[Quality assurance and maintenance of percutaneous nephrostomy drainage].
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Catheterization↗
Biomedical subjects
L Pedersen
Publications and source records attributed to L Pedersen.
Efficient gene transfer into primary human CD8+ T lymphocytes by MuLV-10A1 retrovirus pseudotype.
Efficient and stable gene transfer into primary human T lymphocytes would greatly improve their use for adoptive transfer to treat acquired disorders, viral diseases, and cancer. We have constructed retroviral vector pseudotypes of amphotropic murine leukemia viruses (A-MuLV, MuLV-10A1), gibbon ape leukemia virus (GaLV), and feline endogenous virus (RD114) containing the enhanced green fluorescent protein (GFP) as a marker gene. Transduction of primary human CD8+ T lymphocytes by the different GFP-retrovirus pseudotypes revealed the superiority of MuLV-10A1 in comparison with A-MuLV, GaLV, and RD114, respectively. The superior transduction efficacy of CD8+ T cells by MuLV-10A1 correlates with a longer half-life of this pseudotype in comparison with A-MuLV and, as shown by interference analysis with the human T cell line HUT78, by the utilization of both the A-MuLV receptor (Pit2) and the GaLV receptor (Pit1) for cell entry.
CD8-Positive T-Lymphocytes↗
Squalamine is not a proton ionophore.
Squalamine, an aminosterol antibiotic isolated from the dogfish shark, creates relatively large defects in phospholipid bilayers, allowing the unrestricted translocation of small molecules across these compromised membranes (B.S. Selinsky, Z. Zhou, K.G. Fotjik, S. R. Jones, N.R. Dollahon, A.E. Shinnar, Biochim. Biophys. Acta 1370 (1998) 218-234). However, an aminosterol structurally similar to squalamine was found to act as a proton ionophore in anionic phospholipid vesicles. In contrast with squalamine, gross membrane disruption was not observed with this synthetic analog (G. Deng, T. Dewa, S.L. Regen, J. Am. Chem. Soc. 118 (1996) 8975-8976). In this report, the ionophoric activity of squalamine was tested in anionic and zwitterionic phospholipid vesicles. No ionophoric activity was observed for squalamine in vesicles comprised of phosphatidylglycerol (PG), phosphatidylcholine (PC), or a mixture of the two lipids. Experiments using radiolabeled squalamine indicated that all of the squalamine added to PG vesicles remained with the vesicles, while approximately one-half of the squalamine added to PC vesicles was incorporated. We have synthesized the aminosterol analog of squalamine possessing ionophoric activity, and its ionophoric activity in PG vesicles was confirmed. The synthetic compound possessed no measurable lytic activity when added to preformed phospholipid vesicles. As both compounds possess significant antimicrobial activity, these results suggest that either multiple mechanisms for the antimicrobial activity of aminosterols exist, depending upon the aminosterol structure, or possibly an unrelated common mechanism for antimicrobial activity remains to be discovered.
Animals↗
Hyperemesis gravidarum and sex of child.
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Female↗
Target payments in primary care: effects on professional practice and health care outcomes.
BACKGROUND: The method by which physicians are paid may affect their professional practice. Although payment systems may be used to achieve policy objectives (e.g. improving quality of care, cost containment and recruitment to under-served areas), little is known about the effects of different payment systems in achieving these objectives. Target payments are a payment system which remunerate professionals only if they provide a minimum level of care. OBJECTIVES: To evaluate the impact of target payments on the professional practice of primary care physicians (PCPs) and health care outcomes. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register; the Cochrane Controlled Trials Register; MEDLINE (1966 to October 1997); BIDS EMBASE (1980 to October 1997); BIDS ISI (1981 to October 1997); EconLit (1969 to October 1997); HealthStar (1975 to October 1997) Helmis (1984 to October 1997); health economics discussion paper series of the Universities of York, Aberdeen, Sheffield, Bristol, Brunel, and McMaster; Swedish Institute of Health Economics; RAND corporation; and reference lists of articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series analyses of interventions comparing the impact of target payments to primary care professionals with alternative methods of payment, on patient outcomes, health services utilisation, health care costs, equity of care, and PCP satisfaction with working environment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Two studies were included involving 149 practices. The use of target payments in the remuneration of PCPs was associated with improvements in immunisation rates, but the increase was statistically significant in only one of the two studies. REVIEWER'S CONCLUSIONS: The evidence from the studies identified in this review is not of sufficient quality or power to obtain a clear answer to the question as to whether target payment remuneration provides a method of improving primary health care. Additional efforts should be directed in evaluating changes in physicians' remuneration systems. Although it would not be difficult to design a randomised controlled trial to evaluate the impact of such payment systems, it would be difficult politically to conduct such trials.
