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Biomedical subjects

R S Roberts

Publications and source records attributed to R S Roberts.

At least 73 records · Page 4Linked to original sources
PubMed1988

Concentration response relationships of amiodarone and desethylamiodarone.

Twelve patients with frequent ventricular premature depolarizations (VPDs) received amiodarone, 600 mg/day, for up to 8 weeks. On days 0, 1, 4, 8, 15, 22, 36, and 57 of treatment, 24-hour ambulatory ECGs were obtained, and multiple blood samples were taken for determination of amiodarone and desethylamiodarone plasma concentrations. All patients had at least 75% suppression of VPDs. The mean duration of therapy before the onset of antiarrhythmic effect was 13.2 days (range 1 to 36 days). Trough amiodarone and desethylamiodarone plasma concentrations at the time of onset of antiarrhythmic effect were 0.86 +/- 0.48 mg/L and 0.23 +/- 0.15 mg/L, respectively. Sixty-seven percent of patients responded at amiodarone concentrations below 1.0 mg/L. For each patient there was a progressive decrease in frequency of VPDs as both amiodarone and desethylamiodarone concentrations increased. Regression modeling indicated that both amiodarone and desethylamiodarone plasma concentrations explained significant variability in the frequency of VPDs, and amiodarone and desethylamiodarone plasma concentrations were highly correlated with each other. There was a trend for desethylamiodarone to explain more variability in frequency of VPDs than amiodarone.

Amiodarone↗
PubMed1988

The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Design, organization, and baseline results.

The Canadian American Ticlopidine Study is a randomized, placebo-controlled, double-blind, multicenter study to assess the efficacy and safety of ticlopidine hydrochloride in patients who have suffered a thromboembolic stroke no less than 1 week and no more than 4 months before entry into the study. The primary assessment of efficacy will be based on the cluster of outcome events recurrent stroke, myocardial infarction, or vascular death. Twenty-five clinical centers, 12 in Canada and 13 in the United States, entered a total of 1,072 patients during a 3-year recruitment period; these patients were randomly allocated to receive either 250 mg ticlopidine or identical-appearing placebo tablets twice daily for up to 3 years. Patient recruitment was completed in December 1986. Patients were followed for a maximum of 3 years or until the close of the study in December 1987; at that time an average follow-up of 25 months had been achieved. We summarize the protocol and organization of the study and document the methods of execution and analysis, with corresponding criteria, before disclosure of the treatment code to any of the study investigators. We also provide a clinical description of the patients at entry into the study.

Aged↗
PubMed1988

An N of 1 service: applying the scientific method in clinical practice.

The N of 1 service at our institution acts as a full referral service for clinicians who want a definitive answer to a difficult management question, and an instructional environment for clinicians who have more time and want to learn to run their own N of 1 RCT. The trial design is a double blind, randomized pair, multiple crossover. A number of methodologic issues are discussed, such as appropriateness of the patients problem to N of 1 trials, feasibility, types of measurement, such as clinical objective measurement and quality of life measurement, as well as timing of these measurements. The analysis issues include developing a reporting method which is statistically powerful and understandable to clinicians with little research background. Some of these issues have been well investigated and some have not.

Clinical Trials as Topic↗
PubMed1988

Methylmercury and the health of autochthons in northwest Quebec.

We conducted a cross-sectional epidemiologic and clinical study to evaluate the nature, magnitude, and frequency of unfavourable health states among residents of northwest Quebec. Of particular interest were the possible occurrence of Minamata disease and any other neurological abnormalities. We also sought to determine whether industrial or naturally-occurring mercury in the region's environment were causally associated with any disorders that might be detected. A total of 321 subjects were studied in four groups with contrasting exposure to point-source mercury from a chlor-alkali plant in the area. Methylmercury in hair served as the marker of subject's ingestion of any organic mercury (natural or industrial). Ten pre-chosen target variables, seven clinical and three neurophysiological, were assessed in all subjects. Relationships between mercury in hair and each target variable were calculated. We determined whether gradients in target variables corresponded to gradients in potential exposure of the subjects to the aquatic emissions of the chlor-alkali plant. Minamata disease was not found. Diabetes and alcohol-related health problems assessed as important clinically plausible confounders, were common. Differences in frequency or magnitude of clinical, toxicological, and physiological findings among the contrast groups were small and not of clinical or statistical significance. There were definite relationships between mercury in hair and four target variables despite the low values of mercury measured and the mild nature of the health problems observed. This would suggest that verifiable biological threshold levels for clinical effects, if such exist, may be substantially lower among Canadians than those currently adopted as policy for adults elsewhere. A gradient was found only for two of the ten target variables. Clinically meaningful alternate hypotheses for observed health effects emerge in the data and agree with observations in the field made by consulting clinical experts.

