Risk of major amputation in patients with intermittent claudication undergoing early revascularization.

BACKGROUND: Revascularization is being used increasingly for the treatment of intermittent claudication and yet few studies have reported the long-term outcomes of this strategy. The aim of this study was to compare the long-term outcome of patients with intermittent claudication who underwent revascularization compared with a group initially treated without revascularization. METHODS: Patients with symptoms of intermittent claudication and a diagnosis of peripheral arterial disease were recruited from outpatient clinics at three hospitals in Queensland, Australia. Based on variation in the practices of different vascular specialists, patients were either treated by early revascularization or received initial conservative treatment. Patients were followed in outpatient clinics using linked hospital admission record data. The primary outcome was the requirement for major amputation. Kaplan-Meier curves, Cox regression and competing risks analyses were used to compare major amputation rates. RESULTS: Some 456 patients were recruited; 178 (39·0 per cent) underwent early revascularization and 278 (61·0 per cent) had initial conservative treatment. Patients were followed for a mean(s.d.) of 5·00(3·37) years. The estimated 5-year major amputation rate was 6·2 and 0·7 per cent in patients undergoing early revascularization and initial conservative treatment respectively (P = 0·003). Early revascularization was associated with an increased requirement for major amputation in models adjusted for other risk factors (relative risk 5·40 to 4·22 in different models). CONCLUSION: Patients presenting with intermittent claudication who underwent early revascularization appeared to be at higher risk of amputation than those who had initial conservative treatment.

Growth and risk factors for expansion of dilated popliteal arteries.

OBJECTIVES: The aims of this study were to investigate the change in maximum diameter of ectatic popliteal arteries during ultrasound surveillance and assess clinical predictors of their expansion. METHODS: Over a ten year period 67 patients with ectasia affecting one (n = 1) or both (n = 66) popliteal arteries entered this surveillance study. Patients were followed for a median of 3.1 years, at a median scan interval of 7.6 months. RESULTS: Growth of ectatic popliteal arteries was typically slow (<1 mm/yr). Initial artery diameter at entry to the study was not found to be predictive of subsequent growth. Seven patients followed for a median of 2 years had an expansion in popliteal artery diameter to >or=20 mm during follow-up. All of these patients had undergone aneurysm repairs at other arterial sites and none of them had diabetes. These participants also had a significantly higher rate of previous intervention of the contralateral popliteal artery in comparison to those that did not reach the 20 mm threshold (p < 0.001). Growth profiles of arteries that underwent significant expansion during surveillance were frequently characterised by a staccato pattern. CONCLUSIONS: Expansion of ectatic popliteal arteries is typically slow but difficult to predict. Trends observed in this study suggest that patients with extra-popliteal aneurysms, patients with previously treated contralateral popliteal artery ectasia and those who are not diabetics may be more prone to significant expansion. Further studies are required to validate these potential growth predictors.

Should we develop a core international curriculum for Vascular and Endovascular Surgery?

Vascular and endovascular surgery has undergone a period of extraordinary change during the last 20 years. This is in part due to changes in patient profiles, the development of new, potent drugs and the technological advances in imaging and interventional products. These changes have effectively resulted in the development of an independent specialty, which has needed to define the competencies required for specialist recognition and credentialing. This paper discusses the key aspects of contemporary training in Vascular and Endovascular Surgery, and raises the possibility of developing an agreed core international curriculum.

Determinants of endothelial function in a cohort of patients with peripheral artery disease.

OBJECTIVES: Endothelial dysfunction assessed by brachial artery flow-mediated dilatation (FMD) has been associated with cardiovascular events. There have been relatively few studies examining FMD or other measures of endothelial function in patients with peripheral artery disease (PAD). The aim of this study was to examine determinants of FMD in a homogenous cohort of patients with PAD. METHODS: We prospectively assessed patients presenting with life style-limiting intermittent claudication to establish the presence of cardiovascular risk factors, obesity and metabolic syndrome. Fasting serum was assayed for lipids, C-reactive protein, adiponectin, leptin, resistin and osteoprotegerin (OPG). FMD was measured by high-resolution ultrasound. RESULTS: Serum concentrations of OPG were elevated in patients with obesity and metabolic syndrome. FMD was impaired in patients with obesity and metabolic syndrome and negatively correlated with serum concentrations of OPG. By multiple regression analysis, metabolic syndrome was independently associated with impaired FMD after adjustment for age, smoking, ischaemic heart disease, cerebrovascular disease and severity of PAD. CONCLUSIONS: Our findings suggest that metabolic syndrome is an important determinant of endothelial function in patients with PAD, and OPG may be a useful biomarker of this effect.

