Biomedical subjects
Publications and source records attributed to M J O'Hara.
This article addresses issues related to the detection of HIV infection in children, primary care guidelines and modifications, treatment of HIV-associated problems, and supportive therapies within the context of family-centered care. This article also addresses the ongoing medical care of HIV-infected children and the necessity to coordinate efforts between parents and health care providers.
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1. Although incurable, HIV infection is treatable. Advances in antiretroviral therapy, prophylaxis to prevent opportunistic infections, treatment of opportunistic infections, and aggressive nutritional intervention allow for prolonged survival with a reasonable quality of life for many infected children. 2. HIV-infected children tolerate the majority of surgical procedures well; HIV infection alone is not a contraindication to surgery. Because of the multiple laboratory abnormalities that occur in children with HIV, nurses must assess that the appropriate laboratory testing has been completed and that the results have been reviewed. 3. Symptoms in children with HIV result from multiple causes and present in a variety of ways. As the lives of children are extended with better supportive and antiviral treatment, additional manifestations of HIV are being noted.
To examine the benefits and risks of combined diltiazem and propranolol therapy, 23 patients who had completed a double-blind placebo-controlled cross-over comparison between diltiazem and propranolol and who continued to develop angina despite treatment were studied. The patients received the previous dose of diltiazem (180 or 360 mg/day) combined with propranolol 120 mg daily for 4 weeks and if they still developed angina on exercise testing, they went on to propranolol 240 mg daily for a further 4 weeks. Efficacy and safety were evaluated by computer-assisted maximal treadmill tests, ambulatory heart rate monitoring, and resting systolic time intervals at the end of each 4-week treatment period. Low-dose combination therapy abolished treadmill angina in 6 patients, but 2 patients had to be withdrawn. The high-dose combination abolished treadmill angina in 5 of 15 patients. The exercise time and 1-mm ST depression time increased with each increment of combination therapy in patients on both doses of diltiazem. The resting, maximal, and ambulatory heart rates progressively decreased with each increment of combined therapy. Left ventricular function, as evaluated clinically and by the systolic time intervals, was not impaired, but severe sinus bradycardia (heart rate less than 40 beats/min) appeared in 3 patients. Two died during 6 months of follow-up. Only 11 of the 23 patients completed 6 months of combined therapy without an adverse reaction. Although combined diltiazem and propranolol therapy relieved angina and increased exercise tolerance in patients refractory to single drug therapy, it should be used with caution in such patients, since bradycardia can pose serious problems.
We have treated eleven patients with chronic stable angina pectoris with slow-release oxprenolol (160 mg and 320 mg) in a double-blind crossover study and evaluated its efficacy objectively by exercise testing between 180 and 240 min after dosing. The mean exercise time increased significantly from 6.2 min on placebo to 7.2 min and 7.3 min on oxprenolol 160 mg and 320 mg respectively. No overall beneficial effects could be demonstrated for the higher dose. A further 20 patients received slow release oxprenolol 160 mg and 10/170 mg "Oros" (osmotic release) oxprenolol in a double-blind crossover study using exercise testing and ambulatory electrocardiographic monitoring at 21-23 h after dosing. The mean exercise time increased significantly from 7.0 min on placebo to 8.3 min on slow-release oxprenolol and to 8.1 min on "Oros" oxprenolol. The effects of the 2 treatments on exercise and ambulatory heart rates were comparable. Two patients were withdrawn during the double-blind treatment period while receiving oxprenolol slow-release, one because of unstable angina and another because of throbbing headache. These findings confirm that slow-release oxprenolol is effective in treating chronic stable angina pectoris at the 160-mg dose. "Oros" oxprenolol 10/170 mg has a profile of action closely similar to but without any additional benefit over slow-release oxprenolol 160 mg.
