Ocular and retrobulbar blood flow in ocular hypertensives treated with topical timolol, betaxolol and carteolol.

The purpose of this study was to evaluate the effect of topical timolol 0.5%, betaxolol 0.5% and carteolol 2% on the blood flow velocity of the central retinal artery (CRA), the posterior ciliary artery (PCA) and the ophthalmic artery (OA) in patients with ocular hypertension. A group of 14 patients with ocular hypertension and a group of 11 normals were studied. The color Doppler was used to measure the peak systolic flow velocity (PSFV) and the end diastolic flow velocity (EDFV) of the CRA, the PCA and the OA in the normals and in the patients. The normals were under no treatment, while the patients were studied before and after treatment with topical timolol 0.5%, betaxolol 0.5% and carteolol 2%. In the systolic phase, there was a significant increase in the flow velocity of the CRA with all three drugs. In the diastolic phase of the CRA, the increase was significant for timolol 0.5% and carteolol 2% but not for betaxolol 0.5%. The flow velocity of the PCA and OA remained unchanged. In this study of 14 patients with ocular hypertension, topical timolol 0.5%, betaxolol 0.5% and carteolol 2% led to a significant increase in the flow velocity of the CRA without creating a steal or decrease in the flow velocity of the PCA.

Nomograms used to define the short-term treatment with PGE(1) in patients with intermittent claudication and critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study.

Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.

Expanded polytetrafluoroethylene in external valvuloplasty for superficial or deep vein incompetence.

The authors evaluated the long-term safety of expanded polytetrafluoroethylene (ePTFE) implants used in external valvuloplasty for treatment of incompetence of the long saphenous and common and superficial femoral veins. During a 15-year period patients with superficial and/or deep venous disease and hypertension due to pure superficial or deep vein incompetence underwent an external valvuloplasty with ePTFE sutures, or an ePTFE cardiovascular patch placed as a sleeve around the incompetent vein segment, or an ePTFE tubular graft placed around the venous segment. Postoperative follow-up evaluations consisted of clinical examinations, high-resolution ultrasonography, and color duplex scanning, and a complete blood count performed at 1, 3 and 6 months, and repeated for at least 4 years, every 2 years after the procedure. A total of 101 patients (38 men and 63 women; mean [+/- sd] age, 44+/-12 years) underwent external valvuloplasty between January 1983 and December 1998; 82 of them completed the 4-year follow-up. Forty of the 82 patients had been operated on for superficial vein incompetence, 42 for deep vein incompetence. Overall, the mean follow-up time was 7.8+/-3.6 years (range, 4 to 13). There were no infections, thromboses,foreign-body reactions to the ePTFE implants, or other prosthesis-related complications requiring explantation. One granuloma (noninfected) developed in association with a tubular ePTFE implant around a long saphenous vein, but it did not necessitate implant removal. Seven patients required (at least after 4 years) a second procedure for recurrent or new venous incompetence. Therefore, in this observational study, ePTFE implants used to treat or correct venous incompetence were well tolerated on a long-term basis.

Ocular and orbital blood flow in cigarette smokers.

OBJECTIVE: To report the effect of cigarette smoking on the blood flow velocity of the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary artery (PCA) in patients who smoke at least 20 cigarettes a day. METHODS: The color duplex scanner was used to measure the systolic and diastolic flow velocity of the OA, CRA, and PCA in 10 smokers and 11 nonsmokers. RESULTS: Both the systolic and diastolic flow velocity decreased in the OA, CRA, and PCA in smokers compared with nonsmokers. The systolic flow decreased by as much as 36% and the diastolic flow by as much as 52%. This decrease was significant for the flow velocity of the CRA and PCA but not for the OA. An increase in the resistance index was also found. CONCLUSION: The authors believe that the decrease in the flow velocity of these vessels may be due to an increase in the vascular resistance of the vessels of the retina and optic nerve head in smokers. This may be important in patients with eye disease in whom altered blood flow already contributes to the ocular or orbital pathology.

Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis.

