[Consensus on evaluation and management of apparent life-threatening events in infancy (ALTE)]. / Consenso sobre el manejo de eventos de aparente amenaza a la vida del lactante (ALTE). Comisión de Sueño, Sociedad Chilena de Neumología Pediátrica 2013.

Apparent life threatening events are defined as an acute episode in which the observer fears an infant < 1 year may die. ALTE is characterized by some combination of apnea, color or muscle tone change, chocking and has to be followed by cardiorespiratory reanimation. The present consensus paper reviews international and national evidence concerning diagnosis, etiologies, hospitalization criteria and indications for home monitoring.

Tropical forests were the primary sources of new agricultural land in the 1980s and 1990s.

Global demand for agricultural products such as food, feed, and fuel is now a major driver of cropland and pasture expansion across much of the developing world. Whether these new agricultural lands replace forests, degraded forests, or grasslands greatly influences the environmental consequences of expansion. Although the general pattern is known, there still is no definitive quantification of these land-cover changes. Here we analyze the rich, pan-tropical database of classified Landsat scenes created by the Food and Agricultural Organization of the United Nations to examine pathways of agricultural expansion across the major tropical forest regions in the 1980s and 1990s and use this information to highlight the future land conversions that probably will be needed to meet mounting demand for agricultural products. Across the tropics, we find that between 1980 and 2000 more than 55% of new agricultural land came at the expense of intact forests, and another 28% came from disturbed forests. This study underscores the potential consequences of unabated agricultural expansion for forest conservation and carbon emissions.

[Clinical characteristics of respiratory infection due to Mycoplasma pneumoniae in hospitalized children]. / Características clínicas de la enfermedad respiratoria causada por Mycoplasma pneumoniae en niños hospitalizados.

INTRODUCTION: Studies on Mycoplasma pneumoniae infection are scarce in Chile. OBJECTIVE: To describe clinical characteristics associated with M. pneumoniae in children requiring hospitalization. MATERIAL AND METHODS: All children with a respiratory infection requiring hospitalizations between 2000-2005, whom had a M. pneumoniae specific IgM > or = 1:32, were analyzed. RESULTS: Fifty children meeting study criteria were identified with an average length of hospitalization of 4 days (range: 1-10); mean age was 5.4 years (46% were younger than 5 years). Common clinical features were cough (92%), fever (82%), malaise (74%) and respiratory distress (72%). At admission 40/45 children had hypoxemia. Chest-X ray showed interstitial pattern (69.3%), consolidation (51%) and hyperinsuflation (28.5%). Six patients had pleural effusion. Eighty four percent of patients had a favorable clinical outcome; eight children required admission to the PICU all of whom recovered. CONCLUSION: Respiratory infections associated with M. pneumoniae in our series of children had a highly variable and non-specific clinical spectrum. Chest-X rays showed different pattern in concordance with previous publications.

Fatal poisoning in Nordic drug addicts in 2002.

The present study from 2002 includes medicolegally examined fatal poisonings among drug addicts in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition "drug addict" is applied by the participating countries. The number of deaths, age, sex, place of death, main intoxicant and other drugs present in the blood are recorded in order to obtain national data, as well as comparable Nordic data and data comparable to earlier studies from 1997 and 1991. The Icelandic results are commented on separately due to the low number of cases. The most fatal overdoses are seen in Norway, in both the death rate (number per 100,000 inhabitants=8.44) and in absolute number (n=232). The comparable figures for the other four countries are Denmark 5.43 (n=175), Iceland 3.6 (n=6), Finland 2.93 (n=94) and Sweden 2.56 (n=136). In earlier studies from 1991 and 1997, the highest death rate is seen in Denmark, with Norway as number two. Denmark is the only country where the death rate decreases from 1997 to 2002. A relatively large increase in deaths in the younger age groups (<30 years) is noted from 1997 to 2002, except in Denmark, where only a small increase in overdose deaths in very young people (15-19 years) is observed. Females account for 12-20% of the overdoses (three out of six deaths in Iceland). Relatively fewer deaths are recorded in the capital areas in 2002 than in 1997 and 1991, suggesting more geographically widespread drug use in the Nordic countries. Heroin/morphine is the single most frequently encountered main intoxicant, varying from 10% of the cases in Finland to 72% of the cases in Norway. Finland differs from the other countries in that a high percentage of the fatal overdoses in Finland are not caused by an illicit drug; buprenorphine overdoses are seen, and relatively few deaths resulting from heroin are seen. Methadone is the main intoxicant in 41% of the Danish overdose cases, 15% of the Norwegian cases, 4% of the Swedish cases and none of the Finnish overdose cases, an observation probably linked to different national prescription rules for methadone. The analytical screening reveals extended polydrug use. Frequently seen substances, in addition to the main intoxicant are amphetamine, tetrahydrocannabinol (THC), benzodiazepines and ethanol.

