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Biomedical subjects

David Johnson

Publications and source records attributed to David Johnson.

At least 91 records · Page 5Linked to original sources
PubMed2003

Parental compliance with after hours telephone triage advice: nurse advice service versus on-call pediatricians.

To compare parental compliance with after-hours triage advice provided by telephone advice nurses and on-call pediatricians, a randomized controlled trial was undertaken at a university general pediatrics practice that enrolled parents or guardians calling for after-hours advice. Advice calls were randomized to a call center advice nurse or the on-call pediatrician. Parental compliance with the triage advice and agreement of the parental report of advice with the pediatrician/nurse report of advice given was evaluated. There were 566 participants in the pediatrician and 616 in the nurse group. Compliance with advice (pediatrician v. nurse) was not significantly different for emergent/urgent care (75.8% v. 72.6%) and self care (74.3% v. 77.2%) but was significantly higher in the pediatrician group for office care (51.5% v. 29.6%; 95% CI of difference, 8.9%-34.2%). Overall agreement between the caller reported and physician or nurse advice was 84.5% for emergent/ urgent, 42.7% for office care, and 93.7% for self-care.

After-Hours Care↗
PubMed2003

A comprehensive screen of genes implicated in craniosynostosis.

Recent advances in human molecular genetics have identified mutations in the TWIST, FGFR-1, FGFR-2 and FGFR-3 genes to be important causes of craniosynostosis. Despite this, however, mutations cannot be identified in the majority of patients. This study reports the first comprehensive screen of mutations in TWIST, FGFR-1, FGFR-2 and FGFR-3 genes in a cohort of patients with craniosynostosis. This has led to the identification of Saethre-Chotzen syndrome to be a new microdeletion disorder and reports the first example of a gene-environment interaction leading to craniosynostosis. In addition, investigation of the expression patterns of the Fgfr and Twist genes in the normal developing mouse coronal suture has identified the TWIST protein to be important in cranial suture initiation and biogenesis. These findings have significant clinical implications and will form the basis of future attempts to develop novel therapies aimed at inhibiting cranial suture fusion.

Craniosynostoses↗
PubMed2003

Workflow management of HIS/RIS textual documents with PACS image studies for neuroradiology.

Reviewing brain tumor patients' complete medical record is a daunting task for any clinician. In current practice, the radiologist examines the most recent documents and then dictates an assessment of the patient's condition based on a review of the most current imaging study and compared with the most recent previous image study. Occasionally, the radiologist searches other clinical documents when more precise detail is needed. The purpose of this research is to develop effective methods to review all of the pertinent information in a patient medical record incorporating HIS (Hospital Information Systems), RIS (Radiology Information Systems) and PACS (Picture Archiving and Communications Systems) information in three distinct ways: filtering the document worklist for pertinent clinical data, identification of key clusters of clinical information, and an automatic hanging protocol that displays the MR images for optimal image comparison.

Algorithms↗
PubMed2002

An economic evaluation of activated protein C treatment for severe sepsis.

BACKGROUND: Recombinant human activated protein C was shown in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study to reduce mortality among patients with severe sepsis. A post hoc reanalysis by the Food and Drug Administration (FDA) of data from this study suggested that the reduction in mortality was restricted to patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores of 25 or more. METHODS: We estimated the cost effectiveness of activated protein C as compared with conventional care for patients with severe sepsis. We performed an economic analysis involving all patients, as well as analyses of subgroups defined according to age and severity of illness. The probabilities of transition between clinical states and the estimates of resource use were derived from a population-based cohort of patients with severe sepsis. We used data on the effectiveness of activated protein C from the PROWESS study and analyses by the FDA. RESULTS: The cost per life-year gained by treating all patients with activated protein C was $27,936. It was more cost effective to treat patients with an APACHE II score of 25 or more ($24,484 per life-year gained) than those with a lower APACHE II score ($35,632 per life-year gained). The cost effectiveness of treating patients with an APACHE II score of 24 or less increased to $575,054 per life-year gained when the FDA's estimates of effectiveness were considered. For patients with an APACHE II score of 25 or more, the cost per life-year gained increased with age ($16,309 for patients less than 40 years of age; $28,100 for those 80 years of age or older). CONCLUSIONS: Activated protein C is relatively cost effective when targeted to patients with severe sepsis, greater severity of illness (an APACHE II score of 25 or more), and a reasonable life expectancy if they survive the episode of sepsis. Further research is needed to determine the cost effectiveness of activated protein C for patients with sepsis and less severe illness.

