Psychiatrists' attitudes to euthanasia.
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Biomedical subjects
Publications and source records attributed to J Bonelli.
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OBJECTIVE: To determine the effect of repeated annual influenza immunization on the host's serum antibody. DESIGN: Ten year observational study with cohort design. SETTING: Cystic Fibrosis Center at St. Vincent's Hospital and Medical Center, New York City, NY. PATIENTS: Thirty-eight children and young adults with cystic fibrosis (CF). MEASUREMENTS: Serum hemagglutination inhibition (HI) antibody titers were determined at the time of vaccination and 4 weeks later each year in the fall before the influenza epidemic. Shwachman scores were determined each year. RESULTS: While the pre-vaccination and post-vaccination geometric mean serum HI antibody titers varied from year to year, no upward or downward trend was evident over the 10 year period. The reciprocal of the post-vaccination geometric mean HI titers ranged annually from 32 to 74 for the influenza A (H3N2) vaccine strains, from 53 to 133 for the influenza A (H1N1) strains, and from 18 to 174 for influenza B strains. In addition, the majority of vaccinees had a presumably protective post-vaccination serum HI titer > or = 1:40 each year for all three vaccine strains. The initial mean Shwachman score of the group was 77. The final score of 76 after 10 years was not significantly different. CONCLUSIONS: Annual influenza vaccination appears to regularly induce presumably protective serum antibody levels in most CF children and young adults studied over a 10 year period.
The time to the appearance of a peak serum antibody response to influenza virus vaccine is not clearly defined. We compared the most commonly used time intervals described in the literature--4 and 6 weeks after vaccination. We studied 118 elderly patients from three different geographic sites. The 1992 to 1993 trivalent inactivated influenza virus vaccine containing influenza virus A/Beijing/353/89 (H3N2), influenza virus A/Texas/36/91 (H1N1), and influenza virus B/Panama/45/90 was used. No statistically significant differences were found at the 4- and 6-week intervals after vaccination.
The purpose of this study was to determine whether acetaminophen impairs the immune response to influenza vaccine. Influenza vaccine is an under-utilized preventive measure, partly because of the unfounded perception that fever and myalgias frequently follow vaccination. While acetaminophen may decrease these infrequent side effects, it may also alter the immune response to vaccination. We compare the effect of acetaminophen with placebo on the humoral immune response to the 1991-1992 commercially available influenza vaccine. We studied 60 healthy, elderly subjects from a geriatric clinic and 20 infirm, elderly subjects from a nursing home. The subjects were randomly assigned to receive placebo or acetaminophen (1,000 mg every 6 h) for 2 days. Acetaminophen did not depress or enhance the immune development of serum hemagglutination inhibition antibody to the three vaccine antigens. The systemic side effects of fever and myalgia were uncommon in both groups. The healthy elderly subjects mounted a significantly better immune response to the influenza virus A/Taiwan/1/86 (H1N1) vaccine strain than did the infirm elderly subjects (geometric mean titer, 115 versus 51; P = 0.003). The functional activity score obtained by using the chronic healthy evaluation component of the Acute Physiology and Chronic Health Evaluation system could be used to distinguish the healthy from the infirm elderly (scores of 1.27 versus 3.75, P < 0.001). Acetaminophen neither depressed nor enhanced the serum antibody response to the vaccine in the healthy and infirm elderly subjects studied.
Influenza viruses related to the markedly antigenically divergent strains B/Yamagata/16/88 and B/Victoria/2/87 are circulating in human populations. Adults develop cross-reacting antibodies against recent and earlier influenza B virus strains after vaccination with B/Yamagata/16/88, probably because of previous influenza B virus infections or immunizations. Vaccines containing B/Yamagata/16/88 should adequately protect adults against B/Victoria/2/87 infections.
10 patients (6 females and 4 males with an average age of 75 years) with stable angina pectoris were treated transdermally with mepindolol in a balanced, randomized, controlled, crossover study to compare the anti-ischemic effects of 12-hour overnight, and 24-hour applications. The number of angina pectoris attacks, the oral nitrate consumption and the ischemic parameters in 24-hour ECG, i.e. episodes of manifest (MMI) and silent (SMI) myocardial ischemia, the total duration of ischemia and 24-hour heart rate profiles were investigated. Both application schemes showed typical systemic beta blocker effects in all patients and significant clinical efficacy. A dose/effect relationship and a time/effect relationship between the two different application schemes were demonstrated across all the parameters investigated. Systemic and local tolerance of the therapy was good. 2 patients showed transient, mild skin irritation, but only during one phase of the study. Premature discontinuation was not necessary in any cases. There were no relevant changes in the clinical-chemistry. The new therapeutic concept of 24-hour treatment for a. pectoris with 12-hour overnight transdermal applications showed both good clinical efficacy and a good safety profile.
