[Improved product characteristics of nicotine gums: an unexplored area for higher compliance with nicotine replacement therapy]. / Verbesserte Produktmerkmale der Nikotinkaugummis. Ein unerforschter Bereich zur Erhöhung der Compliance bei der Nikotinersatztherapie.

OBJECTIVE: To assess consumer acceptance of new flavoured nicotine gums in comparison with existing nicotinegums. METHOD: A total of 607 adult smokers who intended to cut down or give up smoking were included in two randomised, single-blind, central location, acceptance tests. A new fruit-flavoured nicotine gum (Gum A = Nicorette Freshfruit) was compared with an existing fruit-flavoured nicotine gum (Gum B = Nicotinell fruit), and a new menthol-flavoured gum (Gum N = Nicorette Icy White) was compared with two existing mint-flavoured gums (Gum M = Nicotinell mint; Gum Q = NiQuitin mint). For all gums, the nicotine 2 mg and 4 mg strengths were tested. Each subject compared two of the nicotine gums, either 2 mg or 4 mg and either fruit-flavoured or menthol/ mint-flavoured, and assessed several characteristics, including sweetness, flavour, crunchiness, and overall liking, at predefined intervals. RESULTS: For the fruit-flavoured gums the percentage of subjects who rated sweetness and flavour to be "just right"after 5 minutes of chewing was significantly higher for Gum A than for Gum B at both strengths. Comparison of the mint/menthol-flavoured gums revealed significantly superior ratings for Gum N over both Gum M and Gum Q. With regard to expectations of which gum would be more likely help quit smoking, significantly more participants expressed greater confidence in Gum A than Gum B for the fruit-flavoured gums. Similarly, for the mint/menthol-flavoured gums significantly more subjects had greater confidence in Gum N than Gum Mor Gum Q. CONCLUSIONS: Product characteristics of nicotine gums, such as crunchiness, sweetness and flavour, appear to be crucial for the expectations that smokers have in the likelihood that any particular nicotine gum will help them to quit smoking. Thus, improved organoleptic characteristics of nicotine gums may lead to higher compliance, resulting in higher plasma nicotine levels and thereby in a higher quit rate.

Sociodemographic predictors of success in smoking intervention.

AIM: To examine the role of sociodemographic factors as predictors of sustained smoking cessation for the population who volunteer to participate in intervention programmes. METHOD: Data for the 3575 smokers who participated in the CEASE (collaborative European anti-smoking evaluation) trial, a European multicentred study that used transdermal nicotine patches as an adjunct to smoking cessation in the chest clinic, were analysed. The effects of age, sex, smoking habit, socioeconomic status (housing conditions, education, and employment), disease, smoking habits of relatives, and baseline markers of tobacco use on sustained smoking cessation (self-reported abstinence and expired carbon monoxide < 10 parts per million) were assessed using logistic regression modelling (odds ratio (OR), 95% confidence interval (CI)). RESULTS: 477/3575 smokers were sustained abstainers one year after the intervention (overall success rate 13.3%). In the univariable logistic regression models an effect of active treatment on smoking cessation was observed (OR 1.50, 95% CI 1.15 to 1.96), and additional effects on outcome were found for age (OR 1.02, 95% CI 1.01 to 1.03), sex (men v women: OR 1.38, 95% CI 1.14 to 1.68), housing conditions (OR 1.43, 95% CI 1.25 to 1.65), current respiratory (OR 0.79, 95% CI 0.67 to 0.92) or cardiac disease (OR 0.46, 95% CI 0.28 to 0.75), and markers of tobacco use (cigarettes per day: OR 0.79, 95% CI 0.69 to 0.90; expired carbon monoxide: OR 0.98, 95% CI 0.97 to 0.99). Education and employment did not have a significant effect on the outcome. The effect of the variables associated with success in smoking cessation persisted after adjustment for covariates. CONCLUSION: Age, sex, and housing conditions have a major effect on smoking cessation in European smokers participating in smoking cessation programmes.

Smoking reduction in smokers compliant to a smoking cessation trial with nicotine patch.

