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At least 1,657 records · Page 92Linked to original sources
PubMed1995

Comprehensive review: neuromuscular blocking agents in critical care.

Administration of neuromuscular blocking agents (NMBAs) in critical care units has become tremendously controversial. The increased use of these agents without a defined indication or research base has resulted in dangerous and costly complications and serious concerns. Areas of controversy include mounting adverse effects (especially prolonged paralysis and weakness from long-term overdosing), an inconsistent and deficient knowledge base among all levels of health care professionals, inadequate concurrent sedation and analgesia, and a lack of effective monitoring to ensure the lowest possible doses. There is a great need for research to define the practice and protocols that would optimize safe and efficacious use. Pharmacologic paralysis should be restricted to a very specific patient population after careful evaluation, and therapy should be discontinued at the earliest possible time. Chemical paralysis can be a safe and effective therapy for a select few patients when judicious care, multidisciplinary efforts, and prevention of adverse effects minimize the complications, growing costs, and unintended suffering.

Critical Care↗
PubMedDate not supplied

Perceptual capabilities with the cochlear implant: implications for aural rehabilitation.

While the cochlear implant provides only limited auditory information, profoundly deaf children continue to show significant gains in hearing performance and speech production abilities. The evidence has indicated that children receiving consistent auditory training demonstrate more progress with the implant than those children in less auditory-type environments. As a result, the House Ear Institute is developing extended training protocols to help optimize implant performance. A three-component framework is detailed to include: (1) the production/perception model, (2) a comprehension/bottom-up approach, and (3) strategical methods of delivery (multisensory versus unisensory). The purpose of such development is to integrate "hearing" into home, classroom, and individualized therapy settings to better facilitate growth in listening skills and speech development within a psycholinguistic context.

Achievement↗
PubMedDate not supplied

Three-dimensional helical CT of intrahepatic venous structures: comparison of three rendering techniques.

OBJECTIVE: To define the advantages and disadvantages of various rendering techniques to obtain three-dimensional (3D) displays of intrahepatic venous structures with helical CT data. MATERIALS AND METHODS: After rapid preprocessing segmentation of the liver, helical CT data (8 mm slice thickness overlapped every 4 mm) from 10 patients were reconstructed using maximum intensity projection (MIP), volume rendering, and surface rendering algorithms. Three-dimensional imaging was evaluated blindly and independently by three observers for presence of artifacts and overall quality. RESULTS: Three-dimensional displays showed the hepatic veins and fifth order portal branches with the volume and MIP rendering techniques. Best overall quality in the 3D representation of the liver was achieved with the MIP technique (p < 0.05). Small details in venous anatomy and portal involvement by tumor were better imaged with the MIP technique. "Stair-step" artifacts markedly degraded the 3D displays obtained with the surface rendering technique, making it inappropriate for imaging the intrahepatic venous structures. CONCLUSION: Maximum intensity projection appears to be an adequate technique to perform 3D imaging of intrahepatic venous structures with helical CT data when 8 mm slice thicknesses overlapping every 4 mm are used. However, optimization of imaging protocols needs to be done and compared in a larger series.

Aged↗
PubMed1983

Renal allograft survival in the baboon using a pretreatment protocol with cyclosporine.

Cyclosporine extends kidney allograft survival in the chacma baboon, and this study explores various administration protocols to generate optimal serum concentrations of the drug, assessed by radioimmunoassay and by inhibition of lymphocyte transformation by phytohemagglutinin and allogeneic lymphocytes in culture. Serum levels commensurate with concentrations that have been shown to be immunosuppressive in humans (150-400 ng/ml) are reached after 14 days of pretreatment with 10 mg cyclosporine/kg, and after 7 days with 20 and 30 mg cyclosporine/kg. The 10-mg dose prolongs median graft survival from 11 to 21 days, which is the same as that obtained with 20 mg/kg administered after transplantation. Further increases in the pretreatment dose to 20 or 30 mg/kg result in survivals of 27 and 31 days, respectively. All the animals died from rejection during therapy and the T-cell-binding avidity, and absorptive or degradative processes may necessitate doses far in excess of those currently used in transplantation.

Absorption↗
PubMed2003

Liquid-based pap smears as a source of RNA for gene expression analysis.

