Intravenous iron products.
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Anemia, Iron-Deficiency↗
Biomedical subjects
C A Johnson
Publications and source records attributed to C A Johnson.
Simulation of longitudinal threshold visual field data.
PURPOSE: To describe and evaluate a computer model that simulates longitudinal visual field data. METHODS: A computer model was designed using factors that influence thresholds of normal and glaucomatous visual fields. The simulation model was used to quantify the effects of fluctuation on the outcomes of pointwise linear regression by comparison with simulated gold standard data with no variability. RESULTS: Serial sets of 10 stable and 10 progressive visual fields with different fluctuation levels were generated by simulation and were analyzed using pointwise linear regression. Regression outcome measures used were slopes of -1 dB/year or worse and slopes of -1 dB/year or worse that were also statistically significant. In stable visual fields, the number of locations with regression slopes worse than -1 dB/year increased with fluctuation and defect size and was inversely related to the number of fields. The number of locations with statistically significant slopes remained low and appeared unaffected by these variables. In progressive visual fields, analysis of a small number of visual field test results (<8) overestimated the number of locations with regression slopes worse than -1 dB/year and underestimated the number of locations with statistically significant slopes. CONCLUSIONS: Computer simulation may be used to provide a gold standard outcome that permits evaluation of statistical tools for monitoring progressive glaucomatous visual field loss.
Computer Simulation↗
Predicting binocular visual field sensitivity from monocular visual field results.
PURPOSE: To compare methods of predicting binocular visual field sensitivity of patients with glaucoma from monocular visual field data. METHODS: Monocular and binocular visual fields were obtained for 111 patients with varying degrees of glaucomatous damage in one or both eyes, using the Humphrey 30-2 full-threshold procedure. Four binocular sensitivity prediction models were evaluated: BEST EYE, predictions based on individual values for the most sensitive eye, defined by mean deviation (MD); AVERAGE EYE, predictions based on the average sensitivity between eyes at each visual field location; BEST LOCATION, predictions based on the highest sensitivity between eyes at each visual field location; and BINOCUIAR SUMMATION, predictions based on binocular summation of sensitivity between eyes at each location. Differences between actual and predicted binocular sensitivities were calculated for each model. RESULTS: The average difference between predicted and actual binocular sensitivities was close to zero for the BINOCULAR SUMMATION and BEST LOCATION models, with 95% of all predictions being within +/-3 dB of actual binocular sensitivities. The best eye (MD) prediction had an average error of 1.5 dB (95% confidence limits [CL], +/-3.7 dB). The average eye prediction was the poorest, with an average error of 3.7 dB (95% CL, +/-4.6 dB). CONCLUSIONS: The BINOCULAR SUMMATION and BEST LOCATION models provided better predictions of binocular visual field sensitivity than the other two models, with a statistically significant difference in performance. The small difference in performance between the BINOCULAR SUMMATION and BEST LOCATION models was not statistically significant. For evaluations of functional visual field influences on task performance, daily activities, and related quality-of-life issues, either the BINOCULAR SUMMATION or BEST LOCATION model provides good estimates of binocular visual field sensitivity.
Glaucoma↗
The natural history of cervical cryosurgical healing. The minimal effect of debridement of the cervical eschar [see comment].
BACKGROUND: Cryosurgery is a favored treatment method for cervical intraepithelial neoplasia (CIN) among family physicians, in part because it is inexpensive and requires the least technical training and skill. Although cervical cryosurgery has been used for more than 30 years, the natural history of the postprocedure process has never been described. The primary purpose of our study was to describe the natural history of the healing process after cervical cryosurgery. A secondary purpose was to determine the effect of mechanical debridement of the cervical eschar on the symptoms of healing. METHODS: We conducted a prospective multicentered trial in which women who had a histologic ally documented CIN lesion underwent cervical cryosurgery. Forty-six women were randomized to undergo eschar debridement at 48 hours after cryosurgey, and 38 women received standard care. All women were followed up and given preweighed sanitary pads for hydrorrhea (watery discharge) collection and a diary to record the severity and number of days of odor, pain, cramping, and hydrorrhea that were experienced. RESULTS: The average total amount of hydrorrhea or discharge was 288 g, which required using an average of 41 sanitary pads during a period of 12.4 days. The duration of odor was 8.9 days, and the pain and cramping experienced after cryosurgery lasted 4.7 days. Women who were obese had greater hydrorrhea and pad usage than nonobese women. Debridement of the cervical eschar did not significantly change the signs and symptoms of healing after cryosurgery. CONCLUSIONS: There are significant symptoms patients experience after cryosurgery that are not ameliorated by debridement. The expectations of the cryosurgical healing process should be disclosed to women before the procedure.
