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Biomedical subjects

J Reed

Publications and source records attributed to J Reed.

At least 19 recordsLinked to original sources
PubMed2007

Human hydration level monitoring using embedded piezoresistive microcantilever sensors.

Embedded piezoresistive microcantilever (EPM) sensors were used to measure osmolality changes in both saliva mimic solutions and true human saliva. Osmolality changes in human saliva or urine may prove to be reliable, simple, and easy to measure markers for tracking human hydration levels. EPM sensors used in these experiments show good response to osmolality changes in both NaCl-based saliva mimic solutions and to human saliva. The addition of zero-point offset correction to EPM sensors allows for tracking of saliva osmolality changes with high accuracy. Also, the same EPM sensors exhibit a large enough range of osmolality response to make them potentially suitable for urine or blood serum osmolality monitoring.

Biosensing Techniques↗
PubMed2006

Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy.

BACKGROUND: Lenalidomide is active and well tolerated in relapsed and refractory multiple myeloma. We conducted a phase I/II trial of the combination of lenalidomide and chemotherapy to evaluate the safety and efficacy of the combination. METHODS: The 62 patients enrolled received liposomal doxorubicin 40 mg/m(2) i.v. and vincristine 2 mg i.v. on day 1, dexamethasone 40 mg p.o. on days 1-4 (DVd), and lenalidomide on days 1-21 in 28-day cycles. Primary end points were maximum tolerated dose (MTD) of lenalidomide with DVd chemotherapy and overall response rate (ORR) by Southwest Oncology Group criteria of the combination. FINDINGS: The median age was 62 years, 70% of patients were males and 65% had refractory multiple myeloma. The MTD of lenalidomide with DVd chemotherapy was 10 mg and the dose-limiting toxicity was non-neutropenic sepsis. After 7.5 months of median follow-up, the ORR of the combination was 75%, with 29% of patients achieving a complete or near complete remission. The median progression-free survival was 12 months, while the median overall survival has not yet been reached. INTERPRETATION: The combination of lenalidomide and DVd chemotherapy was well tolerated and resulted in high response rates in this mostly refractory patient population. Evaluation of this combination in newly diagnosed patients is warranted.

Aged↗
PubMed2006

Endoscopic laser speckle imaging of tissue blood flow: applications in the human knee.

This work represents the first clinical data acquired with the endoscopic laser speckle imaging (eLSPI) system, a new diagnostic tool developed for real-time imaging of tissue blood flow during endoscopic surgical procedures. eLSPI was used to image tissue perfusion in the medial compartment of the knee of five patients requiring arthroscopic knee surgery. The effectiveness of eLSPI as a diagnostic tool was tested by measuring changes in tissue perfusion resultant from tourniquet application, and intra-articular epinephrine. eLSPI produced real-time perfusion video images of tissue blood flow in the knee joint. Tourniquet applications produced consistent decreases in mean perfusion index measurements (29.3% +/- 5.1% in meniscus; 39.5% +/- 8.2% in synovium with an intra patient variability of 6%-9%). A dose-dependent vasoconstrictive response to the administration of intra-articular epinephrine was measured, with maximum dose producing a mean decrease in perfusion of 31.0%-9.3% in meniscus and 41.2%-10.9% in synovium. eLSPI consistently detects decreases in articular tissue blood flow resultant from tourniquet inflation or from the administration of increasing concentrations of epinephrine. These are the first in vivo results indicating physiologic changes in articular tissue as a function of two commonly applied practices in endoscopic joint surgery.

Adolescent↗
PubMed2006

Jaw complications associated with bisphosphonate use in patients with plasma cell dyscrasias.

