Current awareness of delirium in the intensive care unit: a postal survey in the Netherlands.

BACKGROUND: Delirium in the ICU can compromise the recovery process, prolong ICU and hospital stay and increase mortality. Therefore, recognition of delirium is of utmost importance. METHODS: To ascertain current attitude pertaining to delirium in critically ill patients a simple questionnaire was sent to all intensive care units (ICUs) throughout the Netherlands. RESULTS: Seventy-five questionnaires were sent and 44 returned. A delirium protocol was present in the majority of cases (n=35, 80%), although implementation had occurred in only 22 ICUs (50%). The reported general incidence of delirium varied widely (25% of ventilated patients (n=33, 75%) and in patients older than 70 (n=38, 86%). Most participating centres reported that they could certainly (n=9, 20%) or most certainly (n=22, 50%) identify delirium. A geriatrician or a psychiatrist predominantly diagnosed delirium (n=30, 68%), while a diagnostic instrument such as the CAM -ICU was used in a minority of cases (n=11, 25%). A geriatrician or a psychiatrist was consulted when patients were agitated (n=40, 90%), or when routine pharmacological treatment had failed (n=40, 91%). CONCLUSION: In the Netherlands, delirium is considered an important problem in the ICU, although its incidence is estimated to be low by the ICU team. The diagnosis of delirium is most frequently established by a geriatrician or psychiatrist after consultation, while diagnostic instruments are infrequently used. Efforts should be undertaken to implement delirium protocols and a routinely applied diagnostic instrument in the ICU.

Deadly vasospasm.

A patient with Prinzmetal's variant angina (PVA) developed a cardiac arrest due to coronary vasospasm and subsequent myocardial infarction. After resuscitation postanoxic brain injury was diagnosed. After an initial improvement of consciousness he deteriorated rapidly on the seventh day after admission due to severe brain ischaemia apparently caused by cerebral vasospasm, until ultimately brain death was diagnosed. To our knowledge, the association between PVA and cerebral vasospasm has never been described. The combination suggests that this patient had a generalized vasospastic disorder.

[Aortic involvement in patients with temporal arteritis and polymyalgia rheumatica]. / Ziekte van de aorta bij arteriitis temporalis en polymyalgia rheumatica.

In 4 patients with temporal arteritis or polymyalgia rheumatica, women aged 60, 57, 83 and 73 years respectively, signs of aortic involvement were established. The first patient presented with signs of systemic inflammation without signs of temporal arteritis or aortitis. In the second, an acute symptomatic thoracoabdominal aneurysm developed. In the third, temporal arteritis was associated with chronic progressive dilatation ofthe thoracic aorta. The fourth developed signs of intermittent claudication of the extremities. The clinical manifestations in all patients were attributed to chronic inflammation of the aorta caused by giant cell arteritis. Aortic giant cell arteritis frequently accompanies temporal arteritis, but is rarely diagnosed. Up to 75% of patients with temporal arteritis may have some degree of aortic involvement. Thoracic aneurysms, complicated by rupture or dissection, are the most serious complications. Aortic disease associated with signs of systemic inflammation should trigger the suspicion of giant cell arteritis. Corticosteroids are the most important part of treatment. Three patients recovered following treatment; the first two received an endoprosthesis; in the woman aged 83 years, this was not technically possible; she died after 1.5 years.

C-type natriuretic peptide-induced vasodilation is dependent on hyperpolarization in human forearm resistance vessels.

Animal studies have demonstrated that CNP causes endothelium-independent vasodilation, which is limited by neutral endopeptidase (NEP) activity. However, the vasodilating mechanism of CNP in humans is still unknown. Therefore, we investigated the vasodilator actions of CNP in human forearm resistance vessels before and after inhibition of nitric oxide (NO) and then prostacyclin production and after inhibition of Ca(2+)-dependent potassium channel activation and NEP activity. Three separate studies were performed. In each study, forearm blood flow was recorded by venous occlusion plethysmography in 8 healthy nonsmoking subjects. Brachial artery infusion of CNP (70, 140, 280, and 560 ng per 100 mL forearm volume per minute) caused significant forearm vasodilation in all studies (forearm blood flow from 3.94 to 8.50 mL per 100 mL forearm volume per minute). Inhibition of the endogenous generation of NO by L-N(G)-monomethyl arginine (by use of the NO-clamp technique) did not block the maximal vasodilating effects of CNP (forearm blood flow from 3.69 to 6.93). In addition, when the cyclooxygenase system was inhibited by 600 mg of acetylsalicylic acid (aspirin) administered orally 30 minutes before start of measurements, the rise in forearm blood flow remained intact (forearm blood flow from 3.31 to 8.27 mL per 100 mL forearm volume per minute). However, inhibition of Ca(2+)-dependent potassium channels with tetraethylammonium chloride (0.1 mg per 100 mL forearm volume per minute) significantly attenuated vasodilation caused by CNP (forearm blood flow from 2.28 to 3.06 mL per 100 mL forearm volume per minute), which suggests that CNP opens vascular potassium channels. Vasodilation to all doses of CNP was significantly increased when activity of NEP was blocked with thiorphan (30 nmol/min), which suggests that NEP activity limits vasodilation of CNP. CNP is a dilator of human resistance vessels that mediates its effects through hyperpolarization of the vessel wall independent of the NO and prostaglandin system. Inhibition of local NEP activity increases CNP bioavailability. This may be of relevance to cardiovascular disease, given that vascular tone is well balanced between NO and an endothelium-derived hyperpolarizing factor, which suggests that in pathological situations, impaired NO activity can be compensated for by enhanced endothelium-derived hyperpolarizing factor release to maintain vascular homeostasis.

