Effect of long-term cytostatic therapy on the hematopoietic stem cells]

CFU-C and diffusion chamber studies were performed in patients with teratocarcinoma, who underwent long term chemotherapy. No significant decline of bone marrow CFU-C or diffusion chamber cell recovery was found during twelve months of cytotoxic treatment. In contrast to the results in these patients the CFU-C-content of the remission marrow in leukemic patients showed a significant decrease in relation to the duration of remission and chemotherapy.     

Gene therapy for peripheral arterial disease

Our understanding of the molecular biology of vascular disease is rapidly expanding, and this scientific growth has brought with it new opportunities for therapeutic intervention at the molecular and genetic levels. Although our tools for genetic manipulation in vivo and our knowledge of potential molecular targets are still crude and incomplete, the early application of these concepts to clinical problems is already underway, both in the pre-clinical and clinical arenas. The treatment of peripheral vascular disease, although greatly improved over recent decades by surgical and minimally-invasive techniques, remains limited by vascular proliferative lesions and by our inability to modulate the progression of native disease. This review explores some of the evolving concepts of therapeutic gene manipulation and their initial application in the peripheral circulation.     

Long-term results of aorto-iliac occlusive disease treatment with implantation of the Polish vascular prosthesis]

The author analyses distant results of the Polish vascular prostheses implantation to 227 patients with aorto-iliac occlusive disease. Eighty two (29.6%) patients died within 5 years following the operation. Therefore, an analysis of the distant results of therapy included 145 patients. An excellent result was achieved in 20.7% of the treated patients, satisfactory result in 53.9%, no improvement or worsening in 20.7% of cases. Statistically significant relationship between the degree of pre-operative ischemia and outcome of surgery has been noted. Considering blood hypertension, diabetes mellitus, obesity, hypercholesterolemia, and tobacco smoking prior to and after surgery as risk factors, no statistically significant relationship between the distant result of the treatment and the number of risk factor in a single patient has been observed.     

Native fluorescence of platelets from patients with occlusive arterial disease

Healthy platelets exhibit a fluorescence band with a peak at 475 nm if excited at 360 nm. This peak increases first with the progression of occlusive arterial disease (OAD) followed by a decrease at an advanced stage. Concomitantly, a new fluorescence band at 445 nm will appear, which increases steadily with the progression of OAD. These findings can be explained by the oxidation of NADH (fluorescence at 475 nm) to NAD (445 nm) and support, thus, the assumption that oxidative processes are involved in the formation of OAD.     

Localization of a gene for peripheral arterial occlusive disease to chromosome 1p31

Peripheral arterial occlusive disease (PAOD) results from atherosclerosis of large and medium peripheral arteries, as well as the aorta, and has many risk factors, including smoking, diabetes, hypertension, and hyperlipidemia. PAOD often coexists with coronary artery disease and cerebrovascular disease. Cross-matching a population-based list of Icelandic patients with PAOD who had undergone angiography and/or revascularization procedures with a genealogy database of the entire Icelandic nation defined 116 extended families containing 272 patients. A genomewide scan with microsatellite markers revealed significant linkage to chromosome 1p31 with an allele-sharing LOD score of 3.93 (P=1.04 x 10(-5)). We designate this locus as "PAOD1." Subtracting 35 patients with a history of stroke increased the LOD score to 4.93. This suggests that, although PAOD and other vascular diseases share risk factors, genetic factors specific to subtypes of vascular disease may exist.     

Effect of iloprost on plasma asymmetric dimethylarginine and plasma and platelet serotonin in patients with peripheral arterial occlusive disease

BACKGROUND: Iloprost, a prostacyclin analogue, is used in the treatment of peripheral arterial occlusive disease at Leriche-Fontaine stages III-IV, through intravenous infusion for at least 21 days. Recently, iloprost has been shown to be safe and effective in critical limb ischemia patients when administered per 7 days. We investigated in patients at Leriche-Fontaine stages III-IV the effect of 1-week treatment with iloprost on plasma asymmetric dimethylarginine (ADMA), plasma and platelet serotonin, and on clinical response. METHODS AND RESULTS: Twenty-four critical limb ischemia patients (16 men and 8 women, mean age 76+/-9.7 years) were included in the study and treated with intravenous iloprost (titrated from 0.5 up to 1.5 ng/kg/min) for 16 h a day for seven consecutive days. Blood samples were drawn before infusion on days 1, 4 and 8 of treatment, under the same conditions. Clinical assessment was performed by clinical evaluation, ankle/brachial pressure index and treadmill exercise test. During treatment with iloprost patients clinically improved and plasma levels of ADMA significantly decreased (p<0.001). We also observed a significant increase of serotonin (p<0.01) in platelets and a significant decrease of serotonin (p<0.001) in plasma. Similar variations of ADMA and serotonin were found in two subgroups of patients, diabetics and non-diabetics. CONCLUSIONS: One-week treatment with iloprost in critical limb ischemia patients induced changes of peripheral markers of endothelial dysfunction and atherosclerosis, such as ADMA and serotonin, associated to a clinical improvement.     

Preclinical models of human peripheral arterial occlusive disease: implications for investigation of therapeutic agents.