APACHE↗
PubMed2002

Crystal structure of the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain.

Cytoskeleton-associated proteins (CAPs) are involved in the organization of microtubules and transportation of vesicles and organelles along the cytoskeletal network. A conserved motif, CAP-Gly, has been identified in a number of CAPs, including CLIP-170 and dynactins. The crystal structure of the CAP-Gly domain of Caenorhabditis elegans F53F4.3 protein, solved by single wavelength sulfur-anomalous phasing, revealed a novel protein fold containing three beta-sheets. The most conserved sequence, GKNDG, is located in two consecutive sharp turns on the surface, forming the entrance to a groove. Residues in the groove are highly conserved as measured from the information content of the aligned sequences. The C-terminal tail of another molecule in the crystal is bound in this groove.

Amino Acid Sequence↗
PubMed2002

Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection.

BACKGROUND: Lopinavir is a newly developed inhibitor of human immunodeficiency virus (HIV) protease that, when formulated with ritonavir, yields mean trough plasma lopinavir concentrations that are at least 75 times as high as that needed to inhibit replication of wild-type HIV by 50 percent. METHODS: We conducted a double-blind trial in which 653 HIV-infected adults who had not received antiretroviral therapy for more than 14 days were randomly assigned to receive either lopinavir-ritonavir (400 mg of lopinavir plus 100 mg of ritonavir twice daily) with nelfinavir placebo or nelfinavir (750 mg three times daily) with lopinavir-ritonavir placebo. All patients also received open-label stavudine and lamivudine. The primary efficacy end points were the presence of fewer than 400 HIV RNA copies per milliliter of plasma at week 24 and the time to the loss of virologic response through week 48. RESULTS: At week 48, greater proportions of patients treated with lopinavir-ritonavir than of patients treated with nelfinavir had fewer than 400 copies of HIV RNA per milliliter (75 percent vs. 63 percent, P<0.001) and fewer than 50 copies per milliliter (67 percent vs. 52 percent, P<0.001). The time to the loss of virologic response was greater in the lopinavir-ritonavir group than in the nelfinavir group (hazard ratio, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001). The estimated proportion of patients with a persistent virologic response through week 48 was 84 percent for patients receiving lopinavir-ritonavir and 66 percent for those receiving nelfinavir. Both regimens were well tolerated, with the rate of discontinuation related to the study drugs at 3.4 percent among patients receiving lopinavir-ritonavir and 3.7 percent among patients receiving nelfinavir. Among patients with more than 400 copies of HIV RNA per milliliter at some point from week 24 through week 48, resistance mutations in HIV protease were demonstrated in viral isolates from 25 of 76 nelfinavir-treated patients (33 percent) and none of 37 patients treated with lopinavir-ritonavir (P<0.001). CONCLUSIONS: For the initial treatment of HIV-infected adults, a combination regimen that includes lopinavir-ritonavir is well tolerated and has antiviral activity superior to that of a nelfinavir-containing regimen.

Adult↗
PubMed2002

HIV-1 Subtype A, D, G, AG and unclassified sequences identified in South Africa.

HIV-1 subtype C accounts for the vast majority of infections in South Africa. However, increasingly non-C subtypes are being detected. Here we report 10 viruses that contain sequences that group with subtypes A, D, and G as well as CRF02_AG and 1 that could not be classified. Most of these individuals were from other countries in Africa. Some of these sequences were in combination with subtype C, possibly indicating local recombination events. Although there is no indication of endemic spread of these viruses, continued monitoring is warranted to track genetic changes, which may impact on diagnostic testing, therapeutic responses to antiretroviral therapies, and vaccine design.

