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Biomedical subjects

S Ward

Publications and source records attributed to S Ward.

At least 199 records · Page 11Linked to original sources
PubMed1992

Short-term use of fluoxetine in asymptomatic obese subjects with sleep-related hypoventilation.

Disordered nocturnal breathing with significant arterial oxygen desaturation and sleep apnoea is a feature of extreme obesity which is often difficult to manage in the short term. We have evaluated the effect of fluoxetine, a centrally acting 5-HT re-uptake inhibitor, on sleep-breathing patterns in asymptomatic extremely obese subjects. A double-blind cross-over study was used to compare fluoxetine (60 mg for three days) to placebo. Eleven obese subjects (ten males, one female, mean weight +/- s.d. 131 +/- 2 kg) slept overnight in a sleep laboratory with the polysomnographic study recorded after an initial acclimatization night. The obese subjects had normal respiratory function and normal fully awake arterial oxygen saturation (%SaO2 97 +/- 1). Marked O2 desaturation was seen in all the subjects during sleep but the average asleep %SaO2 did not differ between the two treatment phases (placebo 90 +/- 5; fluoxetine 92 + 2%). However, fluoxetine significantly increased the minimum %SaO2 recorded during the study night either by abolishing or reducing REM sleep (placebo 73 +/- 2%; fluoxetine 81 +/- 8%; P < 0.05, 95% CI -12.3 to -2.03). Frequent hypopnoea was observed in all subjects in both REM and non-REM sleep whereas apnoea was uncommon. The total apnoea/hypopnoea index fell in six subjects during the fluoxetine night, the largest reduction being seen in the most severely affected. In five of the six the improvement was associated with the abolition of REM sleep. Total sleep time did not differ between the placebo and fluoxetine nights nor did a qualitative assessment of sleep using a visual analogue score.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The long-term effects of 5-fluorouracil and sodium butyrate on human Tenon's fibroblasts.

The use of subconjunctival 5-fluorouracil (5-FU) in the first weeks after filtration surgery may ensure long-term bleb survival despite a continuing proliferative stimulus such as in eyes with neovascular glaucoma. In addition, long-term side effects may occur, such as increasing bleb thinning. To ascertain the long-term effects of 5-FU and sodium butyrate, an agent with differentiating and antiproliferative properties, we exposed proliferating human Tenon's capsule fibroblasts to different concentrations of the drugs. The cells were exposed to 5-FU for 1-12 d. The cells were subsequently observed for up to 30 d. Cell proliferation was assessed using cell counting and bromodeoxyuridine uptake, and cell viability was assessed with trypan blue uptake. 5-FU and sodium butyrate inhibited fibroblast proliferation during the treatment period. Higher concentrations of 5-FU (100 and 1000 micrograms/ml) for as little as 1 d resulted in no significant increase in the number of fibroblasts for at least 29 d after treatment was stopped, despite continued stimulation with serum. When treatment with sodium butyrate was stopped, there was greater recovery of proliferation. At a constant concentration of 1000 micrograms/ml of 5-FU for 3 or more days, or a concentration of 100 mmol/l sodium butyrate for 12 d, the entire fibroblast population gradually died over the 30 d period. Thus, short-term treatment with 5-FU may result in long-term inhibition of proliferation of fibroblasts. Long-term inhibition depends on the duration of treatment or on the concentration of 5-FU. Short-term treatment may be affecting the ability of the tissues at the bleb site to heal in the long term. Different dosage regimens may have advantages and are discussed.

Adolescent↗
PubMed1991

Early pregnancy assessment with transvaginal ultrasound scanning.

OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal ultrasonography so that gestational age can be determined and to correlate the sonographic findings with serum human chorionic gonadotropin (hCG) levels calibrated against the first international reference preparation standard. SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the diameter of the gestational sac through transvaginal ultrasonography. MAIN RESULTS: The gestational sac could not be visualized when the hCG level was less than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold values for sac diameter, serum hCG level and gestational age below which the yolk sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the corresponding values above which the yolk sac was always visible were 6.7 mm, 5800 IU/L and 40 days. The threshold values below which cardiac activity was not visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L and 46 days. The mean gestational ages and the 95% confidence and prediction intervals were tabulated so that measurement of the gestational sac diameter could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS: Transvaginal ultrasonography enables detection of an intrauterine sac and reliable estimation of gestational age on the basis of sac dimensions before an embryo can be seen.

Chorionic Gonadotropin↗
PubMed1991

Submicromolar manganese dependence of Golgi vesicular galactosyltransferase (lactose synthetase).

