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Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 145 records · Page 8Linked to original sources
PubMed1998

Anticoagulation therapy in pediatric patients with sinovenous thrombosis: a cohort study.

OBJECTIVE: To assess the use of anticoagulant therapy in a consecutive cohort study of children with sinovenous thrombosis (SVT). METHODS: A single institutional pilot study of anticoagulant therapy was conducted from January 1992 to December 1996 at the Hospital for Sick Children, Toronto, Ontario. Consecutive children with the diagnosis of SVT, made by computed tomography, magnetic resonance imaging (MRI), MRI with venography, ultrasonography, nuclear brain scanning, or conventional angiography were eligible for anticoagulant therapy. RADIOGRAPHIC EVALUATION: Most children underwent multiple radiographic tests for evaluation of the central nervous system. Of the 32 episodes of SVT, CT was performed in 30, MRI with or without venography in 26, ultrasonography in 11, and nuclear brain scanning in 5. The majority of the SVTs were located at the superior sagittal sinus (50%) and right lateral sinus complex (44%). RESULTS: There were 30 consecutive children with 32 episodes of SVT during the 5-year study (2 girls had recurrent SVT). The median age was 6.2 years (age range, 3 days to 18 years), and the sex of the patients was evenly distributed (15 girls and 15 boys). The primary associated clinical conditions consisted of systemic lupus erythematosus (n = 5), renal disease (n = 3), perinatal distress (n = 2), congenital heart disease (n = 1), cerebral arteriovenous malformation (n = 1), and neurosurgery for refractory seizures (n= 1). The remainder were previously healthy children older than 1 month (n = 10) and newborns (n = 7). Eight children were ineligible for anticoagulant therapy because of an associated intracranial hemorrhage (n = 6), a postoperative bleeding risk after neurosurgery (n = 1), or a prolonged delay from the diagnosis to the time of referral (n = 1). Ten children received standard heparin, and 12 children received low-molecular-weight heparin (LMWH) (enoxaparin sodium). Eighteen children were treated with oral anticoagulants for 3 months after initial heparin therapy, and 4 patients received LMWH for the entire course of treatment. There was no intracranial hemorrhage in the 12 patients treated with LMWH, but there was 1 case of clinically silent bleeding in the standard heparin group. CONCLUSIONS: The results of this pilot study suggest that anticoagulant therapy, in particular LMWH, is safe and may have a role in the treatment of children with SVT. A randomized controlled trial is warranted.

Adolescent↗
PubMed1998

Severe viral respiratory infections in infants with cystic fibrosis.

Limited data in children with cystic fibrosis (CF) suggest that respiratory viral infections during infancy result in substantial morbidity. Eighty of 101 (79%) infants with CF diagnosed by neonatal screening during 1991-1996 were recruited into a prospective, multiple-birth cohort study. We aimed to perform an initial, then annual bronchoalveolar lavage (BAL) for bacterial and viral culture, cytology, IL-8, and elastolytic activity over the following 2 years. When possible, BAL was also performed during any hospitalization for a pulmonary exacerbation, and additional specimens for viral culture were collected by nasopharyngeal aspiration. Thirteen infants undergoing bronchoscopy for congenital stridor served as disease controls. During infancy, 31 children (39%) were hospitalized for respiratory disease and 20 (65%) cases had an etiologic agent identified. Respiratory viruses were detected in 16/31 (52%) cases, including four with simultaneous bacterial infection. Another four were infected with Staphylococcus aureus. Respiratory syncytial virus predominated and was found in seven infants. In the absence of bacteria, those with viral infections had acute onset of respiratory distress, were not treated with antibiotics, and had an uncomplicated hospital course. Compared to noninfected CF subjects and controls, infected infants had elevated BAL inflammatory indices (P < 0.01). Eleven of 31 (35%) hospitalized infants followed for 12-60 months acquired Pseudomonas aeruginosa, compared with only three of 49 (6%) subjects not hospitalized for respiratory symptoms during infancy (risk ratio 5.8, CI 1.9, 24). We conclude that respiratory viruses are important causes of hospitalization in CF infants. While viral infections were self-limited, they were accompanied by airway inflammatory changes, and admission to hospital was associated with early acquisition of Pseudomonas aeruginosa and persistent respiratory symptoms.

Bronchoalveolar Lavage↗
PubMed1998

IL-10 suppresses LPS-induced KC mRNA expression via a translation-dependent decrease in mRNA stability.

