Detection of varicose vein recurrence by duplex ultrasound: intra- and interobserver reproducibility.

In a long-term follow-up study comparing saphenofemoral ligation and stripping with endovenous laser ablation, the groin is examined yearly by duplex ultrasound (DUS) to detect postoperative varicose vein recurrence. Clear criteria are needed for the uniformity of DUS observations. Physicians taking care of the follow-up were evaluated by an intra- and interobserver analysis. DUS films of 22 patients with no recurrence and 22 patients with recurrence of varicose veins were twice interpreted in two sessions. Observations were analysed by a kappa test. Interpretations of DUS by experienced observers show a kappa >7. Improved kappa results were measured over time in our physician in training. In conclusion, the reproducibility of DUS studies performed by the experienced observers of the study is excellent.

Randomised controlled trial comparing sapheno-femoral ligation and stripping of the great saphenous vein with endovenous laser ablation (980 nm) using local tumescent anaesthesia: one year results.

OBJECTIVES: Comparison of sapheno-femoral ligation and stripping (SFL/S) versus endovenous laser ablation (EVLA, 980-nm) in the treatment of great saphenous vein (GSV) insufficiency, using local tumescent anaesthesia. DESIGN: Randomised, single centre trial. MATERIALS AND METHODS: Patients with GSV incompetence and varicose veins were randomised to either SFL/S or EVLA. At days 1, 2, 3, 7, 10, and 14 post-treatment, patients completed questionnaires on pain and quality of life. Recurrent varicose veins were evaluated by Duplex ultrasound (DUS) performed at 1 and 6 weeks, and 6 and 12 months. RESULTS: 130 legs in 121 patients were treated by SFL/S (n=68) or EVLA (n=62). Significantly more post-treatment pain was noted after EVLA at days 7, 10 and 14 (p<0.01; p<0.01; p=0.01), more hindrance in mobility at days 7 (p<0.01) and 10 (p=0.01), and in self care (p=0.03) and daily activities (p=0.01) at day 7 compared to SFL/S. DUS at 1-year follow-up showed 9% recurrences (5/56) after EVLA and 10% (5/49) after SFL/S. CONCLUSION: Both SFL/S and EVLA, using local tumescent anaesthesia, were well tolerated, with no difference in short-term recurrence rate. In the second week after EVLA, patients experienced significantly more pain resulting in restricted mobility, self care and daily activity compared to SFL/S.

Genome-wide linkage in three Dutch families maps a locus for abdominal aortic aneurysms to chromosome 19q13.3.

OBJECTIVES: Elucidation of the genetic background of familial abdominal aortic aneurysm (AAA) suggests a genetic etiology. METHODS AND RESULTS: We carried out a genome-wide scan in three Dutch families with four or five affected siblings. Suggestive loci were further studied by subsequent fine mapping of the locus performed in 101 affected sib-pairs. The genome-wide scan was performed with 400 DNA markers and results were given as non-parametric, multipoint linkage scores (NPL). We observed a suggestive linkage for AAA (NPL score 3.25 at D19S902, 72.72 cM) on chromosome 19q in the three families. After fine mapping on chromosome 19, the NPL score became nominal in the 101 affected sib-pairs. A separate analysis of the three families with fine mapping revealed a peak with significant evidence for linkage (NPL score 3.95 at D19S904, 78.08 cM) on chromosome 19q. This peak was situated to the right compared to the region found in a previously published article for familial AAA on chromosome 19q. CONCLUSIONS: Our results identified a candidate locus in three Dutch families with AAA at chromosome 19q13.3. Separate analysis of these three families provides evidence for genetic heterogeneity.

Genetic linkage of candidate genes in families with abdominal aortic aneurysms?

OBJECTIVES: to examine possible involvement of several candidate genes in the aetiology of familial abdominal aortic aneurysm (AAA). DESIGN: after reviewing the literature on the genetics of familial AAA, betaine homocysteine methyltransferase (BHMT), collagen type Ialpha2 (COL1A2) and cathepsin H (CTSH), were selected as potential candidate genes, which influence structure, strength, elasticity and mechanical resistance of the aortic wall. MATERIALS: forty-eight families with 110 family members and AAA were included in the affected sib-pair analysis. One large family of three generations was analysed separately because in this family also other clinical symptoms were involved. METHODS: genetic linkage analysis was performed with DNA markers in the region of BHMT, COL1A2 and CTSH. RESULTS: In the overall sib-pair analysis, the LOD scores for BHMT, COL1A2 and CTSH were 0.7, 0.2 and -0.7, whereas in the large family these numbers were -0.6, -2.2 and -2.7, respectively. CONCLUSIONS: none of the candidate genes selected showed a suggestive linkage with AAA. Exclusion of the COL1A2 and CTSH genes was possible in the large family that was analysed separately.

