Mechanisms of progression and regression of coronary artery disease by PET related to treatment intensity and clinical events at long-term follow-up.

Changes in regional myocardial perfusion throughout the entire coronary vascular tree, as opposed to changes in the worst regional perfusion defect, have not been described during long-term regression or progression of coronary artery disease (CAD) or related to clinical outcomes. METHODS: Four-hundred nine patients with CAD undergoing dipyridamole PET at baseline and after 2.6 +/- 1.4 y were followed over 5 more years for coronary events. PET images were objectively quantified by automated software for changes in severity of the (i) baseline worst quadrant, indicating the worst flow-limiting stenosis at baseline PET; (ii) follow-up worst quadrant, indicating the worst stenosis on follow-up PET; and (iii) maximal change quadrant, indicating the largest change of any same quadrant pair from baseline-to-follow-up images. RESULTS: At follow-up PET, new regional perfusion defects were seen in 40% of patients. In 77% of patients, the greatest change was in a quadrant different from the worst baseline defect. The maximal change quadrant improved in 70% of patients on intense lifestyle and pharmacologic lipid treatment, in 48% on moderate treatment, and in 39% on poor treatment (P < 0.0001). Combined quadrant changes integrated throughout the heart independently predicted cardiovascular events at long-term follow-up. In contrast, changes of any single baseline-to-follow-up quadrant pair did not. CONCLUSION: By PET, 77% of patients with CAD had the greatest perfusion changes in areas different from the baseline worst perfusion defect and 40% had new perfusion defects. Changes in perfusion defects throughout the entire coronary vascular tree predicted coronary events, whereas changes in the worst flow-limiting stenosis at baseline or in any one segment of myocardium did not. To our knowledge, these data provide the first direct evidence on mechanisms for disproportionately greater reduction in cardiac events than changes in single stenosis severity with lipid treatment.     

Splenic abscess in patients on hemodialysis

We describe two patients on hemodialysis who developed staphylococcal splenic abscesses. Both patients previously had staphylococcal septicemia secondary to infection at the dialysis access site. We postulate that access-site infections may predispose hemodialysis patients to splenic abscess, and that these patients should be investigated for a splenic abscess if they should develop unexplained fever.     

Temporal lobe epilepsy caused by domoic acid intoxication: Evidence for glutamate receptor–mediated excitotoxicity in humans

We describe the development of temporal lobe epilepsy in an 84-year-old man who had suffered domoic acid intoxication. Following intoxication he had nausea, vomiting, confusion, and coma. Generalized convulsions and complex partial status epilepticus progressively developed. After 3 weeks he improved and was seizure free with severe residual memory deficit. Electroencephalograms initially showed periodic epileptiform discharges, later evolving to epileptic abnormalities over frontotemporal regions with diffuse slow waves. Eight months after the intoxication the electroencephalogram was normal. One year after the acute episode, complex partial seizures developed. Electroencephalograms showed epileptic discharges independently over both temporal lobes, with left-sided predominance. Magnetic resonance imaging revealed a hyperintense T2-weighted signal and atrophy of both hippocampi; a positron emission tomographic scan showed bitemporal decreased glucose metabolism. Pneumonia developed and the patient died 31/4 years after the intoxication. Autopsy disclosed severe bilateral hippocampal sclerosis. The seizures following acute domoic acid intoxication, the postmortem pathology, and the fact that temprol lobe epilepsy developed 1 year after intoxication indicate that the human hippcampus is also vulnerable to kainate receptor excitotoxicity, and provide strong evidence supporting the role of excitotoxic injury in epileptogenesis. This report provides a unique human parallel to, and validates the animal model of, Kainate-induced epilepsy as an important tool for studying temporal lobe epilepsy.     

Malignant fibrous histiocytoma of the temporal bone with endocranial extension.

Cranial malignant fibrous histiocytomas are rare tumors. Most are hypervascular, destructive masses that are similar to other malignant lesions and to malignant fibrous histiocytomas found elsewhere in the body. We describe a myxoid malignant fibrous histiocytoma of the temporal bone, possibly of dural origin, with features that more closely resembled a meningioma at CT, MR imaging, and angiography.     

Pleuroperitoneal shunt for recurrent malignant pleural effusions.

The therapeutic options available for the management of malignant pleural effusions associated with a restricting malignant cortex remain unsatisfactory. The efficacy of pleuroperitoneal shunts was evaluated in 16 patients with recurrent malignant effusions. There were no operative deaths; one patient died on the third postoperative day as a result of lymphangitis carcinomatosa. The median hospital stay was five (range 3-21) days. Palliation was obtained in all but one of the other 15 patients. There was no appreciable reaccumulation of pleural fluid as judged by radiography. Two patients developed occlusion of the shunt. In one case this was due to blood clots in the pleural catheter and necessitated insertion of a new shunt. The other shunt was removed because of obstructing infected fibrin debris, and a rib resection was performed. There were eight deaths related to the underlying malignancy after a mean interval of 7.3 (range 1.5-23) months. The other six patients are still alive, with a mean survival of 11.0 (range 5-20) months, and have achieved good symptomatic relief. The insertion of a pleuroperitoneal shunt can offer effective palliation for patients with recurrent malignant pleural effusions.     

