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Various triacsin C analogs, containing different alkenyl chains and carboxylic acid bioisoteres including 4-aminobenzoic acid, isothiazolidine dioxide, hydroxylamine, hydroxytriazene, and oxadiazolidine dione, were synthesized and their inhibitions of long chain fatty acyl-CoA synthetase (ACSL) were examined. Two methods, a cell-based assay of ACSL activity and an in situ [(14)C]-palmitate incorporation into extractable lipids were used to study the inhibition. Using an in vivo leukocyte recruitment inhibition protocol, the translocation of one or more cell adhesion molecules from the cytoplasm to the plasma membrane on either the endothelium or leukocyte or both was inhibited by inhibitors 1, 9, and triacsin C. The results suggest that inhibition of ACSL may attenuate the vascular inflammatory component associated with ischemia reperfusion injury and lead to a decrease of infarct expansion., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques. While Endoscopic Vein Harvest (EVH) has been demonstrated to improve early morbidity compared to Open Vein Harvest (OVH), recent literature suggests that this may be at the expense of graft patency at one year and survival at three years., Methods: We undertook a retrospective single-centre, single-surgeon, case-control study of EVH (n = 89) and OVH (n = 182). The primary endpoint was death with secondary endpoints including acute coronary syndrome, revascularisation or other major adverse cardiac events. Freedom from angina, wound complications and self-rated health status were also assessed. Where repeat angiography had been performed, this was reviewed., Results: Both groups were well matched demographically and for peri-operative characteristics. All cause mortality was 2/89 (2%) and 11/182 (6%) in the EVH and OVH groups respectively. This was shown by Cox Log-Rank analysis to be non-significant (p = 0.65), even if adjusting for inpatient mortality (p = 0.74). There was no difference in the rates of freedom from angina (p = 1.00), re-admission (p = 0.78) or need for further anti-anginals (p = 1.00). There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group (EVH: 7%; OVH: 28%; p = 0.0008) and the skew of high patient self-rated health scores in the EVH group (61% compared to 52% in the open group) approached statistical significance (p = 0.06)., Conclusions: While aware of the limitations of this small retrospective study, we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre. More robust evidence is still required to elucidate the implications of endoscopic techniques on conduit patency and patient outcome, but until the results of a large, prospective and randomised trial are available, we believe we can confidently offer our patients the option and benefits of EVH.

Catalytic steam reforming of glycerol for H(2) production has been evaluated experimentally in a continuous flow fixed-bed reactor. The experiments were carried out under atmospheric pressure within a temperature range of 400-700 degrees C. A commercial Ni-based catalyst and a dolomite sorbent were used for the steam reforming reactions and in situ CO(2) removal. The product gases were measured by on-line gas analysers. The results show that H(2) productivity is greatly increased with increasing temperature and the formation of methane by-product becomes negligible above 500 degrees C. The results suggest an optimal temperature of approximately 500 degrees C for the glycerol steam reforming with in situ CO(2) removal using calcined dolomite as the sorbent, at which the CO(2) breakthrough time is longest and the H(2) purity is highest. The shrinking core model and the 1D-diffusion model describe well the CO(2) removal under the conditions of this work.

Introduction: The objectives of this study were to: (i) assess the feasibility of minimally invasive endoscopic harvesting of the long saphenous vein or radial artery for use as conduit during coronary artery bypass surgery in the NHS setting; and (ii) investigate the results of endoscopic vein harvesting with regards to postoperative complications, ability to mobilise, and patient satisfaction., Patients and Methods: In this prospective audit, 25 consecutive patients, aged 52-90 years, undergoing either coronary artery bypass grafting alone or together with valve surgery or atrial fibrillation ablation were studied. All data were entered in purpose-designed proforma. Pre-operative risk factors including increasing age, diabetes, peripheral vascular disease, obesity, renal impairment, tobacco consumption and steroid use were documented. Time taken for harvest and conversion to traditional open vein harvest, quality of harvested vein in terms of number of repairs and vein damage were recorded. Postoperatively, we recorded harvest site wound complications, number of days to mobilise and total hospital stay. Pain score and patient satisfaction were also assessed., Results: There was one death due to myocardial infarction; another patient had postoperative cerebrovascular accident. A total of 43 lengths of grafts were harvested, 41 were long saphenous vein and two radial artery. Vein harvest time reduced significantly from a maximum of 94 min to 34 min for two lengths of long saphenous vein. Three patients required conversion from endoscopic vein harvesting to open vein harvest. The only postoperative complication directly related to endoscopic harvesting was bruising along the tunnel created by the passage of the instruments. None of the patients had any wound complication; none required antibiotics or wound debridement. Mean time to mobilise was 3.4 days. All patients who underwent successful endoscopic vein harvesting expressed satisfaction with regards to postoperative pain and cosmetic result., Conclusions: Competence and ability to harvest conduit in an acceptable time frame are obtainable after a relatively low number of cases. The procedure is associated with a low number of postoperative complications and very high patient satisfaction.

