PERIPHERAL ARTERIOSCLEROSIS—Present Concepts of Management

Three hundred patients with clinical manifestations of ischemia due to peripheral arteriosclerosis were studied. An accurate demonstration of the extent of the arterial occlusive process by means of aortography was of major importance in determining therapy and prognosis.The results from thromboendarterectomy to restore the arterial lumen in cases of segmental thrombosis or stenosis greatly exceeded those obtained from other methods of therapy for peripheral arteriosclerosis. The indications for and the limitations of lumbar sympathectomy as a palliative procedure are described. Medical treatment, except for the use of specific protective measures, was of little value in altering either the symptoms or prognosis.     

Peripheral arteriosclerosis; present concepts of management

Three hundred patients with clinical manifestations of ischemia due to peripheral arteriosclerosis were studied. An accurate demonstration of the extent of the arterial occlusive process by means of aortography was of major importance in determining therapy and prognosis. The results from thromboendarterectomy to restore the arterial lumen in cases of segmental thrombosis or stenosis greatly exceeded those obtained from other methods of therapy for peripheral arteriosclerosis. The indications for and the limitations of lumbar sympathectomy as a palliative procedure are described. Medical treatment, except for the use of specific protective measures, was of little value in altering either the symptoms or prognosis.     

Effect of Age and Arteriosclerosis on the Response of Parkinsonian Patients to Levodopa

Twenty-four patients with Parkinsonism were treated with levodopa for up to one year. Ten were aged under 65, 12 were aged 65 or over, and two were specifically included because they were considered to have arteriosclerotic Parkinsonism. These two patients showed no response to treatment. The 10 younger patients showed less clinical evidence of arteriosclerosis than the older ones, and responded significantly better to treatment with levodopa. Mean improvement was 61% in the younger group after 12 months'' treatment and 28% in the older group. Improvement was greatest within three months of starting treatment. Abnormal movements which resulted from treatment with levodopa could be reduced with only slight loss of therapeutic benefit by the addition of tetrabenazine.     

Ischemic Colitis

Twenty cases of ischemic colitis are reviewed; 19 were obtained from autopsy files and the diagnosis in one was made from a surgical specimen. The majority of the patients were elderly with generalized arteriosclerosis. In approximately two-thirds of the patients the ischemic colitis was precipitated by preceding trauma, operation or congestive heart failure. Clinically, ischemic colitis is characterized by abdominal pain, distension and bleeding per rectum. Perforation of large bowel may occur. The lesions tend to be localized around the splenic flexure and junction of the descending and sigmoid colon, and in cases following aortic graft surgery the rectum is involved. Microscopically, there is necrosis, hemorrhage and ulceration. In less severe cases the mucosa only is affected. Cases with perforation show necrosis of all layers. It is considered that ischemic colitis is comparatively frequent and should be distinguished from other inflammatory conditions of the colon.     

The Relationship Between Genito-Urinary Hæmorrhage and Diseases of the Vascular System: (Section of Urology)

The diseases of the vascular system which cause h?morrhage from the genito-urinary tract are:-(1) Those in which changes are noted in the blood and capillary endothelium, and(2) Those in which alterations of a pathological nature are taking place in the walls of both large and small blood-vessels, but in which there is no change in the blood itself.In the first group are the purpuras; in the second arteriosclerosis, hyperpiesis and atheroma.This paper is confined to a discussion of the latter group of diseases in relation to genito-urinary h?morrhage.Little attention has been paid to sudden loss of blood from the kidney, bladder, or genitalia in support of a diagnosis of a vascular lesion, other than angioma. H?morrhage in these cases may be purely renal, vesical, or penile.Investigations consist of examination of the superficial arteries, estimation of the blood-pressure, examination of the blood and cystoscopy. Surgical lesions must be excluded by the usual well-known methods.A careful record has been kept of fifteen cases of arteriosclerosis in which h?morrhage from the genito-urinary tract has been the predominant manifestation of the disease. Details are given of nine patients with renal, one with vesical and three with urethral h?morrhage. Two cases of thrombosis of the penis are also included.From a study of the literature here the cases of urethral h?morrhage and thrombosis of the penis, recorded as due to arterial disease, appear to be unique.     

