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Background It is important for the physician and the patient to have a mutual understanding of the possible consequences of different treatment alternatives in order to achieve a partnership in decision-making. Objective The aim of this study was to explore to which degree first-time consultations for discussion of climacteric discomfort achieved shared understanding of the risks and benefits associated with hormone therapy in the menopausal transition. Methods Analysis of structure and content of transcribed consultations (n = 20), and follow-up interviews of the women (n = 19 pairs of consultations and interviews), from first-time visits for discussion of climacteric discomfort and/or HT with five physicians at three different outpatient clinics of gynecology in Sweden. Results Four distinctively different interpretations of risk, depending on whether or not benefits were discussed in the same context, emerged from the analysis. On average, five advantages (range 0-11) and two (0-3) disadvantages were mentioned during the consultations. In the interviews, the women expressed on average four advantages (0-7) and one disadvantage (0-3). There were major variations between advantages and disadvantages expressed in the consultation and the following interview. Conclusion Even though the consultations scored high in patient involvement, the information in most consultations was not structured in a way that made it possible to achieve a shared or an informed decision-taking. [ABSTRACT FROM AUTHOR]

Objective: Many commonly used pharmaceuticals, such as antidepressants and neuroleptics as well as some illegal drugs, are metabolised by the cytochrome P 450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Of Caucasians, 7-10% lack this enzyme, which can, upon administration of drugs in normal therapeutic doses, lead to adverse reactions and unexpected intoxication, leading in turn even to a fatal outcome in some cases. Methods: Individuals (n = 242) who had died due to intoxication by pharmaceuticals were genotyped for CYP2D6 and CYP2C19 and compared with a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. Four CYP2C19 alleles *1 (wt), *2, *3 and *4 were also identified by SNP analysis. Results: The prevalence of the CYP2D6 poor metaboliser (PM) genotypes in individuals with fatal intoxication was lower (4.7%) than expected from the frequencies of these genotypes in the blood donors (8.5%). A significantly lower frequency Pc 0.005 (0.03 with correction according to Bonferroni) was found for the CYP2D6*4 allele among the fatal intoxication cases. The CYP2C19 genotype analyses showed the same results for the fatal intoxication cases and for the blood donors. Conclusions: The findings in this study confirm our earlier observations of a lower frequency of CYP2D6 PM genotypes in cases of fatal intoxication. To our knowledge, it has not been shown previously that intoxication victims might have a lower frequency of PMs than the general population. [ABSTRACT FROM AUTHOR]

The cost to society and the individual of treating asthma has been increasing in developed countries. This has given rise to studies of the efficacy of complementary treatments. The aim of this study was to evaluate the efficacy of traditional Chinese Acupuncture in patients with mild asthma. The method used for evaluation of efficacy was total airway resistance at 5Hz (R5) as measured by impulse oscillometry (IOS)--a forced oscillation technique, at baseline and after a bronchial challenge with voluntary isocapnic hyperventilation of cold air (IHCA). The study was a parallel group randomised placebo controlled trial with evaluator blinding. Twenty-seven asthmatics were recruited and 24 completed the study, 10 of them received acupuncture and 14 received a placebo treatment (mock-TENS). Treatment continued for 15 weeks, and efficacy was tested two weeks following the last treatment. Randomisation resulted in female over representation in the acupuncture group, but lung-function and bronchial responsiveness to IHCA were comparable in the two populations before the start of treatment (p>0.05 vs. p > 0.05). There were no statistically significant effects of the treatment before (p > 0.05) or after IHCA (p > 0.05) in either of the groups. The statistical power of the study to show a clinically relevant difference in bronchial responsiveness to IHCA after treatment was near 80%. We conclude that there were no significant effects of traditional Chinese Acupuncture on airway status in our patients with asthma. [ABSTRACT FROM AUTHOR]