Osteonecrosis of the jaw has been linked with bisphosphonate use in breast cancer and multiple myeloma patients. We report 17 cases of patients with plasma cell dyscrasia being treated with bisphosphonate who developed osteonecrosis/osteomyelitis of the jaw. Seventeen patients evaluated at our institution between 1998 and 2005 are reported. All were being treated with bisphosphonates for a median of 5 mo prior to the onset of jaw symptoms. Sixteen of the 17 patients are 51 yr or older. None of the patients had been irradiated in the jaw nor had obvious osseous manifestation of multiple myeloma in the jaw. Thirteen patients were receiving zoledronic acid and four patients were receiving pamidronate at the onset of jaw symptoms. Six of the 17 did receive both agents at some time and all of these individuals were receiving zoledronic acid at diagnosis. Microorganisms were isolated in 7/17 patients with the most common organism being actinomycosis. We have initiated the following guidelines in an effort to ameliorate the incidence of this complication. Patients should have a full dental examination at the time of diagnosis of the plasma cell dyscrasia especially if bisphosphonates are to be considered as part of the therapy. In addition, bisphosphonates are held for a period of 3 mo prior to invasive dental procedures to allow for the osteoclastic recovery, therefore enhanced debris removal and lessening the chance of creating a fertile bacterial medium. Following the dental procedure we would re-introduce bisphosphonates only after the healing process is complete. Finally, multiple myeloma patients diagnosed with jaw osteonecrosis probably have a concurrent infection and should be aggressively treated with antibiotics.

Adult↗
PubMed2005

Hydration level monitoring using embedded piezoresistive microcantilever sensors.

A new MEMS based sensor technology, embedded piezoresistive microcantilever (EPM) sensors, may be useful in the real-time monitoring of hydration levels in athletes or other individuals whose activities may result in dehydration. In these devices, organic polymers or functionalized polymeric materials respond to osmolality changes in a person's saliva by expanding or contracting volumetrically. These volumetric changes are measured by tiny piezoresistive microcantilevers embedded in the polymeric material. In this report, we have tested a prototype device utilizing UV crosslinked poly(vinyl acetate) as the active sensing material. This device was able to reliably respond to 1% changes in sodium chloride concentration in solution or alternately to 1% changes in relative humidity.

Biosensing Techniques↗
PubMed2004

Nucleotide sequence, genome organization and phylogenetic analysis of Strawberry pallidosis associated virus, a new member of the genus Crinivirus.

The complete nucleotide sequence of Strawberry pallidosis associated virus (SPaV), a newly identified member of the genus Crinivirus, family Closteroviridae has been determined. RNA 1 is 8067 nucleotides long and encodes at least three open reading frames (ORFs). The first ORF (ORF 1a) specifies a multifunctional protein that has papain-like proteinase, methyltransferase and RNA helicase domains. The RNA-dependent-RNA polymerase is encoded in ORF 1b and is probably expressed by a +1 ribosomal frameshift. The 3' ORF of RNA 1 encodes a small protein with two potential transmembrane helices. RNA 2 is 7979 nucleotides long and encodes 8 ORFs, similar in amino acid sequence and arrangement with those of other criniviruses. SPaV encodes the largest structural protein of closteroviruses sequenced to date as the minor coat protein of the virus has molecular mass of approximately 80 kDa. The 3' non-translated regions share nucleotide sequence identities of about 56% and the predicted folding of the non-translated regions is similar. Phylogenetic analyses reveal that SPaV is related most closely to Abutilon yellows virus and Beet pseudo-yellows virus, another virus that has been identified recently to cause identical symptoms on strawberry indicator plants as SPaV.

Capsid Proteins↗
PubMed2003

Reef-coral proteins as visual, non-destructive reporters for plant transformation.

Recently, five novel fluorescent proteins have been isolated from non-bioluminescent species of reef-coral organisms and have been made available through ClonTech. They are AmCyan, AsRed, DsRed, ZsGreen and ZsYellow. These proteins are valuable as reporters for transformation because they do not require a substrate or external co-factor to emit fluorescence and can be tested in vivo without destruction of the tissue under study. We have evaluated them in a large range of plants, both monocots and dicots, and our results indicate that they are valuable reporting tools for transformation in a wide variety of crops. We report here their successful expression in wheat, maize, barley, rice, banana, onion, soybean, cotton, tobacco, potato and tomato. Transient expression could be observed as early as 24 h after DNA delivery in some cases, allowing for very clear visualization of individually transformed cells. Stable transgenic events were generated, using mannose, kanamycin or hygromycin selection. Transgenic plants were phenotypically normal, showing a wide range of fluorescence levels, and were fertile. Expression of AmCyan, ZsGreen and AsRed was visible in maize T1 seeds, allowing visual segregation to more than 99% accuracy. The excitation and emission wavelengths of some of these proteins are significantly different; the difference is enough for the simultaneous visualization of cells transformed with more than one of the fluorescent proteins. These proteins will become useful tools for transformation optimization and other studies. The wide variety of plants successfully tested demonstrates that these proteins will potentially find broad use in plant biology.

