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K Alexander

Publications and source records attributed to K Alexander.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Dose-dependent side effects of acetylsalicylic acid therapy. Results of a prospective randomized clinical study in patients with peripheral arterial occlusive disease].

BACKGROUND AND METHODS: In 359 patients with peripheral arterial occlusive disease who had undergone percutaneous transluminal angioplasty (PTA), a randomized double-blind, controlled clinical study was done to investigate the tolerability of acetyl salicylic acid (ASA) given for reocclusion prophylaxis. A comparison was made between a conventional daily dose of 900 mg ASA and a dose of 50 mg ASA. RESULTS: Within an observation period of one year following PTA, 35 patients (20%) in the 900 mg group, and 32 patients (17%) in the 50 mg group left the trial because of side effects (p = NS). Under the higher dose, however, severe gastrointestinal side effects (ulcer, haemorrhagic gastritis requiring transfusion) were significantly more common (nine patients delta 5.1% vs two patients delta 1.1%, respectively; p = 0.03). Overall, 107 patients (30%) reported subjective side effects such as upper abdominal pain, a sensation of fullness or nausea during the course of the trial. 62 of these patients were from the 900 mg group (35%) as compared with 45 patients (24%) in the 50 mg group (p = 0.02). Self-scoring of epigastric pain on the basis of a visual analogue scale revealed a score of 1.3 (95% confidence interval 0.9 to 1.6) in the 900 mg group and 0.8 (95% confidence interval 0.6 to 1.0) in the 50 mg group. The subjective pain intensity showed a uniform time course for all three types of symptom, with a maximum after three months. CONCLUSION: Our results confirm the superior tolerability of the lower dose, in particular in elderly patients. For long-term treatment, the smallest possible effective dose should be chosen.

Aged↗
PubMed1993

Characterization of a divergent glycosomal microbody phosphoglycerate kinase from Trypanosoma brucei.

There are 3 loci in the phosphoglycerate kinase (PGK) gene complex of Trypanosoma brucei. The PGK-A gene product, which we term 56PGK, is targeted to glycosomal microbodies and is highly homologous to the parasite's 2 known PGKs (one cytoplasmic and one glycosomal). However, 56PGK contains an 80 amino acid insertion as well as numerous substitutions compared to the other PGKs. The complementation and kinetic analyses described here demonstrate that 56PGK is an authentic phosphoglycerate kinase--the largest yet described. When expressed in Escherichia coli, 56PGK complements the pgk- phenotype. 56PGK was expressed as a fusion protein and purified to near homogeneity. The Michaelis constants are similar to those of other PGKs, being 0.12 and 2.4 mM for Mg-ATP and 3-phosphoglycerate, respectively. As with other T. brucei PGKs, ATP but not GTP or ITP can serve as a phosphate donor during catalysis. No evidence was obtained for phosphate transfer to atypical substrates. 56PGK shows sulfate inhibition at all concentrations tested, rather than the sulfate activation observed with yeast PGK.

Amino Acid Sequence↗
PubMed1993

Dose-dependent effect of aspirin on carotid atherosclerosis.

BACKGROUND: Antiplatelet treatment with aspirin is well established as secondary prophylaxis after a transient ischemic attack or minor ischemic stroke, but the effect of aspirin treatment on the course of carotid atherosclerosis is unknown. We investigated the effect of aspirin on the initial stages of carotid atherosclerosis. METHODS AND RESULTS: Patients were recruited from a prospective, randomized, double-blind clinical trial to compare two doses of aspirin (900 mg versus 50 mg daily) with regard to restenoses after lower limb angioplasty. Of the 383 patients admitted to the angioplasty trial, 27 patients with 104 small carotid atheroma (< 50% lumen narrowing) were examined at entry and after 1 year of aspirin treatment with the use of a high-resolution ultrasound duplex system. Disease progression and regression were defined by a change of maximal plaque area (as measured by longitudinal ultrasound sections) of more than 2 SDs of the method. The change in plaque area was significantly different for the treatment groups: Average plaque size remained unchanged after treatment with 900 mg aspirin daily but increased markedly after treatment with 50 mg aspirin daily (p = 0.011). There were significantly more lesions in the 50-mg group showing progression than in the 900-mg group (23 plaques [47%] versus 13 plaques [24%], p = 0.025). Ultrasonic disappearance of a lesion was observed only in the 900-mg group in nine cases (seven soft plaques and two ulcerative plaques, p = 0.018). The six patients on 50 mg aspirin who continued smoking during the study showed significantly more progression compared with the seven nonsmokers in the 50-mg group (17 plaques [59%] versus six plaques [30%], p = 0.038). CONCLUSIONS: The results of our study indicate that aspirin treatment slows carotid plaque growth in a dose-dependent fashion, with a dose of 900 mg daily more efficient than 50 mg daily.

Aspirin↗
PubMed1993

[Conservative therapy of peripheral arterial occlusive diseases].

