Neointimal proliferation within carotid stents is more pronounced in diabetic patients with initial poor glycaemic state.

AIMS/HYPOTHESIS: We studied the influence of initial hyperglycaemia on neointimal proliferation within carotid Wallstents. METHODS: A total of 112 patients were followed by duplex sonography after carotid stenting for 24 months. Patients were assigned to three groups: non-diabetic subjects (group A) and diabetic patients, who were assigned according to their baseline HbA(1)c values, to group B1(HbA(1)c6.5%). RESULTS: At baseline the groups did not differ with respect to other vascular risk factors and residual stenosis on angiograms. The maximal thickness of the layer between the stent and the perfused lumen was measured at the duplex follow-ups. At 3 months the typical ultrasonic structure of the neointima was clearly discernible. From this point on, group B2 differed significantly ( p<0.001) compared with B1 and A with respect to the maximal thickness of neointima and the time course of its ingrowth: group A vs B1 vs B2 was 0.51+/-0.39 vs 0.52+/-0.33 vs 0.56+/-0.35 at 3 months, 0.91+/-0.27 vs 0.90+/-0.38 vs 1.14+/-0.48 at 6 months, 1.02+/-0.24 vs 0.97+/-0.34 vs 1.21+/-0.44 at 12 months and 1.09+/-0.23 vs 1.10+/-0.31 vs 1.23+/-0.37 at 24 months. CONCLUSION/INTERPRETATION: Initial hyperglycaemia seems to be a predictor of more pronounced neointimal proliferation after carotid stenting independent of diabetes. As intimal hyperplasia is known to be responsible for stent restenosis, strict optimisation of the hyperglycaemic state should be aimed at before elective carotid artery stenting.

Influence of lipoprotein(a) on restenosis after femoropopliteal percutaneous transluminal angioplasty in Type 2 diabetic patients.

OBJECTIVE: The influence of vascular morphology and metabolic parameters including lipoprotein(a) (Lp(a)) on restenosis after peripheral angioplasty has been compared in Type 2 diabetes (DM) vs. non-diabetic patients (ND). RESEARCH DESIGN AND METHODS: The clinical course and risk profile of 132 (54 DM vs. 78 ND) patients with peripheral arterial occlusive disease (PAD) were observed prospectively following femoropopliteal angioplasty (PTA). Clinical examination, oscillometry, ankle brachial blood pressure index (ABI) and the toe systolic blood pressure index (TSPI) were used during follow-up. Duplex sonography and reangiography were also used to verify suspected restenosis or reocclusion. RESULTS: At the time of intervention patients with DM had a lower median Lp(a) of 9 vs. 15 mg/dl (P < 0.01) in patients without diabetes. Recurrence within 1 year after PTA occurred in 25 diabetic (= 46%, Lp(a) 12 mg/dl) and 30 non-diabetic (= 38%, Lp(a) 48 mg/dl) patients. DM patients with 1 year's patency had a median Lp(a) of 7 vs. 11 mg/dl in non-diabetic patients (P < 0.05). However, 12 months after angioplasty Lp(a) correlated negatively with the ABI (r = -0.44, P < 0.01) in diabetic and in non-diabetic patients (r = -0.20, P < 0.05). The probability of recurrence after PTA continuously increased with higher levels of Lp(a) in each subgroup of patients. CONCLUSIONS: Our data indicate that Lp(a) is generally lower in those with peripheral arterial occlusive disease and Type 2 diabetes than in non-diabetic individuals. The increased risk for restenosis with rising levels of Lp(a) is set at a lower Lp(a) in diabetes and may be more harmful for diabetic patients.

Microcirculation is similar in ischemic and venous ulcers.