The Papanicolaou smear has contributed to a decrease in cervical cancer rates in populations that receive regular screening. However, treatment of women with mildly abnormal cells is problematic because the majority of these women do not develop neoplasia. Thus, new techniques for identification of truly precancerous cells are needed. Characterization of cellular gene expression patterns is now possible through microarray techniques that survey the expression of large numbers of genes simultaneously. Here we have assessed the feasibility of combining new microscopic and molecular technologies to determine gene expression patterns in cervical intraepithelial neoplasia grade 3 cells recovered from liquid cytology-based Papanicolaou smear slides. Laser capture microdissection was used to retrieve cervical cells from ThinPrep prepared slides. The quality of RNA recovered from these cells proved suitable for reverse transcription polymerase chain reaction and for T7 RNA polymerase-based linear amplification of messenger RNA. We developed an optimized RNA amplification protocol that permitted microarray gene expression profiling in samples of as few as 20 cervical cells. This approach combining laser capture microdissection, linear RNA amplification, and microarray gene expression analysis will enable comparison of gene expression patterns between cytologically abnormal and normal cells taken from a single slide and may assist in the differential diagnosis of histologically difficult cases.

Biomarkers↗
PubMed2004

Sedation with ketamine during intradiscal electrothermal therapy.

STUDY DESIGN: A technical report. OBJECTIVES: To present a new and improved method to sedate patients during intradiscal electrothermal therapy (IDET). SUMMARY OF BACKGROUND DATA: The current standard of practice is to sedate patients with short-acting benzodiazepines and opioids during the coagulation phase of intradiscal electrothermal therapy. There are few data on the subject, but it is estimated that between 5% and 20% of IDET procedures are either aborted early or switched to a lower heating temperature because patients cannot tolerate the optimal, recommended heating protocol. A priori, one must assume these patients are more likely to fail their treatment than those who are able to tolerate complete heating. METHODS: The authors treated 9 patients receiving intradiscal electrothermal therapy who were unable to tolerate the latter portion of their heating protocol secondary to axial low back pain despite high doses of opioids, with low dose ketamine. This paper outlines our experience with "rescue" doses of ketamine, along with the rationale and guidelines for its use. RESULTS: After receiving ketamine, all patients were able to complete the full intradiscal electrothermal therapy heating protocol. The rescue dosages of ketamine ranged from 15 to 55 mg. The dosages of midazolam used to prevent the psychomimetic effects of ketamine ranged from 3 to 7 mg. Oxygen saturation and hemodynamic parameters did not change significantly after ketamine was administered, and all patients remained responsive throughout the procedure. There were no adverse effects or complications reported. CONCLUSIONS: When used judiciously to treat axial back pain during intradiscal electrothermal therapy heating, ketamine is a safe and effective rescue medication.

Adult↗
PubMed2004

Consistent immunostaining for cyclin D1 can be achieved on a routine basis using a newly available rabbit monoclonal antibody.

Rabbit monoclonal antibody (MAb), which has become available only recently, theoretically combines the advantage of the high affinity attributable to its rabbit origin and the high specificity due to its monoclonal nature. Since immunohistochemical demonstration of cyclin D1 is notoriously difficult, this study aims to assess whether a newly available rabbit MAb against cyclin D1 (SP4) can improve the consistency of immunostaining, especially for the diagnosis of mantle cell lymphoma (MCL). A total of 150 cases of lymphoproliferative lesions, including 30 cases of MCL, histologic mimickers of MCL, and various types of lymphomas and leukemias, were studied. Immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections using a labeled streptavidin-biotin peroxidase system in an automated immunostainer. All cases of MCL expressed cyclin D1, with a higher median staining score (8 out of a maximum of 12) compared with mouse MAb DCS-6 (score 4). In addition, 2 of 15 cases of B-cell chronic lymphocytic leukemia (B-CLL), 3 of 12 cases of multiple myeloma, and 2 of 5 cases of hairy cell leukemia were also positive. Comparable staining results could also be achieved by an optimized manual staining protocol. This study thus confirms the superior performance of the rabbit MAb SP4, which should permit consistent immunostaining for cyclin D1 to be readily achieved. The value of cyclin D1 immunohistochemistry in the differential diagnosis of MCL from other low-grade B-cell lymphomas is also affirmed, but with the caveat that rare cases of B-CLL can also be cyclin D1 positive.

Animals↗
PubMedDate not supplied

Trabecular bone structure obtained from multislice spiral computed tomography of the calcaneus predicts osteoporotic vertebral deformities.

