Case of parathyroid carcinoma with a highly aggressive clinical course.

We describe a 59-year-old woman who presented with pathological osteoporosis, cerebral infarction, hypercalcemia, and markedly high parathyroid hormone levels. The diagnosis was primary hyperparathyroidism, and parathyroidectomy was performed. Histopathological examination showed parathyroid adenoma. Surgical exploration for recurrent parathyroid carcinoma was undertaken at 2 and 3 years after the initial neck resection. Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. The prognosis for parathyroid carcinoma is often difficult to predict due to recurrence.

Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells.

INTRODUCTION: In systemic lupus erythematosus (SLE) patients, the prevalence of arteriosclerosis obliterans (ASO) is high despite a lack of common risk factors for ASO. The main objective of this study was to investigate a possible direct role of anti-phospholipid antibodies (aPLs), which are frequently detected in SLE patients, in the pathogenesis of ASO. MATERIALS AND METHODS: We examined tissue factor (TF) expression on the monocyte surface by flow cytometric analysis in 89 SLE patients with or without ASO and/or aPLs and studied the in vitro effect of purified IgG fractions from plasma of SLE patients or normal healthy volunteers (aPLs(+) IgG, n=8; aPLs(-) IgG, n=6; Normal IgG, n=6) on the expression of TF and production of TNF-α and IL-1ß in healthy peripheral blood mononuclear cells (PBMCs) or isolated monocytes. RESULTS: We confirmed that high expression of monocyte TF was strongly associated with the prevalence of ASO and the presence of aPLs. Treatments of PBMCs with aPLs(-) IgG or normal IgG did not significantly increase expression of TF, TNF-α, and IL-1ß messenger RNA (mRNA) and the production of TNF-α and IL-1ß. However, stimulation of PBMCs with aPLs(+) IgG caused significant increase in expression of TF, TNF-α, and IL-1ß mRNA. Moreover, aPLs(+) IgG stimulated PBMCs and significantly enhanced the production of TNF-α and IL-1ß. CONCLUSION: These results suggest that IgG-aPLs cause persistently high TF expression and inflammatory cytokine production by interacting with peripheral blood monocytes and lymphocytes, which may be an important mechanism in the pathogenesis of ASO peculiar to SLE patients.

[The experience with thoracoscopic sympathectomy for the treatment of distal lesions of limb arteries].

The study included 107 patients with distal lesions of limb arteries treated with the use of thoracoscopic sympathectomy. The best results in the early postoperative period were obtained in patients with Raynaud's disease. Modifications introduced into the methods of its treatment permitted to retain effectiveness of sympathectomy till the late postoperative period in 90% of the patients. Surgery for obliterative endarteritis and atherosclerosis was viewed as a possibility to preserve the supporting function of the limb. This purpose was attained in 73.2 and 62.5% of the patients respectively in the early and in 62 and 25% in the late postoperative periods.

Risk of macrovascular disease stratified by stage of chronic kidney disease in type 2 diabetic patients: critical level of the estimated glomerular filtration rate and the significance of hyperuricemia.

BACKGROUND: Although a high prevalence of macrovascular disease (MVD) has been reported in patients with stage 3 chronic kidney disease (CKD), few studies have reported its risk with respect to the underlying cause of kidney disease. This study investigated the prevalence of MVD in type 2 diabetic patients with CKD stratified by CKD stage, as defined by estimated glomerular filtration rate (eGFR), as well as the risk factors for MVD. METHODS: 1493 patients with diabetic CKD (1273 males, 220 females) were stratified by CKD stage (stage 1: 39, stage 2: 272, stage 3: 1052, stage 4: 101, stage 5: 29) based on eGFR calculated by the Japanese formula and averaged over 8 months. MVD was defined as one of the following: coronary heart disease (CHD), stroke or arteriosclerosis obliterans (ASO). RESULTS: The prevalence of MVD was 18.6%. A significant increasing trend in MVD prevalence was observed from stage 3 (17.78%) to 4 (52.48%). According to a receiver operating characteristic curve analysis on MVD prevalence in stage 3 patients, an eGFR of 46.4 ml/min/1.73 m(2) was determined to be a critical cut-off level. Proteinuria, eGFR <60 ml/min/1.73 m(2) and hyperuricemia were independent risk factors for MVD. CONCLUSIONS: In patients with diabetic CKD, a significant increase in MVD prevalence was observed from stage 3 to 4. An eGFR of 46.4 ml/min/1.73 m(2) is a critical level that affects MVD prevalence. From the perspective of cardiorenal association, CKD stage 3 should be divided into two substages. As hyperuricemia is related to an increased risk of MVD, uric acid control may be important in reducing MVD risk in diabetic CKD.