Snoring, pregnancy-induced hypertension, and growth retardation of the fetus.

STUDY OBJECTIVE: Our purpose was to study the relationship between snoring and pregnancy-induced hypertension and growth retardation of the fetus. DESIGN: Retrospective, cross-sectional, consecutive case series. SETTING: The Department of Gynecology and Obstetrics, University Hospital, Umeâ, Sweden. PARTICIPANTS AND MEASUREMENTS: On the day of delivery, 502 women with singleton pregnancies completed a questionnaire about snoring, witnessed sleep apneas, and daytime fatigue. Data concerning medical complications were taken from the women's casebooks. RESULTS: During the last week of pregnancy, 23% of the women reported snoring every night. Only 4% reported snoring before becoming pregnant. Hypertension developed in 14% of snoring women, compared with 6% of nonsnorers (p < 0.01). Preeclampsia occurred in 10% of snorers, compared with 4% of nonsnorers (p < 0.05). An Apgar score < or = 7 was more common in infants born to habitual snorers. Growth retardation of the fetus, defined as small for gestational age at birth, had occurred in 7.1% of the infants of snoring mothers and 2.6% of the remaining infants (p < 0.05). Habitual snoring was independently predictive of hypertension (odds ratio [OR], 2.03; p < 0.05) and growth retardation (OR, 3.45; p < 0.01) in a logistic regression analysis controlling for weight, age, and smoking. CONCLUSIONS: Snoring is common in pregnancy and is a sign of pregnancy-induced hypertension. Snoring indicates a risk of growth retardation of the fetus.

Uncertainty in estimating blood ethanol concentrations by analysis of vitreous humour.

AIMS: To determine the concentrations of ethanol in femoral venous blood (FVB) and vitreous humour (VH) obtained during forensic necropsies. The ratios of ethanol concentrations in VH and FVB, the reference interval, and the associated confidence limits were calculated to provide information about the uncertainty in estimating FVB ethanol concentrations indirectly from that measured in VH. METHODS: Ethanol concentrations were determined in specimens of FVB and VH obtained from 706 forensic necropsies. The specimens were analysed in duplicate by headspace gas chromatography (HS-GC), with a precision (coefficient of variation) of 1.5% at a mean ethanol concentration of 500 mg/litre. The limit of detection of ethanol in body fluids by HS-GC in routine casework was 100 mg/litre. RESULTS: In 34 instances, ethanol was present in VH at a mean concentration of 154 mg/litre, whereas the FVB ethanol concentration was reported as negative (< 100 mg/litre). These cases were excluded from the statistical analysis. The concentration of ethanol in FVB was higher than in VH in 93 instances, with a mean difference of 160 mg/litre (range 0 to 900). The mean concentration of ethanol in FVB (n = 672) was 1340 mg/litre (SD, 990) compared with 1580 mg/litre (SD, 1190) in VH. The arithmetic mean VH/FVB ratio of ethanol was 1.19 (SD, 0.285) and the 95% range was 0.63 to 1.75. The mean and SD of the differences (log VH - log FVB) was 0.063 (SD, 0.109), which gives 95% limits of agreement (LOA) from -0.149 to 0.276. Transforming back to the original scale of measurement gives a geometric mean VH/FVB ratio of 1.16 and 95% LOA from 0.71 to 1.89. These parametric estimates are in good agreement, with a median VH/FVB ratio of 1.18 and 2.5th and 97.5th centiles of 0.63 and 1.92. CONCLUSIONS: The ethanol distribution ratios (VH/FVB) show wide variation and this calls for caution when results of analysing VH at necropsy are used to estimate the concentration in FVB. Dividing the ethanol concentration in VH by 2.0 would provide a very conservative estimate of the ethanol content in FVB, being less than the true value, with a high degree of confidence.

Survival and 2-year outcome with expectant management of second-trimester rupture of membranes.

