Tromboembolismo pulmonar séptico secundário à síndrome de Lemierre / Septic pulmonary thromboembolism due to Lemierre syndrome

Descrita pela primeira vez em 1900 por Coumont e Cade, a tromboflebite séptica da veia jugular interna (síndrome de Lemierre) é uma condição rara. Acomete indivíduos jovens e possui elevada morbimortalidade. Relatamos o caso de uma paciente atendida inicialmente como portadora de amigdalite bacteriana e que retornou com piora do quadro, associado à trombose da veia jugular interna, evoluindo, na internação, com embolia séptica pulmonar. Além de relatar o caso, fazemos breve revisão da literatura e chamamos a atenção sobre este importante assunto.(AU)

First described in 1900 by Coumont and Cade, septic thrombophlebitis of the internal jugular vein (Lemierre's syndrome) is relatively rare. It affects young patients and has high morbidity and mortality. We describe the case of a woman first diagnosed with a bacterial tonsillitis, who returned to the hospital with worsening of the condition, associated with internal jugular vein thrombophlebitis, that developed to pulmonary embolism during her hospitalization. We reported the case, and made a brief review of the literature, highlighting the details of this important condition.(AU)

Calcium micro-depositions in jugular truncular venous malformations revealed by Synchrotron-based XRF imaging.

It has been recently demonstrated that the internal jugular vein may exhibit abnormalities classified as truncular venous malformations (TVMs). The investigation of possible morphological and biochemical anomalies at jugular tissue level could help to better understand the link between brain venous drainage and neurodegenerative disorders, recently found associated with jugular TVMs. To this end we performed sequential X-ray Fluorescence (XRF) analyses on jugular tissue samples from two TVM patients and two control subjects, using complementary energies at three different synchrotrons. This investigation, coupled with conventional histological analyses, revealed anomalous micro-formations in the pathological tissues and allowed the determination of their elemental composition. Rapid XRF analyses on large tissue areas at 12.74 keV showed an increased Ca presence in the pathological samples, mainly localized in tunica adventitia microvessels. Investigations at lower energy demonstrated that the high Ca level corresponded to micro-calcifications, also containing P and Mg. We suggest that advanced synchrotron XRF micro-spectroscopy is an important analytical tool in revealing biochemical changes, which cannot be accessed by conventional investigations. Further research on a larger number of samples is needed to understand the pathogenic significance of Ca micro-depositions detected on the intramural vessels of vein walls affected by TVMs.

c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits, and intimal hyperplasia in human saphenous veins.

Coronary artery bypass graft failure represents an unsolved problem in interventional cardiology and heart surgery. Late occlusion of autologous saphenous vein bypass grafts is a consequence of neointima formation underpinned by smooth muscle cell (SMC) migration and proliferation. Poor long term patency and the lack of pharmacologic agents that prevent graft failure necessitate effective alternative therapies. Our objective here was to evaluate the effect of targeted inhibition of the bZIP transcription factor c-Jun on intimal hyperplasia in human saphenous veins and vein graft stenosis after autologous end-to-side transplantation. DNAzymes targeting c-Jun attenuated intimal hyperplasia in human saphenous vein explants. Adenovirus-forced c-Jun expression stimulated SMC proliferation, proliferating cell nuclear antigen, and MMP-2 expression. c-Jun DNAzymes abrogated Adeno-c-Jun-inducible SMC growth and wound repair and reduced intimal thickening in jugular veins of New Zealand white rabbits 4 weeks after autologous end-to-side transplantation to carotid arteries. Conversely, in a DNAzyme-free setting, Adeno-c-Jun potentiated neointima formation in the veins compared with Adeno-LacZ. Inducible c-Jun expression is ERK1/2- and JNK-dependent but p38-independent. Injury- and shear-inducible c-Jun controls early growth response-1. These data demonstrate that strategies targeting c-Jun may be useful for the prevention of vein graft stenosis. Control of one important shear-responsive transcription factor by another indicates the existence of transcriptional amplification mechanisms that magnify the vascular response to cell injury or stress through inducible transcriptional networks.

Insular carcinoma of the thyroid with jugular vein invasion.

