Changes in anticoagulant prescription in Dutch patients with recent-onset atrial fibrillation: observations from the GARFIELD-AF registry.

BACKGROUND: For the improvement of AF care, it is important to gain insight into current anticoagulation prescription practices and guideline adherence. This report focuses on the largest Dutch subset of AF-patients, derived from the GARFIELD-AF registry. METHODS: Across 35 countries worldwide, patients with newly diagnosed 'non-valvular' atrial fibrillation (AF) with at least one additional risk factor for stroke were included. Dutch patients were enrolled in five, independent, consecutive cohorts from 2010 until 2016. RESULTS: In the Netherlands, 1189 AF-patients were enrolled. The prescription of non-vitamin K antagonist oral anticoagulants (NOAC) has increased sharply, and as per 2016, more patients were initiated on NOACs instead of vitamin K antagonists (VKA). In patients with a class I recommendation for anticoagulation, only 7.5% compared to 30.0% globally received no anticoagulation. Reasons for withholding anticoagulation in these patients were unfortunately often unclear. CONCLUSIONS: The data from the GARFIELD-AF registry shows the rapidly changing anticoagulation preference of Dutch physicians in newly diagnosed AF. Adherence to European AF guidelines in terms of anticoagulant regimen would appear to be appropriate. In absence of structured follow up of AF patients on NOAC, the impact of these rapid practice changes in anticoagulation prescription in the Netherlands remains to be established.

Regional differences in elastic recoil after percutaneous transluminal coronary angioplasty: a quantitative angiographic study.

The immediate result of percutaneous transluminal coronary angioplasty is influenced by both plastic and elastic changes of the vessel wall. To evaluate the amount of elastic recoil after coronary balloon angioplasty, the minimal luminal cross-sectional area of the largest balloon used at highest inflation pressure was compared with the minimal luminal vessel cross-sectional area directly after final balloon deflation in 607 lesions (526 patients). Elastic recoil was defined as the difference between balloon cross-sectional area and minimal luminal cross-sectional area of the dilated coronary segment immediately after balloon withdrawal. A videodensitometric analysis technique was used to avoid geometric assumptions on stenosis morphology directly after angioplasty. Mean balloon cross-sectional area was 5.3 +/- 1.6 mm2 and minimal luminal cross-sectional area after angioplasty was 2.8 +/- 1.4 mm2. Reference areas before and after angioplasty did not differ (6.0 +/- 2.6 and 6.2 +/- 2.6 mm2, respectively). Univariate analysis revealed that asymmetric lesions, lesions located in less angulated parts of the artery and lesions with a low plaque content showed more elastic recoil. Lesions located in distal parts of the coronary tree were also associated with more elastic recoil probably related to relative balloon oversizing in these distal lesions.

Which angiographic variable best describes functional status 6 months after successful single-vessel coronary balloon angioplasty?

OBJECTIVES: The aim of this study was to determine which quantitative angiographic variable best describes functional status 6 months after coronary balloon angioplasty. BACKGROUND: Several angiographic restenosis criteria have been developed. These can be divided into those that describe the change in lesion severity and those that merely describe lesion severity at follow-up angiography. The functional significance of these criteria is unknown. METHODS: We studied 350 patients with single-vessel coronary artery disease who underwent a single-site balloon dilation. Sensitivity and specificity curves were constructed for the prediction of anginal status and exercise electrocardiography of four quantitative angiographic variables that describe restenosis. The point of highest diagnostic accuracy for the variables was determined at the intersection of the sensitivity and specificity curves. Results of exercise electrocardiography were considered indicative for ischemia 6 months after angioplasty if horizontal or downsloping ST segment depression > or = 1 mm occurred. RESULTS: The points of highest diagnostic accuracy of the angiographic variables were similar for both anginal status and exercise electrocardiography: 1.45 and 1.46 mm for the minimal lumen diameter measurements, 45.5% and 46.5% for the percent diameter stenosis measurements at follow-up, -0.30 and -0.32 mm for change in minimal lumen diameter and -10% and -10% for the change in percent diameter stenosis at follow-up. CONCLUSIONS: Angiographic variables reflecting a change in lesion severity at follow-up angiography were only slightly less accurate than variables that describe lesion severity at follow-up. The large study group and the fact that the same optimal values for diagnostic accuracy of the various quantitative angiographic variables were obtained for the prediction of two different markers of ischemia suggests that these values reflect the lesion severity or increase in lesion severity in major epicardial vessels at which coronary flow reserve is unable to meet myocardial demands.