Adult↗
Healing experiences after cervical cryosurgery.
BACKGROUND: Treatment for cervical intraepithelial neoplasia with cryosurgery is uncomfortable for many women. The subsequent healing process is also thought to bring discomfort. The purpose of our study was to describe women's experiences after cryosurgery, and how obesity, age, and gravidity affected, the healing process. METHODS: We developed a survey from focus group results to measure the unpleasantness of hydrorrhea (watery discharge) from cryosurgery, the pad protection required, and the odor associated with the hydrorrhea. The cryosurgical experiences were compared with normal menses for the use and frequency of pad protection, medications used, and any activity restrictions. RESULTS: Cryosurgical experiences were unpleasant for 78.3% of the women because of the pain and cramping of the procedure and the resulting hydrorrhea, odor, and necessity of wearing pads for protection. These experiences after cryosurgery caused 38.6% to restrict their activities and 67.1% to take medications, a significantly greater proportion than the 16.9% whose activities were restricted normal menses and the 26.8% who took medications for normal menses (P=-.004, P <.001, respectively). In addition to these experiences, obese, multigravid, and older women were more bothered by the duration of wearing pads than their counterparts (P=.0246, =.0061, and P=.0159, respectively). CONCLUSIONS: Our study showed that the cryosurgical healing process was not pleasant, and was least tolerable for obese, multigravid, and older women. As many as 50% of women undergoing cryosurgery will perceive the hydrorrhea, its odor, and the wearing of pads to be worse than normal menses, especially if their menses are usually light.
Adolescent↗
Regulation of arachidonic acid mobilization in lipopolysaccharide-activated P388D(1) macrophages by adenosine triphosphate.
Murine P388D(1) macrophages exhibit a delayed prostaglandin biosynthetic response when exposed to bacterial lipopolysaccharide (LPS) for prolonged periods of time that is dependent on induction of the genes coding for Group V secretory phospholipase A(2) and cyclooxygenase-2. We herein report that LPS-induced arachidonic acid (AA) metabolite release in P388D(1) macrophages is strongly attenuated by the P2X(7) purinergic receptor antagonists periodate-oxidized ATP and pyridoxal-phosphate-6-azophenyl-2', 4'-disulfonic acid, and this is accompanied by suppression of the expression of both Group V secretory phospholipase A(2) and cyclooxygenase-2. The effect appears to be specific for LPS, because the P2 purinergic receptor antagonists do not affect P388D(1) cell stimulation by other stimuli such as platelet-activating factor or the Ca(2+) ionophore A23187. Moreover, extracellular nucleotides are found to stimulate macrophage AA mobilization with a pharmacological profile that implicates the participation of the P2X(7) receptor and that is inhibited by periodate-oxidized ATP. Collectively these results demonstrate coupling of the P2X(7) receptor to the AA cascade in P388D(1) macrophages and implicate the participation of this type of receptor in LPS-induced AA mobilization.
Adenosine Triphosphate↗
Regulation of cyclooxygenase-2 expression by phosphatidate phosphohydrolase in human amnionic WISH cells.
Prostaglandins are known to play a key role in the initiation of labor in humans, but the mechanisms governing their synthesis in amnion are largely unknown. In this study, we have examined the regulatory pathways for prostaglandin E(2) (PGE(2)) production during protein kinase C-dependent activation of human WISH cells. In these cells, PGE(2) synthesis appears to be limited not by free arachidonic acid availability but by the expression levels of cyclooxygenase-2 (COX-2). Concomitant with the cells being able to synthesize and secrete PGE(2), we detected significant elevations of both COX-2 protein and mRNA levels. Specific inhibition of COX-2 by NS-398 totally ablated PGE(2) synthesis. All of these responses were found to be strikingly dependent on an active phosphatidate phosphohydrolase 1 (PAP-1). Inhibition of PAP-1 activity by three different strategies (i.e. use of bromoenol lactone, propranolol, and ethanol) resulted in inhibition of COX-2 expression and hence of PGE(2) production. These data unveil a novel signaling mechanism for the regulation of PGE(2) production via regulation of COX-2 expression and implicate phosphatidate phosphohydrolase 1 as a key regulatory component of eicosanoid metabolic pathways in the amnion.
Amnion↗
Group V phospholipase A(2)-dependent induction of cyclooxygenase-2 in macrophages.
