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Biomedical subjects

R Carlson

Publications and source records attributed to R Carlson.

At least 19 recordsLinked to original sources

Prometheus: Io's wandering plume.

Unlike any volcanic behavior ever observed on Earth, the plume from Prometheus on Io has wandered 75 to 95 kilometers west over the last 20 years since it was first discovered by Voyager and more recently observed by Galileo. Despite the source motion, the geometric and optical properties of the plume have remained constant. We propose that this can be explained by vaporization of a sulfur dioxide and/or sulfur "snowfield" over which a lava flow is moving. Eruption of a boundary-layer slurry through a rootless conduit with sonic conditions at the intake of the melted snow can account for the constancy of plume properties.

Cold Temperature↗

The "stable" ruptured abdominal aortic aneurysm gives a false sense of security.

BACKGROUND: Operative mortality for ruptured abdominal aortic aneurysms (rAAA) has not changed over the past 4 decades. Previous studies have attempted to identify preoperative risk factors that impact upon survival. METHOD: A retrospective review of 25 patients with rAAA treated during a 2-year period was performed. Patients were divided into groups based upon the presence (GpI), absence (GpIIa), or subsequent development of preoperative hypotension (GpIIb). Time intervals from initial presentation to arrival in the operating room (IP-OR), to cross clamp application (IP-XC), and from observed hypotension to cross clamp (HYPO-XC) were recorded. RESULTS: Average time intervals for IP-OR and IP-XC were significantly shorter for GpI compared with GpIIa and GpIIb. No difference in HYPO-XC was noted between GpI and GpIIb. Mortality was 33% for GpI, 25% for GpIIa, and 87.5% for GpIIb. CONCLUSIONS: Normal admission blood pressure led to a decreased sense of urgency, creating avoidable delays and missed opportunities for salvage.

Aged↗

WY-50295 tromethamine: a 5-lipoxygenase inhibitor without activity in human whole blood.

The 5-LO inhibitor, WY-50295 tromethamine (T) prevented leukotriene release (LTB4 production) in calcium ionophore stimulated, purified human and rat neutrophils. However, whereas WY-50295T inhibited both in vitro and ex vivo rat whole blood leukocyte LTB4 formation (IC50= 40 microM and oral ED50 of 18 mg/kg, respectively), it did not inhibit LTB4 production in calcium ionophore stimulated human whole blood at concentrations to 200 microM. To reduce binding of WY-50295T to serum albumin, 250 microM of a naphthalene sulfonic acid (> 99.9% binding to albumin primarily at the carboxylic site) and 250 microM sulfanilamide (binding to nonspecific sites) separately or in combination were preincubated in whole blood prior to addition of WY-50295T; however, WY-50295T still did not inhibit 5-LO and free drug blood levels were unchanged. When purified human neutrophils in the presence of fatty acid saturated albumin (fraction V) was employed, the 5-LO inhibitory activity of WY-50295T was prevented. Zileuton (5 microM) inhibited LTB4 production by 99% in the presence of these albumins. Also, rat albumin presented WY-50295T to purified rat neutrophils more effectively than human albumin (i.e. WY-50295T was more active in the presence of rat albumin). These results suggest that the high affinity binding of WY-50295T to human albumin and possibly the reduction of drug uptake (passive diffusion) using purified human vs rat neutrophils may account for the inactivity of WY-50295T in the human whole blood assay.

Animals↗

Aberrant nodulation response of Vigna umbellata to a Bradyrhizobium japonicum NodZ mutant and nodulation signals.

The (Brady)rhizobium nodulation gene products synthesize lipo-chitin oligosaccharide (LCO) signal molecules that induce nodule primordia on legume roots. In spot inoculation assays with roots of Vigna umbellata, Bradyrhizobium elkanii LCO and chemically synthesized LCO induced aberrant nodule structures, similar to the activity of these LCOs on Glycine soja (soybean). LCOs containing a pentameric chitin backbone and a reducing-end 2-O-methyl fucosyl moiety were active on V. umbellata. In contrast, the synthetic LCO-IV(C16:0), which has previously been shown to be active on G. soja, was inactive on V. umbellata. A B. japonicum NodZ mutant, which produces LCO without 2-O-methyl fucose at the reducing end, was able to induce nodule structures on both plants. Surprisingly, the individual, purified, LCO molecules produced by this mutant were incapable of inducing nodule formation on V. umbellata roots. However, when applied in combination, the LCOs produced by the NodZ mutant acted cooperatively to produce nodulelike structures on V. umbellata roots.