Restenosis after directional coronary atherectomy and balloon angioplasty: comparative analysis based on matched lesions.

OBJECTIVES: Late lumen narrowing after directional coronary atherectomy was assessed by quantitative coronary angiography and compared with that after balloon angioplasty. BACKGROUND: Directional coronary atherectomy has been introduced as an alternative technique for balloon angioplasty and may reduce the incidence of restenosis. METHODS: A prospectively collected consecutive series of 87 native coronary artery lesions successfully treated with atherectomy were matched with 87 coronary artery lesions selected from a consecutive series of lesions that had been successfully dilated by balloon angioplasty. Late angiographic analysis was performed in 158 lesions. The net gain index represents the ultimate gain in minimal lumen diameter at follow-up study, normalized for the vessel size. This index is the result of the relative gain attained during the procedure (the ratio of the change in minimal lumen diameter and reference diameter) and the relative loss observed during the follow-up period (the ratio of the change in minimal lumen diameter during the follow-up period and the reference diameter). RESULTS: Matching for clinical and angiographic variables resulted in two comparable groups with similar baseline stenosis characteristics. Atherectomy resulted in a more pronounced increase in minimal lumen diameter than did balloon angioplasty (mean +/- SD 1.17 +/- 0.29 to 2.44 +/- 0.42 mm vs. 1.21 +/- 0.38 to 2.00 +/- 0.36 mm, p < 0.001). However, this favorable immediate result was subsequently lost during late angiographic follow-up, so that the minimal lumen diameter at follow-up and the net gain index did not differ significantly between the two groups (1.76 +/- 0.62 vs. 1.77 +/- 0.59 mm, p = 0.93, and 0.18 +/- 0.19 vs. 0.17 +/- 0.17, p = 0.70). Consequently, the relative gain and relative loss were higher in the atherectomy group. For both techniques, the relative gain was linearly related to the relative loss but the slope of the regression line was steeper for atherectomy, suggesting that the relative loss in the atherectomy group is proportionally even larger for a given relative gain compared with that in the angioplasty group. CONCLUSIONS: In matched groups of patients, atherectomy induces a greater initial gain in minimal lumen diameter than does balloon angioplasty. However, the vascular wall injury induced by the device is of a different nature (debulking vs. dilating) that leads to more relative loss over the follow-up period in the atherectomy group.

Therapeutic dissection after successful coronary balloon angioplasty: no influence on restenosis or on clinical outcome in 693 patients. The MERCATOR Study Group (Multicenter European Research Trial with Cilazapril after Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis).

OBJECTIVES: The objective of this study was to examine the relation between an angiographically visible coronary dissection immediately after successful coronary balloon angioplasty and a subsequent restenosis and long-term clinical outcome. BACKGROUND: The study population comprised all 693 patients who participated in the MERCATOR trial (randomized, double-blind, placebo-controlled restenosis prevention trial of cilazapril, 5 mg two times a day). METHODS: Cineangiographic films were processed and analyzed at a central angiographic core laboratory, without knowledge of clinical data, with use of an automated interpolated edge detection technique. Dissection was judged according to the National Heart, Lung, and Blood Institute classification. Angiographic follow-up was obtained in 94% of patients with 778 lesions. Two approaches were used to assess the restenosis phenomenon: 1) categoric, using the traditional cutoff criterion of greater than 50% diameter stenosis at follow-up, and 2) continuous, defined as absolute change in minimal lumen diameter (mm) between the postcoronary angioplasty and follow-up, adjusted for the vessel size (relative loss). Clinical outcome was ranked according to the most serious adverse clinical event per patient during the 6-month follow-up period, ranging from death, nonfatal myocardial infarction, coronary revascularization and recurrent angina requiring medical therapy to none of these. RESULTS: Dissection was present in 247 (32%) of the 778 dilated lesions. The restenosis rate was 29% in lesions with and 30% in lesions without dissection (relative risk 0.97; 95% confidence interval 0.77 to 1.23). The relative loss in both groups was 0.10 (mean difference 0; 95% confidence interval -0.03 to 0.03). Clinical outcome ranged from death in 4 patients (0.9%) without dissection and 1 patient (0.4%) with dissection; nonfatal myocardial infarction in 4 (0.9%) without and 8 (3.2%) with dissection; coronary revascularization in 73 (16.6%) without and 32 (12.7%) with dissection; recurrent angina requiring medical therapy in 88 (20%) without and 47 (18.7%) with dissection to no serious adverse event in 272 (61.7%) without and 114 (65.1%) with dissection. CONCLUSIONS: These data indicate that a successfully dilated coronary lesion with an angiographically visible dissection is no more likely to develop restenosis, and is not associated with a worse clinical outcome, at 6-month follow-up than is a dilated lesion without visible dissection on the post-balloon angioplasty angiogram.