Genotyping of Mycobacterium bovis isolates from badgers in four areas of the Republic of Ireland by restriction fragment length polymorphism analysis.

An analysis of the molecular epidemiology of Mycobacterium bovis in badgers was made in four selected areas of the Republic of Ireland in which an intensive badger removal programme was being carried out over a period of five years. Tissue samples from 2310 badgers were cultured. Restriction fragment length polymorphism (RFLP) analysis with IS6110, polymorphic GC-rich sequence (PGRS) and direct repeat sequence (DR) probes was applied to the isolates from 398 badgers, and 52 different rflp types were identified. Most of the isolates belonged to seven predominant types, and the other 45 types were represented by few isolates. An analysis suggests that some of these 45 types may have been introduced by the inward migration of badgers and others may have been the result of genetic changes to one of the prevalent types. The badgers were divided into groups on the basis of the sett at which they were captured, and RFLP typing was applied to isolates from two or more badgers from 85 groups. Multiple RFLP types were identified among isolates from 50 of these groups, suggesting that badgers probably moved frequently between group territories.

A survey of the causes of sudden cardiac death in the under 35-year-age group.

CRY (Cardiac Risk in the Young) is a registered Irish charity established by parents who are bereaved as a result of sudden cardiac death. The aim of this study is to establish the incidence and causes of sudden cardiac death in Dublin city in the 10-year period from 1st January 1993 to 31st December 2002. All sudden cardiac deaths in the under 35-year age group which were reported to the city coroner in the study period were examined. Details regarding age, sex, previous symptoms, investigations, circumstances of death and main pathological finding were recorded in each case. A total of 72 cases of sudden cardiac death in the under-35 year age group were reported. 52 were men. The median age was 26.5 years (range 12-34 years). The cause of death in 20 cases was reported as atherosclerotic Coronary Artery Disease. The second commonest cause of death (24% cases) was Hypertrophic Cardiomyopathy. Hypertrophic Cardiomyopathy was the commonest cause of death under the age of 25 years. Overall atherosclerotic coronary artery disease was the commonest cause of death in this group. The importance of Hypertrophic Cardiomyopathy is highlighted by the fact it was the commonest cause of death in the under 25-year age group. Screening those at high risk of sudden cardiac death especially the relatives of those affected by Hypertrophic Cardiomyopathy need to be discussed and implemented.

Pathogenesis of varicose veins.

BACKGROUND: varicose veins are present in up to 40% of the population. They may be associated with considerable morbidity. Around 70% of patients with chronic venous insufficiency have evidence of superficial venous incompetence on duplex imaging. METHODS: in this publication we review the evidence available regarding the pathogenesis of varicose veins. RESULTS: a number of theories have been suggested. The present data suggests that abnormalities in the venous endothelium and smooth muscle cells result in vein wall dilatation with secondary valvular incompetence. However, there is also evidence to support acquired venous valve failure. Congenital venous valve abnormalities have not been well studied. CONCLUSION: further work is required on this relatively neglected topic. The use of improved imaging such as high-resolution ultrasound is likely to significantly improve our understanding of venous valve function and pathology.

Selection of elastomeric materials for compliant-layered total hip arthroplasty.

A selection procedure has been developed to identify suitable commercial materials for use in compliant-layer artificial hip joints. Mechanical requirements, notably hardness and strength, as well as biocompatibility, constituted the specification for the compliant layer. Applying these constraints, candidate materials were identified in a broad range of polymeric material classes. Detailed sourcing and literature searching helped to identify materials appropriate to the application, with suitable mechanical and physical properties, as well as a history of successful clinical use. Some likely materials were identified but were prohibited from further consideration by limited commercial availability. Physical and mechanical characterization together with literature data were used to determine the relative ranking of the candidate materials and through a weighted materials property selection procedure the materials of choice were identified. The linear segmented aromatic polyurethanes, Tecothane 1085 and Estane 5714F1, emerged as the preferred materials.

Virulence-associated protein characterisation of Rhodococcus equi isolated from bovine lymph nodes.