1. Manganese(II) buffers were set up with inorganic triphosphate, trimethylenediaminetetraacetate and tetramethylenediaminetetraacetate to study the Mn dependence of beta 1,4-galactosyltransferase (lactose synthetase) in preparations of rat mammary gland. 2. In intact particulate preparations, treated with the calcium ionophore A23187, lactose synthesis was abolished by chelators and restored by bivalent transition metal ions in a manner characteristic of activation site I of the pure enzyme. Ni(II) also activated, as did Mg at high concentration. 3. Only Mn(II) could restore endogenous rates, giving an apparent Km of 0.1-0.2 microM, and eliciting about 70% full activity without addition of a site II activator. 4. In purified Golgi membrane vesicles, Mn gave an apparent Km of 0.4 microM. This increased sharply to about 10 microM on permeabilization with filipin, lysis with detergents, solubilization with Triton X-100, or in the pure enzyme. Preparations of chemically undamaged Golgi vesicles, known to include a proportion of the enzyme on exposed membranes, exhibited both low-Km and high-Km components. 5. The response of particulate galactosyltransferase to apparently physiological concentrations of free Mn(II) ion is interpreted as either due to a sensitizing factor within the Golgi lumen, or to the accumulation of Mn at elevated concentrations. Alternatively, the high Km of the soluble enzyme may reflect proteolytic damage.

Animals↗
PubMed1991

pH-sensitive control of arginase by Mn(II) ions at submicromolar concentrations.

The manganese dependence of arginase was reinvestigated with extracts of mouse liver to see whether more physiological properties were displayed than have been reported for the purified enzyme. In a preincubation with Mn(II) ions at 37 degrees C the enzyme underwent a slow and reversible activation. At least 90-95% of the activation achieved was dependent on Mn2+. However, no Mn2+ was required for catalytic activity in the assay. The activation showed little dependence upon pH over the range 6.5-9.5, whereas the catalytic activity increased 12-fold in apparent accord with the titration curve of an ionizable group of pKa 7.9. The Mn2+ dependence of arginase activation obeyed Michaelis-Menten kinetics, with Kd varying from 0.3 microM at pH 6.8 to 0.08 microns at pH 7.7. Free Mn2+ concentrations were established in these assays with a trimethylenediaminetetraacetate-Mn buffer. Vmax increased about three-fold over this range. The calculated arginase activity at 0.05 microM Mn2+ increases about nine-fold over this physiological pH range. An enzyme model is proposed to explain these findings. The activity of arginase at "physiological" [Mn2+] and the pronounced pH dependence conferred upon it are consistent with a recently revised role for the urea cycle in the control of bicarbonate and pH in the body. It appears possible that arginase loses Mn2+ sensitivity during the usual purification.

Animals↗
PubMed1991

The pharmacokinetics of ethynylestradiol in the presence and absence of gestodene and desogestrel.

Single doses of ethynylestradiol (30 micrograms) were given alone and in combination with either gestodene (75 micrograms) or desogestrel (150 micrograms) to 10 healthy female volunteers. The doses of steroids were given both orally and by i.v. infusion over 5-7 minutes. Blood samples were taken at regular intervals over 24 hours. The area under the plasma concentration versus time curve (AUC) for oral EE2 alone was 867 +/- 338 pg/ml x h, for oral EE2 in the presence of gestodene it was 795 +/- 206 pg/ml x h and for oral EE2 in the presence of desogestrel it was 614 +/- 132 pg/ml x h. With either gestodene or desogestrel present, the AUC of EE2 was not significantly different from that found when EE2 was given alone. In addition, there was no significant difference between EE2 + gestodene and EE2 + desogestrel. Comparing the relative oral and iv doses, the bioavailability of EE2 (alone) was 59.0 +/- 13% (n = 6), for EE2 plus gestodene it was 62.1 +/- 10% and for EE2 in the presence of desogestrel it was 62.1 +/- 4.4%. The clearance of EE2 (alone) was 19.9 +/- 5.5 l/h and in the presence of gestodene it was 19.4 +/- 9.6 l/h. The clearance of EE2 in the presence of desogestrel appeared slightly greater at 27.7 +/- 8.9 l/h but none of these clearance values were significantly different from each other. The urinary excretion of 6-beta-hydroxy cortisol was similar after all 6 doses of EE2. These data strongly suggest that following single dose administration, neither gestodene nor desogestrel have any inhibitory effect on the metabolism of EE2 or alter its kinetics to any clinically significant extent.

Administration, Oral↗
PubMed1991

Effect of the progestogens, gestodene, 3-keto desogestrel, levonorgestrel, norethisterone and norgestimate on the oxidation of ethinyloestradiol and other substrates by human liver microsomes.

