Fentanyl-Norfentanyl Concentrations During Transdermal Patch Application: LC-MS-MS Urine Analysis.

Poklis and Backer published a survey of the concentrations of fentanyl and norfentanyl that could be expected in urine from patients using Duragesic®, a transdermal fentanyl patch. That study employed a relatively small number of patient data points and analysis by Gas Chromatography/Mass Spectrometry. This work examines a larger population of patient positives for fentanyl and norfentanyl to determine whether more than a decade later the original report remains accurate in predicting the range and median levels of fentanyl and norfentanyl concentrations physicians can expect to see from their patients. Additionally, these data were transformed to develop a model that results in a near Gaussian distribution of urine drug test results. This retrospective approach was developed to transform and normalize urine drug testing results to provide a historical picture of expected patient values for this important analgesic. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from urine drug testing.

Validation of a standardised gait score to predict the healing of tibial fractures.

There is no absolute method of evaluating healing of a fracture of the tibial shaft. In this study we sought to validate a new clinical method based on the systematic observation of gait, first by assessing the degree of agreement between three independent observers regarding the gait score for a given patient, and secondly by determining how such a score might predict healing of a fracture. We used a method of evaluating gait to assess 33 patients (29 men and four women, with a mean age of 29 years (15 to 62)) who had sustained an isolated fracture of the tibial shaft and had been treated with a locked intramedullary nail. There were 15 closed and 18 open fractures (three Gustilo and Anderson grade I, seven grade II, seven grade IIIA and one grade IIIB). Assessment was carried out three and six months post-operatively using videos taken with a digital camera. Gait was graded on a scale ranging from 1 (extreme difficulty) to 4 (normal gait). Bivariate analysis included analysis of variance to determine whether the gait score statistically correlated with previously validated and standardised scores of clinical status and radiological evidence of union. An association was found between the pattern of gait and all the other variables. Improvement in gait was associated with the absence of pain on weight-bearing, reduced tenderness over the fracture, a higher Radiographic Union Scale in Tibial Fractures score, and improved functional status, measured using the Brazilian version of the Short Musculoskeletal Function Assessment questionnaire (all p < 0.001). Although further study is needed, the analysis of gait in this way may prove to be a useful clinical tool.

Depression does not influence basal ganglia-mediated psychomotor speed in HIV-1 infection.

The authors examined the effects of depressive mood (Hamilton Rating Scale for Depression [Ham-D]) on basal ganglia-mediated psychomotor speed (motor test battery) in 202 HIV-1 seropositive homosexual males with no prior history of antiretroviral treatment. HIV-1 seropositive patients showed a significant slowing of most rapid alternating movements (MRAM) and significantly prolonged contraction times (CT) compared with 66 HIV-1 seronegative male control subjects. Factor analysis of Ham-D scores isolated a factor containing the items depressed mood, suicide, and psychic and somatic anxiety. This factor did not correlate with MRAM or CT. Depression and psychomotor speed are independent in HIV-1infection.

Treatment of malignant neoplasms of the lateral cranial base with the combined frontotemporal-anterolateral approach: five-year follow-up.

Technical advances in accessing the lateral cranial base have permitted disease in this area previously deemed inoperable to be resected. The procedures required to effect an oncologically adequate resection are often long and accompanied by the potential for serious, even life-threatening, complications. Although it has been demonstrated that such disease can be extirpated, the question of whether such heroic surgery improves long-term survival remains unanswered. We retrospectively reviewed the records of 25 patients who underwent a combination of frontotemporal craniotomy with other, more conventional, anterolateral procedures (eg, infratemporal fossa approach, maxillectomy, orbitectomy, mandibulopharyngectomy) to resect stage IV malignant disease of the lateral to midcranial base between 1983 and 1990. Perioperative deaths occurred in 2 patients, 1 patient died of unrelated causes free of disease, and 2 patients were lost to follow-up, leaving 20 patients with a minimum 5-year evaluation. Five (25%) of the 20 patients we monitored were free of disease. Of those patients in whom recurrent disease developed, local control was achieved in about 50%; however in 80% of those with recurrence, metastatic disease developed. Surgical treatment of selected stage IV malignant disease of the lateral to midcranial base appears to have provided long-term disease-free survival to 25% of patients in this series who would otherwise have had little hope of survival.

Disposition of valproic acid in a case of fatal intoxication.

The case history and toxicological findings of a fatal suicidal valproic acid overdose are presented. Valproic acid concentrations were determined in body tissues and fluids by gas-liquid chromatography (GLC) following both direct extraction and the method of standards addition and quantitative fluorescence polarization immunoassay. The quantitative results obtained by the three procedures were in good agreement. Qualitative identification of valproic acid as its methylated derivative was by ion-trap gas chromatography-mass spectrometry. Toxicological analysis by direct extraction GLC yielded the following valproate concentrations (mg/mL or mg/kg): blood, 1050; bile, 713; brain, 510; heart, 670; kidney, 1580; liver, 985; and vitreous, 516. A total of 15.1 g of valproate was recovered in the stomach contents. These findings far exceed those associated with valproate therapy and are similar to the limited valproate disposition data reported in prior fatal overdoses.

