Whole-brain CT perfusion measurement of perfused cerebral blood volume in acute ischemic stroke: probability curve for regional infarction

PURPOSE: To determine the probability curve for regional cerebral infarction as a function of percentage normalized perfused cerebral blood volume (pCBV) in patients with acute ischemic stroke. MATERIALS AND METHODS: The authors retrospectively analyzed whole-brain computed tomographic (CT) perfusion scans from 28 patients with acute stroke (<6 hours) due to major arterial occlusion, without intracranial hemorrhage. Each patient had a positive follow-up CT scan 1-4 days later, without interval thrombolysis. Normalized pCBV, expressed as a percentage of contralateral normal brain pCBV, was determined in the core infarction and in regions just inside and outside the boundary between infarcted and noninfarcted brain. These regions were dichotomized into infarcted (core and inner band) and noninfarcted (outer band) categories. Logistic regression analysis was then used to create a reference curve of probability of infarction as a function of percentage normalized pCBV. RESULTS: Normalized pCBV values in the core, inner band, and outer band were 24.5% +/- 2.3, 36.3% +/- 2.4, and 72.1% +/- 2.4, with corresponding probabilities of infarction of .99, .96, and .11. The normalized pCBV at which the probability of survival reached .5 was 58.0% +/- 0.5. Sensitivity, specificity, and accuracy of the reference probability curve were 90.5% (209 of 231), 89.5% (212 of 237), and 90.0% (421 of 468), respectively. Negative and positive predictive values were 90.6% (212 of 234) and 89.3% (209 of 234), respectively. R2 was 0.73, and differences in perfusion between core and inner and outer bands were highly significant (P <.0001). CONCLUSION: A probability of infarction curve can help predict the likelihood of infarction as a function of percentage normalized pCBV.     

Phase I-II parallel study of docetaxel on a bimonthly schedule in refractory metastatic breast carcinoma

Background. The 3-week schedule with docetaxel (DTC) 75–100 mg/m² is associated with severe neutropenia, gastro-intestinal side-effects and fluid retention in a significant proportion of patients, which may be of concern in more elderly or poor performance status patients. A phase I–II trial was carried out to test the feasibility and the activity of a new bimonthly schedule of DCT. Patients and methods. The trial included a phase I study which aimed at the identification of dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of DCT on a bimonthly schedule. The first group of three patients received DCT 40 mg/m², and in absence of DLT, DCT dosage was escalated by 10 mg/m²/cycle until DLT was reached. In the phase II study, patients were randomized to receive: (a) standard 3-weekly DCT at the dose of 75 mg/m² (calibration arm); or (b) bimonthly schedule with DCT at the dose recommended in the phase I study. All patients were pretreated with chemotherapy, mostly anthracycline-based regimens, for advanced/metastatic disease. Analysis of response rates, toxicity, and dose-intensity were the main aims of the study. Results. The DLT was represented by severe myelosuppression which was recorded in all patients treated at 70 mg/m² dose level. Therefore, the MTD was 60 mg/m² on a bimonthly schedule. However, the dose recommended for the phase II trial was 50 mg/m², because no difference in delivered dose-intesity was seen between the 50 and 60 mg/m² dose levels, and the latter dosage was still associated with grade 3 neutropenia in most patients. The parallel phase II study showed that the bimonthly schedule of DCT (50 mg/m²) allows to deliver the same dose-intensity of DCT 75 mg/m² every 3 weeks. Grade 3–4 side-effects were rather infrequent in patients treated with the bimonthly schedule. Overall response rate (ORR) was 41 and 44% for the DCT 50 mg/m² bimonthly and the DCT 75 mg/m² every 3 weeks, respectively. Conclusions. Data achieved in the phase I part of the study showed that DCT 50 mg/m² every 15 days is the recommended dose for phase II studies, while results achieved in the phase II trial suggest that DCT 50 mg/m² in a bimonthly schedule is active as second-line chemotherapy for MBC being able to induce an ORR in the range reported for DCT 75–100 mg/m² every 3 weeks. The bimonthly schedule is, however, associated with relatively low toxicity. This characteristic may render the bimonthly schedule particularly attractive for future phase II trials of DCT in combination with other antineoplastic agents.     

Treatment of desmoids and mesenteric fibromatosis in familial adenomatous polyposis with raloxifene

BACKGROUND: Among the great variety of extracolonic manifestations of familial adenomatous polyposis, the most serious are desmoids and fibromatosis of the abdominal cavity. These may be a danger to the patient and a concern to the clinician. Pharmacological management of this relentless problem is favored by surgical intervention. At present, however, beneficial actions of medical therapy are not separable from undesirable side effects. METHODS: We studied the effects of 120 mg daily of raloxifene, a non-steroidal benzothiophene, on progressive desmoid tumors and mesenteric fibromatosis by evaluation of lesion size and symptoms in 13 patients with familial adenomatous polyposis, selected on the basis of intra-abdominal localization of the lesion, on refractoriness to other medical treatments, and on estrogen receptor-alpha expression. RESULTS: The patients had a significant response to raloxifene therapy, with complete remission in 8 cases and partial response in 5 cases, evaluated by regression of symptoms and tumor size. Serum biochemical parameters did not show any significant changes. Side effects were never observed. CONCLUSIONS: Although the number of patients included in the study is limited and in spite of some limitations, the available results support that, in the evaluation of response, daily therapy with raloxifene decreases desmoid tumor and mesenteric fibromatosis size and symptoms and does not cause side effects. These findings offer a novel option in the pharmacological treatment of desmoids, leading to medical therapy of these neoplastic lesions in familial adenomatous polyposis patients.     