Objectives: To compare perceived symptoms between patients undergoing antihypertensive therapy and hypertensive patients without drug treatment, and to assess reasons for change of antihypertensive medication in routine clinical practice.Design: Population-based multicentre study. Consecutive patients from a randomized sample of centres were given a standardized questionnaire to assess symptoms as well as opinions about their antihypertensive drugs.Setting: Fifty-five Swedish primary health care centres and 11 clinics of internal medicine.Patients: One thousand and thirteen hypertensive patients on their individually prescribed antihypertensive medication and 13 5 without antihypertensive therapy.Main Outcome Measures: Prevalence and perception of symptoms with and without antihypertensive drug therapy, changes of medication and reasons for this.Results: Amongst the group of patients on antihypertensive medication, 57% spontaneously reported having had symptoms of high blood pressure before they started their drug therapy. Amongst the patients without antihypertensive drugs, 52% reported having such symptoms. When answering direct questions about different symptoms related to current drug treatment or increased blood pressure, patients with and without medication reported symptoms to a similar extent: 80 and 85%, respectively. A majority of patients (64%) had changed their medication during the course of treatment (range 0-61 years). The mean number of changes was 2.4 times over 12 years. The most common reported cause for changing drug treatment was side-effects (42%).Conclusions: The study shows that patients in general perceive symptoms from hypertension. Antihypertensive medication decreases the frequency and intensity of symptoms that might be related to high blood pressure but adds other symptoms linked to the medication. Changes in medication were mostly related to side-effects. The follow-up should pay attention to patients' experience of treatment. A sign of a well-managed hypertension population would be a decrease of symptoms over time. [ABSTRACT FROM AUTHOR]

Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66% significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis. [ABSTRACT FROM AUTHOR]

In order to study the relations between plasma cyclic guanosine monophosphate (cGMP) and anthropometric variables, plasma atrial natriuretic factor (ANP) and serum angiotensin-converting enzyme activity (ACE), a population study with random selection of 217 subjects (49% men) 18-69 years old was performed. Venous blood was drawn at 08.00 h and ambulatory blood pressure (ABP) recording was then performed. There was no gender-difference in cGMP levels (men 2.2 ± 1.1 nmol L[sup -1], women 2.2 ± 1.1 nmol L[sup -1]). A weak negative correlation was seen between cGMP and systolic ABP in both genders 20-44 years of age (r = -0.3, p = 0.05 for both), but this correlation did not persist in multivariate analysis with correction for ANP, age and ACE. In women, cGMP correlated positively with ANP (r = 0.27, p = 0.005) independently of ANP, ACE, ABP and age. ACE correlated negatively with cGMP in men (all; r = -0.22, p = 0.03, 45-69 years of age r = -0.49, p = 0.0002) and this correlation was independent of ANP, ACE, ABP and age. ACE catalyses the breakdown of bradykinin, which stimulates the release of NO. As the second messenger of NO is cGMP, the negative correlation between ACE and cGMP in men might be a reflection of reduced production of NO. Our results also suggest that there are gender differences in the stimuli for basal cGMP production. [ABSTRACT FROM AUTHOR]

The article focuses on antidepressant drugs and their possible intoxication with the femoral blood that may lead to death. Between 1992-2005, approximately 95 percent of the autopsies done in Sweden were screened to have antidepressant drugs on their femoral blood samples. In addition, levels for each drug should be provided and the results should be assessed to determine the risk of toxicity and be able to come up with counter-measures.

We present a fatal drug poisoning case involving venlafaxine (VEN). The deceased took his medication regularly (including 150 mg VEN twice daily), and nothing in the case or autopsy findings pointed towards suicide. The toxicological assessment concluded that the cause of death was most likely due to a poisoning with a combination of VEN, oxycodone and ethanol, and the manner of death was considered to be an accident. The blood concentration of VEN was high (4.5 mg/kg), and the ratio of the VEN metabolite O-desmethylvenlafaxine (ODV) to VEN was exceptionally low (0.006). Mechanistic pharmacokinetic simulations suggested that the low metabolite ratio was the result of combined poor metabolizer (PM) status of cytochrome P450 (CYP) 2C19 and CYP2D6. This hypothesis was confirmed by genetic analysis. Simulations revealed that it was likely that the combined missing CYP2D6 and CYP2C19 activity would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations combined with genotyping were considered very useful in this fatal drug poisoning case. [ABSTRACT FROM AUTHOR]

Many commonly used pharmaceuticals such as antidepressants and neuroleptics as well as some illegal drugs are metabolised by the Cytochrome P450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Seven to ten percent of Caucasians lack this enzyme which can lead to adverse reactions and in some cases to unexpected intoxication even with fatal outcome, upon administration of drugs in normal therapeutic doses. 236 individuals who had died due to intoxication of pharmaceuticals were genotyped for CYP2D6 and compared to a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. The prevalence of the CYP2D6 PM genotype in the fatal intoxications was lower (4.7%) compared to the blood donors (8.5%). A significant decrease (p<0.005) was found in the CYP2D6*4 allele frequency among the fatal intoxications. [Copyright &y& Elsevier]