This study examines the mechanism of interleukin-10 (IL-10)-mediated suppression of KC chemokine gene expression in mouse macrophages. Suppression of KC mRNA levels by IL-10 occurred late in the time course of response to lipopolysaccharide (LPS). Equivalent IL-10-mediated suppression was observed when the agent was added 1 h before, simultaneous with, or 1 h after LPS. IL-10 did not inhibit KC gene transcription but rather produced a decrease in the stability of KC mRNA. The suppressive action of IL-10 was prevented in macrophages that were also treated with inhibitors of protein synthesis even when added 2 h after LPS and IL-10. These results suggest that IL-10 acts to destabilize LPS-induced KC mRNA through a process that depends on coincident KC mRNA translation.

Animals↗
PubMed1998

Oxidized LDL modulates activation of NFkappaB in mononuclear phagocytes by altering the degradation if IkappaBs.

Oxidized low density lipoprotein (oxLDL) is known to alter the expression of inflammatory gene products in mononuclear phagocytes. The mechanisms involved in this effect were studied by examining the activation of nuclear factor kappaB (NFkappaB), a transcription factor known to be important in controlling the expression of such genes. Pretreatment of peritoneal macrophages with oxLDL modulated the activation of NFkappaB in response to either lipopolysaccharide (LPS) or the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). In macrophages pretreated with oxLDL the nuclear translocation of Rel family members (RelA and c-Rel) is delayed (LPS) or markedly diminished (IFN-gamma/IL-2) and results in delayed or reduced appearance of kappaB binding activity within the nucleus. These changes in NFkappaB activation result from alterations in the stimulus-dependent degradation of IkappaB alpha and IkappaB beta. The effects of oxLDL on NFkappaB activation depend both on the degree of LDL oxidation (most potent with extensive oxidation) and on the time of exposure of the cells to the lipoprotein preparation (a minimal exposure of 6 h is required before inhibitory effects are observed). The modulation of IkappaB/NFkappaB function in cells exposed to oxLDL appears to be responsible for previously reported effects of oxLDL on chemoattractant cytokine gene expression where both inhibition and delay of such stimulus-dependent events has been observed.

Animals↗
PubMed1998

Cerebellar arteriovenous malformations in children.

We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome.

Adolescent↗
PubMed1998

Revealed identity: a study of the process of genetic counselling.

This paper describes a qualitative study of the processes employed within a genetic counselling consultation. These processes, it is argued, can be seen to provide the patient with a genetic identity. But unlike the new identity conferred by the diagnosis of many chronic medical conditions a genetic identity is presented as an old one that is now revealed. This represents a reversal of the stigmatising process: instead of a spoiled identity replacing an actual one, the genetic consultation involves revealing an actual identity in the place of a previously presumed one. In this way, genetic counselling reconstructs identity in the past as well as in the future.

Communication↗
PubMed1998

Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation.

The E6-AP ubiquitin ligase (human/mouse gene UBE3A/Ube3a) promotes the degradation of p53 in association with papilloma E6 protein, and maternal deficiency causes human Angelman syndrome (AS). Ube3a is imprinted with silencing of the paternal allele in hippocampus and cerebellum in mice. We found that the phenotype of mice with maternal deficiency (m-/p+) for Ube3a resembles human AS with motor dysfunction, inducible seizures, and a context-dependent learning deficit. Long-term potentiation (LTP) was severely impaired in m-/p+ mice despite normal baseline synaptic transmission and neuroanatomy, indicating that ubiquitination may play a role in mammalian LTP and that LTP may be abnormal in AS. The cytoplasmic abundance of p53 was increased in postmitotic neurons in m-/p+ mice and in AS, providing a potential biochemical basis for the phenotype through failure to ubiquitinate and degrade various effectors.

Acoustic Stimulation↗
PubMed1998

Premature peripheral vascular disease: clinical profile and abnormal lipid peroxidation.

