Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans.

BACKGROUND: The metabolism of tryptophan (Trp) along the kynurenine pathway has been shown to carry strong immunoregulatory properties. Several experimental studies indicate that this pathway is a major regulator of vascular inflammation and influences atherogenesis. Knowledge of the role of this pathway in human atherosclerosis remains incomplete. OBJECTIVES: In this study, we performed a multiplatform analysis of tissue samples, in vitro and in vivo functional assays to elucidate the potential role of the kynurenine pathway in human atherosclerosis. METHODS AND RESULTS: Comparison of transcriptomic data from carotid plaques and control arteries revealed an upregulation of enzymes within the quinolinic branch of the kynurenine pathway in the disease state, whilst the branch leading to the formation of kynurenic acid (KynA) was downregulated. Further analyses indicated that local inflammatory responses are closely tied to the deviation of the kynurenine pathway in the vascular wall. Analysis of cerebrovascular symptomatic and asymptomatic carotid stenosis data showed that the downregulation of KynA branch enzymes and reduced KynA production were associated with an increased probability of patients to undergo surgery due to an unstable disease. In vitro, we showed that KynA-mediated signalling through aryl hydrocarbon receptor (AhR) is a major regulator of human macrophage activation. Using a mouse model of peritoneal inflammation, we showed that KynA inhibits leukocyte recruitment. CONCLUSIONS: We have found that a deviation in the kynurenine pathway is associated with an increased probability of developing symptomatic unstable atherosclerotic disease. Our study suggests that KynA-mediated signalling through AhR is an important mechanism involved in the regulation of vascular inflammation.

A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion.

CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.

Smoking alters circulating plasma microvesicle pattern and microRNA signatures.

Circulating plasma microvesicles (PMVs) and their microRNA content are involved in the development of atherosclerosis and could serve as biomarkers for cardiovascular disease (CVD) progression. However, little is known on how smoking influences the levels of PMVs and microRNA signatures in vivo. Therefore, we aimed to investigate the effects of smoking on circulating PMV levels and CVD-related PMV-derived microRNAs in young, healthy smokers. Twenty young (10 female, 10 male; 25 ± 4 years) healthy smokers (16 ± 6 cigarettes per day for 8 ± 4 years) and age- and sex-matched controls were included in this study. While complete blood count revealed no differences between both groups, smoking significantly enhanced intracellular reactive oxygen species in platelets and leukocytes as well as platelet-leukocyte aggregate formation. Total circulating PMV counts were significantly reduced in smokers, which could be attributed to decreased platelet-derived PMVs. While the number of endothelial PMVs remained unaffected, smoking propagated circulating leukocyte-derived PMVs. Despite reduced total PMVs, PMV-derived microRNA-profiling of six smoker/control pairs revealed a decrease of only a single microRNA, the major platelet-derived microRNA miR-223. Conversely, miR-29b, a microRNA associated with aortic aneurysm and fibrosis, and RNU6-2, a commonly used reference-RNA, were significantly up-regulated. Smoking leads to alterations in the circulating PMV profile and changes in the PMV-derived microRNA signature already in young, healthy adults. These changes may contribute to the development of smoking-related cardiovascular pathologies. Moreover, these smoking-related changes have to be considered when microRNA or PMV profiles are used as disease-specific biomarkers.

The joint contribution of tumor phenotype and education to breast cancer survival disparity between Hispanic and non-Hispanic white women.

