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Biomedical subjects

K Shaw

Publications and source records attributed to K Shaw.

At least 37 records · Page 2Linked to original sources

Effect of ethnicity on denial of authorization for emergency department care by managed care gatekeepers.

OBJECTIVE: After a pilot study suggested that African American patients enrolled in managed care organizations (MCOs) were more likely than whites to be denied authorization for emergency department (ED) care through gatekeeping, the authors sought to determine the association between ethnicity and denial of authorization in a second, larger study at another hospital. METHODS: A retrospective cohort design was used, with adjustment for triage score, age, gender, day and time of arrival at the ED, and type of MCO. RESULTS: African Americans were more likely to be denied authorization for ED visits by the gatekeepers representing their MCOs even after adjusting for confounders, with an odds ratio of 1.52 (95% CI = 1.18 to 1.94). CONCLUSIONS: African Americans were more likely than whites to be denied authorization for ED visits. The observational study design raises the possibility that incomplete control of confounding contributed to or accounted for the association between ethnicity and gatekeeping decisions. Nevertheless, the questions that these findings raise about equity of gatekeeping indicate a need for additional research in this area.

Adolescent↗

cis-acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging.

The parts of the RNA genome of infectious bronchitis virus (IBV) required for replication and packaging of the RNA were investigated using deletion mutagenesis of a defective RNA (D-RNA) CD-61 (6.1 kb) containing a chloramphenicol acetyltransferase reporter gene. A D-RNA with the first 544, but not as few as 338, nucleotides (nt) of the 5' terminus was replicated; the 5' untranslated region (UTR) comprises 528 nt. Region I of the 3' UTR, adjacent to the nucleocapsid protein gene, comprised 212 nt and could be removed without impairment of replication or packaging of D-RNAs. A D-RNA with the final 338 nt, including the 293 nt in the highly conserved region II of the 3' UTR, was replicated. Thus, the 5'-terminal 544 nt and 3'-terminal 338 nt contained the necessary signals for RNA replication. Phylogenetic analysis of 19 strains of IBV and 3 strains of turkey coronavirus predicted a conserved stem-loop structure at the 5' end of region II of the 3' UTR. Removal of the predicted stem-loop structure abolished replication of the D-RNAs. D-RNAs in which replicase gene 1b-derived sequences had been removed or replaced with all the downstream genes were replicated well but were rescued poorly, suggesting inefficient packaging. However, no specific part of the 1b gene was required for efficient packaging.

3' Untranslated Regions↗

HIV adolescents show improved immune function following massage therapy.

HIV+adolescents (M CD4=466 mm3) recruited from a large urban university hospital's outpatient clinic were randomly assigned to receive massage therapy (n=12) or progressive muscle relaxation (n=12) two-times per week for 12 weeks. To assess treatment effects, participants were assessed for depression, anxiety and immune changes before and after treatment the 12 weeks treatment period. Adolescents who received massage therapy versus those who experienced relaxation therapy reported feeling less anxious and they were less depressed, and showed enhanced immune function by the end of the 12 week study. Immune changes included increased Natural Killer cell number (CD56) and CD56+CD3-. In addition, the HIV disease progression markers CD4/CD8 ratio and CD4 number showed an increase for the massage therapy group only.

Adolescent↗

Effects of educational and psychosocial interventions for adolescents with diabetes mellitus: a systematic review.

