11-dehydro thromboxane B2 levels after percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease during a one year follow-up period.

The aim of our study was to determine if the generation of thromboxane is altered in patients with peripheral arterial occlusive disease following percutaneous transluminal angioplasty (PTA) during a one year follow-up period. In this study, 175 patients diagnosed with peripheral arterial occlusive disease (PAOD) and demonstrating short-distance claudication or ischemic rest pain, requiring PTA in either the iliac, femoral, or popliteal arteries, were enrolled. The excretion of 11-dehydro thromboxane B2 (TXB2) was measured in urine samples by high-performance liquid chromatography-mass spectrometry and recalculated based on the creatinine concentration. The urine samples were collected the morning prior to PTA, immediately following PTA and the day after PTA. All of the study subjects were then observed for a period of 12 months. Urine samples were also collected during the follow-up visits, and the levels of 11-dehydro TXB2 were measured at 1 month (1458.1 pg/mg creatinine ± 1240.8), 3 months (1623.3 pg/mg creatinine ± 1362.2), 6 months (1314.8 pg/mg creatinine ± 1378.7) and 12 months (1473.2 pg/mg creatinine ± 1455.2) after the PTA procedure. All of the patients were taking 75 mg of aspirin per day throughout the course of the study, as well as 75 mg of clopidogrel for six weeks following PTA. Overall, the mean TXB2 values immediately after PTA were significantly higher than either before the procedure (1524.4 pg/mg creatinine ± 1411.1 vs. 2098.1 pg/mg creatinine ± 1661.8; P = 0.00002), the day after PTA, or at any other point during the study. Moreover, preoperative TXB2 levels correlated well with the composite endpoints of death, myocardial infarction and stroke during the follow-up period (OR 7.42 [CI 95% = 1.2-48.8]; P = 0.02). Our findings suggest that clinicians should consider the use of TXA2 synthase inhibitors and receptor antagonists in combination with peripheral percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease.

Are pharmacological properties of anticoagulants reflected in pharmaceutical pricing and reimbursement policy? Out-patient treatment of venous thromboembolism and utilization of anticoagulants in Poland.

OBJECTIVES: Pharmacotherapy with vitamin K antagonists (VKA) and low-molecular-weight heparins (LMWH) is a major cost driver in the treatment of venous thromboembolism (VTE). Major representatives of anticoagulants in Europe include: acenocoumarol and warfarin (VKA), enoxaparin, dalteparin, nadroparin, reviparin, parnaparin and bemiparin (LMWH). Aim of this report is to measure and critically assess the utilization of anticoagulants and other resources used in the out-patient treatment of VTE in Poland. To confront the findings with available scientific evidence on pharmacological and clinical properties of anticoagulants. MATERIALS AND METHODS: The perspectives of the National Health Fund (NHF) and the patients were adopted, descriptive statistics methods were used. The data were gathered at the NHF and the clinic specialized in treatment of coagulation disorders. RESULTS: Non-pharmacological costs of treatment were for the NHF 1.6 times higher with VKA than with LMWH. Daily cost of pharmacotherapy with LMWH turned out higher than with VKA (234 times for the NHF, 42 times per patient). Within both LMWH and VKA the reimbursement due for the daily doses of a particular medication altered in the manner inversely proportional to the level of patient co-payment. Utilization of long-marketed and cheap VKA was dominated by LMWH, when assessed both through the monetary measures and by the actual volume of sales. Pharmaceutical reimbursement policy favored the more expensive equivalents among VKA and LMWH, whereas in the financial terms the patients were far better off when remaining on a more expensive alternative. CONCLUSIONS: The pharmaceutical pricing and reimbursement policy of the state should be more closely related to the pharmacological properties of anticoagulants.

The treatment of venous thromboembolism with low-molecular-weight heparins. A meta-analysis.

