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Biomedical subjects

D Kramer

Publications and source records attributed to D Kramer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Sensitive and controversial ethical issues subject of groundbreaking Toronto exhibit.

Medical research and practice have always posed many ethical dilemmas for scientists and physicians, but technologic advances mean that the questions are becoming even more difficult. That is why an exhibit, A Question of Truth, that is being prepared at Toronto's Ontario Science Centre is so timely. It examines the biases and political climates in which science operates, as well as the relative subjectivity of truth, knowledge and reality.

Behavioral Research↗
PubMed1996

A simple mechanism for detecting low curvatures.

We measured thresholds for detecting the direction of curvature in slightly bent stimuli such as arcs and sinusoidal lines, and the direction of bend in chevrons and trapezoids in an initial experiment. Stimulus length varied over a wide range from 8.3 to 267 min arc. For sufficiently long stimuli, the angle between the stimulus and its chord was constant at 0.2-0.3 deg at detection threshold. The constant threshold implies that performance might be limited by the sensitivity of a single mechanism, in this case one that detects the orientation difference between the stimulus and its imaginary chord. In a second experiment, we investigated the two-dimensional extent of curvature sensitive units by measuring thresholds for detecting curvature of arcs that were flanked by straight lines on both sides. Thresholds remained unaffected at flank distances above 6 min arc but increased at lower distances independently of arc length, compatible with the assumption of a local, orientation sensitive mechanism. In a third experiment, we measured curvature detection with stimuli of different shapes to examine psychophysically the putative role of odd side margin receptive fields. We propose that low curvatures might be analysed by orientation sensitive units with a size around 20 x 8 min arc.

Form Perception↗
PubMed1996

First data on background levels of non-ortho and mono-ortho PCBs in blood of residents from southern Germany.

Blood-fat concentrations of polychlorinated biphenyls (PCB) congeners: no. 105, 118, 156 (mono-ortho-substituted) and no. 77, 126, 169 (non-ortho-substituted) and PCB congeners no. 28, 52, 101, 138, 153 and 180 were measured. The investigations were carried out in pooled samples from children and in individual samples from adults. Additionally polychloro-p-dibenzodioxins and -furans (PCDD/PCDF) were investigated.

Adipose Tissue↗
PubMed1996

Hyaluronate levels in donor organ washout effluents: a simple and predictive parameter of graft viability.

The principal cause of primary non-function in orthotopic liver transplantation is thought to be preservation injury to the microvasculature. We, therefore, evaluated if effluent levels of hyaluronate, whose uptake is an endothelial cell marker, could predict early graft function and ultimate graft outcome in orthotopic liver transplantation. A total of 102 cases were studied in two phases. In the first phase, we attempted to determine if a correlation existed between effluent hyaluronate levels, early graft function and ultimate graft outcome. This phase of the study was also used to determine hypothetical cut-off values for hyaluronate which could discriminate between good and bad livers. Thirty-two livers orthotopically transplanted to randomly selected primary recipients were studied. After varying periods of static cold storage (4 degrees C) in University of Wisconsin solution, the livers were reinfused with cold (4 degrees C) lactated Ringer's solution. The first 50 ml of the reperfusion effluent was collected from the infrahepatic vena cava. Effluent samples were analyzed for hyaluronate. Linear regression analysis demonstrated a significant correlation between effluent hyaluronate levels and post-operative aspartate and alanine aminotransferase levels (p < 0.001 for both). Logistic regression demonstrated a highly significant correlation (p = 0.0056) between effluent hyaluronate levels and ultimate graft outcome. Generation of Receiver Characteristics Curves indicated that a level between 400 and 430 micrograms.l-1 could possibly discriminate between good livers and those at risk of early graft failure. The authenticity of this hyaluronate cut-off level was further confirmed in the second phase of the study where 70 consecutive primary crossmatch-negative transplants were performed. A highly significant difference was observed in peak aspartate and alanine aminotransferase levels in the first week (p < 0.0006 and p < 0.0005, respectively) between livers with effluent hyaluronate levels < or = 400 micrograms.l-1 and livers with hyaluronate levels higher than 400 micrograms.l-1. Logistic regression revealed a highly significant correlation between effluent hyaluronate levels and graft success (p = 0.0001). Since hyaluronate uptake by the microvascular endothelial cell is significantly greater than production, high hyaluronate effluent levels in failed livers would be due to decreased hyaluronate uptake by the injured microvascular endothelial cell. We therefore conclude that effluent hyaluronate levels may prove to be a reliable preoperative test to assess early graft function and outcome in clinical orthotopic liver transplantation.