Microcirculation of 15 ischemic and 15 venous ulcers, their scars, and intact surrounding skin were examined in order to demonstrate their similarities in the development and healing process. Subpapillary and nutritive perfusion of four areas were investigated by a laser Doppler perfusion imager (arbitrary units) and capillary microscopy (capillaries/mm2): one ulcer area without granulation tissue (no wound healing) and one with granulation tissue (ulcer healing); one skin area adjacent to the ulcer (1-8 mm) (scar developed from ulcer areas) and one distant (12-25 mm; intact skin). Areas without granulation tissue in ischemic and venous ulcers were similar, demonstrating a lack of capillaries (0.13 +/- 0.52; 0.93 +/- 2.09) and low laser Doppler flux (0.81 +/- 0.69; 1.47 +/- 1.17; P > 0.05 for each). In granulation tissue of both ulcers there was a tendency to a higher capillary density (0.67 +/- 1.40; 5.60 +/- 2.32; P < 0.0001 for venous ulcers) and a higher laser Doppler flux (1.15 +/- 0.67; 4.04 +/- 1.62; P < 0.0001 for venous ulcers) than in areas without granulation tissue. In scars of ischemic and venous ulcers capillary density (8.18 +/- 8.84; 13.60 +/- 5.45) and laser Doppler flux (1.72 +/- 1.00; 1.94 +/- 1.45) were similar (P > 0.05). In skin distant from ischemic ulcers very high capillary density (24.63 +/- 1.89) was associated with low laser Doppler flux (0.99 +/- 0.59); distant from venous ulcer capillary density was moderate (10.47 +/- 3.42) while laser Doppler flux was high (3.77 +/- 1.62; P < 0.0001 between both groups). The development and healing process of ischemic and venous ulcers is similar. Nutritive and subpapillary perfusion are involved in ulcer healing. In intact skin surrounding ischemic and venous ulcers, microcirculation is different due to the underlying pathophysiology.

Prosthetic valve endocarditis due to Candida tropicalis complicated by multiple pseudoaneurysms.

Candida endocarditis is an unusual but severe complication caused by Candida albicans or other fungal species. We describe a case of prosthetic valve endocarditis due to Candida tropicalis, complicated by multiple pseudoaneurysms.

Carotid artery stenting: effect of learning curve and intermediate-term morphological outcome.

PURPOSE: To assess the impact of learning on the rate of success and complications of carotid stenting in a single-center, one-operator series and prospectively follow a patient cohort with regard to restenosis. METHODS: In 303 patients (mean age 70 +/- 8.8 years), 320 internal carotid arteries (ICA) were treated with carotid stenting for stenoses > or = 70%. Four groups of 80 consecutive interventions were compared with regard to primary technical success and periprocedural complications. Stent patency in follow-up was assessed using duplex scanning. RESULTS: Stenting was successful in 298 (93%) arteries. The combined neurological complications (transient ischemic attacks and all strokes) and 30-day death rate was 8.2% (n = 25), but the all stroke and 30-day death rate was 3.0% (n = 9). A significant reduction in the frequency of neurological complications after the initial 80 interventions was observed (p = 0.03), but technical success was not appreciably improved with increasing experience thereafter. Over a median 12 months (interquartile range 6 to 24), cumulative patency rates were 91%, 90%, and 91% at 6, 12, and 36 months, respectively. CONCLUSIONS: Elective carotid stenting can be performed with excellent technical success, an acceptable frequency of periprocedural complications, and good intermediate-term patency. However, our findings suggest that a larger number of interventions should be performed to overcome the negative effects of the initial learning phase.

Microcirculation in chronic venous insufficiency.

In this review, the anatomy and physiology of the venous system and its pathophysiology are described. Theories regarding the possible causes of disturbances in venous microangiopathy are summarized. The theories concern the deoxygenation of red blood cells, arteriovenous shunts, fibrin cuffs, and the trapping of growth factors and/or white blood cells. Furthermore, microlymphatic, neurologic and hemorheologic disturbances in venous disease are outlined. Findings in venous microangiopathy obtained from histology, capillary microscopy, microlymphography, laser Doppler fluxmetry and transcutaneous oxygen partial pressure are detailed. Finally, the recently discovered pattern of perfusion in microcirculation within and around venous ulcers is discussed.

Vasospasmus: a rare manifestation of homocystinuria.