The currently recommended method of venous thromboembolism (VTE) treatment is the application of vitamin K antagonists (VKA) in most patients, and low-molecular-weight heparins (LMWH) in selected groups. The VKA dose adjustment is difficult which might well render the treatment ineffective. The study aimed to compare LMWH with VKA in treating VTE in terms of efficacy and safety. A systematic review of literature and the meta-analysis of the treatment results were performed. The main differences between LMWH and VKA in terms of their respective effectiveness in treating VTE consist in appreciably more advantageous effects of LMWH in preventing deep venous thrombosis (DVT). The key difference in terms of respective safety is the greater effectiveness of LMWH inpreventing minor bleedings. The advantage of LMWH in cancer patients consists predominantly in a significantly better protection against DVT episodes, whereas the advantage of LMWH in non-cancer patients is mainly owed to better protection against minor bleedings. In none of the analysed outcomes of VTE treatment, the application of VKA proved to hold any advantage over LMWH. Although, arguably, there might well be sufficient medical grounds to propose more widespread use of LMWH, it still remains a debatable issue whether the currently used therapeutic standard should also be modified accordingly. Apart from the actual findings of the present meta-analysis, pertinent economic considerations must also be addressed.

Value of transthoracic echocardiography for the detection of high-grade coronary artery stenosis: prospective evaluation in 50 consecutive patients scheduled for coronary angiography.

We prospectively evaluated the feasibility of direct, transthoracic evaluation of coronary arteries to diagnose flow-limiting lesions. Second harmonic mode in B-mode and fundamental mode for Doppler examinations was used. A stenosis was diagnosed when maximal flow velocity at least doubled in comparison with that of the adjacent segment or when local velocity was at least 2 m/s. Of the left anterior descending coronary artery segments assessed, 34 were proximal, 35 middle, and 34 distal segments. The corresponding figures for circumflex coronary artery segments were 17 proximal and 11 middle segments and for the right coronary artery, 14 proximal and 15 distal segments. No distal circumflex and only 1 mid right coronary artery segment was visualized. Twenty-eight stenoses were diagnosed. Specificity for stenosis detection was 96% to 100% and sensitivity was 62% to 66%. Echo-cardiography was unable to document occlusions. Transthoracic echocardiography allows for coronary artery assessment in a significant portion of patients scheduled for coronary angiography. It may be used to document the presence of coronary artery stenosis. With further technologic improvements, transthoracic echocardiography could enable the monitoring of the restenosis process after percutaneous transluminal coronary angioplasty/stent intervention and coronary artery luminal narrowing after heart transplantation.

Effect of verapamil on systolic and diastolic coronary blood flow velocity in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy.

OBJECTIVE: To assess non-invasively the effect of verapamil treatment on coronary blood flow velocity in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy. DESIGN: High frequency transthoracic Doppler echocardiography was used to compare resting phasic coronary blood flow velocity before and after a one month period of verapamil treatment in 17 patients (14 men and three women) with non-obstructive hypertrophic cardiomyopathy. Eighteen healthy subjects formed an age and sex matched control group. Systolic and diastolic coronary blood flow velocity was measured in the distal portion of left anterior descending coronary artery using high frequency transthoracic Doppler echocardiography. Blood flow velocity before and after verapamil was compared in the patients with cardiomyopathy and with the results in the control group. RESULTS: Compared with the controls, patients with hypertrophic cardiomyopathy had increased diastolic coronary blood flow velocity (41.8 (8.1) v 59.9 (21.9) cm/s, p < 0.01) and a lower mean systolic coronary blood flow velocity (18.7 (10.8) v -11.2 (27.5) cm/s, p < 0. 01) before verapamil treatment. A backward pattern of systolic flow, manifested by negative values of coronary blood flow velocity, was recorded in eight of the patients, while no negative values were found in the controls. After verapamil treatment the retrograde systolic blood flow was restored to an anterograde pattern in only one patient. The mean value of systolic coronary blood flow velocity did not change significantly and remained lower than the systolic forward flow velocity in the controls (-3.6 (31.8) v 18.7 (10.8) cm/s, p < 0.05). However, diastolic coronary blood flow velocity decreased significantly after verapamil (59.9 (21.9) v 50.7 (19.5) cm/s p < 0.05), reaching a level comparable with that in the controls (50.7 (19.5) v 41.8 (8.1) cm/s, p > 0.05). CONCLUSIONS: In contrast to healthy subjects, in non-obstructive hypertrophic cardiomyopathy the systolic pattern of coronary blood flow was heterogeneous (both retrograde and anterograde), and diastolic coronary blood flow velocity was abnormally increased, despite a lack of significant symptoms. Verapamil treatment did not restore the forward pattern of systolic blood flow but decreased diastolic blood flow velocity to a level comparable with that in healthy subjects.