[Management of prosthetic graft occlusion after lower extremity bypasses].

OBJECTIVE: Report the experience of management of graft occlusion in patients with lower extremity bypasses and discuss the appropriate treatment strategy. METHODS: From Oct. 2004 to Oct. 2009, 104 cases of graft occlusion were treated in 53 patients with lower extremity arterial bypasses, including medical therapy for 10 cases and redo operations for 94 cases: graft thrombectomy alone for 26 cases, redo bypass or extension bypass with prosthetic or autologous vein grafts for 23 cases, graft thrombectomy plus balloon angioplasty for 18 cases, major amputation for 14 cases, graft thrombectomy plus femoral or popliteal artery endarterectomy for 10 cases, removal of occluded graft with infection for 2 case, and autologous stem cell transplantation for 1 case. RESULTS: 77 reconstructive procedures were applied and graft failures recurred in 49 cases (63.6%). One patient died of acute renal failure during peri-operative period and 9 patients died during follow-up; 6 patients were lost to follow-up. The remaining 37 patients were followed: major amputation for 12 patients, patent grafts after reconstruction in 18 patients, and medical therapy after graft occlusion for 7 patients with limb salvage. Kaplan-Meier survival analysis revealed 3-year survival of 77.4%, limb salvage of 64.7%, and graft patency of 45.7%. Effect of different procedures on cumulative patency was of no statistical significance. CONCLUSIONS: Graft occlusions after lower extremity bypasses may result in high rate of reocclusion and amputation. Optimal management should be based on a thorough analysis of individual condition.

Characteristics of revascularization treatment for arteriosclerosis obliterans in patients with and without hemodialysis.

BACKGROUND: Limb ischemia is a major complication in patients who are receiving hemodialysis (HD). In this study, distinctive features and factors affecting the outcome of HD patients with limb ischemia are identified. METHODS AND RESULTS: One hundred and eighty consecutive symptomatic limb ischemic patients who were or were not receiving HD and who successfully underwent surgical bypass grafting (bypass, n=75) or endovascular angioplasty (percutaneous transluminal angioplasty (PTA), n=105) were retrospectively compared at our hospital. The endpoint of this study was amputation of the ischemic leg or death. Median follow up was 2.25 years. The amputation-free survival of HD patients was significantly lower than that of non-HD patients (P<0.0001). In the bypass group, the amputation-free survival of HD patients was significantly lower than that of non-HD patients (P=0.0002), even if the graft was patented or not (P=0.77). In contrast, in the PTA group, the amputation-free survival of HD patients was lower than that of non-HD patients (P=0.03), and with a significantly lower patency rate (P=0.0004). Predictors of amputation-free survival differed between HD and non-HD patients; predictors were diabetes mellitus and gender in HD patients, while they were Fontaine classification and hyperlipidemia in non-HD patients. The infectious death rate was higher in HD patients than in non-HD patients (53% vs 22%, P<0.05). CONCLUSIONS: This study clearly showed a poorer prognosis in HD patients than in non-HD patients especially after bypass surgery, even if the the graft was patented or not.

[Ultrastructural changes of vascular endothelium in patients with chronic ischemia of the extremities after conduction of multipotent stromal cells from adipose tissue transplantation].

