Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non‐small cell lung cancer

Urokinase plasminogen activator (uPA) cleaves its three‐domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II‐III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non‐small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time‐resolved fluoroimmunoassays (TR‐FIAs) measuring intact uPAR(I‐III) (TR‐FIA 1), uPAR(I‐III) + uPAR(II‐III) (TR‐FIA 2) and uPAR(I) (TR‐FIA 3) were applied. The Spearman rank correlations between plasma and serum levels of uPAR(I‐III), uPAR(I‐III) + uPAR(II‐III), and uPAR(I) were 0.89, 0.94 and 0.68 respectively. Survival analysis demonstrated that high levels of all uPAR forms were associated with shorter survival. Adjusted for histological subtype high plasma uPAR(I‐III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis in NSCLC.     

Idiopathic free-floating thrombus of the common carotid artery

BACKGROUND: The observation of an intraluminal common carotid artery thrombus overlying a wall defect at ultrasonography or angiography is unusual. To our knowledge, there are no previous reports of a free-floating thrombus in the common carotid artery. CASE REPORT: A 45-year-old woman who was previously healthy and on no medications presented with acute hemiparesis and aphasia. Following testing that included carotid duplex and transcranial Doppler ultrasonography, diffusion-weighted magnetic resonance imaging, and digital subtraction angiography, the patient underwent emergency open embolectomy. No underlying wall defect was seen at the time of imaging or surgery. No obvious hypercoagulable state could be identified. Her NIH Stroke Scale score improved from 26 at admission to 2 at three months and 1 at one year. CONCLUSIONS: Multimodal imaging may have improved diagnosis and management in this patient with a unique finding. The source of the thrombus remains obscure.     

A clinical and epidemiologic study morsicatio buccarum/labiorum

abstract – A study of habitual self mutilation of the buccal and/or labial mucosa by biting was conducted on 8,589 persons attending the Royal Dental College, Copenhagen. Forty-two cases were found. The youngest patient was 5 years old and the oldest was 47. The condition occurred most frequently (1.77%) among persons aged 15–19 years. There was no difference in prevalence between males and females. Combined mutilation of cheek(s) and lip(s) was more frequent (62%) than isolated mutilation of the cheek(s) (24%) or isolated mutilation of the lip(s) (14%). Bilateral biting of the cheeks was more frequent than unilateral biting, and biting of the lower lip was more frequent than biting of the upper lip. Ninety-three per cent of the patients were aware of their habit, and most of them stated that they had been biting for years. Twenty patients were re-examined; in all but one patients the biting persisted but in 7 patients the location of the lesions had changed. In several cases a link could be traced to personal problems and mental stress. It was further noticed that many patients were students and white-collar workers, suggesting that "intellectual" work may predispose for the habit.     

Efficacy of treatment of severe carotid bifurcation stenosis by using self-expanding stents without deliberate use of angioplasty balloons

BACKGROUND AND PURPOSE: One of the limitations of carotid artery angioplasty is the potential for embolic stroke. Our purpose was to assess whether the force of a self-expanding stent alone is usually sufficient to dilate severely stenotic atherosclerotic plaques without the deliberate use of an angioplasty balloon. If so, the procedural stroke risk might be reduced. METHODS: Over a 30-month period, 21 consecutive patients were prospectively identified with severe symptomatic carotid artery stenosis (>70% NASCET [North American Symptomatic Carotid Endarterectomy Trial]) and relative indications for endovascular treatment. All underwent treatment with the aim of deploying a self-expanding stent across the stenosis without the use of angioplasty balloons or distal protection devices. RESULTS: Stent deployment was successful in 20/21 patients. In one patient, the stent could not be deployed without balloon predilatation and a stroke occurred. In the other 20 patients, angiography before and immediately after stent deployment showed a reduction in the mean stenosis from 83% to 49%. A second periprocedural stroke occurred as a result of early stent thrombosis at 4 days in a patient who stopped Acetylsalicylic acid while undergoing bowel preparation for colon surgery. He made a good recovery. Average duration of follow-up imaging was 19 months (range, 1-44 months). During the follow-up period there were four deaths, all unrelated to the carotid disease, and no major strokes. At 5-11 months, the average residual stenosis was 21%, which remained stable in 16 of the 18 patients studied between 12 and 44 months (average, 24 months). At last follow-up, in these 16 the mean peak systolic velocity was 123 cm/s (range, 60-238 cm/s) and the mean internal-to-common carotid ratio was 1.8. The other two patients were long-term failures of the "stent-only" approach. In one patient, a heavily calcified plaque prevented stent expansion and the artery occluded at 18 months with a minor stroke. In the second patient, a recurrent stenosis developed at 16 months with one episode of transient ischemic attack. CONCLUSION: Deployment of a self-expanding stent alone resulted in a favorable and more gradual reduction of severe symptomatic carotid stenosis. Improvements in stent profile and chronic outward force may widen the indications for simple stent placement without the use of balloons or adjunctive protection devices.     

PSYCHOLOGICAL EFFECTS OF AN EPIDEMIOLOGICAL STUDY OF BENIGN PROSTATIC HYPERTROPHY

SUMMARY The psychological impact of an epidemiological study of benign prostatic hypertrophy (BPH) was assessed in a representative sample of practice list patients. Of the 889 men completing a general health self-report questionnaire previously validated in a screening programme, 75% knew nothing of problems of the prostate, and 84.5% were not at all worried about prostate problems prior to commencement of the study. Receiving the letter of invitation and the procedures neither increased nor reduced anxiety levels for 69% and 70% respectively. In the 227 men referred to hospital for further investigation the procedure increased anxiety in 28%, decreased anxiety in 20%, and had no effect on the remainder. The sample of 137 (16%) men who, prior to interview, were in some way worried about problems of the prostate had significantly more urinary tract symptoms than those who were not at all worried about prostatic problems. Despite being worried about prostatic problems and having significant urinary symptoms, this group was no more likely to have attended a GP for investigation and/or treatment. Results are discussed in relation to the possible psychological effects of general health screening and the reluctance of men to attend for consultation despite awareness and concern regarding urinary symptomatology.