Endothelial cell dysfunction in homocystinuria

Abstract. This report describes the isolation and culture of venous endothelial cells from the umbilical cord of an obligate heterozygote for homocystinuria. The effect of different sulphur-containing amino acids on the viability and function of these cells was studied and compared with cultured normal endothelial cells. When endothelial cells were cultured in the presence of methionine (10 mmol/l) or homocystine (10 mmol/l), differences occurred between the viability and function of the heterozygote and normal cells in terms of ⁵¹Cr release and ability to prevent platelet adherence. The Cr release corrected for spontaneous release increases for the heterozygote cells after incubation for 21 h in the presence of methionine to 81.3% (control cells, range: 0–23.3%, n = 5) and in the presence of homocystine to 141% (control cells, range: 13.5–55.2%, n = 5). The total number of platelets that adhere to confluent monolayers increases for heterozygote cells cultured in the presence of methionine to 0.98 ± 10⁷ platelets cm^-2 (normal cells, range: 0.56–0.72 ± 10⁷ platelets cm^-2) and in the presence of homocystine to 1.41 ± 10⁷ platelets cm^-2 (normal cells, range: 0.94–1±06 ± 10⁷ platelets cm^-2). Both normal and control cells were sensitive to homocysteine. This study indicates for the first time what vascular endothelial cells, derived from an obligate heterozygote, are (partly) deficient in cysthathionine synthase and are more susceptible to methionine- and homocystine-mediated injury than normal endothelial cells. Consequently, in homocystinuria, due to dysfunction of the endothelial cells, toxic sulphur-containing amino acids may accumulate in these cells, causing injury of these cells.     

Moving from hospital into a care home – the nurse's role in supporting older people

• ? Discharge planning has received much attention in the nursing literature over the past few years, and there has been particular concern over the discharge of older people back into their domestic environment.
• ? The practical and logistical problems of managing such a discharge are considerable, but in this paper we argue that discharging older people from hospital to care homes is equally problematic, though in different ways.
• ? This is a neglected area of research, perhaps because discharge into a care home seems to present fewer organizational problems.
• ? There is, however, an extensive body of literature from a range of different disciplines which suggests that the loss of home and entry into a strange environment can be very stressful.
• ? This paper outlines this literature and explores the implications for nursing practice.

     

Angiotensin II, aldosterone and arginine vasopressin in plasma in congestive heart failure

Angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined during basal conditions in seventeen patients with congestive heart failure and in seventeen control subjects. The same parameters were measured before and 1, 2 and 3 h after an oral water load of 20 ml (kg body weight)-1 together with urine volume (V) and free water clearance (CH2O) in seven patients with congestive heart failure and in seven control subjects. AII, Aldo and AVP were significantly higher in heart failure than in control subjects (AII:81 and 12 pmol l(-1) (medians), P less than 0.01; Aldo: 411 and 103 pmol l(-1), P less than 0.01; AVP: 5.3 and 2.0 pmol l)-1), P less than 0.01). AVP was positively correlated to Aldo in both heart failure (p = 0.593, n = 17, P less than 0.02) and control subjects (p = 0.511, n = 17, P less than 0.05), but in neither of the groups to AII. V and CH2O were significantly lower in heart failure when compared to control subjects (maximum increase in CH2O 3.55 and 5.86 ml min-1, P less than 0.02), but did not correlate directly with either A II, Aldo or AVP. Creatinine clearance was reduced in heart failure. It is concluded that the activity of both the renin-angiotensin-aldosterone system and the osmoregulatory system is enhanced in congestive heart failure, presumably as a compensatory phenomenon in order to maintain arterial blood pressure. It is suggested that the decrease in free water clearance may be attributed to both an elevated level of vasopressin and a reduced glomerular filtration rate.     

