Is intracerebral hemorrhage a time-dependent phenomenon after successful combined intravenous and intra-arterial therapy?

BACKGROUND AND PURPOSE: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy. METHODS: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2. RESULTS: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33). CONCLUSIONS: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset.

Glucose uptake, utilization, and signaling in GLUT2-null islets.

We previously reported that pancreatic islet beta-cells from GLUT2-null mice lost the first phase but preserved the second phase of glucose-stimulated insulin secretion (GSIS). Furthermore, we showed that the remaining secretory activity required glucose uptake and metabolism because it can be blocked by inhibition of oxidative phosphorylation. Here, we extend these previous studies by analyzing, in GLUT2-null islets, glucose transporter isoforms and glucokinase expression and by measuring glucose usage, GSIS, and glucose-stimulated insulin mRNA biosynthesis. We show that in the absence of GLUT2, no compensatory expression of either GLUT1 or GLUT3 is observed and that glucokinase is expressed at normal levels. Glucose usage by isolated islets was increased between 1 and 6 mmol/l glucose but was not further increased between 6 and 20 mmol/l glucose. Parallel GSIS measurements showed that insulin secretion was not stimulated between 2.8 and 6 mmol/l glucose but was increased by >4-fold between 6 and 20 mmol/l glucose. Stimulation by glucose of total protein and insulin biosynthesis was also markedly impaired in the absence of GLUT2. Finally, we re-expressed GLUT2 in GLUT2-null beta-cells using recombinant lentiviruses and demonstrated a restoration of normal GSIS. Together, these data show that in the absence of GLUT2, glucose can still be taken up by beta-cells, albeit at a low rate, and that this transport activity is unlikely to be attributed to GLUT1 or GLUT3. This uptake activity, however, is limiting for normal glucose utilization and signaling to secretion and translation. These data further demonstrate the key role of GLUT2 in murine beta-cells for glucose signaling to insulin secretion and biosynthesis.

Thromboangiitis obliterans: a rare cause of a reversible Raynaud's phenomenon.

A 25-year-old woman with progressive Raynaud's phenomenon and digital necrosis is presented. Systemic sclerosis and other connective tissue disorders as well as atherosclerosis and arterial emboli were excluded with appropriate laboratory examinations. Arteriography revealed multiple palmar and digital occlusions with corkscrew-shaped vessels. Based on these characteristic arteriographic and clinical findings, the diagnosis of thromboangiitis obliterans was finally retained. With intravenous perfusion of the prostacyclin analogue iloprost (2 ng/kg/min, 6 h daily during 21 days), a complete healing of Raynaud's phenomenon and of the digital necrosis was observed. There was no recurrence during the 1-year follow-up. This observation demonstrates that thromboangiitis obliterans is a potential reversible cause of severe Raynaud's phenomenon in young women even in the absence of lower limb involvement. Early recognition is important to avoid irreversible complications such as loss of digits.

Syndrome hypothénarien du marteau: étiologie peu connue de phénomène de Raynaud secondaire [Hypothenar hammer syndrome: little-known etiology of secondary Raynaud's phenomenon]

Hypothenar hammer syndrome is an uncommonly encountered cause of Raynaud's phenomenon associated with professional or recreational activities. We report 6 consecutive cases seen in our angiology unit between 1988 and 1990. Clinical findings include a history of repeated microtraumatisms of the dominant hand, male sex, unilaterality, sudden onset, and severe Raynaud's phenomenon of the last three fingers. Investigations reveal an aneurysm or thrombosis of the distal cubital artery or of the superficial palmar branch, associated with occlusion of digital arteries. Avoidance of the aggravating conditions or resection and/or plasty of the affected vascular segment usually leads to disappearance of the symptoms.

Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion.

GLUT2-null mice are hyperglycemic, hypoinsulinemic, hyperglucagonemic, and glycosuric and die within the first 3 weeks of life. Their endocrine pancreas shows a loss of first phase glucose-stimulated insulin secretion (GSIS) and inverse alpha to beta cell ratio. Here we show that reexpression by transgenesis of either GLUT1 or GLUT2 in the pancreatic beta cells of these mice allowed mouse survival and breeding. The rescued mice had normal-fed glycemia but fasted hypoglycemia, glycosuria, and an elevated glucagon to insulin ratio. Glucose tolerance was, however, normal. In vivo, insulin secretion assessed following hyperglycemic clamps was normal. In vitro, islet perifusion studies revealed that first phase of insulin secretion was restored as well by GLUT1 or GLUT2, and this was accompanied by normalization of the glucose utilization rate. The ratio of pancreatic insulin to glucagon and volume densities of alpha to beta cells were, however, not corrected. These data demonstrate that 1) reexpression of GLUT1 or GLUT2 in beta cells is sufficient to rescue GLUT2-null mice from lethality, 2) GLUT1 as well as GLUT2 can restore normal GSIS, 3) restoration of GSIS does not correct the abnormal composition of the endocrine pancreas. Thus, normal GSIS does not depend on transporter affinity but on the rate of uptake at stimulatory glucose concentrations.