Pharmacokinetics and pharmacodynamic effects of ABT-627, an oral ETA selective endothelin antagonist, in humans.

AIMS: Endothelins (ETs) may play a role in the pathogenesis of a variety of cardiovascular diseases. The present study was designed to investigate the pharmacokinetic and pharmacodynamic effects of the orally active ETA selective receptor antagonist ABT-627 in healthy humans. METHODS: Healthy volunteers were included in two studies with cross-over design. Subjects received single or multiple dose (an 8 day period) administration of oralABT-627 or matched placebo, in a dose range of 0.2-40 mg. The pharmacokinetics of ABT-627 were described and its effects on systemic haemodynamics under resting conditions and on forearm vasoconstriction in response to ET-1 were assessed. RESULTS: ABT-627 was generally well tolerated in both studies, with transient headache being the most reported adverse event (in 62% vs 4% during placebo, P < 0.05, for Study 1 and in 42% vs 60%, P = 0.2, for Study 2). ABT-627 was rapidly absorbed, reaching maximum plasma levels at approximately 1 h post dose. Single dose ABT-627, at a dose of 20 and 40 mg, inhibited ET-1 induced forearm vasoconstriction at 8 h post dose. Eight days ABT-627 treatment, at a dose level of 5 mg and above, also effectively blocked forearm vasoconstriction to ET-1. ABT-627 caused a significant reduction in peripheral resistance as compared with placebo (16 +/- 1 vs 19 +/- 1, 18 +/- 2 vs 23 +/- 3, 15 +/- 1 vs 17 +/- 1 AU at 1, 5, 20 mg in Study 2) with only a mild decrease in blood pressure (79 +/- 2 vs 84 +/- 3, 80 +/- 4 vs 90 +/- 5, 75 +/- 3 vs 79 +/- 1 at 1, 5, 20 mg in Study 2). ABT-627 caused a moderate dose-dependent increase in circulating immunoreactive ET levels (a maximal increase of 50% over baseline at the 20 mg dose level). CONCLUSIONS: The oral ETA receptor blocker ABT-627 is well tolerated, rapidly absorbed, effectively blocks ET-1 induced vasoconstriction and causes a decrease in total peripheral resistance and mean arterial pressure. Our data suggest that ABT-627 may be a valuable tool in treatment of cardiovascular disease.

Bradykinin-induced vasodilation of human forearm resistance vessels is primarily mediated by endothelium-dependent hyperpolarization.

Bradykinin (BK) stimulates endothelial cells to release a number of relaxing factors, such as NO, prostanoids (PGs), and an endothelium-derived hyperpolarizing factor (EDHF). However, the contributions of NO, PG, and EDHF in the vascular relaxation to BK vary with species and anatomic origin of blood vessels used. Therefore, the present study was designed to investigate the contributions of NO, PG, and EDHF in vasodilation caused by BK in human forearm resistance vessels. Forearm blood flow (FBF) was recorded with venous occlusion plethysmography in healthy nonsmoking subjects. At first, studies were performed to validate the NO clamp technique for its ability to inhibit endogenous NO generation. Brachial artery infusion of serotonin (0.6, 1.8, and 6 ng. 100 mL forearm volume [FAV](-1). min(-1)) caused significant forearm vasodilation (2.6 to 4.6 mL. 100 mL FAV(-1). min(-1)), which is known to be NO mediated. Indeed, during the NO clamp, cumulative doses of serotonin caused no vasodilation (2.4 to 2.6 mL. 100 mL FAV(-1). min(-1)), indicating that the generation of endogenous NO was completely blocked. Thereafter, the vasodilative actions of BK were investigated. Brachial artery infusion of BK (50, 100, and 200 ng. 100 mL FAV(-1). min(-1)) caused significant forearm vasodilation in all studies (from 3.1 to 20.4 mL. 100 mL FAV(-1). min(-1)). After the inhibition of cyclooxygenase and NO synthase activity through the use of aspirin and the NO-clamp technique, BK increased FBF in a similar manner (3.9 to 18.9 mL. 100 mL FAV(-1). min(-1)), indicating that the vasodilative actions of BK are independent of NO and PG generation. However, vasodilation caused by the 2 lower doses of BK were significantly attenuated after K(Ca) channel activity was blocked with tetraethylammonium chloride (0.1 mg. 100 mL FAV(-1). min(-1)), suggesting that in the lower dose range, BK mediates vasodilation through the opening of vascular potassium channels. In conclusion, BK is a potent vasodilator peptide in human forearm resistance vessels, causing vasodilation through hyperpolarization of the vascular wall independent of NO and PG production. In addition, the NO-clamp technique is a valid instrument to investigate the contribution of NO in the vasodilative response to different agents.