In this study, 294 patients with acute proximal DVT (deep venous thrombosis) were randomly assigned to receive intravenous standard heparin in the hospital (98 patients) or low-molecular-weight heparin (LMWH) (nadroparin 0.1 mL [equivalent to 100 AXa IU] per kg of body weight subcutaneously twice daily) administered primarily at home (outpatients) or alternatively in hospital (97 patients) or subcutaneous calcium heparin (SCHep) (99 patients, 0.5 mL bid) administered directly at home. The study design allowed outpatients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early. Patients treated with standard heparin or LMWH received the oral anticoagulant starting on the second day, and heparin was discontinued when the therapeutic range (INR 2-3) had been reached. Anticoagulant treatment was maintained for 3 months. Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants. Patients were evaluated for inclusion and follow-up with color duplex scanning. Venography was not used. In case of suspected pulmonary embolism (PE) a ventilatory-perfusional lung scan was performed. Endpoints of the study were recurrent or extension of DVT, bleeding, the number of days spent in hospital, and costs of treatments. Of the 325 patients included, 294 completed the study. Dropouts totaled 31 (10.5%); six of the 325 included patients (1.8%) died from the related, neoplastic illness. Recurrence or extension of DVT was observed in 6.1% of patients in the LMWH group, in 6.2% in the standard heparin group, and in 7.1% in the SCHep group. Most recurrences (11/17) were in the first month in all groups. Bleedings were all minor, mostly during hospital stay. Hospital stay in patients treated with LMWH was 1.2+/-1.4 days in comparison with 5.4+/-1.2 in those treated with standard heparin. There was no hospital stay in the SCHep group. Average treatment costs in 3 months in the standard heparin group (US $2,760) were considered to be 100%; in comparison costs in the LMWH group was 28% of the standard heparin and 8% in the SCHep group. This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost.

Shock waves (SW) noninvasive extracorporeal thrombolysis treatment (NISWT).

A group of 24 patients were considered for noninvasive shock waves thrombolysis (NISWT). Of these, 15 patients gave their informed consent. NISWT was attempted in eight patients (while seven patients were randomized for follow-up only). NISWT was possible in six of seven patients. In one patient randomized for NISWT, local inguinal scarring, due to previous surgery, made impossible the visualization of the femoral vein, and therefore focusing of shock waves (SWs). No side effects were reported in the days after SWs administration during the 4-month follow-up. In patients treated with NISWT it was possible to observe just after the SWs session the presence of echolucent "acoustic holes" and flow (by color and power Doppler) within the "holes." All "echolucent holes" produced at the first session were still present at 4 months, and color flow imaging also detected new flow channels in echogenic areas of thrombi previously not visible. In one patient thrombolysis was achieved after the first treatment, but at 3 and 4 months the thrombus was completely avascular. In conclusion, thrombolysis using SWs was obtained in selected cases and it was still persisting at 4 months in six of the seven treated patients. NISWT appears feasible and promising. These results should be confirmed by larger, prospective trials.

External femoral vein valvuloplasty with limited anterior plication (LAP): a 10-year randomized, follow-up study.

The aim of this study was to evaluate the effects after 10 years of external valvuloplasty of the femoral vein (limited anterior plication or LAP). After informed consent patients with venous hypertension due to deep and superficial venous incompetence were randomized into two treatment groups. Both groups were treated with superficial vein surgery (ligation and section of the major incompetent superficial veins). Group 2 was treated with the same procedure and with LAP. External valvuloplasty of the superficial femoral vein was performed with plication of the anterior vein wall after limited dissection of the vein. Results were evaluated with color-duplex scanning and ambulatory venous pressure (AVP) measurements. Endpoints were AVP, refilling time (RT), presence/absence of reflux at the superficial femoral vein, the variation in the diameter of the vein, and quality of life score (QLS). No complications were observed. All femoral veins treated with LAP were competent after 10 years. Significantly lower AVP and longer RT were observed in the LAP group. Also the average diameter of the vein was smaller in the LAP group. Moreover, QLS was significantly better in the LAP group after 10 years. In conclusion, in selected subjects, with moderate deep venous incompetence, functional cusps, or incompetence mainly due to relative enlargement of the femoral vein, LAP may be an effective alternative to external valvuloplasty.