Some studies suggest that Hispanic women are more likely to have ER- and triple-negative (ER-/PR-/HER2-) tumors and subsequently poorer prognosis than non-Hispanic white (NHW) women. In addition, only a handful of studies have examined period-specific effects of tumor phenotype and ethnicity on breast cancer survival, leaving the time-varying effects of hormonal status and ethnicity on breast cancer survival poorly defined. This study describes short and long-term breast cancer survival by ethnicity at 0-5 years and 5+ years post-diagnosis using data from the New Mexico Health, Eating, Activity, and Lifestyle cohort of Hispanic and NHW women ages 29-88 years newly diagnosed with stages I-IIIA breast cancer. The survival rate for Hispanics at 0-5 years was 82.2 % versus 94.3 % for NHW. Hispanics were more likely to have larger tumors, more advanced stage, and ER- phenotypes compared to NHW women. There was a significantly higher risk of breast cancer mortality in Hispanics over 5 years of follow-up compared to NHW (HR = 2.78, 95 % CI 1.39-5.56), adjusting for age, tumor phenotype, stage, and tumor size. This ethnic difference in survival, however, was attenuated and no longer statistically significant when additional adjustment was made for education, although a >1.5-fold increase in mortality was observed. In contrast, there was no difference between ethnic groups for survival after 5 years (HR = 1.08, 95 % CI 0.36-3.24). Our results indicate that the difference in survival between Hispanic and NHW women with breast cancer occurs in the first few years following diagnosis and is jointly associated with tumor phenotype and socio-demographic factors related to education.

[Chylothorax in an 87-year-old patient]. / Chylothorax bei einer 87-jährigen Patientin.

An 87-year-old woman presented with a left-sided pleural effusion. The milky aspirate fulfilled the criteria of a chylothorax. Thorax computed tomography (CT) showed characteristic multiple cysts and consequently the rare diagnosis of post-menopausal pulmonary lymphangioleiomyomatosis was made. In the diagnostic work-up of pleural effusion the determination of triglycerides should be considered to confirm the diagnosis of chylothorax. In the presence of a chylothorax the differential diagnosis of lymphangioleiomyomatosis should be included even in advanced age.

Zurich Fabry study - prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA.

BACKGROUND AND PURPOSE: The etiology of stroke in young patients remains undetermined in up to half of the cases. Data on prevalence of Fabry disease (FD) in young people with cryptogenic ischaemic stroke are limited and controversial. We aimed to evaluate the frequency of unrecognized FD in a cohort of stroke patients at a tertiary stroke center. METHODS: Patients suffering from first cryptogenic ischaemic stroke or transient ischaemic attack (TIA) at the age of 18-55 years were screened for the presence of FD. We measured the serum activity of α-galactosidase (α-GAL) in all patients. In addition, sequencing of α-GAL gene was performed in men with low enzyme activity and in all women. RESULTS: Between January, 2006, and October, 2009, we recruited 150 patients (102 men, 48 women) with a mean age of 43 ± 9 years at symptom onset (135 ischaemic stroke, 15 TIA). The α-GAL activity was low in nine patients (6%; six men and three women). Genetic sequencing in six men with low enzyme activity and all 48 women detected no α-GAL gene mutation. CONCLUSION: Our study suggests that the yield of screening for FD in patients with first cryptogenic ischaemic stroke or TIA is very low. Further large-scale studies are needed to investigate the importance of FD amongst patients with recurrent cryptogenic strokes.

[Knee disarticulation and through-knee amputation]. / Knieexartikulation und transgenikuläre Amputation.

OBJECTIVE: A knee disarticulation or a through-knee stump is superior compared to a transfemoral stump. The thigh muscles are all preserved, and the muscle balance remains undisturbed. The range of motion of the hip joint is not limited. The bulbous shape of the stump allows full weight bearing at the stump end and can easily be fitted with a prosthesis. An amputee with a bilateral knee disarticulation is able to walk "barefoot". INDICATIONS: A more distal amputation level, e.g., an ultra-short transtibial amputation, is not possible. Important alternative to transfemoral amputations. Possible for any etiology except for Buerger-Winiwarter's disease. New indications are infected and loosened total knee replacements. CONTRAINDICATIONS: Preservation of the knee joint is possible. SURGICAL TECHNIQUE: Knee disarticulation is a very atraumatic procedure, compared to transfemoral amputations. Neither bones nor muscles have to be severed, just skin, ligaments, vessels, and nerves. Even the meniscal cartilages may be left in place to act as axial shock absorbers. The cartilage of the femur is not resected, but only bevelled in case of osteoarthritis. There are no tendon attachments or myoplastic procedures necessary. The patella remains in place and is held in position only by the retinacula. Skin closure must be performed without the slightest tension, and if possible not in the weight-bearing area. Transcondylar amputations across the femoral condyles only are indicated when there are not sufficient soft tissues for wound closure of a knee disarticulation. Alternatives as the techniques of Gritti, Klaes, and Eigler, the shortening of the femur and the Sauerbruch's rotation plasty [14] are presented and discussed. POSTOPERATIVE MANAGEMENT: The risk of decubital ulcers is rather high. Correct bandaging of the stump is, therefore, particularly important. Prosthetic fitting is possible 3-6 weeks after surgery. The type of prosthesis depends on the amputee's activity level. RESULTS: The superior performance of amputees with knee disarticulations in sports prove the superiority of that amputation level compared to transfemoral amputees. However, because less than 5% of amputations are knee disarticulations, statements about statistical significance cannot be made. On the other hand, one should do everything to preserve an ultra-short transtibial stump.