The Effect of Age on the Electrophysiological and Autonomic Correlates of Sudden Death After Acute Myocardial Infarction

To examine the influence of age on the autonomic and electrophysiological correlates of sudden death after myocardial infarction, 223 patients aged <60 and 195 patients aged ≥60 were followed up for a mean of 790 days. The patients had Holter monitoring and a signal-averaged EGG 5–11 days after infarction. A mean ventricular ectopic beat frequency >10 beats/ hour (VE10) was present in 17.0% of young versus 28.2% of old patients (P < 0.01); a low heart heart variability index in 17.9% of young but in 32.3% of old patients (P < 0.001) and late potentials in 17.5% but 32% of young and old patients, respectively (P < 0.01). There was no difference in the incidence of sudden death between young and old patients (3.6% vs 3.1%). However, sudden death accounted for 50%, compared with 24% of all deaths in the young and old groups, respectively (P < 0.01). Sudden death was more closely associated with low heart rate variability and VE10 in the young than in the older group. The predictive values of a heart rate variability index <20 units with VE10 in younger patients were a sensitivity of 50%, a positive predictive accuracy (PPA) of 33% and risk ratio (RR) of 18 (P < 0.001); these values did not reach significance in older patients (16.7%, 4.3% and 1.4%, respectively.) Late potentials had a sensitivity of 50%, a PPA of 12.1%, and an RR of 4.7 in young patients (P < 0.05): the corresponding values in the older group were 80%, 8.9, and 8.4 (P < 0.02). It is concluded that sudden death is a more predominant mode of death and is more strongly associated with lower heart rate variability and with the VE10 incidence in young than in older postinfarction patients. Age should be taken into account when assessing the risk of sudden death after myocardial infarction.     

Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator

The nature of the enhanced blood fibrinolytic activity which is known to occur during cardiopulmonary bypass is not understood. We show here that the cause is an increase in extrinsic (tissue-type) plasminogen activator. In six patients, the nature of the enhanced blood fibrinolytic activity that evolved during cardiopulmonary bypass was characterized by differential inhibition using the fibrin plate method and was shown to be C1-inactivator-resistant (extrinsic-activator activity). The C1-inactivator-resistant-activator activity was completely quenched by an antibody against extrinsic (tissue-type) plasminogen activator but not by antiurokinase, proving that the activity was due to the presence of extrinsic (tissue-type) plasminogen activator. The concentration of extrinsic (tissue-type) plasminogen activator increased during cardiopulmonary bypass and disappeared rapidly thereafter. Fibrinogen, plasminogen and alpha 2-antiplasmin were not consumed during cardiopulmonary bypass, while no increase or occasionally a moderate one in fibrinogen degradation products occurred. This is in accord with the property of extrinsic (tissue-type) plasminogen activator which activates plasminogen predominantly at sites where fibrin is present and not in the free circulation.     

Pressure‐Guided Cryoballoon Isolation of the Pulmonary Veins for the Treatment of Paroxysmal Atrial Fibrillation

Pressure‐Guided Cryoballoon Pulmonary Vein Isolation. Background: Pulmonary vein (PV) isolation using a balloon‐mounted cryoablation system is a new technology for the percutaneous treatment of atrial fibrillation (AF). Complete PV occlusion during balloon ablation has been shown to predict successful electrical isolation. The aim of this study was to correlate mechanical PV occlusion with changes in a pressure curve recorded at the distal tip of the cryoballoon catheter. Methods and Results: We analyzed 51 PVs in 12 patients (61 ± 6 years old) with paroxysmal AF. At first, PV occlusion via the cryoballoon was documented by changes in the pressure curve. Once the PV is occluded, the pressure curve registered in the vein converts from a left atrial pressure curve to a pulmonary artery pressure curve: the PV wedge curve. Occlusion was then confirmed by transesophageal echocardiography (TEE). Following 2 cryoablation applications, electrical PV isolation was assessed with a circumferential mapping catheter. Under the exclusive guidance of changes in the pressure curve at the tip of the cryoballoon, mechanical occlusion confirmed by TEE was achieved in 47 of 51 PVs (92%). Three PVs required further TEE guidance to achieve occlusion. All 50 occluded veins were electrically isolated after cryoablation. One right inferior vein, which could not be occluded with the balloon, displayed conduction post cryoablation and was isolated by focal ablation. Conclusions: Occlusion and electrical isolation of PVs during cryoballoon ablation can be predicted by the appearance of a PV wedge curve at the tip of the catheter. This new straightforward parameter may facilitate the procedure. (J Cardiovasc Electrophysiol, Vol. 21, pp. 120‐125, February 2010)     

