NP perspectives on an American tragedy.
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Adolescent↗
Biomedical subjects
L Pearson
Publications and source records attributed to L Pearson.
Stress-less: a modern fable.
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Adaptation, Psychological↗
Pramlintide, a synthetic analog of human amylin, improves the metabolic profile of patients with type 2 diabetes using insulin. The Pramlintide in Type 2 Diabetes Group.
OBJECTIVE: To examine the effects of 4 weeks of subcutaneous administration of pramlintide, a synthetic analog of human amylin, on metabolic control in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS: Serum fructosamine, HbA1c, and fasting plasma lipids were measured in 203 patients in a randomized double-blind placebo-controlled parallel-group multicenter trial using doses of 30 micrograms q.i.d., 60 micrograms t.i.d., and 60 micrograms q.i.d. RESULTS: Statistically significant reductions in serum fructosamine concentrations were observed in the pramlintide 30 micrograms q.i.d. group (17.5 +/- 4.9 mumol/l, P = 0.029), the pramlintide 60 micrograms t.i.d. group (24.1 +/- 4.9 mumol/l, P = 0.003), and the 60 micrograms q.i.d. group (22.6 +/- 4.1 mumol/l, P = 0.001) compared with the placebo group (3.5 +/- 3.8 mumol/l). There were also statistically significant shifts in the proportion of patients with an abnormal serum fructosamine concentration at baseline that normalized at week 4 within the pramlintide 60 micrograms t.i.d. group and the 60 micrograms q.i.d. group. Consistent with the fructosamine results, there were statistically significant reductions in HbA1c in the pramlintide 30 micrograms q.i.d. group (0.53 +/- 0.07%, P = 0.0447), the pramlintide 60 micrograms t.i.d. group (0.58 +/- 0.07%, P < 0.0217), and the pramlintide 60 micrograms q.i.d. group (0.51 +/- 0.08%, P = 0.0242) compared with the placebo group (0.27 +/- 0.08%). Total cholesterol concentrations were also statistically significantly reduced in both the pramlintide 60 micrograms t.i.d. group (8.4 mg/dl, P < 0.01) and 60 micrograms q.i.d. group (10.5 mg/dl, P < 0.01) compared with placebo (1.2 mg/dl). Body weight decreased in both of the pramlintide 60 micrograms groups, but the trend did not achieve statistical significance. The incidence of hypoglycemia was similar in all treatment groups. CONCLUSIONS: Reductions in serum fructosamine, plasma total and LDL cholesterol concentrations, and HbA1c support the hypothesis that pramlintide may improve metabolic control in patients with type 2 diabetes using insulin.
Adult↗
Alternative therapy: a cautionary tale.
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Brain Neoplasms↗
Effects of 4 weeks' administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations.
The effects of 4 weeks' administration of pramlintide, an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 microg four times per day (breakfast, lunch, dinner, and evening snack), 30 microg three times per day (breakfast, lunch and dinner [BLD]), 30 microg three times per day (breakfast, dinner and evening snack [BDS]), and 60 microg twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 microg four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (-1.4 +/- 0.5 vs 0.3 +/- 0.5 micromol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 +/- 10 micromol/l in the pramlintide 30 mg four times per day group, 43 +/- 7 micromol/l in the pramlintide 30 microg three times per day (BLD) group, 47 +/- 6 micromol/l in the pramlintide 30 microg three times per day (BDS) group, 46 +/- 7 micromol/l in the pramlintide 60 microg twice per day group, and 29 +/- 8 micromol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA1c as the measurement of glycaemic control are warranted.
Adolescent↗
Predictive assessment of vocal efficiency (PAVE). A method for voice therapy outcome measurement.
A prospective study was carried out to examine the degree to which a standard voice assessment could discriminate between the potential benefits of two different voice therapy programmes for individual patients. The study encompassed 200 dysphonia subjects who were referred for voice therapy and had completed treatment within a prescribed two-year period. A standard assessment procedure was carried out on first attendance for each patient and guidelines were used to assign patients to different treatment programmes on the basis of the assessment results. The assessment discriminated well between patients requiring voice therapy to change physiological parameters of voice usage and patients able to self adjust voice usage, and provided an objective means of measuring outcomes.
Humans↗
Validation of the heat treatment step used in the production of diaspirin crosslinked hemoglobin (DCLHb) for viral inactivation--effect of crosslinking.