Adult↗
PubMed1995

Purification and characterization of the cytochrome b6 f complex from Chlamydomonas reinhardtii.

A protocol has been developed for the purification of the cytochrome b6 f complex from the unicellular alga Chlamydomonas reinhardtii. It is based on the use of the neutral detergent Hecameg (6-O-(N-heptylcarbamoyl)-methyl-alpha-D-glycopyranoside) and comprises only three steps: selective solubilization from thylakoid membranes, sucrose gradient sedimentation, and hydroxylapatite chromatography. The purified complex contains two b hemes (alpha bands, 564 nm; Em,8 = -84 and -158 mV) and one chlorophyll alpha (lambda max = 667-668 nm) per cytochrome f (alpha band, 554 nm; Em,8 = +330 mV). It is highly active in transferring electrons from decylplastoquinol to oxidized plastocyanin (turnover number 250-300 s-1). The purified complex contains seven subunits, whose identity has been established by N-terminal sequencing and/or peptide-specific immunolabeling, namely four high molecular weight subunits (cytochrome f, Rieske iron-sulfur protein, cytochrome b6, and subunit IV) and three approximately 4-kDa miniproteins (PetG, PetL, and PetX). Stoichiometry measurements are consistent with every subunit being present as two copies per b6 f dimer.

Amino Acid Sequence↗
PubMed1995

Use of 4-fluoro-L-ornithine to monitor metabolic flux through the polyamine biosynthetic pathway.

The mechanistic effectiveness of various polyamine analogs and enzyme inhibitors is typically determined by their ability to deplete intracellular polyamine pools. In this study, we describe an assay that may prove useful in augmenting this relatively static assessment of drug action. The assay relies upon the substitution of 4-fluoro-L-ornithine (Fl-Orn) for ornithine as a polyamine precursor to provide a means to measure metabolic flux through polyamine pools. At concentrations up to 500 microM, the analog did not inhibit the growth of L1210 murine leukemia cells during incubations of up to 72 hr. Using HPLC, the analog was processed metabolically over time to what was deduced to be 2-fluoroputrescine, 6-fluorospermidine and 6-fluorospermine. The relative proportion of fluorinated polyamine analog to the natural polyamine increased with time and Fl-Orn concentration. The sum of the two was found to be nearly identical to the respective polyamine pool of control cells exposed instead to 500 microM ornithine. This indicates that Fl-Orn was recognized and utilized as a precursor at a rate very similar to that of ornithine itself. Using L1210 cells at different stages of cell growth, it was determined that the metabolic flux through the pools, as indicated by the rate of appearance of individual fluorinated polyamine species, reflected the proliferation status of the cells--non-growing cells failed to incorporate the analog. Likewise, in cell types with varying polyamine pool profiles, such as polyamine enzyme overproducers or those with constitutively different spermidine of spermine ratios, the incorporation of the fluorinated analogs into pools was found to be proportional to the size to the natural polyamine pool. In cells treated with inhibitors of S-adenosylmethionine decarboxylase, Fl-Orn incorporation indicated a total blockade of polyamine synthesis at that enzyme site. Overall, the Fl-Orn assay has demonstrated that polyamine pool profiles generally reflect the rate of flux through the pathway in proliferating cells, suggesting that most intracellular polyamines are freely exchangeable with those undergoing metabolic flux.

Adenosylmethionine Decarboxylase↗
PubMed1995

Stable amplification of the S-adenosylmethionine decarboxylase gene in Chinese hamster ovary cells.