When exposed for prolonged periods of time (up to 20 h) to bacterial lipopolysaccharide (LPS) murine P388D(1) macrophages exhibit a delayed prostaglandin biosynthetic response that is entirely mediated by cyclooxygenase-2 (COX-2). Both the constitutive Group IV cytosolic phospholipase A(2) (cPLA(2)) and the inducible Group V secretory phospholipase A(2) (sPLA(2)) are involved in the cyclooxygenase-2-dependent generation of prostaglandins in response to LPS. Using the selective sPLA(2) inhibitor 3-(3-acetamide-1-benzyl-2-ethylindolyl-5-oxy)propane sulfonic acid (LY311727) and an antisense oligonucleotide specific for Group V sPLA(2), we found that induction of COX-2 expression is strikingly dependent on Group V sPLA(2), which was further confirmed by experiments in which exogenous Group V sPLA(2) was added to the cells. Exogenous Group V sPLA(2) was able to induce significant arachidonate mobilization on its own and to induce expression of the COX-2. None of these effects was observed if inactive Group V sPLA(2) was utilized, implying that enzyme activity is crucial for these effects to take place. Therefore, not only delayed prostaglandin production but also COX-2 gene induction are dependent on a catalytically active Group V sPLA(2). COX-2 expression was also found to be blunted by the Group IV cPLA(2) inhibitor methyl arachidonyl fluorophosphonate, which we have previously found to block Group V sPLA(2) induction as well. Collectively, the results support a model whereby Group IV cPLA(2) activation regulates the expression of Group V sPLA(2), which in turn is responsible for delayed prostaglandin production by regulating COX-2 expression.
Animals↗
Trainees' activities and experiences after a clinical pharmacy dialysis traineeship.
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Adult↗
Group-specific assays that distinguish between the four major types of mammalian phospholipase A2.
Phospholipase A2 (PLA2) constitutes a diverse superfamily of enzymes which catalyze the deacylation of phospholipids. At least four types of PLA2 are potentially involved in arachidonic acid release in cells and tissues. Since all of them catalyze the same enzymatic reaction, it is difficult to distinguish between them in mixtures of enzymes normally present in biological samples. Utilizing specific properties of each PLA2, we have designed distinct assay procedures which selectively and sensitively detect each type: Group VI Ca2+-independent PLA2, Group IV cytosolic Ca2+-dependent PLA2, Groups V and IIA secreted PLA2s. Each specific assay procedure is selective for a particular PLA2 type by at least fourfold and as high as four orders of magnitude relative to the other three enzymes. All assays can detect PLA2 activity with as low as subnanogram quantities of enzyme. Importantly, these assays are able to differentiate and quantitate the biochemically and structurally related enzymes, Group IIA and V sPLA2s in crude biological samples. Employing this system, we have found that iPLA2 is the dominant PLA2 in rat brain, and cPLA2 is the most abundant PLA2 in P388D1 macrophages and human amnionic WISH cells.
Animals↗
Regulation of delayed prostaglandin production in activated P388D1 macrophages by group IV cytosolic and group V secretory phospholipase A2s.
Group V secretory phospholipase A2 (sPLA2) rather than Group IIA sPLA2 is involved in short term, immediate arachidonic acid mobilization and prostaglandin E2 (PGE2) production in the macrophage-like cell line P388D1. When a new clone of these cells, P388D1/MAB, selected on the basis of high responsivity to lipopolysaccharide plus platelet-activating factor, was studied, delayed PGE2 production (6-24 h) in response to lipopolysaccharide alone occurred in parallel with the induction of Group V sPLA2 and cyclooxygenase-2 (COX-2). No changes in the level of cytosolic phospholipase A2 (cPLA2) or COX-1 were observed, and Group IIA sPLA2 was not detectable. Use of a potent and selective sPLA2 inhibitor, 3-(3-acetamide 1-benzyl-2-ethylindolyl-5-oxy)propanesulfonic acid (LY311727), and an antisense oligonucleotide specific for Group V sPLA2 revealed that delayed PGE2 was largely dependent on the induction of Group V sPLA2. Also, COX-2, not COX-1, was found to mediate delayed PGE2 production because the response was completely blocked by the specific COX-2 inhibitor NS-398. Delayed PGE2 production and Group V sPLA2 expression were also found to be blunted by the inhibitor methylarachidonyl fluorophosphonate. Because inhibition of Ca2+-independent PLA2 by an antisense technique did not have any effect on the arachidonic acid release, the data using methylarachidonyl fluorophosphonate suggest a key role for the cPLA2 in the response as well. Collectively, the results suggest a model whereby cPLA2 activation regulates Group V sPLA2 expression, which in turn is responsible for delayed PGE2 production via COX-2.
Animals↗
A specific human lysophospholipase: cDNA cloning, tissue distribution and kinetic characterization.