Rhodococcus equi has a low pathogenicity in cattle, but it occasionally causes lymph node granulomas, which are detected at abattoir post mortem inspection, and must be distinguished from tuberculous granulomas. Lymph node lesions were detected in 6719 cattle, from a total of 3,263,622 cattle examined post mortem in abattoirs, in the Republic of Ireland, during 1997 and 1998. Histological examination was performed on all lesions, principally for the purpose of identifying animals with tuberculosis. A total of 1122 of the lesions were cultured on blood agar and on Stonebrinks and Lowenstein-Jensen medium containing pyruvate, because the histological findings were difficult to interpret or were suggestive of R. equi infection. R. equi was isolated from 264 lesions. Almost all of the R. equi granulomas were confined to a single lymph node, and were present predominantly in the retropharyngeal, bronchial and mediastinal lymph nodes. R. equi granulomas were present in a significantly higher proportion of the lesions detected in steers and heifers compared to cows. The prevalence in the total population of 3.3 million cattle examined post mortem was 0.008%. The 15-17kDa antigens, associated with virulence in this organism, and the 20kDa antigen, associated with intermediate virulence, were not detected in isolates from 146 cattle, analysed by immunoblot assays. A PCR assay to detect the plasmid gene encoding the 15-17kDa antigens was also negative for isolates from these 146 animals. Plasmids were not detected in 30 isolates which were examined.

Na+/myo-inositol symporters and Na+/H+-antiport in Mesembryanthemum crystallinum.

Mitr1 and Mitr2 from Mesembryanthemum crystallinum (common ice plant) are members of a family of genes homologous to H+[or Na+]/myo-inositol symporters (ITRs), not previously studied in plants. MITR1 complemented an Itr1-deficient yeast strain. Mitr1 is strongly expressed in roots, moderately in stems, and weakly in leaves. Its transcripts increased in all organs, most dramatically in roots, under salinity stress. Mitr2 constitutes a rare transcript, slightly upregulated by salt stress in leaves only. Mitr1 transcripts are present in all cells in the root tip, but become restricted to phloem-associated cells in mature roots. Peptide antibodies against the two proteins indicated the presence of MITR1 in all organs and of MITR2 in leaves. Both are located in the tonoplast. MITR1 acts in removing sodium from root vacuoles, correlated with findings of low root sodium, while leaf vacuoles accumulate sodium in the ice plant. Up-regulation in leaves and stems is also found for Na+/H+-antiporter (Nhx-type) transcripts. Under comparable stress conditions, Nhx-and Itr-like transcripts in Arabidopsis were regulated differently. In the ice plant, co-ordinate induction of Na+/H+-antiporters and Na+/myo-inositol symporters transfers sodium from vacuoles in root cells into the leaf mesophyll as a halophytic strategy that lowers the osmotic potential. The tissue-specific differential expression of Itr- and Nhx-type transcripts suggests that the vacuolar sodium/inositol symporters function to reduce sodium amounts in cells of the root and vascular tissue, while sodium/proton antiporters in leaf tissues function to partition sodium into vacuoles for storage.

A survey of the causes of sudden death in sport in the Republic of Ireland.

BACKGROUND: Sudden death in sport is rare, but when it occurs the effects are devastating. There have not been any reports to date describing the frequency and causes of sudden death in sport in the Republic of Ireland. AIM: To describe the incidence, possible causes, associated factors, and pathological findings in people who died while exercising in the Republic of Ireland in the 10 year period from January 1987 to December 1996. METHODS: All 49 regional coroners in the Republic of Ireland were approached and details on all cases of sudden death in sport from 1 January 1987 to 31 December 1996 were requested. A questionnaire was used to document age, sex, participating sport, previous symptoms, previous medical investigations, circumstances of death, and main pathological finding in all reported cases. RESULTS: Of the 49 coroners surveyed, 45 replied. A total of 51 cases of sudden death in sport were identified. The median age was 48 (range 15-78). Fifty of the deaths were of men. Golf was the most popular participating sport. In 42 cases, the pathological cause of death was atherosclerotic coronary artery disease. CONCLUSIONS: This is the first time the incidence of sudden death in sport in the Republic of Ireland has been described. The main cause of death in all age groups was atherosclerotic coronary artery disease.

Expression of water channel proteins in Mesembryanthemum crystallinum.