Nifedipine improves endothelial function in hypercholesterolemia, independently of an effect on blood pressure or plasma lipids.

OBJECTIVE: Dihydropyridine calcium antagonists have been shown to retard atherogenesis in animal models and to prevent the development of early angiographic lesions in human coronary arteries. Endothelial dysfunction is an early event in the pathogenesis of cardiovascular disease. We investigated whether nifedipine could improve endothelial function in hypercholesterolemia, independently of changes in blood pressure or plasma lipids. METHODS: First, we compared in vivo forearm vascular responses to the endothelium-dependent and independent vasodilators serotonin (5-HT) and sodium nitroprusside (SNP) in 11 patients with familial hypercholesterolemia before and after 6-weeks treatment with nifedipine GITS (60 mg, OD) and in 12 matched controls. In a subgroup of six control subjects forearm vascular function was also assessed before and after 6-weeks nifedipine GITS treatment. In vitro, we subsequently explored possible mechanisms underlying the effect of nifedipine on endothelial function. We investigated the effects of nifedipine on both NO production by recombinant endothelial NO synthase (eNOS) and endothelial cells, using 3H-arginine conversion, as well as on superoxide generation by endothelial cell lysates, using lucigenin enhanced chemiluminescence. RESULTS: In hypercholesterolemia 5-HT-induced vasodilation was impaired (47 +/- 9% increase in forearm bloodflow vs. 99 +/- 8% in controls). Treatment with nifedipine completely restored 5-HT-induced vasodilation (113 +/- 13%), whereas it did not influence basal forearm vasomotion or SNP-induced vasodilation. Nifedipine did not alter forearm vascular responses in control subjects and did not alter blood pressure or plasma lipids. In vitro, we found no direct effect of nifedipine on NO production by recombinant eNOS or endothelial cells. However, we did observe a reduction in endothelial superoxide generation. CONCLUSIONS: Our data show that nifedipine improves endothelial function in hypercholesterolemia. It is suggested from our in vitro experiments that this effect is due to reduced NO degradation.

Nitric oxide availability in diabetes mellitus.

Diabetes mellitus is associated with early development of cardiovascular complications. Under physiological conditions the endothelium protects against the development of atherosclerosis. Endothelial cells produce, e.g., nitric oxide (NO), a substance which is capable of keeping vascular tone, coagulation and inflammation well balanced. However, in pathological conditions, such as in diabetes mellitus, impaired NO activity may be present. Decreased NO activity can be caused by impaired production of NO, due to uncoupling of receptor-mediated signal transduction, a deficiency of the NO synthase (NOS) substrate L-arginine, or a decreased availability of one or more cofactors essential for optimal functioning of NOS. However, hyperglycaemia also stimulates the production of advanced glycosylated end products, enhances the polyol pathway and activates protein kinase C. These conditions may lead to increased oxidative stress. Reactive oxygen species rapidly inactivate NO leading to the formation of peroxynitrite. Peroxynitrite is a toxic oxidant capable of damaging many biological molecules. Reduced NO availability may not only be of relevance to the development of atherosclerotic complications in diabetes but may also interfere with insulin-mediated postprandial glucose disposal and possibly contribute to the development of insulin resistance. Understanding of the complex metabolic disturbances interacting with the NO system may provide us with further therapeutic options to decrease cardiovascular morbidity and mortality in diabetes mellitus.

Primary thyroid lymphoma.

A 71-year-old woman presented with a rapidly growing goitre which was diagnosed as chronic autoimmune thyroiditis. Despite treatment with levothyroxine, she developed progressive airway obstruction. Biopsy revealed a primary thyroid lymphoma which was successfully treated with radiotherapy.

Dysfunctional postures of the hand as part of a conversion reaction.

A dysfunctional posture of the hand could be due to an anatomical disorder or a conversion reaction. A conversion reaction implies that an unconscious intrapsychic conflict is expressed in a physical dysfunction. Treatment of dysfunctional postures due to conversion reactions is often difficult, and case reports are used to outline management. The need for a multidisciplinary approach is stressed.

An anomalous flexor digitorum superficialis to the index finger.

An anomalous, digastric flexor digitorum superficialis in addition to a normal flexor digitorum superficialis to the index finger, is reported. To our knowledge, this is an anatomic variation never described before. The anomalous muscle belly presented as a progressive pseudotumor of the palm and needed exploration to provide the final diagnosis.