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Biomedical subjects

D Palmer

Publications and source records attributed to D Palmer.

At least 55 records · Page 3Linked to original sources

Clinical practice guidelines in pediatric and newborn medicine: implications for their use in practice.

Clinical practice guidelines are becoming pervasive in pediatrics and newborn medicine. They have spanned a wide range of primary care practice parameters from treating otitis media with effusion, to performing complex surgery for congenital heart disease, and management of respiratory distress syndrome and coordinating discharge from the neonatal intensive care unit. Administrators believe that using clinical practice parameters reduces health care costs, improves quality of care, and limits malpractice liability. Practice parameters and guidelines have grown in use because powerful interests-third-party payers, insurers, and health maintenance organizations, as well as hospital administrators bent on reducing variable costs of care and contracting for capitated care-champion their development, implementation, and monitoring. Economic credentialing of physicians with excessive variances without risk-adjusting for other than average patients is problematic and remains unchecked partly because of the fundamental characteristics of the evolving health care industry in which costs are more easily measured than quality. For highly autonomus physicians this standardization of medical decision making may represent a difficult transition into corporate practice by realigning traditional values of the doctor-patient relationship. However, because guidelines are almost certainly here to stay, pediatricians and neonatologists need to think critically about how their content and method of implementation, monitoring, and modification may influence medical teaching and decision making in the future. If guidelines are introduced primarily as a cost savings or containment tool that ignores the impact on the quality of care and restricts necessary care for infants and children, especially those with chronic illness or who are developmentally at risk, then neonatologists and pediatricians must be quick and determined to challenge the potentially damaging use of practice parameters or guidelines. Furthermore, there are many medicolegal implications of guideline implementation that may not favor physicians and leave to hospitals, insurers, and ultimately the courts decisions regarding evidence-based practice. In this review article, we pay special attention to the guidelines developed in newborn medicine. We discuss why and how guidelines are developed and critically evaluate the available evidence describing potential benefits and drawbacks of guidelines in general. There are legal implications to the implementation of guidelines, and guidelines may increase provider susceptibility to malpractice allegations. Neonatologists and pediatricians should critically analyze the following questions when guidelines are being developed: Are clinical practice parameters the most effective means to reduce the costs of health care, or improve the quality of health care services while reducing the need for and protecting physicians from malpractice suits? Or do clinical practice guidelines more closely resemble an audit system developed by health care organizations, insurers, and others including government-sponsored health care to appease powerful interests-with limited evidence for promise and perhaps potential negative cost, quality, and malpractice liability implications? In pediatric and newborn medicine there is limited evidence that guidelines have achieved the desired goals and further analysis of their process of care and the costs of implementation is warranted.

Health Services↗

Clinical applications of a new parenteral antibiotic in the treatment of severe bacterial infections.

Cephalosporins are one of the mainstays of antibiotic therapy, and third-generation cephalosporins are first-line agents for the treatment of many types of serious infections, including those of nosocomial origin. Gaps in activity of currently available third-generation cephalosporins such as cefotaxime, cefoperazone, ceftriaxone, and ceftazidime, and increasing reports of gram-negative bacilli resistance to some of these agents, especially Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp., make it necessary to investigate new compounds. Cefepime, a fourth-generation cephalosporin with a wide range of activity against gram-positive and gram-negative bacteria, including multi-resistant strains of Enterobacteriaceae, was evaluated in comparison with ceftazidime for the treatment of serious infections in hospitalized patients. Ceftazidime is a commonly prescribed third-generation cephalosporin used for empiric treatment of serious infections such as pneumonia, urinary tract infection, and skin and skin-structure infection. This investigation was an open, randomized comparative study involving 882 patients in North America. Cefepime 2 g every 12 hours demonstrated similar efficacy to that of ceftazidime 2 g every 8 hours for the treatment of pneumonia and urinary tract infection (including cases associated with concurrent bacteremia), and skin and skin-structure infections. The bacteriologic responses were generally >85%. The most common pathogens isolated were Escherichia coll, Streptococcus pneumoniae, P. aeruginosa, K. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus, group B. Overall, approximately 94% of pathogens isolated in pretreatment cultures were susceptible to cefepime and ceftazidime. Cefepime and ceftazidime were well tolerated; only 3% of patients in each group discontinued therapy because of an adverse event. The most common adverse events were headache, diarrhea, nausea, vomiting, pruritus, and rash. The results of this study indicate that cefepime is a promising, effective, and safe single-agent therapy for serious infections in hospitalized patients.

