[Fatal ecstasy intoxication]. / Letalt forløbende ecstasyforgiftning.

A case of full-blown, lethal MDMA intoxication, owing to abuse of ecstasy is described. The increasing popularity of ecstasy among young, otherwise healthy, people prompts health care providers to recognise better the symptoms of systemic intoxication in order to initiate early treatment, such as rehydration, cooling in cases of hyperthermia, seizure treatment, correction of cardiac arrhythmia, and metabolic and electrolyte abnormalities.

Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis.

Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia. The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital centers or their blood supply. The presence of three common point mutations seen in families with thrombophilia (1691G-->A in the coagulation factor V gene, 677C-->T in the methylenetetrahydrofolate reductase gene, and the 20210G-->A mutation in the prothrombin gene) could increase the risk for thrombosis in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome. The frequency of homozygous 1691G-->A mutation in SIDS cases was higher than expected (odds ratio: 7.3, 95% confidence interval, 1.2-45.8). The allele frequencies (theta;) in cases of sudden infant death syndrome of the 1691G-->A, 677C-->T, and 20210G-->A alleles was 2.6% (1.0-5.5), 32.6% (26.8-38.9), and 0.9% (0.1-3.4), respectively. None of the allele frequencies found in the background population (3.4% for the 1691G-->A allele, 29% for the 677C-->T allele, and 1% for the 20210G-->A allele) differed significantly from that in cases of sudden infant death syndrome. In 5,251,027 inhabitants in Denmark, the incidence of venous thromboembolism was 0.9 per 1000 per year in the background population, and less than one-thousandth of these were children. Consequently it is not likely that venous thrombosis is a major cause of sudden infant death syndrome. On the other hand, this does not exclude other known or unknown risk factors for thrombosis as possible etiological factors for sudden infant death syndrome. It is likely that we must continuously employ the exclusion principle on possible etiological causes in genetic material from a large group of victims of sudden infant death syndrome if the phenomenon of sudden infant death syndrome is to be ascribed to a specific hereditary disorder.

Interactions of infectious symptoms and modifiable risk factors in sudden infant death syndrome. The Nordic Epidemiological SIDS study.

The aim of the study was to investigate the effect of infection on sudden infant death syndrome (SIDS) and to analyse whether modifiable risk factors of SIDS, prone sleeping, covered head and smoking act as effect modifiers. In a consecutive multicentre case-control study of SIDS in Denmark, Norway and Sweden, questionnaires on potential risk factors for SIDS were completed by parents of SIDS victims, and for at least two controls matched for gender, age and place of birth. All SIDS cases were verified by an autopsy. The study comprised 244 SIDS cases and 869 controls, analysed by conditional logistic regression. Significantly more cases than controls presenting symptoms of infectious diseases during the last week and/or last day were treated with antibiotics and had been seen by a physician. The finding is consistent with the hypothesis of an infectious mechanism in SIDS induced by local microorganism growth and toxin or cytokine production, and also adds further support to a possible association between infection and SIDS by loss of protective mechanisms, such as arousal. The risk of SIDS among infants with the combined presence of infectious symptoms and either of the other modifiable risk factors, prone sleeping, head covered or parental smoking, was far greater than the sum of each individual factor. These risk factors thus modify the dangerousness of infection in infancy.

Whipple's operation for carcinoma of the pancreatic head and the ampullary region. Short-and long-term results.

BACKGROUND AND METHODS: In this retrospective review short- and long-term perspectives have been evaluated for 108 patients who, during 1982 through 1992, had Whipple's operation performed for carcinoma of the pancreatic head (PC, n=63) or the ampullary region (AC, n=45). In 24 patients the operation was not radical (21 with PC and 3 with AC). RESULTS: Total perioperative morbidity was 60%, and 13 patients (12%) died within 30 days of operation. This decreased from 15.2% in the first half of the study period to 8.2% in the second half. Recurrence occurred in 56.2% of the remaining 73 patients, with no significant differences between PC and AC. Recurrence was related to regional lymph node metastases and poor tumour differentiation. Overall 5-year survival was 7.4% for PC and 24.8% for AC. For patients with radically excised tumours surviving 30 days the 5-year survival rates were 13.1% for PC and 30% for AC. CONCLUSION: Careful preoperative evaluation is still of great importance.

Fatty acid oxidation disorders as primary cause of sudden and unexpected death in infants and young children: an investigation performed on cultured fibroblasts from 79 children who died aged between 0-4 years.