HIV Infections↗
PubMed2002

Vascular endothelial growth factor-mediated angiogenesis inhibition and postoperative wound healing in rats.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic factor that acts by binding to specific high-affinity tyrosine kinase receptors. SU5416 is an antiangiogenic agent that acts as a potent and selective inhibitor of the VEGF Flk-1/KDR receptor tyrosine kinase. SU5416 has been shown to inhibit VEGF-dependent mitogenesis of human endothelial cells and to decrease the growth of xenografts of melanoma, lung carcinoma, ovarian carcinoma, and gliomas. The effect of pre- or perioperative use of this drug on angiogenesis and wound healing in the postoperative setting has not been shown. We sought to analyze the efficacy and safety with respect to functional dosing of SU5416 in the setting of wound healing. This represents an important step forward in the use of this and similar drugs in the perioperative setting of treatment for multiple types of cancers. The use of an inhibitor of VEGF receptors such as SU5416 is distinct and it is likely complementary to other agents in the treatment of such cancers. METHODS: We injected 8-week-old male Sprague-Dawley rats with SU5416 (8 or 12 mg/kg) or dimethyl sulfoxide intraperitoneally, daily for 14 days. We then performed a right pulmonary lobectomy and 6-mm full-thickness punch biopsies of the back. Tissue perfusion measured via laser Doppler on Postoperative Day 2 was 1.65, 1.22, and 1.14 perfusion units (P < 0.0004) for control, 8 mg/kg, and 12 mg/kg groups, respectively. RESULTS: We successfully treated a murine model with functional doses of the anti-VEGF drug SU5416 so as to achieve decreased vascularity and blood flow in postoperative wounds. There was no effect on gross wound healing or infection in either control or treatment groups. Also, no drug-related impairment of histologic healing or decrease in wound tensile strength was demonstrated at either 6 or 14 days. CONCLUSION: Preoperative therapy with functional dosing of SU5416 does not appear to have any major effect on postoperative morbidity or mortality in rats. We additionally conclude that preoperative therapy with SU5416 should be investigated further with careful attention to wound integrity.

Angiogenesis Inhibitors↗
PubMed2002

Arctic microorganisms respond more to elevated UV-B radiation than CO2.

Surface ultraviolet-B radiation and atmospheric CO2 concentrations have increased as a result of ozone depletion and burning of fossil fuels. The effects are likely to be most apparent in polar regions where ozone holes have developed and ecosystems are particularly sensitive to disturbance. Polar plant communities are dependent on nutrient cycling by soil microorganisms, which represent a significant and highly labile portion of soil carbon (C) and nitrogen (N). It was thought that the soil microbial biomass was unlikely to be affected by exposure of their associated plant communities to increased UV-B. In contrast, increasing atmospheric CO2 concentrations were thought to have a strong effect as a result of greater below-ground C allocation. In addition, there is a growing belief that ozone depletion is of only minor environmental concern because the impacts of UV-B radiation on plant communities are often very subtle. Here we show that 5 years of exposure of a subarctic heath to enhanced UV-B radiation both alone and in combination with elevated CO2 resulted in significant changes in the C:N ratio and in the bacterial community structure of the soil microbial biomass.

Arctic Regions↗
PubMed2002

Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis.

