PubMed Health⌕ Search

Biomedical subjects

David R Fowler

Publications and source records attributed to David R Fowler.

15 recordsLinked to original sources

Simultaneous quantification of methamphetamine, cocaine, codeine, and metabolites in skin by positive chemical ionization gas chromatography-mass spectrometry.

A positive chemical ionization gas chromatography-mass spectrometric method was validated to simultaneously quantify drugs and metabolites in skin collected after controlled administration of methamphetamine, cocaine, and codeine. Calibration curves (2.5-100 ng/skin biopsy) for methamphetamine, amphetamine, cocaine, norcocaine, benzoylecgonine, cocaethylene, norcocaethylene, anhydroecgonine methyl ester, morphine, codeine, and 6-acetylmorphine (5-100 ng/skin biopsy for ecgonine methyl ester and ecgonine ethyl ester) exhibited correlation coefficients >0.999 and concentrations +/-20% of target. Intra- and inter-run precisions were <10%. This procedure should be useful for postmortem analysis; data are included on drug concentrations in skin after controlled drug administration.

Calibration↗

Heat stroke deaths caused by electric blankets: case report and review of the literature.

Heat stroke is the most serious and potentially life-threatening condition of the heat-related illnesses. Heat stroke deaths caused by electric blanket are rarely reported. In this paper, we report 2 cases of fatal heat stroke caused by overheating from electric blankets in winter. One was a 41-year-old man who was found unresponsive in bed on an electric blanket. His wife shared the same bed with him and was found unconscious. The wife's axillary temperature was 40 degrees C (104 degrees C) when she was admitted to the hospital. She fully recovered after medical treatment. The husband was pronounced dead at scene, with rectal temperature at 41.2 degrees C (106.2 degrees C). The other was a 13-year-old girl who was found dead in bed on an electric blanket, with rectal temperature at 41 degrees C (105.8 degrees F). The literature is reviewed, and the pertinent findings, including scene investigations, postmortem examination, the risk and mechanism of fatal heat stroke caused by using electric blanket, are discussed.

Adolescent↗

Fatal dog maulings associated with infant swings.

We present three cases of fatal dog maulings of infants placed in mobile infant swings, a phenomenon not previously described in the literature. In each case, the victim was left in a mobile swing, unsupervised by an adult, and the attacking dog was a family pet. Case 1 involved an 18-day-old male infant attacked by a pit bull; Case 2 involved a 3-month-old male infant attacked by a Chow Chow and/or a Dachshund, and Case 3 involved an 18-day-old female infant attacked by a Labrador-pit bull mix. These cases not only underscore the importance of not leaving young children unattended in the presence of pet dogs, but also raise the possibility that mobile swings may trigger a predatory response in dogs and thus may represent an additional risk factor for dog attack.

Animals↗

Concentration of carbon monoxide (CO) in postmortem human tissues: effect of environmental CO exposure.

We studied how carbon monoxide (CO) is distributed within the human body through quantitation of CO concentrations in postmortem tissue samples from fatalities including possible CO exposure. Stored, frozen tissues were diced, sonicated in water, and 0.01-8.0 mg wet weight (ww) tissues were incubated with sulfosalicylic acid in CO-purged, septum-sealed vials. CO released into the headspace was quantitated by reduction gas chromatography. Mean tissue CO concentrations (pmol/mg ww) from subjects diagnosed to have no known CO exposure (control, N=14), died from fire (N=13), and CO asphyxiation (N=7), respectively, were: adipose (2;13;9), brain (3;13;65), muscle (15;97;297), heart (30;99;371), kidney (22;432;709, lung (54;690;2638), spleen (73;1366;3548), and blood (162;2238;5070). Carboxyhemoglobin concentrations were 1.4%, 25.2%, and 69.1% of total hemoglobin, respectively. We conclude that measurements of CO concentration in a variety of tissues can be used as markers for the degree of exogenous CO exposure and the identification of possible causes of death.

Adipose Tissue↗

Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study.