BACKGROUND: Insulin-dependent diabetes mellitus, also known as type 1 diabetes, is a life-threatening condition and is the third most common chronic illness among young people. As a result of minimal or non-existent insulin production, people with diabetes must take over the normally automatic task of regulation of blood glucose levels. This is achieved by a complex regimen involving multiple, daily administrations of insulin coordinated with dietary intake and energy expenditure and monitored by blood glucose testing. OBJECTIVES: To examine the effectiveness of educational and psychosocial interventions for adolescents with type 1 diabetes designed to improve their diabetes management. Specifically, it addressed the following research questions: (1) Do educational and psychosocial interventions for adolescents with type 1 diabetes have beneficial effects on biological and psychosocial outcomes? (2) Are there types or features of interventions that have been shown to be more effective than others? (3) What evidence is there of the cost-effectiveness of interventions? METHODS: A search strategy was formulated, piloted and refined. Three journals were handsearched, 11 electronic databases were searched and personal contacts, flyers, conferences and websites were used to notify the research community of the review to access further literature. This process generated 10,535 abstracts, which, after screening, resulted in 367 articles identified for retrieval. This number was augmented by hand-searching, personal contact and exploding references, and a final total of 457 articles were scrutinised. Of these, 64 reports describing 62 studies were identified as empirical papers evaluating educational or psychosocial interventions. The relevant data were extracted from the papers and summary tables for each study were prepared. Where possible, effect sizes were computed for outcomes from studies that included a randomised control group (CG) and other relevant information. RESULTS: A descriptive analysis of the 62 studies was undertaken. Most studies (67.7%) were conducted in the USA and 41% were randomised controlled trials (RCTs), none of which were UK-based. Only 48% of the reports provided an explicit theoretical rationale for the intervention. The mean number of participants was 53.8. The studies took place in various settings, evaluated a variety of interventions, involved various interventionists, addressed various components and assessed the effects by a range of outcomes, including measures of metabolic control and psychological and behavioural outcomes. Follow-up assessments were relatively rare. RESULTS - THE EFFECTIVENESS OF INTERVENTIONS: The 25 RCTs were examined in more detail and three of the most effective were described in depth. Effect sizes could be calculated for 14 studies. The mean (pooled) effect size for psychosocial outcomes was 0.37 and 0.33 for glycated haemoglobin with outliers (0.08 without outliers), indicating that these interventions have small to medium beneficial effects on diabetes management outcomes. A narrative review of the 21 pre-post studies with no CG was performed, including evaluations of interventions conducted at summer camps, interventions for poorly controlled patients and educational interventions. All studies reported beneficial effects. RESULTS - COST-EFFECTIVENESS: Few studies addressed economic considerations associated with interventions, and the lack of information on costs and the diversity of outcomes included by investigators impeded cost- effectiveness comparisons. Shorter hospitalisation at diagnosis is at least as effective in achieving control and avoiding complications in adolescence as longer stays. Home care may result in improved outcomes but may not be cheaper than hospital care at diagnosis. Targeting poorly controlled subjects may reduce adverse events and hospitalisations and may be more cost-effective than generic interventions. There is a need for rigorous cost-effectiveness studies of educational and psychosocial interventions for adolescents with type 1 diabetes that include longer-term considerations. CONCLUSIONS: The following conclusions were drawn from this review: (1) Educational and psychosocial interventions have small to medium beneficial effects on various diabetes management outcomes. (2) Well-designed trials of such interventions are needed in the UK (no completed RCTs of educational or psychosocial interventions for adolescents with type 1 diabetes conducted in the UK were found). (3) The evidence, arising primarily from studies in the USA, provides a starting point for the design of interventions in the UK. (4) Quantitative and narrative analysis of the evidence suggested that interventions are more likely to be effective if they demonstrate the inter-relatedness of the various aspects of diabetes management. (ABSTRACT TRUNCATED)

Adolescent↗

Managed care purchasing under SCHIP: a nationwide analysis of freestanding SCHIP contracts.

This Policy Brief is the third in a series that examines the State Children's Health Insurance Program (SCHIP), in particular, those state programs that operate directly under the authority of Title XXI of the Social Security Act rather than as an expansion of Medicaid (or a Medicaid demonstration initiative). This series is designed to examine how states structure and administer insurance programs for low-income children when they elect to administer separate SCHIP plans that exist outside of the requirements and constraints of Medicaid. Understanding how states use their flexibility under "separate SCHIP programs" (as they are termed) has become an increasingly important policy question, in the face of heightened interest on the part of Governors, the Bush Administration, and others in comprehensive Medicaid reform. The first two policy briefs in this series analyzed the entitlement status of separately administered SCHIP programs, as well as issues related to coverage design and the definition of medical necessity. This Policy Brief provides the first nationwide overview of how separate SCHIP programs structure "freestanding" SCHIP managed care contracts, i.e., contracts that exist independently of a state's Medicaid managed care agreements. Fifteen such "freestanding" contracts existed as of Calendar Year 2000, and we report here on their general terms of coverage, access, and care coordination. A forthcoming related study will examine behavioral health care in freestanding SCHIP agreements. Following a brief background and discussion of research methods, we present our principal findings and discuss their implications.

Child↗

Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1.

