Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia

Bone marrow and peripheral blood samples from 362 patients with acute lymphoblastic leukaemia (ALL) proliferating cell and 90 patients with acute myeloid leukaemia (AML) were analysed for S-phase fractions, Ki67 antigen, and proliferating cell nuclear antigen expression. The S-phase fractions were correlated with in vitro drug resistance to 15 different anticancer agents. Leukaemia cells isolated from bone marrow had higher S-phase fractions than leukaemia cells isolated from peripheral blood (in initial ALL, median values resp. 6.9 and 2.7%, in initial AML resp. 5.3 and 1.3%; both P<0.01). Relapse ALL samples derived from bone marrow showed increased S-phase fractions (median 9.9%) compared with initial ALL samples (median 6.9%; P<0.01). ALL samples obtained at initial diagnosis showed higher S-phase fractions (median 6.9%) and higher Ki67 expression (median 30%) than initial AML samples (median resp. 5.3 and 14%; both P<0.05). The S-phase fractions were not related to white blood cell count, age, or gender. Within initial ALL, the S-phase fraction correlated significantly but modestly strong (rho=0.3-0.5; P<0.05) with sensitivity to antimetabolites (cytarabine, mercaptopurine, thioguanine), L-asparaginase, teniposide, and vincristine. Similar results were found within subgroups of initial ALL (nonhyperdiploid and common/precursor-B-lineage ALL). In relapsed ALL and AML such correlations were not found. In conclusion, cell proliferation differs between leukaemia subgroups and increased proliferation is associated with increased in vitro sensitivity to several anticancer agents in initial ALL.     

Misplacement of a femoral venous catheter into the ascending lumbar vein: repositioning using ultrasonographic guidance

A 5-week-old infant with congenital chylothorax required long-term intravenous access for parenteral nutrition. Cannulation of the inferior vena cava via the left femoral vein was attempted, but the catheter was misplaced into the left ascending lumbar vein. Catheter removal is advised when such malposition is identified. We were able successfully to redirect the catheter into the inferior vena cava using ultrasonographic guidance. This procedure has not been described previously in children. We propose that repositioning of incorrectly placed vascular catheters can be achieved using ultrasound guidance at the bedside.     

Intra-operative tachycardia and peri-operative outcome

Background Intra-operative tachycardia is a common adverse event, often recorded as an indicator for process quality in quality assurance projects in anaesthesia.Methods This retrospective study is based on data sets of 28,065 patients recorded with a computerised anaesthesia record-keeping system from 23 February 1999 to 31 December 2000 at a tertiary care university hospital. Cases were defined as patients with intra-operative tachycardia; references were automatically selected according to matching variables (high-risk surgery, severe congestive heart failure, severe coronary artery disease, significant carotid artery stenosis and/or history of stroke, renal failure, diabetes mellitus and urgency of surgery) in a stepwise fashion. Main outcome measures were hospital mortality, admission to the intensive care unit (ICU) and prolonged hospital stay. Differences in outcome measures between the matched pairs were assessed by univariate analysis. Stepwise regression models were developed to predict the impact of intra-operative tachycardia on the different outcome measures.Results In our study 474 patients (1.7%) were found to have had intra-operative tachycardia. Matching was successful for 99.4% of the cases, leading to 471 cases and references. The crude mortality rates for the cases and matched references were 5.5% and 2.5%, respectively (P=0.020). Of all case patients, 22.3% were treated in an ICU, compared to 11.0% of the matched references (P=0.001). Hospital stay was prolonged in 25.1% of the patients with tachycardia compared to 15.1% of the matched references (P=0.001).Conclusions In this study, patients with intra-operative tachycardia who were undergoing non-cardiac surgery had a greater peri-operative risk, leading to increased mortality, greater frequency of admission to an ICU and prolonged hospital stay.Financial support for this study was provided in part by a grant from IMESO GmbH, Hüttenberg, Germany. The founding agreement ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the reportM. B. is a partner of the IMESO GmbH (Hüttenberg, Germany) and employee of the University Hospital of Giessen. None of the other authors or participants has any financial interest in the subject matter, materials, or equipment discussed, or in competing materialsA part of the results has been presented as a lecture at the 50th German Congress of Anaesthesiology (DAC 2003, 9–12 April) in Munich     

The renin-angiotensin system and progression of renal disease: from hemodynamics to cell biology

The renal community is faced with an ever increasing number of patients reaching end-stage renal failure. Clinical studies have provided clear evidence that angiotensin-converting enzyme (ACE) inhibitors, and probably also AT1 receptor antagonists, at least in patients suffering from type 2 diabetes, slow disease progression to end-stage renal failure. This protective effect of drugs interfering with the renin-angiotensin system (RAS) are in part independent of reduction in systemic blood pressure, but involve normalization of glomerular hyperperfusion and hyperfiltration, restoration of altered glomerular barrier function, and reduction of stimulated tubular fluid reabsorption. Angiotensin II (ANG II) has emerged in the last decade as a multifunctional cytokine exhibiting many non-hemodynamic properties such as acting as a growth factor and profibrogenic cytokine, and even having proinflammatory properties. This review tries to bridge the classical hemodynamic actions of ANG II in the kidney with the more recently characterized effects of this vasopeptide. Finally, clinical implications are suggested based on data from clinical studies. A thorough understanding of the RAS is important to recognize the potential of nephroprotective strategies through inhibition of its components.     

