Search PubMed⌕ Search

Biomedical subjects

W Burke

Publications and source records attributed to W Burke.

At least 91 records · Page 5Linked to original sources
PubMed1993

Effect of the platelet-activating factor antagonist UK-74,505 on the early and late response to allergen.

The effect of UK-74,505, a specific platelet-activating factor (PAF) antagonist, on the early (EAR) and late asthmatic response (LAR) to inhaled allergen was studied in a randomized, double-blind, placebo-controlled crossover study. A total of eight adult male atopic asthmatic subjects completed the protocol (one withdrew after screening), all having demonstrated a dual response to inhaled allergen (EAR, > 20% fall in FEV1 between 0 and 1 h; LAR, > 15% fall in FEV1 between 4 and 8 h after challenge). Subjects were studied on 2 days at least 10 days apart. After measurement of baseline FEV1, subjects ingested a single oral dose of 100 mg UK-74,505 or matched placebo (P). Allergen challenge was performed 3 h later and the FEV1 was then measured for 8 h. There was no difference between UK-74,505 and placebo in the maximum percentage change from baseline (+/- SEM) for either EAR or LAR (EAR, UK-74,505 -25.6 +/- 4.8%, P -24.0 +/- 3.3%; LAR, UK-74,505 -20.8 +/- 4.4%, P -25.7 +/- 3.8%). There was no significant difference in the area under the percentage change from baseline FEV1-time curve. Ex vivo platelet aggregation to PAF was measured at 0, 2, 6, 8, and 10 h after the dose. There was marked inhibition of platelet aggregation to PAF for 10 h following UK-74,505 but not placebo (% maximum aggregation to PAF, UK-74,505, -69.9%; P, 0.13%; p = 0.0001). Histamine challenge was performed in five patients the day before and after each study day. There was no significant difference between UK-74,505 and placebo in PD20 to histamine (mean PD20 before and after UK-74,505, 1.31 and 0.96 mumol; P, 1.32 and 1.17 mumol). UK-74,505 did not affect either the EAR or the LAR to inhaled allergen or bronchial responsiveness, despite its potency and long duration of action. This suggests that PAF does not have a major role in the acute response to inhaled allergen.

Adolescent↗
PubMed1993

Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF. The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes. Recombinant human DNase I (rhDNase) reduces the viscosity of CF sputum in vitro. To test the hypothesis that rhDNase would improve pulmonary function in children and adults with CF, we compared the efficacy and safety of 10-day administration of three doses of aerosolized rhDNase (0.6, 2.5, or 10.0 mg twice daily) in 181 outpatients using a randomized, placebo-controlled parallel design. Forced vital capacity (FVC) improved 10 to 12% (p < 0.05 to 0.001), and forced expiratory volume in one second (FEV1) improved 10 to 15% (p < 0.001) across all doses of rhDNase compared with placebo. The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 (p < 0.001). rhDNase was associated with a decreased perception of dyspnea and an improved perception of well-being. No patients developed detectable anti-rhDNase antibodies or bronchial reactivity to rhDNase. Some patients experienced mild upper airway irritation, but no major adverse events were reported. Administration for 10 days of aerosolized rhDNase to pediatric and adult outpatients with CF improves lung function and is well tolerated. Although all three doses were efficacious, the greatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups.

Adolescent↗
PubMed1993

Nontuberculous mycobacterial disease in adult cystic fibrosis patients.

This study was conducted to determine the prevalence of mycobacterial disease in an adult cystic fibrosis (CF) population and to determine if there were any patients at higher risk for this disease within the group. Sixty-four patients (28 women, 36 men), ranging in age from 17 to 50 years were screened. One-step purified protein derivative skin testing with controls was performed and sputum was taken for examination. Eight of 64 had positive sputum culture for nontuberculous Mycobacterium. The CF patients with positive mycobacterial sputum cultures tended to be older and to have lower clinical scores than those who did not have Mycobacterium organisms in sputum. Guidelines to determine whether mycobacterial disease or colonization is present should be pursued for the CF population.

Adolescent↗
PubMed1992

Do we still need primary care tracks?

Primary care tracks in internal medicine residency programs were initiated in the late 1970s in response to the need for more primary care physicians. These programs have shown that internists can be trained effectively in ambulatory settings. Graduates of primary care tracks are more likely to choose careers in general internal medicine than are other internal medicine graduates. Primary care internist training has been accompanied by the growth of academic general internal medicine divisions and by the enhancement of the scientific base for ambulatory care practice and medical education. Expanded ambulatory training opportunities, modeled after current primary care tracks, should be offered to all residents in internal medicine. At the same time, primary care tracks should be revised to address deficiencies in current ambulatory training. These tracks should be designed to commit most resident time to ambulatory care settings, to involve residents in community-based and interdisciplinary health care, and to expose residents to conditions outside of the medical sector that affect health. Revised primary care tracks can serve as pathfinder programs for ongoing reform in internal medicine residency training. Three models for organizing and funding such reform are presented.

