Intestinal ischemia as a single manifestation of thromboangiitis obliterans--a case report

Thromboangiitis obliterans (TAO) is an inflammatory, nonocclusive, and nonatherosclerotic vascular disease. It commonly affects arteries, veins, and surrounding neural elements and is directly related to smoking. Although distal vessels of lower and upper extremities are the most commonly involved, other vessels such as intestinal arteries can be rarely affected. The authors describe a 41-year-old white male smoker who presented with abdominal pain for 3 months and developed an acute bowel ischemia. He underwent urgent surgery, and segmental enterectomy was performed. Histopathologic findings were suggestive of TAO, showing typical involvement of small-sized veins and arteries with intact internal elastic lamina, preserved media, a local nonspecific inflammatory reaction, with new and older arterial and venous thromboses associated. Although mesenteric arteries are seldom injured by TAO, this diagnosis must be considered when the usual causes of intestinal ischemia are ruled out. In this case, even without any other clinical symptoms of TAO, this rare diagnosis could be made.     

Sustained classic clinical spectrum of thromboangiitis obliterans (Buerger's disease)

Thromboangiitis obliterans (TAO) has been reported to become less common in general population but more common in women, and in elderly patients. The authors looked at the clinical characteristics of TAO in Poland where there was no significant decrease of smoking and the extent of aging of the general population is less profound. They retrospectively reviewed the records of 377 patients with the diagnosis of TAO hospitalized in their institution from 1970 to 1995. If young smoking males demonstrated distal-extremity ischemia with no bruits audible over major arteries, upper limbs involvement, or superficial thrombophlebitis, the diagnosis of TAO was considered certain. When at least one of those criteria was missed, and in men older than 35 years, but in all females, typical arteriographic findings were required for the diagnosis of TAO. Connective-tissue disease, hyperlipidemia, diabetes, and hypercoagulable state were excluded. Three hundred forty-two men (91%), and 35 (9%) women had a mean age of 29.5 years at the onset of the disease (the oldest patient was 50 years old). The prevalence of TAO in southwest Poland is 8.1/100,000 and the incidence of the disease steadily declines; there was no increase of TAO in women. Three hundred thirty-seven (89%) experienced rest pain, 321 (85%) had ischemic necrosis, and 233 (62%) thrombophlebitis at some (continued on next page) time in the course of the disease. Raynaud's phenomenon occurred in only 39 patients (10%). Those patients who had quit smoking had a 50% decrease of the disease recurrences compared to their smoking period. Because the cause of declining incidence of TAO is obscure, the authors critically evaluated previously used explanations of this phenomenon. They did not confirm the observation of a change in the TAO clinical spectrum: occurrence in women did not increase, the aging of the TAO population was not observed. In Poland TAO is still a disease affecting the peripheral circulation of young smoking males with recurrent episodes of superficial thrombophlebitis and common involvement of the upper extremities; Raynaud's phenomenon is rather infrequent. Smoking cessation ameliorates the course of the disease but does not invariably stop further exacerbations.     

Lower limb occlusive arteriopathy: retrospective analysis of 73 patients with onset before the age of 50 years

OBJECTIVES: Juvenile peripheral obstructive arterial diseases (POAD) have been poorly investigated but account for 1 to 7% of POAD. We analyzed retrospectively a cohort of patients with onset before the age of 50 years. PATIENTS AND METHODS: Seventy-three patients (60 males and 13 females) were divided into 4 groups (Buerger's disease: TAO, atheromatous PAOD, auto-immune POAD, arteriopathy of undetermined origin). RESULTS: The first symptoms occurred at 38 +/- 8 years of age. Fourteen patients (20%) had TAO, 51 (70%) atheromatous POAD, 4 (5%) POAD with systemic or autoimmune disease, and 4 (5%) undetermined POAD. Age of onset was earlier in TAO (35 +/- 8 vs 40 +/- 8 years, p=0.046), smoking greater in the atheroma group (33 +/- 16 vs 24 +/- 14 pack-years, p=0.033). Fifty-three POAD patients had dyslipidaemia and 26% hypertension. Regular cannabis intake was more frequent in the TAO group (21 vs 8%). At the time of medical care, Fontaine's stage was more frequently stage II in atheroma patients (57 vs 14%) and stage IV in TAO patients (86 vs 35%). TAO was diagnosed in 43% cannabis users and in 19% non users. CONCLUSION: The main etiology of juvenile POAD is atheroma, followed by TAO. Cannabis users account for at least 10% of these patients. They are characterized by lower tobacco intake, more distal lesions, more frequent involvement of the upper limbs. They present more frequently as TAO.     

