Bone marrow punctures and pain

We prospectively analysed pain in 263 patients induced by a frequent diagnostic procedure for oncologists, specifically the bone marrow puncture. Substantial pain (5 and more out of 10 on a numerical rating scale) was reported by 30.4% of patients, but physicians did not realize this procedure-related pain of patients in more than 50% of such punctures. The necessity for improved analgesia is emphasized by the fact, that at least 50% of patients experiencing substantial pain wished to receive concomitant medication in future punctures. Duration of the procedure was identified as sole independent predictive factor for patients’ pain intensity, while patients’ characteristics like gender, age and body-mass index (BMI) played only a minor role. As premedication with analgesics or anxiolytics may be associated with significant side-effects and an early identification of patients prone to experience severe pain is therefore difficult, further studies are warranted to establish an adequate approach in terms of pain control and feasibility in an ambulatory setting. In the meantime, daily physicians’ practice should be changed, as a pain-focused patient interview and presented indicators can be used in order to increase physicians’ awareness to procedure-related pain and augment their application of analgesics.     

Das Jo-1-Syndrom und seine klinischen Manifestationen

Namensgebend für das Jo-1-Syndrom sind Autoantikörper gegen das Jo-1-Antigen, die bei diesem Krankheitsbild im Serum der betroffenen Patienten nachgewiesen werden. Der Name Jo-1 leitet sich von dem ersten Patienten (John P.) ab, bei dem diese Antikörper gefunden wurden. Dieser Patient litt an einer Polymyositis und fibrosierenden Alveolitis. Das Jo-1-Antigen ist identisch mit der Histidyl-Transfer-RNA-Synthetase im Zytosol. Das Jo-1-Syndrom gehört zu einer Familie von Autoimmunerkrankungen, die als Anti-Synthetase- Syndrome bezeichnet werden. Diese Syndrome haben gemeinsam, dass jeweils Autoantikörper gegen unterschiedliche Aminosäure-Transfer-RNASynthetasen nachweisbar sind. Klinisch handelt es sich beim Jo-1-Syndrom um eine Sonderform der Poly- bzw. Dermatomyositis von bisher ungeklärter Ätiologie. Neben einer Muskelbeteiligung kommt es charakteristischerweise zu einer interstitiellen Lungenbeteiligung, die auch prognostisch das Krankheitsbild bestimmt. Zusätzlich können klinisch eine Polyarthritis und weitere Symptome bestehen, die dem klinischen Bild anderer Kollagenosen ähneln. Ebenso wie die Polymyositis und Dermatomyositis kann sich das Jo-1-Syndrom in sog. Myositis-Overlap-Syndromen präsentieren. Zu dieser Diagnose führt ein Symptomenkomplex, der die klare Zuordnung zu einer einzelnen Erkrankung nicht möglich macht. Häufig werden in solchen Fällen U1-RNP-Antikörper nachgewiesen. Therapeutisch spricht das Jo-1-Syndrom auf die Gabe von Kortikosteroiden und—falls notwendig—Azathioprin, Methotrexat und Cyclophosphamid an. Eine Kurzbeschreibung von zwei klinischen Fällen stellt das Krankheitsbild anschaulich dar.     

Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

TGF-beta promotes the establishment of renal cell carcinoma bone metastasis.

Bone metastases develop in approximately 30% of patients with RCC, and the mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1 stimulation of RCC bone metastasis cells promotes tumor growth and bone destruction possibly by stimulating paracrine interactions between tumor cells and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the specific mechanisms of RCC interaction with bone have been scarcely studied despite the inability to prevent or effectively treat bone metastasis. Bone is a reservoir for various growth factors including the pleiotropic cytokine TGF-beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced cancers and evidence suggests its involvement in promoting the development of breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1 in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF-beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and osteolysis was determined by histological and radiographic analysis, respectively, of athymic nude mice after intratibial injection of parental, empty vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF-beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells significantly reduced tumor establishment and osteolysis observed in vivo after injection into the murine tibia, although no effect on tumor establishment was observed after injection of RBM cells subcutaneously or into the renal subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth, suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo. CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor growth and subsequent osteolysis in vivo, likely through the initiation of tumor-promoting paracrine interactions between tumor cells and the bone microenvironment. These data suggest that inhibition of TGF-beta1 signaling may be useful in the treatment of RBM.     

The validity of a separate classification of cryptogenic localization related epilepsy amongst childhood epilepsies.