To examine the effect of diltiazem 60 mg thrice daily and propranolol 80 mg thrice daily on myocardial ischaemia during unrestricted daily life, we have studied 14 patients with established effort-induced chronic stable angina pectoris in a double-blind crossover study. Ambulatory electrocardiographic monitoring was performed using frequency modulated (FM) tape recorder after 2 weeks of placebo therapy and at the end of each 4 week treatment period for a minimum of 24 h. The mean (+/- SEM) number of episodes of ST-segment depression greater than 1 mm during placebo treatment were 97 +/- 28, and these fell to 54 +/- 27 during diltiazem treatment (p less than 0.05) and to 12 +/- 6 during propranolol treatment (p less than 0.02). The maximal depth of ST-segment depression in 24 h, which indicates the severity of the episode, was 3.3 +/- 0.4 mm during placebo, 2.5 +/- 0.2 mm during diltiazem (p less than 0.05), and 1.6 +/- 0.5 mm during propranolol (p less than 0.01). Both diltiazem and propranolol treatment produced significant reduction in the total area of ST-segment depression observed during 24 h. A uniform reduction in the mean heart rate during the 24 h was observed during propranolol therapy and not during diltiazem therapy. Both diltiazem and propranolol treatment improved indices of myocardial ischaemia during daily normal unrestricted life, as measured by ambulatory ST-segment monitoring in patients with established chronic stable angina pectoris. Their differing effects on heart rate suggest that they act by different mechanisms.
An objective assessment of the efficacy of bevantolol was performed in 21 patients with chronic, stable angina using computer-assisted exercise testing and ambulatory ST-segment monitoring. Given once daily, 200 mg of bevantolol was compared with 200 mg of bevantolol given twice daily and with placebo, using a double-blind crossover technique. The mean exercise time with placebo was 7.4 +/- 0.6 minutes; this increased to 10.6 +/- 0.9 minutes (p less than 0.001) with once-daily bevantolol and to 9.4 +/- 0.9 minutes (p less than 0.001) with twice-daily bevantolol. The mean heart rate at rest was 80 +/- 3 beats/min with placebo; it decreased to 63 +/- 2 beats/min (p less than 0.001) with once-daily bevantolol and to 66 +/- 2 beats/min (p less than 0.001) with twice-daily bevantolol. The maximum exercise heart rate of 118 +/- 6 beats/min with placebo was reduced to 99 +/- 4 beats/min (p less than 0.001) on once-daily and 101 +/- 4 beats/min (p less than 0.001) on twice-daily bevantolol. There was a corresponding decrease in the rate-pressure product. The corrected maximum ST-segment depression was reduced from 0.3 +/- 0.06 mm min-1 with placebo to 0.2 +/- 0.03 mm min-1 (p less than 0.02) with once-daily and 0.2 +/- 0.04 mm min-1 (p less than 0.05) with twice-daily bevantolol. The mean hourly ambulatory heart rate was significantly reduced for 21 hours with once-daily and 22 hours with twice-daily bevantolol. The lowest mean minimum heart rate was 55 beats/min during twice-daily treatment. The mean number of episodes of ST depression over 24 hours in lead CM5 was decreased from 6.89 +/- 1.7 with placebo to 2.50 +/- 0.6 (p less than 0.001) with once-daily and to 3.72 +/- 1.3 (p less than 0.001) with twice-daily bevantolol. Three patients were withdrawn during the once-daily bevantolol regimen due to adverse experiences, and another patient was admitted for coronary artery bypass surgery after 25 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Seventy three patients (63 males and 10 females) aged 41-75 years with established stable exertional angina pectoris were studied in a double-blind fashion to confirm the efficacy of 80 mg propranolol administered three times daily and also to examine its effect on ST-segment changes in the electrocardiogram by ambulatory ST-segment monitoring and exercise testing using on-line computer analysis. During ambulatory monitoring, episodes of ST-segment depression in lead CM5 were significantly reduced from 6.5 +/- 0.7 during placebo to 3.4 +/- 0.6 during propranolol therapy (p less than 0.001). The total duration of ST-segment depression was also significantly reduced and the maximal depth of ST-segment depression improved from 2.6 +/- 0.2 mm during placebo to 1.7 +/- 0.2 mm during propranolol therapy (p less than 0.001). The mean +/- SEM exercise time of 5.5 +/- 0.2 minutes on placebo increased to 8.6 +/- 0.4 minutes on propranolol 240 mg daily (p less than 0.001). The 1 mm ST-segment depression time of 3.5 +/- 0.2 minutes on placebo in lead CM5 was prolonged to 6.2 +/- 0.3 minutes during propranolol therapy (p less than 0.001). Propranolol treatment significantly reduced the resting and maximal heart rates (p less than 0.001). The maximal ST-segment depression during exercise in lead CM5 was reduced from 2.3 +/- 0.1 mm on placebo to 1.9 +/- 0.1 mm with propranolol (p less than 0.01). Similarly, the rate-pressure product at peak exercise of 188 +/- 5 units on placebo was reduced to 144 +/- 3 units with propranolol (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