Lysophospholipases are critical enzymes that act on biological membranes to regulate the multifunctional lysophospholipids; increased levels of lysophospholipids are associated with a host of diseases. Herein we report the cDNA cloning of a human brain 25 kDa lysophospholipid-specific lysophospholipase (hLysoPLA). The enzyme (at both mRNA and protein levels) is widely distributed in tissues, but with quite different abundances. The hLysoPLA hydrolyzes lysophosphatidylcholine in both monomeric and micellar forms, and exhibits apparent cooperativity and surface dilution kinetics, but not interfacial activation. Detailed kinetic analysis indicates that the hLysoPLA binds first to the micellar surface and then to the substrate presented on the surface. The kinetic parameters associated with this surface dilution kinetic model are reported, and it is concluded that hLysoPLA has a single substrate binding site and a surface recognition site. The apparent cooperativity observed is likely due to the change of substrate presentation. In contrast to many non-specific lipolytic enzymes that exhibit lysophospholipase activity, hLysoPLA hydrolyzes only lysophospholipids and has no other significant enzymatic activity. Of special interest, hLysoPLA does not act on plasmenylcholine. Of the several inhibitors tested, only methyl arachidonyl fluorophosphonate (MAFP) potently and irreversibly inhibits the enzymatic activity. The inhibition by MAFP is consistent with the catalytic mechanism proposed for the enzyme - a serine hydrolase with a catalytic triad composed of Ser-119, Asp-174 and His-208.
Amino Acid Sequence↗
Preventive services received by adolescents with cystic fibrosis and sickle cell disease.
OBJECTIVE: To determine the proportion of adolescents with cystic fibrosis (CF) or sickle cell disease (SCD) who reported speaking with their physicians about health-promoting and risky behaviors and whether the rate of discussions varied by whether the main physician was a primary care provider or specialist. HYPOTHESIS: Adolescents reporting a primary care provider as their main physician would be more likely to have received risk behavior counseling and other preventive services. DESIGN: Survey. SETTING: Comprehensive CF and SCD centers in 5 North Carolina referral hospitals. PARTICIPANTS: Three hundred twenty-one (74%) of 437 adolescents aged 12 through 19 years (mean age, 15.6 years; 51% male) with CF or SCD identified through center registries. MAIN OUTCOME MEASURES: Sources of health care, main physician, and recall of discussions with physicians regarding sexual issues, substance use, weight or dieting, safety issues, depression, and violence. RESULTS: Adolescents with CF (53%) or SCD (46%) most commonly reported a specialist as their main physician. For those (83%) who saw their main physician in the past year, adolescents with SCD reported counseling rates ranging from 43% for sexuality to 15% for weapon carrying or fighting. For adolescents with CF, rates ranged from 65% for weight and dieting to 30% for sexuality and 6% for weapon carrying or fighting. Adolescents whose main physician was a primary care provider were no more or less likely to report counseling for any topic (all P>.05). CONCLUSIONS: Physicians, regardless of specialty, infrequently discussed common behavioral issues with these adolescents with CF or SCD. A coordinated effort between primary care physicians and specialists may be helpful in delivering optimal preventive services to this population.
Adolescent↗
Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada.
Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.
Adolescent↗
Patterns of medical practice in cystic fibrosis: part I. Evaluation and monitoring of health status of patients. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.
This report characterizes patterns of evaluation and monitoring of the health status of patients with cystic fibrosis (CF) as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF), and compares these practices to published guidelines. All patients (18,411) who enrolled in ESCF at 194 study sites in the United States and Canada from December 1, 1993 to December 31, 1995 were considered for study. Patients enrolled before January 1, 1995 with >/=1 healthcare encounters during 1995 (12,631) were included in the analysis. Patients enrolled after January 1, 1995 (5,266), or who died (354), withdrew from the study (128), or were lost to follow-up (21) were excluded. Frequency of encounters (outpatient and hospital), spirometry, respiratory tract cultures, and chest radiographs were recorded during a 1-year period (1995) and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The 12,631 patients had 53,024 outpatient visits. In 57.5% of patients, the recommended criteria of >/=4 total visits per year were met. Only 27.4% of all patients had >/=4 routine visits; 3.1% had only sick visits, and 59.0% had no sick visits. One third (34.6%) were hospitalized at least once, for a total of 8,561 hospitalizations. Older patients with lower pulmonary function and Pseudomonas in their respiratory tract had fewer routine visits and more sick visits, and were hospitalized more than were younger patients. In three fourths (75.8%) of patients the recommended criterion of two spirometry assessments per year was met, whereas in 79.3% the criterion of one culture was met, and in 68.3% the criterion of one radiograph/year was met. We conclude that in the majority of CF patients, the recommended criteria for routine evaluation and monitoring were met. However, in a rather substantial number they were not. An increase in the utilization of healthcare resources was observed in patients with more severe disease. This information will help to establish benchmarks for future quality assessment programs.