BACKGROUND: Gross angioinvasion with intraluminal tumor thrombus is rarely seen in thyroid cancer, with few cases reported in the literature. METHODS: We report an insular carcinoma of the thyroid displaying this aggressive local invasion and angioinvasion of the internal jugular chain. Complete surgical removal of the intraluminal disease, regional metastasis, and primary tumor was carried out. RESULTS: Adjuvant external beam radiation therapy and iodine-131 were administered, and the patient died with pulmonary metastases 30 months after surgery. No locoregional recurrence was noted at last follow-up. CONCLUSIONS: Treatment of insular carcinoma of the thyroid with invasion of the internal jugular vein is amenable to surgical resection. Postoperative radioactive iodine and external beam radiotherapy can achieve locoregional disease control and prolonged survival.

A single treatment with a specific chymase inhibitor, TY-51184, prevents vascular proliferation in canine grafted veins.

In this study, we evaluated whether a specific chymase inhibitor, TY-51184 (2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl]oxazole-4-carboxylicacid), prevents the vascular proliferation in canine grafted veins. In the placebo-and chymase inhibitor-treated groups, the external jugular vein was infiltrated with saline and 10 microM TY-51184, respectively, and then it was grafted to the ipsilateral carotid artery. The non-surgical dogs were used as the control group. By 28 days after grafting, the chymase and ACE activities were significantly increased in the injured arteries. TY-51184 significantly reduced the chymase activity in the grafted veins, while it did not affect the ACE activity. The intimal areas in the placebo- and TY-51184-treated groups were 3.32 +/- 0.16 and 1.96 +/- 0.52 mm(2), respectively, and this difference was significant. The ratios of intimal area to medial area in the placebo- and TY-51184-treated groups were 66.8 +/- 3.5% and 34.9 +/- 9.2%, respectively, and this difference was also significant. There was a significant relationship between vascular proliferation and chymase activity, but not ACE activity. In this study, we demonstrated that a single treatment with a specific chymase inhibitor, TY-51184, could prevent the vascular proliferation in canine grafted veins.

Characterization of dopamine-mediated relaxation in experimental vein bypass grafts.

BACKGROUND: Dopamine is an endogenous inotropic agent commonly used during coronary artery surgery and in the medical therapy of a revascularized patient. In this study the responses of intimal hyperplastic vein grafts to dopamine are examined. METHODS: The in vitro isometric tension responses to dopamine of common carotid jugular vein bypass grafts in New Zealand White rabbits were determined. The responses were compared to those obtained in the jugular vein and in the common carotid artery. Both endothelialized and denuded vessels were precontracted with prostaglandin F(2alpha) and the responses to dopamine were assessed. The contributions of nitric oxide and prostanoids to the response were also determined. RESULTS: Each vessel showed a biphasic dose response to dopamine with relaxation at low concentrations followed by contraction at high concentrations. Dopamine relaxation in the jugular vein was endothelial independent while in the carotid artery it was endothelial dependent and decreased. The sensitivity of both vessels was significantly greater than the vein graft (6.62 +/- 0.12; P < 0. 05); however, after endothelial denudation, the sensitivity of dopamine-mediated relaxation of the vein graft (8.91 +/- 0.09) was significantly enhanced. Preincubation with L-NMMA (to block NO synthesis) inhibited vein graft relaxation to dopamine and preincubation with indomethacin (to block cyclooxygenase activity) inhibited carotid artery relaxation to dopamine. Addition of phenoxybenzamine, a broad alpha-adrenergic antagonist, enhanced dopamine relaxation in the jugular vein and depressed the relaxation in the carotid artery. There was no effect on the dopamine response in the vein graft. Jugular vein and carotid artery responded to dopamine with cholera toxin-sensitive (Galpha(s)) responses. In contrast, dopamine relaxation in the vein graft was enhanced by inhibition of Galpha(s). CONCLUSION: Dopamine relaxation in vein grafts is mediated in part by NO but not by either prostanoids or alpha-adrenergic receptor activation. It is diminished compared to native vessels due to an endothelium-dependent, Galpha(s)-mediated pathway.