We report about a patient suffering from multiple spastic stenoses of varying degree of both iliac arteries and from occlusion of the left tibiofibular trunc. Laboratory investigations revealed increased levels of homocysteine and the diagnosis of homocystinuria was confirmed by fibroblast cell culture. The spasms responded well to vasodilative therapy with nitroglycerine, molsidomine (cGMP mediated) and prostaglandine E1 but not with nifedipine (Ca influx blocker). Our review of literature demonstrated that this arterial spastic abnormality is a very rare complication in patients suffering from homocystinuria.

[Glomus caroticum chemodectoma. Review on current diagnosis and therapy]. / Glomus caroticum--Chemodectom. Ubersicht über die aktuelle Diagnostik und Therapie.

Carotid body tumors are rare neoplasms arising from the small chemoreceptor organ in the adventitia of the common carotid bifurcation. Patients with carotid body tumours usually present with a gradually enlarging non-tender anterolateral neck mass. Differential diagnosis includes metastatic lymph nodes, carotid artery aneurysm, salivary gland tumour, branchial cleft cyst, and neurogenic or thyroid tumours. When such a lesion is suspected, a non-invasive Doppler colour flow ultrasonography enables the clinician to arrive at a definite diagnosis. Subsequent arteriography is mandatory, because the finding of an intensely blushing hypervascular mass spreading into the carotid bifurcation further supports the diagnosis and provides accurate preoperative information concerning arterial blood supply. Computed tomography scanning is appropriate to delineate the relation of the tumour to adherent structures, while magnetic resonance tomography demonstrates the relation of the tumour to the adjacent internal jugular vein and the carotid artery. Selective embolization should be performed for safe surgical removal with less bleeding. Early surgery is the treatment of choice and is recommended in order to minimize major risks. Subadventitial resection is the most established technique. Radical resection prevents local recurrence and has the best long-term results. Removal of the internal or common carotid arteries can become mandatory in selected cases of extensive disease. Surgical treatment by an experienced team is associated with considerably low mortality and morbidity.

Colour duplex sonography-guided local lysis of occlusions in the femoro-popliteal region.

BACKGROUND: To evaluate colour duplex sonographic guidance of local lysis of occlusions in the femoropopliteal region. METHODS: Thirteen consecutive patients (8 female, mean age 67) with peripheral artery disease with acute and subacute occlusions in the superficial femoral or popliteal artery were included in this study. The lesions were identified by colour duplex ultrasound (Acuson 128 XP/10) After anterograde puncture the guidewire was advanced through the arterial lesions under B-mode image control. The Mewissen Infusion Catheter and a Katzen infusion wire were then accurately positioned within the lesion under B-mode image control. The fibrinolytic drugs were then inserted into the occlusions, initially 2.5 mg rt-PA as a bolus followed by Urokinase (50,000 IU/h) for 24 hours. After control duplex sonography (over 24 hours) the additional angioplasty was performed either under fluoroscopic or exclusively under ultrasound guidance. RESULTS: Eleven of 13 patients with occlusions in the femoro-popliteal region were partially recanalised after ultrasound guided local lysis and after the additional angioplasties (nine under fluoroscopic and three under ultrasound guidance) the arteries were completely recanalised. CONCLUSIONS: Our data show that not only is the positioning of the catheter and the guidewire for local lysis exclusively under colour duplex guidance possible, but also the surveillance of the local lysis and the additional angioplasty. In the case of any complications, however, easy access to angiography should be possible.

Impact of different therapeutic alternatives in treatment of severe limb ischemia: experiences on 190 consecutive patients at a department of medical angiology.