Familial abdominal aortic aneurysm: a systematic review of a genetic background.

BACKGROUND: Familial clustering of the abdominal aortic aneurysm (AAA) is clear, 12-19% of AAA patients have one or more first-degree relatives with an aneurysm and 4-19% is detected with ultrasound screening. OBJECTIVES: To review the genetic background of AAA. DESIGN, METHODS AND MATERIALS: Computer searches of the MEDLINE, EMBASE, SUMsearch database and the Cochrane Library and searched reference lists of English language articles concerning the genetics of AAA, candidate gene approach and linkage analysis. RESULTS: Brothers of AAA patients are at high risk to develop an AAA. The candidate gene approach was performed to detect defects in one of the components of the connective tissue, i.e. type I and III collagen, elastin and fibrillin, the inflammatory cell-derived matrix metalloproteinase, there inhibitors, auto-immune components and components related to atherosclerosis. CONCLUSION: These studies give us insight in the pathology but do not lead to the specific genetic factor(s) responsible for (familial) AAA. Considering the supposed autosomal dominant inheritance, a gene mutation in one of the structural proteins of the connective tissue is expected. In the future, linkage analysis may resolve the genetic background of AAA.

The role of type III collagen in family members of patients with abdominal aortic aneurysms.

OBJECTIVES: type III collagen is responsible for the tensile strength of the aorta-wall. To determine if genetic defect in the type III collagen production is associated with familial clustering of AAA. METHODS: fifty-six patients with AAA and 82 first-degree family members participated. The medical and family histories were obtained. All these relatives were screened by ultrasound for AAA. In 58 relatives of 20 families, skin biopsies were taken for protein analysis to measure type III collagen production in cultured fibroblasts. RESULTS: only one new AAA was detected in a brother of a patient. Four other relatives were already known with AAA. Three AAA patients had a type III collagen deficiency, but type III collagen was normal in all family members. CONCLUSION: type III collagen deficiency does not appear to be an aetiological factor in the development of AAA.

The role of type III collagen in the development of familial abdominal aortic aneurysms.

OBJECTIVES: to evaluate the prevalence of familiar abdominal aortic aneurysm (AAA) and the role of type III collagen deficiency. METHODS: fifty-six consecutive patients coming for aneurysm repair were asked if one or more first-degree relatives had an AAA. During operation, a skin biopsy was taken from the patients for protein analysis to measure the type III collagen production in cultured fibroblasts. RESULTS: a positive family history was found in 28.6% of the AAA patients. Six (10.7%) of the AAA patients had a type III collagen deficiency (mean 4.3% (S.D.+/-0.5)). In this group three men, mean age 65.3 years (S.D.+/-5.0), had a positive family history and a type III collagen deficiency. Segregation analysis with an intragenic marker in the type III collagen gene in a single family was in favour of linkage with the gene for type III procollagen (COL3A1) locus. CONCLUSIONS: the high prevalence of familial AAA suggests a genetic aetiology. A small group of patients have a type III collagen deficiency. Linkage with the COL3A1 gene could not be proven or excluded in the families studied.

Spermatogenetic clones developing from repopulating stem cells surviving a high dose of an alkylating agent.

We investigated stem cell renewal and differentiation in 10- and 15-days-old spermatogonial clones developing in mouse seminiferous epithelium after an extremely large cell loss, inflicted by high doses of the alkylating agent Myleran. The spermatogonial clones arise from cells that resemble the Ais spermatogonia but have a larger nuclear diameter. In spite of their mitotic activity these 'repopulating stem cells' lie mainly isolated or in pairs. This explained by migration and differentiation. Migration appeared to occur at random in all directions along the basement membrane of the seminiferous tubule. After one or more divisions of the stem cells, a second type of cell appears, which is called the 'differentiating spermatogomium'. The time elapsing before this type of cell appears, depends on the dose of Myleran: the larger the dose the later differentiation starts. A relation could be demonstrated between the stage of the cycle of the seminiferous epithelium and the start of differentiation. Differentiating cells were found isolated or in groups of two, four, eight or sixteen cells. Hence we concluded that at least up to their fourth division differentiating cells divide synchronously without degenerations. Three types of division of repopulating stem cells were distinguished, producing (1) two repopulating stem cells, (2) one repopulating stem cell and one cell starting spermatogonial differentiation, or (3) two differentiating cells. Type 1 divisions were found most frequently.