Lumen narrowing after percutaneous transluminal coronary balloon angioplasty follows a near gaussian distribution: a quantitative angiographic study in 1,445 successfully dilated lesions.

To determine whether significant angiographic narrowing and restenosis after successful coronary balloon angioplasty is a specific disease entity occurring in a subset of dilated lesions or whether it is the tail end of a gaussian distributed phenomenon, 1,445 successfully dilated lesions were studied before and after coronary angioplasty and at 6-month follow-up study. The original cohort consisted of 1,353 patients of whom 1,232 underwent repeat angiography with quantitative analysis (follow-up rate 91.2%). Quantitative angiography was carried out off-line in a central core laboratory with an automated edge detection technique. Analyses were performed by analysts not involved with patient care. Distributions of minimal lumen diameter before angioplasty (1.03 +/- 0.37 mm), after angioplasty (1.78 +/- 0.36 mm) and at 6-month follow-up study (1.50 +/- 0.57 mm) as well as the percent diameter stenosis at 6-month follow-up study (44 +/- 19%) were assessed. The change in minimal lumen diameter from the post-angioplasty angiogram to the follow-up angiogram was also determined (-0.28 +/- 0.52 mm). Seventy lesions progressed toward total occlusion at follow-up. All observed distributions approximately followed a normal or gaussian distribution. Therefore, restenosis can be viewed as the tail end of an approximately gaussian distributed phenomenon, with some lesions crossing a more or less arbitrary cutoff point, rather than as a separate disease entity occurring in some lesions but not in others.

Postangioplasty restenosis rate between segments of the major coronary arteries.

Conflicting data have been published regarding the rate of postangioplasty restenosis observed in diverse segments of the coronary tree. However, these studies may be criticized for their biased selection of patients, methods of analysis, and definitions of restenosis. In the present study, 1,353 patients underwent a successful coronary dilatation of greater than or equal to 1 site. In all, 1,234 patients (91%) had a follow-up angiogram after 6 months, or earlier when indicated by symptoms. All films were processed and analyzed at the thoraxcenter core laboratory with the coronary angiography analysis system (automated contour detection). Restenosis was considered present if the diameter stenosis at follow-up was greater than 50%. No differences in restenosis rates were observed between coronary segments using this categorical definition. A continuous approach was also used; absolute changes in minimal luminal diameter adjusted for vessel size were used in order to allow comparison between vessels of different sizes (relative loss). No significant differences were observed between the coronary segments with this continuous approach. These results suggest that restenosis is a ubiquitous phenomenon without any predilection for a particular site in the coronary tree.

Usefulness of quantitative and qualitative angiographic lesion morphology, and clinical characteristics in predicting major adverse cardiac events during and after native coronary balloon angioplasty. CARPORT and MERCATOR Study Groups.

Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after > or = 1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p < 0.0001), (2) type C lesion (OR 2.53; p < 0.004), (3) lesion location at a bend > 45 degrees (OR 2.34; p < 0.004), and (4) stenosis located in the middle segment of the artery dilated (OR 1.88; p < 0.03); and with the following postprocedural variable: angiographically visible dissection (OR 5.39; p < 0.0001). Multivariate logistic analysis was performed to identify variables independently correlated with the occurrence of major adverse cardiac events. The preprocedural multivariate model entered unstable angina (OR 3.77; p < 0.0003), lesions located at a bend > 45 degrees (OR 2.87; p < 0.0005), and stenosis located in the middle portion of the artery dilated (OR 1.95; p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative quantitative angiographic analysis of directional coronary atherectomy and balloon coronary angioplasty.

