01). The total stainable liver iron was comparable between twin pairs in the TTTS and non-TTTS groups. This study fails to provide evidence of iron overload in the recipient and depletion in the donor twins and, thereby, questions the validity of the conventional theory of inter-twin transfusion as the cause of TTTS.

Erythrocyte Count↗

Erythropoietin in monochorionic twin pregnancies in relation to twin--twin transfusion syndrome.

Fetal erythropoietin (Epo) concentrations were studied in monochorionic (MC) twin pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal blood samples in utero were obtained from MC twins with TTTS (n = 15) and without TTTS (n = 6). In a second group of five sets of twin pairs with or without TTTS, immunolocalization of Epo was performed in archived paraffin wax sections of liver and kidney collected at autopsy. Epo was measured using a chemiluminescence assay and expressed as gestation independent Z-scores and given as mean +/- 95% confidence intervals (CI). Fetal Epo concentrations in utero were higher in MC twins with TTTS than the non-TTTS as a group (P < 0.001). There was no difference in Epo concentrations between TTTS and non-TTTS twin pairs. Fetal Epo concentrations were correlated with pO(2) in the recipient (r = 0.64; P < 0.01), donor (r = 0.64; P < 0.01) and control twins (r = 0.76; P < 0.01). Immunostaining of the fetal kidney localized Epo primarily to the cytoplasm of the proximal convoluted tubules. The intensity of staining in the kidney and liver was comparable between TTTS and non-TTTS twin pairs. Fetal Epo concentrations were higher in the TTTS than non-TTTS twin pairs and were correlated with the degree of hypoxaemia. However, Epo concentrations were comparable between donor and recipient twins, perhaps due to similar production rather than inter-twin transfusion of blood.

Acid-Base Equilibrium↗

Genes or placenta as modulator of fetal growth: evidence from the insulin-like growth factor axis in twins with discordant growth.

To determine whether fetal growth is regulated by placental and/or fetal factors, we measured maternal and fetal concentrations of insulin-like growth factor-I (IGF-I), IGF-II and insulin-like growth factor binding protein-1 (IGFBP-1) (total and non-phosphorylated) in dichorionic (DC) and monochorionic (MC) twins with (DC, n = 13; MC, n = 12) or without (DC, n = 13; MC, n = 12) discordant birth weight. In the discordant MC pregnancy, growth-restricted (IUGR) twins had lower IGF-II concentrations (P < 0.001) but similar IGF-I concentrations compared to the appropriate for gestational age(AGA) co-twin. The differences in IGF-II concentrations showed a positive association with percentage birth weight discordance (r = 0.60; P < 0.05) in MC twins. In contrast, IUGR DC twins had lower IGF-I concentrations (P < 0.05) but similar IGF-II concentrations compared to the AGA co-twins. There was a positive correlation between IGF-I concentrations and birth weight (r = 0.47; P < 0.05) in DC twins. Total IGFBP-1 concentrations were higher in both MC and DC IUGR twins (P < 0.05) compared to AGA twins. A negative association was found between total IGFBP-1 concentrations and birthweight of both MC (r = 0.47; P < 0.05) and DC (r = 0.58; P < 0.01) twins. No such differences in IGF concentrations were found between concordant MC and DC twin pairs. The maternal IGF concentrations were comparable between the MC and DC groups. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in either IGF-I or IGF-II/IGFBP-1, depending upon the functioning of the placenta.

Female↗

Experience with a clinical guideline for the treatment of ventilator-associated pneumonia.