Humans↗
Capitation, salary, fee-for-service and mixed systems of payment: effects on the behaviour of primary care physicians.
BACKGROUND: It is widely believed that the method of payment of physicians may affect their clinical behaviour. Although payment systems may be used to achieve policy objectives (e.g. cost containment or improved quality of care), little is known about the effects of different payment systems in achieving these objectives. OBJECTIVES: To evaluate the impact of different methods of payment (capitation, salary, fee for service and mixed systems of payment) on the clinical behaviour of primary care physicians (PCPs). SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register; the Cochrane Controlled Trials Register; MEDLINE (1966 to October 1997); BIDS EMBASE (1980 to October 1997); BIDS ISI (1981 to October 1997); EconLit (1969 to October 1997); HealthStar (1975 to October 1997) Helmis (1984 to October 1997); health economics discussion paper series of the Universities of York, Aberdeen, Sheffield, Bristol, Brunel, and McMaster; Swedish Institute of Health Economics; RAND corporation; and reference lists of articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series analyses of interventions comparing the impact of capitation, salary, fee for service (FFS) and mixed systems of payment on primary care physician satisfaction with working environment; cost and quantity of care; type and pattern of care; equity of care; and patient health status and satisfaction. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Four studies were included involving 640 primary care physicians and more than 6400 patients. There was considerable variation in study setting and the range of outcomes measured. FFS resulted in more primary care visits/contacts, visits to specialists and diagnostic and curative services but fewer hospital referrals and repeat prescriptions compared with capitation. Compliance with a recommended number of visits was higher under FFS compared with capitation payment. FFS resulted in more patient visits, greater continuity of care, higher compliance with a recommended number of visits, but patients were less satisfied with access to their physician compared with salaried payment. REVIEWER'S CONCLUSIONS: It is noteworthy that so few studies met the inclusion criteria. There is some evidence to suggest that the method of payment of primary care physicians affects their behaviour, but the findings' generalisability is unknown. More evaluations of the effect of payment systems on PCP behaviour are needed, especially in terms of the relative impact of salary versus capitation payments.
Capitation Fee↗
Structural basis for nucleotide exchange and competition with tRNA in the yeast elongation factor complex eEF1A:eEF1Balpha.
The crystal structure of a complex between the protein biosynthesis elongation factor eEF1A (formerly EF-1alpha) and the catalytic C terminus of its exchange factor, eEF1Balpha (formerly EF-1beta), was determined to 1.67 A resolution. One end of the nucleotide exchange factor is buried between the switch 1 and 2 regions of eEF1A and destroys the binding site for the Mg(2+) ion associated with the nucleotide. The second end of eEF1Balpha interacts with domain 2 of eEF1A in the region hypothesized to be involved in the binding of the CCA-aminoacyl end of the tRNA. The competition between eEF1Balpha and aminoacylated tRNA may be a central element in channeling the reactants in eukaryotic protein synthesis. The recognition of eEF1A by eEF1Balpha is very different from that observed in the prokaryotic EF-Tu:EF-Ts complex. Recognition of the switch 2 region in nucleotide exchange is, however, common to the elongation factor complexes and those of Ras:Sos and Arf1:Sec7.
Binding Sites↗
Birth outcomes in women exposed to anticonvulsant drugs.
