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S Newman

Publications and source records attributed to S Newman.

At least 55 records · Page 3Linked to original sources
PubMed1998

Long-term effectiveness of antimalarial drugs in rheumatic diseases.

OBJECTIVE: The purpose of this study was to compare the long-term effectiveness between chloroquine (CQ) and hydroxychloroquine (HCQ). METHODS: Medical charts of all patients seen by eight rheumatologists practising in two tertiary care centres and starting antimalarial treatment between January 1985 and December 1993 were reviewed. Patient characteristics, disease, and treatment information were collected. The main outcome measures were the cause of and the time to the discontinuation of antimalarial drugs resulting from all causes, principally toxicity or inefficacy, or both. Bivariate analysis including t tests and chi 2 tests were used to assess differences between means and proportions respectively. Survival curves were evaluated using the Kaplan-Meier method. Multivariate analysis (Cox regression) was used to adjust for potential confounders. RESULTS: After all medical records were reviewed, 1042 eligible cases were identified. From these, 940 (90%) had usable information and they represent the cohort. Five hundred and fifty eight had rheumatoid arthritis, 178 had systemic lupus erythematosus, 127 had palindromic arthritis, and 77 had other diagnoses. Fifty seven per cent of the patients received CQ and 43% HCQ. The proportion of patients with side effects taking HCQ and CQ was 15% and 28% respectively (p = 0.001). Using Cox regression model to adjust for age at the onset of antimalarial treatment, physician differences, sex, disease type, disease duration before treatment, and rank selection, there were no differences in the hazard ratio (HR) for overall discontinuations between CQ and HCQ. While the HR for discontinuations because of toxicity was lower for HCQ (HR = 0.6, 95% CI 0.4, 0.9), the HR for discontinuations because of inefficacy was significantly higher for HCQ (HR = 1.4, 95% CI 1.1, 1.9). CONCLUSIONS: After adjusting for time and several confounders HCQ was less toxic but less effective than CQ. Only one case of probable/possible retinopathy was found. Therefore, we propose a careful baseline ophthalmological evaluation by an expert and then one or every two years if proper doses are used.

Adult↗
PubMed1998

zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila.

In Drosophila as well as many vertebrate systems, germ cells form extraembryonically and migrate into the embryo before navigating toward gonadal mesodermal cells. How the gonadal mesoderm attracts migratory germ cells is not understood in any system. We have taken a genetic approach to identify genes required for germ cell migration in Drosophila. Here we describe the role of zfh-1 in germ cell migration to the gonadal mesoderm. In zfh-1 mutant embryos, the initial association of germ cells and gonadal mesoderm is blocked. Loss of zfh-1 activity disrupts the development of two distinct mesodermal populations: the caudal visceral mesoderm and the gonadal mesoderm. We demonstrate that the caudal visceral mesoderm facilitates the migration of germ cells from the endoderm to the mesoderm. Zfh-1 is also expressed in the gonadal mesoderm throughout the development of this tissue. Ectopic expression of Zfh-1 is sufficient to induce additional gonadal mesodermal cells and to alter the temporal course of gene expression within these cells. Finally, through analysis of a tinman zfh-1 double mutant, we show that zfh-1 acts in conjunction with tinman, another homeodomain protein, in the specification of lateral mesodermal derivatives, including the gonadal mesoderm.

Animals↗
PubMed1997

Viscosity and elasticity during collagen assembly in vitro: relevance to matrix-driven translocation.