The anti-anginal efficacy of tiapamil, a new calcium channel blocking agent was studied in 24 patients with established effort induced chronic stable angina pectoris. The patients were allocated randomly in a double-blind fashion to tiapamil 300 mg thrice daily or placebo for 2 weeks and thereafter all the patients received tiapamil 300 mg thrice daily in a single-blind fashion for a further 2 weeks. All patients performed symptom limited multistage graded exercise testing with computer-assisted analysis of the electrocardiogram before entering the study and at the end of the double-blind and single-blind phases. The mean exercise time to develop angina during the control test in the group which received placebo during the double-blind phase was 7.1 min; this increased to 8.5 min after 2 weeks of placebo and 9.7 min after 2 weeks of subsequent tiapamil therapy. Similarly in the group which received tiapamil during the double-blind phase the mean exercise time on control test was 6.4 min, increasing to 9.7 min and 9.7 min after 2 and 4 weeks of tiapamil therapy respectively. There were no statistical significant differences between the changes from control, seen with tiapamil and placebo during the double-blind phase. However, the changes observed between control and active therapy in the tiapamil group did reach statistical significance (p = 0.003). Similarly, 1 mm ST-segment depression time was prolonged by tiapamil therapy. The heart rate at rest and maximal exercise remained unaltered with tiapamil therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
The state of left ventricular function and myocardial perfusion are important determinants of prognosis in patients with coronary artery disease and information on both can be valuable for planning individual patient management. We have studied the feasibility of simultaneous measurement of left ventricular ejection fraction with ultra short-lived gold-195 m (half life 30.5 seconds) and myocardial perfusion with thallium-201, at rest and after exercise with a single-crystal gamma camera. The results with first-pass radionuclide angiocardiography (RNA) using gold-195 m at rest were reproducible and agreed closely with the results obtained using technetium-99 m equilibrium radionuclide angiocardiography (r = 0.93). Ejection fraction by first-pass gold-195 m RNA during semi-supine ergometric exercise decreased by greater than 5% in 13 out of 18 patients with coronary artery disease and stable angina. Simultaneous myocardial imaging with thallium-201 was abnormal in all patients. The change in regional wall motion abnormality score during exercise correlated with the change in myocardial perfusion (r = 0.71, P less than 0.01) and with the change in global left ventricular ejection fraction (r = 0.77, P less than 0.001). The widely differing energy levels and half-lives of gold-195 m and thallium-201 made it possible to separate clearly the images due to each radionuclide. This study has demonstrated the feasibility of simultaneous or sequential assessment of left ventricular function and myocardial perfusion during a single exercise test, a technique which can offer advantages in clinical evaluation of patients with coronary artery disease.
The high count sensitivity of the non-imaging nuclear probe affords the possibility of measuring left ventricular ejection fraction continuously during short term interventions. The nuclear probe was used to examine the pattern of change of left ventricular function during dynamic exercise and its temporal relation to ST segment depression in 12 patients with stable exertional angina. After in vivo blood pool labelling with technetium-99m the left ventricular time-activity waveform was detected by the nuclear probe and was continuously recorded on a strip chart. The 15 beat mean ejection fraction and the ST segment level 80 ms after the J point were measured at rest and every 30 seconds during maximal ergometric exercise and during recovery. The mean ejection fraction was 54.3% (range 46-64%) at rest and fell during exercise in all subjects by a mean of 16.8% (range 6-25%). In contrast, in a control group of 16 healthy male volunteers the mean ejection fraction was 55.9% (range 47-64%) at rest and increased in all by a mean of 10.2% (range 3-19%) during exercise. The difference of ejection fraction response to exercise between the patients and controls was due to pronounced increases in relative end diastolic and especially end systolic volumes in the patients. Relative stroke volume differed between patients and controls only at peak exercise. ST segment depression greater than 1 mm developed in 11 of the 12 patients. A decrease of greater than 5% in ejection fraction occurred within 1 minute of starting exercise in nine of the 12, and in 11 patients it preceded the beginning of ST depression. In most of this selected group of patients the ejection fraction had fallen during exercise before the appearance of ischaemic electrocardiographic changes.