A new transdermal beta-blocker containing system (Mepindolol BIO TSD) was compared in a placebo controlled cross over trial with a transdermal nitrate system in 14 patients suffering from coronary heart disease with stable angina pectoris. Under Mepindolol TSD both the incidence of angina pectoris attacks and the consumption of oral nitroglycerin dropped significantly. Under ergometry it resulted in an improvement in the maximum exercise tolerance and in a significant reduction in the ischemic ST-Segment deviation. Under Holter monitoring the number of manifest (MMI) and silent (SMI) ischemic episodes was significantly reduced. In addition the total duration of ischemia was significantly reduced. All the examined parameters showed Mepindolol BIO TSD to be significantly more effective than transdermal nitrate, and the duration of action was longer. No clinically relevant adverse events were observed in any of the therapeutic regimes.
A new transdermal system (BIO TSD) containing the beta-adrenergic blocker mepindolol was assessed in a placebo controlled clinical trial in 12 patients with coronary heart disease. On therapy, the number of anginal attacks and the consumption of oral nitroglycerin (glyceryl trinitrate) were reduced significantly. During ergometer exercise the exercise tolerance was improved and the ischemic ST-segment depression was reduced significantly. Holter monitoring revealed significant reductions of the number of manifest and silent episodes and the total duration of ischemia. No relevant side effects were observed.
The hemodynamic effects of dobutamine were compared with those of digoxin in seven patients with severe diffuse dilatative cardiomyopathy. Dobutamine (7.5 micrograms per kg of body wt per min) was given intravenously for 30 min and then discontinued until hemodynamics returned towards base line. Digoxin (12.5 micrograms per kg) was then given intravenously and hemodynamics were recorded for 120 min. Thereafter, dobutamine was again given at the previous dose. Dobutamine increased cardiac and stroke volume index and decreased pulmonary occlusive (wedge) pressure and systemic vascular resistance without changing heart-rate or arterial pressure. Digoxin also increased cardiac and stroke volume index and decreased pulmonary wedge pressure and systemic vascular resistance with digoxin without changing arterial pressure. In contrast to dobutamine, heart-rate was decreased with digoxin indicating reduced myocardial oxygen demand. Re-infusion of dobutamine did not have any notable hemodynamic effect, with the exception of an increase in heart-rate-systolic pressure production. These data indicate that the positive inotropic properties of digoxin and dobutamine are not additive. Furthermore, concerning the effect of digoxin on the heart-rate, its use seems preferable to the use of sympathomimetic agents such as dobutamine, in patients with diffuse chronic dilatative myocardiopathy.
The hemodynamic effect of methylepoxyproscillaridin (3'-methyl-4'-5'-epoxy-proscillaridin) (P35) was studied according to the Swan Ganz thermodilution method in 6 patients with latent cardiac insufficiency. Both at rest and under ergometer exercise, the stroke volume and the systolic blood pressures increased under P35. Moreover, under physical exercise the heart rate decreased significantly, while cardiac output increased. The hemodynamic effect of P35 can therefore be regarded as typical of cardiac glycosides.
The pharmacokinetic data of methylepoxyproscillaridin (3'-methyl-4'-5'-epoxyproscillaridin) (P35) after 1 mg i.v. or oral administration in two different galenic preparations (hard and soft gelatin capsules) in randomized succession were studied in 9 healthy volunteers, showing a bioavailability of 88 +/- 10.5% (soft gelatin capsule) and 81 +/- 12% (hard gelatin capsule). The half-life of P35 was calculated to be 80 +/- 13.3 h.
