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Biomedical subjects

D Howard

Publications and source records attributed to D Howard.

At least 91 records · Page 5Linked to original sources
PubMed1997

Controlled trial of 4-ASA in ulcerative colitis.

A six-week placebo-controlled trial of the efficacy and safety of 6 g per day of 4-aminosalicylic acid (4-ASA) was conducted in 30 subjects with mild to moderately severe ulcerative colitis. Subjects were stratified into groups having distal (< 60 cm) or more extensive (> 60 cm) disease. Diarrhea, bleeding, sigmoidoscopic and biopsy appearance, and physician global assessment were scored to judge efficacy. Safety was evaluated by monitoring untoward symptoms and laboratory values. Median percent improvement was significantly greater (P < 0.05) in the 4-ASA > 60-cm group (42.7%) than in the placebo > 60-cm group (21.2%), but 4-ASA was not better than placebo for the < 60-cm group or the total study group. Severe dyspepsia (one subject), abnormal AST (transient in five, persistent in one) and elevated lipase without pancreatitis (six subjects) were noted. Thus 6 g 4-ASA for six weeks was more effective than placebo in mild to moderate ulcerative colitis extending more than 60 cm above the anus, but not in distal disease, and the drug was generally well tolerated.

Aminosalicylic Acid↗
PubMed1997

Possible nosocomial transmission of psittacosis.

OBJECTIVES: To investigate a cluster of seven pneumonia cases among persons exposed to a pet-shop worker hospitalized with psittacosis. DESIGN: Epidemiological study of the outbreak, sero-diagnostic evaluation of exposed persons with pneumonia; and retrospective review of the pneumonia cases. SETTING: 450-bed teaching community hospital. PARTICIPANTS: Employees of the nursing unit where the patient with psittacosis was hospitalized. RESULTS: The index case had laboratory and clinical evidence of psittacosis. Four of the seven exposed persons who developed pneumonia had serologic results that met criteria for a diagnosis of psittacosis, and three met criteria for Chlamydia pneumoniae infection, possibly reflecting cross-reactivity between the microimmunofluorescence assays for the two diseases. The epidemiological graph suggested a relationship between the index case and the cluster of pneumonias in exposed individuals. CONCLUSIONS: Psittacosis may have been transmitted person to person in a hospital setting.

Chlamydophila psittaci↗
PubMed1996

Successfully treated invasive pulmonary aspergillosis associated with smoking marijuana in a renal transplant recipient.

Invasive pulmonary aspergillosis (IPA) is often a lethal entity in transplant recipients (up to 90%). We report the successful treatment of a case of IPA in a renal transplant recipient whose only risk for exposure was habitual marijuana smoking. Although marijuana smoking has been linked to the development of IPA in patients immunosuppressed for a variety of reasons, this case is the first report involving a solid organ transplant recipient. The patient's clinical course and treatment are described and the literature is reviewed with respect to environmental and patient risk factors. In this case, IPA was associated with the patient's heavy usage of marijuana during the immediate posttransplant period. Treatment was successful and included the experimental amphotericin product amphotericin B colloidal dispersion. Contemporaneous exposure to a large amount of inocula of Aspergillus within 30 days of receiving high doses of steroids appeared to be the most important factor that predisposed this patient to IPA. Transplant recipients should be specifically proscribed from marijuana use during periods of high steroid administration.

Antifungal Agents↗
PubMed1996

Hearing and saying. The functional neuro-anatomy of auditory word processing.

The neural systems involved in hearing and repeating single words were investigated in a series of experiments using PET. Neuropsychological and psycholinguistic studies implicate the involvement of posterior and anterior left perisylvian regions (Wernicke's and Broca's areas). Although previous functional neuroimaging studies have consistently shown activation of Wernicke's area, there has been only variable implication of Broca's area. This study demonstrates that Broca's area is involved in both auditory word perception and repetition but activation is dependent on task (greater during repetition than hearing) and stimulus presentation (greater when hearing words at a slow rate). The peak of frontal activation in response to hearing words is anterior to that associated with repeating words; the former is probably located in Brodmann's area 45, the latter in Brodmann's area 44 and the adjacent precentral sulcus. As Broca's area activation is more subtle and complex than that in Wernicke's area during these tasks, the likelihood of observing it is influenced by both the study design and the image analysis technique employed. As a secondary outcome from the study, the response of bilateral auditory association cortex to 'own voice' during repetition was shown to be the same as when listening to "other voice' from a prerecorded tape.