OBJECTIVE: To evaluate the perinatal and 2-year outcomes in pregnancies complicated by preterm premature rupture of membranes (PROM) during the second trimester. METHODS: Fifty-three consecutive singleton pregnancies with PROM at 14 to 28 weeks of gestation were studied retrospectively. Management goals were to prolong the pregnancies to 32 weeks through expectant management and to avoid fetal compromise through closer monitoring and active intervention, when necessary, after 23 weeks. Outcome of the surviving infants was based on neurologic, audiometric, and ophthalmologic examinations at 2 years of corrected age. RESULTS: Rupture of membranes occurred at 14-19 weeks (mean 17.4 weeks) in 10 women, at 20-25 weeks (mean 24.0 weeks) in 24, and at 26-28 weeks (mean 27.6 weeks) in 19. The median latency periods to delivery were 72 days, 12 days, and 10 days when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively. The overall incidence of chorioamnionitis was 28%. There were no fetal deaths and nine neonatal deaths. When rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, the perinatal survival rates were 40%, 92%, and, 100%, respectively. Pulmonary hypoplasia accounted for seven deaths. Of the live-born infants, 81% were alive at 2 years of corrected age. Survival without major impairment was observed in 75%, 80%, and 100% of the survivors when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively. CONCLUSION: Expectant management of second-trimester PROM offers better perinatal and long-term survival than previously thought.

Serum levels of placental alkaline phosphatase in high-risk pregnancies.

A recently developed radioimmunoassay (RIA) for placental alkaline phosphatase (paf) was used to estimate the maternal serum levels of the enzyme in 51 women with various complications of pregnancy. The results were compared with a reference group of 242 women with apparently normal pregnancies. Women with intrauterine growth retardation (IUGR) or severe or mild preeclampsia had significantly low weight of the fetoplacental unit. Simultaneous determinations of PAF in maternal serum and the urinary total estrogen/24 hr gave a clear differentiation of the IUGR group from the other pregnancies at risk. All PAF values from risk pregnancies were below the mean values of normal pregnancy.

A double antibody solid phase radioimmunoassay for placental alkaline phosphatase.

A solid-phase "direct" radioimmunoassay for determination of placental alkaline phosphatase in serum was developed. The assay is highly sensitive, with a minimum detectable dose of 9 ng protein per ml. The specificity for the placental type of the enzyme, in comparison to other serum alkaline phosphatases, was found to be convincing. The choice of genetic types of either placental alkaline phosphatase or antiserm was found not to influence the radioimmunoassay. With the described technique the serum concentration of this enzyme during normal pregnancy was measured. A 25-fold increase from low levels during the first trimester up to 252 +/- 70 ng/ml (mean +/- S.D.) in gestation week 40 was observed.

Vaginal rings for continuous low-dose release of oestradiol in the treatment of urogenital atrophy.

Silicone vaginal rings for the continuous release of 17 beta-oestradiol (E2) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women. The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium. After a brief initial peak, the serum levels of E2 over 3 mth of treatment remained close to the detection limit. The 'undetectable' E2 release pattern was reflected only in increased levels of oestrone sulphate. There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent. Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients.

Effect of microamperage stimulation on the rate of wound healing in rats: a histological study.

BACKGROUND AND PURPOSE: This study examined cutaneous wound healing after microamperage stimulation (MS). SUBJECTS: Twelve female Sprague-Dawley rats were studied. METHODS: The treatment (wound reduction) group (n = 6) received 100 microA of current at 0.3 Hz on a 50% duty cycle for 2 hours a day for 14 days. The control group (n = 6) received the same handling and electrode placement, but no current was applied. Wound size was measured daily following each treatment. Histological analysis included measurement of epithelial thickness, vascularity, and fibroblast density from tissue sections taken at the end of the experiment. RESULTS: An analysis of variance showed no significant difference between the two groups with respect to the change in wound size over the 14 treatment days. A series of t tests showed no significant differences between the groups for any of the histological measurements. CONCLUSION AND DISCUSSION: The results of this study do not support the hypothesis that MS accelerates acute cutaneous wound healing.

Fatal seizures associated with trimipramine poisoning.

The present report describes a witnessed, fatal attack of seizures. Very high levels of trimipramine were found in the blood collected at autopsy. The cause of death would most likely have been misinterpreted as a suicidal intoxication if the attack had not been witnessed. Conversely, if toxicologic examination had not been undertaken, the fatality would probably have been registered as epilepsia.

Fatal intoxication by dextromethorphan: a report on two cases.

A report is given of two young people who died after intake of dextromethorphan, one by suicide and the other for uncertain reasons. To our knowledge this is the first reported fatal intoxications with this drug.

Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism.

The concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N=628) or chronic alcoholism (N=647). In alcohol poisoning deaths both UAC and BAC were higher by about 2g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74 g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean+/-standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18+/-0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74 g/l (N=457) the mean+/-S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30+/-0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74 g/l (N=190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r=0.84, residual S.D.=0.47 g/l) and in chronic alcoholism deaths (r=0.95, residual S.D.=0.41 g/l). For both causes of death (N=1275), the correlation between BAC and UAC was r=0.95 and the residual S.D. was 0.46 g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18:1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30:1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.

