Beliefs and policies of Maryland nursing home medical directors regarding tetanus immunization.

Tetanus is more common in the elderly, who have a higher case-fatality rate than younger age groups. Immunization against tetanus is recommended for all elderly, including nursing home residents, but the tetanus immunization policies of nursing homes are unknown. Nursing home medical directors in Maryland were surveyed about their beliefs concerning tetanus and the tetanus immunization policies of their nursing homes. One hundred twenty-five directors of 212 responded (59%). In most of the nursing homes, no policies existed for routine tetanus immunization. Medical directors graduating from medical school after 1960 and medical directors with more than 50 nursing home patients were more likely to believe that tetanus immunization is cost-effective in nursing home patients. Only 3% of the respondents always immunize their nursing home patients with chronic skin ulcers. We believe tetanus immunization is an uncommon practice in Maryland nursing homes. Nursing home medical directors should establish policies to promote tetanus immunization.

Saline catharsis: effect on aspirin bioavailability in combination with activated charcoal.

The effect of a saline cathartic combined with activated charcoal or activated charcoal alone on aspirin bioavailability was characterized in six healthy volunteers. Using a random, Latin-square design, subjects were given 975 mg aspirin followed by either water alone, 15 Gm activated charcoal (AC), or 15 Gm activated charcoal plus 20 Gm sodium sulfate (AC + SS) separated by one week. Both AC (44.16 +/- 16.85 microgram/ml) and AC + SS (58.61 +/- 10.63 microgram/ml) decreased (P less than 0.001) the maximal plasma salicylate concentration (Cpmax) compared to control (86.61 +/- 12.69 microgram/ml). Urinary salicylate recovery was decreased (P less than 0.01) for AC (57.88 +/- 16.26 per cent) and AC + SS (61.00 +/- 11.49 per cent) as compared to control (93.73 +/- 6.83 per cent), while for area under the plasma concentration-time curve (AUC) only AC showed a decrease (P less than 0.01) compared to control. Neither AC nor AC + SS differed from each other for Cpmax, AUC, or cumulative urinary recovery. Our findings indicate that the addition of sodium sulfate to activated charcoal has no added effect on limiting aspirin adsorption relative to activated charcoal alone.

Meperidine and normeperidine distribution in the rhesus monkey.

Previous work has shown that both meperidine and normeperidine are transferred across the placenta to the fetus. Little is known in primates, however, about the tissue deposition of these compounds. Four pregnant, dated rhesus monkeys within one week of term were anesthetized for cesarean delivery. An equal mixture of meperidine and normeperidine was administered as an intravenous bolus 10 minutes before delivery (1.25 mg/kg). The infants were then sacrificed at 20 minutes after birth and the concentration of the compounds in various organ systems were analyzed by gas-liquid chromatography and mass spectroscopy (GLC-MS). The infant serum 20 minutes after delivery revealed a meperidine concentration of 2.23 micrograms/ml and a normeperidine level of 0.67 micrograms/ml (3:1). In contrast, the tissues analyzed showed a much higher concentration of the metabolite in the liver (1:7), gallbladder (1:3), and brain (1:2). Other tissues, such as muscle and kidney, demonstrated equal levels of the two compounds. The authors conclude that normeperidine is quickly transferred to fetal tissues and to a greater degree than the parent compound in certain organs. The increased distribution, particularly in the brain, could account for the toxic actions in the cerebrum of the derivatives of meperidine.

Direct analysis of anticonvulsant drugs in vitreous humour by HPLC using a column switching technique.

A method is described for the rapid HPLC analysis of a number of anticonvulsant drugs in vitreous humour by injection directly onto a preconcentration column without the need for prior extraction. The conditions for optimum precision and accuracy were investigated and the method was subsequently applied to the analysis of phenytoin in a number of overdose cases. Sensitivity was 0.05 microgram/ml on a 0.5 ml vitreous sample. The mean blood/vitreous ratio for phenytoin was found to be 2.8 (range: 1.4-5.1). The relationship between blood and vitreous levels had a correlation coefficient of 0.85. Vitreous was found to be a very clean, stable sample, ideally suited to this technique.

Effective column extraction from decomposed tissue in a suspected overdose case involving maprotiline and amitriptyline.

This paper describes the use of a Celite 560 column extraction technique in the initial separation of drugs from the contents of the skull of a severely decomposed body. Analysis of the extract obtained resulted in the determination of the presence of amitriptyline, and maprotiline and two of its metabolites. As a consequence, the laboratory was able to provide the medical examiner with information concerning an extremely difficult case.

Rapid screening for 100 basic drugs and metabolites in urine using cation exchange solid-phase extraction and high-performance liquid chromatography with diode array detection.

A system involving the combination of cation exchange solid-phase extraction and gradient elution HPLC with diode array detection was developed for the isolation and identification of basic drugs in urine. At least 100 basic drugs commonly encountered in urinary drug screening and many popular illicit drugs could be identified. Detailed study of 30 of these compounds showed that in addition to the procedure's simplicity and convenience, recoveries were close to 100% in most cases. The method was compared with an existing liquid-liquid extraction/capillary gas chromatography procedure and was at least as effective for extracting and identifying basic drugs, and especially effective at extracting problematic compounds including morphine, benzoylecgonine, temazepam, and oxazepam. Additional advantages of solid-phase extraction technology include the elimination of time-consuming shaking and centrifugation steps, elimination of reusable glassware, and reduced sample-operator contact with potentially infectious samples.