Anthozoa↗
PubMed2001

Peptide mimics of SNARE transmembrane segments drive membrane fusion depending on their conformational plasticity.

SNARE proteins are essential for different types of intracellular membrane fusion. Whereas interaction between their cytoplasmic domains is held responsible for establishing membrane proximity, the role of the transmembrane segments in the fusion process is currently not clear. Here, we used an in vitro approach based on lipid mixing and electron microscopy to examine a potential fusogenic activity of the transmembrane segments. We show that the presence of synthetic peptides representing the transmembrane segments of the presynaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) synaptobrevin II (also referred to as VAMP II) or syntaxin 1A, but not of an unrelated control peptide, in liposomal membranes drives their fusion. Liposome aggregation by millimolar Ca(2+) concentrations strongly potentiated the effect of the peptides; this indicates that juxtaposition of the bilayers favours their fusion in the absence of the cytoplasmic SNARE domains. Peptide-driven fusion is reminiscent of natural membrane fusion, since it was suppressed by lysolipid and involved both bilayer leaflets. This suggests transient presence of a hemifusion intermediate followed by complete membrane merger. Structural studies of the peptides in lipid bilayers performed by Fourier transform infrared spectroscopy indicated mixtures of alpha-helical and beta-sheet conformations. In isotropic solution, circular dichroism spectroscopy showed the peptides to exist in a concentration-dependent equilibrium of alpha-helical and beta-sheet structures. Interestingly, the fusogenic activity decreased with increasing stability of the alpha-helical solution structure for a panel of variant peptides. Thus, structural plasticity of transmembrane segments may be important for SNARE protein function at a late step in membrane fusion.

Amino Acid Sequence↗
PubMed2001

Methodologic pitfalls in the determination of genetic anticipation: the case of Crohn disease.

BACKGROUND: The term genetic anticipation is used when genetically transmitted disease manifests at increasingly younger ages with each succeeding generation: that is, if the offspring of patients develop the disease, they will tend to do so at an earlier age than their parents. In some monogenetic disorders, genetic anticipation has a biological basis in expanded genetic triplet repeats; however, some have claimed that it occurs in polygenic disorders, such as Crohn disease, in which its mechanism cannot be explained. OBJECTIVE: To show how apparent changes in age at diagnosis of Crohn disease between generations, which could suggest genetic anticipation, can be an artifact of inadequate analysis based on age at diagnosis in cohorts that have not been followed for a sufficiently long time. DESIGN: Comparison of ages at diagnosis of Crohn disease among different birth cohorts, before and after adjustment for observation time. SETTING: Meyerhoff Center for Inflammatory Bowel Disease, Johns Hopkins Hospital, Baltimore, Maryland. PATIENTS: 928 consecutive outpatients with Crohn disease. MEASUREMENTS: Trends in age at diagnosis of Crohn disease among birth cohorts were determined by calculating Pearson correlation coefficients and performing Kaplan-Meyer analysis before and after adjustment for observation time. Adjustment for observation time was performed by ensuring that the time during which all included patients were at risk for Crohn disease was equal and that all patients had developed disease by the end of the risk period. RESULTS: Mean age at diagnosis decreased by approximately 5 years with each subsequent 10-year birth cohort on the basis of crude cross-sectional data that could suggest genetic anticipation between generations. However, after adjustment for observation time, the age at diagnosis decreased minimally, if at all, with each successive generation. CONCLUSIONS: Apparent genetic anticipation can be explained by observational biases without invoking any additional genetic influences. Claims for genetic anticipation must be based on methods that properly account for the duration of observation in all persons being studied.

Age of Onset↗
PubMed2001

Influence of myristoylation, phosphorylation, and deamidation on the structural behavior of the N-terminus of the catalytic subunit of cAMP-dependent protein kinase.