OBJECTIVES: To examine the risk of malformations and fetal growth in women treated with anticonvulsant drugs in North Jutland County, Denmark. MATERIAL AND METHODS: All women treated with anticonvulsant drugs in the county were identified in a Pharmaco-Epidemiological Prescription Database and linked to the Danish Medical Birth Registry and the Regional Hospital Discharge Registry. RESULTS: We identified 235 pregnancies exposed to anticonvulsants around conception and/or during pregnancy as well as 17,259 unexposed pregnancies where the mother had not received any prescription. There was 1 case of neural tube defect among 15 malformations in the exposed cohort. The overall risk of malformations was 2.2 (95% confidence intervals 1.3-3.8). The risk of low birth weight and preterm delivery was 1.5 (95% confidence intervals 0.6-3.7) and 1.6 (95% confidence intervals 1.0-2.5), respectively. CONCLUSION: We found an increased risk of congenital malformations and a tendency to growth retardation in children of women exposed to anticonvulsants.
Abnormalities, Drug-Induced↗
A 13-amino-acid Pit1-specific loop 4 sequence confers feline leukemia virus subgroup B receptor function upon Pit2.
Feline leukemia virus subgroup B (FeLV-B) and gibbon ape leukemia virus (GALV) utilize the human protein Pit1 but not the related protein, Pit2, as receptor. A stretch of 9 amino acids, named region A, was identified in the putative fourth extracellular loop of Pit1 (residues 550 through 558) as critical for FeLV-B and GALV receptor function. However, the presence of Pit1 region A did not confer receptor function for FeLV-B upon Pit2, while it did so for GALV. We have here shown that the presence of two Pit1-specific loop 4 residues (tyrosine 546 and valine 548) in addition to Pit1 region A is sufficient to make Pit2 an efficient FeLV-B receptor; that is, a stretch of 13 amino acids encompassing all loop 4 amino acid differences between Pit1 and Pit2 comprises a C-terminal determinant for FeLV-B receptor function. Thus, the same limited receptor region is sufficient to confer receptor function for both viruses upon Pit2.
3T3 Cells↗
Birth outcomes in pregnant women treated with low-molecular-weight heparin.
BACKGROUND: Pregnancy and puerperium are associated with an increased risk of venous thromboembolism. Low-molecular-weight heparin is the anticoagulant of choice in pregnant women because, unlike warfarin, it does not cross the placenta. However, there are limited data on the risk of adverse birth outcomes following use of low-molecular-weight heparin in pregnancy. PATIENTS AND METHODS: We performed a population-based cohort study to examine the safety of low-molecular-weight heparin use in pregnancy using data from the Pharmacoepidemiological Prescription Database, The Danish Medical Birth Registry and the Regional Hospital Discharge Registry in North Jutland County, Denmark. The birth outcomes in a cohort of 66 pregnant women treated with low-molecular-weight heparin between 1991-98 were compared with the birth outcomes of 17,259 pregnant women who did not receive any prescriptive drugs during pregnancy. RESULTS: No increased risk of malformations, low birth weight or stillbirth was found. However, an increased risk of pre-term delivery was found (odds ratio: 2.11, 95%, confidence interval: 0.96-4.65), which could reflect inherited thrombophilia as an indication of low-molecular-weight heparin. CONCLUSION: We have provided additional evidence of the safety of low-molecular-weight heparin use in pregnancy.
Abnormalities, Drug-Induced↗
Crystal structure of human catecholamine sulfotransferase.
Sulfonation, like phosphorylation, can modify the activity of a variety of biological molecules. The sulfotransferase enzymes sulfonate neurotransmitters, drugs, steroid hormones, dietary carcinogens and proteins. SULT1A3 specifically sulfonates catecholamines such as dopamine, adrenaline and noradrenaline. The crystal structure of SULT1A3 with a sulfate bound at the active site, has been determined at 2.4 A resolution. Although the core alpha/beta fold is like that of estrogen and heparan sulfotransferases, major differences occur in and around the active site. Most notably, several regions surrounding the active site, including a section of 40 residues, are disordered in SULT1A3. Regions that are topologically equivalent to the disordered parts of SULT1A3 are involved in substrate and cofactor binding in estrogen and heparan sulfotransferase. Flexibility in these regions suggests that ligand binding elicits a disorder-order transition in and around the active site of sulfotransferases and might contribute to the broad substrate specificity of these enzymes.