BACKGROUND: Disorders of fatty acid metabolism are known to be responsible for cases of sudden and unexpected death in infancy. At least 14 disorders are known at present. 120 cases of sudden infant death syndrome (SIDS) had been examined for a prevalent mutation (G985) causing medium chain acyl CoA dehydrogenase deficiency, which is inherited in an autosomal recessive mode. No over-representation of either homozygous or heterozygous cases was found. AIMS: To investigate a broader spectrum of fatty acid oxidation disorders in a wider range of sudden deaths in infants and young children. METHODS: Seventy nine cases of unexpected death in infants and young children younger than 4 years old were examined for a minimum of nine fatty acid oxidation disorders, using the global [9, 10-3H] myristic acid oxidation assay in cultured fibroblasts from achilles tendon biopsies taken at postmortem examination. RESULTS: Three cases with fatty acid oxidation disorders and two carriers of the G985 mutation were found, all categorized as non-SIDS or borderline SIDS. The global assay used has the advantage of simplicity. CONCLUSIONS: These results indicate that disorders of fatty acid oxidation play a small but significant role in the cause of unexpected death in infants and young children, and that infants and children dying in this way should be regarded as high risk candidates for metabolic diseases.

Use of proteinase K for RT-PCR of cytokine mRNA in formalin fixed tissue.

Fresh tissue from cases of sudden infant death syndrome is becoming increasingly scarce and therefore researchers interesting in studying the aetiology of this syndrome have had to resort to archival tissue, usually in the form of paraffin wax sections. A simple method for isolating mRNA from formalin fixed, paraffin wax embedded material of sufficient purity for reverse transcription (RT)-PCR is described. Proteinase K treatment of formalin fixed, wax embedded tissue followed by RNA STAT-60 extraction was successful in isolating mRNA suitable for RT-PCR. Interleukin (IL)-1alpha, IL-6 and tumour necrosis factor (TNF) transcripts were amplified successfully from heart, but not thyroid, kidney or liver tissue, of a patient who died following rejection of a transplanted heart, and IL-1alpha, but not IL-6 or TNF, transcripts from lung tissue of a six month old baby who died of viral pneumonia. Transcripts of a housekeeping gene were detected in all tissues. This method should be useful for examining gene expression in archival material.

Prenatal diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited disease with a carrier frequency of approximately 1:100 in most Caucasian populations. The disease is implicated in sudden unexpected death in childhood. A prevalent disease-causing point mutation (A985G) in the MCAD gene has been characterized, thus rendering diagnosis easy in the majority of cases. Since the clinical spectrum of MCAD deficiency ranges from death in the first days of life to an asymptomatic life, there are probably other genetic factors--in addition to MCAD mutations--involved in the expression of the disease. Thus, families who have experienced the death of a child from MCAD deficiency might have an increased risk of a seriously affected subsequent child. In such a family we have therefore performed a prenatal diagnosis on a chorionic villus sample by a highly specific and sensitive polymerase chain reaction (PCR) assay for the G985 mutation. The analysis was positive and resulted in abortion. We verified the diagnosis by direct analysis on blood spots and other tissue material from the aborted fetus and from family members.

[Overheating and sudden infant death. Temperature regulation in relation to the prone position, the possible pathogenesis of sudden infant death]. / Overopvarmning og pludselig uventet spaedbørnsdød. Temperaturregulering i relation til maveleje, den mulige patogenese for pludselig spoedbørnsdød.

The incidence of sudden infant death syndrome (SIDS) in Denmark varied in the period 1982-1991 between 1.5 and 1.9 per 1000 livebirths. In December 1991 recommendations concerning infants' sleeping position were published by The Danish National Board of Health in order to reduce the risk of SIDS. Babies were recommended to be placed in the supine or side position when sleeping. Parents have followed the guidelines. Most Danish infants are now sleeping on their back or in the side position. Simultaneously, the number of SIDS dropped from about 110 to 40 per year. The incidence decreased to 1.2 in 1992 and was further reduced in 1993 to 0.6 per 1000 live births. Referring to our knowledge of the infant's temperature regulation we discuss why the prone position is a risk factor for SIDS. The head is the site of up to 85% of heat loss in an infant in bed. Placed in the prone position, the infant is more likely to suffer a rise in body temperature, especially if this is combined with having a cold, being heavily wrapped and sleeping in a heated room. Preceding sudden death many infants are reported to have suffered from minor viral infections. These might per se increase the body temperature. Parents often wrap infants that have an infection too heavily, which in an infant sleeping in the prone position might increase the body temperature to a higher level than if sleeping supine. The body temperature influences the production of toxins from normal intestinal flora and from pathogenic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

The frequency of a disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase in sudden infant death syndrome.