Objectives: To investigate the importance of age and other variables on the prevalence of secondary forms of hypertension in a hypertension referral center., Design: Over the past 18 years 4429 patients have been referred by their physicians for a 1-day blood pressure study to investigate secondary causes of hypertension., Methods: The 1-day blood pressure study included a history and physical examination by a physician, and measurements of serum sodium, potassium, creatinine, thyroxine, thyroid stimulating hormone, stimulated plasma renin activity, blood pressure response to the angiotensin II analogue saralasin, recumbent and upright plasma catecholamines, and plasma cortisol and aldosterone after infusion of 2 liters 0.9% saline over 3-4 h., Results: The prevalence of secondary forms of hypertension was 10.2%, including renovascular hypertension (3.1%), primary aldosteronism (1.4%), Cushing's syndrome (0.5%), pheochromocytoma (0.3%), primary hypothyroidism (3.0%) and a serum creatinine > 2.0 mg/dl (1.8%). There was a very significantly increased prevalence with age of secondary forms of hypertension associated with renovascular hypertension, primary hypothyroidism and renal insufficiency. The concomitant presence of atherosclerosis significantly increased the prevalence of renovascular hypertension (9.5%) and renal insufficiency (8.0%)., Conclusions: Increasing age and coexisting atherosclerosis have significant effects on the prevalence of secondary forms of hypertension.

Patients with essential hypertension (n = 2969) who had not been taking any blood pressure medication for longer than 1 week were classified as furosemide-sensitive (FS) if their diastolic BP after furosemide fell > or = 10% and furosemide-resistant (FR) if it fell less than that. The FS group was significantly (P < or = .05) older, and had higher blood pressure than the FR group. In patients over age 50, the prevalence of cardiovascular complications (myocardial infarction, stroke, angina, congestive heart failure, and intermittent claudication) in the FR group (12.3%) was significantly (P = .0039) more than in the FS group for all patients, and especially for women (P = .0053). This was not explained by plasma renin activity, plasma norepinephrine, obesity index, cholesterol, blood sugar, or smoking history, and was associated in the FR group with a lower BP. This study characterizes the furosemide response of BP in hypertensive subjects and demonstrates an increased prevalence of cardiovascular complications in women over age 50 in the furosemide resistant group.

Thiazide diuretics cause hypokalemia in some, but not all patients. Adding a second diuretic with a different mechanism of action greatly increases the chance of inducing hypokalemia. Suggestive causative factors include hyperaldosteronism, acid-base status, and the degree of natriuresis. Atrial natriuretic hormone (ANH), a circulating peptide secreted primarily by the heart in response to changes in intravascular volume, induces a natriuresis by a mechanism distinct from the thiazides. It was previously shown that furosemide and thiazide diuretics can increase plasma ANH levels in some patients, but reduce ANH levels in others. This phenomenon was investigated in 26 patients with uncomplicated essential hypertension to observe the relationships between ANH and changes in serum potassium (K+) in response to chronic hydrochlorothiazide therapy (HCTZ, 50 mg/day for 1 month). Regression analysis demonstrated significant correlations between K+ level after HCTZ and initial ANH (r = 0.68, P less than .001), change in K+ level and initial ANH (r = 0.40, P less than .05), K+ level after HCTZ and change in ANH (r = -0.64, P less than .001), and change in K+ levels and change in ANH levels (r = -0.38, P less than .05). By multivariate analysis, initial ANH level, but not the plasma aldosterone level, was significantly (P less than .05) related to the change in K+ after HCTZ. These results suggest that initial plasma ANH levels are a marker predictive for diuretic-induced hypokalemia.

A pheochromocytoma is a tumor of the chromaffin cells of the adrenal gland medulla that produces excessive amounts of norepinephrine. It is difficult to diagnose and complicated to treat because of its variable symptoms and location in the body. The tumor is most likely to cause uncontrolled hypertension, nervousness, diaphoresis, and palpitations, but, at other times, may show no symptoms at all. The diagnosis is established by measuring the plasma levels of the catecholamine hormones, norepinephrine and epinephrine. Although 10% of pheochromocytomas are extra-adrenal, most appear in one adrenal gland. If a tumor can be located by radiological techniques, it can be cured by surgical removal. Since these tumors may recur, it is necessary to reevaluate the patient periodically by measuring catecholamine levels and by radiological studies. We present a case study of one patient with a malignant pheochromocytoma, outlining the diagnosis, treatment, and postadrenalectomy follow-up.