Aportaciones de la SjO2 en la detección precoz de la muerte encefálica / SjO2 contribution in early detection of brain death

El estudio de la sangre venosa obtenido del bulbo de la yugular interna se utiliza como un parámetro más, de la monitorización rutinaria del enfermo neurocrítico. De ello, se infieren parámetros metabólicos cerebrales, por esto, se ha considerado que podría también ser de utilidad para la detección precoz de la situación de muerte encefálica. Se ha realizado una revisión de la literatura, que específicamente abordaba este tema, clasificando sus resultados según el nivel de evidencia con que eran aportados sus datos (AU)

Combination therapy of cholesterol reduction and L-arginine supplementation controls accelerated vein graft atheroma.

Hyperlipidemia contributes to the development of intimal hyperplasia and accelerated atheroma in vein bypass grafts. Dietary cholesterol reduction and oral supplementation with L-arginine have been shown to reduce accelerated atheroma in experimental vein grafts. This study extends these observations by examining the effect of the combination therapy of cholesterol reduction and L-arginine supplementation on the development of intimal hyperplasia in vein grafts in hypercholesterolemic animals. Thirty New Zealand White rabbits had a carotid vein bypass graft performed and were sacrificed at 28 days postoperatively either for morphology (light and electron microscopy) and videomorphometry, or for in vitro contractile studies. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery. This diet was continued until harvest in ten animals. Ten cholesterol-fed animals received L-arginine supplementation (2 g/kg/day, p.o.) for 7 days preoperatively and thereafter until harvest and in addition were returned to a normal diet on the day of surgery. The last ten animals were controls (normal diet). Combined cholesterol reduction and L-arginine supplementation prevented accelerated atheroma in vein grafts, halted the change in enhanced smooth muscle cell contractility, and improved endothelial cell function. Early postoperative therapy targeting atheroma development in the high-risk patient could offer significant morphological and functional benefits.

Management of the neck in thyroid cancer.

The incidence of nodal metastasis in differentiated thyroid cancer ranges between 40% to 75%. Elective neck dissection is generally not advised in patients with differentiated thyroid cancer; however, if clinically apparent nodal disease is noted in the tracheoesophageal groove during surgery, central compartment clearance is advised. If clinically apparent nodal disease is present in the lateral compartment of the neck, modified neck dissection preserving the sternomastoid, accessory nerve, and jugular vein is advised. The "berry picking procedure" is generally not recommended because of the higher incidence of regional recurrence. Due consideration should be given for parathyroidal transplantation if the blood supply to the parathyroids is damaged during central compartment clearance. The incidence of lymph node metastasis is highest in young patients, however, lymph node metastasis has no bearing on long-term survival. There seems to be a higher incidence of regional recurrence in elderly individuals. If patients present with bulky nodal disease, consideration may be given for postoperative radioactive iodine dosimetry and ablation if necessary. Differentiated thyroid cancer represents a unique disease in the human body, where lymph node metastasis has no prognostic implication. Aggressive surgical clearance is advised in patients with medullary thyroid cancer in the central compartment and the jugular chain lymph nodes.

L-arginine inhibits smooth muscle cell proliferation of vein graft intimal thickness in hypercholesterolemic rabbits.

OBJECTIVE: The effect of the chronic administration of L-arginine on intimal thickness and the kinetics of smooth muscle cell proliferation in autovein grafts in hypercholesterolemic rabbits were examined. METHODS: Male rabbits were fed a 1% cholesterol diet (control group) and a 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water (arginine group). Each group underwent reversed autologous vein bypass grafting of the left common carotid artery using the left external jugular vein. At 2 or 4 weeks after operation, intimal cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and intimal thickness of the graft was measured with an ocular cytometer. At 4 weeks after operation, endothelium-dependent responses were examined by isometric tension recording. RESULTS: At 4 weeks after operation, the level of plasma arginine and citrulline are significantly higher in the arginine group (n = 7), compared with the control (n = 7). Intimal thickness in the arginine group (n = 7) was significantly reduced, compared with that of the control (n = 7). At 2 weeks after operation, the BrdU labeling index of the control (n = 5) was significantly higher than that of the arginine group (n = 5). At 4 weeks after operation, ACh caused endothelium-dependent relaxation in the arginine group (n = 4), while in the control (n = 4), ACh did not relax. CONCLUSIONS: These results suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts during hypercholesterolemia occurs at an early stage after graft implantation, prior to the development of intimal thickness. Intimal thickness of vein graft during hypercholesterolemia was reduced by chronic administration of dietary L-arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO production in the blood vessel wall may therefore be useful for preventing late graft failure.