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The aim of this study was to investigate the haemodynamics of the beta 1-selective beta-blocker bisoprolol at plasma concentrations that would be expected to block completely the cardiac beta-receptors. Seven patients with stable exercise-dependent angina pectoris received 40 mg bisoprolol, and six patients received 10 mg bisoprolol orally as a single dose. Before and 1.5 h after administration, the following parameters were measured at rest and during physical exercise within the framework of an invasive diagnostic investigation: cardiac output, blood pressure in the systemic and pulmonary circulation, heart rate, and ST-segment change. Further haemodynamic factors were derived from these parameters. Before beta-blockade, the change from rest to exercise resulted in an increase in heart rate, blood pressure, and cardiac index, and also in an increase in pulmonary capillary wedge pressure as an indication of ischaemically induced left-ventricular dysfunction. After 40 mg bisoprolol, under exercise conditions, the cardiac index decreased as a consequence of reduced heart rate, and the mean pulmonary capillary wedge pressure increased slightly, compared with baseline. This finding was attributable to clearer changes in three patients; however, as an overall result, an improvement of oxygen consumption also was achieved in these patients. Measured by reduction in cardiac index, no appreciable increase in effect was achieved at bisoprolol plasma concentrations greater than 60 ng/ml. In angina pectoris patients, bisoprolol possesses the typical haemodynamic profile of a beta-adrenoceptor antagonist. There was no indication of a beta-blockade-independent negative inotropic effect of bisoprolol. Forty mg bisoprolol was shown to be an unnecessarily high dose. It may be deduced that the therapeutic dose range of bisoprolol is between 5 and 20 mg.
UNLABELLED: The present study seeks to examine the question of the etiology, the diagnostic criteria and therapeutic consequences of exsiccosis in the elderly. The study includes 14 patients (9 males, 5 females) with an average of 76,8 +/- 4,8 years of age, all hospitalized because of dehydration. Following an exact diagnostic procedure a controlled therapy including a discontinuation of treatment was introduced in order to allow an evaluation of the development of dehydration. RESULTS: 1. The diagnosis of senile exsiccosis requires a synthesis of the patient's history, an exact physical examination and laboratory analysis. The central venous pressure (CVP) can be regarded as the most reliable parameter (it was lower than normal in 100% of the patients). There was a strikingly high incidence of increased mean corpuscular volume (MCV)-more than 105 rm3 in 86% of the cases. 2. The mean liquid-deficit of elderly patients with exsiccosis was 4,8 +/- 2,81. 3. The reason for the frequent incidence of exsiccosis in advanced age is to be found in a relative adipsia (the average daily deficit of liquid-intake was 815 +/- 47 ml per patient). Combined with a diminished renal concentration capacity (78,5% of the patients did not reach a specific weight of urine more than 1020 after a concentration test). 4. As a preventive measure, patients with tendency for exsiccosis should receive instructions as to the necessity of daily liquid-intake following exact balancing; furthermore regular weight-controls should be performed.
The effect of isometric exercise on hemodynamic parameters before and after beta blockade were investigated in two groups of six male volunteers, ages 25-28 years. On the basis of a randomized scheme, the subjects received either 15 mg propranolol i.v. or 0.5 mg mepindolol sulfate i.v. Cardiac output (CO) was determined by means of the Swan-Ganz thermodilution technique, and blood pressure was measured invasively in the radial artery. Analysis of the results pointed to the following conclusions. Isometric contraction brings about a reflex constriction of arterial and venous vessels, and thus an increase in blood pressure, pulmonary artery wedge pressures (PAWP) and CO, as well as a reduction in stroke volume (SV). The circulatory reflex mechanism operative during isometric exercise cannot be significantly influenced by beta blockade with propranolol or mepindolol sulfate. The increase in heart rate during isometric exercise is therefore unlikely to be the result of sympathetic activation, but rather of other (vagal?) reflex mechanisms.
In a single-blind test vs placebo in two crossover therapy phases, each lasting 4 weeks, it was shown in six clinical cases of hyperkinetic heart syndrome that 2 X 2.5 mg mepindolol sulfate daily is able to (1) lower significantly the HR and the systolic BP at rest and during exercise on the ergometer, (2) normalize or increase by 100% the restricted effective working capacity, and (3) improve the subjective symptoms. Mepindolol sulfate can accordingly be regarded as an effective therapeutic agent in hyperkinetic heart syndrome.
In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy volunteers were treated daily with either 0.3 mg metildigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In patients receiving metildigoxin therapy the ratio of beta-methyldigoxin/digoxin in the serum was determined by HPLC. The digoxin levels in patients with cirrhosis treated with metildigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. The higher total serum-digoxin levels in patients with cirrhosis of the liver after moderate saturation with metildigoxin are caused by reduced demethylation of beta-methyldigoxin to digoxin due to impaired liver function. A comparison with healthy volunteers showed that the reduced hepatic metabolism in the cirrhotic patients caused changes in the pharmacokinetics: a reduced metildigoxin clearance and a smaller distribution volume were found. According to our findings there is more danger of digitalis toxicity in patients with cirrhosis of the liver on a standard dosage of metildigoxin than on a standard dosage of beta-acetyldigoxin.
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