Are there "CO2 sensors" in the lung?
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Biomedical subjects
Publications and source records attributed to R L Lin.
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Death from heroin body packing has been well described in the forensic literature. Most fatalities are due to drug leakage and consequent acute heroin toxicity. Recently, drug traffickers have become more sophisticated in their packaging, and the risk of rupture of drug packets is more remote. Though intestinal obstruction is a recognized risk of body packing, rarely has this resulted in death. We describe four cases of heroin body packing presenting to the Regional Medical Examiner Office in New Jersey. Death in three of these cases was due to intestinal obstruction, with resultant intestinal rupture and peritonitis. Toxicologic evaluation in these three cases was negative for opiates or other drugs of abuse. In one case, death was due to acute heroin toxicity, validated by toxicologic analysis. We briefly discuss the differing drug packaging found in these four cases and the ramifications of packaging as it relates to intestinal obstruction.
A retrospective clinical study was carried out on 227 pathologically proven cases of bronchogenic carcinoma from eastern Taiwan, between October 1986 and March 1990. The ratio of males to females was low (2.15:1). The most common cell type was adenocarcinoma (39.2%), with squamous cell carcinoma (36.1%) being the second most common. Adenocarcinoma contributed to 51.4% of the bronchogenic carcinoma in women and 33.5% in men. History of cigarette smoking was strongly associated with squamous cell carcinoma and small cell carcinoma. The most common symptom was a cough (69%). The majority of small cell carcinoma and squamous cell carcinoma appeared to be of the central type in location while most adenocarcinoma appeared to be of the peripheral type. Bronchoscopic examination was the most valuable method for confirming the diagnosis of bronchogenic carcinoma. Most patients presented late and only 19 cases (8.4%) underwent surgery. Aborigines have a lower risk of developing bronchogenic carcinoma. The clinical manifestations of bronchogenic carcinoma in eastern Taiwan are similar to those found in Taiwan as a whole.
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Of the 12,000 fire-related deaths occurring annually in the United States, it is estimated that 60 to 80 per cent are due to smoke inhalation. Plastic and synthetic materials which have been introduced in home construction and furnishings produce a more toxic smoke when burned. Efforts to identify a "supertoxin" in this smoke have been unsuccessful to date. An alternative approach is to examine why victims are unable to escape, and become exposed to smoke for lethal periods of time. The authors examined the circumstances of death in 39 fire victims (27 adults, 12 children) over a 25-month period. Detailed examination of the fire scene, autopsy studies, and toxicologic analysis were carried out. Position of the victim, and escape efforts were noted. Carbon monoxide was elevated in all victims, with "lethal" levels (= greater than 50%) in 21/39 victims. Cyanide was detected in 24/29 victims, but none had lethal (3 mg/L) levels present. Ethanol was detected in 21/26 adults (80%) and 0/12 children (0%). 18/26 adult victims had ethanol levels above the statutory level of intoxication (10 mg%). Victims found in bed (no escape attempt) had a mean blood ethanol level of 268 mg%, compared with a mean level of 88 mg% in those victims found near an exit (P = .006). Ethanol intoxication significantly impairs the ability to escape from fire and smoke and is a contributory factor in smoke-related mortality.
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The general toxicology unknown often presents challenges and interests to toxicologists. A systematic analytical approach to search for drugs or poisons is presented here. The preliminary screening analyses were as follows: alcohol by gas chromatography (GC), ethchlorvynol colorimetric analysis, enzyme multiplied immunoassay technique (EMIT), basic drug screening by GC, and neutral and weakly acidic drug screening by GC. Other additional analyses were performed depending on the special circumstance of each individual case and the results of these preliminary analyses. Positive findings were confirmed by computerized gas chromatography/mass spectrometry when practical. Quantitation was performed by GC whenever possible.
A general toxicology unknown case is presented to demonstrate our systematic approach. A 20-year-old male was found dead with multiple suicide notes. Overdose was suspected but substances were not known. Blood alcohol was negative. Urine was analyzed by enzyme-multiplied immunoassay technique and was negative for all drugs assayed. Urine was then extracted with ethyl acetate:hexane (1:1) at pH 10 and back-extracted into 1.0N sulfuric acid. The acidic layer was adjusted to pH 10, and re-extracted with ethyl acetate:hexane (1:1). The residue was analyzed by gas chromatography (GC) on a 3% OV-101 column. It was found to be negative for all commonly screened substances. However, several unknown peaks were observed. Electron impact mass spectra of these unknown peaks were obtained and searched for in our computer library of more than 25000 mass spectra. These unknown peaks were identified as doxylamine and pyrilamine by gas chromatography/mass spectrometry. The base peak and molecular ion for pyrilamine were at m/z 121 and 285, respectively. The base peak for doxylamine was at m/z 58. No molecular ion was observed for doxylamine. Both doxylamine and pyrilamine are antihistamines, but are promoted and used in the management of insomnia. Quantitation was performed on a GC using dexbrompheniramine as an internal standard. Blood concentrations for doxylamine and pyrilamine were 0.7 and 7.0 mg/L, respectively. Concentrations in other tissues were determined. Death was caused by combined doxylamine and pyrilamine intoxication; the manner of death was suicide.
