Components of arterial systolic pressure and RR-interval oscillation spectra in a case of baroreflex failure, a human open-loop model of vascular control.

The baroreflex control of circulation is always operating and modulates blood pressure and heart rate oscillations. Thus, the study of cardiovascular variability in humans is performed in a closed-loop model and the physiology of post-sinoaortic denervation is completely unknown in humans. We dissected for the first time the different components of systolic arterial pressure (SAP) and RR-interval spectra in a patient with 'baroreflex failure' (due to mixed cranial nerve neuroma) who represents a human model to investigate the cardiovascular regulation in an open-loop condition. Interactions among cardiovascular variability signals and respiratory influences were described using the multivariate parametric ARXAR model with the following findings: (1) rhythms unrelated to respiration were detected only at frequencies lower than classical low frequency (LF; Slow-LF, around 0.02 Hz) both in SAP an RR spectra, (2) small high-frequency (HF) modulation is present and related with respiration at rest and in tilt (but for SAP only) and (3) the Slow-LF fluctuations detected both in SAP and RR oscillate independently as the multivariate model shows no relationships between SAP and RR, and these oscillations are not phase related. Thus, we showed that in a patient with impaired baroreflex arc integrity the Slow-LF rhythms for RR have a central origin that dictates fluctuations on RR at the same rhythm but unrelated to the oscillation of SAP (which may be related with both peripheral activity and central rhythms). The synchronization in LF band is a hallmark of integrity of baroreflex arc whose impairment unmasks lower frequency rhythms in SAP and RR whose fluctuations oscillate independently.

Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia.

We describe an extremely rare case of megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. The patient had a very high platelet count and developed an ischemic stroke with seizures. She was treated with hydroxyurea, platelet apheresis, ARA-C, and idarubicin in order to obtain a prompt reduction of thrombocytosis and then with imatinib 600 mg/die PO. The therapy induced a complete hematological remission with a resolution of neurological signs within 4 weeks.

Comparison of a daily fixed 2.5-mg warfarin dose with a 5-mg, international normalized ratio adjusted, warfarin dose initially following heart valve replacement.

Patients starting oral anticoagulant therapy after heart valve replacement initially require a lower target international normalized ratio (INR) (2.0, range 1.5 to 2.6) because of a higher risk of bleeding until pericardial wires are removed. In a previous retrospective analysis, we observed a higher sensitivity to warfarin in these patients compared with nonsurgical patients. In a randomized clinical trial, we compared a fixed, lower dose of warfarin (2.5 mg) with the standard treatment consisting of a 5-mg loading dose, then adjusted to the target INR during the first 5 days of anticoagulation. INRs were measured daily, but the fixed dose was only modified on day 3 if the INR was <1.5 or >3.0. One hundred ninety-seven patients were considered eligible for the study. The 2 groups were well matched according to age, gender, body mass index, concomitant treatments, and type of valves implanted. The proportion of INRs >2.6 during the study period was 42.5% in the 5-mg group and 26.2% in the 2.5-mg group (p <0.05), and the proportion of INRs >3.0 on day 3 was 23.9% and 9.5% (p <0.05), respectively. In the 2.5-mg group, 35.7% of patients had an INR <1.5 on day 3 and had the dose increased (vs 3.5%, p <0.001); however, in the 5-mg group, 95.6% had the initial dose reduced, 49.6% had the dose withheld for at least 1 day, and the mean dose during the 5 days of study was 3.08 mg. Average time to achieve therapeutic range was higher in the 2.5-mg group (2.72 vs 1.98 days, p <0.0001), but the approach to the targeted INR was more regular, and the gap between target and mean INR on day 5 was smaller. There were no bleeding or thromboembolic complications in either group. Thus, a lower loading dose of warfarin in patients after heart valve replacement reduces excessive anticoagulation and offers a more regular achievement of the therapeutic target by reducing the number of dose adjustments. Daily monitoring of the INR is still recommended.