Amino Acid Sequence↗
New tricks for modelers from the crystallography toolkit: the particle mesh Ewald algorithm and its use in nucleic acid simulations.
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Algorithms↗
Physician contact with older community patients: is there an association with physical fitness?
BACKGROUND: Contact with family physicians by older adults may be linked to their physical fitness in addition to other health, behavioral, and sociodemographic determinants. We studied a stratified random sample of urban community-dwelling elderly patients in London, Ontario, Canada, to describe the interaction of physical fitness measures and a number of health and lifestyle behaviors and sociodemographic outcomes with family physician contact over 1 year. We hypothesized that physician contact would be associated with lower indices of physical fitness and that association would be similar to other known determinants of physician utilization. METHODS: Three hundred seventy-five noninstitutionalized elderly men (N = 185) and women (N = 190) ages 55 to 84 years were recruited from the municipal tax assessment list for the city of London (population 280,000). Four categories of independent variables were selected to reflect common determinants of health (physical fitness, self-reported and clinically measured health, lifestyle behaviors, and sociodemographics). The association between these categories of variables and self-reported contact with family physicians and a variety of health professionals was determined for the year prior to the study. RESULTS: Forty-six percent of the subjects had at least one physician contact in the month prior to the study and 79% within the previous year. None of the other health professions (including nursing, chiropractic, physiotherapy, homemaking, and dentistry) were contacted more than once in the previous year. Lifestyle and sociodemographic variables including activity habits, smoking, income, marital status, and education were not associated with physician contact, whereas poor self-reported cardiovascular health and use of cardiovascular and pulmonary medications were associated with physician contact. Interestingly, physical fitness variables including maximal aerobic capacity, grip strength, and hip flexibility were not associated with physician contact. CONCLUSIONS: The absence of an association among physical fitness, lifestyle, and sociodemographic variables and physician contact was not anticipated and may be due to the selection of individuals who were independent, active community dwellers. It may be that most of the physician contact in this relatively healthy and physically fit sample was preventive in nature, for example, monitoring common chronic disease states in the elderly including cardiovascular and pulmonary disease. This paper reports baseline data from a longitudinal study of the interaction between physical fitness and health outcomes in groups of older community-dwelling individuals. As this group ages further, it would be interesting to determine the use of the health care system in relation to their changing functional and health status. In particular, do chronic health conditions such as cardiovascular disease, which increase in prevalence with age, become modified through maintenance of physical fitness and does this impact on health service use?
Aged↗
Prognostic comparison of three classifications for medullary carcinoma of the breast.
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Breast Neoplasms↗
Quantification of microvessel density of breast carcinoma: an assessment of the inter- and intraobserver variation.
The density profile of microvessels (MVD) has recently emerged as a prognostically independent morphological marker of various malignancies, including carcinoma of the breast. MVD-scoring may thus afford the pathologist the opportunity to identify subsets of early stage breast cancer patients, which may benefit from adjuvant therapy. Reproducibility studies are, however, mandatory. Fifty sections of invasive breast carcinoma, immunolabelled for Factor VIII-related antigen, were scored independently by two observers for the number of vessel-profiles (v-p) in the following manner: 1) 250 randomly selected high power fields (HPF) were scored by two analysts to evaluate the agreement of the counting per se; and 2) the hot spot(s), i.e. the zones considered the most vessel rich, in the 50 sections were identified and scored twice to evaluate the agreement on selecting hot spots. When the observers evaluated MVD in the very same 250 HPF a median deviation of 2 v-p (10%) was produced. The interobserver disparity was further accentuated when the participants independently had to identify the hot spots with a median deviation of 6 v-p (13%). Intraobserver variation was approximately equal to the interobserver discordance. Divergences were most conspicuous in fields with a complex vasculature. In conclusion the v-p scoring resulted in substantial inter- and intraobserver variation both in selecting hot spots and in performing the scoring per se. Alternative-scoring techniques, including strict stereological principles, should be considered in the morphological evaluation of angiogenesis.