The aim of this study was to determine any biochemical differences between early-onset peripheral vascular disease and typical onset atherosclerosis, and age-matched controls. A subset of patients present at a young age ( < 50 years) with peripheral vascular disease which pursues an aggressive course. As lipid oxidation seems important in atherosclerosis, total lipid peroxides, oxidized subfractions, and Trolox equivalent antioxidant capacity (TEAC) were studied in patients with premature peripheral vascular disease. Charts were reviewed of patients operated on for vascular occlusive disease over a 5-year period. Patients with early-onset peripheral vascular disease (group I) were evaluated for biochemical abnormalities and compared with typical onset atherosclerotics (group II) and age-matched controls (group III). Sixteen patients with early-onset peripheral vascular disease underwent biochemical evaluation. Conventional lipid profiles did not differ statistically from those of age-matched controls, except for mild elevations in LDL and VLDL in patients with vascular occlusive disease (207 and 195 mg/dl in groups I and 11 versus 157 mg/dl in group III). Total oxidative potential was significantly elevated (P = 0.006) 3.04, 2.15 and 2.04 nmol/ml in groups I, II and III, respectively. Levels of oxidized LDL and VLDL were even more significantly elevated (P = 0.0009) for premature peripheral vascular disease, (1.2, 0.58 and 0.47 nmol/ml in groups I-II). TEAC values did not differ significantly between groups (0.83, 0.82, 0.82 nmol/ml) and did not correlate with total lipid peroxide values for individual patients. In conclusion, lipid peroxides were significantly elevated in patients with premature peripheral vascular disease, the most marked changes being seen in oxidized LDL and VLDL subfractions. Lipid peroxides were elevated when standard lipid profiles were only mildly abnormal. The poor long-term prognosis in these patients suggests the need for aggressive evaluation and treatment of lipid abnormalities.

Adult↗
PubMed1998

Community occupational structure, medical and economic resources, and coronary mortality among U.S. blacks and whites, 1980-1988.

PURPOSE: To examine the association between coronary heart disease (CHD) mortality, economic and medical resources, and county occupational structure. METHODS: U.S. counties were classified into five occupational structure categories based on the percentage of workers in white-collar occupations. Directly age-adjusted CHD mortality rates (from vital statistics and Census data) and economic and medical care data (from Census and Area Resource File data) were calculated for each occupational structure category. Participants were black and white, men and women, aged 35-64 years, in the U.S. during 1980-88. CHD mortality rates and economic and medical care data were compared across occupational structure categories. RESULTS: Among blacks, CDH rates were highest in counties with intermediate levels of occupational structure; rates among whites were inversely associated with occupational structure. Per capita levels of income and numbers of medical-care providers were positively associated with occupational structure. CONCLUSION: Strategies to improve the resources of disadvantaged communities and the access of black workers to local occupational opportunities may be important for CHD prevention in high risk populations.

Adult↗
PubMed1998

Editorial

We are pleased that the International Journal of Infectious Diseases (IJID) has been indexed in MEDLINE and Index Medicus. It is a tribute to those of you who have submitted excellent papers, case reports, and reviews and to those who have contributed thoughtful editorials. We expect that heightened exposure both online and in libraries will result in increased submissions and that this will soon warrant publication at bimonthly and eventually monthly intervals. Increased frequency of publication depends on members of the International Society for Infectious Diseases (ISID) and other colleagues and their submission of more manuscripts of the highest scientific merit. We also welcome more letters and encourage critical and spirited commentaries. We urge you to tell your libraries about the IJID and to suggest that they subscribe. Likewise, colleagues who could not attend our biannual meeting should be asked to subscribe as well as to submit the results of their observations and investigations. Much of the credit for the success of IJID goes to its editors and reviewers. The peer review process works because of the expertise, diligence, and timeliness of the reviewers and the experience and judgment of the editors. The editors select reviewers, consider their comments, and determine how to respond to potential contributors. The overall objective is to present information about infectious diseases that has international significance. Since these data frequently originate from regions where English is not the primary language, our staff will provide assistance in editing manuscripts to improve grammar and usage. Command of the English language is not a criterion for acceptance or rejection of a manuscript. However, it does make it easier for the reviewers if a native English speaker has read and revised the manuscript. The recent meeting of the ISID in Boston was clearly a huge success, and the presentations were outstanding. We trust that many of you who participated in this meeting will submit articles to the IJID. Suggestions for supplements from this meeting or from other meetings also are welcomed. Our second issue comprised the proceedings at the Jenner Symposium of the 7th International Congress for Infectious Diseases in Hong Kong, June 10-13, 1996. An independent supplement on fungal infections came from a symposium at the meeting of the International Immunocompromised Host Society, June 23-26, 1996, Assisi, Italy.