Auditory Perception↗
PubMed1996

The effect of oral antiplatelet agents on tissue plasminogen activator-mediated thrombolysis in a rabbit model of thromboembolic stroke.

OBJECTIVE: The success of thrombolytic therapy in acute stroke relies on timely reperfusion. The current study examines the efficacy of antiplatelet agents as adjuvants for thrombolytic therapy. METHODS: Using an established rabbit model of clot embolization and a randomized blinded design, rabbits (n = 8 in each group) were orally pretreated daily for 5 days with adjuvant aspirin (1 mg/kg of body weight or 20 mg/kg), ticlopidine (100 mg/kg), or vehicle (sodium carbonate). On the 6th day, tissue plasminogen activator (6.3 mg/kg administered intravenously over 2 h), was initiated 1 hour after embolization. RESULTS: In all groups, cerebral blood flow (CBF) was reduced to < 10 ml/100 g/min immediately after clot embolization. After the initiation of tissue plasminogen activator (t-PA), there was significant restoration of CBF in the control (t-PA only) and ticlopidine groups (P < 0.05) only. Restoration of CBF generally correlated with brain infarct size (percent hemisphere, mean +/- standard error of the mean), which was 18.0 +/- 7.0 in the t-PA only group versus 11.0 +/- 3.3, 26.5 +/- 5.8, and 21.5 +/- 3.4 in the ticlopidine, low-dose aspirin, and high-dose aspirin groups, respectively (ticlopidine versus aspirin, P < 0.05). Clot lysis was identical in the control and ticlopidine groups, with 6 of 8 animals demonstrating complete clot lysis. Aspirin antagonized clot lysis in a dose-related manner, with low-and high-dose aspirin groups noting clot lysis in four of eight and two of eight animals, respectively. CONCLUSIONS: Pretreatment with ticlopidine significantly reduced brain infarct size when compared with aspirin treatment (P < 0.05). Moreover, whereas ticlopidine treatment did not affect clot lysis or CBF relative to t-PA alone, aspirin therapy resulted in antagonism of clot lysis and was associated with a more modest restoration of blood flow. This study provides a background for a more comprehensive understanding of the balance of thrombogenicity and thrombolysis and may assist in the development of novel therapies to expedite cerebrovascular patency and reduce ischemic and reperfusion-mediated neuronal injury.

Animals↗
PubMed1996

Time-based lag sequential analysis and the functional assessment of challenging behaviour.

This paper describes the application of time-based lag sequential analysis to the functional assessment of challenging behaviours shown by people with severe learning disabilities. The potential uses of the approach are illustrated with regards to identifying: (1) aspects of the stimulus control of challenging behaviour; (2) antecedents to the occurrence of challenging behaviour; and (3) the environmental consequences of challenging behaviour. The uses and limitations of the approach are discussed.

Adolescent↗
PubMed1995

Violent crime in the United States. An epidemiologic profile.

OBJECTIVES: To determine if (1) there was an increase in the rates of acts of violence in the United States from 1973 to 1992 and (2) there were disproportionate changes in rates of violent crime among specific demographic groups. METHODS: Crime data from the Uniform Crime Reporting Program and the National Crime Victimization Survey beginning in January 1973 and ending in December 1992 were examined. Homicide data from 1970 to 1991 were examined with the National Center for Health Statistics mortality data from the Centers for Disease Control and Prevention. Analyses were performed for overall crime rates as well as for specific demographic groups. RESULTS: Rates of victimization from all types of violent crime have increased among adolescents and young adults (from ages 10 through 25 years), regardless of gender or race. Absolute rates were highest among African Americans and males. Both the highest rates and the greatest increases in homicide from 1971 to 1990 were among adolescents and young adults, while rates for those aged 25 years and older decreased. A substantial increase in firearm-related homicides among adolescents and young adults occurred as well, with rates decreasing for those aged 25 years and older. Overall rates of homicide have remained relatively constant during the past two decades. Data addressing overall trends in the rates of non-fatal violence during the past 20 years are inconclusive. CONCLUSIONS: Adolescents are now experiencing the highest and most rapidly increasing rates of lethal and non-lethal violence. The increase in violence among youths 10 to 14 years of age is especially important and alarming. The concentration of violence among children and adolescents has important intervention implications. Because adolescence is a time of great developmental changes, approaches to understanding and preventing violence among our nation's youths should incorporate a developmental perspective that also focuses on the relationship and interactions between individuals and their environments, at the family, community, and societal levels.

