Medizin - Open Access LMU - Teil 13/22 Archiv

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years.

Introduction: The treatment of Charcot neuroarthropathy in the feet of diabetic patients has undergone fundamental changes in the last few years. Formerly, treatment was almost exclusively limited to nonoperative measures; since the late 1990s, however, current practice has shifted to early, stage-appropriate surgical therapy. The objective of this prospective study was to investigate the value of two types of positron emission tomography (PET) in the preoperative evaluation of diabetic patients with Charcot foot deformities. Materials and Methods: Ring 18FFDG (2-fluoro-2-deoxy-glucose) and hybrid PET were compared to magnetic resonance imaging (MRI). MRI, ring PET, and hybrid PET imaging were used as part of the preoperative evaluation of 16 patients with type II diabetes mellitus. The diagnosis of Charcot neuropathy of the foot requiring operative treatment had been made on the basis of clinical and radiographic criteria. Results: Of 39 Charcot lesions confirmed at surgery, 37 were detected by ring PET, 30 by hybrid PET, and 31 by MRI. Conclusions: PET (ring or hybrid) can be used in the evaluation of patients with metal implants that would compromise the accuracy of MRI. Another advantage of PET is its ability to distinguish between inflammatory and infectious soft-tissue lesions, and between osteomyelitis and Charcot neuroarthropathy. The differentiation between Charcot neuroarthropathy and florid osteomyelitis provides the surgeon with important additional information that often is unavailable from MRI. Because it provides important additional data, ring PET may be preferable to radiography and MRI in the preoperative evaluation of patients with Charcot neuroarthropathy of the foot. Hybrid PET, because of its poorer resolution compared to ring PET, appears less suitable for routine clinical application.

Previous studies revealed changes of pericentromeric heterochromatin arrangements in postmitotic Purkinje cells (PCs) during postnatal development in the mouse cerebellum (Manuelidis, 1985; Martou and De Boni, 2000). Here, we performed vibratome sections of mouse cerebellum (vermis) at P0 (day of birth), at various stages of the postnatal development (P2-P21), as well as in very young (P28) and 17-months-old adults. FISH was carried out on these sections with major mouse satellite DNA in combination with immunostaining of the nucleolar protein B23 (nucleophosmin). Laser confocal microscopy, 3D reconstructions and quantitative image analysis were employed to describe changes in the number and topology of chromocenters and nucleoli. At all stages of postnatal PC development heterochromatin clusters were typically associated either with nucleoli or with the nuclear periphery, while non-associated clusters were rare (

The diagnosis of Creutzfeldt- Jakob disease (CJD) is still made by exclusion of other dementias. We now evaluated lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) as a possible additional diagnostic tool. CSF LDH levels of patients with CJD ( n = 26) were compared with those in other dementias ( n = 28). LDH isoenzymes were determined in a subset ( n = 9). Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients. We conclude that in addition to established CSF parameters, LDH and its isoenzymes might serve as a further help to discriminate between CJD and other dementias. Copyright (C) 2004 S. Karger AG, Basel.

Background: White matter hyperintensities (WMH) on MRI scans indicate lesions of the subcortical fiber system. The regional distribution of WMH may be related to their pathophysiology and clinical effect in vascular dementia (VaD), Alzheimer's disease (AD) and healthy aging. Methods: Regional WMH volumes were measured in MRI scans of 20 VaD patients, 25 AD patients and 22 healthy elderly subjects using FLAIR sequences and surface reconstructions from a three-dimensional MRI sequence. Results: The intraclass correlation coefficient for interrater reliability of WMH volume measurements ranged between 0.99 in the frontal and 0.72 in the occipital lobe. For each cerebral lobe, the WMH index, i.e. WMH volume divided by lobar volume, was highest in VaD and lowest in healthy controls. Within each group, the WMH index was higher in frontal and parietal lobes than in occipital and temporal lobes. Total WMH index and WMH indices in the frontal lobe correlated significantly with the MMSE score in VaD. Category fluency correlated with the frontal lobe WMH index in AD, while drawing performance correlated with parietal and temporal lobe WMH indices in VaD. Conclusions: A similar regional distribution of WMH between the three groups suggests a common (vascular) pathogenic factor leading to WMH in patients and controls. Our findings underscore the potential of regional WMH volumetry to determine correlations between subcortical pathology and cognitive impairment. Copyright (C) 2004 S. Karger AG, Basel.