Animals↗
PubMed1987

Clinical significance of a test for slime production in ventriculoperitoneal shunt infections caused by coagulase-negative staphylococci.

Coagulase-negative staphylococci (CNST) are the most-common cause of ventriculoperitoneal shunt infections. Some of these strains produce a slime-like substance. We reviewed 19 episodes of ventriculoperitoneal shunt infections due to CNST in 17 patients. Eleven episodes of infection were caused by slime-producing CNST and eight by non-slime-producing CNST. Shunt obstruction and abdominal pain occurred more frequently when infectious episodes were due to slime-producing CNST than to non-slime-producing CNST (P less than .05). Despite appropriate antimicrobial therapy, the mean duration of fever was longer and the failure to eradicate the infecting organisms was more frequent when the infectious episodes were due to slime-producing CNST than to non-slime-producing CNST (P less than .025). Discriminate function analysis found, however, that only failure to eradicate the infecting organism (by antimicrobial therapy) occurred more frequently in infectious episodes due to slime-producing CNST than to non-slime-producing CNST (P = .01).

Adolescent↗
PubMed1987

Airway responsiveness to methacholine during the natural menstrual cycle and the effect of oral contraceptives.

Exacerbations of symptoms have been reported in some women with asthma just prior to and during menstruation. We examined changes in airway responsiveness to methacholine during 2 consecutive menstrual cycles in 17 well-controlled asthmatics with a wide range of airway responsiveness. In 10 women with regular natural cycles, measurements were made 1 wk before and 1 wk after the start of menstruation to coincide with the highest and lowest progesterone levels. The mean concentration of methacholine to cause a fall in FEV1 of 20% (PC20) premenstruation was 1.49 mg/ml, which was not significantly different from the mean postmenstruation PC20 of 1.34 mg/ml (p = 0.45). Although there were only 10 subjects, the power was 96%, indicating little likelihood of any difference between the 2 phases. In 7 women taking oral contraceptives, the mean PC20, measured within 1 wk of completing a 21-day course, was 1.19 mg/ml, which was not different from the mean PC20 of 0.97 mg/ml measured after the start of menstruation but before restarting medication (p = 0.17). The power was 98%. In both groups, there was no difference in FEV1 or medication use during the cycle, but symptoms were worse during menstruation. The results suggest that the fluctuations in serum progesterone levels that occur during natural menstrual cycles are insufficient to alter airway responsiveness in an unselected sample of asthmatic women. They also demonstrate that changes in symptoms occur during the cycle both in women with natural cycles and those using contraceptives and that these changes are not related to serum progesterone levels or airway responsiveness.

Adult↗
PubMed1986

Airway responses to hyperventilation of cold dry air: duration of protection by cromolyn sodium.

The magnitude and duration of the inhibitory effect of three doses of cromolyn sodium on the airway response to hyperventilation of cold dry air was examined in a double-blind, randomized controlled trial. Eight subjects with well controlled asthma were studied. On 4 separate days, doses of either 2 mg, 10 mg, 20 mg, or placebo were administered by metered-dose inhaler. Twenty minutes, 2 hours, and 4 hours after each medication, airway responsiveness to isocapnic hyperventilation of cold dry air was measured by use of a standardized dose-response method. At 20 minutes, all three doses inhibited bronchoconstriction, and there was no evidence of any difference in the magnitude of the inhibition between the doses. All three doses progressively provided less protection with time. By 2 hours, the inhibition induced by 2 mg was no longer different from placebo, and by 4 hours, only 20 mg still provided significant protection. The results demonstrate that, although the initial magnitude of inhibition may not be different between 2 mg and 20 mg, the rate at which the protective effect wears off is dose related.

Adolescent↗
PubMed1986

Polyethylene glycol-modified ragweed extract: comparison of two treatment regimens.

