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Biomedical subjects

M Gregersen

Publications and source records attributed to M Gregersen.

At least 19 recordsLinked to original sources

The iodinated radiographic contrast medium iohexol mimics the vasodilator effect seen with small increases in extracellular K+ in the isolated rabbit central ear artery.

PURPOSE: To investigate whether iodinated radiographic contrast media (IRCM) mimic the hyperpolarizing and vasodilator effects of K+ by comparing the vasodilator effect of a transient rise in extracellular K+ with that of the IRCM iohexol. MATERIAL AND METHODS: Immersed rabbit central ear arterial rings with and without endothelium and pre-contracted with phenylephrine (PE) were used to investigate the dependency of the endothelium in K+-induced vasodilatation. Perfused rabbit central ear arteries, pre-contracted with PE, were used to study the effects of bolus administrations of the IRCM iohexol or KCl on arterial tone under conditions that mimic those employed during clinical arteriography. RESULTS: A small rise in K+ caused an endothelium-independent and ouabain-sensitive relaxation of PE-constricted rabbit central ear artery rings. The relaxation was not changed in the presence of barium. The IRCM iohexol and KCl, injected as boluses into perfused PE-constricted rabbit ear arteries, caused transient decreases in perfusion pressure. Iohexol- and K+-induced pressure decreases were significantly reduced in the presence of 10 microM ouabain alone or in combination with 30 microM barium. Neither iohexol- nor K+-induced pressure decrease was significantly changed in the presence of barium alone compared to controls. CONCLUSION: The vasodilator effect of IRCM mimics the vasodilator effect seen upon small increase in extracellular K+. Under the experimental conditions employed in the present study, a considerable part of the IRCM-induced vasodilatation appears to be due to activation of Na+/K+-ATPase in the smooth muscle cells.

Analysis of Variance↗

Unidentified bodies/skulls found in Danish waters in the period 1992-1996.

In the period 1992-1996 a total of 89 unidentified bodies/skulls found in Danish waters were investigated at the three University Institutes of Forensic Medicine in Denmark. Males constituted 79% of the total material. Open water was the finding place in half the cases, about one-fourth was found on shore and another fourth in a harbor basin. Totally 73 bodies and one skull were identified. Danes constituted 57% of the material. Almost all non-Danes originated from countries with borders to the waters surrounding Denmark. The cause of death was in 71% stated as presumably/possibly drowning, in 5% as severe lesions (precipitation) and in 25% it could not be solved. The manner of death was in non-Danes most often stated as an accident (56%), and according to this the finding place in non-Danes most frequently was the open water (66%). In Danes suicide predominated (71%) and the finding place in Danes was almost equally distributed among open water, shores and harbors, respectively. Among the totally 74 identified cases, 83% of the total material, an initial suggestion of the identity based on effects found on the body was possible in 43 cases (58%). The final identification was performed by means of forensic dental examination in total 58 cases (78%), in Danes in 93% and in non-Danes in 59%. In the remaining 16 cases one or more of the following contributed to the final identification: information about dental condition, clothing, personal papers, X-ray photos, jewelry, tattoos/scars and fingerprints. The importance of a close collaboration between the police, the forensic pathologist and the forensic dental expert in order to reach a fair number of positive identifications is emphasized.

Adolescent↗

[Poisonings with the herbicides glyphosate and glyphosate-trimesium].

Generally the herbicide glyphosate is considered harmless to humans. Glyphosate-trimesium is labelled harmful (Xn), whereas glyphosate-isopropylamine carries no warning sign. As cases of serious poisoning have emerged contacts to the Poison Information Centre have been reviewed. The persons exposed were mainly smaller children and adults 20 to 59 years of age. Oral exposure was recorded in 47 persons, inhalation exposure in 24 and topical contact in 42. About one fourth of the exposed persons were asymptomatic. Most of the symptomatic poisonings demonstrated complaints from the mouth, the gastrointestinal tract and the airways. Eleven patients were admitted to hospital. Two died, one of them having ingested the isopropylamine salt, the other the trimesium salt. Death ensued quickly in the latter patient. A similar fate was observed in a child--not included in the present material--who had also ingested the trimesium compound.

Adult↗

[Deaths among inmates in the institutions of the Prison Service. Deaths in prisons, county jails etc].

