Hyperthyroidism associated with papilloedema and pyramidal tract involvement

Summary In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q₁₀ (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.     

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.     

Chronic encapsulated intracerebral hematoma associated with cavernous angioma: a case report

The case of a patient with a chronic encapsulated intracerebral hematoma associated with a cavernous angioma is reported. In spite of a huge space-occupying lesion in the frontal lobe, our patient showed no focal neurological deficit. The clinical picture suggested a slowly growing brain tumor. Intraoperative findings revealed a liquefied intracerebral hematoma with a thick capsule. Pathological investigations demonstrated a capsule rich in neovascularity with a cavernous angioma attached to it. It is presumed that initial bleeding from the cavernous angioma encouraged capsule formation similar to the membrane of chronic subdural hematomas and that repeated bleeding from the capillaries of the capsule allowed the expansion of the hematoma.     

Role of reactive oxygen in phospholipase A2 activation by ischemia/reperfusion of the rat kidney

Purpose. To investigate the role of phospholipase A₂ (PLA₂) in reperfusion injury of the kidney in an in vivo animal model, renal mitochondrial PLA₂ activity was measured under three different conditions. Methods. Male Wistar rats (n = 72) anesthetized with pentobarbital underwent renal ischemia surgically for 45 min and were reperfused for the indicated time (renal ischemia/reperfusion). Treatments included reperfusion for various predetermined periods (phase 1), exposure to hyperbaric oxygen (phase 2), and administration of reactive oxygen species (ROS) scavenger (phase 3). Thereafter, each kidney was harvested, and mitochondrial PLA₂ activity was measured by a radioisotope technique. Results. Ischemia/reperfusion resulted in time-related PLA₂ activation in the renal mitochondria up to 48 h of reperfusion after renal ischemia. Renal mitochondrial PLA₂ activity was further augmented by hyperbaric oxygen exposure prior to reperfusion, whereas administration of the ROS scavengers suppressed mitochondrial PLA₂ activity. Conclusion. These data suggest that ROS may play an important role in the in vivo activation of PLA₂ associated with renal ischemia/reperfusion. Received for publication on July 6, 1998; accepted on November 30, 1998     

Inhibition of P-selectin attenuates neutrophil-mediated myocardial dysfunction in isolated rat heart

The expression of P-selectin on postischemic endothelium after reperfusion has been shown to trigger neutrophil attachment and the subsequent inflammatory responses. Extensive studies have demonstrated that P-selectin is involved in the progression of neutrophil-mediated myocardial infarction and no-reflow phenomenon. In the present study, we examined the effects of selectin inhibitors, sialyl Lewis X-oligosaccharide and anti-P-selectin monoclonal antibody, PB1.3 on neutrophil-dependent left ventricular dysfunction in isolated rat heart. The hearts were subjected to global ischemia for 20 min and then reperfused for 45 min with rat plasma in the presence of human neutrophils during the first 5 min of the reperfusion. Left ventricular developed pressure and other parameters of the left ventricular function deteriorated throughout the reperfusion period in a neutrophil-dependent manner. In contrast, the coronary flow was reduced early on (< 15 min) but recovered to the level in the hearts reperfused with no neutrophils 45 min after the reperfusion. We examined the effects of selectin inhibitors under experimental conditions in which the hearts were perfused with 30 million neutrophils. The treatment with sialyl Lewis X-oligosaccharide at a dose of 0.3 mg/min resulted in amelioration of left ventricular developed pressure to 57.2 +/- 14%, compared to 26.1 +/- 4.3% in the saline-treated group (P < 0.05). Similarly, the treatment with mouse anti-human P-selectin monoclonal antibody (IgG1) PB1.3 at a dose of 0.6 mg/min resulted in the prominent recovery of left ventricular developed pressure after 45 min of reperfusion (59.9 +/- 9.3% vs. 26.1 +/- 4.3% in the saline-treated group, P < 0.05). PB1.3 also attenuated the elevation of left ventricular end-diastolic pressure compared to that of the saline-treated group during the reperfusion period. Moreover, the treatment with PB1.3 ameliorated the recovery of coronary flow until 10 min after the reperfusion and the recovery of coronary flow 10 min after the reperfusion was 55.2 +/- 9.2%, as compared to 28.2 +/- 7.7% in saline-treated hearts (P < 0.05). To our knowledge, this is the first direct demonstration that the specific inhibition of P-selectin results in the inhibition of neutrophil-mediated left ventricular dysfunction or myocardial stunning.     

Effects of pirarubicin,an antitumor antibiotic,on the cardiovascular system

Summary In the present study we examined the effects of pirarubicin [(2R)-4-0-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39–3.13 mg/kg, i. v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5×10^–6–1.5×10^–5 m, THP markedly relaxed a contraction induced by 10^–7 m norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02–0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5×10^–5–1.5×10^–4 m), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10^–6–5×10^–5 m), chlorpheniramine (3×10^–7–3×10^–5 m), and tripelennamine (3×10^–7–3×10^–5 m) but not by propranolol (10^–6 m), cimetidine (10^–5 m), diltiazem (10^–6 m), or ryanodine (10^–8 m). THP given i. v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.     

A new thrombolytic agent,monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial

Background Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered. Methods This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured. Results Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 ± 4 vs 20 ± 2 ng/mL, P < .01) and in Group II (36 ± 3 vs 27 ± 2 ng/mL, P < .05). In the high PAI-1 level subgroup (≥27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P < .01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald χ²= 3.94, P = .02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II. Conclusion Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI. (Am Heart J 2002;144:e5.)