Acute Disease↗

Early signal transduction by the receptor to the chemokine monocyte chemotactic protein-1 in a murine T cell hybrid.

Members of the C-C family of chemotactic cytokines promote chemotaxis and adhesion of leukocytes. In this study, we have identified a murine T cell hybrid that expresses receptors to the chemotactic cytokine monocyte chemotactic protein-1 (MCP-1). This cell line was used to examine MCP-1 receptor-mediated signal transduction events in a homologous system in the absence of interference with other receptors. Our results show that in the 3B4 M1.9 T cell hybrid, MCP-1 receptors mediate intracellular calcium mobilization and extracellular calcium import without detectable increases in total water-soluble inositol phosphates. In addition, MCP-1 regulates the tyrosine phosphorylation of specific substrates at 42 and 44 kDa and induces mobility shift of p42/44 mitogen-activated protein kinases. MCP-1-mediated calcium responses, tyrosine phosphorylation, and the electrophoretic mobility shift of p42/44 mitogen-activated protein kinases can be inhibited by pretreatment of cells with pertussis toxin, indicating a role for Gi-like G proteins in coupling the MCP-1R to signal transduction.

Animals↗

Prospective study of the aetiology of infusion phlebitis and line failure during peripheral parenteral nutrition.

Four techniques of administering peripheral parenteral nutrition (PPN) were examined prospectively to investigate the role of mechanical trauma in the development of infusion phlebitis. Patients in group 1 (n = 15) were fed via a standard 18-G Teflon cannula which was removed on completion of the infusion and was rotated to the contralateral arm every day. Group 2 patients (n = 15) had a similar catheter sited in each forearm simultaneously, with rotation of the side of infusion each day. Patients in group 3 (n = 17) had a 15-cm Silastic rubber catheter inserted into a forearm vein and a standard cannula sited in the contralateral forearm, with alternation of infusion each day. Those in group 4 (n = 13) had a fine-bore 23-G silicone catheter sited in one arm only. Patients in groups 1, 2 and 3 were fed over 12-h cycles and those in group 4 for a 24-h continuous cycle. A total of 408 patient-days of PPN were given. Mean duration of PPN in groups 1-4 was 7.5, 9, 5.5 and 5 days respectively. Infusion phlebitis was not recorded in patients who had a daily change of cannula (group 1), but occurred in four patients in group 2, eight in group 3 and eight in group 4. Phlebitis scores were 0, 9, 15 and 12 for groups 1-4 respectively. Severe phlebitis and line occlusion occurred more frequently in patients with a 15-cm catheter (group 3) and in those fed continuously over 24 h (group 4). These results suggest that mechanical trauma is an important factor in the aetiology of infusion phlebitis. This can be minimized by reducing the time for which the vein wall is exposed to nutrient infusion and by reducing the amount of prosthetic material within the vein.

Adult↗

Administration of peripheral parenteral nutrition: a prospective study comparing rotation of venous access sites with ultrafine cannulas.