Exacerbation of thyroid associated ophthalmopathy after arterial embolization therapy in a patient with Graves’ disease

A novel treatment approach to Graves’ disease (GD), embolization of the thyroid gland arteries, is evaluated with respect to its indications and adverse effects. We describe an exacerbation of thyroid associated ophthalmopathy (TAO) following thyroid artery embolization in a woman with GD and mild stable TAO (NOSPECS classification, class I grade a). A 45-year-old woman with GD and inactive TAO, in whom thyroid function was stable following blockade of hormone release combined with replacement therapy, underwent embolization of three thyroid arteries. Initially, there were neither adverse effects nor complications; however, the patient developed severe TAO (NOSPECS classification, class IV grade b) 3 months after the arterial embolization. Steroid pulse treatments followed by total thyroidectomy resulted in improvement of the eye signs and symptoms. The clinical course and the serial changes of the thyroglobulin and thyroglobulin-antibody titers suggested that the destruction of thyroid follicles, induced by the arterial embolization, triggered the exacerbation of her TAO. Our experience argues for the use of caution when arterial embolization is considered for GD patients with even the mildest TAO (NOSPECS classification, class I).     

The influence of age, sex, smoking, and diabetes on lower limb transcutaneous oxygen tension in patients with arterial occlusive disease

A retrospective study involving 129 patients (256 limbs) with unilateral or bilateral arterial occlusive disease was performed to assess the effects of age, sex, smoking, and diabetes on lower limb transcutaneous oxygen tension (TcPo2) measurements of were made according to a standard protocol, and the severity of lower limb arterial occlusive disease was estimated using the clinical signs and symptoms of disease or the ankle/brachial blood pressure index. The results demonstrated that age, sex, and smoking had no major effects on limb TcPo2 or disease severity; however, both limb TcPo2 and clinical disease severity were adversely affected by diabetes. When limbs with similar occlusive disease severity were compared, TcPo2 remained consistently lower in diabetic than in nondiabetic patients. We conclude that diabetes causes a reduction in limb TcPo2 beyond that which can be accounted for by large-vessel arterial occlusive disease alone.     

Angiographic patency and clinical outcome after balloon‐angioplasty for extensive infrapopliteal arterial disease

Background and objective : Restenosis‐rate after balloon‐angioplasty of long segment tibial arterial disease is largely unknown. We investigated the restenosis‐rates angiographically in patients with critical limb ischemia (CLI) due to extensive infrapopliteal lesions. Methods : Angioplasty for infrapopliteal lesions exclusively ≥80 mm in length was performed using dedicated 80–120 mm long low‐profile balloons. Follow‐up included angiography at 3 months and clinical assessment at 3 and 15 months. Results : Angioplasty was performed in 77 infrapopliteal arteries of 62 limbs of 58 CLI patients with a Rutherford class 4 in 16 (25.8%) limbs and Rutherford class 5 in 46 limbs (74.2%). Average lesion length was 18.4 cm. Treated arteries were stenosed in 35.1% and occluded in 64.9%. After 3 months, a clinical improvement (marked reduction of ulcer‐size or restpain) was seen in 47 (75.8%) limbs, 14 (22.6%) limbs were clinically unchanged and 1 (1.6%) limb showed a clinical deterioration. Angiography at 3 months showed no significant restenosis in 24 of 77 (31.2%) treated arteries, a restenosis ≥50% in 24 (31.2%) arteries and a reocclusion in 29 of 77 (37.6%). At 15 months death rate was 10.5%. After repeat angioplasty in case of restenosis cumulative clinical results at 15 months were minor amputations in 8.1%, no major amputations resulting in a limb‐salvage rate of 100% with no patient requiring bypass surgery. Conclusions : Restenosis‐rate after angioplasty of extensive infrapopliteal arterial disease is high and occurs early after treatment. Despite this the clinical results are excellent, especially given the length of the arterial segments diseased. © 2010 Wiley‐Liss, Inc.     

