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Biomedical subjects

C Beck

Publications and source records attributed to C Beck.

At least 19 recordsLinked to original sources

Successful autologous stem cell transplantation in a severely immunocompromised patient with relapsed AIDS-related B-cell lymphoma.

There is now evidence that the tolerability and response to systemic chemotherapy in HIV-infected patients with AIDS-related lymphoma (ARL) is significantly improved by highly active antiretroviral therapy. Here we report an severely immunocompromised AIDS patient with recurrent ARL who was successfully treated with autologous stem cell transplantation (ASCT). We also review the current literature of ASCT in HIV-infected patients.

Adult↗

Comparison of invasive and less-invasive techniques of cardiac output measurement under different haemodynamic conditions in a pig model.

BACKGROUND AND OBJECTIVE: Despite the introduction of various less-invasive concepts of cardiac output measurement, pulmonary arterial thermodilution is still the most common measurement technique. METHODS: This prospective controlled study was designed to compare different methods of cardiac output measurement simultaneously. Pulmonary arterial thermodilution, transpulmonary thermodilution (PiCCO), trans-oesophageal echo-Doppler probe (HemoSonic) and partial carbon dioxide rebreathing technique (NICO monitor) were evaluated against a peri-aortic transit-time flow-probe as reference method in a clinically relevant animal model. After approval from the Local Ethics Committee on Animal Research, the investigations were conducted in nine anesthetized domestic pigs. Systemic haemodynamics were modulated systematically by the application of catecholamines, caval occlusion and exsanguination. Statistical analysis was performed with Bland-Altman and linear regression. RESULTS: A total of 366 paired cardiac output measurements were carried out at a reference cardiac output between 0.5 and 7 L min(-1). The correlation coefficients for pulmonary arterial and transpulmonary thermodilution against reference were 0.93 and 0.95, for trans-oesophageal Doppler and partial rebreathing technique 0.84 and 0.77. Pulmonary arterial thermodilution and transpulmonary thermodilution showed comparable bias and limits of agreement. Where HemoSonic showed an overestimation of cardiac output at a higher precision, NICO overestimated low and underestimated higher cardiac output values. CONCLUSIONS: Our data suggest that pulmonary arterial thermodilution and PiCCO may be interchangeably used for cardiac output measurement even under acute haemodynamic changes. The method described by Bland and Altman demonstrated an overestimation of cardiac output for both thermodilution methods. HemoSonic and NICO offer non-invasive alternatives and complementary monitoring tools in numerous clinical situations. Trend monitoring and haemodynamic optimizing can be applied sufficiently, when absolute measures are judged critically in a clinical context. The use of the NICO system seems to be limited during acute circulatory changes.

Algorithms↗

Proliferation-based T-cell selection for immunotherapy and graft-versus-host-disease prophylaxis in the context of bone marrow transplantation.

Graft-versus-host disease (GvHD) caused by alloreactive T cells within the graft is a major drawback of allogeneic BMT, but depletion of T cells leads to higher rates of relapse, opportunistic infections and graft failure. Therefore, selective removal of GvHD-inducing alloreactive T cells might be beneficial. We describe here the separation of alloresponsive T cells, based on carboxyfluorescein succimidyl ester labeling, in vitro allostimulation and FACS-sorting. In vivo effects of the separated cell populations were investigated in the context of allogeneic BMT in murine models: in vitro resting T cells were shown to survive in the allogeneic host and retain immunoreactivity against 'third-party' antigens. As demonstrated in two different transplantation models, elimination of proliferating cells significantly reduces GvHD but offers no advantages to using T-cell-depleted bone marrow alone concerning engraftment and tumor control. Transplanting T cells that proliferate in response to tumor antigens in vitro may narrow down the spectrum of antigens recognized by T cells and therefore reduce GvHD while maintaining graft-facilitating function and tumor control. Therefore, selecting tumor-reactive T cells on the basis of their proliferative response in vitro may be beneficial for the recipient, less time consuming than T-cell cloning and still reduce the extent of GvHD.

Animals↗

Myelodysplastic syndrome of donor origin subsequent to successful treatment of myeloid/NK-cell precursor leukaemia with allogeneic PBSCT: two very rare conditions in one patient.