Peripheral veins have been used successfully for patients requiring short- to medium-term total parenteral nutrition. This study prospectively compares two methods of peripheral parenteral nutrition (PPN). Forty-six patients requiring parenteral nutrition (PN) were identified prospectively. Fifty courses of PPN were prescribed using a standardized PPN formula of 9.3 g nitrogen, 1400 kCal, 2500 ml (KABI II, Pharmacia). Patients were randomized to receive PPN via 23G, 15 cm flexane catheters (Nutriline) inserted into an antecubital vein which remained in-situ with a continuous infusion over 24 h, or to receive 12-h cyclical infusions through peripherally sited 18G catheters (Venflon) which were removed postinfusion and reinserted into the contralateral forearm on alternate days. Data collected included duration, complications and cost of materials for each prescribed course. A scoring system to determine patient anxiety and depression and a questionnaire regarding patients' perspectives were evaluated. Fifty courses were prescribed, 26 by rotation of veins (RV) and 24 by Nutriline (N). Mean duration of feeding was 7.9 and 8.6 days, respectively; cost of materials were comparable 6.48/day (RV) vs 5.17/day (N); 2 RV patients failed to complete their course (no access [P< 0.05], whilst 9 N patients failed to complete their course (4 severe phlebitis, 2 no venous access, 2 septicaemia, 1 dislodged). Five patients required CPN (RV, N 3) while 4 remaining patients were fed by an alternative PPN method. The overall incidence of anxiety was 20% and of depression 16%, with no significant difference between groups. The majority of patients (87%) found mobility restricted. Twelve-hourly infusions via alternate forearm veins were significantly more successful than continuous infusions via Nutriline, both in terms of completion of the prescribed course and less venous morbidity. This study confirms that rotation of forearm veins allows affordable and successful PN administration to the majority of patients, with low PN-related morbidity.

Journal Article↗

Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors.

5-Hydroxytryptamine elicits its physiological effects by interacting with a diverse group of receptors. Two of these receptors, the 5-HT1D beta and the 5-HT1E receptors, are approximately 60% identical in the transmembrane domains that presumably form the ligand binding site yet have very different pharmacological properties. Analysis of the pharmacological properties of a series of chimeric 5-HT1D beta/5-HT1E receptors indicates that sequences in the sixth and seventh transmembrane domains are responsible for the differential affinity of 5-carboxamidotryptamine for these two receptors. More detailed analysis shows that two amino acid differences in the sixth transmembrane domain (Ile333 and Ser334 in the 5-HT1D beta receptor, corresponding to Lys310 and Glu311 in the 5-HT1E receptor) are largely responsible for the differential affinities of some, but not all, ligands for the 5-HT1D beta and 5-HT1E receptors. It is likely that these two amino acids subtly determine the overall three-dimensional structure of the receptor rather than interact directly with individual ligands.

Amino Acid Sequence↗

Nitrate and nitric acid concentrations at two Rocky Mountain baseline monitoring sites.

A two-tiered, Teflon/nylon filterpack system was used to characterize spatial and temporal patterns of particulate nitrates and nitric acid vapors at two monitoring sites in the Rocky Mountains. Geometric means for particulate nitrates were 38.9 and 52.8 ng/m(3) for the upper and lower sites, respectively. For nitric acid, geometric means of 70.4 ng/m(3) for the upper site and 295 ng/m(3) for the lower site were observed. The relatively low concentrations found at these two sites are comparable to published values for these materials at other remote sites. Atmospheric concentrations of nitrates and nitric acid were correlated significantly at each site, and the total nitrate concentrations (NO(3)(-) plus HNO(3)) were correlated between sites. Comparisons between the two sites indicate that nitric acid concentrations were statistically greater at the lower elevation site, whereas nitrate concentrations were not significantly different. No general seasonal or annual pattern of nitrate or nitric acid concentrations were evident when comparable sampling periods were examined.

Journal Article↗

Histopathologic changes following irradiation for uveal tract melanoma.

Histopathologic studies were performed on 38 eyes in patients with uveal melanoma who had enucleation. Of the 38 eyes examined, enucleation was required in 11 (29%) following episcleral radioactive plaque therapy (RPT), which was performed in 83 patients. The reasons for enucleation in the 11 patients who had RPT were progressive tumor in 5 and treatment complications in 6 eyes. The histologic findings in these 11 patients were compared to those seen in 7 patients (18%) who received a planned course of preoperative external beam radiotherapy (RT) prior to enucleation and with 20 uveal melanoma patients (53%) who were treated with enucleation alone. Tumor necrosis was found in the eyes of patients from all three groups examined. It was, however, seen more frequently and to a greater extent in the 11 RPT patients as compared to the 7 preoperative RT and 20 enucleation alone patients, p = .01. There was no difference in the incidence or extent of tumor necrosis in the 7 preoperative RT patients as compared to the 20 primary enucleation patients, p = .18. In all 3 study groups, no correlation was found between tumor size and necrosis. In the 11 RPT patients, necrosis was independent of cell type and the radiation dose. As expected, the RPT patients had a greater incidence of neovascularization on the iris and scleral necrosis than those of the other two study groups (70 vs. 12.5% and 33 vs 0%, respectively), p = .004. A major effort needs to be made to optimize episcleral RPT in order to reduce treatment complications and increase the incidence of primary tumor control.