[Ischemic ulcer in Madelung disease]. / Owrzodzenie niedokrwienne w chorobie Madelunga.

We describe a 50 years old man with multiple symmetric lipomatosis (Madelung disease) and two years history of intermittent claudication who was hospitalized because of persistent ulcer of left foot. Lipomata were located on the neck, shoulders and chest; they enlarged gradually over a few years, becoming huge in size. Ulceration of the foot appeared a few weeks before hospitalization and its ischaemic origin was uncertain because of atypical character (painless, ankle/brachial index > 0.5). After angiographic examination patient was assigned for conservative treatment. Intravenous infusions of alprostadil were given with poor effect. Because of gradual enlargement of the ulceration, pain intensification and relatively favourable angiographic picture aorto-bifemoral prosthesis implantation was performed with satisfactory short-therm effect. In addition, patient required vitamin B12 supplementation due to megalocytic anemia.

Comparison of the effect of verapamil and propranolol on response of coronary vasomotion to cold pressor test in symptomatic patients with hypertrophic cardiomyopathy.

Impaired endothelium-dependent vasodilatation of coronary resistance vessels has been demonstrated in patients with hypertrophic cardiomyopathy (HC). The aim of this study was to compare the effect of verapamil and propranolol on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to the cold pressor test (CPT) in symptomatic HC patients. In 15 patients with HC, the CBFV was measured in the distal portion of the left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. Peak diastolic CBFV and coronary vascular resistance index (calculated as ratio of mean aortic pressure/CBFV ratio) were measured at baseline and after CPT. Changes of these parameters induced by the CPT (expressed as percentage of baseline values) were compared after verapamil and propranolol treatment in a crossover study. The same measurements were obtained in nine healthy control subjects. CPT induced an increasing pattern of CBFV during verapamil therapy, which was absent in CPT after propranolol administration (10.1 +/- 5.6% vs. -0.9 +/- 4.1%, P < 0.01). In healthy controls CBFV increased in response to CPT more than in HC patients receiving verapamil or propranolol (23.1+/- 12.8% P < 0.01 and P < 0.05, respectively). The coronary vascular resistance index increased during the CPT significantly less on verapamil than on propranolol treatment (3.5 +/- 9.2% vs. 18.1 +/- 13.5%, P < 0.01). In healthy controls the coronary vascular resistance index decreased during CPT -4.5 +/- 8.5% (P < 0.05 vs. verapamil and P < 0.01 vs. propranolol). Verapamil improved the coronary vasomotor response to CPT in relation to propranolol. Verapamil blunted the increase of the coronary vascular resistance index to the CPT in comparison with its change at CPT after propranolol. Thus, coronary endothelial dysfunction in symptomatic HC patients may be partially reduced by verapamil in comparison with propranolol treatment.

[Advanced abdominal angina due to atherosclerosis with atypical celiac arteries]. / Ciezka angina brzuszna spowodowana miazdzyca w nietypowo przebiegajacych tetnicach trzewnych.