[Transtibial amputation]. / Unterschenkelamputation.

OBJECTIVE: To make a transtibial stump as long as possible, free from local and phantom pain with a maximum of terminal load bearing. In order to preserve the knee joint, an ultra-short tibial stump of 5-6 cm may be indicated. INDICATIONS: A hindfoot amputation level is not possible to achieve. CONTRAINDICATIONS: In amputations for peripheral vascular diseases, amputations through the distal third of the tibia are not recommended. If they still heal, the level selection might have been too proximal. SURGICAL TECHNIQUE: According to Verduyn and Burgess, a long posterior muscular flap covering the stump is attached ventrally to a short anterior flap. Modifications: fibular bone bridge (Guedes), resection of the soleus muscle (Baumgartner), Myodesis (Bowker), and Brückner's procedure. Alternative: rotation plasty according to Borggreve-van Nes-Winkelmann. POSTOPERATIVE MANAGEMENT: Special diagonal elastic bandaging over the knee that must be changed daily. Early prosthetic fitting (in general after 4-6 weeks) after wound has healed. Physical therapy: gait training with 2 crutches or parallel bars with or without an inflatable "prosthesis". Isometric training of the quadriceps. A stump requires several months until it has achieved its final form. During this time, the prosthesis must be adjusted accordingly. Modifications in the home, workplace, and automobile must be made. Sport for the disabled! RESULTS: In order to preserve a maximum of stump length, wound healing problems are to be taken into consideration, requiring surgery and sometimes even reamputation through or above the knee joint. If it is possible to preserve the knee joint, the rehabilitation results, even with an ultra-short transtibial stump, are far superior to any more proximal amputation level.

[Forefoot and midfoot amputations]. / Amputationen an Vor- und Mittelfuß

OBJECTIVE: Partial foot amputations are feasible regardless of the causal condition, including peripheral vascular disease with a few exceptions. Compared to higher amputation levels, a good foot stump permits full end bearing and enables the patient, even with a hindfoot stump, to walk without the need for a prosthesis. The more peripheral the amputation level selected, the greater the need for gentle tissue handling and meticulous postoperative care, but also the greater the risk of a breakdown requiring stump revision surgery. In the forefoot, partial amputation of the metatarsals preserves the length of the stump and, thus, minimizes the loss of weight-bearing surface. The resection of metatarsal and midfoot bones without removing the toes, called a "hidden" amputation, is more acceptable to the patient who does not feel as if he/she has become an amputee. In addition, no neuroma or phantom pain is experienced. Biomechanically, this amputation hardly differs from a classical amputation. INDICATIONS: Amputation cannot be avoided by any conservative or operative means. CONTRAINDICATIONS: Absolute: rapidly progressing peripheral arterial diseases, i.e., Buerger-Winiwarter's disease. Relative: renal failures requiring dialysis or kidney transplantation. SURGICAL TECHNIQUE: Patient in prone position, keep foot and calf free, protect heel from pressure. Mark the skin incisions. A long plantar flap covers the bones and is sutured to the short dorsal flap at the dorsum of the foot. Begin with the dorsal incision down to the bones. After separating the bones, turn the distal part down and separate the plantar soft tissue flap. The bones are well aligned and shaped. Longitudinal amputations preserve a larger load-bearing surface and, therefore, are preferred, if possible. Another alternative is the "hidden" amputation. Except for amputations in peripheral vascular diseases, the digits and their neurovascular supplies are preserved. Only the bones are resected, from transmetatarsal to Chopart. The toes will retract within a few weeks. The patients do not feel as if she/he has become an amputee, although the biomechanics of the foot are about the same as after a total amputation. In case of infection, wound debridement, open wound treatment, and delayed primary closure are recommended. POSTOPERATIVE MANAGEMENT: Full plantar weight bearing in plaster cast or walker is possible 4-6 weeks after surgery. In the case of diabetic foot, healing can require weeks. Total contact prosthesis without limiting the range of motion (ROM) of the ankle and the subtalar joint after 6 weeks. Best results are obtained with prostheses using the silicone technique. Alternative: orthopedic footwear. RESULTS: It is desirable to maintain the greatest length possible; wound healing disorders are observed in over half of all cases. Operative stump corrections are justified in 20-30%; a transtibial amputation is seldom necessary.