It has been known for several years that heterozygous mutations of three members of the fibroblast growth-factor-receptor family of signal-transduction molecules-namely, FGFR1, FGFR2, and FGFR3-contribute significantly to disorders of bone patterning and growth. FGFR3 mutations, which predominantly cause short-limbed bone dysplasia, occur in all three major regions (i.e., extracellular, transmembrane, and intracellular) of the protein. By contrast, most mutations described in FGFR2 localize to just two exons (IIIa and IIIc), encoding the IgIII domain in the extracellular region, resulting in syndromic craniosynostosis including Apert, Crouzon, or Pfeiffer syndromes. Interpretation of this apparent clustering of mutations in FGFR2 has been hampered by the absence of any complete FGFR2-mutation screen. We have now undertaken such a screen in 259 patients with craniosynostosis in whom mutations in other genes (e.g., FGFR1, FGFR3, and TWIST) had been excluded; part of this screen was a cohort-based study, enabling unbiased estimates of the mutation distribution to be obtained. Although the majority (61/62 in the cohort sample) of FGFR2 mutations localized to the IIIa and IIIc exons, we identified mutations in seven additional exons-including six distinct mutations of the tyrosine kinase region and a single mutation of the IgII domain. The majority of patients with atypical mutations had diagnoses of Pfeiffer syndrome or Crouzon syndrome. Overall, FGFR2 mutations were present in 9.8% of patients with craniosynostosis who were included in a prospectively ascertained sample, but no mutations were found in association with isolated fusion of the metopic or sagittal sutures. We conclude that the spectrum of FGFR2 mutations causing craniosynostosis is wider than previously recognized but that, nevertheless, the IgIIIa/IIIc region represents a genuine mutation hotspot.

Acrocephalosyndactylia↗
PubMed2002

Hospital practice more than specialty influences the choice of regional or general anesthesia for Cesarean section.

PURPOSE: Describe the influence of specialty certification and practice style upon the anesthetic technique used for Cesarean deliveries. METHODS: Alberta physician claims and hospital abstracts between April 1, 1998 to March 31, 2000 were used to determine the technique of anesthesia (regional or general). The influence of practice (volume of deliveries, geographic location, presence of regional analgesia providers) and specialty (anesthesiologist or family/general practice) is explored by logistic regression. RESULTS: Hospital abstracts of 13,884 Cesarean sections were analyzed. Anesthesiologists performed 76% of the anesthetics: epidural (33%), spinal (45%), and general anesthesia (22%). Comparing only regional and metropolitan hospitals, the percent of general anesthesia performed by anesthesiologists varied between 5% to 50%. After adjusting for other factors, we found, in order of importance, the following determined the use of general anesthesia for Cesarean sections: 1) hospitals with more epidural procedure providers during labour were 3% less likely to have providers choose general anesthesia; 2) larger, regional and metropolitan hospitals were less likely to have providers choose general anesthesia; 3) hospitals with a high volume epidural procedure provider during labour were 64% less likely to have providers choose general anesthesia; 4) anesthesiologists were 32% less likely to choose general anesthesia. CONCLUSION: The overall use of regional anesthesia for Cesarean sections in Alberta is high. The chance of receiving a general anesthetic for a Cesarean delivery varies across the province and was more related to practice environment than specialty.

Adult↗
PubMed2002

Declining hemoglobin during chemoradiotherapy for locally advanced non-small cell lung cancer is significant.

BACKGROUND AND PURPOSE: Tumor hypoxia and anemia have been linked to poor overall survival and local control in carcinomas of both the uterine cervix and the head and neck for patients undergoing radiotherapy. Little is known about the effect of these factors on the outcome of NSCLC patients with locally advanced disease undergoing chemoradiation therapy. MATERIALS AND METHODS: To examine the impact of anemia in stage III NSCLC patients undergoing combined modality therapy, we reviewed our database from three sequential trials of concurrent weekly paclitaxel +/- carboplatin and radiation therapy. 115 pts from 17 institutions were enrolled from 4/94 to 5/97. In this series, hemoglobin values were collected before treatment and weekly during radiotherapy. We correlated baseline Hb and Hb changes during chemoradiation treatment with overall survival. RESULTS: Although pretreatment anemia was common (30% Hb = 110-130 g/l, 16% Hb <110 g/l), log-rank analyses of presenting Hb, average Hb and minimum Hb during treatment were not statistically significantly predictive of survival. However in a Cox model, declining hemoglobin during chemoradiation had a statistically significant impact on survival. CONCLUSIONS: These analyses reveal that a decline in hemoglobin during chemoradiation for stage III NSCLC has a statistically significant correlation with overall survival. Strategies maximizing hemoglobin during combined modality therapy need further exploration in well-planned randomized trials.

