Prediction of response to recombinant human erythropoietin (r-HuEPO/epoetin-alpha) therapy in cancer patients.
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Anemia↗
Biomedical subjects
D Henry
Publications and source records attributed to D Henry.
Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients.
The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.
Adolescent↗
Infection due to parvovirus B19 in patients infected with human immunodeficiency virus.
Parvovirus B19 has been described as a cause of chronic anemia in immunosuppressed patients, including those infected with human immunodeficiency virus (HIV). In this study serological assays and the polymerase chain reaction (PCR) were used to establish the prevalence of both prior and active infection due to parvovirus B19 among a general population of 105 HIV-infected individuals (cohort I) and among 22 HIV-infected patients with anemia (cohort II). Eight individuals in cohort I (7.6%) had IgG antibodies to parvovirus B19, while none had B19-specific IgM antibodies. In cohort II, four patients (18.2%) had B19-specific IgG antibodies and none had IgM antibodies. Only one person in cohort I (0.95%) and one person in cohort II (4.5%) had evidence on PCR of persistent infection with parvovirus B19; both of these patients lacked IgG and IgM antibodies to parvovirus. Both individuals with B19 viremia were anemic and had CD4 lymphocyte counts suggesting advanced immunosuppression (< 50/mm3). The observed low prevalences of B19 seropositivity and active B19 infection differ from the rates documented in previous studies and indicate that infection with parvovirus B19 is uncommon in some groups of HIV-infected patients.
AIDS-Related Opportunistic Infections↗
Benzodiazepine use as a cause of cognitive impairment in elderly hospital inpatients.
BACKGROUND: Benzodiazepine drugs are used very frequently by the elderly and have been associated with a number of untoward events in them. In an earlier publication, we showed that there was an association between benzodiazepine use and episodes of confusion in hospital. The purpose of this study was to examine that association in more detail by studying only patients with intact cognitive function on admission and by taking into consideration a range of demographic, drug use, and clinical confounders. METHODS: A prospective cohort study was carried out of inpatients who had normal cognitive function on admission to hospital. The subjects were 418 hospital inpatients who had a normal result of a Mini-Mental State Examination (MMSE) performed within 24 hours of admission. They were aged 59-88 years. A clinical history and detailed drug use history were taken on admission and then the patients were followed prospectively for 10 days or until discharge, whichever was sooner. The MMSE was repeated every 2 days and all significant clinical events and episodes of delirium noted. RESULTS: 10.8% (95% Confidence Interval [CI]: 7.8-13.8%) of patients developed cognitive impairment (as indicated by a decrease in the MMSE). Factors that were statistically significantly related to the development of cognitive impairment included admission diagnoses of cancer or central nervous system (CNS) disease, alcohol consumption > 40 gms/day, hypoxia, and presence of benzodiazepines in the urine on admission. After adjusting for age, alcohol consumption, and admission diagnoses, those who reported taking benzodiazepines in daily doses equivalent to 5 mg or more of diazepam were at significantly higher risk of cognitive impairment than those who had not taken benzodiazepines (adjusted odds ratio = 3.5; 95% CI: 1.4-8.8). Twenty-one (5.0%, 95% CI: 2.9-7.1%) patients developed delirium as defined by the DSM-IIIR criteria. Age and hypoxia were statistically significantly related to the development of delirium. Due to the small number of cases of delirium, the power of the study to detect significant associations was low. CONCLUSIONS: Elderly hospital inpatients who have intact cognitive function on admission to hospital have a low risk of developing cognitive impairment and delirium during their hospital stay. In this population, however, benzodiazepine use accounted for 29% of cases of cognitive impairment which did occur. The data also suggest that dehydration, urinary retention, and an admission diagnosis of CNS disease may be important risk factors for delirium.
Aged↗
Effectiveness of short-course therapy (5 days) with cefuroxime axetil in treatment of secondary bacterial infections of acute bronchitis.