We report a 36-year-old male with myeloid/natural killer (NK)-cell precursor acute leukaemia with a complex aberrant karyotype, who was treated according to an acute-myeloid-leukaemia (AML) treatment protocol (idarubicine, cytarabine, and etoposide) followed by high-dose cytarabine consolidation and achieved complete remission. He underwent allogeneic matched unrelated donor (MUD) peripheral blood stem-cell transplantation (PBSCT) and remained in remission throughout his remaining life. Seven months posttransplantation, a myelodysplastic syndrome (MDS) with (20q-) of donor origin was diagnosed causing severe thrombocytopenia and finally leading to infection and death. This patient represents one of the few cases published achieving remission for a significant period of time after being diagnosed with myeloid/NK-cell precursor acute leukaemia, a very rare malignant disease. We conclude, despite the fatal outcome due to infection, that allogeneic PBSCT is a therapeutic option for patients with this entity. In addition, the development of a myelodysplastic syndrome of donor origin is extremely rare and only very few cases are published worldwide.

Acute Disease↗

Activated sludge wastewater treatment plants optimisation to face pollution overloads during grape harvest periods.

The principal objective of our study was to optimise a municipal activated sludge wastewater treatment plant (WWTP) to face high organic flows due to viticulture effluents inputs. Treatment file optimization consisted in testing different treatment lines, changing the number and volume of biological basins and clarifiers, with or without a buffer basin upstream, with a view to achieving a better reduction of COD. The actual WWTP biological stage is composed of two aerated basins whose total volume is 1365 m3. The studied cases are successively, the installation of a single basin of 1365 m3, then of several basins whose total volume remains constant and equal to 1365 m3. Another case was also considered, that of an aerated basin followed by a first clarifier and then, by another aerated basin and a second clarifier. All scenarios presented below were evaluated, for standard dry weather conditions and for high organic load conditions, as encountered during the grape harvest period. The method used was to carry out various simulations, using numerical modelling, and to compare the impact of different process line scenarios and management strategies on the activated sludge WWTP efficiencies.

Agriculture↗

Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1.

Matrix metalloproteinase 19 (MMP-19) is able to process various proteins of the basement membrane. To investigate the impact of MMP-19 activity on endothelial cells in the context of tumor extracellular matrix (ECM), we treated Matrigel matrix with an active recombinant MMP-19 and analyzed its effect on capillary-like formation. Human microvascular endothelial cells (HMEC-1) could not form capillary-like formation on Matrigel treated with recombinant MMP-19. Analyzing the Matrigel proteins, we found that MMP-19 preferentially cleaved nidogen-1. The cleavage site of nidogen-1 was mapped to Thr867-Leu868. This cleavage separates the G3 globular domain containing the binding site for the gamma1 chain of laminin-1 and collagen IV and thus abolishes the capacity of nidogen-1 to cross-link ECM proteins. Anti-nidogen antibodies directed against the G3 domain of nidogen-1 inhibited the capillary-like structure formation to a similar extent as MMP-19. Since nidogen-1 is thought to stabilize microvessels, MMP-19 might be one of the enzymes that interferes with stabilization or maturation of nascent vasculature.

Cell Division↗

[Designer-drugs in tumor treatment].

Targeted approaches to treat malignant diseases in hematology and oncology based on the molecular basis of the disease represent a major breakthrough in modern medicine. Knowledge acquired in basic sciences such as functional understanding of products generated by chromosomal translocations, definition of surface molecules or molecular requirements of tumor-cell survival allow to specifically aim at the cause of or at a requirement for malignancy. This is in sharp contrast to conventional chemotherapy which mainly influences the ubiquitous pathways of nucleic acid metabolism and cell division. In addition to superior efficacy of these approaches one should-on the long run-expect a superior profile of side effects compared to standard regimens. These "designer-approaches" are mainly based on small molecules or monoclonal antibodies. Out of the broad spectrum of current concepts we would like to summarize some of the strategies that have already found their way from bench to bedside.

