Biomedical subjects
Publications and source records attributed to D Stevenson.
In breast cancer patients discontinuing chronic tamoxifen therapy, the serum elimination of metabolites X, Y and E paralleled that of tamoxifen, whereas that of metabolite Z did not. The serum elimination of tamoxifen and metabolites X and B was increased by amino-glutethimide treatment, whereas that of metabolites Z, Y, and E was not.
In a multicenter, double-blind, placebo-controlled trial conducted at 23 hospitals in the United States, a single prophylactic 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal) or air placebo was administered shortly after birth to 215 infants with birth weights of 500 to 699 gm. Despite stratification at entry by birth weight and gender, by chance female infants predominated in the air placebo group and male infants predominated in the surfactant group. Among infants receiving synthetic surfactant, improvements in oxygen requirements were significant at 2 hours after birth (p = 0.014) and persisted for 3 days (p = 0.001); improvements in the alveolar-arterial partial pressure of oxygen gradient were significant at 6 hours after birth (p = 0.01) and persisted for 3 days (p = 0.008). Improvements in mean airway pressure were not significant at 2 or at 6 hours after birth (p = 0.622 and 0.083, respectively), but became significant thereafter and persisted for 3 days (p = 0.002). Pneumothorax was reduced by slightly more than half (25 vs 11; p = 0.014); death from respiratory distress syndrome (RDS) was also reduced (26 vs 15; p = 0.046). Overall neonatal mortality, however, was not significantly reduced (58 vs 46; p = 0.102). Other complications of RDS and prematurity were not altered, except that pulmonary hemorrhage occurred significantly more frequently in infants receiving synthetic surfactant (2 vs 12; p = 0.006). These findings indicate that a single prophylactic dose of synthetic surfactant in infants weighing 500 to 699 gm at birth improves lung function, incidence of air leak, and death from RDS but not overall mortality. The only safety problem identified was an increase in pulmonary hemorrhage.
The protein predicted to be encoded by varicella-zoster virus (VZV) gene 61 exhibits limited amino acid sequence similarity to the herpes simplex virus type 1 nuclear phosphoprotein Vmw110, which functions as a transcriptional activator. The gene 61 protein was expressed in its entirety, or as an amino- or carboxy-terminal fragment in Escherichia coli and vaccinia virus recombinants, and monospecific rabbit antisera were raised against an E. coli fusion between beta-galactosidase and the majority of the gene 61 protein. Use of the antisera showed that the gene 61 protein is present in VZV-infected cell nuclei as a heterogeneous phospho-protein of Mr62K to 65K. Phosphorylation occurs in the amino- and, to a lesser extent, carboxy-terminal portions of the protein. The carboxy-terminal region directs transport of the protein to the nucleus, whereas the amino-terminal region, which contains a potential zinc-binding domain, is responsible for a punctate distribution. Preliminary mapping data indicated that gene 61 is transcribed as a 1.8 kb mRNA which initiates about 65 bp upstream from the translation initiation codon, at a position located appropriately with respect to potential regulatory elements.
This method involved one step solvent extraction of milk with ethyl acetate-acetone-methanol by ultrasonication. The supernatants were further cleaned-up and enriched by solid-phase extraction using octadecyl (C18)-bonded silica cartridges, then assayed by capillary gas-liquid chromatography with electron capture detection. The recoveries of eleven organochlorine pesticides (OCPs) from raw milks were quantitative, ranging from 90-110% at 10 times the limit of detection (LOD). The LOD ranged from 0.5 micrograms/l whole milk for alpha-hexachlorocyclohexane to 2.5 micrograms/l whole milk for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane. The day-to-day variation of the method was evaluated over 7 days using 3 different pools of spiked cow milks (at the LOD, 5 and 10 times the LOD). The coefficient of variations (C.V.s) were 16 +/- 6, 10 +/- 2 and 9 +/- 3% (mean S.D.), respectively. The method showed no emulsion problems common with conventional non-polar solvent extraction, and the use of solid-phase extraction considerably reduced the sample clean-up process compared with the existing methods. The method also showed that OCPs in milk could be extracted quantitatively without extraction of total fat, and that OCPs spiked into cows milk could be used to construct calibration curves for human milk determinations.
Experience with depot forms of hormonal preparations suggests that severe adverse reactions are infrequent and immediate hypersensitivity reactions are rare. We report a case of recurrent anaphylaxis to a depot form of GnRH analogue requiring both acute and chronic management.