OBJECTIVE: To evaluate a clinical guideline for the treatment of ventilator-associated pneumonia. DESIGN: Prospective before-and-after study design. SETTING: A medical intensive care unit from a university-affiliated, urban teaching hospital. PATIENTS: Between April 1999 and January 2000, 102 patients were prospectively evaluated. INTERVENTIONS: Prospective patient surveillance, data collection, and implementation of an antimicrobial guideline for the treatment of ventilator-associated pneumonia. MEASUREMENTS AND MAIN RESULTS: The main outcome evaluated was the initial administration of adequate antimicrobial treatment as determined by respiratory tract cultures. Secondary outcomes evaluated included the duration of antimicrobial treatment for ventilator-associated pneumonia, hospital mortality, intensive care unit and hospital lengths of stay, and the occurrence of a second episode of ventilator-associated pneumonia. Fifty consecutive patients with ventilator-associated pneumonia were evaluated in the before period and 52 consecutive patients with ventilator-associated pneumonia were evaluated in the after period. Severity of illness using Acute Physiology and Chronic Health Evaluation II (25.8 +/- 5.7 vs. 25.4 +/- 8.1, p =.798) and the clinical pulmonary infection scores (6.6 +/- 1.0 vs. 6.9 +/- 1.2, p =.105) were similar for patients during the two treatment periods. The initial administration of adequate antimicrobial treatment was statistically greater during the after period compared with the before period (94.2% vs. 48.0%, p <.001). The duration of antimicrobial treatment was statistically shorter during the after period compared with the before period (8.6 +/- 5.1 days vs. 14.8 +/- 8.1 days, p <.001). A second episode of ventilator-associated pneumonia occurred statistically less often among patients in the after period (7.7% vs. 24.0%, p =.030). CONCLUSIONS: The application of a clinical guideline for the treatment of ventilator-associated pneumonia can increase the initial administration of adequate antimicrobial treatment and decrease the overall duration of antibiotic treatment. These findings suggest that similar types of guidelines employing local microbiological data can be used to improve overall antibiotic utilization for the treatment of ventilator-associated pneumonia.

APACHE↗

A representational approach to patient education.

PURPOSE: To describe the theoretical basis for a representational approach to patient education and the application of this approach to the development, implementation, and preliminary evaluation of a representational intervention for pain management. ORGANIZING CONSTRUCT: Leventhal's common sense model (CSM) was a guide for this approach to patient education. The CSM is based on the idea that people have common sense beliefs, or representations, that guide how they cope with health problems. Theoretically based interventions derived from the CSM have not been reported. METHODS: Steps included: (a) designing a general approach to educational interventions, centered on illness representations; (b) specifying an intervention (RIDPAIN) to facilitate coping with cancer pain; (c) pilot-testing and revising the intervention; and (d) testing feasibility and acceptability of the intervention with 61 patients in a Midwestern American city. FINDINGS: The RIDPAIN intervention was useful in eliciting misconceptions of pain and pain management from patients experiencing cancer pain. Many patients found RIDPAIN to be meaningful and useful, and they perceived it to have an effect on pain-related beliefs and behaviors. CONCLUSIONS: This theory-driven approach should be effective and widely applicable because it includes patients as active participants in all phases of the learning continuum, from information acquisition to behavior change.

Adaptation, Psychological↗

A herpes simplex virus type 1 gamma34.5 second-site suppressor mutant that exhibits enhanced growth in cultured glioblastoma cells is severely attenuated in animals.

We describe here the neurovirulence properties of a herpes simplex virus type 1 gamma34.5 second-site suppressor mutant. gamma34.5 mutants are nonneurovirulent in animals and fail to grow in a variety of cultured cells due to a block at the level of protein synthesis. Extragenic suppressors with restored capacity to replicate in cells that normally do not support the growth of the parental gamma34.5 deletion mutant have been isolated. Although the suppressor virus reacquires the ability to grow in nonpermissive cultured cells, it remains severely attenuated in mice and is indistinguishable from the mutant gamma34.5 parent virus at the doses investigated. Repairing the gamma34.5 mutation in the suppressor mutant restores neurovirulence to wild-type levels. These studies illustrate that (i) the protein synthesis and neurovirulence defects observed in gamma34.5 mutant viruses can be genetically separated by an extragenic mutation at another site in the viral chromosome; (ii) the extragenic suppressor mutation does not affect neurovirulence; and (iii) the attenuated gamma34.5 mutant, which replicates poorly in many cell types, can be modified by genetic selection to generate a nonpathogenic variant that regains the ability to grow robustly in a nonpermissive glioblastoma cell line. As this gamma34.5 second-site suppressor variant is attenuated and replicates vigorously in neoplastic cells, it may have potential as a replication-competent, viral antitumor agent.

Animals↗

Fetal leptin influences birth weight in twins with discordant growth.