PURPOSE: To compare multislice computed tomography (MSCT)-derived parameters of the trabecular bone structure of the calcaneus with bone mineral density (BMD) in their ability to differentiate between donors with and without osteoporotic fractures of the spine and to optimize CT scan protocols. METHODS: Forty-two postmortem calcanei (81.2 +/- 10 years) were imaged with a 16-detector row MSCT system using 4 different scan protocols varying spatial resolution (12-24 lp/cm) and radiation dose. Structural parameters of trabecular bone were derived from these images, and BMDs of the calcanei were determined using dual x-ray absorptiometry. Vertebral deformities of the spine were radiographically classified using the Spinal Fracture Index. Diagnostic performance in differentiation between donors with and without vertebral fractures was assessed using receiver operating characteristic (ROC) analysis. RESULTS: There were significant case-control differences for many of the structural parameters measured (P < 0.05). The highest ROC values were found for apparent trabecular thickness using the high-resolution and high-dose protocols. Statistically significant correlations were found between most structure parameters and BMD (up to r = 0.85, P < 0.01). CONCLUSION: Structural parameters of trabecular bone as obtained from high-resolution MSCT images of the calcaneus can be used to differentiate between donors with and without osteoporotic vertebral fractures, using a high-resolution and high-dose CT protocol.

Absorptiometry, Photon↗
PubMed1994

Computing genetic similarity coefficients from RAPD data: the effects of PCR artifacts.

Random amplified polymorphic DNA (RAPD) markers have been used for many types of genetic analyses, including genome mapping, genotype fingerprinting, phylogeny reconstruction, and measuring genetic similarities. They suffer from one potential limitation, however, because the PCR that is used to produce informative amplification products often produces artifactual products as well. Optimization of PCR protocols to eliminate artifactual bands completely is often too costly or too time-consuming to be practical. Other methods for handling RAPD artifacts, such as deleting inconsistent or faint bands or using only those bands that are reproducible, introduce false negatives into the data. Simply ignoring artifacts and using all bands introduces false positives. When RAPD data are used to compute genetic similarity coefficients, such artifacts can cause significant bias in the estimation. The three coefficients most widely used with RAPD data, the simple matching coefficient, Jaccard's coefficient and Nei and Li's coefficient, differ in the amount of bias produced by a given level of artifactual bands. The simple matching coefficient and Nei and Li's coefficient always exhibit less percent bias than Jaccard's coefficient. For closely related organisms, Nei and Li's coefficient displays less percent bias than the simple matching coefficient. If new DNA samples possessing RAPD markers not present in the previously analyzed samples are added to a study, values of the simple matching coefficient will need to be computed for all samples, not just the new ones. Jaccard's and Nei and Li's coefficients, however, will not need to be recomputed. Furthermore, only Nei and Li's coefficient has a direct biological meaning (it is an estimate of the expected proportion of amplified fragments shared by two samples because they were inherited from a common ancestor). On the basis of these results, Nei and Li's coefficient is recommended for routine computation of genetic similarities using RAPD data, particularly if PCR artifacts are present.

Artifacts↗
PubMed2003

In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling.

Applications of microarray technologies to mouse embryology/genetics have been limited, due to the nonavailability of microarrays containing large numbers of embryonic genes and the gap between microgram quantities of RNA required by typical microarray methods and the miniscule amounts of tissue available to researchers. To overcome these problems, we have developed a microarray platform containing in situ-synthesized 60-mer oligonucleotide probes representing approximately 22,000 unique mouse transcripts, assembled primarily from sequences of stem cell and embryo cDNA libraries. We have optimized RNA labeling protocols and experimental designs to use as little as 2 ng total RNA reliably and reproducibly. At least 98% of the probes contained in the microarray correspond to clones in our publicly available collections, making cDNAs readily available for further experimentation on genes of interest. These characteristics, combined with the ability to profile very small samples, make this system a resource for stem cell and embryogenomics research.

Animals↗
PubMed2006

Complete deterministic linear optics Bell state analysis.

We show how hyperentanglement allows us to deterministically distinguish between all four polarization Bell states of two photons. In this proof-of-principle experiment, we employ the intrinsic time-energy correlation of photon pairs generated with high temporal definition in addition to the polarization entanglement obtained from parametric down-conversion. For the identification, no nonlinear optical elements or auxiliary photons are needed. The new possibilities this complete Bell measurement offers are demonstrated by realizing an optimal dense coding protocol.

Journal Article↗
PubMed2006

Squeezed-state purification with linear optics and feedforward.

A scheme for optimal and deterministic linear optical purification of mixed squeezed Gaussian states is proposed and experimentally demonstrated. The scheme requires only linear optical elements and homodyne detectors, and allows the balance between purification efficacy and squeezing degradation to be controlled. One particular choice of parameters gave a tenfold reduction of the thermal noise with a corresponding squeezing degradation of only 11%. We prove optimality of the protocol, and show that it can be used to enhance the performance of quantum informational protocols such as dense coding and entanglement generation.