Two experiments were performed to assess viral inactivation during the crosslinking and heat treatment steps of the DCLHb manufacturing process. Stroma free hemoglobin (SFHb) collected from a large scale manufacturing lot was tested in a 1:680 scaled down system in which the key parameters used in the manufacturing process were replicated. In the first study Porcine Parvovirus (PPV), a non-enveloped virus, was used to assess inactivation, while in the second study Bovine Viral Diarrhea Virus (BVDV), an enveloped virus, was utilized. In both experiments, the SFHb solution was deoxygenated and an aliquot of virus suspension was added. To initiate the crosslinking reaction, a solution of bis (3,5-dibromosalicyl) fumarate (DBBF) in HEPES buffer was added to the test solution. In both experiments the reaction times and the degree of crosslinking were normal. After crosslinking, the reaction mixtures were heated to 74 +/- 1 degrees C over 30 minutes, held at 74 +/- 1 degrees C for 90 minutes, and cooled to less than 10 degrees C over 30 minutes. In each experiment the degree of crosslinking of final product was 100% and yield of hemoglobin recovery was normal. Samples were removed prior to crosslinking, after crosslinking and before, during and after heat treatment for determination of virus titer and evaluation of key process parameters. The results from these experiments were consistent with those obtained from the full scale manufacturing process for the deoxygenation, crosslinking and the heat treatment step during the production of DCLHb. The results of virus assays showed that crosslinking has no effect on viruses and their subsequent inactivation by heat treatment.
Animals↗
Proximal promoter elements of the human zeta-globin gene confer embryonic-specific expression on a linked reporter gene in transgenic mice.
We have investigated the transcriptional regulation of the human embryonic zeta-globin gene promoter. First, we examined the effect that deletion of sequences 5' to zeta-globin's CCAAT box have on zeta-promoter activity in erythroid cell lines. Deletions of sequences between -116 and -556 (cap = 0) had little effect while further deletion to -84 reduced zeta-promoter activity by only 2-3-fold in both transiently and stably transfected erythroid cells. Constructs containing 67, 84 and 556 bp of zeta-globin 5' flanking region linked to a beta-galactosidase reporter gene (lacZ) and hypersensitive site -40 (HS-40) of the human alpha-globin gene cluster were then employed for the generation of transgenic mice. LacZ expression from all constructs, including a 67 bp zeta-globin promoter, was erythroid-specific and most active between 8.5 and 10.5 days post-fertilisation. By 16.5 days gestation, lacZ expression dropped 40-100-fold. These results suggest that embryonic-specific activation of the human zeta-globin promoter is conferred by a 67 bp zeta-promoter fragment containing only a CCAAT and TATA box.
Animals↗
Engineering of DNA binding proteins into site-specific cutters: reactivity of Trp repressor-1,10-phenanthroline chimeras.
Trp repressor (TrpR) can be converted into a site-specific nuclease by chemical modification of the cysteine mutants TrpR D46C or TrpR E49C with 5-iodoacetamido-1,10-phenanthroline (OP). In the presence of cupric ion and 3-mercaptopropionic acid, TrpR-regulated operators are cleaved. The properties of these semisynthetic scission reagents have been compared. The E49C construct cleaves efficiently at two sites within the operator and the D46C cleaves at multiple sites. Molecular modeling indicates that the reason for the focused reactivity of E49C is that the OP is rigidly oriented in the protein-DNA complexes whereas the OP can adopt several orientations in TrpR D46C. Mutations and reaction conditions that increase the affinity of the repressor enhance the scission efficiency which approaches 100% within the acrylamide matrix. TrpR E49C-OP smoothly cleaves the trpEDCBA operator in a plasmid in a reaction dependent on the corepressor L-tryptophan. In the absence of tryptophan, non-specific cleavage of the plasmid is observed under the same conditions. Therefore, tryptophan not only directs cleavage to a specific site but also blocks it at non-specific sites. The analysis of the cleavage pattern of the trpEDCBA operator provides strong evidence for the tandem binding model in which protein-protein interactions stabilize binding on the DNA. TrpR E49C-OP should serve as the basis for the engineering of a family of highly specific semisynthetic scission reagents.
Bacterial Proteins↗
Mode of action of a lysostaphin-like bacteriolytic agent produced by Streptococcus zooepidemicus 4881.
Electron microscopy of zoocin A-treated sensitive streptococcus cells revealed cytoplasmic disruption and ultimately complete rupture of the cell wall. Culture viability and optical density were shown to decrease rapidly and simultaneously in Streptococcus pyogenes FF22 but less quickly in the relatively more resistant Streptococcus mutans 10449. Zoocin A was shown to cleave hexaglycine in a colorimetric cell-free microtiter assay system, and it is concluded that the killing action of zoocin A, like that of lysostaphin, is most probably the result of direct cleavage of the peptidoglycan cross-links in the cell wall. The relationship between sensitivity to zoocin A and the peptidoglycan cross-linkage structure of Streptococcus zooepidemicus, Lactococcus spp., S. pyogenes, Streptococcus gordonii, Streptococcus oralis, S. mutans, and Streptococcus rattus has been evaluated.
