A novel miniature ventricular assist device for hemodynamic support.

The HemoDynamics Systems enabler is a new cardiac assist pump that can expel blood from the left ventricle and provide pulsatile flow in the aorta. We evaluated the efficacy of the 18 Fr enabler. The enabler was inserted from the left ventricular apex into the ascending aorta in eight sheep. Heart failure (mild, moderate, and severe) was induced by microsphere injection into the coronary arteries to reduce cardiac output by 10-30%, 31-50%, and more than 50% from baseline, respectively. The enabler was activated, and its flow was increased to approximately 2.0 L/min. Hemodynamic variables were recorded before and after activation. In moderate heart failure, cardiac output and mean aortic pressure increased from 2.3 +/- 0.6 L/min and 59 +/- 12 mm Hg before assist to 2.8 +/- 0.6 L/min and 70 +/- 8 mm Hg at 30 minutes after activation, respectively (p < 0.01). Left atrial pressure decreased from 17 +/- 3 to 13 +/- 4 mm Hg (p < 0.05). Similar findings were observed in mild and severe heart failure. Despite its small diameter, the enabler significantly improved the hemodynamics of failing hearts and may potentially serve as a means of peripheral left ventricular support. Further study is warranted.

The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine.

OBJECTIVE: This multicenter, open-label study was designed to assess the efficacy and tolerability of olanzapine in patients with chronic schizophrenia who are resistant to therapy with classic neuroleptic agents and are either not responsive to or unable to tolerate clozapine. METHODS: Patients received olanzapine orally once daily for 18 weeks at doses ranging from 5 to 25 mg. The primary efficacy measure was change in the total score on the Positive and Negative Syndrome Scale (PANSS) from baseline to end point. Secondary efficacy measures were the total score on the Brief Psychiatric Rating Scale (BPRS); the PANSS positive, negative, general psychopathology, and mood subscores; and the Clinical Global Impression improvement score. Also recorded were spontaneously reported adverse events; extrapyramidal symptoms (assessed by the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, and Barnes Akathisia Scale); vital signs; and clinical laboratory test results. RESULTS: Forty-eight patients were treated with olanzapine; of these, 45 were assessable over the full 18-week study period. Total scores on the PANSS and BPRS were reduced from baseline by an average of 17.7 (14.2%) and 9.8 points (20.2%), respectively. Eighteen patients (40.0%) experienced a treatment response, defined as a reduction in PANSS total score of > or = 20%. A total of 25 patients (55.6%) achieved a similar reduction in BPRS total score. Significant reductions were seen in both the positive and negative symptom scores on the PANSS (P < 0.001). Olanzapine was well tolerated, with minimal treatment-emergent adverse events or clinically relevant changes in vital signs or clinical laboratory test results. No clinically significant blood dyscrasias were observed in olanzapine-treated patients, including those who had discontinued clozapine because of treatment-associated leukopenia or neutropenia. CONCLUSION: The results of this study suggest that olanzapine may be of benefit in patients who are refractory to or unable to tolerate clozapine.

The enabler right ventricular circulatory support system for beating heart coronary artery bypass graft surgery.

BACKGROUND: Beating heart coronary artery bypass graft surgery of the left anterior descending, diagonal, and right coronary artery can be performed safely with the Octopus Stabilization System. However, tilting of the heart, which is necessary to reach the obtuse marginal and distal right coronary arteries, causes hemodynamic instability. This study was performed to investigate the possible role of the Enabler right ventricular circulatory support system in counteracting this instability. METHODS: In 8 sheep, the Enabler cannula was introduced via the jugular vein and positioned with the inlet valve in the right atrium and outlet valve in the pulmonary artery. The Octopus was used to expose the inferior wall and the posterior wall of the left ventricle. The hemodynamic effects of this tilting with and without Enabler right ventricular support were recorded, including Pressure Volume (PV) loops measured by conductance catheters in both ventricles. RESULTS: Tilting caused a reduction in stroke volume (inferior 31%, posterior 17%) and Enabler activation increased stroke volume (inferior 13%, posterior 31%). CONCLUSIONS: Tilting the heart has severe hemodynamic consequences that can be partially counteracted by the use of the Enabler for right ventricle support.

Emergence of obsessive--compulsive symptoms and tics during clozapine withdrawal.