[Progressive dyspnoea in two patients with carcinoid syndrome]. / Progrediente Dyspnoe bei Karzinoidsyndrom.

In patients with carcinoid syndrome, there has always to be considered cardiac impairment. We report about two patients with hepatic and bone metastases of a neuroendocrine tumor of the midgut, who suffered from progressive dyspnea. This was caused in both cases by a right-to-left atrial shunt, in case 1 based on a patent foramen ovale (PFO), in case 2 based on a secundum atrial septal defect. Symptoms were significantly reduced by percutaneous closure of PFO and ASD, respectively. Right-to-left atrial shunt was facilitated by right-sided carcinoid induced endocardial fibrosis with the consequence of severe tricuspid regurgitation, leading to an increase of right atrial pressure.

Vascular risk factors and morphometric data in cervical artery dissection: a case-control study.

BACKGROUND: Limited knowledge exists on vascular risk factors, body height and weight in patients with spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: In this case-control study, major vascular risk factors, body weight, body height and body mass index (BMI) of 239 patients obtained from a prospective hospital-based sCAD registry were compared with 516 age- and sex-matched healthy controls undergoing systematic health examinations in the Clinical and Preventive Investigations Center, Paris. Gender-specific analyses were performed. RESULTS: The mean body height was higher in sCAD patients than in controls (171.3 cm (SD 8.6) vs 167.7 cm (8.9); p<0.0001) and sCAD patients had a significantly lower mean body weight (67.5 (12.2) kg vs 69.3 (14.6) kg; p<0.001) and mean BMI (22.9 (3.3) kg/m2 vs 24.5 (4.2) kg/m2; p<0.0001) than controls. The overall frequency of hypertension, diabetes, current smoking, past smoking and hypercholesterolaemia did not differ significantly between sCAD patients and controls. The mean total plasma cholesterol level was identical in both groups (5.5 mmol/l, SD 1.1). Gender specific subgroup analyses showed similar results for men and women. CONCLUSION: Patients with sCAD had a higher body height and a lower body weight and BMI than controls, while major vascular risk factors were similar in sCAD patients and controls.

Triple and quadruple spontaneous cervical artery dissection: presenting characteristics and long-term outcome.

