Lack of correlation of functional scintigraphy with (99m)technetium-methoxyisobutylisonitrile with histological necrosis following induction chemotherapy or measures of P-glycoprotein expression in high-grade osteosarcoma.

In osteosarcoma, some studies have suggested P-glycoprotein expression is a prognostic factor. The clearance of (99m)technetium hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been used in some tumor systems as an in vivo measure of P-glycoprotein-mediated efflux. In this study we explored the correlation between (99m)Tc-MIBI clearance and histological necrosis following induction chemotherapy and P-glycoprotein expression in osteosarcoma. The primary tumors of 20 patients with high-grade osteosarcoma were imaged at diagnosis with (99m)Tc-MIBI, and the uptake ratios and biological half-lives were calculated. P-Glycoprotein expression in the tumor tissue was determined immunohistochemically and by measuring mRNA expression of the multidrug resistance-1 gene. The histological necrosis following induction chemotherapy was assessed by the Huvos grading system. The biological half-life of (99m)Tc-MIBI ranged from 1.4 to 52.5 h. Seven of the 20 tumor samples had a favorable extent of necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio showed no correlation with histological necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio did not correlate with either measure of P-glycoprotein expression. The results of this pilot study indicate that (99m)Tc-MIBI imaging is not an effective predictor of histological necrosis following induction chemotherapy in high-grade osteosarcoma. (99m)Tc-MIBI imaging did not correlate with measures of P-glycoprotein expression in the tumor tissue.

Dysphagia due to cervical osteophytes.

A case of a 64-year-old man is presented with painless dysphagia and loud noise on swallowing due to large anterior cervical osteophytes demonstrated on plain radiographs and magnetic resonance imaging accompanied by a brief review of the literature.

Bilateral symmetrical basal ganglia infarction after intravenous use of cocaine and heroin.

A case is reported of a young man who developed bilateral symmetrical basal ganglia infarcts after intravenous use of cocaine and heroin. Ischemic infarcts of the brain are a known complication of to cocaine use, alone or in combination with heroin (speed balling). This symmetrical occurrence of infarction, however, is unusual and has not been reported after cocaine use.

Seizures in the critically ill: the role of imipenem.

PURPOSE: To determine the risk of seizures in critically ill patients receiving the antibiotic imipenem, a broad-spectrum antibiotic that has been associated with seizures. Reports generally have not considered other contributing factors such as dose, seizure history, and morbidity index of the underlying illness necessitating the antibiotic. METHODS: Charts of all patients in a 450-bed municipal hospital who received imipenem in a 6-month period, as determined by pharmacy records, were reviewed for dosage and duration of imipenem use, occurrence of seizures. and mortality outcome. Attention was paid to demographic features; pattern of seizure occurrence during, before, and after imipenem use; renal function; and correction for dosage based on size. RESULTS: Seventy-five charts were reviewed. Sixty-three patients had no seizures during the hospitalization, four had seizures while receiving imipenem, and eight had seizures during the hospitalization but before or after imipenem use. The incidence of seizures was 4/1,000 patient-days on, and 3.9/1,000 patient-days off imipenem (not significant). The risk of seizure in both groups was considerably higher in those patients with a history of seizures before hospitalization. The presence of other factors that could contribute to increased concentration of imipenem in the brain, such as renal failure or acute stroke, did not contribute to seizure incidence. Metabolic derangement, anoxia, and phenytoin discontinuation did contribute to seizure incidence. CONCLUSIONS: Seizure incidence is increased in all critically ill patients (16% of patients studied), but with no added risk during the period patients received imipenem. Determining the proper dose based on a patient's body mass, correction of dose in the presence of renal failure, and avoidance of excess of 2 g/day of imipenem removes any added risk for seizures from imipenem. Despite experimental data to suggest action of imipenem on the glutamate/N-methyl-d-aspartate receptor, or interference with binding to the gamma-aminobutyric acid receptor, and early clinical studies that warned against its use because of seizure risk, we found that careful use of this antibiotic is safe.