Curriculum↗
PubMed1992

Myoclonus in the decerebrate cat produced by gallamine.

After intravenous infusion maintaining a neuromuscular blocking concentration very little gallamine enters the cerebrospinal fluid (CSF) of the intact anesthetized cat even after several days. After a similar intravenous infusion in the decerebrate cat gallamine enters the CSF slowly over 4 days eventually reaching a concentration similar to that in the plasma. This procedure is accompanied by very strong twitching in many muscles and the occurrence of slow waves in the inferior olive in synchrony with the twitches. A large dose (4 mg) of gallamine triethiodide injected directly into the cisterna magna of an intact anesthetized cat produced twitching within 1 min and slow waves in the inferior olive in good synchrony with the twitches; the effects lasted at least 43 h. Injection of a quantity of gallamine triethiodide (about 130 micrograms) sufficient to mimic the concentration in the CSF obtained after 3-4 days of neuromuscular block in the decerebrate cat (50-120 micrograms/ml gallamine) had extremely weak effects lasting for at most 1 h. However, this weak effect is probably due to the anesthetic because injection of a similar quantity into an (unanesthetized) decerebrate cat at any time after decerebration had strong effects. After intracisternal injection of gallamine the concentration in the CSF reaches very low levels within 12 h but twitching and activity in the inferior olive persists for 1-2 days. The reasons for this prolonged action are now being investigated. The effects of gallamine are compared with the condition of reticular reflex myoclonus.

Animals↗
PubMed1992

Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis. A phase 1 study.

OBJECTIVE: To evaluate the safety of recombinant human DNase (rhDNase) in normal subjects and in patients with cystic fibrosis. DESIGN: Nonrandomized trial in which individuals inhaled rhDNase three times a day Monday through Friday on two consecutive weeks. SETTING: The study was performed in the Clinical Research Center at the University of Washington, Seattle. Patients were recruited from the Cystic Fibrosis Center at the University of Washington. SUBJECTS AND PATIENTS: Twelve normal subjects and 14 patients with cystic fibrosis were studied (12 patients completed the protocol). The subjects and patients had to be aged 18 to 65 years and have a negative pregnancy test, if female. The normal subjects had to have a normal chest roentgenogram, be nonsmokers, and have normal pulmonary function testing. The patients with cystic fibrosis had to have a forced vital capacity greater than 40% predicted normal and have no recent exacerbation (within 2 weeks) of their lung infection or change in their medication. INTERVENTIONS: The study design was a repetitive dose escalation of aerosolized rhDNase. The subjects inhaled rhDNase three times a day, Monday through Friday, on 2 consecutive weeks and were rechallenged with a single dose 21 days after the last dose. Spirometry was measured before and 30 minutes after every rhDNase dose. MAIN OUTCOME MEASURES: Pulmonary function testing, serum DNase concentrations, and anti-DNase antibodies. Secondary outcome measures were dyspnea score and quantitative bacterial culture. MAIN RESULTS: Inhalation of rhDNase was well tolerated by all persons. There were no serious adverse reactions, and no allergic reactions were observed, even on rechallenge. No individual developed rhDNase antibodies. Improvement in both lung function and dyspnea score was observed in the adults with cystic fibrosis. Forced vital capacity was 3.2 +/- 0.3 L (mean +/- SE) on day 1 and was 3.5 +/- 0.3 L on day 12. Forced expiratory volume in 1 second was 2.1 +/- 0.2 L (mean +/- SE) on day 1 and was 2.3 +/- 0.3 L on day 12. CONCLUSIONS: Aerosolized rhDNase appears safe in normal subjects and in adults with cystic fibrosis and may improve lung function with short-term therapy.

Administration, Inhalation↗
PubMed1992

Effects of selective pressure block of Y-type optic nerve fibers on the receptive-field properties of neurons in the striate cortex of the cat.