In order to better understand the gelation process associated with collagen assembly, and the mechanism of the in vitro morphogenetic phenomenon of "matrix-driven translocation" [S.A. Newman et al. (1985) Science, 228, 885-889], the viscosity and elastic modulus of assembling collagen matrices in the presence and absence of polystyrene latex beads was investigated. Viscosity measurements at very low shear rates (0.016-0.0549 s(-1)) were performed over a range of temperatures (6.9-11.5 degrees C) in a Couette viscometer. A magnetic levitation sphere rheometer was used to measure the shear elastic modulus of the assembling matrices during the late phase of the gelation process. Gelation was detected by the rapid increase in viscosity that occurred after a lag time tL that varied between O and approximately 500 s. After a rise in viscosity that occurred over an additional approximately 500 s, the collagen matrix was characterized by an elastic modulus of the order of several Pa. The lag time of the assembly process was relatively insensitive to differences in shear rate within the variability of the sample preparation, but was inversely proportional to the time the sample spent on ice before being raised to the test temperature, for test temperatures > 9 degrees C. This suggests that structures important for fibrillogenesis are capable of forming at 0 degrees C. The time dependence of the gelation process is well-described by an exponential law with a rate constant K approximately 0.1 s(-1). Significantly, K was consistently larger in collagen preparations that contained cell-sized polystyrene beads. From these results, along with prior information on effective surface tension differences of bead-containing and bead-lacking collagen matrices, we conclude that changes in matrix organization contributing to matrix-driven translocation are initiated during the lag phase of fibrillogenesis when the viscosity is < or = 0.1 Poise. The phenomenon may make use of small differentials in viscosity and/or elasticity, resulting from the interaction of the beads with the assembling matrix. These properties are well described by standard models of concentrated solutions.

Animals↗
PubMed1997

EEG changes during cardiopulmonary bypass surgery and postoperative neuropsychological deficit: the effect of bubble and membrane oxygenators.

OBJECTIVE: Quantitative electroencephalography was used during cardiopulmonary bypass surgery to determine the point in time of most neuronal functional change which may result in postoperative neuropsychological deficit. It was also used to determine any relationship between quantitative electroencephalography changes and type of oxygenator used in surgery. METHODS: We studied 61 coronary artery bypass graft patients. Anaesthesia included thiopental, fentanyl and N2O. Surgery was performed with hypothermic bypass (28 degrees C), arterial pressure of 50-70 mmHg, and alpha-stat, using bubble (Harvey 1700), or membrane (Cobe CML) oxygenators, both with arterial line filters (Pall 40 microns). RESULTS: The main finding was a significant increase in delta power at the end of perfusion (P < 0.01), which showed a positive association with delta power before the start of perfusion. Marked quantitative electroencephalography change at the end of perfusion was not related to systemic hypotension, temperature, type of oxygenator, bypass time, or patient age. Intraoperative quantitative electroencephalography changes found in most patients were transient and could not be related to postoperative cerebral function. However, 16 of the 18 patients who had neuropsychological deficit 2 months after surgery, also had a significant quantitative electroencephalography change at the end of perfusion. CONCLUSIONS: While no difference in anaesthetic technique was found between patients, the variation in quantitative electroencephalography power before perfusion may indicate a difference in individual response to anaesthetic. Usefulness of quantitative electroencephalography to predict postoperative cerebral functional deficit remains doubtful.

Aged↗
PubMed1997

Children's views on aging: their attitudes and values.

Children's perceptions and attitudes about aging and older adults are investigated using a version of Children's Views on Aging (CVoA), a four-part validated instrument designed to assess school-age children's views on older adults and aging. The instrument has been adapted to enable children to make value judgements about their responses to questions on the CVoA. The study reports children's perceptions and attitudes about aging are not as negative as adults conclude. Children are positively affected by interactions with older adults, they describe physical signs of aging without judgement, and respond negatively to some of the unpleasant conditions associated with aging.

Aged↗
PubMed1997

Neottialges neopelagicus new species (Acari:Hypoderatidae) from the pelagic cormorant (Aves:Phalacrocoracidae:Pelecaniformes).