Picture Archive and Communication Systems (PACS), which allow the electronic acquisition, storage, transportation, and viewing of medical images, hold the eventual promise of reduced costs, improved image-management logistics, and ultimately, improved patient care. But at what point in the future will PACS really cost less than film-based image management for a given hospital size; and how are these costs affected by the choice of the digital communication network? To address these questions, a static differential cost model has been constructed. PAC systems based on two high-speed networks (less than 150 megabytes per second Mbps) and two low-speed networks, as well as film, were considered for five different sized hospitals (ranging from 15,000 to 125,000 procedures per year) and two time periods (1995 and 2000). PACS equipment was assumed to have a payoff of five years. The model considered all capital and supply costs and personnel costs for the PACS and for film storage and retrieval. It did not consider any possible cost savings from logistics improvement likely to result from the adoption of a PACS. Based on the assumptions outlined, high-speed-network PACS are less costly than those based on low-speed networks for all scenarios considered. Further, even though all possible PACS cost savings were not considered, high-speed network PACS appear to be less costly than film for hospitals larger than 60,000 procedures in 1995 and larger than 15,000 in 2000, while low-speed-network PACS should cost less than film for 60,000 and 30,000 procedure hospitals in 1995 and 2000 respectively.
This paper explores the methods that nursing has used to introduce new practice to the clinical environment. The implementation of the nursing process will provide an example of how nursing has attempted to change practice in totality and why the methods used perhaps undermined the original objectives. The use of 'change-agents' and action research to effect change in the ward environment will then be discussed. Particular attention will be paid to the idea of an 'energy crisis'--which may be an inevitable side effect of the change process--and how the programme of development at Ladywell Hospital has taken account of, and acted upon, this problem.
One of the body's natural defense mechanisms against tumor cells is lysis of the invading cell by cytotoxic T-cells and natural killer (NK) cells. Five human hepatocellular carcinoma cell lines were found to have different sensitivities to killing by peripheral blood monocytes in a 51Cr release assay. This killing was demonstrated to be due to NK cell lysis. Electrical recording measurements of the membrane potentials of these five cell lines showed different values for each line, all below values reported for normal hepatocytes. Correlation between mean cell membrane potential, and sensitivity to NK lysis, revealed an inverse relationship. In this study we demonstrate that the lower the mean membrane potential of a human hepatocellular carcinoma cell line, the more sensitive it is to NK cell cytolysis. Cell surface positive potential did not correlate with NK cytolysis and only a weak correlation was found between cell membrane negative potential and cell surface positive potential between cell lines.
A previous retrospective study showed an increased frequency of neonatal hyperbilirubinemia at high altitude in Colorado. In a prospective study we found that 39% of newborns at 3100 m altitude vs 16% at 1600 m exhibited hyperbilirubinemia, defined as a day 3 serum bilirubin level of 205 mumol/L or higher. Increased bilirubin production at 3100 m vs 1600 m was shown by increased levels of corrected carboxyhemoglobin. This finding was supported by increased erythropoietin and bilirubin values in cord blood and increased hematocrit values at day 3 among infants at 3100 m vs 1600 m. The sustained elevation in bilirubin for breast-fed vs formula-fed infants at 1600 m was observed for both feeding types at 3100 m. The findings suggested that there is a hematologic response to decreased oxygen availability at high altitude, resulting in increased bilirubin production accompanied by delayed bilirubin clearance.
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In an attempt to resolve conflicting evidence from the literature concerning the existence of a paternal age effect in 46,X,i(Xq) Turner's syndrome, we have analysed data on all known cases ascertained in the main population centres of Scotland and on others ascertained in England, using population controls matched for year of birth. There was a significant (P = 0.02) increase of 2.3 years in the mean paternal age of the Scottish cases, and a smaller and non-significant increase in their mean maternal age. Logistic regression analysis confirmed that the primary association was with paternal, rather than maternal, age. For the English cases, however, there were small and non-significant decreases in their mean maternal and paternal ages. The differences between the two groups were also significant, but cannot be explained by any likely source of ascertainment bias. We therefore conclude that there is no evidence for a universal paternal age effect in this condition, but that at least one mechanism of origin, occurring with variable frequency, may be associated with increased paternal age. Using data from this and earlier published studies, we estimate the incidence of individuals with a 46,X,i(Xq) cell line to be between 3.3 and 13 per 10(5) female livebirths.
