Acetazolamide-Loaded Dynamic 7T MR Quantitative Susceptibility Mapping in Major Cerebral Artery Steno-Occlusive Disease: Comparison with PET.

BACKGROUND AND PURPOSE: Dynamic changes in cerebrovascular reactivity after acetazolamide administration vary markedly among patients with major cerebral arterial steno-occlusive disease. MR quantitative susceptibility mapping can dynamically quantify the cerebral magnetic susceptibility. The purpose of this study was to determine whether dynamic changes in susceptibility after administration of acetazolamide on 7T quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in the cerebral hemispheres with major cerebral arterial steno-occlusive disease. MATERIALS AND METHODS: Sixty-five patients underwent 7T MR imaging at baseline and at 5, 10, 15, and 20 minutes after acetazolamide administration. Differences between the susceptibility of venous structures and surrounding brain tissue were calculated in the quantitative susceptibility mapping images. Susceptibility differences at 5, 10, 15, and 20 minutes after acetazolamide administration relative to baseline were calculated in 97 cerebral hemispheres with major cerebral arterial steno-occlusive disease. CBV and the cerebral metabolic rate of oxygen were also calculated using 15O-gas PET in the resting state. RESULTS: Dynamic changes of susceptibility after acetazolamide administration were classified into 3 patterns: abnormally increasing 5 or 10 minutes after acetazolamide administration; abnormally decreasing within 20 minutes after acetazolamide administration; and remaining unchanged after acetazolamide administration. CBV was significantly greater in the first pattern than in the latter 2. The cerebral metabolic rate of oxygen differed significantly in descending order from the first to middle to last pattern. CONCLUSIONS: Dynamic changes of susceptibility after acetazolamide administration on 7T MR quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in major cerebral arterial steno-occlusive disease.

Application of ultrasonography to postmortem examination. Diagnosis of pericardial tamponade.

In postmortem examination, it is difficult to diagnose pericardial tamponade in a dead body from the findings of conventional external examination alone. However, ultrasonography is a common diagnostic tool for pericardial tamponade in clinical practice. We studied the postmortem diagnosis of pericardial tamponade at external examination level by applying an ultrasonographic device. The ultrasonographic findings were compared with the conventional autopsy findings. Among 455 cases of forensic autopsy in Hamburg and Tokyo conducted within 5 days after death, we successfully diagnosed 11 cases of pericardial tamponade by ultrasound imaging prior to autopsy, and failed to diagnose pericardial tamponade in only two cases. In addition, 79 cases of external examination conducted at the Tokyo Medicinal Examiner's Office were also examined with ultrasonography, and we diagnosed three cases of pericardial tamponade and five cases of pericardial effusion. The differences in ultrasonographic findings between tamponade and effusion were relatively clear. Although autopsy provides definitive evidence for the cause of death, sometimes autopsy cannot be performed due to some social factors. In such cases, conventional external examination alone cannot establish a cause of death by pericardial tamponade, and application of diagnostic imaging technique will be helpful. While CT and/or MRI may provide more detailed information than ultrasound imaging, these techniques require special equipment, room and specialist, and most of all involves high cost, which is perhaps the most important consideration in the present atmosphere of medical cost containment. On the other hand, the ultrasonographic devices we use are compact, and can be used directly at the scene of death. Postmortem application of ultrasonography may be a valuable adjunct in the work of medical examiners and forensic pathologists.

Application of compact ultrasound imaging device to postmortem diagnosis.

In regions with low autopsy rates, forensic examiners often have to rely on external findings. Imaging techniques can assist the external examination and provide a more objective diagnosis. The SonoSite 180, a portable ultrasound device, was used for the examination of dead bodies. The influence of different degrees of decomposition was estimated. Even in cases with intestinal gas formation images of internal organs could be obtained with special techniques. Various pathological findings were detected by ultrasound and verified by autopsy (e.g. pericardial tamponade, cardiac hypertrophy, fatty liver, aortic aneurysm, metastatic liver, etc.). The experiences with the SonoSite 180 are promising. The device can be carried to the death scene or to the morgue and therefore serve as a valuable tool for medicolegal applications.

[Changes of fatty acid composition of brain synaptosomal phospholipids in isoflurane exposure rat].