Taking into account the impossibility of performance in some situations of reconstructive operative interventions on arteries, it is necessary to look for new methods of indirect revascularization for the extremities ischemia. Adipose tissue constitutes an accessible and sufficient source of multipotent stromal cells (MSC). Experimental investigations were made in a frame of preclinical trial on laboratory animals with the extremity ischemia simulation, and there was proved the essential stimulation of angiogenesis processes after transplantation performance of stromal-vascular fraction of adipose tissue. The work objective was to study the influence of own adipose tissue MSC transplantation on vascular endothelium changes in patients, suffering chronic ischemia of the extremities. Using electron microscopy method there was proved on microstructural level, that in clinical environment the patients, suffering chronic ischemia of the extremities of various etiology, gain undoubted effect of MSC autotransplantation performed with the objective to stimulate the processes of angiogenesis in the ischemic affection region.

[Haemodynamic role of blood-plasma circulating cell-free DNA and contained therein high-molecular-weight CpG-rich fraction in pathogenesis of arterial hypertension and atherosclerosis obliterans of carotid arteries].

The hydrodynamic resistance (HR) of blood is one of the components of the total peripheral resistance. High-molecular-weight DNA appears to decrease the HR in accordance with the Toms's effect. The present study was undertaken to investigate the HR and properties of cell-free DNA circulating in the blood plasma (hereinafter referred to as pDNA) of the control donors, patients suffering from either arterial hypertension (AH) alone or that combined with atherosclerotic lesions of the carotid arteries (CAs). Within the normal concentrations of pDNA, we revealed an inverse dependence of the HR thereupon and upon the content in pDNA of the high-molecular-weight CpG-rich fraction (CpG-DNA), i. e., a transcribed region of the ribosomal repeat (rDNA). A decrease or an increase in the pDNA concentration in all the patients examined was accompanied by an elevation of the rDNA concentration in the blood plasma. Exceeding a certain level thereof appeared to give rise to an increase in both the HR and arterial pressure (AP). Patients presenting with degree I essential AH were found to have a decreased endonuclease activity of the blood plasma, with the pDNA concentration being more than two-fold higher with no change in the rDNA content. Their HR appeared to be increased (p<0.01). Patients diagnosed as having degree II AH were characterized by a normal or decreased level of pDNA and an elevated content of pDNA, with the HR being slightly lowered. In patients presenting with atherosclerosis obliterans of the ACs, the initial manifestations of the lesions of the carotid arteries were typically revealed on the background of a lowered HR (p<0.05). All patients suffering from atherosclerotic lesions of the ACs could be subdivided into two groups, which in our opinion is probably associated with different various mechanisms of destructive damage to the arterial intima. In some of them, the pDNA concentration does not differ from the normal values, but in its composition, there is an increased content of rDNA, elevating as obliteration of the vessels' lumen increases, with the HR being decreased. The majority of them have degree II AH. In others, the pDNA concentration is by an order of magnitude higher than the normal values, while the rDNA content in pDNA is decreased, with the HR being elevated. Most of them have degree III AH. Pronounced and rough stenoses take an asymptomatic course in patients with decreased values of the HR and a slightly elevated level of pDNA and/or rDNA in the blood plasma. A higher level thereof leads to a rise in the HR and to the appearance of neurological symptomatology. Hence, CpG-DNA circulating in the composition of pDNA is a constantly acting endogenous blood factor decreasing the HR (the Toms's effect) and normalizing AP under physiological conditions, being however a cause of their increase and impairment of blood circulation in the pathogenesis of AH and atherosclerosis obliterans of the CAs.

[Hemorheologic disturbances in patients with obliterative atherosclerosis of peripheral arteries and type 2 diabetes mellitus].

The aim of this work was to assess hemorheologic variations and factors influencing them in 529 patients with obliterative atherosclerosis of the lower limbs and type 2 diabetes mellitus. Blood viscosity and hematocrit volume were measured. Statistical treatment of the results was performed using the STATISTICA 6.0program (StatSoft Inc., USA). Differences between observed and normal distributions were described in terms of medians and quartiles. Independent groups were compared using Mann-Whitney U-test, 2-sample Kolmogorov-Smirnov test, and Kruskal-Wallis method. Differences were considered significant atp < 0.05. Results of the study confirm disturbances in the hemorheologic system in patients with obliterative atherosclerosis of the lower limbs and diabetes. Variations of blood viscosity and hematocrit volume in these patients have multidimensional character and depend on such factors as age, gender, smoking, duration of diabetes, degree of compensation of metabolic processes, and severity of arterial circulation problems.

