Effect of 7.2% Hypertonic Saline/6% Hetastarch on Left Ventricular Contractility in Anesthetized Humans

Background: Although a positive inotropic effect of hypertonic saline has been demonstrated in isolated cardiac tissue as well as in animal preparations, no information exists about a possible positive inotropic action of hypertonic saline in humans. The aim of this investigation was to determine whether a clinically relevant positive inotropic effect can be demonstrated in humans.

Methods: Twenty-six patients without cardiovascular disease were randomized to receive 4 ml/kg of either 7.2% hypertonic saline/6% hetastarch or 6% hetastarch (control) at a rate of 1 ml *symbol* kg sup -1 *symbol* min sup -1 while under general endotracheal anesthesia. Transesophageal echocardiography was used to evaluate left ventricular function. Arterial pressure, heart rate, and left ventricular end-systolic and end-diastolic diameter, area, and wall thickness were measured immediately before and after administration of either solution. Fractional area change, end-systolic wall stress, and the area under the end-systolic pressure-length relationship curve (ESPLRarea) were calculated. ESPLRarea was used to assess left ventricular contractility.

Results: Administration of hypertonic saline/hetastarch resulted in a significant decrease of mean arterial pressure and end-systolic wall stress from 77 plus/minus 14 (mean plus/minus SD) to 64 plus/minus 17 mmHg (P < 0.01) and from 52 plus/minus 14 to 32 plus/minus 11 103 dyne/cm2 (P > 0.01), respectively. End-diastolic area and fractional area change increased from 16.5 plus/minus 2.9 to 21.7 plus/minus 3.3 cm2 (P < 0.01) and from 0.53 plus/minus 0.07 to 0.70 plus/minus 0.06 (P < 0.01), respectively, whereas there was only a minor change of ESPLRarea from 38 plus/minus 13 to 44 plus/minus 13 mmHg.cm (P < 0.05).     

Pion radiotherapy of unresectable soft tissue sarcomas at the Swiss Institute for Nuclear Research

The Swiss Institute for Nuclear Research SIN at Villigen is one of the three centres in the world (LAMPF, Los Alamos; TRIUMF, Vancouver) where pion therapy is possible. A dynamic, tumour conforming spot scan technique for the treatment of deep-seated tumours has been in use since November 1981. With this technique with a favorable integral dose distribution, curative irradiation also of advanced tumours in the retroperitoneum and pelvis is possible. Only at SIN, the treatment of non-resectable soft tissue sarcomas with pions is part of the clinical program. Between 1983 and 1985 totally nine patients were treated, 1/9 with three manifestations, 1/9 with palliative intent. In 20 fractions over five weeks (four fractions a week) total doses of 30 to 36 Gy (90% isodose) were applied. In a follow-up period of eleven to 43 months (median 18 months) only 1/10 tumour manifestations treated with greater than or equal to 30 Gy failed locally. The two-year survival rate (Kaplan-Meier) is 56%. Metastases were the cause of death in 3/5 patients, 1/5 heart disease, 1/5 local tumour progression. Even though 9/11 tumours were located in the retroperitoneum or pelvis, no radiogenic morbidity of the bowel was found. These preliminary results stimulate the intensification of this clinical program. 1986 the same number of patients with non-resectable soft tissue sarcomas was treated as in the whole period 1982 to 1985 before.     

Antibodies for targeted cancer therapy -- technical aspects and clinical perspectives.

The efficacy of traditional anti-cancer agents comes with the price of toxicity to normal cells, which limits the success of therapy. In the past 2 decades, greater understanding of the molecular differences between malignant and normal cells has led to the development of therapies that more specifically target human tumors. These include new anti-cancer agents directed against intracellular targets associated with malignant alterations, such as increased proliferation, impaired apoptosis or angiogenesis. In addition, antibodies have been developed that are directed towards tumor-associated antigens and provide tailor-made effector functions by inhibiting cell growth, inducing apoptosis or constituting cytotoxic drug delivery systems. Since the targeted approach of anti-cancer therapies increases the exposure of malignant cells and at the same time reduces the exposure of normal tissues, it offers the promise of enhanced efficacy and lower side effects. Antibodies, immunoconjugates and liposomal drug delivery systems derived thereof are now mainstream cancer therapeutics, and by the end of 2003 17 marketed antibody-based products generated several billion in combined annual sales. This study highlights the most recent breakthroughs in antibody technology and summarizes major achievements in antibody-based cancer therapy in oncology trials.     