Journal Article↗
PubMed1998

Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-alpha, vascular endothelial growth factor and platelet-derived growth factor.

To test the hypothesis that oxidative damage associated with tissue hypoxia plays a role in neovascularization, a lipid hydroperoxide (LHP) was injected into the vitreous of rabbits. Single injections of LHP (50-600 microg) caused a sustained retinal neovascularization visualized clinically by ophthalmoscopy and confirmed by microscopy. Vasodilators, i.e. histamine and nitric oxide, peaked at 6h and 7 days, respectively. The levels of both tumor necrosis factor-alpha and interleukin-1alpha peaked at 12h and dropped to basal levels by 24h. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta peaked at 24h and were sustained throughout the following 3 weeks, and platelet-derived growth factor was also elevated throughout the same period. Upregulation of these five angiogenic cytokines, but not basic fibroblast growth factor, occurred prior to the appearance of neovascularization. Leakage of fluorescein at the tips of new vessels was demonstrated by fluorescein angiography. Linoleic hydroperoxide induced neovascularization, but saturated or unsaturated native C-18 fatty acids had no effect. The cascade of multiple, angiogenic cytokines induced by LHP may interact to promote sustained neovascularization.

Journal Article↗
PubMed1998

High concentrations of ammonia, but not volatile amines, in gastric juice of subjects with Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) produces large amounts of ammonia. Based on higher readings obtained with an ammonia-sensitive electrode when compared to a specific enzymatic assay, it has been claimed that H. pylori also produces potentially toxic volatile amines. METHOD: We measured ammonia concentrations (NH3) in gastric aspirates from 11 H. pylori positive subjects (22-40 y, 6 M), using an ammonia electrode sensitive to ammonia and amines, and an enzymatic assay specific for ammonia. Continuous aspiration was performed overnight and 220 aspirates were analyzed before and 6 weeks after cure of H. pylori. Gastric samples were diluted 1:3 (before cure) and 1:1 (after cure) according to dilution curves constructed prior to the assays. RESULTS: Median (95% CI) NH3 detected by the electrode/enzymatic assay were 4.34 mM[4.12-4.61]/4.50 mM [4.28-4.68] (p > .05) before cure and 0.54 mM[0.42-0.60]/0.73 mM[0.71-0.81] after cure (p > .05). Intra-class correlation coefficient between the two methods was 0.91 before cure and 0.90 after cure (p < .001). Without dilution, the enzymatic assay was linear for NH3 from 0.01 to 1 mM and saturated at 2.5 mM; the electrode was linear for NH3 from 0.01 to 20 mM. When appropriate dilutions were performed, the enzymatic assay was accurate for NH3 greater than 2.5 mM. CONCLUSION: In subjects with H. pylori infection there is a high NH3 in gastric juice; production of volatile amines appears to be negligible in vivo. An ammonia-sensitive electrode and a specific enzymatic assay are both suitable methods for determining NH3 in the gastric juice of subjects with H. pylori infection.

Adult↗
PubMed1998

Evaluation of an interdisciplinary re-isolation policy for patients with previous Clostridium difficile diarrhea.

BACKGROUND: Diarrhea caused by Clostridium difficile is increasingly recognized as a nosocomial problem. The effectiveness and cost of a new program to decrease nosocomial spread by identifying patients scheduled for readmission who were previously positive for toxin was evaluated. METHODS: The Memorial Sloan-Kettering Cancer Center is a 410-bed comprehensive cancer center in New York City. Many patients are readmitted during their course of cancer therapy. In 1995 as a result of concern about the nosocomial spread of C difficile, we implemented a policy that all patients who were positive for C difficile toxin in the previous 6 months with no subsequent toxin-negative stool as an outpatient would be placed into contact isolation on readmission pending evaluation of stool specimens. Patients who were previously positive for C difficile toxin were identified to infection control and admitting office databases via computer. Admitting personnel contacted infection control with all readmissions to determine whether a private room was required. RESULTS: Between July 1, 1995, and June 30, 1996, 47 patients who were previously positive for C difficile toxin were readmitted. Before their first scheduled readmission, the specimens for 15 (32%) of these patients were negative for C difficile toxin. They were subsequently cleared as outpatients and were readmitted without isolation. Workup of the remaining 32 patients revealed that the specimens for 7 patients were positive for C difficile toxin and 86 isolation days were used. An additional 25 patients used 107 isolation days and were either cleared after a negative specimen was obtained in-house or discharged without having an appropriate specimen sent. Four patients (9%) had reoccurring C difficile after having toxin-negative stools. We estimate (because outpatient specimens were not collected) the cost incurred at $48,500 annually, including the incremental cost of hospital isolation and equipment. CONCLUSION: Our policy to control the spread of nosocomial C difficile required interdisciplinary cooperation between infection control and the admitting department. By identifying patients who were positive for toxin through admitting, we were able to place all potentially infected patients into isolation. Our positivity rate of 15% on readmission demonstrates the importance of this policy. The cost of controlling C difficile can be significantly lowered by clearing patients who were previously positive for toxin before hospital readmission.