The aim of this retrospective analysis was to assess the extent of smoking reduction in smokers who were compliant to a smoking cessation trial with nicotine patch, and failed to completely quit smoking. Out of 297 smokers in total, 237 participants received active treatment (60 received placebo). Eighty treated subjects attended all the scheduled visits and were classified as either abstainers (nonsmokers), regular smokers or occasional smokers. Compared to the remaining 157 participants, these 80 subjects had significantly lower mean baseline daily cigarette consumption (24 versus 30; p < 0.001), expired carbon monoxide levels (25 versus 33 ppm; p < 0.001), plasma nicotine and cotinine levels, and Fagerström Tolerance Questionnaire score (5.7 versus 7.0; p < 0.001). All subjects received active treatment for up to 18 weeks (full dose for 12 weeks plus tapering dose for 6 weeks), with follow-up visits scheduled up to 1 yr. A statistically significant reduction in cigarette consumption (versus baseline) was observed among both the occasional (-99%) and regular (-77%) smokers between week 1 and week 52 (p < 0.001). Concomitant smoking and patch use was well tolerated since adverse events were infrequent, mild and transient. Thus, in addition to those subjects who successfully quit smoking, a further group of subjects who attended all the follow-up visits during the smoking cessation trial significantly reduced their mean daily cigarette consumption.

Plasma concentrations of reputed tumor-associated soluble CD44 isoforms (v5 and v6) in smokers are dose related and decline on smoking cessation.

There is some evidence to suggest that smoking may affect circulating levels of CD44 (sCD44) molecules. Therefore, we investigated the effect of smoking on the circulating level of sCD44 by comparing the change in total sCD44, sCD44v5, and sCD44v6 concentrations over 1 year in a group of people who quit smoking (n = 30) and a control group of people who continued to smoke (n = 30). Smoking status and compliance were monitored by analysis of plasma cotinine and expired CO levels and also by self-reported tobacco use. We show a dose-dependent relationship between smoke intake and baseline plasma concentrations of reputed tumor-associated CD44 variant isoforms (sCD44v5 and sCD44v6) in smokers (n = 60). There was a significant decline in the level of both sCD44v5 and sCD44v6 in quitters as compared with continuing smokers [-13.2 (95% confidence interval, -7.6 to -18.8; P < 0.001) and -62.2 ng/ml (95% confidence interval, -33.9 to -90.6; P < 0.001), respectively], but not in the total sCD44 concentration. These results show that the increased concentrations of sCD44v5 and sCD44v6 in smokers are dose related and reversible and suggest that the attributed diagnostic specificity and prognostic value of sCD44 molecules in malignant and inflammatory disease may be affected by smoking status.

Dramatic decline in circulating intercellular adhesion molecule-1 concentration on quitting tobacco smoking.

The concentration of soluble ICAM-1 (sICAM-1) is significantly elevated in smokers, but it is unclear if smoking is the direct cause of elevated sICAM-1 levels, if the relationship between smoking and sICAM-1 level is dose-dependent, and if smoking cessation may lead to a decline in sICAM-1. We sought to clarify the relationship between smoking and sICAM-1 in a group of smokers who quit smoking for 1 year (n = 30) and a control group who continued to smoke (n = 30). A dose-dependent relationship between plasma sICAM-1 concentration and daily cigarette consumption (P = 0.02), plasma cotinine level (P = 0.02), and expired CO level (P = 0.007) was observed at baseline (n = 60). The mean change in sICAM-1 concentration after 52 weeks was greater for quitters than for continuing smokers (mean difference = -71.1 ng/ml, P < 0.001). The influence of smoking on sICAM-1 needs to be carefully considered in clinical trials. Soluble ICAM-1 remains bioactive and may contribute to pathogenic processes; therefore, reduction in the concentration of circulating ICAM-1 molecules may directly contribute to the health benefits associated with smoking cessation.

Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial.

A randomised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate (MA) on the quality of life (QoL), appetite, weight and survival of patients with advanced, incurable, hormone-insensitive cancer. QoL was assessed at the start of treatment and at 4, 8 and 12 weeks, using the EORTC-QLQ-C30 instrument. 255 patients were randomised to 320 mg of MA daily or placebo for 12 weeks. 244 patients were assessable at baseline, 190 at 4 weeks (placebo 94; MA 96), 150 at 8 weeks (placebo 69; MA 81) and 112 at 12 weeks (placebo 55; MA 57). A beneficial effect of MA on appetite loss was observed at week 4 (P < 0.0001) and possibly at week 8 (P = 0.058). Further weight loss during treatment was significant only in the placebo group. In the first 8 weeks, changes in mean global QoL were small and similar in both groups. By 12 weeks the decrease in mean global QoL was more pronounced in the MA group (P = 0.028), which was related to a deterioration in physical function, while psychosocial function was not affected. Survival was not affected by MA, and side-effects were mild. The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity. However, MA does not appear to improve global QoL as measured by the EORTC QLQ-C30.

Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society.

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates.

Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up.

OBJECTIVE: To evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year. DESIGN: Placebo controlled, double blind trial. SETTING: Reykjavik health centre. SUBJECTS: 237 smokers aged 22-66 years living in or around Reykjavik. INTERVENTIONS: Nicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment. MAIN OUTCOME MEASURE: Sustained abstinence from smoking. RESULTS: Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (odds ratio 1.97, 95% confidence interval 1.17% to 3.32; P=0.011(chi2), 37% v 25% after 3 months (1.76, 1.01 to 3.08; P=0.045), 31% v 16% after 6 months (2.40, 1.27 to 4.50; P=0.005), 27% v 11% after 12 months (3.03, 1.50 to 6.14; P=0.001), and 16% v 9% after 6 years (2.09, 0.93 to 4.72; P=0.08) [corrected]. CONCLUSIONS: Short and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch.

Transurethral incision versus resection of the prostate for small to medium benign prostatic hyperplasia.

OBJECTIVE: To compare the effects of transurethral incision and resection of the prostate in patients with small to medium benign prostatic hyperplasia. PATIENTS AND METHODS: Patients were assessed preoperatively using the Madsen-Iversen symptom score, post- void residual urine volume, urinary flow and cystoscopy. Those eligible for the study were randomized to undergo either transurethral incision or resection of the prostate. Follow-up visits were scheduled at 2-3.6, 12, 24 and 60 months post-operatively with an assessment by symptom score and urinary flow rate; most patients also underwent cystoscopy at 24 and 60 months. RESULTS: The maximum urinary flow rate was significantly higher in those undergoing resection than incision at all but the last follow-up visits. Cystoscopy 24 months after surgery showed adhesions between the lateral lobes, closed incisions or obstructing prostatic lobes in most of the patients undergoing incision, but not in those resected (P < 0.001, chi-square test). During follow-up, a second transurethral procedure was carried out for persistent or recurrent symptoms, combined with a maximum urinary flow rate of < 10.0 mL/s, in 10 patients who underwent incision and in three who were resected (P = 0.039, chi-square test). CONCLUSION: Transurethral resection is preferable to transurethral incision of the prostate in the treatment of small to medium benign prostatic hyperplasia.

Prognostic importance of p15INK4B and p16INK4 gene inactivation in childhood acute lymphocytic leukemia.

PURPOSE: The present study explores the prognostic importance of p16INK4/p15INK4B gene inactivation in childhood acute lymphocytic leukemia (ALL). MATERIALS AND METHODS: Cells from 79 pediatric ALL patients were investigated for inactivation of the p15INK4B and p16INK4 genes or loss of heterozygosity (LOH) for chromosome 9p markers by use of Southern hybridization, restriction fragment length polymorphism (RFLP) analysis, microsatellite analysis as well as single-strand conformation polymorphism (SSCP) analysis, and nucleotide sequencing of the p15INK4B and p16INK4 genes. Genetic data were correlated to clinical outcome and established prognostic factors. RESULTS: Inactivation of the p15INK4B and/or p16INK4 genes by homozygous deletion or loss of one allele and mutation of the other was detected in 24 cases (30%). Another 12 patients (15%) showed loss of one allele. A statistically significant correlation was found between inactivation of the p15INK4B/p16INK4 genes and poor prognosis (P < .01). Furthermore, inactivation proved to be an independent factor that predicted relapse, ranking second to WBC count. The trend toward overrepresentation of treatment failure was strongest in the high-risk (HR) group patients with p16INK4/p15INK4B gene inactivation. Patients with deletion of genetic material on 9p21 and normal coding sequence of the remaining p16INK4 and p15INK4B genes had a similar prognosis to that of nondeleted cases. CONCLUSION: The data suggest that analysis of p15INK4B/p16INK4 genes may contribute prognostic information in pediatric ALL.

Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch.

Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation, but has a low success rate after one year (9-18%). We tested whether this was attributed to insufficient nicotine replacement. We conducted a randomized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values. Two hundred and ninety seven adult smokers were enrolled. Those with baseline cotinine < or = 250 ng.ml-1 (low cotinine) were randomly assigned to placebo (LC-P) or to 15 mg 16 h nicotine patches (LC-15), and those with baseline cotinine > 250 ng.mL-1 (high cotinine) were randomly assigned to 15 mg (HC-15) or 25 mg (HC-25) 16 h nicotine patches. Plasma nicotine and cotinine values, expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment. Smokers in the LC-15 group had a significantly higher success rate than placebo (28 vs 9%). Smokers with high baseline cotinine had lower success rates, and a high dose of nicotine did not increase success rate (HC-25 9% vs HC-15 11%). Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group. Replacement was similar in groups LC-15 and HC-25, but the success rate was significantly lower in HC-25 group, despite similar levels of withdrawal symptoms. We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values. Determination of plasma cotinine values may be, thus, helpful in identifying smokers who could benefit from transdermal nicotine replacement.

Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice.

The transdermal nicotine patch has proved an effective aid to smoking cessation. The ease of securing good compliance gives it a potential advantage over nicotine gum as an adjunct to brief advice and support in primary care settings where the major public health impact is obtained. In a preliminary report of half the sample of a randomized placebo controlled trial, we showed the patch to be effective in a general practice setting. We report here the definitive results of the full sample, including dose effects, predictors of outcome and other issues of theoretical and practical interest. A total of 1200 heavy smokers (> or = 15 per day), attending 30 general practices in 15 English counties received brief GP advice, a booklet and 16 hours per day patch treatment for 18 weeks. Dose increase and abrupt vs. gradual reduction of patch dosage were also randomized and follow-ups conducted at 1, 3, 6, 12, 26 and 52 weeks. Outcome was measured by self-reported complete abstinence from week 3 to 52 with biochemical validation at all follow-up points. Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year (nicotine 9.6%, placebo 4.8%, p < 0.01); it most likely worked by reducing withdrawal symptoms. It enhanced cessation during the first week and reduced relapse during the second week. The dose increase after week 1 produced no sustained increase in cessation. Gradual reduction was no better at preventing relapse than abrupt withdrawal of patches after week 12. Whether relapse would have increased by ending treatment at some point between weeks 3 and 12 was not tested. Although pre-treatment dependence on cigarettes was prognostic of failure, the patches were equally helpful to both highly and less dependent smokers. Patches were particularly helpful to smokers with pre-treatment subclinical dysthymic symptoms. All but one of the 96 subjects eventually achieving long-term abstinence in the study quit during the first week of cessation.

Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial.

BACKGROUND: Smoking is considered as an addiction to nicotine for most subjects consuming 10 cigarettes or more per day. Hence, nicotine replacement therapy by way of gum, patch, or spray has been advocated. The rationale of this study is to evaluate the possible beneficial effects of adding nicotine gum to the routine of subjects using the nicotine patch. The effect of the nicotine patch against the placebo, both groups receiving placebo nicotine gum, has also been assessed. METHODS: Healthy subjects (374) were randomized at their work-setting in a 1-year double-blind placebo-controlled trial: 149 subjects to active nicotine patch + active gum (group 1), 150 to active nicotine patch + placebo gum (group 2), and 75 to placebo patch + gum (group 3). Treatment duration was 12 weeks with a 16-hr transdermal patch of 15 mg, followed by a 6 + 6-weeks weaning period on respectively 10 and 5 mg patches. Gum use was not restricted during the first 6 months, with recommendations to use at least four pieces a day. A strict definition of smoking abstinence was used in this study, which did not allow smoking any cigarette after Week 1. Nonsmoking status at each visit, as reported by the subjects, was verified by CO below 10 ppm in expired air. RESULTS: Abstinence rates in group 1 against group 2 were 34.2 and 22.7% (P = 0.027) at 12 weeks, 27.5 and 15.3% (P = 0.010) at 24 weeks, and 18.1 and 12.7% (P = 0.191) at 52 weeks. In group 3, abstinence rates were 17.3, 14.7, and 13.3% respectively at 12, 24, and 52 weeks. Using logistic regression with adjustment for six baseline covariates, odds ratios for abstinence (with 95% CI) were computed. For group 1/group 2, OR at 12, 24, and 52 weeks were 1.72 (1.03-2.94) (P = 0.039), 2.04 (1.14-3.57) (P = 0.018), and 1.47 (0.76-2.76) (P = 0.125). No significant differences in OR were observed when comparing groups 2 and 3. Time to relapse is significantly longer in group 1 as compared to that of group 2 (P = 0.041), whereas no significant differences between groups 2 and 3 were observed. No significant differences between the three groups in systemic and local adverse drug events were observed. CONCLUSION: Adding active gum use to active patch use in subjects smoking 10 cigarettes or more a day increased abstinence rates, which are statistically significant up to 24 weeks.