A new species of hypoderatid deutonymph is described from the subcutaneous adipose tissues of the pelagic cormorant, Phalacrocorax pelagicus Pallas, from Alaska. Neotialges neopelagicus n. sp. is similar to the 3 other Neottialges spp. from cormorants. N. neopelagicus closely resembles N. tasmaniensis Fain & Domrow except the genital apodeme is incomplete in the latter, but the sclerotized T-shaped extremities are connected by a thin line of sclerotization to form a complete central apodeme in N. neopelagicus. There also are minor differences in leg chaetotaxy of these 2 species. The genital apodeme is heavily sclerotized throughout its length in N. evanis Fain and N. pelagicus OConnor. In both these species, seta d4 is long and resembles other middorsal idiosomal setae, whereas it is short and hairlike in N. tasmaniensis and N. neopelagicus. In N. pelagicus terminal seta as on tarsus IV is smooth; it is serrated in the other three species. The single pelagic cormorant we found infected with N. neopelagicus shared this host with N. pelagicus, emphasizing the possibility of coexistence of 2 very similar species of hypoderatids in the same host individual.

Animals↗
PubMed1997

New records of subcutaneous mites (Acari:Hypoderatidae) in birds, with examples of potential host colonization events.

New host, geographic records, or both are established for 14 species of hypoderatid deutonymphs from 14 species of birds in North America. Ten of these records are regarded as examples of a potential host colonization event where these hypopi have become established in hosts other than those with which they are normally associated. Herein, potential host colonization events by hypoderatid deutonymphs are regarded as more of an ecologically determined than physiologically specific phenomenon, often specifically related to sharing of nesting sites in the same rookeries by different host taxa. Neottialges ibisicola Young & Pence is placed as a junior synonym of Neottialges plegadicola Fain. The taxonomic status of Hypodectes propus from columbid versus ardeid hosts needs further study.

Animals↗
PubMed1997

Fate determination and migration of progenitors in the postnatal mammalian CNS.

Using replication-deficient retrovirus to transfer marker genes into immature cells, we have characterized spatial and temporal patterns of glial progenitor migration and differentiation in the early postnatal rat forebrain and cerebellum, and interneuron differentiation in the cerebellum. Progenitors do not migrate randomly, but follow discrete paths, largely confined to a coronal plane in forebrain and a sagittal plane in cerebellum. Radial glia provide one substrate for migration. In vitro studies suggest that radial glia contribute a permissive pathway along which progenitors in an immature, migratory state. Local environmental cues that progenitors encounter during migration may influence fate decisions substantially. Not all progenitors differentiate; some remain in an immature, proliferative state in which they do not complete differentiation, but can be induced to do so by pathological conditions.

Animals↗
PubMed1997

Airway deposition and airway effects of antiasthma drugs delivered from metered-dose inhalers.

Many different metered-dose inhalation devices are becoming available for the treatment of airway diseases. Each of these inhalers differs in its delivery characteristics. An assessment of the efficacy of drug delivery by these inhalers is essential, in view of their therapeutic use. A review of the literature on the relationship between airway deposition and airway effects of drugs delivered from metered-dose inhalers is presented. Nebulizers or spacers are not discussed. The effect of an inhaler depends on the characteristics of the inhaler and the inhalation manoeuvre performed by the patient. This review focuses on the influence of inhaler characteristics on the airway deposition and airway effects. Data from several studies show that there is a significant relationship between the amount of drug deposited in the airways and the airway effects of the drug. Studies on the relationship between airway deposition and airway effect have been troubled by methodological problems, such as the absence of multiple dose comparisons and the difficulty in obtaining steep dose-response curves. The techniques for measuring airway deposition of inhaled drugs, namely the scintigraphic and the pharmacokinetic method, are discussed and compared. The appropriate use of these techniques can help to define and compare the drug delivery characteristics of different devices, thus enabling inhaled therapy to be optimized.

Administration, Inhalation↗
PubMed1997

The short-term impact of Botox injections on speech disability in adductor spasmodic dysphonia.

This study investigates the impact of Botox injections on speech disability in a group of patients with adductor spasmodic dysphonia. Patient-perceived disability was assessed on the Speech Disability Questionnaire. A factor analysis on speech disability yielded five factors. Four of these, social isolation (p < 0.001), negative communication (p < 0.005), public avoidance (p < 0.05) and limited understanding (p < 0.01), showed significant change from prior to and one week post injection. Speech and language therapists' assessment also showed changes in voice quality over the same period. These findings are discussed in terms of the relationship between voice quality, disability and handicap, in adductor spasmodic dysphonia.