PERIPHERAL ARTERIOSCLEROSIS—Arterial Grafting Procedures—Indications and Results—Part II: Arteriosclerotic Arterial Occlusion

Arteriosclerotic thrombotic lesions involving the arteries to the lower extremities may be conveniently grouped into three categories. Lesions of the aorta-common-iliac level (Category I) appear to be most satisfactorily treated by thromboendarterectomy. Lesions in the femoral artery (Category II) are particularly amenable to bypass arterial grafts. Advanced lesions (Category III) involving both areas may be treated by one or the other method or a combination of both. Aortography is a necessary prerequisite in the selection of patients for operation and the determination of the method of surgical approach.     

C-peptide promotes lesion development in a mouse model of arteriosclerosis

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show elevated serum levels of the proinsulin cleavage product C-peptide and immunohistochemical data from our group revealed C-peptide deposition in early lesions of these individuals. Moreover, in vitro studies suggest that C-peptide could promote atherogenesis. This study examined whether C-peptide promotes vascular inflammation and lesion development in a mouse model of arteriosclerosis. ApoE-deficient mice on a high fat diet were treated with C-peptide or control injections for 12 weeks and the effect on lesion size and plaque composition was analysed. C-peptide treatment significantly increased C-peptide blood levels by 4.8-fold without having an effect on glucose or insulin levels, nor on the lipid profile. In these mice, C-peptide deposition in atherosclerotic plaques was significantly increased compared with controls. Moreover, lesions of C-peptide-treated mice contained significantly more macrophages (1.6 ± 0.3% versus 0.7 ± 0.2% positive area; P < 0.01) and more vascular smooth muscle cells (4.8 ± 0.6% versus 2.4 ± 0.3% positive area; P < 0.01). Finally, lipid deposition measured by Oil-red-O staining in the aortic arch was significantly higher in the C-peptide group compared with controls. Our results demonstrate that elevated C-peptide levels promote inflammatory cell infiltration and lesion development in ApoE-deficient mice without having metabolic effects. These data obtained in a mouse model of arteriosclerosis support the hypothesis that C-peptide may have an active role in atherogenesis in patients with diabetes and insulin resistance.     

Peripheral arteriosclerosis; arterial grafting procedures; indications and results. II. Arteriosclerotic arterial occlusion

Arteriosclerotic thrombotic lesions involving the arteries to the lower extremities may be conveniently grouped into three categories. Lesions of the aorta-common-iliac level (Category I) appear to be most satisfactorily treated by thromboendarterectomy. Lesions in the femoral artery (Category II) are particularly amenable to bypass arterial grafts. Advanced lesions (Category III) involving both areas may be treated by one or the other method or a combination of both. Aortography is a necessary prerequisite in the selection of patients for operation and the determination of the method of surgical approach.     

Relationship Between Myocardial Bridging and Coronary Arteriosclerosis

The objective of the study was to explore the prevalence and characteristics of myocardial bridging in patients who underwent coronary angiography and to also evaluate the correlation between bridged coronary segments and atherosclerosis. For this purpose, clinical materials of 1,500 patients who had received coronary angiography were retrospectively analyzed. The location and length of the myocardial bridge were recorded as well as the extent and location of coronary artery stenosis was described. Segments proximal and distal to the bridging were evaluated for coronary arteriosclerosis as were the remaining coronary segments. We found that myocardial bridging was present in 179 (11.9 %) patients. Bridges were frequently (84.9 %) localized in the mid-distal segment of the left anterior descending (LAD) artery. Myocardial bridging was not considered a significant risk factor for coronary atherosclerosis (odds ratio 0.58) compared with traditional cardiovascular risk factors. The incidence of coronary arteriosclerosis in the distal segments was significantly less affected than the proximal segments (P < 0.01). It was, therefore, concluded that myocardial bridging frequently localized in the mid-distal segment of the LAD artery. The presence of myocardial bridging promotes proximal atherosclerosis but it is not an additional risk factor for coronary atherosclerosis.     

Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance

Background

Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects.

