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Biomedical subjects

R Burns

Publications and source records attributed to R Burns.

At least 19 recordsLinked to original sources

Primary mutations in calmodulin prevent activation of the Ca(++)-dependent Na+ channel in Paramecium.

Paramecium tetraurelia behavioral mutant cam12 displays a "fast-2" behavioral phenotype: it fails to respond to Na+ stimuli. Electrophysiologically, it lacks a Ca(++)-dependent Na+ current. Genetics and DNA sequencing showed the primary defect of cam12 to be in the calmodulin gene (Kink et al., 1990). To correlate calmodulin structure and function in Paramecium, we elucidated the primary structure of cam12 calmodulin. Peptide sequencing confirmed the two point mutations predicted by the DNA sequence: a glycine-to-glutamate substitution at position 40 and an aspartate-to-asparagine substitution at position 50. Our results further showed that lysine 13 and lysine 115 were methylated normally in cam12. It is likely that the electrophysiological abnormalities of cam12 are a direct reflection of the amino-acid substitutions, as opposed to improper posttranslational modification.

Amino Acid Sequence

Decrease of depression during stroke and amputation rehabilitation.

Clinical observation had suggested that mild depression occurs after admission for acute medical treatment and then decreases during further hospitalization for rehabilitation treatment. The Geriatric Depression Scale (GDS) was given on admission and discharge to 14 stroke and 17 amputee rehabilitation patients. Each of the two groups showed decreasing GDS scores from beginning to end of the rehabilitation admission. Suggested reasons included: (1) the gradually diminishing effects of stroke and amputation as life crises during the 1-2 month admission, (2) effects of physical improvement on mood and affect, (3) milieu effects of the medical ward, and (4) tendencies for all psychopathology scale scores to decrease on retest.

Activities of Daily Living

Increase of medical hospital length of stay by depression in stroke and amputation patients: a pilot study.

Past studies have found that medical patients with the diagnosis of depression (comorbidity) have longer hospital lengths of stay (LOS) than those without the diagnosis of depression. This suggested that scores on a depression scale would be positively correlated with LOS. On a rehabilitation ward, 14 stroke and 17 amputee patients were given the Geriatric Depression Scale (GDS) and lengths of stay were recorded. Correlations between GDS scores and LOS were +0.575 for stroke and +0.266 for amputee patients, both in the hypothesized direction. Explanations considered included: (1) depression and medical illness each produce morbidity which summate to require increased LOS; (2) depression delays medical recovery as well as the appearance of medical recovery, and (3) discharge planning is complicated by depression. When depression is associated with inpatient medical illness, DRGs may need to be reevaluated.

Activities of Daily Living

The stop/glide boundary shift: modelling perceptual data.

Research in speech perception has suggested that listeners often adjust category boundary locations for differing contexts. The stop/glide (e.g.,/ba/vs./wa/) boundary shift occurring with changes in syllable duration has been interpreted as reflecting 'rate normalization' by some, whereas others have suggested an auditory basis for the shift. Clarification of both the causes and the effects of the stop/glide shift is being sought through experimentation intended to expand our knowledge of variations in the shift across different experimental treatments. The present study extends research on the stop/glide shift by (1) showing that the shift is not an artifact of a particular stimulus pattern that had been present in all the previous studies of the effect, (2) further demonstrating the nonlinear character of the identification shift, (3) providing additional evidence of the role of presentation format (mixed vs. blocked) in the identification shift, and (4) exploring boundary locations in various discrimination paradigms. The complex outcomes of the studies reported here as well as a variety of previous results are interpreted as compatible with expanded versions of the durational contrast hypothesis. Two versions are considered, one in which the shift is seen as due to a mechanism of contrastive perception that applies to events of comparable duration, and one in which the shift is seen as a perceptual error that occurs when the auditory system attempts to track frequency trajectories that change (i.e., pivot) over time.

Adult

A randomized, controlled trial of a geriatric assessment unit in a community rehabilitation hospital.