Five hundred thirty-seven patients were enrolled in two independent, investigator-blinded, multicenter, randomized clinical trials comparing the clinical and bacteriologic efficacies and the safety of 5- or 10-day treatment with cefuroxime axetil with those of 10-day treatment with amoxicillin-clavulanate in the treatment of secondary bacterial infections of acute bronchitis. Patients received either 5 or 10 days of treatment (n = 177 in each group) with cefuroxime axetil at 250 mg twice daily or 10 days of treatment (n = 183) with amoxicillin-clavulanate at 500 mg three times daily. Patients in the cefuroxime axetil (5 days) group received placebo on days 6 to 10. Bacteriologic assessments were based on sputum specimen cultures obtained preceding and, when possible, following treatment. Organisms were isolated from the pretreatment sputum specimens of 242 of 537 (45%) patients, with the primary pathogens being Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Staphylococcus aureus (28, 25, 13, 9, and 8% of isolates, respectively). Pathogens were eradicated or presumed to be eradicated in 87% (52 of 60), 91% (53 of 58), and 86% (60 of 70) of bacteriologically evaluable patients treated with cefuroxime axetil (5 days), cefuroxime axetil (10 days), and amoxicillin-clavulanate, respectively. A satisfactory clinical outcome (cure or improvement) was achieved in 82% (107 of 130), 86% (117 of 136), and 83% (130 of 157) of the clinically evaluable patients treated with cefuroxime axetil (5 days), cefuroxime axetil (10 days), and amoxicillin-clavulanate, respectively. Treatment with amoxicillin-clavulanate was associated with a significantly higher incidence of drug-related adverse events than was treatment with cefuroxime axetil for either 5 or 10 days (P = 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (37 versus 19 and 15%, respectively; P < 0.001), particularly diarrhea and nausea. These results indicate that treatment with cefuroxime axetil at 250 mg twice daily for 5 days is as effective as treatment for 10 days with either the same dose of cefuroxime axetil or amoxicillin-clavulanate at 500 mg three times daily in patients with acute bronchitis. In addition, treatment with cefuroxime axetil for either 5 or 10 days is associated with significantly fewer gastrointestinal adverse events, particularly diarrhea and nausea, than is 10-day treatment with amoxicillin-clavulanate.
Acute Disease↗
Health status instruments / utilities.
Rheumatologists and other interested professionals at the OMERACT II conference formed small groups to discuss whether it was sensible to use a generic health status instrument in musculoskeletal disease trials. These instruments promise the possibility of comparison of health status between disease states. However, data is lacking on validity of the current generation of instruments to support their use. Participants had little personal experience with these instruments. After inspection, many voiced strong concerns over comprehensiveness and responsiveness. Many dimensions of health relevant for patients with this group of diseases were felt to be underrepresented. The dimension of adverse effects was universally absent, although this is more a problem of state of the art in trial methodology than a problem of these measures. Although there is little data, the small number of response categories in the dimensions covered, plus the lack of comprehensiveness, make it likely that responsiveness will be low. Further research, especially the adoption of one or more generic measures alongside specific measures, both in trials and in observational studies, is necessary to validate and improve the current generic measures. Until that time, valid conclusions and health policy regarding musculoskeletal diseases cannot be based on generic measures of health status.
Health Status↗
Nitric oxide mediates the sustained opening of NMDA receptor-gated ionic channels which follows transient excitotoxic exposure in hippocampal slices.
In the rat hippocampal slice, a brief exposure to glutamate and glycine increased MK-801 binding to 246% of controls. Increased binding persisted 90 min after removal of those amino acids from the incubation medium. Posttreatment with the competitive substrate inhibitor of nitric oxide synthase, N omega-nitro-L-arginine or with hemoglobin, which binds NO extracellularly, inhibited this postexcitotoxic increase in MK-801 binding. L-Arginine reversed this inhibitory effect but D-arginine did not. The combination of tetrodotoxin and low Ca2+, which blocks transmitter release prevented the poststimulation increase in MK-801 binding, suggesting a presynaptic component. These findings suggest that the sustained opening of NMDA receptor-gated ionic channels seen after transient glutamate/glycine stimulation is mediated by NO.
Animals↗
Nitric oxide participates in excitotoxic mechanisms induced by chemical hypoxia.
Changes in the activity of the NMDA receptor-gated ionic channels induced by potassium cyanide were studied in rat hippocampal slices utilizing a [3H]MK-801 binding technique. A 30-min exposure of slices to potassium cyanide (KCN) increased MK-801 binding by 252%. Co-application of N omega-nitro-L-arginine (NNLA), a competitive antagonist of nitric oxide (NO) synthase, reduced this increase by 72%. This inhibition by NNLA was completely reversed by an excess of L-arginine, a substrate for NO synthase, suggesting that the KCN-induced increase in MK-801 binding is mediated by NO synthase activity. KCN had no effect on MK-801 binding in synaptic membranes. In Ca(2+)-containing medium, KCN increased the release of glutamate, aspartate and glycine by 4- to 5-fold, and this was blocked by application of NNLA. NNLA inhibition was reversed by an excess of L-arginine, indicating that KCN-stimulated release of these amino acids is mediated by NO synthase activity. In Ca(2+)-free medium, a KCN-induced increase in MK-801 binding and in excitatory amino acid release was also observed, however, this increase was not influenced by NO-related agents, suggesting that these changes were not mediated by NO synthase activation. NNLA given after the end of exposure to KCN did not reverse the increase in MK-801 binding. These findings suggest that NO is involved in the initial activation of NMDA receptor-gated ionic channels and in the enhanced amino acid transmitter release induced by KCN, but that KCN can also induce some of these effects by a Ca(2+)- and NO-independent mechanism.