The CC chemokine receptor-1 (CCR1) is a prime therapeutic target for treating autoimmune diseases. Through high capacity screening followed by chemical optimization, we identified a novel non-peptide CCR1 antagonist, R-N-[5-chloro-2-[2-[4-[(4-fluorophenyl)methyl]-2-methyl-1-piperazinyl ]-2-oxoethoxy]phenyl]urea hydrochloric acid salt (BX 471). Competition binding studies revealed that BX 471 was able to displace the CCR1 ligands macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemotactic protein-3 (MCP-3) with high affinity (K(i) ranged from 1 nm to 5.5 nm). BX 471 was a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression, and leukocyte migration. BX 471 demonstrated a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors. Pharmacokinetic studies demonstrated that BX 471 was orally active with a bioavailability of 60% in dogs. Furthermore, BX 471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis. This study is the first to demonstrate that a non-peptide chemokine receptor antagonist is efficacious in an animal model of an autoimmune disease. In summary, we have identified a potent, selective, and orally available CCR1 antagonist that may be useful in the treatment of chronic inflammatory diseases.

Administration, Oral↗

Leader switching occurs during the rescue of defective RNAs by heterologous strains of the coronavirus infectious bronchitis virus.

A defective RNA (D-RNA), CD-61, derived from the Beaudette strain of the avian coronavirus infectious bronchitis virus (IBV), was rescued (replicated and packaged) using four heterologous strains of IBV as helper virus. Sequence analysis of the genomic RNA from the four heterologous IBV strains (M41, H120, HV10 and D207) identified nucleotide differences of up to 17% within the leader sequence and up to 4.3% within the whole of the adjacent 5' untranslated region (UTR). Analysis of the 5' ends of the rescued D-RNAs showed that the Beaudette leader sequence, present on the initial CD-61, had been replaced with the corresponding leader sequence from the helper IBV strain but the adjacent 5' UTR sequence of the rescued D-RNAs corresponded to the original CD-61 Beaudette sequence. These results demonstrated that the phenomenon of leader switching previously identified for the coronaviruses murine hepatitis virus and bovine coronavirus (BCoV) also occurred during the replication of IBV D-RNAs. Three predicted stem-loop structures were identified within the 5' UTR of IBV. Stem-loop I showed a high degree of covariance amongst the IBV strains providing phylogenetic evidence that this structure exists and is potentially involved in replication, supporting previous observations that a BCoV stem-loop homologue was essential for replication of BCoV defective interfering RNAs.

5' Untranslated Regions↗

Expression of reporter genes from the defective RNA CD-61 of the coronavirus infectious bronchitis virus.

The defective RNA (D-RNA) CD-61, derived from the Beaudette strain of the avian coronavirus infectious bronchitis virus (IBV), was used as an RNA vector for the expression of two reporter genes, luciferase and chloramphenicol acetyltransferase (CAT). D-RNAs expressing the CAT gene were demonstrated to be capable of producing CAT protein in a helper-dependent expression system to about 1.6 microgram per 10(6) cells. The reporter genes were expressed from two different sites within the CD-61 sequence and expression was not affected by interruption of the CD-61-specific ORF. Expression of the reporter genes was under the control of a transcription-associated sequence (TAS) derived from the Beaudette gene 5, normally used for the transcription of IBV subgenomic mRNA 5. The Beaudette gene 5 TAS is composed of two tandem repeats of the IBV canonical consensus sequence involved in the acquisition of a leader sequence during the discontinuous transcription of IBV subgenomic mRNAs. It is demonstrated that only one canonical sequence is required for expression of mRNA 5 or for the expression of an mRNA from a D-RNA and that either sequence can function as an acceptor site for acquisition of the leader sequence.

Animals↗

Patient education. Behaviour management strategies in ADHD.

Attention deficit hyperactivity disorder or ADHD is a condition characterised by inattention, hyperactivity and impulsiveness. It is often managed by a combination of medication and behaviour modification techniques. This sheet outlines some useful strategies parents and teachers may undertake.

Attention Deficit Disorder with Hyperactivity↗

Are stimulants addictive in children? What the evidence says.

BACKGROUND: Prescription stimulants are widely used to treat attention deficit hyperactivity disorder in clinical practice. OBJECTIVE: A systematic review of the literature was performed to assess available evidence regarding the propensity for abuse and addiction liability of these medications. METHOD: Trials were searched in computerised general databases (Medline, Psychlit and Embase) and specialised (Cochrane Controlled Trials Register, Cochrane Collaboration); by checking reference lists of relevant articles; by handsearching relevant specialist journals; and by contacting relevant authors where appropriate. Publications in all languages were sought. Studies had to have sufficient description of study methodology and statistical analysis to permit critical evaluation. Randomised controlled clinical trials, crossover studies, cohort studies and case control studies were included. Human studies only were considered for inclusion. RESULTS: Sixty-eight trials were located using the specified search strategy. Of these, fifteen trials met inclusion criteria: five randomised controlled trials; nine crossover studies and one cohort study. The propensity for abuse of prescription stimulants was demonstrated by analysis of drug self administration, discriminatory ability and comparison studies. Insufficient evidence was available regarding the addiction liability of stimulants. DISCUSSION: Prescription stimulants have the propensity for abuse. There is insufficient evidence available to assess their addictive potential.