Background: Molecular mechanisms regulating leukocyte sequestration into the tissue during endotoxemia and/or sepsis are still poorly understood. This in vivo study investigates the biological role of murine PECAM-1 and VCAM-1 for leukocyte sequestration into the lung, liver and striated skin muscle. Methods: Male BALB/c mice were injected intravenously with murine PECAM-1 IgG chimera or monoclonal antibody (mAb) to VCAM-1 ( 3 mg/kg body weight); controls received equivalent doses of IgG2a ( n = 6 per group). Fifteen minutes thereafter, 2 mg/kg body weight of Salmonella abortus equi endotoxin was injected intravenously. At 24 h after the endotoxin challenge, lungs, livers and striated muscle of skin were analyzed for their myeloperoxidase activity. To monitor intravital leukocyte-endothelial cell interactions, fluorescence videomicroscopy was performed in the skin fold chamber model of the BALB/c mouse at 3, 8 and 24 h after injection of endotoxin. Results: Myeloperoxidase activity at 24 h after the endotoxin challenge in lungs (12,171 +/- 2,357 mU/g tissue), livers ( 2,204 +/- 238 mU/g) and striated muscle of the skin ( 1,161 +/- 110 mU/g) was significantly reduced in both treatment groups as compared to controls, with strongest attenuation in the PECAM-1 IgG treatment group. Arteriolar leukocyte sticking at 3 h after endotoxin (230 +/- 46 cells x mm(-2)) was significantly reduced in both treatment groups. Leukocyte sticking in postcapillary venules at 8 h after endotoxin ( 343 +/- 69 cells/mm(2)) was found reduced only in the VCAM-1-mAb-treated animals ( 215 +/- 53 cells/mm(2)), while it was enhanced in animals treated with PECAM-1 IgG ( 572 +/- 126 cells/mm(2)). Conclusion: These data show that both PECAM-1 and VCAM-1 are involved in endotoxin-induced leukocyte sequestration in the lung, liver and muscle, presumably through interference with arteriolar and/or venular leukocyte sticking. Copyright (C) 2004 S. Karger AG, Basel.

Diagnosis and treatment of chronic lymphatic leukaemia (CLL) are currently undergoing great change. New knowledge of prognosis factors and the numerous new therapeutic procedures now available, such as purine analogues, high-dose treatment and monoclonal antibodies are making major contributions to this progress. As a consequence, the options for treatment of CLL are considerably more diverse now than a few years ago, and now include procedures that take into account age and risk. At the same time, it should be emphasized that many important questions regarding the treatment of CLL remain unresolved. It is anticipated that these questions will be answered over the coming few years by including patients in multicentre studies like those being carried out by the German CLL study group.

Background: Even today patients who suffer from mantle cell lymphoma have a poor prognosis, especially when the CNS is involved. To confirm the diagnosis of meningeosis lymphomatosa, asservation of the liquor cerebrospinalis is necessary. During this procedure, intrathecal chemotherapy may be given if there is clinical evidence of meningeosis. If lumbar puncture cannot be performed, a lateral suboccipital puncture may be an alternative approach. Patient and Methods: We report the case of a 65-year-old patient who suffered from mantle cell lymphoma stage IV. The patient presented with symptoms of progressive paraparesis of both legs and incontinence, with tumor mass intradural from the 12th thoracic vertebra to the level of S1. During irradiation, the patient developed symptoms of diffuse meningiosis lymphomatosa. The conventional lumbar puncture was impossible, because of tumor present in the thoracico-lumbar junction. Results: A suboccipital puncture was performed for both collecting cerebrospinal fluid and application of chemotherapy ( cytosine arabinoside/dexamethasone). This lead to remarkable improvement of the patient's clinical symptoms. Conclusion: The suboccipital cervical puncture was performed without complications. A variation of the intrathecal approach is described, which may serve as alternative when conventional lumbar puncture is not possible.