Fatigue in neuroimmunological diseases

Journal of Neurology - Fatigue is a widespread symptom in numerous neuroimmunological diseases like multiple sclerosis (MS), myasthenia gravis, morbus Behcet, neurosarcoidosis, neuroborreliosis or...     

Aspirin in coronary artery bypass surgery: new aspects of and alternatives for an old antithrombotic agent.

The success of coronary artery bypass graft surgery (CABG) depends mainly on the patency of the graft vessels. Aortocoronary vein graft disease is comprised of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia and atherosclerosis. Early thrombosis is a major cause of vein graft attrition during the first month after CABG, while during the remainder of the first year, intimal hyperplasia forms a template for subsequent atherogenesis, which thereafter predominates. Platelets play a crucial role in the pathophysiology of graft thrombosis and aspirin is the primary antiplatelet drug that has been shown to improve vein graft patency within the first year after CABG. Nevertheless, a significant number of grafts still occlude in the early postoperative period despite 'appropriate' aspirin treatment. Moreover, laboratory investigations showed that the expected inhibition of platelet function is not always achieved. This has been called 'aspirin nonresponse' or 'aspirin resistance', although a uniform definition is lacking. The finding that a considerable number of patients show an impaired antiplatelet effect of aspirin after CABG brought new insight into the discussion concerning poor patency rates of bypass grafts: the early period after CABG shows a coincidence of an increased risk for bypass thrombosis (amongst others, due to platelet activation and endothelial cell disruption of the graft) and an increased prevalence of aspirin resistance. Hitherto, the underlying mechanisms of aspirin resistance are uncertain and largely hypothetical; amongst others, increased platelet turnover, enhanced platelet reactivity, systemic inflammation, and drug-drug interaction are discussed. Up to now available data concerning the clinical outcome of aspirin resistant CABG patients are limited, and there is evidence that platelets of patients with graft thrombosis are more likely to be resistant to aspirin compared with patients without thrombotic events. Many publications concerning aspirin resistance are available today, but reports addressing this topic in CABG patients are sparse. This review summarises recent insights into the antiplatelet treatment after CABG and describes the clinical benefit, but also the therapeutic failure of the well-established drug aspirin. Moreover, possible pharmacological approaches to improve antithrombotic therapy in aspirin nonresponders among CABG patients are discussed.     

Heart Transplantation in a 68-Year-Old Patient with Senile Systemic Amyloidosis

Senile systemic amyloidosis (SSA) results from deposition, predominantly in the heart, of amyloid fibrils derived from wild-type transthyretin (T TR) molecules. Cardiac autopsies indicate that SSA progressively increases in subjects 80 years of age and older. However, only a few cases of patients with SSA and cardiac failure have been recognized by cardiac biopsies during life. Here, we report a case of heart transplantation in a 68-year-old male patient with SSA. After cardiopulmonary resuscitation in October 1998, he underwent complete evaluation. Myocardial biopsies revealed the presence of amyloid deposition. Immunohistochemical staining of the amyloid indicated T TR. Genomic DNA analysis of the T TR exons did not result in any identification of a mutation. In 2001, heart transplantation was performed because progressive heart failure occurred. At the 1-year follow-up, no amyloid deposits were found in the donor heart. At the 2-year follow-up, the patient's physical and mental health was excellent. We conclude that heart transplantation can be an effective treatment in progressive heart failure due to SSA.     

Three-dimensional recording of the human face with a 3D laser scanner.

Three-dimensional recording of the surface of the human body or of certain anatomical areas has gained an ever increasing importance in recent years. When recording living surfaces, such as the human face, not only has a varying degree of surface complexity to be accounted for, but also a variety of other factors, such as motion artefacts. It is of importance to establish standards for the recording procedure, which will optimise results and allow for better comparison and validation. In the study presented here, the faces of five male test persons were scanned in different experimental settings using non-contact 3D digitisers, type Minolta Vivid 910). Among others, the influence of the number of scanners used, the angle of recording, the head position of the test person, the impact of the examiner and of examination time on accuracy and precision of the virtual face models generated from the scanner data with specialised software were investigated. Computed data derived from the virtual models were compared to corresponding reference measurements carried out manually between defined landmarks on the test persons' faces. We describe experimental conditions that were of benefit in optimising the quality of scanner recording and the reliability of three-dimensional surface imaging. However, almost 50% of distances between landmarks derived from the virtual models deviated more than 2mm from the reference of manual measurements on the volunteers' faces.