Flunitrazepam: an evaluation of use, abuse and toxicity.

The benzodiazepine flunitrazepam is extensively prescribed to patients with insomnia in many countries, but has also become popular among alcohol- and drug abusers. Several reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. Furthermore, flunitrazepam is involved in many fatal intoxications in Sweden. This study was designed and conducted to explore the negative consequences of flunitrazepam abuse in Sweden, and to assess the trends in its use and abuse. The occurrence of flunitrazepam in cases referred to the Department of Forensic Chemistry in Linköping, Sweden 1992-1998, was investigated in detail. The detections were studied separately for different groups; medicolegal death investigations, drug abuse cases, driving under influence cases, and other medicolegal cases. These data were further compared with the sales, and seizures by the Swedish Customs and the Swedish Police. During 1992-1998, 641 fatalities occurred, where the cause of death was attributed to intoxication with flunitrazepam solely (130) or in combination with other drugs, or concomitant conditions (511). In 78% of all driving under influence cases, where flunitrazepam was detected, the analyses also disclosed the presence of illicit drugs. A similar association was seen in drug abuse cases. The seizures reported by the Swedish Customs revealed a substantial and increasing illegal trade. Cases, where flunitrazepam seemingly induced violent behavior were identified, and one of these is described in some detail. It is concluded that the abuse pattern and the toxicity of flunitrazepam should be kept in mind by forensic investigators and that this panorama also should be considered when decisions about the registration and classification of flunitrazepam are made in different countries.

Drugs in motorists traveling Swedish roads: on-the-road-detection of intoxicated drivers and screening for drugs in these offenders.

This paper deals with the police officer's or police doctor's ability to find drivers under the influence of drugs. We have also studied whether the protocol on the driver's previous histories of drug intake is useful for directing the chemist in his analytical approach to revealing intoxicants in the suspects' body fluids. A comprehensive procedure for screening traffic-hazardous drugs in the urine was found necessary and is described. By using this method, we have studied the incidence of drunken drivers with detectable medicinal or illicit agents. The results demonstrate that 91% of those drivers found by the officer or doctor of the police to be on intoxicants other than ethanol, carried some kind of traffic-hazardous drug in their body fluids, and that the doctor was a better judge than the police in identifying these offenders. By using a series of chemical methods for drug screening, we found that every third driver suspected of drunken driving due to ethanol, but not to other intoxicants, held some kind of a traffic-hazardous drug substance in his urine; benzodiazepines and cannabinoids were the most common findings. The data imply that 34% of these suspects revealed their intakes of traffic-dangerous intoxicants. We conclude that the judgements of both the officer and doctor of the police are needed for an efficacious detection of drivers under the influence of drugs. Moreover, the results infer that the chemist has to screen for intoxicants to reveal these in a suspect driver. We also conclude that drugs, particularly the benzodiazepines or cannabinoids, may be commonly encountered in drunken drivers, suspected of being inebriated by ethanol but no other toxicants.

High concentrations of diazepam and nordiazepam in blood of impaired drivers: association with age, gender and spectrum of other drugs present.

A zero-concentration limit for controlled scheduled drugs in the blood of motorists was introduced in Sweden in 1999 and the annual number of arrests for driving under the influence of drugs (DUID) has since increased eight-fold. However, for prescription drugs that might cause impairment (e.g. benzodiazepines) additional proof is needed to justify prosecution, such as whether the medication was being misused. Over a 2-year period, we found 94 cases of DUID in which the concentrations of diazepam in blood was 1.1 microg/g or more. Diazepam (D) and nordiazepam (ND) were determined in whole blood by capillary gas chromatography with a limit of quantitation of 0.05 microg/g for each compound. The mean (median) and maximum concentrations of D were 2.0 microg/g (1.7 microg/g) and 7.8 microg/g and the corresponding ND concentrations were 1.5 microg/g (1.0 microg/g) and 7.6 microg/g, respectively. The concentration of D in blood exceeded 2 microg/g in 21% of cases and was over 3.0 microg/g in 11% of cases. D and ND were the only drugs present in eight cases (seven men and one women) and in another five cases ethanol was present at concentrations ranging from 0.81 to 1.98 mg/g. Polydrug use was very common in these DUID suspects and D and ND coexisted with amphetamine in 20% of cases, tetrahydrocannabinol in 18% of cases and with both these illicit drugs in 12% of cases. The next most prevalent drug combination was D, ND and morphine (mostly derived from heroin), seen in 13% of cases. Other psychoactive prescription drugs were identified in blood including alprazolam, flunitrazepam, oxazepam, zolpidem and zopiclone. This case series of DUID suspects demonstrate the high frequency of polydrug use showing preference for illicit drugs like amphetamine, cannabis and heroin, in that order. Furthermore, Swedish traffic delinquents frequently overdose with prescription drugs as exemplified here by unusually high concentrations of D and its active metabolite ND.