Pattern of occlusive peripheral vascular disease in India. (clinicopathological study of 79 cases).

The pattern of peripheral vascular disease in India was studied in 89 patients undergoing amputation for vascular insufficiency. A control group of 26 limbs was studied for aging changes. Clinically, cases were classified into TAO (25), ASO (54) and thrombo-embolic disease (10). Angiographic, macroscopic and microscopic study of dissected vascular tree was done in view of clinical diagnosis. No significant difference was noted in the frequency and extent of involvement of limb arteries in TAO and ASO. Histologically angiitis was noted in 4 cases of TAO and one of ASO but these did not form a distinct clinical group. Primary thrombotic occlusion was seen in 21 cases of TAO and 23 cases of ASO. Atheroma with and without thrombosis was found in 26 cases. In 4 cases the arterial tree was normal. Atheromatous lesions were not seen in control group. In the groups under study they were thought to represent old thrombi rather than degenerative lesions predisposing to thrombosis. In view of these findings it was felt that Buerger's disease was primarily a thrombotic disorder. Angiitis was rare and was probably secondary. The two clinical groups TAO and ASO are not pathologically distinct as very high percentage of the latter showed primary thrombosis. The genesis of thrombosis in two groups however may be different.     

Thromboangiitis Obliterans (Buerger’s Disease)

Thromboangiitis obliterans (TAO) is a devastating nonatherosclerotic disease that often leads to digit and limb loss as well as intractable ischemic rest pain. Patients with TAO are uniformly heavy users of tobacco. This disorder is characterized as a miscellaneous form of vasculitis affecting small- and medium-sized arteries and veins. TAO causes painful ischemic ulcers of the digits and unusually painful and inflammatory superficial thrombophlebitis. The key to early diagnosis of TAO is a high clinical index of suspicion in the appropriate patient scenario, exclusion of any other potential cause, abnormal results from an Allen's test, and arteriographic findings of segmental digital arterial occlusions with "corkscrew" collateral vessels. The primary and clearly most effective therapy for TAO is cessation of the use of all tobacco products, with avoidance of any environmental tobacco smoke inhalation. There has been recent enthusiasm for prostaglandin E therapy and the intramuscular injection of angiogenic growth factors. For patients in whom the disease is identified late or for those who are unable to discontinue cigarette smoking, however, a frequent result is multiple limb amputations.     

Etiopathogenesis, clinical diagnosis and treatment of thromboangiitis obliterans - current practices

Thromboangiitis obliterans (TAO) is a segmental inflammatory occlusive disorder that affects small- and medium-sized arteries, and arm and leg veins of young smokers. Several different diagnostic criteria have been offered for the diagnosis of TAO. Clinically, it manifests as migratory thrombophlebitis or signs of arterial insufficiency in the extremities. It is characterized by highly cellular and inflammatory occlusive thrombi, primarily of the distal extremities. Thromboses are often occlusive and sometimes display moderate, nonspecific inflammatory infiltrate, consisting mostly of polymorphonuclear leukocytes, mononuclear cells and rare multinuclear giant cells. The immune system appears to play a critical role in the etiology of TAO. However, knowledge about immunological aspects involved in the progression of vascular tissue inflammation, and consequently, the evolution of this disease, is still limited. There are several studies that suggest the involvement of genetic factors and results have shown increasing levels of antiendothelial cell antibodies in patients with active disease. Vasodilation is impaired in patients with TAO. TAO disorder may actually be an autoimmune disorder, probably initiated by an unknown antigen in the vascular endothelium, possibly a component of nicotine. There are various therapies available for treatment of TAO, but the major and indispensable measure is smoking cessation. Except for discontinuation of tobacco use, no forms of therapy are definitive. Sympathectomy, cilostazol and prostaglandin analogues (prostacyclin or prostaglandin E) have been used in specific conditions. Recently, therapeutic angiogenesis with autologous transplantation of bone marrow mononuclear cells has been studied in patients with critical limb ischemia.     