An attempt to assess the "utility" of directional atherectomy was made using a new quantitative angiographic index. This index can be subdivided into an initial gain component and a restenosis component. The initial gain index is the ratio between the gain in diameter during intervention and the theoretically achievable gain (i.e., reference diameter). The restenosis index is the ratio between the decrease at follow-up and the initial gain during the procedure. The net result at long-term follow-up is characterized by the utility index, which is the ratio between the final gain in diameter at follow-up and what theoretically could have been achieved. For this purpose, 30 coronary artery lesions were selected from a consecutive series of successfully dilated primary angioplasty lesions and were matched with the initial 30 successfully treated primary atherectomy lesions. Matching by location of stenosis and reference diameter resulted in 2 comparable groups with identical preprocedural stenosis characteristics. Atherectomy resulted in an increase in minimal luminal diameter 2 times larger than angioplasty (1.53 vs 0.77 mm; p less than 0.0001). However, at follow-up there was a significant decrease in minimal luminal diameter and a significant increase in percent diameter stenosis in the groups with atherectomy and angioplasty (1.69 +/- 0.58 vs 1.57 +/- 0.58 mm, p = not significant [NS], and 37 +/- 18 vs 47 +/- 18%, p = NS, respectively). The decrease in minimal luminal gain was more pronounced in the group with atherectomy than in that with angioplasty (0.92 +/- 0.69 vs 0.35 +/- 0.51 mm; p = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative angiographic assessment of elastic recoil after percutaneous transluminal coronary angioplasty.

Little is known about the elastic behavior of the coronary vessel wall directly after percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal cross-sectional areas of 151 successfully dilated lesions were studied in 136 patients during balloon inflation and directly after withdrawal of the balloon. The circumvent geometric assumptions about the shape of the stenosis after PTCA, a videodensitometric analysis technique was used for the assessment of vascular cross-sectional areas. Elastic recoil was defined as the difference between balloon cross-sectional area of the largest balloon used at the highest pressure and minimal luminal cross-sectional area after PTCA. Mean balloon cross-sectional area was 5.2 +/- 1.6 mm2 with a mean minimal cross-sectional area of 2.8 +/- 1.4 mm2 immediately after inflation. Oversizing of the balloon (balloon artery ratio greater than 1) led to more recoil (0.8 +/- 0.3 vs 0.6 +/- 0.3 mm, p less than 0.001), suggestive of an elastic phenomenon. A difference in recoil of the 3 main coronary branches was observed: left anterior descending artery 2.7 +/- 1.3 mm2, circumflex artery 2.3 +/- 1.2 mm2 and right coronary artery 1.9 +/- 1.5 mm2 (p less than 0.025). The difference was still statistically significant if adjusted for reference area. Thus, nearly 50% of the theoretically achievable cross-sectional area (i.e., balloon cross-sectional area) is lost shortly after balloon deflation.

Angiographic risk factors of luminal narrowing after coronary balloon angioplasty using balloon measurements to reflect stretch and elastic recoil at the dilation site. The CARPORT Study Group.

Because many ongoing clinical restenosis prevention trials are using quantitative angiography to assess whether a drug is capable of reducing the amount of intimal hyperplasia, quantitative angiographic risk factors for angiographic luminal narrowing after balloon angioplasty were determined, including stretch and elastic recoil at the dilatation site. Quantitative analysis was performed on 666 lesions in 575 patients during angioplasty and at 6-month follow-up. Stretch was defined as balloon diameter minus minimal luminal diameter (MLD) before angioplasty/reference diameter, and recoil as balloon diameter minus MLD after angioplasty/reference diameter. Multivariate analysis was used to yield independent risk factors for luminal narrowing at follow-up. Predictors of absolute change in MLD were (1) relative gain at angioplasty (gain in millimeters normalized for reference diameter) and (2) lesion length. To allow risk stratification, logistic regression analysis was applied using the decrease in MLD as a binary outcome variable. A decrease in MLD at follow-up of greater than or equal to 0.72 mm was considered significant. Variables retained in the model were: relative gain greater than 0.3 mm (rate ratio 2.9), relative gain 0.2 to 0.3 (rate ratio 2.1), stenosis length greater than or equal to 6.8 (rate ratio 1.7), and thrombus after angioplasty (rate ratio 2.6). Although stretch was significantly related to luminal narrowing at univariate analysis, it was not retained in the multivariate models. A large gain in lumen diameter at angioplasty, dilation of long lesions, and angiographically determined thrombus after angioplasty were found to be accompanied by more severe luminal narrowing at follow-up.