On the use of the WHO handicap classification in a population study of 73- and 76-year-old men and women.

The WHO ICIDH classification of handicap was used in a population sample studied at 73 (n = 504) and 76 (n = 649) years of age. In the sample, there was either no handicap at all or the degree of handicap was generally low. In most handicap categories, however, the grades increased from 73 to 76 years. The self-rated activity level and the handicap category Occupation showed only low correlation. Good agreement was found between the handicap category Physical independence and assessments of Personal and Instrumental ADL and there was also a correlation between Mobility and maximal walking speed. Correlations were found between the handicap categories and the dimensions in the Nottingham Health Profile (NHP), but r-values were generally rather low. The highest correlation was that with the dimension of Physical mobility. The difference between self-assessed health aspects of quality of life and observer ratings using given norms is stressed.

Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches.

OBJECTIVES: (a) To evaluate the efficacy of transdermal nicotine patches as an aid to stopping smoking when used as an adjunct to brief advice and support in a general practice setting; (b) to see whether an increase in nicotine patch dosage enhances the rate of initial cessation. DESIGN: Randomised double blind placebo controlled parallel group study with one year of follow up. SETTING: 30 general practices in 15 English counties. SUBJECTS: 600 dependent heavy smokers (> or = 15 cigarettes daily) who were well motivated to give up. INTERVENTIONS: Brief general practitioner advice, booklet, and 16 hours per day patch treatment for 18 weeks with brief support and follow up at one, three, six, 12, 26, and 52 weeks. MAIN OUTCOME MEASURES: Self reported complete abstinence for up to one year with biochemical validation at all follow up points. RESULTS: Nicotine patches reduced the severity of craving and adverse mood changes in the first weeks of withdrawal and doubled the rate of initial cessation at week 3 (nicotine group 36% of patients (144/400), placebo group 16.5% of patients (33/200)) and of continuous abstinence throughout one year (nicotine group 9.3% (37), placebo group 5.0% (10)). A dose increase at week 1 among patients experiencing difficulty in quitting increased the proportion who achieved abstinence at week 3. There were no adverse systemic effects attributable to nicotine, but the incidence of moderate or severe local irritation or itching at the patch site was 16.4% (63 patients), compared with 3.8% (seven) with placebo. CONCLUSION: Transdermal nicotine patches used as an adjunct to brief advice and support in a general practice setting are an effective aid to long term cessation of smoking in highly dependent smokers.

Diagnostic methods in the detection of prostate cancer: a study of a randomly selected population of 2,400 men.

We investigated the value of digital rectal examination, transrectal ultrasonography and prostatic specific antigen (PSA) analysis as aids in general clinical practice and in the early detection of prostate cancer. Of a randomly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination, transrectal ultrasound and PSA analysis, 1,782 (74%) accepted and prostate cancer was detected in 65 (3.6%). When the transrectal ultrasound results were also considered the detection rate of digital rectal examination (2.3%) was increased by 50% and the number of stage T2A or less tumors was doubled. At reexamination due to markedly high PSA values (7 micrograms/l. or more) only a few additional cancers (5%) were detected. However, it is noteworthy that 80% of the detected cancers were found among the subgroup with abnormal PSA values (4 micrograms/l. or more) and comprising 17% of the study population, which suggests the possibility of selecting a risk group at mass screening. Moreover, the positive predictive value increased from 4% (when only digital rectal examination was positive) to 71% for the combination of positive digital rectal examination, positive transrectal ultrasound and an increased PSA concentration (that is 7 micrograms/l. or greater).

Prehospital thrombolysis in suspected acute myocardial infarction: results from the TEAHAT Study.