Cancer Care Facilities↗
PubMed1998

Perspectives on switching oral acyclovir from prescription to over-the-counter status: report of a consensus panel.

The proposed switching of oral acyclovir from prescription to over-the-counter (OTC) status for the 5-day episodic treatment of genital herpes was considered by a consensus panel. It was concluded that self-diagnosis/misdiagnosis, misuse, and adverse drug effects were potential problems with the OTC use of acyclovir. While acyclovir reduces asymptomatic shedding of herpes simplex virus type 2, the reduction in transmission of virus potentially resulting from increased acyclovir use was felt to be of unknown extent but likely to be of benefit overall. The availability of acyclovir would likely be improved. There were differences in opinion as to whether widespread availability of acyclovir (prescription or OTC) may speed the development of viral resistance. However, all panel members felt that granting OTC status may set an undesirable precedent for the switch from prescription to OTC use of other systemically administered antiinfective agents. The effect of this precedent, in terms of accelerating development of multidrug-resistant bacteria, was a major concern of all panel members. The consensus was that the switch of acyclovir to OTC status could not be supported.

Acyclovir↗
PubMed1998

Objectives of genetic counselling: differing views of purchasers, providers and users.

BACKGROUND: This study aimed to compare the views of purchasers, providers and users about the objectives of genetic counselling. METHODS: A modified Delphi technique was used, incorporating two postal questionnaires that were sent to six study groups with a three-month interval: purchasers (public health doctors (n = 37) and regional advisers in general practice (n = 35)); providers (clinical geneticists (n = 33) and genetic counsellors (n = 25)); and users (out-patients (n = 36) and members of genetic support groups (n = 32)). The response rate for the first questionnaire was 115/198 (58 per cent) and for the second, 102/198 (52 per cent). The first questionnaire asked an open-ended question about what the objectives of genetic counselling should be and asked respondents to rank order them. The second questionnaire summarized the views expressed in the first questionnaire and asked respondents to rank order the most frequently cited and most highly ranked five objectives. RESULTS: The five most frequently cited and highly ranked objectives from Questionnaire One were, in descending order: provide information, give support, facilitate decision-making, assess risk and achieve understanding. In response to Questionnaire Two, purchasers differed from providers and users in rating 'facilitate decision-making' more highly than did providers and users. By contrast, providers and users rated 'give information' more highly than did purchasers. CONCLUSIONS: Purchasers hold different views from providers and users about what the objectives of genetic counselling should be. This raises two questions: (1) Which views are or should be most influential in the future development of genetic counselling? (2) By what processes can more than one view on genetic counselling be integrated?

Attitude of Health Personnel↗
PubMed1998

Gender differences in motivational style: a comparison of measures and curriculum area.

BACKGROUND: Gender has long been implicated in school-based performance with gender differences varying across curriculum domains. Motivational differences have often been cited as a possible cause. However, evidence for the pattern of motivational difference between the genders is unclear. AIMS: This study compares the motivational responses of girls and boys in the curriculum areas of mathematics and English. Two different measures of motivation are employed. SAMPLES: The sample consists of all pupils from years 7, 9 and 11 in two secondary schools in Northern England. A total of 435 yr 7, 389 yr 9 and 357 yr 11 students was available. METHODS: Students completed two assessments of motivation, one based on self-report measures of goal strength and the other on performance over four tasks. Some school performance data were also available. RESULTS: The two motivation measures produce different patterns of results. The task-based measure shows no gender based differences while the other indicates a pattern of differences broadly suggestive of an advantage for girls. CONCLUSIONS: Future exploration of gender effects in motivation needs to give careful consideration to the type of motivation under consideration. Univariate models are unlikely to be adequate.

Achievement↗