Nitric oxide synthase-positive neurons in the rat superior colliculus: colocalization of NOS with NMDAR1 glutamate receptor, GABA, and parvalbumin

We analyzed the potential input and output components of nitric oxide synthase (NOS)-containing neurons in the rat superior colliculus (SC). To identify whether NOS-positive neurons receive glutamatergic input we investigated the colocalization of NOS with NMDA receptor subunit R1 (NMDAR1). In addition, to examine whether putative nitric oxide synthesizing neurons represent a neurochemically specific or distinct subpopulation of cells in the SC we studied the colocalization of NOS with the neurotransmitter GABA, the calcium-binding proteins parvalbumin, calbindin and calretinin and with neuropeptides such as somatostatin, substance P and neuropeptide Y. We found that 90% of NOS-positive neurons in the superficial layers of the rat SC express NMDAR1. Nearly 20% of the population of nitridergic neurons also expresses GABA and 15% of them express parvalbumin. NOS-positive neurons in the superior colliculus did not contain calretinin, calbindin or either of the neuropeptides tested. The results of this study show that the capacity for synthesizing NO in the SC is largely restricted to neurons that receive glutamatergic inputs and that some of these neurons express GABA or parvalbumin.     

Long-term results of radiation synovectomy: a clinical follow-up study

Radiation synovectomy by intra-articular injection of beta-emitting radionuclides is a reliable and easy-to-perform therapy without harmful side effects for the treatment of inflammatory rheumatoid as well as degenerative joint diseases. The indication for radiation synovectomy is based on both clinical symptoms and on proven hyperperfusion, with active synovitis being seen on a pre-therapeutic three-phase bone scan. In this study, the clinical response after 6-18 months, evaluated by a standardized questionnaire, was compared with the reduction of synovitis seen on three-phase bone scintigraphy after treatment of 475 joints in 151 patients. The best clinical results were obtained in cases of true rheumatoid arthritis (73.4%), with less in other kinds of arthritis (48.8%) such as psoriatic or reactive arthritis. Because of the inflamed synovium being the main target tissue, clinical results in osteoarthritis with severe bone destruction are poorer (33.9%). However, synovitis can be markedly reduced (in approximately 70%), regardless of the underlying diagnosis, as shown by post-therapeutic three-phase bone scanning. Radiation synovectomy can be recommended in all kinds of arthritis. It should also be considered in cases of osteoarthritis as a last therapeutic option prior to joint replacement.     

PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas.

Imaging of somatostatin receptors (SSTRs) using [111In]diethylenetriaminepentaacetic-acid-octreotide (DTPAOC) has proven to be helpful in the differentiation of meningiomas, neurinomas or neurofibromas, and metastases as well as in the follow-up of meningiomas. A drawback of the SPECT method is its limited sensitivity in detecting small meningiomas. Because of PET's increased spatial resolution and its ability to absolutely quantify biodistribution, a PET tracer for SSTR imaging would be desirable. METHODS: 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic-acid-D-Phe1-Tyr3-octreotide (DOTATOC) was labeled using the positron-emitting generator nuclide 68Ga. We acquired dynamic PET images over 120 min after intravenous injection of 175 MBq [68Ga]DOTATOC in 3 patients suffering from 8 meningiomas (WHO I degrees; 7- to 25-mm diameter). Patients' heads had been fixed using individually shaped fiber masks equipped with an external stereotactic localizer system to match PET, CT, and MRI datasets. RESULTS: [68Ga]DOTATOC was rapidly cleared from the blood (half-life alpha, 3.5 min; half-life beta, 63 min). Standardized uptake values (SUVs) of meningiomas increased immediately after injection and reached a plateau 60-120 min after injection (mean SUV, 10.6). No tracer could be found in the surrounding healthy brain tissue. All meningiomas (even the 3 smallest [7- to 8-mm diameter]) showed high tracer uptake and could be visualized clearly. Tracer boundaries showed a good correspondence with the matched CT and MRI images. PET provided valuable additional information regarding the extent of meningiomas located beneath osseous structures, especially at the base of the skull. CONCLUSION: According to our initial experiences, [68Ga]DOTATOC seems to be a very promising new PET tracer for imaging SSTRs even in small meningiomas, offering excellent imaging properties and a very high tumor-to-background ratio.