Effects of triflusal on arteriosclerosis progression assessed with high-resolution arterial ultrasound.

In order to evaluate the effect of triflusal (2-acetyloxy-4-trifluoromethyl benzoic acid), an orally active antiplatelet agent, on arteriosclerosis progression, a pilot, parallel, double-dummy, double-blind clinical trial vs acetylsalicylic acid (ASA) was carried out in patients with subclinical atherosclerotic lesions. The trial consisted of a 2-week run-in placebo phase, followed by a 12-month oral treatment with triflusal (600 mg/day) or ASA (300 mg/day). The primary variable was identified in the ultrasonic biopsy (UB) score; the secondary variables were the UB class changes of each arterial site, the rate of progression (ROP), the intima-media thickness (IMT), and the symptoms of arteriosclerosis. Data were evaluated by use of analysis of variance and Chi-square test. Forty-three patients (31 men, 12 women, mean age 62.8 +/- 8.4 SD) were randomized to triflusal (15 men, 6 women, mean age 64.3 +/- 6.7) or to ASA (16 men, 6 women, mean age 61.3 +/- 9.6). The analysis of variance on the UB score showed no difference between treatments: the patients' UB scores remained unchanged with no progression, thus indicating that no patient worsened during treatment. When all arterial sites under evaluation are considered, 86% of the sites in the triflusal group and 85% in the ASA group remained unchanged. No relevant change was recorded in vital signs and routine laboratory tests. Gastric disturbances were reported by two and three patients treated with triflusal and ASA, respectively. In conclusion, triflusal appears as effective as ASA in slowing arteriosclerosis progression.

The edema tester in the evaluation of swollen limbs in venous and lymphatic disease.

BACKGROUND: Edema is a common condition in most venous and lymphatic diseases. The ACI edema testers (ET) have been developed to objectively evaluate the presence of edema. Two types of testers have been developed. ET1 is a soft plastic plate (5 x 2 cm) characterised by two parallel protrusions while the ET2 is characterised by two lines of 7 holes. METHODS: The ETs are applied onto the internal perimalleolar region with the protrusions/holes in contact with the skin. A blood pressure cuff is applied over the area (pressure maintained at 50 mmHg for a period between 1-3 minutes). When the cuff is removed, with the ET1 skin marks are usually just visible in normal limbs (they disappear in a few minutes). We studied 22 normal limbs, 19 with varicose veins, 22 with chronic venous insufficiency, 5 with primary lymphedema and 8 with severe chronic lymphedema. RESULTS: In limbs with severe edema the whole length of the protrusions is visible; with moderate edema only a part of the protrusions is visible. With the ET2 skin marks are just visible in normal limbs (only the larger holes). Marks disappear in a few minutes in normal limbs while in limbs with edema the number of visible holes is increased (in severe edema all holes are visible). There were significant differences between normals and patients (considering skin mark length, number of visible holes and disappearance times). CONCLUSIONS: The two testers separated patients with different severity of edema due to chronic venous or lymphatic problems. In severe lymphatic problems all parameters were different (p < 0.02) from those observed in venous disease. A reproducibility study indicated that the ET tests have minimal variations in mark visibility or length or hole numbers (for the ET2).

Ocular and orbital blood flow in patients with essential hypertension treated with trandolapril.