BACKGROUND: Spontaneous cervicocephalic artery dissection (sCAD) of more than two cervical arteries is rare. PATIENTS AND METHODS: Vascular and potential sCAD risk factors, triggering events, clinical and neuroimaging findings, and outcome of patients with multiple sCAD were studied. Patients were drawn from prospective hospital-based sCAD registries. RESULTS: Of 740 consecutive patients with sCAD, 11 (1.5%) had three, and one had four (0.1%) sCAD. Eight of these 12 patients were women. One patient had additional dissections of the celiac trunk and hepatic artery. Vascular risk factors included hypertension (n = 1), hypercholesterolaemia (n = 6), current smoking (n = 5) and migraine (n = 6). No patient had a family history of sCAD, fibromuscular dysplasia (FMD) or connective tissue disease. SCAD was preceded by a minor trauma in five and infection in four patients. Clinical manifestations included ischaemic stroke (n = 8), transient ischaemic attack (n = 3), headache (n = 9), neck pain (n = 4), Horner syndrome (n = 5), pulsatile tinnitus (n = 2) and dysgeusia (n = 1). Brain MRI revealed ischaemic infarcts that affected one vessel territory in seven and two territories in two patients. The 3-month outcome was favourable (modified Rankin scale score 0-1) in 10 patients (83%). No new recurrent stroke or sCAD occurred during a mean follow-up of 50 (SD 29) months. CONCLUSION: Multiple sCAD occurred preferentially in women and caused clinical symptoms and signs mainly in one vascular territory. In none of the patients was FMD or any other underlying arteriopathy apparent. The majority of multiple sCAD was preceded by a minor trauma or infection. Clinical outcome was favourable in most patients, and long-term prognosis benign. The data suggest that transient vasculopathy may be a major mechanism for multiple sCAD.

Inhalation of vasoactive intestinal peptide in pulmonary hypertension.

Pulmonary hypertension (PH) leads to an increased right ventricular workload, cardiac failure and death. In idiopathic pulmonary arterial hypertension (PAH) the vasodilating vasoactive intestinal peptide (aviptadil) is deficient. The aim of the present study was to test the acute effects on haemodynamics and blood gases, and the safety, of a single dose of inhaled aviptadil in chronic PH. A total of 20 patients with PH (PAH in nine, PH in lung disease in eight and chronic thromboembolic PH in three) inhaled a single 100-microg dose of aviptadil during right-heart catheterisation. Haemodynamics and blood gases were measured. Aviptadil aerosol caused a small and temporary but significant selective pulmonary vasodilation, an improved stroke volume and mixed venous oxygen saturation. Overall, six patients experienced a pulmonary vascular resistance reduction of >20%. In patients with significant lung disease, aviptadil tended to improve oxygenation. The pulmonary vasodilating effect of aviptadil aerosol was modest and short-lived, did not cause any side-effects and led to a reduced workload of the right ventricle without affecting systemic blood pressure. Aviptadil inhalation tended to improve oxygenation in patients with significant lung disease. Further studies are needed to evaluate the full therapeutic potential of aviptadil aerosol, including higher doses and chronic treatment.

Single center experience with provisional abciximab therapy in complex lower limb interventions.

BACKGROUND: Abciximab, a glycoprotein IIb/IIIa antagonist has been shown to improve patency and clinical outcome in patients undergoing endovascular recanalization of femoro-popliteal occlusions. However, data on abciximab therapy in complex peripheral catheter interventions of lower limbs are quite limited. The objective of this retrospective study was to evaluate the clinical and hemodynamic outcomes of patients treated with provisional abciximab during complex peripheral catheter interventions. PATIENTS AND METHODS: Analysis of a consecutive series of 44 patients with provisional abciximab therapy in complex peripheral catheter interventions with imminent risk of early rethrombosis defined as revascularization of arterial occlusions associated with one or more of the following additional circumstances named as time-consuming intervention > 3 hours, compromised contrast flow not solved by stenting, distal embolization not solved by mechanical thromboembolectomy, and peri-interventional notice of thrombus evolution despite adequate heparin adjustment of lower limbs. Adjunctive abciximab therapy was started in accordance to percutaneous coronary bailout situations. The decision to add abciximab was based on the decision of the operator and went along with the judgement that there is a rising risk of reocclusion due to the progressive complexity of an individual intervention. A bolus of 0.25 mg per kilogram of body weight, followed by a maintenance infusion of 0.125 microg/kg/min (up to a maximum dosage of 10 microg/min) for 12 hours was administered. Clinical and hemodynamic outcome was prospectively assessed at discharge, three and six months after the index procedure. RESULTS: The occluded artery of 44 limbs was in the iliac (2%), in the femoro-popliteal (73%) or below the knee segment (25%). Overall, occlusion length was 11.5 +/- 6.5 cm. Technical success rate was 95%. Mean ABI increased from 0.5 +/- 0.16 to 0.88 +/- 0.19 (p < 0.001) with immediate hemodynamic improvement of 91%. Overall, sustained clinical improvement was 84% and 66% at three and six months follow-up, with best results in iliac (100%), followed by below the knee (73%) and by femoro-popliteal segment (63%) at six months, respectively. Overall, secondary clinical improvement was 86% at six months. Minor and major bleeding complications were 16% and 9%, respectively. CONCLUSION: Abciximab should be noticed as medical adjunct in the interventional armamentarium to prevent imminent rethrombosis in complex peripheral catheter interventions.