Pharmacokinetics of meperidine in pregnancy.

The disposition of meperidine was studied in 11 term pregnant humans after the administration of a single 50 mg intravenous dose of meperidine through 48 h post-injection. Half-lives of the rapid and terminal elimination phases were calculated as 2.3 and 13.3 h, respectively. These values are much greater than previously reported half-lives which were based on data collected over less than 8 h after injection. An accurate value for t1/2 beta may be particularly important in sequential dosing of analgesic medication. These pharmacokinetic constants calculated on data collected through 48 h in this study may have important clinical correlates.

High-performance liquid chromatography with column switching for the determination of cocaine and benzoylecgonine concentrations in vitreous humor.

A sample concentration technique was adapted for the determination of cocaine and benzoylecgonine (BE) concentrations in vitreous humor. Vitreous humor (0.5 mL) was diluted 1:1 with water and applied through a filter onto a 3-cm preconcentration column. Following a simple wash step, the analytes were flushed directly onto a reversed-phase analytical high-performance liquid chromatography (HPLC) system. Absolute recoveries were high (above 90%) and the chromatograms were free from interference. Analysis for the drug and its breakdown product was performed using ultraviolet (UV) visible photodiode array detection, which allowed confirmation of peak identity. Recognizable UV spectra could be measured with as little as 20 ng on column. Comparison of the drug levels in 27 blood and vitreous humor samples showed that, while there was only a low correlation between the blood and vitreous concentrations (R = 0.70), vitreous cocaine and BE determinations were good indicators of antemortem cocaine use. In almost all cases, the vitreous BE concentrations were higher than the cocaine concentrations. The technique was easy to perform and the vitreous samples were especially compatible with this low-labor analytical procedure.

Liquid/solid extraction on diatomaceous earth for drug analysis in postmortem blood.

Absorption extraction on diatomaceous earth was examined and found to be compatible with typical postmortem blood specimens encountered in forensic toxicology. The effects of solvent, solvent volume, eluate flow rate, and pH on drug recovery and extract quality were investigated. It was concluded that the best method was not necessarily that with the highest recoveries, but that considerations of extract quality were also required. The optimized method was compared with a single-step liquid/liquid extraction method and found to be superior in terms of ease of operation, extract quality, and absolute recovery. The results indicated also that although useful for screening, quantitative methods using liquid/solid extraction may be prone to error.

Disopyramide (Norpace) distribution at autopsy of an overdose case.

A 44-year-old female died as the result of an overdose of disopyramide. An analytical method was developed and the distribution of the drug in various tissues was determined. Analysis of the blood sample indicated a drug concentration far exceeding that of the therapeutic concentration.

Theophylline and dyphylline levels in serum by liquid chromatography.

The widespread use of theophylline and dyphylline as bronchodilators in the treatment of acute and chronic obstructive airway disease, and recognition of the need to control the therapeutic drug level has created a demand for fast accurate measurement techniques. Measurement of theophylline levels by ultraviolet spectrophotometric techniques is hindered by interferences from barbiturates and caffeine, and thermal lability of the drug necessitates derivatization if gas chromatography is to be used. Because of these factors, a liquid chromatographic method has been developed which allows separation of the underviatized drug from interfering compounds, and quantitation of the theophylline in a single operation. In addition, the drug-containing fraction can be readily collected and subjected to mass spectral examination if there is any question as to its identify. The latter feature has particular significance in medico-legal cases.

Improving the use of advance directives.

Advance directives are a valuable form of medical planning and well-accepted by patients. They are part of preventive health care and should be included as routine care. Completion of these documents is a process requiring patient/physician communication and can be effectively completed over several visits. Periodic reassessment of patient attitudes is important. Finally, including these documents in the patient record and communication of this information is important, as it helps shepherd the patient through the medical system. Physician investment in the use of advance directives is minimal, while the rewards are prodigious.

Information resources useful in forensic toxicology.

This paper addresses information resources available to forensic toxicologists. The approach taken here is to discuss those resources found useful in problem solving situations. First, attempt to obtain information from someone familiar with the problem. This is generally the most efficient mechanism to use. The next most efficient mechanism is to search the published literature, electronically using bibliographic databases, if possible. The least efficient method of obtaining information is to go into the laboratory and generate the desired information. In many situations, however, the problem must be solved, or the information confirmed, in the laboratory. Suggested sources of information have been listed in the appendices. These are not intended to be exhaustive, but rather to stimulate and direct the access to information resources.

High-pressure liquid chromatography and enzyme immunoassay compared with gas chromatography for determing phenytoin.

We compared a gas-chromatographic method for determination of phenytoin with a high-pressure liquid chromatographic technique and with enzyme immunoassay by three instrumental procedures. More than 100 sera from patients being treated with this drug were assayed by all these techniques. The coefficient of variation was the lowest (4.0%) with liquid chromatography, but all methods gave a CV of less than 10%. The correlation coefficients for all methods exceeded 0.97 when compared to gas chromatography. Operation costs varied with the number of tests per batch, reagent costs, and operator labor costs. All assays gave comparable values for the therapeutic range, so it would be plausible to use more than one method in a situation where (e.g.) satellite laboratories handle different quantities of assays. In any of these techniques, interferences from carbamazepine, mephenytoin, phenobarbital, and primidone were negligible.