Central Nervous System Stimulants↗

Comparative studies of Nsc and Fmoc as N(alpha)-protecting groups for SPPS.

2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) is an alternative base-labile N(alpha)-protecting group to 9-fluorenylmethoxycarbonyl (Fmoc) for amino acids. The UV spectrum of the Nsc group exhibits moderate absorption at 380 nm which is excellent for real-time monitoring of the deprotection process. It also decreases the rearrangement of X-Asp, which can be a serious problem in SPPS.

Amino Acids↗

Revisiting the role of routine retropleural drainage after repair of esophageal atresia with distal tracheoesophageal fistula.

PURPOSE: The aim of this study was to review routine retropleural drainage in esophageal atresia with distal tracheoesophageal fistula (TEF). METHODS: The charts of 52 patients diagnosed with TEF between 1987 and 1997 were reviewed. Data collected included gestational age, birth weight, associated congenital anomalies, respiratory status, operative technique and timing, size of gap, tension on the anastomosis, complications related to the drain, and esophageal anastomotic leak (incidence, diagnosis, and treatment). RESULTS: A total of 52 cases of TEF were identified. Data on sex, gestation age, birth weights, and malformations are summarized. Forty-seven patients underwent a single-stage extrapleural repair. Only one leak was identified in the single-stage group on routine day 7 esophagogram: a Waterson C patient who was clinically well with minimal drainage. The only other leak was in a class C patient who had undergone a staged repair because of an initial long gap. None of the favorable Waterston class patients suffered a leak. CONCLUSIONS: A routine retropleural drain placed near the anastomosis may not be necessary in all cases of TEF. Good prognosis patients (Waterston class A and B) who undergo an uncomplicated extrapleural repair without undue tension do not appear to benefit from having a chest drain in place, and there is potential for complications. In complicated cases, however, retropleural drainage remains a reasonable adjunct.

Anastomosis, Surgical↗

Prenatal percutaneous needle drainage of cystic sacrococcygeal teratomas.

Prenatal ultrasound (US) permits in utero diagnosis of sacrococcygeal teratoma (SCT), follow-up of tumor size, and the early identification of complications, allowing for a more timely and appropriate delivery. The recommended management of large SCTs is delivery by cesarean section (CS) to prevent dystocia, tumor rupture, hemorrhage, and death. However, even delivery by CS can be difficult, necessitating a large hysterotomy that adds to maternal morbidity. The authors report two cases of cystic SCTs in which prenatal percutaneous drainage allowed for an uncomplicated vaginal delivery. In the first case, a large unilocular cystic SCT was diagnosed at 31 weeks' gestation on prenatal US. The fetal presentation was breech, and the mass was steadily increasing in size, preventing spontaneous version. At 37 5/7 weeks, the cyst was percutaneously drained under US guidance allowing for successful external version. Repeat drainage just before induction of labor permitted a successful vaginal delivery. In the second case, the cystic SCT was percutaneously drained just before induction of labor at full term, again allowing for an uncomplicated vaginal delivery. Prenatal percutaneous needle drainage of cystic SCTs offers an alternative to CS that results in decreased risks for both mother and fetus.

Adult↗

25 years' experience with lymphangiomas in children.