PURPOSE: To study the effect of essential hypertension on flow velocity in the central retinal (CRA) and posterior ciliary arteries (PCA). Flow velocity was also evaluated in these arteries in patients with hypertension treated with trandolapril, an oral angiotensin-converting enzyme inhibitor. METHODS: Using the duplex scanner, flow velocity of the CRA and PCA was measured in 12 medication-free patients with hypertension and 10 normal controls. The hypertensive patients were then treated with oral trandolapril, 1 mg/day for 1 week. After 1 week of treatment, flow velocity was again measured in the arteries of the patients with hypertension. RESULTS: There was a significant reduction in systolic and diastolic flow velocity of the vessels tested in the medication-free hypertensive patients when compared with those in the normal controls. In controls, the CRA had a peak systolic flow velocity (PSFV) of 34 cm/sec and an end diastolic flow velocity (EDFV) of 14 cm/sec; the PCA had a PSFV of 38 cm/sec and an EDFV of 16 cm/sec. In the hypertensive patients off medication, the CRA had a PSFV of 16 cm/sec and an EDFV of 6 cm/sec; the PCA had a PSFV of 17 cm/sec and an EDFV of 5 cm/sec. The diastolic component also was significantly decreased in the patients with hypertension. Flow velocity significantly increased in the hypertensive patients treated with trandolapril for 1 week, but did not reach the level of flow measured in normal controls. CONCLUSION: The decreased flow velocity in hypertensive patients may result from a peripheral vasospasm in the vessels of the eye and orbit. This decreased flow velocity may be important in eyes that already have ocular disease. Improvement in flow velocity was noted with oral trandolapril but it did not reach the levels seen in normal controls.

[Edema tester. Assessment of edema of the legs]. / Edema tester. Valutazione dell'edema negli arti inferiori.

BACKGROUND: The aim of this study was the clinical evaluation of an original device produced to evaluate edema in a semi-quantitative way, the ACI Medical, Edema Tester (ET). ET1, is a soft plastic plate characterised by two parallel conic pyramidal protrusions. One side of the protrusion is rounded while the other side has an angular edge. The two protrusions are placed on the plate in inverse decreasing height. ET2 is characterised by two lines of 7 holes placed in the plate. The ET is applied at the internal perimalleolar region with the conic pyramidal protrusions in contact with the skin. A standard sphygmomanometer cuff is applied over the area and pressure is maintained at 50 mmHg for a period between 1 an 3 minutes. The cuff is then removed. ET1: skin marks are usually just visible in normal subjects without edema and disappear in a few minutes. When edema is moderate some half of each protrusion is visible as a skin mark. In limbs with severe edema the whole length of the protrusion is clearly visible. ET2: skin marks are usually just visible in normal limbs without edema and disappear in a few minutes. In limbs with edema the number of holes visible on the skin is increased and in severe edema all holes are visible. METHODS: To evaluate semi-quantitatively the level of edema the length of the two skin marks can be measured and for the ET2 the numbers of visible holes can be counted, as they are generally proportional to the degree of edema. The ET testers were evaluated in 22 normal subjects, 19 limbs with varicose veins, 22 patients with CVI and lipodermatosclerosis, 5 patients with initial primary lymphedema and in 8 subjects with severe, chronic, lymphedema and skin alterations. RESULTS: The results showed a significant difference between normal limbs an patients. CONCLUSIONS: In conclusion, the method of evaluating edema with ET can be used to supplement the clinical and noninvasive evaluation. In general practice the presence of edema measurable with ET indicate the need for treatment. The several degrees of skin marks visibility and disappearance time may be used as a general guideline to indicate the need for different types and length of treatment.

Treatment of severe intermittent claudication with PGE1--a short-term vs a long-term infusion plan--a 20 week, European randomized trial--analysis of efficacy and costs.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied by comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 109 patients (96 completed the study) with an average total walking distance of 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks). In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP, phase 2 treatment was performed in 2 days by a 2-hour infusion (1st day: morning 20 microg, afternoon 40 microg; 2nd day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate reduced tolerability or side effects. Full dosage (60 microg b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of the 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% STP vs 107.3% LTP), and at 20 weeks (351% STP vs 242% LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. Average cost of LTP was approximately 6,588 ECU; for STP the average cost was approximately 1,881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,937 ECU vs 550 ECU with STP (p<0.02). The cost of PGE1 (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). In summary, between-group-analysis favors STP, in terms of walking distance and costs. Results indicate good efficacy and tolerability of PGE1 treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation, and may be used in a larger number of nonspecialized units available to follow the protocol.