The diagnostic usefulness of the timed intravenous pyelogram (IVP), isotopic renal flow study (renal flow), stimulated plasma renin activity (SPRA), saralasin infusion test, and renal vein renins (RVR) in detecting possible renal vascular hypertension was studied in relation to age. Among patients who had been off medication for 2 weeks and who had normal renal X-ray findings, the percentage of those with a high SPRA dropped from 22.3% in those aged 20-29 to 4.2% in those aged 60-69 years, and that in those showing a positive saralasin test dropped from 8.3% in those aged 20-29 to 4.3% in those aged 60-69. But among those with abnormal renal X-ray findings, the percentage rose from 5.7% to 20% (high SPRA) and from 16.3% to 33% (positive saralasin test). A high SPRA or positive saralasin detected a renal abnormality in 11.7% and 50%, respectively, of patients aged 20-29, and 75% and 85.7%, respectively, of those aged 60-69. The percentage of all patients on or off medication with abnormal renal X-ray findings and a renal vein renin ratio > 1.5 increased from 14.2% among those aged 20-29 to 84.2% among those aged 60-69. The results indicate an increasing usefulness with age of a high SPRA or a positive saralasin test in indicating an abnormal renal X-ray and an abnormal renal vein renin ratio, and thus a potentially correctable lesion.

This study was designed to compare changes in performance on the Wechsler Adult Intelligence Scale over a 5- to 6-year test interval for normotensives and medically treated, uncomplicated essential hypertensives. The results indicated that normotensives improved from Time 1 to Time 2 on the Verbal scale but not on the Performance scale. Hypertensives exhibited no significant improvement or decline on either scale, although they performed less well on the Verbal scale at Time 2 than did normotensives. They also performed more poorly on the Performance scale when Time 1 and Time 2 scores were averaged. Participants who returned for Time 2 testing and those who participated only at Time 1 were compared. Verbal scaled scores at Time 1 were higher for returning than for nonreturning hypertensives, but, for normotensives, no differences were observed for those who returned for Time 2 testing and those who did not.

One hundred and six patients were determined to have renovascular hypertension (RVH) out of 3520 patients with hypertension referred by their physicians for a 1-day blood pressure study (1-day BP study) to evaluate the presence of secondary forms of hypertension. The clinical indices (including serum potassium and creatinine concentrations) most likely to predict RVH were analyzed. Patients unlikely to have RVH were those with a diastolic blood pressure (DBP) less than or equal to 90 mm Hg (with or without BP medication) with a serum potassium concentration less than 3.4 mEq/L. A two- to threefold increased prevalence of RVH was associated with DBP greater than 110 mm Hg, an age of onset of hypertension of 51-69 years, or age of onset greater than 60 years with a DBP less than or equal to 100 mm Hg. A four- to sixfold increase came with an age of onset greater than 60 years, serum potassium (with or without BP medication) 2.9-3.3 mEq/L, or serum potassium less than 3.4 mEq/L with DBP greater than 90 mm Hg. A seven- to ninefold increase came with age of onset greater than 60 years with DBP greater than 110 mm Hg or serum potassium (with or without BP medication) of 2.3-2.8 mEq/L.

The work reported here examines the quantitative ultrastructure of cat carotid body type I cells, and the effects of hypoxia on the cells. On the basis of size and density of electron-dense cored vesicle (EDCV) we were unable to identify more than one major population of type I cells. Prior ventilation of the animals with 10% O2 resulted in an increase in the volume percentage (Vv%) of mitochondria and a decrease in the Vv% of EDCV as compared to the values after ventilation with 100% O2. The lack of effect of prior denervation of the carotid body on the hypoxic changes suggests that the effects are not mediated via an efferent pathway.

The general structure and results of quantitative studies of rat carotid body type I cells are described. In contrast to previous reports, there was no change in mitochondrial V/v% on stimulating the carotid body with 10% oxygen. The volume of cytoplasm occupied by electron-dense cored vesicles was significantly increased, whilst their density per square micrometre of cytoplasm was decreased during hypoxia. Thus, the size of vesicles is increased by hypoxic stimulation. On the basis of vesicle diameter and density we were unable to find evidence of more than one variety of type I cell.

Performance on the Wechsler Adult Intelligence Scale was followed over two 5- to 6-year intervals for essential hypertensive Ss (EH; n = 22) free from medical complications and for normotensive Ss (N; n = 20). EH were treated with adrenergic beta-blocking drugs, diuretics, or both. Mean age was 46 years (SD = 12.6 years), initially (Time 1). Results were unaltered by adjustment for initial age. N improved modestly on the Verbal scale, from Time 1 to Time 2 only. EH neither improved nor declined on the Verbal scale. Scores remained unchanged for both EH and N Ss for the Performance scale. Overall, and at Times 2 and 3, Verbal scores were lower for the EH group. It was concluded that neither decline nor improvement in cognitive function over time are necessary outcomes of modest, carefully treated, uncomplicated hypertension in the middle years.