Early and mid–term results of the Shelhigh stentless bioprosthesis in patients with active infective endocarditis

Summary Aims This study investigated the early and mid–term results following valve replacement with the new Shelhigh^? stentless bioprosthesis made entirely of biological material in patients with active infective endocarditis (AIE). Material and methods Between 02/2000 and 12/2004, 164 patients (n = 122 men, mean age 59, 18–85 years) received implantation of an AIE Shelhigh^? stentless bioprosthesis in the aortic, mitral, tricuspid or pulmonary position. A total of 119 patients (72.6%) had native AIE and 45 (27.4%) prosthetic AIE. A large proportion of the patients reached the operating room in a condition of cardiac decompensation: 37 (22.6%) patients were intubated, 40 (24.4%) had protracted septic shock and 41 (25.0%) required intensive catecholamine treatment. Surgery was regarded as urgent in 94 patients (57.4%) and was performed as an emergency procedure in 70 (42.6%). The mean follow–up time is 1.5 ± 0.11 years (range, 5 months to 5.2 years). Echocardiographic follow–up examinations were performed early postoperatively and after 12 months. Results In terms of the operative indication, we found a highly significant difference in the survival rate between patients who were operated on urgently vs in an emergency. In patients who died within 30 days, the main cause of death was septic multiorgan failure (67.6%). Only three patients required reoperation due to reinfection of the Shelhigh^? bioprostheses; this represents a reinfection rate of 1.8% in relation to the whole cohort. The postoperative echocardiographic examinations showed the Shelhigh^? valves to have very good hemodynamics without relevant pressure gradients. Conclusion Our experience in the use of Shelhigh^? bioprostheses in patients with native and prosthetic endocarditis show the early and mid–term results, in particular the low reinfection rate and the good hemodynamics, to be comparable with the results achieved using homografts. Since these prostheses are readily available and their implantation straightforward, they are increasingly being used in patients with endocarditis. These promising results need to verified in the long term. This paper was presented at a lecture held at the 71^st annual meeting of the German Society for Cardiology, Mannheim, 31. March—2. April 2005. Disclosure Form: The following study discloses my relationship with any corporate sponsor that might relate in some way to the subject presented.     

Novel molecular aspects of prostate carcinogenesis.

Prostate adenocarcinoma is one of the most frequently diagnosed forms of cancer in the male population of the Western world. The pivotal role of androgen and its receptor in this disease has been abundantly documented and indeed, chemical castration and treatment with antiandrogens are now standard therapies. However, relapse is often observed after 18-24 months, due to the remarkable ability of prostate tumour cells to adapt to low or undetectable androgen levels. Amplification and mutations of the androgen receptor (AR) gene have been described as well as alterations in cofactor expression and crosstalk with other signalling pathways. Another recent line of research focused on the re-programming of gene expression taking place in prostate tumours. Global expression profiling of normal and cancerous prostate tissues led to the identification of tumour-distinctive patterns. Validation studies are currently underway to identify novel drug targets as well as diagnostic and outcome prediction markers.     

Peripartale Kardiomyopathie

Peripartum cardiomyopathy (PPCM) is a rare and potentially life-threatening heart disease of unknown etiology that is restricted to the last month of pregnancy and up to 6 months postpartum. The morphology similates that of idiopathic dilated cardiomyopathy with a rapid progression to end-stage heart failure and is associated with a high morbidity and mortality rate. PPCM is treated with standard therapy for heart failure in accordance with the current guidelines. New findings suggest that elevated oxidative stress in the postpartum phase promotes cleavage of the nursing hormone prolactin into a toxic 16-kDa fragment that affects microcirculation and cardiomyocyte metabolism. Thus prolactin blocking using bromocriptine as a more specific therapy option showed promising early clinical results and is currently being tested in larger randomized trials. Frequent symptoms such as general fatigue, dyspnea and dry cough are often misinterpreted as pregnancy-related disturbances, and diagnosis is therefore often late. Interdisciplinary management, early diagnosis and more disease-specific therapy options appear to promote cardiac recovery in PPCM patients.     

Pyruvate-modified perfadex improves lung function after long-term hypothermic storage.

