Prolongation of platelet survival in hypercholesterolaemic rabbits by CGS 12970 (3-methyl-2-(3-pyridyl)-1 indoleoctanoic acid) and dazoxiben

In rabbits receiving a normal laboratory diet the platelet half-life was 40.4 ± 2.5h (mean ± S.D., N=35). In animals fed the cholesterolenriched diet for 12 weeks the platelet half-life was reduced to 31.6 ± 3.6h (mean ± S.D., N=35). Treatment of cholesterol-fed animals with a single daily dose of CGS 12970 (a long acting inhibitor of thromboxane synthase) normalised the platelet half-life. Single daily doses of the relatively shorter acting thromboxane synthase inhibitors (CGS 13080 and dazoxiben) failed to correct the reduced platelet survival. However, twice daily dosing with dazoxiben was effective. The cyclooxygenase inhibitors, aspirin and sulphinpyrazone, failed to correct the reduced platelet survival.     

Pharmacodynamic behaviour of isolated resistance vessels obtained from hypertensive-diabetic rats

Summary— The influence of various vasodilator and constrictor drugs was studied in isolated mesenteric arteries obtained from obese and lean Zucker rats. The obese Zucker rats were moderately hypertensive and their isolated small arteries were not hypertrophied. All vasoconstrictor agents studied (noradrenaline, methoxamine, serotonin, calcium chloride, potassium chloride) caused the same effects in isolated arteries taken from obese and lean (control) Zucker rats, respectively. In vessels from obese Zucker rats, the vasodilator responses to sodium nitroprusside, methacholine, the K+-channel opener cromakalim and nifedipine were the same as in control preparations. In conclusion, isolated mesenteric arteries from obese Zucker rats do not show relevant structural changes, and the pharmacodynamic behaviour of such vessels appears to be the same as that of control preparations. Neither the diabetic hyperinsulinaemic state nor the hyperlipoproteinaemia in the obese Zucker rats appear to cause serious vascular damage.     

Influence of the endothelium on Ca2+ dependency of angiotensin II-induced contractions of rat aortic rings

Summary— Endothelium-dependent relaxation has been demonstrated to be involved in the regulation of vascular tone and extracellular Ca²⁺ was found to play a prominent role in this process. Since the dependency on extracellular Ca²⁺ appeared to differ considerably within the arterial tree, possibly as a consequence of vessel-related endothelium-dependent mechanisms, we investigated the effects of different compounds affecting Ca²⁺ entry (nifedipine, CoCl₂) on angiotensin II-induced contractions of rat aortic rings with and without endothelium as well as the responses in a Ca²⁺–“free” solution. For this purpose, rat aortic rings were either undone from their endothelial layer by gentle mechanical rubbing or care was taken to keep the intima intact in case rings where endothelium were required. The presence of an intact endothelium was confirmed by acetylcholine-induced relaxation. A stronger responsiveness towards angiotensin I, both after a complete concentration-response curve and after a single maximal concentration of angiotensin II was observed in arterial segments without endothelium. The maximal contraction to a single concentration of angiotensin II (0.1 μM) in the rings without endothelium amounted to 75.8 ± 3.8% of the preceding response to a supramaximal concentration of noradrenaline (= E_max). In rings without the endothelial layer, the contraction was 34.8 ± 3.7% of E_max. This indicates an endothelium-induced relaxation in aortic rings with endothelium. After incubation with the Ca²⁺ entry blocker nifedipine (1 μM) both rings with and without endothelium were inhibited to the same extent, contractions amounted to 30.7 ± 1.8% and 19.6 ± 1.3% of E_max, respectively. However, incubation in a Ca²⁺-“free” medium for 5 min resulted in similar contractions for rings without endothelium (16.4 ± 1.4% of E_max) as for rings with endothelium (15.0 ± 1.6% of E_max). Moreover, CoCl₂ in a concentration of 300 μM hardly inhibited the contraction of rings with an intact endothelium, a contractile response of 30.5 ± 2.8% of E_max was observed. The results of the study suggest that the influx of Ca²⁺ions is indeed responsible for the endothelium-mediated relaxation. However, this influx, which cannot be antagonized by nifedipine, but has shown to be affected by CoCl₂, suggests that channels intensitive to organic Ca²⁺ entry blockers may be involved.     

Palpable solid breast masses: retrospective single- and multimodality evaluation of 201 lesions

The diagnostic virtues and limitations of single- and multimodality testing in the evaluation of solid palpable breast masses were studied. Two hundred one consecutive patients who had a solid palpable breast mass and who underwent biopsy between September 1982 and July 1986 were included for blinded retrospective analysis of their physical examination, mammographic, ultrasonographic (US), thermographic, and pathologic characteristics. Benign breast disease was diagnosed histologically in 106 women, while carcinoma was established in 95. The sensitivities of physical examination, mammography, US, and thermography were 0.88, 0.94, 0.78, and 0.49, respectively. US alone had the highest sensitivity in correct diagnosis of a benign solid breast mass and had the highest accuracy (0.84). Use of four modalities increased the preoperative diagnostic true-positive rate to 0.97, with some decline in specificity. Multimodality testing seems particularly beneficial in pre- and perimenopausal patients.     

Rheumatoid arthritis: similarity of radiographic abnormalities in men and women

To test the hypothesis that there are significant differences in the radiographic appearance of rheumatoid arthritis between men and women, the authors blindly evaluated bilateral hand and wrist radiographs in 32 men with definite rheumatoid arthritis and 32 age- and disease duration-matched women (mean age, 56.4 years; mean disease duration, 10.5 years). Radiographically, disease distribution and severity were identical in these matched groups. Superimposed osteoarthritis was frequent in both groups and related to age. Ill-defined bone proliferation was present in 13 of 64 hands in both groups. Cystic changes and well-defined erosions were present in 12 of 64 male hands and six of 64 female hands, but this difference was not statistically significant. In women, presence of cysts and bone proliferation was related to disease duration, whereas men exhibited these atypical features independent of disease duration. There was no statistically significant difference in the frequencies of typical and atypical features of rheumatoid arthritis between the two sexes, and the authors postulate that previously reported differences relate to patient selection and lack of adequate matching.     

Liver volume measurements and three-dimensional display from MR images

A method was investigated for measuring the volumes of human livers in vivo from magnetic resonance images and subsequently displaying these livers in three dimensions. Volumetric image sets of phantoms, healthy volunteers, and patients with cirrhotic livers were processed. Two image-processing approaches were compared for accuracy of liver measurements, intrasubject and interobserver variation, and speed of processing. Results indicated that both processing methods had a high degree of volume-measuring accuracy (within 8%), the interobserver measurements had a high coefficient of correlation (r = .9994), the intrasubject measurements had a low coefficient of variation (1.8%), and one method was four to five times faster than the other. The faster and easier of the two image-processing approaches provided satisfactory results for measuring liver volumes, but the slower approach provided more realistic-looking three-dimensional images of the liver.