Alcohol,tobacco and illicit drug use among six culturally diverse communities in Sydney

Introduction and Aims. A survey was conducted in 2004–2005 to investigate the risk of drug‐related harm among Chinese, Vietnamese, Italian, Pasifika, Arabic‐speaking and Spanish‐speaking communities in Sydney. Design and Methods. A self‐completion questionnaire, available in six languages, was distributed by bilingual field staff. A representative multistage clustered sampling design was used. Comparisons were made with the New South Wales general population using the results from the 2004 National Drug Strategy Household Survey. Results. The obtained sample was 2212 respondents; 50% completed the questionnaire in English. Daily tobacco use was higher than the general population among Vietnamese men (30%), Italian men (22%) and Pasifika men and women (25%). Reported use of alcohol and other drugs was lower than the general population in all six surveyed communities. Of the six communities, Pasifika had the highest rate of short‐term risky drinking (22%). Discussion and Conclusions. Smoking cessation programs should prioritise communities with higher or equal rates of daily smokers compared with the wider New South Wales population. Focus areas vary between the communities, and include increasing help seeking and improving quitting success rates. Short‐term risky drinking was not as prevalent among the surveyed communities; however, results suggest a need for prevention targeting Pasifika communities. Understanding the prevalence of substance use among culturally and linguistically diverse communities provides a crucial foundational component in developing culturally sensitive prevention and treatment programs. These results demonstrate the need for programs to be tailored to the needs and contexts of particular communities, rather than treating those from diverse backgrounds as one homogenous group.[Donato‐Hunt C, Munot S, Copeland J. Alcohol, tobacco and illicit drug use among six culturally diverse communities in Sydney. Drug Alcohol Rev 2012;31:881–889]     

无锡市锡山区体检人员HBsAg、HBeAg和ALT检测结果分析

目的了解无锡市锡山区体检人员HBsAg携带情况,结合丙氨酸转氨酶（ALT）及HBeAg分析,探讨HBV感染者与肝功能异常的相关性。方法采用酶联免疫吸附试验（ELISA）法检测HBsAg,对其中部分阳性者进行HBeAg检测,同时用全自动生化分析仪检测血清中ALT。结果2006-2008年92349名体检人员,HBsAg携带率为3．47％,有呈逐年下降的趋势,各年度间差异有统计学意义（Х^2=8．046,P〈0．05）;其中1452例HBsAg阳性者中HBeAg阳性的人员ALT异常率为31．79％,与HBeAg阴性人员的ALT异常率14．10％之间差异有统计学意义（Х^2=51．37,P〈0．01）。结论要加强宣传乙型肝炎相关防护知识,对HBsAg阳性者应做乙肝标志物并结合肝功能（ALT）来判断其病情和传染性。     

Pain and the administration of analgesia: what nurses say

? Pain of moderate to severe intensity continues to be an important problem for many hospitalized patients. ? Nurses spend more time with patients than any other health professional group and have a key role to play in the management of patients' pain. ? This paper reports the findings from a series of focus group interviews which were undertaken to explore nurses' perceptions regarding pain and the administration of narcotic analgesia. ? Themes identified from participants' comments related to (1) the pivotal role of nurses in pain management; (2) nursing assessment and pain management decisions (3) individual factors influencing nurses' pain management decisions and (4) the influence of others on nurses' pain management decisions. ? These findings have implications for further research and the development of innovative educational strategies.