Effect of SR 49059, a V1a vasopressin receptor antagonist, in Raynaud's phenomenon.

OBJECTIVE: To assess whether vasopressin V1a receptor blockade reduces the abnormal vasoactive response to cold in patients suffering from Raynaud's phenomenon (RP). METHODS: SR 49059, an orally active, non-peptidic vasopressin V1a receptor antagonist, was given orally (300 mg once daily) to 20 patients with RP in a single-centre, double-blind, placebo-controlled, randomized cross-over study with two 7-day periods of treatment separated by 21 days of washout. Bilateral finger systolic blood pressure and skin temperature were assessed before and after immersion of the hand in cold water for 3 min (15 degrees C) during the screening phase and three times (before and 2 and 4 h after drug intake) on days 1 and 7 of each of the two treatment periods. Recovery of digital pressure and skin temperature was measured 0, 10, 20 and 32 min after the end of the cold immersion test. RESULTS: SR 49059 significantly attenuated the cold-induced fall in systolic pressure by 14.5% (95% confidence interval 0-29; P = 0.045) on the most affected hand on day 7 compared with placebo. Temperature recovery after the end of the cold test showed a trend to enhancement 2 and 4 h after SR 49059 on day 7 (P = 0.060 and P = 0.062 respectively). The beneficial effects on finger pressure and temperature recovery were obtained without changes in supine blood pressure or in heart rate. CONCLUSION: SR 49059 given orally once a day for 7 days to patients with RP showed favourable effects compared with placebo on finger systolic pressure and temperature recovery after cold immersion, without inducing side-effects.

Amplitude envelope synchronization in coupled chaotic oscillators.

A peculiar type of synchronization has been found when two Van der PolDuffing oscillators, evolving in different chaotic attractors, are coupled. As the coupling increases, the frequencies of the two oscillators remain different, while a synchronized modulation of the amplitudes of a signal of each system develops, and a null Lyapunov exponent of the uncoupled systems becomes negative and gradually larger in absolute value. This phenomenon is characterized by an appropriate correlation function between the returns of the signals, and interpreted in terms of the mutual excitation of new frequencies in the oscillators power spectra. This form of synchronization also occurs in other systems, but it shows up mixed with or screened by other forms of synchronization, as illustrated in this paper by means of the examples of the dynamic behavior observed for three other different models of chaotic oscillators.

Chaotic systems with a null conditional Lyapunov exponent under nonlinear driving.

Control of a chaotic system by homogeneous nonlinear driving, when a conditional Lyapunov exponent is zero, may give rise to special and interesting synchronizationlike behaviors in which the response evolves in perfect correlation with the drive. Among them, there are the amplification of the drive attractor and the shift of it to a different region of phase space. In this paper, these synchronizationlike behaviors are discussed, and demonstrated by computer simulation of the Lorentz model [E. N. Lorenz, J. Atmos. Sci. 20 130 (1963)] and the double scroll [T. Matsumoto, L. O. Chua, and M. Komuro, IEEE Trans. CAS CAS-32, 798 (1985)].

Prognostic significance of nailfold capillary microscopy in patients with Raynaud's phenomenon and scleroderma-pattern abnormalities. A six-year follow-up study.

The aim of this study was to assess the prognostic significance of scleroderma capillary pattern (SD-pattern) in patients with Raynaud's phenomenon. Thirty patients with a capillaroscopy examination suggestive of scleroderma (megacapillaries and/or avascularity) but without clinical criteria of scleroderma (ARA criteria) were reevaluated 6 years after the initial clinical and capillaroscopy examinations. SD-pattern abnormalities were classified according to a semiquantitative method. Eight out of the 28 evaluated patients (28%) developed a scleroderma spectrum disorder (SDS). The presence of avascularity and/or a mean of more than two megacapillaries digit greatly enhanced the percentage of evolution toward SDS (70%/88% respectively). Most of the patients with few enlarged capillaries and no capillary rarefaction at entry had primary acrocyanosis (11/15). None of them developed SDS. The microangiopathy disappeared during the follow-up period in most of these patients (14/15). These results confirm the prognostic value of SD-pattern capillary abnormalities for SDS. Primary acrocyanosis, a benign clinical entity should be considered in presence of few megacapillaries and without capillary rarefaction.

The null divergence factor

Let (P, Q) be a C 1 vector field defined in a open subset U ⊂ R2 . We call a null divergence factor a C 1 solution V (x, y) of the equation P ∂V + Q ∂V = ∂P + ∂Q V . In previous works ∂x ∂y ∂x ∂y it has been shown that this function plays a fundamental role in the problem of the center and in the determination of the limit cycles. In this paper we show how to construct systems with a given null divergence factor. The method presented in this paper is a generalization of the classical Darboux method to generate integrable systems.