Bacterial Proteins↗

Comparison of total blood volume in normal, preeclamptic, and nonproteinuric gestational hypertensive pregnancy by simultaneous measurement of red blood cell and plasma volumes.

OBJECTIVE: Our purpose was to demonstrate reduced blood volume in preeclampsia compared with nonproteinuric gestational hypertension and normal pregnancy by use of independent measures of red blood cell and plasma volumes. STUDY DESIGN: Red blood cells labeled with a nonradioactive stable isotope of chromium and Evans' blue were infused in subjects with preeclampsia or gestational hypertension and normotensive pregnant controls. Blood was sampled eight times over 60 minutes for dye concentration and at 30 minutes for chromium analysis. RESULTS: Total blood and plasma volumes are decreased in preeclampsia (2660 +/- 382 mL/m2 and 1790 +/- 332 mL/m2, respectively) compared with normotensive subjects (3217 +/- 391 mL/m2, P < 0.001 and 2279 +/- 325 mL/m2, P < .001) and gestational hypertension (3139 +/- 272 mL/m2, P < .001 and 2132 +/- 265 mL/m2, P = .003). Total body/peripheral hematocrit ratio is increased in preeclampsia. CONCLUSIONS: Blood volume, by measurement of red blood cell and plasma volumes, is reduced and has altered distribution in preeclampsia but is normal in gestational hypertension.

Adult↗

The Bradyrhizobium japonicum noeD gene: a negatively acting, genotype-specific nodulation gene for soybean.

Bradyrhizobium japonicum strain USDA 110 is restricted for nodulation by soybean genotype PI 417566. We previously reported the identification of a USDA 110 Tn5 mutant, strain D4.2-5, that had the ability to overcome nodulation restriction conditioned by PI 417566 (S. M. Lohrke, J. H. Orf, E. Martínez-Romero, and M. J. Sadowsky, Appl. Environ. Microbiol. 61:2378-2383, 1995). In this study, we report the cloning and characterization of the negatively acting DNA region mutated in strain D4.2-5 that is involved in the genotype-specific nodulation of soybean. The Tn5 integration site was localized to a 5.2-kb EcoRI fragment isolated from wild-type USDA 110 genomic DNA. Saturation Tn5 mutagenesis of this 5.2-kb region and DNA homogenitization studies indicated that a 0.9-kb DNA region was involved in the genotype-specific nodulation of PI 417566. A single open reading frame (ORF) of 474 nucleotides, encoding a predicted protein of 158 amino acids, was identified within this region by DNA sequencing. This ORF was named noeD. Computer comparisons with available data bases revealed no significant similarities between the noeD DNA or predicted amino acid sequence and any known genes or their products. However, comparisons done with the region upstream of noeD revealed a high degree of similarity (about 76% similarity and 62% identity) to the N-terminal regions of the Rhizobium leguminosarum bv. viciae and R. meliloti nodM genes, which have been postulated to encode a glucosamine synthase. Southern hybridization analysis indicated that noeD is not closely linked to the main or auxiliary nodulation gene clusters in B. japonicum and that both nodulation-restricted and -unrestricted B. japonicum serogroup 110 strains contain a noeD homolog. High-performance liquid chromatography and fast atom bombardment-mass spectrometry analyses of the lipo-chitin oligosaccharide (LCO) nodulation signals produced by an noeD mutant showed a higher level of acetylation than that found with wild-type USDA 110. These results suggest that specific LCO signal molecules may be one of the factors influencing nodulation specificity in this symbiotic system.

Amino Acid Sequence↗

Characterization of genes involved in biosynthesis of a novel antibiotic from Burkholderia cepacia BC11 and their role in biological control of Rhizoctonia solani.