Treatment with clozapine may be associated with the appearance of obsessive-compulsive (OC) symptoms in up to 10% of schizophrenic patients. We present the first report of the emergence of de novo OC symptoms during clozapine withdrawal in two schizophrenic patients, associated in one with Tourette's syndrome-like tics. Resumption of clozapine led to the complete disappearance of the OC symptoms and a substantial alleviation of the tics. It is suggested that an imbalance between the dopamine and serotonin systems may account for this complication.

[CA15-3 tumor marker in early detection of breast cancer].

CA15-3 is a tumor marker associated with mammary tumors. Increased levels have been observed in patients with breast cancer, while normal low levels are usually found in women with no evidence of disease. The potential clinical uses of this marker include monitoring of patients with breast cancer, prognosis, and early detection of recurrence. Tumor markers are not usually used for diagnosis, as only in a few patients are elevated levels found. But when high levels of tumor markers are detected at an early stage, it may be of diagnostic value. In this study we describe a patient we believe to be the first in whom the CA15-3 tumor marker indicated breast cancer, while physical examination and the initial mammography were without suspicious findings. We also show sections of formalin-fixed, paraffin-embedded tissue stained by the CA15-3 indirect immunoperoxidase method.

Idiopathic ventricular fibrillation: inducibility and beneficial effects of class I antiarrhythmic agents.

Ventricular fibrillation in patients without recognizable heart disease is uncommon and electrophysiologic data on such patients is limited. Over a 7 year period, five patients (three men and two women, ranging in age from 24 to 52 years) without demonstrable heart disease underwent electrophysiologic studies with pharmacologic drug testing because of single (four patients) or multiple (one patient) documented episodes of ventricular fibrillation. The arrhythmic event was unrelated to myocardial ischemia or infarction, metabolic or electrolyte disturbances, drug toxicity, preexcitation, or prolonged QT syndromes. In all three patients receiving no antiarrhythmic drugs and in two pretreated with amiodarone, a rapid poorly tolerated ventricular tachyarrhythmia requiring cardioversion was induced by programmed ventricular stimulation with up to two extrastimuli. In all instances, addition of either oral quinidine or oral disopyramide prevented the induction of sustained ventricular arrhythmias. All five patients were placed on antiarrhythmic drug regimens found effective during electrophysiologic studies and remained asymptomatic during follow-up periods ranging from 12 to 93 (mean 52) months. We conclude that in the patients with idiopathic ventricular fibrillation in our study: programmed ventricular stimulation reliably replicated the spontaneous arrhythmia, class I antiarrhythmic agents effectively prevented induction of the arrhythmia in the laboratory, and in contrast to the severity of the presenting arrhythmia, a benign clinical course was observed during long-term therapy with class I antiarrhythmic agents.

Steady-state serum amiodarone concentrations: relationships with antiarrhythmic efficacy and toxicity.

The relationship of apparent steady-state serum concentrations of amiodarone and its metabolite, desethylamiodarone, to therapeutic and toxic effects was assessed in 127 patients who had treatment-resistant ventricular or supraventricular arrhythmias or were intolerant to other agents. After at least 2 months (mean, 9.8) of treatment with daily maintenance doses of 200 to 600 mg, arrhythmias were effectively suppressed in 78% of patients. Arrhythmias recurred in 47% of patients with serum amiodarone concentrations of less than 1.0 mg/L, whereas only 14% of patients with higher concentrations had recurrences (p less than 0.005). Side effects, most of them mild, occurred in 57%; only 9 patients required discontinuation of drug therapy. The risk of developing adverse reactions was related to serum amiodarone concentrations (p less than 0.0001). Adverse reactions were common in patients with serum values exceeding 2.5 mg/L, although pulmonary complications did occur at lower concentrations. Monitoring serum amiodarone concentrations may differentiate failure of drug therapy from suboptimal dosing and reduce the incidence of concentration-related side effects.

Amiodarone: individualizing dosage with serum concentrations.

The purpose of the present report is to review the available pharmacokinetic information on amiodarone with an emphasis on our own experience in monitoring serum amiodarone concentrations. We have found that 400 mg should be the maximal maintenance dose; if that treatment fails, careful addition of other antiarrhythmic agents is preferable over an increase in amiodarone dosage. Serum concentrations below 2.5 mg/L will significantly improve amiodarone's benefit-to-risk ratio.