Journal Article↗
PubMed2005

Optimum in vitro expansion of human antigen-specific CD8 T cells for adoptive transfer therapy.

Increasing evidence suggests that adoptive transfer of antigen-specific CD8(+) T cells could represent an effective strategy in the fight against chronic viral infections and malignancies such as melanoma. None the less, a major limitation in the implementation of such therapy resides in the difficulties associated with achieving rapid and efficient expansion of functional T cells in culture necessary to obtain the large numbers required for intravenous infusion. Recently, the critical role of the cytokines interleukin (IL)-2, IL-7 and IL-15 in driving T cell proliferation has been emphasized, thus suggesting their use in the optimization of expansion protocols. We have used major histocompatibility complex (MHC) class I/peptide multimers to monitor the expansion of antigen-specific CD8 T lymphocytes from whole blood, exploring the effect of antigenic peptide dose, IL-2, IL-7 and IL-15 concentrations on the magnitude and functional characteristics of the antigen-specific CD8(+) T cells generated. We show here that significant expansions of antigen-specific T cells, up to 50% of the CD8(+) T cell population, can be obtained after a single round of antigen/cytokine (IL-2 or IL-15) stimulation, and that these cells display good cytolytic and interferon (IFN)-gamma secretion capabilities. Our results provide an important basis for the rapid in vitro expansion of autologous T cells from the circulating lymphocyte pool using a simple procedure, which is necessary for the development of adoptive transfer therapies.

Adoptive Transfer↗
PubMed1995

Failure of complete suppression of endogenous glucose production by euglycaemic hyperinsulinaemia in normal humans.

In normal subjects, endogenous glucose production (EGP) is usually assumed to be completely suppressed during euglycaemic clamp studies performed at high insulin levels (> 100 mU L-1). However, this assumption is based on non-steady-state tracer measurements of EGP which are prone to negative errors. We have used purified [6-(3)H]glucose in an optimal tracer infusion protocol to assess the suppression of EGP during 4 h euglycaemic clamps in eight normal men. An insulin infusion rate of 5 mU kg-1 min-1 was chosen to achieve supraphysiological (> 500 mU L-1) plasma insulin concentrations. Using a labelled exogenous glucose infusion, plasma glucose (mean +/- SEM 5.3 +/- 0.1 mmol L-1) and glucose specific activities (mean 100 +/- 3% of basal) were maintained constant from 80 to 240 min. During hyperinsulinaemia, isotopically determined glucose appearance rates (Ra) were greater than glucose infusion rates (GIR) throughout the euglycaemic clamp period (P < 0.001) and EGP (Ra-GIR) was always greater than zero. In seven of the eight subjects studied EGP was partly suppressed but showed a wide variation (EGP 5 to 91% of basal at 80-120 min and 12 to 87% of basal at 200-240 min) while in one subject EGP rose above basal (by 72% at 80-120 min and 49% at 200-240 min). We conclude that EGP is not completely suppressed during euglycaemic clamps at high insulin levels.

Adult↗
PubMed1992

Highly efficient transfection of mammalian cells by electric field pulses. Application to large volumes of cell culture by using a flow system.

We have transfected mammalian cells with plasmid DNA by application of electric pulses. Chinese hamster ovary cells were chosen as a model in order to study and to optimize the transfection protocol. A plasmid carrying the gene coding for beta-galactosidase activity was used to determine transient expression of the electrotransferred activity at the cell level. Optimum transient expression for cells in suspension was obtained by application of 10 square wave pulses of 5-ms duration and 0.6-kV/cm intensity. Under the best conditions, transfection frequencies as high as 50-60% could be obtained and appeared to be highly dependent on the age of the cell culture. The method was applicable to plated cells growing in a petri dish or on microcarriers. The possibility of extension of the technique to large volumes of cells is presented. A flow system, composed of a peristaltic pump connected to the electropulser chamber, allowed large volumes of cells to be treated with flow rates in the order of several milliliters/minute. Transfection frequencies for the large volumes were 25% for cells in suspension and 35% for cells on microcarriers. These results open new perspectives in large-scale transfection technology of cells however they are grown.

Animals↗
PubMed1996

Pros-Eight transurethral radiofrequency thermotherapy for benign prostatic hyperplasia: preliminary clinical results.