A Chinese hamster ovary cell subline (CHO/664) > 1000-fold resistant to the S-adenosylmethionine decarboxylase (AdoMetDC) inhibitor, CGP-48664 (4-(aminoiminomethyl)-2,3-dihydro-1H-inden-1-one diaminomethylenehydrazone), has been developed and characterized. The cells were also cross-resistant to the highly specific nucleoside analog inhibitor of AdoMetDC, MDL-73811. These unique cells stably overexpress AdoMetDC due to a 10-16-fold amplification of the AdoMetDC gene, which resulted in a similar increase in AdoMetDC transcript levels. In the presence of 100 microM CGP-48664, the CHO/664 cells displayed AdoMetDC activities similar to the parental line. Following removal of the inhibitor, AdoMetDC activity increased steadily over 20 days to 10-12 times that found in parental CHO cells. Decarboxylated (dc) AdoMet pools accumulated rapidly from < 5 pmol/10(6) cells to approximately 1000-1500 pmol/10(6) cells at 3 days due to diffusion away of intracellular inhibitor and to the depletion of putrescine and spermidine as aminopropyl acceptors in dcAdoMet-mediated synthase reactions. Polyamine pools shifted as putrescine, and spermidine pools were processed forward to spermine. During the period from 3 days to 20 days, dcAdoMet pools fell steadily and eventually stabilized at 100-200 pmol/10(6) cells. Providing excess putrescine at this time as an aminopropyl acceptor rapidly lowered dcAdoMet pools and led to a near normalization of polyamine pools, indicating that both dcAdoMet and putrescine are essential in maintaining steady-state polyamine pool profiles. As with cell line variants that overproduce ornithine decarboxylase, polyamine transport was found to be increased in CHO/664 cells due to an apparent inability of the system to down-regulate polyamine transport in response to polyamine excess. Given the unique metabolic disturbances seen in these cells, we anticipate that in addition to providing a useful system for evaluating the specificity of newly developed AdoMetDC inhibitors, they will undoubtedly prove valuable for investigating the various regulatory interrelationships involved in polyamine homeostasis and possibly other aspects of purine metabolism.

Adenosylmethionine Decarboxylase↗
PubMed1995

Immunoglobulin G lymphocytotoxic antibodies in clinical liver transplantation: studies toward further defining their significance.

Twenty-two consecutive liver allograft recipients, who tested positive for immunoglobulin G (IgG) lymphocytotoxicity were subjected to pretransplantation and posttransplantation immunologic monitoring of anti-donor IgG lymphocytotoxic antibody titers, total hemolytic complement activity (CH100), circulating immune complexes (CIC), and platelet counts in an effort to improve our understanding of the preformed antibody state in clinical hepatic transplantation. Ten contemporaneous liver transplant recipients whose crossmatch results were negative and who experienced severe hepatocellular damage early after transplantation were included as controls. Crossmatch test results were negative 1 day after transplantation and during the 1 month follow-up remained negative in 14 of 22 (64%) sensitized recipients, most of whom had relatively low (< or = 1:16) anti-donor IgG antibody titers before transplantation. After transplantation, this group and the control group experienced no thrombocytopenia, no increase of CIC, and a gradual increase in CH100 activity that reached normal levels within 1 week. A strong negative correlation between prothrombin time (PT) and CH100 activity in these groups of patients suggested that changes in CH100 activity (P < .0005) were tightly linked to liver synthetic function. In contrast, the crossmatch test results remained positive after transplantation in 8 of 22 (36%) sensitized recipients, all of whom had relatively high (> 1:32 to 1024) pretransplantation titers of anti-donor IgG antibodies. After transplantation these patients developed a syndrome that was characterized by decreased CH100 activity and increased CIC compared with pretransplantation levels and refractory thrombocytopenia that was associated with a 50% allograft failure rate because of biopsy-proven humoral and acute (cellular) rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Regional cerebral blood flow and CO2 reactivity in fulminant hepatic failure.

