Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 micro g/day) for 5 consecutive days. On day 5, PBSCs were collected, sorted from blood circulation of patients, and then intramuscularly injected into their ischemic lower limbs. A significant improvement of clinical manifestations including severe pain, skin temperature and ulcer, was observed, without obvious adverse effect. The patient's limb was successfully saved. Satisfactory remission was obtained 3 months after transplantation as shown by significant improvement in ankle-brachial pressure index (ABI), blood flow in personal vascular laboratory (PVL), laser Doppler blood perfusion, and the angio-graphic scores. Our data suggest for the first time that autologous transplantation of mobilized PBSCs provides a practical, safe, and effective method of treatment for lower limb ischemia.
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PMID:Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. 1498 38

A 78-year-old woman with arteriosclerosis obliterans was admitted with complaints of progressive ischemic change and resting pain of the left leg. She had severe ischemic limb in stage IV of the Fontaine classification. Angiography showed total occlusion of the three main arteries with poor collateral flow at the left crus. Autologous transplantation of bone-marrow mononuclear cell to her left leg was performed to achieve therapeutic angiogenesis. One month later, follow-up angiography showed excellent angiogenesis of collateral vessels at the left crus. Her pain was relieved and leg amputation was not necessary. Recently, the TACT study in Japan showed the efficacy of angiogenesis by autologous bone-marrow transplantation for peripheral artery disease. This case illustrates the efficacy of this therapy.
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PMID:[Therapeutic angiogenesis by autologous transplantation of bone-marrow cells in a patient with progressive limb ischemia due to arteriosclerosis obliterans: a case report]. 1512 82

Therapeutic angiogenesis using angiogenic growth factors is expected to be a new treatment for patients with critical limb ischemia (CLI). Because hepatocyte growth factor (HGF) has potent angiogenic activity, we investigated the safety and efficiency of HGF plasmid DNA in patients with CLI as a prospective open-labeled clinical trial. Intramuscular injection of naked HGF plasmid DNA was performed in ischemic limbs of 6 CLI patients with arteriosclerosis obliterans (n=3) or Buerger disease (n=3) graded as Fontaine III or IV. The primary end points were safety and improvement of ischemic symptoms at 12 weeks after transfection. Severe complications and adverse effects caused by gene transfer were not detected in any patients. Of particular importance, no apparent edema was observed in any patient throughout the trial. In addition, serum HGF concentration was not changed throughout the therapy period in all patients. In contrast, a reduction of pain scale of more than 1 cm in visual analog pain scale was observed in 5 of 6 patients. Increase in ankle pressure index more than 0.1 was observed in 5 of 5 patients. The long diameter of 8 of 11 ischemic ulcers in 4 patients was reduced >25%. Intramuscular injection of naked HGF plasmid is safe, feasible, and can achieve successful improvement of ischemic limbs. Although the present data are conducted to demonstrate the safety as phase I/early phase IIa, the initial clinical outcome with HGF gene transfer seems to indicate usefulness as sole therapy for CLI.
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PMID:Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease. 1523 69

It is widely, but mistakenly, believed that ischemic heart disease (IsHD) and its complications are the sole and direct result of reduced coronary blood flow by obstructive coronary artery disease (CAD). However, cardiac angina, acute myocardial infarction (AMI), and sudden cardiac death (SCD) occur in 15%-20% of patients with anatomically unobstructed and grossly normal coronaries. Moreover, severe obstructive coronary disease often occurs without associated pathologic myocardiopathy or prior symptoms, ie, unexpected sudden death, silent myocardial infarction, or the insidious appearance of congestive heart failure (CHF). The fact that catecholamines explosively augment oxidative metabolism much more than cardiac work is generally underappreciated. Thus, adrenergic actions alone are likely to be more prone to cause cardiac ischemia than reduced coronary blood flow per se. The autonomic etiology of IsHD raises contradictions to the traditional concept of anatomically obstructive CAD as the lone cause of cardiac ischemia and AMI. Actually, all the signs and symptoms of IsHD reflect autonomic nervous system imbalance, particularly adrenergic hyperactivity, which may by itself cause ischemia as in rest angina. Adrenergic activity causing ischemia signals cardiac pain to pain centers via sympathetic efferent pathways and tend to induce arrhythmogenic and necrotizing ischemic actions on the cardiovascular system. This may result in ischemia induced metabolic myocardiopathy not unlike that caused by anatomic or spasmogenic coronary obstruction. The clinical study and review presented herein suggest that adrenergic hyperactivity alone without CAD can be a primary cause of IsHD. Thus, adrenergic heart disease (AdHD), or actually adrenergic cardiovascular heart disease (ACVHD), appears to be a distinct entity, most commonly but not necessarily occurring in parallel with CAD. CAD certainly contributes to vulnerability as well as the progression of IsHD. This vicious cycle, which explains the frequent parallel occurrence of arteriosclerosis and IHD, an association that appears to be linked by the same cause, comprises a common vulnerability to deleterious adrenergic actions on the myocardium, lipid metabolism, and vascular system alike, rather than viewing CAD and IsHD as having a putative cause and effect relationship as commonly thought. Adrenergic actions can also cause the abnormal lipid metabolism that is associated with CAD and IsHD by catecholamine-induced metabolic actions on lipid mobilization by activation of phospholipases. This may also be part of toxic catecholamine hypermetabolic actions by enhancing deleterious cholesterol and lipid actions in damaging coronary vessels by plaque formation as well as inducing obstructive coronary spasm and platelet aggregation. This may also cause direct toxic necrosis on the myocardium as well as atherosclerosis in blood vessels. In fact, drugs that inhibit adrenergic actions like propranolol, reserpine, and guanethidine all inhibit arteriosclerosis induced by hypercholesterolemia in experimental animals and prevent carotid vascular disease (associated with stroke) in humans. The concomitant development of myocardiopathy and coronary vascular lesions or coronary and carotid artery intimal medial thickening by catecholamine toxicity is reflected by the frequent primary presentation of patients with catecholamine-secreting pheochromocytoma with cardiovascular disease, ie, hypertension arrhythmias, AMI, SCD, CHF, and vascular disease, which represents a clear example of the primary deleterious impact of catecholamines on the entire cardiovascular system causing adrenergic cardiovascular disease. Thus, like myocardiopathy, CAD and atherosclerosis in general may be the consequences of or a complication of catecholamine actions rather than its putative cause. This report shows how prophylactic bretylium not only prevents arrhythmias but prevents myocardial necrosis, shock, CHF, maintains or restores normal contractility, and lowers mortality in AMI patients by inducing adrenergic blockade.
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PMID:Prevention of ventricular fibrillation, acute myocardial infarction (myocardial necrosis), heart failure, and mortality by bretylium: is ischemic heart disease primarily adrenergic cardiovascular disease? 1535 32