Fatal fentanyl intoxication following excessive transdermal application.

The case history and toxicological findings of a fatal fentanyl intoxication due to the application of multiple transdermal patches are presented. An 83 year-old white female with terminal cancer was found dead with three 100 mg/h fentanyl patches on her chest. The autopsy and subsequent histological studies revealed extensive areas of gastric carcinoma, a large atrial tumor, ulceration of esophagus, metastasis of peripancreatic lymph nodes and a recent surgical removal of part of the lower lobe of the left lung. Toxicological analysis by GC/MS yielded fentanyl concentrations of blood, 25 ng/mL; brain, 54 ng/g; heart 94 ng/g; kidney 69 ng/g; and liver 104 ng/g. The cause of death was determined to be fentanyl overdose and the manner of death was ruled undetermined as the investigation was unable to conclusively establish whether this was an accidental overdose, a suicide, an assisted suicide, or possible a homicide. This case demonstrates the need for caution in self-administration of transdermal fentanyl patches, in particular, the dangers inherent in the application of multiple patches which can result in the release of potentially toxic or lethal doses.

Fatal ephedrine intoxication.

A 28-year-old white female with a history of two prior suicide attempts was found dead in her home by her common law husband. Autopsy findings were unremarkable except for partially dissolved ephedrine tablets in the stomach contents. Quantitation of ephedrine was by gas chromatography/mass spectrometry (GC/MS) following liquid/liquid extraction from alkaline samples and pentafluoropropionic acid derivatization. Significant toxicological finding included ephedrine; blood, 11 mg/L; liver, 24 mg/kg; kidney, 14 mg/kg; brain, 8.9 mg/kg; and amitriptyline; blood, 0.33 mg/kg; liver 7.8 mg/kg. The ephedrine values found far exceed those associated with therapeutic administration and are consistent with the few reported cases of severe ephedrine intoxication. The cause of death was determined to be fatal ephedrine intoxication and manner of death suicide.

Surgical management of transcranial hypoglossal schwannomas.

Hypoglossal schwannomas are rare cranial base neoplasms that originate in the posterior cranial fossa and extend through the hypoglossal canal in a dumbell fashion. Recent experience with this unusual neoplasm prompted a search for an operative approach to remove the lesion with a minimization of postoperative morbidity from bleeding and iatrogenic cranial nerve deficits. This report describes the use of the transcondylar approach with monitoring of the lower basal cranial nerves to totally remove a transcranial hypoglossal schwannoma with no new-onset cranial nerve palsies. The regional anatomy of the hypoglossal nerve and canal is reviewed in relation to the operative approach.

MRI of intradural spinal arteriovenous fistula associated with ischemia and infarction of the cord.

This report presents a patient with an intradural spinal arteriovenous fistula complicated by infarction of the cord. The diagnosis of an arteriovenous malformation was made on the magnetic resonance imaging (MRI) study with the demonstration of intraspinal serpentine areas of low signal intensity (flow voids). The presence of other MRI findings believed to represent spinal cord ischemia included multisegmental swelling of the cord associated with T1 and T2 prolongation and gadolinium enhancement. The location of the malformation, as well as arterial supply and venous drainage, were defined on selective spinal arterial digital subtraction angiography (DSA). Following surgical resection, the clinical condition stabilized, but with poor return of lost function. The repeat MRI 6 months after surgery demonstrated diffuse thoracic cord atrophy.

Neurologic recovery associated with anterior decompression of spine fractures at the thoracolumbar junction (T12-L1).

Between 1981 and 1990, twenty-two patients with incomplete neurologic deficits after thoracolumbar junction fractures were treated by anterior decompression and stabilization. Two patients were unavailable for follow-up examination, eleven underwent spinal canal decompression within 48 hours of injury (Group A); and nine patients underwent surgical decompression in an average of 61 days after injury (Group B). Neurologic recovery was analyzed by a modified Frankel grading system, the ASIA motor point scale and conus medullaris function. Patients were followed for an average of 3.5 years (range, 6-92 months). No patients had any deterioration in neurologic function after surgery. Patients in Group A had a modified Frankel grade improvement with a median of two grades and a mean American Spine Injury Association motor point improvement of 21.1 +/- 4.1. Four of nine patients with conus medullaris deficits demonstrated complete functional bladder and bowel return postoperatively. Those patients in Group B had a modified Frankel grade improvement with a median of one grade and a mean ASIA motor point improvement of 7.6 +/- 1.7. None of the six patients with conus medullaris injuries showed complete improvement in bladder or bowel function postoperatively. The modified Frankel grade and ASIA motor point score improvements were significant when the two groups were compared (P less than 0.04 and P less than 0.01, respectively). In this series of patients, early anterior decompression for traumatic injuries at the thoracolumbar junction was associated with improved rates of neurologic recovery when compared to late decompression.

Drug screening with EMIT reagents: a quantitative approach to quality control.