In an aseptic operation under surgical anesthesia, one optic nerve of a cat was exposed and subjected to pressure by means of a special cuff. The conduction of impulses through the pressurized region was monitored by means of electrodes which remained in the animal after the operation. The pressure was adjusted to selectively eliminate conduction in the largest fibers (Y-type) but not in the medium-size fibers (X-type). The conduction block is probably due to a demyelination and remains complete for about 3 weeks. Within 2 weeks after the pressure-block operation, recordings were made from single neurons in the striate cortex (area 17, area V1) of the cat anesthetized with N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate. Neurons were activated visually via the normal eye and via the eye with the pressure-blocked optic nerve ("Y-blocked eye"). Several properties of the receptive fields of single neurons in area 17 such as S (simple) or C (complex) type of receptive-field organization, size of discharge fields, orientation tuning, direction-selectivity indices, and end-zone inhibition appear to be unaffected by removal of the Y-type input. On the other hand, the peak discharge rates to stimuli presented via the Y-blocked eye were significantly lower than those to stimuli presented via the normal eye. As a result, the eye-dominance histogram was shifted markedly towards the normal eye implying that there is a significant excitatory Y-type input to area 17. In a substantial proportion of area 17 neurons, this input converges onto the cells which receive also non-Y-type inputs. In one respect, velocity sensitivity, removal of the Y input had a weak but significant effect. In particular, C (but not S) cells when activated via the normal eye responded optimally at slightly higher stimulus velocities than when activated via the Y-blocked eye. These results suggest that the Y input makes a distinct contribution to velocity sensitivity in area 17 but only in C-type neurons. Overall, our results lead us to the conclusion that the Y-type input to the striate cortex of the cat makes a significant contribution to the strength of the excitatory response of many neurons in this area. However, the contributions of Y-type input to the mechanism(s) underlying many of the receptive-field properties of neurons in this area are not distinguishable from those of the non-Y-type visual inputs.

Animals↗
PubMed1992

Effects of selective pressure block of Y-type optic nerve fibers on the receptive-field properties of neurons in area 18 of the visual cortex of the cat.

Recordings were made from single neurons in area 18 of anesthetized cats (N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate) in which one optic nerve had been pressure blocked to selectively block conduction in the largest (Y-type) fibers. Cortical neurons were stimulated visually via the normal eye or via the eye with the pressure-blocked optic nerve ("Y-blocked eye"). Several properties of the receptive fields such as their spatial organization (S or C cells), orientation tuning, and the presence and strength of end-zone inhibition appear to be unaffected by removal of the Y input. By contrast, the removal of the Y input resulted in a small but significant reduction in the size of the discharge field and in the direction-selectivity index. In three respects, peak response discharge rate, eye dominance, and velocity sensitivity, removal of the Y input had strong and highly significant effects. Thus, the mean peak discharge frequency of responses evoked by the stimulation of binocular neurons via the Y-blocked eye was significantly lower than that of responses evoked by the stimulation via the normal eye. Accordingly, the eye-dominance histogram was shifted markedly towards the normal eye (more so than in the homologous experiment conducted on area 17-Burke et al., 1992). Finally, the mean preferred velocity of responses of cells activated via the normal eye was in the vicinity of 145 deg/s, whereas for cells activated via the Y-blocked eye the value was about 35 deg/s. Overall, the results of the present study imply that (1) apart from Y-type excitatory input there are significant excitatory non-Y-inputs to area 18; these inputs at least partially consist of indirect X-type input relayed via area 17; (2) in neurons of area 18 that receive both Y-type and non-Y-type excitatory inputs, the Y-type input has a major influence on strength of the response and velocity sensitivity and a lesser influence on the direction selectivity and size of the discharge fields; and (3) area 18 contains mechanisms determining such receptive-field properties as S- or C-type organization, orientation tuning, and direction selectivity which can be accessed either by the Y input or by non-Y input.

Afferent Pathways↗
PubMed1992

Large de novo DNA deletion in a patient with sporadic neurofibromatosis 1, mental retardation, and dysmorphism.

A mildly dysmorphic, mentally retarded male with neurofibromatosis 1 (NF1) was found to have a de novo deletion of chromosome 17. The deletion occurred on the paternally derived chromosome 17 as shown by the absence of a D17S73 paternal allele. Densitometric analysis indicated that, in addition to the D17S73 locus, the patient has only one copy of four other adjacent loci. The deletion involved the loci D17S120, NF1, D17S57, D17S115, and D17S73 and was estimated to encompass more than 380 kb of DNA. The deletion of the entire paternal NF1 allele argues strongly that this disorder is not caused by the action of an abnormal NF1 protein. The extent of the deletion suggests that the mental retardation and dysmorphism of this patient may result from a deletion involving both the NF1 gene and contiguous genetic material.

Abnormalities, Multiple↗
PubMed1992

Variable severity of pulmonary disease in adults with identical cystic fibrosis mutations.

