Smoking and hypertension: effects on clinical, biochemical and pathological variables due to isolated or combined action on cardiovascular system

Changes in clinical, biochemical and pathological variables characterize cardiovascular damage from smoking and hypertension when it acts independently. However, combined action of these major risk factors increases the rate of cardiovascular events. Ischaemic heart disease with stable effort angina, myocardial infarction and post-infarction arrhythmias may affect cardiovascular system because of smoking exposure. Among cerebrovascular disease, there is evidence that stroke would be related primarily to active smoking. Isolated hypertension plays significantly major action to cause cerebrovascular disease including stroke, recurrent stoke and transient ischaemic attack. Among cardiac events, heart failure is, often, the end-point of hypertensive disease, even if manifestations of ischaemic heart disease similar to those caused by smoking may be increased in rate. Combined action of smoking and hypertension usually increases the rate of cardiovascular complications and leads to a progression of atherosclerosis with narrowing and plaque primarily at the the level of coronary, carotid and cerebrovascular arteries. A pattern specific of both active and passive smoking exposure, but not hypertension, is the thromboangiitis obliterans that dramatically worsens in continuing smokers while it can be improved by stopping smoking.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.     

Development of the Manchester framework for the evaluation of emergency department pharmacy services

International Journal of Clinical Pharmacy - Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as...     

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases

Background  The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon.
Objective  This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods  The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30⁺ cutaneous T-cell lymphoma (2 patients), CD4⁺ small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed.
Results  The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion  The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

Conflicts of interest

None declared.     

SELECTIVE ENDOSCOPY IN MANAGEMENT OF INGESTED FOREIGN BODIES OF THE UPPER GASTROINTESTINAL TRACT: IS IT SAFE?

During a four-year period, 308 patients presented following ingestion of foreign bodies. Ingestion was accidental in 272 cases (88.3%) and deliberate in the remainder. Symptoms at presentation included dysphagia, odynophagia, nausea and vomiting, chest pain and pharyngeal discomfort. Sixty-eight patients were asymptomatic. A policy of expectant management and selective endoscopy was employed. Following initial assessment 202 patients (65.6%) were discharged without treatment, 30 (9.7%) of whom were later reviewed as outpatients and did not require admission. Forty-nine patients (16%) were admitted for treatment; 27 had oesophagoscopy, five bronchoscopy and two had foreign body extraction with direct laryngoscopy. In nine patients who were endoscoped, no foreign body was identified. Twenty-seven others were referred to the otorhinolaryngology service in another hospital. There were no deaths in the group and morbidity was 1.2%. We conclude that a policy of selective endoscopy is safe and effective in the management of patients following ingestion of foreign bodies.     

15The effect of Lower Esophageal Sphincter (LES) electrical stimulation on LES pressure

Background: Electrical stimulation (ES) of the stomach has been shown to modulate LESP. Electrical stimulation, using neural high frequency stimulation (NGES) can induce contractions of the smooth muscle of the gut. The purpose of this study was to determine if electrical stimulation of the LES can affect LESP. Methods: Four female hound dogs, weight: 20–25 kg, underwent an esophagostomy that allowed the introduction of a sleeve manometry catheter into the esophagus. They were also implanted with a pair of electrodes along the longitudinal axis of the LES. After 3 weeks of recovery, they underwent esophageal manometry recording during control and ES, performed randomly on separate days, using 4 different stimulations: 1‐Low frequency: freq: 6 cycles/min, pulse: 350 milisec, amp: 5 mAmp; 2 High‐frequency: freq: 50 Hz, pulse: 1 milisec, amp: 5 mAmp; 3‐ NGES: freq: 50 Hz, pulse:20 milisec, amp:10 volts; 4‐ High‐frequency, circular: freq: 20 Hz, pulse:1 milisec, amp:5 mAmp. All recordings were performed 1 hour after consumption of 3 ounces of canned dog food, to prevent fluctuations in LESP and under mild sedation (acepromazine 0.5 mg kg^­1). Tests consisted, during ES days, of 3 periods of 20 minutes each: control , stimulation and post stimulation. The effect of NGES was also tested under anesthesia and following administration of L‐NAME 50 mg kg^­1 IV. and also atropine 0.05 mg kg^­1 IV. Analysis: area under the curve (AUC) and pressure were compared among the 3 periods. Data shown as mean ± SD, ANOVA and t‐test, p < 0.05. Results: Sustained increase in LESP was observed during low frequency stimulation, 32.1 ± 12.8 vs. 42.4 ± 18.0 vs. 50.1 ± 23.6, control vs. stimulation vs. post stimulation respectively, p = 0.013. AUC also significantly increased during and after stimulation, 39,320.3 ± 15,722 vs. 51,294 ± 21,826 vs. 59,823.6 ± 28,198.4 mmHgxsec, control vs. stimulation vs. post stimulation respectively, p = 0.01. There was no significant change with other types of ES. NGES induced an initial rise in LESP followed within few seconds by relaxation with slow resumption of pressure over a 1 minute period. L‐NAME increased LESP and augmented the initial rise in LESP following NGES but markedly diminished or abolished the relaxation phase. Atropine lowered LESP and abolished the initial rise in LESP induced by NGES. Conclusions: Low frequency ES of the LES increases LESP in conscious dogs. NGES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.     

Juvenile angiofibroma of the maxillary sinus. A case report.

The clinicopathological features of a rare case of juvenile angiofibroma originating from the maxillary sinus of a 13-year-old boy are reported. This tumor was composed of angiomatous and fibrous structures. The analysis of nucleolar organizer regions (NOR) of the various components of this tumor indicated that the fundamental elements were the fibroblastic cells, rather than the vascular endothelial cells.