Time-related secretion of gonadotrophins after a single injection of steroid-free bovine follicular fluid in prepubertal and adult female rats.

The time-related changes in gonadotrophin concentrations after a single injection of steroid-free bovine follicular fluid (bFF), which contains material with inhibin-like activity, were studied in 25-day-old and adult female rats which either were intact or had been ovariectomized 2 days before. In ovariectomized and intact rats administration of bFF caused a selective suppression of FSH after 4--8 h in 25-day-old rats and after 3--4 h in adult rats. No systematic changes in concentrations of LH after bFF injection were observed. Relative suppression of FSH levels in adult rats was more pronounced and of longer duration than in 25-day-old rats. Moreover, the total period of suppression lasted longer in ovariectomized than in intact rats (12 and 8 h for 25-day-old and 24 and 15 h for adult rats respectively). Hypersecretion of FSH was found in intact rats after the initial suppression; this phenomenon was more pronounced and of long duration in adult than in 25-day-old rats. No clear change in the numbers of healthy growing follicles was observed after injection of bFF into intact rats. These results indicate that the pituitary secretion of FSH responds quickly and selectively after administration of bFF to intact and ovariectomized, 25-day-old and adult female rats. The hypersecretion of FSH in intact rats might compensate for the initial suppression of this gonadotrophin, and may thus ensure the maturation of a normal number of follicles.

Involvement of inhibin in the regulation of follicle-stimulating hormone concentrations in prepubertal and adult, male and female rats.

Administration of steroid-free bovine follicular fluid (bFF), containing inhibin-like activity, depressed levels of FSH measured 4 h after injection in intact adult and 35-day-old female rats, but not in younger females. Suppression of FSH was also observed in intact male rats, aged 55 days, but not in older and younger male rats. Eight hours after injection of bFF, FSH levels were depressed in 15-day-old and older immature and adult rats of both sexes. Male and female rats, gonadectomized 2 days earlier, responded similarly to bFF treatment as did the intact animals. In a second experiment it was found that the rise of FSH levels, occurring within 8 h of gonadectomy, decreased with age in male and increased with age in female rats. Steroid treatment was found to prevent the rise in FSH levels partially in 15-day-old male and completely 25-day-old female rats, whereas treatment with bFF was fully effective in blocking the FSH rise in both immature and adult rats of both sexes. It is concluded that inhibin might be a major physiological factor in a fast-acting control of FSH concentrations from at least the age of 25 days onwards in female rats. In male rats its physiological significance might be limited to the prepubertal period, despite the fact that pituitary secretion of FSH is suppressed by exogenous inhibin-like activity at all ages studied.

Effects of single injections of bovine follicular fluid on gonadotrophin concentrations throughout the oestrous cycle of the rat.

A single injection of steroid-free bovine follicular fluid (bFF), which contains inhibin-like activity, was given to adult female rats at 09.00 h on dioestrus-2 (the day after metoestrus), dioestrus-3, pro-oestrus or oestrus. peripheral concentrations of gonadotrophins were measured at 2-h intervals after injection. Compared with values in control animals treated with bovine plasma, injection of bFF did not influence concentrations of LH. In contrast, at all days studied injection of bFF resulted in suppressed concentrations of FSH, during a period which started between 4 and 10 h after injection and lasted 4-12 h, depending on the day of the cycle. With the exception of pro-oestrus, the period of suppression was followed by one in which fluctuating levels of FSH were found; in general, resulting levels were higher though not significantly increased. This latter effect was most pronounced on dioestrus-2 and dioestrus-3, when levels of FSH, which were already low in control animals, were first suppressed during the 6 h after injection of bFF. These data, in conjunction with results from an earlier study in rats at dioestrus-1, showed that administration of bFF induces a fast and selective suppression of FSH secretion on all days of the cycle. This period of suppression was followed by one with fluctuating levels of FSH which showed a tendency to be higher, indicating that disturbances in FSH secretion, such as are caused by bFF, can be compensated for quickly. In this way the process of follicular maturation might be protected.

Pharmacological approaches to the prevention of restenosis following angioplasty. The search for the Holy Grail? (Part I).