Adult↗
PubMed1997

Varices with thrombosis in the cervix and uterus of a mare.

Cervical and uterine varices with thrombosis were observed at the necropsy of a virgin 16-year-old Peruvian Paso that had previous episodes of hemorrhage from the uterus. Practitioners and pathologists should be alert to the possibility of ruptured varices in mares with hemorrhage into the uterus or from the vulva.

Animals↗
PubMed1996

Stimulation of GLUT1 glucose transporter expression in response to inhibition of oxidative phosphorylation: role of reduced sulfhydryl groups.

Treatment of Clone 9 cells incubated in the absence of serum with 5 mM azide for 24 h results in an 8- and 3-fold induction in GLUT1 mRNA and GLUT1 protein, respectively. To explore the pathways mediating the induction of GLUT1 mRNA, we first examined whether inhibition of oxidative phosphorylation by other agents results to a similar response. Exposure of cells to 5 microM carbonyl cyanide m-chlorophenylhydrazone (CCCP), 0.15 microM oligomycin B, or 5 mM azide resulted in near-equivalent increases in GLUT1 mRNA content. The inhibition of oxidative phosphorylation is associated with increased cell lactate content and in extracellular lactate to pyruvate ratio, reflecting a rise in cytosolic NADH/NAD+ ratio. We next tested the possibility that an increase in cell SH/SS ratio mediates the enhancement of GLUT1 mRNA in response to azide. We show that treatment of cells with 10 mM mercaptoethanol, an agent that increases cell SH/SS ratio, results in a approximately 6-fold increase in GLUT1 mRNA content. Moreover, incubation of cells in the presence of 0.3 mM diamide, a known intracellular sulfhydryl oxidizing agent, completely abolishes the induction of GLUT1 mRNA by azide. The results suggest that an increase in cell SH/SS ratio plays a critical role in the induction of GLUT1 mRNA in response to inhibition of oxidative phosphorylation.

Animals↗
PubMed1996

Lipocortin 1 and the control of cPLA2 activity in A549 cells. Glucocorticoids block EGF stimulation of cPLA2 phosphorylation.

Epidermal growth factor (EGF) rapidly stimulates the release of arachidonic acid in A549 cells by a mechanism that is sensitive to pertussis toxin [1]. We show that EGF treatment of A549 cells stimulates phosphorylation of cytosolic phospholipase A2 (cPLA2) through a mechanism that is similarly inhibited by pertussis toxin. The level of cPLA2 expression is, apparently, not changed during this period. Pretreatment of cells with dexamethasone (10-100 nM) for 3 hr prevents this activation of cPLA2 by EFG, without changing the level of cPLA21 expression. The effect of dexamethasone is reversed in the presence of the neutralizing antilipocortin Mab 1A but not by the nonneutralizing antilipocortin 1 control Mab 1B. This strongly suggests that lipocortin 1 mediates the effect of dexamethasone by inhibiting activation of cPLA2. This concept is supported by the fact that a peptide Lc13-25 (10-200 micrograms/mL), derived from the N-terminus of lipocortin 1, also inhibits activation of cPLA2 by EGF in these cells.

Adenocarcinoma↗
PubMed1996

The impact of routine obstetric ultrasonographic screening in a low-risk population.

