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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 361 records · Page 20Linked to original sources

Cytomegalovirus retinitis in AIDS patients: influence of cytomegaloviral load on response to ganciclovir, time to recurrence and survival.

OBJECTIVES: Despite life-long maintenance therapy, cytomegalovirus (CMV) retinitis frequently progresses in patients with AIDS. Virological markers that could clarify pathogenesis and identify risk factors for progression are required. DESIGN AND METHODS: We prospectively recruited 45 patients with CMV retinitis. Blood and urine samples were collected before and after induction therapy, and on a monthly basis thereafter during routine medical and ophthalmological assessment, and at any time retinitis progressed. CMV load was measured by quantitative-competitive polymerase chain reaction (PCR). RESULTS: The median time to first progression of retinitis was 78 days and to death was 8.7 months. Eighty-five per cent of patients who were PCR-positive at diagnosis of retinitis became PCR-negative after 21 days of ganciclovir induction therapy. Six patients who remained PCR-positive after 21 days of treatment had a significantly higher CMV load at presentation (P = 0.005), and a shorter time to first progression of retinitis of 40 days. High CMV loads in blood at presentation were associated with a shorter time to progression (P = 0.16; relative hazard, 1.57) and a significantly shorter time to death (P = 0.004; relative hazard, 1.76). This significant relationship with survival remained after adjustment for potential confounding variables (CD4 count, age, method of drug administration). CONCLUSIONS: We conclude that CMV load in the blood of AIDS patients is an important factor in the pathogenesis of retinitis, and quantification of CMV could be used to both select patients for controlled clinical trials and to optimize individual anti-CMV induction therapy.

AIDS-Related Opportunistic Infections↗

Efficacy of convective removal of plasma mediators of endotoxic shock by continuous veno-venous hemofiltration.

Continuous veno-venous hemofiltration (CVVH) has been reported to provide beneficial effects during endotoxic shock. This experiment was designed to determine if selective removal of plasma mediators occurs during CVVH and if plasma concentrations of these mediators are reduced. A swine endotoxic-shock model with three groups was used (lipopolysaccharide (LPS) only (n = 6); LPS followed by CVVH (n = 6); and LPS followed by sham CVVH (n = 4). Plasma and filtrate samples were collected at frequent intervals for 5 h. Lactic acid (LA), eicosanoids [prostacyclin (6-keto PGF1 alpha), thromboxane (TxB2), and prostaglandin E2 (PGE2)] and tumor necrosis factor (TNF) were measured in plasma and filtrate. Plasma concentrations of 6-keto PGF1 alpha, TxB2, TNF, and LA were not significantly different in any group. LA, PGE2, 6-keto PGF1 alpha, and TXB2 concentrations were similar in filtrate and plasma. TNF did not move across the membrane into the filtrate, CVVH, as used in this experiment, did not significantly reduce plasma concentrations of any of these mediators.

Animals↗

Biotin synthase from Arabidopsis thaliana. cDNA isolation and characterization of gene expression.

The full-length BIO2 cDNA from Arabidopsis thaliana was isolated using an expressed sequence tag that was homologous to the Escherichia coli biotin synthase gene (BioB). Comparisons of the deduced amino acid sequence from BIO2 with bacterial and yeast biotin synthase homologs revealed a high degree of sequence similarity. The amino terminus of the predicted BIO2 protein contains a stretch of hydrophobic residues similar in composition to transit peptide sequences. BIO2 is a single-copy nuclear gene in Arabidopsis that is expressed at high levels in the tissues of immature plants. Expression of BIO2 was higher in the light relative to dark and was induced 5-fold during biotin-limited conditions. These results demonstrate that expression of at least one gene in this pathway is regulated in response to developmental, environmental, and bio-chemical stimuli.

Amino Acid Sequence↗

Skin surface lipids in HIV-positive patients with and without seborrheic dermatitis.