On those maternity wards where "rooming in" is not practiced, infants are fed according to fixed schedules. The purpose of this study was to investigate possible differences between two common feeding regimens, three-hourly vs. four-hourly feeds during the first 3 days of life. A group of 152 singleton, full-term infants with birth weights 2,500-2,990 g, born at Bikur Cholim Hospital in Jerusalem from February 1988, to August 1988, were randomly assigned to one of two breast-feeding groups and followed prospectively. The study group (62 infants) was breast-fed every 4 hours, and the control group (90 infants) every 3 hours. The two groups were statistically similar for mean maternal age, parity, ethnic origin, social class, neonatal Apgar scores, birth percentile, and mean birth weights. Infants who breast-fed every 4 hours did not have greater transitional weight loss or higher serum bilirubin levels compared to infants fed at 3 hour intervals.
A randomized parallel design has been validated for the study of tamoxifen bioavailability. Strong evidence was presented for the bioequivalence of Tamoplex 10 mg and four Nolvadex 10 mg preparations. Interbatch differences were of the same magnitude as differences between Tamoplex 10 mg and Nolvadex 10 mg. No in vitro--in vivo relationship could be established. Distribution and metabolism are the dominating factors in tamoxifen pharmacokinetics.
The bioavailability of two tamoxifen preparations (Tamoplex and Nolvadex) was compared in a multiple dose two-way cross-over design in twelve breast cancer patients. The formulations were found to be bioequivalent. Mean steady-state serum levels of tamoxifen and N-desmethyltamoxifen were 133 ng/ml and 242 ng/ml, respectively, at a single daily dose of three tablets of Tamoplex 10 mg and 128 ng/ml and 248 ng/ml, respectively, at a single daily dose of three tablets of Nolvadex 10 mg. While there was a large interpatient as well as intrapatient variability in steady-state levels of tamoxifen and N-desmethyltamoxifen, their ratio appeared to be constant in the individual patient.
We describe a case of neonatal infarction involving both upper extremities. Oligohydramnios, resulting in compression of both arms within the uterus, is proposed as the cause of this congenital gangrene. Despite attempted conservative management, both arms became flaccid and moist. By the third day of life, the infant's worsening cardiovascular status necessitated amputation. This rare disorder has varying degrees of presentation. Limbs have been salvaged with conservative management of the extremity, coupled with appropriate surgical intervention, and neonatal intensive care.
Tamoxifen and N-desmethyltamoxifen plasma concentrations were determined in a single dose cross-over study with Tamoplex and Nolvadex at the dose height of 40 mg in 18 healthy male volunteers with a wash-out period of at least 140 days. ANOVA, power analysis and novel bioequivalence tests on AUC, Cmax and tcmax, including a non-parametric one, demonstrated bioequivalence of Tamoplex and Nolvadex 10 mg tablets. The mean AUC ( +/- SD) values of tamoxifen after administration of Tamoplex or Nolvadex tablets were 1076 +/- 265 and 1131 +/- 301 h ng ml-1, respectively. ANOVA on the AUC values gave a p value of 0.450 with a power of 0.85 and a 95% confidence interval of 81.8-108.5% was obtained. The 0.8 power test showed a determined difference of 18.9%, whereas the actual difference was 4.9%. Interindividual and intraindividual variation was assessed. The pharmacokinetic data, well established for 34 hr, constitute a basis for further studies on tamoxifen distribution, elimination and metabolism.
UNLABELLED: To assess the validity of skinfold thickness estimates of body fatness in formerly morbid obese adults, 23 patients (17 women, 6 men) who had completed a protein-sparing modified fast were studied. Mean +/- SD weight loss was 60.7 +/- 20.6 kg for men and 42.6 +/- 11.5 kg for women. Body density and percent body fatness were determined after weight loss according to four commonly used skinfold equations: Pollock (P); Durnin-Rahaman (D-R); Durnin-Womersley (D-W); and, Jackson-Pollock (J-P). The validity of these measurements was assessed by hydrostatic weighing, which revealed a percent body fatness of 20.4 +/- 6.5 for men and 29.8 +/- 8.4 for women. The mean difference and total error (square root of the mean of squared deviations) between skinfold predicted and hydrostatically-determined percent body fatness for each skinfold equation were: P, 2.0 and 4.9; D-R, 4.2 and 6.6; D-W, 7.1 and 8.4; and, J-P, 0.7 and 4.4. With the exception of the latter equation, all significantly overestimated (p less than 0.01) hydrostatically-determined percent body fatness. CONCLUSION: Select skinfold equations may result in a marked overestimation of body fatness in formerly obese patients.