We have characterized transcripts for nine major intrinsic proteins (MIPs), some of which function as water channels (aquaporins), from the ice plant Mesembryanthemum crystallinum. To determine the cellular distribution and expression of these MIPs, oligopeptide-based antibodies were generated against MIP-A, MIP-B, MIP-C, or MIP-F, which, according to sequence and functional characteristics, are located in the plasma membrane (PM) and tonoplast, respectively. MIPs were most abundant in cells involved in bulk water flow and solute flux. The tonoplast MIP-F was found in all cells, while signature cell types identified different PM-MIPs: MIP-A predominantly in phloem-associated cells, MIP-B in xylem parenchyma, and MIP-C in the epidermis and endodermis of immature roots. Membrane protein analysis confirmed MIP-F as tonoplast located. MIP-A and MIP-B were found in tonoplast fractions and also in fractions distinct from either the tonoplast or PM. MIP-C was most abundant but not exclusive to PM fractions, where it is expected based on its sequence signature. We suggest that within the cell, MIPs are mobile, which is similar to aquaporins cycling through animal endosomes. MIP cycling and the differential regulation of these proteins observed under conditions of salt stress may be fundamental for the control of tissue water flux.

Restriction fragment length polymorphism analysis of Mycobacterium avium isolates from animal and human sources.

Restriction fragment length polymorphism (RFLP) analysis using probes derived from the insertion sequences IS901, IS1245 and IS1311, was carried out on Mycobacterium avium isolates obtained from 18 human patients, 44 deer, 14 pigs and five cattle in the Republic of Ireland. Forty-two of the cervine isolates and two of the bovine isolates contained IS901, while this insertion sequence was absent from all of the human and porcine isolates. RFLP analysis with IS901 probe differentiated the 44 field isolates which contained this element into three types. All of the IS901-positive isolates had a characteristic three-band IS1245 hybridisation pattern and a characteristic single-band IS1311 hybridisation pattern. The IS901-negative isolates exhibited highly polymorphic IS1245 and IS1311 hybridisation patterns which differentiated the human and porcine isolates into a wide diversity of strain types.

Cardiac assessment with thallium scanning prior to aortic aneurysm repair.

Coronary artery disease occurs commonly in patients with aortic aneurysms and is a major cause of morbidity and mortality. The role of screening and intervention for cardiac disease prior to aneurysm repair is controversial. The outcome after cardiac screening with thallium scanning and/or angiography in 102 consecutive patients undergoing aortic aneurysm repair was documented. Significant coronary artery disease was found in 34 (33%) patients and two patients had either coronary artery bypass or angioplasty prior to aneurysm repair. There was no cardiac mortality after aneurysm repair and the overall mortality on an intention-to-treat basis was 2%. There was good correlation between prior history of cardiac events, electrocardiography (ECG) and the results of screening with thallium scanning and angiography. There was no correlation between cardiac history, ECG and the incidence of cardiac events in the postoperative period. Significant coronary artery disease was found in 33% of patients without a cardiac history or abnormal ECG. Cardiac screening with thallium scanning confirmed a high incidence of significant coronary disease in patients with aortic aneurysm. In this study, cardiac intervention followed by expedient aneurysm repair in 20 patients was associated with zero mortality. The short-term benefit of such a policy is difficult to prove and its main advantage may be better long-term survival.

Study of restriction fragment length polymorphism analysis and spoligotyping for epidemiological investigation of Mycobacterium bovis infection.

Restriction fragment length polymorphism (RFLP) analysis with probes derived from the insertion element IS6110, the direct repeat sequence, and the polymorphic GC-rich sequence (PGRS) and a PCR-based typing method called spacer oligonucleotide typing (spoligotyping) were used to strain type Mycobacterium bovis isolates from the Republic of Ireland. Results were assessed for 452 isolates which were obtained from 233 cattle, 173 badgers, 33 deer, 7 pigs, 5 sheep, and 1 goat. Eighty-five strains were identified by RFLP analysis, and 20 strains were identified by spoligotyping. Twenty percent of the isolates were the most prevalent RFLP type, while 52% of the isolates were the most prevalent spoligotype. Both the prevalent RFLP type and the prevalent spoligotype were identified in isolates from all animal species tested and had a wide geographic distribution. Isolates of some RFLP types and some spoligotypes were clustered in regions consisting of groups of adjoining counties. The PGRS probe gave better differentiation of strains than the IS6110 or DR probes. The majority of isolates from all species carried a single IS6110 copy. In four RFLP types IS6110 polymorphism was associated with deletion of fragments equivalent in size to one or two direct variable repeat sequences. The same range and geographic distribution of strains were found for the majority of isolates from cattle, badgers, and deer. This suggests that transmission of infection between these species is a factor in the epidemiology of M. bovis infection in Ireland.

Differential expression of a polygalacturonase gene family in Arabidopsis thaliana.