A number of different progestogens, levonorgestrel (LNG), norethisterone (NET), gestodene (GSD), desogestrel (DG) and norgestimate (NORG) are used in combination with the oestrogen ethinyloestradiol (EE2) in oral contraceptive steroid preparations. All the progestogens are acetylenic steroids and previous studies have indicated the potential of acetylenic steroids to cause mechanism-based or "suicide" inactivation of cytochrome P-450. We have compared the effects of the different progestogens on EE2 2-hydroxylation (a reaction catalyzed by enzymes from the P-450IIC, P-450IIIA and P-450IIE gene families) and also the oxidative metabolism of other drug substrates (cyclosporin, diazepam, tolbutamide) by human liver microsomes. On coincubation with EE2 as substrate, GSD, 3-keto desogestrel (3-KD, the active metabolite of desogestrel) and LNG produced some concentration-dependent inhibition of EE2 2-hydroxylation (maximum 32% inhibition at 100 microM 3-keto desogestrel). Ki values determined for GSD and 3-KD were 98.5 +/- 12.3 and 93.2 +/- 10.3 microM (mean +/- SD; n = 4), respectively. Preincubation of progestogens in a small volume (50 microliters) incubation for 30 min in the presence of an NADPH-generating system enhanced the inhibitory potential of all the steroids (at 100 microM, inhibition was for GSD 39%, 3-KD 46%, LNG 46%, NET 51% and NORG 43%). Inhibitory effects were therefore comparable and also similar to the macrolide antibiotic troleandomycin. The most marked inhibition seen was of diazepam N-demethylation and hydroxylation by GSD (71 and 57%, respectively) and 3-KD (62 and 50%, respectively). In preincubation studies involving cyclosporin as the substrate, the order of inhibitory potency was GSD greater than 3-KD greater than NET greater than LNG for production of both metabolite M17 and M21. The results of the study indicate that all the progestogens in common use have the propensity to inhibit a number of oxidative pathways but there is little evidence for one progestogen being more markedly inhibitory than others.

Contraceptives, Oral↗
PubMed1991

Effect of beta radiation on proliferating human Tenon's capsule fibroblasts.

The effects of different doses of beta radiation from a strontium-90 source on the proliferation of human Tenon's capsule fibroblasts were studied. The cultured fibroblasts were exposed to doses of 100, 250, 500, 750, 1000, 1500, and 3000 rads, and cell numbers were counted at days 3, 7, and 14. Treatment inhibited the proliferation of the fibroblasts. At seven days the cells exposed to 3000 rads showed a decrease relative to the starting cell numbers, and at 14 days the cells exposed to 1500 and 3000 rads showed a decrease in cell numbers. The doses of radiation which inhibited cell proliferation more than 50% (at day 7 and 14) and yet did not cause a decrease in the cell population were 500, 750, and 1000 rads. beta Radiation reduces the proliferation of human Tenon's capsule fibroblasts, and at higher doses this effect may be more pronounced one and two weeks after irradiation.

Beta Particles↗
PubMed1991

Implementation of a patient classification system: using current resources to achieve organizational goals.

DeGroot describes five key activities and attitudes needed to successfully implement a PCS: commitment, coordination, education, involvement, and communication. As a result of careful planning by the nurse executive, these factors were present at PGH. This nursing organization's response to change was believed to be typical of most small community hospitals. The description of strategies used to facilitate a smooth transition to a computerized PCS, however, demonstrates one method of managing change. This organizational culture, similar to many nursing cultures, was once committed to preserving the status quo and is now committed to adaptation. As hospitals strive for economic survival, the nurse executive continues to have a pivotal role in developing proactive strategies to promote effective and efficient patient care delivery systems. Selecting and implementing a PCS is one strategy to achieve that goal.

Hospital Bed Capacity, 100 to 299↗
PubMed1990

Signal transduction through the T cell receptor-CD3 complex. Evidence for heterogeneity in receptor coupling.

T cell receptor-CD3 complex (TCR-CD3)-mediated signal transduction was analyzed in HPB-ALL and Jurkat T cell lines. Both cell lines express high levels of TCR-CD3 complex on the cell surface, but provide different model systems for TCR-CD3 signaling in T cells. Jurkat responds with both inositol phosphate generation and intracellular Ca2+ mobilization after triggering of TCR-CD3, whereas TCR-CD3 triggering of HPB-ALL induces Ca2+ mobilization without detectable inositol phosphate generation. By employing a permeabilized cell system, we show that the HPB-ALL line expressed normal levels of Ca2(+)-induced phospholipase C activity. However, the TCR-CD3 on this cell line seems to be uncoupled from phospholipase C activation. In agreement with this result we also show, by analysis of protein kinase C-dependent phosphorylation of three distinct substrates, that TCR-CD3 in HPB-ALL is apparently uncoupled from protein kinase C activation. These findings may have implications for understanding signal-transducing pathways in T cells at various stages of differentiation.