Methods

Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day) or the cilostazol group (100–200 mg/day) in this international, 2-year, prospective follow-up interventional study.

Results

The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index.

Conclusion

This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.     

DICUMAROL AND QUINIDINE IN THE AMBULATORY TREATMENT OF CHRONIC AURICULAR FIBRILLATION

Thirty-three patients with chronic auricular fibrillation were treated with digitalis and quinidine and in addition were given Dicumarol® to reduce the risk of embolism. In 21 of the patients the fibrillation was caused by rheumatic heart disease, and in 12 by arteriosclerosis or hypertension. Normal sinus rhythm was restored in 55 per cent of the 33 patients, in 67 per cent of those with arteriosclerosis or hypertension, and in 45 per cent of those with rheumatic heart disease. Embolism did not occur.     

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.     

TRIIODOTHYRONINE—Clinical Effects in Patients with Suboptimal Response to Other Thyroid Preparations

Thirty patients with evidence of hypometabolism or a clinically related condition were given triiodothyronine after suboptimal response to thyroxin or desiccated thyroid. DL- and L-isomers of triiodothyronine were used and compared. Thirteen patients (43.3 per cent) were improved and 17 (56.6 per cent) were unimproved or became worse. Side effects occurred in 9 of 34 trials (26 per cent), and could not always be eliminated by decreasing the dosage. The highest percentage of good response occurred in a small group (four of five) who received a combination of desiccated thyroid or thyroxin with supplemental triiodothyronine. Despite careful analysis of the data, no basis was found on which to predict which patients would receive benefit from the triiodothyronine. However, the occasional improvement, sometimes dramatic, suggested that a therapeutic trial with triiodothyronine in difficult or unresponsive cases of hypometabolism or hypothyroidism is justified.     

Identification of novel prognostic markers in relapsing localized resectable neuroblastoma

Patients with localized resectable neuroblastoma (NB) generally have an excellent prognosis and can be treated by surgery alone, but approximately 10% of them develop local recurrences or metastatic progression. The known predictive risk factors are important for the identification of localized resectable NB patients at risk of relapse and/or progression, who may benefit from early and aggressive treatment. These factors, however, identify only a subset of patients at risk, and the search for novel prognostic markers is warranted. This review focuses on the recent advances in the identification of new prognostic markers. Recently we addressed the search of novel genetic prognostic markers in a selected cohort of patients with stroma-poor localized resectable NB who underwent disease relapse or progression (group 1) or complete remission (group 2). High-resolution array-comparative genomic hybridization (CGH) DNA copy-number analysis technology was used. Chromosome 1p36.22p36.32 loss and 1q22qter gain, detected almost exclusively in group 1 patients, were significantly associated with poor event-free survival (EFS). Increasing evidence points to anaplastic lymphoma kinase (ALK) as a fundamental oncogene associated with NB. The immunohistochemical analysis of sporadic NB localized resectable primary tumors (stage 1-2) showed a correlation between aberrant ALK level of expression and tumor progression and clinical outcome. Moreover, other factors that might influence the clinical behavior of these tumors will be reviewed.     

Triiodothyronine; clinical effects in patients with suboptimal response to other thyroid preparations

Thirty patients with evidence of hypometabolism or a clinically related condition were given triiodothyronine after suboptimal response to thyroxin or desiccated thyroid. DL- and L-isomers of triiodothyronine were used and compared. Thirteen patients (43.3 per cent) were improved and 17 (56.6 per cent) were unimproved or became worse. Side effects occurred in 9 of 34 trials (26 per cent), and could not always be eliminated by decreasing the dosage. The highest percentage of good response occurred in a small group (four of five) who received a combination of desiccated thyroid or thyroxin with supplemental triiodothyronine. Despite careful analysis of the data, no basis was found on which to predict which patients would receive benefit from the triiodothyronine. However, the occasional improvement, sometimes dramatic, suggested that a therapeutic trial with triiodothyronine in difficult or unresponsive cases of hypometabolism or hypothyroidism is justified.     

Individual assessment of arteriosclerosis by empiric clinical profiling

Background

Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient.

Methodology/Principal Findings

269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient''s disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125).