Fifty ragweed-sensitive subjects were each administered a course of 12 injections of polyethylene glycol-modified ragweed extract. To investigate the effect of two treatment regimens, subjects were paired according to their skin sensitivity to ragweed extract and the severity of their rhinoconjunctivitis the previous year. One of each pair was randomly allocated to receive injections at weekly intervals, and the other subject was to receive injections daily until a local or systemic adverse reaction occurred and then to switch to a weekly schedule for the rest of the course. Blood was obtained immediately before each injection and at the end of the study to examine the rates of change of ragweed-specific IgE and IgG antibody levels and to evaluate whether these or other variables could be used to predict the occurrence of adverse reactions. Immediate reactions were minimal in both groups, but more late reactions occurred in subjects receiving the modified rush regimen; therefore, although the total number of injections received by the two groups was similar, the total dose of protein injected in the rush group was only half that achieved in the weekly group. Treatment induced increases in ragweed-specific IgE and IgG antibodies in both groups; the increase in IgE was similar in the two groups, but the increase in IgG was higher in the weekly group. There was a marked decrease in skin sensitivity to ragweed extract after treatment that was directly related to the IgG antibody response, and therefore, these changes were greater in the weekly group.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1985

Effect of beclomethasone dipropionate on bronchial responsiveness to histamine in controlled nonsteroid-dependent asthma.

We investigated the possibility that corticosteroids can reduce bronchial responsiveness to histamine by mechanisms other than change in airway caliber. Ten adult asthmatic subjects were selected because their symptoms were controlled by bronchodilators alone, they had no recent respiratory infection or allergen exposure that might have temporarily altered responsiveness, their spirometry was more than 70% predicted, and they had a range of histamine bronchial hyperresponsiveness. They received, in random order and double-blind manner, beclomethasone dipropionate (400 micrograms daily) or placebo for 4 wk and then, after a 2-week washout period, they crossed over to the other treatment for 4 wk. Treatment with beclomethasone induced a small but significant reduction in bronchial responsiveness to histamine (p = 0.014). Although the improvement was too small to be considered of clinical significance, its importance lies in the mechanisms by which it was produced. Part of the improvement was related to improvement in airway caliber, but, even when the data was adjusted for this, there was still a significant difference between beclomethasone and placebo treatment (p = 0.018). The results suggest that regular treatment with corticosteroids can alter bronchial responsiveness through mechanisms other than change in airway caliber.

Adult↗
PubMed1985

Asymptomatic bronchial hyperresponsiveness in rhinitis.

Methacholine inhalation tests are used to help in the diagnosis of asthma when spirometry is normal. However, the significance of increased methacholine responsiveness in patients with rhinitis and no symptoms of asthma is not known. One possibility is that it is a false positive result; another possibility is that it indicates subclinical asthma. We investigated these possibilities in 25 patients with rhinitis, whose attending physician had not made a diagnosis of asthma, by comparing responsiveness to methacholine expressed as the provocation concentration to cause a fall in FEV1 of 20% (PC20) with responsiveness to the natural stimulus of isocapnic hyperventilation of cold air and the diurnal variation of peak flow rate. Asthma was recognized objectively by variable airflow obstruction documented by one of the latter two tests. The PC20 ranged between 4 and greater than 64 mg/ml. In 10 patients the PC20 was less than 16 mg/ml. Five of these patients had bronchoconstriction in response to hyperventilation, and a further two patients demonstrated increased variability of peak flow rates. Thus, in seven of 10 patients, increased bronchial responsiveness was confirmed by the use of two different methods, although they were asymptomatic, and the increased response to methacholine was not a false positive result. In the remaining three patients the PC20 was borderline increased (8 to 16 mg/ml). The results indicate that methacholine responsiveness in the asthmatic range in patients with rhinitis is associated with variable airflow obstruction and subclinical asthma.

Adolescent↗
PubMed1985

Polyethylene glycol-modified ragweed pollen extract in rhinoconjunctivitis.

Sixty-two ragweed-sensitive adult subjects volunteered to take part in a 2-year, placebo-controlled efficacy study of polyethylene glycol (PEG)-modified ragweed extract, in ragweed pollen-induced rhinoconjunctivitis. At the beginning of the study, subjects were stratified according to skin sensitivity to ragweed extract and PEG-modified ragweed and the severity of hay fever in the previous year. There was random allocation of half to active treatment and half to placebo treatment. Before the first ragweed pollen season the 36 most sensitive subjects received 10 weekly injections (group 1), and the remaining 26 received six injections (group 2). Before the second season all subjects received 10 injections. Doses increased by half a log concentration each week unless there were adverse reactions. The mean total dose received by group 1 in year 1 was 385 micrograms of protein (28.9 micrograms AgE) and received by group 2 was 218 micrograms of protein (16.4 micrograms AgE). In year 2 the mean total dose was 1829 micrograms (137.2 micrograms AgE). Sixty-six percent of injections elicited no reaction or a mild local reaction; the remaining injections produced local redness and swelling more than 2 inches in diameter. Four percent of injections produced systemic symptoms. PEG-modified ragweed stimulated increases in ragweed specific IgG antibody both years, but increases in ragweed specific IgE antibody were significant only in group 1 in year 1. The magnitude of the IgG antibody changes was directly related to the total dose injected. At the beginning of the second year, PEG-modified ragweed-treated subjects still had elevated IgG antibody levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

The effect of inhaled hexamethonium bromide and atropine sulphate on airway responsiveness to histamine.