[Chronic angiospastic arterial ischemia of limbs in the patients of elderly and senile age].

The experience of examination and treatment of about 3000 patients having chronic arterial ischemia of extremities allowed to determine that such a clinical presentation appears as a result of functional organic diseases of arteries of extremities: arterial vasoconstriction and obliterating disease of arteries (obliterating atherosclerosis, obliterating endoarteritis, diabetic angiopathy). Chronic ischemia of extremities develops from arterial vasoconstriction of central genesis and then obliterating disease of arteries joins the process. The paper is devoted to the first phase of development of chronic arterial ischemia of extremities: vertebragenous angiospastic disease of arteries of extremities and its treatment for patients of middle and old age.

Serum adiponectin and markers of endothelial injury in hemodialysis patients with arteriosclerosis obliterans.

BACKGROUND: Arteriosclerosis obliterans (ASO) in hemodialysis patients is the dominant cause of morbidity evolving from arteriosclerosis. Adiponectin is an adipose-derived cytokine which, because of its modulation of endothelial adhesion molecules, has potential anti-inflammatory and anti-atherogenic properties. However, the implications of adiponectin and endothelial function in ASO of hemodialysis patients has not been fully elucidated. METHODS: In this study we measured serum levels of adiponectin, adhesion molecules (VCAM-1 and ICAM-1), and an endothelial cell injury marker (CD146) in patients with ASO. We sought to determine clinical and laboratory correlates of ASO in ESRD patients. A total of 80 hemodialysis patients and 82 patients with normal serum creatinine levels were enrolled. Serum levels of adiponectin, ICAM-1, VCAM-1, and CD146 were measured by ELISA. RESULTS: Serum adiponectin levels in 41 hemodialysis patients with ASO were significantly lower than in 39 patients without ASO. Serum CD146 levels in hemodialysis patients with ASO were significantly higher than in patients without ASO. There were no significant differences between levels of ICAM-1 and VCAM-1 in these two groups. Similar results were obtained for patients with normal renal function. Serum adiponectin was related to hemodialysis duration and BMI in hemodialysis patients. In patients with normal renal function, adiponectin was related to HDL-cholesterol, triglyceride, and ICAM-1. CONCLUSION: A decrease in serum adiponectin levels and an increase in serum CD146 may be closely associated with the development of ASO, regardless of renal function. However, there are different mechanisms determining serum adiponectin levels in patients with normal kidney function and in hemodialysis patients.

[Analysis of peripheral arterial obstructive disease related factors among diabetic population aged > or = 50].

OBJECTIVE: To analyze the peripheral arterial obstructive disease (PAD) related factors among diabetic population aged > or = 50 in China. METHODS: The clinical data of 1397 diabetic patients aged > or = 50 with at least one of the following risk factors: smoking, hypertension, and hyperlipidemia, from 15 Class III Grade A hospitals in 7 major cities of China were collected. Diagnosis of PAD was based on the ankle brachial index (ABI) < 0.9, and diagnosis of arteriosclerosis was based on pulse wave velocity (PWV) > 1400 cm/s. Regression studies were made to analyze the relations among PAD and various risk factors: age, sex, body mass index (BMI), smoking, hypertension, hyperlipidemia, history of cerebral vascular disease (CVD), history of ischemia heart disease (IHD) etc. RESULTS: The current prevalence rate of PAD was 19.47% among the 1397 patients, 18.3% (122/664) among the male patients, and 20.4% (150/733) among the female patients. The prevalence of PAD in the patients aged > or = 70 was as high as 31.9%. The duration of diabetes course was positively correlated with the prevalence of PAD (chi2 = 11.9, P = 0.0026). The ABI abnormality rate was 15.78% among those with a diabetic course of 5 years and was 23.84% among those with a diabetic course of 10 years. The abnormal ABI rate of the patients with CVD was 30.57%, significantly higher than that of hose without CVD (17.29%, chi2 = 21.49, P < 0.0001). The abnormal ABI rate of the patients with IHD was 24.64%, significantly higher than that of the patients without IHD (18.20%, chi2 = 5.85, P = 0.0155). The HbA1c value of the PAD patients was significantly higher than that of the patients without PAD (chi2 = 5.10, P = 0.0239) Odd risk analysis showed that age increase of 10 years increased the PAD risk by 1.64 times (OR = 1.6444, P = 0.0001). The PAD risk of the smokers was 1.68 times higher than that of the non-smokers (OR = 1.6852, P = 0.0001). Increase of 10 mm Hg in systolic blood pressure (SBP) increased the PAD risk by 1.19 times (OR = 1.1926, P = 0.01). The PAD risk of the patients with abnormal HbAlc was 2.44 times higher than that of the patients with normal HbA1c (OR = 2.4473, P = 0.0001). One-year's increase of the hypertension course increased the PAD risk by 1.02 times (OR = 1.0194, P = 0.03). Logistic analysis indicated that the relations among PWV and the risk factors were almost the same among ABI abnormality and the risk factors. CONCLUSION: Approximately one fifth of diabetic patients aged > or = 50 in China suffer from PAD. Age, course of diabetes, blood glucose level, SBP, IHD, and CVD are risk factors for PAD. Early intervention and treatment of hypertension and hyperglycemia, and quitting smoking are important in reducing the occurrence of PAD. ABI and PWV are not only diagnostic means for PAD, but also alarm guide indexes for cerebral vascular disease (CVD).