Amino Acids↗
Cloning and nucleotide sequence of a cDNA encoding a major fucoxanthin-, chlorophyll a/c-containing protein from the chrysophyte Isochrysis galbana: implications for evolution of the cab gene family.
We investigated the primary structure of a cDNA encoding a light-harvesting protein from the marine chrysophyte Isochrysis galbana. Antibodies raised against the major fucoxanthin, chlorophyll a/c-binding light-harvesting protein (FCP) of I. galbana were used to select a cDNA clone encoding one of the FCP apoproteins. The nucleic acid and deduced amino acid sequences reveal conserved regions within the first and third transmembrane spans with Chl a/b-binding proteins and with FCPs of another chromophyte. However, the amino acid identity between I. galbana FCP and other cab genes of FCPs is only ca. 30%. Phylogenetic analyses demonstrated that the FCP genes of both diatoms and chrysophytes sequenced to date are more closely related to cab genes encoding LHC I, CP 29, and CP 24 of higher plants than to cab genes encoding LHC II of chlorophytes. We propose that LHC I, CP 24 and CP 29 and FCP might have originated from a common ancestral chl binding protein and that the major LHC II of Chl a/b-containing organisms arose after the divergence between the chromophytes and the chlorophytes.
Amino Acid Sequence↗
Retroviral diseases in hematology.
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AIDS-Related Opportunistic Infections↗
Neuroprotection against nitric oxide injury with inhibitors of ADP-ribosylation.
We investigated the effect of nitric oxide (NO) upon CA1 neurons of the hippocampal slice. NO was given via perfusate without oxygen and with glucose concentration increased to 10 mM to prevent hypoxic injury. Exposure to NO for 10 min produced severe neuronal injury, with CA1 orthodromic and antidromic population spike regaining only 3 +/- 3% and 9 +/- 3% of initial amplitude after 1 h recovery. Hypoxic controls in contrast, showed orthodromic and antidromic recovery of 98 +/- 5% and 93 +/- 7%. Good protection from NO-induced injury was seen with 10 mM nicotinamide, an inhibitor of poly-ADP-ribosylation, with CA1 PS recovering to 116 +/- 10% orthodromically, and 96 +/- 4% antidromically. Protection was also seen with 3'-aminobenzamide, another poly-ADP-ribosylation inhibitor, suggesting that poly-ADP-ribosylation may play an important role in NO-mediated neuronal injury.
Adenosine Diphosphate Ribose↗
Association between availability of non-prescription beta 2 agonist inhalers and undertreatment of asthma.
OBJECTIVE: To determine whether the availability of beta 2 agonist inhalers without prescription leads to undertreatment of asthma. DESIGN: Cross sectional study of adequacy of treatment in asthmatic subjects who purchased beta 2 agonist inhalers and subjects who obtained inhalers by prescription. SETTING: Community pharmacies in New South Wales, Australia. SUBJECTS: 403 eligible consecutive asthmatic subjects aged 13 to 55 purchasing salbutamol metered dose inhalers over the counter or by prescription; 197 attended for follow up and spirometry and 139 returned 14 day symptom, peak flow, and medication diaries. MAIN OUTCOME MEASURES: Severity of asthma assessed on frequency of day time and night time wheezing, frequency of inhaler use, and peak expiratory flow rates. Adequacy of treatment according to published guidelines. RESULTS: Of the 139 patients who completed the diary 83, (60%) purchased their inhalers without prescription and 83 were undertreated. The characteristics of patients in the prescription and purchasing groups were similar. Multiple logistic regression analysis identified use of non-prescribed salbutamol as being associated with a 2.9-fold increase in the odds of undertreatment (95% confidence interval 1.3 to 6.8). Smoking increased the odds of undertreatment (3.3, 1.2 to 9.5) and use of a peak flow meter reduced the odds (0.11, 0.04 to 0.34). Adjustment for frequency of consultation made use of non-prescription salbutamol insignificant (1.4, 0.55 to 3.8). Attitudes to services provided by doctors and pharmacists were favourable and not associated with undertreatment. CONCLUSION: Over the counter purchase of salbutamol is associated with infrequent consultation with doctors and undertreatment of asthma.
Administration, Inhalation↗
Nonsteroidal anti-inflammatory drugs and peptic ulcer hospitalization rates in New South Wales.