Reduction in temporal N-acetylaspartate and creatine (or choline) ratio in temporal lobe epilepsy: does this 1H-magnetic resonance spectroscopy finding mean poor seizure control?

BACKGROUND—Proton magnetic resonance spectroscopy(¹H-MRS) is a potentially useful tool in the in vivoinvestigation of brain metabolites in intractable temporal lobeepilepsy (TLE). Focal N-acetylaspartatate (NAA) reductions have beencorrelated with mesial temporal sclerosis (MTS) in surgically resectedepileptogenic foci.
OBJECTIVE—To evaluate the abnormalities in themetabolites NAA, creatine+ phosphocreatine (Cr), and cholinecontaining compounds (Cho) in the temporal lobe of medically refractorypatients with temporal lobe epilepsy, seizure free patients withtemporal lobe epilepsy, and normal controls.
PATIENTS AND METHODS—Ten refractory patients, 12 seizure free patients with temporal lobe epilepsy, and 10 age matchednormal controls were studied by ¹H-magnetic resonancespectroscopy. All patients had consistently unilateral temporal EEGabnormalities and a normal brain MRI. Proton MR spectra were obtainedfrom an 8 ml volume in the medial temporal lobes in patients withtemporal lobe epilepsy (ipsilateral to EEG foci) and the normalcontrols. The signals measured were expressed in terms of NAA/Cr,NAA/Cho, and Cho/Cr.
RESULTS—When compared with seizure free patientswith temporal lobe epilepsy and normal controls, the 10 refractorypatients with temporal lobe epilepsy had a lower mean (SEM) NAA/Crratio (1.65(0.53) v 2.62 (0.60), and 2.66 (0.73);p<0.002 and p<0.006) and a lower mean NAA/Cho ratio (1.59 (0.79)v 2.83 (1.33) and 2.58(0.67); p<0.02 andp<0.007).Furthermore, the two patients showing the lowest NAA/Cr ratios (1.47 and 1.73) in the seizure free group had had a past period of poorseizure control.
CONCLUSIONS—There were reduced temporal NAA/Cr andNAA/Cho ratios, suggesting neuronal loss or damage, associated withpast or present poor seizure control in the patients with temporal lobeepilepsy, but it does not exclude the possibility of a future completeseizure control (seizure free patients with temporal lobe epilepsy at the time of ¹H-MRS). This study warrants further¹H-MRS investigation with a larger series of patients withtemporal lobe epilepsy.

     

“Helper:” A critical events prompter for unexpected emergencies

Objective. The medical practitioner is faced with an increasing list of protocols and algorithms related to patient care. These recommendations are often difficult to recall, particularly in stressful emergency situations. Using advanced cardiac life support (ACLS) protocols, we built a computer-based system to exhibit precompiled response plans for medical emergencies. To validate the usefulness of this prompting device, we tested application of two of the nine ACLS algorithms, pulseless ventricular fibrillation/ventricular tachycardia (Vfib/Vtach) and bradycardia, in a simulated operating room (OR) environment.Methods. The system utilized the software authoring system IconAuthor (Aimtec Inc., Nashua, NH) and a touch-screen monitor (DiamondScan, Microtouch, Methuen, MA). Prior to testing our system, all 39 subjects were given time to familiarize themselves with its operation. Subsequently, all subjects were videotaped while managing a standard simulated anesthetic. During the anesthetic, the subjects were presented with two emergency scenarios, not viewed during the familiarization period. The electrocardiographic (EKG) signals for normal sinus rhythm, ventricular fibrillation, and second-degree heart block were presented. By random selection, the prompter was available to half of the subjects for help with arrhythmia management (experimental group), while to half it was not (control group).Results. A total of 39 subjects completed the exercise. Use of the prompter enabled significantly more subjects to administer correct drugs and dosages during ventricular fibrillation. The correct lidocaine dose was chosen more often by the experimental group than by the control (p=0.015); similarly MgSO₄ was appropriately ordered more often in the experimental group (p=0.003). During second-degree heart block, atropine was correctly followed with a dopamine infusion (p=0.004), and epinephrine infusion was ordered for refractory bradycardia (p=0.002) more often in the experimental than the control group.Conclusions. These data demonstrate the value of a prompting device at the anesthesia workstation. We foresee the use of such prompters in many areas of medicine.This study was made possible by a grant from the Anesthesia Patient Safety Foundation. Results were presented, in part, at the meeting of the STA/SEA Orlando, Florida, January 1994.     

Biochemical and biological activity of the anthracycline analog, 4-demethyl-6-0-methyl-doxorubicin

Summary The chromophore-modified derivative of doxorubicin, 4-demethyl-6-0-methyl-doxorubicin, has been tested for antitumor activity in a range of experimental murine tumor systems. In contrast to the inactive 6-0-methyl derivative of daunorubicin, 4-demethyl-6-0-methyl-doxorubicin provided antitumor effects comparable to that of the parent compound. In addition, detailed DNA-interaction studies showed that the doxorubicin derivative retains the ability to bind DNA by the intercalation mechanism. However, the binding affinity was appreciably reduced following structural modification in the anthraquinone chromophore. On the basis of the proposed models of intercalation, these results could be rationalized in terms of steric influence of the bulky methoxy group. The results of this study are in agreement with the correlation already observed between DNA binding and relative antitumor activity of anthracyclines.