BACKGROUND: Seborrheic dermatitis (SD) is a frequent complication of infection with the human immunodeficiency virus (HIV). Most studies examining the cause of SD have concentrated on the roles of Pityrosporum ovale and sebaceous lipids. Previous studies of skin surface lipid from patients with SD have produced conflicting results, with some authors reporting an abnormal lipid composition and others finding little or no abnormality. METHODS: The composition of skin surface lipid was studied in 15 HIV-positive and 10 HIV-negative men with SD, in 14 HIV-positive men without SD, and in 16 unaffected controls. Total lipids were extracted from unaffected forehead skin into petroleum ether and separated into lipid classes by thin layer chromatography. The lipid classes were quantitated by densitometry after charring with sulfuric acid. RESULTS: Patients, HIV-positive with SD, had significantly lower proportions of free fatty acid (FFA) and higher levels of triglyceride than normal controls. Patients, HIV-positive without SD, had a significantly increased proportion of FFA compared to HIV-positive patients with SD. Patients with SD, both HIV-positive and HIV-negative, had a similar pattern of skin surface lipid. Levels of FFA were lower and those of triglyceride higher than in the patients unaffected by SD, whether HIV-positive or not. There was no significant difference found between groups in free cholesterol, wax esters, and squalene. CONCLUSIONS: Abnormalities of skin surface lipid composition may play a part in the development of SD in both HIV-positive and HIV-negative men.

Adult↗

Classifying nursing-sensitive patient outcomes.

This report describes research at the University of Iowa College of Nursing to develop a comprehensive classification of nursing-sensitive patient outcomes. The Nursing-Sensitive Outcomes Classification (NOC) completes the nursing process elements of the Nursing Minimum Data Set (NMDS). We describe resolution of conceptual and methodological problems that define the inductive approach taken to develop the NOC. Strategies used to develop NOC included review of the literature, clinical databases and instruments; concept analysis; and surveys of nurse experts. Examples of outcomes, definitions, and indicators are presented. The NOC provides standardized patient outcomes for determining the effectiveness of nursing interventions and enables inclusion of these data in data sets for healthcare effectiveness research.

Adult↗

Antibody responses to Haemophilus influenzae type b conjugate vaccine in sickle cell disease.

OBJECTIVE: To investigate the immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines in children with sickle cell disease. DESIGN: Open study. SETTING: Haemoglobinopathy clinic. SUBJECTS: Children with homozygous haemoglobin SS disease (HbSS), sickle haemoglobin C disease (HbSC), and sickle-beta thalassaemia disease (HbS-beta Thal). INTERVENTIONS: Children over the age of 2 years received a single dose of Hib-tetanus toxoid conjugate vaccine (PRP-T). MAIN OUTCOME MEASURES: Antibody response to Hib polysaccharide (PRP) approximately one month after vaccination. RESULTS: 77 children over the age of 2 years were studied,, 55 with HbSS, 16 with HbSC, and six with HbS-beta Thal. Before vaccination, 44% had anti-PRP IgG titres less than the level associated with long term protection (1.0 microgram/ml). After a single dose of PRP-T all children mounted an antibody titre > 1 microgram/ml. Geometric mean anti-PRP IgG titre achieved postvaccination (45.2 micrograms/ml 95% confidence interval (CI) 31.6 to 64.8) was comparable to that of a healthy population. Children with HbSC, however, had a significantly higher antibody titre postvaccination (91.1 micrograms/ml; 95% CI 32.7 to 254.4) than the children with HbSS (36.7 micrograms/ml; 95% CI 25.1 to 52.9). CONCLUSIONS: Children with a diagnosis of sickle cell disease who are over the age of 2 years make a vigorous antibody response to a single dose of PRP-T vaccine and hence we suggest unimmunised individuals in this group should receive a single dose of a Hib conjugate vaccine.

Adolescent↗

Aldosterone and insulin stimulate amiloride-sensitive sodium transport in A6 cells by additive mechanisms.

The individual effects of aldosterone and insulin on amiloride-sensitive Na+ transport in model renal epithelia have been well characterized. However, in the physiological state, many hormones are present concurrently and their interactions need to be addressed. We have found that, over 5 h, the effects of insulin and aldosterone are additive. This indicates that the biochemical pathways are largely independent. To delineate the signaling pathways, we examined the requirement for tyrosine kinases by using genistein, a tyrosine kinase inhibitor. Genistein blocks basal (constitutive) Na+ transport and inhibits insulin- and aldosterone-stimulated Na+ transport. From these results, we conclude that a tyrosine phosphorylation is an important component of amiloride-sensitive Na+ transport.

Aldosterone↗

Neoplastic fever.