This phase 1 clinical trial tested the safety of intramuscular gene transfer by using naked plasmid DNA encoding the gene for VEGF, and analyzed the potential therapeutic benefits in patients with severe peripheral arterial disease (PAD). This study was an open-labeled, dose- escalating, single-center trial on nine male patients with severe debilitating PAD who had not responded to conventional therapy. Seven had Buerger's disease and two had arteriosclerosis obliterans. Plasmid DNA (pCK) containing human VEGF165 was given by eight intramuscular injections in and around the area in need of new blood vessels. The study evaluated three escalating total doses (2, 4, and 8 mug of pCK- VEGF165), with half of each total dose given four weeks apart. The follow-up duration was nine months. The gene injections were well tolerated without significant side effects or laboratory abnormalities related to gene transfer. Three patients showed transient edema in their extremities. Ischemic pain of the affected limb was relieved or improved markedly in six of seven patients. Ischemic ulcers healed or improved in four of six patients. The mean ankle-brachial index (ABI) improved significantly. Six of nine patients showed an increase in collateral vessels around the injection sites demonstrated by digital subtraction angiography. However, there was no relationship between the degree of ABI improvement and the dose given. Mean plasma levels of VEGF did not increase significantly. In conclusion, intramuscular injections of pCK- VEGF165 can be performed safely to induce therapeutic angiogenesis in patients with severe PAD.
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PMID:Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral artery disease. 1536 52

Due to the lack of correlation between symptom severity and electrophysiology or nerve function, the 'container hypothesis' has emerged as a new concept in carpal tunnel syndrome (CTS). This proposes that symptoms relate to connective tissue alteration rather than to nerve fibre pathology. This study was conducted to investigate the pathology of the flexor tenosynovium and its relationship with symptomatology. The subjects comprised 40 patients with electrophysiologically proven CTS who underwent open carpal tunnel release (age range: 31-79 years). In all patients, subjective symptom severity was assessed with a Likert scale and symptom duration was recorded preoperatively. Flexor tenosynovium biopsied during surgery was analysed for arterial and connective tissue alteration. Proliferative arteriosclerosis was graded using the modified Banff score. Gelatin zymography and immunohistochemistry were also performed to investigate the role of gelatinase in CTS. Relationships were evaluated using Spearman rank correlation coefficients. Proliferative arteriosclerosis occurred with disease progression in the flexor tenosynovium, in the absence of inflammation. This event did not correlate with patient age but correlated closely with symptom duration. Immunohistochemistry with antibodies against MMP-2 and elastic van Gieson staining revealed that arterioles express high levels of MMP-2 within 3 months of symptom onset and that intimal hyperplasia proceeded rapidly between 4 and 7 months, resulting in severe vascular narrowing. Gelatin zymography showed that MMP-2 activity correlated negatively with symptom duration and positively with pain severity.
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PMID:MMP-2 expression is associated with rapidly proliferative arteriosclerosis in the flexor tenosynovium and pain severity in carpal tunnel syndrome. 1568 8