We examined effects of inhalational anesthetic drug, isoflurane, on phospholipid and fatty acid in brain synaptosome. Wistar strain male rat was treated by inhalation of isoflurane. Rats were divided into 3 groups each 6 rats, one was 1 minimum alveolar concentration (MAC) exposure group, 1MAC group, and another was 2 times of MAC exposure group, 2MAC group, and the other was non exposure group, control group. The animals were kept in to box (0.343 m3) and the gas flow rate was set in 4 L/min by anesthetic instrument. After 60 minutes of exposure, rats were decapitated. Immediately, cerebrums were removed and fraction of synaptosome was sampled. In 2MAC group, C14:0 of phosphatidylcholine (PC) increased significantly as compared to the control group, but C16:1, C18:0, C18:2 and C20:3 decreased significantly. And also, C18:2 and C20:3 decreased significantly in 1MAC group. In terms of phosphatidylethanolamine(PE), C18:1 in 1MAC group, C14:0 and C16:1 in 2MAC group increased, but C20:3, C20:4 and C22:5 in 2MAC group decreased significantly as compared to the control group. Regarding phosphatidylserine + phosphatidylinositol, C14:0 in 2MAC group increased, but C22:5 decreased. In lysophosphatidylcholine, C12:0 and C14:0 in 2MAC group and C18:0, C20:4 in 1MAC group increased significantly, but C18:1 in 2MAC decreased. The changes of phospholipids and fatty acid in synaptosome were due to the metabolism of phospholipids of basic matrix and this was caused by effects of isoflurane on neural cellular membrane. The results indicated the suppression of membrane activity. Isoflurane has physiological activity on metabolism of phospholipid of cellular membrane. Thus, it has effects on neural cellular functions in brain.

[Tracing of analysis and prophylaxis on medical malpractice in Japan].

The role of drugs, especially injectables, in medical treatment is extremely important. In Japan, accidents associated with injections were not uncommon. Post-injection neuroparalysis of the radial nerve and sciatic nerve was associated with problems in textbooks, which described injection sites at the regions of neural passage. Then, in the 1970s, quadriceps femoral muscle contracture and deltoid muscle contracture became a social problem. When the author examined the osmotic pressure of various injectables, some injectables were found to deviate from the physiological range. When 335 injectables were evaluated for the potential to cause hemolysis, many injectables marketed for intramuscular injection gave strong hemolytic reaction, which attracted attention. Next, 89 types of injectables were tested for the potential to cause muscle damage by injecting into the femoral muscle of rabbits, and severe muscular damages were observed with antipyretics, analgesics, and antibiotics. The group lawsuit of Yamanashi Prefecture was settled at the Tokyo High Court in 1989, with the pharmaceutical company agreeing to pay over 2.95 billion yen as settlement. Giving drugs to patients occupies an important place among medical act. Medical disputes concerning accidents of wrong drugs and wrong usage are common. Obviously health care workers should exercise great caution in their duties, but without measures taken against medical equipment and drugs, such as containers and seals, this type of accidents will not be reduced. Through giving numerous speeches and lectures on medical accidents throughout the years, the author had felt strongly the need for teaching materials such as video tapes that can be used for self-learning. In 1999, the video entitled "Medical Accident-Learning from Actual Cases-" was finally completed, which consists of 6 parts (1. General consideration, 2. Blood transfusion, 3. Drug administration, 4. Surgery, 5. Examinations, 6. Management). For each area, typical incidents are presented as reproduced video taping. Then the criminal responsibility, civil responsibility and administrative responsibility of the doctor or nurse concerned are questioned in the form of questionnaires. Subsequently, the author also published a commentary book for the video that provides commentaries of the cases.

Genetic polymorphisms of orosomucoid ORM1 and ORM2 in Egyptians, Sudanese, and Qataris: occurrence of two new alleles.

Isoelectric focusing was used to investigate the genetic variants of the human plasma orosomucoid ORM1 and ORM2 gene loci in samples of Egyptians, Sudanese, and Qataris. The study populations were classified into 28 ORM phenotypes determined by 10 ORM1 and 9 ORM2 alleles that included 2 new alleles, designated ORM1*B13 and ORM2*H21. Family studies of these new alleles are in accordance with codominant autosomal inheritance. A new interpretation for two previously reported alleles, ORM1*C6 and ORM2*H17, is also presented.

An improved high resolution single method for orosomucoid ORM1 and ORM2 phenotyping.

An improved high resolution single method for orosomucoid ORM1 and ORM2 phenotyping using isoelectric focusing (IEF) in wide-scales ultrathin layer polyacrylamide gels of pH range 4.2 to 4.9 is presented. The method is reliable, simple, and provides an alternative for the three currently required ones for typing this genetic system.

Paternity testing by the detection of D1S80 VNTR using fluorescence image analyzer (Dualcolour system).

An improved method for DNA polymorphism typing of D1S80 VNTR locus and its application to paternity testing are described. For accurate estimation of the length of polymorphic DNA fragments, the size marker was labeled with fluorescence different from that of PCR primers, and co-electrophoresed as an internal standard. The dualcolour system of fluorescence image analyzer was used to detect the fragments and determine their size. This internal marker method could successfully overcome the problems of band pattern distortion and tailing, besides it allows easy and accurate interpretation of the DNA types. Our results indicate that the internal marker method is much more accurate than the method of using size marker in gel, even with the presence of distortion or tailing of the band patterns. Family studies applying this method showed complete agreement between the observed and predicted types.