Adolescent↗
PubMed1995

Aphasic naming: what matters?

This paper investigates the factors which affect naming performance for two groups of aphasic subjects. The effects of word age-of-acquisition, operativity, frequency, familiarity, imageability, concreteness, length and the visual complexity of the stimulus picture were examined. In contrast to previous studies, we found remarkably small effects of word frequency on naming performance; these studies, we argue, have failed to control sufficiently for the effects of variables which intercorrelate with frequency. However, many patients were significantly affected by age-of-acquisition even when any effects of frequency and familiarity had been accounted for. Operativity, imageability and word length were also predictive of naming performance for some of the patients investigated, unlike visual complexity. The applicability of conclusions drawn from groups of aphasics is again thrown into doubt, as these two groups showed different patterns of predictor variables, and the variables affecting the performance of individuals could be different from those affecting the group.

Adult↗
PubMed1995

Why people don't learn from diabetes literature: influence of text and reader characteristics.

The study was designed to identify text and reader characteristics that impede learning. Twenty-six adults with diabetes mellitus took a 15-item test for prior knowledge of diabetes, a 20-item vocabulary test, and a Need for Cognition questionnaire. Immediately after reading an excerpt from a commonly used diabetes pamphlet, they could recall an average of only eight of the 108 ideas in it. Readers seldom monitored their comprehension. Also, the topics that they thought were important differed from the topics that a physician thought were important. Many readers lacked reading skills, but those with high need for cognition and higher vocabulary scores recalled more topics. Even with an appropriate reading level, text characteristics that could hinder comprehension included lack of organization and clarity.

Adult↗
PubMed1995

Phonological errors in aphasic naming: comprehension, monitoring and lexicality.

This paper investigates the production of phonological errors in aphasic naming, examining the relationship between these errors and deficits in comprehension. The predictions of Dell and O'Seaghda's (1991) computational model of speech production were tested by lesioning. The set of lesioned models demonstrated a strong correlation between proportion of phonologically related errors in naming and comprehension accuracy. In contrast, no correlation between proportion of phonological errors in naming and comprehension accuracy was found for a group of fifteen aphasics. This paper also examines monitoring behaviours, such as the presence of self-corrections and interrupted responses, again finding no relationship with auditory comprehension. There was also no evidence for a lexical bias in the phonological errors for these aphasic subjects. Phonologically related errors were argued to be words only by chance; this was supported by the fact that they occurred more frequently on short words than long words, and that the proportion of real word errors was not significantly different to that observed in a pseudocorpus of errors. We conclude that a production-based monitor would be compatible with these results but that any comprehension-based monitor is not reliably employed by some or all of the aphasic subjects examined here. Additionally, these data are incompatible with models of language processing where speech input and output share the same processing components.

Adult↗
PubMed1995

Comparison of the infusion requirements and recovery profiles of vecuronium and cisatracurium 51W89 in intensive care unit patients.