Animals↗

Escalation/de-escalation patterns of behavioral symptoms of persons with dementia.

Behavioral and psychological symptoms of dementia (BPSD) may be framed within the Needs Driven Dementia-Compromised Behavior (NBD) Model. Current literature suggests that BPSD may escalate. Several researchers have described a sequence of behavioral escalation that has a clear starting point and ending point. This 'ideal' or concatenated sequence is used to explain behavior that begins with relatively calm behavior and progresses through a prescribed sequence of behaviors that end in violence. This article presents two studies, a descriptive study and an intervention study that examine the escalation and de-escalation patterns of BPSD. Results of the descriptive study indicate a dominant pattern of agitation, aggression, and agitation while results of the intervention study, using sequential analysis indicate persistence of behavior from one 20-minute period to another. The persistence of vocalization at intensity level 2 changed from pre-intervention (mean conditional probability 29%) to post-intervention (mean conditional probability 13%). Taken together these studies shed light on the pattern of escalation and de-escalation of BPSD and suggest an intervention to alter behavior persistence. This article discusses methodological challenges of measuring the escalation and de-escalation of BPSD and offers suggestions for analysis and design such as time series and sequential analysis.

Aged↗

Effect of recombinant human deoxyribonuclease on the expression of cell adhesion molecules of thawed and processed cord blood hematopoietic progenitors.

BACKGROUND AND OBJECTIVES: The integrity of granulocytic cells and platelets is compromised within cryopreserved stem cell transplants, and consequent DNA release during the thawing procedure can therefore lead to clotting phenomena or microaggregate formation and that in turn may cause loss of progenitor cells. To circumvent this problem a new processing protocol was introduced using recombinant human deoxyribonuclease (rhDNase) to prevent cell aggregate formation. In addition, the impact of this new processing protocol on CD34+ umbilical cord blood (UCB) cells was assessed. MATERIALS AND METHODS: Fifty samples derived from 7 buffy coat (BC) volume reduced UCB units were cryopreserved, thawed, and processed with washing solutions that were supplemented with rhDNase in various concentrations. Thereafter, clotting and microaggregate formation was scored microscopically. In addition, expression of the adhesion molecules leukocyte function-associated antigen 1 (LFA-1, n = 6), intercellular adhesion molecule-1 (ICAM-1, n = 11), and L-selectin (n = 11) on CD34+ UCB cells was analyzed by flow cytometry after incubating the samples with either dimethyl sulfoxide (DMSO) 5.5%, rhDNase 10 or 50 U/mL, or a combination of DMSO 5.5% and rhDNase 50 U/mL. RESULTS: At a minimal concentration of 10 U rhDNase/mL, clotting or microaggregate formation could be prevented for all tested samples, whereas cell clots could be observed for concentrations up to 8 U/mL. The expression of adhesion molecules on untreated CD34+ UCB cells (L-selectin: 64.6 +/- 18.8%; LFA-1: 62.6 +/- 7.5%; ICAM-1: 14.8 +/- 4.1%) did not show any significant difference compared with cells that were incubated with up to 50 U/mL rhDNase (L-selectin: 62.2 +/- 19.3%; LFA-1: 63.1 +/- 5.9%; ICAM-1: 17.5 +/- 6.7%). However, after a combined treatment with DMSO 5.5% and rhDNase 50 U/mL, a slight but significant decrease in L-selectin expression could be observed (P < 0.03). CONCLUSION: The supplementation of rhDNase to a final concentration of 10 U/mL cell suspension proved to be effective in preventing clot formation under the conditions examined and did not lead to decreased expression levels of adhesion molecules. We therefore recommend the use of rhDNase for the prevention of clot formation and cell loss during the processing of thawed UCB transplants.

Antigens, CD34↗

Renal dysplasia and urinary tract infection in a Bull Mastiff puppy.

Renal dysplasia and concurrent pyelonephritis were diagnosed in a 15-week-old female Bull Mastiff which presented with clinical signs compatible with chronic renal failure. Ultrasound examination was consistent with renal dysplasia and clinical pathology supported a diagnosis of chronic renal failure and urinary tract infection. Renal histological examination demonstrated inflammation and scarring with concurrent tubular dysplasia and persisting primitive glomeruli, although the presence of chronic inflammation complicated interpretation. It is uncertain whether renal dysplasia was inherited or due to a urinary tract infection acquired in the neonatal period. Renal dysplasia has not previously been reported in the Bull Mastiff breed.