The objective of this study was to determine the plasma leptin concentrations in twin pregnancies in relation to chorionicity and discordant fetal growth. We studied 53 twin pregnancies of which 26 had growth discordance of > or =20% and 27 were concordant for growth (discordance of < or =10%). Paired maternal and fetal blood samples were obtained at birth. Plasma leptin concentrations were measured by RIA. In discordant monochorionic pregnancies, fetal plasma leptin concentrations in the intrauterine growth-restricted twins were lower than the co-twins with normal growth (mean difference, 3 ng/mL; 95% CI, 2.2 to 3.3 ng/mL; p < 0.001), whereas no such differences were present between concordant monochorionic twin pairs (mean difference, 0.1 ng/mL; 95% CI, -0.2 to 0.5 ng/mL; NS). Similarly, fetal plasma leptin concentrations in appropriate-for-gestational-age twins were higher than in the intrauterine growth-restricted twins of the discordant dichorionic pregnancies (mean difference, 2.4 ng/mL; 95% CI, 1.8 to 3.1 ng/mL; p < 0.001). No such differences were present between the concordant dichorionic twin pairs (mean difference, 0.2 ng/mL; 95% CI, -0.1 to 0.5 ng/mL; NS). Maternal plasma leptin concentrations were comparable among all four groups and were higher than the fetal levels. Fetal plasma leptin concentrations of the intrauterine growth-restricted twins of discordant monochorionic and dichorionic pregnancies were comparable. There was a positive association between cord plasma leptin concentrations and the birth weight of twin pairs (y = 0.002x - 0.32; r = 0.63; p < 0.001; n = 106). A significant positive association was also found between percent differences in birth weight and fetal delta plasma leptin concentrations of the discordant monochorionic and dichorionic twin pairs (y = 0.057x + 0.93; r = 0.60; p < 0.001, n = 26). In conclusion, irrespective of chorionicity, plasma leptin concentrations in intrauterine growth-restricted twins were 2-fold lower than their co-twins with normal growth. These differences may be attributed to placental factors.

Birth Weight↗

Placental regulation of insulin-like growth factor axis in monochorionic twins with chronic twin-twin transfusion syndrome.

To test the hypothesis that severe growth restriction (intrauterine growth retardation) in donor twins with chronic twin-twin transfusion syndrome (TTTS), a common complication of monochorionic twin pregnancy, is due to an aberration in the insulin-like growth factor (IGF) axis, we studied 25 sets of monochorionic twins with (n = 13) and without (n = 12) TTTS. Maternal and cord blood samples were collected at birth and analyzed for IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-1 phosphorylation status. Fetal IGF-II levels in the recipient twins with TTTS were higher than those in the donor twins (829 +/- 45 vs. 543 +/- 60 ng/mL; P < 0.001), but were comparable with those in the non-TTTS twin pairs. IGF-I levels in recipient and donor twin pairs were similar. The total IGFBP-1 concentration was higher in the donor twins than in the recipients (1153 +/- 296 vs. 419 +/- 108 ng/mL; P < 0.001) and non-TTTS twin pairs (P < 0.01). The percent less phosphorylated IGFBP-1 was higher in the recipients than in the donor twins (P < 0.05). There were no differences in IGF-I, IGF-II, and IGFBP-1 levels between non-TTTS twin pairs. Maternal levels of IGFs were comparable in the two groups. In the TTTS group, fetal birth weight gave a positive correlation with serum IGF-II levels (y = 0.25x + 361.1; r = 0.47; P < 0.05), and a negative association with IGFBP-1 levels (y = -0.72x + 1593.6; r = 0.58; P < 0.01). Our data argue against intertwin transfusion as the cause of intrauterine growth retardation in the donor twin and provide evidence that the placenta is the key regulator of the fetal IGF axis, especially when fetal genotype and maternal environments are similar.

Female↗

Metabolic power, mechanical power and efficiency during wind tunnel flight by the European starling Sturnus vulgaris.

We trained two starlings (Sturnus vulgaris) to fly in a wind tunnel whilst wearing respirometry masks. We measured the metabolic power (P(met)) from the rates of oxygen consumption and carbon dioxide production and calculated the mechanical power (P(mech)) from two aerodynamic models using wingbeat kinematics measured by high-speed cinematography. P(met) increased from 10.4 to 14.9 W as flight speed was increased from 6.3 to 14.4 m s(-1) and was compatible with the U-shaped power/speed curve predicted by the aerodynamic models. Flight muscle efficiency varied between 0.13 and 0.23 depending upon the bird, the flight speed and the aerodynamic model used to calculate P(mech). P(met) during flight is often estimated by extrapolation from the mechanical power predicted by aerodynamic models by dividing P(mech) by a flight muscle efficiency of 0.23 and adding the costs of basal metabolism, circulation and respiration. This method would underestimate measured P(met) by 15-25 % in our birds. The mean discrepancy between measured and predicted P(met) could be reduced to 0.1+/-1.5 % if flight muscle efficiency was altered to a value of 0.18. A flight muscle efficiency of 0.18 rather than 0.23 should be used to calculate the flight costs of birds in the size range of starlings (approximately 0.1 kg) if P(met) is calculated from P(mech) derived from aerodynamic models.