Shock waves in vascular diseases: an in-vitro study.

UNLABELLED: Three human aortic specimens were used for this in-vitro study on the effects of shock waves on the arterial wall. Specimen one was from a normal (for age) healthy aorta. The full abdominal length was used (including mesenteric and renal arteries and the aortoiliac bifurcation), divided into six pieces (3 cm). The pieces were placed and fixed into degassed water. Shock waves (SW) were focused onto the aortic wall by means of a B-mode ultrasound imager. An SW generator (Minilith SL1, Storz Medical AG, Kreuzlingen, Switzerland) was used for setting of energy flux density between 0.03 and 0.5 mJ/mm2. The six aortic pieces (excluding piece 1, placed in water and left untreated as control) were treated with SW at increasing energy levels. A second aortic specimen of a man with arteriosclerotic plaques was also used and the experiment repeated at energy levels 1, 5, and 8. Another specimen of normal thoracic aorta was exposed at energy levels 1 and 8 only. Energy levels delivered onto the aortic walls were selected from theoretically destructive levels to minimal levels known not to alter vascular tissues. High-resolution ultrasounds of the aortic segments were performed with a 10 MHz high-resolution, broad-band (ATL 3000, USA) probe in water before and after SW application to detect structural changes in the wall after SW. Histology was performed with a standard hematoxylin-eosin staining. RESULTS: The aortic pieces did not show macroscopic damages at visual examination, and at the ultrasound examination no visible changes were observed even at higher levels of SW energy. Also no effects were seen by histology. In conclusion, no damaging effects were observed, visually, by ultrasound, or by histology. At these energy levels SW appear to be safe and do not produce any damage to the aortic wall. Therefore, SW could be considered a safe, nondamaging procedure for potential treatment (ie, thrombolysis) in which vessel walls could be involved. Theoretically it is possible that functional changes could be observed in vivo including cell permeability modifications and other alterations (including changes in the potential of the cells in SW fields to modify themselves and to divide). At the energy levels described in this study SW could, theoretically be, safely used for vascular applications (ie, treating venous and arterial thrombi or in arterial plaques modification) without altering major, structural, arterial wall characteristics. Lesions or alterations that have a different density from the normal wall (thrombi or plaques) could be differently sensitive to the same dosage of SW. These differences in acoustic impedance characteristics could be used for potential treatments with SW without damaging the arterial wall.

[Control of the progress of arteriosclerosis in high risk subjects treated with mesoglycan. Measuring the intima media]. / Controllo della progressione dell'arteriosclerosi in soggetti ad alto rischio trattati con mesoglicano. Misurazione dell'intima-media.

BACKGROUND: Noninvasive ultrasonic biopsy (UB) can be used to classify arteriosclerotic lesions and their progression in the carotid and femoral bifurcation. Also the evaluation of intima-media thickness (IMT) is useful to quantify the progression of early arteriosclerosis. METHODS: Two randomly selected groups of asymptomatic subjects were included in a 18 month, open study. One group was treated with oral mesoglycan (200 mg/day) and one group was followed-up as control. The two groups were comparable for age and sex distribution. RESULTS: The average UB score was 14.4 +/- 5 in the treatment group and 14.3 +/- 8 in the control group. After 18 months the UB score was 15.7 +/- 4 in the treatment and 16.2 +/- 6 in the control group. The average increase in IMT in 18 months in the treatment group was 0.016 mm equivalent to 0.0106 mm per year. In the control group the average increase was 0.119 equivalent to 0.0793 per year. Therefore the increase in IMT was 7.48 times greater in the control group. These differences were significant (p < 0.05). Two drop-outs were recorded in the treatment group and 1 in the control group. CONCLUSIONS: In conclusion IMT measurements showed a decreased level of IMT progression in subjects under mesoglycan treatment. These results need to be confirmed by a larger randomised study.

[Analysis of costs and results of prostaglandin (PGE1 alpha-cyclodestrin) therapy of peripheral arterial diseases]. / Analisi di costi e risultati del trattamento con prostaglandine (PGE1 alpha-ciclodestrina) in pazienti con arteriopatie periferiche.