We investigated the precision, linearity, accuracy, and stability of quantitative results for five drugs of abuse [amphetamines, benzoylecgonine, opiates, phencyclidine, and the cannabinoid-tetrahydrocannabinol (THC)-9-acid metabolite], analyzed in control specimens by using EMIT d.a.u. reagents (Syva Co.) with a Monarch 2000 analyzer with a nonlinear interpolation curve-fitting algorithm. The within-day and between-days coefficients of variation (CVs) were less than 5% for all drugs except THC-9-acid, which had a CV between 10% and 20%. The drift of control values during a 30-day stability study was less than 10% from target values for three weeks after a single calibration, except for THC-9-acid control values, which were stable for only two to three days. Daily calibration reduced the drift away from target values during the 30-day stability study and produced optimum precision of all drug assays. Mean control values near the National Institute on Drug Abuse cutoff limits were within 10% of their target values.

Transcranial Doppler ultrasound following closed head injury: vasospasm or vasoparalysis?

Nine patients suffering closed head injury were studied using transcranial Doppler ultrasound recording of the basal cerebral arteries. On admission, six patients had Glasgow Coma Scores of 7 or less, while three had initial scores of 8-10. Eight of the nine patients (82%) developed abnormally high mean velocities (greater than or equal to 110 cm/s) in one or more vessels. The onset, duration, and amplitude of the altered flow velocities were somewhat different from those that are seen with vasospasm after aneurysmal subarachnoid hemorrhage, which tend to occur later. Cerebral angiography in one of the study patients confirmed the presence of vasospasm. Multivariate regression analysis showed a definite correlation between the velocities recorded, even when abnormally elevated, and concurrent pH and PCO2 measurements (p = 0.01, R2 = 0.23). Although these results suggest that the cerebral vasculature retains its vasoreactivity following head injury, arguing against vasoparalysis, inconsistencies found in some of the patients lead us to think that both vasospasm and vasoparalysis may occur following head trauma but that they may have different temporal profiles.

Carisoprodol concentrations from different anatomical sites: three overdose cases.

Three cases involving overdoses of carisoprodol are presented. Concentrations of carisoprodol and its major metabolite meprobamate, were determined in urine, vitreous humor, heart, and femoral blood. All drugs were quantified by gas chromatography/mass spectrometry (GC/MS).

Fatal unintended carbon monoxide poisoning in West Virginia from nonvehicular sources.

Based on medical examiner reports and state vital records, 1978-84, nonvehicular carbon monoxide (CO) caused 62 unintended deaths, representing 42 percent of all unintended fatal CO poisonings in West Virginia. Sources were almost always heating or cooking appliances associated with incomplete combustion of fuels (methane, butane, or propane) not commonly recognized for their potential to produce CO. Hazards included failure to provide recommended venting, neglected maintenance, or use in small areas without natural ventilation.

Fatality resulting from cyclizine overdose.

A case involving an overdose fatality of cyclizine is presented. Toxicological analysis revealed a cyclizine blood concentration of 80 micrograms/mL. The drug was quantified by gas chromatography/mass spectrometry (GC/MS). Qualitative analyses of urine and stomach contents were performed.

Unintentional deaths from carbon monoxide in motor vehicle exhaust: West Virginia.

We investigated the circumstances of unintended carbon monoxide deaths from motor vehicle exhaust. Of 64 episodes involving 82 deaths investigated by the West Virginia Office of the Chief Medical Examiner, 1978-84, 50 occurred outdoors in older vehicles with defective exhaust systems and 14 occurred in enclosed or semi-enclosed home garages. Blood alcohol was detected in 50 (68 per cent) of 74 victims tested; 34 had blood alcohol concentrations greater than or equal to 0.10 g/dl. We suggest increasing public awareness of the hazards of motor vehicle exhaust and enforcing vehicle inspection regulations.

The imaging of an intraspinal cervical dermoid tumor by MR, CT, and sonography.

Epidermoid and dermoid tumors are uncommon lesions and within the spinal cord are rare. Magnetic resonance imaging has proved sensitive to their detection in the intracranial cavity but the pattern of signal intensities on T1 and T2 weighted images has not been uniform. Utilizing a 0.6 T superconductive magnet an intramedullary cervical dermoid tumor was examined. The correlation between CT demonstrated regions of fat density and the MRI appearance of comparable regions of high intensity signal on T1 weighted images has only rarely been demonstrated in such tumors that have no histologic evidence of adipose tissue. MRI provided all of the information needed pre-operatively.

Amoxapine overdose: report of two cases.

Two deaths are described involving amoxapine. Toxicological analysis in Case 1 revealed an amoxapine blood concentration of 5.7 micrograms/mL, and in Case 2, a concentration of 3.2 micrograms/mL. Qualitative analysis of other body fluids were performed.

Preliminary report on the application of a high performance liquid chromatographic method for alprazolam in postmortem blood specimens.

A high performance liquid chromatographic (HPLC) method for the determination of alprazolam in postmortem blood specimens is described. The method is sensitive, reproducible, and gives good resolution between other benzodiazepines. Recovery of alprazolam from spiked blood specimens at 100 ng/mL was 89%. The procedure was applied to a case of suicidal ingestion of alprazolam and a blood concentration of 177 ng/mL was determined.