Luminal renarrowing after balloon angioplasty still hampers the long term vessel patency in a substantial percentage of patients. Morphologically, the restenotic lesion comprises hyperplasia of intimal tissue, which is mainly characterised by proliferation of smooth muscle cells of the synthetic type with abundant extracellular matrix production, chiefly composed of proteoglycans. Unravelling the underlying pathophysiological process enables more specific intervention in basic interactions and cell responses. Critical events in the development of restenotic tissue are platelet aggregation and thrombus formation, while the release of several mediators promotes proliferation and migration of various cell types. All of these steps give access for a diversity of pharmacological interventions. With this in mind, antithrombotic, antiplatelet, antiproliferative, antiinflammatory, calcium channel blocking and lipid-lowering drugs have been investigated in the prevention of restenosis. Part II of this article reviews newer approaches, such as antibodies to growth factors, gene transfer and antisense oligonucleotides.

Pharmacological approaches to the prevention of restenosis following angioplasty. The search for the Holy Grail? (Part II).

Part I of this article reviewed the results of studies investigating the effectiveness of antithrombotic, antiplatelet, antiproliferative, anti-inflammatory, calcium channel blocker and lipid-lowering drugs in preventing or reducing restenosis after angioplasty. However, despite 15 years of clinical experience and research in the field of restenosis prevention, this has not yet resulted in the revelation of unequivocal beneficial effects of any particular drug. Other newer approaches likely to receive more attention in the future include antibodies to growth factors, gene transfer therapy and antisense oligonucleotides. Whether there is a feasible monotherapy, whether we have to focus on a drug combination, or whether we are only searching for 'the Holy Grail' remain to be answered.

Estimation of inhibin-like activity in spent medium from rat ovarian granulosa cells during long-term culture.

Granulosa cells were isolated from antral follicles of intact, adult female rats by treatment with EGTA and hypertonic sucrose, and were kept in culture for 1, 15 or 37 days. The amount of inhibin-like activity in spent rat granulosa-cell media (rGCCM) was assessed by using a bioassay for inhibin (measurement of the unstimulated release of FSH and LH by pituitary cells in culture). After 1 day in culture, inhibin-like activity was detected in rGCCM of 0.016-0.8 X 10(5) cultured granulosa cells per dish. In the bioassay, maximal suppression of FHS occurred when 0.8 X 10(5) granulosa cells were plated. With this or a larger number of cells in long-term cultures, pooled rGCCM, collected up to 37 days after plating, suppressed levels of FSH (and not of LH) in the inhibin bioassay in parallel with the suppression found after addition of charcoal-treated bovine follicular fluid (bFF), which served as a standard. The amount of inhibin-like activity of rGCCM (relative to the amount present in bFF, which was given a potency of 1) ranged between 0.05 and 0.90 X 10(-3). Release of inhibin-like activity could not be estimated on day 4, and was low from days 29 to 37 in culture. Except after 1 day of culture, no substantial amounts of progesterone were detected in the media. It is concluded that granulosa cells collected from adult, intact female rats have and retain the capacity to secrete inhibin-like activity in vitro, under basal conditions in long-term cultures.

Investigation into the heredity of congenital lateral patellar (sub)luxation in the Shetland pony.

A breeding experiment was carried out in a group of Shetland ponies in order to investigate the heredity of congenital lateral patellar (sub)luxation. A breeding herd was established and consisted of stallions and mares acquired at different times. Some were free from, and others were affected by lateral patellar (sub)luxation in either one or both femoropatellar joints. Over a period of 20 years, 49 foals were born from different mating combinations. Some offspring were free from the defect and others showed the abnormality. Though the number of foals bred during the experiment is rather small, there is sufficient evidence to suggest a monogenic autosomal recessive hereditary transmission of the defect.

[Taxonomy of sheep (genus Ovis, Linnaeus, 1758)]. / De taxonomie van het schaap (genus Ovis, Linnaeus, 1758).

Until recently, mainly comparative morphology was used to classify animals into species, but this method has not led to consensus about the genus sheep (Ovis). However, advanced research techniques, such as cytodiagnosis, provide greater certainty and it is anticipated that these techniques will enable agreement to be reached about the taxonomy of the sheep.

[The European mouflon, Ovis musimon]. / De Europese moeflon, Ovis musimon.

Until a couple of decades ago, the European mouflon found on the islands of Corsica, Sardinia, and Cyprus was considered an independent wild species and last representative of the European wild sheep. However, recent research has shown that there have not been wild sheep in Europe since the late Pleistocene. Archeological investigation in Corsica has shown that the mouflon is not a wild sheep but a primitive domestic sheep brought to the islands by farmers from the Near East and which then became wild (feral).