INTRODUCTION: One-third of children with epilepsy are classified as having a cryptogenic localization related epilepsy (CLRE). In cohort studies CLRE is often grouped together with either symptomatic localization related epilepsy (SLRE) or idiopathic generalized epilepsy (IGE). Therefore, this categorization is not specific enough and will not lead to prognostic or treatment information. We objectified the classification differences between these categories. METHODS: A total of 114 children admitted to our epilepsy centre underwent a standardized clinical analysis, which yielded age at onset, duration of the epilepsy, seizure frequency, seizure type, percentage of interictal epileptiform activity on EEG (IEA), type of treatment, and full scale IQ. These variables are regarded the characteristics of the epilepsy, and used in a discriminant function analysis. RESULTS: IEA was found to be the only variable to distinguish between groups of epilepsy. SLRE could easily be distinguished significantly from IGE and CLRE, while the latter two did not differ significantly. Discriminant function analysis combined the variables into two functions, applicable to classify the children. By applying this statistical analysis method, the groups clinically classified as SLRE and IGE were mostly classified as SLRE (71.4%) and IGE (57.9%). However, CLRE appeared difficult to classify (49.2%), and most children were classified as either SLRE (19%) or IGE (31.7%). CONCLUSION: The current opinion that CLRE is 'probably symptomatic' cannot be confirmed in all cases in this study. It is most likely that the current CLRE population consists of both children with eventually SLRE, as well as yet to be described syndromes to be classified as idiopathic epilepsies. We emphasize the need for separate studies regarding children with 'probably symptomatic' (cryptogenic) localization related epilepsy, as this will maximally help children, caretakers and treating physicians to achieve the best possible outcome.     

Corticomotoneuronal dysfunction in ALS patients with different SOD1 mutations.

OBJECTIVE: To examine corticomotoneuronal function in amyotrophic lateral sclerosis (ALS) patients carrying superoxide dismutase 1 (SOD1) mutations using peristimulus time histograms (PSTH). METHODS: Six I113T, 3 A4V, one G41D and one G114A patient were studied along with 21 healthy control subjects. Analyses included comparison with previously reported data from 8 D90A homozygous and 12 sporadic ALS (SALS) patients examined by the authors using identical methodology. RESULTS: Cortical threshold was significantly reduced in A4V patients (41.3%) compared to I113T (58%), SALS (57%) and D90A (71%) patients, as well as healthy controls (49.7%). Estimated excitatory postsynaptic potentials (EPSPs) were significantly larger in A4V patients (4.39 mV) compared to healthy controls (2.95 mV), I113T (2.71 mV) and SALS (2.39 mV) patients. Clinical features and PSTH parameters in I113T were similar to SALS, however, PSTH primary peaks (PP) were significantly more dispersed, 9.5 ms compared to 4ms in SALS. PSTHs from single G41D and G114A patients were unremarkable, apart from large EPSP amplitudes in the G114A patient. CONCLUSIONS: ALS patients with A4V and I113T SOD1 mutations have distinctive corticomotoneuronal changes that are different from those in D90A homozygous and SALS patients. SIGNIFICANCE: PSTH studies should be considered for future in vivo studies of SOD1 pathophysiology in ALS.     

New surface modification for Ti-6Al-7Nb alloy: oxygen diffusion hardening (ODH)

PVD-TiN coating and N+ implantation of Ti-6Al-7Nb alloy resulted in surface hardening to a depth of less 3 microns. The new oxygen diffusion hardening (ODH) treatment increased the hardness gradually to 50 microns. PUD-TiN showed an improvement in the tribological properties, while N+ implantation increased the PE wear rate. The wear rate of the ultrahigh-molecular-weight as well as the friction coefficient were reduced to one-half of the values achieved with the combination of CoCrMo-alloy when paired against the ODH-treated surface. In pairing with ZrO2-containing bone cement the ODH-treated surface showed only a minimal reaction.     

Nicardipine improves myocardial perfusion in systemic sclerosis

Primary scleroderma myocardial disease may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. We evaluated the effect of the calcium channel blocker nicardipine on myocardial perfusion assessed by thallium-201 scanning in 16 patients with systemic sclerosis. Thallium-201 single photon emission computerized tomography was performed at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SD) number of left ventricular segments with perfusion defects significantly decreased from 6.0 +/- 2.0 at baseline to 4.1 +/- 2.3 after nicardipine (p less than 0.01). The mean global perfusion score significantly increased from 10.2 +/- 1.9 at baseline to 11.9 +/- 2.6 after nicardipine (p less than 0.02). Our study demonstrates short-term improvement in thallium-201 myocardial perfusion with nicardipine in patients with systemic sclerosis.