Neoplastic fever, that is fever arising solely as a manifestation of malignancy, is not as common as was thought but still constitutes a troublesome symptom and is difficult to manage. The mechanism of neoplastic fever production involves cytokines such as tumour necrosis factor (TNF), interleukins 1 and 6 (IL-1, IL-6) and interferon (IFN), produced either by host macrophages in response to tumour, or sometimes by the tumour itself. The cytokines stimulate production of prostaglandins which act on the hypothalamus causing a change in the thermostatic set point. This mechanism is similar to that of infective fever. Paracetamol (acetaminophen) will often only partially lyse neoplastic fever but nonsteroidal anti-inflammatory drugs have been shown to be effective. On the basis of small studies, naproxen has been proposed as a useful test to discriminate between neoplastic and infective fever. If this is so, it must be acting through a pathway hitherto undescribed and specific to neoplastic fever. Other work shows that this group of drugs effectively lyses both types of fever. Therefore larger studies are needed to confirm or refute the "Naproxen test' and neoplastic fever remains a diagnosis of exclusion. In the future, cytokine antagonists may have a role in managing neoplastic fever, but, until their actions are better understood, nonsteroidal anti-inflammatory drugs remain the medication of choice if standard antipyretics have failed.

Analgesics, Non-Narcotic↗

A method to produce sedation in critically ill patients.

OBJECTIVE: To evaluate a protocol based on continuous infusion of a benzodiazepine and morphine to produce apnea/decreased respiratory effort as an adjunct to complex mechanical ventilation in patients with respiratory failure. DESIGN: Observational report of consecutive patients. SETTING: University medical intensive care unit. PATIENTS: Seventeen consecutive patients with acute respiratory failure requiring high levels of sedation and/or paralysis to facilitate mechanical ventilation were studied. INTERVENTIONS: Patients were started on a continuous infusion of a benzodiazepine and morphine soon after mechanical ventilation was instituted. The dosages of the benzodiazepine and morphine were increased to the end point of diminished respiratory effort or apnea depending on the clinical status of the patient and ventilatory mode. This regimen was supplemented with single doses of neuromuscular blocking agents (NMBAs) only as the dosages of benzodiazepine/narcotic were being titrated. The benzodiazepine/narcotic agents were then gradually reduced as the patient's condition improved, often using an oral route of administration. MEASUREMENTS AND RESULTS: The benzodiazepine/morphine combination produced apnea and diminished respiratory effort in patients requiring sedation from 2 to 50 days, including those with hemodynamic instability, hepatic dysfunction, renal dysfunction, and sepsis. The combination allowed the use of NMBAs to be minimized. There was no evidence of worsened hemodynamic instability as a result of the administration of these agents. The gastrointestinal tract could be used for nutrition in 8 of the 17 patients. CONCLUSIONS: Continuous infusion of a benzodiazepine and morphine controlled the respiratory rate in patients with severe respiratory failure requiring complex mechanical ventilatory support.

APACHE↗

The reliability and characteristics of the brief syntactic analysis.

BACKGROUND: Linguistic analysis is of great potential benefit to psychiatry as a research and assessment tool, but the skill and time it demands means that it has not been widely used. This paper describes a much simplified form of syntactic analysis. METHOD: A detailed protocol for the Brief Syntactic Analysis (BSA) was written, based on earlier work by Morice and Ingram. Three psychiatrists were trained in its use, and inter-rater reliability established through independent ratings of 12 transcripts taken from a mixed group of psychiatric patients and a group of non-psychiatric controls. Concurrent reliability of the BSA against the Morice and Ingram analysis was established by comparing measures from the two methods on 16 transcripts of mixed patients. RESULTS: There were high levels of agreement between the three psychiatrists and between the BSA and the Morice and Ingram analysis, although one-way ANOVA indicated that for some variables there were small but statistically significant absolute differences between the two. The reasons for this were discussed. A principal components analysis confirmed the presence of three factors corresponding closely to the three families of linguistic variables. CONCLUSIONS: The results indicate that psychiatrists can be trained to use a syntactic analysis with high levels of agreement. The BSA, which takes much less time to complete, produces measures that are comparable with the original analysis from which it was derived.

Cognition Disorders↗

Speech and language in first onset psychosis differences between people with schizophrenia, mania, and controls.