Behaviors underlying the use of nonvitamin nonmineral dietary supplements in a healthy elderly cohort.

OBJECTIVE: The purpose of the study was to examine factors underlying the decision to use nonvitamin, nonmineral (NVNM) dietary supplements in a healthy elderly cohort. DESIGN: Questionnaires were administered to probe for perceived health status, health insurance coverage, income level, monthly expenditure for supplements, duration of supplement use, information source, disclosure of supplement taking to physician, reasons for NVNM supplements use and perceived benefits, use of supplements to replace or complement a medication, and usual purchasing place. SETTING/PARTICIPANTS: Between 1999- 2001, 418 elderly males (34.7%) and females (65.3%) ages 60-96 years were surveyed. RESULTS: Nonvitamin nonmineral supplement "consumers" and "non-consumers" were not significantly different for sex, age, ethnicity, perceived health status, income level, and health insurance access. The average consumer took three NVNM supplements and spent significantly more money on supplements than non-consumers (p < 0.001). Over 44% of consumer's responses indicated that they had been using NVNM supplements for over 2 years. Literature/media were predominately the source of information with mail order being the most frequent method of purchase. Over 39% of consumer's responses showed that supplement use was revealed to a physician. Arthritis, memory improvement, and general health and well-being were the main reasons to use NVNM supplements. Less joint pain/improved mobility was the main perceived improvement from taking NVNM supplements. Overall, over 53% of consumer's responses showed that no change was noticed from taking NVNM supplements. CONCLUSIONS: Although the most commonly reported responses by those noticing change from NVNM supplement use were improved mobility and less joint pain, over half of the responses indicated that they did not feel any benefit from taking supplements, yet continued to purchase and take them. Communication of NVNM supplement use to their physician was low. More studies are needed to investigate what influences the decision to continue supplement use regardless of the lack of efficacy, considerable cost, and potential risks.

Influence of secondary infection on amputation in chronic critical limb ischemia.

OBJECTIVES: To evaluate the influence of secondary infection on major amputation in chronic critical leg ischemia (CLI). DESIGN: Prospective, controlled observational study. MATERIALS AND METHODS: Sixty-seven patients with CLI and ischemic lesions participated in the study. Presence of infection was defined by clinical, laboratory and radiological criteria. Patients were categorized as having no local infection, soft tissue infection or osteomyelitis treated without antibiotics, amoxicillin/clavulanacid for 1 month or ciprofloxacin and clindamycin for 3 months, respectively. Clinical outcome was assessed at 2, 6 and 12 months. Study endpoints were major amputation and mortality. Analyses were performed using the Kaplan-Meier method. RESULTS: Forty-seven of 67 patients had a local infection. Major amputation was lower in patients with successful revascularization as compared to patients unsuitable for or with failed (without) revascularization (0% vs 26%, p<0.01). In patients with successful revascularization the probability of complete healing was lower with secondary infection (23% vs 71%, p=0.03). In patients without revascularization complete healing was rare (<10%), but secondary infection did not influenced major amputation, mortality or serious adverse events. CONCLUSION: Secondary infection reduces the likelihood of successful healing following revascularisation of CLI.

Low frequency of colorectal dysplasia in patients with long-standing inflammatory bowel disease colitis: detection by fluorescence endoscopy.