Adults with CF followed in a university center were assessed for the presence of the most common CF gene mutation, delta-F508. Excluding one member of a sibling pair, 29 of 55 subjects had two copies of delta-F508 (homozygotes), 23 had one copy of delta-F508 with the other CF mutation not identified (complex heterozygotes) and three were lacking delta-F508. A wide range of clinical severity was seen among individuals carrying two copies of the delta-F508 gene, who are genetically identical at the CF gene locus. The number of individuals diagnosed with CF as adults was significantly lower in the homozygote group (1 of 29) as compared with the heterozygote group (7 of 24). No differences were detected between groups in pulmonary function, non-pulmonary complications or overall clinical severity. These results suggest that environmental or background genetic factors contribute significantly to the variability in pulmonary and other complications seen among individuals with CF.

Adolescent↗
PubMed1991

Analysis and quantitation of the beta-amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients with a monoclonal antibody-based immunoassay.

One of the major clinical findings in Alzheimer's disease (AD) is the formation of deposits of beta-amyloid protein in amyloid plaques, derived from the beta-amyloid precursor protein (beta-APP). To determine the possible use of beta-APP as a diagnostic marker for AD in CSF, a monoclonal antibody-based immunoassay specific for this protein was developed. The assay does not differentiate between beta-APP695 and beta-APP751 forms but does preferentially recognize beta-APP751 complexed with a protease. Of the two sets of CSF samples tested, one set, obtained from living patients, gave a slightly lower level of beta-APP in AD and Parkinson's disease patients relative to controls, whereas the other set, composed of postmortem samples, showed no significant differences between the AD and control groups.

Alzheimer Disease↗
PubMed1990

Primary care internal medicine: a challenging career choice for the 1990s.

A career in primary care internal medicine can be challenging and rewarding, yet during the last decade fewer medical students have selected training in internal medicine. We wish to inform medical students, their advisors, and other physicians about the field of primary care internal medicine. We define the discipline, compare it with traditional internal medicine and with family practice, and describe features of strong primary care internal medicine training programs. We discuss common misconceptions and concerns about training programs and the career and give examples of career paths chosen by graduates of primary care programs. We encourage students to consider the option of primary care internal medicine when making career decisions and provide faculty advisors unfamiliar with primary care internal medicine training programs with a reference resource.

Career Choice↗
PubMed1990

Analysis of tyrosine hydroxylase and insulin transcripts in human neuroendocrine tissues.

We have previously shown that the mRNA for human tyrosine hydroxylase (TH) exists in one of 4 forms as a result of alternative splicing of intron 1. In order to determine the tissue-specific expression of the multiple human transcripts we have utilized specifically primed polymerase chain reactions (PCR) in combination with reverse-transcribed RNA. Using PCR analysis we determined that many human neuronal tissues express all 4 forms of human TH (hTH-1-4); however, hTH-3 and -4 are generally expressed at less than 1% of the other two. Of all tissues examined, only pancreatic beta-islet cells expressed a single form of human TH mRNA (hTH-2). The mRNA for rat TH is present in only one form, the equivalent of hTH-1. Since we have shown that the human genes for TH and insulin are only 2.7 kb apart and several groups have reported insulin-like expression in neuronal tissues, we looked for insulin transcription in the same central and peripheral nervous system samples. Insulin mRNA was not present within the limits of detection.

Animals↗
PubMed1989

Representation of the temporal raphe within the optic tract of the cat.

The retinal topography of the cat's optic tract was determined by means of injections of the enzyme horseradish peroxidase (HRP) into the tract. This analysis was accomplished by the subtraction of all HRP injection sites not labeling a defined retinal area from those injection sites which resulted in ganglion cell labeling (Venn diagram analysis). Using this method, the following correspondences were demonstrated for the ipsilateral and contralateral projections: superior retina represented in medial optic tract; inferior retina in lateral tract; and area centralis in a dorsocentral location (which was part of a larger area representing the visual streak). The temporal raphe was represented in the ipsilateral tract as a band curving from the area centralis region toward the dorsomedial border of the tract. Contralateral fibers from a region superior to the optic disc were found to be displaced with respect to the general retinal representation in the optic tract and this appeared to be related to retinal development. The ratio of contralateral to ipsilateral fibers was determined and found to be nonuniform within the tract. Injection of HRP into the optic tract of the cat also allowed the axons from labeled retinal ganglion cells to be traced within the retina and optic disc. Axons from ganglion cells lying temporal to the raphe curve around the area centralis enter the optic disc on the lateral and inferior aspects. Ganglion cells lying nasal to the raphe send their axons more directly to enter the optic disc on its superior aspect. A schema is proposed whereby the retina is mapped onto the optic tract.

Animals↗