BACKGROUND: Several studies have revealed linguistic differences between diagnostic groups. This study investigates the extent to which these differences are accounted for by factors such as chronicity, or disturbances in cognition associated with acute psychosis. METHOD: Transcripts of interviews with patients suffering from RDC schizophrenia (n=38), mania (n=11) and controls (n=16) were examined using the Brief Syntactic Analysis (BSA). Patients were within two years of first onset of psychotic symptoms, and received tests of working memory and attention. RESULTS: The speech of patients with schizophrenia was syntactically less complex than that of controls. Patients with schizophrenia and mania made more errors than controls. These differences were, to some extent, related to group differences in social class, working memory and attention, although significant group differences in language persisted after the effects of covariates were removed. CONCLUSIONS: The study confirms the existence of differences in the speech of psychiatric patients. Low complexity appears to be a particular feature of speech in schizophrenia, even in the earliest stages of the condition. The importance of this finding is discussed in relation to two recent theories of schizophrenia: Crow's evolutionary model, and Frith's neuro-psychological model.

Bipolar Disorder↗

Stable activation and desensitization of beta 2-adrenergic receptor stimulation of adenylyl cyclase by salmeterol: evidence for quasi-irreversible binding to an exosite.

The relaxation of tracheal smooth muscle by the beta 2-adrenergic receptor (beta AR) agonist salmeterol displays several unusual properties: (i) slow onset of action (t1/2 = 5-15 min), (ii) prolonged activation (t1/2 = 8-14 hr), and (iii) the ability to recover from beta AR blockade. These properties led to the hypothesis that salmeterol binds with very high affinity to an exosite in addition to the beta AR activating site. Despite extensive characterization of salmeterol-induced bronchodilation, little is known about the molecular actions of salmeterol. We report the unique properties of salmeterol binding to the beta AR, activation of adenylyl cyclase, and desensitization of the hamster beta AR expressed in L cells. First, we found that salmeterol activation of adenylyl cyclase, although rapid and potent (low EC50 relative to epinephrine), was nevertheless remarkably inefficient relative to the full agonist epinephrine. Reduced coupling efficiency of salmeterol was demonstrated using formulations recently introduced by our group. Second, we found that pretreatment of L cells with salmeterol led to a stable activation of adenylyl cyclase that survives extensive wash procedures and sucrose step gradient purification of plasma membrane fractions. This activation of basal adenylyl cyclase did not require salmeterol binding to the classic active site during pretreatment, as it occurred in the presence of an excess of a beta AR antagonist. Third, we found that the rapid phase of salmeterol-induced desensitization was much reduced relative to epinephrine, consistent with its poor coupling efficiency and with its prolonged activation of adenylyl cyclase. These unique properties of salmeterol support the proposal that it binds reversibly to the activating or active site and as well to an extremely high affinity exosite from which it has access to the active site.

Adenylyl Cyclases↗

Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup.

OBJECTIVE: Nebulized budesonide and nebulized adrenaline have been shown to be effective in the treatment of moderately severe croup. However, there has been no direct comparison of these therapies. We undertook a multicenter, randomized, double-blind, parallel group study in 66 hospitalized children with viral or spasmodic croup. METHODS: Children 0.5 to 6 years of age were assessed using a validated croup symptom score (stridor, 0 through 4; cough, 0 through 3; retractions, 0 through 3; dyspnea, 0 through 3; and color, 0 through 4) at 0.5, 1, 1.5, 2, 12, and 24 hours after nebulization. Patients received either budesonide (2 mg/4 mL) or L-adrenaline (4 mg/4 mL) via nebulization. The primary outcome measure was change in the total croup symptom score. RESULTS: Thirty-five children received budesonide and 31 received adrenaline. There was no significant difference in baseline features, including croup score (mean [95% confidence interval]: budesonide, 7.1 [6.7-7.5]; adrenaline, 7.7 [7.3-8.1]). All patients had significant improvement from baseline, and there was not significant difference between the two treatments, as measured by change in croup scores, change in oxygen saturation, duration of hospitalization, number of subsequent treatments with systemic steroids or adrenaline, and adverse events. No child required intubation. CONCLUSION: This study does not show any difference in efficacy and safety between nebulized budesonide and nebulized adrenaline in the treatment of acute upper airway obstruction in patients with moderately severe croup.

Administration, Topical↗

Fluticasone propionate: safety profile.

Fluticasone propionate is a potent fluorinated corticosteroid used for the topical therapy of dermatoses and as inhalation therapy for bronchial asthma and allergic rhinitis. This agent has a good safety profile with a low propensity for systemic side effects, such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis, and a low incidence of local side effects such as pruritus, burning, or skin atrophy. The pharmacologic properties of fluticasone propionate-including high lipophilicity, high selectivity and affinity for the glucocorticoid receptor, low systemic absorption, and rapid metabolism and clearance-combine to give fluticasone propionate a high therapeutic index.