A number of rare inherited metabolic disorders are known to lead to death in infancy. Deficiency of medium-chain acyl CoA dehydrogenase has, on clinical grounds, been related particularly to sudden infant death syndrome. The contribution of this disorder to the etiology of sudden infant death syndrome is still a matter of controversy. The present study investigated 120 well-defined cases of sudden infant death syndrome in order to detect the frequency of the most common disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase (G985) compared with the frequency in the general population. A highly specific polymerase chain reaction assay was applied on dried blood spots. No over-representation of homo- or heterozygosity for G985 appears to exist in such a strictly defined population, for which reason it may be more relevant to look at a broader spectrum of clinical presentations of inherited metabolic disorders and examine a wider range of sudden death in infancy.

Cytokine release from human peripheral blood leucocytes incubated with endotoxin with and without prior infection with influenza virus: relevance to the sudden infant death syndrome.

Previous work with a neonatal ferret model for human SIDS had indicated that inflammation caused by a combination of influenza virus and bacterial endotoxin may be a cause of human SIDS. To determine whether cytokines may be involved in this inflammatory response, levels of interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha were examined, using ELISA assays, in culture supernatants of human peripheral blood leucocytes infected with influenza virus and subsequently incubated with endotoxin. Levels of TNF-alpha were increased compared to cells incubated with virus or endotoxin alone. Levels of IL-1 beta were also increased whereas levels of IL-6 were generally not enhanced. Cytokines appeared within 1-2 h of stimulation with virus or endotoxin and increased subsequently to reach maximum titres between 16 and 20 h post treatment. While levels of cytokine were much lower when determined using bioassays rather than ELISA assays, the pattern of increased yields from cells incubated with virus and endotoxin compared with either alone was still evident. The possible importance of these observations for SIDS victims is discussed.

Long-term treatment of nocturnal enuresis with desmopressin. A follow-up study.

Eight patients with monosymptomatic nocturnal enuresis (age 11-24 years) were investigated prior to and after 24 weeks of desmopressin treatment in order to evaluate the impact on the endogenous vasopressin secretion and urinary output. No effect on plasma vasopressin, diurnal urinary volume, and urinary osmolality were found after this long-term treatment. Overall no changes in either body weight, blood pressure, or hematological variables were demonstrated. This supports previous findings that the treatment appears to be well tolerated and free of side effects in longer term.

Chlamydia and sudden infant death syndrome. A study of 166 SIDS and 30 control cases.

Chlamydia inclusions could be demonstrated by an immunofluorescence assay in formalin-fixed lung sections in 32 of 166 cases (19.4%) of Sudden Infant Death Syndrome (SIDS) and in the lungs of only 1 of 30 infants with a known cause of death (3.3%). The difference is statistically significant (P = 0.04). Chlamydia trachomatis is an agent of pneumonia in 1-4 month-old infants who have acquired the disease from an infected cervix during birth, but other chlamydia species are also capable of causing pneumonia. The lung sections of the 32 chlamydia positive SIDS cases did not show typical histological signs of pneumonia. Even though chlamydia inclusions were detected in the lungs of 32 SIDS cases a causal relation between chlamydia infection and SIDS could not be demonstrated.

Detection of Chlamydia in postmortal formalin-fixed tissue.

A procedure to detect Chlamydia in postmortal formalin-fixed tissue is described. Monoclonal antibodies against a genus specific chlamydia epitope were used in immunofluorescence to detect chlamydia inclusions in formalin-fixed tissue sections. Lung sections from chlamydia-infected mice were examined and the effect of autolysis and tetracycline treatment was evaluated. Furthermore, lung tissue from two patients who died of ornithosis was examined. Inclusions detected in lung sections showed a bright apple-green fluorescence, and had a characteristic and easily recognizable morphology. Background and non-specific fluorescence were reduced by treating the tissue sections with trypsin, rabbit serum and Evans blue counterstain. Besides giving an exact diagnosis at autopsy, the method provides the possibility of determining the occurrence of chlamydia infections in various tissues, based on retrospective investigations in formalin-fixed tissues.