OBJECTIVES: Our goal was to develop a framework for evaluating the current controversy regarding routine obstetric ultrasonography in a population of low-risk pregnancies. STUDY DESIGN: A retrospective chart review was performed for all low-risk pregnancies from a single obstetric practice during 1990 to 1994, to determine the accuracy of screening ultrasonography for fetal anomalies. All patients received a routine ultrasonographic examination at 18 to 20 weeks' gestation. Neonatal records for all patients were evaluated for the presence of both major and minor anomalies. The data were analyzed with attention to the classification of anomalies (all anomalies vs major anomalies, detectable vs nondetectable). RESULTS: A total of 860 fetuses in 854 pregnancies were evaluated. Anomalies were present in 5.35% (46/860); these were major anomalies in 1.16% (10/860) and minor anomalies in 4.19% (36/860). The sensitivity, specificity, and positive and negative predictive values for the diagnosis of all anomalies were 8.7%, 99.9%, 80%, and 95.7%, respectively. However, if only major anomalies detectable by ultrasonography are included, these values become 75%, 100%, 100%, and 99.9%, respectively. There was one false-positive diagnosis not affecting outcome, a small ventriculoseptal cardiac defect. Postnatal ascertainment of anomalies was excellent, as determined by an incidence of ventriculoseptal defects of 1 in 120. CONCLUSION: Distinguishing between major and minor anomalies and between ultrasonographically detectable versus nondetectable anomalies is essential in the evaluation of the diagnostic accuracy of screening ultrasonography. Any comparisons of studies examining the effectiveness of prenatal screening for congenital anomalies with ultrasonography should use the same outcome: major anomalies identifiable by ultrasonography.

Congenital Abnormalities↗
PubMed1996

Alpha-stat acid-base regulation during cardiopulmonary bypass improves neuropsychologic outcome in patients undergoing coronary artery bypass grafting.

Neuropsychologic impairment in patients undergoing cardiopulmonary bypass may be associated with cerebral blood flow changes arising from different management protocols for carbon dioxide tension during bypass. Seventy patients having coronary artery bypass grafting were randomized to either pH-stat or alpha-stat acid-base management during cardiopulmonary bypass with a membrane oxygenator. In each patient, cerebral blood flow (xenon 133 clearance), middle cerebral artery blood flow velocity (transcranial Doppler sonography), and cerebral oxygen metabolism (cerebral metabolic rate and cerebral extraction ratio) were measured during four phases of the operation: before bypass, during bypass (at hypothermia and at normothermia), and after bypass. A battery, of neuropsychologic tests were also conducted before and 6 weeks after the operation. During hypothermic (28 degrees C) bypass, cerebral blood flow was significantly (p < 0.001) greater in the pH-stat group (41 mlx100 gm(-1)xmin(-1); 95% confidence interval 39 to 43 mlx100 gm(-1)xmin(-1)) than in the alpha-stat group (24 mlx100 gm(-1)xmin(-1); confidence interval 22 to 26 mlx100 gm(-1)xmin(-1)) at constant pressure and How. Arterial carbon dioxide tensions were 41 mm Hg (40 to 41 mm Hg) and 26 mm Hg (25 to 27 mm Hg), respectively; pH was 7.36 (7.34 to 7.38) and 7.53 (7.51 to 7.55), respectively. Middle cerebral artery flow velocity was significantly (p < 0.05) reduced in the alpha-stat group to 87% (77% to 96%) of the prebypass value, whereas it was significantly (p < 0.05) increased (152%; 141% to 162%) in the pH-stat group. Cerebral extraction ratio for oxygen demonstrated relative cerebral hyperemia during hypothermic (28 degrees C) bypass in both the pH-stat and alpha-stat groups (0.12 [0.11 to 0.14] and 0.25 [0.22 to 0.28], respectively); however, hyperemia was significantly more pronounced in the pH-stat group, indicating greater disruption in cerebral autoregulation. Neuropsychologic impairment criteria of deterioration in results of three or more tests revealed that a significantly (Fisher's exact test, p = 0.02) higher proportion of patients in the pH-stat group fared poorly than in the alpha-stat group at 6 weeks (17/35, 48.6% [32% to 65.1%], and 7/35, 20% [6.7% to 33.2.2%], respectively). In conclusion, patients receiving alpha-stat management had less disruption of cerebral autoregulation during cardiopulmonary bypass, accompanied by a reduced incidence of postoperative cerebral dysfunction.

Acid-Base Equilibrium↗
PubMed1996

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Adolescent↗