Administration, Topical↗

Acute cholecystitis treated urgently by nonselective laparoscopic cholecystectomy.

Beginning in 1990, all patients encountered by the author requiring cholecystectomy were attempted by laparoscopy. This study reports the results of 83 patients with acute cholecystitis who were urgently treated, nonselectively, by laparoscopic cholecystectomy. Acute cholecystitis was diagnosed clinically by the presence of right upper quadrant peritoneal pain, gallbladder phlegmon and fever, and/or increased white blood cell count. In addition, a confirming pathology report and/or elevated white blood cell count was present in all 83 patients. Age ranged from 18 to 82 years with an average of 39.4 years. Fifteen patients were male and 68 female. Insufflation was obtained in all patients without a complication. Discharge occurred by postoperative Day one for 24 patients, Day two for 66 and by Day three for 75 patients (range 19-300 hours). No patient had common duct stones. Most patients had stones impacted in the cystic duct, including one patient who had Mirizzi's syndrome. Operative time ranged from 28 to 300 minutes, with an average of 106.3 minutes. No conversion to open cholecystectomy was required. Complications included bile spillage in five patients, stone spillage in ten, and ileus in three patients. One patient with Mirizzi's syndrome required a postoperative radiological procedure for removal of a cystic duct stone remnant that was not completely removed at the time of operation. The high complication rate initially associated with laparoscopic cholecystectomy probably resulted from violating cardinal principles of surgery, not from the inappropriateness of laparoscopy. In conclusion, it is recommended that urgent laparoscopy is an appropriate initial approach for patients with acute cholecystitis.

Acute Disease↗

Evaluating physical functional outcomes: one category of the NOC system.

All professional health care disciplines are now being held accountable to demonstrate the outcomes they produce. It is imperative that nurses demonstrate the difference they make in patient care to justify the cost of professional nursing. Standardized language is needed to aggregate data and report information on nursing interventions and associated outcomes. The Nursing Outcomes Classification (NOC) system is the first comprehensive classification of nursing-sensitive patient outcomes. In this review, the development of this classification system with specific results related to physical functional status and implications of NOC for nursing practice are discussed.

Activities of Daily Living↗

The effect of co-administration of zolpidem with fluoxetine: pharmacokinetics and pharmacodynamics.

Since early treatment of depression with Selective Serotonin Reuptake Inhibitor (SSRI) can be associated with insomnia, daytime antidepressive therapy with SSRI is often combined with nighttime administration of a hypnotic. This study attempted to evaluate the pharmacokinetic and pharmacodynamic interactions between zolpidem 10 mg, a short-acting hypnotic, and fluoxetine 20 mg, an SSRI. Twenty-seven healthy male volunteers (mean age 23.5 years, range 20 - 29) received zolpidem and fluoxetine in the following open design: zolpidem on night 1, a morning dose of fluoxetine daily from day 2 through day 18 and zolpidem on night 18. Using HPLC, plasma levels of zolpidem, fluoxetine, and norfluoxetine were determined throughout night 1 for zolpidem, night 18 for zolpidem, fluoxetine, and norfluoxetine on days 16 and 17 for fluoxetine and norfluoxetine. Morning psychomotor tests were performed on days 1, 2, 18, and 19. Statistical analysis of data consisted of repeated measures of ANOVA. There was no significant difference in AUC, C(max), and T1/2 of zolpidem plasma concentrations between night 1 (zolpidem) and night 18 (zolpidem and fluoxetine). There was a significantly higher zolpidem plasma level at 0.5 hours after dosing together with a significantly shorter T(max) on night 18 compared to night 1. There was no significant difference in C(min) of plasma fluoxetine and norfluoxetine levels between day 16 and 17 of fluoxetine dosing, and there was no difference in T(max) between day 17 (fluoxetine) and day 18 (fluoxetine and zolpidem). There was a 3 - 4% increase in AUC and C(max) of fluoxetine and norfluoxetine plasma concentrations in the presence of zolpidem. There was no difference in the next morning performance tests after nighttime treatment of zolpidem alone after 17 consecutive days of fluoxetine treatment, or after zolpidem in the presence of steady-state plasma concentrations of fluoxetine. Both zolpidem and fluoxetine were well tolerated alone or in combination. It is concluded that the onset of action of zolpidem may possibly be shortened in the presence of fluoxetine, but no other significant pharmacokinetic or pharmacodynamic interactions occurred between zolpidem and fluoxetine.

Adult↗