Animals↗

Stereotactic core biopsy of breast microcalcifications: comparison of film versus digital mammography, both using an add-on unit.

OBJECTIVE: The goal of this study was to assess the accuracy of an add-on stereotactic unit for core biopsy of indeterminate breast microcalcifications and to compare digital with conventional stereotactic guidance. MATERIALS AND METHODS: We conducted a retrospective review of 232 lesions with indeterminate microcalcifications in 218 women who underwent stereotactically guided breast biopsies. All biopsies were performed using a standard mammography machine with an add-on unit, 121 with conventional and 111 with digital stereotactic guidance. Successful sampling of the lesion was determined by the detection of microcalcifications on specimen radiography or at pathology. RESULTS: Using the add-on unit, 219 (94.4%) of the 232 targeted lesions were successfully sampled. The size, location, number of cores per lesion, and histology of the lesions were not different between the conventional and digital stereotactic biopsy groups (p > 0.1). Indeterminate microcalcifications were missed on biopsy in nine (7.4%) of 121 cases using conventional radiography and in only four (3.6%) of 111 cases using digital imaging. Digital stereotactic guidance allowed sampling of lesions with fewer calcifications per square centimeter (p < 0.001). CONCLUSION: Sampling of indeterminate microcalcifications using a standard mammography machine and an add-on unit has a high accuracy, similar to rates reported for dedicated prone biopsy tables. An add-on unit offers the advantage of considerable cost and space savings. Relative to conventional radiography, digital stereotactic guidance allows lesions with fewer calcifications to be sampled and achieves a greater biopsy success rate. Immediate digital images in the biopsy room also permit rapid adjustment of alignment and minimize patient movement.

Adult↗

Explaining retrospective reports of symptoms in patients undergoing chemotherapy: anxiety, initial symptom experience, and posttreatment symptoms.

This study evaluated different perspectives on the relationship of trait anxiety to symptom report. Baseline trait anxiety was related to (a) initial symptoms reported 2 days after beginning chemotherapy, (b) posttreatment symptoms reported 2 days after cessation of medication, and (c) retrospective reports of initial symptoms (made concurrently with posttreatment reports). Associations were significant for vague psychophysiological symptoms but not for concrete visible symptoms. Path models indicated that the relationship of anxiety to retrospective report of vague symptoms was due to both enhanced encoding and facilitated recall of symptoms. Further analyses revealed, however, that this relationship reflects symptoms stability rather than anxiety-related differences in attention. Anxious and nonanxious patients appear to be equally accurate in their retrospective report of symptoms.

Adult↗

Methanococcus jannaschii ORF mj0608 codes for a class C inorganic pyrophosphatase protected by Co(2+) or Mn(2+) ions against fluoride inhibition.

Openreading frame mj0608 of the Methanococcus jannaschii genome, recognized by its sequence similarity to that of the gene coding for class C inorganic pyrophosphatase in Bacillus subtilis, was cloned and over-expressed in Escherichia coli. The protein was purified and characterized by SDS-PAGE, M(r), and N-terminal sequence. Under suitable conditions it catalyzed the specific hydrolysis of PPi at about 600 micromol x min(-1) x mg(-1) at 25 degrees C, and at 8000 micromol x min(-1) x mg(-1) at 85 degrees C. Therefore this protein is a specific inorganic pyrophosphatase. The activities of Mg(2+), Mn(2+), Co(2+), and Zn(2+) ions as cofactors for hydrolysis of PPi were compared at pH 7.5 and 9.0. Unlike the class C pyrophosphatase of B. subtilis, this enzyme required no prior activation by low concentrations of Mn(2+) or Co(2+) ions. However, prior exposure to these ions afforded striking protection against inhibition by sodium fluoride, to which the enzyme was otherwise very sensitive.

Amino Acid Sequence↗