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Context: Amlodipine is the most common calcium channel blocker (CCB) on the Swedish market, and poison center (PC) consultations for amlodipine overdoses are increasing. The clinical picture is dominated by vasodilation with relative preservation of cardiac function. CCBs selectively dilate vessels on the afferent side of the capillary network which, in states of preserved or increased blood flow may lead to edema formation, including non-cardiogenic pulmonary edema (NCPE). This complication has been considered rare in CCB poisoning. In this cohort study of nineteen amlodipine poisonings with high amlodipine blood levels, the incidence and clinical significance of NCPE in severe amlodipine poisoning are explored. Methods: During 2017-2018 the Swedish PC prospectively encouraged the gathering of blood samples in amlodipine poisonings with symptoms requiring treatment with inotropes or vasopressors. Samples were sent by mail to the Forensic Toxicology Division at the Swedish National Board of Forensic Medicine for screening and quantification of relevant toxicants. Patients with blood amlodipine levels >0.25 µg/mL were included in a cohort whose case details were gathered from medical records and PC-case notes with a special focus on signs of NCPE. Results: Nineteen patients met the blood amlodipine inclusion criteria. Four (21%) died and one patient was treated with VA-ECMO. Nine patients developed NCPE defined as a need for positive pressure ventilation (PPV) while having an echocardiographically normal left ventricular function. Conclusion: In this prospective cohort study of consecutive and analytically confirmed significant amlodipine poisonings NCPE was a common finding occurring in 47% of the whole cohort and in 64% of patients who did not go on to develop complete hemodynamic collapse.

Most patients with advanced cancer experience severe pain and are often treated with opiates. Cancer patients are especially susceptible to opportunistic infections due to treatment with immunosuppressive and cytostatic drugs. Since opiates have been demonstrated to have immunomodulatory effects, it is of clinical importance to evaluate potential differences between commonly used opiates with regard to their effect on the immune system. The aim of this study was to evaluate the effect of morphine, tramadol, fentanyl and ketobemidone on the functioning of the immune system with special reference to TNF and IL-8 release. Method. U-937 cells were preincubated with different concentrations of opioids followed by stimulation with LPS 100 μg/ml for three hours. The effect of opioids on the levels of cytokine mRNA was studied using RT-PCR. Erk and Akt phosphorylation was also measured by Western blot. Results. All opioids with the exception of fentanyl were capable of inhibiting TNF release from U-937 cells. Morphine had no effect on IL-8 release but the effect of other opiates was almost the same as the effect on TNF. All opioids with the exception of fentanyl were capable of inhibiting production of mRNA for TNF and IL-8. The observed effects of opiates were not always reversible by naloxone, suggesting that the effects might be mediated by other receptors or through a non-receptor mediated direct effect. Although preliminary evidence suggests the involvement of Erk and Akt pathways, further studies are needed to unravel the intracellular pathways involved in mediating the effects of opiates. Our data suggests that the order of potency with regard to inhibition of cytokine release is as follows: tramadol > ketobemidone > morphine > fentanyl. Conclusion. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of tramadol and ketobemidone and to improve opioid treatment strategies in patients with cancer.

Background: The toxicological analysis of blood and urine samples from victims of alleged sexual assault represents a crucial part of the forensic evidence when this crime is investigated., Material and Methods: We searched a national forensic toxicology database (TOXBASE) to find cases registered as sexual assault, rape, including date-rape that the police had requested the analysis of ethanol and other drugs. Between 2008 and 2010, N = 1460 such cases met this criteria. After immunological screening of urine or blood samples, all positive results were verified by more specific analytical methods, such as gas chromatography-mass spectrometry (GC-MS) for illicit drugs. A large number of prescription drugs and their metabolites were determined by capillary GC with nitrogen-phosphorous (N-P) detector. GC with flame ionization detector (FID) was used to analyze ethanol and gamma-hydroxybutyrate (GHB) in blood at limits of quantitation (LOQ) of 0.1 g/L and 8 mg/L, respectively., Results: The average age (± standard deviation) of all victims was 24 ± 10.3 years and 72% were between 15 and 29 years. Ethanol and other drugs were not detected in 31% of cases (N = 459). Blood-ethanol was positive in N = 658 cases at mean, median and highest concentrations of 1.23 g/L, 1.22 g/L and 4.3 g/L, respectively. Ethanol plus drugs were present in N = 188 cases (13%) and one or more other drugs alone in N = 210 cases (14%). Cannabis (marijuana) and amphetamines were the major illicit drugs, whereas diazepam, alprazolam, zopiclone as well as newer antidepressants were the major prescription drugs identified., Conclusions: The mean age of victims of sexual assault in Sweden, the proportion of drug positive to drug negative cases, the predominance of ethanol positive cases as well as the types of other drugs showed a remarkably good agreement in two studies spanning a period of 8 years.

Between 60 and 80% of all deaths related to fire are attributed to toxic fumes. Carbon monoxide (CO) is commonly thought to be the major cause. However, hydrogen cyanide (HCN) is also formed. Still, the exact contribution of HCN to fire-related fatalities is unknown. The aim of the study was to investigate the impact of HCN in relation to CO as a cause of death in fire victims. Data on carboxyhemoglobin (COHb) and blood cyanide from deceased fire victims in the period 1992-2009 were collected from two Swedish nationwide forensic databases (ToxBase and RättsBase). The databases contain data on COHb and/or cyanide from 2303 fire victims, whereof 816 on both COHb and cyanide. Nonparametric statistical tests were used. Seventeen percent of the victims had lethal or life-threatening blood cyanide levels (>1 µg/g) and 32% had lethal COHb levels (>50% COHb). Over 31% had cyanide levels above 0.5 µg/g, an indication of significant HCN exposure. The percentages may be underestimates, as cyanide is quickly eliminated in blood also after death. Our results support the notion that HCN contributes more to the cause of death among fire victims than previously thought.

Objective: Caffeine is widely available in beverages and in different over-the-counter products, including tablets containing 100 mg caffeine. Because intentional fatal intoxications with caffeine occur, the maximum quantity of caffeine tablets that can be bought over the counter in a single purchase was restricted from 250 to 30 in Sweden in the year 2004. The objective of this article was to study the effect of this decision on the number of fatal caffeine intoxications., Method: In Sweden 95% of all cases undergoing forensic autopsy are screened for a number of drugs including caffeine. All cases during January 1993-September 2009 with a caffeine concentration above 80 microg/g blood were recorded., Results: During the study period toxicological investigations were performed in 83,580 forensic autopsies. Caffeine contributed to the fatal outcome in 20 cases (0.02%). Thirteen (65%) of these fatalities occurred before the introduction of the sales restriction. However, no fatal intoxications where caffeine contributed to the cause of death was recorded between May 2007 and September 2009., Conclusion: Overdoses of tablets containing caffeine can be fatal, suicides as well as accidents occur. Restricting the maximum quantity of caffeine tablets available over the counter seemed to be effective in preventing suicides because of caffeine although some time elapsed until the effect was noted. Further monitoring is required to ensure that the observed lower caffeine mortality is a sustained effect.

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.

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.

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-1, women 2.2 +/- 1.1 nmol L-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.