Serum concentrations of proinflammatory cytokines in Graves' disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking

OBJECTIVE: In the present study we have measured the concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) in the serum of patients with Graves' disease (GD). By multivariate analysis, we have evaluated the effect of antithyroid treatment, thyroid function, the presence or absence of active thyroid-associated ophthalmopathy (TAO), the patient's smoking habits and the relation to circulating anti-thyrotropin (TSH) receptor (TRAb) and anti-thyroperoxidase antibodies (TPOAb). SUBJECTS: We studied 84 GD patients, 51 untreated and 33 receiving methimazole (MMI) therapy. Twenty-three (45%) untreated patients and 18 (54%) patients on MMI had active TAO. We also studied 67 normal subjects as controls. Thirty-one GD patients (43%) and 16 controls (36%) were smokers. RESULTS: Serum IL-6 concentrations were significantly higher in both untreated patients (P<0.001) and treated patients (P<0.006), when compared with controls. Serum sIL-6R concentrations were significantly affected by treatment (P=0.001). Serum IL-1Ra concentrations were not different in GD patients, whether treated or untreated, compared with controls. Serum IL-6 concentrations were not influenced by thyroid function and there was a significant interaction between treatment and the presence of active TAO (P=0.003). In hyperthyroid patients with active TAO serum, sIL-6R concentrations were significantly higher than in those with inactive TAO (P=0.003). In untreated GD patients there was no significant effect of thyroid function and TAO activity on the serum concentrations of TNF-alpha and IL-1 beta. Serum IL-1Ra concentrations were not affected by the presence of TAO. Smoking had no effect on serum IL-6, sIL-6R, TNF-alpha, IL-1 beta and IL-1Ra concentrations, even in the presence of an active TAO. Serum concentrations of IL-6, sIL-6R, TNF-alpha and IL-1 beta and IL-1Ra were not different in patients with and without TRAb or TPOAb, in relation to either thyroid function, TAO activity or smoking. CONCLUSIONS: Our work shows that: (i) the proinflammatory cytokine pattern in GD is greatly influenced by antithyroid drug treatment; (ii) the increased circulating IL-6/sIL-6R concentrations observed in patients with active TAO may derive from the activation of humoral reactions in sites other than the thyroid; and, (iii) cigarette smoking has no effect on serum IL-1/IL-1Ra concentrations in TAO.     

Vascular remodelling in intramyocardial resistance vessels in hypertensive human cardiac transplant recipients.

OBJECTIVE: Cardiac transplant recipients often develop hypertension as a side effect of immunosuppressive treatment. The aim of this study was to use the serial endomyocardial biopsies taken to monitor rejection to study the early and sequential arterial changes in human myocardial resistance arteries as hypertension develops. METHODS: At least 14 biopsies were studied from each of 23 patients, divided into a normotensive group (12 patients with a diastolic pressure never greater than 90 mm Hg) and a hypertensive group (11 patients with more than 10% of diastolic pressure measurements above 100 mm Hg). Morphometric analysis of between 30 and 50 arteries and arterioles in two widely separated histological levels from each biopsy was undertaken using an Optomax image analyser. RESULTS: There was a correlation between blood pressure, particularly diastolic pressure, and rate of medial thickening of intramyocardial coronary resistance arteries and arterioles (P = 0.0025). There was also a correlation between serum cyclosporin A concentrations and mean artery wall thickness (P = 0.003). CONCLUSIONS: Hypertension and cyclosporin A treatment are associated with significant wall thickening of intramyocardial resistance vessels in cardiac allograft recipients. These changes may be functionally and clinically important.     