Serum levels of S-glutathionylated proteins as a risk-marker for arteriosclerosis obliterans.

BACKGROUND: Oxidative stress plays a role in the development of chronic peripheral arterial disease (PAD) because under these conditions redox regulation is impaired, inducing the S-glutathionylation of proteins. A method of estimating the levels of S-glutathionylated proteins has been developed using biotinylated glutathione S-transferase, which allows the study of their crucial role in the oxidative stress-related progression of PAD. METHODS AND RESULTS: The serum levels of S-glutathionylated proteins were examined in 41 patients with arteriosclerosis obliterans (ASO) and 38 age-matched non-ASO patients using biotinylated glutathione S-transferase. The levels were higher in the patients with ASO, even early on, and positively correlated with the ankle/brachial index. In vitro, the levels of S-glutathionylated proteins were reduced in the presence of glutathione and glutaredoxin. CONCLUSIONS: Serum levels of S-glutathionylated proteins are a sensitive risk-marker for ASO at an early stage.

Estudo da ativação de monócitos e produção de citocinas em pacientes com aterosclerose obliterante periférica / Study of the activation of monocytes and peripheral production of cytokines in patients with atherosclerosis obleterans

O presente trabalho teve como objetivos avaliar em pacientes com aterosclerose obliterante periférica os níveis plasmáticos das citocinas pró e anti-inflamatórias fator de necrose tumoral-alfa (TNF-alfa) interleucina 6 (IL-6), interferon – gama (IFN-gama), interleucina 10 (IL-10) e fator transformador de crescimento beta (TGF- beta), assim como o grau de ativação de monócitos do sangue periférico, através da capacidade dessas células liberarem peróxido de hidrogênio (H2O2) e desenvolverem atividade fungicida contra Cândida albicans (C. albicans). Foram avaliados 8 indivíduos do sexo masculino, acima de 60 anos portadores de claudicação intermitente moderada e 8 indivíduos do sexo masculino acima de 60 anos que não apresentam doença arterial periférica. Observamos que os níveis plasmáticos de todas as citocinas testadas foram significativamente mais elevados nos pacientes, quando comparados aos detectados nos indivíduos controle. A capacidade das células de indivíduos controle e pacientes de liberarem H2O2 foi avaliada antes e após a incubação com citocinas envolvidas no processo de ativação dessas células, como o IFN-gama e TNF- alfa. Observamos que monócitos de indivíduos controle não ativados liberaram níveis substanciais do metabólito que, no entanto, aumentaram significativamente após a ativação com IFN-gama ou TNF-alfa. As células dos pacientes apresentaram um perfil de resposta semelhante aos apresentados pelos indivíduos controles. No entanto, quando comparamos a resposta dos dois grupos detectamos que os monócitos dos pacientes antes e após o processo de ativação, apresentam respostas menores que os indivíduos controle. Resultados semelhantes foram detectados nos ensaios de avaliação da atividade fungicida isto é, células de controles e pacientes apresentaram um aumento da atividade fungicida após a ativação tanto com IFN-gama como com TNF-alfa. No entanto, os resultados dos pacientes foram sempre significativamente menores que os detectados para con...