The degree of protection against inhaled histamine achieved by inhalation of the ganglion blocker hexamethonium bromide plus placebo, hexamethonium plus atropine sulphate, and placebo plus placebo was examined in six atopic subjects, four of whom had current asthma. Hexamethonium was administered until there was systemic evidence of ganglionic blockade with a postural drop in blood pressure of 31 +/- 7.5 mm Hg (mean +/- SD) (p = 0.01) and an increase in heart rate of 30 +/- 3.1 bpm (mean +/- SD) (p = 0.01). Atropine was inhaled in a dose (18 mg nebulized during tidal breathing) known to produce systemic inhibition of cardiac and salivary cholinergic (muscarinic) receptors. The airway effects were measured by FEV1. Hexamethonium caused bronchoconstriction in all four subjects with asthma, which was reversed by atropine. The mean provocation concentration of histamine to provoke a 20% fall in FEV1 was 2.97 mg/ml after premedication with placebo, it was not different at 2.84 mg/ml after hexamethonium alone, and it increased slightly to 5.31 mg/ml after both hexamethonium and atropine (p = 0.06). The results suggest that the main effect of inhaled histamine is not by reflex bronchoconstriction but rather through stimulation of H1-receptors on airway smooth muscle. Therefore, histamine hyperresponsiveness in asthma is not primarily caused by a defect in the parasympathetic nervous supply to the airway.

Adult↗
PubMed1985

Lactation and phenylketonuria.

Many young women who were diagnosed as having phenylketonuria (PKU) during routine neonatal screening and effectively treated during childhood are now of childbearing age. Recent reports suggest that maternal dietary therapy instituted before conception may improve the likelihood of a successful pregnancy and normal offspring. However, it is not known whether the intake of phenylalanine (phe) should be restricted during lactation. While phe levels in breast milk from women with PKU are markedly elevated, to our knowledge serum phe levels have not been measured in nursing newborn infants of PKU mothers. The present case report describes the pregnancy and early lactation of a mother with PKU, including serial measurements of serum phe levels in her offspring while being breast-fed.

Adult↗
PubMed1985

Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis.

In a previous study on 27 patients with chronic bronchitis we found that only three developed bronchoconstriction in response to hyperventilation of cold, dry air despite an increased responsiveness to methacholine inhalation. We therefore investigated bronchial responsiveness to hyperventilation with cold, dry air and methacholine in 27 patients with stable asthma who had a similar range of baseline FEV1 values but who developed bronchoconstriction that could be reversed to give an FEV1 more than 70% of the predicted value. Baseline FEV1 was 0.88-3.98 l (37-114% predicted). All but one subject developed bronchoconstriction in response to hyperventilation. There was a linear relationship between baseline FEV1 and response to methacholine (r2 = 0.37, p less than 0.001) and the relationship was significantly different from that found in the bronchitic subjects (F2.50 = 24.94, p less than 0.001). In general, the response to methacholine was greater in the asthmatic than in the bronchitic subjects for any baseline FEV1. The results suggest that there are different mechanisms underlying the increased responsiveness to methacholine in asthma and chronic bronchitis.

Adolescent↗
PubMed1985

Upper extremity compartment syndromes following pit viper envenomation.

The treatment of pit viper envenomation by fasciotomy continues to be controversial because elevated intracompartment pressures have never been previously documented. Two patients with severe pit viper envenomation of the thumb had signs and symptoms of elevated intracompartment pressures. Elevated intracompartment tissue pressures were documented in both cases. Immediate fasciotomies were necessary to decompress the thenar and forearm compartments and, in one case, the upper arm as well. Ischemic tissues were noted at the time of the operation and confirmed the clinical and objective tissue pressure measurements of compartment syndromes. Both patients made complete functional recoveries following delayed primary closure. Intracompartment pressure monitoring should be routinely used in the management of pit viper envenomation to avoid disastrous sequellae.

Adolescent↗