Effects of bezafibrate on erythrocyte membrane phospholipids in alcohol-treated rats.

Male rats of the Wistar strain were divided 4 groups, and give a liquid diet of control feed, bezafibrate (150 mg/kg), ethanol, and ethanol plus bezafibrate for 5 week. The effect of bezafibrate supplementation on rats fed ethanol was examined in terms of the fatty acid composition of the phospholipids in the erythrocyte membrane. In the phospholipids profiles of erythrocyte membranes, PI was significantly decreased. The decrease in PI caused by bezafibrate appeared to substantially affect the membrane and consequently lead to changes in the membrane anchor. In the fatty acid composition of the PC, C20: 4 was significantly decreased in the group receiving alcohol (p < 0.05) but increased in the groups receiving bezafibrate (p < 0.05). In the fatty acid composition of the PE, C16: 0 was significantly increased in the three groups when compared with the control, and C20: 4 was decreased in the alcohol group (p < 0.05). In the fatty acid of SM and PI, C20: 4 was decreased and C18: 0 increased in the alcohol group. In the PS, C14: 0 was increased in the alcohol group, and decreased in the alcohol plus bezafibrate group (p < 0.01). The levels of arachidonic acid in the total fatty acids that constituted the membrane phospholipids were decreased in the rats given ethanol (p < 0.05). However, arachidonic acid in the group of bezafibrate supplementation on rats fed ethanol were elevated in comparison with the alcohol group (p < 0.05). With decreasing arachidonic acid as a marker of alcohol tissue injury following chronic alcohol intake, the effects of bezafibrate supplementation appear to contribute to membrane fluidity by altering the biochemical flexibility of the membrane.

[Arterial oxygen saturation monitoring of sleeping infants by pulse-oximeter--effect of sleeping position on arterial oxygen saturation in infants].

Monitoring of the arterial oxygen saturation (SaO2) in two sleeping infants was reported. They were a couple of female twins and had grown up normally after admission to NICU (Neonatal Intensive Care Unit) for a month. We investigated their SaO2 with the puls-oximeter at the terms between the 2nd and the 10th month. There was no significant difference between SaO2 in prone positions (n = 29) and that in supine positions (n = 30). In the infant with the sniffing conditions, however, SaO2 in prone positions seemed to be slightly lower than that in the healthy conditions. The slightly low SaO2 would give no effects on the healthy infants, but it may cause ALTE (Apparent Life Threatening Event) or death from SIDS (Sudden Infant Death Syndrome) to some infants who are not in good health and/or who are prone to get into ALTEA or SIDS. Especially, in the sniffing condition with hyperthermia, as the oxygen dissociation curve sifts to right and SaO2 degradation appears easily, sudden infant death may be possible to happen in prone position.

Frequency of D1S80 and HLA DQ alpha alleles in a Chinese population.

Allele frequency distributions for the D1S80 (MCT118) and HLA DQ alpha loci were determined in a Chinese population sample using the polymerase chain reaction (PCR). A total of 25 alleles and 100 phenotypes were observed for D1S80. The frequency of allele 18 was higher than allele 24 only in this Chinese population when compared to other reported populations. A total of 6 alleles and 21 possible phenotypes were observed for HLA DQ alpha. The power of discrimination was 0.97 and 0.93 for D1S80 and HLA DQ alpha, respectively.

Simultaneous measurement of alcohols and hydrogen cyanide in biological specimens using headspace gas chromatography.

We attempted to analyze biological specimens simultaneously for alcohols and hydrogen cyanide. A headspace gas chromatographic method with thick film wide bore column (PEG 20M) for the simultaneous determinations of methanol, ethanol, n-propanol and hydrogen cyanide in blood has been developed. This method was applied for the determinations of methanol, ethanol and hydrogen cyanide in a forensic autopsy case and animal experiments.

[Recommendations for preventing transmission of infection with biohazard in the practice of legal medicine (2). Equipment and practical applications. The Medico-Legal Society of Japan, Committee on Expert Opinions].

In May, 1993, our committee of the Medico-Legal society of Japan published an article entitled "Recommendations for Preventing Transmission of Infection with Biohazard in the Practice of Legal Medicine" in The Japanese Journal of Legal Medicine. Concerning this article, we received a lot of useful comments and opinions from many members of the society, for which we are very grateful. We also received a lot of requests for further information concerning details on the equipment and its practical applications. Since a lot of departments of Legal Medicine at several universities throughout Japan at present are remodelling their facilities in order to be able to perform autopsies, with respect to such circumstances, our committee felt the need to provide information on basic conditions concerning the prevention of transmission of infections with hazards.

