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Biomedical subjects

C V Wetli

Publications and source records attributed to C V Wetli.

At least 19 recordsLinked to original sources

High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims.

Cocaine mediates its powerful reinforcement by binding to recognition sites on the dopamine (DA) transporter. The pharmacological identity of cocaine recognition sites and their relevance to dopamine transport function has remained unclear. Ligand binding studies with transport inhibitors and cocaine congeners have provided evidence for multiple sites or "states" of the DA transporter. The potent cocaine congener [3H]WIN 35,428 ((CFT), 2B-carbomethoxy-3 beta-(4-fluorophenyl)-tropane) has been shown to recognize high and low affinity binding sites on the DA transporter. We have used [3H]WIN 35,428 to map and quantify the high affinity cocaine recognition site on the DA transporter in victims of fatal cocaine overdose. Region-of-interest densitometric analysis of the autoradiograms demonstrated a 2- to 3-fold elevation in the apparent density of [3H]WIN 35,428 binding in particular sectors of the striatum from victims of cocaine overdose as compared to age-matched and drug-free control subjects. The most marked increase in [3H]WIN 35,428 binding was seen in the nucleus accumbens. The apparent increase in the density of high affinity sites was confirmed by saturation binding analysis of [3H]WIN 35,428 to putamen membranes. Saturation analysis revealed high and low affinity binding components with affinities (KD values) of 4.3 +/- 1.2 and 84.7 +/- 19.7 nM (mean +/- S.E.) and densities of 9.9 +/- 4.0 and 193.0 +/- 28.6 pmol/g of tissue, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Positional asphyxiation in adults. A series of 30 cases from the Dade and Broward County Florida Medical Examiner Offices from 1982 to 1990.

Over a 9-year period, 30 cases of positional (or postural) asphyxia were identified in the Dade and Broward County (Florida) Medical Examiner Offices. The victims had an average age of 50.6 years with no significant sex or racial differences as compared with the general medical examiner population. Chronic alcoholism or acute alcohol intoxication was a significant risk factor in 75% of cases and these had an average postmortem ethanol concentration of 0.24 g%. Signs of mechanical asphyxiation (petechiae and/or combined lung weights greater than 900 g) were present in 93% of cases. Victims were commonly (43%) found in a restrictive position producing hyperflexion of the head and neck. Two deaths involved restraint vests ("poseys") in elderly, demented, wheel-chair-confined victims. Scene photographs of the undisturbed decedent are extremely helpful in confirming a suspicion of postional asphyxia.

Adolescent

Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter.

Concurrent cocaine and alcohol use is common practice in the general population, as indicated by recent prevalence studies. In the presence of ethyl alcohol, cocaine is metabolized to its ethyl homolog, cocaethylene. The transesterification of cocaine and ethanol to cocaethylene takes place in the liver and represents a novel metabolic reaction. Cocaethylene was detected in postmortem blood, liver, and neurological tissues in concentrations equal to and sometimes exceeding those of cocaine. In vitro binding studies demonstrate that cocaethylene has a pharmacological profile similar but not identical to that of cocaine at monoamine transport sites assayed in the human brain. Cocaethylene was equipotent to cocaine at inhibiting [3H]mazindol binding to the dopamine transporter. The blockade of dopamine reuptake in the synaptic cleft by cocaethylene may account for the enhanced euphoria associated with combined alcohol and cocaine abuse.

Adult

Emerging patterns of cocaine use and the epidemic of cocaine overdose deaths in Dade County, Florida.

With the increasing use of cocaine in the United States, cocaine overdose deaths are being reported with increasing frequency. To describe patterns of cocaine use involved in cocaine overdose deaths, we reviewed the postmortem records from the Metropolitan Dade County Medical Examiner Department, Miami, Fla. We identified 239 cocaine overdose deaths from 1971 through 1987. During this period, the incidence of cocaine overdose deaths increased 20-fold, with the largest proportional increases occurring among persons aged older than 24 years, white persons, and men. The percentage of deaths that involved use of cocaine by nonparenteral routes, as well as newer and unknown preparations of cocaine (such as "crack" and "free-base" cocaine), increased. For example, the percentage of deaths that involved use of crack or free-base cocaine increased from 8% in 1981 to 20% in 1987. Persons who died after smoking crack or free-base cocaine had lower blood cocaine levels at autopsy (median level, 0.3 mg/L) than persons who died as a result of using cocaine hydrochloride (median level, 3.7 mg/L). Patterns of cocaine use involved in the epidemic of cocaine overdose deaths are changing. The data suggest that the newer preparations of cocaine, such as crack or free-base cocaine are playing an increasingly important role in this epidemic and that these preparations may be more toxic than cocaine hydrochloride.

Age Factors

Accidental death from a black-powder rifle breech plug.

Authentic black-powder muzzle-loader weapons and replicas are used today primarily for hunting game such as deer and hogs. The following is a case presentation of accidental death from cerebral trauma caused by a .45-caliber black-powder-rifle breech plug implanting in the victim's brain.

Accidents

Tattoos of the Marielitos.