BACKGROUND: We have developed a new transurethral thermotherapy device using 8MHz radiofrequency (RF) for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). We report the safety and effectiveness of the initial clinical experience with this device. METHODS: Sixty patients with symptomatic BPH were subjected to a single 1-hour treatment under local anesthesia. The treatment device uses extracorporeal RF capacitive heating in combination with radiative heating and conductive cooling of the urethra. RESULTS: In the 49 patients evaluable at 3 months, the mean International Prostate Symptom Score decreased from 17.8 to 13.1 (P < 0.0001) and the Quality of Life score decreased from 4.4 to 3.4 (P < 0.0005). Maximum flow rate increased from 8.1 to 9.7 mL/s (P < 0.05) at 3 months. Overall effectiveness by Homma's response criteria was as follows; excellent 4.1%, good 10.2%, fair 38.8% and poor 46.9%. Side effects were minimal. Gross hematuria was seen in 3 patients and erosion of the external urethral meatus was seen in 2 patients, but none had urinary retention. CONCLUSIONS: In this initial clinical trial, transurethral RF thermotherapy was safe and resulted in modest symptomatic improvement. Further investigations for optimizing the treatment protocol seem warranted.

Aged↗
PubMed2005

Early outcomes of active surveillance for localized prostate cancer.

OBJECTIVE: To describe the preliminary clinical outcomes of active surveillance (AS), a new strategy aiming to individualize the management of early prostate cancer by selecting only those men with significant cancers for curative therapy, and illustrate the contrast with a policy of watchful waiting (WW). PATIENTS AND METHODS: Eighty men with early prostate cancer began AS at the authors' institution between 1993 and 2002. Eligibility included histologically confirmed prostatic adenocarcinoma, fitness for radical treatment, clinical stage T1/T2, N0/X, M0/X, a prostate specific antigen (PSA) level of < or = 20 ng/mL, and a Gleason score of < or = 7. PSA was measured and a digital rectal examination conducted at 3-6 month intervals. The decision between continued monitoring or radical treatment was informed by the rate of rise of PSA, and was made according to the judgement of each patient and clinician. During the same period, 32 men with localized prostate cancer (any T stage, N0/X, M0/X, any PSA, Gleason score < or = 7) were managed by WW; hormonal treatment was indicated for symptomatic prostate cancer progression. The PSA doubling time (DT) was calculated using linear regression of ln(PSA) against time, using all pretreatment PSA values. RESULTS: At a median follow-up of 42 months, 64 (80%) of the 80 patients on AS remained under observation, 11 (14%) received radical treatment and five (6%) died from other causes. No patient developed evidence of metastatic disease, none started palliative hormone therapy, and there were no deaths from prostate cancer. Of the 11 patients who received radical treatment all remained biochemically controlled with no clinical evidence of recurrent disease. The median PSA DT while on AS was 12 years. Twenty (62%) of the 32 patients on WW remained on observation, eight (25%) received palliative hormonal therapy and four (12%) died, including one from prostate cancer. CONCLUSIONS: AS is feasible in selected men with early prostate cancer. The natural history of this disease often appears extremely indolent, and most men on AS will avoid radical treatment. There is a marked contrast between AS (with radical treatment for biochemical progression) and WW (with palliative treatment for symptomatic progression). Ongoing studies are seeking to optimize the AS protocol, and to compare the long-term outcomes with those of immediate radical treatment.

Adenocarcinoma↗
PubMed2006

Characterization of an extended receptive ligand repertoire of the human olfactory receptor OR17-40 comprising structurally related compounds.

Molecular properties of odorant compounds essential for activation of the human olfactory receptor hOR17-40 were investigated using a collection of 23 variants of its cognate ligand helional. Coupling receptor activation to an optically detectable intracellular Ca(2+) ion flux allowed dose-dependent screening of different odorant molecules in human embryonic kidney (HEK)293 cells. We found an extended collection of activating ligands and provide first evidence for hOR17-40-specific antagonists. The C-terminal fusion of enhanced green fluorescent protein to the hOR17-40 retained full receptor function and permitted the selection of cells with defined receptor expression levels, which was an essential step for optimizing our screening protocol. Interestingly, cells with a low EGFP fluorescence intensity exhibited efficient hOR17-40 cell surface targeting and odorant-evoked signal transduction; in contrast, highly fluorescent cells displayed mainly incorrectly targeted, intracellular receptors. Fluorescence-activated cell sorting was used to separate hOR17-40-expressing cells on the basis of their endogenous EGFP fluorescence intensity, thereby increasing the fraction of odorant-responsive cells to up to 80% of the total cell number.

Calcium↗