It is generally accepted that the abdominal angina develops only when at least two of the three splanchnic vessels-mesenteric arteries and the celiac trunk exhibit a critical obstruction. That common opinion does not, however, take into account anatomical variants of arteries supplying the blood to the intestines. We present a case of a wasted, 40 year old male with a wide spread arteriosclerosis and postprandial pain. The ultrasound examination revealed total occlusion of the superior mesenteric artery (SMA). Celiac trunk (CT) and inferior mesenteric artery (IMA) were patent. The ultrasound indicated that only one splanchic vessel was obstructed; the systemic disorder, the neoplasm, as well as the malabsorption were ruled out. An arteriography of the abdominal aorta and of splanchnic arteries confirmed patency of CT and IMA, also lack of flow in the SMA. Atypical origin of the middle colic artery originating from the bed of CT was also shown. Lack of collaterals between IMA and SMA, typically conducting a sufficient blood flow, resulted in a fully symptomatic abdominal angina. Symptoms were relieved following surgical revascularization.

Verapamil improves the response of coronary vasomotion to cold pressor test in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy.

Impaired endothelium-dependent vasodilatation of coronary resistance vessels was previously demonstrated in patients with hypertrophic cardiomyopathy (HC). Therefore, we decided to assess the effect of verapamil administration on the response of diastolic coronary blood flow velocity (CBFV) and the coronary vascular resistance index to the cold pressor test in asymptomatic and mildly symptomatic HC patients. In 10 patients with nonobstructive HC, the CBFV was detected in the distal portion of the left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. Peak diastolic CBFV, the velocity-time integral of diastolic CBF, and the coronary vascular resistance index (calculated as the mean aortic pressure/CBFV ratio) were measured at baseline and after the cold pressor test. The percentage changes from baseline to the cold pressor test of these parameters were compared before and after 1 month of verapamil therapy. Open-label verapamil changed the decrease in CBFV into an increase in response to the cold pressor test (from -4.1 +/- 6.4% to +11 +/- 10.9%, P < 0.01). A similar reversibility of changes in the velocity-time integral of CBF in response to the cold pressor test after verapamil therapy was observed (from -3.3 +/- 8.3% to +9.6 +/- 10.3%, P < 0.05). Verapamil reversed the response of coronary resistance vessels to the cold pressor test from a +12 +/- 9.8% increase to a -5.2 +/- 10.2% decrease in the coronary vascular resistance index (P < 0.01). We concluded that in asymptomatic and mildly symptomatic HC patients in response to the cold pressor test, treatment with open-label verapamil increased CBF parameters and decreased the coronary vascular resistance index. Verapamil reversed the abnormal vasoconstrictor to vasodilator response of coronary resistance vessels to the cold pressor test. The restoration of the vasodilator response to the cold pressor test by verapamil suggests the potential positive effect of verapamil on endothelium-dependent coronary vasodilation in HC patients. Thus, a randomized blinded trial is now required.

Impaired response of the forearm resistance but not conductance vessels to reactive hyperemia in hypertrophic cardiomyopathy.

It has been suggested that in hypertrophic cardiomyopathy (HC), vascular abnormalities are not restricted to the heart. Flow-mediated dilation of peripheral conductance arteries (reflecting their endothelial function) has not yet been studied in HC. Our aim was to assess both flow-dependent dilation of the brachial artery and flow responses (dependent on resistance vessels) during forearm reactive hyperemia (RH) in nontreated HC patients. The authors studied 13 HC patients and 14 age- and sex-matched healthy controls. None of them exhibited any factors known to be associated with endothelial dysfunction. Using 7 MHz ultrasound, brachial artery diameter and Doppler flow velocity were measured continuously at baseline and throughout 1 min of RH following 5 min of forearm ischemia induced by inflation of a blood pressure cuff. Arterial diameter and RH flow are expressed as percent changes with respect to the baseline. Flow-dependent dilation was similar in the HC patients and control subjects (7.2 +/- 9.5% vs 9.9 +/- 10.4%, p>0.05). Compared to the control group, RH flow in HC was decreased; however, differences did not reach statistical significance until 60 sec of RH (112 +/- 102% vs 261 +/- 217%, p<0.05; HC vs controls). In HC patients, endothelial function of peripheral conductance arteries is preserved. Hence, a defect in the forearm arterial bed in HC seems to be limited to mechanisms maintaining the dilation of resistance vessels during decreasing RH flow.