A cluster of fentanyl-related deaths among drug addicts in Sweden.

During a 16-month period, nine fatalities occurred among white male drug-addicts, where fentanyl was detected at postmortem toxicological analysis. The street samples associated with these cases confirmed the presence of fentanyl as an additive in low-concentration amphetamine powders with caffeine, phenazone and sugar as cutting agents. In seven of the cases, an acute intoxication by fentanyl was considered to be the immediate cause of death, and in one case, it was likely, but no analysis of fentanyl was performed in blood, and in another case the death was suicide by hanging. This appears to be the first report of a cluster of fentanyl-related deaths outside the United States, and the occurrence of fentanyl in combination with amphetamine has not previously been reported. In addition, in all cases, femoral blood was collected, and samples were handled and analysed according to standardized, quality-controlled procedures. The previous history, circumstances surrounding the death, autopsy findings, histology and toxicology examination of each case are presented. The gas chromatographic-mass spectrometric method for fentanyl is also described. Fentanyl concentrations ranged from 0.5 to 17 ng g-1 blood, and from 5 to 160 ng ml-1 urine. Other drugs found were amphetamine (8 cases), ethanol (5 cases) and benzodiazepines (5 cases). Morphine was found in only one case. The average age of men was 33.9 years (range 22-44); six were found in their own of friend's apartment, two inside buildings (stairways) and one was found outdoors. We conclude that fentanyl is a dangerous substance that should be considered in drug-addict deaths even outside the United States, particularly when the remaining toxicology is unremarkable, and the cause of death cannot be ascertained

Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results.

Debrisoquine hydroxylase (CYP2D6) is involved in the metabolism of many toxicologically important drugs. The gene encoding for this enzyme displays a polymorphic distribution in all populations examined. We report a study on 46 cases, where analyses of the CYP2D6 gene were conducted on postmortem femoral blood in order to investigate the occurrence of poor metabolizers (PM). A polymerase chain reaction (PCR) method, designed and routinely used for therapeutic drug monitoring, was employed, only slightly modified. Samples from 22 cases, where the parent drug to metabolite ratio was unexpectedly high were analyzed as well as samples from 24 control cases. Genotyping could be carried out in all but one case. Previous freezing or addition of potassium fluoride as preservative did not prevent analysis. Only one PM (from the control group) was discovered, implying an occurrence of only 2.2% as compared to the reported frequency of approx. 7% in Sweden. Among the extensive metabolizers (EM), however, a number of individuals with mutated genes were identified. Although it seems reasonable to suspect a PM genotype in cases with a high concentration of a drug metabolized by CYP2D6, but without suspicion of acute overdose, our study does not support the opinion that this interpretation pitfall is particularly common. This study rather indicates that drug interactions in EMs constitute a more frequent and important problem.

The prevalence of dextropropoxyphene in autopsy blood samples.

The prevalence of dextroproxyphene (DXP) in the total medico-legal autopsy material in Sweden during 1992 to 1996 was examined. Simultaneous findings of paracetamol and alcohol in the blood were considered in the analyses. DXP in peripheral blood was found in 1782 (7.5%) of the 23,691 cases analysed during 1992-1996. The autopsy prevalence of DXP increased by 25% from 1992 to 1996. The mean blood DXP concentration was 1.62 micrograms/g (the blood level of DXP after a therapeutic dose is 0.05-0.75 microgram/g). The blood DXP level was < 0.75 microgram/g in 947 cases and > or = 0.75 microgram/g in 835 cases. The cases < 50 years of age had a significantly higher mean concentration (2.36 micrograms/g) than those > or = 50 years (1.04 micrograms/g). Paracetamol in the blood was found in 53% of the DXP cases (mean 75.0 micrograms/g; therapeutic level 2.5-25 micrograms/g) and alcohol in 43% (mean level 0.14%). According to the death certificates 54% (956) died from fatal poisoning. Among these, 74% (707) showed a blood DXP concentration > or = 0.75 microgram/g. Other Scandinavian countries, Denmark and Norway have reduced the rate of fatal DXP poisonings through government regulations for prescription. As the defined daily dose/1000 inhabitants during a 12-month period (DDD) of DXP preparations in Sweden (14.4 in 1996) is six times as high as in Denmark and nine times as high as in Norway, introduction of similar regulations in Sweden should be considered.