Adolescent↗
Patterns of medical practice in cystic fibrosis: part II. Use of therapies. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.
This report describes the prescribing pattern of therapeutic interventions in the management of patients with cystic fibrosis (CF), as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF). Use of 20 therapies by 12,622 patients was recorded from each health care encounter (53,024 outpatient visits and 8,561 hospitalizations) during a 1-year period (1995), and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The percentage of patients using the following pulmonary therapies was observed (in descending order): airway clearance techniques (88.2%); inhaled bronchodilators (82.2%); oral antibiotics (excluding quinolones) (68. 2%); dornase alfa (52.9%); intravenous antibiotics (34.4%); oral quinolones (34.4%); inhaled antibiotics (34.3%); mast cell stabilizers (29.5%); inhaled corticosteroids (25.9%); oral corticosteroids (17.1%); oral bronchodilators (16.2%); oxygen (8. 1%); inhaled mucolytic agent acetyl cysteine (6.5%); and diuretics (1.4%). The percentage of patients using nutritional therapies was: pancreatic enzymes (96%); oral nutritional supplements (31.1%); enteral nutrition (7.3%); and parenteral nutrition (0.7%). The percentage of patients using other therapies was: nonsteroidal anti-inflammatory drugs (7.9%); and insulin or oral hypoglycemic agents (6.1%). The general trend was for therapies to be used more by older patients, those with lower pulmonary function, and by those with Pseudomonas in their respiratory tract. Exceptions to this trend occurred for airway clearance, oral antibiotics, mast cell stabilizers, and pancreatic enzymes. Four therapies (oral nutritional supplements, parenteral nutrition, diuretics, and pancreatic enzymes) were used more by males than females. However, there was no gender difference for this group of therapies on pulmonary or nutritional status.
Adolescent↗
Histone deacetylases: complex transducers of nuclear signals.
Histone acetylation influences both gene transcription and chromatin assembly after DNA replication and the enzymes that regulate this property of chromatin are likely to play a key role in regulating these crucial genomic functions. The steady-state level of histone acetylation is established and maintained by multiple histone acetyltransferases (HATs) and deacetylases (HDACs). Both groups of enzymes contain numerous family members, most of which have been highly conserved through evolution. The HDACs have been implicated in repression of gene expression by facilitating chromatin condensation and, like the HATs, operate as part of multi-protein complexes. The non-catalytic components of these complexes can either target the catalytic subunit to specific sites on the genome or regulate its enzymatic specificity. Kinase and phosphatase activities of intracellular signal transduction pathways may modify components of these complexes and thereby regulate their assembly, targeting or enzymatic function.
Amino Acid Sequence↗
The influence of ocular pulsatility on scanning laser Doppler flowmetry.
PURPOSE: To determine the effect of the cardiac cycle on scanning laser Doppler flowmeter measurements of retinal capillary blood flow in rhesus monkeys and humans. METHODS: Multiple scanning laser Doppler flowmetry images of rhesus monkey and human retinal capillary blood flow over a range of heart rates were obtained. Average flow values were determined for the 64 scan lines that compose the two-dimensional flow map. Cutaneous blood flow was measured simultaneously with a laser Doppler flowmeter. The temporal relationships between retinal capillary blood flow, peripheral arterial pulse, and cutaneous blood flow were determined. In addition, human retinal capillary blood flow in a 10 x 10-pixel area during different phases of the cardiac cycle was compared. RESULTS: Regular oscillations in human and rhesus monkey retinal capillary blood flow are evident as alternating bright and dark horizontal bands in scanning laser Doppler flowmetry images. These fluctuations are temporally correlated with cutaneous blood flow. Linear regression of actual vs predicted heart rate based on peaks in retinal capillary flow yielded r = 0.999 in a rhesus monkey and 0.938 in a human. Retinal capillary blood flow in a 10 x 10-pixel area fluctuated as much as 50% depending on the phase of the cardiac cycle. CONCLUSIONS: The alternating bright and dark banding pattern observed in scanning laser Doppler flowmetry scans of retinal capillary blood flow is related to the cardiac pulse. The errors introduced by pulse-related fluctuations in retinal capillary blood flow are significant and must be minimized or corrected for accurate and reproducible measurements of ocular hemodynamics.
Animals↗