Outcome of immunosuppressive treatment of a patient with renal failure due to retroperitoneal fibrosis

Retroperitoneal fibrosis (RPF) is an uncommon disease of unclear aetiology. The review of the literature over the past 20 years revealed 160 published cases. Till now, no accepted diagnostic or therapeutic strategy exist. Most of patients diseases progress to end-stage renal failure without pharmacological treatment. In the paper we report a case of a 58-year old man admitted to the department of urology due to body mass loss, lower-back pain, vomiting, development of oliguria and anuria and intermittent claudication. On physical examination arterial hypertension (180/100 mm Hg), peripheral oedema, tenderness of the enlarged kidneys and lower limbs ischemia were found. Creatinine serum level (Pcr) was 232 micromol/l (2.69 mg/dl). On ultrasonography, symmetrical hydronephrosis and the existence of a hypoechogenic mass along of the aorta and below of renal arteries was found. The diagnosis of RPF was confirmed with MRI. Ureteral catheters were inserted with subsequent decompression of both kidneys and the patient was discharged from the hospital. Seven months later he still presented symptoms of lower limbs ischemia, arterial pressure was high and Per decreased to 138 micromol/l (1.55 mg/dl). The patient was admitted to the department of internal diseases. The treatment with prednisone at the dose of 40 mg/d during 6 weeks was introduced, and the dose was decreased gradually to 10 mg/d within 6 months. Simultaneously, the patient received intravenous therapy with cyclophosphamide 600 mg/infusion once monthly during 6 months. Two month after starting immunosuppressive treatment the intermittent claudication disappeared and after six months MRI examination demonstrated the regression of RPF. The ureteral catheters were removed. After 18 months of follow up, no recurrence of RPF is observed and the kidney function is normal.     

Octreoscan in thyroid-associated ophthalmopathy.

Until recently, there was no imaging technique available that could be considered as a reliable measure of inflammation in thyroid-associated opthalmopathy (TAO). Pentetreotide (a synthetic derivative of somatostatin) labeled with 111In has been used to visualize somatostatin receptors in endocrine-related tumours in vivo. It has also been used to measure the orbital uptake in patients with TAO. An increased uptake in the orbit was found in patients with active disease. It was suggested that it is caused by the expression of somatostatin receptors on activated T-lymphocytes. Thus, a positive orbital octreoscan indicates clinically active eye disease in which immunosuppressive treatment might be of therapeutic benefit, in contrast to the fibrotic end stage. Indeed, successful immunosuppression with prednisone, orbital irradiation, or very recently with somatostatin analogues, has been demonstrated in patients with TAO and positive octreoscan. It is inferred that an orbital octreoscan is mainly indicated to select patients with TAO who will benefit from immunosuppression. However, limitations such as cost, nonnegligible radiation burden, nonspecific examination for TAO, and finally, lack of evaluation of eye muscle swelling restrict the widespread use of this technique. It remains to be seen if orbital octreoscan will become a widely available tool in the management of patients with TAO.     

Sub acute ischemia of a lower limb in a patient with juvenile peripheral arterial disease and arterial cocaine toxicity

A 35-year-old woman was hospitalized for subacute ischemia of the left leg following an intermittent claudication for some weeks. She also presented paleness and coldness of both hands. The radial pulses could not be palpated. Smoking was the only cardiovascular risk factor. Duplex ultrasonography and angiography revealed a left popliteal thrombus combined with low diameter leg arteries and in the upper limbs stenosis of the left radial artery and thrombosis of the right radial artery. Search for a metabolic, embolic or thrombophilic etiology was negative. More minute history taking revealed use of cannabis and recent nasal administration of cocaine. Her condition improved with heparin therapy except for the upper limbs with ischemia of the hands and disabling Raynaud's phenomenon. This report highlights the combined arterial toxicity of drugs often used together by drug addicts. The association of cannabis use and tobacco smoking is not rare in patients with Buerger-like juvenile arteriopathy and cocaine may provoke peripheral vascular disease by embolism or in situ thrombosis. Interrogation of a patient presenting with Buerger-like peripheral arterial disease should insist on detecting use of drugs in association with tobacco smoking.     

Randomised, double blind comparison of omeprazole and cimetidine in the treatment of symptomatic gastric ulcer.