OBJECTIVE: Coronary atherosclerotic plaque composition of diabetic subjects and localization of receptor for advanced glycation end products (RAGE) and its ligands have not been extensively studied. METHODS AND RESULTS: Hearts from diabetic subjects and age, race, and sex-matched nondiabetic subjects dying suddenly were examined. Coronary arteries were dissected and lesions were evaluated for plaque burden, necrotic core size, and inflammatory infiltrate. The expression of RAGE, the RAGE-binding protein (S100-A12, EN-RAGE), and cell death (apoptosis) were also determined. Lesions from type II diabetic subjects had larger mean necrotic cores (P=0.01) and greater total and distal plaque load (P<0.001) than nondiabetic subjects. Necrotic core size correlated positively with diabetic status, independent of other risk factors. Intimal staining for macrophages, T-cells, and HLA-DR was also significantly greater in diabetic subjects (P=0.03, P=0.003, and P<0.0001), respectively. The association of increased macrophage infiltrate was independent of cholesterol levels and patient age. Expression of RAGE and EN-RAGE was significantly greater in diabetic subjects (P=0.004) and was associated with apoptotic smooth muscle cells and macrophages. CONCLUSIONS: In sudden coronary death, inflammation and necrotic core size play a greater role in the progression of atherosclerosis in diabetic subjects. The expression of RAGE and EN-RAGE may further compromise cell survival and promote plaque destabilization.

Adult↗

Hydroxycarbazepine distribution in three postmortem cases.

This paper presents three cases investigated by the Office of the Chief Medical Examiner where hydroxycarbazepine, the active metabolite of the anticonvulsant prodrug oxcarbazepine, was detected in the biological specimens submitted for toxicological analysis. Hydroxycarbazepine was quantitated using a single-step pH 5 extraction and detection on a DB-5 column by gas chromatography-nitrogen-phosphorus detection. In the three cases, the heart blood concentrations were 34.6, 40.5, and 3.7 mg/L, respectively. In cases 2 and 3, the peripheral blood concentrations were 36 and 4.1 mg/L, respectively. In each case, the medical examiner ruled that the hydroxycarbazepine was an incidental finding to the cause of death.

Anticonvulsants↗

Fatal hemothorax due to rupture of an intrathoracic extramedullary hematopoietic nodule.

Intrathoracic extramedullary hematopoiesis (TEMH) is an unusual but well-described entity, which is typically found in patients who have chronic hemolytic anemias, myelofibrosis, or myeloproliferative disorders. It is seldom symptomatic, rarely fatal. We report a case of a 26-year-old African-American male with a past medical history of sickle cell trait/beta thalassemia who developed multiple intrathoracic nodules of extramedullary hematopoiesis. One of these nodules spontaneously ruptured and produced a fatal hemothorax.

Adult↗

Intraplaque hemorrhage and progression of coronary atheroma.

BACKGROUND: Intraplaque hemorrhage is common in advanced coronary atherosclerotic lesions. The relation between hemorrhage and the vulnerability of plaque to disruption may involve the accumulation of free cholesterol from erythrocyte membranes. METHODS: We stained multiple coronary lesions from 24 randomly selected patients who had died suddenly of coronary causes with an antibody against glycophorin A (a protein specific to erythrocytes that facilitates anion exchange) and Mallory's stain for iron (hemosiderin), markers of previous intraplaque hemorrhage. Coronary lesions were classified as lesions with pathologic intimal thickening, fibrous-cap atheromas with cores in an early or late stage of necrosis, or thin-cap fibrous atheromas (vulnerable plaques). The arterial response to plaque hemorrhage was further defined in a rabbit model of atherosclerosis. RESULTS: Only traces of glycophorin A and iron were found in lesions with pathologic intimal thickening or fibrous-cap atheromas with cores in an early stage of necrosis. In contrast, fibroatheromas with cores in a late stage of necrosis or thin caps had a marked increase in glycophorin A in regions of cholesterol clefts surrounded by iron deposits. Larger amounts of both glycophorin A and iron were associated with larger necrotic cores and greater macrophage infiltration. Rabbit lesions with induced intramural hemorrhage consistently showed cholesterol crystals with erythrocyte fragments, foam cells, and iron deposits. In contrast, control lesions from the same animals had a marked reduction in macrophages and lipid content. CONCLUSIONS: By contributing to the deposition of free cholesterol, macrophage infiltration, and enlargement of the necrotic core, the accumulation of erythrocyte membranes within an atherosclerotic plaque may represent a potent atherogenic stimulus. These factors may increase the risk of plaque destabilization.

Animals↗

Organ weight effects of drowning and asphyxiation on the lungs, liver, brain, heart, kidneys, and spleen.