BACKGROUND: Different therapies in consecutive patients (1987-1992) with chronic critical limb ischemia at a department of medical angiology, their short- and long-term outcome were investigated. PATIENTS AND METHODS: 190 patients (112 males, 78 females; age: 67 +/- 12 years); 78 in grade II, 112 in grade III according to Rutherford's classification. Therapeutic regimen: 1. vascular recanalisation by percutaneous transluminal angioplasty [PTA], local or systemic lysis; 2. surgical vascular reconstruction in case of impossibility or failure of catheter procedures; 3. prostanoids and/or antibiotics; 4. local wound treatment including amputations. RESULTS: Vascular recanalisation was attempted in 156/190 (82.1%): PTA in 116/190, surgical vascular reconstruction in 50/190, local in 24/190 and systemic lysis in 8/190 patients. Prostanoids were applied in 89/190 and antibiotics in 73/190 patients. At the time of dismissal 164/190 (86.3%) patients were clinically improved; 11/190 (5.8%) unchanged, 13/190 (6.8%) had undergone major amputations and 2/190 (1.1%) had died. After 2.6 +/- 2.2 years 77 of the 141 patients, who were still alive, were reexamined. Among these 77 patients 84.4% were in grade 0 or 1, 15.6% in chronic critical limb ischemia. Furthermore 13.0% had been amputated since dismissal. Forty-nine of 190 (25.8%) patients had died 3.2 +/- 1.9 years after dismissal from hospital. CONCLUSION: Catheter techniques, mostly PTA, is possible in the majority of patients with chronic critical limb ischemia. Cooperation with vascular surgeons in case of technical impossibility or failure of catheter recanalisation is mandatory. Such a regimen yields satisfactory short- and long-term results and a low rate of complications.

Ticlopidine induced prolonged leucopenia in a patient with immunocytoma and chronic hepatitis C.

Ticlopidine is increasingly used in the secondary prophylaxis in patients with arterial occlusive diseases. Neutropenia is a well known side effect of this drug. We report a case of a 73 year old woman who was admitted because of severe prolonged ticlopidine induced leucopenia. The past medical history included an immunocytoma of the IgM-kappa type diagnosed seven years ago with less than 10% infiltration of the bone marrow and a chronic hepatitis C. On admission the white cell count was 1000/microL. Ticlopidine was stopped. The white cell count did not increase within one week, thus filgastrim was applied on two consecutive days. The leucocyte count promptly increased to 6000/microL but consecutively dropped within the next fortnight again to levels below 500/microL forcing daily filgastrim application for another 9 days. Four months after the initiation of the therapy with filgastrim the patient had a white cell count of 4300/microL. We therefore conclude that in patients with a history of potentially bone marrow suppressing diseases the use of ticlopidine has to be carefully weighed against possible myelosuppressive effects.

Penetration of ciprofloxacin into the interstitial space of inflamed foot lesions in non-insulin-dependent diabetes mellitus patients.

Interstitial ciprofloxacin concentrations were measured by microdialysis in inflamed foot lesions of non-insulin-dependent diabetes mellitus patients following intravenous administration of 0. 2 g of ciprofloxacin. Interstitial ciprofloxacin concentrations were significantly lower than corresponding serum concentrations. There was no significant difference in the penetration of ciprofloxacin into inflamed and unaffected tissue (area under the concentration-time curve(infection)/area under the concentration-time curve(unaffected tissue) = 0.99 +/- 0.15 [mean +/- standard error], n = 6). Thus, inflammation appears to have little or no effect on the penetration of ciprofloxacin into tissue.

Microcirculation in venous ulcers and the surrounding skin: findings with capillary microscopy and a laser Doppler imager.

BACKGROUND: To obtain more information about microcirculatory disturbances in venous ulcers, we studied their laser Doppler flux images and capillary densities. MATERIALS AND METHODS: On photographs of venous ulcers and the adjacent skin of 17 patients, four regions of interest were marked: one non-granulation tissue area (NGTA) within the venous ulcer, one granulation tissue area (GTA) within the ulcer, one adjacent skin area (ASA) and one distant skin area (DSA). Within these four regions the average laser Doppler area fluxes and capillary densities were determined for each patient using a laser Doppler imager and capillary microscopy respectively. RESULTS: The laser Doppler area flux (mean +/- SD in AU) was significantly lower in NGTA (1.39 +/- 1.12) than in GTA (4.06 +/- 1. 52) or DSA (3.86 +/- 1.54) (P < 0.00001). In addition, the ASA flux (1.95 +/- 1.39) was significantly lower than the GTA or DSA flux (P < 0.0001). Capillary density (capillaries per mm2) in NGTA (0.82 +/- 1.98) was significantly lower than that in GTA (6.00 +/- 2.55), ASA (13.88 +/- 5.16) or DSA (10.29 +/- 3.41) (P < 0.0001). In addition, the capillary density of ASA was significantly higher than that of GTA or DSA (P < 0.05). CONCLUSION: The four areas showed the following characteristics: NGTA, low laser Doppler area flux and lowest capillary density (possible sign of ulcer area without healing tendency); GTA, high laser Doppler area flux and second lowest capillary density (possible sign of wound healing); ASA, low laser Doppler area flux and highest capillary density (possible sign of healing process nearly completed; scar); DSA, high laser Doppler area flux and second highest number of capillaries (sign of microcirculation of chronic venous disorder).