Using patient surveys to measure the quality of outpatient care in Kraków, Poland.

OBJECTIVE: To test the feasibility of using patient reported information to create indicators of quality (access, patient experience--including satisfaction, and clinical quality) with the goal of providing Kraków city clinic managers (and potentially other audiences) with information about the quality of outpatient care in selected clinics. Setting and methods. Almost 2,000 patients from 19 outpatient clinics in Kraków, Poland were surveyed in November and December 1997 and January 1998. We prepared a self-completed questionnaire to capture data about the patient's experience with access to services, interactions with registration staff, communication with the doctor, information received from the doctor, and receipt of preventive services. RESULTS: Access varied across clinics. For example, 84% of patients waited less than 10 minutes at registration, whereas only 53% of patients waited less than 30 minutes to see the doctor. Among those who tried to register by telephone, only 72% were successful. Satisfaction was highest with the doctor visit (satisfaction=79, on a scale of 1-100) and lowest with telephone registration (satisfaction = 59). Preventive health care screening was generally disappointing, particularly for Papanicolaou smear and clinical breast examination, although frequent users of a clinic (with more opportunities for screening) generally had higher rates of screening. CONCLUSION: We demonstrated the feasibility of constructing indicators of multiple dimensions of the quality of outpatient care using patient-reported information. Quality dimensions captured by survey included access, patient experience and clinical quality. Results were successfully summarized in easy to read and understand formats for clinic managers and city health department officials.

[Balloon angioplasty of branches of the aortic arch]. / Angioplastyka balonowa duzych galezi luku aorty.

Balloon angioplasty has become a first-line therapy of symptomatic brachiocephalic occlusive disease. We review our own results of treatment of these lesions for the last two years. 16 patients (18 vessels--6 occlusions) with chronic limb ischaemia (9 cases), vertebrobasilar insufficiency (4 cases), ischemic stroke (2 cases); in one case angioplasty was performed as prevention before major abdominal surgery. Femoral approach was predominantly used; in 3 occlusions brachial approach was chosen. Stents were implanted in 4 cases of poor angioplasty result with severe limb ischaemia. Lesions were crossed in all stenoses and in 4 of 6 occlusions. Residual stenosis < 30% was attained in 10 pts. In 11 cases transstenotic gradient was relieved and a normal flow in vertebral artery was reestablished. There were two cases of acute upper limb ischaemia, one needed surgery. Reversible ulnar nerve paresis was noted in one patient, transient symptoms of postreperfusion syndrome in two. At follow up (mean 12 mo, range 1-30 mo) 1 restenosis was recorded. Balloon angioplasty is easy, safe and effective for treating brachio-cephalic stenoses. Recanalisation of occlusions is more difficult and risky. Treatment of stenoses should not be undully postponed; recanalisation should be reserved for patients with more advanced symptoms of the disease.

[Diagnostic difficulties in cases with spurious thrombocytopenia]. / Trudnosci diagnostyczne w przypadkach maloplytkowosci rzekomej.

Pseudothrombocytopenia (PTP) is a rare laboratory phenomenon of falsely low platelet count in the presence of anticoagulant, most often EDTA. It may be confused with true thrombocytopenia, leading to the refusal of further invasive procedures and inappropriate diagnosis and treatment. PTP is due to presence of antiplatelet antibodies--agglutinins--usually temperature dependent. Here we present two cases of such spurious thrombocytopenia and discuss the differential diagnosis.

