Long-term changes in the magnetic resonance image after chemonucleolysis

Summary After treatment of a symptomatic herniated disc with chymopapain, 14 patients were re-examined by magnetic resonance imaging (MRI) at a mean follow-up of 72 months. Well-defined MRI findings before chemonucleolysis were compared with those after the procedure by an independent observer. Five MRI parameters were assessed. No significant change was noted in the signal intensity of the affected disc, the extent of osteochondrosis and endplate reaction of the affected segment. The height of the affected disc as well as the size of the disc herniation were reduced significantly. The loss of the height is seen as a direct result of chymopapain activity, whereas the alteration of the size of the herniation seems to depend on the natural history of a disc herniation and is probably not a simple result of the treatment.     

Patterns of abnormal motor cortex excitability in atypical parkinsonian syndromes.

OBJECTIVE: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal-ganglionic degeneration (CBGD) are all clinically characterized by an akinetic-rigid syndrome together with a variety of additional signs. We hypothesised that these atypical parkinsonian syndromes (APS) will show distinctive patterns in their motor output upon transcranial magnetic stimulation (TMS) due to their different underlying anatomico-functional deficits. METHODS: We performed single and paired-pulse TMS and assessed inhibitory and excitatory response parameters from the first dorsal interosseus muscles in 13 patients with MSA, 18 with PSP, 13 with CBGD, 15 patients with Parkinson's disease and 17 healthy subjects. RESULTS: PSP and MSA patients had significantly enlarged response amplitudes at rest, reduced intracortical inhibition (ICI) and prolonged ipsi- and contralateral silent periods, whereas CBGD patients showed significantly increased motor thresholds, smaller response amplitudes at rest, shortened contralateral silent period, reduced transcallosal inhibition and a reduced ICI. In 22% of APS patients ipsilateral motor responses occurred in upper limb muscles irrespective of the underlying disease. CONCLUSIONS: Our results indicate that motor cortex disinhibition is predominant in patients with PSP and MSA. In CBGD more severe neuronal cell loss in the motor cortex itself may lead to hypoexcitability of corticospinal and transcallosal pathways.     

Low-dose endotoxin in allergic asthmatics: effect on bronchial and inflammatory response to cat allergen

BACKGROUND: Endotoxin was proposed to increase the severity of asthma. Endotoxin levels greatly differ according to settings. In domestic environments, airborne concentrations may be dramatically low compared with levels reported in occupational settings. OBJECTIVE: Our first objective was therefore to assess the effect of inhalation of low-level lipopolysaccharide (LPS) on the immediate and late-phase asthmatic bronchial response. Our second objective was to evaluate the effect of exposure to LPS on the local and systemic inflammatory response. METHODS: Nineteen asthmatics sensitized to cat underwent on two separate occasions a bronchial challenge test to cat allergen (cat BCT) preceded randomly by a pre-exposure to either saline or LPS (2 microg). Methacholine challenge test was performed 24 h before exposure to LPS or saline. The Borg scale for dyspnoea and lung function were recorded before and after exposure to LPS or saline, and before and after cat BCT. Induced sputum and blood samples were collected before and after cat BCT, and analysed for cell counts and eosinophil cationic protein (ECP) levels. RESULTS: Inhalation of 2 microg LPS did not induce any changes in forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), FEF 25-75 and Borg scale of dyspnoea. It neither modified Fel d 1 PD20 (45.03 ng as compared with 87.03; P=0.42). As well, there was no significant difference in late-phase reaction. Pre-exposure to LPS did not influence eosinophil counts or ECP levels in blood and sputum. CONCLUSION: Our study demonstrated that pre-exposure to LPS at low levels, which may be encountered in domestic environment, had no significant effect on the immediate and late-phase bronchial response to cat allergen. It neither modified local and systemic eosinophilic inflammation.     

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.