Differential inhibition of thrombin activity and thrombin generation by a synthetic direct thrombin inhibitor (napsagatran, Ro 46-6240) and unfractionated heparin in patients with deep vein thrombosis. ADVENT Investigators.

BACKGROUND: Direct thrombin inhibitors belong to a new class of antithrombotic drugs whose effects on blood coagulation in vivo in patients suffering from acute thrombotic conditions have not yet been fully explored. METHODS AND RESULTS: One hundred and five patients with acute proximal deep-vein thrombosis were randomized to receive a continuous intravenous infusion of napsagatran, a novel synthetic thrombin inhibitor, at a fixed dose of 5 mg/h (n = 36) or 9 mg/h (n = 25) for five days, or APTT-adjusted unfractionated heparin (UFH, n = 44) for the same time. In these patients, thrombin activity and thrombin generation could be assessed by measuring thrombin-antithrombin III complexes (TAT) and prothrombin fragment 1+2 (F1+2), respectively, on three occasions. At baseline, TAT and F1+2 did not differ among the three groups. On Day 2 (steady state), TAT significantly decreased in all groups, and the decrease was significantly more pronounced in the patients given higher-dose napsagatran. F1+2 decreased significantly only in UFH-treated patients. Two hours after cessation of the infusion, the TAT levels increased in the two napsagatran groups but not in the UFH group, whilst F1+2 went back to the baseline levels in the napsagatran-treated patients but remained low in the UFH-treated patients. There was no rebound effect. CONCLUSIONS: The data presented suggest that direct thrombin inhibition with napsagatran at 9 mg/h is more potent than UFH in attenuating thrombin activity, but is less potent than UFH in inhibiting thrombin generation. The real significance of these findings will have to be substantiated in further trials with clinically relevant endpoints.

Laser Doppler imaging and capillary microscopy in ischemic ulcers.

The local distribution of laser Doppler flux (mainly thermoregulatory perfusion) and capillary density (nutritive circulation) within 25 ischemic leg ulcers and their adjacent skin were investigated. For this purpose the technique of laser Doppler imaging and capillary microscopy were applied. In each ulcer a non granulation tissue area (NGTA), a granulation tissue area (GTA) and in adjacent skin a skin area (SA) were defined. In these areas the average laser Doppler area flux (arbitrary units, AU) and the number of capillaries/mm2 were determined for each patient. The mean+/-S.D. of laser Doppler area fluxes were: NGTA 1.30+/-1.93, GTA 2.13+/-1.53 and SA 1.21+/-0.77 AU, respectively. The differences between GTA and NGTA or SA was statistically significant (p < 0.001, each) The mean+/-S.D. of capillary densities were as follows: NGTA: 0.56+/-2.06, GTA 6.76+/-8.39 and SA 16.80+/-7.38 capillaries/mm2, respectively. The following differences were statistically significant: NGTA versus GTA (p < 0.01) and SA versus NGTA or GTA (p < 0.001, each). In conclusion following characteristics of the three areas can be described: In NGTA low laser Doppler area flux is combined with very low capillary density (ulcer area without healing). In GTA the highest laser Doppler area flux of all three areas and an intermediate capillary density (wound healing) is found. In SA an intermediate laser Doppler area flux is associated with the highest capillary density of all three areas with the healing process nearly completed and no granulation tissue.

Color duplex sonography guided stent placement in a stenosis of the superficial femoral artery. A case report.