Brachytherapy↗

Characterization of the genes controlling the biosynthesis of the polyketide phytotoxin coronatine including conjugation between coronafacic and coronamic acid.

Pseudomonas syringae pv. glycinea PG4180 produces a chlorosis-inducing phytotoxin, coronatine (COR), which consists of a polyketide component, coronafacic acid (CFA), which is coupled via amide bond formation to coronamic acid (CMA), an ethylcyelopropyl amino acid (aa) derived from isoleucine. P. syringae pv. syringae strains PS51 and PS61, which do not synthesize coronafacoyl compounds (conjugates between CFA and aa), acquired the ability to produce CFA and COR when transformed with p4180A, a 90-kb indigenous plasmid in PG4180. Tn5 mutagenesis indicated that the COR biosynthetic genes in PG4180 are clustered within a 30-kb region on p4180A. The phenotype of selected COR-defective mutants was determined by supplying them with CFA and CMA and by complementation studies with cloned DNA from the COR biosynthetic cluster. Using this approach, the regions encoding CFA and CMA synthesis and coupling activity were localized to the 24-, 12.5- and 2.3-kb regions of the cluster, respectively. Mutants in a 6-kb region required the addition of both CFA and CMA for COR synthesis, which may indicate a regulatory role for this part of the cluster. PS51 and PS61 transconjugants containing cloned DNA from the coupling region produced COR when supplied with CFA and CMA, indicating that coupling activity was cloned and expressed in bacteria lacking the COR biosynthetic cluster.

Amino Acids↗

A deletion mutation in the third cytoplasmic loop of the mouse m1 muscarinic acetylcholine receptor unmasks cryptic G-protein binding sites.

Mutations were introduced in the highly conserved carboxyl-terminal region of the third cytoplasmic loop of the mouse m1 muscarinic acetylcholine receptor (mAChR) gene by site-directed mutagenesis. The effects of these mutations on ligand binding and on mAChR coupling to phosphoinositide turnover have been examined following expression in mouse Y1 adrenal carcinoma cells, Chinese hamster ovary (CHO) cells, and Rat-2 fibroblasts. Point mutations in the region proximal to the sixth transmembrane domain had no effect on antagonist binding but did result in decreased agonist affinity. A deletion of four amino acids in the same region effectively uncoupled the receptor from phosphoinositol turnover in Y1 adrenal carcinoma cells but had no effect in either CHO cells or Rat-2 fibroblasts. Differential sensitivity to pertussis toxin indicates that the m1 mAChR can interact with multiple G-proteins in CHO cells and Rat-2 cells via distinct recognition sites on the receptor. These data demonstrate multiple G-proteins can interact with an individual receptor, that the same receptor may couple to different second messenger pathways, and that these responses can vary in a cell type-specific manner.

Amino Acid Sequence↗

Generation and characterization of an HLA-DR alpha-specific monoclonal antibody using L-cell transfectants expressing human and mouse class II major histocompatibility dimers.

Among the HLA-DR-specific monoclonal antibodies (mAbs) that have been characterized previously, there is a marked shortage of DR alpha chain-specific mAbs which stain unfixed cells. This may result from the high degree of sequence similarity between the alpha 1 domains of HLA-DR and H-2E leading to a state of cross-tolerance to DR alpha in H-2-expressing mice. BALB/b (E-negative) mice were immunized with DR1-transfected mouse L cells. The chain specificity of the resulting DR-specific mAb was determined using a panel of transfectants expressing hybrid mouse/human class II heterodimers. A DR alpha-specific mAb was generated which was capable of immunoprecipitating DR alpha beta dimers and inhibiting the anti-DR alloresponse of human T-cell clones. The present study demonstrates that, with the selection of a suitable recipient strain, transfectants can be useful in the generation and definition of chain-specific mouse mAbs.

Animals↗