Hepatocyte growth factor is a mesenchyme-derived pleiotropic factor that regulates the growth, motility and morphogenesis of various types of cells, and is also a member of the angiogenic growth factors. Hepatocyte growth factor is secreted by vascular endothelial cells and smooth muscle cells, and the hepatocyte growth factor receptor, c-met, was also observed in these vascular cells. Treatment of human aortic endothelial cells with recombinant hepatocyte growth factor resulted in a significant increase in cell proliferation, accompanied by mitogen-activated protein kinase and Akt/protein kinase B phosphorylation. Recently, a novel therapeutic strategy for ischemic diseases using angiogenic growth factors to augment collateral artery development has been proposed. As preclinical study of gene therapy using hepatocyte growth factor to treat peripheral arterial disease, naked hepatocyte growth factor plasmid was intramuscularly injected into the ischemic hind limb of rabbits in order to evaluate its angiogenic activity. Intramuscular injection of hepatocyte growth factor plasmid once on day 10 following surgery, produced significant augmentation of collateral vessel development in the ischemic limb on day 30. In the clinical setting, the authors further investigated the safety and efficacy of hepatocyte growth factor plasmid DNA in patients with critical limb ischemia, in a prospective open-labeled trial. Intramuscular injection of naked plasmid DNA was performed in the ischemic limbs of six patients with critical limb ischemia with arteriosclerosis obliterans (n = 3) or Buerger disease (n = 3) graded as Fontaine III or IV. In the efficacy evaluation, a reduction of pain scale of more than 1 cm on a visual analog pain scale was observed in five out of six patients. An increase in ankle pressure index of more than 0.1 was observed in five out of five patients. The long diameter of eight out of 11 ischemic ulcers in four patients was reduced by more than 25%. Intramuscular injection of naked hepatocyte growth factor plasmid is safe, feasible and can achieve successful improvement of ischemic limbs. Although the present data were obtained to demonstrate safety in a Phase I/early Phase II trial, the initial clinical outcome with hepatocyte growth factor gene transfer seems to indicate its usefulness as sole therapy for critical limb ischemia. Randomized placebo-controlled clinical trials of alternative dosing regimens of gene therapy will be required to define the efficiency of this therapy.
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PMID:Hepatocyte growth factor as potential cardiovascular therapy. 1588 78

Cholesterol crystal embolism (CCE) is an infrequent entity that primarily appears in males over the age of 60 with generalized arteriosclerosis after angiographic procedures, vascular surgery or, more rarely, with oral anticoagulant treatment with heparin or with fibrinolytics. We present the case of a patient with several risk factors for CCE, who presented with the pathognomonic triad of leg and foot pain, livedo reticularis and palpable pedal pulses. The diagnosis was based on the fact that cholesterol crystals were seen in the arterioles in the skin biopsy. Due to the frequency with which the skin manifestations appear and the importance of early diagnosis and treatment, an awareness of these crystals is fundamental in diagnosing these processes.
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PMID:[Cholesterol crystal embolism]. 1647 62

The diabetic micro- and macroangiopathy leads to retinopathy, nephropathy, peripheral arteriosclerosis and coronary heart disease. Diabetic patients with identified comorbidity, such as nephropathy and peripheral arteriosclerosis, have the highest mortality after heart surgery. Long-term survival is better after coronary surgery compared to catheter angioplasty without or with stent implantation. Compared to "on-pump" surgery using a cardiopulmonary bypass, "off-pump surgery is associated with a lower incidence of acute renal failure. In order to prevent acute renal failure in the course of heart surgery in diabetic patients, the following recommendations should be followed: i) the degree of renal damage (as indicated by the parameters: creatinine-clearance, albuminuria and blood pressure) has to be known before start of surgery; ii) the volume status (central venous pressure, central venous oxygen saturation) should be controlled tightly starting 12 hours before surgery; iii) if the volume status gets out of control post surgery, intensive care treatment using dopamine or loop diuretics should be stopped after 12-24 hours in case of treatment failure; iv) reduce the dose of or better avoid nephrotoxic substances (radio contrast media, antibiotics, non-steroidal pain killers; v) start effective renal replacement therapy early (daily intermittent or continuous hemodialysis, hemofiltration or hemodiafiltration).
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PMID:[Diabetic nephropathy and heart surgery--prevention of perioperative acute renal failure]. 1659 49

The patient was a 41-year-old man who had suffered from diabetes for 24 years and had been on insulin therapy for 17 years. The patient had commenced hemodialysis in 1999. Some of his toes on both feet had been amputated in 2000 due to diabetic gangrene. The patient was admitted to our hospital in early March 2005 complaining of a painful ulcer on the tip of the penis. At the time of admission, multiple ulcers and necrosis were observed on the prepuce and penis, as well as an ulcer on the left foot and gangrene of the left great toe. Imaging studies demonstrated severe arteriosclerosis with calcification of both large and small arteries. After penile amputation was performed because of severe pain, the wound became ulcerated, and a rectal ulcer as well as skin ulcers also developed in the bilateral inguinal regions. The penile necrosis, skin ulcers, and rectal ulcer were thought to have been caused by calciphylaxis. Calciphylaxis is a disorder in which necrosis occurs at sites of arterial obstruction and calcification, and the prognosis is poor. Seventeen patients with penile necrosis due to calciphyalxis, including our patient, have been reported in Japan. They all had a long history of diabetes, and 15 of the 17 patients were on dialysis.
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PMID:Penile necrosis by calciphylaxis in a diabetic patient with chronic renal failure. 1760 38


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