[Secondary prevention and conservative therapy of obliterative arteriosclerosis]. / Az arteriosclerosis obliterans szekunder prevenciója és belgyógyászati kezelése.

The author gives an overview of the main ways of medical therapy for patients with peripheral arterial obliterative disease. The importance of possible modification of the risk factors is emphasized especially beneficial effects of supervised walking-based exercise program. It is considered proven that the antiplatelet therapy and antilipidemic treatment reduce the risk of progressive atherosclerotic processes. The author summarizes the mechanisms and clinical effects of drugs influencing haemostation and haemorheology as well as vasodynamic agents. The results of clinical trials show a marked improvement of intermittent claudication by combination of preventive and therapeutic ways in majority of patients with peripheral arterial obliterative disease.

[Arteriosclerosis obliterans(ASO) in diabetic patients].

The major risk factors of arteriosclerosis obliterans(ASO) in diabetic patients are age, male gender, smoking, poor glycemic control, hypertension, and dyslipidemia. Thus, to prevent the development and progression of ASO, intensive intervention in the risk factors should be required. HOPE study reported that treatment of ACE-inhibitor in the patients with ASO for 5 years clearly decreased the relative risk for incidence of cardiovascular events comparing with the placebo group. Furthermore, UKPDS Group demonstrated that the adjusted odds ratios to the development of ASO for each 1% HbA1c increase and each 10 mmHg systolic blood pressure increase were respectively 1.28 and 1.25 from multivariate analysis. However, optimal levels of HbA1c and blood pressure for prevention of ASO still have not been suggested. Therefore, large-scale intervention trial in Japanese diabetic subjects should be needed.

[Why are cardiologists to be concerned about obliterating arterial disease of the lower leg?]. / Perché il cardiologo deve occuparsi dell'arteriopatia obliterante degli arti inferiori?

Peripheral arterial disease, which is caused by atherosclerotic stenosis or occlusion of the leg arteries, is an important manifestation of systemic atherosclerosis. The age-adjusted prevalence of symptomatic and asymptomatic peripheral arterial disease is approximately 12% in the general population. The overall prevalence and incidence of the disease is likely to increase with the aging of the population. Peripheral arterial disease is a relatively benign condition in terms of local disease. Five years after the diagnosis, 75% of the patients remain clinically stable. On the contrary, life expectancy, even in the absence of any history of myocardial infarction or ischemic stroke, has decreased by 10 years. These patients have approximately the same relative risk of death from cardiovascular causes as do patients with history of coronary or cerebrovascular disease. Moreover, the severity of peripheral arterial disease is closely associated with the risk of myocardial infarction and death from vascular disease. The lower the ankle-brachial index, the greater the risk of cardiovascular events. Furthermore, peripheral arterial disease is a significant independent predictor for cardiovascular mortality also in coronary patients. The risk factors associated with peripheral arterial disease are essentially the same as for coronary heart disease: older age, cigarette smoking, diabetes mellitus, hypertension, and hyperlipidemia. The excess morbidity and mortality for cardiovascular disease in these patients has not been fully explained. Patients with peripheral arterial disease show a systemic endothelial dysfunction and an increase in the serum concentration of activated white blood cells, endothelin, and C-reactive protein that may trigger acute coronary syndromes. In peripheral arterial disease the functional status is often severely impaired. Peak exercise performance has decreased to about 50% of that of age-matched controls, equivalent to moderate-severe heart failure. Epidemiological studies support the concept that patients affected by peripheral arterial disease, without established coronary heart disease, have a coronary heart disease high risk equivalent. In spite of this, peripheral arterial disease remains an underdiagnosed and undertreated disease. As the role of cardiologists is expanding, the purpose of this review was to awaken the clinician to the significance of lower limb atherosclerotic occlusive diseases.