The purpose of the study is to investigate the number and the character of deaths during stays in prisons, county goals etc. During the study period from 1992-1996 with approx. 38,000 imprisonments per year there were 74 deaths, 71 males and three females. The average age was 32.4 years. Approximately 16% had foreign citizenship. Twenty had leave, legal or illegal when death occurred. There were 34 suicides, 22 accidents, 3 homicides and 15 cases of natural death. Several deaths took place relatively shortly after the arrival at the institution, one third within a week. The most frequently used suicidal method was hanging. The accidents were dominated by poisoning deaths, often with morphines, possibly in combination with alcohol or other drugs. Two of the three homicides took place during leave. Among natural deaths, heart death was the most frequent cause of death with six of 10 unexpected deaths. Among expected deaths in prison there were three AIDS patients. Fourteen of the fifteen natural deaths had a substantial alcohol consumption and/or drug abuse. There ought to be a central registration of deaths in prisons and similar institutions. The autopsy frequency should be high, and forensic chemical investigation should be used more often. Drug dependent inmates should be informed about reduced tolerance to drugs in relation to release and leave.

Accidents↗

Iodinated radiographic contrast media inhibit shear stress- and agonist-evoked release of NO by the endothelium.

1 We have used isolated arterial preparations from the rabbit and dog to investigate whether non-ionic iodinated radiographic contrast media (IRCM) modulate nitric oxide (NO) release. The tri-iodinated monomers iopromide and iohexol were compared with the hexa-iodinated dimer iodixanol. 2 The vasodilator effects of iohexol (300 mg ml-1) and iodixanol (320 mg ml-1) were assessed in cascade bioassay. Increasing concentrations of iohexol or iodixanol caused concentration-dependent relaxations of the detector tissue which were insensitive to 100 microM NG-nitro L-arginine methyl ester (L-NAME) and 10 microM indomethacin, whereas viscosity-associated relaxations induced by the 'inert' agent dextran (MW 80,000; 1-4%) were attenuated by inhibition of NO synthesis. 3 Relaxations of endothelium-intact rings to acetylcholine (ACh) were attenuated by preincubation with iohexol or iodixanol, whereas relaxations to sodium nitroprusside (SNP) in endothelium-denuded rings were unaffected. Inhibitory activity did not correlate with either molarity or iodine concentration. Mannitol caused inhibition of both ACh- and SNP-induced responses. 4 In isolated perfused arteries the depressor responses to iodixanol (320 mg ml-1) and iopromide (300 mg ml-1) administered as close arterial bolus attained a plateau with maximal dilatations of approximately 25% and approximately 60%, respectively. Addition of 100 microM NG-nitro L-arginine (L-NOARG) and/or 10 microM indomethacin to the perfusate had no effect on the responses to either agent. 5 We conclude that IRCM exert direct effects on the endothelium that inhibit NO production rather than its action on vascular smooth muscle. Shear stress-induced stimulation of NO production by IRCM is unlikely to contribute to their vasodilator activity in vivo when administered during angiography despite high intrinsic viscosity.

Acetylcholine↗

Rapid lethal intoxication caused by the herbicide glyphosate-trimesium (Touchdown).

Two cases of rapid lethal intoxication with the herbicide glyphosate-trimesium (Touchdown) are presented. A 6-year-old boy who accidentally ingested a mouthful of glyphosate-trimesium died within minutes. The same happened to a 34-year-old woman who intentionally ingested approximately 150 ml of glyphosate-trimesium. The post-mortem examination revealed gastric content and oedema of the mucus membranes of the airways, erosion of the mucus membranes of the gastrointestinal tract, pulmonary oedema, cerebral oedema, and dilated right atrium and ventricle of the heart. The speed of which death occurs is much more rapid than lethal intoxications with the herbicide glyphosate (isoprophylamine), also known as 'Roundup'. It is suggested that the lethal mechanism between the two herbicides may be different. The component, trimethylsulfonium, of the glyphosate-trimesium may facilitate the absorption after oral ingestion. This difference can be crucial in the treatment of human intoxication. We propose that containers with glyphosate-trimesium must be labelled because of the apparent effect of lethal intoxication.

Adult↗

Mercury accumulations in brains from populations exposed to high and low dietary levels of methyl mercury. Concentration, chemical form and distribution of mercury in brain samples from autopsies.