The selection and administration of neuromuscular blocking (NMB) drugs in intensive care unit (ICU) patients remain controversial. We compared the dose-response and recovery pharmacodynamics of a new intermediate-acting NMB drug, cisatracurium besylate, to the intermediate-acting NMB drug, vecuronium (VEC), in a prospective, randomized, double-blind, multicenter study in critically ill adults. After informed consent, 58 mechanically ventilated ICU patients from five medical centers were randomized to receive either cisatracurium or VEC. Fifty-four of the 58 patients received NMB drugs before entering this study but demonstrated at least partial recovery (> or = one twitch) in the train-of-four (TOF) response before initiation of the NMB study drug. NMB drug infusion was titrated by peripheral nerve stimulation to maintain at least one twitch in the TOF response. NMB drugs were infused for 1-5 days. After discontinuation of NMB drug infusion, recovery of neuromuscular transmission was monitored with an accelerometer. NMB drug infusion for 28 cisatracurium patients averaged 2.6 +/- 0.2 (mean +/- SEM) micrograms.kg-1.min-1 with a mean duration of 80 +/- 7 h. After discontinuing cisatracurium administration, recovery to 70% TOF ratio averaged 68 +/- 13 min. The mean infusion rate for 30 VEC patients was 0.9 +/- 0.1 micrograms.kg-1.min-1 with a mean duration of 66 +/- 12 h. Neuromuscular recovery after VEC averaged 387 +/- 163 min, which was significantly longer (P = 0.02) than that after cisatracurium. Prolonged recovery of neuromuscular function after discontinuation of NMB drug infusion (identified by the primary investigator at each medical center) was reported in two cisatracurium patients and 13 VEC patients (P = 0.002), and occurred despite the routine use of neuromuscular twitch monitoring. Seven VEC and one cisatracurium patients died during the infusion of study drug or within 48 h after discontinuation of the NMB drug infusion. In summary, we found recovery of neuromuscular function after discontinuation of NMB drug infusion in ICU patients is significantly faster with cisatracurium than with VEC. In addition, routine neuromuscular monitoring was not sufficient to eliminate prolonged recovery and myopathy in ICU patients.

Adult↗
PubMed1995

Impaired responsiveness to gamma interferon of macrophages infected with lymphocytic choriomeningitis virus clone 13: susceptibility to histoplasmosis.

Lymphocytic choriomeningitis virus clone 13 (LCMV clone 13), a variant isolated from the spleens of neonatally infected mice, causes persistent infections in mice infected as adults. Such persistently infected mice succumb to a normally sublethal dose of Histoplasma capsulatum, and their macrophages contain overwhelming numbers of yeast cells of the fungus. Both LCMV clone 13 and H. capsulatum yeast cells target and replicate in macrophages of the host. We sought to study the effects of LCMV clone 13 on the ability of macrophages to control growth of H. capsulatum in vitro. We show that the growth of H. capsulatum within macrophages was not directly affected by the presence of LCMV clone 13. However, macrophages containing LCMV clone 13 did not respond fully to gamma interferon (IFN-gamma) stimulation. Such unresponsiveness resulted in proliferation of the fungus within macrophages cultured in the presence of IFN-gamma. The addition of anti-IFN-alpha/beta antibodies to LCMV clone 13-infected macrophage cultures restored macrophage responsiveness to IFN-gamma. These results indicate that production of IFN-alpha/beta by LCMV clone 13-infected macrophages antagonizes their responsiveness to IFN-gamma. Such antagonism may be one of the mechanisms by means of which certain viruses cause immune suppression and susceptibility to opportunistic infections.

Animals↗
PubMed1994

The treatment of acquired aphasia.

A number of large-scale trials have established that language therapy with acquired aphasic patients can result in significant improvement. However, such trials use a variety of different treatments with patients with qualitatively varying disorders. The group results give no information about the treatments that were effective for particular types of problem. More recent studies of treatment have examined the effects of more closely defined treatments for more closely defined disorders. Treatment based on the facilitation of word retrieval show quite long-lasting effects from limited amounts of treatment, when the treatment gives either semantic or phonological information about the word, but the improvements are mostly limited to the items involved in treatment. The establishment of strategies for word retrieval based on patients' retained abilities results in more generalized improvement. The need for studies that relate analysis of a patient's disorder more closely to the process of treatment is discussed.

Anomia↗
PubMed1994

Isolation of Arabidopsis thaliana mutants hypersensitive to gamma radiation.

A screening method for mutants of Arabidopsis thaliana hypersensitive to gamma-radiation has been devised. Plants grown from ethyl methanesulfonate (EMS)-treated seeds were irradiated at the seedling stage, which is highly radiosensitive due to extensive cell division. Severe growth inhibition of mutant plants by a gamma-ray dose which only slightly affects wild-type plants was the selective criterion. Twelve true-breeding hypersensitive lines were isolated from a total of 3394 screened plants. Genetic analysis of five of the lines revealed five new genes, designated RAD1-RAD5. These Arabidopsis RAD mutants are phenotypically similar to mutants in the RAD52 epistasis group of Saccharomyces cerevisiae, which are highly sensitive to ionizing radiation but not hypersensitive to UV light. One possibility is that the Arabidopsis mutants are defective in a nonhomologous or illegitimate recombination mechanism used by plants for repair of chromosome breaks.