Sleep-related changes in baroreflex sensitivity and cardiovascular autonomic modulation

OBJECTIVE: We examined the effects of the various sleep stages on baroreflex sensitivity (BRS), and heart rate and blood pressure (BP) variability, and tested the hypothesis that there is a different behavior of the baroreflex control of the sinus node in response to hypertensive and hypotensive stimuli and in relation to different cycles of the overnight sleep. DESIGN: Polygraphic sleep recordings were performed in 10 healthy males. The BP and the RR interval were continuously recorded during sleep. METHODS: BRS was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate the RR-interval and BP variabilities. RESULTS: During rapid eye movement (REM) sleep BRS significantly increased in response to hypertensive stimuli in comparison with non-rapid eye movement (NREM) sleep and the awake state, whereas it did not change in response to hypotensive stimuli. In the first sleep cycle, BRS significantly increased during NREM in comparison with wakefulness, whereas during REM BRS in response to hypertensive stimuli did not show significant changes as compared with the awake state and/or with NREM. During REM occurring in the sleep cycle before morning awakening, BRS showed a significant increase in response to hypertensive stimuli in comparison with both NREM and the awake state. CONCLUSIONS: During sleep, arterial baroreflex modulation of the sinus node is different in response to hypotensive and hypertensive stimuli particularly during REM. Furthermore, baroreflex control of the sinus node shows a non-uniform behavior during REM occurring in different nocturnal sleep cycles. These findings suggest that the arterial baroreflex is more effective in buffering the increased sympathetic activation associated with REM at the end of sleep than in the early night.     

A long-term continuous infusion via a sciatic catheter in a 3-year-old boy

We describe the case of a 3-year-old boy with a subtotal amputation of the right foot who received treatment for pain via a peripheral catheter positioned at the level of the sciatic nerve (lateral approach).We administered a continuous infusion of 0.2% ropivacaine, 0.4 mg x kg(-1) x h(-1) plus clonidine 0.12 microg x kg(-1) x h(-1) for 21 days. Pain relief was complete and the patient did not require any further rescue analgesia throughout the period even during medications and surgical treatment in our intensive care unit. We discuss the safety and efficacy of the use of a peripheral continuous infusion in children compared with other techniques of analgesia.     

Sutureless Skin Closure in Varicose Vein Surgery: Preliminary Results

OBJECTIVE: To describe the preliminary results of a special method of wound closure in varicose vein surgery using the tissue adhesive butyl-2-cyanoacrylate. METHODS: Eighteen consecutive young women (mean age 23 years) underwent partial stripping of the greater saphenous vein for varicose veins of the lower limbs by an external phleboextractor. Their wounds were closed without sutures by means of the adhesive butyl-2-cyanoacrylate. The cutaneous edges were drawn together by linear traction between forceps and the adhesive was applied and allowed to set. Less than 0.5 ml of adhesive was required to complete the entire procedure. Wounds were evaluated at 7 days for infection, dehiscence, and tissue reactions. At 6 months all wounds were rated for cosmesis using a validated visual analog scale, that is, a 100 mm line with "worst scar" at the right end of the line and "best scar" at the left end. All patients were interviewed about their acceptance of tissue adhesive skin closure. RESULTS: The mean time required to close the epidermis with the adhesive was 117 seconds. All patients were followed up for 6 months. At 7 days no adverse outcomes had occurred. Results of wound evaluation at 6 months by the visual analog scale showed scores of 22.2 +/- 13.8 mm (optimal). The percentage of optimal scores was 94.4%, and only one patient (5.6%) had a suboptimal score. Inquiry into the patient's opinions suggested that this procedure was very acceptable. CONCLUSION: Preliminary results with sutureless skin closure in varicose vein surgery have been very encouraging. This fast and cosmetic method of wound repair can replace the need for skin sutures in varicose vein surgery.     

Cerebral Sinovenous Thrombosis

Opinion statement  |

Cardiovascular complications in patients with pheochromocytoma: A mini-review

Phaeochromocytomas are rare neuroendocrine tumours secreting high levels of catecholamines, able to exert serious metabolic and cardiovascular effects. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines, especially noradrenaline, the main transmitter released from sympathetic nerve terminals. Hypertension, tachycardia, pallor, headache and anxiety, usually dominate the clinical presentation. Occasionally, patients with predominantly epinephrine-secreting tumours present hypotension or even shock. Other cardiovascular complications of pheochromocytoma include ischaemic heart disease, acute myocardial infarction, cardiac arrhythmias, heart failure due to toxic cardiomyopathy, or pulmonary edema. Catecholamines have been shown to influence the extracellular matrix with collagen deposition and subsequent fibrosis in the arterial wall and in the myocardium. These morphofunctional changes of the myocardium and of arterial wall can be emphasized by ultrasound imaging. Indeed, ultrasound imaging of the myocardium and arterial wall not only identifies wall thickness but also contains information on texture that may be revealed by acoustic tissue characterization. The latter can be quantified through videodensitometric analysis of echographic images or through ultrasonic integrated backscatter signal analysis. This paper reviews cardiovascular complications in patients with pheochromocytoma and utility of the new ultrasound technique as backscatter signal. It is useful for evaluating preclinical pathological morphofunctional changes of the myocardium and arterial wall, characterized by increased collagen content in pheochromocytoma patients. The recognition of early catecholamine-induced alterations in patients with pheochromocytoma, is important to prevent at least morbidity and mortality, before surgical treatment.