Anti-Bacterial Agents↗
Multidrug resistance-1 (MDR1) expression and functional dye/drug efflux is highly correlated with the t(8;21) chromosomal translocation in pediatric acute myeloid leukemia.
Resistance to chemotherapy is a major problem in acute myeloid leukemia (AML). An important resistance mechanism in adult AML is active drug efflux mediated by the multidrug resistance protein-1 (MDR1). To determine if MDR1 is important in childhood AML, we examined MDR1 expression and functional dye/drug efflux in 20 pediatric/adolescent AML patients; results were correlated with cytogenetics and clinical outcome. Using flow cytometry, MDR1 protein expression on the leukemic blasts was measured with the antibody MRK16, while efflux was measured by extrusion of the fluorescent dye DiO(C2)3 in the presence/absence of cyclosporin A (CsA). Six of 20 cases expressed MDR1. While all six MDR1+ cases were efflux+, three of 14 MDR1- cases also demonstrated efflux. Both MDR1 and efflux were strongly correlated with the t(8;21). All six MDR1 +/efflux+ cases and 2/3 MDR1 -/efflux+ cases had a t(8;21), while no MDR1-/efflux- cases had a t(8;21) (P < 0.0005). This correlation between MDR1, efflux, and the t(8;21) in pediatric AML was not found in 11 adult t(8;21) cases similarly studied. Although the clinical relevance of MDR1 in pediatric AML awaits larger studies, our results suggest a biologic subset of pediatric AML patients may benefit from regimens which include MDR1-reversing agents or non-MDR1 substrates.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Nucleic acid chemistry of the cuprous complexes of 1,10-phenanthroline and derivatives.
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Base Sequence↗
Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.
The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1.
Animals↗
A rationale for mouth care: the integration of theory with practice.
Mouth care is a commonly performed nursing procedure in which the aim is to ensure that patients' mouths are cared for. However, there is evidence that unless dental plaque is removed from the tooth surfaces and the gingival margin, the mouth is in danger of becoming unhealthy and, therefore, uncared for. It appears from the dental literature that the use of a toothbrush is one of the best and most widely used tools in the Western world for removing dental plaque (Addy, Slayne & Wade 1992), other methods being ineffective, dangerous, or poorly researched (Trenter-Roth & Creason 1986). However, a review of the nursing literature indicates that toothbrushes are not the tools of choice for mouth care by nurses (Howarth 1977, Harris 1980). Thus, there appears to be a gulf between the knowledge base from the dental literature and the reality of nursing practice resulting in 'mouth care' becoming a misleading misnomer. The aim in this paper is to present a rationale for mouth care based upon the dental literature and to apply such knowledge to nursing practice, especially in intensive therapy units (ITUs), so that nurses may be in a better position to provide 'mouth care' which lives up to its name.
Clinical Nursing Research↗
Natural assemblages of marine bacteria exhibiting high-speed motility and large accelerations.
Natural communities of marine bacteria, an isolate (FMB-Bf3) from one marine community, and Escherichia coli were examined by video microscopy for the magnitude and uniformity of their speed. Natural communities formed tight microswarms that showed higher speeds (mean = 230 microns s-1) than did E. coli (15 microns s-1) or FMB-Bf3 (mean = 62 microns s-1). Outside the microswarms, the marine bacteria slowed to 45 microns s-1. Between turns, in mid run, and while travelling in straight lines, the natural-community bacteria accelerated up to 1,450 microns s-2 while the cultured bacteria showed maximum accelerations of 70 and 166 microns s-2. The frequency distribution of speed change for the marine bacteria was skewed towards a few large negative accelerations and a range of positive accelerations. The general pattern was one of relatively slow increases in speed followed by abrupt declines. The results indicate that the mechanical generation and energetic maintenance, as well as the environmental function, of bacterial motility need reappraisal. We conclude that the standard bacterial motility parameters of low and uniform speed, derived from culture-based studies, are not necessarily applicable to marine bacterial communities.
Escherichia coli↗
Report on the 1994 readership survey on NP experiences with malpractice issues.
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Costs and Cost Analysis↗
Inhibition of prokaryotic and eukaryotic transcription by the 2:1 2,9-dimethyl-1,10-phenanthroline-cuprous complex, a ligand specific for open complexes.
The redox-stable, tetrahedral cuprous chelate of neocuproine (2,9-dimethyl-1,10-phenanthroline) binds to the single-stranded DNA formed in open complexes and is an effective inhibitor of eukaryotic and prokaryotic transcription. Despite the many kinetic and structural differences between prokaryotic and eukaryotic transcription systems, they are all similarly inhibited by neocuproine copper, suggesting that all open complexes may share a homologous structure.
Base Sequence↗