[Concentrations of ethanol and ethanol metabolites and symptoms of acute alcohol-intoxicated patients].

Five patients who presented to an emergency room and did not have other injury and disease with acute alcohol intoxication were analyzed about blood and urine ethanol, acetaldehyde, acetate and acetone levels. The average concentrations of ethanol, acetaldehyde, acetate and acetone in blood were 37.0 mM (1.7 mg/ml), 18 microM, 1.00 mM and 18 microM, respectively and the concentrations in urine were 50.8 mM (2.3 mg/ml), 37 microM, 0.79 mM and 47 microM, respectively. Clinical symptoms were concerned with both ethanol concentration and concentrations of ethanol metabolites. Their symptoms of acute alcohol-intoxicated patients were caused by the ethanol concentrations which was less than the levels reported in early studies.

An analysis of low side molecular weight proteins in human seminal plasma by capillary electrophoresis.

Semen was obtained from 45 healthy males, and its plasma proteins of low side molecular weight obtained by filtration with a Molcut II (Millipore) were analyzed by means of capillary electrophoresis (CE) for an application to forensic medicine, with a phosphoric acid of pH 4.5 and a column of 100 cm x 75 microns ID. There were noted 27 to 36 peaks on the chromatograms, two sections of which showed individual differences in the chromatographic patterns. The chromatographic patterns between 20.0 and 22.0 minutes were classified into 2 groups: I (66.7%) and II (33.3%). The main peak appearing at about 36 minutes was divided between two patterns: A (53.3%) and B (46.7%). The serum, saliva, and vaginal fluid were also analyzed for low-side-molecular-weight proteins by means of capillary electrophoresis, but their levels contained low and their chromatographic patterns different from those of seminal plasma. The patterns of the whole seminal plasma, saliva and serum with pH 7.0 phosphate buffer were different and appeared to be applicable for identifying such samples.

[Recommendations for preventing transmission of infection with biohazard in the practice of legal medicine. The Medico-Legal Society of Japan, Committee on Expert Opinions].

In Japan recently there arose a sudden need for special guidelines concerning medicolegal autopsy and the handling of medicolegal materials. In this respect, the Medico-legal Society of Japan, Committee on Expert Opinions has produced a guideline, entitled "Recommendations for Preventing Transmission of Infection with Biohazard in the Practice of Legal Medicine", which was then introduced to all members in Legal Medicine. This guideline contains First: Explanations about the most important types of Biohazard diseases, the dangers and ways of transmission. Second: Explanations concerning preventive measures in medicolegal autopsy, for handling of medicolegal materials and investigation samples, also concerning the equipment and tools within the autopsy room, as well as measures for correct disinfection. These guidelines, form the base on each department of the Medico-Legal Society of Japan, are asked to adjust their own practical manual in order to improve the safety of autopsy conditions.

[Metabolism and toxicity of n-pentane and isopentane].

n-Pentane and isopentane have a wide range of use, for example, for cleaning precision machinery, extracting essence and oil, and as liquid fuel for now very popular disposable lighters. They are contained in liquefied petroleum gas and natural gas as trace constituents. In our present experiments, we studied the metabolism and toxicity of these n-pentane and isopentane metabolites. Male mice of ICR strain were exposed to about 5% n-pentane for one hour while the oxygen in the environmental air was maintained at about 20%. Then their blood and liver tissue were collected and analyzed by means of GC and GC-MS. The metabolites thus obtained were 2-pentanol, 3-pentanol and 2-pentanone. The same procedure was repeated with isopentane; 3-methyl-2-butanol, 2-methyl-2-butanol and 3-methyl-2-butanone were detected as the resultant metabolites. In the presence of the NADPH-generating system liver microsomes were made to react to the substrate of saturated n-pentane or isopentane aqueous solution at 37 degrees C for one hour. As a result, the same metabolites were produced as obtained in the exposure experiment. It was therefore suggested that n-pentane and isopentane were metabolized chiefly by liver microsomes. Male mice of ICR strain were fed with 80 mg/kg b.w. of phenobarbital for consecutive four days and exposed to n-pentane or isopentane for one hour. This resulted in an increase in the amount of 2-pentanol and 2-pentanone in the n-pentane inhalation and 2-methyl-2-butanol in the isopentane inhalation experiment. The toxicity of each metabolite was studied on cultured cells. The metabolites were individually mixed with HeLa S3 cell suspension, incubated for three days, and their concentration which inhibited the growth of cells by 50% (IGC 50) were compared. It was demonstrated as a result that the IGC 50 for any of the metabolites was lower than that for methanol, ethanol or acetone used as control.