L-arginine supplementation improves venous endothelial cell but not smooth muscle cell dysfunction induced by prolonged diet-induced hypercholesterolemia.

Hypercholesterolemia induces venous vasomotor dysfunction. This study examines the endothelial and smooth muscle cell vasoreactivity of external jugular veins from rabbits fed either a normal or a 1% cholesterol diet for 8 weeks with and without L-arginine supplementation (2 g/kg day-1 orally for the last 5 weeks). Isometric tension studies were performed on harvested jugular veins. Concentrations of serum cholesterol were 20-fold higher than controls and serum L-arginine twofold higher than untreated animals. Hypercholesterolemia induced hypersensitivity to norepinephrine (p < .05), bradykinin (p < .05), and histamine (p < .05) with a contractile response to serotonin compared to controls. L-Arginine supplementation decreased bradykinin hypersensitivity but had no effect on the changes in norepinephrine serotonin and histamine responses compared to controls. Hypercholesterolemia interfered with relaxation induced by acetylcholine but with L-arginine, normal acetylcholine-induced, endothelium-dependent relaxation returned (54 +/- 10%, compared to 40 +/- 14% in control veins; p > .05). Non-endothelium-dependent relaxation to sodium nitroprusside of precontracted veins was unaffected by the presence of high cholesterol concentrations. This study suggests that L-arginine therapy may ameliorate hypercholesterolemia-induced functional abnormalities in endothelial cells.

Suppression of intimal hyperplasia in experimental vein grafts by oral l-arginine supplementation and single ex vivo immersion in deferoxamine manganese.

PURPOSE: Vein grafts undergo morphologic and functional changes after insertion into the arterial circulation with the development of intimal hyperplasia, as well as significant alterations in endothelial and smooth muscle cell physiologic responses. METHODS: Forty New Zealand white rabbits underwent jugular vein interposition grafting of the common carotid artery. Ten animals were controls, 10 animals received 2.25% L-arginine supplementation in their drinking water (200 ml/day; 2 gm/kg) 7 days before surgery and continued thereafter until harvest, in 10 animals the veins were immersed in deferoxamine manganese (DFMn; 10(-3) mol/L in heparinized Ringer's lactate for 15 minutes) before implantation, and 10 received both L-arginine supplementation and either histologic (n=6) or isometric tension studies (n=4). The function of the vein grafts was compared with that of jugular veins. RESULTS: Treatment with DFMn, l-arginine, amd DFMn L-arginine produce increases in mean intimal thickness of 39% (51 +/ -7 microm; p<0.05), 51% (41 +/- 7 microm; p<0.05), and 65% (29 +/- 6 microm; p< 0.01), respectively, compared with control vein grafts (83 +/- 12 microm). Compared with the control group, the intimal ratio ([intima]/[intima + media]) decreased by 16% (difference not significant), 8% (difference not significant), and 47% (p<0.01) in the DFMn-, L-arginine- and and DFMn/L-arginine-treated vein grafts, respectively. Jugular veins relaxed to acetylcholine (53% +/- 12% maximal relaxation), whereas control vein grafts did not relax. In contrast, vein grafts from each of the experimental groups relaxed to acetylcholine with maximal relaxations of 26% +/- 7% (p<0.05 compared with the jugular vein), 22% +/- 8% (p<0.05), and 44% +/- 14% (difference not significant) in the DFMn, L-arginine, DFMn/L-arginine groups, respectively. Neither DFMn nor l-arginine had a significant effect on the alterations in smooth muscle contractility that occur in control vein grafts. CONCLUSION: This study demonstrates that an agent that modulates free radical production combined with a precursor of nitric oxide formation will lead to a significant decrease in the formation of intimal hyperplasia in arterial vein grafts with the preservation of endothelial-derived relaxation.