Forty-one patients were studied in a randomized double-blind placebo-controlled crossover trial to compare the antianginal actions of nicardipine 30 mg thrice daily and nifedipine 10 mg thrice daily. Efficacy was assessed using objective criteria from computer-assisted multistage graded exercise testing, performed after a two-week placebo run-in period and at the end of each four-week active treatment period. Thirty-seven patients completed both legs of the crossover trial. The mean (+/- standard error of the mean) baseline exercise time to development of angina was 6.7 +/- 0.4 min and this increased to 9.5 +/- 0.6 min on nicardipine (p less than 0.001) and 9.5 +/- 0.5 min on nifedipine (p less than 0.001 vs baseline; NS vs nicardipine). Both drugs significantly prolonged the time to the development of 1mm ST segment depression. The baseline resting heart rate of 83 +/- 2 beats/min increased to 87 +/- 3 beats/min during nicardipine (p less than 0.05) and remained unaltered at 83 +/- 2 beats/min during nifedipine therapy (p = NS vs baseline and p less than 0.02 vs nicardipine). Similarly, both drugs increased significantly the maximal heart rate at peak exercise. One patient was lost to follow-up during the placebo run-in period and four patients (two each on nicardipine and nifedipine) were withdrawn due to adverse effects. Our results indicate that nicardipine is comparable in efficacy to nifedipine and has a similar adverse effect profile and can also be considered a useful therapeutic agent for the treatment of chronic stable angina pectoris.
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The anti-anginal effects of KB-944 (Fostedil), a new calcium ion antagonist with a half life of approximately 23-28 hr, were evaluated in 20 patients with exertional angina pectoris in a placebo-controlled single-blind dose titration trial. Ambulatory monitoring and multistage treadmill exercise with computer-assisted electrocardiographic analysis was performed after 2 weeks of placebo therapy and after two 2-weekly periods of KB-944 therapy. The mean (+/- SEM) exercise time to the development of angina on treadmill walking increased from 6.9 +/- 0.4 min on placebo to 9.4 +/- 0.5 min on KB-944 100 mg/day (P less than 0.001) and 9.7 +/- 0.8 min on KB-944 200 mg/day (P less than 0.001 vs placebo and not significant vs KB-944 100 mg/day). The time to the development of 1 mm ST-segment depression of 5.3 +/- 0.4 min on placebo increased to 6.5 +/- 0.5 and 6.6 +/- 0.5 min on KB-944 100 and 200 mg/day, respectively (P less than 0.01 vs placebo). The heart rate at rest of 77 +/- 3 beats/min on placebo was reduced to 68 +/- 3 beats/min on KB-944 100 mg/day (P less than 0.001) and 71 +/- 2 beats/min on KB-944 200 mg/day (P less than 0.01). The maximal heart rate and the rate-pressure product were not altered by KB-944 therapy. One patient developed unstable angina during the treatment phase of KB-944 200 mg/day and was withdrawn. Five patients complained of dyspepsia and one of headache and lethargy during KB-944 200 mg/day. One patient developed ventricular tachycardia during treadmill testing while on KB-944 200 mg/day. The 24-hr ambulatory monitoring data confirmed the findings of exercise testing. KB-944 (Fostedil) in a dose of 100 mg once daily was well tolerated as compared to KB-944 200 mg once daily and both the doses were equally effective. The drug merits further evaluation for the treatment of exertional angina pectoris.
Brucella ovis DNA was analysed by using 11 different restriction endonucleases. The most clearly resolved DNA fragment patterns were obtained after digestion with the enzyme Hind III. When DNA preparations from 35 strains of B. ovis were digested with this enzyme, the fragment patterns appeared to be identical. The patterns obtained after Hind III digestion of DNA from one strain each of B. abortus, B. canis and B. melitensis were more similar to each other than to the B. ovis pattern.