BACKGROUND AND STUDY AIM: Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colonic dysplasias. Dysplastic changes in flat mucosa are likely to be missed by conventional colonoscopy. Endoscopic fluorescence imaging, using 5-aminolevulinic acid (5-ALA) as photosensitizer, has evolved as a new technique to differentiate between normal colonic mucosa and dysplasia. We combined this technique with random biopsies to prospectively evaluate the occurrence of dysplasias in patients with long-standing IBD. PATIENTS AND METHODS: 52 colonoscopies were performed in 42 consecutive patients (n = 28 with ulcerative colitis, n = 11 with Crohn's colitis, n = 3 with indeterminate colitis; mean age 43 years, range 21 - 78) with long-standing IBD colitis (median disease duration 14 years, range 3 - 40). All patients were in clinical remission. Patients were examined using both conventional white light and by fluorescence colonoscopy using oral 5-ALA. Four biopsies were taken every 10 cm from mucosa of normal appearance. In addition, macroscopically suspicious and fluorescence-positive areas were biopsied. RESULTS: A total of 688 biopsies of red-fluorescent (n = 20) and nonfluorescent (n = 662) areas of mucosa were taken. Dysplasia was detected histopathologically in only two of the biopsies. These biopsies were taken from two polypoid lesions which were fluorescence-negative. CONCLUSIONS: The rate of colonic dysplasia in patients with long-standing IBD colitis may be lower than previously reported.

Management of asymptomatic carotid stenosis in patients undergoing general and vascular surgical procedures.

Current available data do not seem to support the strategy for carotid endarterectomy prior to surgical intervention in patients with asymptomatic carotid stenosis. However, in patients with coronary artery disease, synchronous carotid endarterectomy and coronary artery bypass grafting should be considered where there is a proven surgical risk of <3% with unilateral asymptomatic stenosis >60% or bilateral carotid stenosis >75% on the same side as the most severe stenosis. Clarification of the optimal strategy requires an adequately powered, multicentre, randomised clinical trial.

Malignant seminoma with metastasis, Sertoli cell tumor, and pheochromocytoma in a spotted dolphin (Stenella frontalis) and malignant seminoma with metastasis in a bottlenose dolphin (Tursiops truncatus).

Seminoma with metastasis was diagnosed in a spotted dolphin (Stenella frontalis) and an Atlantic bottlenose dolphin (Tursiops truncatus). Sertoli cell tumor and pheochromocytoma were also diagnosed in the spotted dolphin. The spotted and bottlenose dolphins were adult males that stranded and died on the coasts of northwest Florida and southeast North Carolina, respectively. Neoplasia is infrequently reported in cetaceans. This is the first report of seminoma, Sertoli cell tumor, and pheochromocytoma in a dolphin, the first report of three distinct neoplasms in a dolphin, and one of the few reports of malignant neoplasia in dolphins.

Traumatic cervical artery dissection.

Traumatic cervical artery dissection (TCAD) is a complication of severe blunt head or neck trauma, the main cause being motor vehicle accidents. TCAD are increasingly recognized, and incidences of up to 0.86% for internal carotid and 0.53% for traumatic vertebral artery dissections (TVAD) among blunt trauma victims are reported. Diagnostic evaluation for TCAD is mandatory in the presence of (1) hemorrhage of potential arterial origin originating from the nose, ears, mouth, or a wound; (2) expanding cervical hematoma; (3) cervical bruit in a patient >50 years of age; (4) evidence of acute infarct at brain imaging; (5) unexplained central or lateralizing neurological deficit or transient ischemic attack, or (6) Horner syndrome, neck or head pain. In addition, a number of centers screen asymptomatic patients with blunt trauma for TCAD. Catheter angiography is the standard of reference for diagnosis of TCAD. Color duplex ultrasound, computed tomographic, and magnetic resonance angiography are noninvasive screening alternatives, but each method has its diagnostic limitations compared to catheter angiography. Anticoagulants and antiplatelet drugs may prevent ischemic stroke, but bleeding from traumatized tissues may offset the benefits of antithrombotic treatment. Endovascular therapy of dissected vessels, thrombarterectomy, direct suture of intimal tears, and extracranial-intracranial bypass should be considered in exceptional cases. Neurological outcome is probably worse in TCAD compared to spontaneous CAD, although it is unclear whether this is due to dissection-induced ischemic stroke or associated traumatic lesions.