In a randomised, double blind, parallel group study in patients with symptomatic gastric ulcer (94% greater than or equal to 5 mm diameter), 102 received omeprazole 20 mg om and 87 cimetidine 400 mg bd. After four weeks 73% and 58% (p less than 0.05) respectively had healed (eight weeks: 84% and 75%, ns). After four weeks, a greater proportion (81%) of omeprazole treated patients was symptom free than of those receiving cimetidine (60%; p less than 0.01). Over the first two weeks, patients receiving omeprazole had less day pain, less night pain and took fewer antacids than those receiving cimetidine (all p less than 0.05). The difference between omeprazole and cimetidine was not appreciably affected by age, smoking, size of the ulcer and trial centre. Tolerability was similar in the two treatment groups. In the treatment of symptomatic gastric ulcer, omeprazole relieves the symptoms more quickly than cimetidine and heals a greater proportion of ulcers within four weeks.     

Value of duplex scanning in differentiating embolic from thrombotic arterial occlusion in acute limb ischemia

BackgroundManagement of acute limb ischemia (ALI) is largely based on the etiology of arterial occlusion (embolic vs. thrombotic). To our knowledge, the ability of duplex scanning to differentiate embolic from thrombotic occlusion has not been previously reported.PurposeTo determine the ability of duplex scanning to differentiate embolic from thrombotic acute arterial occlusion.MethodsWe prospectively recruited 97 patients (50.3±19.7 years; 55% males) with 107 nontraumatic ALI in native arteries. All patients underwent surgical revascularization. Preoperative duplex scan detected arterial occlusion in the following arteries: iliac (11), femoral (38), popliteal (38), infrapopliteal (3), subclavian (3), axillary (1), brachial (9), and forearm arteries (4). We measured the arterial diameters at the site of occlusion (d_occl) and at the corresponding contralateral healthy side (d_CONTRA). The difference (Δ) between the two diameters was calculated as d_OCCL?d_CONTRA. Duplex scan was also used to assess the state of the arterial wall whether healthy or atherosclerotic and the presence of calcification or collaterals. According to surgical findings, limbs were classified into embolic (E group=55 limbs) and thrombotic (T group=52 limbs) groups.ResultsBoth groups were comparable regarding age, diabetes, hypertension, smoking, atrial fibrillation, and time of presentation. The status of arterial wall at the site of occlusion and presence of calcification or collaterals were all similar in both groups. Δ in the E group was 0.95±0.92 mm vs. ?0.13±1.02 mm in the T group (P<.001). A value of ≥0.5 mm for Δ had 85% sensitivity and 76% specificity for the diagnosis of embolic occlusion (CI 0.72–0.90, P<.001), whereas a value of less than ?0.5 mm for Δ had 85% sensitivity and 76% specificity for thrombotic occlusion (CI 0.72–0.90, P<.001).ConclusionIn acute arterial occlusion, ≥0.5 mm dilatation or diminution in the occluded artery diameter is a useful duplex sign for diagnosing embolic or thrombotic occlusion, respectively.     

Current status of thromboangiitis obliterans (Buerger's disease) in Japan

We analysed clinical features and outcome in 850 patients with thromboangiitis obliterans (TAO), based on the 1993 Nationwide Survey of Vasculitis database collected from 3722 clinical sites in Japan. The survey was designed to assess clinical manifestation categorized by Fontaine's classification, distribution of lesions (arterial involvement and migratory superficial phlebitis), response to medical and surgical treatment, and outcome. There were 771 males (90.7%) and 79 females (9.3%), with a mean age of 50.8+/-0.4 (range: 17-81) years. Clinical manifestations at the first consultation were Fontaine I in 8.0%, Fontaine II in 29.6%, Fontaine III in 23.9%, and Fontaine IV in 38.1%. These symptoms had been significantly improved by the time of survey. Ulcer formation in the past history had occurred in 45.2%, which was the most common in toes (85.9%). Failure of smoking cessation significantly affected the risk of ulcer formation (odds ratio=1.71, 95% CI=1.19-2.47; P=0.004) and amputation (odds ratio=2.73, 95% CI=1.86-4.01; P<0.0001). Clinical features in female patients with TAO were equal to those in male patients, except for the fact that non-smokers were more common in female patients. Abstinence from tobacco significantly reduces the risk of ulcer formation and amputation, and thus improves the quality of life in patients with TAO.     