Autopsy samples from 17 Greenlanders and 12 Danes were analysed for total and organic mercury by atomic absorption spectrophotometry, and for cellular localisation by autometallography. The concentration of total mercury in the Greenlanders (median: 174 micrograms Hg/kg wet weight brain tissue, range 59-4782, highest in cerebellum: 492) was found to be significantly higher than in the Danish group (3.7 micrograms Hg/kg w.w., range 1.2-11.8). Furthermore, the total concentration of mercury was positively correlated to age (rho = 0.56, p < 0.05), and the fraction of methyl mercury was negatively correlated to age (rho = -0.66, p < 0.01) among the Greenlanders. This suggests an age dependent accumulation of total mercury and a slow transformation of methyl mercury to inorganic mercury in the brain. The autometallographically demonstrable mercury was primarily located in glia cells.

Adult↗

[Fatal accidents in house fires. The most significant causes, such as smoking and alcohol abuse, multiplied by four the incidence during the last 40 years].

A population-based descriptive investigation of housefire accidents in Denmark was carried out for the two five year periods 1953-58 and 1988-93, based on death certificates, police reports and autopsy reports. The number of deaths due to housefire accidents in Denmark has increased (1953-58: 136 (66 men and 70 women), 1988-93: 363 (212 men and 150 women), mostly due to an increase in tobacco-smoking related fire accidents. In 1988-93 the three common causes of housefire deaths were tobacco-smoking, often in combination with alcohol intoxication or handicap (51%), cooking-accidents (10%) and accidents with candles (9%). The largest risk groups were chronic alcoholics, handicapped and elderly people. In conclusion, warnings should be issued against smoking in bed and use of loose-fitting clothing while cooking on an open fire. Protective aprons and devices for use while smoking, self-extinguishing cigarettes and use of fireproof materials in furniture and clothing may prevent ignition. Smoke-alarms may secure early warning.

Accidents, Home↗

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.

Acyl-CoA Dehydrogenase↗

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.

Acyl-CoA Dehydrogenase↗

Visipaque is isotonic to human and rat blood plasma.

Even at its highest concentration, 320 mg I/ml, Visipaque - based on the nonionic dimer iodixanol - is isoosmotic to blood plasma, whereas Omnipaque (300 mg I/ml) - based on the nonionic monomer iohexol - has an osmolality of about twice that of the plasma. However, the fact that the solution is isoosmotic to plasma does not necessarily mean that it is isotonic to plasma. An isoosmotic solution can still cause a net movement of water over the plasma membranes of, for example, erythrocytes and endothelial cells. Determination of the tonicity of Visipaque 320 mg I/ml and comparison with that of Omnipaque 300 mg I/ml and hypertonic NaCl have been performed. No change in the water content of human erythrocytes was seen after mixing whole blood 10:1 with either Visipaque 320 mg I/ml or 155 mM NaCl, whereas a significant decrease in water content occurred with Omnipaque 300 mg I/ml and 620 mM NaCl. No difference in the water content of rat erythrocytes was evident after mixing whole blood with Visipaque 320 mg I/ml or isotonic NaCl. However, as with human erythrocytes, a significant decrease in water content occurred after rat blood was mixed with Omnipaque 300 mg I/ml. In conclusion, Visipaque 320 mg I/ml does not cause any net movement of water over the human or the rat erythrocyte plasma membrane, i.e., Visipaque is isotonic to human and rat blood plasma.

Animals↗

The crash of the Partnair Convair 340/580 in the Skagerrak: traumatological aspects.

In September 1989 an aircraft carrying 55 people crashed into the sea north of Denmark. There was no warning of the crash. The medico-legal investigation of the accident concentrated on finding clues to the cause of the accident, and identifying the victims, all of whom perished. These were found in two groups--31 were immediately recovered from the surface of the sea and 19 were collected from the sea or shore during the following months. The injuries in the two groups differed, indicating that the aircraft broke up in mid-air. One group probably fell into the sea after a free fall, while the other probably remained in the wreckage until hitting the surface. The victims' injuries showed no evidence of fire or explosion. The technical investigators concluded that the aircraft broke up due to a structural failure in the tail.

Accidents, Aviation↗

The crash of the Partnair Convair 340/580 in the Skagerrak: identification of the deceased.