Ramipril and experimental vein graft intimal hyperplasia.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the intimal proliferation in animal models of arterial angioplasty and vein bypass grafting. This study examines the effect of high-dose ramipril, an ACE inhibitor that does not contain a sulfhydryl group, on the development of intimal hyperplasia in experimental vein bypass grafts. Twenty New Zealand White rabbits underwent common carotid interposition bypass grafting. Twelve were treated with ramipril (2 mg/kg/day; po) five days prior to surgery and thereafter until harvest. The remaining 8 animals were used as controls. Vein grafts were harvested at twenty-eight days by pressure fixation (80 mmHg). The grafts were sectioned into proximal, middle, and distal thirds, and the thickness of the intima and the media and the area of the lumen from each segment were determined by videomorphometry. The effect of ramipril on the [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells (culture passage 6 to 12) was also assessed. There was a 50% mortality rate in the rabbits that received ramipril, and this was assumed to be related to the high dose of the drug. Ramipril treatment reduced mean vein graft intimal area by 34% (P > 0.05), but this was accompanied by an increase of 73% in the mean medial area of the vein grafts as compared with controls. These changes resulted in a decrease in the mean intimal ratio (intima/[intima + media]) by 39% in the ramipril group as compared with controls. Ramipril did not inhibit [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cod-liver oil on intimal hyperplasia in vein grafts used for arterial bypass.

Cod-liver oil rich in eicosapentaenoic acid, an unsaturated fatty acid, has been shown to inhibit platelet aggregation. To determine the effect of this acid on vein-graft intimal hyperplasia, 46 segments of undistended external jugular vein were interposed between the bilaterally divided femoral arteries of 26 mongrel dogs. The animals received a 2% cholesterol diet for 1 week before and 6 weeks after the operation. Eight control animals received the diet alone, eight received cod-liver oil containing 1.8 g of eicosapentaenoic acid daily, for 1 week before and 6 weeks after operation, and seven animals received 1.8 g of eicosapentaenoic acid daily for 6 weeks after operation. Intimal thickness was measured at 6 weeks with a Zeiss computerized interactive image analysing system from multiple cross-sections of vein graft; 395 +/- 10 measurements were made from each graft. The intima measured 4 +/- 0.2 micron (SEM) before implantation and increased to 83 +/- 10 micron in the controls. Eicosapentaenoic acid administered before and after operation reduced intimal hyperplasia to 24 +/- 2.5 micron (p less than 0.001) and to 30 +/- 5 micron in animals receiving eicosapentaenoic acid after operation only (p less than 0.001). These results indicate that the acid inhibits intimal hyperplasia of canine vein grafts but that it is more effective when given before operation (p less than 0.01).

Cod-liver oil in the prevention of intimal hyperplasia in autogenous vein grafts used for arterial bypass.

Cod-liver oil, rich in eicosapentaenoic acid, an unsaturated fatty acid, was administered to 14 mongrel dogs to determine if this acid would prevent platelet-mediated intimal hyperplasia. Twenty-eight 1 cm segments of undistended jugular vein were interposed between bilaterally divided femoral arteries. Seven control animals were fed a 2% cholesterol diet 1 week before and for 6 weeks after the operation. A further seven animals received cod-liver oil capsules containing 1.8 gm of eicosapentaenoic acid daily 1 week before and for 6 weeks after autogenous vein implantation, in addition to the lipid-supplemented diet. Baseline serum cholesterol was 4.6 +/- 0.4 mmol/L. The rise in serum cholesterol was similar in the two groups and increased to 7.4 +/- 0.6 mmol/L (control group) and to 6.8 +/- 0.2 mmol/L (eicosapentaenoic acid group) (p less than 0.001). Prothrombin time, partial thromboplastin time, bleeding time, and platelet counts were unchanged in the two groups. Vein grafts, harvested at 6 weeks, were fixed in formaldehyde. Mean intimal thickness was measured from multiple vein graft cross sections with a Zeiss computerized interactive image analyzing system. A mean of 140 +/- 11 measurements were computed from each graft. Marked intimal hyperplasia occurred in the control group and increased from 4.3 +/- 0.3 to 86.4 +/- 14 micron. In contrast, a high eicosapentaenoic acid diet inhibited intimal hyperplasia, with intimal thickness only increasing from 4.0 +/- 0.4 to 24.8 +/- 2.7 micron (p less than 0.001). These data indicate that eicosapentaenoic acid inhibits platelet-mediated intimal hyperplasia and suggest that cod-liver oil could be used to prevent intimal hyperplasia in vein grafts used for myocardial revascularization.