Multiple skeletal muscle mitochondrial DNA deletions in patients with unilateral peripheral arterial disease

Peripheral arterial disease (PAD) is associated with metabolic derangements and accumulation of the common 4977 bp mitochondrial DNA (mtDNA) deletion mutation. The current study was undertaken to test the hypothesis that PAD is associated with multiple mtDNA deletions. Gastrocnemius biopsies were obtained from nine patients with unilateral PAD. DNA extracted from the biopsies was analyzed for mtDNA deletions using a primer-shift PCR strategy. Multiple primers and strict, prospective criteria were used to identify deletions. PAD was associated with multiple mtDNA deletions (average of 8.2 distinct deletions in muscle from the hemodynamically affected limb). mtDNA injury was present in both the worse- and less-affected limbs of the unilateral PAD patients, and the estimated degree of mtDNA injury was strongly correlated in the two limbs on an intra-subject basis. The 4977 bp deletion was frequently identified, but was not always the deletion of highest frequency in individual samples. The estimated relative frequency of the 4977 bp deletion was correlated with the overall mtDNA injury in the biopsies. In summary, PAD is associated with mtDNA injury as reflected by multiple deletion mutations. As the mutations are not limited to the ischemic limb in unilateral patients, they are unlikely to contribute to the pathophysiology of claudication.     

Coronary arterial remodeling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis

Coronary arterial remodeling is a compensatory mechanism that may limit the adverse effects of coronary obstructive lesions by expansion of the entire vascular segment. To determine if this compensatory anatomic change occurs in patients, high-frequency epicardial echocardiography using a 12 MHz transducer was performed during open heart surgery in 33 patients (10 with normal coronary arteries undergoing valvular surgery and 23 with coronary atherosclerosis). From stop-frame videotape high-frequency epicardial echocardiographic images, cross-sectional measurements of luminal area and total arterial area (lumen, intima, media and dense adventitia) were made in the patients with atherosclerosis at the site of arterial lesions and from the most proximal portion of the same artery. Remodeling was defined as enlargement of the total arterial area. In normal arteries measurements were made from proximal and midarterial locations. In the patients with normal coronary arteries, total arterial area, as determined by high-frequency echocardiography, decreased from the proximal site to the midportion of the artery (from 10.4 +/- 0.9 to 8.4 +/- 1.0 mm2, p less than 0.05); luminal area also decreased (from 6.0 +/- 0.6 to 4.5 +/- 0.7 mm2, p less than 0.05). In patients with coronary arterial lesions, luminal area also decreased from the proximal site to the arterial lesion site (from 5.3 +/- 0.6 to 2.3 +/- 0.3 mm2, p less than 0.05), but total arterial area increased (from 11.6 +/- 1.0 to 13.0 +/- 1.0 mm2, p less than 0.05). Of the 25 coronary arteries evaluated, only 4 had angiographic evidence of coronary collateral formation. These data indicate that coronary arterial remodeling is an important compensatory mechanism in obstructive coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mycophenolate mofetil as a therapeutic agent for interstitial lung diseases in systemic sclerosis

Systemic sclerosis (SSc) is an intractable disease that causes fibrosis in all organs. Approximately 40% of patients with SSc have some degree of interstitial lung disease (ILD). One third of patients with SSc and ILD, approximately 15% of all patients, have pulmonary lesions, which slowly progress to respiratory failure resistant to corticosteroid and other treatments.A randomized controlled trial conducted in the United States indicated that one year of treatment with oral cyclophosphamide in patients with SSc-ILD had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and health-related quality of life. However, all the effects, except for a sustained impact on dyspnea, disappeared approximately one year after stopping oral administration of cyclophosphamide. A randomized controlled trial using cyclophosphamide and mycophenolate mofetil (MMF) was then held in the United States for 142 patients with SSc-ILD. Treatment of SSc-ILD with MMF for two years or cyclophosphamide for one year both resulted in significant improvements in lung function over the 2-year course of the study. Leukopenia and thrombocytopenia occurred less often in patients administered MMF than in those administered cyclophosphamide.MMF is currently not approved for the treatment of SSc-ILD in Japan. Both MMF and cyclophosphamide were effective against ILD associated with SSc and, in particular, MMF was useful in terms of tolerability. When MMF is approved, it should be positioned as one of the first treatment options for SSc-ILD, which will further enhance the treatment of this disease in Japan.