BACKGROUND/PURPOSE: The management of lymphangioma in children is challenging because complete resection is difficult to achieve in some cases, and recurrences are common. The authors reviewed their experience to assess the risk factors for recurrence and the role of nonoperative treatment. METHODS: A retrospective study over a period of 25 years was carried out. One hundred eighty-six patients with 191 lesions (five patients with de novo lesions in different sites) were treated. There were 98 boys and 88 girls. The average age at diagnosis was 3.3 years (range, fetal life to 17 years) and the average size 8 cm in diameter. Histocytological confirmation was obtained in all patients. The involved sites were head and neck, 89 patients (48%); trunk and extremities, 78 patients (42%); internal or visceral locations (eg, abdominal and thorax), 19 patients (10%). The treatment consisted of macroscopically complete excision in 145 patients (150 lesions, of which five were recurrences in different sites), partial excision in 10 patients, aspiration in five patients, laser excision in 10 patients, biopsy only in four patients, drainage and biopsy in two patients, and injection of sclerosing agents in 10 patients. RESULTS: There were 54 recurrences; 44 underwent excision (five of them more than once), and five regressed spontaneously on follow-up. Five other recurrences were stable and not progressing. Recurrences, (defined as clinically obvious disease), were found to be 100% after aspiration, 100% after injection, 40% after incomplete excision, 40% after laser excision, and 17% after macroscopically complete excision. The recurrence rate in the last group was the highest in the head (33%), the least in the internal locations (0%), and intermediate for the cervical location (13%). There were no significant differences, in terms of outcome, between those who had their surgery immediately at the time of diagnosis (n = 101) and those who had delayed surgery (n = 85). CONCLUSIONS: There were fewer recurrences after macroscopically complete excision. Aspiration and injection had the highest recurrence rate. Risk factors for recurrence included location, size, and complexity of lesions. A period of observation may be useful for infants to facilitate complete excision. In the present series, spontaneous regression was infrequent and was seen more often with recurrent lesions.

Abdominal Neoplasms↗

Complex post-transcriptional regulation of EGF-receptor expression by EGF and TGF-alpha in human prostate cancer cells.

The epidermal growth factor receptor (EGFR) plays an important role in the development and progression of prostate cancer and its overexpression is associated with decreased survival. With progression, prostate cancer cells switch from epidermal growth factor (EGF) to transforming growth factor alpha (TGF-alpha) synthesis, which contributes to autocrine growth and unrestrained proliferation. To define the molecular mechanisms involved in the regulation of EGFR expression by EGF and TGF-alpha we studied three human prostate cancer cell lines, androgen-responsive (LNCaP) and -unresponsive (DU145 and PC3). Here we show that TGF-alpha stabilized EGFR mRNA two- to threefold in all three cell lines, whilst EGF stabilized EGFR mRNA approximately twofold in LNCaP and DU145 cells, but not in PC3 cells. Both ligands increased EGFR transcription in LNCaP and DU145 cells, with less effect in PC3 cells. In all three cell lines EGF reduced total EGFR protein levels more than TGF-alpha, but this was associated with a greater increase in de novo protein synthesis with EGF compared to TGF-alpha. Only EGF, however, shortened EGFR protein stability (half-life decreased from 5 h to 120 min), resulting in rapid disappearance of newly synthesized EGFR protein. Both ligands increased total LNCaP and DU145 cell numbers. These studies demonstrate that the EGF- and TGF-alpha-induced upregulation of EGFR mRNA and protein in human prostate cancer cell lines is complex and occurs at multiple, transcriptional and post-transcriptional levels. Taken together, these data provide novel insight into the molecular mechanisms by which TGF-alpha would preferentially maintain an autocrine loop in human prostate cancer cells. Furthermore, this work suggests that in human prostate cancer cells ligand-specific differential intracellular trafficking of the EGFR plays a major role in regulating its expression.

Androgens↗

Treatment adherence in juvenile rheumatoid arthritis--a review.

Adherence to long-term complex treatment in children with Juvenile Rheumatoid Arthritis (JRA) is a major problem. This article reviews psychosocial factors that compromise treatment adherence and discusses ways to improve long-term adherence. Child-centred information, therapy management, behaviour modification, and parental monitoring are described as adherence facilitating strategies for clinical and non-clinical settings. Finally, the implications for further practice and research are discussed.

Adolescent↗

An endoplasmic reticulum retrieval signal partitions human foamy virus maturation to intracytoplasmic membranes.

Among all retroviruses, foamy viruses (FVs) are unique in that they regularly mature at intracytoplasmic membranes. The envelope glycoprotein of FV encodes an endoplasmic reticulum (ER) retrieval signal, the dilysine motif (KKXX), that functions to localize the human FV (HFV) glycoprotein to the ER. This study analyzed the function of the dilysine motif in the context of infectious molecular clones of HFV that encoded mutations in the dilysine motif. Electron microscopy (EM) demonstrated virion budding both intracytoplasmically and at the plasma membrane for the wild-type and mutant viruses. Additionally, mutant viruses retained their infectivity, but viruses lacking the dilysine signal budded at the plasma membrane to a greater extent than did wild-type viruses. Interestingly, this relative increase in budding across the plasma membrane did not increase the overall release of viral particles into cell culture media as measured by protein levels in viral pellets or infectious virus titers. We conclude that the dilysine motif of HFV imposes a partial restriction on the site of viral maturation but is not necessary for viral infectivity.

Animals↗