Adult↗
PubMed2002

Influence of aboriginal and socioeconomic status on birth outcome and maternal morbidity.

OBJECTIVE: To assess the association of Aboriginal and socioeconomic status with birth outcome and maternal morbidity in Alberta. METHODS: A retrospective cohort study using Alberta health service and vital statistics data from 1997 to 2000. Aboriginal women registered with the Department of Indian and Northern Development (DIAND) were linked to a personal health number. Low socioeconomic status was defined as either receiving subsidization for the Alberta Health Care Insurance premium or receiving welfare. RESULTS: Women registered with DIAND and women receiving subsidy or welfare were younger, more often unmarried, smoked more, consumed more alcohol, and abused more illicit drugs than other women in Alberta during the time period studied. Fewer women registered with DIAND and women receiving subsidy or welfare had physician prenatal visits, attended prenatal classes, had forceps or vacuum deliveries, and more of these women frequently had gestation ages less than 37 weeks. Women registered with DIAND had more deliveries in smaller, non-metropolitan facilities; and more of these women delivered outside their region of residence; more had longer lengths of hospital stay; more mothers and neonates were re-admitted to hospital within 28 days of discharge after delivery; fewer delivered small for gestational age neonates; fewer delivered neonates with birth weight less than 2500 g, but more delivered neonates with birth weight greater than 4000 g. There were fewer Caesarean sections in women registered with DIAND (OR = 0.84, 95% CI 0.76-0.93) and in women receiving subsidy or welfare (OR = 0.88, 95% CI 0.82-0.93). CONCLUSION: Women receiving subsidy or welfare and women registered with DIAND had many demographic similarities and generally had worse maternal and neonatal outcomes than other women in Alberta. Medical system interaction may be different for these two groups of women than it is for other women in Alberta.

Adolescent↗
PubMed2002

Cost analysis of ongoing care of patients with end-stage renal disease: the impact of dialysis modality and dialysis access.

BACKGROUND: Care of patients with end-stage renal disease (ESRD) is important and resource intense. To enable ESRD programs to develop strategies for more cost-efficient care, an accurate estimate of the cost of caring for patients with ESRD is needed. METHODS: The objective of our study is to develop an updated and accurate itemized description of costs and resources required to treat patients with ESRD on dialysis therapy and contrast differences in resources required for various dialysis modalities. One hundred sixty-six patients who had been on dialysis therapy for longer than 6 months and agreed to enrollment were followed up prospectively for 1 year. Detailed information on baseline patient characteristics, including comorbidity, was collected. Costs considered included those related to outpatient dialysis care, inpatient care, outpatient nondialysis care, and physician claims. We also estimated separately the cost of maintaining the dialysis access. RESULTS: Overall annual cost of care for in-center, satellite, and home/self-care hemodialysis and peritoneal dialysis were US $51,252 (95% confidence interval [CI], 47,680 to 54,824), $42,057 (95% CI, 39,523 to 44,592), $29,961 (95% CI, 21,252 to 38,670), and $26,959 (95% CI, 23,500 to 30,416), respectively (P < 0.001). After adjustment for the effect of other important predictors of cost, such as comorbidity, these differences persisted. Among patients treated with hemodialysis, the cost of vascular access-related care was lower by more than fivefold for patients who began the study period with a functioning native arteriovenous fistula compared with those treated with a permanent catheter or synthetic graft (P < 0.001). CONCLUSION: To maximize the efficiency with which care is provided to patients with ESRD, dialysis programs should encourage the use of home/self-care hemodialysis and peritoneal dialysis.

Adult↗
PubMed2002

Regulation of eosinophil-active cytokine production from human cord blood-derived mast cells.