Arabidopsis↗
PubMed1994

Improving the quality of antibiotic prescription patterns in general practice. The role of educational intervention.

OBJECTIVE: To assess the quality of antibiotic prescribing by Victorian general practitioners, and the effectiveness of educational intervention techniques in improving prescribing. DESIGN: A randomised, controlled, parallel group trial. SETTING AND PARTICIPANTS: In rural and metropolitan Victoria, 182 general practitioners (78 control, 104 intervention) began and 103 (41 control, 62 intervention) completed the study. INTERVENTION: Participants recorded their antibiotic prescribing for tonsillitis. The intervention group received an educational mailing campaign. A project pharmacist visited each doctor to discuss campaign messages. MAIN OUTCOME MEASURE: The percentages of prescriptions of antibiotics for tonsillitis complying with those recommended in Antibiotic guidelines. RESULTS: In the intervention group, prescriptions consistent with recommendations in the guidelines increased from 60.5% before the campaign to 87.7% afterwards. Improvement also occurred in the control group, from 52.9% to 71.7% of prescriptions. The improvement within the intervention group was significantly greater than that within the control group. CONCLUSIONS: The educational campaign significantly improved the prescribing of appropriate antibiotics for tonsillitis by general practitioners.

Anti-Bacterial Agents↗
PubMed1994

Brain activity during reading. The effects of exposure duration and task.

Brain activity during reading tasks was investigated using PET. The aim was to account for differences in the results of two previous studies [those of Petersen et al. (Science 1990; 249: 1041-4) and Howard et al. (Brain 1992; 115: 1769-82)] by systematically varying the type of reading task and the exposure duration of the word stimuli. Both variables strongly influenced patterns of brain activity. There were three types of task: (i) reading aloud; (ii) reading silently; and (iii) lexical decision on visually presented words and pseudowords. Reading aloud and reading silently engaged the left middle and superior temporal regions, confirming the important role of these areas in visual word processing. The areas principally engaged during lexical decision were the left inferior and middle frontal cortices and the supplementary motor area; activity in these areas suggests that the subjects were using a phonological strategy to perform the task. There was also a significant effect of exposure duration, with activity being greater for short (150 ms) exposure durations than for long (1000 ms or 981 ms) exposure durations. We conclude that until we understand how subtle variations in experimental design influence brain activity during reading tasks, the association of specific processing functions with individual anatomical areas activated during reading is premature.

Adult↗
PubMed1994

Precursor pools of protein synthesis: a stable isotope study in a swine model.

The accuracy of using other free pools in lieu of tRNA for calculation of tissue protein synthesis in liver (L), skeletal muscle (SM), and heart (H) was assessed in six adult miniature swine using L-[1-13C]leucine and L-[ring-2H5]phenylalanine as tracers. L leucyl-tRNA enrichment was higher than arterial plasma leucine and ketoisocaproate (KIC) enrichments, and L phenylalanyl-tRNA enrichment was higher than arterial phenylalanine enrichment (P < 0.05). No such differences were noted in SM and H. Leucyl- and phenylalanyl-tRNA enrichments in L were best predicted by the respective amino acid enrichments in tissue fluid [TF; Leu: slope (m) = 0.954 +/- 0.035; Phe: m = 1.011 +/- 0.032] using linear regression analysis to determine the accuracy of the prediction, whereas plasma phenylalanine reasonably predicted phenylalanyl-tRNA (artery: m = 0.821 +/- 0.032; vein: m = 0.947 +/- 0.135). In SM, plasma KIC (artery: m = 0.846 +/- 0.046; vein: m = 0.881 +/- 0.043) and TF leucine (m = 0.788 +/- 0.034) predicted leucyl-tRNA with high accuracy. In H tissue, TF (m = 0.991 +/- 0.044) was the best predictor of leucyl-tRNA enrichment, whereas arterial phenylalanine (m = 0.912 +/- 0.015) was the most reliable predictor of phenylalanyl-tRNA enrichment. The relationships between aminoacyl-tRNA and other free pools in the same species under the same study conditions differ in different tissues. Use of KIC in lieu of leucyl-tRNA for calculating muscle protein synthesis is supported by this study.

Animals↗