An examination of the organ weights associated with victims of drowning, asphyxiation and trauma was undertaken to determine (a) the effects of asphyxiation compared to a trauma group, and in turn, (b) the effects of drowning compared to an asphyxiation group. Included in the study were 217 drowning deaths, 166 pure asphyxiation deaths and 381 trauma deaths. The effects of asphyxiation (compared to trauma) resulted in elevated mean organ weights for the lungs, liver, kidneys and spleen (with mean increases of 17.8, 10.5, 10.3 and 23.4%, respectively). Effects of drowning (compared to asphyxiation) resulted in elevated mean organ weights only with the lungs and kidneys (with mean increases of 30.0 and 4.4%, respectively). Only the mean heart and brain weight remained constant across all experimental groups. A picture of drowning is suggested in which elevated lung and kidney weights are the result of both asphyxiation and the aspiration of water that occurs with drowning, whereas elevated spleen and liver weights in drowning victims are associated with only the effects of asphyxiation. In addition, the common autopsy finding of a small, anemic spleen in drowning, rather than caused by some pathophysiological mechanism of death, is hypothesized to be a postmortem phenomenon.

Adolescent↗

Mixed drug intoxication involving zaleplon ("Sonata").

Zaleplon ("Sonata") is a pyrazolopyrimidine derivative approved for use in the United States for the treatment of insomnia. To date, there has been little data in the toxicological literature where zaleplon has been implicated as causing a fatal intoxication, either alone or in combination with other drugs. This report documents a case where zaleplon was identified in a suicide by multiple drug ingestion. The following zaleplon concentrations were found: heart blood 2.2mg/l; bile 8.6mg/l and urine 1.4mg/l. Zaleplon was also detected but not quantitated in the kidney and liver.

Acetamides↗

Organ weight effects of drowning and asphyxiation on the lungs, liver, brain, heart, kidneys, and spleen.

An examination of the organ weights associated with victims of drowning, asphyxiation and trauma was undertaken to determine (a) the effects of asphyxiation compared to a trauma group, and in turn, (b) the effects of drowning compared to an asphyxiation group. Included in the study were 217 drowning deaths, 166 pure asphyxiation deaths and 381 trauma deaths. The effects of asphyxiation (compared to trauma) resulted in elevated mean organ weights for the lungs, liver, kidneys and spleen (with mean increases of 17.8, 10.5, 10.3 and 23.4%, respectively). Effects of drowning (compared to asphyxiation) resulted in elevated mean organ weights only with the lungs and kidneys (with mean increases of 30.0 and 4.4%, respectively). Only the mean heart and brain weight remained constant across all experimental groups. A picture of drowning is suggested in which elevated lung and kidney weights are the result of both asphyxiation and the aspiration of water that occurs with drowning, whereas elevated spleen and liver weights in drowning victims are associated with only the effects of asphyxiation. In addition, the common autopsy finding of a small, anemic spleen in drowning, rather than caused by some pathophysiological mechanism of death, is hypothesized to be a postmortem phenomenon.

Adolescent↗

Tissue distribution of xylazine in a suicide by hanging.

Xylazine (Rompun, Sedazine, AnaSed) is currently the most commonly used sedative-analgesic in veterinary medicine. There are nine published cases of xylazine's involvement in human drug-related deaths and impairment. However, blood concentrations were reported in only four of these cases. Three of these nine cases were fatalities involving xylazine, two of which involved xylazine alone but did not report blood concentrations because of extensive decomposition of the bodies. This report documents a case in which xylazine alone was identified in a suicide by hanging. The following xylazine concentrations were found: 2.3 mg/L in heart blood; 2.9 mg/L in peripheral (subclavian) blood; 6.3 mg/L in bile; 0.01 mg/L in urine; 6.1 mg/kg in liver; and 7.8 mg/kg in kidney.

Adult↗

Failure to detect elevated levels of carboxyhemoglobin in infants dying from SIDS.

Carboxyhemoglobin (COHb) levels were determined in stored blood samples from 91 infants diagnosed to have died from the sudden infant death syndrome (SIDS) (0.59+/-0.41%, excluding one outlying value of 10.83%); 48 age-matched controls (0.53+/-0.38%); and three individuals who died from fire related causes (41+/-20%). No statistical differences in COHb levels were detected between blood from SIDS and control infants (p = 0.43).

Carboxyhemoglobin↗

Analysis of metformin in antemortem serum and postmortem specimens by a novel HPLC method and application to an intoxication case.

A case of intoxication from the oral hypoglycemic drug metformin is presented. A number of published liquid chromatographic methods were combined to enable a simplified analysis of metformin in both antemortem and postmortem specimens. The method involved direct injection of a protein-free filtrate into the liquid chromatograph. The method was sufficiently sensitive to detect therapeutic use of metformin; no common therapeutic or abused drugs interfered with the assay. In the presented case, the hospital admission serum metformin concentration was 141 mg/L, or approximately two orders of magnitude above therapeutic concentrations. The medical examiner concluded that the cause of death in this case was metformin intoxication, and the manner of death was suicide.

Administration, Oral↗