A clinical approach to the management of a patient with suspected renovascular disease who presents with leg ischemia.

Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive renal failure, and recurrent pulmonary edema. It typically occurs in high risk patients with coexistent vascular disease elsewhere. Most patients with ARAS are likely to die from coronary heart disease or stroke before end-stage renal failure occurs. Recent controlled trials have shown that most patients undergoing angioplasty to treat renovascular hypertension still need antihypertensive agents 6 or 12 months after the procedure. Nevertheless, the number of antihypertensive agents required to control blood pressure adequately is lower following angioplasty than for medication alone. Trials assessing the value of revascularization for preserving renal function or preventing clinical events are only in the early recruitment phase. Revascularization should be undertaken in patients with ARAS and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive, hypolipidemic and antiplatelet agents is necessary in almost all cases.     

Thrombolysis and the femorofemoral bypass graft: a new technique.

Two patients with acutely thrombosed femorofemoral bypass grafts are presented. Recombinant human tissue-type plasminogen activator (rt-PA) was used successfully in thrombolysis of the occluded grafts. Utilizing a new technique the grafts were punctured directly and bolus doses of rt-PA administered.     

Altered filtrability of white blood cells after myocardial infarction

Abnormal white blood cell rheological behaviour has been implicated as a cause of blood flow disturbances under conditions of ischaemia and reduced perfusion pressure. Accordingly, we have tested the mechanical properties of white cells following myocardial infarction by measuring the rate at which suspension of these cells cause plugging of Nuclepore filters. The number of clogging particles in a standard white cell suspension increased by the third day after infarction but subsequently decreased to the control levels. Since white cells can cause blockage of narrow blood vessels, it is assumed that such changes in cellular properties may influence the eventual extent of infarction.     

Delay between pregnancy confirmation and sickle cell and [corrected] thalassaemia screening: a population-based cohort study.

BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. AIM: To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. METHOD: Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated.     

Quantitative study of capillary density in the skin of the foot in peripheral vascular disease

BACKGROUND: The aim of this study was to investigate possible differences in capillary density of the skin of the foot between normal subjects and patients with peripheral vascular disease. METHODS: Using in vivo video microscopy, a method was developed to measure the average capillary density (ACD) of the skin of the foot and toes. In a cross-sectional observational study, 21 patients with intermittent claudication and 23 patients with rest pain or ischaemic ulceration were compared with 19 age- and sex-matched controls. RESULTS: Mean(s.e.m). values of ACD of the foot were 33.7(1.9) and 34.4(1.7) per mm2 in the right and left sides respectively for controls, 31.2(1.8) per mm2 (P not significant) and 31.9(2.6) per mm2 (P not significant) in the symptomatic and contralateral sides respectively for patients with claudication, and 22.0(1.8) per mm2 (P < 0.001) and 24.3(1.7) per mm2 (P < 0.001) in the symptomatic and contralateral sides respectively for patients with rest pain or ulceration. CONCLUSION: Capillary density of the skin of the foot is significantly reduced in patients with arterial ulceration compared with that in patients with claudication and healthy subjects.     

Lower-extremity arteriosclerosis as a reflection of a systemic process: implications for concomitant coronary and carotid disease

Peripheral arterial occlusive disease (PAOD), coronary artery disease (CAD), and cerebrovascular disease (CVD) are all manifestations of atherosclerosis or atherothrombosis, and therefore it is not surprising that the three conditions commonly occur together. Knowledge of the magnitude of co-existing cardiovascular disease and its prognosis is essential for the physician treating IC so that he can treat the local disease in its systemic context. The prevalence of CAD in patients with IC is 40% to 60%, although this may be asymptomatic and increases with the severity of the PAOD. Not surprisingly, the converse is also true; among individuals with CAD, the prevalence of PAOD is higher than in non-CAD individuals. The link between PAOD and CVD seems to be weaker than that with CAD, but again up to 60% of claudicants have some evidence of CVD. The prevalence of patients with CVD increases as the ABPI decreases. The evidence available from all of the relevant studies suggests that approximately 60% of patients with PAOD will have significant disease in the cardiac or cerebral circulation, and approximately 40% of patients with coronary disease or significant cerebral circulatory disease also will have PAOD.     