Genetic manipulation of fluorescent pseudomonads has provided major insight into their production of antifungal molecules and their role in biological control of plant disease. Burkholderia cepacia also produces antifungal activities, but its biological control activity is much less well characterized, in part due to difficulties in applying genetic tools. Here we report genetic and biochemical characterization of a soil isolate of B. cepacia relating to its production of an unusual antibiotic that is very active against a variety of soil fungi. Purification and preliminary structural analyses suggest that this antibiotic (called AFC-BC11) is a novel lipopeptide associated largely with the cell membrane. Analysis of conditions for optimal production of AFC-BC11 indicated stringent environmental regulation of its synthesis. Furthermore, we show that production of AFC-BC11 is largely responsible for the ability of B. cepacia BC11 to effectively control the damping-off of cotton caused by the fungal pathogen Rhizoctonia solani in a gnotobiotic system. Using Tn5 mutagenesis, we identified, cloned, and characterized a region of the genome of strain BC11 that is required for production of this antifungal metabolite. DNA sequence analysis suggested that this region encodes proteins directly involved in the production of a nonribosomally synthesized lipopeptide.

Amino Acid Sequence↗

Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-Analysis Group in Cancer.

BACKGROUND: Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response. PURPOSE: Because of the high cost of hepatic arterial infusion, we undertook a cost-effectiveness analysis that related the cost of such therapy to its medical efficacy. METHODS: The patient population was drawn from the seven randomized clinical trials included in the meta-analysis and included individual data on 654 patients. Of these seven trials, five compared hepatic arterial infusion and intravenous chemotherapy and two compared hepatic arterial infusion and a control group in which some patients could be left untreated. Patients assigned to receive hepatic arterial infusion made up the hepatic arterial infusion group; the other patients constituted the control group. The measures of efficacy were survival and tumor response. Health-care costs (in 1995 U.S. dollars) were computed over the duration of patient follow-up and were derived from actual costs in two centers, one at Henri Mondor Hospital (Paris, France) and the other at Stanford University Medical Center (Palo Alto, CA). The total cost of treatment included the initial procedure, chemotherapy cycles, and main complications. RESULTS: The mean gain in life expectancy in the hepatic arterial infusion group compared with the control group was 3.2 months (standard error = 1.0 month). For patients treated by hepatic arterial infusion in Paris, the hepatic arterial infusion pump, initial hospitalization, and the entire process (including follow-up and complications) cost, on average, $8400, $15172, and $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208, respectively. For patients in the control groups in Paris and Palo Alto, the total treatment costs were, on average, $9926 and $5928. The additional costs of hepatic arterial infusion over control treatment were $19636 in Paris and $19280 in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the additional benefit) with respect to survival of the patients in the hepatic arterial infusion group compared with the patients in the control group was $73635 per life-year in Paris and $72300 per life-year in Palo Alto. CONCLUSIONS AND IMPLICATIONS: The cost-effectiveness of localized chemotherapy for colorectal liver metastases is within the range of accepted treatments for serious medical conditions, although it might be considered borderline by policy-makers in some countries. Prospective clinical trials should be conducted to more definitively answer this question.

Antimetabolites, Antineoplastic↗

Near-infrared spectroscopy and spectral mapping of Jupiter and the Galilean satellites: results from Galileo's initial orbit.

The Near Infrared Mapping Spectrometer performed spectral studies of Jupiter and the Galilean satellites during the June 1996 perijove pass of the Galileo spacecraft. Spectra for a 5-micrometer hot spot on Jupiter are consistent with the absence of a significant water cloud above 8 bars and with a depletion of water compared to that predicted for solar composition, corroborating results from the Galileo probe. Great Red Spot (GRS) spectral images show that parts of this feature extend upward to 240 millibars, although considerable altitude-dependent structure is found within it. A ring of dense clouds surrounds the GRS and is lower than it by 3 to 7 kilometers. Spectra of Callisto and Ganymede reveal a feature at 4. 25 micrometers, attributed to the presence of hydrated minerals or possibly carbon dioxide on their surfaces. Spectra of Europa's high latitudes imply that fine-grained water frost overlies larger grains. Several active volcanic regions were found on Io, with temperatures of 420 to 620 kelvin and projected areas of 5 to 70 square kilometers.

Ammonia↗

Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer.