In a randomized, double-blind study, rt-PA vs. placebo treatment in early suspected acute myocardial infarction (AMI) was evaluated in patients both in hospital and prehospitally. The inclusion criteria were as follows: (a) age less than 75 years; and (b) chest pain indicative of AMI, of no longer than 2.75 h duration before first examination. In the prehospital setting a mobile coronary-care unit, accompanied by a cardiologist, was sent out by the ambulance services to 350 patients, of whom 205 (59%) were classified as non-eligible when examined by the cardiologist. Of the 145 patients who fulfilled the inclusion criteria, 44 were excluded due to contraindications to thrombolytic treatment. Thus 101 patients were randomized to blinded treatment outside hospital. The median time interval between onset of pain and treatment was 75 min, 45 min less than for those subjects who were randomized in hospital. The prevalence of confirmed AMI was 42% in the prehospital group, compared to 66% in the hospital group. Bleeding and cardiac complications for prehospital treatment were few, and similar to those for hospital treatment. In conclusion, prehospital thrombolysis was feasible, and delay times prior to treatment were significantly reduced. However, the specificity and diagnostic accuracy were lower than those achieved with in-hospital therapy.

Early treatment with thrombolysis and beta-blockade in suspected acute myocardial infarction: results from the TEAHAT Study.

Independent trials of early administration of beta-blockers and thrombolytic agents have shown beneficial effects on both short- and long-term prognoses in acute myocardial infarction (AMI). The effects of a combination of the two strategies have not been thoroughly documented. Three hundred and fifty-two patients, of less than 75 years of age, with chest pain indicative of AMI, and onset less than 2 h and 45 min before first examination, were randomized to treatment with rt-PA or placebo. All patients without contraindication were given intravenous metoprolol 15 mg acutely and then 200 mg orally daily. Treatment was started either at the prehospital stage or in hospital. Thirty-seven per cent of patients had contraindications to beta-blockade, the most frequent of which were heart rate less than 60 beats min-1 and hypotension. The remaining 63% were given intravenous beta-blockade. No side-effects of metoprolol, alone or in combination with rt-PA, were observed during the prehospital phase. Overall, toleration of the treatment was good. Reduction in enzymatically estimated infarct size by rt-PA was more pronounced in patients who were also treated with metoprolol (41%, P less than 0.001) than in those with contraindications to beta-blockade (15%, NS). Patients who were also treated with metoprolol also had a lower incidence of Q-wave infarctions, congestive heart failure and ventricular fibrillation than those who were not given intravenous beta-blockade. In conclusion, toleration of intravenous administration of rt-PA and metoprolol was good, and this was also the case in the prehospital phase.(ABSTRACT TRUNCATED AT 250 WORDS)

On the prenatal diagnosis of congenital adrenal hyperplasia (CAH) by measurement of amniotic fluid 17-alpha-hydroxyprogesterone, aldosterone and cortisol.

Forty amniotic fluid samples of both sexes were collected in the 16th gestational week and analysed for 17 alpha-hydroxyprogesterone (17-OHP), cortisol, and aldosterone. Hormone concentrations were also analyzed in amniotic fluid of a male fetus postnatally diagnosed as having the salt-losing form of congenital adrenal hyperplasia (CAH). The mother also had CAH of the non-salt-losing type. Hormone concentrations were also determined prenatally in two pregnancies at risk. Amniotic fluid from the pregnancy with the CAH fetus had an approx. six-fold elevated 17 alpha-hydroxyprogester one level, whereas cortisol and aldosterone levels were within the normal range when compared with controls. Hormone concentrations in the two pregnancies at risk were within normal limits and subsequently a healthy boy and a healthy girl were born. Institution of cortisone in the mother during early pregnancy was made in one of the pregnancies. The treatment was withdrawn when normal amniotic hormonal levels were obtained. No sex difference in concentrations of 17-OHP or cortisol was found in the controls, whereas there was a marked sex difference in aldosterone levels (p less than 0.005) with male fetuses having higher concentrations. Diagnosis of CAH in the 16th gestational week can be made by analysing amniotic fluid concentrations of 17 OHP. As cortisol and aldosterone levels were within normal range of the CAH-fetus, they are probably of little use for the prenatal diagnosis of CAH-fetuses/or to differentiate the simple virilizing and the salt-losing forms of CAH. Restriction fragment length polymorphism (RFLP)- analyses of the 21-hydroxylase gene in the fetus gave little further information.