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Volume 4, Number 4:April  2001

Characteristics of Heparin-Induced Platelet Aggregates in Chronic Hemodialysis with Long-Term Heparin Use

Cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous NIDDM.

Use of arteriography for the initial evaluation of patients with intermittent lower limb claudication.

Quality of life in patients with intermittent claudication using the world health organisation (who) questionnaire.
 



Characteristics of Heparin-Induced Platelet Aggregates in Chronic Hemodialysis with Long-Term Heparin Use.
                      Reference: Haemostasis 2000;30(5):249-257.

                       This study investigated the usefulness of a new platelet aggregometer with a laser-scattering
                       method for detection of heparin-induced small platelet aggregates in chronic hemodialysis
                       patients. Using this device, small platelet aggregates (particle size 9-25 ?m) were detectable, but
                       these aggregates could not be detected using a conventional light transmittance aggregometer.
                       The laser-scattering intensity of the small aggregates was increased with an increasing dosage of
                       heparin as agonist. These aggregates were disaggregated by heparin neutralization with protamine
                       sulfate. Induction of small platelet aggregates by heparin was inhibited by preincubation with
                       nafamostat mesilate, a synthetic protease inhibitor, and cilostazol, a platelet phosphodiesterase
                       inhibitor, but not by the therapeutic doses of aspirin or argatroban, a selective thrombin inhibitor.
                       The dialysis patients with long-term heparin use could be divided into two groups: responders to
                       heparin, who formed small aggregates with a scattering intensity over 0.51 x 10(5) V after
                       addition of 0.5 IU/ml of heparin obtained from normal platelet-rich plasma without inductor, and
                       nonresponders, who showed an intensity under 0.51 x 10(5) V. The rate of heparin responders
                       among dialysis patients was significantly higher than the rate among normal subjects.
                       Heparin-induced small aggregates were detected in 13 (36.1%) of 36 normal subjects with no
                       history of heparin infusion and in 37 (62.7%) of 59 dialysis patients who received heparin
                       anticoagulation during each dialysis session. Dialysis patients with coronary heart disease did not
                       have a significantly higher rate of heparin responders than patients without complications. There
                       was no significant difference in the positivity rate between cases complicated by diabetes and
                       those without diabetes. In patients who had more than 2 episodes of thrombotic occlusions of an
                       arteriovenous fistula, the rate of responders and the enhancement of scattering intensity of small
                       aggregates by heparin were significantly increased compared with these in patients without
                       occlusions during the preceding 2 years. Moreover, dialysis patients with a positive heparin
                       response showed a marked increase in scattering intensity of small aggregates after heparin
                       infusion in each dialysis session. Determination of the response to heparin prior to heparin use in
                       dialysis patients with repeated thromboembolic complication may be useful in choosing
                       anticoagulant regimens. 



Cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous NIDDM.
 

                      Reference: Diabetes Obes Metab 1999;1(1):37-41.

                       AIM: Angiotensin converting enzyme inhibitors and alpha1-adrenergic blockers improve insulin
                       sensitivity, the mechanism of which was considered, at least in part, to be due to the increased
                       blood flow to muscle. The present study aimed to clarify whether cilostazol, a phosphodiesterase
                       inhibitor, improves insulin sensitivity in a model of spontaneous non-insulin dependent diabetes
                       mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHODS: OLETF
                       rats were divided into the two groups at the age of 16 weeks: the cilostazol-supplemented group
                       (cilostazol 40 mg/kg/day) and the normal-diet group. As a non-diabetic control, we used
                       Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Oral glucose tolerance test and
                       hyperinsulinemic euglycemic clamp was performed at the ages of 23 and 25 weeks, respectively.
                       Serum levels of lipids and leptin were measured. RESULTS: Body weight and abdominal fat was
                       increased in OLETF rats but cilostazol supplementation did not alter them. Insulin sensitivity, as
                       measured by the hyperinsulinemic euglycemic clamp technique, was significantly decreased in
                       OLETF rats (glucose infusion rate: 73.5 +/- 10.0 vs. 41.5 +/- 9.8 micromol/min/kg body weight,
                       p < 0.01). Cilostazol supplementation improved insulin sensitivity partially but significantly 51.0
                       +/- 5.7 micromol/min/kg body weight, p < 0.05) in OLETF rats at 25 weeks of age, although it
                       did not decrease serum levels of glucose, lipids or leptin. However, this effect was not observed
                       in non-diabetic rats. CONCLUSION: Cilostazol, which is used in diabetic patients for the
                       treatment of obstructive disease of artery, is expected to have a beneficial effect on insulin
                       sensitivity in NIDDM.



Use of arteriography for the initial evaluation of patients with intermittent lower limb claudication.

                       Reference: Sao Paulo Med J 2001;119(2):59-61.

                      CONTEXT: Many patients with intermittent claudication continue to be forwarded to the
                       vascular surgeon for initial evaluation after arteriography has already been accomplished.
                       OBJECTIVE: The main objective of this work was to analyze the usefulness and the need for this
                       procedure. TYPE OF STUDY: Retrospective study. SETTING: The patients were divided into
                       two groups: Group 1, with the arteriography already performed and Group 2 without the initial
                       arteriography. PARTICIPANTS: One hundred patients with intermittent claudication were
                       retrospectively studied. Other specialists had forwarded them for the first evaluation of
                       intermittent claudication, without any previous treatment. MAIN MEASUREMENTS: All
                       patients were treated clinically for at least a 6-month period. The total number of arteriographies
                       performed in the two groups was compared and the need and usefulness of the initial
                       arteriography (of Group 1) was also analyzed. RESULTS: The evolution was similar for both
                       groups. The total number of arteriographies was significantly higher in Group 1 (Group 1 with 53
                       arteriographies vs. Group 2 with 7 arteriographies). For this group, it was found that
                       arteriography was only useful in five cases (10%), because the surgeries were based on their
                       findings. However, even in those cases, no need for arteriography was observed, as the
                       procedure could have been performed at the time of surgical indication. CONCLUSION: There
                       are no indications for arteriography in the early evaluation of patients with intermittent
                       claudication, because it does not modify the initial therapy, independent of its result. In cases
                       where surgical treatment is indicated, this procedure should only be performed prior to surgery.



Quality of life in patients with intermittent claudication using the world health organisation (who) questionnaire.

                       Eur J Vasc Endovasc Surg 2001;21(2):118-22.

                       Objective: to assess quality of life (QOL) in patients with intermittent claudication. Design: a
                       prospective, open study. Material and method: one hundred and fifty-one consecutive claudicants
                       (100 men, 51 women), and 161 healthy controls (70 men and 91 women) completed an adapted
                       version of the World Health Organisation Quality of Life Assessment Instrument-100. Results:
                       patients scored significantly worse on the domains Physical health and Level of independence, as
                       well as on the facets Pain and discomfort, Energy and fatigue, Mobility, Activities of daily living,
                       Dependence on medication and treatments, Working capacity, Negative feelings, Recreation and
                       leisure and Overall QOL and general health. Increasing disease to incapacitating claudication
                       affected only the facet Mobility and the domain Level of independence. Conclusion: QOL in
                       patients with intermittent claudication is reduced in many aspects. Where co-morbidity seems to
                       affect QOL strongly, the effect of walking distance on QOL might be small. These findings may
                       justify a reserved attitude towards invasive, even minimally invasive treatment of these patients.