We report the first case of a successful stent placement under color coded ultrasound guidance alone in the superficial femoral artery of a 73-year-old woman suffering from intermittent calf claudication following restenosis after an uncomplicated angioplasty five months previously. Because of a hemodynamically residual stenosis after three attempts at dilatation, a percutaneous transluminal angioplasty and stent insertion were performed under the sole guidance of color coded ultrasound. The intervention was performed without complication and at the six-month follow-up examination, the patient was symptom-free and the stent was morphologically intact and hemodynamically functional. This case shows that successful stent placement under ultrasonic guidance alone, without fluoroscopic control is possible, provided that there is adequate sonographic visualization.

Brachytherapy for prophylaxis of restenosis after long-segment femoropopliteal angioplasty: pilot study.

PURPOSE: To evaluate in a pilot study the feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA) without stent implantation in a group of patients with a high risk of restenosis. MATERIALS AND METHODS: Ten patients (six women, four men; mean age, 68 years) with long-segment (mean length, 16 cm; range, 9-22 cm) restenosis underwent PTA followed by endovascular irradiation with high-dose-rate afterloading of an iridium-192 rod. A dose of 12 Gy was targeted to the inner intimal layer of the vessel. Follow-up examinations until 12 months after PTA included measurement of the ankle-brachial index, color duplex ultrasonography (US) with calculation of the peak velocity ratio, and intraarterial angiography when recurrence was suspected. RESULTS: Irradiation was technically feasible in all patients without complications. In six patients, the dilated and irradiated segment remained widely patent at color US, with corresponding excellent hemodynamic and clinical results after 12 months. In four patients, clinical and laboratory findings indicated recurrence and arteriography demonstrated restenosis with a diameter reduction of 60%, 70%, 80%, or 90%. CONCLUSION: Considering the negative selection of patients with a high risk of restenosis, the results of our pilot study are promising concerning the possibility of reduction of restenosis by means of endovascular brachytherapy after long-segment femoropopliteal PTA without stent implantation. The value of this approach should now be determined definitively in randomized trials.

Blood rheology in patients with native heart valve disease and after valve replacement.

Patients with heart valve disease have rheologic abnormalities that are more pronounced in double valve disease than in mitral or aortic valve disease; after valve replacement surgery, the degree of rheologic abnormality is more pronounced in patients with mechanical and biological prostheses than in those with homografts and pulmonary autografts. Rheologic abnormalities seen in these patients might be related to the different incidences of thromboembolism in the presence of various valve defects and various types of prostheses.

Reproducibility of laser Doppler imager flux measurements within ischemic or venous ulcers and adjacent skin.

BACKGROUND/AIMS: The laser Doppler imager (LDI) is a device that maps the local distribution of the laser Doppler flux of tissues. To facilitate the interpretation of LDI measurements, we investigated their reproducibility. METHODS: We measured 10 arterial ulcers, 10 venous ulcers and their adjacent skin by the use of a LDI. The means were calculated of individual coefficients of variation ± standard error of mean (meanCV ±SEM) of measurements on the same day, on 5 different days and at specific time points (0, 30, 60, 90 and 120 min) during the application of PGE, on 2 different days. RESULTS: The meanCV ±SEM of measurements on the same day were 9.3±0.9% (ulcer), 9.8±0.9% (skin), and on 5 different days they were 21.9±1.9% (ulcer) and 28.6±2.4% (skin). Ulcer measurements on 5 different days were significantly more reproducible than skin measurements, if differences were calculated for all 20 patients or for the 10 patients with venous ulcers separately (P<0.05). During the application of PGE, for 120 min, meanCV ±SEM ranged from 19.2±4.0% to 26.9±5.0% (ulcer) and from 20.5±4.1% to 29.5+3.9% (skin). CV of skin measurements of all 20 patients at 0 min were significantly lower than those after 120 min of PGE(1) -application (P<0.05). CONCLUSION: Our results show an excellent reproducibility of LDI measurements on a single day. The reproducibility of measurements on 5 different days or during the application of PGE1 over a period of 120 min was poorer. Because of the poorer reproducibility, more patients are needed to study long-term or drug effects.