In 1989, a Norwegian Convair aircraft crashed into the sea near the northwest coast of Jutland. Apparently, the aircraft had disintegrated in midair. On board were 50 passengers and a crew of 5. There were no survivors. Immediately after the crash 31 bodies were found. During the next 10 days, 11 bodies were recovered from the seabed and within the next 6 months, a further 8 bodies were found. Five bodies were never recovered. All the bodies found were positively identified based on personal effects combined with medical and dental findings. Different models for cooperation between the Primary ID-group, who were responsible for the final identification, and the ID-teams, who performed the examination of the bodies, were tested. It was concluded that the fastest and most reliable results were obtained when the ID-teams responsible for the examination of the bodies also took part in the reconciliation sessions.

Accidents, Aviation↗

The value of immunohistochemistry of pleural biopsy specimens in the differential diagnosis between malignant mesothelioma and metastatic carcinoma.

The aim of the present study was to evaluate the aid of immunohistochemistry in the differential diagnosis between pleural malignant mesothelioma (MM) and secondary pleural carcinoma in pleural biopsy specimens. A series of MM (epithelial or biphasic type) (n = 39), and a series of secondary pleural carcinomas (n = 25) were studied with a panel of monoclonal antibodies against Ber-EP4, CEA, and Leu-MI (CD-15). Considering the markers one, two or three at a time, computer analysis was conducted to identify the immunophenotype with the highest sensitivity and specificity for both MM (n = 39) and adenocarcinoma (n = 19). The CEA/CD-15 marker combination had the highest specificity (MM = 100%; adenocarcinoma = 82.1%), and sensitivity (MM = 82.1%; adenocarcinoma = 100%) considering both categories of tumours. Positive reaction for CEA and/or CD-15 was the best indicator of metastatic adenocarcinoma. Negative reaction for CEA/CD-15 and Ber-EP4/CD-15 showed up to be 100% specific for MM. Positive reaction for one, two or even all these antigens, however, occurred in nine tumours predetermined as MM according to their gross appearance, and absence of other primary malignancies at autopsy. Ultrastructural examination (n = 7) of these tumours strongly supported the diagnosis in one case, and did by no means exclude the diagnosis MM in the other six cases. Neither did any of the tumours reveal ultrastructural signs of adenomatous differentiation, and they did not express PAS/diastase resistant globules, amylase or surfactant. Anti -Ber-EP4 was the antibody most frequently expressed in MM (n = 8). Until antibodies specific for MM are available, the limitation of immunohistochemistry to solve the diagnosis in all cases of pleural malignant tumours has to be considered.

Carcinoma↗

[Fatal poisonings in Jutland 1980-1989].

A description is given of trends in the pattern of fatal poisonings examined at the Department of Forensic Medicine, Aarhus University during the period 1980 through 1989 (638 men and 391 women). These cases comprised 36% of all fatal poisonings in the area during the decade. In more than half of the medicolegally examined cases, death was categorized as accident. In two thirds of the examined cases death was caused by drugs, whereas non-medical substances (alcohol, carbon monoxide etc.) accounted for one third of the deaths. During the ten-year period, a decline was seen in the number of barbiturate-related deaths, whereas the number of deaths caused by analgesics increased. Propoxyphene was the drug found to have caused most deaths during the period, and developments concerning fatal poisonings involving this drug must still be watched closely.

Accidents↗

Fatal poisonings in Jutland (Denmark) during the 1980s.

During the period 1980 through 1989 a total of 1029 cases of fatal poisoning (638 men and 391 women) were examined at the Department of Forensic Medicine, Aarhus University, Denmark. In 68% of the cases death had been caused by drugs, whereas acute alcohol poisoning and carbon monoxide accounted for 15% and 14% of the cases, respectively. Alcohol was detected in more than half of the 1029 fatal poisoning cases, and in 42% of all cases the blood alcohol concentration was above 0.8 g/kg. In 57% of the cases death was categorized as accidental, only in 31% of the cases as suicide. Accidental deaths were especially predominant amongst drug and/or alcohol abusers. Propoxyphene was the drug found to have caused most fatal poisonings during the decade (30% of the drug-related deaths). Most of the propoxyphene-related deaths occurred during the early and mid-eighties. Barbiturate poisonings were quite frequent during the first half of the eighties. However, the number of deaths caused by barbiturates decreased significantly after 1986, when most barbiturates were withdrawn from the market. The number of deaths caused by narcotics and analgesics increased during the survey period, while no specific tendency was observed concerning antidepressants.

Accidents↗