By systematic sequencing of a flower bud cDNA library from Arabidopsis thaliana, we have identified four cDNAs encoding polygalacturonase. The corresponding genes, together with seven other A. thaliana genes present in the databases, form a small gene family. Sequence comparisons of the deduced polypeptides within the gene family or with other plant polygalacturonases allow classification of the genes into different clades. Five polygalacturonases, including all those isolated from the flower buds, are closely related to the enzyme in pollen. Of the six remaining polygalacturonases, three are more closely related to the abscission-specific type of enzyme and two others to the fruit polygalacturonase. The last one is more distantly related to the others and might correspond to a new type of polygalacturonase. Expression of the different genes was analysed on Northern blots and by a PCR-based strategy. Results indicate that if, as expected, the cDNAs isolated from the flower bud library are strongly expressed in pollen, other genes are expressed at a low level in young developing tissues, such as in seedlings and roots, suggesting that they could be implicated in the cell wall modifications observed during cell elongation and/or expansion which occur in these tissues.

A prospective randomized trial evaluating the haemodynamic role of incompetent calf perforating veins.

AIM: This study was undertaken to determine the haemodynamic effect of incompetent calf perforating veins in patients with uncomplicated varicose veins and long saphenous incompetence. METHODS: Thirty-eight limbs from 35 patients were studied. All patients had uncomplicated varicose veins with both long saphenous and calf perforator incompetence on duplex ultrasonography. Patients were randomized to have incompetent calf perforators ligated or left intact, in addition to saphenofemoral junction ligation, strip of long saphenous vein to knee and stab avulsion of any visible varicosities in the leg. Patients were assessed with air plethysmography pre-operatively and 3 months postoperatively. RESULTS: Superficial venous surgery improved venous volume, venous filling index and ejection fraction in the patient cohort. No significant haemodynamic difference was demonstrated between the two groups of patients who were randomized. CONCLUSIONS: At present, the results of this study do not support the use of routine perforator ligation during superficial surgery for uncomplicated varicose veins.

A study of cattle-to-cattle transmission of Mycobacterium bovis infection.

Twenty steers, positive to the single intradermal comparative tuberculin test (SICTT), were selected from herds with a recent history of Mycobacterium bovis infection. Ten steers, negative to SICTT, were selected from herds with no history of M. bovis infection and served as in-contact animals. The animals were divided into 10 groups, each consisting of two SICTT-positive (reactor) animals and one in-contact animal. Each group was housed in an individual loose-box for a period of 1 year. Five of the groups were fed a restricted diet for part of the experiment. All cattle were slaughtered at the end of the study period and examined at post mortem. Transmission of infection to an in-contact animal occurred in four of the 10 groups. One of the four in-contact animals, which became infected, had a retropharyngeal lymph node tubercle and M. bovis was isolated from lymph nodes without visible lesions from the other three. Two of the infected in-contact animals without visible lesions did not show any detectable cell-mediated immune response. There was no evidence that dietary, restriction had any effect on transmission of disease.

Impact of femoro-distal bypass on major lower limb amputation rate.

BACKGROUND: Limb salvage is one of the cardinal aims of vascular surgery, but the influence of distal bypasses on amputation rates has been difficult to demonstrate. METHODS: The incidence and indications for major limb amputations and infrapopliteal bypass during two consecutive 16-month periods were analysed. RESULTS: There was a decrease in the number of major amputations from 34 during the first period to 13 in the second, while the number of bypasses to the infrapopliteal arteries increased from four in the first period to 21 in the second. CONCLUSIONS: An increase in the incidence of bypasses to the infrapopliteal arteries was matched by a decrease in the number of major amputations. Factors that may have contributed to the increase in the incidence of distal bypass and the decrease in the number of amputations include the availability of digital subtraction angiography, and a change in referral patterns within the hospital so that, except for trauma, all patients who were considered to be candidates for major amputation were assessed by a vascular surgeon.

Performance of the single intradermal comparative tuberculin test in identifying cattle with tuberculous lesions in Irish herds.

The sensitivity of the single intradermal comparative tuberculin test, as applied in the Republic of Ireland, was estimated in 353 cattle with tuberculous lesions. These cattle had been removed from 47 herds which were depopulated owing to chronic or extensive infection with Mycobacterium bovis. The test had a sensitivity of 90.9 per cent, because 321 (90.9 per cent) of the 353 cattle with tuberculous lesions gave a positive or inconclusive result, and 32 gave a negative result. These 32 negative cattle came from 17 (36 per cent) of the 47 depopulated herds.