BACKGROUND: In this study patients with peripheral vascular disease were treated with PGE1 alpha-ciclodestrina. In the intermittent claudication group (walking distance at inclusion between 200-600 m) we included 55 patients treated with PGE1 alpha-ciclodestrina (15 diabetics) and 22 controls (not treated with PGE1 alpha-ciclodestrina). In the critical ischemia group 46 patients were treated and 47 patients followed up as controls (rest pain or necrotic lesions had been present for more than 2 weeks). METHODS: Patients with intermittent claudication were evaluated by a treadmill test (walking distance was the endpoint) and in those with critical ischemia the number of minor and major amputations in 12 months were considered as endpoints. A dose of PGE1 alpha-ciclodestrina (60-80 micrograms/day for 2 days) was repeated either every 6 or, in alternative, every 10 weeks. In the control group only antiplatelet agents, support treatment (control of risk factors) and exercise were used. RESULTS: All subgroups of patients treated with PGE1 alpha-ciclodestrina with intermittent claudication increased their walking distance (including the subgroup of diabetics). In critical ischemia there were no major amputations (only 2 minor amputations) in the PGE1 alpha-ciclodestrina group vs 10.6% (of major amputations) in the control group. Also an evaluation of laser Doppler flow, volume flow and transcutaneous PO2 indicated in subgroups of patients an improvement of microcirculation and limb perfusion with PGE1 alpha-ciclodestrina. CONCLUSIONS: The cost analysis and the quality of life evaluation indicated a benefit of preserving limbs from amputation.

[European trial of PGE1 alpha cyclodextrin. Short-term vs. long-term therapy in intermittent claudication]. / Il trial europeo PGE1 alpha-ciclodestrina. Short-term verso long-term nella claudicatio intermittens.

BACKGROUND: The efficacy, safety and cost of prostaglandin E1 (PGE1 alpha-ciclodestrina) in the treatment of severe intermittent claudication was studied comparing a long term treatment protocol (LTP) with a short term treatment protocol (STP) in a randomised, 20-week study. METHODS: The study has selected 120 patients (109 were included and 99 completed the study). The average total walking distance at inclusion was 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP phase 2 was the main treatment phase. The treatment was performed with 2-hour infusions (60 micrograms PGE1 alpha-ciclodestrina, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 alpha-ciclodestrina was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in two days with a 2-hour infusion (1st day: morning 20 micrograms, afternoon 40 micrograms; 2nd day 60 micrograms, morning and afternoon). The reduced dosage was used only at the first cycle to evaluate reduced tolerability or side effects. Full dosage (60 micrograms b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, 12 (phase 3). The observation period was between weeks 12 and 20 (phase 4). For both protocols a treadmill test was performed at inclusion, at the beginning of each phase and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors plan was used in both groups. RESULTS: Intention-to-treat analysis indicated an increase in walking distance which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% in STP vs 107.3% in LTP) and at 20 weeks (351% in STP vs 242% in LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild, adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. The average cost of LTP was approximately 6.588 ECU; for STP the average costs was approximately 1881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; P < 0.02). For an average 100% increase in walking distance LTP cost was 1937 ECU vs 550 ECU with STP (P < 0.02). The cost of PGE1 alpha-ciclodestrina (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). CONCLUSION: In summary between-group-analysis favours STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE1 alpha-ciclodestrina treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation and may be used in a larger number of non-specialised units available to follow the protocol.

[Intra-arterial infusion of PGE1 alpha cyclodextrin]. / Infusione intra-arteriosa di PGE1 alpha-ciclodestrina.