BACKGROUND: Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear. PURPOSE: A meta-analysis was carried out to provide an objective and quantitative appraisal of the benefits of HAI in terms of tumor response rate and overall patient survival. METHODS: The meta-analysis was based on individual data provided by the principal investigators of six individual trials and on summary data for one trial. Of the seven trials, five compared HAI with floxuridine (5-fluoro-2'-deoxyuridine; FUDR) and intravenous chemotherapy (IVC) with FUDR (three trials) or fluorouracil (5-FU) (two-trials), and two compared HAI with FUDR and an ad libitum control group in which some patients could be left untreated. Response data were analyzed by use of a Mantel-Haenszel test on all randomized patients. Survival data were analyzed by the use of stratified logrank test. Multivariate analyses were performed with use of the logistic regression model for tumor response and the Cox regression model for survival. All P values resulted from two-sided statistical tests. The analyses were performed by an independent secretariat and were reviewed by the collaborators. RESULTS: The tumor response rate was 41% for patients allocated to HAI with FUDR or 5-FU (CR, 2%; PR, 12%). This difference was highly significant, with a response odds ratio of 0.25 (95% confidence interval = 0.16-0.40; P < 10 (-10)). Survival analyses showed a statistically significant advantage for HAI with FUDR compared with control when trials were taken into account (P = .0009) but not when the survival analysis was restricted to trials comparing HAI with FUDR and IVC with FUDR or 5-FU (P = .14). CONCLUSION: These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer. IMPLICATIONS: The therapeutic benefit of use of HAI with FUDR in these patients should be judged together, with an overall evaluation of this therapy in terms of convenience, toxicity, and costs. These end points should be considered in addition to tumor response and survival in further trials involving HAI.

Antimetabolites, Antineoplastic↗

Using continuous quality improvement tools to improve pediatric immunization rates.

BACKGROUND: In August 1992 the medical director of the 19 Group Health medical clinics (now part of HealthPartners) in Minnesota chartered a continuous quality improvement (CQI) team to improve the pediatric (two-year-old) immunization rates. THE TEAM'S WORK: The team created a process flow for the current immunization process, collected data on the process, determined the causes of late or missed immunizations, collected data on children not up-to-date with immunization, analyzed the data, acted on recommendations, and obtained buy-in. The chief reasons for the child's not being up-to-date on immunizations included missed opportunities (when the child is in the clinic receiving care, perhaps for an acute illness, and could have safely received the immunization but did not), no previous visits or chart, and parents instructed to have their child return at two years. INTERVENTION: Recommendations pertained to missed opportunities, record keeping, and enhanced patient and provider responsibility. For example, providers were given algorithms for catch-up of patients not on schedule or with incomplete immunizations. Another CQI team was launched to address and simplify the myriad locations in a medical record for recording information on immunizations. An automated vaccine administration record is now being piloted at two clinics. RESULTS: Immunizations have increased from a mean of 53.5% before the team started to meet to a mean of 86.5% for the most recent four quarters for which data are available. CONCLUSIONS: A problem is best addressed by the very people who will have to bring about the necessary changes for the desired improvements.

Algorithms↗

Models of speech synthesis.

The term "speech synthesis" has been used for diverse technical approaches. In this paper, some of the approaches used to generate synthetic speech in a text-to-speech system are reviewed, and some of the basic motivations for choosing one method over another are discussed. It is important to keep in mind, however, that speech synthesis models are needed not just for speech generation but to help us understand how speech is created, or even how articulation can explain language structure. General issues such as the synthesis of different voices, accents, and multiple languages are discussed as special challenges facing the speech synthesis community.

Automation↗

Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1.

The isozymes of prostaglandin G/H synthase (PGHS) are shown to be differentially inhibited in vitro by currently marketed nonsteroidal anti-inflammatory drugs (NSAIDs) using microsomal rhPGHS-1 and rhPGHS-2. Comparison of selectivity ratios (IC50 rhPGHS-1/IC50 rhPGHS-2) demonstrated a 10-fold selectivity of etodolac (Lodine) for rhPGHS-2, whereas the other NSAIDs evaluated demonstrated no preference or a slight preference for inhibition of rhPGHS-1. In vitro enzyme results were supported by a human whole blood assay where etodolac also demonstrated a 10-fold selectivity for inhibition of PGHS-2 mediated TxB2 production. Taken together, these data may be key to explaining the clinically observed gastrointestinal safety of etodolac versus other marketed NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