Human mast cells are multifunctional tissue-dwelling cells that play a crucial role in eosinophil-dependent disorders, such as asthma and parasitic diseases, by the secretion of eosinophil-active mediators. Mast cell-derived cytokines, generated in response to cross-linking of the high-affinity IgE receptor, can regulate eosinophil activation, survival, and chemotaxis. In this study, mast cells generated from human cord blood progenitors (stem cells) were studied for eosinophil-active inflammatory cytokine expression. Cord blood-derived mast cells (CBDMC) expressed typical intracellular scroll granules and microvilli-like structures on their cell surfaces, demonstrated the presence of tryptase, and elaborated prostaglandin D2 (PGD2) after cross-linkage of the high-affinity receptor for IgE (FcepsilonRI). CBDMC expressed tumor necrosis factor-alpha (TNF-alpha) and the eosinophil-active growth factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation. (IL-1beta greatly enhanced IgE-dependent production of these cytokines in response to FcepsilonRI cross-linkage, suggesting a role for bystander/phagocytic cells in modulating mast cell function. In contrast, interferon-alpha (IFN-alpha) inhibited IL-5 and GM-CSF generation, and the glucocorticoid, dexamethasone (Dex), inhibited production of IL-5 and GM-CSF from CBDMC. A macrophage-mast cell-eosinophil axis may exist in vivo that may be susceptible to pharmacologic manipulation.

Cells, Cultured↗
PubMed2002

The association between heart rate and in-hospital mortality after coronary artery bypass graft surgery.

UNLABELLED: Avoidance of tachycardia is a commonly described goal for anesthetic management during coronary artery bypass graft (CABG) surgery. However, an association between increased intraoperative heart rate and mortality has not been described. We conducted an observational study to evaluate the association between preinduction heart rate (heart rate upon arrival to the operating room) and in-hospital mortality during CABG surgery. Data were collected on 5934 CABG patients. Fifteen percent of patients had an increased preinduction heart rate > or =80 bpm. Crude mortality was significantly more frequent among patients with increased preinduction heart rate (P(trend) = 0.002). After adjustment for baseline differences among patients, preinduction heart rate > or =80 bpm remained associated with increased mortality (P(trend) < 0.001). The increased heart rate may be a cause of the observed mortality. Alternatively, faster heart rate may be either a marker of patients with irreversible myocardial damage, or a marker of patients with limited cardiac reserve at risk for further injury. Lastly, faster heart rate may be a marker for under-use of beta-adrenergic blockade. Because the use of preoperative beta-adrenergic blockade in CABG patients is associated with improved in-hospital survival, further investigation concerning the effect of intraoperative treatment of increased heart rate with beta-adrenergic blockers on mortality after CABG surgery is warranted. IMPLICATIONS: We conducted an observational study to evaluate the association between heart rate upon arrival to the operating room (preinduction heart rate) and in-hospital mortality during coronary artery bypass graft surgery. After adjustment for baseline differences among patients, preinduction heart rate > or =80 bpm was associated with an increased in-hospital mortality after coronary artery bypass graft surgery.

Adrenergic beta-Antagonists↗
PubMed2002

Intraparenchymal tension pneumatocele complicating frontal sinus osteoma: case report.

OBJECTIVE AND IMPORTANCE: A relatively rare condition of intraparenchymal tension pneumatocele secondary to a frontal sinus osteoma eroding posteriorly and breaching dura mater is described. The scanty body of literature on this subject is briefly summarized, and the importance of this condition as a result of its life-threatening but readily treatable intracranial mass effect is outlined. CLINICAL PRESENTATION: The patient presented with acute deterioration in conscious state and lateralizing signs from the mass effect of gas under tension. Two weeks earlier, he had experienced vague and subtle changes in personality noticeable only to his family. INTERVENTION: The patient was cured by a frontal craniotomy, partial excision of the osteoma, and suture repair of the dural defect after evacuation of the pressurized air cavity. CONCLUSION: This rare condition should be urgently treated in the event of acute deterioration. To prevent a life-threatening situation from arising, elective surgery should be considered for patients known to have air sinus osteomas that are at risk of erosion into the cranial cavity.

Craniotomy↗