[Effect of thromboxane A2 synthetase inhibitor and prostacyclin analogue on arterial blood pressure, fibrinolysis and platelet function in patients with hypertension]. / Wplyw inhibitora syntetazy tromboksanu A2 i analogu prostacykliny na cisnienie tetnicze, fibrynolize i czynnosc krwinek plytkowych u chorych na nadcisnienie tetnicze.

An effect of the specific thromboxane A2 synthetase inhibitor and stable prostacyclin analogue on arterial blood hypertension was investigated in 12 patients with spontaneous hypertension of II degree and in 12 healthy subjects. The patients were given a 3-hour intravenous infusion of Iloprost (Schering) in the dose of 2 ng/kg b.w. per minute and OKY-046 (ONO, Japan) in a single oral dose of 400 mg. Iloprost shortened euglobin fibrinolysis time without an effect on tissue plasminogen activator levels or blood pressure. OKY-046 decreased TBX2 to undetectable values, increased 6-keto-PGF1 alpha by 8-fold, and significantly reduced both systolic and diastolic blood pressures in hypertensive patients. Such effects may dependent upon an increase in the endogenous prostacyclin or an inhibition in thromboxane production in the affected arterial walls. If the present observations would be confirmed by double blind trial, they would constitute the base for new pharmacotherapy of hypertension.

Fibrinolytic activity of prostacyclin and iloprost in patients with peripheral arterial disease.

We studied the effects of prostacyclin (PGI2) and its stable analog, iloprost, on blood fibrinolytic activity in 33 patients with peripheral arterial disease. Ten subjects (group A) received three 5-hour infusions of iloprost on three consecutive days. The remaining 23 patients received three different 5-hour infusions (placebo, iloprost 2 ng/kg/min, PGI2 5 ng/kg/min). Tissue plasminogen activator (t-PA), total plasma fibrinolytic activity and euglobulin clot lysis time (ECLT) were determined in patients before and after each infusion, both in freely flowing blood samples and following 10 min venous occlusion. In patients of group A, ECLT at rest was significantly shortened after all three iloprost infusions (on average by about 5-11%). First and third infusions produced also shortening of ECLT after venostasis (by 21 and 32%). Statistically significant rise in t-PA activity (by about 68% on average) accompanied only the first infusion. In patients of the group B iloprost provoked significant fall in ECLT at rest (by about 19% on average) only. PGI2 shortened ECLT both at rest and after venous occlusion (by about 17% and 20% on average, respectively) and led to a rise in t-PA activity after venous occlusion by about 33% on average. Our results indicate that prostacyclin and its stable analog, iloprost, enhance fibrinolytic activity in man by releasing or facilitating the release of tissue plasminogen activator from the vessel wall.

Bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1.

We evaluated in a double-blind study the bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1 (PGE1-carbinol), described recently as a nonirritant bronchodilator in animals. Fifteen asthmatic patients received by inhalation single doses of 1, 10, and 30 micrograms PGE1-carbinol, 55 micrograms PGE2, and placebo (10% ethanol in normal saline, which was also used as diluent for the PGs). Such pulmonary function tests as forced expiratory volume in 1 second, forced vital capacity, and maximal expiratory flow were monitored during 2 hours following inhalation of each compound. 10 and 30 micrograms PGE1-carbinol produced significant but short-acting bronchodilation, similar to that caused by 55 micrograms PGE2. One-third of the patients reported mild cough and throat irritation during and shortly after inhalation of 30 micrograms PGE1-carbinol or 55 micrograms PGE2. Placebo and 1 microgram PGE1-carbinol produced minimal side effects, but neither agent caused bronchodilation. In an adjunctive, unblinded trial, the same patients received 400 micrograms fenoterol. Fenoterol caused greater bronchodilation 15 and 30 minutes after inhalation than did the PGs in the double-blind study.