Alterations in cerebral hemodynamics are postulated to contribute to brain herniation, a major cause of death in patients with severe hepatic encephalopathy due to fulminant hepatic failure (FHF). In an effort to identify these changes in cerebral hemodynamics, regional and global cerebral blood flow (CBF) and CO2 reactivity were measured using stable xenon-enhanced computed tomography (Xe/CT) in 24 patients within 72 h of onset of severe hepatic encephalopathy. Regional variations in CBF, most notably, a relative decrease in CBF in the anterior circulation and an increase in CBF in the posterior circulation were found. CBF was significantly lower in FHF patients compared with controls, however, these values are well out of the established ischemic range. FHF patients also showed significant impairment in CBF response to hypoventilation, while the CBF response to hyperventilation remained intact. This study suggests that FHF patients demonstrate early changes in both CBF patterns and CO2 reactivity. The relatively "normal" CBF values obtained in FHF patients in severe hepatic encephalopathy coupled with the lack of vasodilatation to hypoventilation suggest a state of uncoupled CBF and metabolism or "luxury perfusion" that could theoretically contribute to vasogenic edema, brain swelling, and cerebral herniation.

Adult↗
PubMed1995

Differential age effects of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery.

Central nervous system dysfunction is a common consequence of otherwise uncomplicated cardiac surgery. Many mechanisms have been postulated for the cognitive dysfunction that is part of these neurologic sequelae. The purpose of our investigation was to evaluate the effects of mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) and the rate of rewarming on cognitive decline after cardiac surgery. Two hundred thirty-seven patients completed preoperative and predischarge neuropsychologic testing. MAP and temperature were recorded at 1-min intervals using an automated anesthesia record keeper. MAP area less than 50 mm Hg (time and degree of hypotension), as well as the maximal rewarming rate, were determined for each patient. Multivariable linear regression revealed that the rate of rewarming and MAP were unrelated to cognitive decline. However, interactions significantly associated with cognitive decline were found between age and MAP area less than 50 mm Hg on one measure, and between age and rewarming rate in another, identifying susceptibility of the elderly to these factors. Although MAP and rewarming were not the primary determinates of cognitive decline in this surgical population, hypotension and rapid rewarming contributed significantly to cognitive dysfunction in the elderly.

Aged↗
PubMed1995

Measurement of breast implant volume with magnetic resonance imaging.

In principle, tomographic imaging of breast implants provides the information needed to compute implant volume. We have investigated the reliability of this measurement as a means of diagnosing the loss of gel from the implant. We find that measurement errors, postimplantation changes of the implant, uncertainties in the patients' records, and lack of knowledge of the implant temperature in the body can lead to significant discrepancies, making this measurement unreliable as a diagnostic tool.

Breast Implants↗
PubMed1995

MRI findings in subjects with breast implants.

One-hundred and nineteen implants were imaged in an open-sided low-field magnetic resonance imaging system. Thirty-four of these implants were removed, and postoperative reports were made available. We found a variety of signs associated with the implants, including internal structures, loss of saline in double-lumen implants, intracapsular and extracapsular fluid accumulations, signal dropout regions most likely associated with calcifications, and debris and fluid in the silicone, as well as degradation of the silicone, disruptions of the capsule and bulging, and extracapsular silicone. Conclusions of intact versus ruptured were made on the basis of these findings and found to be confirmed in 32 of 34 cases, with 1 false-positive and 1 false-negative result. Based on MRI criteria for a broad sample of the population, 27 percent of the implants were considered ruptured.

Adult↗
PubMed1995

Resident service hours in emergency medicine. SAEM Education Committee.