Peripheral arterial occlusive disease (PAOD) is now recognized as a combination of clinical syndromes that are associated with significant morbidity and mortality. The primary pathophysiology of PAOD is impaired perfusion to the lower extremity. Effective pharmacotherapy designed to increase perfusion in PAOD is lacking, and revascularization options are suboptimal. New and more efficacious therapies that improve blood flow are definitely needed, and thus designing, describing, and validating these new therapies in preclinical PAOD models will be essential. This study describes the various preclinical PAOD models presently in use, correlates the models to human PAOD, and reviews the available end points that can be used to detect a response to therapy.     

Analysis of early results of combined treatment with glucocorticoids and telecobalt therapy for Graves' disease ophthalmopathy]

Early results of combined use of glucocorticoid administration and irradiation with radioactive cobalt for treatment of oedematous-infiltrative ophthalmopathy associated with Graves' disease have been analyzed in a group of 33 patients including 28 women and 5 men of age between 25 and 66 years (mean age 47.3 years). The combined therapy was a modification of the original method of Bartalena et al. which consisted in the gradual increase of the initial dose of glucocorticoids and prolongation of the period of administration of the drug. The ophthalmic lesions were assessed by thorough ophthalmologic examination and classified according to Werner. The ophthalmopathy index was calculated according to Donaldson. Satisfactory results of treatment have been obtained in 32 patients, with 9 patients being completely relieved from any objective or subjective ophthalmic symptoms (very good results), and 23 patients having still small afflictions originating from the soft tissues of the eye socket, exophthalmos, diplopia during marginal vision and a decreased visual acuity (good results). The clinical recovery was mostly connected with the improvement in the condition of soft tissues of the eye socket, cornea and external ocular muscles and, to a smaller extent, exophthalmos which persisted to some degree and acuity of vision not always attaining normal values. In one person the results of treatment were unsatisfactory despite some improvement. Very good and good results obtained in 97% of patients indicate that the administration of glucocorticoids combined with the irradiation of retrobulbar tissues with radioactive cobalt can now be regarded as the most effective method of treatment of the progressive oedematous-infiltrative ophthalmopathy.     

Effects of intravenous oxygen on prostacyclin and thromboxane formation in patients with peripheral occlusive arterial disease.

Oxygen infusion is used in complementary medicine for treatment of peripheral occlusive arterial disease. The mechanism of action is unknown. Thus, we determined the effects of oxygen infusion on prostacyclin, thromboxane and nitric oxide synthesis. Twelve patients with peripheral occlusive arterial disease received oxygen 40 ml/d intravenously for 3 weeks. Study parameters, analyzed by gas chromatography-mass spectrometry on day 1, 3, 10, 16, 21: 2,3-dinor-6-oxo-PGF(1alpha), colour invisible 2,3-dinor-TXB2 and nitrate in one-hour-urine before and after oxygen infusion, reflecting prostacyclin, thromboxane and nitric oxide synthesis. Urinary 8-iso-PGF2alpha, indicating oxidative stress, was assessed in one patient. Urinary 2,3-dinor-6-oxo-PGF1alpha rose from baseline more than 4-fold after oxygen infusion. In contrast, urinary 2,3-dinor-TXB2 excretion remained unchanged. Oxygen infusion had no effect on urinary nitrate excretion. Urinary 8-iso-PGF(2alpha) was not influenced by oxygen infusion with and without diclofenac pretreatment. Our data demonstrate a shift of the prostacyclin/thromboxane ratio toward prostacyclin by oxygen infusion. Thus, a mechanism of action is provided and clinical trials with intravenous oxygen find a rational basis.     

Early and late results of treating peripheral arterial injuries]

Forty six patients with injuries to the great peripheral arteries were treated at the III Department of Surgery, Medical Academy in Cracow in 1968-1987. An injury to the blood vessels was accompanied by bone fractures or joint dislocation in 9 (19.5%) patients whereas 35 (76%) patients suffered also from vein injuries and nervous trunks trauma. In 13 (28%) cases an accident took place when the victims were drunk. Favourable result of the treatment, i.e. return of peripheral pulse, was achieved in 33 (75%) patients, acceptable result, i.e. an increase in limb temperature, in 11 (23%) patients. Two patients underwent an amputation of the limb because of its necrosis. One patient died. Anti-thrombolytic agents were given intra- and postoperatively, and in 9 patients with extensive contusions fasciotomy proved successful. Late results were similar to early ones.     

Clinical trial with long-term therapy of generalized plasmacytoma]

The authors report on findings in long-term therapy made by means of a combination of cyclophosphamide as attack dosis (partially also with polychemotherapy--COP, COPP-scheme) and double plasmapheresis. Since 1967 33 patients have been treated in this way. A group (6 patients) only received cyclophosphamide in a attack therapy of 15...25 mg/5g per body weight; a second group of 14 patients received the same dosis in combination with a double plasmapheresis. The third group of 13 patients in an advanced stage of the illness was treated polychemotherapeutically according to various schemes (COP-cyclophosphamide, vincristine, prednisone; COPP with Natulan) likewise in combination with double plasmapheresis. The observations made for 4 years in the two groups first mentioned showed favourable results in the second group with an average survival time of 35 months. In the third group only experiences of two years can be reported and thus a final answer cannot be given. However, it can already be stated that a clinical success requires the cytostatic therapy to be continued for a long time in combination with plasmapheresis.