We conducted a randomized trial in a community rehabilitation hospital to determine the effect of treatment in a geriatric assessment unit on the physical function, institutionalization rate, and mortality of elderly patients. Functionally impaired elderly patients (mean age, 78.8 years) who were recovering from acute medical or surgical illnesses and were considered at risk for nursing home placement were randomly assigned either to the geriatric assessment unit (n = 78) or to a control group that received usual care (n = 77). The two groups were similar at entry and were stratified according to the perceived risk of an immediate nursing home placement. After six months, the patients treated in the geriatric assessment unit had significantly more functional improvement in three of eight basic self-care activities (P less than 0.05). Those in the lower-risk stratum had significantly more improvement in seven of eight self-care activities. Both six weeks and six months after randomization, significantly more patients treated in the geriatric assessment unit than controls (79 vs. 61 percent after six months) were residing in the community. During the year of follow-up, the control patients had more nursing home stays of six months or longer (10 vs. 3; P less than 0.05). However, there was no difference between the groups in the mean number of days spent in health care facilities (acute care hospital, nursing home, or rehabilitation hospital). Survival analysis showed a trend toward fewer deaths among the patients treated in the geriatric assessment unit, and mortality was significantly reduced in the patients considered to be at lower risk of immediate nursing home placement (P less than 0.05). We conclude that the treatment of selected elderly patients in a specialized geriatric rehabilitation unit improves function, decreases the risk of nursing home placement, and may reduce mortality. The beneficial effects on mortality and function appear greatest for patients at a moderate rather than high risk of nursing home placement.

Follow-Up Studies

Effects of Vasocon-A in the allergen challenge model of acute allergic conjunctivitis.

The ophthalmic combination product of 0.05% naphazoline hydrochloride and 0.5% antazoline phosphate (Vasocon-A) was evaluated as an antiallergic agent in 100 subjects with a known allergic history to cat dander, ragweed, or bluegrass pollen. Three independent study sites were used. The allergen challenge model of acute allergic conjunctivitis was selected to assess the agent as it provided a standardized and precise way to measure drug effectiveness for this indication. In a double-masked randomized fashion, the subjects were assigned to one of three groups that received one drop of Vasocon-A in one eye and one drop of either 0.05% naphazoline (group 1), 0.5% antazoline (group 2), or placebo (group 3) in the contralateral eye. After 10 minutes, the dose of allergen shown to elicit a 2+ redness and itching reaction was instilled bilaterally. Signs and symptoms of allergic conjunctivitis were evaluated after 3, 5, and 10 minutes. Subjects were then rechallenged 2 hours after drug administration to assess the duration of action of the agents. Vasocon-A was found to significantly inhibit all five major signs and symptoms of allergic conjunctivitis: itching, redness, chemosis, lid swelling, and tearing, for more than 85% of the comparisons when compared over time with placebo, naphazoline alone, or antazoline alone. The results of this study indicate that the combination of naphazoline and antazoline was more effective in inhibiting redness than naphazoline and more effective in inhibiting itching than antazoline. These findings support the use of such a combination for the treatment of allergic conjunctivitis.

Allergens

Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics. Does aminophylline add any benefit?