PY-108-068 (PY) has calcium antagonist and coronary dilatory activity in animals, suggesting that it may be useful for the treatment of angina pectoris. We have studied its effects in 19 patients with stable exertional angina. After a 2-week single-blind placebo run-in phase, patients were randomised double-blind to either 75 mg or 150 mg of the drug (in three divided doses) daily for 2 weeks, crossing over to the alternate dose for a further 2 weeks. Maximal treadmill tests with computer-assisted electrocardiographic analysis were used to evaluate efficacy. The mean +/- SEM exercise time to onset of angina increased from 6.1 +/- 0.5 min on placebo to 9.3 +/- 0.8 min on PY 75 mg (P less than 0.001) and to 9.2 +/- 0.8 min on PY 150 mg (P less than 0.001) vs placebo; NS vs 75 mg). The time to development of 1 mm ST-segment depression in lead CC5 also increased from 5.0 +/- 0.7 min on placebo to 6.4 +/- 0.9 min on PY 75 mg (P less than 0.01) and to 7.0 +/- 0.8 min on PY 150 mg (P less than 0.01 vs placebo; NS vs 75 mg). Unlike other calcium antagonists, treatment with PY-108-068 did not significantly alter the resting or maximal heart rates or the heart rate gain during exercise. Resting blood pressure was reduced at the higher dose level but peak blood pressure during exercise and peak double product were unaltered by PY-108-068 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
One hundred and three patients who underwent coronary arteriography were studied by thallium imaging and the results analysed by Bayesian principles to assess the usefulness of semiquantitative stress thallium imaging for predicting the presence or absence of multivessel coronary disease. Significant disease was found in 80 patients, of whom 77 had abnormal thallium scans (sensitivity 96%). Thallium images were normal in 15 of 23 patients with no significant disease (specificity 65%). Multiple thallium segmental defects were found to be 90% sensitive and 65% specific for multivessel coronary artery disease and were present in 80% of patients with left main stem disease and in 93% of patients with triple vessel disease. A single thallium defect or normal scan excluded multivessel, left main, and triple vessel disease with 81%, 94%, and 91% predictive accuracy respectively. By Bayesian analysis the predictive accuracy for excluding multivessel disease was greater than 90% in patients with a pretest probability of multivessel disease of less than or equal to 40%. Coronary arteriography to exclude multivessel disease is therefore unnecessary in a high proportion of patients with known or suspected coronary artery disease.
The long-term efficacy of diltiazem, 360 mg/day, in patients with grade II or III stable exertional angina pectoris (Canadian Cardiovascular Society criteria) was assessed by multistage graded exercise tests. Seventeen patients undertook a placebo-controlled, double-blind, dose-titration protocol and all received long-term therapy. Exercise tests were performed at the end of 2 weeks of placebo treatment and after 6, 18, 26, 40 and 52 weeks of diltiazem, 360 mg/day. All patients had angina during treadmill testing with placebo and the mean (+/- standard error of the mean) exercise time was 5.8 +/- 0.7 minutes. This increased to 10.8 +/- 1.0 minutes after 6 weeks, 11.3 +/- 1.1 minutes after 18 weeks, 11.4 +/- 1.1 minutes after 26 weeks, 12.9 +/- 1.2 minutes after 40 weeks and 11.6 +/- 1.3 minutes after 52 weeks of continuous diltiazem therapy (p less than 0.001 vs placebo at all stages). Four patients were withdrawn after 26 weeks of treatment; one patient underwent coronary artery bypass surgery and 3 patients required the addition of beta-adrenoreceptor blocking agents. In 1 patient an irritant rash developed on the torso, legs and arms after 39 weeks of diltiazem and disappeared after discontinuing the drug. One patient complained of swelling and stiffness of the fingers and 3 patients complained of shoulder and elbow pain. Another patient had a myocardial infarction after 8 weeks of diltiazem treatment and died. No other adverse effects were observed during this study.(ABSTRACT TRUNCATED AT 250 WORDS)