BACKGROUND: Consumption of nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDS) increased substantially during the 1980s. The effects of this trend on hospitalization rates for peptic ulcer in different age groups in New South Wales, Australia, was investigated. METHODS: A population model based on sales of NANSAIDS and aspirin, age specific estimates of the relative risk of ulcer complications with these drugs, and hospitalization data for 1979 through 1988 was created. RESULTS: All age groups increased consumption of NANSAIDS. The increases were greatest in elderly subjects, with women over age 65 years increasing the prevalence of their use of the drugs from 11.9% in 1979 to 22.5% in 1988 and males over age 65 increasing use from 9.7% to 20%. Aspirin use remained relatively unchanged in all age groups. Hospitalization rates for peptic ulcer decreased in both sexes under age 64 despite increasing use of NANSAIDs. Hospitalization increased in males and females over age 65, but in females the increase was substantially greater than predicted by the computer model. In women and men over age 75 the increases in hospitalization rates predicted by the model were only 18% and 33%, respectively, of the observed rises. CONCLUSIONS: The increasing hospitalization rate for peptic ulcer among elderly subjects was only partly explained by the increasing consumption of NANSAIDS. Further research is needed.
Adult↗
Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs.
BACKGROUND: We have assessed the extent to which the risk of serious gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) varies with the age and sex of recipients, use of aspirin or alcohol, administration by the oral or rectal route, and dose and choice of drug. METHODS: A case-control study was performed with prospective recruitment of cases of gastrointestinal bleeding or ulcer perforation and age- and sex-matched controls. Information on preadmission drug use obtained by structured interview. RESULTS: Six hundred forty-four patients and 1268 controls were recruited. The odds ratio for upper gastrointestinal complications in users compared with nonusers of NANSAIDs increased with age: < or = 59 years, odds ratio 2.0; 60-79 years, odds ratio 3.0; > or = 80 years, odds ratio 4.2; and was higher in women (5.4) than in men (1.9). There was a linear dose-response curve that was steeper in women than in men. Combined exposure suggested additive risks: NANSAIDs and aspirin, odds ratio 6.7; NANSAIDs and alcohol, odds ratio 6.0 NANSAIDs by the oral route were associated with an odds ratio of 2.3, compared with 11.4 with rectal administration. Piroxicam was associated with the highest risk, odds ratio 4.8; and ibuprofen the lowest risk, odds ratio 0.7. CONCLUSIONS: A number of factors can alter the risk of major gastrointestinal complications with NANSAIDs and need to be considered when individual prescribing decisions are made.
Administration, Oral↗
Selective and sustained pulmonary vasodilation with inhalational nitric oxide therapy in a child with idiopathic pulmonary hypertension.
Low doses of inhaled nitric oxide caused selective and sustained pulmonary vasodilation in an infant with pulmonary hypertension without causing systemic hypotension, despite the failure of treatment with other vasodilators.
Administration, Inhalation↗
Sexually abused children at high risk for post-traumatic stress disorder.
Ninety-two sexually abused children were studied using structured interviews and standardized instruments to determine the frequency of post-traumatic stress disorder (PTSD) and associated symptoms. Of these sexually abused children, 43.9% met DSM-III-R PTSD criteria; 53.8% of children abused by fathers, 42.4% abused by trusted adults, and 10% of those abused by strangers met criteria as opposed to none of the children abused by an older child. No relationship was observed between the time lapsed since last abusive episode and the presence of PTSD. Many children not meeting full criteria exhibited partial PTSD symptoms. Only one standardized instrument (Child Behavior Checklist) detected group differences with PTSD children exhibiting more symptoms. This study replicates an earlier pilot study and underscores the need for further PTSD research.
Adolescent↗
Physiological analysis of mutants of Saccharomyces cerevisiae impaired in sulphate assimilation.
The assimilation of sulphate in Saccharomyces cerevisiae, comprising the reduction of sulphate to sulphide and the incorporation of the sulphur atom into a four-carbon chain, requires the integrity of 13 different genes. To date, the functions of nine of these genes are still not clearly established. A set of strains, each bearing a mutation in one MET gene, was studied. Phenotypic studies and enzyme determinations showed that the products of at least five genes are needed for the synthesis of an enzymically active sulphite reductase. These genes are MET1, MET5, MET8, MET10 and MET20. Wild-type strains of S. cerevisiae can use organic metabolites such as homocysteine, cysteine, methionine and S-adenosylmethionine as sulphur sources. They are also able to use inorganic sulphur sources such as sulphate, sulphite, sulphide or thiosulphate. Here we show that both of the two sulphur atoms of thiosulphate are used by S. cerevisiae. Thiosulphate is cleaved into sulphite and sulphide prior to utilization by the sulphate assimilation pathway, as the metabolism of one sulphur atom from thiosulphate requires the presence of an active sulphite reductase.
Cysteine↗
Implications of the Australian guidelines for the United States.
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Australia↗