The natural history of claudication: risk to life and limb

Although a patient with intermittent claudication (IC) will fear progression to severe disease and amputation, this is a relatively rare outcome of claudication, with only 1% to 3% of claudicants ever requiring major amputation over a 5-year period. Indeed, in one study, 50% of claudicants became symptom free during 5 years' follow-up. All the new evidence over the last 40 years has not altered the impression that only about one fourth of patients with IC will ever significantly deteriorate, and that deterioration is most frequent during the first year after diagnosis (6 to 9%) compared with 2% to 3% per annum thereafter. Smoking is the most important risk factor for the progression of local disease in the legs, with an amputation rate 11 times greater in smokers than nonsmokers. Diabetes, male gender, and hypertension are also important risk factors for progression. Because cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial occlusive disease (PAOD) coexist, PAOD and IC should be regarded as a marker for increased risk from fatal and nonfatal cardiovascular event, and 2% to 4% of claudicants have a nonfatal cardiovascular event every year. The risk is higher in the first year after developing IC than in a long-standing stable claudicant, and the average claudicant is more likely to have a nonfatal myocardial infarction (MI) or stroke in the next year that of ever requiring a major amputation for his leg ischemia. The mortality in claudicants is 30% at 5 years, 50% at 10 years, and 70% at 15 years, without any clear decrease in these figures over the last 30 to 40 years. The mortality of claudicants is approximately two and a half times that of an age-matched general population.     

Acute limb ischemia

Although there is little information on the incidence of acute limb ischemia (ALI) in the general population, it is estimated to be 14 per 100,000 and to compose 10% to 16% of the vascular workload. Also, as surgical intervention has become an option for ALI, the numbers actually referred appear to be increasing. The two main causes of ALI are either an embolism or a thrombosis, and differentiation based on history and clinical examination alone may be clinically impossible in 10% to 15% of cases. However, with the advent of thrombolysis, the distinction between emboli and thrombotic occlusions has become less important from the point of view of management. The natural history of ALI has remained largely unchanged despite the advent of the Fogarty catheter and thrombolysis. Patients presenting with ALI continue to have a particularly severe short-term outlook both in terms of loss of the leg and mortality, with 30-day amputation rates of between 10% and 30% and a mortality rate of around 15%. A patient with an embolic cause for an ischemic leg is at a higher risk of death because of the associated underlying cardiac disease, whereas patients with a thrombotic cause are more likely to lose a limb. The fact that overall mortality rates after intervention for acute ischemia have not improved dramatically over the past 20 years no doubt reflects the severity of the underlying diseases in these high-risk patients.     

The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study.

OBJECTIVES: This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI). BACKGROUND: People with type 2 diabetes have an increased incidence of MI compared with the general population. Those with diabetes and MI have a worse prognosis than nondiabetic patients with cardiovascular disease. METHODS: The PROactive study was a prospective, multicenter, double-blind, placebo-controlled trial of 5,238 patients with type 2 diabetes and macrovascular disease. Patients were randomized to either pioglitazone or placebo in addition to their other glucose-lowering and cardiovascular medication. Treatment of diabetes, dyslipidemia, and hypertension was encouraged according to the International Diabetes Federation guidelines. Patients were followed for a mean of 2.85 years. The primary end point was the time to first occurrence of macrovascular events or death. Of the total cohort, the subgroup of patients who had a previous MI (n = 2,445 [46.7%]; n = 1,230 in the pioglitazone group and n = 1,215 in the placebo group) was evaluated using prespecified and post-hoc analyses. RESULTS: Pioglitazone had a statistically significant beneficial effect on the prespecified end point of fatal and nonfatal MI (28% risk reduction [RR]; p = 0.045) and acute coronary syndrome (ACS) (37% RR; p = 0.035). There was a 19% RR in the cardiac composite end point of nonfatal MI (excluding silent MI), coronary revascularization, ACS, and cardiac death (p = 0.033). The difference in the primary end point defined in the main PROactive study did not reach significance in the MI population (12% RR; p = 0.135). The rates of heart failure requiring hospitalization were 7.5% (92 of 1,230) with pioglitazone and 5.2% (63 of 1,215) with placebo. Fatal heart failure rates were similar (1.4% [17 of the 92] with pioglitazone versus 0.9% [11 of the 63] with placebo). CONCLUSIONS: In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS. (PROspective pioglitAzone Clinical Trial In macroVascular Events; http://www.clinicaltrials.gov/ct/show/NCT00174993?order = 1; ISRCTN NCT00174993).     

Synovial fluid copper and related variables in rheumatoid and degenerative arthritis.

Copper, caeruloplasmin, transferrin, albumin, and total protein were measured in the serum and synovial fluid of 40 patients with rheumatoid arthritis and 40 patients with osteoarthrosis. A raised synovial fluid copper and caeruloplasmin have been found to be characteristic of rheumatoid effusions. The relation between copper and caeruloplasmin in synovial fluid differs from that in serum. Synovial fluid caeruloplasmin was increased disproportionately in relation to other plasma proteins present in rheumatoid effusions.