A method for the identification and quantitation of two tricyclic antidepressants, amoxapine (Asendin) and trimipramine (Surmontil) is presented here. Samples were extracted with hexane at pH 10, back-extracted with 1.0N sulfuric acid. The acidic layer was adjusted to pH 10 and re-extracted with hexane. Electron impact mass spectra were obtained. The base peak and molecular ion for amoxapine were at m/z 245 and 313, respectively. The base peak and molecular ion for trimipramine were at m/z 58 and 294, respectively. There were three forensic toxicology cases involving amoxapine in Cook County, IL, in 1980 and 1981. The concentrations of amoxapine in blood for these three cases were 1.66 mg/L, 7.16 mg/L, and 2.95 mg/L, respectively.
A 24-year-old black female presented a live birth of six-months gestation. The 700-g neonate survived for 11 h. After toxicology revealed the presence of pentazocine and tripelennamine (T's and Blues), the mother admitted to using this combination intravenously 9 h previous to admission. Concentrations of pentazocine and tripelennamine were simultaneously determined by gas-liquid chromatography (GLC) combined with nitrogen selective detection. Analyses were performed on a 3% OV-101 column, with the added internal standard, dexbrompheniramine. Both pentazocine and tripelennamine were qualitatively confirmed by their electron impact mass spectra. Concentrations of pentazocine and tripelennamine in various fluids and tissues were determined.
A 64-year-old white female was given Purinethol (6-mercaptopurine) in place of propylthiouracil. A gas chromatographic method for the determination of 6-mercaptopurine in blood and other biological tissues has been developed. Samples were extracted with chloroform/isopropanol (4:1) at pH 7.0 and back-extracted into 0.5N sodium hydroxide (NaOH). The NaOH fraction was neutralized and buffered at pH 7.0 and extracted with chloroform/isopropanol (4:1). Quantitation was made by gas chromatography following methylation of the drug with trimethylanilinum hydroxide on an OV-101 or OV-225 column, using an internal standard. 6-Mercaptopurine was identified in all tissues by gas chromatography/mass spectrometry. The derivatized drug was identified by its electron impact mass spectrum as a dimethylated compound that has a molecular ion at m/e 180, which is also the base peak. The highest concentration of Purinethol was found in blood (110 mg/L). Concentrations in other tissues have been given. This is probably the first reported death by Purinethol.
This report describes a sensitive gas chromatographic method with the use of a nitrogen detector for the determination of fluphenazine at therapeutic concentrations in human plasma. Fluphenazine was measured as its acetyl derivative. Perphenazine, a structurally similar phenothiazine, was used as an internal standard. The acetylated derivatives were identified by GC/MS. Within-day coefficient of variation of the method over the concentration range 0.5 to 10 ng/ml fluphenazine was 6.7%. Fluphenazine concentrations in the plasma of patients receiving the drug orally (as dihydrochloride) or intramuscularly (as decanoate) were measured. There were large interindividual variations both in plasma levels and half-lives of fluphenazine in different patients treated with the same doses.
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Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation.
Tetrahydrofolic acid exerts a product inhibition on the methyltetrahydrofolic acid-mediated methylation of indolethylamines. Kinetic studies showed that this inhibition was competitive with respect to methyltetrahydrofolic acid and non-competitive with respect to N-methylserotonin. Chromatographic separation of S-adenosylmethionine-dependent indolethylamine N-methyltransferase and methyltetrahydrofolic acid-dependent methyltransferase from rabbit lung was obtained. There was no cross reaction of the two enzymes to tetrahydrofolic acid, S-adenosylhomocysteine, N, N-dimethyltryptamine or bufotenin.
Glutamine-dependent carbanoyl phosphate synthase [ATP6carbamate phosphotransgerase (dephosphorylating), EC 2.7.2.9], aspartate transcarbamoylase (carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydroorotate amidohydrolase, EC 3.5.2.3), are copurified as a high-molicular-weight complex from extracts of unfertilized eggs of Rana catesbeiana. UTP is required to maintain the integrity of the complex during the last two purification steps. Removal of the nucleotide results in dissociation of the complex. Based on sedimentation behavior in glycerol gradients, the dissociated carbamoyl phosphate synthase has an apparent molecular weight of 260,000 +/- 20,000 and that of dihydroorotase is estimated at 280,000 +/- 20,000. Aspartate transcarbamoylase is broadly distributed over the gradient. The addition of ATP, 5-phosphoribosyl-1-pyrophosphate, Mg++, or inorganic phosphate to the dossociated complex results in the appearance of a peak of aspartate transcarbamoylase activity with an apparent molecular weight of 110,000 +/- 10,000. Icubation of a mixture of the dissociated enzymes with UTP and Mg++ leads to their reassociation into the high-molecular-weight complex.
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