Placebos, placebo effect, and the response to the healing situation: the evolution of a concept.

In spite of its impressive progress, medicine has been strongly criticized for relying on its modern biomedical tradition to the neglect of the psychosocial aspects of health. This neglect may account for patients' dissatisfaction and eventual use of alternative health approaches. The concept of placebo has sustained dramatic "protean" metamorphoses through the ages. For centuries, placebos have been regarded as powerful deceptive therapies. From the middle of the twentieth century, however, conventional medicine has used placebos as methodologic tools to distinguish the specific from the nonspecific ingredients in treatments. In modern medical research, the double-blind, placebo-controlled, randomized clinical trial has been established as the gold standard for the assessment of any new treatment. Recently a new trend regarding placebos seems to have emerged. The placebo and other nonspecific effects elicited by the "healing situation" have been independently subjected to scientific study. Progress in this area may promote useful clinical applications, enabling physicians to broaden their perspectives on the healing process. We present the historical changes of the concept of placebo and the ethical issues raised by their use.

Administration of citalopram before ECT: seizure duration and hormone responses.

From theoretical and clinical perspectives, it is important to know if selected serotonin-reuptake inhibitors (SSRIs), often administered concurrently with electroconvulsive therapy (ECT), modify seizure duration. In a study with a double-blind, cross-over design, the authors evaluated the effect of citalopram, the most selective SSRI available, on the length of electrically induced seizures and on hormone secretion during ECT. Ten depressed women were given either 20 mg citalopram or placebo orally 2 hours before the third and fourth ECT sessions. Seizure duration was assessed by the cuff technique and from electroencephalographic recordings, whereas blood for prolactin, thyrotropin, and cortisol assessment was sampled before ECT and 5, 10, 20, 30, 40, and 60 minutes after ECT. No adverse effects after the administration of citalopram were recorded. The length of seizures was not statistically different in the citalopram (29.3+/-8.4 seconds) and placebo sessions (28.2+/-9.4 seconds). Neither pre-ECT plasma hormone levels measured 2 hours after citalopram or placebo administration nor the patterns of ECT-induced hormone secretions differed between the two drug and placebo conditions. The lack of effect of citalopram on hormones in this study may be a result of possible deficiencies of the monoaminergic (i.e., serotoninergic) systems in depression. Although safety and efficacy issues were not fully addressed by coadministering citalopram for the long term and throughout the course of ECT, these findings support the view that challenges the typical clinical practice of discontinuing SSRIs before ECT.

Relation of cocaine use to seizures and epilepsy.

PURPOSE: Cocaine can provoke seizures, exacerbate a preexisting seizure disorder, or cause an ischemic or hemorrhagic stroke that leads to seizures. To determine the importance of cocaine use in patients with and without epilepsy, we studied these relations and other risk factors for seizures and the mode of cocaine use. METHODS: We reviewed all charts of emergency department visits and hospitalizations of patients with discharge diagnoses simultaneously listing seizures, epilepsy, and cocaine use during a 24-month period. Data collected included patient age, sex, route of cocaine use, seizure description and duration of epilepsy, provocative factors, results of electroencephalography and computed tomography, treatment, and outcome. RESULTS: Of 67,668 adult emergency department visits and 25,768 adult admissions, 1,900 were cocaine related, and 58 of these also had seizures or epilepsy. Seizure occurrences were approximately equally distributed among groups with idiopathic epilepsy, remote symptomatic localization-related epilepsy, cerebrovascular disease, and acute symptomatic seizures due to cocaine use alone. Less frequently, seizures were cryptogenic or symptomatic of metabolic abnormalities. CONCLUSIONS: Cocaine use can reduce seizure threshold in patients with underlying epilepsy as a direct toxic effect or indirectly by contributing to poor compliance with antiepileptic drug treatment, poor diet, or poor sleep habits. In 12 of the 58 patients, cocaine appeared to be the only provocative factor. This may be a less significant risk factor for epilepsy than either alcohol or head trauma.