Animals↗

Use of recombinant human deoxyribonuclease (DNase) for processing of a thawed umbilical cord blood transplant in a patient with relapsed acute lymphoblastic leukemia.

This case report describes for the first time the use of a recombinant human enzyme deoxyribonuclease (rhDNase) containing solution for the processing of a thawed umbilical cord blood (UCB) unit prior to successful transplantation to avoid cell losses by clotting phenomena. A 6-year-old boy received an unrelated 2/6 HLA antigen mismatched UCB transplant for high-risk Burkitt type acute lymphoblastic leukemia. The UCB unit was provided as a volume-reduced sample after buffy coat separation with a final volume of 36 ml. To avoid the loss of nucleated cells due to cell clumping during thawing procedure cells were washed with a solution containing the rhDNase. No visible clotting of the resuspended unit occurred, and the patient was transplanted with 2.9x10(7) nucleated cells/kg body weight without any acute or chronic side effects due to rhDNase. On day +35, PCR analysis of bone marrow aspirate showed complete chimerism, and the child engrafted with an absolute neutrophil count greater than 0.5x10(9)/l on day +47. Platelet transfusion independence was achieved on day +120. In conclusion, the supplementation of rhDNase to the washing and resuspension solutions of a thawed UCB unit is effective to prevent cell losses prior to transplantation. However, further investigations must be performed to confirm the safety of this procedure.

Blood Transfusion↗

Reported practices of primary care physicians in the diagnosis and management of dementia.

The shortage of geriatric specialists in the US may require that primary care physicians (PCPs) receive more education on diagnosing and managing dementia since the number of older Americans with dementia will increase from about five million in 2010 to up to 14 million in 2050. Thus, we administered a brief, anonymous questionnaire to determine PCPs' diagnostic, referral, and management practices to a convenience sample of 142 PCPs in Arkansas. We reworded a Scottish survey to conform to terminology used in the US and added items on referral practices. The PCPs who reported difficulty establishing the diagnosis of dementia had more difficulty telling the diagnosis (O.R = 3.59, p < 0.004). The PCPs were less likely (p < 0.001) to tell the patient if they suspected dementia (73%) than if they were sure the patient had dementia (88%). In both cases, they were more likely to tell the family (92% & 100%, respectively), although this difference was not statistically significant. The PCPs discussed disease progression and driving risks with patients and families, but few referred them to social workers or community agencies. Findings support training PCPs in the diagnosis and management of persons with dementia and providing tools to improve care.

Arkansas↗

Clinical findings in patients presenting with sore throat. A study on inter-observer reliability.

BACKGROUND: Several clinical prediction scores have been developed to help practitioners assess the probability of streptococcal throat infection. Prior to this study, it was not known how reliably doctors assess the signs that contribute to these decision aids. OBJECTIVE: The aim of this study was to measure the inter-observer reliability of clinical findings related to sore throat. METHODS: Consecutive patients presenting with sore throat in five primary care practices in Germany took part (n = 126). Each patient was assessed independently by two doctors with regard to lymph nodes, pharynx, soft palate and tonsils. RESULTS: Agreement among practitioners was not satisfactory. CONCLUSIONS: Results suggest that the performance of clinical scoring systems can be improved by training on how to elicit relevant clinical signs. Our findings cast some doubt on the effectiveness of under- and post-graduate training in this area.

Child, Preschool↗

Exophthalmos due to a wooden foreign body in a dog.

An 8-year-old Golden Retriever dog was presented with a 10-month history of right-sided exophthalmos. Radiographs and CT demonstrated a linear density, suggestive of a foreign body, in the region of the ramus of the right mandible. A 7 cm stick, located medial to the right zygomatic arch, was removed during exploratory surgery. The dog recovered with the aid of antibiotics, however was left with a residual facial nerve paralysis.

Animals↗