Antigens, CD↗
PubMed1990

Identification of a Caenorhabditis elegans histone H1 gene family. Characterization of a family member containing an intron and encoding a poly(A)+ mRNA.

The isolation and properties of a gene encoding a histone H1 protein of Caenorhabditis elegans, his-24, are described. The predicted protein sequence is similar to histone H1 proteins of other eukaryotes. However, the gene structure of his-24 is atypical for a histone H1 gene; it contains an intron and encodes a polyadenylated mRNA. A family of approximately five histone H1 genes is defined by cross-hybridization to his-24. All appear to encode polyadenylated mRNAs. One gene is expressed specifically in male germ cells. These histone H1 genes are dispersed individually in the genome, apart from the previously described clusters of core histone genes (H2A, H2B, H3 and H4), which probably all encode non-polyadenylated mRNAs. This histone gene organization, with clustered core histone genes, encoding non-polyadenylated transcripts, and dispersed, histone H1 genes from which it appears only polyadenylated messages arise, suggests that C. elegans is at a stage of evolution of the histone gene family intermediate between lower eukaryotes (e.g. yeast) and the most advanced forms.

Amino Acid Sequence↗
PubMed1990

Developing a test of knowledge of surgical options for breast cancer.

Because many women now have a choice regarding the type of surgery they prefer for early stage breast cancer, it is important for clinicians to provide comprehensive information about these options and to determine whether patients have understood this information. The purpose of this study was to develop a short, easily administered, valid and reliable test of women's knowledge of surgical treatment options for early stage breast cancer. Instrument development was carried out in two phases: (a) content domains were established and items were generated and examined for content validity and clarity; and (b) the known-groups technique was used to determine construct validity and to generate data for reliability testing. The test was administered to 44 student nurses, 21 women with breast cancer, and 24 practicing nurses. An 18-item test--the BCIT-R (Breast Cancer Information Test-Revised)--with modest internal consistency and very good construct validity resulted from these steps. Nurses scored significantly better than either students or patients. The instrument is discussed in terms of psychometric issues and clinical use.

Adult↗
PubMed1990

Comparison of the glycolipid receptor specificities of Shiga-like toxin type II and Shiga-like toxin type II variants.

The antigenically distinct Shiga-like toxins (SLTs) SLT-1 and SLT-II are cytotoxic for both Vero and HeLa cells and use Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer (Gb3) molecules as functional receptors. SLT-II-related variants SLT-IIvp and SLT-IIvh, produced by a porcine isolate and a human isolate, respectively, are cytotoxic for Vero but not HeLa cells. To investigate the basis for these differences in cytotoxic specificity among SLTs, the nature of the receptor for the SLT-II variants was examined. First, the patterns of binding of SLT-II and the SLT-II variants to Gb3 receptor analogs Gal alpha 1-4Gal-bovine serum albumin and Gal alpha 1-4Gal beta 1-4Glc-bovine serum albumin were compared. SLT-IIvp bound the trisaccharide neoglycoprotein preferentially, while SLT-IIvh bound both analogs equally but with less affinity than did SLT-II. Next, the glycolipids to which the SLT-II variants bound in Vero and HeLa cells were identified by thin-layer chromatography. SLT-IIvp bound to Gb3, GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer (Gb4), and Gal beta 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer (Gb5) in Vero cells but only Gb3 in HeLa cells. However, SLT-IIvh bound to Gal alpha 1-4Gal beta 1-1Cer (Gb2) and Gb3 in HeLa cells but only Gb3 in Vero cells. In addition, hybrid toxins (SLT-IIvp subunit A with SLT-II subunit B or SLT-II subunit A with SLT-IIvp subunit B) were used to show that the receptor specificities of the SLTs was B subunit specific. These differences in receptor specificities are important in vivo, as evidenced by a 400-fold difference in the 50% lethal doses of purified SLT-IIvp and SLT-II (200 versus 0.5 ng, respectively) for mice. These data indicate that SLT-II-cytotoxic variants can occur as a consequence of differences in receptor specificity and affinity.

Animals↗
PubMed1990

OR turnaround: looking at problem areas.

This is the fourth in a series on management strategies for "turning around an OR." The first three articles appeared in the January, April, and June issues of OR Manager.

Administrative Personnel↗