Conclusions/Significance

Empiric clinical profiling and the disease activity score that are based on accessible, available and affordable clinical data are valid markers for symptomatic arteriosclerosis.     

Detection of localized caspase activity in early apoptotic cells by laser scanning cytometry

BACKGROUND: Caspase activation is a critical early step in the onset of apoptosis. Cell-permeable fluorogenic caspase substrates have proven valuable in detecting caspase activation by flow cytometry. Nevertheless, detection of early low-level caspase activation has been difficult using conventional area or peak fluorescence analysis by flow cytometry, despite the apparent presence of these cells as observed by microscopy. We describe a method utilizing maximum fluorescence pixel analysis by laser scanning cytometry (LSC) to detect early apoptotic cells. METHODS: The PhiPhiLux-G(1)D(2) caspase 3/7 substrate was used in combination with DNA dye exclusion and annexin V binding to identify several stages of apoptosis in EL4 murine thymoma cells by both traditional flow and LSC. LSC analysis of maximum pixel brightness in individual cells demonstrated an intermediate caspase-low subpopulation not detectable by flow or LSC integral analysis. LSC analysis of caspase activity was then carried out using the larger UMR-106 rat osteosarcoma cell line to determine if this apparent early caspase activity could be correlated with localized, punctate caspase activity observed by microscopy. RESULTS: The caspase-low subpopulation found in apoptotic EL4 cells was also observable in UMR-106 cells. Relocation to cells with low fluorescence due to caspase activity and subsequent examination by microscopy demonstrated that these latter cells indeed show punctate, highly localized caspase activation foci that might represent an early stage in caspase activation. CONCLUSIONS: Cells with low-level, localized caspase expression can be detected using maximum pixel analysis by LSC. This methodology allows an early step of apoptotic activation to be resolved for further analysis.     

Perfusion Lung Scans Provide a Guide to Which Patients With Apparent Primary Pulmonary Hypertension Merit Angiography

There is hesitancy, based on the perceived risk, to do pulmonary angiography in patients believed to have primary pulmonary hypertension. Yet pulmonary hypertension due to major-vessel, chronic thromboembolism mimics primary pulmonary hypertension clinically and on standard laboratory tests. Because thromboembolic pulmonary hypertension is potentially remediable by thromboendarterectomy and primary pulmonary hypertension is not, differentiating between these disorders is essential. Angiography is required in patients with thromboembolic pulmonary hypertension to define the anatomic location of the thrombi. In evaluating perfusion lung scans of 110 patients with pulmonary hypertension to determine whether the scan might provide a guide to selecting those patients who merit angiography, no segmentalsize perfusion defects were noted on the scans of 64 patients with primary pulmonary hypertension, whereas all 46 patients with thromboembolic hypertension had one or more defects that were segmental in size or larger. These data indicate that a perfusion lung scan should be done in patients with pulmonary hypertension of uncertain cause and that those with one or more segmental or larger defects merit pulmonary angiography before being diagnosed as having primary pulmonary hypertension.     

SUPRACONDYLAR AMPUTATION IN THE AGED

Of 105 consecutive supracondylar amputations done at the San Diego County General Hospital during the five-year period, 1953-58, 88 were in patients more than 60 years of age. Occlusive arterial disease was the reason for operation in 85 of the 88 cases.Presenting complaints at the time of amputation were gangrene in 45 cases, pre-gangrene associated with severe pain in 34. Acute arterial occlusion as a cause of thigh amputation was infrequent.The average age of patients requiring thigh amputation from complications of arteriosclerosis obliterans was 78.3 years; for those with diabetic arteriosclerosis or embolism it was about seven and a half years less.Supracondylar amputation was considered the procedure of choice in the elderly debilitated patients with far-advanced occlusive diffuse arteriosclerosis, complicated by gangrene, ulcer and infection of the toes or feet. Sympathectomy and direct arterial operation if done early in the course of the disease may postpone or prevent subsequent amputation.The surgical mortality rate (first two weeks) for supracondylar amputation was 12.5 per cent. More than two-thirds of the deaths were due to bronchopneumonia.