A number of isoenzymes of the catalytic subunit of cAMP-dependent protein kinase arise through posttranslational modifications of the enzyme outside the catalytic domain; the biological significance of these is not yet fully clear. A clustering of sites for such modification exists at the N-terminus of the protein, where myristoylation (of Gly1), phosphorylation (at Ser10), and deamidation of Asn2 have been observed. As the first two are known to govern membrane binding and thus subcellular compartmentalization in some proteins, it was of interest to see whether the local structure of the N-terminus was being influenced by one or more of these modifications. A series of synthetic peptides mimicing the 16 N-terminal residues of the catalytic subunit Calpha was produced covering the full range of possible modifications, singly and in combination, and tested for possible effects on local structure by measuring the circular dichroism under varying polarity. It was found that myristoylation and phosphorylation modify the structure in this region in opposite ways and in a manner designed to amplify the action of a potential myristoyl/electrostatic switch. To what extent deamidation of Asn2 may oppose a potential membrane binding is unknown. Deamidation, however, had no effect on the structure of the peptide either alone or in combination with acylation and/or phosphorylation, suggesting that the change of the nuclear/cytoplasmic disribution in cells caused by deamidation [Pepperkok et al. (2000) J. Cell Biol. 148, 715-726] is due to a more complex signaling mechanism. The structural implications of the data are discussed.

Acylation↗
PubMed2001

Splenic injury after intraoperative transesophageal echocardiography.

A 55-year-old woman underwent coronary artery bypass grafting and mitral valve repair using intraoperative transesophageal echocardiography (TEE). Postoperatively she had hemodynamic instability associated with an increase in abdominal size and a drop in hemoglobin. At laparotomy, a splenic hilar laceration was discovered, which was presumed to be associated with intraoperative TEE. She underwent emergent splenectomy. This case demonstrates that although rare, serious complications can occur with TEE.

Coronary Artery Bypass↗
PubMed2001

Suicidal intent in patients with chronic pain.

Suicidal ideation among individuals suffering from chronically painful conditions has not been widely studied, although rates of completed suicide are believed to be elevated in this population relative to the general population. The psychiatric literature on suicide documents the importance of controlling for the severity of depression when studying factors associated with suicidal ideation, attempts, or completion. The present study examined the relationships between suicidal ideation and the experience of pain, pain-related disability, and pain coping efforts among a sample of individuals experiencing chronically painful conditions. Of 200 patients evaluated on an inpatient rehabilitation unit in a psychiatric service, 13 individuals (6.5%) reported suicidal intent on a commonly used self-report measure of symptoms of depression, the Beck Depression Inventory. This group was compared to a matched (age, sex, pain duration) group of similarly depressed individuals (N=13) and a matched group of non-depressed individuals (N=13) on measures of pain, disability, pain beliefs, and pain coping strategies. A history of a suicide attempt was associated with suicidal intent. Family history of substance abuse was significantly more prevalent among the depressed groups, regardless of suicidal thinking. The depressed/suicidal group and depressed/non-suicidal groups reported higher levels of pain, higher levels of pain-related disability, lower use of active coping, and higher use of passive coping compared to the non-depressed group. The depressed groups did not differ from one another on any of the measures of pain experience. Depression, not suicidal status, consistently predicted level of functioning. The prevalence of suicidal intent was comparable to rates observed in other studies and relatively low. When individuals with chronic pain report suicidal intent, it is imperative that measures preventing self-harm be implemented immediately and the patient's depression be treated aggressively.

Activities of Daily Living↗
PubMed2001

Characterization of peptide substrates and viral enzyme that affect the cleavage site specificity of the human spumaretrovirus proteinase.

Oligopeptides that correspond to proteolytic cleavage site junctions of the native Gag and Pol proteins are specifically cleaved by retroviral aspartate proteases (PRs). The role of the flap subdomain of the PR of the human spumaretrovirus (HSRV) and of substrate peptides in cleavage site specificity was analyzed by site-directed mutagenesis. Native and mutant peptides were subjected to proteolysis by the authentic and mutated recombinant viral enzyme. The results reveal that Glu residue 54 of the HSRV PR is an essential specificity determinant for proteolytic processing of the structural proteins. Peptides that represent in vivo cleavage sites were susceptible to proteolysis by the recombinant HSRV PR, but one peptide located at the junction between the PR and reverse transcriptase domains was completely resistant to cleavage. Thus the data indicate that a proteolytic cleavage between these domains does not occur in vivo. Naturally occurring and mutant forms of the cleavage-resistant peptide were therefore analyzed by circular dichroism to determine if differences existed in the secondary structures of the peptides that did or did not serve as substrates. The data show that differences in the secondary structure of the native and mutant peptides analyzed does not seem to play a crucial role for cleavage site specificity in HSRV PR. Instead highly conserved hydrophobic residues at distinct positions of the HSRV cleavage site junctions contribute to the specificity observed as reported for HIV-1 PR.