Tattoos on Cuban refugees, particularly those who entered the United States during the Mariel Boatlift of 1980, have been associated with both criminal activity and religious affiliations. In an effort to understand better the significance and meanings of these tattoos, a series of interviews (initially informal, followed by a formal survey instrument) were conducted. Examples of the various tattoos were gleaned from the files of the Dade County Medical Examiner Department. In general, tattoos on Cuban refugees signify prior incarceration in Cuban prisons, usually do not reflect criminal specialization, and often reflect affiliation to Afro-Caribbean cults (especially Santeria, Palo Mayombe, and the Abakua Secret Society). In addition, many tattoos reflect the values and attitudes of Cuban jail subculture.

Cuba

Aortoesophageal fistula and sudden death. A report of two cases and review of the literature.

Two cases of aortoesophageal fistula are presented. The etiology, symptoms, and diagnosis of aortoesophageal fistula are reviewed. Signs and symptoms of gastrointestinal hemorrhage followed by sudden collapse hours to days later should prompt consideration of an aortoesophageal fistula. Accidental ingestion of foreign bodies, particularly by children, is a frequent etiology.

Adult

The forensic significance of conjunctival petechiae.

Conjunctival petechiae were mentioned in 227 (4.5%) of 5,000 consecutive autopsy reports of the Dade County Medical Examiner Department. They were most frequently observed in those who had died natural deaths (particularly due to cardiovascular disease), followed by those who had died from asphyxia, head injury, and central nervous system disorders. The incidence of conjunctival petechiae in victims of homicidal asphyxiation was 78%. These data suggest that conjunctival petechiae most often are the result of hypoxia coupled with an acute increase in cephalic vascular pressure. The latter factor may be the consequence of mechanical vascular obstruction or acute right heart failure.

Airway Obstruction

Cocaine and sudden "natural" death.

The cardiovascular effects of cocaine may culminate in clinical episodes of angina pectoris, myocardial infarction, arrhythmias, and intracranial hemorrhage. To clarify whether or not cocaine causes fatalities by these mechanisms, we studied 24 cases of sudden, apparently natural deaths as a result of coronary arteriosclerosis (15 cases), hypertensive cardiovascular disease (4 cases), and intracranial hemorrhage (5 cases) associated with cocaine use. In 11 cases, cocaine was found in the blood (average concentration: 0.57 mg/L, range: 0.05 to 1.45 mg/L), whereas in the remainder, cocaine or its major metabolite was found in the urine or other tissues. In the majority of decedents, autopsy disclosed the existence of severe natural disease which could have been exacerbated by the administration of stimulant drugs, including cocaine. These data, and a review of the current medical literature, indicate that cocaine may precipitate the sudden death of an individual with undiagnosed cardiovascular disease. A contributory role of cocaine should be considered in any apparently natural death occurring in a population where cocaine abuse is prevalent.

Adult

Radiographic evaluation of the cocaine smuggler.

A retrospective analysis of the plain abdominal films of 53 "body packer" drug smugglers was performed to ascertain the importance of radiographic studies in the diagnosis and management of these patients. Eighty-nine percent had studies diagnostic for foreign body ingestion. Multiple, well-defined, homogeneous oval or oblong densities, especially if surrounded by a crescent of air (double-condom sign), are key findings. If these densities were found in the proximal ascending colon or upper gastrointestinal tract, the diagnosis was almost assured. Six percent of patients exhibited complications suggested on serial radiographs, proving the necessity for follow-up studies until complete expulsion or removal of the foreign body. Radiologic evaluation is essential in the diagnosis and management of the cocaine smuggler.

Adult

Intravenous amphetamine abuse, primary cerebral mucormycosis, and acquired immunodeficiency.

Two intravenous amphetamine abusers had fatal, rapidly progressive cerebral mucormycosis with abscess formation in the presence of absolute lymphopenia. Postmortem examination confirmed the primary nature of the fungal cerebritis, documented by postmortem culture and histology. The clinical and pathologic features of these cases are compared to previously reported occurrences of primary fungal cerebritis (and abscess) among intravenous drug abusers, including cocaine users. Primary fungal cerebritis associated with intravenous abuse of stimulant drugs is discussed as a possible variant of the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome

Cocaine-induced psychosis and sudden death in recreational cocaine users.

Fatal cocaine intoxication presenting as an excited delirium is described in seven recreational cocaine users. Symptoms began with the acute onset of an intense paranoia, followed by bizarre and violent behavior necessitating forcible restraint. The symptoms were frequently accompanied by unexpected strength and hyperthermia. Fatal respiratory collapse occurred suddenly and without warning, generally within a few minutes to an hour after the victim was restrained. Five of the seven died while in police custody. Blood concentration of cocaine averaged 0.6 mg/L, about ten times lower than that seen in fatal cocaine overdoses. Police, rescue personnel, and emergency room physicians should be aware that excited delirium may be the result of a potentially fatal cocaine intoxication; its appearance should prompt immediate transport of the victim to a medical facility. Continuous monitoring, administration of appropriate cocaine antagonists, and respiratory support will hopefully avert a fatal outcome.

Adult