Journal Article↗
Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study.
BACKGROUND: There are few epidemiologic data about the risk of acute pancreatitis in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk of a first episode of acute pancreatitis in patients with Crohn's disease and ulcerative colitis in the total Danish population. METHODS: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis registered in the Danish National Registry of Patients in the period from 1977 to 1992. The first episode of acute pancreatitis was identified in the cohort. The observed number of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute pancreatitis was increased both in patients with Crohn's disease (SIR = 4.3; 95% confidence interval (CI), 2.9-6.1) and in those with ulcerative colitis (SIR= 2.1; 95% CI, 1.6-2.8). CONCLUSION: Patients with chronic inflammatory bowel disease seem to be at increased risk of acute pancreatitis. Further validation and refinement of this registration-based study are needed.
Acute Disease↗
How should we pay doctors? A systematic review of salary payments and their effect on doctor behaviour.
We reviewed the published and unpublished international literature to determine the influence of salaried payment on doctor behaviour. We systematically searched Medline, BIDS Embase, Econlit and BIDS ISI and the reference lists of located papers to identify relevant empirical studies comparing salaried doctors with those paid by alternative methods. Only studies which reported objective outcomes and measures of the behaviour of doctors paid by salary compared to an alternative method were included in the review. Twenty-three papers were identified as meeting the selection criteria. Only one of the studies in this review reported a proxy for health status, but none examined whether salaried doctors differentiated between patients on the basis of health needs. Therefore, we were unable to draw conclusions on the likely impact of salaried payment on efficiency and equity. However, the limited evidence in our review does suggest that payment by salaries is associated with the lowest use of tests, and referrals compared with FFS and capitation. Salary payment is also associated with lower numbers of procedures per patient, lower throughput of patients per doctor, longer consultations, more preventive care and different patterns of consultation compared with FFS payment.
Family Practice↗
Amphotropic murine leukemia virus entry is determined by specific combinations of residues from receptor loops 2 and 4.
Pit2 is the human receptor for amphotropic murine leukemia virus (A-MuLV); the related human protein Pit1 does not support A-MuLV entry. Interestingly, chimeric proteins in which either the N-terminal or the C-terminal part of Pit2 was replaced by the Pit1 sequence all retained A-MuLV receptor function. A possible interpretation of these observations is that Pit1 harbors sequences which can specify A-MuLV receptor function when presented in a protein context other than Pit1, e.g., in Pit1-Pit2 hybrids. We reasoned that such Pit1 sequences might be identified if presented in the Neurospora crassa protein Pho-4. This protein is distantly related to Pit1 and Pit2, predicted to have a similar membrane topology with five extracellular loops, and does not support A-MuLV entry. We show here that introduction of the Pit1-specific loop 2 sequence conferred A-MuLV receptor function upon Pho-4. Therefore, we conclude that (i) a functional A-MuLV receptor can be constructed by combining sequences from two proteins each lacking A-MuLV receptor function and that (ii) a Pit1 sequence can specify A-MuLV receptor function when presented in another protein context than that provided by Pit1 itself. Previous results indicated a role of loop 4 residues in A-MuLV entry, and the presence of a Pit2-specific loop 4 sequence was found here to confer A-MuLV receptor function upon Pho-4. Moreover, the introduction of a Pit1-specific loop 4 sequence, but not of a Pit2-specific loop 4 sequence, abolished the A-MuLV receptor function of a Pho-4 chimera harboring the Pit1-specific loop 2 sequence. Together, these data suggest that residues in both loop 2 and loop 4 play a role in A-MuLV receptor function. A-MuLV is, however, not dependent on the specific Pit2 loop 2 and Pit2 loop 4 sequences for entry; rather, the role played by loops 2 and 4 in A-MuLV entry can be fulfilled by several different combinations of loop 2 and loop 4 sequences. We predict that the residues in loops 2 and 4, identified in this study as specifying A-MuLV receptor function, are to be found among those not conserved among Pho-4, Pit1, and Pit2.
Amino Acid Sequence↗