Amino Acid Sequence↗
PubMed2001

Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help.

OBJECTIVE: The purpose of this study was to identify the risk factors that are associated with increased neonatal morbidity in patients who were treated for sonographic evidence of internal os dilation and distal cervical shortening during the second trimester. STUDY DESIGN: From May 1998 to June 2000 patients between 16 and 24 weeks of gestation with the following sonographic criteria were randomly assigned to McDonald cerclage or no cerclage: internal os dilation and either membrane prolapse into the endocervical canal at least 25% of the total cervical length but not beyond the external os or a shortened distal cervix <2.5 cm. Before randomization, all patients were treated identically with an amniocentesis, multiple urogenital cultures, and therapy with indomethacin and clindamycin for 48 to 72 hours. Except for the cerclage, all patients were treated identically after randomization. Multiple variables of perinatal outcome were analyzed. A regression model with gestational age at delivery as the dependent variable was constructed and repeated with neonatal morbidity as the dependent variable. This model was applied to 3 populations: the cerclage group, the no cerclage group, and both groups combined. RESULTS: Of the 135 patients, 20 patients declined randomization, and 2 patients were diagnosed with acute chorioamnionitis. Of the 113 patients remaining, 55 patients were randomly assigned to the cerclage group, and 58 patients were randomly assigned to the no cerclage group. There were 8 rescue cerclage procedures (4 in each group). Regression analysis showed that readmission for preterm labor, chorioamnionitis, and abruption were consistently associated with early gestational age at delivery and increased morbidity. Cerclage did not affect perinatal outcome. CONCLUSION: The sonographic findings of second trimester internal os dilation, membrane prolapse, and distal cervical shortening likely represent a common pathway of several pathophysiologic processes. Use of cerclage does not alter any perinatal outcome variables. Increased neonatal morbidity in these patients appears to be associated with subclinical infection, preterm labor, and abruption.

Abruptio Placentae↗
PubMed2001

Can cardiac sonography and capnography be used independently and in combination to predict resuscitation outcomes?

OBJECTIVE: To measure the ability of cardiac sonography and capnography to predict survival of cardiac arrest patients in the emergency department (ED). METHODS: Nonconsecutive cardiac arrest patients prospectively underwent either cardiac ultrasonography alone or in conjunction with capnography during cardiopulmonary resuscitation at two community hospital EDs with emergency medicine residency programs. Cardiac ultrasonography was carried out using the subxiphoid view during pauses for central pulse evaluation and end-tidal carbon dioxide (ETCO(2)) levels were monitored by a mainstream capnograph. A post-resuscitation data collection form was completed by each of the participating clinicians in order to assess their impressions of the facility of performance and benefit of cardiac sonography during nontraumatic cardiac resuscitation. RESULTS: One hundred two patients were enrolled over a 12-month period. All patients underwent cardiac sonographic evaluation, ranging from one to five scans, during the cardiac resuscitation. Fifty-three patients also had capnography measurements recorded. The presence of sonographically identified cardiac activity at any point during the resuscitation was associated with survival to hospital admission, 11/41 or 27%, in contrast to those without cardiac activity, 2/61 or 3% (p < 0.001). Higher median ETCO(2) levels, 35 torr, were associated with improved chances of survival than the median ETCO(2) levels for nonsurvivors, 13.7 torr (p < 0.01). The multivariate logistic regression model, which evaluated the combination of cardiac ultrasonography and capnography, was able to correctly classify 92.4% of the subjects; however, of the two diagnostic tests, only capnography was a significant predictor of survival. The stepwise logistic regression model, summarized by the area under the receiver operator curve of 0.9, furthermore demonstrated that capnography is an outstanding predictor of survival. CONCLUSIONS: Both the sonographic detection of cardiac activity and ETCO(2) levels higher than 16 torr were significantly associated with survival from ED resuscitation; however, logistic regression analysis demonstrated that prediction of survival using capnography was not enhanced by the addition of cardiac sonography.

Capnography↗