Treatment of peripheral arterial occlusive disease depends upon pathogenesis, localization, and severity of disease. For patients with intermittent claudication the goal should be an increased reserve capacity, and in critical limb ischemia therapy should aim at restitution of the basal metabolism. Hemodynamic as well as hemorheologic improvements act in this way. Considering the pathophysiological, pathobiochemical, and clinical aspects of the individual patient, both mechanisms can be used systematically. The efficacy of therapeutic principles in angiology has not been confirmed through large-scale, randomized, placebo-controlled, long-term follow-up studies until now, in contrast to the field of cardiology.

Anti-Bacterial Agents↗
PubMed1993

Variability of TcPO2-measurements at 37 degrees C and 44 degrees C in patients with claudication in consideration of provocation tests.

With regard to the increasing use of tcPO2-measurements for the assessment of peripheral arterial occlusive disease, the variability of the method needs more consideration. We studied the reproducibility of tcPO2 measured at 37 degrees C and 44 degrees C, especially under the influence of provocation tests, in 21 patients with severe claudication (ankle artery pressures (AP) 30-100 mmHg) without skin lesions. On 6 days within 2 weeks tcPO2 was recorded on the forefoot at 37 degrees C and 44 degrees C electrode core temperatures a) in supine position, b) in sitting position, c) during O2-breathing, d) during reactive hyperemia (RH). In measurements at 37 degrees C variation coefficients (VC) were high (mean +/- S.D.: 74 +/- 27%) and could not be improved by oxygen inhalation nor by the sitting position. Only during RH, VC decreased significantly to 49 +/- 23%. At 44 degrees C VC were still quite high (mean: 42 +/- 24%) and were inversely correlated with AP. Mean tcPO2 increased under all provocation maneuvers. However, only in the sitting position VC decreased significantly to 18.7 +/- 8.4% (p < 0.001). Single tcPO2 measurements, both at 37 degrees C and 44 degrees C, are of low value in patients with severe claudication. For the evaluation of the individual patient repeated measurements are demanded. Reduced variability may be achieved by measurements at 44 degrees C in a sitting position.

Adult↗
PubMed1992

Fluorescence energy transfer analysis of calmodulin-peptide complexes.

The interactions between calmodulin and the tryptophan residues of synthetic peptides corresponding to the calmodulin binding domains of skeletal muscle myosin light-chain kinase and the plasma membrane calcium pump were examined. The single tryptophan residue contained in each peptide became relatively immobilized and inaccessible to iodide ion upon binding to calmodulin, indicating that the indole side chain was inserted into a hydrophobic cleft in the surface of calmodulin. Fluorescence energy transfer from peptidyl tryptophan residues to an AEDANS moiety attached to cysteine-26 of spinach calmodulin was measured. Included in these analyses was a tryptophan-containing peptide analog of the calmodulin binding domain of neuromodulin. These data indicated that the indole ring of each peptide inserted 32-35 A away from cysteine-26 and may therefore interact with the carboxyl-terminal lobe of CaM in its "bent" conformation [Persechini & Kretsinger (1988a) J. Cardiovasc. Pharmacol. 12 (Suppl 5), S1-S12; Ikura et al. (1992) Science 256, 632-638; Vorherr et al. (1992) Eur. J. Biochem. 204, 931-937]. The interchange of tryptophan-3 and phenylalanine-21 of the calcium pump peptide increased the efficiency of energy transfer to the AEDANS-moiety approximately 12-fold, reducing the calculated distance to 20 A. These data suggest that phenylalanine-21 of the calcium pump peptide interacts with the hydrophobic cleft in the amino-terminal lobe of CaM.

Amino Acid Sequence↗
PubMed1992

Duplex scanning of the peripheral arteries: correlation of the peak velocity ratio with angiographic diameter reduction.

The correlation of the peak systolic velocity (PSV) and the peak velocity ratio (PVR, calculated as intrastenotic PSV divided by proximally recorded PSV) with percent diameter reduction was studied in 62 patients with peripheral arterial occlusive disease. PSV values correlated well with angiographic diameter reduction (r = 0.81, n = 106 stenoses), but due to large variability the sensitivity and specificity in the detection of greater than 50% stenoses were only 66% and 80% (for a cutoff value of 180 cm/s). The PVR showed less interindividual variability and exhibited a strong correlation with percent diameter reduction (r = 0.93,n = 106 stenoses). A 2.4 fold increase of the peak systolic velocity values with respect to the proximal site (i.e., PVR = 2.4) or more indicated a more than 50% stenosis with a sensitivity of 87% and a specificity of 94%. Figures for PVR are provided to quantitate the degree of stenoses in the 50-99% range. Calculation of PVR may normalize for patient variation and allow noninvasive quantification of lumen narrowing with high sensitivity and specificity.

Arterial Occlusive Diseases↗