STUDY OBJECTIVE: To determine the efficacy of intravenous aminophylline in the treatment of adult patients hospitalized for exacerbation of asthma. DESIGN: Randomized, double-blind, placebo-controlled trial throughout the study. SETTING: University Hospital Clinical Research Center. PATIENTS: Forty-four patients admitted from the emergency room with a primary diagnosis asthma; 39 patients completed the study. INTERVENTIONS: Patients received either intravenous aminophylline or placebo in addition to frequent nebulized albuterol; prednisone 0.5 mg/kg body weight every 6 h orally; and supplemental oxygen. Aminophylline infusion rates were adjusted to achieve serum theophylline concentrations of 10 to 20 micrograms/ml. Changes were made in placebo infusion rates to maintain the double blind design. MEASUREMENTS AND RESULTS: Forced expiratory volume in 1 s (FEV1) and other spirometric measurements every 8 h by a blinded investigator or trained respiratory therapist. Subjective patient response and duration of hospitalization were compared. No difference in spirometric measurements was observed between the two groups at any time point. On admission to the study, FEV1 in the placebo group was 41.5 (+/- 2.9) percent predicted and in the aminophylline group 34.7 (+/- 2.3) percent predicted (p = 0.08). At discharge, FEV1 was 70.4 (+/- 2.9) percent predicted in the placebo group and 63.7 (+/- 2.8) percent predicted in the theophylline group (p = 0.10). There was no difference in subjective patient rating or duration of hospitalization between the two groups (placebo 1.95 days and aminophylline 1.78 days, p = 0.51). CONCLUSIONS: Our results suggest that aminophylline therapy does not add significant benefit to other standard therapies in hospitalized adult asthmatic patients. Because of the risks and cost of aminophylline treatment in the hospital setting, further research is needed to determine if there are subgroups of adult asthmatics who may benefit from the addition of aminophylline to other standard optimal therapies.

Acute Disease

Pitfalls in headache management.

The diagnosis of serious causes of headache depends on a careful history, a high index of suspicion of the unusual presentations and the judicious use of CT scanning. It is important not to overlook subarachnoid haemorrhage, intracerebral haemorrhage, meningitis, cerebral tumours, cerebral malformations and giant cell arteritis. Iatrogenic causes such as drugs and spinal procedures should also be considered.

Adult

Tissue plasminogen activator: Toronto (TPAT) placebo-controlled randomized trial in acute myocardial infarction.

The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) administered on a dosing per weight basis was evaluated in a randomized, placebo-controlled, double-blind trial in 115 patients with acute myocardial infarction. The principal outcomes were global and regional left ventricular function in the distribution of the qualifying myocardial infarction, determined 9 days after the onset of symptoms. Global and regional ejection fraction values were significantly better for patients treated with rt-PA than for placebo-treated patients (the differences were 5.8 +/- 2.7% units [p = 0.017] and 7.1 +/- 3.1% units [p = 0.012], respectively). This benefit was also evident from visual assessment of left ventricular segmental wall motion. After adjustment for differences in important prognostic variables at baseline, the estimates of treatment effect were 4.0 +/- 2.4% units (p = 0.048) for global and 4.3 +/- 2.6% units (p = 0.047) for regional ejection fraction. Early patency of the infarct-related vessel was demonstrable in 7 (29%) of 24 placebo-treated patients and 18 (78%) of 23 rt-PA-treated patients, whereas 15 (56%) of 27 patients in the placebo group and 23 (72%) of 32 in the rt-PA group had a patent infarct-related vessel at hospital day 9. There was no significant difference in irreversible or reversible defect size as assessed by thallium scintigraphy on day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method

Animals in research.

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Animal Testing Alternatives

Cost effectiveness in the treatment of hypertension.

Treatment of hypertensive elderly patients reduces cardiovascular mortality. The drug regimen selected affects the cost per prevented death. Drug regimens may have a tenfold difference in cost per cardiovascular death prevented.

Aged

Cerebrovascular disease.

Cerebrovascular disorders producing transient or permanent symptoms and signs are very common, but they are not the only causes of a sudden neurologic deficit. Careful examination of the cardiovascular system may indicate the likely cause of the lesion, while accurate neurologic localization is also useful in establishing a diagnosis and prognosis. The CT scan is very helpful in distinguishing infarction from haemorrhage. In the management of the acute lesion, treatable disorders such as systemic diseases, potentially fatal rostro-caudal herniation, haematomas and aneurysms always need to be positively exlcuded. Endarterectomy, platelet inhibitors and anticoagulants are advised in certain situations, although their place in the management of cerebrovascular disorders still remains somewhat controversial.

Auscultation