BACKGROUND: Intra-arterial infusion of PGE1 alpha-ciclodestrina was achieved by intrafemoral catheter in critical limb ischemia. METHODS: The acute infusion of 10 micrograms in 20 minutes, in 50 ml of saline was followed by chronic infusion 20 micrograms/die of PGE1 alpha-ciclodestrina for 5 days. Three male patients (age 65 +/- 12) with severe critical ischemia and rest pain with initial, localised (> 0.5 cm in diameter) necrosis were treated. There was no possibility of revascularisation in these patient. RESULTS: No side effects due to the intra-arterial infusion were observed. After the acute infusion skin flux (measured with laser Doppler at the dorsum of the foot) was increased on average 15.2 times (P < 0.01). The increase in flux was still present 10 days after the initial intra-arterial infusion. Pain was greatly decreased or disappeared in the three following 3 weeks. CONCLUSION: In conclusion, even on the basis of limited clinical data, intra-arterial infusion acutely improves skin perfusion in critical limb ischemia. It could be considered a fast acting treatment in critical ischemia and also a rapid method to evaluate the possibility of improving distal perfusion with PGE1 alpha-ciclodestrina (i.e. patients not responding to intra-arterial infusion could be considered for amputation).

[Circadian variations of cutaneous blood flow in normal subjects and in patients with peripheral arteriopathies. Effect of PGE1 and alpha-cyclodextrin]. / Variazioni circadiane di flusso cutaneo in soggetti normali ed in pazienti con arteriopatie periferiche. Effetto della PGE1 alpha-ciclodestrina.

BACKGROUND: In this study the circadian skin flux pattern was evaluated in 10 normal reference subjects and in 35 patients (mean age 68 +/- 11) subdivided in groups (10 with intermittent claudication (200-400 m of walking distance), 10 diabetics with claudication, 7 patients with rest pain and 8 with localised gangrene). METHODS: A laser Doppler flowmeter was used to monitor skin flux for 24 hours. In patients with intermittent claudication the circadian pattern was comparable to normal subjects. In diabetics the daily curve showed several irregular peaks mostly dissociated from activity or rest. RESULTS: In patients with critical ischaemia severe alterations of the circadian pattern were observed (the daily curve was flattened and dissociated from activity or rest) particularly in gangrene. PGE1 alpha-ciclodestrina treatment (60 micrograms/day) partially restored the circadian pattern and increased the average values of the 24-hour curve. In rest pain and gangrene the infusion of PGE1 alpha-ciclodestrina in the late evening increased the average night flux (which tended to fall to very low levels causing pain) and prevented or abolished night rest pain.

[Intramuscular injections of PGE1 in patients with severe claudication]. / Iniezione intramuscolare di PGE1 in pazienti con claudicatio severa.

BACKGROUND: In this pilot study we selected 12 patients with short range claudication and treated, after informed consent, 6 patients (mean age 63 +/- 5; range 55-65) with severe claudication (walking distance < 100 m). Selection criteria were patent common and deep femoral artery, occluded superficial femoral artery with patent popliteal artery, with posterior tibial Doppler pressure > 50 mmHg and anterior tibial > 40 mmHg. METHODS: Patients were evaluated with a treadmill test performed to their walking limit. PGE1 was used by intramuscular injections (for a total of 80 micrograms, divided in 4 injections). The injections were about 2 cm deep in the posterior calf muscles. An exercise program was associated. Patients were required to walk 20 minutes just after the injections and to follow an exercise program (walking slowly at least 30 minutes, 3 times daily, in the following 4 weeks). RESULTS: Both the PGE1 group and a comparable control group (12 patients mean age 62 +/- 4; range 56-65) were treated with ASA and pentoxyfillin (400 mg t.i.d.). In the PGE1 group the average total walking distance at inclusion was 25 +/- 16 (range 0-52); it increased to 113 +/- 55 (range 50-289) (after 1 week) and to 117 +/- 27 (range 30-1020) at 4 weeks. No important changes were observed in the control group (54 +/- 6 m at inclusion, 58 +/- 8 after one week and 63 +/- 7 after 4 weeks). There were no important side effects. One patient experienced important injection pain which disappeared in a few hours. No significant changes in tibial pressures were observed. CONCLUSIONS: Intramuscular injection of PGE1 may be an interesting treatment option in patients with severe intermittent claudication but these preliminary findings should be verified in larger randomised studies.