OBJECTIVE: The number of hours worked by residents in all specialties has become a controversial issue. Residents often are expected to competently conduct patient care activities and to take educational advantage of clinical experiences in spite of frequent fatigue and sleep deprivation. This survey of residency directors was designed to assess the scheduled clinical time for emergency medicine (EM) residents. METHODS: A 13-question survey dealing with time commitments of EM residents was sent to the residency directors of all accredited EM residency programs in the United States in the fall of 1991. Residency directors were asked to indicate the number of shifts, hours, and days off per week; and the number of night shifts and weekend days off per month for each postgraduate year of residency training (PGY1-PGY4). Directors also were asked whether shifts were scheduled randomly or predictably with progression from days to nights with time off after nights. RESULTS: Seventy of 71 (98.6% response rate) residency directors responded. Residents were scheduled for an average of 49.1 hours per week. Scheduled hours decreased from an average of 51.9 at the PGY1 level to an average of 44.5 at the PGY4 level. A similar progression with year of training was noted for scheduled night shifts/month, days off/week, and weekend days off/month. A PGY1 trainee averaged 7.0 night shifts/month, 1.9 days off/week, and 3.0 weekend days off/month; while a PGY4 trainee averaged 5.3, 2.4, and 3.2, respectively. Only 40% of the directors reported predictable scheduling progressing from days to nights. CONCLUSION: Emergency medicine resident schedules, as reported by residency directors, fall well within current specialty-specific requirements and compare favorably with the reported numbers for other specialties. However, because large ranges in scheduling parameters were reported, the data may be of value to residency directors, residents, and prospective residents. Most programs did not report a predictable schedule progression of shifts.

Appointments and Schedules↗
PubMed1995

Effects of continuous lateral rotation therapy on pulmonary complications in liver transplant patients.

BACKGROUND: When liver transplant candidates and recipients suffer from pulmonary complications of immobility, the results can be life-threatening. Continuous lateral rotation therapy has been reported to decrease complications of immobility. OBJECTIVES: To determine whether continuous lateral rotation therapy decreases the duration of mechanical ventilation, intensive care unit length of stay, incidence or resolution of atelectasis, incidence or onset time of lower respiratory tract infection and pneumonia. METHODS: Sixty-nine subjects admitted to a liver transplant intensive care unit at a university teaching hospital were randomly assigned to continuous lateral rotation therapy or a stationary bed. All subjects were mechanically ventilated for 24 hours and had a Glasgow Coma Scale score of 11 or less upon admission to the study. Subjects were followed until out of bed, unable to rotate for 3 consecutive days, or transferred from the intensive care unit. Data and chest roentgenogram results were collected on admission and daily during the study. Sputum culture results were obtained if available as part of normal patient care. RESULTS: Incidence of lower respiratory tract infection was significantly lower and length of time to occurrence of lower respiratory tract infection was significantly longer in the continuous lateral rotation therapy group than in the stationary bed group. CONCLUSIONS: Although continuous lateral rotation therapy did not affect duration of mechanical ventilation, length of stay, or incidence of atelectasis, it was effective in decreasing the incidence of, and increasing onset time to, lower respiratory tract infection in the liver transplantation population.

Adolescent↗
PubMed1994

Antiproliferative properties of polyamine analogues: a structure-activity study.

A basis set of polyamine analogues was designed and synthesized. These compounds were used to initiate a systematic investigation of the role of chain length, terminal nitrogen alkyl group size, and symmetry of the methylene backbone in the antineoplastic properties of polyamine analogues. New synthetic methods predicated on our earlier polyamine fragment synthesis are described for accessing the tetraamines of interest. An unsymmetrically substituted diamine reagent, N-(tert-butoxycarbonyl)-N,N'-bis(mesitylenesulfonyl)-1,4-diaminobu tane, was developed for entry into unsymmetrical tetraamines. All of the tetraamines synthesized were first evaluated in a murine leukemia L1210 cell IC50 assay at 48 and 96 h. In an attempt to correlate this behavior with some aspect of polyamine metabolism, each compound was tested for its ability to compete with spermidine for the polyamine uptake apparatus, its impact on the polyamine biosynthetic enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), and its effect on the polyamine-catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) and on polyamine pools. While there was no obvious correlation between the 48 and 96 h IC50's and the impact of the analogues on polyamine metabolism, there were other structure-activity relationships. Correlations were observed to exist between chain length and IC50's and between terminal alkyl substituents and impact on Ki, ODC, and AdoMetDC. Also, preliminary studies suggest a relationship may exist between the 48 and 96 h IC50 activities and the analogue's chronic toxicity in vivo. Finally, when the overall length of the polyamine backbone was held constant, the symmetry of the methylene chains of the polyamine fragments was shown to be unimportant to the compound's activity.

Acetyltransferases↗