BACKGROUND: Lungs harvested for transplantation are stored while inflated with oxygen, which can serve to support oxidative metabolism. However, strategies aimed at increasing graft metabolism during storage have received little attention. In this study, we added pyruvate to the preservation solution Perfadex and measured the effects on oxidative metabolism and reperfusion lung function. METHODS: Rat lungs were stored for 6 and 24 hours in low-potassium dextran solution at 10 degrees C containing either 5 mmol/liter uniformly carbon-13 (U-(13)C) labeled glucose (Perfadex), 32 mmol/liter 3-(13)C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of (13)C into tricarboxylic acid cycle intermediates by magnetic resonance spectroscopy. Additional groups of lungs with each substrate modification were preserved for 6 or 24 hours and then reperfused. RESULTS: Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast, enrichment was significantly increased in both the pyruvate group (50% and 59%, respectively) and combined group (39% and 54%, respectively) compared with the Perfadex group (p<0.01). Graft function was excellent after 6-hour storage in all groups. All lungs stored for 24 hours exhibited inferior lung function, but oxygenation, pulmonary artery pressures, and airway pressures in the combined group were significantly improved compared with the Perfadex group (p<0.05). CONCLUSIONS: Preservation solution substrate composition influences graft metabolism during storage. The addition of pyruvate to Perfadex increases metabolism during storage and improves reperfusion lung function.     

The role of the human acetylation polymorphism in the metabolic activation of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

The metabolic activation of the heterocyclic food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by two human cytochrome P450 monoxygenases (P4501A1 and P4501A2) and two human N-acetyltransferases (NAT1 and NAT2) was investigated. Various combinations of these enzymes were functionally expressed in COS-1 cells. DNA adducts resulting from the activation of IQ were assayed quantitatively by the 32P-postlabeling procedure. The highest adduct frequency was observed in cells expressing both CYP1A2 and NAT2. CYP1A2 in combination with NAT1 was 3-6 times less active. When expressed alone these enzymes gave rise to low adduct frequencies. Experiments with N-acetyl-IQ as substrate suggest that NAT1 and NAT2 in addition to their known role in N-acetylation display arylhydroxamic acid N, O-acetyltransferase (AHAT) activity. Quantitative differences in adduct formation between IQ and N-acetyl-IQ indicated that metabolic activation of these arylamines preferentially occurs by P4501A2-catalyzed N-hydroxylation followed by O-acetylation mediated through NAT1 and/or NAT2. These data, in combination with the known genetic polymorphism of NAT2, may explain the clinical observation that the acetylation polymorphism constitutes a risk factor in the carcinogenic activation of environmental mutagens.     

Percutaneous needle trephination. Experience in 200 cases

Summary For many years percutaneous needle and classic burr-hole trephination with insertion of plastic catheters for external ventricular drainage are in use. The shortcomings of the conventional puncture needles were compensated for by the development of a modified instrument in recent years.In this prospective study we tried to define advantages and disadvantages of percutaneous ventriculostomy with this modified needle in a large number of patients. We treated and followed a total number of 200 patients with external ventricular drainage for various reasons (42% obstructive hydrocephalus, 27% haematocephalus, 11% malresorptive hydrocephalus, 11% elevated ICP and 9% infections). The ventriculostomy is performed — after percutaneous trepheication with a 1.5 mm drill and 1.2 mm needle under the local aesthesia as a bedside procedure. The modified blunt needle is provided with markings and a set screw which allows insertion to a prefixed depth and a sharp guide which is withdrawn after penetration of the dura. It is then bent rostrally and fixed by a plaster cast. The mean duration of drainage was 9 days (1–30 days). Mean operating time for the whole procedure including fixation and connection to the drainage system was 20 minutes. Overall complication rate was 13% (N=26). Two intracerebral haemorrhages (1%) occurred, of which one was caused by overdrainage. Five (3%) infections in primarily not infectious cases (N=182) were seen. Only one case of infection occurred without loosing of the needle on day 17. In 19 patients (10%) the needles had loosened. Fifteen times this complication was repaired in time and no infection occurred. The overall complication rate (13%) and the needle related risk of bleeding (0.5%) seem average. The true risk of infection with correct handling (0.5%) is very low despite the very long average duration of drainage. The main risk lies in the markedly high danger of loosening (10%), which entails a disproportionally high demand for nursing care. Nevertheless, we regard percutaneous needle trephination as the ventriculostomy method of choice because of its better practicability and low infection rate.     

RELATIONSHIP BETWEEN PLATELET CYTOSOLIC FREE CALCIUM CONCENTRATION AND PLASMA RENIN ACTIVITY

1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects. 2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject. 3. These results are consistent with the hypothesis that angiotensin II causes a concentration-dependent calcium mobilization.